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Biomedical subjects

R Bahl

Publications and source records attributed to R Bahl.

At least 19 recordsLinked to original sources

Effect of vitamin A administered at Expanded Program on Immunization contacts on antibody response to oral polio vaccine.

OBJECTIVE: Vitamin A supplementation to mothers in the postpartum period and to their infants at routine immunization contacts is being considered to reduce vitamin A deficiency in infancy. This study was conducted to determine the impact of maternal and infant vitamin A supplementation on antibody response to oral polio vaccine (OPV). DESIGN: Randomized, double blind, placebo-controlled trial. INTERVENTIONS: Mothers in the intervention group received 60 mg retinol equivalent (RE) vitamin A 3-4 weeks after delivery and their infants 7.5 mg RE with each OPV dose at 6, 10 and 14 weeks of age. The control group mothers and their infants received a placebo at each of these contacts. MAIN OUTCOMES: Geometric mean (GM) titer of neutralizing antibodies and proportion of children with protective titer to the three polioviruses at 26 weeks of age. RESULTS: Vitamin A supplementation increased the proportion of infants with protective antibody titer against poliovirus type 1 (relative risk (RR) 1.15, 95% confidence interval (CI) 1.03-1.28) and the GM antibody titer (ratio of GM 1.55, 95% CI 1.03-2.31) following immunization. The proportion of infants with protective antibody titer against poliovirus type 2 (RR 0.99, 95% CI 0.94-1.05) or type 3 (RR 1.05, 95% CI 0.96-1.15) was not significantly different in vitamin A and placebo groups. The GM antibody titer for poliovirus type 2 (ratio of GM 0.99, 95% CI 0.64-1.54) or poliovirus type 3 (ratio of GM 1.10, 95% CI 0.69-1.75) also did not differ across groups. CONCLUSIONS: Vitamin A given to the mothers in the postpartum period and their infants with OPV did not interfere with the antibody response to any of the three polioviruses and enhanced the response to poliovirus type 1.

Adult↗

Localization of protein Ser/Thr phosphatase 5 in rat brain.

Protein phosphatase 5 is a recently discovered Ser/Thr phosphatase that is structurally related to calcineurin and protein phosphatases 1 and 2. Northern blot and in situ hybridization studies have shown that protein phosphatase 5 mRNA is present at high levels in brain and is localized to discrete regions. In the present study, we used immunocytochemistry and immunoblot analyses to examine the regional and subcellular distribution of this enzyme in brain. Our work demonstrates that protein phosphatase 5 is widely expressed throughout brain, but is not uniformly distributed. The most intense staining occurred in neurons of the cerebellum, cerebral cortex, and the supraoptic nucleus of the hypothalamus. Other areas also contained immunoreactive cell bodies, including the globus pallidus, hippocampus, thalamus, lateral preoptic area of the hypothalamus, substantia nigra and other brainstem nuclei. Staining in these cells was observed primarily in perikarya and proximal processes.

Animals↗

Food supplementation with encouragement to feed it to infants from 4 to 12 months of age has a small impact on weight gain.

It is unclear whether a substantial decline in malnutrition among infants in developing countries can be achieved by increasing food availability and nutrition counseling without concurrent morbidity-reducing interventions. The study was designed to determine whether provision of generous amounts of a micronutrient-fortified food supplement supported by counseling or nutritional counseling alone would significantly improve physical growth between 4 and 12 mo of age. In a controlled trial, 418 infants 4 mo of age were individually randomized to one of the four groups and followed until 12 mo of age. The first group received a milk-based cereal and nutritional counseling; the second group monthly nutritional counseling alone. To control for the effect of twice-weekly home visits for morbidity ascertainment, similar visits were made in one of the control groups (visitation group); the fourth group received no intervention. The median energy intake from nonbreast milk sources was higher in the food supplementation group than in the visitation group by 1212 kJ at 26 wk (P < 0.001), 1739 kJ at 38 wk (P < 0.001) and 2257 kJ at 52 wk (P < 0.001). The food supplementation infants gained 250 g (95% confidence interval: 20--480 g) more weight than did the visitation group. The difference in the mean increment in length during the study was 0.4 cm (95% confidence interval: -0.1--0.9 cm). The nutritional counseling group had higher energy intakes ranging from 280 to 752 kJ at different ages (P < 0.05 at all ages) but no significant benefit on weight and length increments. Methods to enhance the impact of these interventions need to be identified.

Body Height↗

Oxidative stress status: possible guideline for clinical management of critically ill patients.

