Showing papers by "Veterans Health Administration published in 1977"

Vulnerability--a new view of schizophrenia.

Abstract: Although descriptive and etiological approaches to psychopathology have made notable advances, they seem to have reached a plateau. After reviewing the six approaches to etiology that now preempt the field—ecological, developmental, learning, genetic, internal environment, and neurophysiological models—a second-order model, vulnerability, is proposed as the common denominator, and methods for finding markers of vulnerability are suggested in the hope of revitalizing the field. It is assumed that exogenous and/or endogenous challengers elicit a crisis in all humans, but depending on the intensity of the elicited stress and the threshold for tolerating it, that is, one's vulnerability, the crisis will either be contained homeostatically or lead to an episode of disorder. Vulnerability and episode stand in a trait-state relation, and markers for each must be provided to distinguish between them.

Myocardial imaging with thallium-201 at rest and during exercise. Comparison with coronary arteriography and resting and stress electrocardiography.

Abstract: Myocardial imaging with intravenous thallium-201 (201Tl) was performed at rest and following maximal treadmill exercise in 101 patients with suspected coronary artery disease. Results were interpreted from Polaroid scintiphotos by three independent observers with complete interobserver agreement in 79%. Of 25 patients with no or insignificant coronary artery disease (less than 50% diameter stenosis), one (4%) had a resting 201Tl image defect, one (4%) had an exercise 201Tl defect, none had an ECG Q wave, and four (16%) had exercise ST-segment depression. Among 76 patients with coronary artery disease (greater than or equal to 50% diameter stenosis), 58 (76%) had a defect on either the rest or exercise 201Tl image. The proportion of patients with an exercise image defect (50/76, 66%) was greater than the proportion with exercise ST depression alone (34/76, 45%; P less than 0.02). Overall, 69 of the 76 (91%) patients with coronary artery disease had either a positive rest or exercise myocardial image and/or a positive rest (ECG Q waves) or exercise (ST depression) electrocardiogram. This exceeded the proportion with only rest or exercise electrocardiographic abnormalities (50/76, 65%; P less than 0.001). We conclude that rest and exercise myocardial imaging with 201Tl is easily accomplished with readily available imaging equipment. The image data enhanced the diagnostic sensitivity of stress electrocardiography, and provided spatial identification of the abnormal segment(s) of myocardium.

Clindamycin-Associated Colitis Due to a Toxin-Producing Species of Clostridium in Hamsters

Abstract: Clindamycin-associated enterocolitis in hamsters was studied to detect and characterize a transmissible agent. It was found that the disease could be transferred by cecal contents and filtrates of cecal contents (pore size of filter, 0.02 micron) obtained from animals after administration of clindamycin. Subsequent work showed that enterocolitis could be produced with broth cultures of a species of Clostridium recovered from cecal contents of animals with clindamycin-induced disease. The cell-free supernatant of this strain also caused enterocolitis. Cecal contents from animals with clindamycin-induced disease incubated with gas gangrene antitoxin failed to cause intestinal lesions. These experiments indicate that clindamycin-associated colitis in hamsters is due to a clindamycin-resistant, toxin-producing strain of Clostridium.

The capsular polysaccharide of Bacteroides fragilis as a virulence factor: comparison of the pathogenic potential of encapsulated and unencapsulated strains.

Abstract: The pathogenic potentials of encapsulated and unencapsulated strains of Bacteroides fragilis were compared by use of a rat model of intraabdominal sepsis. Implantation of encapsulated B. fragilis alone resulted in abscesses in most recipients, whereas unencapsulated strains seldom produced this effect unless they were combined with another organism. Implants of heat-killed, encapsulated B. fragilis also resulted in abscess formation. Subsequent experiments suggested that the abscess-potentiating ability of encapsulated B. fragilis is related to the capsular polysaccharide. Implantation of 200 microgram of the purified capsular material alone or in conjuction with unencapsulated strains caused abscess formation in a majority of animals. Comparable results were not obtained with capsular polysaccharide from Escherichia coli O7:K1(L)"NM or with heat-killed Streptococcus pneumoniae type III. The capsular polysaccharide of B. fragilis appears to potentiate abscess formation and may represent a virulence factor for this species.

Adrenomyeloneuropathy A probable variant of adrenoleukodystrophy: II. General pathologic, neuropathologic, and biochemical aspects

Abstract: Histopathologic features were studied in postmortem examination of two men with adrenomyeloneuropathy, and biochemical studies were performed on one of these individuals. The histopathologic picture of one case included dying-back features in the nervous system and lamellar cytoplasmic inclusions in the brain, adrenal gland, and testis similar to those in adrenoleukodystrophy. Biochemical studies of the cerebral white matter of this individual revealed increased amounts of long-chain saturated fatty acids in cholesterol esters, an abnormality characteristic of adrenoleukodystrophy. Despite differences in clinical presentation and neuropathology, adrenomyeloneuropathy probably represents a distinct variant of adrenoleukodystrophy.

