Archana Kumar

Delta-aminolevulinic acid dehydratase inhibition and oxidative stress in relation to blood lead among urban adolescents

To explore lead-induced oxidative stress among urban adolescents, the present study, the first from India, was designed to determine the proportion of urban adolescents with blood lead > 10 μg/dL and its impact on selected oxidative stress parameters and delta-aminolevulinic acid dehydratase (δ-ALAD) inhibition, which could be used as biomarkers of lead intoxication. A total of 39, urban, male adolescents, drawn from Lucknow and adjoining areas, were recruited to determine lead, d-ALAD, malondialdehyde (MDA) and glutathione (GSH) in blood and catalase (CAT) in RBCs. Mean level of blood lead was 9.96 ± 3.63 μg/dL (4.62 - 18.64); 43% of adolescents crossed the Centre for Disease Control (CDC) intervention level of 10 mg/dL blood lead. On the basis of blood lead levels (BLLs), adolescents were categorized into two groups: Group I and Group II had a blood lead < 10 μg/dL (7.40 ± 1.62) and < 10 μg/dL (13.27 ± 2.67), respectively, with significantly different mean values (P < 0.001). Age, sex, body mass index (BMI), Hb level (malnutrition), and area of living as confounders of lead exposure and toxicity were not statistically different between the two groups. However, d-ALAD activity was significantly lower (P < 0.001), while CAT activity was higher in Group II than in Group I (P < 0.01). MDA level was also significantly higher in Group II compared to Group I (P < 0.001). There were significant negative correlation of BLL with d-ALAD (r = -0.592, P < 0.001), and positive correlations with CAT (r= -0.485, P < 0.01) and MDA (r = -0.717, P < 0.001). Interestingly, d-ALAD, in turn, had significant negative correlations with CAT (r = -0.456, P <0.01) and MDA (r = -0.507, P < 0.01). Results of the present pilot study provide clues to the possible low level of lead-induced oxidative stress in urban adolescents, suggesting that lead-induced d-ALAD inhibition can also be an indicator of oxidative stress. The potential of oxidative stress parameters to be used as biomarkers of lead toxicity warranted further investigation.

Causes, outcome and prevention of abandonment in retinoblastoma in India.

The high‐cure rates of 90% in retinoblastoma are not replicated in developing countries due to late presentation and poor compliance to treatment. The present study takes a closer look at causes of abandonment of therapy and effectiveness of counselling in reducing abandonment.

Blood lead levels in children of Lucknow, India.

After implementing measures to control lead pollution in many countries, blood lead levels (BLLs) in children have been declined. The phase‐out of leaded petrol began in Lucknow, the capital of most populated state, Uttar Pradesh in India on April 1, 2000. We evaluated the mean BLL and associated risk factors for lead exposure in Lucknow children (3–12 years) after petrol lead phase‐out activity. The mean BLL of the 200 children was 9.3 μg/dL (range: 1.0–27.9 μg/dL). Seventy‐four children (37%) had BLL above the Centre for Disease Control and Preventions (CDC) level of concern (10 μg/dL). When these data were compared with BLLs determined by the George Foundation among the children of Mumbai, Bangalore, Kolkata, Chennai, Hyderabad, and Delhi during the year 1997 when leaded petrol was in use, where 62%, 62%, 87%, 96%, 43%, and 95%, respectively, then exceeded the CDC intervention level. Further, BLL of present study was very close to Mumbai children (age ≤12 years) estimated following the introduction of unleaded petrol, and 33% children had BLL above the CDC concern level with an average 8.4 μg/dL. Low socioeconomic status, proximity of home to traffic density, and mothers illiteracy were the factors associated with elevated BLLs in Lucknow children (P < 0.05). Overall, results indicate a declining trend of BLL in Lucknow children when compared with those reported from other cities of India when leaded petrol was in practice. A national population‐based study is recommended to determine the prevalence of elevated BLLs after the phase‐out of leaded‐petrol. In addition, future studies on other sources of lead exposure in Lucknow are warranted for public health purposes.

