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- Centre d'Investigation Clinique -
Réponses affichées : 82
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Not all lactic acid bacteria are probiotics, ...but some are
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AZAIS-BRAESCO V, BRESSON JL, GUARNER F, CORTHIER G
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2010 - Br J Nutr 103(7):1079-81 |
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Unité(s) :
CIC
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Long-term follow-up of bezafibrate treatment in patients with the myopathic form of carnitine palmitoyltransferase 2 deficiency
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BONNEFONT JP, BASTIN J, LAFORET P, AUBEY F, MOGENET A, ROMANO S, RICQUIER D, GOBIN-LIMBALLE S, VASSAULT A, BEHIN A, EYMARD B, BRESSON JL, DJOUADI F
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2010 - Clin Pharmacol Ther 88(1):101-8 |
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Carnitine palmitoyltransferase 2 (CPT2) deficiency is a rare mitochondrial fatty acid oxidation (FAO) disorder characterized by myalgia, exercise intolerance, and rhabdomyolysis. We evaluate the efficacy of bezafibrate (BZ), a hypolipidemic drug, as a treatment for this form of CPT2 deficiency. A pilot trial was conducted with BZ in six patients for 6 months. There was a follow-up period of 3 years. The oxidation rates of the long-chain fatty acid derivative palmitoyl-CoA, measured in the mitochondria of the patients' muscles, were markedly lower than normal before treatment and increased significantly (+39 to +206%; P = 0.028) in all patients after BZ treatment. The evaluation of the therapeutic effects by the patients themselves (using the Short Form Health Survey (SF-36)), as well as by the physicians, indicated an improvement in the condition of the patients; there was an increase in physical activity and a decline in muscular pain. The results suggest that BZ has a therapeutic effect in the muscular form of CPT2 deficiency.
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Unité(s) :
Biochimie Métabolique, CIC, Métabolisme, U781
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Is the recommended once daily dose of lamivudine optimal in West African HIV-infected children (ANRS 12103)?
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BOUAZZA N, HIRT D, BARDIN C, DIAGBOUGA S, NACRO B, HIEN H, ZOURE E, ROUET F, OUIMINGA A, BLANCHE S, VAN DE PERRE P, TRELUYER JM, MSELLATI P, URIEN S
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2010 - Antimicrob Agents Chemother 54(8):3280-86 |
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We aimed in this study to describe lamivudine concentration-time courses in treatment-naive children after once-daily administration, to study the effects of bodyweight and age on lamivudine pharmacokinetics and to simulate an optimized administration scheme. For this purpose, lamivudine concentrations were measured in 49 children after at least 2 weeks of didanosine - lamivudine - efavirenz treatment. A total of 148 lamivudine plasma concentrations were measured and a population pharmacokinetic model was developed with NONMEM. The influence of individual characteristics was tested using a likelihood ratio test. Children were divided into two groups, according to their pharmacokinetic parameters, thanks to tree regression analysis. For each patient, area under the curve was derived from estimated individual pharmacokinetic parameters. Different once daily doses were simulated in each group, to obtain same exposition in children as the mean effective exposition in adults (8.9 mg/L.h). A two-compartment model where the slope of distribution is assumed to be equal to the absorption rate constant adequately described the data. Parameter estimates were standardized for a mean standard bodyweight using an allometric model. Children were then divided in 2 groups, according to bodyweight: CL/F was significantly higher in children weighing less than 17 kg (1.12 L/h/kg) than in children over 17 kg (0.95 L/h/kg, p=0.01). The target mean AUC of 8.9 mg/L.h was obtained with a 10 mg/kg once daily 3TC dose for children below 17kg, the recommended dose of 8 mg/kg seems to be sufficient in children weighing more than 17 kg. These assumptions should be prospectively confirmed.
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Unité(s) :
CIC
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[Ten years of gene therapy: thoughts and perspectives.]
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CAVAZZANA-CALVO M, HACEIN-BEY AS, FISCHER A
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2010 - Med Sci (Paris) 26(2):115-118 |
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Unité(s) :
Biothérapie, CIC-BT, Immunologie-Hématologie Pédiatriques, U768
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Comparative Validation of the Growth Hormone-Releasing Hormone and Arginine Test for the Diagnosis of Adult Growth Hormone Deficiency Using a Growth Hormone Assay Conforming to Recent International Recommendations
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CHANSON P, CAILLEUX-BOUNACER A, KUHN JM, WERYHA G, CHABRE O, BORSON-CHAZOT F, DUBOIS S, VINCENT-DEJEAN C, BRUE T, FEDOU C, BRESSON JL, DEMOLIS P, SOUBERBIELLE JC
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2010 - J Clin Endocrinol Metab 95(8):3684-92 |
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Context: The GHRH plus arginine (GHRH+Arg) test is a promising alternative to the insulin tolerance test (ITT) for diagnosis of adult GH deficiency (AGHD). Objectives: The objectives of the study were to validate the GHRH+Arg test for diagnosis of AGHD, using the ITT as comparator and a GH assay calibrated according to recent international recommendations, and to study the repeatability and tolerance of both tests. Design: This was a multicenter, randomized, open-label, phase III study. Setting: The study was conducted at 10 French university hospitals. Subjects: Sixty-nine subjects (38 and 15 with high and low probability of GH deficiency, respectively, and 16 healthy controls) were randomized: 35 to the GHRH+Arg-GHRH+Arg-ITT test sequence and 34 to the ITT-ITT-GHRH+Arg test sequence. Interventions: Each subject underwent three tests of GH secretion separated by 24 h or more. Main Outcome Measures: The primary variable used for response assessments was serum peak GH response. Test results were compared with the final AGHD diagnosis. Results: Peak GH responses in the two tests were strongly correlated. A cutoff value of 7.89 mug/liter for GHRH+Arg corresponding to 3 mug/liter for ITT was calculated. The cutoff value leading to 95% specificity with the GHRH+Arg test was measured at about 3.67 mug/liter (sensitivity 79.0%). Intermethod agreement and repeatability were high. Both tests were well tolerated. A preference for the GHRH+Arg test was expressed by 74% of subjects. Conclusions: The GHRH+Arg test demonstrated good accuracy and repeatability, was at least as sensitive as the ITT, and was associated with better subject acceptability. The GHRH+Arg test represents a good alternative to the ITT for the diagnosis of AGHD.
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Unité(s) :
CIC, U845 (GF)
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Gene therapy for primary immunodeficiencies
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FISCHER A, S. H-B, CAVAZANNA-CALVO M
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2010 - Immunol Allergy Clin North Am 30(2):237-48 |
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The concept of gene therapy emerged as a way of correcting monogenic inherited diseases by introducing a normal copy of the mutated gene into at least some of the patients' cells. Although this concept has turned out to be quite complicated to implement, it is in the field of primary immunodeficiencies (PIDs) that proof of feasibility has been undoubtedly achieved. There is now a strong rationale in support of gene therapy for at least some PIDs, as discussed in this article.
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Unité(s) :
Biothérapie, CIC-BT, Immunologie-Hématologie Pédiatriques, U768
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20 years of gene therapy for SCID
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FISCHER A, S. H-B, CAVAZZANA-CALVO M
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2010 - Nat Immunol 11(6):457-60 |
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Unité(s) :
Biothérapie, CIC-BT, Immunologie-Hématologie Pédiatriques, U768
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Hypothermie controlee du nouveau-ne a terme apres asphyxie perinatale
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MEAU-PETIT V, TASSEAU A, LEBAIL F, AYACHI A, LAYOUNI I, PATKAI J, GAUDIN A, HUON C, CHABERNAUD JL, DUGELAY F, KERMORVANT-DUCHEMIN E, LODE N, DUCROCQ S, BOITHIAS C, PEJOAN H, BOISSINOT C, HARVEY B, OTHMANI K, BOLOT P, VERMERSCH AI, ZUPAN-SIMUNEK V
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2010 - Arch Pediatr 17(3):282-9 |
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Unité(s) :
CIC
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The readability of information and consent forms in clinical research in France
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MENONI V, LUCAS N, LEFORESTIER JF, DIMET J, DOZ F, CHATELLIER G, TRELUYER JM, CHAPPUY H
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2010 - PLoS ONE 5(5):e10576 |
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BACKGROUND: Quantitative tools have been developed to evaluate the readability of written documents and have been used in several studies to evaluate information and consent forms. These studies all showed that such documents had a low level of readability. Our objective is to evaluate the readability of Information and Consent Forms (ICFs) used in clinical research. METHODS AND FINDINGS: Clinical research protocols were collected from four public clinical research centers in France. Readability was evaluated based on three criteria: the presence of an illustration, the length of the text and its Flesch score. Potential effects of protocol characteristics on the length and readability of the ICFs were determined. Medical and statutory parts of the ICF form were analyzed separately. The readability of these documents was compared with that of everyday contracts, press articles, literary extracts and political speeches. We included 209 protocols and the corresponding 275 ICFs. The median length was 1304 words. Their Flesch readability scores were low (median: 24), and only about half that of selected press articles. ICF s for industrially sponsored and randomized protocols were the longest and had the highest readability scores. More than half (52%) of the text in ICFs concerned medical information, and this information was statistically (p<0.05) more readable (Flesch: 28) than statutory information (Flesch: 21). CONCLUSION: Regardless of the field of research, the ICFs for protocols included had poor readability scores. However, a prospective analysis of this test in French should be carried out before it is put into general use.
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Unité(s) :
CIC, Médecine d'Urgence, EA 3620
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Bone marrow transplantation for primary immunodeficiency diseases
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SZABOLCS P, CAVAZZANA-CALVO M, FISCHER A, VEYS P
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2010 - Pediatr Clin North Am 57(1):207-37 |
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Advances in immunology have led to a breathtaking expansion of recognized primary immunodeficiency diseases (PID) with over 120 disease-related genes identified. In North America alone more than 1000 children have received allogeneic blood or marrow transplant over the past 30 years, with the majority surviving long term. This review presents results and highlights challenges and notable advances, including novel less toxic conditioning regimens, to transplant the more common and severe forms of PID. HLA-matched sibling donors remain the ideal option, however, advances in living donor unrelated HSCT and banked umbilical cord blood grafts provide hope for all children with severe PID.
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Unité(s) :
Biothérapie, CIC-BT, Immunologie-Hématologie Pédiatriques
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Strong Correlations of Anti-Viral Capsid Antigen Antibody Levels in First-Degree Relatives from Families with Epstein-Barr Virus-Related Lymphomas
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BESSON C, AMIEL C, LE-PENDEVEN C, PLANCOULAINE S, BONNARDEL C, RANQUE B, ABBED K, BRICE P, FERME C, CARDE P, HERMINE O, RAPHAEL M, BRESSON JL, NICOLAS JC, GESSAIN A, DETHE G, ABEL L
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2009 - J Infect Dis 199(8):1121-1127 |
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Background. Markers of Epstein-Barr virus (EBV) infection include anti-viral capsid antigen (VCA) immunoglobulin (Ig) G. High anti-VCA titers are associated with EBV-related lymphoproliferation, such as Burkitt lymphoma (BL) and Hodgkin lymphoma (HL). Methods. Intrafamilial correlations of anti-VCA IgG levels were studied in 3 settings: 127 families recruited through patients with HL in France (population A), 31 families recruited through patients with BL in Uganda (population B), and 74 large families from a general population in Cameroon (population C). Titers were determined by enzyme-linked immunosorbent assay (populations A and C) or by immunofluorescence analysis (population B). Results. In populations A and B, the anti-VCA IgG titers of the relatives of patients with HL or BL increased significantly ([Formula: see text] and [Formula: see text], respectively) with those of the index case patient. In all 3 populations, anti-VCA IgG titers were significantly correlated ([Formula: see text] for A, [Formula: see text] for B, and [Formula: see text] for C) between genetically related individuals (father-offspring, mother-offspring, and sibling-sibling) but not between spouses. Similar results were obtained for population A after adjustment for total IgG levels. In all cases, the pattern of correlations was consistent with a polygenic model, with heritability ranging from 0.32 to 0.48. Conclusion. These results provide evidence for the genetic control of anti-VCA IgG titers and pave the way for identification of the loci involved.
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Unité(s) :
Hématologie Adulte, CIC, U550
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Molecular analyte profiling of the early events and tissue conditioning following intravesical bacillus calmette-guerin therapy in patients with superficial bladder cancer
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BISIAUX A, THIOUNN N, TIMSIT MO, ELADAOUI A, CHANG HH, MAPES J, MOGENET A, BRESSON JL, PRIE D, BECHET S, BARON C, SADORGE C, THOMAS S, ALBERT EB, ALBERT PS, ALBERT ML
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2009 - J Urol 181(4):1571-80 |
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PURPOSE: We characterized the innate immune response to intravesical bacillus Calmette-Guerin therapy using a systems approach based on proteomic and cytometric screens. MATERIALS AND METHODS: Blood and urine were collected from patients receiving intravesical bacillus Calmette-Guerin therapy before, and 2 and 4 hours after bacillus Calmette-Guerin treatment, at the first and third instillation. Proteomic and cytometry based screens were performed. RESULTS: Molecular analyte profiling revealed a prime/boost pattern to the innate response to intravesical bacillus Calmette-Guerin. We identified 36 statistically significant changes in the proteins induced during the third instillation compared to the initial treatment. These analytes were classified into 3 categories of 1) plasma proteins that leaked into the urine, 2) cytokines/chemokines produced locally during the first hours of inflammation and 3) other innate molecules that modulate the bladder microenvironment. To characterize the marked increase in the inflammatory response after multiple treatments we evaluated the cells present in the urine and again a prime/boost response was revealed. For the locally produced analytes it was possible to define the cell source(s) and, thus, provide a first generation map of what occurs during the initial phase of bacillus Calmette-Guerin therapy. CONCLUSIONS: This study provides in vivo information concerning the ability of bacillus Calmette-Guerin to sensitize the tissue microenvironment to enhance innate responses and establishes a framework for improving vaccination strategies while decreasing adverse events.
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Unité(s) :
Explorations Fonctionnelles, CIC, U845 (GF), Urologie
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Does regular blood transfusion prevent progression of cerebrovascular lesions in children with sickle cell disease?
