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Biomedical subjects

D Kumar

Publications and source records attributed to D Kumar.

At least 235 records · Page 13Linked to original sources

Preventive effects of sodium molybdate in lead intoxication in rats.

The role of sodium molybdate (1 mg/kg, intraperitoneally, once daily) supplementation during the course of lead exposure (0.1% lead acetate in drinking water for 4 weeks) in preventing the accumulation of lead in blood and soft tissues and in restoring altered lead-sensitive biochemical variables and the levels of hepatic glutathione, lipid peroxidation, blood Na, blood K, and serum ceruloplasmin was investigated in rats. The data indicate that sodium molybdate significantly protected the uptake of lead in blood, liver, and kidneys and restored the lead-induced inhibited activity of blood delta-aminolevulinic acid dehydratase, elevation of blood zinc protoporphyrin, hepatic lipid peroxidation, and serum ceruloplasmin. The results suggest a significant role of sodium molybdate in preventing plumbism.

Animals↗

Scintigraphic defecography: quantitative and dynamic assessment of anorectal function.

PURPOSE: Conventional assessment of anorectal function with defecating videoproctography is semiquantitative and the high radiation exposure precludes prolonged or repeated testing. The aim of this study was to develop a dynamic scintigraphic method of assessing anorectal function. METHODS: Fourteen patients with fecal incontinence, 18 patients with chronic constipation, and 8 control subjects were assessed by scintigraphic defecography. This involves introduction of a technetium-99m-radiolabeled artificial stool into the rectum of the subject and acquisition of gamma camera images during evacuation. RESULTS: Mean evacuation rate was 2.8 percent/second in incontinent patients and 0.9 percent/second in constipated patients (P < 0.001). The mean anorectal angles were 136 degrees and 133 degrees, respectively. There were 18 cases of pelvic floor descent and 6 rectoceles. Scintigraphic defecography provides quantitative information on rectal evacuation. Anorectal angle and pelvic floor movement can be examined. The radiation dose to pelvic organs is significantly less than with videoproctography. CONCLUSION: We believe that scintigraphic defecography is the investigation of choice for objective and dynamic assessment of anorectal function.

Adult↗

C-peptide and the classification of diabetes mellitus patients in the Early Treatment Diabetic Retinopathy Study. Report number 6. The ETDRS Research Group.

The Early Treatment Diabetic Retinopathy Study (ETDRS), conducted at 22 clinical centers during the period 1980 to 1989, collected baseline data on C-peptide levels after ingestion of Sustacal in 582 patients with diabetes mellitus, prior to enrollment in the trial. Data on several clinical factors associated with diabetes were also collected from all 3711 enrolled patients. C-peptide data were used to develop sets of clinical criteria for the classification of ETDRS patients and to compare and contrast definitions of type of diabetes used in previous studies. The distribution of C-peptide levels was strikingly bimodal, suggesting a division of study participants into two groups--those with levels at 80 pmol/L or less and those with more than 80 pmol/L of C-peptide after Sustacal ingestion. Constellations of clinical characteristics that could serve as proxies for C-peptide level were ascertained. The result was two sets of clinically developed definitions for type of diabetes in the ETDRS. According to the more restrictive set of definitions, three groups were identified, compared to two groups using the "broad" set of definitions. Discriminant analysis was also used to classify ETDRS patients, yielding similar results. A comparison of definitions of type of diabetes used in the ETDRS and in previous studies revealed that even in the absence of C-peptide data, clinically derived definitions provided good discrimination between type I and type II diabetes.

Adult↗

Insulin antibodies: reduction in various anti-insulin IgG subclasses with human insulin therapy.

The insulin-induced antibodies decrease on substitution of bovine-porcine with human insulin. In order to test whether there is a preferential reduction of certain anti-insulin IgG subclass, we investigated the composition of insulin antibodies. In serum samples collected from 23 bovine-porcine insulin-treated patients with clinical manifestations of insulin-induced immune problems (12 insulin resistant cases, 11 with lipodystrophy and/or local insulin allergy), the amounts of 125I-bovine insulin bound with IgG1, IgG2, IgG3 and IgG4 subclasses were 27.0 +/- 4.7, 7.8 +/- 2.3, 39.0 +/- 11.6 and 55.1 +/- 10.9 ng/ml respectively. Thus, there was an abundance of insulin antibodies of IgG4 subclass, and a relative paucity of IgG2. When the bovine-porcine insulin was changed to rDNA human insulin in 15 patients, the total insulin-binding IgG antibodies decreased by 58.6% with concomitant reductions in IgG1 (from 26.7 +/- 6.6 to 16 +/- 5.3), IgG3 (from 5.9 +/- 3.1 to 4.3 +/- 2.1), and IgG4 (from 46.4 +/- 15.6 to 18.4 +/- 7.9 ng of insulin bound/ml) subclasses. These observations suggest that in a selected subset of patients with insulin-induced immune problems, the bovine-porcine insulin induces antibodies of all four IgG subclasses but the IgG4 response predominates. With the substitution to human insulin, a reduction in the immune stimulus occurs followed with decreases in the IgG1, IgG3 and IgG4 subclasses.

