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560 results on '"MESH : Adult"'

1. Factors related to the relative survival of patients with diffuse large B-cell lymphoma in a population-based study in France: does socio-economic status have a role?

Author

Alain Monnereau, Sébastien Orazio, Olivier Dejardin, Sandra Le Guyader-Peyrou, Marc Maynadié, Xavier Troussard, Registre des hémopathies malignes de la Gironde, Institut Bergonié - CRLCC Bordeaux, Cancer environnement ( EPICENE ), Bordeaux population health ( BPH ), Université de Bordeaux ( UB ) -Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bordeaux ( UB ) -Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Cancers et préventions, Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Registre des hémopathies malignes de Côte d'Or, Registre des hémopathies malignes de Basse-Normandie, CHU Caen, Laboratoire d'hématologie biologique [Caen], Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Caen, Cancer environnement (EPICENE ), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Registre des hémopathies malignes de Basse-Normandie [CHU Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), université de Bourgogne, LNC, and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, 0301 basic medicine, Pediatrics, Multivariate analysis, MESH: Registries, MESH : Aged, MESH: Comorbidity, Comorbidity, MESH : Lymphoma, Large B-Cell, Diffuse, MESH: Aged, 80 and over, 0302 clinical medicine, International Prognostic Index, MESH : Child, MESH: Child, MESH : Population Surveillance, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, MESH : Female, Registries, Young adult, Child, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, MESH : Prognosis, Relative survival, MESH: Patient Outcome Assessment, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Articles, Hematology, Middle Aged, MESH : Adult, Prognosis, MESH : Patient Outcome Assessment, 3. Good health, MESH: Young Adult, Population Surveillance, MESH: Survival Analysis, 030220 oncology & carcinogenesis, MESH : Comorbidity, Marital status, Female, France, Lymphoma, Large B-Cell, Diffuse, Non-Hodgkin Leukemia, Adult, medicine.medical_specialty, Adolescent, MESH : Male, MESH: Factor Analysis, Statistical, MESH : Young Adult, MESH : Factor Analysis, Statistical, MESH: Prognosis, MESH: Population Surveillance, MESH: Social Class, Young Adult, 03 medical and health sciences, MESH : Adolescent, Internal medicine, MESH : Social Class, medicine, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, MESH : France, Survival analysis, Aged, MESH: Adolescent, MESH: Humans, business.industry, MESH : Humans, MESH: Adult, medicine.disease, Survival Analysis, MESH: Male, Patient Outcome Assessment, MESH: France, 030104 developmental biology, Social Class, MESH: Lymphoma, Large B-Cell, Diffuse, MESH : Survival Analysis, Factor Analysis, Statistical, business, MESH: Female, Diffuse large B-cell lymphoma, MESH : Registries
Abstract

IF 7.702; International audience; The survival of patients with diffuse large B-cell lymphoma has increased during the last decade as a result of addition of anti-CD20 to anthracycline-based chemotherapy. Although the trend is encouraging, there are persistent differences in survival within and between the USA and European countries suggesting that non-biological factors play a role. Our aim was to investigate the influence of such factors on relative survival of patients with diffuse large B-cell lymphoma. We conducted a retrospective, multicenter, registry-based study in France on 1165 incident cases of diffuse large B-cell lymphoma between 2002 and 2008. Relative survival analyses were performed and missing data were controlled with the multiple imputation method. In a multivariate analysis, adjusted for age, sex and International Prognostic Index, we confirmed that time period was associated with a better 5-year relative survival. The registry area, the medical specialty of the care department (onco-hematology versus other), the time to travel to the nearest teaching hospital, the place of treatment (teaching versus not-teaching hospital -borderline significance), a comorbidity burden and marital status were independently associated with the 5-year relative survival. Adjusted for first-course treatment, inclusion in a clinical trial and treatment discussion in a multidisciplinary meeting were strongly associated with a better survival outcome. In contrast, socio-economic status (determined using the European Deprivation Index) was not associated with outcome. Despite therapeutic advances, various non-biological factors affected the relative survival of patients with diffuse large B-cell lymphoma. The notion of lymphoma-specific expertise seems to be essential to achieve optimal care management and reopens the debate regarding centralization of these patients' care in hematology/oncology departments.

Published
2016
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2. Effectiveness of bacteriophages in the sputum of cystic fibrosis patients

Author

Raphaël Chiron, Laurent Debarbieux, Frédérique Carrié, Nicolas Molinari, Isabelle Sermet, Isabelle Vachier, Jean-Paul Pirnay, Emilie Saussereau, Nicolas Dufour, Benoit Godbert, Daniel De Vos, Debarbieux, Laurent, Cellule Pasteur UPMC, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP), Biologie Moléculaire du Gène chez les Extrêmophiles (BMGE), Institut Pasteur [Paris] (IP), Département des Maladies Respiratoires [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Service de Pneumologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de recherche Croissance et signalisation (UMR_S 845), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cellule Pasteur, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital [Brussels], PHAGESPOIRS, Mathématiques, Informatique et STatistique pour l'Environnement et l'Agronomie (MISTEA), Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), This work was supported by Vaincre la Mucoviscidose, the French Cystic Fibrosis Foundation [RC20120600714/1/1/141], and Programme Transversal de Recherches [417] from Institut Pasteur and Assistance Publique Hôpitaux de Paris., Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris], Institut Pasteur [Paris], Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA), PRES Sorbonne Paris Cité-Université Paris Diderot - Paris 7 (UPD7), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut Pasteur [Paris], Biologie Moléculaire du Gène chez les Extrêmophiles ( BMGE ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Centre de recherche Croissance et signalisation ( UMR_S 845 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Diderot - Paris 7 ( UPD7 ) -PRES Sorbonne Paris Cité, Mathématiques, Informatique et STatistique pour l'Environnement et l'Agronomie ( MISTEA ), and Institut National de la Recherche Agronomique ( INRA ) -Institut national d’études supérieures agronomiques de Montpellier ( Montpellier SupAgro )

Subjects
Male, Time Factors, Cystic Fibrosis, medicine.medical_treatment, Antibiotics, pulmonary infection, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, medicine.disease_cause, MESH: Bacterial Load, Cystic fibrosis, MESH : Cross-Sectional Studies, MESH: Sputum, MESH : Female, MESH: Microbial Viability, MESH: Middle Aged, biology, MESH: Pseudomonas Infections, General Medicine, MESH : Adult, MESH : Pseudomonas aeruginosa, Middle Aged, MESH : Pseudomonas Infections, 3. Good health, Biological Therapy, Chronic infection, medicine.anatomical_structure, Infectious Diseases, MESH: Young Adult, Pseudomonas aeruginosa, MESH: Pseudomonas aeruginosa, Female, MESH : Bacterial Load, medicine.symptom, Pseudomonas Phages, MESH : Time Factors, Adult, Microbiology (medical), phage therapy, Phage therapy, Adolescent, MESH: Cystic Fibrosis, medicine.drug_class, MESH : Male, MESH : Young Adult, MESH: Pseudomonas Phages, Microbiology, Young Adult, MESH: Cross-Sectional Studies, MESH : Adolescent, MESH : Cystic Fibrosis, medicine, Humans, MESH : Middle Aged, Pseudomonas Infections, MESH: Adolescent, Microbial Viability, MESH: Humans, MESH : Humans, MESH: Time Factors, MESH : Microbial Viability, Sputum, MESH: Adult, medicine.disease, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bacterial Load, MESH: Male, Cross-Sectional Studies, MESH : Pseudomonas Phages, MESH : Sputum, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Biological Therapy, MESH: Female, MESH : Biological Therapy, Bacteria, Respiratory tract
Abstract

International audience; Bacteriophages have been shown to be effective for treating acute infections of the respiratory tract caused by antibiotic-resistant bacteria in animal models, but no evidence has yet been presented of their activity against pathogens in complex biological samples from chronically infected patients. We assessed the efficacy of a cocktail of ten bacteriophages infecting Pseudomonas aeruginosa following its addition to 58 sputum samples from cystic fibrosis (CF) patients collected at three different hospitals. Ten samples that did not contain P. aeruginosa were not analysed further. In the remaining 48 samples, the addition of bacteriophages led to a significant decrease in the levels of P. aeruginosa strains, as shown by comparison with controls, taking two variables (time and bacteriophages) into account (p = 0.024). In 45.8% of these samples, this decrease was accompanied by an increase in the number of bacteriophages. We also tested each of the ten bacteriophages individually against 20 colonies from each of these 48 samples and detected bacteriophage-susceptible bacteria in 64.6% of the samples. An analysis of the clinical data revealed no correlation between patient age, sex, duration of P. aeruginosa colonization, antibiotic treatment, FEV1 (forced expiratory volume in the first second) and the efficacy of bacteriophages. The demonstration that bacteriophages infect their bacterial hosts in the sputum environment, regardless of the clinical characteristics of the patients, represents a major step towards the development of bacteriophage therapy to treat chronic lung infections.

Published
2014
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3. An immunoproteomic approach revealed antigenic proteins enhancing serodiagnosis performance of bird fancier's lung

Author

Gabriel Reboux, Jean-Charles Dalphin, Adeline Rouzet, Benoît Valot, Laurence Millon, Thierry Balliau, Sandrine Roussel, Anne Gondouin, Paul De Vuyst, Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Génétique Quantitative et Evolution - Le Moulon (Génétique Végétale) (GQE-Le Moulon), Centre National de la Recherche Scientifique (CNRS)-AgroParisTech-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Recherche Agronomique (INRA), Service de parasitologie et mycologie [CHU de Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Service de Pneumologie [Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz-Université de Franche-Comté (UFC), Erasme Hospital, Brussels, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Besancon University Hospital [2015-A01803-46], Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Service de Pneumologie, Hôpital Jean-Minjoz, Centre Hospitalier Universitaire de Besançon, Université de Franche-Comté, Besançon, France., Génétique Quantitative et Evolution - Le Moulon (Génétique Végétale) ( GQE-Le Moulon ), Institut National de la Recherche Agronomique ( INRA ) -Université Paris-Sud - Paris 11 ( UP11 ) -AgroParisTech-Centre National de la Recherche Scientifique ( CNRS ), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)

