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Biomedical subjects

S Bhatnagar

Publications and source records attributed to S Bhatnagar.

At least 19 recordsLinked to original sources

Efficacy of massive dose oral gentamicin therapy in nonbloody persistent diarrhea with associated malnutrition.

Overgrowth of aerobic and anaerobic bacteria in the upper small intestine is a common finding in persistent diarrhea. We hypothesized that a large dose of broad spectrum, nonabsorbable oral antibiotic would hasten recovery from persistent diarrhea by eradicating aerobic bacterial overgrowth. Sixty-eight patients were randomly assigned to treatment with either oral gentamicin (n = 33) or placebo (n = 35) for a period of 6 days. The two groups were comparable in their clinical features, stool weights, duodenal and fecal microflora, during an initial 24 h observation period before randomization. The proportion of patients recovering within 6 days post-treatment was similar in the antibiotic (45.2%) and placebo (50%) groups. The stool weights in the two groups during 24-72, 72-120, and 120-168 h of the study did not differ significantly. The percent mean weight gain (g) at 168 h post-treatment in the antibiotic (1.0 +/- 5.1) and placebo (1.4 +/- 5.3) groups also did not differ significantly (p = 0.8). A similar proportion of antibiotic- (61.3%) and placebo- (60.7%) treated patients had started to gain weight by the last day of the study. We conclude that oral gentamicin was no more effective than placebo in reducing purge rates, in achieving earlier recovery from diarrhea, and in promoting the earlier onset of weight gain in this study.

Administration, Oral

Is small bowel bacterial overgrowth of pathogenic significance in persistent diarrhea?

Bacterial overgrowth in the upper small intestine is postulated to cause persistent diarrhea. We compared the fecal and upper intestinal flora in 82 patients with persistent diarrhea aged < or = 36 months and weight-for-length < or = 90% of National Center for Health Statistics standards (NCHS) and 39 non-diarrheal children with age < or = 36 months, nutritionally matched with the patients and residing in the same environment. In the age groups < or = 12 months and > 12 months the duodenal fluid bacterial counts > or = 10(5)/ml were found with similar frequency in patients and controls for aerobic (p = 0.33; p = 0.1) and anaerobic (p = 1.0; p = 1.0) bacteria. However, the duodenal isolation rates of any aerobic bacteria (p < 0.05) without regard to counts and Enterobacteriaceae (p = 0.06) were higher in patients than in controls. Colonization with Enterobacteriaceae was directly correlated with increased stool weight over a 7-day observation period (p < 0.05; p < 0.01). One or more pathogens were isolated in the feces of 58% of the patients and 43.8% of the controls. Enteroadherent E. coli of the localized [EAEC-L] (p < 0.01) and aggregative [EAggEC] (p = 0.22) phenotypes were isolated more commonly from the feces of patients. The duodenal fluid detection rates for Klebsiella were significantly greater (p < 0.01) in patients, while Giardia lamblia was detected more commonly in the duodenal fluid of controls (p < 0.01). The presence of specific pathogens in the feces did not seem to be related to the extent of small bowel colonization.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effect of five-membered heterocycles against Leishmania donovani infection.

Impact of change of heteroatom in pentavalent heterocycles, viz., pyrroles, isoxazoles, imidazoles and crotonates on the profile of antileishmanial activity against amastigotes of L. donovani using in vivo test system and macrophage-amastigote culture system has been studied. Sixty-three compounds were tested. Nine imidazoles showed marginal activity in vivo, whereas 3 out of 10 compounds of isoxazolone series and 2 out of 4 substituted aminocrotonates exhibited antileishmanial activity. Of the 30 substituted pyrroles, except 8 all showed antileishmanial activity in vivo on day 7 post treatment.

Animals

The effects of neonatal handling on the development of the adrenocortical response to stress: implications for neuropathology and cognitive deficits in later life.

