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The differentiation of delayed serologic and delayed hemolytic transfusion reactions: incidence, long-term serologic findings, and clinical significance. Delayed serologic transfusion reactions (DSTRs) and delayed hemolytic transfusion reactions (DHTRs) were studied in a large tertiary-care hospital. A DSTR was defined by the posttransfusion finding of a positive direct antiglobulin test (DAT) and a newly developed alloantibody specificity. A DHTR was defined as a DSTR case that showed clinical and/or laboratory evidence of hemolysis. Thirty-four cases of DSTR, 70 percent of which were due to anti-E and/or -Jka, were documented prospectively over a 20-month period. Retrospective review of the medical records found clinical evidence of hemolysis in only 6 (18%) of the 34. Thus, the incidence of DSTR was 1 (0.66%) of 151 recipients with posttransfusion samples available for testing, whereas the incidence of DHTR was only 1 (0.12%) of 854 patients tested. Fifteen of the 34 patients were followed for up to 174 days after reaction. Twelve of the 15 still demonstrated a positive DAT with anti-IgG only. Eluate studies indicated that the persistence of a positive DAT after DSTR or DHTR may involve several immunologic mechanisms, including the development of posttransfusion autoantibodies. This study indicates 1) that DSTRs are a frequent finding in multiply transfused patients, although most cases are benign and fail to meet rigid criteria for DHTR, and 2) that the persistence of a positive DAT after DSTR or DHTR is common.

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.

Selective spatial attention in patients with visual extinction. The present study was designed to verify the attentional performance of patients with parietal lesions in the experimental condition in which they had to pay attention to 3 spatial positions located on the left, on the right and directly above the fixation stimulus (Experiment 1) and to only 1 of the 3 spatial positions at a time (Experiment 2). Twelve patients (6 subjects with right parietal lesions and 6 subjects without neurological deficits) participated in the experiment. The results of Experiment 1 showed that in patients with right parietal lesions the speed and accuracy of response to horizontally aligned stimuli increased gradually from right to left, whereas the control group showed only the effect due to the different retinal eccentricities of the 3 stimuli, that is, responses to central stimuli were faster and more accurate than responses to left and right stimuli. The results of Experiment 2 showed that both the neurological and control groups were faster to respond to central than to left and right stimuli, and that the neurological group was faster to respond to right than left stimuli, whereas no difference in RTs between two visual fields was obtained in the control group. Furthermore, when the patients had to respond to 3 spatial locations aligned horizontally (Experiment 1), the speed and accuracy of response to the right stimulus were the same as when they had to focus attention on it (Experiment 2). These results showed that the focus of attention in patients with visual extinction is on the rightmost stimulus and that the increased attention to the right is accompanied by a decreased attention to the left.

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.

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.

Balloon rupture due to lesion morphology during coronary angioplasty. We report a case of coronary angioplasty of a left anterior descending artery lesion that was complicated by the rupture of three successive balloon catheters. Each rupture occurred as a pinhole jet of contrast into a diagonal side branch, causing subintimal staining. This case demonstrates that balloon rupture may result from lesion morphology.

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.

Percutaneous balloon valvotomy for patients with mitral stenosis: initial and follow-up results. Percutaneous double balloon mitral valvotomy (PMV) was performed in 25 patients with severe mitral stenosis who were followed for at least 6 months after the procedure. There were 22 women and 3 men, with a mean age of 51 +/- 14 years (range, 27 to 74). Hemodynamic and angiographic findings were evaluated before and after PMV and clinical status was assessed at follow-up. There was a significant decrease in mitral gradient following PMV, from 15.4 +/- 5.1 to 5.0 +/- 2.6 mm Hg (p less than .0001); an increase in cardiac output, from 4.6 +/- 1.1 to 5.2 +/- 1.1 L/min (p less than .01); and an increase in calculated mitral valve area, from 0.9 +/- 0.2 to 2.2 +/- 0.6 cm2 (p less than 0.0001). Mitral regurgitation developed or increased in severity in six patients (24%). At the time of follow-up (mean, 12 +/- 5 months), three patients required elective mitral valve replacement for symptomatic mitral regurgitation and 91% (20 of 22) of the remaining patients had continued improvement in functional class. PMV can safely be performed in properly selected patients with symptomatic mitral stenosis with good immediate and follow-up results.

Loss of endothelium-dependent relaxant activity in the pulmonary circulation of rats exposed to chronic hypoxia. To determine whether exposure to chronic hypoxia and subsequent development of pulmonary hypertension induces alterations of endothelium-dependent relaxation in rat pulmonary vascular bed, we studied isolated lung preparations from rats exposed to either room air (controls) or hypoxia (H) during 1 wk (1W-H), 3 wk (3W-H), or 3W-H followed by 48 h recovery to room air (3WH + R). In lungs pretreated with meclofenamate (3 microM), the endothelium-dependent vasodilator responses to acetylcholine (10(-9)-10(-6) M) and ionophore A23187 (10(-9)-10(-7) M) were examined during conditions of increased tone by U46619 (50 pmol/min). Acetylcholine or A23187 produced dose-dependent vasodilation in control lungs, this response was reduced in group 1W-H (P less than 0.02), abolished in group 3W-H (P less than 0.001), and restored in group 3WH + R. In contrast, the endothelium-independent vasodilator agent sodium nitroprusside remained fully active in group 3W-H. The pressor response to 300 pM endothelin was greater in group 3W-H than in controls (6.8 +/- 0.5 mmHg vs. 1.6 +/- 0.2 mmHg, P less than 0.001) but was not potentiated by the endothelium-dependent relaxing factor (EDRF) antagonists: hydroquinone (10(-4) M); methylene blue (10(-4) M); and pyrogallol (3 x 10(-5) M) as it was in controls. It was similar to controls in group 3W-H + R. Our results demonstrate that hypoxia-induced pulmonary hypertension is associated with a loss of EDRF activity in pulmonary vessels, with a rapid recovery on return to a normoxic environment.

Near fatal subacute thallium poisoning necessitating prolonged mechanical ventilation. The authors describe a case of severe sensory-motor polyneuropathy caused by subacute thallium-intoxication rapidly progressing to respiratory failure due to complete muscle paralysis. After more than 2 months of mechanical ventilation, weaning from the ventilator was possible. Further intensive physical rehabilitation required an additional 6 months hospital stay, and 18 months later, neurological recovery was complete except for the distal lower limbs muscles. The authors discuss the different forms of thallotoxicosis and the present treatment is reviewed. Maximal prolonged therapeutic support should be offered in severe thallotoxicosis because of possible near complete recovery.

Cervicocephalic kinesthetic sensibility in patients with cervical pain. Head orientation in space makes use of multiple sensory afferents, among which the cervical proprioceptive cues could play a predominant role. To quantify the alteration of neck proprioception in patients with cervical pathology, we proposed a test for the clinical evaluation of the ability to relocate the head on the trunk after an active head movement, for 30 healthy subjects and 30 patients with cervical pain. The data demonstrated that this ability was significantly poorer in the patient group, indicating an alteration in neck proprioception. This test permits a discriminant classification of healthy and sick subjects, justifies proprioceptive rehabilitation programs, and allows a quantitative evaluation of their results.

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.

Blood pressure level, trend, and variability in Dunedin children. An 8-year study of a single birth cohort In a birth cohort of children in the Dunedin Multidisciplinary Health and Development Study in New Zealand, resting blood pressures were recorded biennially five times from age 7 to 15 years. Using previously described methods, we examined the level, trend, and variability of blood pressures in those children with at least three readings. The level, trend, and variability of height, weight, and body mass index were compared among six separate groups of children. Two groups were categorized on the basis of high systolic pressure levels, one with low variability and the other with high variability, which was thought to resemble adult labile hypertension. Two additional groups were categorized on the basis of increasing and decreasing blood pressure trends; the fifth group had consistently low blood pressures, and the sixth group consisted of the remaining children. There were significant differences among the groups for the level of all the physical measurements and for the trend of body mass index. No significant differences were found among the groups for gender or socioeconomic status. A parental history of high blood pressure, stroke, or heart attack was significantly more common in the first two groups.

Sinus node-atrioventricular node isolation: long-term results with the "corridor" operation for atrial fibrillation The "corridor" operation is designed to restore sinus rhythm to patients with atrial fibrillation by electrically isolating the sinus node, a band of atrial tissue and the atrioventricular (AV) node from the remaining atrial tissue. Nine patients with drug-refractory atrial fibrillation underwent this operation; four patients had chronic atrial fibrillation and five had paroxysmal atrial fibrillation; the mean duration of symptoms was 12 +/- 8 years. Patient ages ranged from 25 to 68 years (mean 48 +/- 12). At preoperative electrophysiologic study, no patient had evidence of an accessory AV pathway or AV node reentry. Sinus node recovery time could not be determined in five patients because of recurrent atrial fibrillation during or before programmed stimulation. At operation the corridor of atrial tissue connecting the sinus and AV nodes was successfully isolated from the remaining left and right atrial tissue in all patients. One patient required early reoperation for recurrent atrial fibrillation before hospital discharge. At the predischarge electrophysiologic study, the corridor remained isolated in all patients except for one patient who had intermittent conduction between the corridor and excluded right atrium. One patient had nonsustained atrial fibrillation and one had atrial tachycardia evident in the corridor. Atypical AV node reentry of uncertain significance was induced in one other patient. Over a total follow-up of 191 patient months (mean 21 +/- 20), seven patients remained free of atrial fibrillation. Two patients had recurrent atrial fibrillation, which in one patient was effectively controlled by a single antiarrhythmic agent. A permanent pacemaker was implanted in four patients for sinus node dysfunction.

