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Biomedical subjects

F Guyon

Publications and source records attributed to F Guyon.

At least 19 recordsLinked to original sources
PubMed2006

Sensitive quantification of diphemanil methyl sulphate in human plasma by liquid chromatography-tandem mass spectrometry.

A simple detection system with a high-performance liquid chromatography (HPLC) with positive ionisation-tandem mass spectrometry (ESI-MS/MS) for determining diphemanil methylsulphate (DMS) levels in human plasma using 4-diphemanylmethylene,1-methylpiperidine as an internal standard (I.S.), is proposed. The acquisition was performed with the multiple reactional monitoring (MRM) mode, by monitoring the transitions: m/z 278>262 for DMS and m/z 263>247 for the I.S. The method involved a simple single-step deproteinisation with acetonitrile. The analyte was chromatographed on a Zorbax C18 reversed-phase chromatographic column by isocratic elution with 10(-3)M ammonium acetate and 10(-3)M hexafluorobutyric acid, adjusted to pH 7.0 with ammoniac/acetonitrile (40/60, v/v). The results were linear over the studied range (0.5-50.0 ng mL(-1)) and the total analysis time for each run was 10 min. The mean extraction apparent recoveries expressed at the 95% intervals of confidence were 94-104% for DMS and 92-106% for the I.S. The intra- and inter-assay precisions were 4.6-8.4% and 2.9-10.6%, respectively. The limit of quantification was 0.15 ng mL(-1). The devised assay was successfully applied to the residual concentrations monitoring in infant.

Chromatography, High Pressure Liquid↗
PubMed2006

Stability studies of ionised and non-ionised 3,4-diaminopyridine: hypothesis of degradation pathways and chemical structure of degradation products.

3,4-Diaminopyridine is used to treat some symptoms met in Lambert-Eaton myasthenia syndrome. It was shown efficient to reduce a form of variable muscle weakness and fatigability typical of the disease and correlated to a block of acetylcholine release. In France, 3,4-diaminopyridine is nowadays given to patients under capsules form and the status of hospital preparation. Whatever the diluant used in the formulation, the stability period could not exceed 12 months. Preliminary studies were made on a salt form in order to test the influence of various stress factors and determine if there is interaction between them. From this study, the most influent stress condition, presence of hydrogen peroxide, was selected and a comparative study was performed to compare the stability of molecular and salt species. Solutions of each species were exposed to 5 or 15% of hydrogen peroxide and analyzed at 8, 24, 72 and 216 h of degradation by HPLC-UV. Fractions of detected impurities were purified and collected by semi-preparative HPLC-UV and analyzed by HPLC-UV-ESI-MS and IR spectroscopy in order to determine their structure hypotheses. Theses experiments demonstrate that the salt species were more stable under oxidative stress condition than molecular species. The two main degradation products were collected and identified as 4-amino, 3-nitropyridine and 3,4-diaminopyridine-N-oxide when the molecular form was degraded whereas only 4-amino, 3-nitropyridine was found in less quantity in the salt solutions. Nitrogen pyridine and pyridine amine could not easily be oxidized by hydrogen peroxide in salt comparatively to molecular species due to the lone pair of electron engaged in a bound with hydrogen in the first case and by resonance change of the pyridine in the second case. This modification of structure promoted different pathways of degradation for the salt form which are more dependent of energy. Owing to the better stability of the salt species, a new pharmaceutical form containing it was developed to assess its stability under ICH standard conditions allowing an industrial manufacture of this drug.

4-Aminopyridine↗
PubMed2006

[Perinatal prognosis of pregnancies complicated by placental chronic intervillitis].