Several years ago Levine, Denenberg, Weininger, Ader, and others described the effects of postnatal "handling" on the development of behavioral and endocrine responses to stress. The handling procedure usually involved removing rat pups from their cages, placing the animals together in small containers, and 15-20 min later, returning the animals to their cages and their mothers. The manipulation was performed daily for the first 21 days of life. As adults, handled (H) rats exhibited attenuated fearfulness (e.g., decreased freezing, increased exploration) in novel environments and a less pronounced increase in the secretion of adrenal glucocorticoids in response to a variety of stressors. These findings clearly demonstrated that the development of rudimentary, adaptive responses to stress could be modified by environmental events. We have followed on these earlier handling studies, convinced that this paradigm provides a marvelous opportunity to examine how subtle variations in the early environment alter the development of specific biochemical systems in the brain, leading to stable individual differences in biological responses to stimuli that threaten homeostasis. In this work we have shown how early handling influences the neurochemical development of certain brain regions that regulate the adrenocortical response to stress. Neonatal handling increases the efficiency of this endocrine response to stress, preventing excessive exposure to the highly catabolic adrenal steroids. In later life, this effect appears to protect the animal from potentially damaging effects of these steroids, ensuring the anatomical integrity of brain structures involved in cognitive functioning.

Adrenal Cortex

Cellular mechanisms underlying the development and expression of individual differences in the hypothalamic-pituitary-adrenal stress response.

Several years ago Levine, Denenberg, Ader, and others described the effects of postnatal "handling" on the development of behavioral and endocrine responses to stress. As adults, handled rats exhibited attenuated fearfulness in novel environments and a less pronounced increase in the secretion of the adrenal glucocorticoids in response to a variety of stressors. These findings clearly demonstrated that the development of rudimentary, adaptive responses to stress could be modified by environmental events. We have followed these earlier studies, convinced that this paradigm provides a marvellous opportunity to examine how subtle variations in the early environment alter the development of specific neurochemical systems, leading to stable individual differences in biological responses to stimuli that threaten homeostasis. In this work we have shown how early handling influences the development of certain brain regions that regulate glucocorticoid negative-feedback inhibition over hypothalamic-pituitary-adrenal (HPA) activity. Specifically, handling increases glucocorticoid (type II corticosteroid) receptor density in the hippocampus and frontal cortex, enhancing the sensitivity of these structures to the negative-feedback effects of elevated circulating glucocorticoids, and increasing the efficacy of neural inhibition over ACTH secretion. These effects are reflected in the differential secretory pattern of ACTH and corticosterone in handled and nonhandled animals under conditions of stress. In more recent years, using a hippocampal cell culture system, we have provided evidence for the importance of serotonin-induced changes in cAMP levels in mediating the effect of postnatal handling on hippocampal glucocorticoid receptor density. The results of these studies are consistent with the idea that environmental events in early life can permanently alter glucocorticoid receptor gene expression in the hippocampus, providing evidence for a neural mechanism for the development of individual differences in HPA function.

Animals

Evidence for recent diarrhoeal morbidity as a risk factor for persistent diarrhoea: a case-control study.

The association between persistent diarrhoea and 'recent morbidity' defined as that occurring within the two-month period immediately preceding the onset of persistent diarrhoea was investigated in a population-based case-control study in rural North India. In two separate matched case-control analyses children with persistent diarrhoea (cases) were compared to population controls (five controls matched to each case) and acute diarrhoeal controls (three controls matched to each case). After correcting for possible confounding variables, comparing children with persistent diarrhoea and matched population controls, presence of a recent diarrhoeal illness was significantly associated with persistent diarrhoea with an odds ratio (OR) 2.6 (95%) confidence interval (CI): 1.1-7.1; p less than 0.05); during infancy this OR was 5.2 (95% CI: 1.0-31.9; p less than 0.01). Comparing children with persistent diarrhoea to matched acute diarrhoeal controls, presence of recent diarrhoeal illness was associated with an OR of 5.1 (95% CI: 1.3-20.3) in favour of the episode becoming persistent; in infants this OR was 10.4 (95% CI: 1.1-132.4; p less than 0.001).