Adult immunization in a network of family practice residency programs. A substantial proportion of morbidity and mortality associated with vaccine-preventable diseases occurs among adults. Teaching residents about disease prevention is mandated in the curriculum guidelines for family practice programs. A cooperative study among the Kansas City family practice residency programs was begun to look at immunization behaviors in these teaching programs. A retrospective audit of medical records and a prospective survey of residents and faculty were performed. From the medical records of 400 patients seen for health maintenance examinations, the frequency of tetanus-diphtheria immunizations recorded was 4.75%. The pooled immunization rate recorded for pneumococcal vaccine was 25%, and for influenza vaccine, 24%. Although 93% of respondents knew patients need tetanus-diphtheria immunization every 10 years, on a written questionnaire giving clinical examples, they were less likely to elect to immunize older patients eligible for tetanus-diphtheria vaccine. The following immunization criteria were listed by respondents: for pneumococcal vaccine, age over 65 years (86%); for influenza vaccine, age over 65 years (85%), chronic diseases (69%), residence in a chronic care facility (7%), and being a health care worker (28%). Educational interventions stressing the appropriate criteria and involvement of the patient are planned at the separate programs.

Pathogenesis of ischemic necrosis in random-pattern skin flaps induced by long-term low-dose nicotine treatment in the rat. The objectives of the present experiments were to study the effects of long-term low-dose nicotine treatment on skin hemodynamics, viability, and microvascular morphology in 4 x 10 cm dorsally based acute random-pattern skin flaps in the rat. In addition, the reversibility of the nicotine-induced detrimental effects on skin-flap viability following cessation of nicotine treatment also was investigated. Low-dose nicotine (0.6 mg/kg) administered twice daily and subcutaneously for 24 weeks significantly (p less than 0.05) decreased skin-flap capillary blood flow, distal perfusion, and length and area of skin viability compared with the saline-treated control (n = 15). However, these same parameters in rats (n = 15) whose nicotine treatment had been withheld for 2 weeks prior to skin-flap surgery were not significantly different from the control, thus indicating that the detrimental effects of this long-term, low-dose nicotine treatment were reversible. The mean plasma level of nicotine in the nicotine-treated rats was 8.1 +/- 0.4 micrograms/dl and was within the range of plasma nicotine levels reported for human heavy cigarette smokers. Light and electron microscopic studies did not show evidence of histologic damage to the cutaneous microvasculature in acute random-pattern skin flaps and samples of normal (nonoperated) skin in nicotine-treated rats. It is concluded that long-term plasma levels of nicotine similar to those of heavy cigarette smokers are detrimental to the capillary blood flow and viability of random-pattern skin flaps in the rat. These deleterious effects can be avoided if skin flaps are raised 2 weeks after cessation of nicotine treatment. This low-dose nicotine treatment does not cause histologic damage to the microvasculature. Other pathogenic mechanisms of nicotine-induced skin flap ischemia are discussed.

Sinus arrest induced by trivial nasal stimulation during alfentanil-nitrous oxide anaesthesia. A case is reported of bradycardia and sinus arrest induced by insertion of a nasal temperature probe. Other possible causes of bradycardia and sinus arrest under anaesthesia are reviewed briefly. Evidence for the neurological basis of a nasocardiac reflex, similar to the oculocardiac reflex, is presented. A minor, trivial stimulus may elicit this reflex.

Pulse rate, coronary heart disease, and death: the NHANES I Epidemiologic Follow-up Study. To determine whether associations of elevated resting pulse rate with CHD incidence or death in white men are independent of other risk factors and whether such associations exist for women and blacks, data were examined from the NHANES I Epidemiologic Follow-up Study. Over a follow-up period of 6 to 13 years, elevated RR for CHD incidence were found for older white men with baseline pulse greater than 84 beats/min compared with less than 74 beats/min after controlling multiple risk factors (RR = 1.37, 95% CL 1.02, 1.84). Risks of death from all causes, cardiovascular diseases, and noncardiovascular diseases were also elevated for white men with elevated pulse rate independent of other risk factors. CHD incidence was increased in white women with elevated pulse rate. Risks of death from all causes, cardiovascular diseases, and noncardiovascular diseases, were also elevated for white men with elevated pulse rate independent of other risk factors. CHD incidence was increased in white women with elevated pulse rate. Risk of death from all causes and cardiovascular diseases was elevated in black men and women with elevated pulse rate. Risk of death from noncardiovascular disease was elevated in black men with elevated pulse rate. The association with cardiovascular death was particularly striking in black women, even after adjusting for baseline risk factors (RR 3.03, 95% CL 1.46, 6.28). Further studies are needed to assess associations of pulse rate with CHD in blacks and to elucidate mechanisms in all groups.

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.

Sphincter of Oddi manometry: decreased risk of clinical pancreatitis with use of a modified aspirating catheter. This study was undertaken to determine whether routine use of a modified triple-lumen five French sphincter of Oddi manometry catheter would reduce the frequency and severity of post-manometry pancreatitis and pancreatic enzyme elevation. Seventy-six patients were alternately assigned to undergo sphincter of Oddi manometry (SOM) with a standard perfusion (infused group) catheter or the newly developed aspiration (aspirated group) catheter. After SOM, there were significantly more patients in the infused group with both amylase and lipase values elevated at least two times the upper limits of normal at 2 (p less than 0.001), 6 (p = 0.01), and 18 hours (p = 0.03) after the procedure. As compared with the standard perfusion system, the aspiration catheter was associated with a decreased frequency of clinical pancreatitis (23.5% vs. 3%, p = 0.01) reduced hospital stay (5 +/- 1.83 days, mean +/- SE, versus 1 day; p = 0.03) and milder pancreatitis. The aspiration manometry catheter should be considered for standard use for SOM, particularly if the pancreatic duct sphincter is being evaluated.

Massive hemorrhage from an arterioureteral fistula associated with chronic renal transplant failure. A case of arterioureteral fistula from the graft artery stump of a failed transplant and the native ureter is reported. This case illustrates one of the possible complications of graft anastomosis. The etiological factors involved in the formation of the aneurysm and eventually the fistula are discussed.

Jets over Labrador and Quebec: noise effects on human health. OBJECTIVE: To determine whether the noise from low-level flights over Labrador and Quebec is harmful to human health. DATA SOURCE AND SELECTION: Search of MEDLINE for articles on the effect of noise, particularly impulse noise associated with low-level flights, and a search of the references from identified articles. DATA SYNTHESIS: The noise levels from low-level flights could affect hearing acuity. However, the more important consequences appear to be stress-mediated physiologic effects, especially cardiovascular ones, and psychologic distress, particularly in children. Subjective perception of control over the noise has been found to mitigate some physiologic effects. CONCLUSION: There is sufficient evidence to show that the noise from low-level flights is harmful to human health.

Metabolic studies of radioiodinated serum amyloid P component in normal subjects and patients with systemic amyloidosis. 125I-Serum amyloid P component (SAP), injected intravenously into 10 normal subjects, remained predominantly intravascular with mean (SD) T1/2 (half time) in plasma of 24.5 (5.9) h. The fractional catabolic rate of 68 (19)% of the plasma pool per day was more rapid than other reported human plasma proteins. All radioactivity was excreted in the urine by 14 d. In 16 patients with monoclonal gammopathy or chronic inflammatory diseases, but without amyloidosis, 125I-SAP metabolism was normal. However, among 45 patients with biopsy-proven systemic amyloidosis (25, amyloid A type; 20, amyloid L type), 125I-SAP was cleared from the plasma more rapidly, accumulated in the amyloid deposits, and persisted there. The T1/2 in amyloid, measured directly with 131I-SAP, was 24 d. Repeat studies after 6-18 mo were notably consistent in normals but changed significantly in amyloid patients, generally correlating with clinical signs of disease progression. Measurements of 125I-SAP turnover may thus be of value for diagnosis and monitoring of amyloidosis. Analysis of SAP metabolism in amyloidosis suggests that plasma SAP is in dynamic equilibrium with a very large amyloid pool, and in two autopsies the total mass of SAP in the amyloid deposits was 2,100 and 21,000 mg, respectively.

Changing cancer care in the 1990s and the cost. Progress in cancer research in the 1980s has led to predictions of a technologic explosion in the 1990s. Yet, with this progress there has been a groundswell of protest at the rapidly escalating costs of health care. More than $600 billion was spent on health care in 1989 and estimates of $1.5 trillion are made for the year 2000. Repeated attempts at cost containment have failed. It has been suggested that only by retarding technologic advances will we be able to control costs. Many observers believe that rationing of health care is the only solution, but new technology not only improves cancer care, it often decreases cost. It is not rational to retard advances that may later reduce costs, nor is it humane to retard advances that improve care, even if they cost more. In identifying priorities we should begin with the principle that treatments be restricted to clinical trials unless they have been demonstrated to prolong survival or improve the quality of life. If the payers reimburse procedures in an investigative setting, they will be on firm ground when they deny support for those same procedures outside an investigative setting. This is both an ethical and a fiscally responsible position for the third parties to take. It will not be easy for the profession or for the payers to deal with these problems. Public education and patient education will be key elements of any solution. Shifting the blame from politician to payer to professional will only make the problems worse.

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.