Subjects
Male, Proteomics, MESH : Aged, MESH: Immunoelectrophoresis, MESH : Chromatography, Liquid, law.invention, Feces, MESH: Enzyme Precursors, 0302 clinical medicine, Tandem Mass Spectrometry, MESH : Bird Fancier's Lung, Electrophoresis, Gel, Two-Dimensional, MESH: Animals, MESH: Bird Fancier's Lung, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Electrophoresis, Agar Gel, MESH: Middle Aged, MESH: Proteomics, MESH: Feces, Precipitin, MESH : Enzyme-Linked Immunosorbent Assay, MESH: Case-Control Studies, 3. Good health, MESH: Reproducibility of Results, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Area Under Curve, Recombinant DNA, Antibody, 2D electrophoresis, MESH : Case-Control Studies, Immunology, [ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology, environment/Health, Avian Proteins, 03 medical and health sciences, Antigen, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Humans, Serologic Tests, MESH : Middle Aged, MESH : Predictive Value of Tests, MESH : Birds, MESH : Aged, 80 and over, Aged, MESH: Humans, MESH : Reproducibility of Results, MESH : Humans, MESH: Serologic Tests, MESH : Immunoglobulin Light Chains, Surrogate, MESH: Tandem Mass Spectrometry, MESH: Adult, MESH : Electrophoresis, Gel, Two-Dimensional, Bird fancier's lung, Allergens, MESH: ROC Curve, medicine.disease, MESH: Electrophoresis, Gel, Two-Dimensional, 030104 developmental biology, 030228 respiratory system, Case-Control Studies, MESH : Inhalation Exposure, MESH: Chromatography, Liquid, MESH: Female, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 0301 basic medicine, Immunoelectrophoresis, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Recombinant antigens, Serology, MESH : Proteomics, MESH: Aged, 80 and over, MESH: Avian Proteins, law, Immunology and Allergy, MESH : Female, MESH: Endopeptidases, MESH : Allergens, MESH: Aged, Enzyme Precursors, Inhalation Exposure, Serodiagnosis, medicine.diagnostic_test, MESH : Immunoelectrophoresis, MESH : Enzyme Precursors, MESH : Avian Proteins, MESH: Enzyme-Linked Immunosorbent Assay, Middle Aged, MESH : Adult, MESH : Endopeptidases, MESH: Predictive Value of Tests, MESH : Serologic Tests, MESH: Birds, Female, ELISA, MESH : Tandem Mass Spectrometry, MESH: Inhalation Exposure, Adult, MESH: Allergens, Immunoglobulin Light Chains, Surrogate, MESH : Male, Enzyme-Linked Immunosorbent Assay, Biology, Birds, Predictive Value of Tests, Endopeptidases, medicine, Animals, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Two-dimensional gel electrophoresis, Reproducibility of Results, MESH : Feces, MESH: Immunoglobulin Light Chains, Surrogate, MESH: Male, MESH : Electrophoresis, Agar Gel, ROC Curve, biology.protein, MESH: Area Under Curve, MESH : Animals, MESH : Area Under Curve, MESH: Electrophoresis, Agar Gel, MESH : ROC Curve, Hypersensitivity pneumonitis, Chromatography, Liquid
Abstract

Background Bird fancier's lung (BFL) caused by repeated inhalation of avian proteins is the most common form of hypersensitivity pneumonitis. However, the exact identification of proteins involved is unknown, and serological test use for diagnosis need to be standardized. The objectives of this study were (i) to identify antigenic proteins from pigeon droppings (ii) to provide information about their location in avian matrices and (iii) to produce them in recombinant proteins to evaluate their diagnostic performances. Method Antigenic proteins of pigeon dropping extracts were investigated using 2-dimensional immunoblotting with sera from patients with BFL, asymptomatic exposed controls and healthy volunteers. We investigated the origin of these antigenic proteins by analyzing droppings, blooms and sera using a shotgun proteomic analysis. BFL-associated proteins were produced as recombinant antigens in E. coli and were assessed in ELISA with sera from patients (n = 25) and subject exposed controls (n = 30). These diagnostic performances were compared with those obtained by precipitin techniques (agar gel double diffusion, immunoelectrophoresis). Results We identified 14 antigenic proteins mainly located in droppings and blooms. These proteins were involved in either the digestive or immune systems of pigeons. Using the recombinant BFL-associated proteins: Immunoglobulin lambda-like polypeptide-1 (IGLL1: sensitivity: 76%; specificity: 100%; AUC: 0.93) and Proproteinase E (ProE: sensitivity: 84%; specificity: 80%; AUC: 0.85), the ELISA test showed better performance than precipitin assays with pigeon dropping extracts (sensitivity: 60%; specificity: 93.3%; AUC: 0.76). Conclusion IGLL1 and ProE were identified as the biomarkers of the disease. The use of these highly standardized antigens discriminates BFL cases from exposed subjects in serological assays. The results of this study offer new possibilities for the serological diagnosis of the disease. Clinical trial registration: ClinicalTrials.gov : Identifier NCT03056404 .

Published
2017
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4. Fcγ receptor expression on splenic macrophages in adult immune thrombocytopenia

Author

Bernard Bonnotte, Annemieke G. Laarhoven, Kim Santegoets, Philippe Saas, Maxime Samson, Gestur Vidarsson, Sylvain Audia, Olivier Facy, Timothy R D J Radstake, Pablo Ortega-Deballon, Nona Janikashvili, Laboratory of Translational Immunology [Utrecht, the Netherlands], University Medical Center [Utrecht], Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), Sanquin Research, University of Amsterdam [Amsterdam] (UvA), Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Landsteiner Laboratory, University Medical Center Utrecht [the Netherlands] ( UMC Utrecht ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), University of Amsterdam [Amsterdam] ( UvA ), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer ( LabEx LipSTIC ), Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École pratique des hautes études ( EPHE ) -Institut Gustave Roussy ( IGR ) -Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), and UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)

Subjects
Male, MESH: Spleen, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], MESH : Aged, MESH: Flow Cytometry, Immunoglobulin G, 0302 clinical medicine, MESH : Antigens, CD86, MESH: Autoimmune Diseases, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, CD86, MESH: Immunoglobulins, Intravenous, MESH : Receptors, IgG, MESH : Macrophages, MESH: Immunoglobulin G, MESH: Middle Aged, Immunoglobulins, Intravenous, Flow Cytometry, macrophages, MESH : Phenotype, Splenectomy, Antibody, IgG, Phagocytosis, Immunology, Immunoglobulins, Spleen, MESH: Receptors, IgG, MESH: Phenotype, MESH: Splenectomy, 03 medical and health sciences, MESH : Autoimmune Diseases, Genetic, MESH: Polymorphism, Genetic, Humans, MESH : Middle Aged, Polymorphism, Aged, Polymorphism, Genetic, MESH: Humans, Macrophages, MESH : Humans, MESH: Adult, 030104 developmental biology, spleen, B7-2 Antigen, MESH: Female, 0301 basic medicine, MESH : Polymorphism, Genetic, Receptor expression, medicine.disease_cause, Autoimmunity, immune system diseases, hemic and lymphatic diseases, Receptors, Immunology and Allergy, MESH : Female, MESH: Phagocytosis, MESH: Aged, biology, MESH : Thrombocytopenia, Fc receptors, autoimmunity, MESH : Adult, Middle Aged, Antigens, CD86, medicine.anatomical_structure, Phenotype, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Immunoglobulins, Intravenous, Intravenous, MESH : Spleen, Adult, MESH : Immunoglobulin G, MESH : Flow Cytometry, MESH : Male, chemical and pharmacologic phenomena, MESH: Antigens, CD86, Autoimmune Diseases, All institutes and research themes of the Radboud University Medical Center, MESH : Phagocytosis, medicine, Journal Article, Antigens, Opsonin, MESH : Splenectomy, MESH: Thrombocytopenia, Receptors, IgG, MESH: Macrophages, Original Articles, Thrombocytopenia, MESH: Male, biology.protein, 030215 immunology
Abstract

Summary Splenic macrophages play a key role in immune thrombocytopenia (ITP) pathogenesis by clearing opsonized platelets. Fcγ receptors (FcγR) participate in this phenomenon, but their expression on splenic macrophages and their modulation by treatment have scarcely been studied in human ITP. We aimed to compare the phenotype and function of splenic macrophages between six controls and 24 ITP patients and between ITP patients according to the treatments they received prior to splenectomy. CD86, human leucocyte antigen D-related (HLA-DR) and FcγR expression were measured by flow cytometry on splenic macrophages. The major FcγR polymorphisms were determined and splenic macrophage function was assessed by a phagocytosis assay. The expression of the activation markers CD86 and HLA-DR was higher on splenic macrophages during ITP compared to controls. While the expression of FcγR was not different between ITP and controls, the phagocytic function of splenic macrophages was reduced in ITP patients treated with intravenous immunoglobulin (IVIg) within the 2 weeks prior to splenectomy. The FCGR3A (158V/F) polymorphism, known to increase the affinity of FcγRIII to IgG, was over-represented in ITP patients. Thus, these are the first results arguing for the fact that the therapeutic use of IVIg during human chronic ITP does not modulate FcγR expression on splenic macrophages but decreases their phagocytic capabilities.

Published
2017
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5. Fungal peptides from pneumonitis hypersensitivity etiologic agents are able to induce specific cellular immune response

Author

Anne-Pauline Bellanger, Laurence Millon, Bénédicte Rognon, Houssein Gbaguidi-Haore, Thibaud Lignon, Christophe Borg, Gabriel Reboux, Yann Godet, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d’Hygiène Hospitalière, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Service de parasitologie et mycologie [CHU de Besançon], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), and Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC )

Subjects
Male, MESH : Aged, Epitope, MESH : Antigens, Fungal, Epitopes, 0302 clinical medicine, MESH: Peptide Fragments, Cells, Cultured, MESH: Middle Aged, ELISPOT, Acquired immune system, Healthy Volunteers, 3. Good health, MESH : Mucorales, MESH: Young Adult, Mucorales, MESH: Mucorales, MESH: Cells, Cultured, Antigens, Fungal, MESH: Epitopes, MESH : Dihydrolipoamide Dehydrogenase, T cell, MESH : Alveolitis, Extrinsic Allergic, Immunology, MESH : Young Adult, MESH : Epitopes, Statistics, Nonparametric, [ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology, environment/Health, Interferon-gamma, 03 medical and health sciences, MESH: Mycobacterium, Humans, MESH : Middle Aged, Aged, Dihydrolipoamide Dehydrogenase, MESH: Antigens, Fungal, MESH: Humans, Histocompatibility Antigens Class I, MESH : Humans, Histocompatibility Antigens Class II, MESH: Adult, Peptide Fragments, MESH : Leukocytes, Mononuclear, 030104 developmental biology, Leukocytes, Mononuclear, MESH: Female, 0301 basic medicine, Enzyme-Linked Immunospot Assay, MESH : Enzyme-Linked Immunospot Assay, MESH: Histocompatibility Antigens Class I, ELISPOT assay, Immunology and Allergy, MESH : Female, Interferon gamma, MESH: Healthy Volunteers, MESH: Aged, Immunity, Cellular, MESH: Statistics, Nonparametric, biology, MESH : Antigens, Bacterial, Middle Aged, MESH : Adult, MESH: Leukocytes, Mononuclear, MESH : Histocompatibility Antigens Class II, medicine.anatomical_structure, Female, MESH : Histocompatibility Antigens Class I, Alveolitis, Extrinsic Allergic, medicine.drug, Adult, MESH: Dihydrolipoamide Dehydrogenase, MESH: Interferon-gamma, MESH : Male, MESH: Alveolitis, Extrinsic Allergic, Major histocompatibility complex, Mycobacterium, MESH: Immunity, Cellular, Young Adult, Immune system, MESH : Cells, Cultured, medicine, MESH : Mycobacterium, MESH : Statistics, Nonparametric, MESH : Interferon-gamma, MESH : Healthy Volunteers, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Antigens, Bacterial, MESH: Epitope Mapping, MESH : Peptide Fragments, MESH : Immunity, Cellular, biology.organism_classification, MESH: Male, MESH : Epitope Mapping, biology.protein, MESH: Histocompatibility Antigens Class II, Mycobacterium immunogenum, MESH: Enzyme-Linked Immunospot Assay, Epitope Mapping, Hypersensitivity pneumonitis, MESH: Antigens, Bacterial, 030215 immunology, IFNγ
Abstract

