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Biomedical subjects

D Kumar

Publications and source records attributed to D Kumar.

At least 361 records · Page 20Linked to original sources

Alterations in organization of phospholipids in erythrocytes as factor in adherence to endothelial cells in diabetes mellitus.

Erythrocytes from patients with diabetes mellitus exhibit increased adherence to cultured human vascular endothelial cells. We investigated the alterations in erythrocyte surface characteristics that may contribute to their abnormal adherence. The organization of phospholipids in the lipid bilayer, as determined by phospholipase A2 treatment and chemical labeling with fluorescamine and trinitrobenzene sulfonic acid (TNBS), is altered in erythrocytes from diabetic patients. Specifically, 12-18% of phosphatidylserine in diabetic erythrocytes (n = 25) is accessible to phospholipase A2 hydrolysis and TNBS labeling, compared to none in normal subjects. These results suggest either a loss in lipid asymmetry or in vivo destabilization of erythrocyte membranes in diabetic patients, causing increased accessibility to phospholipase A2 degradation. The dye merocyanine 540 (MC-540), which is sensitive to the packing of lipids in the bilayer of the membrane, revealed more binding and fluorescence in erythrocytes from diabetic patients than in those from normal subjects. On flow cytometric analysis, 64.5 +/- 17.0% red blood cells (RBCs) in diabetic patients, compared to 35.1 +/- 25.9% RBCs in normal subjects, showed positive MC-540 binding, indicating significant (P less than .001) differences in the packing of lipids in the external leaflet of the bilayer. The results of our study suggest that a loss of lipid asymmetry and/or less ordered packing in the outer leaflet of the diabetic erythrocyte membrane may be responsible for the increased propensity of erythrocytes to adhere to vascular endothelium.

Adult↗

Effect of pirenzepine on oesophageal, gastric, and enteric motor function in man.

The effect of pirenzepine on oesophageal, gastric, and enteric motor function was evaluated in six healthy volunteers. Each subject was studied before and after taking pirenzepine, 100 mg/day, for 3 days. Half and complete gastric emptying times of clear liquid, assessed by epigastric impedance, were significantly delayed by the drug: 6.16 +/- 1.74 min and 13.8 +/- 4.64 min versus 16.65 +/- 3.03 min and 25.1 +/- 8.2 min, respectively (p less than 0.05). Enteric motility was assessed by manometry, and variables studied were the duration of the various phases of the migratory motility complex, the frequency of contractions in phase III, and the amplitude of contractions in phases II, III, and in the postprandial period. Only phase I was affected and was significantly prolonged by the drug: 16.08 +/- 5.94 min versus 31.65 +/- 12.88 min (p less than 0.01). Oesophageal motility was assessed by manometry. Variables studied were amplitude and duration of contractions in the body of the oesophagus, and lower oesophageal sphincter pressure. Results were not significantly changed by the drug. We conclude that pirenzepine, given at a dose used for treatment of peptic ulcer disease, significantly delays the gastric emptying of liquids, has minimal effect on enteric motility, and has no effect on oesophageal motility. The effect on gastric emptying may be therapeutically useful by reducing the acid load on the duodenum in duodenal ulcer disease.

Adult↗

Increased adherence of oxidant-treated human and bovine erythrocytes to cultured endothelial cells.

Bovine erythrocytes, which normally lack phosphatidyl choline in their membranes, when treated with either H2O2 or diamide (1-3 mM), showed a partial appearance of phosphatidyl ethanolamine (PE 40%) and phosphatidyl serine (PS, 30-33%) in the external leaflet of the bilayer and a concomitant increased (four- to five-fold) propensity to adhere to cultured bovine aortic endothelial cells. Similar treatment of normal human erythrocytes caused an alteration in the organization of the phospholipid bilayer and also resulted in their increased adherence to endothelial cells derived either from human umbilical vein or bovine aorta. Treatment of RBCs with H2O2 at low concentration (0.5 mM) resulted in cross-linking of spectrin without significant changes in the orientation of aminophospholipids but the RBCs exhibited 15-20% increase in adherence to endothelial cells. Pretreatment of either human or bovine erythrocytes with antioxidants such as vitamin E (2 mM) prevented both oxidant-induced reorganization of phospholipids in the bilayer and enhancement of adherence to endothelial cells. Introduction of either phosphatidyl serine or phosphatidyl ethanolamine but not phosphatidyl choline into erythrocyte membranes increased their adherence to endothelial cells threefold. Oxidant-treated RBCs exhibited enhanced binding and fluorescence of Merocyanine 540 dye (MC-540), which is sensitive to the packing of lipids in the lipid bilayer. On flow cytometric analysis, 78% of H2O2 (0.5 mM)-treated erythrocytes compared to 30% of untreated RBCs exhibited MC-540 binding and fluorescence, indicating differences in the lipid packing in the outer leaflet of the bilayer. Oxidant-treated erythrocytes adhere preferentially to endothelial cells rather than to bovine aortic smooth muscle cells and skin fibroblasts. It is suggested that the alterations in the erythrocyte membrane surface due to spectrin cross-linking and the organization of the phospholipids concomitant with less ordered packing in the external leaflet of the bilayer, either induced by oxidative manipulation in normal RBC or in pathological erythrocytes, play a role in erythrocyte-endothelial cell interaction.