Pancreatic ascites: treatment by continuous somatostatin infusion. Two male patients with recurrent acute pancreatitis due to alcohol abuse were admitted with pancreatic ascites (high concentration of amylase, raised protein concentration, no specific cytologic features). Ultrasound (US) and computed tomography (CT) confirmed gross ascites and inflammation of the pancreas in both patients, and a pseudocyst in the head of the pancreas in one of them. Treatment with total parenteral nutrition (TPN) and a H2-blocking agent was instituted and continued for 4 and 2 wk, respectively. Due to lack of improvement, somatostatin infusion (250 micrograms/h) was started. During the next few days, there was a rapid improvement of the clinical status, and the production of ascites ceased. We conclude that somatostatin infusion should be tried before any invasive diagnostic or therapeutic intervention in patients with pancreatic ascites.

Early detection of acute myocardial infarction in patients presenting with chest pain and nondiagnostic ECGs: serial CK-MB sampling in the emergency department [published erratum appears in Ann Emerg Med 1991 Apr;20(4):420] STUDY OBJECTIVES: Patients presenting to the emergency department with chest discomfort are a difficult problem for emergency physicians. Nearly 50% of patients with acute myocardial infarction (AMI) will initially have nondiagnostic ECGs on ED presentation. The purpose of this study was to determine if patients with AMI having nondiagnostic ECGs could be identified using new immunochemical assays for serial CK-MB sampling in the ED. DESIGN: Chest pain patients, more than 30 years old, with pain not caused by trauma or explained by radiographic findings, were eligible for the study. Serial serum samples were drawn on ED presentation (zero hours) and three hours after presentation, then analyzed for CK-MB using four immunochemical methods and electrophoresis. Standard World Health Organization criteria were used to establish the diagnosis of AMI, including new Q-wave formation or elevation of standard in-hospital serum cardiac enzyme markers. SETTING: A tertiary cardiac care community hospital. MEASUREMENTS AND MAIN RESULTS: The serum from 183 patients hospitalized for possible ischemic chest pain was collected and analyzed. Thirty-one of 183 patients (17%) were found to have AMI by standard in-hospital criteria. Sixteen of the 31 patients (52%) with AMI had nondiagnostic ECGs on presentation. Immunochemical determination of serial CK-MB levels provided a sensitive and specific method for detecting AMI in patients within three hours after ED presentation compared with standard electrophoresis. The four immunochemical methods demonstrated a range in sensitivity from 50% to 62.1% on ED presentation versus 92% to 96.7% three hours later. The immunochemical tests demonstrated specificities ranging from 83.0% to 96.4% at three hours, with three of the four tests having specificities of 92% or greater. Electrophoresis had a sensitivity of 34.5% on ED presentation, increasing to 76.9% at three hours, with a specificity of 98.6%. CONCLUSIONS: Immunochemical CK-MB methods allowed rapid, sensitive detection of AMI in the ED. Early detection of AMI offers many potential advantages to the emergency physician. Early detection of AMI, while the patient is in the ED, could direct disposition of this potentially unstable patient to an intensive care setting. Such information may prevent the ED discharge of patients with AMI having nondiagnostic ECGs. The diagnosis of AMI within a six-hour period after symptom onset may allow thrombolytic therapy to be given to patients with AMI not having diagnostic ECGs. This study served as a pilot trial for a multicenter study of the Emergency Medicine Cardiac Research Group, which is currently ongoing.

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.

Symptomatic carotid endarterectomy trials. The possible benefit of carotid endarterectomy in stroke prevention is being evaluated in three major clinical trials. To date, the European Carotid Surgery Trial has randomized 2,200 patients, 30% of whom have a carotid stenosis of greater than 70% appropriate to their symptoms. The North American Symptomatic Carotid Endarterectomy Trial has randomized 1,000 patients, of whom more than half have this severity of appropriate stenosis. Quality control and the evaluation of outcome events in this trial is achieved by a three-tier review, including review by medical and surgical adjudicators who are blinded to the treatment arm of each patient. Baseline characteristics of the patients eligible but not randomized are similar to those of patients who have been randomized. Two percent of the patients randomized to the surgical arm have declined surgery and crossed over to the medical arm, and 3% have elected surgery after randomization to the medical arm. Both of these studies, as well as a Veterans Administration trial, are continuing to randomize patients.

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.

Effects of spermatic vascular division for correction of the high undescended testis on testicular function. Orchiopexy with division of the spermatic artery and veins is a commonly used technique for correcting the high undescended testis, although the longterm results have not been clearly defined. The left spermatic artery and veins of 22 adult Wistar albino rats were divided while preserving the vessels associated with the vas and cremaster muscle (DT). A sham operation was performed on the left testicle of six additional rats (ST). At 3 weeks postoperatively, both testes from all rats were removed. All testes were viable and bled when incised, although bleeding was considerably reduced in testes with DT. Mean testicular weights after DT were 1,061 +/- 423 mg compared with 1,634 +/- 125 mg for ST rats (p less than 0.02) and 1,508 +/- 119 mg for contralateral testes. The mean tubular diameter after DT was 220 +/- 37 mu compared with 303.1 +/- 10.7 mu for ST testes (p less than 0.02). The testicular biopsy score based upon the morphology of the spermatic tubules was 4.46 +/- 3.32 for DT testes and 8.65 +/- 0.23 for ST testes (p less than 0.02) compared with 8.38 +/- 0.18 for contralateral testes and an absolute normal value of 10. No morphologic abnormalities were observed in the contralateral unoperated testes from any of the rats. The contralateral testes in 12 additional rats were removed before DT. The mean testosterone values in these rats with one testicle was 1.43 +/- 0.75 ng/mL. Three weeks after DT, testosterone values were 0.19 +/- 0.31 ng/mL (p less than 0.01). It is concluded that division of the main spermatic artery and vein in rats produces testicular atrophy with spermatogenic arrest and interstitial cell dysfunction. Although collateral blood flow to the testis may be demonstrated, tissue perfusion is inadequate for normal spermatogenesis and endocrine function.

Landau-Kleffner syndrome: a clinical and EEG study of five cases. In five children with normal initial psychomotor development, a Landau-Kleffner syndrome appeared at age 3-7 years. No neuroanatomic lesions were noted. Aphasia and hyperkinesia were isolated in three patients and associated with global regression of higher cortical functions in one patient. Massive intellectual deterioration and psychotic behavior were associated with transient aphasia in one patient. The epilepsy (focal motor and generalized tonic-clonic seizures, subclinical EEG focal seizures during sleep, and atypical absences) always regressed spontaneously or with antiepileptic drug (AED) treatment. The EEG in waking patients showed focal and generalized spike-wave discharges on a normal background rhythm. Discharge topography and pattern changed frequently. During sleep, discharges always increased. At some time during syndrome development, all patients had bilateral spike-waves for greater than 85% of the sleep period, while at other times the discharges were discontinuous or continuous but focal or unilaterally hemispheric. Discharge topography and abundance changed from night to night. The abnormal EEG and the impaired higher functions developed and regressed together, but not with strict temporal correlation. Our own experience suggests that the Landau-Kleffner syndrome and epilepsy with continuous spike-wave activity in slow-wave sleep cannot be clearly differentiated. They may be different points on the spectrum of a single syndrome.

Cholangiocarcinoma. The diagnosis of cholangiocarcinoma can now be made with greater rapidity and accuracy. In the clinical setting of obstructive jaundice, a CT scan or sonogram may suggest cholangiocarcinoma if dilated intrahepatic ducts are seen with a nondilated extrahepatic biliary tree. The diagnosis is confirmed by cholangiography, and the tumor is staged by the combination of cholangiography and angiography. If the tumor extensively involves both lobes of the liver or involves the main portal vein or hepatic artery, the lesion is considered unresectable. These patients are best palliated nonoperatively, but they should still have an attempt at a tissue diagnosis, as various other lesions can masquerade as cholangiocarcinoma. In comparison, if the tumor is confined to or is distal to the hepatic duct bifurcation, extends into only one lobe of the liver, or involves only the right or the left portal vein or hepatic artery, the lesion may be resectable, and exploration is indicated. As many as half of all patients explored with curative intent will have a successful resection. Various surgical options are appropriate for patients undergoing tumor resection, depending on the site and extent of the lesion. Similarly, several surgical options are possible for palliation in patients with unresectable cholangiocarcinoma. The role of radiotherapy in the management of cholangiocarcinoma is uncertain. Our results, like those of many other retrospective analyses, suggest that radiotherapy prolongs survival after curative resection as well as after palliative stenting. However, further data from randomized studies are necessary to support or refute this impression. Further studies of adjuvant chemotherapy or hormonal therapy will also be necessary to improve patient survival.