The C1q Binding Test for Soluble Immune Complexes: Clinical Correlations Obtained in Patients With Cancer

Abstract: Sera from 134 selected patients with various types of cancer were tested for soluble antigen-antibody complexes by the C1q binding method. Sera from 85 healthy blood bank donors served as normal controls. C1q binding activity (C1q BA) values above the 95th percentile for healthy subjects were found in 83% of sera from patients with neoplastic diseases. The incidence of abnormal C1q BA values among patients with malignant melanoma was 83%, with breast cancer 74%, with colon cancer 75%, with lung cancer 88%, with leukemia and lymphoma 85%, and with miscellaneous tumors 94%. High C1q BA values were found most frequently in sera of patients who had been diagnosed relatively recently (within 5 mo) and who had evident residual disease after surgical treatment. Recurrence or progression of tumor growth occurred significantly more frequently in lung cancer patients with high C1q BA. DNA was not detected in cancer patients' sera and treatment with DNase did not decrease in C1q BA. C1q BA in sera could not be explained by the presence of antiglobulin antibodies. Sucrose density gradient ultracentrifugation studies of the serum C1q BA in 4 cancer patients showed that the major binding activity was found between 19S and 7S.

Chronic progressive poliomyelitis secondary to vaccination of an immunodeficient child.

Abstract: We investigated an immunodeficient child in whom chronic progressive poliomyelitis developed after she had received live oral poliovirus vaccine. Poliovirus, Type II, was isolated from throat and stool during life and from several sites within the brain at autopsy. The brain isolate was classified as vaccine-like on the basis of temperature sensitivity and antigenic markers. However, in the monkey neurovirulence test, the brain isolate produced moderately severe lesions throughout the spinal cord and brain-stem and appeared nonvaccine-like. Thus, the brain isolate demonstrated a dissociation between the antigenic and neurovirulence markers. Our observations suggest that, under unusual circumstances, such as immunodeficiency, attenuated poliovirus can produce a chronic progressive neurologic disease. This case also emphasizes the need to diagnose immunodeficiency as early as possible, so that live-virus vaccines will not be administered. (N Engl J Med 297:241–245, 1977)

Hepatitis B Virus Infection and Primary Hepatocellular Carcinoma

Abstract: Ninety-three patients with biopsy-proven primary hepatocellular carcinoma (PHC) from Uganda, Zambia, and the United States were examined for serologic evidence of hepatitis B virus (HBV) infection. Patients were tested for hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs), antibody to the hepatitis B core antigen (anti-HBc), hepatitis B e antigen (HBeAg), and its antibody (anti-HBe). Active HBV infection, as indicated by positive tests for HBsAg (with or without anti-HBs) and anti-HBc (without anti-HBs), was present in 62% of PHC patients (58 of 93), in contrast with 10% of African controls (9 of 90), and less than 1% of most United States adult populations reported in the literature. The presence of HBeAg or anti-HBe was rare among PHC patients and controls.

Diagnostic accuracy of transtracheal aspiration bacteriologic studies.

Abstract: The diagnostic accuracy of transtracheal aspiration bacteriologic studies was examined in 488 patients. Twenty-three patients had bacteremic pneumonia, and in each instance the blood culture isolate was also recovered from the transtracheal aspirate. Clinical correlations in 119 patients with negative cultures of transtracheal aspirate indicated that 71 had an alternative diagnosis to explain an abnormal chest radiograph, and 44 appeared to have a bacterial infection but had received antimicrobial drugs before specimen collection. According to clinical parameters and final diagnosis, the incidence of false-negative cultures was 1 per cent among patients sampled before administration of antimicrobial drugs, and the incidence of false-positive cultures was 21 per cent.

Unsuccessful treatment of staphylococcal endocarditis with cefazolin.