Animals↗

The contribution of external ligamentous attachments to function of the ileocecal junction.

In 14 human autopsy specimens, obtained within two hours of death, the contribution of external ligamentous attachments to competence against reflux at the ileocecal junction (ICJ) was evaluated. The ascending colon was filled with saline by retrograde flow, and pressures at which coloileal reflux occurred were recorded. Twelve of 14 ICJ's were competent to pressures of up to 80 mm Hg; two incompetent ICJ's refluxed fluid into the ileum at intracecal pressures of approximately 40 mm Hg. Competent specimens were then restudied. Removal of mucosa at the ileocecal junction (N = 6), or a strip of circular muscle (N = 6), did not impair competence to pressures above 40 mm Hg. However, division of fibrous tissues which helped maintain an angulation between the ileum and cecum (superior and inferior ileocecal ligaments) rendered the junction incompetent in all specimens. In four samples tested, surgical reconstruction of the ileocecal angle restored competence. Comparable observations were made in three anesthetized dogs in vivo. These findings suggest that mechanical factors, maintained by the external anatomy, contribute to competence at the ICJ.

Animals↗

Serodiagnosis of porcine cysticercosis by enzyme-linked immunosorbent assay (ELISA) using fractionated antigens.

The sensitivity and specificity of the enzyme-linked immunosorbent assay (ELISA) for the diagnosis of Taenia solium cysticercosis was evaluated in experimentally and naturally infected pigs, using T. solium larval scoleces and its fractionated 1st and 2nd peaks on Sephadex G-200 as antigens. First peak antigen gave maximum sensitivity and highest antibody titres. The overall sensitivity of this test was found to be 91.5, 95.8 and 70.8% with scolex, 1st and 2nd peak antigens, respectively. False positive reactions occurred in 9.09% of uninfected pigs with scolex and 1st peak antigens and cross-reactions occurred in 25% of Taenia hydatigena-infected animals using scolex and 2nd peak antigens. No cross-reaction was observed using 1st peak antigen. The specificity of the test was 92.3, 96.2 and 92.3% with scolex, 1st and 2nd peak antigens, respectively.

Animals↗

Clinical manifestations of trisomy 5q.

A patient with a small deletion of the short arm and a partial duplication of the long arm of chromosome 5 is described. The main clinical features include craniofacial dysmorphism, growth failure, developmental retardation, and congenital heart defect. The mother and male sib each carried an inv(5) (p15.3q35) but were phenotypically normal. The possible clinical manifestations of partial duplication of the long arm of chromosome 5 are discussed with a review of previous published reports.

Abnormalities, Multiple↗

Three-dimensional imaging of the stomach: role of pylorus in the emptying of liquids.

Using the dynamic spatial reconstructor and manometry, we measured gastric emptying, pyloric size, and antral contractile activity in three anesthetized dogs in the prone position. Our objective is to evaluate the effect of intestinal perfusion of equicaloric, neutral, and isosmolar nutrients (Maltose 32.5 mg/ml, casein hydrolysate 32.5 mg/ml, and oleic acid 15.5 mg/ml) at a constant rate of 10 ml/min in the proximal jejunum on the dynamics of the antropyloric region. Isotonic saline perfusion was used as a control solution. Test meal in the stomach was 600 ml of isotonic Gastrograffin. Antral phasic pressure activity was recorded using an antroduodenal six-channel (ports 5 mm apart) perfused probe (2 mm OD). Gastric emptying in response to intestinal perfusion of fat was significantly slower (P less than 0.02) in comparison to other nutrients or isotonic saline. There was no significant difference in the maximum or minimum pyloric diameter in response to the four intestinal perfusates. However, the pylorus was closed for a significantly longer duration (P less than 0.05) during the perfusion of fat in the upper intestine. Antral contractions were related to pyloric opening in an "antral contraction followed by pyloric opening" sequence. This study suggests that the presence of fat in the upper intestine delays gastric emptying and that this effect is regulated in part by increased resistance to flow offered by the pylorus.

Animals↗

Concurrent lupus anticoagulants and prothrombin deficiency due to phenytoin use.

A man with lupus anticoagulant and a prothrombin deficiency was studied before and after cessation of treatment with phenytoin. Multiple abnormal laboratory values of the following partially or completely resolved after the patient's therapy was discontinued: tissue thromboplastin inhibition ratio, prothrombin time, activated partial thromboplastin time, anticardiolipin antibodies, and quantitative measures and abnormal pattern on crossed immunoelectrophoresis of prothrombin. This patient represented an example of a concurrent drug-induced prothrombin deficiency and a lupus anticoagulant.

Adult↗

Fractionation and characterisation of the cysticercus of Taenia solium.