Mortality after 10 1/2 years for hypertensive participants in the Multiple Risk Factor Intervention Trial The Multiple Risk Factor Intervention Trial (MRFIT) is a randomized primary prevention trial that tested the effect of a multifactor intervention program on coronary heart disease (CHD) mortality in 12,866 high-risk men aged 35-57 years. Men were randomly assigned to either a special intervention (SI) program, which consisted of dietary advice for lowering blood cholesterol levels, counseling aimed at cessation for cigarette smokers, and stepped-care treatment for hypertension for those with elevated blood pressure, or to their usual sources of health care within the community (UC). Among the 12,866 randomized men, 8,012 (62%) were hypertensive at baseline. For this subgroup, mortality rates with 10.5 years of follow-up were lower for the SI than for the UC group by 15% (p = 0.19) for CHD and 11% (p = 0.13) for all causes. These results reflected more favorable outcomes for SI compared with UC hypertensive men during the 3.8 posttrial years (March 1982 through December 1985) than during the preceding 6-8 years (through February 1982). During the posttrial years, death rates were lower for SI than for UC men by 26% (p = 0.09) for CHD and 23% (p = 0.02) for all causes. For those with diastolic blood pressure equal to or more than 100 mm Hg, this posttrial trend was a continuation of a trend during the trial; therefore, with 10.5 years of follow-up, death rates were markedly lower for SI than for UC by 36% (p = 0.07) for CHD and 50% (p = 0.0001) for all causes. Similarly, for those without baseline resting electrocardiographic abnormalities, the favorable posttrial outcome for the SI group was a continuation of a trend during the trial. In contrast, for those with baseline diastolic blood pressure of 90-99 mm Hg and for those with baseline resting electrocardiographic abnormalities, the favorable posttrial mortality findings for the SI group were a reversal of unfavorable trends recorded during the trial. Two factors appear to have contributed to this more favorable mortality trend for the SI group: 1) a change in the diuretic treatment protocol for SI men about 5 years after randomization, which involved replacement of hydrochlorothiazide with chlorthalidone at a daily maximum dose of 50 mg; and 2) a favorable effect of intervention on nonfatal cardiovascular events during the trial years. In addition, delay until the full impact of beneficial effects on mortality end points from smoking cessation and cholesterol lowering could have contributed.(ABSTRACT TRUNCATED AT 400 WORDS).

Combined aortic and visceral arterial reconstruction: risks and results. The indications, morbidity, and efficacy of combined reconstruction of the abdominal aorta and visceral arteries (renal and superior mesenteric; excluding suprarenal aortic aneurysms) were analyzed retrospectively in 29 consecutive patients who underwent surgery from June 1984 through February 1990. Seventeen men and 12 women ages 32 to 76 years (mean, 66 years) were studied. Follow-up was complete in all patients to either death or calendar year 1989 to 1990 (mean, 31.9 months; range, 2 to 66 months). All patients underwent bypass of angiographically proven severe lesions of one renal artery (19 patients), both renal arteries (8 patients), or the superior mesenteric artery and renal arteries (2 patients), in concert with synthetic distal aortic replacement for occlusive disease (10 patients) or aneurysm (19 patients). Indications for renal artery repair included severe hypertension in 13 patients, ischemic renal insufficiency in 8 patients, and lesion morphology alone in 8 patients. Operative mortality rate was 3 of 29 (10.3%), and each death was the result of multisystem organ failure. Nonfatal complications occurred in 11 of the 26 survivors (42%), and this group differed significantly from the uncomplicated 15 patients only in having a higher mean preoperative serum creatinine (2.5 +/- 1.1 mg/dl vs 1.6 +/- 0.9 mg/dl, p = 0.04, t test). The mortality rate of patients with preoperative serum creatinine greater than or equal to 2.0 mg/dl, was 15.4% (2/13 patients), compared to 6.2% (1/16) in patients with creatinine less than 2.0 mg/dl. Three late deaths occurred (2 stroke, 1 cancer). Hypertension control improved in 64% of patients overall, and in 7 of 9 patients whose major operative indication was renovascular hypertension. Renal function remained stable or improved in 12 of 15 patients (80%) with renal insufficiency, but 3 patients progressed to require dialysis. Long-term graft patency was demonstrated by angiography or on duplex scan in all studied survivors (21 patients). Although operative risks are clearly increased compared to less complex vascular procedures, careful patient selection and management will yield a favorable outcome in most patients with such combined lesions.

The effect of omental pedicle graft transfer on spinal microcirculation and laminectomy membrane formation. The properties of the omentum and its effect on spinal neurologic disease was investigated. Omental pedicle grafts were transferred to the laminectomized lumbar spines of nine neurologically normal dogs. Grafts were placed on either the dura or the spinal cord. Interruption of the graft's circulation was examined. To study the effect, the artery of the graft was injected with contrast and the graft-dura interface studied histologically. All injected specimens demonstrated vascular connections from the graft to the neural elements. The graft was found to decrease postoperative perineural scarring. The omentum appears to possess properties that could be applied to improve outcomes in spinal surgery.

Testicular calcifications and neoplasia in patient treated for subfertility. A subfertile male with a history of left cryptorchism underwent scrotal ultrasound that revealed stippled calcifications, without associated mass, in the right testicle. Six months later, while on a regimen of clomiphene citrate, a testicular tumor became palpable. This was sonographically confirmed to be surrounding the calcifications. Testicular calcifications are most commonly associated with benign conditions. We review the literature regarding their relationship to neoplasms and the significance of the ultrasonic findings. Furthermore, this is the sixth reported case of testicular tumor developing during hormonal treatment for oligospermia. Although these cases may be circumstantial, closer surveillance and screening ultrasound may be indicated for subfertile males taking clomiphene citrate.

Atypical presentations of Pneumocystis carinii pneumonia in patients receiving inhaled pentamidine prophylaxis. Inhaled pentamidine is used commonly to prevent Pneumocystis carinii pneumonia (PCP) in patients with advanced human immunodeficiency virus infection. Case reports indicate that PCP can recur in patients who receive inhaled pentamidine and that clinical features may be atypical. To determine the magnitude of this problem, we reviewed retrospectively the medical records of patients with proven PCP during a 30-month period at two hospitals. Four (31 percent) of 13 patients with previous PCP who received inhaled pentamidine prophylaxis had recurrent P carinii infection, including one patient with widely metastatic extrapulmonary disease. Chest roentgenographic findings included cavities, pneumothoraces, bilateral and upper lobe interstitial infiltrates, and pleural effusion. False-negative bronchoalveolar lavage and induced sputum examinations were frequent. We conclude that recurrent PCP in patients maintained on a regimen of inhaled pentamidine prophylaxis occurs frequently, causes chest roentgenographic abnormalities other than interstitial infiltrates, and may be difficult to diagnose. Clinicians who choose to use this effective and convenient mode of prophylaxis should be aware of the problems attendant to its use.

The management of atypical non-cardiac chest pain. Atypical, non-cardiac chest pain is common and disabling, and often persists despite negative medical investigations. Aetiology is disputed and management is difficult. A multi-causal model in which both psychological and physical factors play a part is helpful; a fundamental factor is continued misinterpretation of minor physical symptoms as evidence of heart disease. We report supportive evidence and describe a psychological treatment derived from the model. In a randomized trial, cognitive behavioural methods were effective in reducing chest pain, disability and use of medication, in patients both with and without psychiatric disorder. The clinical implications are discussed.

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.

Hormonal treatment of functional ovarian cysts: a randomized, prospective study. Estrogen (E)/progestin therapy for functional ovarian cysts is widely used in clinical practice, but the efficacy of this treatment has not been determined in controlled trials. In this study, we examined the effect of E/progestin administration in a group of infertility patients enrolled in a program of ovulation induction who had cysts identified by transvaginal sonography. Patients were randomized to receive either norethindrone 1 mg/mestranol 0.05 mg/d (group A, n = 24) or no treatment (group B, n = 24) for up to 6 weeks. Patients were re-evaluated by sonography at 3, 6, and 9 weeks after entry into the protocol. The ages, mean cyst diameters, and proportions of patients having received gonadotropins in the previous menstrual cycle were not significantly different among the two groups. All patients who had a sonographic abnormality persisting for 9 weeks were surgically explored and found to have pathological cysts. The rate of disappearance of functional ovarian cysts was not affected by E/progestin treatment.

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.

False aneurysm of the internal mammary artery. Iatrogenic false aneurysm of a branch of the internal mammary artery after sternal wire closure is a very rare occurrence. We describe a case which appeared in a 62 year old woman operated upon for mitral valve replacement and diagnosed after Digital Subtraction Angiography.

Etiology of acute lower respiratory tract infections in Gambian children: II. Acute lower respiratory tract infection in children ages one to nine years presenting at the hospital. Seventy-four children ages 1 to 9 years hospitalized because of severe pneumonia were investigated using blood cultures, lung aspirates, nasopharyngeal aspirates, serology and antigen detection procedures. A bacterial infection was identified in 57 (77%), a viral infection was seen in 25 (34%) and 18 (24%) had mixed viral-bacterial infections. The bacterial pathogens most frequently identified were Streptococcus pneumoniae and Haemophilus influenzae found in 61 and 15% of patients, respectively. The viral pathogen most frequently recovered was respiratory syncytial virus (12%). Evidence of Chlamydia pneumoniae strain TWAR and Mycoplasma pneumoniae infection was found in 12 and 4% of cases, respectively. Overall a potential pathogen was identified in 60 (81%) children, with evidence of polymicrobial infection in 30 cases (40.5%). The study provides information on the relative role of different infectious agents in the etiology of severe pneumonia in children in a developing country.

Synchronous reconstruction for combined aortoiliac and femoropopliteal occlusive lesions. The role of proximal bypass. Between January 1984 and December 1986, 31 patients underwent synchronous revascularization (SR) because of the serious clinical condition of a lower limb and presence of arteriographically visible lesions. Average follow-up was 30 months. Operative mortality was 10%. Two patient populations were identified: Group I (N = 13): patients who underwent ilio-femoral or aorto-femoral proximal revascularization (PR); Group II (N = 18): patients who had axillo-femoral PR. Group I patients were younger than those in Group II (64 yr versus 72 yr; p less than 0.01). An association of pre-operative risk factors (arterial hypertension; coronary, renal or respiratory insufficiency) was twice as frequent in Group II as in Group I (p less than 0.02). The rate of SR compared to PR alone was 15%. However, there was no statistically significant difference between Groups I and II. Comparison of the actuarial survival curves for patients ahd the patency rates of SR in Groups I and II failed to reveal any statistically significant differences. Axillo-femoral bypass can be used for PR when SR is necessary in high risk patients.