International audience; Hypersensitivity pneumonitis (HP) is an immunoallergic disease due to chronic exposure to high quantities of different microorganisms such as Mycobacterium immunogenum (Mi), a mycobacterium, and Lichtheimia corymbifera (Lc), a filamentous fungus. It has recently been demonstrated that the protein DLDH (dihydrolipoyl dehydrogenase), is common to these microorganisms. This study aimed to investigate the immune potential of overlapping peptide pools covering the MiDLDH and LcDLDH.; A selection of 34 peptides, from the MiDLDH and LcDLDH, able to interact with Major Histocompatibility Complex (MHC) 1 and MHC 2, was obtained using three different epitope prediction websites. By means of ELISPOT assays, we compared the frequency of Interferon gamma (IFNγ) secreting peripheral blood mononuclear cells (PBMC) after stimulation with overlapping peptide pools. Tests were performed using cells from 35 healthy blood donors.; One peptide pool containing five peptides from MiDLDH and able to interact with MHC 2 induced a marked IFNγ specific immune response (Pool F, p

Published
2017
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6. Pathologies neurologiques en milieu tropical et rural : expérience malgache d’un centre de santé primaire de la région de Boeny

Author

S. Gaud, M. Sauvée, Marc Debouverie, Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), and Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL)

Subjects
Male, Rural Population, Neurology, Primary health care, soins de santé primaires, MESH: Madagascar, Epilepsy, MESH: Rural Population, Health care, MESH : Female, MESH : Primary Health Care, neurologie, 1. No poverty, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Adult, épilepsie, 3. Good health, MESH : Tropical Climate, Infectious Diseases, MESH: Young Adult, MESH: Tropical Climate, Female, Headaches, medicine.symptom, leprosy, Adult, medicine.medical_specialty, MESH : Madagascar, MESH : Male, MESH : Young Adult, Developing country, MESH: Nervous System Diseases, MESH: Primary Health Care, Young Adult, primary healthcare, Primary headache, Primary health, Madagascar, medicine, Humans, Tropical Climate, MESH: Humans, Primary Health Care, business.industry, neurology, MESH : Humans, Public Health, Environmental and Occupational Health, MESH: Adult, MESH : Nervous System Diseases, medicine.disease, MESH: Male, MESH : Rural Population, lèpre, Family medicine, epilepsy, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Nervous System Diseases, business, MESH: Female
Abstract

International audience; There is, to our knowledge, no study reporting the demand for health care related to neurological diseases in rural tropical areas of developing countries. Neurology is nonetheless more or less closely related to the priority health issues in these countries. Over a 6-week period, 626 patients were seen at the primary health center in the town of Madirovalo, Madagascar. Neurological disorders accounted for 11.1% of the consultations. The neurological disorders most frequently leading to consultations were headaches (42.7%), with primary headaches accounting for 16%; next came leprosy neuropathy (14.7%), with a worrisome total of 8 new cases; other peripheral neuropathies (13.3%), and epilepsy (12%). The relatively low share of the latter seems likely related to families' frequent use of traditional healers rather than Western medicine. Neurological diseases appears to represent a significant part of the health-care demand of people living in rural tropical areas of developing countries, and specific support in this specialization is essential.; La pathologie neurologique représente une part significative de la demande en santé des populations en milieu tropical rural des pays en développement, où un appui spécifique de la discipline neurologique semble indispensable

Published
2014
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7. Genetic and Environmental Influences on the Visual Word Form and Fusiform Face Areas

Author

Stanislas Dehaene, Ghislaine Dehaene-Lambertz, Fabien Fauchereau, Thomas Bourgeron, Eric Artiges, Cyril Poupon, Denis Le Bihan, Philippe Pinel, Christophe Lalanne, Neuroimagerie cognitive - Psychologie cognitive expérimentale (UNICOG-U992), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Saclay (COmUE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chaire Psychologie cognitive expérimentale, Collège de France (CdF (institution)), Recherche Clinique ville-hôpital, Méthodologies et Société (REMES), Université Paris Diderot - Paris 7 (UPD7), Trouble du comportement alimentaire de l'adolescent, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris-Sud - Paris 11 (UP11), Gènes, Synapses et Cognition (CNRS - UMR3571 ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Fondation FondaMental [Créteil], Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Neuroimagerie en psychiatrie (U1000), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), This work was supported by Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'Energie Atomique (CEA) and the James S. McDonnell Foundation., Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Collège de France - Chaire Psychologie cognitive expérimentale, Université Paris-Sud - Paris 11 (UP11)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroimagerie cognitive ( UNICOG-U992 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ), Collège de France ( CDF ), Collège de France ( CdF ), Recherche Clinique ville-hôpital, Méthodologies et Société ( REMES ), Université Paris Diderot - Paris 7 ( UPD7 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris-Sud - Paris 11 ( UP11 ), Gènes, Synapses et Cognition, Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique humaine et Fonctions cognitives - Human Genetics and Cognitive Functions, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Service NEUROSPIN ( NEUROSPIN ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Neuroimagerie en psychiatrie ( U1000 ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Neuroimagerie cognitive (UNICOG-U992), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Collège de France (CDF), Collège de France (CdF), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], and Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
Male, MESH : Oxygen, MESH : Brain Mapping, [ SDV.MHEP.PSM ] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV]Life Sciences [q-bio], Statistics as Topic, MESH : Statistics as Topic, temporal, MESH : Photic Stimulation, Functional Laterality, MESH: Magnetic Resonance Imaging, [SCCO]Cognitive science, 0302 clinical medicine, Face perception, Stress (linguistics), Image Processing, Computer-Assisted, Twins, Dizygotic, Visual word form area, 10. No inequality, MESH: Brain Mapping, Language, Brain Mapping, medicine.diagnostic_test, 05 social sciences, MESH: Gene-Environment Interaction, MESH : Adult, Magnetic Resonance Imaging, MESH: Image Processing, Computer-Assisted, Temporal Lobe, MESH : Twins, Monozygotic, MESH: Photic Stimulation, Pattern Recognition, Visual, MESH: Young Adult, MESH: Language, Visual Perception, [ SCCO ] Cognitive science, MESH: Twins, Monozygotic, Psychology, MESH : Visual Perception, MESH : Image Processing, Computer-Assisted, MESH: Oxygen, VWFA, Cognitive psychology, Adult, MESH : Twins, Dizygotic, MESH : Male, Cognitive Neuroscience, MESH : Young Adult, MESH: Pattern Recognition, Visual, 050105 experimental psychology, Lateralization of brain function, Temporal lobe, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, MESH : Language, reading, MESH : Magnetic Resonance Imaging, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, medicine, Humans, MESH: Temporal Lobe, 0501 psychology and cognitive sciences, MESH: Functional Laterality, MESH : Functional Laterality, MESH : Pattern Recognition, Visual, MESH : Temporal Lobe, MESH: Statistics as Topic, MESH: Humans, [ SDV ] Life Sciences [q-bio], MESH: Visual Perception, MESH: Twins, Dizygotic, MESH : Humans, MESH: Adult, Twins, Monozygotic, Fusiform face area, MESH: Male, MESH : Gene-Environment Interaction, Oxygen, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Gene-Environment Interaction, genetic, FFA, Functional magnetic resonance imaging, Photic Stimulation, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Spoken language
Abstract

International audience; Two areas of the occipitotemporal cortex show a remarkable hemispheric lateralization: written words activate the visual word form area (VWFA) in the left fusiform gyrus and faces activate a symmetrical site in the right hemisphere, the fusiform face area (FFA). While the lateralization of the VWFA fits with the leftward asymmetry of the speech processing network, origin of the rightward asymmetry for faces is still unclear. Using fMRI data from 64 subjects (including 16 monozygotic (MZ) and 13 dizygotic (DZ) twin pairs), we investigated how activations evoked by written words, faces, and spoken language are co-lateralized in the temporal lobe, and whether this organization reflects genetic factors or individual reading expertise. We found that the lateralization of the left superior temporal activation for spoken language correlates with the lateralization of occipitotemporal activations for both written words and faces. Behavioral reading scores also modulate the responses to words and faces. Estimation of genetic and environmental contributions shows that activations of the VWFA, the occipital face area, and the temporal speech areas are partially under genetic control whereas activation of the FFA is primarily influenced by individual experience. Our results stress the importance of both genetic factors and acquired expertise in the occipitotemporal organization.

Published
2014
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8. The global burden of hip and knee osteoarthritis: estimates from the Global Burden of Disease 2010 study

Author

Sandra Nolte, Laura L Laslett, Anthony D. Woolf, Emma Smith, Theo Vos, Damian G Hoy, Ilana N. Ackerman, Marita Cross, Richard H. Osborne, Marlene Fransen, Flavia M. Cicuttini, Lisa Bridgett, Rachelle Buchbinder, Graeme Jones, Lyn March, Sean R.M. Williams, Francis Guillemin, Christopher Hill, Institute of Bone & Joint Research, Royal North Shore Hospital (RNSH)-The University of Sydney, School of Population Health, University of Queensland, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Institute of Public Health [Berlin, Germany], School of Health and Social Development [Deakin University], Deakin University [Burwood], The Royal Melbourne Hospital, Melbourne EpiCentre, Faculty of Health Sciences [University of Sydney], The University of Sydney, School of Medicine [Western Sydney University], Western Sydney University (UWS), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), The Queen Elizabeth Hospital, Adelaide, The Health Observatory [University of Adelaide], University of Adelaide, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia, University of Tasmania (UTAS), Department of Epidemiology and Preventive Medicine, Monash University, Victoria, Australia, Monash University [Clayton], Institute for Health Metrics and Evaluation [University of Washington], University of Washington [Seattle], Cabrini Institute, Monash University [Melbourne], Royal Cornwall Hospital, Royal North Shore Hospital ( RNSH ) -The University of Sydney [Sydney], Charite-Universitatsmedizin Berlin [Berlin], Hôpital universitaire de la Charité de Berlin, Melbourne Medical School-The Royal Melbourne Hospital, The University of Sydney [Sydney], Western Sydney University ( UWS ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université de Lorraine ( UL ) -Université Paris Descartes - Paris 5 ( UPD5 ), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Western Sydney University, and University of Tasmania [Hobart, Australia] (UTAS)

Subjects
Male, MESH : Prevalence, Epidemiology, MESH : Age Distribution, MESH : Aged, MESH: Global Health, Osteoarthritis, MESH : Child, Preschool, Global Health, MESH: Regression Analysis, Severity of Illness Index, Osteoarthritis, Hip, MESH: Aged, 80 and over, MESH : Child, Cost of Illness, MESH : Regression Analysis, MESH: Child, MESH: Osteoarthritis, Knee, Prevalence, Immunology and Allergy, MESH : Cost of Illness, MESH : Female, MESH: Incidence, Young adult, Child, MESH : Sex Distribution, MESH: Aged, Aged, 80 and over, education.field_of_study, MESH: Middle Aged, Incidence, Incidence (epidemiology), MESH: Sex Distribution, MESH : Infant, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Adult, MESH: Cost of Illness, Middle Aged, Osteoarthritis, Knee, MESH: Infant, MESH : Incidence, 3. Good health, MESH: Quality-Adjusted Life Years, MESH: Young Adult, Child, Preschool, Regression Analysis, MESH : Severity of Illness Index, Female, Quality-Adjusted Life Years, MESH : Osteoarthritis, Hip, Adult, musculoskeletal diseases, medicine.medical_specialty, Adolescent, MESH : Male, Immunology, Population, MESH : Young Adult, General Biochemistry, Genetics and Molecular Biology, Knee Osteoarthritis, Young Adult, Age Distribution, Rheumatology, MESH : Adolescent, MESH: Severity of Illness Index, Severity of illness, medicine, Humans, MESH : Middle Aged, MESH : Osteoarthritis, Knee, Sex Distribution, MESH : Aged, 80 and over, education, MESH: Age Distribution, MESH: Prevalence, Aged, MESH: Adolescent, MESH: Humans, business.industry, MESH : Humans, MESH: Child, Preschool, Infant, MESH: Adult, MESH : Quality-Adjusted Life Years, medicine.disease, Obesity, MESH: Male, Quality-adjusted life year, Physical therapy, MESH : Global Health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Osteoarthritis, Hip, business, MESH: Female
Abstract