BACKGROUND: Critical care medicine has developed in the last few years into a separate scientific discipline and studies related to the outcome after intensive care usually suggest a long hospital stay that becomes cost prohibitive. The majority of problems (death) amongst critically ill patients requiring critical care involve sepsis, inflammation, tissue damage-oxidative stress, oxygen tension PO2, lipid peroxidation. The present investigation involves monitoring of serum levels of MDA, SOD as a possible guideline for severity of clinical situations in critically ill patients. METHODS: Fifty critically ill heterogeneous patients requiring intensive care in the ICU of IKDRC were selected as subjects with ages varying from 17 to 75 years. Serum levels of MDA (ng/ml), SOD (U/ml) were determined right from admission to discharge due to improvement / DAMA / death. MDA and SOD were estimated according to the methods of Buege and Aust et al. (1978), Nandi and Chatterji (1988). RESULTS: Critically ill patients irrespective of the disease process indicated significantly very high serum levels of MDA and low levels of SOD at the time of admission (13.28+/-4.26 ng/ml, 3.80+/-2.60 U/ml, respectively) according to the severity of the prevalent clinical situation. The pattern of serum levels of MDA and SOD according to subsequent clinical performance did indicate a decreasing trend of MDA (oxidant) and fluctuating trend of SOD (antioxidant enzyme except in those who inevitably succumbed to death in spite of adequate clinical management. CONCLUSIONS: The results of the present study have amply revealed the utility and relevance of monitoring oxidative stress in critically ill patients as biochemical markers, cost-effectiveness and role in decision making (withdrawal/continuation of different support modalities) as deemed fit.

Adolescent↗

Effect of micronutrient supplementation on linear growth of children.

This review summarizes the results of published, randomized clinical trials that have examined the impact of administration of micronutrients, singly or in combination to infants, preschool and school children on linear growth. Supplementation of single micronutrients resulted in small or no benefits on linear growth. A meta-analysis of zinc supplementation trials confirmed that zinc has a significant but small impact (0.22 sd units) on length gain in children 0-13 years of age. However, a recent study reported a substantially greater benefit (>1 sd) in stunted and non-stunted breast-fed infants 6-12 months of age. With iron supplementation, a beneficial effect was found only in anemic children. Vitamin A supplementation trials have reported little or no benefit on linear growth. Data currently available suggest some impact in children with clinical or biochemical vitamin A deficiency, but this issue needs confirmation. Few studies could be identified where a combination of micronutrients was given as a supplement or as fortified food; in the latter set of studies energy availability was assured. The impact on length without multiple micronutrient supplementation was no greater than that observed with single micronutrients. In conclusion, zinc and iron seem to have a modest effect on linear growth in deficient populations. Vitamin A is unlikely to have an important effect on linear growth. Limited available evidence does not allow us to conclude whether a combination of micronutrients, with or without additional food, would have a greater impact than that seen with zinc alone.

Child↗

Novel polymorphism in p21(waf1/cip1) cyclin dependent kinase inhibitor gene: association with human esophageal cancer.

p21(waf1/cip1), an important regulator of the cell cycle, binds to PCNA and acts as a mediator of the growth suppressing and apoptosis promoting functions of p53. We report a hitherto unobserved polymorphism in the carboxy terminal domain (codon 149) of p21(waf1/cip1) gene, the domain encoding the PCNA binding motif. The codon 149 polymorphism (GAT-->GGT) was observed in 42 of 50 (84%) esophageal squamous cell carcinomas (ESCCs) and eight of 50 (16%) normal individuals. The resultant amino acid substitution from aspartate to glycine may have vital implication in PCNA mediated cell cycle regulation by p21(waf1/cip1). The second polymorphism at codon 31, involving a C-->A transversion at nucleotide 168 (AGC-->AGA) changing the amino acid from serine to arginine, was observed in 2/50 (4%) ESCCs at a relatively lower frequency in the Indian population than that reported in the West. No significant association was observed between p21(wap1/cip1) polymorphism at codon 149 and p21(wap1/cip1) protein expression in ESCC in this cohort of patients. Interestingly, the frequency of p21(wap1/cip1) variants (codon 149) in ESCCs (18 of 19 cases) with wild-type p53 was significantly higher than in tumors with p53 mutations, suggesting that this polymorphism affects the p53 pathway and may play an important role in esophageal tumorigenesis. Analysis of p21(waf1/cip1) expression in relation to p53 gene and protein status revealed its induction by p53-dependent as well as independent pathways in esophageal tumorigenesis.

