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Biomedical subjects

P Hubert

Publications and source records attributed to P Hubert.

At least 55 records · Page 3Linked to original sources
PubMed2001

Exposure of red bone marrow to ionising radiation from natural and medical sources in France.

This paper presents a review of available data on the average level of equivalent dose to the red bone marrow in France, due to natural and some medical exposures. The sources of exposure to ionising radiation which were studied are medical examinations involving x-rays (diagnostic radiology), inhalation of radon and thoron, cosmic irradiation, terrestrial irradiation and intakes of natural radionuclides. This review is based, where possible, on specific data for France. The influence of age on exposure levels is studied when data are available. The total equivalent dose to the red bone marrow is estimated at 2.4 mSv year(-1), 2.7 mSv year(-1) and 5.4 mSv year(-1) respectively for adults (> or =18 years old), children (3-17 years old) and infants (0-1 year old). The high level of exposure for infants is explained by the important contribution of 210Po. The average equivalent dose to the red bone marrow for adults is also compared with the average committed effective dose due to the same exposure sources. The importance of medical exposure and natural exposure due to intake of natural radionuclides emphasises the importance of obtaining more information about these sources of exposure.

Adolescent↗
PubMed2001

Symptoms of anxiety and depression in family members of intensive care unit patients: ethical hypothesis regarding decision-making capacity.

OBJECTIVE: Anxiety and depression may have a major impact on a person's ability to make decisions. Characterization of symptoms that reflect anxiety and depression in family members visiting intensive care patients should be of major relevance to the ethics of involving family members in decision-making, particularly about end-of-life issues. DESIGN: Prospective multicenter study. SETTING: Forty-three French intensive care units (37 adult and six pediatric); each unit included 15 patients admitted for longer than 2 days. PATIENTS: Six hundred thirty-seven patients and 920 family members. INTERVENTIONS: Intensive care unit characteristics and data on the patient and family members were collected. Family members completed the Hospital Anxiety and Depression Scale to allow evaluation of the prevalence and potential factors associated with symptoms of anxiety and depression. MEASUREMENTS AND MAIN RESULTS: Of 920 Hospital Anxiety and Depression Scale questionnaires that were completed by family members, all items were completed in 836 questionnaires, which formed the basis for this study. The prevalence of symptoms of anxiety and depression in family members was 69.1% and 35.4%, respectively. Symptoms of anxiety or depression were present in 72.7% of family members and 84% of spouses. Factors associated with symptoms of anxiety in a multivariate model included patient-related factors (absence of chronic disease), family-related factors (spouse, female gender, desire for professional psychological help, help being received by general practitioner), and caregiver-related factors (absence of regular physician and nurse meetings, absence of a room used only for meetings with family members). The multivariate model also identified three groups of factors associated with symptoms of depression: patient-related (age), family-related (spouse, female gender, not of French descent), and caregiver-related (no waiting room, perceived contradictions in the information provided by caregivers). CONCLUSIONS: More than two-thirds of family members visiting patients in the intensive care unit suffer from symptoms of anxiety or depression. Involvement of anxious or depressed family members in end-of-life decisions should be carefully discussed.

Anxiety↗
PubMed2000

Determination of the enantiomers of 3-tert.-butylamino-1,2-propanediol by high-performance liquid chromatography using mass spectrometric detection.

The chiral synthesis of beta-blockers such as (S)-timolol requires a sensitive analytical method for the enantioseparation of its intermediate, 3-tert.-butylamino-1,2-propanediol, in the ng/ml range. The method developed is based on on-line normal-phase LC-MS-MS using a chiral stationary phase and an atmospheric pressure chemical ionization (APCI) interface. The MS detection of 3-tert.-butylamino-1,2-propanediol was first optimized with a pneumatically-assisted electrospray interface (ionspray). The APCI interface was then selected for LC-MS-MS because of the incompatibility of electrospray with n-hexane. The method was validated for both enantiomers in the 25-500 ng/ml concentration range.

Atmospheric Pressure↗
PubMed2000

Quantitative analysis of N-acetylcysteine and its pharmacopeial impurities in a pharmaceutical formulation by liquid chromatography-UV detection-mass spectrometry.