UNLABELLED: SUBJECT. Massive Chronic Intervillositis is an infrequent inflammation lesion of the placenta, characterized by lymphohistiocytic intervillous infiltration, associated with fibrinoid deposition. The purpose of this study was to evaluate the perinatal outcome of pregnancies complicated by such lesions. MATERIAL AND METHODS: We conducted a descriptive retrospective multicentric analysis of a series of pregnancies for which placenta or products of abortion were analyzed between January 1995 and September 2005, at the University Hospital of Bordeaux. After re-examining the histology slides, we performed a semi-quantitative graduation of the cell infiltration and fibrinoid deposition. RESULTS: Twenty-five women were included (one twin-pregnancy and two histologic recurrences). We found three spontaneous abortions before 22 weeks, four intrauterine fetal deaths and three neonatals deaths. Seven of eight elective inductions pregnancies, were performed for intrauterine growth restriction less than 2.5 percentile. The rate of pregnancy loss was 55% and the perinatal mortality was 29%. 77% of fetuses are small for gestational age. Three mothers were pre-eclamptic. 21% of the fetuses had a congenital malformation. Only 32% of the fetuses were alive one week after birth. Histologically, 25% were associated with lesions of Villitis of Unknown Etiology. 77% of the cell infiltration was grade 3 and seemed to be correlated with severe growth restriction. We describe 3 cases of antenatal diagnosis of Chronic Intervillositis, realised after immunofixation on chorionic villous sampling. CONCLUSION: Massive Chronic Intervillositis is a recurrent lesion with a poor prognosis complicated by spontaneous abortion, intrauterine growth restriction and perinatal fetal death. Currently, there is no treatment. Chorionic villous sampling in severe growth restriction might be useful in order to obtain at the same time the fetal karyotype and an histological probe of the placenta.

Adult↗
PubMed2004

Determination of A 3,4-diaminopyridine in plasma by liquid chromatography with electrochemical detection using solid-phase extraction.

In order to quantify a small amount of a drug, 3,4-diaminopyridine (3,4-DAP), in animal plasma samples, an analytical method was developed. It involved an extraction of 3,4-DAP and phenylephrine, used as internal standard (IS), from plasma with solid-phase extraction (SPE) on C18 cartridges. This analytical method is a hyphenated technique based on high-performance liquid chromatography with electrochemical detection (HPLC-EC) whose purpose is to obtain first a sensitive method and second a satisfying separation between 3,4-DAP and phenylephrine. The analytical method is accurate, specific, and linear between 10 and 500 g of 3,4-DAP per litre. The recovery of 3,4-DAP is estimated at 70.8% with a 95% confidence interval of (66.0 -75.6%). Intermediate precision was evaluated on three quality control samples; the intra-day precision was estimated at 13.5, 9.1, 7.8% and the inter-day precision at 17.9, 8.4, 9.3%. The limit of quantification of the method was evaluated at 10 g l-1. First toxicokinetic parameters determined on dogs plasma samples after one 3,4-DAP oral administration of 1 mg kg-1 were: Cmax=395.7 microg l-1; Tmax =15 min; t1/2=113.6 min; Clearance/F=16.8 ml kg-1 min-1 and Vd/F=2.7 l kg -1.

4-Aminopyridine↗
PubMed2004

Differential expression of the nm23 genes in the developing human trophoblast.

NDP kinases are the non-specific enzymes which catalyse the synthesis of the NTPs through a transfer reaction using ATP as phosphoryl donor. In addition to their enzymatic activity, they display other not yet explained functions related to cell growth, differentiation and apoptosis, embryonic development, tumour progression and metastasis. In this study, the expression patterns of the three highly related NDP kinases A, B and C isoforms were investigated in the developing human trophoblast. Both NDP kinase A and B were found to be primarily present in the villous and extravillous cytotrophoblasts, while NDP kinase C was found almost exclusively in the syncytiotrophoblast layer. This suggests that NDP kinase A and B could be a marker for the mononuclear stage of differentiation of villous trophoblasts, while NDP kinase C could be a marker of the syncytiotrophoblast layer.

Embryonic and Fetal Development↗
PubMed2003

Comparative study of matrix-assisted laser desorption/ionization and gas chromatography for quantitative determination of cocoa butter and cocoa butter equivalent triacylglycerol composition.

The triacylglycerol (TAG) composition study of cocoa butter (CB) and cocoa butter equivalents (CBEs) has been performed by gas chromatography (GC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). These two techniques provided comparable results. The advantage of the MALDI technique was the detection of each compound comprising the triacylglycerol classes (Cn). Moreover, comparison of the data obtained by these two techniques indicated that TAG relative percentages could be obtained quantitatively with the MALDI technique. These techniques have been applied for the composition determination of CB + CBE mixtures. Encouraging results showed that it is possible to quantify an admixture containing as little as 4% of CBE.

Africa↗
PubMed2003

[Importance of thrombocytopenia for the management of HELLP syndrome: a report of 104 cases].

