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Biomedical subjects

S Sazawal

Publications and source records attributed to S Sazawal.

At least 19 recordsLinked to original sources
PubMed2005

Philadelphia-chromosome positive thrombocythemia in a child.

Philadelphia-chromosome positive thrombocythemia without features of chronic myeloid leukemia in peripheral blood has been described in adults. It is rare in children. We present a case of Philadelphia positive thrombocythemia in a child who was managed with a combination of imatinib and hydroxyurea. Although a reduction in the BCR-ABL transcript was documented, the thrombocytosis was refractory to imatinib alone and required the addition of hydroxyurea.

Benzamides↗
PubMed2004

Paucity of TEL-AML 1 translocation, by multiplex RT-PCR, in B-lineage acute lymphoblastic leukemia (ALL) in Indian patients.

A total of 69 patients of B lineage ALL, 35 children (32 males, 3 females) and 34 young adults (27 males, 7 females) were studied by multiplex RT-PCR to determine the relative frequency of t(9;22), t(12;21), t(1;19), and t(4;11,). Translocation (9;22) was seen in 1/35 (2.8%) and t(1;19) in 2/35 (5.7%) children. None of the children showed t(12;21) and t(4;11) translocations. In young adults, t(9;22) and t(1;19) were seen in 5/34 (14.7%) and 2/34 (5.8%) patients, respectively. None of the latter showed t(12;21) or t(4;11) translocations. Thus, there appears to be a significant under representation of the fusion transcripts for TEL-AML, a good prognostic marker, in this study, unlike in the West, where it is seen in 35% of children with ALL. This, together with the generally increased leukemic burden seen in Indian patients, may explain in part, the poor treatment outcome reported.

Adolescent↗
PubMed2004

Zinc supplementation for four months does not affect plasma copper concentration in infants.

AIM: The aim of the present study, which was undertaken as a sub-study within a randomized controlled trial of zinc supplementation, was to evaluate the effect of prolonged zinc supplementation on copper status as assessed by hematological markers. METHODS: Plasma copper and zinc were estimated at baseline and after 120 d of supplementation in a randomly selected infant subset (115) of the children. Of these, 61 children were in a zinc group (Z) getting 10 mg of elemental zinc, and 54 were in a control group (C) getting supplement without zinc. RESULTS: Baseline plasma zinc was comparable in the two groups; post-supplementation zinc was significantly higher (Z 93.0 +/- 3.6 vs C 60.6 +/- 8.0) in the zinc supplementation group. There was no significant difference in the mean/median copper levels between the zinc and control groups. The percentage of children with plasma copper <100 microg/dl was also not significantly different between groups (baseline Z 14.8%, C 11.1%; post-supplementation Z 18.0%, C 11.1%). There were no differences between the zinc and control groups after 120 d of supplementation in hemoglobin (Hgb), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), or number of lymphocytes or granulocytes. CONCLUSION: Zinc supplementation of 10 mg/d for 4 mo in this study did not affect copper status, as assessed by plasma copper concentration and hematological parameters, diagnostics of copper deficiency.

Copper↗
PubMed2001

Significance of MDR1, MRP1, GSTpi and GSTmu mRNA expression in acute lymphoblastic leukemia in Indian patients.

Using, semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in 167 patients of acute lymphoblastic leukemia (ALL) from India at different stages of the disease (presentation 125, remission 33, first relapse nine), MRP1 and GSTpi expression were significantly higher at relapse than presentation (P=0.03 and P=0.01, respectively) and remission (P=0.007 and P=0.003, respectively). MRP1, GSTpi and GSTmu were expressed simultaneously in several samples with significant association of expression levels (P=0.0001). Association with clinicopathological features included higher MDR1 expression with age >15 years (P=0.04) and higher MRP1, GSTpi, GSTmu expression with WBC counts >100x10(9)/l. In 71 patients (age <25 years), inability to achieve CR was associated with a significantly higher MDR1 mRNA expression (P=0.03) indicating a prognostic significance. However, relapse or shorter Event Free Survival was independent of mRNA expression levels of the four genes. In view of the increased mRNA expression of MRP1/GST at the time of relapse and an association with risk factors such as a high WBC count, further studies directed towards investigating the functional aspects of GSH/GST/MRP1 mediated drug transport are warranted.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Incidence, clinical characteristics and early treatment outcome in Indian patients of childhood acute lymphoblastic leukemia with ALL-1 gene rearrangement.