International audience; OBJECTIVE:To estimate the global burden of hip and knee osteoarthritis (OA) as part of the Global Burden of Disease 2010 study and to explore how the burden of hip and knee OA compares with other conditions.METHODS:Systematic reviews were conducted to source age-specific and sex-specific epidemiological data for hip and knee OA prevalence, incidence and mortality risk. The prevalence and incidence of symptomatic, radiographic and self-reported hip or knee OA were included. Three levels of severity were defined to derive disability weights (DWs) and severity distribution (proportion with mild, moderate and severe OA). The prevalence by country and region was multiplied by the severity distribution and the appropriate disability weight to calculate years of life lived with disability (YLDs). As there are no deaths directly attributed to OA, YLDs equate disability-adjusted life years (DALYs).RESULTS:Globally, of the 291 conditions, hip and knee OA was ranked as the 11th highest contributor to global disability and 38th highest in DALYs. The global age-standardised prevalence of knee OA was 3.8% (95% uncertainty interval (UI) 3.6% to 4.1%) and hip OA was 0.85% (95% UI 0.74% to 1.02%), with no discernible change from 1990 to 2010. Prevalence was higher in females than males. YLDs for hip and knee OA increased from 10.5 million in 1990 (0.42% of total DALYs) to 17.1 million in 2010 (0.69% of total DALYs).CONCLUSIONS:Hip and knee OA is one of the leading causes of global disability. Methodological issues within this study make it highly likely that the real burden of OA has been underestimated. With the aging and increasing obesity of the world's population, health professions need to prepare for a large increase in the demand for health services to treat hip and knee OA.

Published
2014
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9. Brain voice processing with bilateral cochlear implants: a positron emission tomography study

Author

Evelyne Ferrary, Yves Samson, Isabelle Mosnier, Emmanuèle Ambert-Dahan, Jean-Luc Martinot, Didier Bouccara, Arnaud Coez, Olivier Sterkers, Eric Bizaguet, Monica Zilbovicius, Equipe Perception et cognition musicales, Sciences et Technologies de la Musique et du Son (STMS), Institut de Recherche et Coordination Acoustique/Musique (IRCAM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche et Coordination Acoustique/Musique (IRCAM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Réhabilitation Chirurgicale mini-Invasive et Robotisée de l'Audition, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'oto-rhino-laryngologie, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut Claude Bernard - Physiologie et Pathologie ((IFR_2)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Neuroimagerie en psychiatrie (U1000), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sciences et Technologies de la Musique et du Son ( STMS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IRCAM-Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IRCAM-Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Service ORL, CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Institut Claude Bernard - Physiologie et Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 ( SCALab ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Neuroimagerie en psychiatrie ( U1000 ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière ( NEMESIS-CRICM ), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière ( CRICM ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.medical_treatment, [ SPI.SIGNAL ] Engineering Sciences [physics]/Signal and Image processing, Sound perception, Audiology, Monaural, MESH : Voice, [ INFO.INFO-CV ] Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], MESH: Cochlear Implants, MESH: Auditory Perceptual Disorders, 0302 clinical medicine, Hearing, Cochlear implant, [ INFO.INFO-TI ] Computer Science [cs]/Image Processing, MESH : Female, 030223 otorhinolaryngology, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, [ INFO.INFO-IM ] Computer Science [cs]/Medical Imaging, MESH: Cerebrovascular Circulation, General Medicine, MESH : Adult, Cochlear Implantation, Temporal Lobe, MESH: Positron-Emission Tomography, MESH : Auditory Perceptual Disorders, MESH: Voice, MESH : Hearing Loss, Bilateral, Cerebrovascular Circulation, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Speech Perception, Female, MESH : Speech Perception, MESH : Cochlear Implantation, MESH : Hearing, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Adult, Sound localization, Auditory perception, medicine.medical_specialty, MESH : Male, MESH: Acoustic Stimulation, Sensory system, Hearing Loss, Bilateral, 03 medical and health sciences, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, otorhinolaryngologic diseases, medicine, Humans, MESH: Temporal Lobe, MESH: Hearing, MESH : Temporal Lobe, MESH: Humans, business.industry, Auditory Perceptual Disorders, MESH : Humans, MESH : Positron-Emission Tomography, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], MESH: Adult, MESH : Acoustic Stimulation, MESH: Speech Perception, MESH: Hearing Loss, Bilateral, MESH: Male, Cochlear Implants, Acoustic Stimulation, MESH: Cochlear Implantation, Otorhinolaryngology, Positron-Emission Tomography, Voice, MESH : Cochlear Implants, MESH : Cerebrovascular Circulation, sense organs, Implant, business, MESH: Female, Binaural recording, 030217 neurology & neurosurgery
Abstract

International audience; Most cochlear implantations are unilateral. To explore the benefits of a binaural cochlear implant, we used water-labelled oxygen-15 positron emission tomography. Relative cerebral blood flow was measured in a binaural implant group (n = 11), while the subjects were passively listening to human voice sounds, environmental sounds non-voice or silence. Binaural auditory stimulation in the cochlear implant group bilaterally activated the temporal voice areas, whereas monaural cochlear implant stimulation only activated the left temporal voice area. Direct comparison of the binaural and the monaural cochlear implant stimulation condition revealed an additional right temporal activation during voice processing in the binaural condition and the activation of a right fronto-parietal cortical network during sound processing that has been implicated in attention. These findings provide evidence that a bilateral cochlear implant stimulation enhanced the spectral cues associated with sound perception and improved brain processing of voice stimuli in the right temporal region when compared to a monaural cochlear implant stimulation. Moreover, the recruitment of sensory attention resources in a right fronto-parietal network allowed patients with bilateral cochlear implant stimulation to enhance their sound discrimination, whereas the same patients with only one cochlear implant stimulation had more auditory perception difficulties.

Published
2013
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10. Factors associated with radiographic lesions in early axial spondyloarthritis. Results from the DESIR cohort

Author

Bijan Ghaleh, Aurélie Lethuaut, M. Blachier, Cécile Poulain, Valérie Farrenq, Bruno Fautrel, Pascal Claudepierre, Philippe Le Corvoisier, Salah Ferkal, Florence Canoui-Poitrine, Sylvie Bastuji-Garin, Maxime Dougados, Laboratoire d'Investigation Clinique (LIC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pôle Recherche Clinique-Santé Publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service de rhumatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rhumatologie, Université Paris Diderot - Paris 7 (UPD7), CIC - CHU Henri Mondor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri-Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Cochin [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) - Institut National de la Santé et de la Recherche Médicale (INSERM) - IFR10, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
MESH: Inflammation, Male, [SDV]Life Sciences [q-bio], Radiography, MESH : Sacroiliac Joint, MESH : Prospective Studies, Severity of Illness Index, MESH: Magnetic Resonance Imaging, Cohort Studies, 0302 clinical medicine, Epidemiology, MESH : Anti-Inflammatory Agents, Non-Steroidal, MESH : Female, Pharmacology (medical), Longitudinal Studies, Prospective Studies, MESH: Sacroiliac Joint, MESH: Longitudinal Studies, MESH: Cohort Studies, MESH : Longitudinal Studies, 0303 health sciences, MESH: Middle Aged, medicine.diagnostic_test, Anti-Inflammatory Agents, Non-Steroidal, MESH : Spondylarthritis, MESH : Adult, Middle Aged, MESH: Anti-Inflammatory Agents, Non-Steroidal, Magnetic Resonance Imaging, 3. Good health, [SDV] Life Sciences [q-bio], Cohort, MESH : Severity of Illness Index, Female, Radiology, MESH: Spine, Adult, medicine.medical_specialty, Alcohol Drinking, MESH : Male, MESH: Spondylarthritis, MESH : Cohort Studies, 03 medical and health sciences, Lumbar, Rheumatology, MESH : Magnetic Resonance Imaging, MESH: Severity of Illness Index, Spondylarthritis, MESH : Spine, medicine, Humans, MESH : Middle Aged, Spondylarthropathies, 030304 developmental biology, Inflammation, 030203 arthritis & rheumatology, Ankylosing spondylitis, MESH : Inflammation, MESH: Humans, business.industry, MESH : Humans, Sacroiliitis, MESH: Adult, Sacroiliac Joint, Magnetic resonance imaging, medicine.disease, MESH: Prospective Studies, MESH: Male, Spine, Surgery, MESH : Alcohol Drinking, business, MESH: Female, MESH: Alcohol Drinking
Abstract

International audience; OBJECTIVE: To assess whether factors such as inflammation by laboratory tests and MRI differ between early axial SpA with and without radiographic lesions. METHODS: Cross-sectional analysis of baseline data from Devenir des Spondylarthropathies Indifferenciées Récentes (DESIR) cohort patients having recent-onset inflammatory back pain and meeting Assessment of SpondyloArthritis international Society criteria. The baseline evaluation included radiographs and MRI of the SI joints (SIJs) and spine. Patients were classified as having radiographic lesions if they had at least one obvious sacroiliitis, grade 2 for at least one vertebral corner or grade 1 for at least two vertebral corners (at the cervical or lumbar level, according to the modified Stoke Ankylosing Spondylitis Spine Score). Associations between baseline characteristics and the presence of radiographic lesions were evaluated by estimating multi-adjusted odd ratios (aORs) and their 95% CIs using a logistic regression model. RESULTS: Of 475 patients, 180 (37.9%) had radiographic lesions. Factors positively associated with radiographic lesions were alcohol use (aOR 2.42; 95% CI 1.31, 4.44; P = 0.005), CRP level (aOR 1.44; 95% CI 1.13, 1.84; P = 0.003) and SIJ inflammation by MRI (aOR 2.25; 95% CI 1.40, 3.60; P = 0.001); negative associations occurred with good NSAID responsiveness (aOR 0.44; 95% CI 0.24, 0.81; P = 0.008); spinal MRI inflammation was associated with radiographic lesions only in smokers (aOR 1.99; 95% CI 1.01, 3.92; P = 0.048). CONCLUSION: Alcohol use, poor responsiveness to NSAIDs, CRP elevation, SIJ MRI inflammation and spinal MRI inflammation in smokers were independently associated with radiographic lesions in early axial SpA.

