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Biomedical subjects

S Sazawal

Publications and source records attributed to S Sazawal.

At least 37 records · Page 2Linked to original sources

Detection of BCR-ABL transcripts in acute lymphoblastic leukemia in Indian patients.

Thirty-three patients with acute lymphoblastic leukemia (ALL) from India were studied for the presence of BCR-ABL chimeric transcripts, by a seminested cDNA-PCR. We report the presence of BCR-ABL chimeric transcripts in 4/17 (24%) children (under 15 years) and 3/16 (19%) adults (15-50 years). This is in sharp contrast to the published literature from the West where the presence of BCR-ABL has been reported in only 2-5% children and 35% adults. Whether the presence of BCR-ABL fusion mRNA, which is generally an attribute of ALL in adults and of poorer prognosis, may contribute to chemo-incurability in young Indian patients, remains to be seen, as a larger number of patients are studied for treatment outcome and survival on uniform therapy protocols.

Adolescent↗

Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial.

BACKGROUND: Increased acute lower respiratory infection incidence, severity, and mortality are associated with malnutrition, and reduced immunological competence may be a mechanism for this association. Because zinc deficiency results in impaired immunocompetence and zinc supplementation improves immune status, we hypothesized that zinc deficiency is associated with increased incidence and severity of acute lower respiratory infection. METHODS: We evaluated the effect of daily supplementation with 10 mg of elemental zinc on the incidence and prevalence of acute lower respiratory infection in a double-blind, randomized, controlled trial in 609 children (zinc, n = 298; control, n = 311) 6 to 35 months of age. Supplementation and morbidity surveillance were done for 6 months. RESULTS: After 120 days of supplementation, the percentage of children with plasma zinc concentrations <60 microg/dL decreased from 35.6% to 11.6% in the zinc group, whereas in the control group it increased from 36.8% to 43.6%. Zinc-supplemented children had 0.19 acute lower respiratory infection episodes/child/year compared with 0.35 episodes/child/year in the control children. After correction for correlation of data using generalized estimating equation regression methods, there was a reduction of 45% (95% confidence interval, 10% to 67%) in the incidence of acute lower respiratory infections in zinc-supplemented children. CONCLUSIONS: A dietary zinc supplement resulted in a significant reduction in respiratory morbidity in preschool children. These findings suggest that interventions to improve zinc intake will improve the health and survival of children in developing countries.

Child, Preschool↗

Efficacy of zinc supplementation in reducing the incidence and prevalence of acute diarrhea--a community-based, double-blind, controlled trial.

A community-based, double-blind, randomized trial was conducted in a population of low socioeconomic status in urban India to determine whether daily zinc supplementation reduces the incidence and prevalence of acute diarrhea, especially in those with zinc deficiency. Children 6-35 mo of age were randomly assigned to zinc (n = 286) and control (n = 293) groups and received a supplement daily for 6 mo. Zinc gluconate (10 mg elemental Zn) was given, with both zinc and control groups also receiving multivitamins. The primary outcome measures determined by home visits every fifth day and physician examinations were the number of acute diarrheal episodes (incidence) and total diarrheal days (prevalence). Zinc supplementation had no effect in children 6-11 mo old. In children aged > 11 mo there was significantly less diarrhea in the zinc group. In boys > 11 mo old, supplementation resulted in a 26% (95% CI: 13%, 38%) lower diarrheal incidence and a 35% (95% CI: 20%, 50%) lower prevalence. In zinc-supplemented girls > 11 mo of age, the incidence was 17% (95% CI: 2%, 30%) lower and the prevalence was 19% (95% CI: 4%, 47%) lower. Overall, zinc supplementation resulted in a 17% (95% CI: 1%, 30%) lower diarrheal incidence in children with plasma zinc concentrations < 9.18 mumol/L at enrollment and a 33% (95% CI: 6%, 52%) lower incidence in children with concentrations < 50 mumol/L. In conclusion, zinc supplementation had a significant effect on acute diarrheal morbidity in children > 11 mo old and in children with low plasma zinc concentrations.

Acute Disease↗

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↗

Effect of zinc supplementation on cell-mediated immunity and lymphocyte subsets in preschool children.