Carcinoma, Squamous Cell↗

Prognostic factors for persistent diarrhoea managed in a community setting.

Two hundred and five cases (mean age 13.4, SD 9.5) of persistent diarrhoea (PD) of 14-28 days duration, attending an urban slum clinic and treated according to standard WHO guidelines, were monitored at weekly intervals to obtain an estimate of treatment failure rates and to identify its clinical predictors. Vitamin and micronutrients (daily 2RDA) were additionally provided. Only 9 (8.2%) of 109 children with criteria for hospital care accepted in-patient care. Weight gain was considered inadequate if the daily increment between enrollment and day 7 of follow up was < 10 g at age 0-3 months, < 5 g at 4-6 months, and any weight loss for those older than 6 months. Recovery was considered delayed if diarrhoea ceased 7 days after enrollment. Overall, 28.3% cases had inadequate weight gain and 25.6% had delayed recovery. The non-breast milk calorie intake was 11.2% during infancy and 40.6% at later ages of the recommended intakes. In a logistic regression model, initial watery stool frequency greater than median (adjusted OR 2.30, p = 0.01), age < or = 6 months (adjusted OR 2.24, p = 0.04) and low consumption of micronutrient mixture (adjusted OR 2.62, p = 0.01) were associated with an increased risk of delayed recovery. In a Cox proportional hazards model for time to recovery from diarrhoea, low consumption of the micronutrient mixture and age < or = 6 months reduced the chances of recovery by 29% and 37% respectively. Low consumption of the prescribed micronutrient mixture (adjusted OR 2.21, p = 0.04), fever (adjusted OR 1.91, p = 0.05) and diarrhoea continuing beyond study day 7 (adjusted OR 2.29, p = 0.03) increased the risk of inadequate weight gain. Breast feeding status and animal milk consumption did not influence weight gain or recovery. Due to the low compliance for advised hospitalisation, approaches for care at community level itself need to be evolved. Focus should be on increasing the overall dietary intake and provision of generous but safe amount of micronutrients; our findings do not support need for routine elimination of animal milk. The efficacy of individual micronutrients needs evaluation in controlled trials.

Community Health Services↗

Frequent alterations in the expression of tumor suppressor genes p16INK4A and pRb in esophageal squamous cell carcinoma in the Indian population.

PURPOSE: Alterations in the cell cycle regulatory p16INK4a/Cyclin D1/pRb pathway play a pivotal role in tumorigenesis. Knowledge of alterations in the tumor suppressor protein pRb and its negative regulator, p16CDKN2/MTS1/INK4a in esophageal squamous cell carcinoma (ESCC) from the Indian subcontinent is meager. To gain insight into the mechanisms underlying tumorigenesis and to search for diagnostic molecular markers for ESCC, we analyzed the expression of p16INK4a and pRb in ESCCs in the Indian population. METHODS: Immunohistochemical analysis of pRb and p16INK4a proteins was carried out in paraffin-embedded sections from 61 surgically resected ESCCs and matched normal tissues, and the results correlated with clinicopathological parameters using chi square and Fisher's exact tests. Dual immunohistochemical analysis has been carried out to demonstrate the concomitant loss of expression of p16INK4a and pRb. RESULTS: Fifty-nine of 61 (97%) cases showed aberration(s) in either or both of these proteins confirming their critical role in esophageal tumorigenesis. Loss of pRb was observed in 51 of the 61 (84%) and loss of p16INK4a was observed in 35 of 61 (57%) cases. Loss of pRb showed significant association with dedifferentiation of the tumor (P = 0.004). p16-/pRb-, and p16+/pRb- phenotypes were significantly associated with nodal metastasis (P = 0.017 and 0.027, respectively), while p16-/pRb+ phenotype was associated with dedifferentiation of the tumor (P = 0.012). CONCLUSION: pRb/p16INK4a pathway plays a critical role in esophageal tumorigenesis in the Indian population. The dual hits (concomitant loss) of pRb and p16INK4a expression suggest that these two components are not mutually exclusive, and can both be altered in a significant proportion of primary ESCCs serving as putative diagnostic markers for esophageal cancer. However, the impact of dual hit on tumor behavior and disease prognosis remains to be determined.

Adult↗

Vitamin A administered with measles vaccine to nine-month-old infants does not reduce vaccine immunogenicity.