Published
2013
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11. Biosimilars of filgrastim in autologous stem cell transplant: reduction in granulocyte-colony stimulating factor costs, but similar effects on bone marrow recovery

Author

Christian Berthou, Marie-Anne Couturier, Pascal Delépine, Jean-Christophe Ianotto, Françoise Ngo Sack, Adrian Tempescul, Nathalie Mugnier, Gaelle Guillerm, Service Hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Hematology service, Hôpital Central de Yaoude, Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Université européenne de Bretagne ( UEB ), Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Eléments transposables, évolution, populations, Département génétique, interactions et évolution des génomes [LBBE] (GINSENG), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université européenne de Bretagne - European University of Brittany (UEB), and Michel, Geneviève

Subjects
Male, Oncology, Cancer Research, Lymphoma, MESH : Retrospective Studies, MESH : Aged, MESH: Multiple Myeloma, MESH: Recombinant Proteins, MESH : Granulocyte Colony-Stimulating Factor, MESH: Drug Costs, hemic and lymphatic diseases, Granulocyte Colony-Stimulating Factor, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, Prospective cohort study, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, Hematopoietic Stem Cell Transplantation, Biosimilar, Hematology, Middle Aged, MESH : Adult, Recombinant Proteins, MESH: Transplantation, Autologous, 3. Good health, Granulocyte colony-stimulating factor, Treatment Outcome, medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Multiple Myeloma, medicine.drug, Adult, medicine.medical_specialty, MESH : Transplantation, Autologous, [SDV.IMM] Life Sciences [q-bio]/Immunology, Filgrastim, MESH: Biosimilar Pharmaceuticals, MESH : Recombinant Proteins, MESH : Male, MESH : Treatment Outcome, Transplantation, Autologous, MESH : Lymphoma, Drug Costs, MESH : Drug Costs, MESH : Hematopoietic Stem Cell Transplantation, Internal medicine, medicine, Humans, MESH : Middle Aged, Biosimilar Pharmaceuticals, MESH: Hematopoietic Stem Cell Transplantation, Aged, Retrospective Studies, MESH: Humans, business.industry, MESH : Humans, MESH: Adult, MESH: Retrospective Studies, Retrospective cohort study, medicine.disease, MESH: Male, Surgery, Transplantation, MESH : Biosimilar Pharmaceuticals, MESH: Granulocyte Colony-Stimulating Factor, Bone marrow, MESH: Lymphoma, MESH : Multiple Myeloma, business, MESH: Female
Abstract

International audience; Granulocyte-colony stimulating factors (G-CSFs) enhance bone marrow (BM) recovery after autologous stem cell transplant (ASCT) in patients with lymphoma and myeloma. Few publications exist that discuss the use of filgrastim biosimilars after ASCT. We conducted a single-center retrospective study in patients with lymphoma and myeloma treated at Brest Hospital to assess the cost reductions related to and the efficiency and safety of filgrastim biosimilars. We identified 65 patients with lymphoma or myeloma treated with filgrastim biosimilars for ASCT and compared 19 parameters of these patients, including BM recovery, side effects, infectious complications and treatment costs, with published historical data on a cohort of 50 patients treated with classic filgrastim. We observed a significant reduction of G-CSF costs in both groups but did not observe a change in total hospitalization costs (representing less than 2% of the costs) between groups. Additionally, we did not observe differences between the two groups in BM recovery, infectious complications, side effects or the other studied parameters. In this retrospective study, the absence of differences between groups after ASCT in lymphoma and myeloma led us to believe that these drugs could be safely and effectively used for such indications without a significant impact on hospitalization costs. A prospective study should be conducted to confirm our results.

Published
2013
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12. Cytokine and gene transcription profiles of immune responses elicited by HIV lipopeptide vaccine in HIV-negative volunteers

Author

Laura, Richert, Sophie, Hue, Hakim, Hocini, Mathieu, Raimbault, Christine, Lacabaratz, Mathieu, Surenaud, Aurélie, Wiedemann, Pascaline, Tisserand, Christine, Durier, Dominique, Salmon, Jean-Daniel, Lelièvre, Geneviève, Chêne, Rodolphe, Thiébaut, Yves, Lévy, C, Desaint, Statistics In System biology and Translational Medicine (SISTM), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'immunologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Essais Therapeutiques et Infection Par Le Vih, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'immunologie clinique [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Bordeaux Segalen - Bordeaux 2 - Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Bordeaux Segalen - Bordeaux 2 - Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria) - Institut National de Recherche en Informatique et en Automatique (Inria), Université Bordeaux Segalen - Bordeaux 2 - Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED) - Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) - Institut National de la Santé et de la Recherche Médicale (INSERM) - IFR10, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11) - Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Cochin [AP-HP] - Assistance publique - Hôpitaux de Paris (AP-HP), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), and CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)

Subjects
CD4-Positive T-Lymphocytes, Male, Enzyme-Linked Immunospot Assay, Transcription, Genetic, MESH : Cytokines, medicine.medical_treatment, MESH : Enzyme-Linked Immunospot Assay, HIV Antibodies, Lymphocyte Activation, 0302 clinical medicine, [STAT.AP] Statistics [stat]/Applications [stat.AP], MESH: Lipopeptides, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Interferon, Immunology and Allergy, MESH : Female, MESH: Double-Blind Method, 030212 general & internal medicine, MESH : HIV Seronegativity, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: HIV Seronegativity, AIDS Vaccines, MESH: Cytokines, [STAT.AP]Statistics [stat]/Applications [stat.AP], 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Middle Aged, MESH : Gene Expression Regulation, Immunogenicity, ELISPOT, Vaccination, MESH: CD4-Positive T-Lymphocytes, MESH : Adult, Middle Aged, MESH: Gene Expression Regulation, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Infectious Diseases, Cytokine, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, MESH : CD4-Positive T-Lymphocytes, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cytokines, Female, Adjuvant, medicine.drug, Adult, MESH : AIDS Vaccines, MESH : Male, Immunology, Biology, Peripheral blood mononuclear cell, MESH : HIV Antibodies, Lipopeptides, 03 medical and health sciences, MESH : Lipopeptides, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, MESH: AIDS Vaccines, Immune system, Double-Blind Method, HIV Seronegativity, medicine, MESH : Double-Blind Method, Humans, MESH : Middle Aged, MESH: Lymphocyte Activation, MESH : Lymphocyte Activation, 030304 developmental biology, MESH: Humans, MESH: HIV Antibodies, MESH: Transcription, Genetic, MESH : Humans, MESH : Transcription, Genetic, MESH: Adult, MESH: Vaccination, MESH: Male, MESH : Vaccination, Gene Expression Regulation, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, MESH: Enzyme-Linked Immunospot Assay, MESH: Female
Abstract

International audience; OBJECTIVE: To dissect the biological mechanisms involved in the cellular responses to a candidate vaccine containing 5 HIV peptides coupled to a palmytoil tail (HIV-LIPO-5) in healthy volunteers, by using extensive immunogenicity assessments with different stimulation durations. DESIGN: Immunogenicity substudy of a randomized phase II prophylactic HIV vaccine trial (ANRS VAC 18). METHODS: HIV-LIPO-5 or placebo was administered at W0, W4, W12 and W24. Peripheral blood mononuclear cells from a subset of participants at W0 and W14 were stimulated with HIV-LIPO-5, Gag peptides contained in the vaccine and control peptides. ELISpot, lymphoproliferation, intracellular cytokine staining (ICS), cytokine multiplex and transcriptomic analyses were performed. Different time points and stimulation conditions were compared, controlling for test multiplicity. RESULTS: Cultured ELISpot and lymphoproliferation responses were detected at W14. Ex-vivo ICS showed mainly interleukin (IL)-2-producing cells. Secretion of interferon (IFN)-γ, tumour necrosis factor (TNF)-α, IL-5 and IL-13 increased significantly after culture and Gag stimulation at W14 compared to W0. Metallothionein genes were consistently overexpressed after HIV-LIPO-5 stimulation at W0 and W14. At W14, significant probes increased substantially, including IFN-γ, CXCL9, IL2RA, TNFAIP6, CCL3L1 and IL-6. Canonical pathway analyses indicated a role of interferon signalling genes in response to HIV-LIPO-5. CONCLUSION: HIV-LIPO-5 vaccination elicited Th1 and Th2 memory precursor responses and a consistent modulation in gene expression. The response profile before vaccination suggests an adjuvant effect of the lipid tail of HIV-LIPO-5. Our combined immunogenicity analyses allowed to identify a specific signature profile of HIV-LIPO-5 and indicate that HIV-LIPO-5 could be further developed as a prime in heterologous prime-boost strategies.

Published
2013
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13. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010

Author

Lakshmi Vijayakumar, H. Ross Anderson, David Singh, Doruk Ozgediz, Ted R. Miller, David Chou, Sumeet S. Chugh, Patricia J. Erwin, Samath D Dharmaratne, Steven E. Lipshultz, Roderick J. Hay, Pon Hsiu Yeh, Luigi Naldi, Valery L. Feigin, Patricia Espindola, Laurie M. Anderson, Beth E. Ebel, Ziad A. Memish, Victor Aboyans, Fiona M. Blyth, Derrick A Bennett, Richard H. Osborne, Mohammad H. Forouzanfar, Maria Segui-Gomez, Ella Sanman, Myles Connor, Esteban Porrini, Don C. Des Jarlais, John R. Condon, Gretchen L. Birbeck, Luc E. Coffeng, Tim Driscoll, David Bartels, Bishnu Pahari, G. Remuzzi, F.G.R. Fowkes, Kyle J Foreman, Joshua A. Salomon, Suzanne Barker-Collo, Mengru Wang, Leslie T. Cooper, Diego Gonzalez-Medina, Ali A. Mokdad, Andrea Panozo Rivero, George A. Mensah, Diana Haring, Julie O. Denenberg, Murugesan Raju, Ralph L. Sacco, Robin Marks, Ian Bolliger, Jeffrey A. Towbin, Rita Krishnamurthi, Dharani Ranganathan, David Phillips, Benjamin C Cowie, Paul S. F. Yip, Charles Mock, Bruno Hoen, Robert G. Weintraub, Frederick P. Rivara, Kaustubh Dabhadkar, Jonathan R. Carapetis, K. Ellicott Colson, Wenzhi Wang, Diego De Leo, Lisa M. Knowlton, Guy B. Marks, Michael S Lipnick, Rashmi Jasrasaria, Flavio Gaspari, Richard F. Gillum, John J. McGrath, Jacqueline Mabweijano, Rogelio Perez Padilla, Marlene Fransen, Allyne Delossantos, Theo Vos, Rafael Lozano, Damian G Hoy, Thomas Roberts, Anthony D. Woolf, Zhi Jie Zheng, Karen Sliwa, Andrew E. Moran, Boris Bikbov, Jessica Singleton, Spencer L. James, Mohsen Naghavi, Kim Mulholland, Saad B. Omer, Yara A. Halasa, Sherine E. Gabriel, Leslie Mallinger, Peter Burney, Imad M. Tleyjeh, Majid Ezzati, Jennifer A. Taylor, Thomas Truelsen, Akira Matsumori, Emelia J. Benjamin, Mary M. McDermott, Kiumarss Nasseri, James Harrison, Honglei Chen, Emmanuela Gakidou, M. Nathan Nair, Jerry Abraham, Karen Courville De Vaccaro, Kenji Shibuya, Rakesh Aggarwal, Stephanie Y. Ahn, Steven D. Colan, Christopher J L Murray, Aref A. Bin Abdulhak, Michael Burch, Tony R. Merriman, Nabila Dahodwala, Sudha Jayaraman, Catherine Michaud, Louisa Degenhardt, C. Arden Pope, Monica Cortinovis, Richard Matzopoulos, Norberto Perico, Matthew A. Corriere, Kelsey Pierce, Charles Atkinson, Tim Adair, Abraham D. Flaxman, Michael F. Macintyre, Gregory R. Wagner, Paul Norman, Herbert C. Duber, Kathryn H. Jacobsen, Peter J. Hotez, Andre Keren, Felipe Rodriguez De Leòn, Samantha M. Colquhoun, Michael H. Criqui, Kavi Bhalla, Soufiane Boufous, Narayanaswamy Venketasubramanian, Alan D. Lopez, Larry M. Baddour, Ana Olga Mocumbi, David B. Rein, Jürgen Rehm, Stephen S Lim, Farshad Pourmalek, Nicole E. Johns, Ganesan Karthikeyan, Martin A. Weinstock, Lyn March, Donald S. Shepard, K.M. Venkat Narayan, Michael Freeman, Chiara Bucello, Nicholas J Kassebaum, Adofo Koranteng, Eduardo A. Undurraga, Kerrianne Watt, Mohammad A. AlMazroa, Marita Cross, Fernando Perez-Ruiz, Rasmus Havmoeller, Uchechukwu Sampson, Emma Smith, Bongani M. Mayosi, Summer Lockett Ohno, Michelle L. Bell, John H. McAnulty, E. Ray Dorsey, Lesley Rushton, Matthew J. Miller, Azadeh Zabetian, James D. Wilkinson, David C. Schwebel, Olive Kobusingye, Katrina F Ortblad, Martin O'Donnell, Jon Paul Khoo, William G. Couser, Miriam Alvarado, Richard C. Franklin, Lisa C. Rosenfeld, Andrew C Steer, Bernadette Thomas, Jeyaraj D Pandian, Sarah Wulf, Kathryn G. Andrews, Neuroépidémiologie Tropicale ( NET ), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST ), Université de Limoges ( UNILIM ) -Université de Limoges ( UNILIM ), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], CHU Limoges, Respiratory Epidemiology and Public Health, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Service des maladies infectieuses et tropicales, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Cisco Systems, CISCO Systems, Inc, Department of dermatology, Milano University-Azienda Ospedaleria Ospedali Riuniti di Bergamo, centre for photomolecular science, Imperial College London, Department of neurology, Miller School of Medicine-University of Miami [Coral Gables], Département Cité des métiers - Cité de la santé - Universcience ( CDM/CDS ), Cité des Sciences et de l'Industrie, Public Health, Cell biology, Cardiothoracic Surgery, Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute [UK], Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, University of Miami [Coral Gables]-University of Miami Leonard M. Miller School of Medicine (UMMSM), and Département Cité des métiers - Cité de la santé - Universcience (CDM/CDS)