OBJECTIVE: In a zinc supplementation trial (with a significant impact on diarrheal morbidity), to evaluate effect of zinc supplementation on cellular immune status before and after 120 days of supplementation. DESIGN: A double blind, randomized controlled trial with immune assessment at baseline and after 120 days on supplement. SETTING: Community based study in an urban slum population. SUBJECTS: Randomly selected children (zinc 38, control 48), had a Multitest CMI skin test at both times. In 66 children (zinc 22, control 34), proportions of CD3, CD4, CD8, CD16, CD20 cells and the CD/CD8 ratio were also estimated using a whole blood lysis method and flowcytometry. INTERVENTION: Zinc gluconate to provide elemental zinc 10 mg daily and 20 mg during diarrhea. MAIN OUTCOME RESULTS: Regarding CMI, the percentage of anergic or hypoergic children (using induration score) decreased from 67% to 47% in the zinc group, while in the control group it remained unchanged (73% vs 71%) (p = 0.05). The percentage of children deteriorating between first and second tests was significantly lower in the zinc group (13% vs 33%, p = 0.03). Regarding lymphocyte subsets, the zinc group had a significantly higher rise in the geometric means of CD3 (25%, p = 0.02), CD4 (64% p = 0.001), and CD4/CD8 ratio (73% p = 0.004) with no difference in CD8 and CD20. The rise in CD4 was significantly higher in the zinc as compared to the control group; the ratio of geometric means was 1.45 (95% CI, 1.03-2.01). CONCLUSION: Zinc supplementation improves cellular immune status, which may have been one of the mechanisms for observed impact of zinc supplementation on diarrheal morbidity.

Child, Preschool↗

Zinc supplementation reduces the incidence of persistent diarrhea and dysentery among low socioeconomic children in India.

Persistent diarrhea (PD) and dysentery (DD) account for most diarrhea-associated deaths among children in developing countries. Zinc deficiency can cause stunting and impaired immune function, both of which are risk factors for these diarrheal illnesses. We investigated the effect of zinc supplementation on the incidence of PD and DD in a community-based, double-blind randomized trial in children 6-35 mo of age. Increase over baseline in plasma zinc concentrations in the supplemented group compared with a control group (3.61 vs. 0.009 mumol.L-1), indicated successful supplementation. The overall reductions in the zinc supplemented group of 21% in the incidence of PD (95% CI -6 to 42%) and 14% in the incidence of dysentery (95% CI -15 to 36%) were not significant. There was a significant interaction of treatment effect with baseline plasma zinc concentration and age for PD and with gender for DD. In the zinc-supplemented group compared with the control group, the incidence of PD was reduced by 73% (P < 0.05; 95% CI 34 to 91%) in children with a baseline zinc < 7.65 mumol.L-1 and by 49% (P < 0.05; 95%CI 24 to 66%) in children > 11 mo of age. Zinc supplementation resulted in a 38% (P < 0.05 95%CI 8 to 59%) reduction in the incidence of DD in boys. There was no effect on PD among children 6-11 mo old or on DD in girls. In conclusion, zinc supplementation had a significant impact on the incidence of persistent diarrhea in children > 1 y old and in children with low plasma zinc, as well as on dysentery in boys. These findings may have important implications for reducing diarrhea-related morbidity and mortality.

Child, Preschool↗

Effect of zinc supplementation on observed activity in low socioeconomic Indian preschool children.

OBJECTIVES: To investigate whether supplementation of zinc in preschool children is associated with improvement in observed activity levels. METHODS: On 2 consecutive days, we performed 5-hour observations with momentary time sampling (instant activity every 10 minutes) in children selected from an ongoing double-blind, randomized trial of zinc supplementation. The study was conducted in Kalkaji, a low-socioeconomic urban population of New Delhi with high diarrheal incidence and rates of malnutrition. A total of 93 children (48 zinc and 45 control) 12 to 23 months of age from an ongoing community-based, randomized, controlled trial received supplements for at least 1 month before study; 71% had received supplementation for more than 120 days. Zinc gluconate (10 mg of elemental zinc) was given daily, with both zinc and control groups receiving vitamins A, B1, B2, B6, D3, and E and niacinamide in addition. RESULTS: Outcomes were percentages of time spent in each of five activity levels and two groups representing high and low movement and overall rating by two activity scores. Children in the zinc group spent 72% more time performing activities in the high-movement group. Among the zinc-supplemented children, the activity rating by the children's activity rating score was 12% higher and by the energy expenditure score was 8.3% higher than in the control group. CONCLUSIONS: In conclusion, zinc supplementation, given along with selected vitamins, was associated with significantly greater activity levels in children. The relationship between the activity increase and locomotor development needs to be investigated, as do the long-term implications of zinc supplementation in terms of developmental status and school performance.