Abstract: Two patients with staphylococcal endocarditis were treated unsuccessfully with cefazolin sodium. One patient relapsed after 52 days of therapy. The second patient had concomitant central nervous system infection and failed to respond to cefazolin therapy. Both patients recovered with methicillin sodium or nafcillin sodium therapy. Other studies report unsuccessful therapy of staphylococcal endocarditis with cefazolin. (JAMA237:569-570, 1977)

Clinical report on the treatment of locally advanced lung cancer

Abstract: This paper discusses the results of the treatment of 345 patients entered in the Veterans Administration Lung Group Protocol 13L. The study was activated March 1972, and closed for the patient accesion March 1975. All patients had a histological diagnosis of primary lung cancer considered clinically non-resectable or inoperable. Patients were equally randomized into two groups, radiotherapy alone or radiotherapy with chemotherapy. The analysis of the data included: treatment regimen, radiation dose, initial performance status, performance status change, cell type, duration of survival, quality of survival and age. The strongest influence on median survival was the level of radiation dose. The small cell carcinoma patients treated with radiotherapy and chemotherapy showed significant improvement in the median survival (38.2 weeks) over the patients treated with radiotherapy alone (20.6 weeks). The patients treated with radiotherapy and chemotherapy also showed improvement in performance status more frequently than the patients treated with radiotherapy alone. Other parameters of the analysis will be presented.

Evaluation of Recent Cerebral Infarction by Computerized Tomography

Abstract: • Twenty patients with cerebral infarction were observed with serial computerized tomographic (CT) scans. Seventy percent of those infarctions showed a mass effect that had disappeared in all patients by the eighth week after the ictus. In 63%, there was enhancement after contrast infusion, with a definite temporal relationship to the day of onset of the neurological deficit. Twenty percent of the patients initially had normal CT scans that became abnormal weeks after the stroke. Radionuclide scans were positive in the patients who showed contrast enhancement, and the area of abnormal uptake correlated well with the area of enhancement. The timing of the performance of the CT scan in relation to the onset of neurological deficit is an important factor to consider when evaluating the stroke syndrome with CT.

Carbohydrate Metabolism in Pregnancy. XIV. Relationships Between Circulating Glucagon, Insulin, Glucose and Amino Acids in Response to a "Mixed Meal" in Late Pregnancy

Abstract: Gestational influences upon the changes in circulating glucose, amino acids, insulin, and glucagon after the ingestion of a "mixed meal" containing carbohydrate (50 g), protein (25 g), and fat (10 g) were examined. Nine subjects were tested during weeks 30-40 of gestation and again 6--8 wk postpartum. The "mixed meal" elicited greater and more prolonged increases in plasma glucose anterpartum, whereas the increments in total serum amino acids were blunted at all time points. In the face of greater glycemic but lesser aminogenic stimulation, the integrated increase in plasma insulin was 60% greater antepartum than post partum, whereas the increment in glucagon was not significantly altered. Thus, integrated insulin/glucagon response was increased during antepartum studies. The insulin preponderance following alimentary challenge with mixed nutrients would suggest that the anabolism of ingested amino acids is "facilitated" during late human pregnancy.

Ultrastructural study of methionine sulfoximine-induced Alzheimer type II astrocytosis.

Abstract: An ultrastructural study of cerebral cortex was performed in rats during the preictal period following the administration of the convulsant methionine sulfoximine (MSO) The morphologic changes were restricted to astrocytes and consisted of cytoplasmic enlargement, mitochondrial and rough endoplasmic reticulum proliferation, accumulation of glycogen, development of cisternal and saccular smooth endoplasmic reticulum, nuclear chromatin clumping, and hydropic degenerative changes These findings resemble those seen in experimental ammonia encephalopathy, suggesting an important role of ammonia in the evolution of these morphologic changes The findings, moreover, suggest that the primary effect of MSO is on astrocytes and that abnormalities in astrocytes may play a role in the development of MSO-induced seizures

Amphotericin B-Induced Myelopathy

Abstract: one patient, and a partial Brown-S\l=e'\quard'ssyndrome in the other. Myelography was normal in both, with no evidence of arachnoiditis. Autopsy findings in the first patient showed a focal area of necrosis in the left half of the spinal cord consistent with the patient's clinical findings during life. The distribution of the lesion corresponded to the area supplied by a central sulcal artery. Amphotericin B may exert a direct toxic effect on the spinal cord or its vascular supply when given intrathecally. (Arch Intern Med 140:1189-1192, 1980) CJymptoms suggesting spinal cord or radicular dysfunc^ tion often occur in patients undergoing treatment with intrathecally administered amphotericin B. These compli¬ cations are usually attributed to arachnoiditis near or at the site of injection.16 The purpose of this report is to present two cases in which clinical, myelographie, and (in one) pathologic evidence failed to support the presence of an amphotericin B-induced arachnoiditis, but rather sug¬ gested direct damage to the spinal cord. This potentially catastrophic complication of intrathecally administered amphotericin may be avoidable, since transient symp¬ toms and signs appear to precede permanent neurologic deficits.

