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Biomedical subjects

M Girard

Publications and source records attributed to M Girard.

At least 19 recordsLinked to original sources
PubMed2007

Serological and molecular variability of watermelon mosaic virus (genus Potyvirus).

Watermelon mosaic virus (WMV, genus Potyvirus) is very common in cucurbits worldwide, but its variability has been little studied. In France, where WMV has been known since 1974, unusually severe symptoms on zucchini squash have been found to be associated with WMV since 1999. We have developed serological and molecular tools to study WMV variability and the origin of severe strains. Eight monoclonal antibodies were obtained, characterized by epitope mapping, and used to assess the serological variability of 42 isolates from different countries. Sequence analysis based on the NIb-CP region revealed an important variability, with three distinct molecular groups. These analyses also suggested frequent intraspecific recombination in WMV.

Amino Acid Sequence↗
PubMed2006

Preschool children's eating behaviours are related to dietary adequacy and body weight.

OBJECTIVE: The aim of this paper is to analyse the relationships between eating behaviours (picky eating, irregular eating and overeating), and dietary adequacy in accordance with nutrition recommendations and body weight during the preschool years. DESIGN AND SETTING: Our analyses were performed using data from the Longitudinal Study of Child Development in Québec (1998-2002), a population-based birth cohort. SUBJECTS: The study followed a representative sample (n=2103) of children born in 1998 in the Canadian province of Québec. METHODS: Eating behaviours were derived from self-administered questionnaires when children were 2.5, 3.5 and 4.5 years. Nutrition data were collected from one 24-hour recall interview conducted at home by trained nutritionists at 4.5 years. Children's weight and height were measured at 4.5 years. Statistical analyses were carried out with SAS (version 8.2). Weighted data adjusted for within-variability were used in the analysis, and the significance level was set at 5%. RESULTS: Picky eaters consume fewer total fats, less energy and less protein than children never reporting picky eating behaviours. Picky eaters were more likely to consume less than dietary recommendations for fruit and vegetables, and meat and alternatives. Overeaters consumed more total energy and more of each macronutrient than children who were never reported as overeaters during the preschool years. These children consumed more servings of grain products and meats and alternatives per day than children not classified as overeaters. Even when the number of servings of grain products consumed was similar for overeaters and children who were never overeaters, overeaters had higher body mass index. CONCLUSION: Given that children as young as 4.5 years are displaying some form of problematic eating behaviour which is shown to be related to dietary adequacy and body weight, public health professionals should be targeting parents of young children to provide messages about strategies for coping with problematic eating behaviours in early childhood.

Body Mass Index↗
PubMed2006

Early determinants of overweight at 4.5 years in a population-based longitudinal study.

OBJECTIVES: The roots of the obesity epidemic need to be traced back as early in life as possible in order to develop effective means for preventing obesity and its health consequences in the future. The aim of this paper is to examine a broad range of factors that may simultaneously contribute to childhood overweight in a population-based cohort of children followed from birth to 4.5 years, to determine which factors exert the most influence in early life. DESIGN: The analyses were performed using data from the Quebec Longitudinal Study of Child Development 1998-2002 (QLSCD). SUBJECTS: The study follows a representative sample (n=2103) of children born in 1998 in the Canadian province of Quebec. MEASURE: Measured height and weight were available for 1550 children aged 4.5 years. At 4.5 years, BMI was analyzed using the US CDC sex- and age-specific growth charts. In order to study children at their highest weights at various ages, odds ratios were presented for high birth weight, weight-for-stature at or above the 95th percentile at 5 months, and BMI at or above the 95th percentile at 4.5 years. Monthly weight gain between birth and five months has been analyzed. Children were also evaluated by the Z-score obtained from the standardized weight divided by height. Factors potentially related to children's weight include sex, gestational age and birth rank, breastfeeding, mothers' smoking status during pregnancy, family type at child's birth, and family income before pregnancy and when the children were 5 months and 4.5 years old. Other parental factors such as height and overweight/obesity (based on BMI) and other maternal factors (age, education, immigrant status) were also part of the analysis. RESULTS: Being in the highest quintiles of weight gain between birth and 5 months, as well as maternal smoking during pregnancy, almost double the odds of being overweight at 4.5 years. Parental overweight or obesity also increased the odds of being overweight at this age, as well as being raised in middle-income or in poor families. A greater proportion of children born to nonsmoking mothers with higher weights (more than 4000 g) were overweight at 4.5 years, the percentage being greatest for those in the highest weight-gain categories from birth to 5 months. The pattern was different for children born to smoking mothers. The greatest proportion of 4.5-year-old overweight children was seen for children born in the normal weight-range category (3000-4000 g) who were in the highest quintiles of weight gain from birth to 5 months, and for children with high birth weights (more than 4000 g) who were in the lowest quintiles of birth-to-5-months weight gain. Children who were overweight at 4.5 years and who had been born to smoking mothers started life with a birth weight around that for the population means, but they gained more weight in the first 5 months of life than did the children of nonsmoking mothers. CONCLUSION: This study indicates that behavioral and social factors exert critical influences on the onset of childhood overweight in preschool years. From a population-health perspective, interventions aimed at preventing childhood obesity would do well to target smoking pregnant women, as well as nonsmoking pregnant women at risk for giving birth to high-birth-weight children, paying particular attention to rapid weight gain in the first months of life.