Acute Disease

Ultrastructural study on the antileishmanial effect of 1,2-dimethyl-3-methoxy carbonyl-4-(2-nitro-4,5-dimethoxyphenyl) pyrrole in hamsters.

An ultrastructure study was carried out on the effect of a standard drug sodium stibogluconate and a newly identified active CDRI compound 87/305 [1,2-dimethyl-3-methoxy carbonyl-4-(2-nitro-4,5-dimethoxyphenyl) pyrrole] on amastigotes of Leishmania donovani in macrophage cells of spleen of infected hamsters. While Na-stibogluconate exerted its effect by activating the digestion capacity of host macrophages, compound 87/305 was directly lethal to the parasites without, exerting any effect on the host cells.

Animals

Alanine-based oral rehydration solution: assessment of efficacy in acute noncholera diarrhea among children.

This randomized, double-blind trial determined whether adding 90 mmol/L of alanine with a reduction in glucose to 90 mmol/L (alanine ORS) improves the efficacy of the standard oral rehydration solution (WHO-ORS). One hundred twenty-nine males aged 3-48 months with weight for length greater than or equal to 70% of NCHS, diarrheal duration less than or equal to 96 h, and clinical signs of mild to moderate dehydration were randomly allocated to either treatment group. During 0-6 h of treatment, ORS was offered at 120 ml/kg for rehydration without food or water. Beyond 6 h, ORS was offered as a volume-to-volume replacement for stool losses and a mixed diet of uniform composition was offered in amounts standardized for body weight. The most frequently isolated pathogens in alanine ORS and WHO-ORS groups were rotavirus (42 and 48%, respectively) and enterotoxigenic Escherichia coli (15 and 12%, respectively). In the 0-6 h period when food was withheld, median urine output in ml/kg (8;5, p less than 0.05) and percentage decrease in total serum solids (9:7%, p = 0.06) was significantly greater in alanine ORS than in WHO-ORS; median ORS intake and stool output were marginally lower in the alanine group but the differences were statistically not significant. Between 0 h and recovery, although the median values for duration of diarrhea (56.5 and 65.0 h), ORS consumption (260 and 323 ml/kg), and stool output (188.4 and 216.3 g/kg) were lower in the alanine ORS group, these differences with the WHO-ORS group were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Detection of M. leprae-specific antigens with dot-ELISA in urine and nasal samples from leprosy patients.

One-hundred-two urine and nasal samples collected from leprosy patients of different classifications of disease were studied for the presence of Mycobacterium leprae antigens, including phenolic glycolipid-I (PGL-I). Lipids were extracted from the urine samples, and nasal washings were concentrated and used as such in the dot-ELISA. Two types of primary antibodies, a polyclonal antibody obtained from lepromatous (LL) leprosy patients' pooled and absorbed sera and an anti-PGL-I monoclonal antibody, were used for the detection of M. leprae antigens from these samples. The polyclonal sera detected 23% to 36% of the paucibacillary (PB) and 100% of the multibacillary (MB) leprosy cases from the urine samples. Corresponding values for nasal detection were 10% to 18% for PB and 100% for MB cases. The monoclonal antibody against PGL-I could not detect tuberculoid (TT) leprosy cases. From the urine samples, however, 16% of the borderline tuberculoid (BT), 25% of the borderline (BB), 80% of the borderline lepromatous (BL), and 100% of the LL leprosy cases were detectable. It was interesting to note that PB, skin-smear negative cases were detectable from urine examination. The specificity and sensitivity of the test is discussed in relation to the crossreacting antigens.

Adolescent

Acute rheumatic polyarthritis. The duration of secondary prophylaxis.