A new method for the simultaneous determination of N-acetylcysteine and its pharmacopeial impurities, cysteine, cystine, N,N'-diacetylcystine and N,S-diacetylcysteine in an effervescent tablet has been developed. The method is based on on-line LC-UV-MS using a pneumatically-assisted electrospray interface (ionspray). The stability of the thiol moieties of the analytes was ensured by the acidic pH of the LC mobile phase. Quantitation of N-acetylcysteine was performed with UV detection to avoid ion-source overloading effect due to its higher concentration, whereas the impurities could be easily separated and quantified in MS. The method was validated in terms of stability, linearity, precision and accuracy.

Acetylcysteine↗
PubMed2000

High interaction alginate-hyaluronate associations by hyaluronate deacetylation for the preparation of efficient biomaterials.

The paper presents fundamental investigations of alginate-hyaluronate association with significant polymer interactions for preparation of efficient biomaterials. For this purpose, acetamide functions of hyaluronate were partly cleaved by hydrazine at high temperature, yielding amino groups accessible to carboxylic functions of the alginate chain. Alginate-hyaluronate association was studied both in dissolved state by rheological measurements and CD, and in the form of gel slabs prepared after calcium diffusion. Appreciable interaction between carboxylic groups of alginate and the released amino groups of hyaluronate was put into evidence by enhanced values of the viscosity of mixed solutions, and by assessment of the properties of the gel formed: moderate deacetylation allowed gels of improved hardness and viscosity. Nevertheless, high deacetylation was observed to hinder the gel formation by Ca(2+) complexation of alginate, by the significant competition of COOH-NH(2) association. Interaction between alginate and modified hyaluronate results in regular gel structure, with small cavities.

Acetylation↗
PubMed2000

Determination of the enantiomers of 3-tert.-butylamino-1,2-propanediol by high-performance liquid chromatography coupled to evaporative light scattering detection.

A method for the separation and quantitation of the enantiomers of 3-tert.-butylamino-1,2-propanediol by high-performance liquid chromatography and evaporative light scattering detection has been developed. Separation of the enantiomers was performed in normal-phase liquid chromatography on a Chiralpak AS chiral stationary phase. The influence of the gas nature, gas pressure and temperature of the drift tube of the evaporative light scattering detector on the detection sensitivity was investigated. The method was validated in terms of linearity, limit of quantitation, accuracy and precision. The enantiomeric excess of (S)-3-tert.-butylamino-1,2-propanediol, used for the industrial synthesis of (S)-timolol, was measured from 0 to 94%.

Chromatography, High Pressure Liquid↗
PubMed2000

Determination of fenofibric acid in human plasma using automated solid-phase extraction coupled to liquid chromatography.

The pharmacokinetic studies of fenofibrate require a rapid, selective and robust method to allow the determination of fenofibric acid, its active metabolite, in different biological matrixes (such as plasma, serum or urine). A new fully automated method for the determination of fenofibric acid in plasma has been developed, which involves the solid-phase extraction (SPE) of the analyte from plasma on disposable extraction cartridges (DECs) and reversed-phase HPLC with UV detection. The SPE operations were performed automatically by means of a sample processor equipped with a robotic arm (ASPEC system). The DEC filled with octadecyl silica was first conditioned with methanol and pH 7.4 phosphate buffer. A 0.8-ml volume of diluted plasma sample containing the internal standard (sulindac) was then applied on the DEC. The washing step was performed with the same buffer (pH 7.4). Finally, the analytes were successively eluted with methanol (1.0 ml) and 0.04 M phosphoric acid (1.0 ml). After a mixing step, 100 microl of the resultant extract was directly introduced into the HPLC system. The liquid chromatographic (LC) separation of the analytes was achieved on a Nucleosil RP-8 stationary phase (5 microm). The mobile phase consisted of a mixture of methanol and 0.04 M phosphoric acid (60:40, v/v). The analyte was monitored photometrically at 288 nm. The method developed was validated. In these conditions, the absolute recovery of fenofibric acid was close to 100% and a linear calibration curve was obtained in the concentration range from 0.25 to 20 microg/ml. The mean RSD values for repeatability and intermediate precision were 1.7 and 3.9% for fenofibric acid. The method developed was successfully used to investigate the bioequivalence between a micronized fenofibrate capsule formulation and a fenofibrate Lidose formulation.