Adult↗
PubMed2006

Community-acquired methicillin-resistant Staphylococcus aureus in Switzerland: first surveillance report.

Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging community pathogen. Community-acquired MRSA (CA-MRSA) has been associated with virulent strains producing Panton-Valentine leukocidin (PVL) and a variety of other exotoxins. In Geneva, PVL-producing CA-MRSA was first reported in 2002 and a surveillance system based on voluntary reporting was set up. Each MRSA-positive culture result with an antibiotic resistance profile different from the endemic strain prevailing in the Geneva healthcare setting diagnosed in a patient without a history of hospital admission in the previous 12 months was notified to the local health department. A questionnaire was completed by the attending physician with demographic, clinical and exposure information. From January 2002 until December 2004, data on 58 cases were reported, including 26 cases grouped in 13 distinct transmission clusters. Most were family related and for two of them, colonisation persisted over a 12 month period despite treatment. Thirty three patients (57%) were male. Median age was 32 years, 22% being younger than 10 years. Forty one cases (71%) were infected and 17 (29%) colonised. Symptomatic skin lesions such as furunculosis, impetigo or abscess were present in 40 (97%) of the 41 infected cases. Most cases had no underlying disease. Thirty eight cases (65%) had travelled abroad. Forty (69%) of 58 isolates carried the PVL toxin. CA-MRSA infections in Geneva appear to be an emerging problem in the canton. Surveillance should continue and should possibly be extended to other parts of the country to better describe transmission patterns and the spread of this pathogen. Prevention and control of CA-MRSA infections represent a challenge for the future, requiring contact tracing, education and treatment of infected and colonised contacts.

Adolescent↗
PubMed2005

Discrepancies in phylogeographical patterns of two European anglerfishes (Lophius budegassa and Lophius piscatorius).

In order to investigate the relative importance of historical processes and life-history traits in shaping the present-day genetic structure of European anglerfishes, 382 Lophius piscatorius and 134 Lophius budegassa were sequenced on the 5' end of the mitochondrial control region. Both species showed a limited genetic structure and some evidence of a demographic expansion that probably occurred not at the end of the Last Glacial Maximum, but earlier in the Pleistocene. The main discrepancy between the two anglerfishes concerned the genetic structure between Atlantic and Mediterranean populations, with weak but significant differentiation observed only in L. budegassa. This genetic structure was congruent with the existence of a phylogeographical break previously reported in several marine species across the Almeria-Oran front. The contrast observed between both anglerfishes was supposed to be induced by a possible more ancient (re)colonisation of the Mediterranean Sea by L. budegassa. Finally, the limited genetic structure and lack of isolation by distance observed in both species suggested high larval dispersal capacities that probably overwhelm the influence of the bathymetric distribution range on migrations of adults and juveniles.

Animals↗
PubMed2004

[Statistical analyses: hypotheses or proof?].

Marc Girard is a mathematician and a physician, psychotherapist and medical expert witness on pharmaceutical drugs. He tells us his reflexions about the limits of Evidence Based Medicine, and introduces us about a critical view of the use of statistics in scientific medicine.