Antistreptococcal prophylaxis was discontinued in a group of 44 children who had acute rheumatic polyarthritis with no carditis or chorea during the initial attack and who had completed a mean period of 5 years of secondary prophylaxis and freedom from recurrences. Patients were then followed up for a mean period of 5 years (an observation period of 216 patient-years). Recurrence of disease occurred in 3 patients, with a recurrence rate of 1.4 per 100 patient-years. There was no evidence of carditis during these recurrences and all patients remained free of rheumatic heart disease 10 years after the initial attack. These data demonstrate the relative safety with which continuous antistreptococcal prophylaxis can be discontinued in a selected group of children with rheumatic fever.

Acute Disease

Immobilization of penicillin G acylase on methacrylate polymers.

Macroporous weak cation-exchange methacrylate polymers were synthesized for the immobilization of penicillin G (Pen G) acylase. The role of certain factors such as pore-generating solvent, cross-linking agent, cross-linking density, and comonomer, in enzyme adsorption and expression was studied. Kerosene was a superior pore-generating solvent to paraffin oil. Ethylene glycol dimethacrylate and acrylic acid served as the best cross-linking agent and comonomer, respectively, in the systems studied. 80.3% of the activity of the enzyme adsorbed onto polymer beads prepared with 0.05 mol of acrylic acid (polymer PM-39) was expressed. Properties of the Pen G acylase, immobilized on PM-39 by adsorption and cross-linking with glutaraldehyde (IME-PM-39) were studied. The optimum pH, optimum temperature and Km of Pen G acylase shifted from 8.0 to 7.5-7.8, 50 degrees C to 55 degrees C and 0.038 mol dm-3 to 2.4-3.0 mol dm-3, respectively, as a result of immobilization on PM-39. IME-PM-39 was used repeatedly for 15 cycles in the production of 6-amino penicillanic acid (6-APA).

Cation Exchange Resins

Glycine, glycyl-glycine and maltodextrin based oral rehydration solution. Assessment of efficacy and safety in comparison to standard ORS.

We evaluated the efficacy and safety of an oral rehydration solution containing glycyl-glycine, glycine, and maltodextrin (GGG-ORS), in comparison to the glucose based ORS (standard ORS). The osmolality of the GGG-ORS (305 mOsm/l) and standard ORS (311 mOsm/l) was similar. Ninety-two children presenting with acute gastroenteritis and moderate dehydration, aged 3 months to 3 years, were randomly assigned to receive standard ORS or GGG-ORS. All the patients were successfully rehydrated orally. The two groups were comparable for baseline characteristics including the microbial etiology. Rotavirus (49%, 36%), ETEC (11%, 18%) or a combination of rotavirus and ETEC (15%, 9%) were the main stool pathogens isolated. There was no significant difference in the mean stool output or duration of diarrhoea between the two groups. Patients in the GGG-ORS group had higher urine output (p less than 0.01) and weight gain (p less than 0.05) in the initial 6 hours when feeding was withheld, but no such differences were observed beyond this period. Hypernatremia did not develop in any patient during the study. We conclude that glycine and glycyl-glycine supplemented oral rehydration solution does not have any therapeutic advantage in the treatment of acute gastroenteritis with moderate dehydration caused predominantly by rotavirus.

Acute Disease

Timing of stress testing in an asymptomatic survivor of inferior myocardial infarction.

Exercise electrocardiography with or without thallium-201 scintigraphy was performed (pre-hospital discharge) in 66 asymptomatic survivors of a first inferior myocardial infarction (IMI). Although coronary angiography revealed an 82% incidence of multivessel coronary artery disease (MV-CAD) in the total cohort, the sensitivity of exercise ECG for MV-CAD in the group with absent anterior ST-depression in the acute phase was low (11%). In contrast the presence of acute phase anterior ST-segment depression improved the yield for MV-CAD to 55%. Forty-six patients agreed to a symptom-limited exercise ECG plus/minus thallium imaging at 8-10 weeks post IMI. The sensitivity of detecting MV-CAD improved by 15% in patients with no acute phase anterior ST-segment depression and 16% in patients with acute phase anterior ST-segment depression. At each exercise protocol, thallium improved the sensitivity of exercise in detecting ischemia in the noninfarct zone. It is concluded that following IMI, a high percentage of asymptomatic patients whose acute phase ECG showed anterior ST-segment depression will have MV-CAD detected by heart-rate limited and, more so, by symptom-limited exercise ECG. The detection rate will double in patients with no anterior ST-segment depression if exercise testing is delayed until 8-10 weeks post IMI.