Subjects
Male, Pediatrics, MESH : Mortality, MESH : Aged, Poison control, Disease, MESH : Child, Preschool, 030204 cardiovascular system & hematology, Global Health, MESH: Cause of Death, MESH: Aged, 80 and over, 0302 clinical medicine, MESH : Child, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cause of Death, MESH: Child, MESH : Female, 030212 general & internal medicine, Child, Cause of death, Aged, 80 and over, MESH: Aged, education.field_of_study, MESH: Middle Aged, Mortality rate, MESH: Infant, Newborn, Age Factors, 1. No poverty, MESH : Infant, General Medicine, Middle Aged, MESH : Adult, MESH: Infant, 3. Good health, MESH : World Health, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Young Adult, Child, Preschool, Female, Adult, medicine.medical_specialty, Adolescent, MESH : Male, MESH : Sex Factors, Population, MESH : Young Adult, MESH : Infant, Newborn, Young Adult, 03 medical and health sciences, Sex Factors, MESH: Sex Factors, SDG 3 - Good Health and Well-being, MESH : Adolescent, Injury prevention, medicine, Humans, MESH : Middle Aged, Mortality, MESH : Aged, 80 and over, education, Aged, MESH : Cause of Death, MESH: Adolescent, MESH: Age Factors, MESH: Humans, MESH: Mortality, business.industry, MESH: Child, Preschool, MESH : Humans, Infant, Newborn, Infant, MESH: Adult, Verbal autopsy, MESH: Male, Years of potential life lost, MESH : Age Factors, business, MESH: Female, MESH: World Health, Demography
Abstract

International audience; BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52*8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24*9% of deaths worldwide in 2010, down from 15*9 million (34*1%) of 46*5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2*5 to 1*4 million), lower respiratory infections (from 3*4 to 2*8 million), neonatal disorders (from 3*1 to 2*2 million), measles (from 0*63 to 0*13 million), and tetanus (from 0*27 to 0*06 million). Deaths from HIV/AIDS increased from 0*30 million in 1990 to 1*5 million in 2010, reaching a peak of 1*7 million in 2006. Malaria mortality also rose by an estimated 19*9% since 1990 to 1*17 million deaths in 2010. Tuberculosis killed 1*2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34*5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1*5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12*9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1*3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5*1 million deaths) was marginally higher in 2010 (9*6%) compared with two decades earlier (8*8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1*3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation.

Published
2012
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14. Patterns of physical activity and sedentary behaviour in the general population in France: cluster analysis with personal and socioeconomic correlates

Author

Joël Coste, Abdou Y. Omorou, Hélène Escalon, Anne Vuillemin, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Institut National de Prévention et d'Education pour la Santé (INPES), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), and Institut National de Prévention et d'Education pour la Santé ( INPES )

Subjects
Male, Pediatrics, MESH : Aged, Poison control, physical activity, Transportation, MESH: Logistic Models, Logistic regression, 0302 clinical medicine, MESH : Child, MESH : Exercise, Surveys and Questionnaires, MESH: Child, MESH : Socioeconomic Factors, Cluster Analysis, MESH : Female, 030212 general & internal medicine, clusters, MESH : Leisure Activities, Child, 2. Zero hunger, MESH: Aged, education.field_of_study, MESH: Middle Aged, 1. No poverty, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, MESH : Adult, Middle Aged, 3. Good health, Homogeneous, MESH: Young Adult, Female, France, MESH : Surveys and Questionnaires, MESH: Sedentary Lifestyle, Adult, medicine.medical_specialty, MESH: Socioeconomic Factors, Adolescent, MESH : Male, Population, Physical activity, MESH : Young Adult, World health, socioeconomic status, 03 medical and health sciences, Young Adult, Leisure Activities, MESH : Adolescent, sedentary behaviour, medicine, MESH : Transportation, MESH : Cluster Analysis, Humans, MESH : Middle Aged, Occupations, MESH: Surveys and Questionnaires, education, MESH : France, Socioeconomic status, Exercise, MESH: Leisure Activities, Socioeconomic differences, Aged, MESH: Adolescent, MESH: Humans, MESH: Occupations, business.industry, MESH: Transportation, MESH : Humans, Public Health, Environmental and Occupational Health, MESH : Occupations, correlates, MESH: Adult, 030229 sport sciences, MESH: Cluster Analysis, MESH: Male, MESH: France, Logistic Models, Socioeconomic Factors, MESH: Exercise, MESH : Sedentary Lifestyle, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Sedentary Behavior, business, MESH: Female, Demography, MESH : Logistic Models
Abstract

International audience; BACKGROUND:Few studies have focused on relating physical activity (PA) and sedentary behaviour (SB) to identify homogeneous groups. This study aimed to identify patterns of PA and SB in France general population and their correlates.METHODS:A sample of 3294 (mean age 44 ± 17 years) from the general population in France was included. PA and SB were assessed by the World Health Organization Global Physical Activity Questionnaire. Cluster analysis was used to identify PA and SB patterns, with polytomous logistic regression to identify their correlates.RESULTS:Five clusters were identified: (i) 'low total PA, active-transportation and low SB' (41%), (ii) 'low total PA and moderate SB' (22%), (iii) 'low total PA, leisure-time PA and high SB' (15%), (iv) 'high total PA, moderate occupational PA and moderate SB' (17%) and (v) 'high total PA, vigorous occupational PA and low SB' (5%). Occupational PA substantially contributed to total PA which depended on socioeconomic status (SES): low total PA and high SB in higher SES and high total PA and low SB in lower SES.CONCLUSIONS:Based on PA and SB, French adults were clustered into groups with socioeconomic differences emphasizing that adapted interventions may be more beneficial for health.

Published
2016
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15. Genetic variability of the forkhead box O3 and prostate cancer risk in the European Prospective Investigation on Cancer

Author

Rudolf Kaaks, Eva Ardanaz, Heiner Boeing, María José Sánchez, Domenico Palli, Nicholas J. Wareham, Tina Karapetyan, Sabina Sieri, Mazda Jenab, Nina Roswall, Kim Overvad, Anne Tjønneland, Ruth C. Travis, Afshan Siddiq, José María Huerta, Anika Hüsing, Angelika Stein, H. Bas Bueno-de-Mesquita, Federico Canzian, Nerea Larrañaga, Mattias Johansson, Kay-Tee Khaw, Lucie Dostal, Jane Nautrup Østergaard, David Cox, Laudina Rodríguez, Daniele Campa, Rosario Tumino, Catalina Bonet, Per Lenner, Naomi E. Allen, Paolo Vineis, Dimosthenis Zylis, Dagmar Drogan, Antonia Trichopoulou, Department of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, German Institute of Human Nutrition Potsdam-Rehbrücke, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Cancer Epidemiology Institute, Danish Cancer Society, Department of Cardiology, Aarhus University Hospital, Public Health and Participation Directorate, Health and Health Care Services Council, Catalan Institute of Oncology, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Granada Cancer Registry, Andalusian School of Public Health [Granada], Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), CIBER de Epidemiología y Salud Pública (CIBERESP), Murcia Regional Health Authority, Navarra Public Health Institute, Leyre 15, School of Clinical Medicine, University of Cambridge [UK] (CAM), Epidemiology Unit, Medical Research Council, Cancer Epidemiology Unit, University of Oxford [Oxford]-Cancer Epidemiology Unit, Department of Hygiene, Epidemiology and Medical Statistics, Molecular and Nutritional Epidemiology Unit, ISPO-Cancer Research and Prevention Institute, Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Cancer Registry, Civile - M.P.Arezzo Hospital, Centre for Environment and Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Human Genetics Foundation (HuGeF), Università degli studi di Torino (UNITO), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Oncology and Radiation Sciences, Oncology, Umea University Hospital, Unit of Nutrition, Environment, and Cancer, Equipe 6, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Department of Epidemiology and Biostatistics, Imperial College London-Faculty of Medicine-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-Imperial College London-Faculty of Medicine-School of public health, Department of Epidemiology and Biostatistics, Department of Genomics of Common Disease, Division of Cancer Epidemiology, German Cancer Research Center, German Cancer Research Center (DKFZ), Aalborg Hospital-Aarhus University Hospital, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública ( CIBERESP ), Andalusian School of Public Health, University of Cambridge [UK] ( CAM ), Azienda Ospedaliera 'Civile M.P.Arezzo', Human Genetics Foundation ( HuGeF ), Università degli studi di Torino ( UNITO ), National Institute for Public Health and the Environment [Bilthoven] ( RIVM ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Department of Epidemiology and Biostatistics, and Imperial College London-Faculty of Medicine-School of public health-Imperial College London-Faculty of Medicine-School of public health

Subjects
Oncology, Male, MESH: Signal Transduction, Cancer Research, MESH : Aged, MESH : Genotype, 030204 cardiovascular system & hematology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Cohort Studies, MESH: Genotype, Prostate cancer, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, genetic variability, MESH: Cohort Studies, media_common, MESH: Aged, 0303 health sciences, education.field_of_study, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, Forkhead Box Protein O3, Longevity, MESH: Genetic Predisposition to Disease, Forkhead Transcription Factors, General Medicine, MESH: European Continental Ancestry Group, MESH : Adult, Middle Aged, prostate cancer, MESH : Risk Factors, MESH: Case-Control Studies, 3. Good health, European Prospective Investigation into Cancer and Nutrition, forkhead box, MESH : Forkhead Transcription Factors, Europe, FOXO3, MESH : Prostatic Neoplasms, Signal Transduction, Adult, medicine.medical_specialty, MESH : Case-Control Studies, Genotype, media_common.quotation_subject, MESH : Male, Population, MESH : Europe, MESH : Cohort Studies, Single-nucleotide polymorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, White People, MESH : European Continental Ancestry Group, 03 medical and health sciences, MESH: Forkhead Transcription Factors, Internal medicine, medicine, Humans, MESH : Middle Aged, Genetic Predisposition to Disease, education, 030304 developmental biology, Aged, MESH : Signal Transduction, MESH: Humans, MESH : Humans, Case-control study, Cancer, Prostatic Neoplasms, MESH: Adult, medicine.disease, MESH: Male, Case-Control Studies, MESH: Prostatic Neoplasms, MESH : Genetic Predisposition to Disease, MESH: Europe
Abstract

International audience; Forkhead box O3 (FOXO3) has a wide range of functions: it promotes tumor suppression, cell cycle arrest, repair of damaged DNA, detoxification of reactive oxygen species, apoptosis and plays a pivotal role in promoting longevity. FOXO3 is a key downstream target of the PI3K-Akt pathway in response to cellular stimulation by growth factors or insulin and has been proposed as a bridge between ageing and tumor suppression. Three SNPs in the FOXO3 gene (rs3800231, rs9400239 and rs479744) that have been shown to be strongly and consistently associated with longevity, were examined in relation to PC risk in a case control study of 1571 incident PC cases and 1840 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). There was no statistically significant association between the SNPs and PC risk regardless of the model of inheritance (dominant, codominant and recessive). The associations were not modified by disease aggressiveness, circulating levels of steroid sex hormones, or IGFs or BMI. We conclude that polymorphisms in the FOXO3 gene that are associated with longevity are not major risk factors for PC risk, in this population of Caucasian men.

