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Biomedical subjects

G Leclerc

Publications and source records attributed to G Leclerc.

At least 19 recordsLinked to original sources

[Fractures of the distal radius treated by osteosynthesis and injectable bone substitute: a prospective study of 39 patients].

PURPOSE OF THE STUDY: Comminution is often neglected in patients presenting fractures of the distal radius. Use of injectable bone substitutes can fill the gap left by comminution, avoiding radial shortening and loss of prono-supination. MATERIAL AND METHODS: Forty-eight patients with a distal fracture of the radius were treated by osteosynthesis and injectable cement between 1998 and 2001. These patients were reviewed at mean follow-up of 46 months (36-56). Dorsal displacement was present in all cases and the AO classification was A (n=26), B (n=15), C (n=7). Fixation was achieved with pins (n=32), posterior plate (n=14), and external fixator (n=2) before injection of the bone substitute. Outcome was evaluated with the Herzberg score, the Gartland and Werley score and DASH by an independent operator. RESULTS: Four patients were lost to follow-up and five who developed a deformed callus after the initial osteosynthesis were excluded from the analysis. The Herzberg functional score reached 84 (range 54-100) and the Gartland and Werley radioclinical score was 4.6 (0-11) with 89% excellent and good outcomes. DASH was 23.6 (5.8-62.7). Ulnar variance was unchanged or changed less than 2 mm between the immediate postoperative period and last follow-up in 88% of patients. There was one carpal tunnel syndrome related to anterior cement leakage. Three biopsies were performed and revealed a "humid sand" aspect six months after injection as well as presence of osteoblasts within the bone substitute. There was no or very little resorption. DISCUSSION: Several authors have demonstrated the biomechanical and functional effects of filling the comminution gap to avoid radial shortening. The first reported cases, then later prospective series, favored the use of injectable cements for patients with comminution. Cement used in our patients allowed preservation enables preservation of normal ulnar variance in addition to filling the gap. Like any bone substitute, it is an attractive alternative to other filling methods (ceramic graft) offering two advantages: adaptation to the bone defect and primary stability. This easy-to-use cement is resorbed slowly. Because of high cost, it may be reserved for patients with important functional needs.

Adult↗

In situ metrology of 85Kr plumes released by the COGEMA La Hague nuclear reprocessing plant.

The IRSN (Institut de Radioprotection et de Sûreté Nucléaire, France) has started an in situ study of the behaviour of atmospheric releases close-by the COGEMA La Hague nuclear reprocessing plant. The study is designed to improve information on the dispersion of radioactive pollutants very close to the emission point--a 100 m height chimney. In this situation, close to the emission and height of the emission, Gaussian models generally used to predict the behaviour of atmospheric releases are not well adapted. The study is based on the characterisation of the 85Kr emitted during normal operations of the reprocessing process. Temporal and spatial variations of the plume shape were investigated with intensive in situ measurements. Live in situ techniques to measure the electrons and the photons emitted by the 85Kr have been implemented and will be described. Preliminary results showing the interest of the techniques were presented. Variations of the dose rates created by the photon flux of a plume were directly measured and correlated to other quantities.

Belgium↗

New series of N-substituted phenyl ketone oxime ethers: synthesis and bovine beta3-adrenergic agonistic activities.

A series of ten novel phenyl ketone oxime ethers substituted on the terminal nitrogen by either 1,3 benzodioxole, alkyl, aralkyl or aryl moiety were synthesized and tested for their activity at bovine beta3-adrenoceptors. The best compound, which was the benzodioxole dicarboxylate derivative, showed potent beta3-adrenergic agonistic activities in Chinese hamster ovary cells expressing the bovine beta3-adrenoceptors with Kact and Ki values better than compound CL 316,243 used as reference (14 +/- 6 nM and 203 +/- 71 nM, respectively). In this series three compounds showed an antagonistic activity. Structure-activity relationships in these ketone oxime ethers are discussed.

Adenylyl Cyclases↗

Concentration and distribution of 210Po in the tissues of the scallop Chlamys varia and the mussel Mytilus edulis from the coasts of Charente-Maritime (France).