Coronary Angiography

Association of antecedent malnutrition with persistent diarrhoea: a case-control study.

To determine the effect of nutritional state on persistent diarrhoea a case-control study was carried out on 756 children followed up prospectively for 18 months. Children who developed persistent diarrhoea were compared with population controls and controls with acute diarrhoea. The mean weight for age in the children with persistent diarrhoea (69.9%) was significantly lower than that in the population controls (77.0%) and the diarrhoeal controls (76.2%). Weight for age of less than or equal to 70% was associated with persistent diarrhoea in both case-control analyses (population controls, matched odds ratio 3.25; diarrhoeal controls, matched odds ratio 2.46). The corrected odds (multiple logistic regression) in the two analyses were 3.2 (95% confidence interval 1.3 to 8.1) and 3.4 (1.2 to 9.1). Weight for age of less than or equal to 70% increases the risk of persistent diarrhoea. In an underweight child there is a higher risk of diarrhoea becoming persistent. Prevention of malnutrition and intensive management of acute diarrhoea in malnourished children should help reduce the risk of the diarrhoea persisting.

Age Factors

Glucocorticoid receptors in brain and pituitary of the lactating rat.

The female rat exhibits elevated corticosterone levels throughout lactation, suggesting a possible dampening of the sensitivity of adrenocortical negative-feedback processes during this period. Negative-feedback within the adrenocortical axis is, in large part, mediated by an enhanced hormone receptor signal at a number of glucocorticoid target sites, including the pituitary, hypothalamus, and hippocampus. In the study reported here we have measured glucocorticoid receptor binding capacity in soluble fractions prepared from these tissues, using an in vitro binding assay with [3H]dexamethasone as radioligand. We found that during at least the first two weeks of lactation the rat shows significantly decreased [3H]dexamethasone binding capacity in the hippocampus, with no change in pituitary or the hypothalamus during lactation. These data provide one possible mechanism whereby a critical target region for adrenocortical negative-feedback might be desensitized to circulating glucocorticoids, thus permitting the sustained elevation in pituitary-adrenal activity.

Adrenal Cortex

Serum anti-gliadin antibody profile in childhood protracted diarrhoea due to coeliac disease and other causes in a developing country.

Serum anti-gliadin antibody (AGA) titres were estimated by diffusion in a gel enzyme-linked immunosorbent assay in children with coeliac disease (n = 11), protracted diarrhoea of non-coeliac causes (n = 110), acute gastroenteritis (n = 20), protein energy malnutrition (n = 20), and asymptomatic, well-nourished children (n = 66). The mean IgG and IgA AGA titres were significantly higher (p less than 0.001) in children with coeliac disease than in any other groups. There was no significant difference (p greater than 0.01) in AGA titres in relation to age, nutritional status, or severity of villous injury. In patients with coeliac disease AGA titres showed a good correlation with disease activity. The specificity and sensitivity of the assay are discussed.

Antibodies, Anti-Idiotypic

Exploration of antileishmanial activity in heterocycles; results of their in vivo & in vitro bioevaluations.

A total of 51 imidazoles, pyrroles, quinolines and isoxazolines compounds were screened for antileishmanial activity in vivo and in vitro, using Leishmania donovani as the test parasite. The screening revealed hitherto unknown antileishmanial activity in these heterocycles. Three of the compounds screened (one belonging to isoxazoline series and two from pyrrole series) showed significant anti-leishmanial activity, ranging from 86-91 per cent inhibition in hamsters. When tested in vitro, using macrophage amastigote culture system, these compounds showed inhibition of 62-78 per cent at 30 micrograms/ml concentration.

Animals