Bias↗
PubMed2004

Somatropin and its variants: structural characterization and methods of analysis.

Human Growth hormone (hGH, somatotrophin) is a 22 kDa, 191 amino-acid single chain protein produced by somatroph cells of the anterior pituitary gland. It is the major physiological regulator of growth, and deficiencies in growth hormone levels have long been recognized as the underlying cause of growth disorders (dwarfism). The ability of exogenous hGH to restore normal rates of growth in both human and animal models of growth retardation has long been recognized and the use of hGH in therapy goes back several decades. Initial preparations were prepared by extraction and purification from cadaveric pituitary tissue, and since 1984, hGH has been prepared by recombinant Deoxyribosenucleic acid (rDNA) technology. As is usually the case with "biologicals", characterization of the drug substance depended on a combination of physico-chemical and biological methods, and the hGH molecule became well characterized fairly early in its life as a drug. Indeed, by 1980 the major degradation forms and structural variants of the hGH molecule had been described and reviewed. Little satisfactory progress had been made in refining biological assays for hGH, and, although in vitro assays were described, potency-defining assays remained dependant on the whole body growth response in rats, and were both invasive and imprecise. In the early 1990's a series of collaborative studies on analysis of recombinant hGH (somatropin) established that available bioassays were much less selective that physico-chemical methods in detecting and quantifying structural degradation, and 1994 saw an international consensus to replace the bioassays with physico-chemical analytical methods for the routine batch release of somatropin. During the last decade in most markets somatropin has, unusually for a protein, been subject to batch release and control dependent entirely on physico-chemical analysis, without the routine use of any form of bioassay. During that time there has been a continuous development and refinement of methods, and the identification of a range of structural variants and degradation products of the molecule. The present review sets out to summarise the current knowledge on physico-chemical analytical methods for somatropin, and the structural variants that have been identified and characterized. A survey of available biological analytical methods is beyond the scope of this review, as is consideration of the earlier pituitary preparations and the recombinant 192 amino-acid methionyl form of the molecule (somatrem), although it is likely that many of the methods and variants described would be equally applicable to somatrem.

Chromatography, High Pressure Liquid↗
PubMed2002

Complete nucleotide sequence of the genomic RNA of a French isolate of Pepino mosaic virus (PepMV). Brief report.

The complete nucleotide sequence of the genomic RNA of a French isolate of Pepino mosaic virus (PepMV) was determined. With a length of 6,425 nucleotides excluding the poly(A) tail at the 3' terminus, the PepMV genome contains five major open reading frames encoding a 164 kDa replicase, triple gene block proteins of 26 kDa, 14 kDa and 9 kDa, and a 25 kDa coat protein. This genome organization, as well as characteristic consensus motifs and high degrees of similarity of PepMV proteins with those of other potexviruses confirmed that PepMV belongs to the Potexvirus genus. Phylogenetic analyses carried out on replicase, triple gene block protein 1 and coat protein amino acid sequences revealed that PepMV is closely related to species Narcissus mosaic virus (NMV), Scallion virus X (SVX), Cymbidium mosaic virus (CymMV), and Potato aucuba mosaic virus (PAMV).

5' Untranslated Regions↗
PubMed2002

The influence of long emersion on biota, ammonium fluxes and nitrification in intertidal sediments of Marennes-Oléron Bay, France.

A comparative study between waterlogged and reflooded intertidal sediments was undertaken in March and June 1999 through statistical analysis of selected sediment parameters (biota, salinity, O2, Eh), pool sizes and benthic fluxes of nutrients (NH4+, NO2-, NO3-) and nitrification rates. In March samples, absence of polychaetes and oligochaetes from upper sediment horizons were due to erosional events sweeping away surface sediments. Presence of richer annelid assemblages in June samples indicated more stable hydrodynamic conditions that favoured the development of benthic microalgae biofilms. Dewatering of sediments during a 3-day emersion period promoted a salinity rise on top layers, migration of pore water ions towards the sediment surface, and created sediment fissures that accelerated water exchange on reflooding. Reflooded and waterlogged sediment systems were comparable with respect to the release of NH4+ to overlying water but were different with respect to nitrification rates. Sediment-water NH4+ fluxes were higher (P = 0.011) in March (3.3 mmol m(-2) day(-1) compared to June (1.4 mmol m(-2) day(-1) due to higher macrofauna biomasses and lower benthic microalgae concentrations in March samples. Potential nitrification rates (range from 19 to 60 mmol NO3- (-2) day(-1)) were not statistically different between March and June. A thinner oxic layer in reflooded compared with waterlogged systems reflects a decrease of O2 diffusion into sediment at high salinities which resulted in the fall of the actual nitrification rates (P < 0.05). Our data suggest that long term dessication of intertidal sediments may depress the nitrification process at the ecosystem level.

