A randomized double-blind controlled trial comparing two regimens of vitamin D supplementation in preterm neonates.

OBJECTIVE: To compare the efficacy of 400 vs 1000 IU oral vitamin D supplementation in preterm neonates of 27 to 34 weeks gestation. METHODS: This double-blind randomized controlled trial allocated preterm babies to receive either 400 or 1000 IU of vitamin D3 (n=60 in each group). Primary outcome was prevalence of vitamin D insufficiency (serum vitamin D levels<20 ng ml(-1)) at 40 weeks of corrected gestational age (CGA). RESULTS: At term CGA vitamin D insufficiency was significantly lower in the 1000 IU group than in the 400 IU group (2% vs 64.6%, P⩽0.001). Although elevated vitamin D levels were seen in 9.8% of babies on 1000 IU per day, this was not associated with clinical or biochemical evidence of toxicity. CONCLUSION: Supplementing preterm babies with 1000 IU of vitamin D3 daily decreases the prevalence of vitamin D insufficiency at term CGA. Excess levels of vitamin D may occur at this dose in some babies.

A common variant in the FTO locus is associated with waist-hip ratio in Indian adolescents.

BACKGROUND: Common variants in the FTO locus, and near MC4R locus, have been shown to have a robust association with obesity in children and adults among various ethnic groups. Associations with obesity traits among Indian adolescents have not been determined. OBJECTIVE: To study the association of rs9939609 (FTO) and rs17782313 (MC4R) to obesity related anthropometric traits in Indian adolescents. METHODS: Subjects for the current study were recruited from a cross-sectional cohort of 1,230 adolescents (age mean ± SD: 17.1 ± 1.9 years) from South India. RESULTS: The variant at the FTO locus was found to be associated with waist-hip ratio (WHR) but not with overall obesity in this population. No significant association was observed for obesity-traits and Mc4R variant rs17782313. CONCLUSION: The common variant of FTO (rs9939609) is associated with body fat distribution during early growth in Indian adolescents and may predispose to obesity and metabolic consequences in adulthood.

Usefulness of alternate prognostic serum and plasma markers for antiretroviral therapy for human immunodeficiency virus type 1 infection.

In developing countries, the usability of peripheral blood constituents that are low-cost alternatives to CD4-positive (CD4+) T-cell and human immunodeficiency virus type 1 (HIV-1) RNA estimation should be evaluated as prognostic markers. The aim of our study was to investigate the use of plasma levels of dehydroepiandrosterone sulfate (DHEAS), albumin, and C-reactive protein (CRP) as alternate prognostic markers for antiretroviral treatment (ART) response in place of HIV-1 load measurements. Paired blood samples were collected from 30 HIV-infected individuals before and after initiation of ART, 13 HIV-infected individuals before and after completion of antituberculosis therapy (ATT), and 10 HIV-infected individuals not on either ATT or ART. Because of the nonavailability of samples, the CRP estimation was done for samples from only 19, 9, and 8 individuals in groups 1, 2, and 3, respectively. The measurements of all three markers, i.e., DHEAS, albumin, and CRP, were carried out with commercial assays. The differences in the albumin levels before and after ART or ATT were significant (P < 0.05), while the differences in DHEAS and CRP levels were not significant (P > 0.05). When levels of DHEAS among the individuals who were followed up were analyzed, 13 (44.8%) in the ART group and 9 (69%) in the ATT group showed an increase following treatment. Prior to treatment of HIV-infected individuals, there was a significant positive correlation of CD4+ T-cell counts and a negative correlation of viral load with albumin and DHEAS levels (P < 0.01). Among the three plasma markers we tested, plasma albumin and, to some extent, DHEAS show promise as prognostic markers in monitoring HIV infection.

Human immunodeficiency virus infection and levels of Dehydroepiandrosterone sulfate in plasma among Indians.

The shift in cytokine profile during human immunodeficiency virus (HIV) disease progression is influenced by dehydroepiandrosterone sulfate (DHEAS) level. Radioimmunoassay was used to measure plasma DHEAS for 30 treatment-naïve HIV-infected and 30 uninfected individuals. There was a significant negative correlation of viral load with DHEAS level (P<0.05). Further studies of the use of DHEAS levels for monitoring HIV patients economically are warranted.

[Medical-surgical treatment of pulmonary infection with Mycobacterium malmoense]. / Infection pulmonaire à Mycobacterium malmoense, traitement médico-chirurgical.

CASE REPORT: We report the case of a patient with chronic obstructive pulmonary disease in whom pulmonary infection due to mycobacterium malmoense was discovered unexpectedly. A diagnostic and therapeutic surgical resection was performed. CONCLUSION: The non-tuberculous mycobacterium was identified by culture of the specimen. Surgery was followed by empirical antibiotic treatment with rifampicin and pyrazinamide for two and a half months. Isoniazid was withdrawn rapidly on account of hepatitis and the treatment was supplemented later with clarithromycin, leading to a total duration of treatment of seven and a half months. This case is unusual because of its medico-surgical management that led to assessment and appropriate treatment of this infection.

Testing switchability of a new microemulsion formulation of cyclosporine.