OBJECTIVES: To evaluate the importance of thrombocytopenia in the management of HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count). MATERIALS AND METHODS: This retrospective study included all patients with HELLP syndrome treated in the three departments of the Pellegrin Maternity Hospital in Bordeaux, between January 1993 and December 2001. One hundred and four patients were included and were divided into two groups according to the severity of thrombopenia: group 1 (platelet count<50000/mm(3)) and group 2 (50000<platelet count/mm(3)<100000). RESULTS: In group 1 complications occurred in 79% of cases and thrombocytopenia put patients at-risk for serious or life-threatening bleeding complications mainly in this group. CONCLUSION: It is crucial to class patients according to severity of thrombocytopenia, on admission. Termination of pregnancy should be considered for patients included in group 1. The other patients are best managed conservatively (depending on gestational age).

Adult↗
PubMed2002

New procedure for selective extraction of polycyclic aromatic hydrocarbons in plants for gas chromatographic-mass spectrometric analysis.

A new solid-phase extraction method for the clean-up and the quantitation by GC-MS of regulated polycyclic aromatic hydrocarbons (PAHs) from lettuce was developed and the experimental conditions were optimized. After ultrasonic extraction using toluene and saponification of samples, a clean-up of extracts through solid-phase extraction was performed. Samples were finally analyzed by gas chromatography-mass spectrometry (GC-MS) using an internal deuterated standard. Saponification by KOH in methanol-water (80:20) was successful allowing a good elimination of the interfering chlorophylls from the extracts containing the PAHs. The average recovery of the 16 regulated PAHs was 70, 74, 79 and 89%, respectively, for naphthalene, acenaphthylene, acenaphthene and chrysene and higher than 94% for the others.

Gas Chromatography-Mass Spectrometry↗
PubMed2002

LC determination of diphemanil methylsulfate: application to stability study of stored pharmaceutical formulations.

Diphemanil methylsulfate (DMS) is a synthetic antimuscarinic agent classically used in infants for vagal hypertonia-related symptoms. A normal-phase, isocratic liquid chromatographic method was developed for the quantitative determination of DMS in bulk drugs and in pharmaceutical forms. The method has been completely validated and robustness of this method has been studied. The limit of detection (LOD) for DMS impurities namely, impurity 1 and 2 were found to be 11 and 46 ng/ml. The limit of quantitation (LOQ) was found to be 49 and 139 ng/ml for impurity 1 and 2, respectively. The stability studies have been performed for 2 and 10 mg DMS tablets subjected at various temperatures: 25 degrees C (long term storage condition) and 40 degrees C (accelerated storage condition) for 18 and 6 months, respectively. At 25 degrees C, the samples were found to be stable for the study period. At 40 degrees C, 2 and 10 mg DMS tablets showed degradation up to 5 and 10% over a 6-month period.

Algorithms↗
PubMed2001

Speciation of arsenic and selenium compounds by ion-pair reversed-phase chromatography with electrothermic atomic absorption spectrometry. Application of experimental design for chromatographic optimisation.

An off-line system is proposed consisting of ion-pair reversed-phase liquid chromatography, collections of fractions at the outflow of the column and furnace atomic absorption spectrometry. The so-called system allowed determination of both arsenic and selenium species mainly found in the environment and in mammals (arsenite, arsenate, monomethylarsonate, dimethylarsinate, selenite, selenate, selenocystamine, selenocystine, selenomethionine and selenoethionine). In order to study the retention behaviour of these compounds and to estimate the optimal conditions for the chromatographic separation, central composite designs were used to evaluate the influence of the eluent parameters such as pH, tetrabutylammonium phosphate (TBA) concentration and sodium hydrogenphosphate amounts. The retention factors of each species and the selectivity were established as response criteria. Response surfaces and isoresponse curves were drawn from the mathematical models and enabled one to determine the optimal conditions and to visualise the method robustness. The predicted optimal zone was situated at pH 5.5-6.5, 4.0 mM Na2HPO4 and 3.0-4.0 mM TBA. Regression models suggested linearity for the studied compounds in the range 25-200 microg selenium and arsenic per litre investigated.

Arsenic↗
PubMed2001

XAS applied to pharmaceuticals: drug administration and bioavailability.