Morphologic comparison of patients with mitral valve prolapse who died suddenly with patients who died from severe valvular dysfunction or other conditions. Clinical and necropsy findings are described in 56 patients with mitral valve prolapse: 15 patients, aged 16 to 69 years (mean 39), died suddenly and mitral valve prolapse was the only cardiac condition found at necropsy (hereafter called isolated mitral valve prolapse); the remaining 41 patients had other conditions that were capable of being fatal. Of the latter 41 patients, 7, aged 17 to 59 years (mean 45), had associated congenital heart disease, and 34 patients, aged 17 to 70 years (mean 52), had no associated congenital cardiac abnormalities. Compared with the 34 patients without associated congenital heart disease and with nonmitral valve prolapse conditions capable in themselves of being fatal, the 15 patients who died suddenly with isolated mitral valve prolapse were younger (mean age 39 +/- 17 versus 52 +/- 15 years; p = 0.01), more often women (67% versus 26%; p = 0.008) and had a lower frequency of mitral regurgitation (7% versus 38%; p = 0.02). The 15 patients dying suddenly with isolated mitral valve prolapse also were less likely to have evidence of ruptured chordae tendineae (29% versus 67%; p = 0.04). The frequency of increased heart weight (67% versus 59%), a dilated mitral valve anulus (80% versus 81%), a dilated tricuspid valve anulus (17% versus 17%), an elongated anterior mitral leaflet (86% versus 54%), an elongated posterior mitral leaflet (79% versus 77%) and fibrous endocardial plaque under the posterior mitral leaflet (73% versus 63%) was similar between the two groups. The severity of the prolapse (mild 20% versus 11%; moderate 27% versus 58%; severe 53% versus 32%) also was similar between the two groups. Thus, persons with mitral valve prolapse dying suddenly without another recognized condition tend to be relatively young women without mitral regurgitation.

Toxic shock syndrome associated with use of latex nasal packing. We treated a previously healthy young man who developed toxic shock syndrome 2 days after elective septoplasty with nonabsorbent latex packing. This case emphasizes that non-menstrual wound-associated toxic shock syndrome can occur after surgery that does not involve absorbent splinting or packing and should be considered in patients who present within a few days after surgery with fever, sunburnlike rash, hypotension, and multisystem complaints and laboratory abnormalities.

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.

Systemic therapy in metastatic colorectal cancer. Fluorouracil-based chemotherapy regimens have been utilized in metastatic colorectal cancer for more than 30 years. Early attempts at defining an optimal treatment schedule and use in combination with other drugs failed to significantly improve results. In contrast, the clinical effectiveness of fluorouracil has been improved by continuous infusion administration and modulation with folinic acid. Both approaches have increased the response rate compared with results achieved with traditional bolus schedules; the effect on survival has been less significant. Unfortunately, expense and, in some instances, toxicity have also been increased, which detracts from their overall usefulness. Clinical studies that evaluate fluorouracil chemotherapy in combination with biological-response modifiers are ongoing and will be areas of intense research during the next few years.

Improved scintigraphic assessment of severe cholestasis with the hepatic extraction fraction. In previous studies, we found that biliary scintigraphy with technetium-99m-labeled iminodiacetic acid ([99mTc]IDA) provided excellent discrimination between intrahepatic and extrahepatic cholestasis, except in patients with profound cholestasis who had poor visualization of the biliary tree. In this study, we have used deconvolution analysis to determine the hepatic extraction fraction (HEF) of a hypothetical single circulatory pass of [99mTc]IDA. Our hypothesis was that extraction of radionuclide from the blood would be normal in patients with extrahepatic obstruction alone, but would be impaired in patients with intrahepatic disease (IHD). The purpose of this study was to compare the HEF in patients with profound cholestasis (bilirubin greater than or equal to 3.0 mg/dl) due to either IHD or common bile duct obstruction (CBDO). Normal subjects (N = 13) had an HEF of 100%. Patients with CBDO (N = 13) had slightly reduced HEF values (92.8 +/- 3.2%) despite profound hyperbilirubinemia (6.1 +/- 1.0 mg/dl). Patients with IHD (N = 23) had a markedly reduced HEF (43.1 +/- 4.1%) which was significantly lower than patients with CBDO and normal subjects (P less than 0.001). We conclude that the determination of the HEF during biliary scintigraphy is helpful in distinguishing between intrahepatic and extrahepatic disease in patients with hyperbilirubinemia (bilirubin greater than or equal to 3.0 mg/dl).

Unique features of Helicobacter pylori disease in children. In a six-year period, 41 children had endoscopically documented duodenal ulcer disease or primary H. pylori antral gastritis without duodenal ulcer. Of 37 children with H. pylori gastritis, group 1 comprised 23 patients with duodenal ulcer disease and group 2 had 14 patients without ulcers (primary H. pylori gastritis). Group 3 comprised four children with duodenal ulcer disease and H. pylori-negative antral biopsies. During the study period, all primary chronic ulcer disease was duodenal; no primary chronic gastric ulcer was present. Two distinct types of duodenal ulcer disease were identified; the majority (85%) was always associated with significant active H. pylori antral gastritis (group 1). The minority (15%) had virtually absent gastritis and no H. pylori (group 3). Native Indian children were represented in group 1 quite out of proportion to the referral population and had the most severe disease. While it is established that a higher prevalence of asymptomatic H. pylori infection exists in non-Caucasians, this appears to be the first demonstration of a higher prevalence of symptomatic ulcer disease in non-Caucasian children or adults. Caucasian children tended to have primary H. pylori gastritis (group 2) or duodenal ulcer without H. pylori (group 3). Antral nodularity was found to be an important specific endoscopic sign, unique to those children with H. pylori disease. It has not been described in adult H. pylori disease. Non-Caucasian children, especially Native Indians, in British Columbia have more prevalent and more severe H. pylori disease than Caucasians. Endoscopy with gastric antral biopsies is necessary to distinguish different types of duodenal ulcer disease and to diagnose primary H. pylori gastritis.

Rectourethral fistula caused by Kaposi's sarcoma. A 35-year-old man with the acquired immunodeficiency syndrome-related complex was evaluated for a persistent urethral discharge, pneumaturia and watery diarrhea. Radiographic and endoscopic procedures established the diagnosis of a rectourethral fistula. Perineal exploration and excision of the fistula revealed the pathological diagnosis of Kaposi's sarcoma. The differential diagnosis of an acquired rectourethral fistula and the significance of Kaposi's sarcoma are discussed.

Ultrasonic debridement during mitral valve reconstruction for calcified mitral stenosis. An ultrasonic device in conjunction with open mitral commissurotomy was applied in 8 patients with heavily calcified, stenosed mitral valves. In 6 patients, reconstruction of the mitral valve by debridement of the leaflet calcification with the device was successful. Two patients required valve replacement because of an increase in preexistent mitral regurgitation caused by excessive decalcification. The ultrasonic device proved to be a useful and effective adjunct for salvaging the heavily calcified mitral valve, which would otherwise have to be replaced.

Maintenance of circulation during ventricular fibrillation with the simultaneous use of two "counterpulsation" devices. Two valveless, single orifice counterpulsation devices, with pumping stroke volumes of 65 ml each, were implanted on the ascending aorta and pulmonary artery of seven open chest anesthetized dogs. After completion of the preparation, ventricular fibrillation was induced. The devices were synchronized to pump simultaneously at a rate of 85-100 bpm. The combined use of the counterpulsation devices provided maximal aortic pressure of 111.4 +/- 25.1 mmHg during ventricular fibrillation for a period of 15-60 min. The mean left ventricular pressure was 17.7 +/- 4.4 mmHg, and the cardiac index 64.5 +/- 23.6 ml/kg/min. Cardioversion of ventricular fibrillation to sinus rhythm restored normal hemodynamics. The counterpulsation device implanted on the ascending aorta was not able to maintain circulation for more than 5 min after the induction of ventricular fibrillation, if used alone. In conclusion, the use of two counterpulsation devices implanted on the ascending aorta and pulmonary artery was able to maintain circulation in experimental animals during ventricular fibrillation.

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.

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.

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.

Actin architecture of cultured human thyroid cancer cells: predictor of differentiation? The actin cytoskeleton is important for cell structure and motility. A disordered actin architecture has been correlated with a high metastatic potential in melanoma, fibrosarcoma, and colon cancer models. Thyrotropin is known to induce growth and differentiation in cultured thyroid cells, whereas the carcinogenic phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) causes dedifferentiation and malignant transformation in many cell lines. We therefore assessed the effect of thyrotropin and TPA on the actin architecture of FTC-133 human follicular thyroid cancer cells in continuous culture. Staining of filamentous actin with rhodamine phalloidin showed that 1 mU/ml or 30 mU/ml thyrotropin-induced actin polymerization was detectable at 1 hour but more notable at 24 hours. Similarly TPA (0.008 to 10 mumol/L) caused rapid actin fiber disruption and redistribution to the cell periphery. Secondary antibody staining for alpha-actinin, a protein that binds and crosslinks actin, was more prominent after treatment with thyrotropin but decreased after TPA. These findings indicate that the actin cytoskeleton has a dynamic response to trophic factors. Thyrotropin promoted actin polymerization, but TPA caused depolymerization. These effects may correlate with cellular alpha-actinin levels. Actin architecture may therefore reflect the state of differentiation of thyroid tumor cells.