After a report of reduced seroconversion to measles in infants, aged 6 mo, given vitamin A with their measles vaccination, serious concerns were raised regarding the safety of the WHO's recommendation that infants be supplemented with vitamin A at the time of measles immunization. To determine the impact of coadministered vitamin A on the antibody response to measles vaccine given to infants aged 9 mo, the more common age for immunization in developing countries, we conducted a randomized, double-blind, placebo-controlled trial in an urban slum community in Delhi. Infants (618) were randomly allocated to receive 30 mg vitamin A or a placebo with the measles immunization. Antibodies to measles were measured by ELISA in serum samples obtained at before (baseline) and 12 wk after immunization. Overall, the seroconversion rates did not differ between vitamin A (89.5%) and placebo (87.6%) groups. There were no significant differences in the geometric mean titers in the two groups (ratio of geometric means, 1.19; 95% confidence interval, 0.97-1.46). Among malnourished infants, the geometric mean titer was significantly greater in the vitamin A group compared to the placebo group (ratio of geometric means, 1.57; 95% confidence interval, 1. 18-2.0), but seroconversion rates did not differ. There were no differences in seroconversion rates and geometric mean titers in the two study groups among the well-nourished children. These results indicate that 30 mg vitamin A does not reduce the immune response to the coadministered vaccine and, therefore, can be continued to be given safely in public health programs.

Antibody Formation↗

Plasma zinc as a predictor of diarrheal and respiratory morbidity in children in an urban slum setting.

The association between low initial plasma zinc concentration and risk of morbidity over the subsequent 3 mo was examined in a cohort of 116 children aged 12-59 mo recovering from acute diarrhea. Children with low initial plasma zinc (< or = 8.4 micromol/L) had more episodes of diarrhea [risk ratio (RR): 1.47; 95% CI: 1.03, 2.49) and severe diarrhea, defined as passage of > or = 5 liquid stools in a 24-h period, (RR: 1.70; 95% CI: 1.06, 2.72) than did children with normal plasma zinc (> 8.4 micromol/L). The mean prevalence rate of diarrhea associated with fever was 4 times higher in the zinc-deficient group (P = 0.01). Overall, the difference in the number of episodes of acute lower respiratory tract infections (ALRIs) between the two groups was not statistically significant (RR: 1.76; 95% CI: 0.88-3.53) but the mean prevalence rate of ALRIs was 3.5 times higher in children with low plasma zinc (P = 0.05). The increased risk of diarrhea and ALRIs episodes in zinc-deficient children was larger in boys than in girls. These results show that children with low plasma zinc concentrations are at risk for increased diarrheal and respiratory morbidity.

Acute Disease↗

The impact of vitamin A supplementation on physical growth of children is dependent on season.

OBJECTIVE: To determine the impact of vitamin A supplementation on physical growth in young children. DESIGN: Randomized, double blind, placebo controlled trial. SETTING: Urban slum community clinic. SUBJECTS: 900 children, aged 12-59 months, attending the community clinic with diarrhea of < or = 7 d were included in the trial. INTERVENTION: Each child was given a single dose capsule containing 200,000 IU vitamin A or placebo at enrollment. MAIN OUTCOME MEASURES: Mean increments in weight and height during the 90 d period post supplementation. RESULTS: In all children, the mean increments in weight following supplementation were 0.66 kg (s.d. 0.5) and 0.64 kg (s.d. 0.6) in the vitamin A and placebo groups (P = 0.5). The mean increments in height were also similar in the two treatment groups (P = 0.5). Serum vitamin A was measured in 40 randomly selected children in each group; the proportion of subclinical deficiency (serum retinol < 20 micrograms/dl) was 62.5% in those enrolled during summer (April through July) as compared to 21.1% in those enrolled during the remaining cooler months of the year (P = 0.02). In the children supplemented with vitamin A during summer, the mean increment in weight was 140 g more than those who received placebo (95% confidence interval CI 30-250); there was also a significant reduction in the proportion of children who were wasted (< -2 weight-for-height Z-score) at end study (Odds Ratio 0.53, 95% CI 0.28-1.0, P = 0.03). There was no significant impact of vitamin A on height increments in children supplemented during summer. CONCLUSION: Vitamin A supplementation in 12-59 month old children improves weight gain in the subsequent three months only in the summer season, but not during the rest of the year.

Body Height↗

Breast-feeding status alters the effect of vitamin A treatment during acute diarrhea in children.