Analysis of Variance↗
PubMed2001

Human Connexin 32, a gap junction protein altered in the X-linked form of Charcot-Marie-Tooth disease, is directly regulated by the transcription factor SOX10.

Mutations in SOX10, a transcription modulator crucial in the development of the enteric nervous system (ENS), melanocytes and glial cells, are found in Shah-Waardenburg syndrome (WS4), a neurocristopathy that associates intestinal aganglionosis, pigmentation defects and sensorineural deafness. Expression of MITF and RET, two genes that play important roles during melanocyte and ENS development, respectively, are controlled by SOX10. The observation that some WS4 patients present with myelination defects of the central and peripheral nervous systems correlates with the recent finding that P(0), a major component of the peripheral myelin, is another transcriptional target of SOX10. These phenotypic features suggest that SOX10 could regulate expression of other genes involved in the myelination process as well. Thus, we tested the ability of SOX10 to regulate expression of MBP, PMP22 and Connexin 32, three major proteins of the peripheral myelin. Our study shows that this factor, in synergy with EGR2, strongly activates Cx32 expression in vitro by directly binding to its promoter. In agreement with this finding, SOX10 and EGR2 mutants identified in patients with peripheral myelin defects fail to transactivate the Cx32 promoter. Moreover, we show that a mutation of the Cx32 promoter previously described in a patient with the X-linked form of Charcot-Marie-Tooth (CMTX) disease impairs SOX10 function. In addition to providing new insights into the molecular mechanisms underlying some of the peripheral myelin defects observed in CMTX disease, these results further extend the spectrum of genes that are regulated by SOX10.

Binding Sites↗
PubMed2001

Inositol hexakisphosphate-mediated regulation of glutamate receptors in rat brain sections.

D-myo-inositol 1,2,3,4,5,6-hexakisphosphate (InsP6), one of the most abundant inositol phosphates within cells, has been proposed to play a key role in vesicle trafficking and receptor compartmentalization. In the present study, we used in vitro receptor autoradiography, subcellular fractionation, and immunoblotting to investigate its effects on alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors. Qualitative and quantitative analysis of 3H-AMPA binding indicated that incubation of frozen-thawed brain sections with InsP6 at 35 degrees C enhanced AMPA receptor binding in several brain regions, with maximal increases in the hippocampus and cerebellum. Moreover, saturation kinetics demonstrated that InsP6-induced augmentation of AMPA binding was due to an increment in the maximal number of AMPA binding sites. At the immunological level, Western blots performed on crude mitochondrial/synaptic (P2) fractions revealed that InsP6 (but not InsP5 and InsP3) treatment increased glutamate receptor (GluR)1 and GluR2 subunits of AMPA receptors, an effect that was associated with concomitant reductions in microsomal (P3) fractions. Interestingly, the InsP6-induced modulation of AMPA receptor binding was blocked at room temperature, and pretreatment with heparin also dampered its action on both AMPA receptor binding and GluR subunits. These effects of InsP6 appear to be specific to AMPA receptors, as neither 3H-glutamate binding to NMDA receptors nor levels of NR1 and NR2A subunits in P2 and P3 fractions were affected. Taken together, our data strongly suggest that InsP6 specifically regulates AMPA receptor distribution, possibly through a clathrin-dependent process.

Animals↗
PubMed2001

[Locoregional neuraxial anesthesia and vascular surgery: the benefits].