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BROUSSE V, HERTZ-PANNIER L, CONSIGNY Y, BRESSON JL, GIROT R, MIRRE E, LENOIR G, DE MONTALEMBERT M
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2009 - Ann Hematol 88(8):785-8 |
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A retrospective study was conducted to assess changes in cerebrovascular lesions, as assessed by magnetic resonance (MR) imaging and angiography in 18 children with sickle cell disease (SCD) receiving optimised chronic transfusions for primary stroke prevention (abnormal transcranial Doppler flow, nine patients, median follow-up 14.3 months (range, 7.9-48.9)) or secondary stroke prevention (nine patients, median follow-up 59.6 months (range, 11.0-127.9)). An experienced neuroradiologist blinded to patient data reviewed the 41 MR scans (median/patient, three (2-4)). Standard scores were used to evaluate parenchymal and vascular abnormalities at baseline and last follow-up. Within-patient score changes evaluated using Wilcoxon's paired rank test indicated lesion progression in the secondary-prevention group (p = 0.027). Optimised transfusion therapy does not prevent progression of cerebral vasculopathy in SCD children with a history of stroke.
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Unité(s) :
Pédiatrie Générale, Radiologie Pédiatrique, CIC, U663
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Basic research tries to decrease the risks of translational medicine
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CAVAZZANA-CALVO M
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2009 - Gene Ther 16(3):309-10 |
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Unité(s) :
Biothérapie, CIC-BT, U768
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Immune reconstitution after haematopoietic stem cell transplantation: obstacles and anticipated progress
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CAVAZZANA-CALVO M, ANDRE-SCHMUTZ I, DAL-CORTIVO L, NEVEN B, HACEIN-BEY S, FISCHER A
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2009 - Curr Opin Immunol 21(5):544-548 |
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Improvement of immune reconstitution after haematopoietic stem cell transplantation (HSCT) is a key issue determining the clinical outcome of this widely used therapeutic approach. To this end, new strategies have been prompted by recent discoveries in immunology. In the setting of human leukocyte antigen (HLA) geno(pheno)identical HSCT, better prevention and treatment of acute and chronic graft-versus-host disease (GvHD) could significantly attenuate the thymic epithelium damage responsible for delayed and incomplete T-cell reconstitution. In a haploidentical setting, methods that would significantly accelerate neothymopoiesis in the months following injection of highly purified CD34+ cells are warranted. If these objectives could be achieved, the haploidentical procedure would become more readily available to patients affected by acquired or inherited disorders of the haematopoietic system.
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Unité(s) :
Immunologie-Hématologie Pédiatriques, Biothérapie, U768, CIC-BT
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[Osteopenia and vitamin D deficiency in children with sickle cell disease.]
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CHAPELON E, GARABEDIAN M, BROUSSE V, SOUBERBIELLE JC, BRESSON JL, DE MONTALEMBERT M
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2009 - Arch Pediatr 16(6):619-21 |
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Unité(s) :
Pédiatrie Générale, CIC
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Osteopenia and vitamin D deficiency in children with sickle cell disease
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CHAPELON E, GARABEDIAN M, BROUSSE V, SOUBERBIELLE JC, BRESSON JL, DE MONTALEMBERT M
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2009 - Eur J Haematol 83(6):572-78 |
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Abstract Objectives: To assess the prevalence in children with sickle cell disease of low bone mineral density (BMD), a feature found in up to 82% of adults but not well known in children. Methods: In 53 children (45 SS, 4 SC, 4 Sbeta-thalassemia) with a mean age of 12.8 +/- 2.4 years, we assessed height; weight; sexual maturation; number of hospitalizations, painful crises, and transfusions in the last 3 years; calcium intake; steady-state hemoglobin and leukocyte count; calcaemia, phosphataemia, and calciuria/creatinuria; serum 25-(OH)D and PTH concentrations; and osteocalcin, urinary deoxypyridinoline, and the C-terminal component of pro-collagen type I. BMD was assessed using dual X-ray absorptiometry. Results: Mean lumbar spine Z-score was -1.1 +/- 1.3 (-3.9 to +1.8). The Z score was significantly lower in girls than in boys in the prepubertal subgroup (-1.74 +/- 0.27 vs. -0.53 +/- 0.31) (P = 0.0169), but not in the pubertal group (-1.15 +/- 0.41 vs. -1.33 +/- 0.70). BMD was not associated with any of the disease-severity markers in girls but was unexpectedly associated with fewer vaso-occlusive crises and hospitalizations in boys. BMD did not correlate with hemoglobin or leukocyte counts. Vitamin D deficiency [25-(OH)D < 12 ng/mL] was found in 76% of patients and secondary hyperparathyroidism (PTH > 46 pg/mL) in 38%. BMD was not related to calcium intake, vitamin D status, osteocalcin, or bone resorption markers. Conclusion: A slight BMD decrease was found in SCD children, starting before puberty and being more marked in females. The decrease was unrelated to disease severity, vitamin D deficiency, or bone hyperresorption, suggesting abnormal bone formation as the underlying mechanism.
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Unité(s) :
Pédiatrie Générale, CIC
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[Medications dosage and adherence.]
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CHAPPUY H, PATTEAU G, TRELUYER JM, CHERON G
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2009 - Arch Pediatr 16(6):968-9 |
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Unité(s) :
CIC, CUDR
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Stem cells and cardiovascular therapy: results in peripheral artery disease
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EMMERCIH J
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2009 - Bull. Acad. Natl. Méd. 193(3):549-557 |
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Critical leg ischemia (CLI) remains a major cause of mortality and morbidity (amputation), and its treatment is a major challenge. Cell therapy designed to stimulate angiogenesis is being evaluated in this setting. Several phase I/II trials have demonstrated that it is safe and feasible to use autologous bone marrow mononuclear cells or peripheral mononuclear cells harvested after G-CSF stimulation. Three trials with more than 40 patients have been performed in France, and more than 700 patients have been treated worldwide, usually in non controlled trials. The main problems encountered with cell therapy in CLI are not only the need to demonstrate its efficacy and safety, but also to identify the patient categories most likely to benefit. The results of randomized trials, and especially the French BALI trial, are eagerly awaited to confirm that this approach is really beneficial. A few trials have also been performed in Buerger's disease. Another exciting possibility is to create artificial vessels in vitro for subsequent grafting in patients with no available venous grafts. Several teams are also testing allogeneic stem cells and autologous progenitor endothelial cells for the treatment of peripheral artery disease but they are encountering significant hurdles.
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Unité(s) :
CIC-BT
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Le programme national nutrition santé (PNNS) : quels effets sur la santé des enfants ?
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GIRARDET JP, BOCQUET A, BRESSON JL, CHOURAQUI JP, DARMAUN D, DUPONT C, FRELUT ML, GHISOLFI J, GOULET O, RIEU D, RIGO J, THIBAULT H, TURCK D, VIDAILHET M
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2009 - Archives Pédiatrie 16(1):3-6 |
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Unité(s) :
CIC, Gastro-Hépatologie et Nutrition Pédiatriques
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Downward trends in the prevalence of childhood overweight in the setting of 12-year school- and community-based programmes
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ROMON M, LOMMEZ A, TAFFLET M, BASDEVANT A, OPPERT JM, BRESSON JL, DUCIMETIERE P, CHARLES MA, BORYS JM
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2009 - Public Health Nutr 12(10):1735-42 |
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OBJECTIVE: A school-based nutrition information programme was initiated in 1992 in two towns in northern France (Fleurbaix and Laventie, FL) and was followed by a number of community-based interventions. We took the opportunity to measure the outcomes in terms of childhood obesity and overweight over the next 12 years. DESIGN: Repeated, cross-sectional, school-based survey. For the school years beginning in 1992, 2000, 2002, 2003 and 2004, the height and weight of all 5- to 12-year-old children attending school were measured in FL. In 2004, the same assessments were made in two comparison towns with similar socio-economic characteristics but no intervention. SETTING: Fleurbaix and Laventie (intervention towns), Bois-Grenier and Violaines (comparison towns), northern France. SUBJECTS: In 2002, 2003 and 2004, respectively 515, 592 and 633 children were measured in FL (participation rate of 95-98% of all eligible individuals); in the comparison towns, 349 children were measured in the 2004 school year (98% of the towns' school population). RESULTS: After an initial increase, trends in mean BMI and prevalence of overweight started to reverse. Compared with 2002, the age-adjusted OR for overweight in FL was significantly lower in 2003 and 2004 (but for girls only). In the 2004 school year, the overweight prevalence was significantly lower in FL (8.8%) than in the comparison towns (17.8%, P < 0.0001). CONCLUSION: These data suggest that, over a long period of time, interventions targeting a variety of population groups can have synergistic effects on overweight prevalence. This gives hope that it is possible to reverse trends towards increasing overweight by actions at the community level.
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Unité(s) :
CIC
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Phenotypic determinants of uncontrolled asthma
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SIROUX V, BOUDIER A, BOUSQUET J, BRESSON JL, CRACOWSKI JL, FERRAN J, GORMAND F, JUST J, LE MOUAL N, MORANGE S, NADIF R, ORYSZCZYN MP, PISON C, SCHEINMANN P, VARRASO R, VERVLOET D, PIN I, KAUFFMANN F
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2009 - J Allergy Clin Immunol 124(4):681-7 e3 |
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BACKGROUND: Although uncontrolled asthma remains frequent, determinants of asthma control are poorly studied. OBJECTIVES: The aim was to estimate the distribution and the phenotypic characteristics of asthma control in 2 groups of subjects defined by the use of inhaled corticosteroids (ICS) in the past 12 months, in the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA). METHODS: Five hundred one adult current patients with asthma who participated in the follow-up of the EGEA study were included. Asthma control was assessed from survey questions reflecting asthma control, as defined in the 2006 Global Initiative for Asthma guidelines. The factors analyzed were age, sex, educational level, body mass index, active and passive smoking, sensitization to aeroallergens, total IgE, rhinitis, chronic cough/phlegm, and age at asthma onset. Analyses were stratified according to ICS use. RESULTS: Uncontrolled asthma was more frequent in ICS users (27.6%, 35.0%, and 37.4% with controlled, partly-controlled, and uncontrolled asthma respectively) compared with non-ICS users (60.0%, 23.9%, and 16.1%, respectively). In ICS users, chronic cough or phlegm and female sex were independently and significantly related to uncontrolled asthma. In non-ICS users, high total IgE and sensitization to molds were associated with uncontrolled asthma. Smoking and rhinitis were not associated with asthma control. CONCLUSION: Optimal asthma control remained unachieved in the majority of patients with asthma in this study. Factors associated with uncontrolled asthma were different in ICS users (chronic cough/phlegm, female sex) and non-ICS users (high total IgE and sensitization to molds).
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Unité(s) :
CIC, Maladies du Développement
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Fate and effects of Camembert cheese micro-organisms in the human colonic microbiota of healthy volunteers after regular Camembert consumption
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FIRMESSE O, ALVARO E, MOGENET A, BRESSON JL, LEMEE R, LE RUYET P, BONHOMME C, LAMBERT D, ANDRIEUX C, DORE J, CORTHIER G, FURET JP, RIGOTTIER-GOIS L
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2008 - Int. J. Food Microbiol. 125(2):176-181 |
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The objective of this study was to determine i) if Camembert cheese micro-organisms could be detected in fecal samples after regular consumption by human subjects and ii) the consequence of this consumption on global metabolic activities of the host colonic microbiota. An open human protocol was designed where 12 healthy volunteers were included: a 2-week period of fermented products exclusion followed by a 4-weeks Camembert ingestion period where 2x40 g/day of Camembert cheese was consumed. Stools were collected from the volunteers before consumption, twice during the ingestion period (2nd and 4th week) and once after a wash out period of 2 weeks. During the consumption of Camembert cheese, high levels of Lactococcus lactis and Leuconostoc mesenteroides were measured in fecal samples using real-time quantitative PCR, reaching median values of 8.2 and 7.5 Log(10) genome equivalents/g of stool. For Ln. mesenteroides, persistence was observed 15 days after the end of Camembert consumption. The survival of Geotrichum candidum was also assessed and the fecal concentration reached a median level of 7.1 Log(10) CFU/g in stools. Except a decreasing trend of the nitrate reductase activity, no significant modification was shown in the metabolic activities during this study.
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Unité(s) :
CIC 9303
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Absence of HIV-1 shedding in male genital tract after 1 year of first-line lopinavir/ritonavir alone or in combination with zidovudine/lamivudine
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GHOSN J, CHAIX ML, PEYTAVIN G, BRESSON JL, GALIMAND J, GIRARD PM, RAFFI F, COHEN-CODAR I, DELFRAISSY JF, ROUZIOUX C
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2008 - J. Antimicrob. Chemother. 61(6):1344-1347 |
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Background New strategies such as boosted-protease inhibitor (PI) monotherapy are being investigated. However, a concern remains regarding the efficacy of this strategy in viral sanctuaries such as the male genital tract. More than 80% of untreated HIV-infected men have detectable HIV-RNA in semen and such a strategy could favour local selection of resistant variants, given the poor penetration of most PIs in semen. Objectives To evaluate the impact of a first-line lopinavir/ritonavir alone or standard triple combination on HIV-1 shedding in the genital tract. Methods HIV-1-infected men enrolled in the Monark randomized trial were eligible for the present study after 48 weeks of a first-line lopinavir/ritonavir alone or in combination with zidovudine and lamivudine. Single-paired samples of blood and semen were collected at week 48. Blood plasma HIV-RNA and seminal plasma HIV-RNA were measured at week 48. Lopinavir and ritonavir concentrations were measured in blood and in semen at week 48 by high-performance liquid chromatography. Results Ten patients were included: five of them received lopinavir/ritonavir monotherapy and five received a triple combination. At week 48, all patients had blood plasma HIV-RNA <1.7 log(10) copies/mL. Median lopinavir and ritonavir concentrations were within the expected therapeutic target range in blood plasma (4896 and 130.5 ng/mL, respectively), whereas both lopinavir and ritonavir were undetectable in all seminal plasma samples (<30 ng/mL). All 10 patients had undetectable seminal plasma HIV-RNA at week 48 (<2.3 log(10) copies/mL). Conclusions No local viral production was evident in semen, despite the local absence of therapeutic antiretroviral drug concentrations in the five patients receiving lopinavir/ritonavir alone.
