Role of adenoviruses in infections of the nervous system.
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Biomedical subjects
Publications and source records attributed to R Subramanian.
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The effect of repetitive brief periods of coronary occlusion on subsequent prolonged ischemic insult was studied using a swine heart model. Four 5-min episodes of left anterior descending coronary artery (LAD) occlusion, each separated by 10 min of reperfusion, did not affect any of the regional or global myocardial functions examined, except that the level of adenosine triphosphate (ATP) dropped to some extent. Sixty minutes of LAD occlusion following four repeated stunnings further reduced the ATP level, but this reduction was significantly lower compared to nonstunned control. Myocardial global functions were not affected significantly by prolonged ischemic insult. Segment shortening (SS) was reduced comparably in both control and stunned groups. However, SS improved significantly during subsequent reperfusion in the stunned group compared to control. The experimental group also demonstrated reduced infarct size and an area of risk compared to nonstunned control. These results indicate that repeated stunning prior to irreversible ischemic insult can attenuate ischemic injury and post-ischemic dysfunction.
111In possesses excellent radiophysical properties suitable for use in immunoscintigraphy of cancerous tissues when attached to an antitumor antibody. However, 111In has a tendency to accumulate in normal tissues such as liver. Instability of the linkage between 111In and antibody may contribute to this problem. To avoid this, we developed a new bifunctional chelating agent, 1,3-bis[N-[N-(2-aminoethyl)-2-aminoethyl]-2-aminoacetamido]-2-(4- isothiocyanatobenzyl)propane-N,N,N',N'',N''',N'''',N''''',N'''''- octaacetic acid (LiLo), that forms a kinetically stable chelate with metal ions such as indium. Using LiLo, indium-111 was conjugated to a human monoclonal antibody, 16.88. Competitive binding analysis revealed that the 16.88-LiLo conjugate is as immunoreactive as the unconjugated native antibody. This conjugate was compared with 111In-16.88, where diethylenetriaminepentaacetic acid dianhydride (DTPAa) was used as the chelating agent. In vitro stability studies showed that 111In was more stably bound to 16.88-LiLo than to 16.88-DTPA. Biodistribution studies in athymic mice bearing colorectal tumor xenografts indicated less liver retention with 16.88-LiLo than with 16.88-DTPA. These results demonstrate that LiLo is superior to DTPAa for attachment of 111In to the monoclonal antibodies.
We report concentrations and distribution of cyclosporine A (CsA) and individual metabolites associated with various organ tissues and whole-blood specimens collected at autopsy from seven transplant patients who received CsA therapy. Solid-phase extraction (SPE) and specific high-performance liquid chromatographic (HPLC) procedures were used to separate and quantitate the cyclosporines. Patterns of deposition were unique for the various tissue types. Metabolites M17, M1, M18, and M8 (in addition to CsA) were the principal compounds detected in significant quantities. On a per weight basis, the sum concentration of CsA and metabolites in organ tissues was up to 53 times greater than in companion whole-blood specimens. Metabolite M17 prevailed in most tissues, except in fat and pancreas, where CsA was predominant. Overall, pancreas specimens contained a greater concentration of cyclosporines (per kilogram of tissue), followed consecutively by spleen, liver, fat, kidney, lung, bone marrow, heart, and whole blood. No CsA-related compounds were detected in brain or spinal cord tissue.
Prior to the development of CT, cardiac and pericardiac masses were evaluated by chest roentgenography, angiocardiography, and echocardiography. In most cases preoperative diagnosis of a specific entity was impossible. Preoperative CT diagnosis of an intrapericardial developmental mass becomes possible because of the presence of fat, fat/fluid level, thick walled cysts, as well as globular calcifications, bones, teeth, water density fluid, and soft tissue. A report of a young woman with a ruptured and infected intrapericardial teratoma and an infant with an intrapericardial bronchial cyst is presented.
The existence of coronary endoarterial cushions (CEC) in the human heart as nonpathological, functional entities has been debated, and CEC have been sparsely reported in animals. Arterial cushions are localized thickenings that protrude into the lumen of specific arteries. We have identified CEC in the rhesus monkey, dog, sheep, goat, pig, rabbit and rat, and in the human heart. Two distinct types are described: the ovoid CEC arranged singly, in pairs, or in groups of three to four, and the less common polypoid CEC seen primarily in humans. The highest incidence of CEC in rabbits and humans was in the left ventricle in arteries 150-488 microns in diameter. Light and electron microscopy demonstrated intimal location with smooth muscle cells surrounded by ground substance, collagen and elastin fibers in a highly organized pattern. Nerve fibers identified by their immunoreactivity with antiserum to the vasodilatory calcitonin-gene-related peptide contacted the CEC along the tunica media and were occasionally seen within CEC. Arrangement and histological composition of CEC suggest a role in the regulation of local blood flow and myocardial perfusion. In human hearts, the CEC density index correlated highly with the degree of heart disease. In subjects with high heart disease rating, increased connective tissue, lipid-like infiltration and calcification was seen within CEC, and foam cells were present in CEC of obese rabbits. This suggests that CEC in coronary arteries could be predisposed sites of atherosclerosis, and that injured CEC can cause coronary artery spasm and ischemia. We conclude that CEC occur in animals and humans as innervated intimal smooth muscle cushions that might have a role in myocardial perfusion and heart disease.
OBJECTIVE: To describe a case of hyperparathyroid crisis manifesting as respiratory failure and congestive heart failure and to emphasize the implications of hypercalcemia and hypophosphatemia in this setting. METHODS: A case report and a review of the pertinent literature are presented. RESULTS: A 71-year-old man was transferred to our care because of respiratory failure and congestive heart failure. He had no change in cardiorespiratory status until the significance of hypercalcemia and hypophosphatemia was recognized and therapy was directed at correction of these abnormalities. Primary hyperparathyroidism was the cause of these electrolyte abnormalities. CONCLUSION: To our knowledge, hyperparathyroid crisis manifesting as respiratory insufficiency and congestive heart failure has not been described previously. Phosphate depletion may account for the neuromuscular features seen in hyperparathyroidism.
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A retrospective cohort study was carried out in 61 patients (30 males, 31 females, age 24.6 +/- 11.8 years) with primary pulmonary hypertension diagnosed by strict clinical and hemodynamic criteria, to obtain an understanding of the natural history and prognostic markers. While 15 patients were alive, 46 patients (76%) had expired during the follow up period. Two, five and ten years survivals were 48%, 32% and 12% respectively. Median survival duration from time of diagnosis was 22 months. The survivors had significantly higher age of onset, cardiac index and significantly lower right atrial mean pressure, right ventricular end diastolic pressure, cardiothoracic ratio from chest rontgenogram and calculated pulmonary vascular resistance as compared to non survivors. While pulmonary artery systolic pressure was not significantly different, pulmonary artery diastolic and pulmonary artery mean pressures were significantly lower in survivors than in non-survivors. Lower New York Heart Association class, right atrial mean pressure < or = 7 mm Hg, right ventricular end diastolic pressure < or = 10 mmHg, cardiac index > 2.5 L/min/m2, pulmonary arterial oxygen saturation > 60%, were associated with significantly longer survival. The degree of pulmonary arterial hypertension had an indirect prognostic effect through the above parameters. Vasodilator therapy did not significantly alter the outcome of patients with primary pulmonary hypertension.
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