Published
2016
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16. Incidence of acute postoperative endophthalmitis after cataract surgery a nationwide study in France from 2005 to 2014

Author

Creuzot Garcher, Catherine, Benzenine, Eric, Mariet, AS, de Lazzer, Aurélie, Chiquet, Christophe, Bron, Alain, Quantin, Catherine, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), OEil, nutrition et signalisation cellulaire [CSGA], Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Service Biostatistiques et Informatique Médicale (CHU de Dijon) ( DIM ), Centre Hospitalier Universitaire de Grenoble, Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris], Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université Bourgogne Franche-Comté ( UBFC ), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques ( CIC-EC ), Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses ( B2PHI ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Université Joseph Fourier - Grenoble 1 ( UJF )

Subjects
MESH : Retrospective Studies, diagnosis, MESH : Age Distribution, MESH : Aged, intracameral antibiotics, MESH: Aged, 80 and over, prevention, MESH: Risk Factors, Ophtalmology, MESH: Postoperative Complications, MESH : Female, MESH: Incidence, MESH : Anti-Bacterial Agents, MESH : F Factor, MESH: Aged, MESH: Middle Aged, MESH: Eye Infections, Bacterial, MESH : Acute Disease, MESH : Phacoemulsification, MESH : Adult, MESH : Risk Factors, MESH : Incidence, [ SDV.MHEP.OS ] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, MESH : Eye Infections, Bacterial, MESH: Acute Disease, prophylaxis, ascrs member survey, MESH: Cefuroxime, MESH : Male, MESH : Endophthalmitis, MESH: Multivariate Analysis, institution, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, MESH: Anti-Bacterial Agents, MESH: Endophthalmitis, MESH : Middle Aged, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, MESH : France, MESH : Aged, 80 and over, MESH: Age Distribution, medicare population, MESH: Humans, MESH: F Factor, MESH : Humans, bacterial endophthalmitis, MESH : Multivariate Analysis, MESH: Adult, MESH: Retrospective Studies, MESH: Male, cefuroxime, MESH: France, injection, MESH : Postoperative Complications, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH : Cefuroxime, MESH: Phacoemulsification
Abstract

International audience; PURPOSE:To report the incidence of acute postoperative endophthalmitis (POE) after cataract surgery from 2005 to 2014 in France.DESIGN:Cohort study.PARTICIPANTS:Patients undergoing operation for cataract surgery by phacoemulsification and presenting acute POE.METHODS:We identified acute POE occurring within 6 weeks after phacoemulsification cataract surgery and the use of intracameral antibiotic injection during the surgical procedure by means of billing codes from a national database.MAIN OUTCOME MEASURES:Incidence of acute POE.RESULTS:From January 2005 to December 2014, 6 371 242 eyes in 3 983 525 patients underwent phacoemulsification cataract surgery. The incidence of acute POE after phacoemulsification decreased from 0.145% to 0.053% during this 10-year period; the unadjusted incidence rate ratio (IRR) (95% confidence interval) was 0.37 (0.32-0.42; P < 0.001). In multivariate analysis, intracameral antibiotic injection was associated with a lower risk of acute POE 0.53 (0.50-0.57; P < 0.001), whereas intraoperative posterior capsule rupture, combined surgery, and gender (male) were associated with a higher risk of acute POE: 5.24 (4.11-6.68), 1.77 (1.53-2.05), and 1.48 (1.40-1.56) (P < 0.001), respectively.CONCLUSIONS:Access to a national database allowed us to observe a decrease in acute POE after phacoemulsification cataract surgery from 2005 to 2014. Within the same period, the use of intracameral antibiotics during the surgical procedures increased.

Published
2016
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17. Surveillance and management of Echinococcus multilocularis in a wildlife park

Author

Jean-Marc Boucher, Frédéric Grenouillet, Amandine Guenon, Damien Montange, Vanessa Hormaz, Franck Boué, Jennifer Lahoreau, Gérald Umhang, Agence Nationale de Sécurité Sanitaire, de l'Alimentation, de l'environnement et du Travail ( ANSES ), ANSES, Laboratoire Génie des procédés papetiers ( LGP2 ), Centre Technique du Papier ( CTP ) -Institut National Polytechnique de Grenoble ( INPG ) -École Française de Papeterie et des Industries Graphiques-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Laboratoire Génie des procédés papetiers (LGP2 ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)

Subjects
Male, 0301 basic medicine, Veterinary medicine, Foxes, Captivity, Lemur catta, Serology, Feces, MESH : Antigens, Fungal, 0302 clinical medicine, Parasite hosting, MESH : Female, MESH : Environmental Monitoring, biology, Arvicolinae, 030108 mycology & parasitology, MESH : Adult, 3. Good health, Intestines, MESH : Air Pollution, Indoor, Infectious Diseases, Liver, Epidemiological Monitoring, MESH: Inhalation Exposure, MESH: Aspergillus fumigatus, MESH: Environmental Monitoring, medicine.drug, Echinococcosis, Hepatic, MESH: Cystic Fibrosis, MESH : Male, 030231 tropical medicine, Animals, Wild, Rodentia, Echinococcus multilocularis, Albendazole, [ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology, environment/Health, 03 medical and health sciences, Echinococcosis, MESH : Cystic Fibrosis, parasitic diseases, medicine, Animals, MESH : France, MESH: Antigens, Fungal, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, MESH: Humans, Lemur, MESH : Humans, MESH : Aspergillosis, Allergic Bronchopulmonary, MESH: Adult, biology.organism_classification, MESH: Male, MESH: DNA, Fungal, MESH: France, Metacestode, MESH: Aspergillosis, Allergic Bronchopulmonary, MESH : Aspergillus fumigatus, Parasitology, MESH : Inhalation Exposure, MESH: Air Pollution, Indoor, MESH : DNA, Fungal, MESH: Female
Abstract

International audience; The fox tapeworm Echinococcus multilocularis is the causative agent of alveolar echinococcosis, a severe zoonotic disease that may be fatal if untreated. A broad spectrum of mammalian species may be accidentally infected even in captivity. In April 2011, liver lesions due to E. multilocularis were observed during the necropsy of a captive-born nutria (Myocastor coypus) in a French wildlife park, leading to initiation of a study to survey the parasite's presence in the park. A comparable environmental contamination with fox's feces infected by E. multilocularis was reported inside (17.8%) and outside (20.6%) the park. E. multilocularis worms were found in the intestines of three of the five roaming foxes shot in the park. Coprological analyses of potential definitive hosts in captivity (fox, lynx, wildcat, genet, wolf, bear and raccoon) revealed infection in one Eurasian wolf. Voles trapped inside the park also had a high prevalence of 5.3%. After diagnosis of alveolar echinococcosis in a Lemur catta during necropsy, four other cases in L. catta were detected by a combination of ultrasound and serology. These animals were treated twice daily with albendazole. The systematic massive metacestode development and numerous protoscoleces in L. catta confirmed their particular sensitivity to E. multilocularis infection. The autochthonous origin of the infection in all the captive animals infected was genetically confirmed by EmsB microsatellite analysis. Preventive measures were implemented to avoid the presence of roaming foxes, contact with potential definitive hosts and contaminated food sources for potential intermediate hosts.

Published
2016

18. Trends of incidence and survival in squamous-cell carcinoma of the anal canal in France: a population-based study

Author

Valérie Jooste, Zoé Uhry, Anne-Marie Bouvier, Jean Faivre, Sophie Grabar, N. Duport, Sylvain Manfredi, Aurélien Belot, Registre Bourguignon des Cancers Digestifs, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), FRANCIM, Réseau des registres français du cancer, Département des maladies chroniques et traumatismes, Institut de Veille Sanitaire (INVS), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Service de Biostatistiques [Lyon], Hospices Civils de Lyon (HCL), Service des Maladies de l'Appareil Digestif [CHU Rennes], CHU Pontchaillou [Rennes], Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National du Cancer (INCA), Santé publique France, Pontchaillou. Service des maladies de l'appareil digestif, Centre Hospitalier Universitaire [Rennes], Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Hospices Civils de Lyon ( HCL ), Centre Hospitalier Universitaire de Rennes, and Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
Male, Epidemiology, MESH : Aged, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Anus Neoplasms, MESH: Research Papers: Gastrointestinal Cancer, 0302 clinical medicine, MESH : Child, MESH: Child, Medicine, MESH: Incidence, MESH : Carcinoma, Squamous Cell, Child, education.field_of_study, MESH: Middle Aged, Obstetrics, MESH : Infant, MESH: Carcinoma, Squamous Cell, MESH: Follow-Up Studies, Anal canal, Anus Neoplasms, Prognosis, Research Papers, MESH: Infant, MESH : Incidence, 3. Good health, Survival Rate, Oncology, MESH: Young Adult, Child, Preschool, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, 030211 gastroenterology & hepatology, medicine.medical_specialty, MESH : Research Papers: Gastrointestinal Cancer, Mitomycin, MESH : Young Adult, United-States, MESH: Prognosis, 03 medical and health sciences, MESH : Adolescent, Humans, Anal cancer, MESH : Middle Aged, MESH : Anus Neoplasms, education, Aged, Gynecology, MESH: Adolescent, MESH: Humans, MESH : Humans, MESH: Child, Preschool, Public Health, Environmental and Occupational Health, Infant, MESH : Follow-Up Studies, MESH: Adult, Epidermoid Carcinoma, medicine.disease, Cervical-cancer, incidence, Randomized-trial, MESH: Female, Cancer Research, MESH: Registries, MESH : Child, Preschool, Risk Factors, MESH: Risk Factors, MESH : Female, Registries, Cervical cancer, MESH: Aged, MESH : Prognosis, Incidence (epidemiology), Smoking, MESH: Infant, Newborn, MESH : Adult, Middle Aged, MESH : Survival Rate, MESH : Risk Factors, medicine.anatomical_structure, Female, France, Adult, Human-Papillomavirus, Risk, Adolescent, MESH: Survival Rate, anal cancer, MESH : Male, Population, Human Papilloma Virus Vaccine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cancer Incidence, MESH : Infant, Newborn, survival, Young Adult, cancer registry, MESH : France, Survival rate, Radiotherapy, business.industry, Infant, Newborn, Cancer, MESH: Male, MESH: France, business, MESH : Registries, Follow-Up Studies
Abstract

IF 2.415; International audience; Data on anal cancer epidemiology are rare. The aim of this study was to report on trends of incidence and survival for anal cancer in France before the implementation of the human papilloma virus vaccine. This analysis was carried out on 1150 squamous-cell carcinomas of the anal canal diagnosed from 1989 to 2004 in a population of 5.7 million people covered by eight population-based cancer registries. Time trends in incidence were modeled using an age-period-cohort model. Net survival rates were obtained using the recently validated unbiased Pohar-Perme estimator. The incidence of squamous-cell carcinoma of the anal canal increased from 0.2 to 0.5/100 000 person-years among men and from 0.7 to 1.3/100 000 person-years among women from 1982 to 2012. Among women, the increase peaked after 2005, with an annual percentage change of +3.4% between 2005 and 2012, as compared with +2.6% among men. The net survival was 56% (95% confidence interval, 49-64) at 5 years and 48% (33-70) at 10 years among men. It was higher among women, at 65% (61-69) and 56% (50-63) at 5 and 10 years, respectively. The prognosis improved between 1989-1997 and 1998-2004. This improvement was slightly greater for men than for women, thus progressively reducing the gap between sexes. The incidence of squamous-cell anal canal cancer increased slightly among both sexes, but the increase was more marked among women than among men. The potential benefit of prophylactic female human papilloma virus vaccination against cervical cancer in France should be further evaluated.