Vitamin A administration in children reduces the incidence of severe diarrhea during the subsequent few months. We therefore examined the effect of treatment with vitamin A during acute diarrhea on the episode duration and severity. In a double-blind controlled field trial, 900 children 1 to 5 y of age with acute diarrhea of < or = 7 d duration were randomly assigned to receive vitamin A (60 mg) or a placebo. Children were followed up at home every alternate day until they recovered from the diarrheal episode. In all study children, those treated with vitamin A had a significantly lower risk of persistent diarrhea [odds ratio (OR) 0.30, 95% confidence interval (CI) 0.07-0.97], but there was no effect on the mean diarrheal duration or the mean stool frequency, in the subgroup of children who were not breast-fed, the mean diarrheal duration [ratio of geometric means (GM) 0.84, 95% CI 0.72-0.97], mean number of stools passed after the intervention (ratio of GM 0.73, 95% CI 0.56-0.95), the proportion of episodes lasting > or = 14 d (P = 0.002) and the percentage of children who passed watery stools on any study day (OR 0.40, 95% CI 0.21-0.77) were significantly lower in those treated with vitamin A. We conclude that administration of vitamin A during acute diarrhea may reduce the severity of the episode and the risk of persistent diarrhea in non-breast-fed children. Similar benefit was not seen in breast-fed children.

Acute Disease↗

Efficacy of antimicrobial treatment in non-dysenteric persistent diarrhoea in a community setting.

OBJECTIVES: To determine the efficacy of antimicrobial treatment in non-dysenteric persistent diarrhoea in a community setting. METHODS: In this double-blind field trial, 156 children aged 4-36 months with persistent diarrhoea not associated with Giardia lamblia infestation seeking treatment in a community outpatient clinic, were randomized to receive a combination of nalidixic acid and metronidazole, metronidazole alone, or placebo for 7 days. RESULTS: In comparison with placebo, metronidazole treatment did not result in a significant reduction in the mean post-enrollment diarrhoeal duration and stool frequency, increase in the proportion of patients recovered by days 3, 5 and 7 of treatment, and increase in weight gain at days 7 and 14. Comparing the combination of nalidixic acid and metronidazole with metronidazole alone, 17.5% more children treated with the combination recovered by day 3 of treatment (p = 0.08) and the mean stool frequency ascertained on day 7 for the previous 24 h was 26.8% less in them (p = 0.05). The weight gains at days 7 and 14 were similar in the two groups. CONCLUSIONS: These findings indicate that metronidazole offers no therapeutic benefit in persistent diarrhoea not associated with Giardia lamblia and nalidixic acid has only a modest clinical benefit, which is not substantial enough to warrant its routine use.

Anti-Infective Agents↗

Increased diarrhoeal and respiratory morbidity in association with zinc deficiency--a preliminary report.

Plasma zinc levels, in a cohort of 116 children aged 12-59 months recently recovered from an episode of acute diarrhoea attending a community health clinic in an urban slum, were related to diarrhoeal and respiratory morbidity in the 3 month period following recovery. Children with low plasma zinc levels (< 60 micrograms dl-1) spent a significantly greater number of days with watery diarrhoea (rate ratio 1.69 (95% confidence intervals 1.03-2.78)), diarrhoea associated with fever (rate ratio 1.88 (95% confidence intervals 1.05-3.34)), and acute lower respiratory tract infections (rate ratio 2.69 (95% confidence intervals 1.64-4.38)).

Child, Preschool↗

Epidemiology & management of persistent diarrhoea in children of developing countries.

Diarrhoea that begins acutely but lasts longer than two weeks is defined to be persistent. Revised estimates in developing countries including India showed that acute diarrhoea accounts for 35 per cent, dysentery 20 per cent and non-dysenteric persistent diarrhoea (PD) for 45 per cent of total diarrhoeal deaths. PD also often changes marginal malnutrition to more severe forms. Factors that increase the risk of acute diarrhoea becoming persistent have been identified in India and other developing countries. These include antecedent malnutrition, micronutrient deficiency particularly for zinc and vitamin A, transient impairment in cell mediated immunity, infection with entero aggregative Escherichia coli and cryptosporidium, sequential infection with different pathogens and lack of exclusive breast feeding during the initial four months of life particularly use of bovine milk. Several issues regarding the management of persistent diarrhoea in hospitalized children in India have been resolved. Diets providing modest amounts of milk mixed with cereals are well tolerated. In those who fail on such diets providing carbohydrate as a mixture of cereals and glucose or sucrose hasten recovery. The role of antimicrobial agents and individual micronutrients in PD is currently being investigated. A management algorithm appropriate for India and other developing countries has been developed and found to substantially reduce case fatality in hospital settings to about 2-3 per cent. Recent epidemiological and clinical research related to persistent diarrhoea is also reviewed.

Animals↗