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Biomedical subjects

R Boulieu

Publications and source records attributed to R Boulieu.

71 records · Page 4Linked to original sources

Comparison of red cell transfusion and polyethylene glycol-modified adenosine deaminase therapy in an adenosine deaminase-deficient child: measurement of erythrocyte deoxyadenosine triphosphate as a useful tool.

The effect of red cell transfusion and polyethylene glycol-modified adenosine deaminase therapy on biochemical abnormalities, clinical status, and immunologic function in an adenosine deaminase-deficient child was investigated. After red cell transfusions, erythrocyte deoxyadenosine triphosphate (dATP) concentrations decreased about 95% and were closely related to adenosine deaminase activities; deoxyadenosine diphosphate concentrations decreased only approximately 30%. The evolution of dATP levels was also closely related to the improvement in clinical status of the patient. However, immune function was not restored. After polyethylene glycol-modified adenosine deaminase therapy, the concentration of erythrocyte dATP decreased to undetectable levels correlated with an increase of T lymphocyte counts and an increase of lymphocyte responses to mitogens. Immune functions were restored only when dATP levels were below 15 mumols/L. It appears that red cell transfusion therapy is not sufficiently effective to reduce and maintain erythrocyte dATP levels at values compatible with normal immune function. On the contrary, polyethylene glycol-modified adenosine deaminase therapy is a suitable treatment to reduce dATP levels to near undetectable values, allowing the immune function to be restored, dATP measurement is a very useful tool for monitoring and evaluating the degree of efficiency of therapy in adenosine deaminase deficiency.

Adenosine Deaminase↗

Homogentisic acid determined in biological fluids by HPLC.

In this rapid, specific, and sensitive high-performance liquid-chromatographic method of analysis for homogentisic acid in biological fluids, homogentisic acid is separated on a column of Nucleosil CN. This method, which we applied to the diagnosis of three cases of alcaptonuria, represents a suitable analytical tool for the diagnosis of alcaptonuria.

Adult↗

[Implication of lipid peroxidation in triethyltin poisoning in the rat].

Triethyltin intoxication induces, in vivo, a significant increase of malondialdehyde concentration in rat brain. After treatment with a Ginkgo biloba extract, an extract known to possess antiedematous and radical scavenging properties, the malondialdehyde level in the brain is significantly decreased. This suggests that a lipid peroxidation process is associated with cerebral oedema induced by triethyltin.

Animals↗

[Use of thiopental in man. Determination of this drug and its metabolites in plasma and urine by liquid phase chromatography and mass spectrometry].

Thiopental is an anaesthetic drug which is currently used for cerebral resuscitation. In this last indication the drug is administrated at high doses over a period of several days. Under clinical trials thiopental and two metabolites namely 5 ethyl-5 (1' methyl-3' hydroxy-butyl) 2 thiobarbituric acid and 5 ethyl-5 (1' methyl-3' carboxy-propyl) 2 thiobarbituric acid have been determined by high performance liquid chromatography and mass spectrometry. In human plasma high concentrations of thiopental and 5 ethyl-5 (1' methyl-3' hydroxy-butyl) 2 thiobarbituric acid and a lower concentration of 5 ethyl-5 (1' methyl-3' carboxy-propyl) 2 thiobarbituric acid have been found. In urine samples these metabolites are excreted in large and approximately equal quantities, whereas small amounts of thiopental were recovered.

Adult↗

Liquid-chromatographic measurement of purine nucleotides in blood cells.

In this anion-exchange "high-performance" liquid-chromatographic method of analysis for purine nucleotides, the nucleotides are separated with high efficiency and selectivity on a weak anion exchanger (Hypersil APS 2, 3-micron particle size) by elution with a gradient of eluent pH and concentration. Applying this method to analysis for these compounds in human blood cells, we determined them in a patient with adenosine deaminase deficiency who was treated with a bone-marrow transplantation, finding that the transplantation did not entirely correct the patient's abnormalities of purine metabolism.

Adenosine Deaminase↗

Hypoxanthine and xanthine concentrations determined by high performance liquid chromatography in biological fluids from patients with xanthinuria.

In the present paper, we report the biochemical features of six cases of xanthinuria. For these studies, the concentrations of hypoxanthine and xanthine have been measured in urine, plasma and also erythrocyte samples by a rapid, sensitive high performance liquid chromatographic (HPLC) method. The analyses of plasma and erythrocyte samples require a very sensitive method relative to physiological concentrations and rigorous sampling conditions in order to achieve accurate results. In the cases reported in the literature, total oxypurine levels (hypoxanthine + xanthine) have been generally measured in plasma and urine by an enzymatic spectrophotometric method. In our studies, using HPLC, we found that xanthine is the major oxypurine compound in plasma and urine samples from patients with xanthinuria. In erythrocytes, a biological sample which has not been analysed up to now, we found that xanthine is present at high concentrations whereas it is not detectable in erythrocytes from healthy subjects.

Adult↗

Hypoxanthine and xanthine levels determined by high-performance liquid chromatography in plasma, erythrocyte, and urine samples from healthy subjects: the problem of hypoxanthine level evolution as a function of time.