PURPOSE: To assess the advantages of neuraxial blockade (NB) during and after vascular surgery and to confront them with the risk of epidural or spinal hematoma. MAIN FINDINGS: NB may reduce the risk of thrombotic occlusion following lower extremity vascular reconstruction. This effect of NB may be attributed to reduced hypercoagulability, decreased peripheral resistance and increased graft flow. In patients under general anesthesia, only those authors using an aggressive perioperative management (pulmonary artery catheter monitoring, intensive care unit admission) were able to report grafts patency rates similar to those obtained with NB. NB facilitates the modulation of the hemodynamic and hormonal stress responses during the perioperative period. It also produces superior postoperative analgesia. Still, the impact of NB on cardiac morbidity following aortic reconstructive surgery remains open to debate. Only very few cases of epidural hematomas associated to NB following vascular surgery have been reported. They implicated patients who received either fibrinolytic medication, continuous heparin infusion, or both. Low molecular weight heparins may increase the risk or epidural hematoma and, should their administration become more frequent during vascular surgery, the safety of NB would then have to be reassessed. CONCLUSION: NB during vascular surgery is a safe and well-established practice. It offers many theoretical and demonstrated advantages. NB is particularly beneficial and economical for lower extremity vascular reconstruction. Still, NB may not be the best approach if the administration of fibrinolityc medication or prolonged heparin infusion is contemplated.

Anesthesia, Conduction↗
PubMed2001

Intrathecal fentanyl does not modify the duration of spinal procaine block.

PURPOSE: To document the clinical characteristics of spinal procaine with or without the addition of fentanyl in light of the failure rate observed previously with procaine 10%. METHODS: In a randomized, prospective, double-blind study, 52 patients received spinal anesthesia with 100 mg procaine and either saline 0.9% (0.4 ml) (CONTROL group) or 20 microg fentanyl (0.4 ml) (FENTANYL group). Sensory anesthesia to needle prick was evaluated each minute for ten minutes, every three minutes for 33 minutes and every five minutes until regression to T10. Motor block was assessed with the Bromage scale. Patients were questioned by telephone for pain suggesting transient radicular irritation (TRI) 48 hr later. RESULTS: Mean time to reach highest sensory level, maximum number of segments blocked and mean time for regression of the sensory level to T10 showed no difference. Time to recuperate to full flexion of knees and feet (Bromage 4) showed no difference. Nine patients had nausea (five in CONTROL group and four in FENTANYL group) and nine had pruritus (three in CONTROL group and six in FENTANYL group). No patient reported pain suggesting TRI. CONCLUSION: Spinal procaine is appropriate for short-duration surgery. Fentanyl does not change the characteristics of the block or the incidence of side effects associated with spinal procaine.

Adolescent↗
PubMed2001

Spinal anesthesia: a comparison of procaine and lidocaine.

PURPOSE: To compare spinal procaine to spinal lidocaine with regard to their main clinical characteristics and incidence of transient radicular irritation (TRI). METHODS: In this randomized, double-blind, prospective study, patients (two groups, n=30 each) received either 100 mg of lidocaine 5% in 7.5% glucose (Group L) or 100 mg of procaine 10% diluted with 1 ml cerebrospinal fluid (Group P). After spinal anesthesia, segmental level of sensory block was assessed by pinprick. Blood pressure and the height of the block were noted each minute for the first ten minutes, then every three minutes for the next 35 min and finally every five minutes until regression of the block to L4. Motor blockade was evaluated using the Bromage scale. To evaluate the presence of TRI, each patient was questioned 48 hr after surgery. RESULTS: Time to highest sensory level and to maximum number of segments blocked showed no difference between groups. Mean time for sensory regression to T10 and for regression of the motor block were shorter in Group P. Eighty minutes following injection, sensory levels were lower in Group P. Five patients had inadequate surgical anesthesia in Group P and only one in Group L. No patient in Group P had TRI (95% CI 10-12%) while eight (27%) in Group L did (95% CI 12-46%). CONCLUSIONS: Procaine 10% was associated with a clinical failure rate of 14.2%. This characteristic must be balanced against an absence of TRI, which occurs more frequently with the use of lidocaine 5%.

Adult↗
PubMed2001

Social position and nutrition: a gradient relationship in Canada and the USA.