Area Under Curve↗
PubMed2000

Enantiomeric separations of drugs using mixtures of charged and neutral cyclodextrins.

An overview on the use of mixtures of neutral and charged cyclodextrins as chiral additives for the enantioseparation of drugs by capillary electrophoresis is presented. These so called dual cyclodextrin systems can often provide unique selectivities. A brief theoretical background illustrating the influence of the chiral discrimination ability and the effective mobility of the two cyclodextrins on the overall selectivity of the enantiomeric separation is given. Typical examples of applications in the pharmaceutical field, based on the simultaneous use of a charged (cationic or anionic) and neutral cyclodextrins, are described.

Cyclodextrins↗
PubMed2000

Automated liquid chromatographic determination of atenolol in plasma using dialysis and trace enrichment on a cation-exchange precolumn for sample handling.

A fully automated method involving dialysis combined with trace enrichment was developed for the liquid chromatographic (LC) determination of atenolol, a hydrophilic beta-blocking agent, in human plasma. The plasma samples were dialysed on a cellulose acetate membrane and the dialysate was reconcentrated on a short trace enrichment column (TEC) packed with a strong cation-exchange material. All sample handling operations can be executed automatically by a sample processor (ASTED system). After TEC conditioning, the plasma sample, to which the internal standard (sotalol, another hydrophilic beta-blocker) was automatically added, was introduced in the donor channel and dialysed in the static/pulsed mode. The dialysis liquid consisted of 4.3 mM phosphoric acid. When the dialysis process was discontinued, the analytes were eluted from the TEC in the back-flush mode by the LC mobile phase and transferred to the analytical column, packed with octyl silica. The LC mobile phase consisted of phosphate buffer, pH 7.0-methanol (81:19; v/v) with 1-octanesulfonate. Atenolol and the internal standard were monitored photometrically at 225 nm. The different parameters influencing the dialysis and trace enrichment processes were optimised with respect to analyte recovery. The influence of two different kinds of cation-exchange material on analyte recovery and peak efficiency was also studied. The method was then validated in the concentration range 25-1000 ng/ml. The mean recovery for atenolol was 65% and the limit of quantitation was 25 ng/ml.

Adrenergic beta-Antagonists↗
PubMed2000

Determination of albendazole and its main metabolites in ovine plasma by liquid chromatography with dialysis as an integrated sample preparation technique.

Albendazole is a benzimidazole derivative with a broad-spectrum activity against human and animal helminth parasites. In order to determine the main pharmacokinetic parameters in sheep after oral and intravenous administration of a new formulation of albendazole (an aqueous solution), a fully automated method was developed for the determination of this drug and its main metabolites, albendazole sulfoxide (active metabolite) and sulfone in ovine plasma. This method involves dialysis as purification step, followed by enrichment of the dialysate on a precolumn and liquid chromatography (LC). All sample handling operations were executed automatically by means of an ASTED XL system. After conditioning of the trace enrichment column (TEC) packed with octadecyl silica with pH 6.0 phosphate buffer containing sodium azide, the plasma sample, in which a protein releasing reagent (1 M HCl) containing Triton X-100 was automatically added, was loaded in the donor channel and dialysed on a cellulose acetate membrane in the static-pulsed mode. The dialysis liquid consisted of pH 2.5 phosphate buffer. By rotation of a switching valve, the analytes were eluted from the TEC in the back-flush mode by the LC mobile phase and transferred to the analytical column, packed with octyl silica. The chromatographic separation was performed at 35 degrees C and the analytes were monitored photometrically at 295 nm. Due to the differences in hydrophobic character between albendazole and its metabolites, a gradient elution was applied. The mobile phase consisted of a mixture of acetonitrile and pH 6.0 phosphate buffer. The proportion of organic modifier was increased from 10.0 to 50.1% in 12.30 min, then from 50.1 to 66.9% in 1.70 min. First, the gradient conditions and the temperature were optimised for the LC separation using the DryLab software. Then, the influence of some parameters of the dialysis process on analyte recovery was investigated. Finally, the method developed was validated. The mean recoveries for albendazole and its metabolites were about 70 and 65%, respectively. The limits of quantification for albendazole and its metabolites were 10 and 7.5 ng/ml, respectively.