We present selected XAS applications, focused towards practical hospital questions of drug administration and bioavailability, where the technique is driven up to its limits of sensitivity. i) XAS was used to study the interactions between the components of parenteral nutrition solutions, in particular zinc and aminoacids, possibly modifying their bioavailability. ii) We studied by EXAFS a series of binary and ternary copper-aminoacid complexes, in view of the development of an efficient oral drug against copper deficiencies in Menkes disease. iii) EXAFS and XANES analysis allowed us to characterise the solution form of a new arsenic containing drug against leukaemia. In parallel to the XAS measurements, we analysed trace elements levels along patients' hairs, using X-ray fluorescence excited by synchrotron radiation. The measurements along the hair allow for a monitoring of essential trace elements during therapy.

Arsenic Trioxide↗
PubMed2001

Stability of stored methacholine solutions: study of hydrolysis kinetic by IP-LC.

Methacholine chloride is a powerful cholinergic bronchoconstrictor agent used during bronchial airway hyper-responsiveness diagnosis. Methacholine is susceptible to hydrolysis in aqueous solutions in acetic acid and beta-methylcholine. In the present work, kinetics of hydrolysis with different solvents (water and phosphate-buffered saline (PBS) pH 7.4) at different temperatures have been studied using a newly developed high-performance liquid chromatography. At 4 degrees C, kinetic determination of hydrolysis in methacholine chloride solutions (50 mg/ml) shows no hydrolysis in either aqueous or phosphate-buffered solutions over a 40-day period. At 30 degrees C, concentration of unbuffered methacholine chloride solutions remained unchanged, but buffered methacholine chloride solutions have degradation up to 5.5% over a 40-day period. At 40 degrees C, concentration of unbuffered methacholine chloride has degradation up to 5% and buffered methacholine chloride solutions have degradation up to 10% over a 40-day period. Methacholine chloride solutions are susceptibly to be used in hospital pharmacy at different concentrations. We have studied pH and osmolality for methacholine solutions prepared with different diluents potentially used in hospital pharmacies, i.e. deionized water, 0.9% NaCl and PBS pH 7.4. We have demonstrated that methacholine solutions prepared with deionized water at 50 mg/ml and diluted with PBS pH 7.4 from 5 to 40 mg/ml are isoosmotic and potentially available for inhalation tests to measure non-specific bronchial hyper-responsiveness.

Bronchoconstrictor Agents↗
PubMed2001

Application of central composite designs for optimisation of the chromatographic separation of monomethylarsonate and dimethylarsinate and of selenomethionine and selenite by ion-pair chromatography coupled with plasma mass spectrometric detection.

Central composite designs (CCDs) were used in the study of the ion-pair chromatographic separation of arsenic and selenium species in tap water: monomethylarsonate, dimethylarsinate, selenomethionine and selenite. The ternary eluent consisted of tetrabutylammonium phosphate (TBA), sodium hydrogenphosphate (Na2HPO4) and 1% acetonitrile. CCD allowed the investigation of the influence of the eluent parameters, which varied from 0.5 to 4.2 mmol l-1 Na2HPO4, 0.5 to 4.2 mmol l-1 TBA and pH 4.9 to 8.2, on the capacity factors (k') of arsenic and selenium compounds. Furthermore, another mathematical model that permitted the variation of the chromatographic selectivity of species, computed from their retention data to be followed, was investigated. This showed the ability to locate the optimum conditions within the experimental design, so that arsenic and selenium species could be simultaneously quantified with good efficiency and resolution. A comparison between the predicted and the experimental response values was made in order to assess the prediction quality of the model. Response surfaces and isoresponse curves obtained from the mathematical models allowed the determination of the optimum chromatographic conditions and the robustness of the method. The predicted optimum zone allowing satisfactory determination of both arsenic and selenium compounds was pH 5.5-6.5, 2.5 mmol l-1 Na2HPO4 and 3.0-4.0 mmol l-1 TBA.

Journal Article↗
PubMed2000

On-line reversed-phase liquid chromatography hydride generation emission spectrometry: speciation of arsenic in urine of patients intravenously treated with As2O3.

Hydride generation inductively coupled plasma-atomic emission spectrometry (HG ICP-AES) was used as a continuous detection system for the determination of arsenic in the eluate from a high-performance liquid chromatographic (HPLC) system. Four arsenic species [arsenite As(III), arsenate As(V), monomethylarsonate (MMA), and dimethylarsinate (DMA)] present in the urine samples of patients treated intravenously with arsenite, were analyzed separately by HPLC-HG-ICP-AES using a non-polar C18 column. This analytical method allowed the sensitive determination of the arsenic species in the submicrogram per liter range. Urine samples collected on different days after arsenite administration were found to contain arsenite predominantly--monomethylarsonate and dimethylarsinate were also detected.