In a series of 185 patients (median age 7 years) of acute lymphoblastic leukaemia (ALL) from India, the overall incidence of ALL-1 gene rearrangement using the Southern blot technique was 11.4% (21/185). The incidence amongst the infants (age < or = 1 year, 70%) was significantly higher when compared to patients > 1 - < or = 10 years (7.4%, P = 0.00001) as well as > 10 years old (9.3%, P = 0.0001). ALL-1 gene rearrangement was associated with significantly higher WBC count (P = 0.01) and CD10 negativity (P = 0.00000001). Complete remission (CR) and relapse rates in 98 patients evaluable for response to therapy on a uniform therapy protocol was independent of ALL-1 gene status.

Adolescent↗
PubMed2001

Zinc and childhood infectious disease morbidity and mortality.

Zinc is an essential mineral and deficiency results in abnormal immune function and higher rates of infectious diseases. Randomized controlled trials of zinc supplementation have been conducted in children in developing countries to determine effects on infectious disease morbidity and mortality. Zinc-supplemented children have been found to have lower rates of diarrhea, pneumonia and malaria in comparison with children not given zinc. Zinc used as an adjunct to fluid and dietary management of acute and persistent diarrhea has been found to reduce diarrheal duration and severity. Preliminary evidence suggests that zinc supplementation in children in poor developing country settings may also reduce infant mortality, but larger trials are needed to address this important issue. Preventive and therapeutic interventions should be implemented in developing countries where zinc deficiency is likely to be prevalent.

Child, Preschool↗
PubMed2001

Zinc supplementation in infants born small for gestational age reduces mortality: a prospective, randomized, controlled trial.

BACKGROUND: Low birth weight infants have been noted to have low zinc concentrations in cord blood, and zinc deficiency in childhood is associated with reduced immunocompetence and increased infectious disease morbidity. This study investigates whether zinc supplementation of infants born full term and small for gestational age affects mortality. METHODS: A randomized, double-blind, controlled trial with 2-by-2 factorial design enrolled 1154 full-term small for gestational age infants to receive in syrup 1 of the following: riboflavin; riboflavin and zinc (5 mg as sulfate); riboflavin, calcium, phosphorus, folate, and iron; or riboflavin, zinc, calcium, phosphorus, folate, and iron. A fixed dosage of 5 mL per child was given daily from 30 to 284 days of age. Household visits were made 6 days per week to provide the syrup and conduct surveillance for illness and death. When a child's death was reported, parental reports and medical records were used to ascertain the cause. The effects of zinc and of the combination of iron, folate, calcium, and phosphorus were analyzed by intent to treat. The mortality analysis was performed using a survival analytic approach that models time until death as the dependent variable; all models had 2 terms as independent variables: 1 for the zinc effect and 1 for the vitamin and mineral (calcium and phosphorus, folate and iron) effect. RESULTS: Zinc supplementation was associated with significantly lower mortality, with a rate ratio of 0.32 (95% confidence interval: 0.12-0.89). Calcium, phosphorus, folate, and iron supplementation was not associated with a mortality reduction, although a statistically nonsignificant trend toward reduction was observed with a rate ratio of 0.88 (95% confidence interval: 0.36-2.15). CONCLUSIONS: Zinc supplementation in small for gestational age infants can result in a substantial reduction in infectious disease mortality.

Communicable Diseases↗
PubMed2000

Pattern of immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements in childhood acute lymphoblastic leukemia in India.

In 120 cases of acute lymphoblastic leukemia (median age 8 years), IgH chain gene was rearranged in 99% B-Cell Precursor (BCP) ALLs and 13% T-ALLs. One or the other TCR locus was rearranged not only in all T-ALLs, but also in 87% of BCP-ALLs. TCR-beta rearrangement in BCP-ALL was associated with a higher mean age at presentation (8.7 vs. 6.2 years, P=0.008), lower mean platelet counts (61.2x10(9)/l vs. 103.7x10(9)/l, P=0.003) and a poorer DFS (% cummulative survival 0 vs. 88.9+/-10.5, P=0.004). TCR-gamma rearrangement in T-ALL was associated with a higher mean WBC count (186.3x10(9)/l vs. 63. 4x10(9)/l, P=0.002). Also, the pattern of rearrangement of these genes appeared to be different from the West; viz. TCR-beta rearrangement in a higher proportion of BCP-ALLs (58%, 95% confidence intervals 45-69%), invariable deletion of Cgamma1 and only monoallelic rearrangement for TCR-delta locus. This repertoire of gene rearrangement may have a bearing on the poor treatment outcome reported previously from our geographic region.

Adolescent↗
PubMed2000

Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials.