Adolescent↗

Effects of aging, diet, and sex on plasma glucose, fructosamine, and lipid concentrations in barrier-raised Fischer 344 rats.

We studied the relationships of plasma glucose, fructosamine, triglycerides, and cholesterol as a function of age, gender, and diet in barrier-raised Fischer 344 rats aged 5 to 26 months, fed a diet either ad libitum or restricted to 60% of the ad libitum caloric intake. The complex relationships of these plasma levels to age, gender, and diet led to the development of a model with age, diet, and sex as covariates. Overall, fasting plasma glucose concentrations were reduced by approximately 25% in rats on the restricted diet, compared to ad libitum-fed animals. There was a significant age-dependent decline in glucose levels in male animals, whereas in females there was an increase in plasma glucose with aging. Plasma fructosamine levels in calorie-restricted animals, overall, were reduced by 7% compared to levels in animals fed ad libitum. There was a significant positive correlation between plasma glucose and fructosamine levels. Mean plasma triglyceride content was decreased by 50% in calorie-restricted rats compared to ad libitum-fed animals. A significant decrease in triglyceride levels with increasing age was seen in male animals, and an increase with aging in females. There was a significant positive correlation between plasma glucose and triglyceride levels. Plasma cholesterol levels in calorie-restricted animals were reduced by 7% compared to levels in ad libitum-fed animals. An increase of cholesterol concentration with aging was significant in both males and females. Analysis of the data showed that there were significant differences between male and female Fischer 344 rats in the response of plasma glucose and fructosamine to aging and calorie restriction. Changes of plasma triglyceride and cholesterol with aging and dietary calorie restriction were also different in males and females. Studies of the effect of aging on glycemia and blood lipid content should take into account the contributions of animal sex.

Aging↗

Recurring phyllodes tumor in aberrant breast tissue of the vulva.

A 20-year-old nulligravida woman presented with bilateral cystic nodules of the vulva, diagnosed after simple excision as benign phyllodes tumor. Breast tissue, which also displayed fibrocystic changes, was also recognized. Follow-up at 2 months revealed no evidence of disease; however, 8 months after surgery she returned with a new mass in the vulva. This was excised and found to be recurrent phyllodes tumor. Although somewhat more cellular than the first lesions, it also was deemed to be benign based on histological features supported by flow cytometric DNA studies.

Adult↗

Epstein-Barr virus-associated T-cell lymphoma in a renal transplant patient.

Posttransplant lymphoproliferative disorders in organ allograft recipients are most commonly of B cell origin, whereas T cell lymphomas are rarely described. We report a case of T cell immunoblastic large cell lymphoma associated with Epstein-Barr virus (EBV) that occurred in a recipient of a cadaveric renal transplant 7 years posttransplantation. On paraffin immunophenotyping, none of the neoplastic cells stained with the T cell-associated markers used, but did show strong CD30 expression. Flow cytometric studies revealed a predominance of T cells without definite evidence of T cell neoplasia. Frozen section immunophenotyping studies revealed a T cell phenotype with aberrant expression, and genotypic studies demonstrated T cell receptor beta gene rearrangement with germline configuration of immunoglobulin heavy chain and kappa light chain genes, confirming a T lineage. EBV-encoded RNA transcripts were demonstrated within the neoplastic cells by in situ hybridization. Southern blot analysis using probes derived from the terminal repeat region of the virus detected a single restriction band indicating a clonal population. We believe this is the first case of a posttransplant T cell lymphoma in which the EBV genome has been demonstrated. This case also illustrates the pitfalls of paraffin immunophenotyping in the diagnosis of T cell lymphoma.

Adult↗

Anal sphincter defects. Correlation between endoanal ultrasound and surgery.