Arsenic↗
PubMed2000

Permeation liquid membrane metal transport: studies of complex stoichiometries and reactions in Cu(II) extraction with the mixture 22DD-laurate in toluene/phenylhexane

The role of lauric acid (LAH) in the transport of copper(II) through a permeation liquid membrane (PLM) comprising 1,10-didecyldiaza-18-crown-6 (22DD) and lauric acid (ratio 1:1) in 1:1 v/v toluene/phenylhexane has been investigated by determining the stoichiometry of metal extraction and of the metal complex formed in the organic phase by performing 1H NMR and liquid/liquid and liquid/membrane extraction measurements. In the absence of copper(II), the 1H NMR data suggest that there is a strong interaction between the proton of LAH and the nitrogen of the 22DD macrocycle but no interaction between the aliphatic long chains of LAH and 22DD. Thus, in the organic solution, the two compounds are associated as (22DD-H)(+)-LA-, the laurate being away from (22DD-H)+. The signal intensity of the acidic proton was found to decrease when the metal Pb(II) was incorporated by the carrier after its extraction from the aqueous phase. Additionally, liquid/liquid as well as liquid/membrane extraction results reveal that Cu(II) extraction proceeds via the loss of two protons from the organic phase. The Cu(II) is found to be located in the 22DD cavity and the stoichiometry of the complex in the organic phase is (22DD-Cu)(2+)-2LA-. Metal extraction is governed by 22DD and laurate acts only as counteranion. An unexpected feature was observed in the liquid/liquid extraction which was that, at low 22DD and LAH concentrations, the slope for log(Kp) = f(pH) was 2 whereas it was much lower at high carrier concentration. This unexpected result seems to stem from impurities present in 22DD: only 0.1 mol% of impurity can indeed influence the exchange ratio of Cu(II) and H+. This type of anomaly, however, is not found in the normal procedure of liquid/membrane extraction possibly due to the lower carrier/metal molar ratio which is used in the classical PLM conditions.

Journal Article↗
PubMed2000

MappetShow: non-linear visualization for genome data.

The genome mapping projects now produce very dense maps with up to several thousands of markers per chromosome. Besides synteny plays a increasing role in mapping: enrichment of poor maps from the maps of close genomes (in terms of evolution) is a high-reward task. We propose a map viewer adapted to this situation: MappetShow gives a clear view of very dense maps and compares efficiently several maps. MappetShow is based on non-linear viewing and is written in Java. A map description language isolates the software from the data sources. This software was easily used on data coming from as different sources as an Object Request Broker, an Object-Oriented Database, or a flat data stream. MappetShow can be browsed at the URL http:¿www.infobiogen.fr/services/Mappet. More generally we discuss how to use the non-linear viewing concept in molecular biology data visualization.

Chromosome Mapping↗
PubMed2000

[Maternal transport to the Bordeaux University Hospital: a retrospective study of 263 cases (1996-1998)].

OBJECTIVES: To describe a population of high risk pregnancies transported to a regional perinatal care centre (level III) and to analyze the advantages and limitations of the organization of this perinatal care network. METHODS: Retrospective study of 263 patients transported to the University Hospital of Bordeaux between September 1996 and September 1998. RESULTS: Maternal transport mainly came from the Gironde department (53%) and from level I care hospitals (66%). The rate of multiple pregnancies was 17%. Principal indications were preterm labor with or without rupture of fetal membranes (52%) and preeclampsia with or without intrauterine growth restriction (28%). The rate of returns to the referring care centre was 2%. The mean term at delivery was 32 WA. Forty-one percent of patients delivered within 24 hours of transport. The rate of caesarean sections was 55%. There were 303 live births. The mean duration of hospitalization of the neonates was 28 days. The rate of perinatal mortality was 6.2%. Among the 96 pregnancies beyond 32 WA, 17 (6.5%) could have been transported to some level IIb care hospitals, nearby the patient's residence, without changing maternal and neonatal prognosis. Neonatal mortality was not significantly different for maternel transport (18%) or neonatal transport (14%) in the group of premature infants born prior to 31 WA in our study. CONCLUSION: Our organization is currently trying to improve transport management (non-emergency situations, collaboration of level II care hospitals) and to increase the rate of returns to the referring care centres.

Adolescent↗