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Unité(s) :
Laboratoire de Microbiologie, CIC 9303, EA3620
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Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1
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HACEIN-BEY S, GARRIGUE A, WANG GP, SOULIER J, LIM A, MORILLON E, CLAPPIER E, CACCAVELLI L, DELABESSE E, BELDJORD K, ASNAFI V, MACINTYRE E, DAL-CORTIVO L, RADFORD-WEISS I, BROUSSE N, SIGAUX F, MOSHOUS D, HAUER J, BORKHARDT A, BELOHRADSKY BH, WINTERGERST U, VELEZ MC, LEIVA L, SORENSEN R, WULFFRAAT N, BLANCHE S, BUSHMAN FD, FISCHER A, CAVAZZANA-CALVO M
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2008 - J. Clin. Invest. 118(9):3132-3142 |
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Previously, several individuals with X-linked SCID (SCID-X1) were treated by gene therapy to restore the missing IL-2 receptor gamma (IL2RG) gene to CD34(+) BM precursor cells using gammaretroviral vectors. While 9 of 10 patients were successfully treated, 4 of the 9 developed T cell leukemia 31-68 months after gene therapy. In 2 of these cases, blast cells contained activating vector insertions near the LIM domain-only 2 (LMO2) proto-oncogene. Here, we report data on the 2 most recent adverse events, which occurred in patients 7 and 10. In patient 10, blast cells contained an integrated vector near LMO2 and a second integrated vector near the proto-oncogene BMI1. In patient 7, blast cells contained an integrated vector near a third proto-oncogene,CCND2. Additional genetic abnormalities in the patients' blast cells included chromosomal translocations, gain-of-function mutations activating NOTCH1, and copy number changes, including deletion of tumor suppressor gene CDKN2A, 6q interstitial losses, and SIL-TAL1 rearrangement. These findings functionally specify a genetic network that controls growth in T cell progenitors. Chemotherapy led to sustained remission in 3 of the 4 cases of T cell leukemia, but failed in the fourth. Successful chemotherapy was associated with restoration of polyclonal transduced T cell populations. As a result, the treated patients continued to benefit from therapeutic gene transfer.
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Unité(s) :
Anatomie Pathologique, Biothérapie, E 0210, Immuno-Hématologie-Rhumatologie Pédiatriques, Laboratoire d'Hématologie, U768, CIC-BT
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New ISSCR guidelines underscore major principles for responsible translational stem cell research
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HYUN I, LINDVALL O, AHRLUND-RICHTER L, CATTANEO E, CAVAZZANA-CALVO M, COSSU G, DE LUCA M, FOX IJ, GERSTLE C, GOLDSTEIN RA, HERMEREN G, HIGH KA, KIM HO, LEE HP, LEVY-LAHAD E, LI L, LO B, MARSHAK DR, MCNAB A, MUNSIE M, NAKAUCHI H, RAO M, ROOKE HM, VALLES CS, SRIVASTAVA A, SUGARMAN J, TAYLOR PL, VEIGA A, WONG AL, ZOLOTH L, DALEY GQ
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2008 - Cell Stem Cell 3(6):607-609 |
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The International Society for Stem Cell Research (ISSCR) task force that developed new Guidelines for the Clinical Translation of Stem Cells discusses core principles that should guide the responsible transition of basic stem cell research into appropriate clinical applications.
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Unité(s) :
Biothérapie, CIC-BT
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Polymorphisms of coding trinucleotide repeats of homeogenes in neurodevelopmental psychiatric disorders
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LAROCHE F, RAMOZ N, LEROY S, FORTIN C, ROUSSELOT-PAILLET B, PHILIPPE A, COLLEAUX L, BRESSON JL, MOGENET A, GOLSE B, MOUREN-SIMEONI MC, GORWOOD P, GALLI T, SIMONNEAU M, KREBS MO, ROBEL L
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2008 - Psychiatr. Genet. 18(6):295-301 |
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OBJECTIVES: Autism (MIMmusical sharp209850) and schizophrenia (MIMmusical sharp181500) are both neurodevelopmental psychiatric disorders characterized by a highly genetic component. Homeogenes and forkhead genes encode transcription factors, which have been involved in brain development and cell differentiation. Thus, they are relevant candidate genes for psychiatric disorders. Genetic studies have reported an association between autism and DLX2, HOXA1, EN2, ARX, and FOXP2 genes whereas only three studies of EN2, OTX2, and FOXP2 were performed on schizophrenia. Interestingly, most of these candidate genes contain trinucleotide repeats coding for polyamino acid stretch in which instability can be the cause of neurodevelopmental disorders. Our goal was to identify variations of coding trinucleotide repeats in schizophrenia, autism, and idiopathic mental retardation. METHODS: We screened the coding trinucleotide repeats of OTX1, EN1, DLX2, HOXA1, and FOXP2 genes in populations suffering from schizophrenia (247 patients), autism (98 patients), and idiopathic mental retardation (56 patients), and compared them with control populations (112 super controls and 202 healthy controls). RESULTS: Novel deletions and insertions of coding trinucleotide repeats were found in the DLX2, HOXA1, and FOXP2 genes. Most of these variations were detected in controls and no difference in their distribution was observed between patient and control groups. Two different polymorphisms in FOXP2 were, however, found only in autistic patients and the functional consequences of these variations of repeats have to be characterized and correlated to particular clinical features. CONCLUSION: This study did not identify specific disease risk variants of trinucleotide repeats in OTX1, EN1, DLX2, HOXA1, and FOXP2 candidate genes in neurodevelopmental psychiatric disorders.
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Unité(s) :
CIC 9303, Génétique Médicale Pédiatrique, U781
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Modulation of Lactobacillus casei in ileal and fecal samples from healthy volunteers after consumption of a fermented milk containing Lactobacillus casei DN-114 001Rif
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ROCHET V, RIGOTTIER-GOIS L, LEVENEZ F, CADIOU J, MARTEAU P, BRESSON JL, GOUPIL-FEILLERAT N, DORE J
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2008 - Can. J. Microbiol. 54(8):660-667 |
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Lactobacillus casei DN-114 001 is a probiotic strain able to interact with the immune system and to interfere with gastrointestinal pathogens. The derived strain DN-114 001Rif was studied during its transit through the upper and distal intestine of human volunteers. Seven volunteers participated in the study, which involved intestinal intubation to sample ileal contents and collection of fecal samples, with a wash-out period of 8 days between the 2 steps. The retrieval of the probiotic was analyzed in the ileum every 2 h for 8 h following the ingestion of one dose of the test product and in the feces prior to, during, and after daily consumption of the test product for 8 days. Persistence of the probiotic amplifiable DNA was assessed using temporal temperature gradient gel electrophoresis and real-time PCR. Fluorescent in situ hybridization allowed analysis of the composition of the dominant digestive microbiota. The ingestion of L. casei DN-114 001Rif led to a significant and transient increase of its amplifiable DNA in ileal and fecal samples. This is related to a high stability in the composition of dominant groups of the gut microbiota. Data from ileal samples are scarce and our study confirms the potentiality for interaction between probiotics and the human immune system.
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Unité(s) :
CIC 9303
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Relationship between gamma-glutamyltransferase and fat mass in a general population of 8-17 years old children. The FLVS II study
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BOTTON J, HEUDE B, ANDRE P, BRESSON JL, DUCIMETIERE P, CHARLES MA
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2007 - Diabetes Metab. 33(5):354-359 |
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AIM: Elevated gamma-glutamyltransferase (GGT) is positively associated with severity of obesity in obese children and with increased BMI and waist circumference in general populations of adults. We aimed to study the relationships between GGT and anthropometric parameters in a general population of children. METHODS: This cross-sectional study was conducted in 219 boys and 214 girls included in the Fleurbaix Laventie Ville Sante II study. Weight, height, four skinfolds and waist circumference were measured. We compared the means of GGT activity according to gender and Tanner stage, and according to overweight status (IOTF definition) and quartiles of anthropometric parameters. We then calculated partial Pearson correlations by gender between GGT and anthropometric parameters taking age and Tanner stage into account. RESULTS: GGT activity was higher in boys than in girls as soon as puberty started (P<0.001). The higher difference was observed for Tanner stage III (GGT=10.2 UI/L, CI95% of mean (9.5, 11.1) vs. 7.8 UI/L (7.2, 8.4)). Anthropometric parameters were significantly associated with GGT, particularly waist circumference (r=0.28 in boys; r=0.24 in girls). After an additional adjustment for sum of skinfolds, this correlation disappeared in boys (r=0.06), and was still significant in girls (r=0.19). CONCLUSION: In a general population of children, overweight and abdominal fat distribution were associated with increased GGT. As some studies have shown that GGT could predict the metabolic syndrome in children and type 2 diabetes in adults, the modest elevation of GGT observed in overweight children may be of pathophysiological importance in the long term.
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Unité(s) :
CIC 9303
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Cardiovascular risk factor levels and their relationships with overweight and fat distribution in children: the Fleurbaix Laventie Ville Sante II study
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BOTTON J, HEUDE B, KETTANEH A, BORYS JM, LOMMEZ A, BRESSON JL, DUCIMETIERE P, CHARLES MA
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2007 - Metabolism 56(5):614-622 |
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This study aimed to document for the first time in a general population of French children the prevalence and levels of cardiovascular risk factors and to assess separately in boys and girls whether these risk factors were associated with fat mass distribution independently of subcutaneous overall adiposity. A cross-sectional analysis of baseline data from 452 children (235 boys and 217 girls) aged 8 to 17 years included in a 1999 population-based epidemiologic study (the Fleurbaix Laventie Ville Sante II study) was made. Overweight was defined according to the International Obesity Task Force references and the 90th percentiles of the French body mass index curves. The thresholds of parameters defining cardiovascular and metabolic risks were the 95th percentile of the Task Force Report on High Blood Pressure in Children and Adolescents for blood pressure and those of the American Academy of Pediatrics for lipids. Anthropometric and biological parameters were described by sex and according to overweight status. Partial correlations between cardiovascular risk factors and anthropometric measures of adiposity (body mass index, sum of 4 skinfold thicknesses, waist circumference, waist-to-height ratio) were calculated. Then, these correlations were additionally adjusted for the sum of 4 skinfold thicknesses. High plasma triglycerides, high insulin concentration, and low plasma high-density lipoprotein cholesterol (HDL-C) concentration were associated with all measures of adiposity (|r| > or = 0.20, P < .002). When obese children were excluded, overweight children already had high triglycerides and low HDL-C levels, respectively, 2 and 20 times more frequently than normal-weight children did. Among overweight children, 7.7% had at least 2 risk factors among high blood pressure, high plasma triglycerides or glucose, and low HDL-C concentration vs 0.25% among normal-weight children (P = .002). After adjusting for the sum of skinfolds, an independent association between the risk factors and waist circumference was found in girls. In conclusion, (a) modest excess weight is associated with increased levels of cardiovascular risk factors. (b) In girls, abdominal fat distribution is associated with cardiovascular risk factors, independently of overall adiposity. (c) International definition of abdominal obesity in children is required to standardize studies and to progress in the evaluation of childhood obesity and its consequences.
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Unité(s) :
CIC 9303
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Safety and immunogenicity of an inactivated split-virion influenza A/Vietnam/1194/2004 (H5N1) vaccine: phase I randomised trial
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BRESSON JL, PERRONNE C, LAUNAY O, GERDIL C, SAVILLE M, WOOD J, HOSCHLER K, ZAMBON MC
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2006 - Lancet 367(9523):1657-1664 |
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BACKGROUND: Pathogenic avian influenza A virus H5N1 has caused outbreaks in poultry and migratory birds in Asia, Africa, and Europe, and caused disease and death in people. Although person-to-person spread of current H5N1 strains is unlikely, the virus is a potential source of a future influenza pandemic. Our aim was to assess the safety and immunogenicity of a vaccine against the H5N1 strain. METHODS: We did a randomised, open-label, non-controlled phase I trial in 300 volunteers aged 18-40 years and assigned one of six inactivated split influenza A/Vietnam/1194/2004 (H5N1) influenza vaccine formulations, comprising 7.5 microg (with adjuvant n=50, without adjuvant n=49), 15 microg (n=50, n=50), or 30 microg (n=51, n=50) of haemagglutinin with or without aluminium hydroxide adjuvant. Individuals received two vaccinations (on days 0 and 21) and provided blood samples (on days 0, 21, and 42) for analysis by haemagglutination inhibition and microneutralisation. We recorded all adverse events. Analyses were descriptive. FINDINGS: All formulations were well tolerated, with no serious adverse events, few severe reactions, and no oral temperatures of more than 38 degrees C. All formulations induced an immune response, and responses were detectable in some individuals after only one dose. The adjuvanted 30 microg formulation induced the greatest response (67% haemagglutinin-inhibition seroconversion rate after two vaccinations). Adjuvant did not improve the response to the lower doses. Two vaccinations of non-adjuvanted 7.5 microg, adjuvanted 15 microg, or non-adjuvanted 15 microg seroconverted more than 40% of participants (haemagglutinin-inhibition test only). Haemagglutinin inhibition and neutralising results were comparable. INTERPRETATION: A two-dose regimen with an adjuvanted 30 microg inactivated H5N1 vaccine was safe and showed an immune response consistent with European regulatory requirements for licensure of seasonal influenza vaccine. We noted encouraging responses with lower doses of antigen that need further study to ascertain their relevance for the choice of the final pandemic vaccine.
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Unité(s) :
CIC 9303
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Pharmacokinetics of hydroxyurea 1,000 mg coated breakable tablets and 500 mg capsules in pediatric and adult patients with sickle cell disease
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DE MONTALEMBERT M, BACHIR D, HULIN A, GIMENO L, MOGENET A, BRESSON JL, MACQUIN-MAVIER I, ROUDOT-THORAVAL F, ASTIER A, GALACTEROS F
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2006 - Haematologica 91(12):1685-1688 |
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Little is known about the pharmacokinetics of hydroxyurea in patients with sickle cell disease (SCD). Our aims were to evaluate bioequivalence between standard hydroxyurea capsules and a new formulation of 1,000 mg coated breakable tablets in adults and to compare pharmacokinetic parameters in adults and children with SCD. Fifteen adults received hydroxyurea capsules and tablets in a randomized cross-over study. Eleven children received hydroxyurea tablets. The results showed bioequivalence between capsules and tablets in adults. Pharmacokinetic parameters were not significantly different between adults and children. Considerable inter-individual variability was noted.