BACKGROUND: Zinc deficiency is prevalent in children in developing countries. Supplemental zinc provides therapeutic benefits in diarrhea. OBJECTIVE: We sought to measure the effect of supplemental zinc given with oral rehydration therapy during recovery from acute or persistent diarrhea. DESIGN: We conducted pooled analyses including all available published and unpublished randomized controlled trials of the effects of supplementary oral zinc in children aged <5 y with acute or persistent diarrhea. We used Cox survival regression analysis to evaluate the overall effect of zinc on continuation of diarrhea and possible differential effects in subgroups divided by sex, age, weight-for-height, and initial plasma zinc concentration. Dichotomous outcomes were analyzed by logistic regression. To assess the effects of excluding studies without original data from the pooled analyses, effect-size was estimated for all studies by using random-effects models. RESULTS: Zinc-supplemented children had a 15% lower probability of continuing diarrhea on a given day (95% CI: 5%, 24%) in the acute-diarrhea trials and a 24% lower probability of continuing diarrhea (95% CI: 9%, 37%) and a 42% lower rate of treatment failure or death (95% CI: 10%, 63%) in the persistent-diarrhea trials. In none of the subgroup analyses were the 2 subgroups of each pair significantly different from each other; however, in persistent diarrhea there tended to be a greater effect in subjects aged <12 mo, who were male, or who had wasting or lower baseline plasma zinc concentrations. CONCLUSION: Zinc supplementation reduces the duration and severity of acute and persistent diarrhea.

Acute Disease↗
PubMed1999

Typhoid fever in children aged less than 5 years.

BACKGROUND: Calculation of the incidence of typhoid fever during preschool years is important to define the optimum age of immunisation and the choice of vaccines for public-health programmes in developing countries. Hospital-based studies have suggested that children younger than 5 years do not need vaccination against typhoid fever, but this view needs to be re-examined in community-based longitudinal studies. We undertook a prospective follow-up study of residents of a low-income urban area of Delhi, India, with active surveillance for case detection. METHODS: A baseline census was undertaken in 1995. Between Nov 1, 1995, and Oct 31, 1996, we visited 8172 residents of 1820 households in Kalkaji, Delhi, twice weekly to detect febrile cases. Blood samples were obtained from febrile patients, and those who tested positive for Salmonella typhi were treated with ciprofloxacin. FINDINGS: 63 culture-positive typhoid fever cases were detected. Of these, 28 (44%) were in children aged under 5 years. The incidence rate of typhoid per 1000 person-years was 27.3 at age under 5 years, 11.7 at 5-19 years, and 1.1 between 19 and 40 years. The difference in the incidence of typhoid fever between those under 5 years and those aged 5-19 years (15.6 per 1000 person-years [95% CI 4.7-26.5]), and those aged 19-40 years (26.2 [16.0-36.3]) was significant (p<0.001 for both). The difference between the incidence of typhoid at 5-19 years and the incidence at 19-40 years was also significant (10.6 [6.3-14.8], p<0.001). Morbidity in those under 5 and in older people was similar in terms of duration of fever, signs and symptoms, and need for hospital admission. INTERPRETATION: Our findings challenge the common view that typhoid fever is a disorder of school-age children and of adults. Typhoid is a common and significant cause of morbidity between 1 and 5 years of age. The optimum age of typhoid immunisation and the choice of vaccines needs to be reassessed.

Adolescent↗
PubMed1999

Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group.

OBJECTIVES: This study assessed the effects of zinc supplementation in the prevention of diarrhea and pneumonia with the use of a pooled analysis of randomized controlled trials in children in developing countries. STUDY DESIGN: Trials included were those that provided oral supplements containing at least one half of the United States Recommended Daily Allowance (RDA) of zinc in children <5 years old and evaluated the prevention of serious infectious morbidity through household visits. Analysis included 7 "continuous" trials providing 1 to 2 RDA of elemental zinc 5 to 7 times per week throughout the period of morbidity surveillance and 3 "short-course" trials providing 2 to 4 RDA daily for 2 weeks followed by 2 to 3 months of morbidity surveillance. The effects on diarrhea and pneumonia were analyzed overall and in subgroups defined by age, baseline plasma zinc concentration, nutritional status, and sex. The analysis used random effects hierarchical models to calculate odds ratios (OR) and 95% CIs. RESULTS: For the zinc-supplemented children compared with the control group in the continuous trials, the pooled ORs for diarrheal incidence and prevalence were 0.82 (95% CI 0.72 to 0.93) and 0.75 (95% CI 0.63 to 0.88), respectively. Zinc-supplemented children had an OR of 0.59 (95% CI 0.41 to 0.83) for pneumonia. No significant differences were seen in the effects of the zinc supplement between the subgroups examined for either diarrhea or pneumonia. In the short-course trials the OR for the effects of zinc on diarrheal incidence (OR 0.89, 95% CI 0.62 to 1.28) and prevalence (OR 0.66, 95% CI 0.52 to 0.83) and pneumonia incidence (OR 0.74, 95% CI 0.40 to 1.37) were similar to those in the continuous trials. CONCLUSIONS: Zinc supplementation in children in developing countries is associated with substantial reductions in the rates of diarrhea and pneumonia, the 2 leading causes of death in these settings.