Albendazole↗
PubMed2000

Priming of CD2-induced p62Dok tyrosine phosphorylation by CD3 in Jurkat T cells.

T lymphocyte activation is triggered through the CD3-TCR complex or the CD2 molecule. Beside common biochemical events, we previously showed that a 62-kDa protein associated with PLCgamma-1 and p21RasGAP was specifically tyrosine phosphorylated after CD2 stimulation in Jurkat T cells. We demonstrated here that it was identical to p62Dok, a docking protein highly phosphorylated in human chronic myelogenous leukemia cells and in murine abl-transformed B cells. Mainly, we showed that p62Dok tyrosine phosphorylation was strengthened by the functional interplay between CD3 and CD2. Primary stimulation of Jurkat cells via CD3 suppressed most of the subsequent CD2-dependent phosphorylation events, except p62Dok tyrosine phosphorylation, which was on the contrary strongly increased. Kinetic studies indicated that a short treatment with anti-CD3 was sufficient to amplify the CD2-induced tyrosine phosphorylation of p62Dok. By contrast, CD2-induced PLCgamma-1 tyrosine phosphorylation and calcium response progressively diminished. Finally, enhanced amounts of tyrosine phosphorylated p62Dok were recruited to p21RasGAP and PLCgamma-1 after CD2 stimulation in CD3-activated cells. CD3 stimulation is known to enhance CD2 avidity for its ligand and to induce the binding of the CD2AP protein to the CD2 cytoplasmic tail. Our results suggest that the CD3-TCR complex rapidly primes the CD2 pathway to activate one of its specific components, p62Dok.

CD2 Antigens↗
PubMed2000

Impact of delayed repair and elective high-frequency oscillatory ventilation on survival of antenatally diagnosed congenital diaphragmatic hernia: first application of these strategies in the more "severe" subgroup of antenatally diagnosed newborns.

OBJECTIVE: a) To analyze the influence of a new management strategy on the outcome of neonates with antenatally diagnosed congenital diaphragmatic hernia (CDH); b) to determine early prognosis respiratory factors with the new strategy. DESIGN: Retrospective study. SETTING: Level III perinatal center. PATIENTS AND METHOD: Between 1985 and 1997, 51 consecutive neonates with antenatally diagnosed CDH were admitted to our level III neonatal intensive care unit. Before 1992 (period 1; n = 19), we used conventional mechanical ventilation and early surgery requiring transfer. Since 1992 (period 2; n = 32), we prospectively tested a new approach including (a) systematically use of high-frequency oscillatory ventilation (HFOV) regardless of the initial clinical severity, (b) delayed surgery following stabilization requiring transfer to a different surgical unit, but (c) no transfer of unstable patients with surgery under HFOV in our neonatal intensive care unit (n = 10). The two cohorts were comparable in terms of potential ante and postnatal prognostic indicators. RESULTS: Survival was improved with the new strategy: 21/32 (66%) vs. 5/19 (26%); P < 0.02. This improvement between periods 1 and 2 was due to a decrease in both preoperative and postoperative deaths in the later period. The better survival during period 2 was associated with the appearance of very late deaths, frequent pleural effusions, and the survival of more severe forms having evolved to a chronic respiratory insufficiency. Survivors were ventilated for longer time with longer duration of oxygen supplementation. The best oxygenation index (OI), alveolar arterial difference and oscillation amplitude (P/P) during the first 24 h, but not the best PaCO2, were the most reliable prognostic indicators during period 2. An OI < or = 10 with a P/P < or = 55 cmH2O was associated with a very good prognosis (94% survival). CONCLUSIONS: The prognosis of antenatally diagnosed CDH was improved by systematic HFOV on admission, no systematic transfer, and delayed surgery. This improvement is associated with modification of postnatal outcome.