We assessed the bioavailability of cyclosporine (CyA) in the test formulation (Cap Arpimune ME) relative to the reference formulation (Cap Sandimmune Neoral) to ascertain the switchability between the two formulations in patients. The study population included 30 patients on maintenance hemodialysis awaiting renal transplantation. The study adopted a randomized open-label, two-way, two-period, two-sequence crossover design. The dose administered was 8 mg/kg/d in two divided doses for 5 days in each study period with a washout period of 1 week between the two periods. A five-point blood sampling (at 0, 1, 2, 3, and 4 hours postdose) was done on the last day of each study period for CyA level monitoring. The study measures included C(max) (maximum blood concentration), AUC (area under the blood CyA concentration versus time curve, 0 to 4 hours) and actual time concentrations at individual sampling times. The differences in mean values for all parameters and the least significant differences were less than 20% of reference mean. Assessment of bioequivalence using log-transformed data showed that the point estimate (ratio test: reference) for C(max) was 0.9717 with a 90% confidence interval (CI) of 0.88 to 1.06 and that for AUC was 1.0053 with a 90% CI of 0.90 to 1.12. The bioequivalence obtained suggests that the test formulation can replace the reference formulation in patients who require CyA therapy.

Pre- and postrenal transplantation pharmacokinetics of cyclosporine microemulsion.

UNLABELLED: The availability of a microemulsion formulation (ME) of cyclosporin (CyA) displays improved bioavailability and reduced inter and intra-patient variability, resulting in improved long-term outcomes. Recent developments in therapeutic drug monitoring stress the need to optimize peak drug levels during the early posttransplant period to obtain long-term benefit. METHODS: We studied early CyA-ME pharmacokinetics, comparing pre- versus immediate posttransplant values, to assess predictability of pre-transplant profiles in 22 patients including 3 diabetics. An 8 mg/kg per day amount in two divided doses was administered, for 5 days pretransplant and 10-14 days posttransplant before performing the pharmacokinetic studies. Drugs interacting with CyA metabolism/absorption were withdrawn and patients with liver disease were excluded the CyA level monitoring used a 5-point blood sampling (at 0 hours, 1 hours, 2 hours, 3 hours, and 4 hours post-dose). The study compared actual concentrations at each individual time and the limited 0-4 hour AUC. RESULTS: The paired values at each point pre- and posttransplant were: C0 = 171 +/- 63 and 215 +/- 112, C1 = 723.86 +/- 345 and 1239.95 +/- 415, C2 = 972 +/- 185 and 1249.95 +/- 336, C3 = 822 +/- 242 and 942.7 +/- 286, and C4 = 601.54 +/- 190 and 670.5 +/- 208 ng/mL respectively. The C1 and C2 values were significantly higher posttransplant (P =.008 and 0.0045 respectively), suggesting a steeper absorption phase, a conclusion consistent with the higher 0-4 hour AUC posttransplant (P =.0089). However, linear regression analysis of pre- versus posttransplant values showed poor correlations. CONCLUSIONS: CyA absorption is significantly lower among patients on maintenance hemodialysis and showed no predictive correlation with posttransplant levels. The possible role of uremia in retarding absorption which may have clinical significance for primary graft dysfunction, needs further evaluation.

Role of arginine 285 in the active site of Rhodotorula gracilis D-amino acid oxidase. A site-directed mutagenesis study.

Arg(285), one of the very few conserved residues in the active site of d-amino acid oxidases, has been mutated to lysine, glutamine, aspartate, and alanine in the enzyme from the yeast Rhodotorula gracilis (RgDAAO). The mutated proteins are all catalytically competent. Mutations of Arg(285) result in an increase ( approximately 300-fold) of K(m) for the d-amino acid and in a large decrease ( approximately 500-fold) of turnover number. Stopped-flow analysis shows that the decrease in turnover is paralleled by a similar decrease in the rate of flavin reduction (k(2)), the latter still being the rate-limiting step of the reaction. In agreement with data from the protein crystal structure, loss of the guanidinium group of Arg(285) in the mutated DAAOs drastically reduces the binding of several carboxylic acids (e.g. benzoate). These results highlight the importance of this active site residue in the precise substrate orientation, a main factor in this redox reaction. Furthermore, Arg(285) DAAO mutants have spectral properties similar to those of the wild-type enzyme, but show a low degree of stabilization of the flavin semiquinone and a change in the redox properties of the free enzyme. From this, we can unexpectedly conclude that Arg(285) in the free enzyme form is involved in the stabilization of the negative charge on the N(1)-C(2)=O locus of the isoalloxazine ring of the flavin. We also suggest that the residue undergoes a conformational change in order to bind the carboxylate portion of the substrate/ligand in the complexed enzyme.

Randomized controlled trial of once vs. twice daily gentamicin therapy in newborn.

OBJECTIVE: To compare the efficacy of once daily gentamicin administration to the conventional twice daily dosage schedule by estimation of serum gentamicin concentrations (SGC) in neonates. DESIGN: Randomized controlled trial. SETTING: Medical college hospital. SUBJECTS: Seventy three neonates of gestational age>32 weeks at risk or with clinical features of sepsis. METHODS: The subjects were divided into preterm and term groups. Babies in each of these groups were randomized to receive a single daily dose (4 mg/kg) or a twice daily dose (2.5 mg/kg) of injection gentamicin intravenously. Trough and peak SGC were estimated half an hour prior and one hour after the second dose. Statistical analysis was done using the equivalence method. RESULTS: In preterm as well as term babies, the mean peak and trough gentamicin levels were comparable in the two regimens. There is statistically significant evidence to show that the effect of once daily and twice daily dosage is similar. CONCLUSION: Once daily gentamicin administration is as effective as twice daily therapy and would be more cost effective.