OBJECTIVE: This study was performed to (1) correlate and sphincter defects, identified by endoanal ultrasound with operative findings, and (2) define the appearance of such sphincter defects as seen at operation. SUMMARY BACKGROUND DATA: Endoanal ultrasonography is a minimally invasive method of imaging the anal sphincter complex and enables identification of anal sphincter defects. Little is known about the accuracy and limitations of endoanal ultrasound in identifying such defects. Furthermore, there are no data about the appearances of these endosonic sphincter defects as seen at operation. METHODS: Forty-four patients (40 women; age range, 26 to 80 years; mean age, 56 years) with fecal incontinence, undergoing pelvic floor repair, were investigated by endoanal ultrasound before operation. Endosonic findings were correlated with the appearances of external anal sphincter, internal anal sphincter, and intersphincteric space, at operation. Diagnosis of the site and type of defect was made by macroscopic appearances. Uncertainty about the type of sphincter defect was resolved by obtaining muscle biopsies for histology. RESULTS: All external sphincter defects seen by endoanal ultrasound (n = 23) were confirmed at operation. Twenty-one of 22 internal sphincter defects identified by endosonography also were confirmed at operation. In ten patients with a neuropathic anal sphincter complex, the morphology was normal on endosonography, and this was confirmed at operation. (Sensitivity and specificity of 100% for external anal sphincter; 100% and 95.5%, respectively, for internal and sphincter) CONCLUSIONS: These data show that endoanal ultrasound is an accurate method of identifying anal sphincter defects.

Adult↗

Measurement of colonic transit time using radionuclide imaging: analysis by condensed images.

A polymer-coated capsule has been used in eight volunteer subjects to deliver 111In-resin into the ileocaecal region. The images were acquired for up to 3 days to follow transit through the colon. Expressing the results of individual studies is difficult and time-activity curves for each region are confusing. Calculation of the geometric centre indicates only where the middle of the activity has reached. We describe a new method of presenting colonic transit data as parametric images. The parametric images show the amount of activity in each area of interest as the study progresses. This is readily understood and allows segmental movement of the isotope, either forward or retrograde, to be examined. The geometric mean of activity in four areas of the colon were also calculated. Four hours after reaching the ileocaecal region, 65% (S.D. 24%) of the activity was in the caecum and 26% (S.D. 20%) in the transverse colon. By 24 h three controls had excreted most of the activity, in two the activity was mainly in the rectum and in two there was still some activity in the transverse colon. A protocol for colonic transit studies, problems with analysis and a new method of presentation of data are discussed.

Acrylic Resins↗

The prevalence of anal sphincter defects in faecal incontinence: a prospective endosonic study.

Forty six patients (median age 61 years; 42 women) with faecal incontinence and 16 age and sex matched controls undergoing a restorative proctocolectomy were assessed by clinical examination, anorectal physiology, and anal endosonography. Forty patients (87%) with faecal incontinence had a sphincter defect demonstrated on anal endosonography (31 external and 21 internal anal sphincter defects). The commonest cause of faecal incontinence was obstetric trauma. This occurred in 35 women, 30 of whom exhibited a morphological defect in the anorectal sphincter complex. In 22 of these patients with a history of a perineal tear or episiotomy, 21 (95%) had a sphincter defect. Sphincter defects were commonly located at the level of the midanal canal.

Adult↗

Antral volume and propulsion-retropulsion in response to upper intestinal nutrients in a canine model.

We measured antral volumes and propulsion-retropulsion for individual peristaltic cycles using the dynamic spatial reconstructor in three female mongrel dogs. Our aim was to quantify the effect of intestinal perfusion of equicaloric, isotonic, and isomolar nutrients (maltose, 32.5 mg/100 ml; casein hydrolysate, 32.5 mg/100 ml; and oleic acid 15.5 mg/100 ml) at a rate of 10 ml/min in the upper small intestine on total antral volume and the propulsion-retropulsion function of the "antral pump." Isotonic saline was used as a control solution. Isotonic gastrografin (600 ml) was instilled intragastrically as a meal. A 6-channel perfused manometric assembly was used to record antral phasic pressure activity. Antral volume was significantly lower (P < 0.05) in response to fat perfusion compared with other nutrients or isotonic saline. The propulsion-retropulsion ratio was also significantly reduced (P < 0.05) in response to fat perfusion in the upper small intestine. Our study, therefore, indicates that the fraction of a liquid meal delivered to the antrum is determined, at least in part, by the upper small intestinal nutrients and also that the presence of fat in the small intestine alters the propulsion-retropulsion function of the antrum.

Animal Nutritional Physiological Phenomena↗

Selective inhibition of the cutaneous late but not immediate allergic response to antigens by misoprostol, a PGE analog. Results of a double-blind, placebo-controlled randomized study.