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.

Ondansetron compared with high-dose metoclopramide in prophylaxis of acute and delayed cisplatin-induced nausea and vomiting. A multicenter, randomized, double-blind, crossover study. OBJECTIVE: To compare the efficacy and side effects of ondansetron with those of high-dose metoclopramide in treating acute and delayed cisplatin-induced nausea and vomiting. DESIGN: Randomized, double-blind, crossover trial. SETTING: Conducted at two university hospitals, a cancer institute, and six community hospitals. PATIENTS: Of 125 patients, 95 were evaluable for the acute phase and 79 for the delayed phase. Major reasons for not being evaluable were no second course (14 patients), protocol violation (5 patients), and change in cisplatin dose (3 patients) for the acute phase, and rescue medication on day 1 (7 patients), protocol violation (3 patients), and inadequate data (4 patients) for the delayed phase. INTERVENTIONS: All patients received cisplatin, 50 to 100 mg/m2 body surface area (median, 75 mg/m2); none had previously received chemotherapy. Thirty minutes before the cisplatin administration, ondansetron was given intravenously over 15 minutes, at a loading dose of 8 mg followed by a continuous infusion of 1 mg/h for 24 hours. Metoclopramide was given at a loading dose of 3 mg/kg body weight, followed by a continuous infusion for 8 hours (4 mg/kg). For the delayed phase (days 2 through 6), the first oral dose was given as soon as the infusion was completed; the oral dose consisted of either metoclopramide, 20 mg three times daily, or ondansetron, 8 mg three times daily for another 5 days. MEASUREMENTS AND MAIN RESULTS: In the acute phase, a major or complete response was seen in 72% of the ondansetron-treated and 41% of the metoclopramide-treated patients (P less than 0.001). Nausea was significantly better controlled among the ondansetron-treated patients (P = 0.04). In the delayed phase, no statistically significant difference was seen between ondansetron- and metoclopramide-treated patients. Nausea was significantly better controlled with metoclopramide (P = 0.016). CONCLUSIONS: Ondansetron is significantly more effective than metoclopramide in preventing acute nausea and vomiting. In the delayed phase, the results of both drugs were disappointing, although metoclopramide's effect on delayed nausea was superior. Patients preferred ondansetron.

Thallium reinjection after stress-redistribution imaging. Does 24-hour delayed imaging after reinjection enhance detection of viable myocardium? BACKGROUND. Thallium reinjection immediately after conventional stress-redistribution imaging improves the detection of viable myocardium, as many myocardial regions with apparently "irreversible" thallium defects on standard 3-4-hour redistribution images manifest enhanced thallium uptake after reinjection. Because the 10-minute period between reinjection and imaging may be too short, the present study was designed to determine whether 24-hour imaging after thallium reinjection provides additional information regarding myocardial viability beyond that obtained by imaging shortly after reinjection. METHODS AND RESULTS. We studied 50 patients with chronic stable coronary artery disease undergoing exercise thallium tomography, radionuclide angiography, and coronary arteriography. Immediately after the 3-4-hour redistribution images were obtained, 1 mCi thallium was injected at rest, and images were reacquired at 10 minutes and 24 hours after reinjection. The stress, redistribution, reinjection, and 24-hour images were then analyzed qualitatively and quantitatively. Of the 127 abnormal myocardial regions on the stress images, 55 had persistent defects on redistribution images by qualitative analysis, of which 25 (45%) demonstrated improved thallium uptake after reinjection. At the 24-hour study, 23 of the 25 regions (92%) with previously improved thallium uptake by reinjection showed no further improvement. Similarly, of the 30 regions determined to have irreversible defects after reinjection, 29 (97%) remained irreversible on 24-hour images. These findings were confirmed by the quantitative analysis. The mean normalized thallium activity in regions with enhanced thallium activity after reinjection increased from 57 +/- 13% on redistribution studies to 70 +/- 14% after reinjection but did not change at 24 hours (71 +/- 14%). In regions with irreversible defects that were unaltered by reinjection, mean regional thallium activity did not differ from the reinjection to the 24-hour studies (57 +/- 17% and 58 +/- 17%, respectively). Twenty-four-hour imaging after reinjection showed improvement in only four of 35 irreversible regions (involving three of the 50 patients). CONCLUSIONS. These data indicate that thallium reinjection at rest after 3-4 hours of redistribution provides most of the clinically relevant information pertaining to myocardial viability in regions with apparently irreversible thallium defects. Hence, thallium reinjection may be used instead of 24-hour imaging in most patients in whom a persistent thallium defect is observed on conventional redistribution images.

Hemolytic transfusion reaction following transfusion of frozen and washed autologous red cells A case of hemolytic transfusion reaction, accompanied by hypotension and followed by transient renal failure, occurred after the transfusion of 1 unit of previously frozen autologous red cells. Subsequent investigation revealed the probable cause of the hemolysis to be inadequate deglycerolization of the unit. The cause of the associated symptoms is unknown. Possibilities include nephrotoxic effects of hemoglobin or stroma, toxic effects of glycerol, or release of vasoactive or thrombogenic substances from lysed red cells. This case of a hemolytic reaction adds to the known risks of autologous transfusion.

Maffucci's syndrome with bilateral cartilaginous tumors of the cerebellopontine angle. Maffucci's syndrome is characterized by the combination of multiple enchondromas (Ollier's disease) and hemangiomatosis. These hemangiomas develop in the subcutaneous tissue and form red-blue tumors dispersed over the whole body. Intracranial involvement is rare, making a preoperative radiological diagnosis and differentiation from other tumors rather difficult. The radiological characteristics and successful removal of the intracranial part of a chondrosarcoma of the cerebellopontine angle in a case of Maffucci's syndrome are reported in this paper.

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.

Adjuvant antiestrogen therapy for breast cancer. Past, present, and future. Laboratory investigations using animal models of breast cancer growth have indicated that the antiestrogenic compound tamoxifen is a tumoristatic agent. It is therefore effective in suppressing, rather than destroying, the breast tumor. Its use as an adjuvant in breast cancer management has been successful, with a proportion of women benefiting from long periods of tamoxifen treatment. All the initial studies recruited postmenopausal women, but tamoxifen is now proposed for the treatment of premenopausal women for an extended time. Naturally, there are many aspects of the toxicology of tamoxifen to consider; however, careful monitoring of clinical trials will determine the safety of the drug for the general patient population.

Fetomaternal bleeding as a cause of recurrent fetal morbidity and mortality. A woman had fetomaternal bleeding of unknown cause during at least three of five pregnancies. Each event was associated with significant fetal morbidity or mortality. Although fetomaternal bleeding has been reported as a cause of unexplained fetal death, its occurrence in subsequent pregnancies has not been described previously.

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.

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.

Effect of activity on supraventricular tachyarrhythmias after coronary artery bypass surgery. The purpose of this study was to evaluate patient activities, professional staff activities, backrest position, and diurnal variations as factors that may contribute to the onset of supraventricular tachyarrhythmias (SVT) after coronary artery bypass surgery (CABG). The activities surrounding the recognition of first-onset SVT, as well as preoperative and postoperative data and patient characteristics were examined in 249 patients having CABG. One hundred seventy-three patients qualified for the study; 28% of these patients (n = 49) had SVT. No statistical difference was found between the subjects with SVT and those without SVT when sex, cross-clamp time, creatine kinase peak, hemoglobin and hematocrit levels, and number of bypasses were examined. Patients who had SVT were older than those who did not: 64.8 years for the SVT group versus 60.7 years for the non-SVT group (p less than 0.01). SVT was rare in the first 24 hours after surgery, whereas 60% of the cases occurred during the next 48 hours, without significant diurnal variation: mean time of onset was 11:50 AM. No particular activity of the patient or nurse influenced the onset of SVT during the postoperative period in this group.

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.

Symptomatic pancreatic heterotopia treated by local excision. Non-ulcer dyspepsia is a continuing problem and in many cases a precise cause is never identified. We present five patients with an allegedly uncommon condition--pancreatic heterotopia. They were managed by local excision of the tumour and after a mean (range) follow up of 42 (9-80) months all remain free of the original symptoms.

Pentostatin induces durable remissions in hairy cell leukemia. Fifty patients with hairy cell leukemia were treated with pentostatin (2'-deoxycoformycin; dCF) for a median of 3 months; 32 (64%) patients achieved complete remission (CR), and 10 (20%) patients achieved partial remission (PR), for an overall response rate of 84%. After reaching maximal response, no maintenance therapy was administered. The median duration of follow-up is now 39 months, and only four of 32 patients in CR and two of 10 patients in PR have relapsed. dCF therapy produces durable long-term, disease-free survival in patients with hairy cell leukemia.

Major clinical diagnoses found among patients with Raynaud phenomenon from the general population. This study of 62 individuals with Raynaud phenomenon (RP) drawn from the general population of South Carolina shows a profile of associated diseases that is different from the one reported from hospital based studies. We found that connective tissue diseases affect a much smaller fraction of patients with RP than previously reported. Compared to RP negative controls, our RP positive group was found to suffer more frequently from a variety of diseases, both RP related and not RP related.