Female↗
PubMed2000

Selective effects of acute exercise and breakfast interventions on mood and motivation to eat.

The effects of exercise and breakfast manipulations on mood and motivation to eat were assessed in 11 healthy females who were regular exercisers and habitual breakfast eaters. The study involved a two by two repeated-measures design, with exercise (or no exercise) and a high-energy breakfast (or low-energy breakfast) as the repeated measures. The exercise or no-exercise session (0800 h) was followed by consumption of the low- or high-energy breakfast (0900 h). An ad libitum lunch test meal was provided 4 hours after the beginning of the exercise session (1200 h). Mood and motivation to eat were continuously tracked from 0800 until 1700 h by an electronic appetite ratings system (EARS). In general, morning subjective mood states (e.g., contentment) were significantly lower in the low-energy breakfast condition, but exercise reversed this effect. Exercise also significantly decreased feelings of lethargy, independent of the breakfast condition. Desire-to-eat and fullness ratings were significantly increased in the low-energy breakfast and high-energy breakfast conditions, respectively. Impairments of mood disappeared in the afternoon after consumption of an ad libitum lunch. In these healthy young adults, the condition inducing the largest energy deficit (exercise and low-energy breakfast) was not associated with the lowest mental states.

Adult↗
PubMed2000

[Severe malaria in children in intensive care. National survey 1990-1995].

BACKGROUND: Severe malaria is a frequent complication of Plasmodium falciparum infections. More than one million children die of malaria each year. MATERIAL AND METHODS: A French survey was carried out on 15 cases admitted to pediatric intensive care units between 1990 and 1995. The aim of this work was to evaluate the occurrence, mortality, morbidity and treatment of severe malaria in French intensive care units. RESULTS: All cases were imported from Africa except one case of airport malaria. Diagnosis of many of these cases was delayed. All cases were treated with quinine, and five children received a loading dose. One child died and one has neurological sequelae. DISCUSSION: Despite improvement in management, the prognosis of severe malaria remains poor. With reference to the literature, we propose management of severe malaria, emphasizing the necessity of a rapid effect with a loading dose of quinine.

Adolescent↗
PubMed2000

Molecular cloning of a truncated p62Dok1 isoform, p22Dok(del).

The p21Ras GTPase activating protein-associated 62-kDa protein, p62Dok1, is an early substrate of various tyrosine phosphorylation pathways. Its recent cloning in human myeloid cells and in murine pre-B cells revealed an N-terminal pleckstrin-homology domain and a tyrosine- and proline-rich C-terminal tail in its sequence. Here, we characterized a new 1261-bp cDNA identical to that of p62Dok1, but with a central 185-bp deletion (bp 456-640). This induced a frameshift leading to a premature stop codon. The deduced protein, designated p22Dok(del), corresponded to a truncated p62Dok1 isoform of 177 amino acids that can be expressed both in vitro and in vivo with an apparent molecular mass of 22 kDa. This newly identified molecule was composed of the N-terminal PH domain of p62Dok1 followed by a new 25-amino acid C-terminal sequence containing a typical class II proline-rich motif, suggesting a specific role for p22Dok(del) in signal transduction pathways.

Amino Acid Sequence↗
PubMed2000

Comparative evaluation of four detectors in the high-performance liquid chromatographic analysis of chiral nonaromatic alcohols.

A comparative evaluation of ultraviolet, polarimetric, refractive index, and evaporative light-scattering detection coupled with high-performance liquid chromatography has been developed for the separation and quantitation of the enantiomers of chiral nonaromatic alcohols, some of which are intermediates in the synthesis of chiral drugs. (R,S)-3-tert-butylamino-1,2-propanediol; (R,S)-glycidol; and (R,S)-1-(4-morpholino)-2-octanol are selected as model compounds in order to compare the detection sensitivity and the linearity of the response with the four detectors. Separation of the enantiomers is performed using chiral stationary phases in normal-phase liquid chromatography. A one-day validation is achieved for (S)-3-tert-butylamino-1,2-propanediol with each detector, and limits of quantitation are determined for the three compounds. Advantages and limitations of the four detectors are discussed.

Alcohols↗