The objective of this study was to investigate the effect of misoprostol on allergen-induced cutaneous immediate- and late-phase allergic reactions in a double-blind placebo-controlled randomized study. We also studied the mechanism of antiallergic effects of misoprostol. A total of 16 dust mite-allergic patients received misoprostol (200 micrograms) or placebo and then had skin testing on 2 different days. The immediate- and late-phase skin response was monitored for 6 h. Skin biopsy was obtained from 5 selected donors at 5 h. In vitro studies included the effect of misoprostol on eosinophil chemotaxis, eosinophil survival, basophil histamine release, and cytokine production by lymphocytes. All subjects developed an immediate wheal reaction and a late-phase induration in response to dust mite allergens after taking placebo. Misoprostol selectively inhibited the late- but not the immediate-phase response (p < 0.05). Histologic studies revealed a trend toward a reduced number of inflammatory cells in the skin dermis after misoprostol treatment. Misoprostol significantly (p < 0.05) inhibited eosinophil chemotaxis and the production of granulocyte-macrophage colony-stimulating factor by lymphocytes at concentrations > or = 10(-8) M. However, at significantly lower concentrations (> or = 10(-12) M) misoprostol blocked cytokine-stimulated eosinophil survival. Thus, misoprostol has potent antiallergic effects and blocks the cutaneous late-phase allergic inflammation.

Adult↗

North-American twins with IDDM. Genetic, etiological, and clinical significance of disease concordance according to age, zygosity, and the interval after diagnosis in first twin.

In 224 twin pairs (132 monozygotic, 86 dizygotic, and 6 of uncertain zygosity) in whom the index twin had developed IDDM before 30 yr of age, 51 of the co-twins (38 monozygotic, 10 dizygotic, and 3 of uncertain zygosity) subsequently became diabetic. On the basis of concordance ratios, which were significantly discrepant (P < 0.01) between monozygotic and dizygotic twins, the substantial genetic role in IDDM etiology is confirmed. For the monozygotic co-twin of an IDDM case, the relative risk is significantly related to an early age at proband diagnosis (P < 0.01 for 0-4 vs. 5-9 yr of age). However, among monozygotic co-twins at any age, IDDM risk decreases as time passes after the proband diagnosis (P < 0.01 for 0-23 vs. > or = 24 mo after a proband diagnosis at 5-9 yr of age). Moreover, a structural-equation analysis suggests a profound contribution to liability (as much as 79%) from the twins' shared environment. Risk to like-sex male dizygotic co-twins is as high as that to monozygotic co-twins, significantly higher than that to like-sex female dizygotic co-twins (P < 0.005), and even higher than that to male co-twins in unlike-sex dizygotic pairs (P < 0.05). Overall, the risk to the dizygotic co-twin of a case is significantly higher (P < 0.001) than that to a non-twin sibling, as reported in the literature. The observed male excess is consistent with reported patterns of IDDM in experimental animals, and in certain circumstances in humans. Taken together, these observations suggest an important early acquired determinant of IDDM, independent of genetic determinants. On the basis of Kaplan-Meier IDDM-free survival curves, if the proband is diagnosed before 15 yr of age, the long-term risk to the co-twin is estimated at 44% (monozygotic) and 19% (dizygotic); it reaches 65% for the co-twin of a monozygotic proband diagnosed before 5 yr of age. An IDDM discordant period of no more than 3 yr was observed in 60% of the pairs destined to become concordant, offering a very brief window for intervention following the recognition of high risk.

Age Factors↗

Adrenal cortical adenoma and adrenal metastasis of renal cell carcinoma: immunohistochemical and DNA ploidy analysis.

Renal cell carcinoma can have solitary adrenal metastasis years or even decades after resection of the primary tumor. The difficulty in distinguishing an adrenocortical adenoma from a solitary metastasis of a renal cell carcinoma prompted us to study 10 adrenal adenomas, 11 primary renal cell carcinomas, and three renal cell carcinomas metastatic to the adrenal gland by immunohistochemical stains and flow cytometry to determine if these techniques could help make the distinction. Immunohistochemical staining was performed for detection of cytokeratin, vimentin, and epithelial membrane antigen (EMA). Cytokeratin, vimentin, and EMA were detected in 10/11, 9/11, and 11/11 primary renal cell carcinomas, respectively, and 1/3, 2/3, and 3/3 metastatic renal cell carcinomas, respectively. All cases of adrenal adenoma were negative for the three antigens. DNA content analysis by flow cytometry showed no evidence of an abnormal DNA stemline in any of the cases except one renal cell carcinoma. We conclude that staining for EMA is consistently strongly positive in primary and metastatic renal cell carcinomas and consistently negative in adrenal adenomas, proving to be a useful distinguishing marker. Cytokeratin and vimentin, although uniformly absent in adrenal adenomas, are variably and often only weakly positive in renal cell carcinomas, and therefore of less help in making the distinction. Flow cytometry analysis has no discriminatory value in these cases.

Adenoma↗