The levels of hypoxanthine and xanthine are determined in plasma, erythrocyte, and urine samples by a reverse-phase high-performance liquid chromatographic (HPLC) method. The hypoxanthine concentration increases in erythrocyte and plasma samples when whole blood is stored at room temperature between sampling and centrifugation. Furthermore, the hypoxanthine concentration increases in erythrocyte samples when they are kept apart at room temperature before analysis, whereas the plasma hypoxanthine level remains constant. This result proves an endogenous formation of hypoxanthine in erythrocytes with time, at room temperature. These studies show the necessity of rigorous conditions for the collection, transport, and treatment of blood samples. In order to achieve accurate results, the blood must be centrifuged immediately after collection. The erythrocyte and plasma samples must be stored frozen until deproteinization and HPLC analysis. Under these conditions, the concentrations of hypoxanthine and xanthine in plasma are 2.5 +/- 1 and 1.4 +/- 0.7 microM, respectively. In erythrocyte samples, hypoxanthine concentration reaches 8.0 +/- 6.2 microM.

Chromatography, High Pressure Liquid↗

High-performance liquid chromatographic determination of hypoxanthine and xanthine in biological fluids.

A rapid and selective reversed-phase high-performance liquid chromatographic method for the simultaneous determination of hypoxanthine and xanthine in biological fluids was developed. The identification of hypoxanthine and xanthine was confirmed by xanthine oxidase reaction. This method was applied to the investigation of purine metabolism in subjects with xanthine oxidase deficiency or gout. Hypoxanthine concentrations three to ten times higher than those determined in plasma were found in erythrocyte samples from normal subjects and from patients with xanthine oxidase deficiency or hyperuricemia under allopurinol therapy.

Allopurinol↗

Pharmacokinetics of midazolam and its main metabolite 1-hydroxymidazolam in intensive care patients.

The pharmacokinetics of midazolam and of its main metabolite, 1-hydroxymidazolam, were investigated in intensive care patients after intravenous bolus of 0.2 mg/kg followed by a 0.1 mg/kg/h intravenous infusion of midazolam over 2 hours. A wide interpatient variability of the main pharmacokinetic parameters of midazolam was found. The mean values of elimination half life and volume of distribution, 4.5 +/- 5.4 h and 1.7 +/- 0.7 l/kg respectively, were higher than those reported in healthy subjects. Total plasma clearance was significantly increased in patients taking drugs that induce hepatic metabolism. Significant concentrations of the unconjugated form of 1-hydroxymidazolam were recovered in plasma. The volume of distribution and the elimination half life of the metabolite were higher than those of the parent drug. These results show that 1-hydroxymidazolam might contribute to the pharmacodynamic effect of midazolam and consequently must be taken into account during pharmacokinetic and pharmacodynamic studies.

Adolescent↗

Evaluation of a bayesian pharmacokinetic program for phenytoin concentration predictions in outpatient population.

The present work evaluates the performances of a Bayesian program (PKS) for phenytoin concentration predictions in an outpatient population. The retrospective study involved 19 epileptic adults receiving oral phenytoin. The program was used to predict estimated serum concentrations from 0, 1, 2 or 3 feedback concentrations. Measurements of prediction bias (ME) decreased as soon as one steady-state concentration (Css) was used for estimations. Precision (MAE) was significantly improved with 1 Css and was even better and stable with 2 and 3 Css. Likewise, RMSE (composite of bias and precision) regularly decreased when the number of Css used increased. On a clinical way, 12% of the estimations were unacceptable (prediction error > 5 mg/l) with 1 Css and less than 3% with 2 or 3 Css. This number of rejected estimations increased to 45% when no feedback concentration was used. Besides, the program was able to predict important rises of serum levels in spite of relative low increase of the dose when 1 Css at least was known. Thus, the phenytoin dosing program has acceptable performances when at least 1 Css is known, and represents a potential tool to assist the clinician in the particular condition of outpatient population.

Adolescent↗

Implementation of a quality system in a therapeutic drug monitoring laboratory.

The concept of quality assurance is emerging in public and private clinical laboratories in France following the introduction of decrees on Hospital Accreditation procedure. We report here the methodology used for the implementation of a quality system in a Therapeutic Drug Monitoring laboratory. The quality manual, which represents the basis of the quality system, was drafted according to the following methodology: Step 1--study of the requirements of ISO 9001 Standard; Step 2--analysis and synthesis of the European EN 45001 Standard and French regulation GBEA system respectively, compared with the 20 headings of the ISO 9001 Standard; Step 3--elaboration of the quality manual on the basis of steps 1 and 2 and relating to: laboratory and staff organization, quality document management, quality planning relating to specific activities relevant to projects or contracts on drug monitoring and pharmacokinetic studies, and operating procedures. The implementation of a quality system in a public hospital laboratory may be considered as a means of improving the laboratory organization and management.

Accreditation↗

[Polyethylene glycol-adenosine deaminase: a new adenosine deaminase deficiency therapy. Value of deoxyadenosine triphosphate determination for therapeutic monitoring].

The effect of polyethylene glycol-adenosine deaminase (PEG-ADA) therapy on biochemical, immunological and clinical abnormalities in an ADA-deficit child with severe combined immunodeficiency has been studied. Following PEG-ADA therapy, total lymphocytes, lymphocyte subsets (CD3, CD4 and CD8) and the response of lymphocytes to non specific mitogens increase significantly. The improvement of immunological functions is closely related to a decrease of erythrocyte deoxyadenosine triphosphate (dATP) concentrations. This study shows that PEG-ADA therapy is sufficiently effective to reduce and to maintain erythrocyte dATP levels at values compatible with normal immune functions. PEG-ADA represents an important progress for the treatment of ADA deficiency associated with severe combined immunodeficiency disease.

Adenosine Deaminase↗