Role of folate status and methylenetetrahydrofolate reductase genotype on the toxicity and outcome of induction chemotherapy in children with acute lymphoblastic leukemia

Abstract The effect of serum folate levels and methylenetetrahydrofolate reductase (MTHFR) genotype on complications and outcome of induction chemotherapy in 150 children with acute lymphoblastic leukemia (ALL) was studied. Folate deficiency in 26% at baseline was more common in children with MTHFR 677 mutations. Folate deficient children had a higher incidence of neutropenia (p = 0.03), thrombocytopenia (p = 0.02) and febrile neutropenia (p = 0.01) and higher transfusion requirement during induction compared to folate sufficient children. Sepsis related induction deaths were more frequent in folate deficient children (p = 0.02) during induction. Children with 677 and 1298 mutations had a higher incidence of cytopenias (p = 0.01) and mucositis (p = 0.007), the risks of which increased with concomitant folate deficiency. A significant fall in folate levels was observed post-induction (p = 0.02), most markedly in mutant 677 genotypes. Multivariate analysis revealed associations of baseline folate deficiency with low counts at day 14 (p = 0.001) and MTHFR 1298 mutations with mucositis (p = 0.02).

Prevalence and genotypic characterization of human parvovirus B19 in children with hemato‐oncological disorders in North India

Human parvovirus B19 (B19V) has been associated with chronic anemia in immuno‐compromised patients. In the present study, the prevalence and genotype distribution of B19V in children from North India, suffering with hemato‐oncological disorders is reported. Children with aplastic anemia/leukemia/chronic hematological disorders, and healthy blood donors were enrolled in the study. Blood samples from cases and blood donors were analyzed for anti‐B19V IgM and anti‐B19V IgG antibodies by ELISA and for B19V‐DNA by PCR. B19V‐DNA positive samples were studied further for determination of viral load in samples and for B19V‐DNA sequence (VP1/VP2 overlapping region) analysis. Total 238 cases (103 leukemia, 77 aplastic anemia and 58 chronic hematological disorders) and 350 blood donors were enrolled in the study. Anti‐B19V IgM was positive in 16 (6.7%) cases, B19V‐DNA was detected in 13 (5.5%) cases and anti‐B19V IgG was positive in 127 (53.4%) cases. Total 223 (63.5%) blood donors were positive for anti‐B19V IgG, however, anti‐B19V IgM and B19V‐DNA was not detected in any blood donor. The prevalence of anti‐B19V IgG was significantly higher in children > 10 years of age. Viral load of B19V decreased with appearance of specific antibodies. Phylogenetic analysis of the VP1/VP2 overlapping region revealed that genotype 1 predominated in these patients (11/13, 84.6%), followed by genotype 3 (2/13, 15.4%). No genotype 2 was detected. All the genotype 1strains were sub‐typed as 1a, except four strains, which matched neither 1a nor 1b and formed a separate cluster. Both the genotype 3 strains were sub‐typed as 3b. J. Med. Virol. 87:303–309, 2015.

Effect of pre-treatment nutritional status, folate and vitamin B12 levels on induction chemotherapy in children with acute lymphoblastic leukemia

ObjectiveTo evaluate pre-treatment undernutrition, and folate and B12 deficiency in children with acute lymphoblastic leukemia, and their correlation with complications and outcome of induction chemotherapy.DesignObservational study.SettingTertiary care teaching hospital in Northern India.Participants50 children with acute lymphoblastic leukemia.ProcedureChildren were assessed for nutritional status (Weight for age Z-score, serum albumin, folate and B12) at presentation, and were followed-up during induction for bone marrow response, counts and outcome. Folate and B12 were repeated twice at monthly intervals after induction. Univariate and multivariate analyses were done to determine the association of nutritional parameters with the outcome variables.ResultsBaseline undernutrition was observed in 66%, hypoalbuminemia in 32.6%, folate deficiency in 41.3% and B12 deficiency in 36.9% of included children. Significant decline in folate levels was noted on serial assays during chemotherapy (P=0.001). Folate deficient children had higher risk for delayed marrow recovery and counts on day 14 (P=0.007 and P=0.001). Hypoalbuminemia (P=0.04), B12 deficiency (P=0.001) and folate (P=0.03) deficiency were associated with toxic deaths during induction.ConclusionBaseline nutritional deficiencies negatively influence the outcome and occurrence of complications during induction chemotherapy in children with acute lymphoblastic leukemia.

