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Biomedical subjects

J M Prévosto

Publications and source records attributed to J M Prévosto.

4 recordsLinked to original sources

Chloroquine self-treatment and clinical outcome of cerebral malaria in children.

Chloroquine is widely used as self-medication for presumptive treatment of malaria despite the existence of parasite resistance to the drug. Recent studies suggest that tumour necrosis factor-alpha (TNF-alpha) overproduction probably has a causal association with poor outcome in cerebral malaria. In addition, chloroquine has been shown to have inhibitory action on TNF-alpha synthesis. The present study aimed at evaluating chloroquine/TNF-alpha interaction in 90 children hospitalized for severe malaria in a malaria-endemic zone. TNF-alpha and chloroquine varied in the same range on admission, but there was an inverse correlation between the two: the higher the chloroquine level, the lower the TNF-alpha level. Parasite resistance to chloroquine in vitro was high. The clinical course in the patients was uneventful, save for two fatal cases and one survivor with neurological sequela. The above data suggest beneficial effects of chloroquine self-medication with respect to anti-TNF-alpha action. Rational use of this tool should be encouraged.

Adolescent↗

New solid-phase extraction for an improved high-performance liquid chromatographic procedure for the quantitation of halofantrine and monodesbutylhalofantrine in blood or plasma.

A rapid, accurate, and sensitive high-performance liquid chromatographic (HPLC) method, with fluorimetric detection, for the simultaneous measurement of halofantrine and desbutylhalofantrine in human plasma or whole blood is described. Sample preparation involved protein precipitation, followed by an efficient solid-phase extraction on a C8 cartridge. Analytes were isolated from 1 ml of the biological fluids and recovered by a 2% acetic acid in ethyl acetate solution. Chromatographic separation was carried out on a LiChrospher 60 RP select B, C8 bonded phase (5 microns particle size, 25 cm x 4 mm I.D.) using a mobile phase of water-acetonitrile (35:65, v/v) containing triethylamine (1%) and adjusted to pH 4 with orthophosphoric acid. The total run time was 14 min. Relative standard deviations of the intra-and inter-assay precisions were less than 5.9%. Assumption of linearity was investigated by studying the y-residuals and by ANOVA (analysis of variance). Because of the wide range of calibration (0.1 to 2.0 microgram/ml) variances were non-homogeneous (Hartley's test) and the weighted regression line was computed in order to allow pharmacokinetic studies. Accuracy was tested using a t-statistic. Limits of decision, detection and quantification were realized from an analysis of the blanks. Application of the method to clinical specimens was demonstrated.

Antimalarials↗

Determination of doxycycline in human plasma and urine samples by high performance liquid chromatography. Application for drug monitoring in malaria chemoprophylaxis.

A reverse-phase high performance liquid chromatographic method with ultraviolet detection is described for the measurement of doxycycline in human plasma and urine. After liquid-solid extraction on a Bond Elut C18 cartridge, doxycycline and demeclocycline (internal standard) are separated on a Novapak C18 column by isocratic elution. The mobile phase consists of acetonitrile-oxalate buffer, pH 2.3 (25:75; v/v). The eluent is monitored with an ultraviolet detector at 355 nm. The lower limit of quantification in plasma is close to 25 ng/ml. No chromatographic interference can be detected from endogenous compounds, tetracycline group antibiotics or antimalarial drugs. The method is accurate and precision is good with inter- and intra-assay relative standard deviations lower than 6.7%. The chromatographic procedure takes 8 minutes and can be used for therapeutic drug monitoring, clinical and pharmacokinetic studies.

Anti-Bacterial Agents↗