Child↗
PubMed1999

Potential interventions for the prevention of childhood pneumonia in developing countries: improving nutrition.

Acute respiratory infections are the leading cause of childhood death in developing countries. Current efforts at mortality control focus on case management and immunization, but other preventive strategies may have a broader and more sustainable effect. This review, commissioned by the World Health Organization, examines the relations between pneumonia and nutritional factors and estimates the potential effect of nutritional interventions. Low birth weight, malnutrition (as assessed through anthropometry), and lack of breast-feeding appear to be important risk factors for childhood pneumonia, and nutritional interventions may have a sizeable effect in reducing deaths from pneumonia. For all regions except Latin America, interventions to prevent malnutrition and low birth weight look more promising than does breast-feeding promotion. In Latin America, breast-feeding promotion would have an effect similar to that of improving birth weights, whereas interventions to prevent malnutrition are likely to have less of an effect. These findings emphasize the need for tailoring interventions to specific national and even local conditions.

Breast Feeding↗
PubMed1998

Expression of genes implicated in multidrug resistance in acute lymphoblastic leukemia in India.

In order to investigate the phenomenon of multidrug resistance as a possible mechanism for poor response to treatment in patients with acute lymphoblastic leukemia (ALL) from India, a series of 32 cases of de novo untreated ALLs were analyzed by a cDNA-PCR approach to estimate the relative mRNA levels of the MDR-associated genes encoding MDR1, MRP, GSTpi, and GSTmu. The expression of beta2 microglobulin served as an internal standard. Quantifiable transcripts were observed in 20 patients for MRP, in 5 for MDR1, in 24 for GSTpi, and in 19 for GSTmu. The values ranged from undetectable to 132% of the control A549 cell line for MRP, undetectable to 49% of the HL60/DNR control cell line for MDR1, undetectable to 268% of A549 control cell line for GSTpi, and undetectable to 247% of A549 control cell line for GSTmu mRNA. Increased MRP levels were associated with increased GSTpi and GSTmu levels (p<0.01 for both), and increased levels of MDR1 were associated with increased GSTpi levels (p<0.05). The present observations showed no correlation between the MDR1 and MRP values with treatment outcome, in terms of either achieving a complete remission or predilection to early relapse. In view of some recent studies that envisage MRP as an energy-dependent pump involved in the efflux of GSH conjugates, the simultaneous up-regulation of transcription of all these genes might well be part of an integrated detoxification response that has been switched on after exposure to an environmental stress.

ATP-Binding Cassette Transporters↗
PubMed1998

Efficacy of milk versus yogurt offered as part of a mixed diet in acute noncholera diarrhea among malnourished children.

We compared the clinical outcome of acute diarrhea in 96 malnourished boys (aged 4 to 47 months) receiving full-strength milk compared with yogurt offered as part of a mixed diet. All had weight for height less than or equal to 80% of the National Centre for Health Statistics median. They were randomly assigned to receive milk formula (MF; 67 cal/100 ml) or yogurt formula (YF; prepared from the same milk formula) at the rate of 120 ml/kg body weight in seven divided feedings. Stool-reducing substances (> 1%) were detected more frequently in the MF group, and the differences were significant for day 3 of the study (p = 0.04). However, the geometric mean (95% confidence interval) of the total stool weights (gm/kg) during 0 to 72 hours (MF 128.8 [103, 161.4]; YF 110.9 [87, 142.2]) was comparable (p = 0.37) as was the median (range) duration of diarrhea (hours) (MF 45 [4, 183]; YF 52 [7, 173] p = 0.94). The treatment failure rates in the MF (8.2%) and YF (6.3%) groups were also similar (p = 0.67). The children consuming milk had higher median percent weight gain at the end of 72 hours of the study (p = 0.04) and at recovery (p = 0.02). Routine substitution of yogurt as small frequent feedings as an addition for semisolid food to malnourished children with acute diarrhea does not achieve any significant clinical benefit versus milk.

Acute Disease↗