Fractionation by chromatography on Sephadex G-200 of a saline extract of Cysticercus cellulosae scolex antigen yielded three distinct fractions associated with distinct peaks. These fractions were analysed by double immunodiffusion (DID) and immunoelectrophoresis (IEP). The three peaks gave five, four and three antigenic determinants, respectively, by DID with homologous hyperimmune rabbit serum. However, the same serum gave nine antigenic determinants of scolex antigen by DID and 11 components by IEP. The IEP demonstrated seven and five antigenic components in the first two peaks. The first peak gave a stronger reaction in indirect haemagglutination than the others. There were common antigenic components in C cellulosae and C tenuicollis antigens.

Animals↗

Cell-mediated immunological status and association of genetic markers in hereditary cerebellar ataxia.

Sixteen unrelated patients with hereditary cerebellar ataxia (HCA) were studied for genetic association with HLA and sixteen other genetic markers. Cell mediated immunological status of these patients was also studied by in vitro lymphocyte transformation tests. HLA typing was done in five three-generation families of patients with autosomal dominant cerebellar ataxia (ADCA). Linkage between HLA and ADCA loci was analysed using LIPED. Negative lod scores were observed in all five families. This lack of evidence for linkage between the HLA and ADCA loci is attributed to genetic heterogeneity of the disease in the families studied. No significant deviation was found in lymphocyte function to mitogen/antigen stimulation. A possible association of B12 (B44) antigen with ADCA is suggested.

Cerebellar Ataxia↗

Hereditary cerebellar ataxia and genetic linkage with HLA.

Five families with at least three generations of members affected with autosomal dominant spinocerebellar ataxia (SCA) were studied. HLA typing was carried out and the coded HLA haplotypes were used to calculate the likelihood of linkage using the LIPED computer program. The combined lod scores from these five families does not, by itself, support linkage. Negative lod scores were observed in all five families, however, when pooled with the previously published data significant lod scores were obtained [Z = 3.343 (theta = 0.20) and +4.286 (theta = 0.30)]. In four families, affected members had clinical features consistent with autosomal dominant cerebellar ataxia (ADCA) type I while in the fifth, ADCA type II was suggested. Clinical heterogeneity within ADCA raises doubts about the significance of summed lod scores. In view of the previous reports probably two genetically heterogeneous types of ADCA exist -- HLA linked and nonlinked.

Adolescent↗

Effects of different types of stress and of "prokinetic" drugs on the control of the fasting motor complex in humans.

Upper small bowel motility was continuously recorded for 36-48 h in 37 healthy ambulant volunteers using twin pressure-sensitive radiotelemetric capsules tethered in the small bowel. Each study began with a 24-h period that was free of applied stress. The second 24-h period included 7 h of intermittent psychological stress during the day and brief episodes of acute stress during the following night, except in the members of a control group to whom no stress was applied. Stress responses were assessed from cardiovascular status and self-reported visual analogue scales. Applied stress during the second day significantly inhibited the incidence of fasting migrating motor complexes compared with the first day; when no stress was applied there was no reduction in migrating motor complexes. Nocturnal stress was less effective in the inhibition of migrating motor complexes. All the stressors induced positive cardiovascular and subjective stress responses. The stress-induced inhibition of migrating motor complexes was reversed by oral metoclopramide; however, the drug did not reverse the cardiovascular or subjective response to stress. In contrast, domperidone did not inhibit the gastrointestinal effects of stress. Neither drug appeared to influence small bowel motility under normal conditions.

Adult↗

Circadian variation in the propagation velocity of the migrating motor complex.

Using twin intraluminal pressure-sensitive radiotelemetric capsules for prolonged monitoring of proximal small bowel motility in healthy volunteers, we observed a significant (p less than 0.001) variation between daytime (6.44 +/- 0.74 cm/min, mean +/- SD) and nocturnal (2.90 +/- 0.35 cm/min) propagation velocities of the migrating motor complex. An identical variation in propagation velocity was observed in patients suffering from the irritable bowel syndrome. These data suggested a circadian variation, but did not exclude alternative hypotheses. Data were therefore compiled from healthy sheep and pigs supplied with ad libitum rations each morning and adapted to a 12 h light, 12 h dark schedule. Recording from implanted electrodes showed a significant (p less than 0.01) reduction in migrating motor complex velocity from 27.8 +/- 5.1 cm/min by day to 16.7 +/- 3.1 cm/min at night in sheep, and from 20.6 +/- 2.4 to 13.4 +/- 1.9 cm/min in pigs. The nocturnal reduction remained when the animals were fed in the evening. These observations suggest a circadian variation in mammalian migrating motor complex propagation velocity that is not merely a function of variation in intraluminal content.

Animals↗

Comparison of effects of fentanyl and alfentanil on intra-ocular pressure. A double-blind controlled trial.

The effects of fentanyl and alfentanil on intra-ocular pressure during anaesthesia were investigated in 50 consecutive patients in a double-blind controlled trial. Both drugs produced a significant reduction in intraocular pressure (p less than 0.01). Alfentanil produced significantly greater reduction (48.5 percent) than fentanyl (28.6 percent) (p less than 0.01). A small but statistically significant reduction in arterial pressure (15 percent approximately) and heart rate (18 percent approximately), were observed with both agents, but no significant differences between them were noted. It is suggested that alfentanil may be a suitable alternative to fentanyl in ophthalmic anaesthesia.

Adjuvants, Anesthesia↗