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Unité(s) :
CIC 9303, Pédiatrie Générale
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Survival of Lactobacillus casei in the human digestive tract after consumption of fermented milk
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OOZEER R, LEPLINGARD A, MATER DD, MOGENET A, MICHELIN R, SEKSEK I, MARTEAU P, DORE J, BRESSON JL, CORTHIER G
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2006 - Appl. Environ. Microbiol. 72(8):5615-5617 |
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A human trial was carried out to assess the ileal and fecal survival of Lactobacillus casei DN-114 001 ingested in fermented milk. Survival rates were up to 51.2% in the ileum and 28.4% in the feces. The probiotic bacterium has the capacity to survive during its transit through the human gut.
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Unité(s) :
CIC 9303
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Effects of orally administered Lactobacillus casei DN-114 001 on the composition or activities of the dominant faecal microbiota in healthy humans
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ROCHET V, RIGOTTIER-GOIS L, SUTREN M, KREMENTSCKI MN, ANDRIEUX C, FURET JP, TAILLIEZ P, LEVENEZ F, MOGENET A, BRESSON JL, MEANCE S, CAYUELA C, LEPLINGARD A, DORE J
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2006 - Br. J. Nutr. 95(2):421-429 |
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The composition and activities of the faecal microbiota in twelve healthy subjects analysed in a single open study were monitored before (1-week baseline step), during (10 d supplementation step) and after (10 d follow-up step) the ingestion of a fermented milk containing Lactobacillus casei DN-114 001. Fluorescent in situ hybridisation with group-specific DNA probes, real-time PCR using L. paracasei group-specific primers and temporal temperature gradient gel electrophoresis (TTGE) using group-specific primers were carried out, together with bacterial enzyme activity and metabolite analyses to monitor the structure and activities of the faecal microbiota. L. casei DNA was detected in the faeces of all of the subjects by TTGE after 10 d supplementation. Its quantification by real-time PCR showed a 1000-fold increase during the test step compared with initial levels. No major modification in either the dominant members of the faecal microbiota or their activities was observed during the trial. In conclusion, the short-term consumption of a milk product containing L. casei DN-114 001 was accompanied by a high, transient increase in the quantity of this strain in the faeces of all of the subjects without markedly affecting biochemical or bacteriological factors.
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Unité(s) :
CIC 9303
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Serum adiponectin and leptin concentrations in HIV-infected children with fat redistribution syndrome
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VERKAUSKIENE R, DOLLFUS C, LEVINE M, FAYE A, DEGHMOUN S, HOUANG M, CHEVENNE D, BRESSON JL, BLANCHE S, LEVY-MARCHAL C
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2006 - Pediat. Res. 60(2):225-230 |
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Human immunodeficiency virus (HIV)-related lipodystrophy is characterized by adipose tissue redistribution, dyslipidemia, and insulin resistance. We hypothesized that fat redistribution and metabolic abnormalities in HIV-infected children are related to alterations in endocrine function of adipose tissue. A multicenter study was conducted in 130 HIV-infected children. Lipodystrophy definition was based on the central to peripheral skinfold ratio. Fasting adiponectin, leptin, insulin concentrations, glycemia, and lipid profile were measured in all children. Fat redistribution syndrome was apparent in 32 children: 14 with atrophic (LPDA) and 18 with hypertrophic lipodystrophy (LPDH). Mean serum adiponectin levels were significantly decreased in LPDA and LPDH groups compared with the group with no lipodystrophy (LPD-). Fasting insulin concentration was significantly higher in LPDA and LPDH groups versus LPD-. Mean serum leptin concentration was significantly increased only in LPDH compared with LPDA and LPD- groups. Triglyceride levels were significantly increased and high-density lipoprotein (HDL)-cholesterol concentration decreased in the LPDA versus LPD- group. Controlling for puberty stage, gender, percentage of total fat mass, serum lipids, HIV treatment, and disease severity, adiponectin was significantly and inversely associated with central obesity and insulin/glucose ratio. Fat redistribution had no significant effect on leptin concentration, which was directly related to the percentage of body fat, female gender, and insulin/glucose ratio. In conclusion, HIV-infected children with symptoms of fat redistribution have decreased levels of adiponectin, associated with insulin resistance and dyslipidemia.
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Unité(s) :
CIC 9303, Immuno-Hématologie Pédiatrique
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Anthropometric relationships between parents and children throughout childhood: the Fleurbaix-Laventie Ville Sante Study
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HEUDE B, KETTANEH A, RAKOTOVAO R, BRESSON JL, BORYS JM, DUCIMETIERE P, CHARLES MA
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2005 - Int. J. Obes. 29(10):1222-1229 |
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BACKGROUND:The study of parent-child anthropometric relationships and their evolution over time may help to better understand familial risk factors for childhood obesity.METHODS:In a population-based cohort of 124 nuclear families (Fleurbaix-Laventie Ville Sante Study (FLVS) I and II), various anthropometric parameters were measured in both parents and their children, first when the children were prepubescent and again at the end of puberty. Troncular adiposity repartition was estimated by calculating troncular to peripheral skinfolds ratio and waist-to-hip circumferences ratio. Birth and infancy heights and weights were also obtained from the children's health booklets. Parent-child correlations were estimated in infancy, before and at the end of the child's puberty. A prospective analysis was performed to predict the changes in the children's measurements over puberty according to their parents' corresponding baseline values.RESULTS:BMI and weight correlations at birth were high (>0.30) with the mother and low (<0.10) with the father, then they converged to an intermediate level at 2 y and remained between 0.2 and 0.3 thereafter. Correlations for waist circumference were already present at the prepubertal period and persisted on the same level at the postpubertal period, whereas correlations for subcutaneous adiposity - measured by four skinfolds - and for adiposity distribution - measured by ratios - were higher at the postpubertal period. Moreover, the prospective approach showed that mother's BMI predicted the evolution of her children's BMI over puberty, whereas this relationship was observed more specifically with the father concerning adiposity distribution parameters.CONCLUSION:Maternal adiposity may act early in life on the adiposity of the child. Maternal and paternal adiposities seem to have quite distinct effects at two key periods of the child's adiposity development such as the prenatal and pubertal periods.International Journal of Obesity (2005) 29, 1222-1229. doi:10.1038/sj.ijo.0802920; published online 29 March 2005.
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Unité(s) :
CIC 9303
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The core-specific precursor T cell response is directed to the N-terminal and central parts of the protein and positively correlates to the viral load in chronically HCV-infected patients
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JANVIER G, CHAIX ML, FONTAINE H, BRESSON JL, POL S, RIVIERE Y
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2005 - Virology 340(2):318-325 |
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The cellular immune response to hepatitis C virus (HCV) plays a critical role in determining the clearance or persistence of HCV. Moreover, in chronic HCV infection, these responses that are insufficient to eradicate virus completely may cause liver injury. In this study, the memory T cells responses specific to the core protein were measured by interferon-gamma Elispot assay after in vitro stimulation of peripheral blood mononuclear lymphocytes from chronically infected subjects. Ten out of the 22 patients studied (45%) present a core-specific response with a preferential recognition of the N-terminal and central parts. There was no relationship between T cell responses and the parameters of disease evolution as determined by ALT (serum alanine transaminase levels), and histologic hepatic damage (Metavir score A and F), but there was a positive relationship between the presence of a core-specific T cell responses and the viraemia.
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Unité(s) :
CIC 9303, Laboratoire de Microbiologie, U370
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Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus survive gastrointestinal transit of healthy volunteers consuming yogurt
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MATER DD, BRETIGNY L, FIRMESSE O, FLORES MJ, MOGENET A, BRESSON JL, CORTHIER G
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2005 - FEMS Microbiol. Lett. 250(2):185-187 |
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To date, there is significant controversy as to the survival of yogurt bacteria (namely, Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus) after passage through the human gastrointestinal tract. Survival of both bacterial species in human feces was investigated by culture on selective media. Out of 39 samples recovered from 13 healthy subjects over a 12-day period of fresh yogurt intake, 32 and 37 samples contained viable S. thermophilus (median value of 6.3 x 10(4) CFU g(-1) of feces) and L. delbrueckii (median value of 7.2 x 10(4)CFU g(-1) of feces), respectively. The results of the present study indicate that substantial numbers of yogurt bacteria can survive human gastrointestinal transit.
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Unité(s) :
CIC 9303
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Chloride transport in nasal ciliated cells of cystic fibrosis heterozygotes
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SERMET-GAUDELUS I, DECHAUX M, VALLEE B, FAJAC A, GIRODON E, NGUYEN-KHOA T, MARIANOVSKI R, HURBAIN I, BRESSON JL, LENOIR G, EDELMAN A
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2005 - Amer. J. Respir. Crit. Care Med. 171(9):1026-1031 |
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Studying subjects heterozygous for mutations of the cystic fibrosis (CF) gene may help clarify the impact on disease onset of CF transmembrane conductance regulator protein (CFTR-)-dependent chloride secretion. CFTR-mediated chloride transport was evaluated in 52 heterozygous subjects, 32 healthy control subjects, and 77 patients with CF with class I or II mutations. We measured the change in nasal potential difference in response to chloride-free isoproterenol solution for each subject and used a video-imaging fluorescent dye assay to assess the percentage of nasal ciliated cells with cAMP-dependent anion conductance. Our findings did not confirm the standard assumption that heterozygosity implies 50% of normal CFTR function. Half the heterozygous subjects had CFTR-mediated chloride transport levels below 50% of the normal range, and one-third had levels similar to those of the patients with CF. This reduced CFTR function was not associated with an elevated prevalence of CF-like symptoms in heterozygous subjects but was highly related to respiratory status in the patients with CF. These data suggest that CFTR-dependent chloride conductance does not directly modulate disease severity but may be part of a more global defect in patients with CF involving other CFTR functions or currently unknown modulatory factors.
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Unité(s) :
CIC 9303, Département de Pédiatrie, U467
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Could treatments with beta-blockers be associated with a reduction in cancer risk?
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ALGAZI M, PLU-BUREAU G, FLAHAULT A, DONDON MG, LE MG
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2004 - Rev. Epidémiol. Santé Publ. 52(1):53-65 |
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BACKGROUND: The relationship between the use of anti-hypertensive drugs and cancer risk remains controversial. The main objective of this study was to assess the potential effect of beta-blocker use on cancer risk. METHODS: In a cohort of 839 patients with cardiovascular disease, followed up prospectively for an average period of 10 years, cancer occurrence was recorded according to the exposure to beta-blockers. The relative risk of cancer associated with beta-blocker use was estimated using a Cox model adjusted on gender and age. Ever- vs never-use of beta-blockers and duration of exposure to the drug were analyzed as time-dependent variables. In addition, the standardized incidence ratios (SIR) were calculated using the corresponding age- and gender-adjusted cancer incidences in the French general population. RESULTS: A total of 326 beta-blocker users and 513 users of other treatments were included in the cohort. During the follow-up period, representing 8,466 person-years, incident cancer cases were 15 and 59 in beta-blocker ever-users versus never-users, respectively. Using the Cox model, the overall relative risk of cancer was 0.51 (95% confidence interval [95% CI]: 0.29-0.90) in the beta-blocker ever-users versus never-users (p=0.02), with a 6% decrease per year of use (95% CI: 1%-12%; p=0.03). The corresponding SIR ratio between these two groups was 0.44 (95% CI: 0.24-0.76). CONCLUSION: In this cohort, the beta-blocker treatments appeared to decrease the cancer risk significantly. However, this result should be considered with caution; further work is needed, as some sources of bias associated with this type of epidemiological study cannot be totally excluded.
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Unité(s) :
Endocrinologie & Médecine de la Reproduction, URC
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Impact of progestagens on activated protein C (APC) resistance among users of oral contraceptives
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ALHENC-GELAS M, PLU-BUREAU G, GUILLONNEAU S, KIRZIN JM, AIACH M, OCHAT N, SCARABIN PY
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2004 - J. Thromb. Homeost. 2(9):1594-1600 |
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Oral contraceptive (OC) use is associated with an increased risk of venous thromboembolism. Previous data reported higher thrombotic risk in women using third-generation combined OC than in those using second generation OC. The difference could be explained by differential effects of progestagens on plasma sensitivity to activated protein C (APC). The main purpose of this cross-sectional study was to assess the influence of a progestagen-only OC (chlormadinone acetate) as well as the effect of several combined OC with different progestagen components on APC resistance. The effect of APC on endogenous thrombin potential (ETP) was investigated in the plasma of healthy women using either combined OC (n=82) or progestagen-only OC (n=28), and in non-users (n=64). Carriers of factor V Leiden were excluded. Compared with non-users, there was no significant change in APC resistance in women using progestagen-only OC. Women who used combined OC were less sensitive to APC than non-users (P < 0.001) and the difference was significantly more pronounced in women using third-generation OC (n=41) than in those who used second-generation OC containing levonorgestrel (n=22) (P < 0.05). Compared with OC containing levonorgestrel, use of norethisterone-containing OC (n = 9) was associated with an increased resistance to APC (P < 0.05). Women who used cyproterone-containing OC (n = 10) were less sensitive to APC than those using third-generation OC (P < 0.05) or second-generation OC containing levonorgestrel (P < 0.05). Protein S, factor II and FVIII levels explained in part the OC-related changes in APC sensitivity variations. ETP-based APC resistance may contribute to explain why different brands of OC can be associated with different levels of thrombogenicity.
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Unité(s) :
URC
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Glucocorticoid pharmacokinetics and growth retardation in children with renal transplants
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CHAVATTE C, GUEST G, PROUST V, LE BIHAN C, GIMENEZ F, MAISIN A, LOIRAT C, MOGENET A, BRESSON JL, HANKARD R, BROYER M, NIAUDET P, SINGLAS E
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2004 - Pediat. Nephrol. 19(8):898-904 |
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Long-term glucocorticoid treatment contributes to the growth retardation in children after renal transplantation. We investigated whether determination of prednisone (PN) and prednisolone (PL) in plasma and PN, PL, and 6-beta-hydroxyprednisolone (betaOH-PL) in urine could help to predict growth. PN and PL pharmacokinetics were studied in 36 children, from 5 to 15 years of age, receiving daily (D) or alternate-day (AD) oral PN treatment. Statural growth velocity was evaluated over a 1-year period. We compared three groups of children according to the growth kinetics during the study year (catch-up, stable, or decline) for clinical and pharmacokinetic parameters. A multiple linear regression analysis was performed in order to determine pharmacokinetic parameters able to explain height 1 year after inclusion. Height at the beginning of the study, creatinine clearance, and type of D or AD treatment explained 94.2% of height variance 1 year after inclusion. Only PL clearance was associated with growth evolution, but introduction of PL clearance in the multivariate model did not improve the variance of height accounted for by the previous model. We, therefore, do not recommend using glucocorticoid pharmacokinetics to predict growth retardation in children with renal transplantation.