Polonium-210 (210Po) has been analysed in the soft parts of two bivalves species, the scallop Chlamys varia and the common mussel Mytilus edulis, from the Bay of La Rochelle and Ré Island, on the French Atlantic coast. Between those sites, the highest 210Po concentrations have been found in whole scallop soft parts from La Rochelle, reaching 1,181 +/- 29 Bq kg(-1) dry weight (dwt), a size effect being related to the highest 210Po concentration in the smallest scallops. The results show a significant difference in concentrations for similar size individuals between species in each site (C. varia > M. edulis) and between sites for each species (Ré Island > Bay of La Rochelle). Very high 210Po concentrations have been found in the digestive gland of C varia, ranging 3,150-4,637 Bq kg(-1) dwt. Thus, the digestive gland contains up to 60% of the radionuclide. Subcellular investigations have shown that approximately 40% of the 210Po contained in the digestive gland is in the cytosolic fraction, suggesting a high bioavailability of the 210Po from this fraction to the trophic upper level. Calculations will show that approximately 4 kg of scallops flesh intake would be necessary to reach the annual incorporation limit of 1 mSv.

Animals↗

Effect of ionizing radiation on thymidine uptake, differentiation, and VEGFR2 receptor expression in endothelial cells: the role of VEGF(165).

PURPOSE: Late thrombosis of irradiated vascular segments may be the consequence of endothelial cell (EC) dysfunction after radiation therapy. We investigated the effects of beta ionizing radiation on human EC viability, thymidine uptake, and differentiation. METHODS AND MATERIALS: Endothelial cells were exposed to (32)P-labeled DNA oligonucleotides in incremental doses of 2, 6, and 10 Gy. The modulation of the VEGFR2 receptor expression after irradiation and the overall potential radioprotective effect of VEGF(165) on these functions were assayed. RESULTS: A dose-dependent inhibitory effect of beta irradiation on ECs' thymidine uptake and differentiation was observed. EC viability, however, was not affected at levels of radiation up to 10 Gy. VEGF(165) proved to have a radioprotective effect as ECs' thymidine uptake, after radiation doses of 2, 6, and 10 Gy, was increased by 1.5-, 2-, and 4-fold, respectively, in the presence of 10 ng/ml of VEGF(165) (p < 0.05 vs. LacZ). This concentration of VEGF(165) also proved beneficial in maintaining cell differentiation at 16 h postirradiation when compared to controls. These biologic effects were in direct correlation with the upregulation of VEGFR2 receptor expression in irradiated ECs. CONCLUSIONS: beta irradiation interacts directly with EC functions by significantly reducing their ability to differentiate and proliferate, associated with upregulation of VEGFR2. These effects can be prevented in part by pretreating cells with VEGF(165), an effect potentially favored by the upregulation of VEGFR2 receptor expression after irradiation.

Adenoviruses, Human↗

Sequences and antimycoplasmic properties of longibrachins LGB II and LGB III, two novel 20-residue peptaibols from Trichoderma longibrachiatum.

Longibrachins are members of the class of natural Aib-containing peptides designated as peptaibols. Six longibrachins, LGA I-IV and LGB II and III, were purified from a Trichoderma longibrachiatum strain by a procedure employing several chromatography steps including reversed-phase HPLC. The amino acid sequence determination was based on a combination of liquid secondary ion mass spectrometry (LSIMS) and two-dimensional 1H and 13C NMR spectroscopy. Longibrachins are 20-residue peptaibols with a C-terminal phenylalaninol and either neutral (LGA; Gln18) or acidic (LGB; Glu18) character. Longibrachins LGB II and III have novel sequences. Both longibrachins LGA and LGB show significant bactericidal activity against mycoplasmas (Acholeplasma, Mycoplasma, and Spiroplasma), with minimal inhibitory concentrations in the range 1.56-12.5 microM (3-25 micrograms/mL), and also perturb the permeability of membrane bilayers. Longibrachin LGA IV is the most potent of the presently known 18-20-residue peptaibols. The antimicrobial and membrane-perturbing properties of longibrachins, which are described here for the first time, were shown to be correlated.

Amino Acid Sequence↗

Effects of radiation therapy on vascular responsiveness.