Comparative evaluation of pan-fungal real-time PCR, galactomannan and (1-3)-β-D-glucan assay for invasive fungal infection in paediatric cancer patients

Limited specific data and investigations are available for the diagnosis of Invasive Fungal Infection (IFI) in paediatrics cancer patients. Three non‐invasive tests; Platelia Aspergillus EIA for galactomannan (GM), β‐D‐glucan (BDG) assay and pan‐fungal real‐time PCR for fungal DNA in blood were evaluated. One hundred twenty‐five paediatrics cancer patients at the high risk of IFI were enrolled. Single blood and serum samples were evaluated by all the three methods. Patients were classified into 10 proven, 52 probable and 63 no IFI cases in accordance with EORTC MSG 2008 revised guidelines. The sensitivity, specificity, PPV and NPV of all the three tests in proven, probable and no IFIs cases were analysed singly and in combination. The sensitivity, specificity, PPV and NPV of GM, BDG and pan‐fungal real‐time PCR were: 87%, 61%, 81%, 69.5% for GM, 88%, 59.5%, 81%, 71.4% for BDG and 89%, 69.2%, 85%, 67.5% for PCR (95% CI). Among different combinations, best combination was found to be GM and PCR with sensitivity, specificity, PPV and NPV of 98.2%, 89.3%, 97.1% and 90% respectively. Single samples must be evaluated by combination of tests.

Glutathione-S-transferase polymorphism and acute lymphoblastic leukemia (ALL) in north Indian children: a case-control study and meta-analysis.

Various studies on association of glutathione S-transferase (GST) polymorphisms and childhood acute lymphoblastic leukemia (ALL) have yielded conflicting results. We examined this association among north Indian children and conducted an updated meta-analysis to overcome sample size-related limitations. GSTM1, GSTP1 and GSTT1 genotypes in 100 children with ALL and 300 healthy controls were compared. GSTT1 null mutation (odds ratio (OR) 2.54, 95% confidence interval (CI) 1.50–4.32) and GSTP1 homozygous mutation (OR 3.13, 95%CI 1.48–6.59) were found to increase the risk of childhood ALL, while GSTM1 did not alter the risk. Meta-analysis included 22, 10 and 20 studies examining the association of childhood ALL with GSTM1, GSTP1 and GSTT1 genotypes, respectively. Only GSTM1 genotype (OR 1.29, 95%CI 1.10–1.62) was associated with increased risk in the overall analysis. However, both GSTM1 (OR 1.54, 95%CI 1.12–2.10) and GSTT1 (OR 1.63, 95%CI 1.32–1.99) null genotypes were associated with increased risk in Asian subjects. The risk of developing childhood ALL was not associated with GSTP1 genotype.

4-Aminoquinazoline Analogs: A Novel Class of Anticancer Agents

4-Aminoquinazoline analogs have been identified as a new class of cancer chemotherapeutic agents with significant therapeutic efficacy against solid tumors. They are potent and highly selective inhibitors of tyrosine kinase (TK) and epidermal growth factor receptor (EGFR). Till date various 4-aminoquinazoline analogs have been synthesized and evaluated for anticancer activity. This review is an attempt to compile the medicinal chemistry of various synthesized 4-aminoquinazoline analogs.

Hospital outbreak of human respiratory syncytial virus (HRSV) illness in immunocompromised hospitalized children during summer.

The human respiratory syncytial virus (HRSV) is a community‐acquired virus that mainly causes acute respiratory tract infection in infants and children. HRSV is increasingly recognized as an important nosocomial pathogen causing morbidity in immunocompromised patients. Here, we are reporting a hospital outbreak of HRSV during summer in children receiving chemotherapy for haematological malignancies. Prompt detection and timely preventive measures could abort the devastating outbreak.