OBJECTIVE: [corrected] To study the existence of a graded relationship between the nutrient content of the diet and some measures of social position. DESIGN AND SETTING: The graded relationship hypothesis was verified by secondary analysis performed on two different nutrition surveys: the Quebec Nutrition Survey (QNS) and the NHANES III, both based on a single 24 h recall. The data of these surveys were collected on a representative sample of two different populations, the first (n=2103) in the province of Quebec (Canada) in 1990 (QNS) and the second in the US population (n=14 877) between 1988 and 1994 (NHANES III). MAIN OUTCOMES MEASURES: The social gradient hypothesis was tested with four different social position indicators. The analyses were performed separately for men and women aged from 18 to 74 y, for all the nutrients available in the databanks. For the USA, the graded relationship for the total population, for the non-Hispanic white population and for respondents sometimes or often experiencing a lack of food was also measured. RESULTS: A graded relationship between almost all nutrients and the studied social position measurements is observed for the consumption of total calorie-adjusted nutrients, for the proportion of people eating in accordance with dietary guidelines and for the proportion of individual not meeting 75% of the respective Recommended Dietary Allowances for their country. The direction of these relationships (positive or negative) is mainly in accordance with the clinical known impacts of nutrients on chronic diseases. CONCLUSIONS: It is possible that nutrition plays a role in the graded distribution of social health inequalities in North America even in the magnitude of this contribution remains to be evaluated.

Adolescent↗
PubMed2001

Parental origin of de novo MECP2 mutations in Rett syndrome.

Rett syndrome (RTT) is a neurodevelopmental disorder occurring almost exclusively in females as sporadic cases. Recently, DNA mutations in the MECP2 gene have been detected in approximately 70% of patients with RTT. To explain the sex-limited expression of RTT, it has been suggested that de novo X-linked mutations occur exclusively in male germ cells resulting therefore only in affected daughters. To test this hypothesis, we have analysed 19 families with RTT syndrome due to MECP2 molecular defects. In seven informative families we have found by DHPLC a nucleotide variant which could be used to differentiate between the maternal and the paternal allele. In each subject investigated from these families, we have amplified specifically each allele and sequenced allele-specific PCR products to identify the allele bearing the mutation as well as the parental origin of each X chromosome. This approach allowed us to determine the parental origin of de novo mutations in all informative families. In five cases, the de novo MECP2 mutations have a paternal origin and in the two other cases a maternal origin. In all transitions at CpG, the de novo mutation observed was of paternal origin. The high frequency of male germ-line transmission of the mutation (71% of RTT informative cases) is consistent with a predominant occurrence of the disease in females.

Base Sequence↗
PubMed2001

On the evolutionary conservation of the cell death pathway: mitochondrial release of an apoptosis-inducing factor during Dictyostelium discoideum cell death.

Mitochondria play a pivotal role in apoptosis in multicellular organisms by releasing apoptogenic factors such as cytochrome c that activate the caspases effector pathway, and apoptosis-inducing factor (AIF) that is involved in a caspase-independent cell death pathway. Here we report that cell death in the single-celled organism Dictyostelium discoideum involves early disruption of mitochondrial transmembrane potential (DeltaPsim) that precedes the induction of several apoptosis-like features, including exposure of the phosphatidyl residues at the external surface of the plasma membrane, an intense vacuolization, a fragmentation of DNA into large fragments, an autophagy, and the release of apoptotic corpses that are engulfed by neighboring cells. We have cloned a Dictyostelium homolog of mammalian AIF that is localized into mitochondria and is translocated from the mitochondria to the cytoplasm and the nucleus after the onset of cell death. Cytoplasmic extracts from dying Dictyostelium cells trigger the breakdown of isolated mammalian and Dictyostelium nuclei in a cell-free system, and this process is inhibited by a polyclonal antibody specific for Dictyostelium discoideum apoptosis-inducing factor (DdAIF), suggesting that DdAIF is involved in DNA degradation during Dictyostelium cell death. Our findings indicate that the cell death pathway in Dictyostelium involves mitochondria and an AIF homolog, suggesting the evolutionary conservation of at least part of the cell death pathway in unicellular and multicellular organisms.

Amino Acid Sequence↗