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Unité(s) :
CIC 9303, Néphrologie Pédiatrique, Pharmacie
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Progestogen-only contraception in women at high risk of venous thromboembolism
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CONARD J, PLU-BUREAU G, BAHI N, HORELLOU MH, PELISSIER C, THALABARD JC
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2004 - Contraception 70(6):437-441 |
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The objective of the study was to evaluate the venous impact of a progestogen-only contraception on women at high risk of venous thromboembolism (VTE). In this retrospective cohort study, 204 consecutive women at high risk of VTE were recruited between January 1992 and June 1997 and were prospectively followed. Women using chlormadinone acetate (CMA) at antigonadotropic doses (n=102) were matched by age and date of referral and history of venous thrombosis with women who had no hormonal contraception (n=102). During follow-up (mean of 33 months), nine episodes of VTE were observed: three in women receiving CMA and six in nontreated women. Using the Cox model to adjust for confounding variables such as age, thrombophilia and body mass index, the relative risk of VTE associated with the use of CMA was not significant [relative risk: 0.8 (0.2-3.9)]. These reassuring results need to be confirmed in other prospective studies.
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Unité(s) :
Endocrinologie & Médecine de la Reproduction, URC
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Penetration of enfuvirtide, tenofovir, efavirenz, and protease inhibitors in the genital tract of HIV-1-infected men
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GHOSN J, CHAIX ML, PEYTAVIN G, REY E, BRESSON JL, GOUJARD C, KATLAMA C, VIARD JP, TRELUYER JM, ROUZIOUX C
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2004 - AIDS 18(14):1958-1961 |
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Unité(s) :
CIC 9303, Infectiologie, Laboratoire de Microbiologie, EA3620
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Single-dose and steady-state pharmacokinetics of tenofovir disoproxil fumarate in human immunodeficiency virus-infected children
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HAZRA R, BALIS FM, TULLIO AN, DECARLO E, WORRELL CJ, STEINBERG SM, FLAHERTY JF, YALE K, POBLENZ M, KEARNEY BP, ZHONG L, COAKLEY DF, BLANCHE S, BRESSON JL, ZUCKERMAN JA, ZEICHNER SL
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2004 - Antimicrob. Agents Chemother. 48(1):124-129 |
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Unité(s) :
CIC 9303, Immuno-Hématologie Pédiatrique
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Death-associated protein kinase loss of expression is a new marker for breast cancer prognosis
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LEVY D, PLU-BUREAU G, DECROIX Y, HUGOL D, ROSTENE W, KIMCHI A, GOMPEL A
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2004 - Clin. Cancer Res. 10(9):3124-3130 |
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PURPOSE: Death-associated protein (DAP)-kinase is a new Ser/Thr kinase involved in cell apoptosis and tumor suppression, the expression of which has been correlated to invasive potential and metastasis in several human neoplastic tissues. We analyzed the level of DAP-kinase expression in breast cancer specimens and its correlation with survival. EXPERIMENTAL DESIGN: One hundred twenty-eight breast cancer specimens were analyzed by immunohistochemistry. Patient records were studied retrospectively for demographic characteristics, clinical data, hormonal treatment, outcome, and survival. DAP-kinase protein expression was also studied in normal breast cells primary cultures under estrogen and antiestrogen treatment. RESULTS: Among the 128 patients, 30 showed a DAP-kinase staining < or = 20%, whereas 98 had a staining over 20%. Mean follow-up time was 62 months. The association between tumor Scarff-Bloom and Richardson grade (P = 0.009), estrogen receptor and progesterone receptor expression (P = 0.002 and 0.001, respectively), tumor size (P = 0.05), Bcl-2 expression (P = 0.004), and DAP-kinase immunostaining in the ductal carcinoma group was highly significant. Overall (64 months) and disease-free (63 months) survival in the high DAP-kinase expression group were significantly longer compared with the women whose tumors showed a loss of DAP-kinase expression (51 and 43 months, respectively). DAP-kinase protein was strongly expressed in normal breast tissue and in human breast epithelial cells primary cultures. Estradiol decreased DAP-kinase expression in these cells, arguing for hormonal regulation of the protein. CONCLUSIONS: Loss of DAP-kinase expression negatively correlates to survival and positively correlates to the probability of recurrence in a very significant manner. DAP-kinase thus constitutes a novel and independent prognosis marker for breast cancer.
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Unité(s) :
URC
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Evaluation of fetal pulmonary vasculature by power Doppler imaging in congenital diaphragmatic hernia
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MAHIEU-CAPUTO D, AUBRY MC, EL SAYED M, JOUBIN L, THALABARD JC, DOMMERGUES M
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2004 - J. Ultrasound Med. 23(8):1011-1017 |
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OBJECTIVE: To evaluate the feasibility of prenatal power Doppler imaging of pulmonary arteries in congenital diaphragmatic hernia and to study its potential to predict outcome. METHODS: A prospective observational study was conducted. Forty-two cases of congenital diaphragmatic hernia (32 left and 10 right) without associated anomalies were analyzed. Qualitative evaluation of pulmonary vasculature was based on power Doppler imaging performed at 26 to 38 weeks. The pulmonary arteries were studied in the lung contralateral to the hernia. Pulmonary Doppler angiography was considered satisfactory when 3 levels of bifurcation defining 3 distinct segments of the pulmonary arteries were imaged and was otherwise considered poor. We also recorded the gestational age at diagnosis, side of the hernia, abdominal circumference below the third percentile, amniotic fluid volume, lung/thoracic area ratio, left/right ventricle ratio, and, in left-sided hernias, stomach position, and we carried out a multivariate analysis to determine the contribution of each factor to predict neonatal mortality. RESULTS: More than 3 divisions of the fetal pulmonary arteries were imaged in 20 cases; 1 or 2 divisions or none were imaged in 22. Neonatal mortality was significantly greater when fewer than 3 divisions of the pulmonary arteries were imaged (18 [82%] of 22) than when 3 divisions could be identified on power Doppler imaging (5 [25%] of 20; P =.0005). However, the lung/thoracic area ratio was the only factor that remained significantly associated with mortality in the multivariate analysis. CONCLUSIONS: An altered pulmonary power Doppler image is associated with neonatal mortality, but estimation of the lung area remains the best predictor of neonatal outcome.
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Unité(s) :
URC, Maternité
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Relationships between physical activity and plasma leptin levels in healthy children: the Fleurbaix-Laventie Ville Sante II Study
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ROMON M, LAFAY L, BRESSON JL, OPPERT JM, BORYS JM, KETTANEH A, CHARLES MA
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2004 - Int. J. Obes. Relat. Metab. Disord. 28(10):1227-1232 |
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OBJECTIVE:: To study the relationships between physical activity and plasma leptin levels in children from a population-based study, taking into account puberty stages. DESIGN:: Subjects were part of the Fleurbaix-Laventie Ville Sante (FLVS) II Study, a longitudinal study on the determinants of weight gain in children and their parents. At baseline examination, 253 girls and 257 boys aged 8-18 y were examined. MEASUREMENTS:: Height and weight were measured, adiposity was assessed by the sum of four skinfold thicknesses (SSK). Pubertal stage was assigned according to Tanner. Leisure-time physical activity (LTPA) was assessed by the Modifiable Activity Questionnaire and ambulatory activity by pedometer recording over a week. A fasting blood sample was obtained to determine plasma leptin and insulin levels. RESULTS:: Plasma leptin was higher in girls compared to boys (8.3 (1.6-36.5) ng/ml vs 2.2 (0.1-15.3) ng/ml, P<0.001). Multivariate analyses were performed with leptin as dependent variable, and number of steps by day, Tanner stage, insulin and SSK as independent variables. In girls, leptin was negatively correlated to number of steps/day (P<0.001) and positively to SSK (P<0.001) and insulinemia (P<0.001). In boys, leptin was correlated to insulinemia (P<0.001), SSK (P<0.001), Tanner stage (P<.0001), but not to physical activity. CONCLUSION:: Physical activity is negatively related to leptin levels in girls only and this association is independent of fasting plasma insulin. In children, fasting insulinemia remains associated with leptin levels after taking into account adiposity, physical activity and Tanner stage.International Journal of Obesity (2004) 28, 1227-1232. doi:10.1038/sj.ijo.0802725 Published online 17 August 2004
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Unité(s) :
CIC 9303
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Three-dimensional ultrasonographic assessment of fetal lung volume as prognostic factor in isolated congenital diaphragmatic hernia
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RUANO R, BENACHI A, JOUBIN L, AUBRY MC, THALABARD JC, DUMEZ Y, DOMMERGUES M
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2004 - Br. J. Obtstet. Gynaecol. - BJOG 111(5):423-429 |
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Objective To evaluate the potential of three-dimensional ultrasound to predict outcome in congenital diaphragmatic hernia. Design Prospective observational study. Setting Tertiary care centre. Population Twelve cases of isolated congenital diaphragmatic hernia (11 left-sided, 1 right-sided) and 109 controls. Methods Fetal lung volume was assessed by three-dimensional ultrasound using the technique of rotation of the multiplanar imaging. In the control fetuses, a logistic transformation was performed to correlate fetal lung volume with gestational age, and the confidence interval was obtained with a bootstrap resampling. A mathematical equation was then obtained allowing calculation of the expected fetal lung volume as a function of gestational age. In fetuses with congenital diaphragmatic hernia, the observed/expected lung volume ratio was compared with postnatal outcome. Main outcome measures Neonatal mortality and pulmonary hypoplasia, which was defined as lung/body weight ratios less than 0.012. Results The expected fetal lung volume was derived from the mathematical equation: Fetal lung volume (mL) = exp (4.72/(1 + exp ((20.32 - gestational age in weeks)/6.05))). The observed/expected fetal lung volume ratio was significantly lower in the congenital diaphragmatic hernia group (median: 0.34, range: 0.16-0.66), than in the control group (median: 1.02, range: 0.62-1.97, P < 0.0001). The distribution of this ratio was significantly downshifted in the infants with congenital diaphragmatic hernia who died (median: 0.19, range: 0.18-0.66) compared with survivors (median: 0.44, range: 0.36-0.66, P= 0.04). The observed/expected fetal lung volume ratio was also correlated with the postmortem lung/body weight ratio. Conclusion In isolated congenital diaphragmatic hernia, fetal lung volume measurement by three-dimensional ultrasound is a potential predictor for pulmonary hypoplasia and postnatal outcome.
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Unité(s) :
URC, Maternité, Endocrinologie & Médecine de la Reproduction
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Fetal lung volume estimated by 3-dimensional ultrasonography and magnetic resonance imaging in cases with isolated congenital diaphragmatic hernia
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RUANO R, JOUBIN L, SONIGO P, BENACHI A, AUBRY MC, THALABARD JC, BRUNELLE F, DUMEZ Y, DOMMERGUES M
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2004 - J. Ultrasound Med. 23(3):353-358 |
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Objective. To assess the agreement of 3-dimensional ultrasonography and magnetic resonance imaging in estimating fetal lung volume in cases with isolated congenital diaphragmatic hernia. Methods. Fetal lung volume was measured in 11 cases of congenital diaphragmatic hernia (10 left and 1 right) by 3-dimensional ultrasonography and magnetic resonance imaging. These examinations were performed during the same week. The operators were blinded to each other's results. Intraclass correlation was used to evaluate the agreement between 3-dimensional ultrasonography and magnetic resonance imaging estimations of the ipsilateral, contralateral, and total fetal lung volume. A Bland-Altman graph was plotted to detect possible discordant observations. Results. The global intraclass correlation coefficient between magnetic resonance imaging and 3-dimensional ultrasonographic measurement of fetal lung volume was 0.94 (95% confidence interval, 0.78-0.98) with no outliers observed on the Bland-Altman plot. Conclusions. There is a good agreement between 3-dimensional ultrasonography and magnetic resonance imaging for fetal lung volume estimation in cases with congenital diaphragmatic hernia.
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Unité(s) :
Maternité, Radiologie Pédiatrique, URC
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Exogenous progestagens and the human breast
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SITRUK-WARE R, PLU-BUREAU G
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2004 - Maturitas 49(1):58-66 |
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The role of progestins (or progestagens) on the breast tissue remains controversial. However, according to the molecule and the duration of application, cell differentiation and apoptosis may predominate over proliferation. Progestins are also used as second-line agents for the treatment of metastatic breast cancer. In young women with benign breast disease, long-term treatment with 19-nortestosterone progestins had a trend to decrease breast cancer risk contrarily to what was observed in postmenopausal women receiving estrogens. Several compounds with progestational activity have been used for HRT. Small differences in the structure of the molecules may lead to pronounced differences in activities, some progestins exerting androgenic effects and some exerting estrogenic or glucocorticoid like activities. While most progestins do not bind to the estrogen receptors, it has been shown that some androgenic progestins stimulate MCF7 cells proliferation while progestins derived from progesterone did not induce cell multiplication in the same cell lines. Therefore, different progestins may induce different effects on the breast cells. Whether the progestins available to date are able to bind specifically to the progesterone receptors PR-A or PR-B and whether this is of clinical relevance to breast cell proliferation is still unclear. Although the relationship between progestin use and breast cancer risk is still the subject of debate and controversy, the data reported to date suggest that 5 years of treatment carry a low risk but further duration of use increases the risk. Further studies are still needed, randomised long-term prospective studies as well as from the laboratory, especially to determine whether a sequential or continuous regimen would be preferable as far as breast-cell response and apoptosis are concerned, and what are the effects of the various molecules used for HRT.