Taste aversion disruption by drug pretreatment: Dissociative and drug-specific effects

Abstract: Disruption of taste aversion learning following the administration of the same drug prior to and during conditioning (intra-agent disruption) was shown to be greater than disruption following the administration of one drug prior to conditioning and another during conditioning (inter-agent disruption) Comparable dosages of ethanol and lithium chloride served as unconditioned stimuli Inter-agent disruptions are attributed to a dissociation of conditioned and unconditioned stimuli, while intra-agent disruptions are attributed to both a dissociative effect and drug-specific effects Intra-agent disruptions are measure of tolerance, suggesting tolerance constitutes at least a portion of the drug-specific effects

Quantitation of countercurrent exchange during passive absorption from the dog small intestine: evidence for marked species differences in the efficiency of exchange.

Abstract: The present investigation was designed to quantitatively assess the possible influence of countercurrent exchange on passive absorption from the small intestine of the dog. Villus blood flow was measured with a modification of the microsphere method. Simultaneously, the absorption from the gut lumen of five diffusible gases (H2, He, CH4, 133Xe, and CO) was determined. Villus blood flow averaged 0.247 +/- 0.03 (SEM) ml/min per g. The observed absorption of H2, He, CH4, and 133Xe was only 16.2 +/- 1.8, 12.8 +/- 2.3, 12.0 +/- 1.8, and 15.8 +/- 1.4 %, respectively, of what this villus blood flow could carry away if it reached perfect equilibrium with the luminal gases. This low absorption rate could result from diffusion limitation to absorption or countercurrent exchange. The diffusive permeability of the barrier seperating the luminal gases and villus blood flow was assessed by measuring the absorption rate of CO. Because absorbed CO binds tightly to hemoglobin, it cannot exchange, and when present in low concentrations its uptake is entirely diffusion limited. Knowledge of the diffusion rate through tissue of the unbound gases relative to that of CO made it possible to calculate the degree to which each of the unbound gases should equilibrate with villus tip blood. The percentage equilibration between lumen and blood at the villus tip for H2, He, CH4, and 133Xe was 99.7, 99.9, 75.6, and 36.0% , respectively. Each of these values greatly exceeded the percentage equilibration of blood leaving the villus (calculated from the observed absorption rate and villus blood flow) and indicated an exchange of 83.8, 87.2, 84.1, and 56.1% of initially absorbed H2, He, CH4, and 133Xe. This result is in accord with theoretical calculations which suggest that countercurrent exchange should be exceedingly efficient in the dog. The striking effect of countercurrent exchange on passive absorption in the dog differs from our previous studies in the rabbit where no exchange was demonstrated. This marked species difference may result from anatomical differences in villus architecture. The dog has long, densely packed villi while the rabbit has broad, widely spaced villi. In the dog, only the villus tips may equilibrate with the lumen, hence a countercurrent gradient may be established in the villus. The entire villus of the rabbit may equilibrate with the lumen and no gradient for countercurrent exchange can therefore be established.

Human Transfer Factor: Fractionation by Electrofocusing and High Pressure, Reverse Phase Chromatography

Abstract: The biologically active fraction of human transfer factor (Sephadex G-25, fraction III) has been separated by exclusion chromatography into two component fractions (IIIa and IIIb). Fraction IIIa transferred donor reactivities to PPD or KLH into 9 of 9 recipients. Fraction IIIb did not transfer donor reactivities (0 of 8 transfers) but did produce both antigen-independent and antigen-dependent dermal reactions in recipients. Fractionation by electrofocusing and high pressure reverse phase chromatography revealed that IIIa has a major UV254 absorbing component and that fraction IIIb has at least three major and three minor UV absorbing components. The major component of IIIa was isolated by preparative electrofocusing, had an isoelectric point of 1.6, and transferred KLH reactivity to four of five recipients.

Effect of 5-hydroxytryptamine on the peripheral chemoreceptors in the rat.

Abstract: 5-Hydroxytryptamine (5-HT), in the doses of 2-5 mug/kg injected into the carotid body area, produced a significant increase in the respiratory rate and carotid sinus nerve activity. Selective ablation of the ipsilateral carotid sinus nerve abolished the respiratory stimulation produced by the drug. On the other hand, the same doses of 5-HT injected into the ascending aorta did not produce stimulation of respiration when the carotid sinus nerves were sectioned. The activity of the aortic nerves did not increase after injecting the drug into the ascending aorta or at the root of the right subclavian artery. These results indicate that 5-HT stimulates the chemoreceptors in the carotid body of the rat. The lack of responses to the injections of the drug in the aortic or subclavian region was due to the absence of chemoreceptors in these regions of the rat.