Toxic carbamazepine concentrations following cardiothoracic surgery and myocardial infarction. Carbamazepine is being used more frequently in the U.S. as an initial agent of choice to treat generalized tonic-clonic, mixed, and partial seizures with complex symptomatology. Carbamazepine is extensively metabolized in the liver; however, there is little information available on its pharmacokinetics in patients following surgery or myocardial infarction, or in those with liver disease. We report a case of a patient who attained toxic carbamazepine serum concentrations (ranging from 18.2 to 21.5 micrograms/mL) two days after cardiothoracic surgery and an intraoperative myocardial infarction, and experienced lethargy, diplopia, dysarthria, diaphoresis, and horizontal and downgaze nystagmus. These alterations in serum carbamazepine concentration normalized ten days after surgery. They may have been due to a combination of changes in protein binding and decreased elimination due to altered intrinsic hepatic clearance. With carbamazepine achieving a more prominent place in anticonvulsant therapy, the influence of various procedures and disease processes on the pharmacokinetics and pharmacodynamics of carbamazepine, as well as the clinical consequences of such changes, need further investigation.

Helicobacter pylori and gastric carcinoma. Serum antibody prevalence in populations with contrasting cancer risks. This investigation examined the correlation between Helicobacter pylori (HP) infection, as reflected in immunoglobulin G serum antibodies, and the risk of gastric cancer. Serum samples were obtained from populations with contrasting gastric cancer risks. The highest prevalence of HP infection, 93%, was observed in the adult population at highest gastric cancer risk, the residents of Pasto, Colombia. In the lower risk Colombian city of Cali, a 63% overall prevalence rate was found. Both children and adults were sampled in New Orleans, Louisiana, where gastric cancer rates are high for blacks but not for whites. The prevalence of HP infection was significantly higher in black than in white adults, 70% versus 43%, P = 0.0001. A higher prevalence was also detected in black compared with white children, 49% versus 32%, P = 0.01; however, an even greater disparity was noted when comparing children from two hospitals, regardless of race, which serve different socioeconomic groups. A prevalence rate of 54% was found at Charity Hospital compared with 24% (P = 0.0001) at Children's Hospital. Our findings indicate that socioeconomic conditions, known to influence gastric cancer risk, are also important determinants of HP infection.

Heterogeneity in progressive aphasia due to focal cortical atrophy. A clinical and PET study. Six patients with a slowly progressive aphasic disorder due to degenerative cortical disease are reported. The length of history varied from 18 months to 6 years. In 5 patients, there was a naming deficit, associated in 4 of these with some abnormalities in comprehension. One patient had a progressive history of reduced speech output, which was associated with an orofacial dyspraxia. All patients were studied neuropsychologically, and in addition regional cerebral metabolism was measured using position emission tomography. A localized left hemisphere deficit was found in all patients except 1, who had the longest history and the most profound clinical deficit, and who also had right hemisphere hypometabolism. The major brunt of the deficit was in the anterior portion of the left temporal lobe in all but 1 case, the patient with poor speech output who had a more severe left posterior frontal deficit. These findings suggest that in progressive aphasia due to focal cortical atrophy there is heterogeneity in the clinical presentation and anatomical site of the deficit, with possible implications for the underlying aetiology.

Features of "near-death experience" in relation to whether or not patients were near death The medical records of 58 patients, most of whom believed they were near death during an illness or after an injury and all of whom later remembered unusual experiences occurring at the time, were examined. 28 patients were judged to have been so close to death that they would have died without medical intervention; the other 30 patients were not in danger of dying although most of them thought they were. Patients of both groups reported closely similar experiences but patients who really were close to death were more likely than those who were not to report an enhanced perception of light and enhanced cognitive powers. The claim of enhancement of cognitive functions despite the likelihood that brain function had probably become disturbed and possibly diminished, deserves further investigation.

Influence of clinical and hemodynamic variables on risk of supraventricular tachycardia after coronary artery bypass. The influence of 45 variables on risk of postoperative supraventricular tachycardia was evaluated by univariate and multivariate analysis of data from 800 consecutive patients who underwent isolated coronary artery bypass during a 6-year interval. Postoperative supraventricular arrhythmias occurred in 186 patients (23%) but did not contribute to any of the six early deaths (30-day mortality rate, 0.8%). Mean (+/- standard deviation) length of hospital stay was longer (9.8 +/- 5.7 versus 8.3 +/- 3.5 days; p less than 0.0001) and mean age was older (65 versus 60 years; p less than 0.002) in patients with postoperative supraventricular tachycardia than in those with regular rhythm. Risk of supraventricular tachycardia was increased in patients with a history of atrial arrhythmias (45% versus 22%; p less than 0.002) or premature atrial contractions on the preoperative electrocardiogram (48% versus 22%; p less than 0.002). Multiple logistic regression analysis identified age 65 years or more, history of atrial arrhythmia or preoperative premature atrial contractions, and preoperative left ventricular end-diastolic pressure 20 mm Hg or more as independent predictors of postoperative supraventricular tachycardia. Six percent of patients converted to sinus rhythm spontaneously; 82% of patients converted within 1.1 +/- 1.9 days after onset of supraventricular tachycardia on treatment with digoxin or beta-adrenergic blocking drugs or both. Only 10% of patients with supraventricular tachycardia required electrical cardioversion. We conclude that the risk of supraventricular tachycardia after coronary artery bypass is influenced by patient-related variables and is effectively managed by conventional therapy. Prophylactic treatment should be reserved for elderly patients, especially those who have atrial arrhythmias or have preoperative left ventricular end-diastolic pressure 20 mm Hg or more.

On-table pancreatography: importance in planning operative strategy. We describe our experience with 124 on-table pancreatograms performed during 117 operative procedures on 112 patients in a wide variety of clinical settings. Endoscopic retrograde cholangiopancreatography (ERCP) was performed on 84 occasions with a 73 per cent success rate for visualization of the main pancreatic duct. On-table pancreatography (OTP) was performed by one of five different techniques: retrograde, prograde or ambigrade ductography, cystography and ascending loopography after pancreaticojejunostomy. OTP provided important information about the main pancreatic duct when endoscopic visualization was unsuccessful (n = 23), incomplete (n = 17) or not performed (n = 33); there was a failure rate of 4 per cent. In 35 patients either the additional information or discrepancies between ERCP and OTP findings resulted in a change of operative plan (19 extra procedures, 16 altered procedures). Complete ductography was especially helpful in the 63 patients with chronic pancreatitis. OTP is technically simple, free from complications and invaluable for planning operative strategy.

Treatment of manifest and impending pathologic fractures of the femoral neck by cemented hemiarthroplasty. Thirty-four patients with manifest or impending pathologic fractures of the femoral neck were treated between 1971 and 1987. Breast carcinoma was the primary tumor in the majority of patients. All patients were treated with cemented hemiarthroplasty. Twenty-seven patients (79%) could walk at an average of nine days postoperatively. All patients experienced relief of pain. Two superficial wound dehiscences, one loosening of the prosthesis, and two prosthetic dislocations were encountered. Mean survival was 17.6 months overall (12 months for manifest fractures and 40 months for impending fractures). These results indicate that cemented hemiarthroplasty for pathologic fractures is a safe procedure resulting in long-lasting palliation without necessitating postoperative irradiation. The importance of tumor excochleation and the advantages of bone cement are emphasized.

Hyperbaric oxygen therapy for necrotizing fasciitis reduces mortality and the need for debridements. Twenty-nine patients with necrotizing fasciitis were treated from 1980 to 1988. This study evaluates how the addition of hyperbaric oxygen (HBO) therapy to surgical treatment has affected mortality and the number of debridements required to achieve wound control in these patients. Two groups of patients were viewed: group 1 (n = 12) received surgical debridement and antibiotics only; group 2 (n = 17) received HBO (90 minutes at 2.5 atm, average 7.4 treatments) in addition to surgery and antibiotics. Both groups were similar in age, race, sex, wound bacteriology, and antimicrobial therapy. Body surface area affected was similar, however, perineal involvement was more common in group 2 (53%) than in group 1 (12%). The admitting conditions of patients in group 1 (non-HBO) were diabetic, 33%; white blood cell count more than 12,000, 50%; and shock, 8%. The admitting conditions of patients in group 2 (HBO) were diabetic, 47%; white blood cell count more than 12,000, 59%; and shock, 29%. Although group 2 patients receiving HBO were more seriously ill on admission, mortality was significantly lower (23%) compared to group 1 (66%) (p less than 0.02). In addition, only 1.2 debridements per group 2 patient were required to achieve wound control versus 3.3 debridements per group 1 patient (p less than 0.03). The addition of HBO therapy to the surgical and antimicrobial treatment of necrotizing fasciitis significantly reduced mortality and wound morbidity (number of debridements) in this study, especially among nonclostridial infections. We conclude that HBO should be used routinely in the treatment of necrotizing fasciitis.

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.

How large must an iridotomy be? Four cases of acute angle closure glaucoma in eyes with a small but patent Nd-YAG laser iridotomy are presented, and similar cases in the literature are reviewed. Theoretically a 15 microns diameter iridotomy should be large enough to prevent angle closure glaucoma due to pupil block. Mechanisms by which larger iridotomies fail to prevent angle closure glaucoma, and the role of provocation tests following iridotomy, are discussed. An iridotomy should be at least 150-200 microns in diameter if acute angle closure glaucoma is to be reliably prevented.

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.