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Unité(s) :
Endocrinologie & Médecine de la Reproduction, URC
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Methodology for small clinical trials
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VRAY M, GIRAULT D, HOOG-LABOURET N, PORCHER R, THALABARD JC
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2004 - Thérapie 59(281-286 |
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Unité(s) :
URC
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Therapeutic immunoglobulin reduces Ca2+ mobilization and von Willebrand factor secretion, and increases nitric oxide release in human endothelial cells
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DAVID-DUFILHO M, SCHUSSLER O, PERNOLLET MG, BRUNET A, MILLANVOYE-VAN BRUSSEL E, LE-QUAN-SANG KH, RENDU F
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2003 - Thromb. Haemost. 90(6):1046-1053 |
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Intravenous gamma-immunoglobulin (i.v.Ig) is commonly used in the treatment of autoimmune and inflammatory vascular disorders to prevent thrombotic complications. The mechanism of action of i.v.Ig is, however, not yet elucidated. In view of this, we investigated the ability of i.v.Ig to modulate i) Ca(2+) signals of fura-2 loaded endothelial cells, and ii) the associated release of nitric oxide (NO) and von Willebrand factor (vWf). NO was measured either indirectly by radioimmunoassay of cGMP in unstimulated cells or directly by electrochemistry at the surface of stimulated endothelial cells from human umbilical cord veins (HUVEC). Short-term treatment of unstimulated HUVEC with intact i.v.Ig decreased the basal cytosolic Ca(2+) concentration by 20% while it activated the NO/cGMP synthesis. Following i.v.Ig treatment of HUVEC, the Ca(2+) liberation from internal stores and the vWf secretion induced by ATP, thrombin or histamine were significantly reduced by 38 and 60%, respectively. The effects on Ca(2+) signals were observed with intact i.v.Ig as well as with the F(ab')2 or the Fc fragments indicating that both portions are involved in the mechanism of action. The i.v.Ig treatment of HUVECs had no effect on the NO release induced by thrombin or histamine. By contrast, the i.v.Ig treatment increased the ATP-activated NO release by amplifying the Ser1177-eNOS phosphorylation. The i.v.Ig also activated the NO-dependent cGMP release in resting and collagen-stimulated platelets. Since NO is a potent inhibitor of platelet activation and vWF is a platelet adhesion cofactor, the beneficial effects of therapeutic i.v.Ig may lie in the inhibition of platelet adhesion to damaged endothelium.
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Unité(s) :
URC
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beta(1)-adrenergic antagonists and melatonin reset the clock and restore sleep in a circadian disorder, Smith-Magenis syndrome
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DE LEERSNYDER H, BRESSON JL, DE BLOIS MC, SOUBERBIELLE JC, MOGENET A, DELHOTAL-LANDES B, SALEFRANQUE F, MUNNICH A
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2003 - J. Med. Genet. 40(1):74-78 |
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Unité(s) :
U393, Génétique Médicale Pédiatrique, Département de Pédiatrie, CIC 9303, Explorations Fonctionnelle
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Inversion of the circadian melatonin rhythm in Smith-Magenis syndrome
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DE LEERSNYDER H, DE BLOIS MC, BRESSON JL, SIDI D, CLAUSTRAT B, MUNNICH A
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2003 - Rev. Neurol. 159(11 Suppl):21-26 |
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Smith-Magenis syndrome (SMS) is a genetic disease ascribed to an interstitial deletion on chromosome 17 (del 17p11); the prevalence is 1/25000 births. The diagnosis is made on high-resolution karyotype confirmed by FISH. Clinical features include mild dysmorphism, short stature, other malformations (heart, renal, neurologic diseases). Mental retardation is constant; there are major behavioral disturbances and severe sleep disorders. We studied sleep disorders and melatonin secretion in SMS children and we have shown inversion of the circadian rhythm of melatonin, abnormally secreted during the day. This is the first biological model of behavioral and sleep disorder in a genetic disease. Therapeutic approach using beta-blockers in the morning and melatonin in the evening, reset circadian rhythm of melatonin, improve behavior and restore sleep.
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Unité(s) :
Génétique Médicale Pédiatrique, CIC 9303, Cardiologie Pédiatrique
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Absence of nephro-protective effect of acetylcysteine in patients with chronic renal failure investigated by coronary angiography
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EL MAHMOUD R, LE FEUVRE C, LE-QUAN-SANG KH, HELFT G, BEYGUI F, BATISSE JP, METZGER JP
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2003 - Arch. Mal. Coeur Vaisseaux 96(12):1157-1161 |
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Recent studies have suggested that an oral dose of acetylcysteine could play a prophylactic role in the prevention of nephrotoxicity from iodine contrast media in patients affected by chronic renal failure. Between June 2001 and September 2002 we selected 120 patients with a basal plasma creatinine level greater than 1.36 mg/dl investigated by coronary angiography. The treatment group included 60 patients who received 600 mg of acetylcysteine in the morning and evening before the day of the examination together with intravenous saline hydration. The control group patients received hydration alone. The clinical characteristics of the groups were comparable as well as the basal plasma creatinine level: 2.01 +/- 1.1 mg/dl in the acetylcysteine group and 1.81 +/- 0.69 in the control group. The plasma creatinine level was measured 24 and 48 hours after coronary angiography. The respective changes in plasma creatinine level at 24 and 48 hours were 0.12 +/- 0.29 and 0.02 +/- 0.29 mg/dl in the acetylcysteine group and 0.06 +/- 0.29 and 0.07 +/- 0.43 mg/dl in the control group (NS). Acute renal failure caused by the contrast medium, defined by an increase of 25% in the plasma creatinine level compared to the basal value, occurred in 3 patients from the acetylcysteine group and 2 patients from the control group. The only predictive factor for acute renal failure was the quantity of contrast medium (316 +/- 141 vs 173 +/- 115 ml, p<0.05). In conclusion, acute renal failure caused by contrast medium is rare in sufficiently hydrated patients with moderate chronic renal failure when a low dose of contrast medium is used. Our study does not confirm a prophylactic effect of acetylcysteine in the prevention of nephrotoxicity from contrast media following coronary angiography in patients with moderate chronic renal failure.
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Unité(s) :
URC
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Hormone replacement therapy use is associated with a lower occurrence of carotid atherosclerotic plaques but not with intima-media thickness progression among postmenopausal women. The vascular aging (EVA) study
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LE GAL G, GOURLET V, HOGREL P, PLU-BUREAU G, TOUBOUL PJ, SCARABIN PY
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2003 - Atherosclerosis 166(1):163-170 |
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BACKGROUND: Information on the impact of hormone replacement therapy (HRT) on carotid atherosclerosis is limited. Moreover, transdermal estrogens have not been investigated. METHODS: We examined association of HRT use with ultrasonographically assessed carotid atherosclerotic plaque occurrence and mean common carotid artery intima-media thickness (CCA-IMT) progression. Within the Vascular Aging (EVA) Study, a community-based cohort, 815 postmenopausal women aged 59-71 have been followed during 4 years. Among these women, 166 had already used HRT. RESULTS: Women who had ever used HRT experienced a lower occurrence of plaques (8.6 versus 19.1%, P=0.003). After adjustment for the main cardiovascular risk factors, odds-ratio for plaque occurrence was 0.41 (95% confidence interval 0.21-0.78, P=0.01) among ever users of HRT compared with never users. When transdermal route of estrogen administration was used, adjusted odds-ratio was 0.66 (95% confidence interval 0.47-0.99, P=0.04). The progression of IMT, which was measured at a plaque-free site and adjusted on initial levels of CCA-IMT did not differ between ever and never users of HRT. It was 0.011 mm per year among ever users and 0.012 mm per year among never users (P=0.61). CONCLUSION: These data suggest that HRT use may prevent the development of atherosclerotic plaques in postmenopausal women, especially when estrogens are administered by transdermal route.
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Unité(s) :
URC
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Pregnancy-associated venous thromboembolism (VTE) in combined heterozygous factor V Leiden (FVL) and prothrombin (FII) 20210 A mutation and in heterozygous FII single gene mutation alone
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SAMAMA MM, RACHED RA, HORELLOU MH, AQUILANTI S, MATHIEUX VG, PLU-BUREAU G, ELALAMY I, CONARD J
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2003 - Br. J. Haematol. 123(2):327-334 |
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The risk of venous thromboembolism (VTE) in the absence of prophylaxis was evaluated in a retrospective study of 47 women (84 pregnancies) with combined thrombophilia [heterozygous factor V Leiden (FVL) plus prothrombin (FII) 20210A mutation (group I)] and in 82 women (193 pregnancies) with the FII alone (group II). VTE was more frequent in group I than in group II [17.8% versus 6.2%, P = 0.003, relative risk (RR) 2.9, 95% confidence interval (CI) 1.4-5.9], ante partum (7.1% and 2.1%) and post partum (11.5% and 4.2%). The risk was higher in index cases than in family members (RR 2.5, 95% CI 1.2-5.2 and RR 2.1, 95% CI 0.2-22.3 respectively) Even women who had no history of VTE before pregnancy had an increased risk (RR 2.2, 95% CI 1.0-4.8). Our results suggest that, during ante partum, prophylaxis is indicated in women with combined thrombophilia and with a VTE before pregnancy. In those without VTE before pregnancy, prophylaxis might be decided for each individual case, taking into consideration all risk factors. In women with the FII mutation alone, the low risk may not justify prophylaxis in the absence of previous VTE. In post partum, prophylaxis is indicated in all cases.
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Unité(s) :
URC
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Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk
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SCARABIN PY, OGER E, PLU-BUREAU G
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2003 - Lancet 362(9382):428-432 |
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BACKGROUND: Oral oestrogen-replacement therapy (ERT) activates blood coagulation and increases the risk of venous thromboembolism (VTE) in postmenopausal women. Transdermal ERT has little effect on haemostasis, but data assessing its effect on thrombotic process are scarce. We aimed to examine the effect of the route of oestrogen administration on VTE risk. METHODS: We did a multicentre hospital-based case-control study of postmenopausal women in France. During 1999-2002, we recruited 155 consecutive cases with a first documented episode of idiopathic VTE (92 with pulmonary embolisms and 63 with deep venous thrombosis), and 381 controls matched for centre, age, and time of recruitment. FINDINGS: Overall, 32 (21%) cases and 27 (7%) controls were current users of oral ERT, whereas 30 (19%) cases and 93 (24%) controls were current users of transdermal ERT. After adjustment for potential confounding variables, the odds ratio for VTE in current users of oral and transdermal ERT compared with non-users was 3.5 (95% CI 1.8-6.8) and 0.9 (0.5-1.6), respectively. Estimated risk for VTE in current users of oral ERT compared with transdermal ERT users was 4.0 (1.9-8.3). INTERPRETATION: Oral but not transdermal ERT is associated with risk of VTE in postmenopausal women. These data suggest that transdermal ERT might be safer than oral ERT with respect to thrombotic risk.
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Unité(s) :
URC
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Influence of plasma amino acid level on vasopressin secretion
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SCHMITT F, BRESSON JL, BERESSI N, BICHET DG, CHAUVEAU D, BANKIR L
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2003 - Diabetes Metab. 29(4 Pt 1):352-361 |
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OBJECTIVES: Vasopressin (VP) is known to be elevated in patients with diabetes mellitus (DM). While the influence of acute hyperglycemia has been ruled out, the mechanism or the osmotically active compound responsible for the increase in VP secretion is still not elucidated. Because the plasma level of several amino acids (AAs) is increased in DM, we evaluated whether AAs could represent an effective osmotic stimulus for VP secretion.RESEARCH DESIGN AND METHODS: In a cross-over study, eight healthy volunteers randomly received an infusion of isotonic saline (control) or mixed AA solution, i.v., at a low or a high rate (2 or 4.5 mg/min/kg BW, respectively). Plasma VP (P(VP)) was measured for two hours before and three hours during AA or control infusion.RESULTS: AA infusion induced a dose-dependent elevation in plasma AA concentration but did not alter P(VP). However, effective plasma osmolality (P(osm)) (osmolality minus urea concentration) remained unchanged because a concommittant fall in plasma sodium concentration (P(Na)), likely due to sodium-linked uptake of AA in peripheral cells, compensated for the rise in plasma AA.CONCLUSION: The stability of effective P(osm) may explain the lack of change observed in P(VP). Because sodium is a very efficient stimulus for VP secretion, it may be assumed that the fall in P(Na) occurring during AA infusion should have reduced VP secretion and thus P(VP). In this setting, the stability of P(VP) suggests that AAs induced an increase in VP secretion which counterbalanced the fall attributable to the decrease in P(Na). In conclusion, in acute experiments, AAs seem to represent an effective stimulus for VP secretion, almost equally potent as sodium. Further studies are needed to evaluate their contribution to the high P(VP) seen in the chronic setting of DM.
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Unité(s) :
Néphrologie Adulte, CIC 9303, Biochimie Générale
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Iron Metabolism and Requirements in Early Childhood: Do We Know Enough?: A Commentary by the ESPGHAN Committee on Nutrition
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AGGETT PJ, AGOSTONI C, AXELSSON I, BRESSON JL, GOULET O, HERNELL O, KOLETZKO B, LAFEBER HL, MICHAELSEN KF, MICHELI JL, RIGO J, SZAJEWSKA H, WEAVER LT
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2002 - J. Pediatr. Gastroenterol. Nutr. 34(4):337-345 |
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Unité(s) :
CIC 9303, Gastroentérologie Pédiatrique
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Recommended diets : Recent data and practice
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BRESSON JL
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2002 - Sci. Aliments 22(6):637-645 |
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Unité(s) :
CIC 9303
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Contribution of a mathematical modelling approach to the understanding of the ovarian function
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CLÉMENT F, MONNIAUX D, THALABARD JC, CLAUDE D
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2002 - C. R. Biol. 325(4):473-485 |
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The biological meaning of folliculogenesis is to free fertilisable oocytes at the time of ovulation. We approached the study of the control of follicular development at the level of follicular granulosa cells, on the experimental as well as mathematical modelling grounds. We built a mathematical model allowing for the processes of proliferation, differentiation and apoptosis. State variables correspond to the numbers of cells undergoing these different processes, while control variables correspond to the cellular transition rates. The model results raised the notion of proliferative resources, which leads to consider the optimal management of these resources and has motivated the settling of an experiment investigating the changes in the growth fraction within the granulosa throughout terminal development. We are now investigating the way gonadotrophins, and especially FSH, operate on granulosa cells, in order to account for the hormonal control of the divergent commitment of granulosa cells towards either proliferation, differentiation or apoptosis. We are thus focusing on the dynamics of cAMP production, which appears to be a keypoint in FSH signal transduction. (C) 2002 Academie des sciences/Editions scientifiques et medicales Elsevier SAS.
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Unité(s) :
Biostatistique, Endocrinologie & Médecine de la Reproduction, URC
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Amniotic fluid beta-endorphin: A prognostic marker for gastroschisis ?