Double-Blind Method↗

Zinc supplementation in young children with acute diarrhea in India.

BACKGROUND: In developing countries the duration and severity of diarrheal illnesses are greatest among infants and young children with malnutrition and impaired immune status, both factors that may be associated with zinc deficiency. In children with severe zinc deficiency, diarrhea is common and responds quickly to zinc supplementation. METHODS: To evaluate the effects of daily supplementation with 20 mg of elemental zinc on the duration and severity of acute diarrhea, we conducted a double-blind, randomized, controlled trial involving 937 children, 6 to 35 months of age, in New Delhi, India. All the children also received oral rehydration therapy and vitamin supplements. RESULTS: Among the children who received zinc supplementation, there was a 23 percent reduction (95 percent confidence interval, 12 percent to 32 percent) in the risk of continued diarrhea. Estimates of the likelihood of recovery according to the day of zinc supplementation revealed a reduction of 7 percent (95 percent confidence interval, -9 percent to +22 percent) in the risk of continued diarrhea during days 1 through 3 and a reduction of 38 percent (95 percent confidence interval, 27 percent to 48 percent) after day 3. When zinc supplementation was initiated within three days of the onset of diarrhea, there was a 39 percent reduction (95 percent confidence interval, 7 percent to 61 percent) in the proportion of episodes lasting more than seven days. In the zinc-supplementation group there was a decrease of 39 percent (95 percent confidence interval, 6 percent to 70 percent) in the mean number of watery stools per day (P = 0.02) and a decrease of 21 percent (95 percent confidence interval, 10 percent to 31 percent) in the number of days with watery diarrhea. The reductions in the duration and severity of diarrhea were greater in children with stunted growth than in those with normal growth. CONCLUSION: For infants and young children with acute diarrhea, zinc supplementation results in clinically important reductions in the duration and severity of diarrhea.

Acute Disease↗

Impact of massive dose of vitamin A given to preschool children with acute diarrhoea on subsequent respiratory and diarrhoeal morbidity.

OBJECTIVE: To assess the impact of vitamin A supplementation on morbidity from acute respiratory tract infections and diarrhoea. DESIGN: Double blind randomised placebo controlled field trial. SETTING: An urban slum area in New Delhi, India. SUBJECTS: 900 children aged 12-60 months attending a local health facility for acute diarrhoea of less than seven days' duration randomly allocated to receive vitamin A 200,000 IU or placebo. MAIN OUTCOME MEASURES: Incidence and prevalence of acute lower respiratory tract infections and diarrhoea during the 90 days after termination of the enrolment diarrhoeal episode measured by twice weekly household surveillance. RESULTS: The incidence (relative risk 1.07; 95% confidence interval 0.92 to 1.26) and average number of days spent with acute lower respiratory tract infections were similar in the vitamin A supplementation and placebo groups. Among children aged 23 months or less there was a significant reduction in the incidence of measles (relative risk 0.06; 95% confidence interval 0.01 to 0.48). The incidence of diarrhoea was also similar (relative risk 0.95; 0.86 to 1.05) in the two groups. There was a 36% reduction in the mean daily prevalence of diarrhoea associated with fever in the vitamin A supplemented children older than 23 months. CONCLUSIONS: Results were consistent with a lack of impact on acute lower respiratory tract related mortality after vitamin A supplementation noted in other trials and a possible reduction in the severity of diarrhoea.

Acute Disease↗

Increased cytosine DNA-methyltransferase activity during colon cancer progression.