The effects of cyclosporin A on eicosanoid excretion in patients with rheumatoid arthritis. Alterations in renal eicosanoid levels have been postulated as a factor in cyclosporin A (CSA) nephrotoxicity. The effects of CSA on renal eicosanoid excretion in rheumatoid arthritis were studied over a 24-week period, during which treatment with nonsteroidal antiinflammatory drugs was discontinued. The initial dosage of CSA was 4 mg/kg/day; at week 24, the mean dosage of CSA was 3.9 mg/kg/day. At week 24, the mean (+/- SD) serum creatinine level (1.04 +/- 0.24 mg/dl) was 32% above the baseline value; renal blood flow had decreased by 21% (P less than 0.03) and the glomerular filtration rate had decreased by 16%. There was a significant increase (P less than 0.03) in the 2,3-dinor thromboxane B2 level at week 2, but there was no significant change in the levels of the other eicosanoids. This study demonstrates that after CSA treatment, there is a selective increase in a thromboxane metabolite that parallels an increase in renal vascular resistance, even in the absence of nonsteroidal antiinflammatory drugs, and with unimpaired formation of other vasodilator eicosanoids.

Brain tumors. Recent advances in experimental tumor biology are being applied to critical clinical problems of primary brain tumors. The expression of peripheral benzodiazepine receptors, which are sparse in normal brain, is increased as much as 20-fold in brain tumors. Experimental studies show promise in using labeled ligands to these receptors to identify the outer margins of malignant brain tumors. Whereas positron emission tomography has improved the dynamic understanding of tumors, the labeled selective tumor receptors with positron emitters will enhance the ability to specifically diagnose and greatly aid in the pretreatment planning for tumors. Modulation of these receptors will also affect tumor growth and metabolism. Novel methods to deliver antitumor agents to the brain and new approaches using biologic response modifiers also hold promise to further improve the management of brain tumors.

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.

Oncocytic glomus tumor of the trachea. An oncocytic variant of glomus tumor of the trachea occurred in a 47-year-old woman. She experienced intermittent cough and hemoptysis for about three years. Bronchoscopy and chest CT scan showed a small reddish polypoid tumor on the lower end of the trachea. Bronchoscopic biopsy was carefully done and was diagnosed as oncocytoma. A wedge resection of the tumor was done. Tumor cells were characterized by strongly eosinophilic granular cytoplasm on light microscopy and by numerous closely packed round or ovoid mitochondria with prominent tubular cristae on electron microscopy. They were arranged in a sheet around small vessels, as a result of which the biopsy diagnosis of oncocytoma was changed to oncocytic glomus tumor. To our knowledge, this is the first report of an oncocytic glomus tumor arising from the trachea.

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.

Technetium-99m-HMPAO brain SPECT in medically intractable temporal lobe epilepsy: a postoperative evaluation. The aim of the present study was to evaluate the predictive value of interictal single-photon emission computed tomography (SPECT) using technetium-99m-labeled hexamethyl propyleneamine oxime (HMPAO) for the outcome after temporal lobectomy in patients with complex partial seizures. Out of 40 patients, 21 underwent right-sided and 19 left-sided temporal lobectomy. EEG and CT/MRI were primarily used to select the side of surgery. SPECT results correlated with temporal lobectomy in 68% of the patients. After surgical intervention, memory function was tested for both sides. Following left-sided temporal lobectomy, verbal memory was impaired in 8% of the patients, if SPECT agreed with the side selected for surgery, but in 83%, if it diverged from it. In the present study, there was no relationship between SPECT concordance with the side of temporal lobectomy and outcome as to seizure frequency and non-verbal memory. We conclude that preoperative interictal HMPAO/SPECT can contribute to the prediction of postoperative verbal memory function and that this method should be considered for use prior to temporal lobectomy.

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.

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.

Restenosis after directional coronary atherectomy: differences between primary atheromatous and restenosis lesions and influence of subintimal tissue resection. Rates of restenosis were evaluated in 70 patients (74 lesions) after successful directional coronary atherectomy. The extent of vascular tissue resection was correlated with restenosis rates for coronary (n = 59) and vein bypass graft (n = 15) lesions. After 6 months, the overall restenosis rate was 50% (37 of 74 lesions); it was 42% (15 of 36 lesions) when intima alone was resected, 50% (7 of 14 lesions) when media was resected and 63% (15 of 24 lesions) when adventitia was resected. Subintimal tissue resection increased the restenosis rate for vein grafts (43% with intimal resection versus 100% with subintimal resection, p = 0.01) but not for coronary arteries (50% versus 48%). There was no overall difference in restenosis rates after atherectomy between primary lesions and restenosis lesions that occurred after balloon angioplasty (46% versus 54%). Among postballoon angioplasty restenosis lesions, a higher rate of restenosis after atherectomy was found with subintimal than with intimal resection (78% versus 32%, p = 0.01). Tissues from patients undergoing a second atherectomy for restenosis after initial atherectomy (n = 8) demonstrated neointimal hyperplasia that appeared histologically identical to restenotic tissue developing after balloon angioplasty (n = 37). These data suggest that the cellular response to directional coronary atherectomy is characterized by neointimal proliferation similar to that which may develop after balloon angioplasty. The extent of fibrous hyperplasia appears to be related to the depth of tissue resection in vein graft lesions and coronary artery restenosis lesions that occur after balloon angioplasty but not in primary atheromatous coronary artery lesions.

What is the best method for assessing the long-term outcome of surgery for accessory pathways and atrioventricular junctional reentrant tachycardias? The success of surgery for supraventricular tachycardia (SVT) is evaluated by a variety of methods in different hospitals. Unfortunately, the predictive values of these methods are not known. We therefore compared the various methods in 261 patients undergoing surgery for SVT at Westmead Hospital since 1981. Surgical outcome was assessed by early tests during the first week after surgery (serial 12-lead electrocardiograms, telemetric monitoring of the electrocardiogram, and electrophysiological study performed using epicardial wires); later tests at 6 months after surgery (12-lead electrocardiograms and electrophysiological study); and symptomatic review done by telephone interview at a median of 34 months after surgery. Early tests were obtained in 97%, later tests were obtained in 76%, and symptomatic review was obtained in 98% of patients. All of the examined tests were inaccurate methods of surgical assessment compared with the late electrophysiological study. A large proportion of the patients proven to be surgical failures at the late electrophysiological study were not detected by early tests (83%), by later electrocardiograms (66%), or by symptomatic assessment (41%). Accurate assessment of surgical outcome requires a late electrophysiological study to permit comparison of surgical techniques. Late electrophysiological study also provides accurate information on the current risks and benefits of proposed surgery for communication to patients to enable them to make an informed decision on future treatment. Most patients are willing to have a late electrophysiological study and usually benefit from clarification of their true surgical outcome.

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.

Characterization and significance of sulfonylurea receptors. This study describes and characterizes a putative sulfonylurea receptor. The radioligand used was [3H]glipizide (9 Ci/mmol). The beta-cell plasma membranes were derived from a transplantable rat insulinoma generated by subcutaneous injection of RINm5F cells and purified by ultracentrifugation on a 15-55% sucrose gradient. Specific binding of [3H]glipizide to purified beta-cell plasma membranes was determined to be maximal at temperatures of 4-23 degrees C, pH 7.3, and an incubation of 2 h. Scatchard analysis indicated a single binding site with Kd = 7 nM and sulfonylurea binding of 0.93 pmol/mg membrane protein. Displacement of [3H]glipizide from the purified beta-cell plasma membranes by various sulfonylureas and their analogues correlated well with their known hypoglycemic and insulin-releasing activities. Various agents, including nutrients, agents affecting Ca2+ flux, gastrointestinal hormones, and pancreatic hormones, had no effect on [3H]glipizide binding to the beta-cell plasma membranes. Putative sulfonylurea receptors on beta-cell and brain cell plasma membranes have been reported by several groups of investigators. Sulfonylurea binding to the beta-cell is hypothesized to close an ATP-sensitive K+ channel, which leads to depolarization of the membrane and activation of a voltage-dependent Ca2+ channel.

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.

Thoracoabdominal repair of a post-traumatic aortorenal vein fistula following a previous transabdominal attempt: case report. Aortorenal vein fistula from trauma is a rare entity. A case is reported in which previous anterior abdominal attempts at repair rendered a thoracoabdominal approach necessary. Previous reports and techniques are compared and discussed.

Vaginal removal of the pedunculated submucous myoma. Historical observations and development of a new procedure. A new method of vaginal removal of submucous fibroids was attempted on 151 patients. The procedure involves dilation of the cervix with Laminaria tents and removal of the submucous fibroid by grasping with appropriate instruments. Myomas were removed successfully in 92% of the patients; hysterectomy and abdominal myomectomy were avoided in all but four of them. Perforation occurred in two patients. Morbidity was minimal. The four patients who desired pregnancy conceived.

Laser recanalization versus endoscopic intubation in the palliation of malignant dysphagia. Forty patients with widely disseminated or locally advanced malignant obstruction of the middle or lower third of the oesophagus underwent endoscopic treatment by either NdYAG laser recanalization or intubation. Groups were matched on the basis of tumour location and swallowing was graded clinically before and after treatment. Technical success was achieved in 17 of 20 laser treated and 18 of 20 intubated patients. Pretreatment swallowing ability, histology, tumour location and overall length were unrelated to functional outcome in both groups. However, circumferential tumour length identified endoscopically strongly influenced the quality of swallowing after laser recanalization. Patients with excellent swallowing quality (n = 7) had significantly shorter circumferential tumour lengths, 3.1(1.0) cm, than those with poorer quality swallowing (n = 10), 6.3(1.6)cm, (P less than 0.001). Both methods of treatment had low complication rates and there was one death in the series in the laser-treated group. Laser recanalization provides a better functional result than intubation for short (less than 4 cm) circumferential tumour. Intubation at a single session seems more appropriate than repeated laser therapy when tumour length exceeds 4 cm.