The use of radiation therapy to inhibit vascular proliferative diseases has produced encouraging results in several clinical trials. However, little is known about the possible side effects of radiation on vascular responsiveness. Our goal was to study the in vitro vascular responses of the rabbit aorta to various agonists immediately after several regimens of radiation therapy administered at doses prescribed in clinical protocols and at two different dose rates. High-dose-rate radiation was administered either by brachytherapy, using a gamma source, iridium 192, or an external electron beam producing beta radiation. Low-dose-rate radiation was administered by brachytherapy using a liquid-filled balloon with the beta emitter 32P. Vascular reactivity after the various regimens of irradiation was determined using the organ bath pharmacology assay. Various agonists were applied to the rabbit aorta to produce full cumulative concentration-response curves. Radiation, administered using an external electron beam, did not alter endothelium-dependent relaxation of the aorta induced by acetylcholine. However, the use of a catheter-based system to deliver radiation disrupted the endothelial cell lining of the vessel, causing a lack of relaxation by acetylcholine. Therefore, to compare all modalities of radiation therapy on vascular responsiveness, the agonists used in this study are known to act directly on the smooth muscle. Radiation therapy had no effect on the contractile responses induced by the following agonists: phenylephrine and potassium chloride. Vascular dilatation induced by nitroglycerin, a nitric oxide donor, was unaffected by radiation therapy. The contractile response induced by des-Arg9-bradykinin, a kinin B1 receptor agonist, was significantly increased twofold to threefold by all types of irradiation under study. This enhanced response is attributable to an increase of mRNA levels coding for this receptor. In all cases, radiation therapy did not alter the effective concentration producing 50% of maximal responsiveness (EC50) and did not reduce the vascular responsiveness induced by agonists. Taken together, we conclude that radiation therapy does not hinder endothelium-independent vascular responsiveness and increases the kinin B1 receptor-mediated vasoconstriction.

Acetylcholine↗

Synthesis and bovine beta 3-adrenergic agonistic activities of a novel series of aryloxypropanolamines.

We synthesized a novel series of 21 aryloxypropanolamine compounds characterized by N-alkyl, aralkyl, and aryl substituents. The compounds showed potent beta 3-adrenergic agonistic activities in Chinese hamster ovary cells expressing the bovine beta 3-adrenoceptors with Kact and Ki values of 4.2 +/- 3.0 nM and 459 +/- 169 nM respectively, for the ligand with the best compromise between potency and affinity. Structure-activity relationships are discussed.

Adenylyl Cyclases↗

Impact of a specific program focusing on the psychological autonomy and actualization of potential of residents in a long term care unit.

In 1996, the Sherbrooke Geriatric University Institute introduced a specific health and services program focusing on actualization of potential and psychological autonomy designed for long term care clients presenting few or no cognitive deficits. Some 30 residents who met specific criteria were moved to the same unit. To determine the impact of this specific program on the residents, a study was done using a quasi-experimental design with a control group. The residents in the experimental and control groups were evaluated three times: at the beginning of the program (1996), 1 year (1997) and 2 years (1998) later. The main variables measured were: actualization of potential, psychological autonomy, psychological well-being, satisfaction with care and services, social relations, and perception of the freedom allowed by the institution in regard to their choices and decisions. The results indicate that the new program had no effect on the residents' psychological autonomy, actualization of potential and social relations. In addition, the residents in the experimental group indicated less well-being and less satisfaction than those in the control group. Despite these negative elements, the experimental residents like being and want to stay together on the same unit but seem somewhat concerned about the program objectives. These results led the research team to propose that the program objectives and activities be reviewed.

Journal Article↗

Stressful life events and psychological distress of the very old: does social support have a moderating effect?

The purpose of this paper was to examine whether social support has a moderating effect on the relationship between exposure to stressful life events and psychological distress. To test this, 224 men and women aged 81-86 were sampled from two municipal regional counties: Sherbrooke (and vicinity) and Trois-Rivières, in the Province of Quebec, Canada. The French version of the Geriatric Scale of Recent Life Events, the Psychiatric Symptom Index, and the Social Provision Scale were used. Multiple regression analyses revealed that social support did not cancel out the deleterious effect of life events on the outcome measure. The negative aspect of social interaction may explain why social support did not have a protective effect. Also, social isolation resulting from psychological distress could reduce the opportunity for instrumental help and emotional support.