BACKGROUND: Molecular changes during progressive stages of colon cancer and other human tumors commonly involve altered regulation of DNA methylation. These changes include overall genomic hypomethylation, regional hypermethylation, and increased levels of messenger RNA (mRNA) for cytosine DNA-methyltransferase (DNA-MTase), the enzyme that catalyzes DNA methylation at CpG (cytosine-phospho-guanine) sites. This increase in DNA-MTase transcripts (mRNA), if accompanied by increased DNA-MTase activity, could play a role in the abnormal DNA methylation patterns that appear early in colon tumor progression. PURPOSE: We sought to determine whether increased DNA-MTase mRNA levels during colon cancer progression are associated with increased cellular DNA-MTase enzymatic activity. METHODS: We adapted a microassay for DNA-MTase and used it to measure activity in human colon carcinoma and in colon mucosa of normal control subjects and of patients with colon cancer or with familial adenomatous polyposis (FAP), which is a risk factor for colon cancer. Steady-state DNA-MTase gene transcripts were measured by a reverse transcriptase polymerase chain reaction assay. To compare DNA-MTase activity with mRNA levels, we determined both variables simultaneously for one colon cancer specimen, its adjacent mucosa, and the colon mucosa of a control patient and compared the values. RESULTS: Compared with DNA-MTase activity in mucosa from normal control subjects, activity was elevated 1.4-fold in FAP mucosa, 1.6-fold in the uninvolved mucosa of patients with cancer, and 5.4-fold in the cancer specimens. All these differences were statistically significant. Fourteen of 15 cancer samples and 47% of the uninvolved adjacent mucosa samples had values that were higher than the highest value in normal mucosa. In one patient who had both a benign adenomatous polyp and a malignant adenocarcinoma, increasing DNA-MTase activity was observed at each stage of tumor progression. CONCLUSION: These results demonstrate that an increased DNA methylation capacity accompanies the increase in DNA-MTase transcripts observed during progressive stages of colon cancer. IMPLICATION: Further studies are needed to determine whether this abnormal methylation capacity plays a role in establishing the abnormal DNA methylation patterns seen in human malignancies.

Adenocarcinoma↗

Protection conferred by neonatal rotavirus infection against subsequent rotavirus diarrhea.

A cohort of newborns in New Delhi who were nosocomially infected with rotavirus during their first days of life were followed twice weekly for 14-23 months to determine whether neonatal infection protected them against subsequent episodes of rotavirus diarrhea. Infection occurred in 60% by the fourth day of life, was asymptomatic, and was caused predominantly by an unusual rotavirus strain (G9 P11) not previously identified in humans. The 148 children with neonatal rotavirus infection had 46% fewer attacks of rotavirus diarrhea in the follow-up period than the 56 infants without nosocomial infection (0.23 vs. 0.42 episodes/child-year, P < .05). This protection was concentrated among infants in their first year of life and was not associated with a significant decrease in disease severity. Consideration of this strain as a vaccine candidate will require further assessment of its natural protection under field conditions.

Cohort Studies↗

Enteroaggregative Escherichia coli may be a new pathogen causing acute and persistent diarrhea.

The role of Hep-2 cell adherent Escherichia coli (EAEC) of localized (EAEC-L), diffuse (EAEC-D) and aggregative (EAggEC) phenotype, was investigated in 254 children aged < or = 48 months seeking treatment for non-bloody diarrhea at an outpatient clinic, and in 107 age-matched controls. The stool excretion rates of single isolates from patients/controls for the different phenotypes of Hep-2 cell adherent E. coli were: EAEC-L, 5.9/2.8%, p = 0.33; EAEC-D, 7.5/12.1%, p = 0.22; and EAggEC, 11.8/3.7%, p = 0.03. When patients were categorized by pre-admission diarrheal duration > or = 14/< 14 days, the excretion rates were EAEC-L, 0/7.1%; EAEC-D, 9.5/7.1%, and EAggEC, 21.4/9.9%, the difference approaching significance only for EAggEC (p = 0.06). These findings suggest that EAggEC may be an important cause of diarrhea in children, with a predilection to cause prolonged disease.

Acute Disease↗

Meta-analysis of intervention trials on case-management of pneumonia in community settings.

To appraise the effectiveness of the pneumonia case-management strategy in improving child survival, we have done a meta-analysis of six published intervention trials. The results of a seventh published study and two unpublished studies were also reviewed. The six published studies satisfied our criteria for methodological soundness. The reduction in mortality rate (control group minus intervention group) was estimated for each study, and for all the studies together. For total infant mortality, the overall reduction was 15.9 (95% confidence interval 10.6-21.1) deaths per 1000 livebirths; infant mortality due to acute lower respiratory infection was reduced by 10.7 (4.8-16.7) deaths/1000 livebirths. Mortality among children under 5 years was decreased by 36 deaths/1000 livebirths. The pooled estimates of relative risk are consistent with a 20% reduction in infant mortality and a 25% reduction in under-5 mortality. There was no clear association across the studies between the effect of the pneumonia case-management and extent of co-interventions such as immunisation and oral rehydration therapy. The consistency of findings of all the studies, despite differences in design and methods, shows that the case-management strategy has a substantial effect on infant and under-5 mortality, at least in settings with infant mortality rates of 90/1000 livebirths or more. It is important to find out the most efficient ways of implementing this strategy and integrating it into primary health care.