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MAHIEU-CAPUTO D, MULLER F, JOUVET P, THALABARD JC, JOUANNIC JM, NIHOUL-FEKETE C, DUMEZ Y, DOMMERGUES M
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2002 - J. Pediat. Surg. 37(11):1602-1606 |
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PURPOSE: The aim of this work was to study amniotic fluid beta-endorphin as a potential predictor for postnatal morbidity in gastroschisis. METHODS: Beta-endorphin was assayed in 43 amniotic fluid samples from 13 pregnant women with fetal gastroschisis undergoing diagnostic amniocentesis or therapeutic amnioinfusion and compared with 33 controls. Within the gastroschisis group, the authors investigated the relationship between postnatal morbidity and the peak value of amniotic fluid beta-endorphin (AFBE). RESULTS: Ten AFBE values in 6 cases of gastroschisis were above the upper limit of the 95% confidence interval derived from controls. Postnatal morbidity was significantly higher when peak AFBE exceeded 10 &mgr;g/L (n = 4 pregnancies) compared with below 5 &mgr;g/L (n = 9 pregnancies), as shown by mean duration of mechanical ventilation (15.2 v 3 days; P =.01), of parenteral feeding (77 v. 18.7 days; P =.04), and of hospitalization (84 v 32.2 days; P =.04). There was no statistically significant association between postnatal morbidity markers and prenatal dilation of fetal bowel. CONCLUSIONS: The most severe cases of gastroschisis are associated with high levels of AFBE. The authors speculate that this fetal hormonal response could result from stress or pain caused by prenatal bowel damage. J Pediatr Surg 37:1602-1606. Copyright 2002, Elsevier Science (USA). All rights reserved.
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Unité(s) :
Chirurgie Pédiatrique, Endocrinologie & Médecine de la Reproduction, Maternité, Biostatistique, URC
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Detection and false-positive rates of maternal serum markers for Down syndrome screening according to maternal age in women over 35 years of age. A study of the agreement of eight dedicated software packages
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MULLER F, THALABARD JC, NGO S, DOMMERGUES M
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2002 - Prenat. Diag. 22(5):350-353 |
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Maternal serum markers for trisomy 21 screening (MSS) can be assayed in women >/=35 years in an attempt to reduce the need for invasive procedures and thereby avoid their side effects. Our objective was to compare, in women >/=35, eight different software packages dedicated to second trimester MSS, thus providing reliable data for patient counselling. A simulation study was carried out on 189 sera from women with Down syndrome fetuses and 11 962 sera from mothers of unaffected babies. The first step was to estimate the joint distribution of alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (beta-hCG). The second step was to calculate trisomy 21 detection and false-positive rates for each software according to maternal age (35-45 years), using the usual 1:250 risk threshold. Agreement between software packages was measured using 2x2 kappa coefficients. Detection rates and false-positive rates increased with maternal age. Depending on the software, 57-71% detection rates were achieved at 35 years with 12-18% false-positive rates. At 45 years, 61-100% detection rates were achieved with 66-95% false-positive rates. Up to 39 years, all softwares were concordant (kappa coefficients >0.75). In the range 35-45 years, false-positive and detection rates increased substantially with maternal age and differences between software packages are observed.
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Unité(s) :
Endocrinologie & Médecine de la Reproduction, Maternité, URC
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Allelic variation in exon 18 of the sulfonylurea receptor 1 (SUR1) gene, insulin secretion and insulin sensitivity in nondiabetic relatives of type 2 diabetic subjects
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REIS AF, HANI EH, BERESSI N, ROBERT JJ, BRESSON JL, FROGUEL P, VELHO G
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2002 - Diabetes Metab. 28(3):209-215 |
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BACKGROUND: We have previously observed associations of the T-allele of the exon 18 variant (ACC --> ACT; Thr759Thr) of the sulfonylurea receptor 1 (SUR1) gene with type 2 diabetes mellitus (T2DM). Here we assess beta-cell function and insulin sensitivity in carriers of different genotypes at this locus.METHODS: Pre-hepatic insulin secretion rates (ISR) derived by deconvolution of circulating C-peptide levels, and glucose clearance were assessed during graded infusions of intravenous glucose in CC-homozygous (n=6) and CT-heterozygous (n=6) nondiabetic relatives of CT-heterozygous type 2 diabetic subjects.RESULTS: Average ISR over the duration of the study, adjusted for sex, age, BMI and prevailing glucose levels, were lower in CT-heterozygous subjects as compared with CC-homozygous subjects (3.91 +/- 0.40 vs. 4.84 +/- 0.28 pmol/kg.min(-1); p=0.048). The correlation curves relating ISR to glucose levels were significantly different in the two groups (analyses of covariance p=0.029). Glucose clearance was similar in both groups.CONCLUSIONS: Insulin secretion rates, but not insulin sensitivity, assessed during graded infusion of glucose were mildly decreased in nondiabetic relatives of type 2 diabetic subjects, who carry the at risk T-allele of exon 18 variant of the SUR1 gene. These results suggest that the at-risk allele might have a small effect on pancreatic B-cell function and contribute to the development of T2DM in these families.
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Unité(s) :
CIC 9303, Métabolisme-Neurologie Génétique Pédiatrique
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Normal Function of the Cystic Fibrosis Conductance Regulator Protein Can Be Associated with Homozygous DeltaF508 Mutation
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SERMET-GAUDELUS I, VALLEE B, URBIN I, TOROSSI T, MARIANOVSKI R, FAJAC A, FEUILLET MN, BRESSON JL, LENOIR G, BERNAUDIN JF, EDELMAN A
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2002 - Pediat. Res. 52(5):628-635 |
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Cystic fibrosis (CF) is caused by mutations of the gene encoding for the CFTR (CF transmembrane conductance regulator) protein. The most frequent mutation, the DeltaF508 mutation, results in a defective cAMP-regulated chloride transport in the epithelial cells. The spectrum of clinical manifestations in patients bearing homozygous DeltaF508 mutations can vary considerably, suggesting that, in the patients with a mild disease, CFTR could be partly functional. To test this hypothesis, we explored in nasal ciliated epithelial cells (NCC) of 9 control subjects and 23 DeltaF508 homozygous patients the anion conductive pathway by a halide sensitive fluorescent dye assay SPQ (6-methoxy-N-3'-sulfopropylquinolinium) and the CFTR transcript levels by RT-PCR. As 50% represented the lowest fraction of the control subjects NCC demonstrating a cAMP-dependent conductance, a CF patient was considered as "cAMP responder" if at least 50% of the NCC tested displayed a cAMP-dependent conductive pathway. According to these criteria, 8 of the 23 patients were considered as cAMP responders. They had a significantly less severe disease considering the respiratory function and infectious status. The amount of CFTR mRNA did not differ between the control subjects and the patients. No statistical correlation could be found between the transcript level and the expression of a cAMP conductive pathway. This cAMP-dependent Cl(-) conductance detected in homozygous NCC could be due to a residual CFTR activity and may explain the mild phenotypes observed in some DeltaF508 homozygous patients.
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Unité(s) :
CIC 9303, Département de Pédiatrie, U467
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Measuring cervical length with ultrasound: evaluation of the procedures and duration of a learning method
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VAYSSIERE C, MORINIERE C, CAMUS E, LE STRAT Y, POTY L, FERMANIAN J, VILLE Y
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2002 - Ultrasound Obstet. Gynecol. 20(6):575-579 |
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OBJECTIVE: To evaluate the learning curve and principal learning steps for a novice ultrasound operator to master the technique for measuring cervical length by transvaginal ultrasound. SUBJECTS AND METHODS: The study involved asymptomatic patients with a singleton pregnancy between 21 and 38 weeks attending for a routine ultrasound scan. Two operators new to cervical ultrasound including one with experience in transvaginal gynecological ultrasound were assessed during their training. After an initial lecture session on the technique of cervical measurement, the trainees had one or two supervised practice sessions, validated by two interobserver agreement studies with 30 patients at a time; these compared the level of agreement between trainer and trainee throughout. Five examinations were performed in the first practice session; a second session was planned if the trainee could not perform all five examinations alone satisfactorily, in agreement with four quality criteria predefined for good cervical measurements. The second session lasted until five consecutive examinations could be performed adequately without the trainer's aid. Agreement between the two operators was assessed by intraclass correlation coefficient (ICC). The ICCs were compared with Fisher's Z transformation. RESULTS: Of the 150 patients included, 2.7% gave birth before term. The trainee with no experience in transvaginal ultrasound required two practice sessions; none of the five ultrasound scans performed in the first session was correct. In the second session, 18 consecutive ultrasound examinations were necessary to obtain five consecutive adequate results. During interobserver studies with the trainer, the ICC progressed from 0.43 in the first study to 0.64 in the second and 0.77 in the third (P = 0.049 between the first and third studies). The trainee with experience in transvaginal ultrasound required only one practice session. The ICC increased from 0.73 to 0.85 in the two interobserver studies with the trainer. CONCLUSIONS: Measurement of cervical length by transvaginal ultrasound examination is a technique that can be learnt rapidly. While roughly 23 supervised ultrasound scans appear necessary for an operator with no experience in transvaginal ultrasound, substantially fewer are required for an operator already familiar with this approach for other indications.
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Unité(s) :
Biostatistique, URC
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Screening for down syndrome using first-trimester ultrasound and second-trimester maternal serum markers in a low-risk population: a prospective longitudinal study
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AUDIBERT F, DOMMERGUES M, BENATTAR C, TAIEB J, THALABARD JC, FRYDMAN R
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2001 - Ultrasound Obstet. Gynecol. 18(1):26-31 |
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Objectives To compare nuchal translucency and second-trimester maternal serum measurements as alternative methods of antenatal screening for Down syndrome in a low-risk population and to evaluate the consequence of combining the results in the estimation of risk. Design In a consecutive series of 4130 women aged less than 38 years with a singleton pregnancy, we examined both the detection rate of Down syndrome by nuchal translucency measurement at 10-14 weeks and maternal serum screening by human chorionic gonadotrophin and alpha-fetoprotein at 14-18 weeks. Women with a nuchal translucency, measurement of greater than or equal to3 mm and women with a maternal serum screening-derived risk greater than or equal to 1/250 were recommended to have amniocentesis. A second-trimester detailed ultrasound scan was also performed in all women. The outcome of all pregnancies was recorded prospectively and the detection rate and false-positive rate of different screening strategies were retrospectively analyzed. Results Out of the 4130 pregnancies that were followed (mean maternal age, 30.1 years), 12 cases of Down syndrome were observed (0.28%), all detected prenatally. Seven of 12 cases had a nuchal translucency measurement of greater than or equal to3 mm (58%), and six out of 10 cases with available maternal serum screening had a calculated risk of greater than or equal to 1/250 (60%). Four of the five Down syndrome cases with a nuchal translucency measurement of < 3 mm were detected by subsequent maternal serum screening. At a threshold giving 5% of positive tests, the sensitivity of nuchal translucency, maternal serum screening and combined risk screening were 75%, 60% and 90%, respectively. Conclusions In screening for Down syndrome, an approach which combines the results from first-trimester nuchal translucency and second-trimester biochemistry, is effective and increases the detection rate compared to the use of any single test. However, this strategy is likely to raise the false-positive rate and the interpretation of maternal serum screening-derived risk should be combined with the first-trimester nuchal translucency measurement. [References: 23]
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Unité(s) :
Biostatistique, Endocrinologie & Médecine de la Reproduction, URC
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Mathematical model of fsh-induced camp production in ovarian follicles
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CLEMENT F, MONNIAUX D, STARK J, HARDY K, THALABARD JC, FRANKS S, CLAUDE D
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2001 - Amer. J. Physiol. - Endocrinol. Met. 281(1):E35-E53 |
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During the terminal part of their development, ovarian follicles become totally dependent on gonadotropin supply to pursue their growth and maturation. Both gonadotropins, follicle-stimulating hormone (FSH) and luteining hormone (LH), operate mainly through stimulatory G protein-coupled receptors, their signal being transduced by the activation of the enzyme adenylyl cyclase and the production of second-messenger cAMP. In this paper, we develop a mathematical model of the dynamics of the coupling between FSH receptor stimulation and cAMP synthesis. This model takes the form of a set of nonlinear, ordinary differential equations that describe the changes in the different states of FSH receptors (free, bound, phosphorylated, and internalized), coupling efficiency (activated adenylyl cyclase), and cAMP response. Classical analysis shows that, in the case of constant FSH signal input, the system converges to a unique, stable equilibrium state, whose properties are here investigated. The system also appears to be robust to nonconstant input. Particular attention is given to the influence of biologically relevant parameters on cAMP dynamics. [References: 38]
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Unité(s) :
Biostatistique, URC
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Glucose-induced insulin hypersecretion in lipid-infused healthy subjects is associated with a decrease in plasma norepinephrine concentration and urinary excretion
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MAGNAN C, CRUCIANI C, CLEMENT L, ADNOT P, VINCENT M, KERGOAT M, GIRARD A, ELGHOZI JL, VELHO G, BERESSI N, BRESSON JL, KTORZA A
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2001 - J. Clin. Endocrinol. Metabol. 86(10):4901-4907 |
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We investigated the effect of a 48 h triglyceride infusion on the subsequent insulin secretion in response to glucose in healthy men. We measured the variations in plasma concentration and urinary excretion of catecholamines as an indirect estimation of sympathetic tone. For 48 h, 20 volunteers received a triglyceride/heparin or a saline solution, separated by a 1-month interval. At time 48 h, insulin secretion in response to glucose was investigated by a single iv glucose injection (0.5 g/kg(-1)) followed by an hyperglycemic clamp (10 mg.kg(-1).min(-1), during 50 min). The triglyceride infusion resulted in a 3-fold elevation in plasma free fatty acids and an increase in insulin and C-peptide plasma concentrations (1.5- and 2.5-fold, respectively, P < 0.05), compared with saline. At time 48 h of lipid infusion, plasma norepinephrine (NE) concentration and urinary excretion levels were lowered compared with saline (plasma NE: 0.65 +/- 0.08 vs. 0.42 +/- 0.06 ng/ml, P < 0.05; urinary excretion: 800 +/- 70 vs. 620 +/- 25 nmol/24 h, P < 0.05). In response to glucose loading, insulin and C-peptide plasma concentrations were higher in lipid compared with saline infusion (plasma insulin: 600 +/- 98 vs. 310 +/- 45 pM, P < 0.05; plasma C-peptide 3.5 +/- 0.2 vs. 1.7 +/- 0.2 nM, P < 0.05). In conclusion, in healthy subjects, a 48-h lipid infusion induces basal hyperinsulinemia and exaggerated insulin secretion in response to glucose which may be partly related to a decrease in sympathetic tone. [References: 48]