Journal Article↗

Allergic contact dermatitis to epoxy resin in microscopy immersion oil: cases from Canada.

The presence of epoxy resin in a reformulated immersion oil for microscopy has caused an epidemic of occupational contact dermatitis in laboratory technicians from some European centers. We report 6 additional cases, the mode of presentation of which was similar to the European patients. All patients were patch tested to the undiluted oil, and some were tested to the European or North American standard series and to an extensive series of glues and adhesives allergens. At 96 hours, all 6 patients displayed a strong 2+ to 3+ reaction to the undiluted oil. Two patients were not further tested, but in the remaining 4, positive reactions were seen to epoxy resin from the standard tray. One patient reacted to cycloaliphatic epoxy resin, and 2 displayed positive tests to the reactive diluents phenyl glycidyl ether and cresyl glycidyl ether. These further cases confirm the strong sensitizing properties of this particular immersion oil. The product, manufactured by Leica Microsystems (Wetzlar, Germany), since has been withdrawn from sale.

Adult↗

[Incidence of the onset of disability and recovery of functional autonomy among the very old after one year].

BACKGROUND: This article measures the survival rate and explores the changes in functional autonomy among both men and women over a one-year period in a sample of 272 subjects aged 80-85. METHODS: Data were taken from the Quebec Longitudinal Study on Aging, a multi-cohort prospective study focusing on health and quality of life. The sample comprises two sub-groups, namely disabled and autonomous subjects. Eligible participants were selected from the Quebec Health Insurance Plan (QHIP) file. However, to obtain the required number of participants, the sample was completed from eligible subjects who volunteered in response to TV, billboard and newspaper advertising about the project. The Functional Autonomy Measurement System (SMAF) was used to assess disability. The SMAF assesses functional disability in 5 domains: activities of daily living (ADL), mobility, instrumental activities (IADL), communication, and mental functioning. RESULTS: After one year, nearly 5% of the subjects had died and 72.5% were still autonomous, i.e., they had a score under 4.5 on the SMAF. The annual incidence of the onset of disability (including death, lengthy hospitalization, functional incapacities and cognitive deficits) was 20%. However, no difference was found between the sexes in regard to the risk of losing autonomy. The main areas where disability occurred among the previously autonomous subjects were, in order of importance, domestic tasks, mobility and communication. The study confirmed that it is possible to recover autonomy, even at this advanced age, particularly for women (11.2%), but less so for men (3.6%). CONCLUSION: This phenomenon of recovering functional autonomy suggests that octogenarians have a residual potential and confirms the effectiveness of preventive and curative measures and the benefits of interventions by community and family networks.

Activities of Daily Living↗

Specific nonpeptide photoprobes as tools for the structural study of the angiotensin II AT(1) receptor.

The aim of this work was to obtain photoactivatable nonpeptide antagonists of the angiotensin II AT(1) receptor. Based on structure-function relationships, two chemical structures as well as appropriate synthetic schemes were chosen as a frame for the design of radiolabeled azido probes. The feasibility of the strategy was first assessed by the synthesis of two tritiated ligands 21 and 22 possessing a high affinity for the AT(1) receptor and a low nonspecific binding to membrane or cell preparations. We then prepared two unlabeled azido derivatives 7 and 14 which retained a fairly high affinity for the AT(1) receptor. The latter compound proved to be suitable for receptor irreversible labeling and was prepared in its tritiated form 28. This tritiated azido nonpeptide probe displayed a K(d) value of 11.8 nM and a low nonspecific binding. It was suitable for specific and efficient covalent labeling of the recombinant AT(1A) receptor stably expressed in CHO cells. The electrophoretic pattern of the specifically labeled entity was strictly identical to that of purified receptor photolabeled with a biotinylated peptidic photoactivatable probe. This new tool should be useful for the mapping of the nonpeptide receptor binding site. These potential applications are discussed in light of the current knowledge of molecular mechanisms of G-protein coupled receptor activation and inactivation.

Angiotensin II↗

Cellular effects of beta-particle delivery on vascular smooth muscle cells and endothelial cells: a dose-response study.

