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Biomedical subjects

D Kumar

Publications and source records attributed to D Kumar.

At least 55 records · Page 3Linked to original sources

Pancreatic nesidioblastosis in adults.

Nesidioblastosis, a condition characterized by diffuse islet cell hyperplasia arising from the ductal epithelium, is often associated with hyperinsulinemic hypoglycemia. This is a childhood disease and is rarely found in adults. Only 10 histologically proven cases have been recorded, including 3 new cases described in this article. Most clinical and biochemical features are identical to those of an insulinoma, except the proinsulin-like component of circulating immunoreactive insulin, which is usually within the normal range in nesidioblastosis. Limited observations show that some patients may be managed medically with diazoxide. Patients who remain hypoglycemic despite medical therapy require pancreatectomy, although greater than 90% resection frequently results in insulin dependency and permanent diabetes.

Adult

Analysis of somatic changes in human tumor DNA using synthetic oligonucleotide probes.

Like most hematologic malignancies, solid cancers may be associated with non-random chromosomal abnormalities. Heterogeneity in the cell population in solid cancers and the chromosomal variations occurring among primary, explant, and passaged cells of a given tumor, however, present a major difficulty in assessment of their cytogenetic changes. Alternative approaches to identifying specific somatic changes in subtypes of solid cancers, without cell culture manipulations, must be developed. This report describes preliminary evidence indicating that oligonucleotide probes, homologous to short tandem repeats, that can determine individual identity, may also be useful tools with which to examine somatic changes in DNA which has been isolated directly from a tumor mass. Two, of the four, bladder tumors (transitional cell carcinomas) analyzed, exhibited oligonucleotide-based DNA fingerprint patterns that differed from those of corresponding constitutive or uninvolved tissue DNA. The changes that were observed included gain or loss of hypervariable DNA fragments or shifts in band intensities.

DNA

Early onset hereditary spinocerebellar ataxia: an autosomal recessive disorder distinct from Friedreich's ataxia.

The important clinical features of seven patients with an early onset slowly progressive heredofamilial spinocerebellar degenerative disorder of probably autosomal recessive inheritance included limb ataxia, retained and/or exaggerated tendon reflexes (biceps and knee), pyramidal weakness of lower limbs and normal sensory action potentials. This rare disorder is probably distinct from Friedreich's ataxia and carries a better prognosis.

Adolescent

Gastro-oesophageal reflux and intestinal malrotation in children.

In a series of 74 children undergoing Nissen fundoplication for persistent gastro-oesophageal reflux unresponsive to intensive medical treatment, there was an unexpectedly high incidence (54 per cent, n = 40) of intestinal malrotation. The series was not homogeneous, 25 of the children having reflux as a complication of a serious congenital abnormality (48 per cent incidence of intestinal malrotation), and 49 presenting with 'idiopathic' reflux (57 per cent incidence of intestinal malrotation). Intestinal malrotation is best detected pre-operatively by careful barium radiology, requiring clinicians to be aware of the association. In our experience, in children over the age of 3 months, both an antireflux operation and Ladd's procedure are often necessary to stop gastro-oesophageal reflux when an intestinal malrotation is present.

Adolescent

Reflux from ileum to colon in the dog. Role of external ligamentous attachments.

In four dogs we quantified the role of external ("coloileal") ligaments in preventing coloileal reflux. All animals were tested under control conditions, and then two had all external ligamentous attachments between ileum and colon divided; the other pair underwent a sham operation. Coloileal reflux was quantified scintigraphically at colonic pressures of 20, 40, and 60 mm Hg, and ileal motility was recorded concurrently. During control experiments and after sham operations, no dogs showed coloileal reflux at colonic pressures of 20 and 40 mm Hg. At a colonic pressure of 60 mm Hg, two control experiments and one in a dog after sham operation resulted in reflux of 9%, 4%, and 8% of counts, respectively. In contrast, both test dogs (after division of the ligaments) refluxed 30-70% of colonic content in all of four experiments at pressure below 20 mm Hg. In control dogs and in those with a continent ileocolonic junction, ileal motility consisted of scattered clusters of phasic contractions. In dogs with coloileal reflux, these clusters occurred with a similar frequency, but they lasted longer (P less than 0.005). Four weeks later, ileal motility indices in control dogs were significantly less (P less than 0.02) than in animals with divided coloileal ligaments. These observations establish an experimental model for coloileal reflux, support the hypothesis that external ligamentous attachments help maintain continence at the ileocolonic junction, and imply that coloileal reflux changes the motor pattern of the terminal ileum.

Animals

Calcium/creatinine ratio and microalbuminuria in the prediction of preeclampsia.

Eighty-eight normotensive gravid women between 24 and 34 weeks of gestation underwent urine evaluation for the presence of microalbuminuria and urinary calcium excretion (calcium/creatinine ratio). Preeclampsia subsequently developed in 83% of patients with a high level of microalbuminuria (greater than or equal to 11 micrograms/ml) and a low calcium/creatinine ratio (less than or equal to 0.04). Conversely, 94% of women who did not demonstrate high microalbuminuria and a low calcium/creatinine ratio remained normotensive at the time of delivery. These results suggest that changes in renal function are present in gravid women who are otherwise free of symptoms in whom preeclampsia will eventually develop. Testing for microalbuminuria and a calcium/creatinine ratio may be a useful screening tool in predicting the subsequent development of preeclampsia.

Albuminuria

The clinical, pathological and genetic aspects of sporadic late onset cerebellar ataxia: observations on a series of ten patients.

Ten patients with sporadic late onset cerebellar ataxia (LOCA) are described. The mean age of onset was 50.4 +/- 7.13 years. The important clinical features were gait ataxia, poor coordination of hands, intention tremors, exaggerated deep tendon reflexes, extrapyramidal symptoms and extensor plantar responses. Computerised tomography (CT) scanning in one patient showed a low density mid-line lesion, suggesting early cerebellar atrophy. Histopathological examination in one patient, clinically diagnosed as multiple sclerosis, revealed complete loss of Purkinje cells from the cerebellar folia with gliosis in the molecular layer and loss of small granular neurones. A marked loss of the neurones from the olivary nuclei with astrocytic proliferation was also seen. The disorder is probably genetically determined although a single Mendelian inheritance is unlikely in the absence of recurrence in the first degree relatives. Recurrence risks for gentic counselling are suggested.

Adult

Unknown syndrome: Hirschsprung's disease, microcephaly, and iris coloboma: a new syndrome of defective neuronal migration.

We describe three children with Hirschsprung's disease and microcephaly, two of whom also have an iris coloboma. Two of the children, one with a coloboma and one without, are from the same consanguineous pedigree. The third case is unrelated and was identified by the matching program of the London Dysmorphology Database. This is the first report of this combination of features which are considered to be secondary to defective neuronal migration. An autosomal recessive mode of inheritance is proposed.

Coloboma

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