Child, Preschool↗

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↗

Type of milk feeding during acute diarrhoea and the risk of persistent diarrhoea: a case control study.

The role of feeding breast milk, unmodified bovine milk or adapted infant formula during acute diarrhoea in protecting against or causing persistence of the episodes was investigated in a population-based case control study in an urban area of north India. After adjustment for confounding variables, exclusive breast-feeding was associated with an odds ratio of 0.06 (95% CI 0.002-2.1), a 16.5 times lower odds in favour of developing persistence of an episode. Infants fed unmodified bovine milk in addition to breast milk had an odds of 2.5 times (95% CI 1.0-9.9) in favour of developing persistence of acute diarrhoea (p = 0.04). In infants receiving unmodified bovine milk and no breast milk, this odds ratio was 11.1 (95% CI 1.0-228.8) (p = 0.05). This study indicates that promoting exclusive breastfeeding may reduce the persistence of diarrhoea over and above its effect in decreasing the incidence of acute diarrhoea. In urban areas of the developing countries where working mothers often use milk supplementation beyond the age of three months, our findings suggest that use of adapted spray dried formula may be safer than unmodified bovine milk with respect to the risk of developing persistent diarrhoea.

Acute Disease↗

Mortality associated with acute watery diarrhea, dysentery and persistent diarrhea in rural North India.

Mortality associated with diarrhea was investigated in a longitudinally followed cohort of children under 6 years of age in rural North India. During the followup, 1663 episodes of diarrhea and 23 diarrhea-related deaths were recorded in 1467 children followed up for 20 months. The case fatality rate was 0.56% for acute watery diarrhea, 4.27% for dysentery, and 11.94% for non-dysenteric persistent diarrhea. Most of the episodes lasted less than a week; 5.2% became persistent (duration 14 days). The case fatality rate was similar in episodes of 1 and 2 weeks duration (0.64% and 0.8%) and increased to 13.95% for persistent episodes. Of the total 86 persistent episodes, 22.1% were dysenteric; the case fatality rate for such dysenteric persistent episodes was 21.1% and for watery persistent diarrhea 11.4%. Diarrheal attack rates were similar among different nutritional groups, but diarrheal case fatality rates progressively increased with increasing severity of malnutrition; these were 24 times higher in children with severe malnutrition (7.48%) compared to those normally nourished (0.31%). With availability and use of oral rehydration therapy, dysentery and persistent diarrhea emerge as major causes of diarrhea-related mortality, with underlying malnutrition as a key associated factor.

Asia↗

Mortality associated with acute watery diarrhea, dysentery and persistent diarrhea in rural north India.

Mortality associated with diarrhea was investigated in a longitudinally followed cohort of children under six years of age in rural North India. During the follow-up, 1663 episodes of diarrhea and 23 diarrhea related deaths were recorded in 1467 children followed up for 20 months. The case fatality rate was 0.56% for acute watery diarrhea, 4.27% for dysentery and 11.94% for non-dysenteric persistent diarrhea. Most of the episodes lasted less than a week; 5.2% became persistent (duration > 14 days). The case fatality rate was similar in episodes of one and two weeks' duration (0.64% and 0.8%) and increased to 13.95% for persistent episodes. Of the total 86 persistent episodes, 22.1% were dysenteric; the case fatality rate for such dysenteric persistent episodes was 21.1% and for watery persistent diarrhea 11.4%. Diarrheal attack rates were similar among different nutritional groups, but diarrheal case fatality rates progressively increased with increasing severity of malnutrition, these were 24 times higher in children with severe malnutrition (7.48%) compared to those normally nourished (0.31%). With availability and use of oral rehydration therapy, dysentery and persistent diarrhea emerge as major causes of diarrhea related mortality, with underlying malnutrition as a key associated factor.

Acute Disease↗

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↗