BACKGROUND: Although endovascular radiotherapy inhibits neointimal hyperplasia, the exact cellular alterations induced by beta irradiation remain to be elucidated. METHODS AND RESULTS: We investigated in vitro the ability of 32P-labeled oligonucleotides to alter (1) proliferation of human and porcine vascular smooth muscle cells (VSMCs) and human coronary artery endothelial cells (ECs), (2) cell cycle progression, (3) cell viability and apoptosis, (4) cell migration, and (5) cell phenotype and morphological features. beta radiation significantly reduced proliferation of VSMCs (ED50 1.10 Gy) and ECs (ED50 2.15 Gy) in a dose-dependent manner. Exposure to beta emission interfered with cell cycle progression, with induction of G0/G1 arrest in VSMCs, without evidence of cell viability alteration, apoptosis, or ultrastructural changes. This strategy also proved to efficiently inhibit VSMC migration by 80% and induce contractile phenotype appearance, as shown by the predominance of alpha-actin immunostaining in beta-irradiated cells compared with control cells. CONCLUSIONS: 32P-labeled oligonucleotide was highly effective in inhibiting proliferation of both VSMCs and ECs in a dose-dependent fashion, with ECs showing a higher resistance to these effects. beta irradiation-induced G1 arrest was not associated with cytotoxicity and apoptosis, thus demonstrating a potent cytostatic effect of beta-based therapy. This effect, coupled to that on VSMC migration inhibition and the appearance of a contractile phenotype, reinforced the potential of ionizing radiation to prevent neointima formation after angioplasty.

Angioplasty, Balloon, Coronary↗

Preparation and pharmacological evaluation of the R- and S-enantiomers of 3-(2-butylamino)-4H- and 3-(3-methyl-2-butylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxide, two tissue selective ATP-sensitive potassium channel openers.

The preparation and the pharmacological evaluation of the R- and S-isomers of 3-(2-butylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxide (BPDZ 42) and 3-(3-methyl-2-butylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxide (BPDZ 44), two potassium channel openers, is described. Their optical purity was estimated by means of capillary electrophoresis (R- and S-BPDZ 42) and chiral HPLC (R- and S-BPDZ 44). The absolute configuration of each isomer of BPDZ 44 was deduced from crystallographic data. Pharmacological assays performed with the R- and S-isomers of BPDZ 44 revealed only slight differences in their activity on pancreatic B-cells but significant differences in their activity on vascular smooth muscle cells: the R-isomer being sixfold more potent than its corresponding S-isomer. The R-isomer of BPDZ 42 was shown to be more potent than its corresponding S-isomer on the endocrine pancreas. S-BPDZ 44 as well as R- and S-BPDZ 42 were found to exhibit tissue selectivity for the pancreatic versus the vascular smooth muscle tissue.

Adenosine Triphosphate↗

New calcium antagonists: synthesis, X-ray analysis, and smooth muscle relaxing effect of 3-[O-(benzyl-substituted)-oximino-ethers]-hexahydroazepin-2,3- diones.

A series of new Z and E 3-[O-(benzyl-substituted)-oximino-ether]-hexahydroazepin-2,3 -diones was prepared from the corresponding hexahydroazepin-2,3-diones and examined as smooth muscle relaxants. E and Z structures were assigned by NMR analysis and confirmed for 16 (E and Z) by an X-ray diffraction using synchrotron radiations. The nitrobenzyl derivative 16 was the most potent in vitro as relaxant of rat trachea precontracted with acetylcholine. The E isomer 16b was more potent than the Z isomer 16a. E isomer 16b is more potent than aminophylline to relax both rat trachea and human bronchus. This derivative acts mainly by inhibiting cellular influx of extracellular calcium since it inhibits potently and dose-dependently the contractions of rat trachea to high concentrations of KCI and to CaCl2 in a depolarizing medium. It appears to act weakly by inducing cGMP and cAMP synthesis. Moreover, its relaxing activity is not related to an inhibition of phosphodiesterases, to opening of potassium channels or to induction of prostaglandin synthesis. Therefore, 16b appears to work mainly as a potent calcium antagonist.

Animals↗