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Unité(s) :
CIC 9303
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Fetal lung volume measurement by magnetic resonance imaging in congenital diaphragmatic hernia
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MAHIEU-CAPUTO D, SONIGO P, DOMMERGUES M, FOURNET JC, THALABARD JC, ABARCA C, BENACHI A, BRUNELLE F, DUMEZ Y
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2001 - Br. J. Obtstet. Gynaecol. 108(8):863-868 |
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Objective To study the potential for prenatal magnetic resonance imaging to predict pulmonary hypoplasia in congenital diaphragmatic hernia. Design Prospective observational study. Setting Tertiary care centre. Participants Thirteen cases of congenital diaphragmatic hernia (11 left, 2 right) without associated anomalies and 74 controls. Methods Measurements by magnetic resonance imaging of fetal lung volume were achieved. In the control fetuses, a regression analysis was performed to associate fetal lung volume with gestational age. This yielded a formula allowing calculation of the expected fetal lung volume as a function of gestational age. In the cases with congenital diaphragmatic hernia, the observed/expected fetal lung volume ratio was compared with perinatal outcome. Main outcome measures Neonatal mortality and pulmonary hypoplasia, which was defined as lung/body weight ratios less than 0.012. C, Results The expected fetal lung volume was derived from the following formula: Fetal lung volume (mL) exp (1.24722 + 0.08939 X gestational age in weeks). The observed/expected fetal lung volume ratio was significantly lower in congenital diaphragmatic hernia (median: 0.31, range: 0.06-0.63), than in controls (median: 0.99, range: 0.42-1.94). This ratio was significantly less in the infants with congenital diaphragmatic hernia who died (median: 0.26, range: 0.06-0.63) compared with those who survived (median: 0.46, range: 0.35-0.56). The observed: expected fetal lung volume ratio was significantly correlated with the postmortem lung: body weight ratio. Conclusion In isolated con-enital diaphragmatic hernia, fetal lung volume measurement by magnetic resonance C imaging is a potential predictor of pulmonary hypoplasia and postnatal outcome. Further studies are required C, to establish the clinical value of macynetic resonance imaging for the prenatal assessment of fetal lungs. [References: 25]
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Unité(s) :
Maternité, Radiologie Pédiatrique, URC
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The effects of transdermal and oral estrogen/progesterone regimens on free and total protein S in postmenopausal women
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MARQUE V, ALHENC-GELAS M, PLU-BUREAU G, OGER E, SCARABIN PY
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2001 - Thromb. Haemost. 86(2):713-714 |
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Unité(s) :
URC
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Association of circulating cellular adhesion molecules with menopausal status and hormone replacement therapy. Time-dependent change in transdermal, but not oral estrogen users
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OGER E, ALHENC-GELAS M, PLU-BUREAU G, MENNEN L, CAMBILLAU M, GUIZE L, PUJOL Y, SCARABIN P
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2001 - Thromb. Res. 101(2):35-43 |
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The incidence of coronary heart disease is lower in premenopausal than in postmenopausal women, and estrogen use may be cardioprotective among postmenopausal women. Cellular adhesion molecules (CAM) are involved in the early stage of atherosclerosis, and short-term administration of oral estrogen decreased plasma concentrations of their soluble forms in postmenopausal women. However, data evaluating transdermal estrogen are sparse and long-term effect of hormone replacement therapy (HRT) on CAM is unknown. Therefore, we have investigated the association of circulating CAM (cCAM) with menopausal status and long-term HRT. Plasma levels of intercellular adhesion molecule-1 (cICAM-1), vascular cell adhesion molecule-1 (cVCAM-1), P-selectin, E-selectin, C-reactive protein (CRP), and fibrinogen were measured in 74 premenopausal women, 60 postmenopausal women not using HRT, 30 postmenopausal women using opposed oral estrogen therapy, and 30 postmenopausal women using opposed transdermal estrogen therapy. All women were apparently healthy and aged between 45 and 54 years. Duration of HRT ranged from 3 to 96 months. Postmenopausal women not receiving HRT had 24% higher mean levels of cICAM-1 than premenopausal women (318 vs. 255 ng/ml, P < .001). In postmenopausal women, users of oral estrogen had 16% lower, and users of transdermal estrogen had 17% lower mean levels of cICAM-1 than non-users (268 and 264 vs. 318 ng/ml, P = .001 for both comparisons). Furthermore, in users of transdermal route, the lowering effect of estrogen on cICAM-1 was dependent on treatment duration, while no time-dependent effect was seen in oral estrogen users. Users of transdermal estrogen had lower cVCAM-1 and P-selectin levels than postmenopausal non-users (327 vs. 364 ng/ml (P = .05) and 18 vs. 23 ng/ml (P = .05). There was no difference in CRP and E-selectin levels between the groups. Adjustment for age and body mass index (BMI) made no substantial change in the results. These data suggest that oral and transdermal estrogen may play a long-term cardioprotective role through favourable changes in endothelial function.
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Unité(s) :
URC
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Long-term follow-up of 246 hyperprolactinemic patients
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TOURAINE F, PLU-BUREAU G, BEJI C, MAUVAIS-JARVIS F, KUTTENN F
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2001 - Acta Obstet. Gynecol. Scand. 80(2):162-168 |
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Background. We wanted to evaluate the very long-term effects of bromocriptine on prolactin (PRL) levels and pituitary tumor size in a large cohort of hyperprolactinemic patients. Methods. We conducted a retrospective cohort study in the Department of Endocrinology from Necker Hospital in Paris, France. Two hundred and forty-six patients consulted primarily for menstrual disorders, with diagnosis of hyperprolactinemia. Patients were followed-up for 99.9+/-3.6 months. One hundred and ninety-one were treated with bromocriptine, 32 underwent surgery, and 23 received no treatment. Results. The mean initial plasma PRL level was 135.0+/-20.2 ng/ml. Presence of an adenoma was detected in 60% of our patients and comprised a microadenoma in 64% of cases. Compared to oligomenorrheic women, amenorrheic patients had significantly higher levels of PRL and larger pituitary tumor size. In the bromocriptine group, PRL levels decreased from 99.6+/-7.9 to 20.0+/-1.5 ng/ml (p=0.00001). The medical treatment was associated with disappearance of the adenoma in 45% of the women and with stabilization of pituitary tumor size in 40% of patients. Surgery led to disappearance of the adenoma in almost all cases, but failed to definitively cure hyperprolactinemia. Conclusion. In this large-scale retrospective study, the medical treatment of mild hyperprolactinemia was shown to be effective and sufficient after 9 years of follow-up. [References: 43]
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Unité(s) :
Endocrinologie & Médecine de la Reproduction, U344, URC
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Resumption of luteinizing hormone pulsatility and hypogonadotropic hypogonadism after endoscopic ventriculocisternostomy in a hydrocephalic patient
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TOURAINE P, PLU-BUREAU G, BERESSI N, DECQ P, THALABARD JC, KUTTENN F
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2001 - Fert. Steril. 76(2):390-393 |
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OBJECTIVE: To study gonadotropin pulsatility before and after surgical cure of hydrocephalus. DESIGN: Case report. SETTING: Department of Endocrinology and Centre d'Investigations Cliniques, Necker Hospital, Paris, France. PATIENT(S): A 29-year-old woman who presented with secondary amenorrhea. INTERVENTION(S): The patient underwent an endoscopic ventriculocisternostomy that led to restoration of normal menses and resolution of hypogonadism. MAIN OUTCOME MEASURE(S): A gonadotropin pulse study was performed before and 2 and 5 months after surgery. RESULT(S): No LH pulse was observed before surgery. Emergence of pulsatility was observed 2 months after surgery, and pulses became clearly individualized after 5 months. CONCLUSION(S): This observation strongly suggests that amenorrhea, in case of chronic hydrocephalus, is indeed due to a hypothalamic dysfunction of the GnRH pulse generator.
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Unité(s) :
Endocrinologie & Médecine de la Reproduction, U344, URC
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Breastfeeding and risk of breast cancer: a metaanalysis of published studies
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BERNIER MO, PLU BUREAU G, BOSSARD N, AYZAC L, THALABARD JC
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2000 - Hum. Reprod. Update 6(4):374-386 |
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Evidence in favour of an association of breastfeeding with a breast cancer risk reduction remains limited and inconsistent. To evaluate the relation between breastfeeding and breast cancer, a meta-analysis based on a review of the literature was carried out, using as variables ever/never breastfeeding and duration of breastfeeding, Menopausal status at the time of diagnosis of breast cancer was considered to be a potential effect modifier, Only case-control studies could be included in the final analysis. A slight but significant decreased risk of breast cancer was observed in ever breastfeeding, compared with never breastfeeding parous women, using both the fixed and random-effect models. This decrease was more pronounced in non-menopausal women at the time of diagnosis of breast cancer and in long-term breastfeeding women. Hence, breastfeeding appeared to be a protective factor but was of small magnitude compared with other known risk factors for breast cancer. Whether this result should imply a modification in the attitude of both health care providers and women towards breastfeeding, which represents one of the few identified protective factors which is under the control of the mother, and is thus (theoretically) modifiable, remains questionable. [References: 84]
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Unité(s) :
Endocrinologie & Médecine de la Reproduction, Biostatistique, URC
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Alterations of protein metabolism by metabolic acidosis in children with chronic renal failure
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BOIRIE Y, BROYER M, GAGNADOUX MF, NIAUDET P, BRESSON JL
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2000 - Kidney Int. 58(1):236-241 |
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Background. Several reports suggest that metabolic acidosis may induce significant alterations in protein metabolism and that its outbreak may even result in growth retardation in children with chronic renal failure (CRF). However, the effects of metabolic acidosis on protein metabolism kinetics have never been investigated in these settings. Methods. Postabsorptive leucine metabolism, a marker of whole-body protein metabolism, was measured by using a primed, continuous intravenous infusion of L-[1-C-13]leucine in 10 CRF children who were one to four years old. Results. Interindividual values of whole-body protein turnover exhibited a very large range, which was mainly accounted for by acidotic status (plasma HCO3-) and body composition [fat-free mass (FFM)]. After correction for differences in FFM, plasma HCO3- was highly correlated with protein breakdown (R-2 = 0.65, P < 0.001), so that CRF children were divided in two groups according to their acid-base status: Group A had a mean plasma HCO3- level of 15.8 +/- 1.5 mmol.L-1 (mean +/- SD, N = 5), whereas group B had near-normal values (HCO3-, 22.6 +/- 3.0 mmol.L-1, N = 5). The leucine rate of appearance from protein breakdown was markedly higher in group A than in group B (4.15 +/-. 1.43 vs. 2.46 +/- 0.47 mu mol.kg(-1).min(-1), respectively, P < 0.05), and the net leucine balance tended to be more negative in group A (-0.73 +/- 0.34 vs. -0.44 +/- 0.26 mu mol.kg(-1).min(-1), respectively). Conclusions. Metabolic acidosis in children with CRF results in an excessive catabolic state, suggesting that acidosis-related protein wasting could contribute to growth retardation. [References: 29]
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Unité(s) :
CIC 9303
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A Markov regression model for the analysis of the postpartum lactational amenorrhea
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LE STRAT Y, THOMAS G, THALABARD JC
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2000 - Commun. Stat.-Stimul. Computa. 29(1125 |
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Unité(s) :
URC
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Influence of sin-1 on platelet ca2+ handling in patients with suspected coronary artery disease: ex vivo and in vitro studies
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LE-QUAN-SANG KH, LE FEUVRE C, BRUNET A, PHAM TD, METZGER JP, VACHERON A, DEVYNCK MA
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2000 - Thromb. Haemost. 83(5):752-758 |
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The 3-morpholinosydnonimine (SIN-1) generates both nitric oxide (NO) and superoxide anion (O-2-). It elicits dose-dependent vasodilation in vivo, in spite of the opposite effects of its breakdown products on vascular tone and platelet aggregation. This study was designed to investigate the influence of intravenous SIN-1 injection on platelet Ca2+ handling in patients undergoing coronary angiography. SIN-1 administration reduced cytosolic [Ca2+] in unstimulated platelets by decreasing Ca2+ influx. It attenuated Ca2+ mobilization from internal stores evoked by thrombin or thapsigargin. In vitro studies were used as an approach to investigate how simultaneous productions of NO and O-2- from SIN-1 modify thrombin- or thapsigargin-induced platelet Ca2+ mobilization. Superoxide dismutase, the O-2- scavenger, enhanced the capacity of SIN-1 to inhibit Ca2+ mobilization but catalase had no effect. This suggests that the effects of SIN-1 on platelet Ca2+ handling resemble those of NO, but are modulated by simultaneous O-2- release, independently of H2O2 formation. [References: 50]
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Unité(s) :
UMR 8604, Cardiologie Adulte, URC
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Plasma 17beta estradiol is inversely correlated with circulating vascular cell adhesion molecule
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OGER E, ALHENC-GELAS M, PLU-BUREAU G, GUIZE L, SCARABIN PY
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2000 - Thromb. Haemost. 84(6):1125 |
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Unité(s) :
URC
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Oral contraception and genetic factors in breast cancer: characteristics and limits of case-only studies
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PLU BUREAU G, BOSSARD N, THALABARD JC
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2000 - Rev. Epidémiol. Santé Publ. 48(3):294-303 |
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The analysis of the interaction between environmental and genetic factors is a matter of increasing interest in cancerology. More particularly the discovery of the BRCAx family and the high cumulated incidence of familial breast cancers related to mutations of these proteins raised the issue of the differential effect of long term and/or early exposure to oral contraceptives in the presence of these mutations. The classical case-control design assumes the presence of a control group, which can be sometimes difficult to obtain from both the technical and ethical points of view. Case-only or case-case studies, which are based only on series of cases, making them apparently attractive, have been proposed to analyze more specifically the interaction term. The aim of the present paper is to review and discuss the methodological basis and main assumptions of the case-only design, and their applicability to breast cancer studies. The measure of the interaction between an environmental factor and a susceptibility genetic factor differs in an important aspect from the measure of the association between an environmental factor and acquired tumoral genetic factor; this aspect is reminded. [References: 27]
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Unité(s) :
Endocrinologie & Médecine de la Reproduction, URC
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