Published
2016
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19. Estimating the Burden of Leptospirosis among Febrile Subjects Aged below 20 Years in Kampong Cham Communities, Cambodia, 2007-2009

Author

Seiha Heng, Arnaud Tarantola, Rekol Huy, Touch Sok, Sopheak Hem, Florian Vogt, Sowath Ly, Mathieu Picardeau, Sovann Ly, Nima Asgari, Irene Votsi, Philippe Buchy, Simon Cauchemez, Bertrand Guillard, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Modélisation mathématique des maladies infectieuses, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), London School of Hygiene and Tropical Medicine (LSHTM), World Health Organization [Phnom Penh] (WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris], Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Ministry of Health [Phnom Penh], National Center of Parasitology (CNM), National Malaria Center [Phnom Penh], This study was supported by the World Health Organization and the European Union and Pediatric Vaccine Dengue Initiative project (PDVI) from the International Vaccine Institute (IVI). Aside from coauthor NA who helped discuss the study results and edit the article, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Institut Pasteur du Cambodge-Réseau International des Instituts Pasteur ( RIIP ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), London School of Hygiene and Tropical Medicine ( LSHTM ), World Health Organization [Phnom Penh] ( WHO ), World Health Organization, Centre National de Référence des Leptospires-Biologie des Spirochètes ( CNR-CC FAO/OMS ), Communicable Disease Department [Phnom Penh] ( CDC MOH ), Ministry of Health, National Center for Malaria Control, Parasitology and Entomology, Ministry of Health of Cambodgia, and This study was supported by the World Health Organization and the European Union and Pediatric Vaccine Dengue Initiative project (PDVI) from the International Vaccine Institute (IVI).

Subjects
MESH : Cambodia/epidemiology, Male, Rural Population, Pathology and Laboratory Medicine, Biochemistry, 0302 clinical medicine, MESH : Immunoglobulin M/blood, MESH : Child, MESH: Rural Population, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Child, Chikungunya, Enzyme-Linked Immunoassays, lcsh:Science, Child, MESH : Dengue/epidemiology, Leptospira, education.field_of_study, MESH : Antibodies, Bacterial/blood, MESH : Infant, MESH: Leptospirosis, Leptospirosis, MESH: Infant, MESH: Immunoglobulin M, 3. Good health, Bacterial Pathogens, Veterinary Diseases, Medical Microbiology, Child, Preschool, medicine.medical_specialty, 030106 microbiology, Immunology, MESH: Social Planning, Microbiology, 03 medical and health sciences, Signs and Symptoms, MESH : Adolescent, MESH : Leptospirosis/blood, Humans, education, Immunoassays, Microbial Pathogens, MESH: Adolescent, MESH: Humans, Bacteria, Public health, MESH : Humans, lcsh:R, MESH: Child, Preschool, Organisms, Infant, Biology and Life Sciences, Proteins, MESH: Adult, Japanese encephalitis, medicine.disease, Tropical Diseases, lcsh:Q, Veterinary Science, MESH: Female, Demography, 0301 basic medicine, Bacterial Diseases, Physiology, lcsh:Medicine, Fevers, MESH: Dengue, MESH : Child, Preschool, medicine.disease_cause, Serology, Dengue fever, Dengue, Geographical Locations, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Zoonoses, Immune Physiology, MESH: Antibodies, Bacterial, Medicine and Health Sciences, MESH : Female, Multidisciplinary, Immune System Proteins, biology, MESH: Infant, Newborn, MESH : Adult, Antibodies, Bacterial, Infectious Diseases, Female, Social Planning, Pathogens, Cambodia, Research Article, Neglected Tropical Diseases, Adult, MESH : Dengue/blood, Asia, Adolescent, MESH : Male, 030231 tropical medicine, Population, MESH : Infant, Newborn, Research and Analysis Methods, Antibodies, MESH : Social Planning, Diagnostic Medicine, medicine, MESH : Leptospirosis/epidemiology, business.industry, MESH: Cambodia, Infant, Newborn, biology.organism_classification, MESH: Male, MESH : Rural Population, Immunoglobulin M, People and Places, Immunologic Techniques, business
Abstract

International audience; BACKGROUND:Leptospirosis is an emerging but neglected public health challenge in the Asia/Pacific Region with an annual incidence estimated at 10-100 per 100,000 population. No accurate data, however, are available for at-risk rural Cambodian communities.METHOD:We conducted anonymous, unlinked testing for IgM antibodies to Leptospira spp. on paired sera of Cambodian patients

Published
2016
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20. GCKR polymorphism influences liver fat content in patients with type 2 diabetes

Author

Jean-Michel Petit, Marie-Claude Brindisi, Laurence Duvillard, Patrick Hillon, Boris Guiu, Fabien Rollot, David Masson, Benjamin Bouillet, Perrine Buffier, Bruno Vergès, Jean-Pierre Cercueil, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de radiologie et d'Imagerie médicale diagnostique et thérapeutique (CHU de Dijon), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon, and Conseil Regional de Bourgogne (AOI)

Subjects
Male, 0301 basic medicine, Magnetic Resonance Spectroscopy, Steatosis, MESH : Polymorphism, Genetic, Endocrinology, Diabetes and Metabolism, MESH : Aged, Type 2 diabetes, Body Mass Index, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, MESH : Diabetes Mellitus, Type 2, MESH : Lipid Metabolism, MESH : Female, MESH : Adaptor Proteins, Signal Transducing, education.field_of_study, Glucokinase regulatory protein, 1H-MR spectroscopy, General Medicine, Middle Aged, MESH : Adult, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH : Non-alcoholic Fatty Liver Disease, Metformin, Liver, Female, medicine.drug, GCKR, Adult, Heterozygote, medicine.medical_specialty, MESH : Heterozygote, MESH : Male, Population, 030209 endocrinology & metabolism, Biology, 03 medical and health sciences, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Humans, MESH : Middle Aged, education, Alleles, Adaptor Proteins, Signal Transducing, Aged, Polymorphism, Genetic, Triglyceride, MESH : Humans, MESH : Liver, Lipid Metabolism, medicine.disease, MESH : Body Mass Index, 030104 developmental biology, Diabetes Mellitus, Type 2, chemistry, biology.protein, MESH : Magnetic Resonance Spectroscopy, MESH : Alleles, Body mass index, Non-alcoholic fatty liver disease
Abstract

IF 3.074; International audience; It has recently been shown that an allele in the glucokinase regulatory protein (GCKR) gene was associated with increased liver fat content in obese children. In this study, we set out to determine whether GCKR rs1260326 polymorphism was associated with liver fat content in patients with type 2 diabetes.Three hundred and eight patients with type 2 diabetes were included in this study. Liver fat content was evaluated using 1H-MR spectroscopy.In our population, carriers of the rs1260326 minor T allele had a higher liver fat content than did carriers of the C allele homozygote (12.4 +/- A 9.6 vs. 10.3 +/- A 9.1 %, p = 0.03). The number of patients with steatosis was significantly higher in minor T allele carriers than in C allele homozygote carriers (70.7 vs. 55.4 %; p = 0.008). In multivariate analysis, the predictive variables for steatosis were BMI [odds ratio (OR) 1.08; 95 % confidence interval (CI) 1.03-1.13; p = 0.002], statin therapy (yes) [OR 0.54; 95 % CI 0.31-0.94; p = 0.03], metformin therapy (yes) [OR 2.67; 95 % CI 1.50-4.75; p < 0.001], and rs1260326 GCKR polymorphism (TT+CT) [OR 1.99; 95 % CI 1.14-3.47; p = 0.01].This study shows that in patients with type 2 diabetes who were not selected for liver abnormalities, liver fat content was related to GCKR rs1260326 polymorphism independent of BMI, triglyceride levels, and age.

Published
2016
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21. Femoro-tibial knee osteoarthritis: One or two X-rays? Results from a population-based study

Author

C. Roux, Joël Coste, Patrice Fardellone, Liana Euller-Ziegler, Jacques Pouchot, Francis Guillemin, Anne-Christine Rat, Evelyne Verrouil, Bernard Mazières, Bruno Fautrel, Alain Saraux, Laboratoire Motricité Humaine Expertise Sport Santé ( LAMHESS ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Université de Toulon ( UTLN ), Service de rhumatologie et réadaptation fonctionelle, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Service de Rhumatologie - AMIENS ( AMIENS - Rhumato ), CHU Amiens-Picardie, Service de Rhumatologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Département de médecine interne - hôpital européen Georges-Pompidou, Service de Rhumatologie [CHU de la Cavale-Blanche], Hôpital de la Cavale Blanche - CHRU Brest ( CHU - BREST ), Immunologie et Pathologie ( EA 2216 ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité d’Epidémiologie et de Biostatistiques [APHP Cochin-Broca-Hôtel Dieu], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Laboratoire Motricité Humaine Expertise Sport Santé (LAMHESS), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université de Toulon (UTLN)-Université Côte d'Azur (UCA), CHU Toulouse [Toulouse], Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Service de Rhumatologie - AMIENS (AMIENS - Rhumato), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Immunologie et Pathologie (EA 2216), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Université de Toulon (UTLN), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP]

Subjects
Male, Knee Joint, MESH : Aged, Osteoarthritis, Osteoarthritis, Hip, MESH : Radiography, 0302 clinical medicine, Diagnosis, MESH: Osteoarthritis, Knee, Medicine, MESH : Female, 030212 general & internal medicine, Femur, MESH: Radiography, Orthodontics, MESH: Aged, MESH: Knee Joint, MESH: Middle Aged, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Middle Aged, Osteoarthritis, Knee, MESH : Adult, musculoskeletal system, X-rays results, MESH: Femur, MESH : Knee Joint, Semi-flexed X-ray, Female, Knee osteoarthritis, MESH : Osteoarthritis, Hip, Adult, musculoskeletal diseases, MESH : Male, MESH: Tibia, 03 medical and health sciences, Rheumatology, MESH : Femur, Humans, MESH : Middle Aged, Tibia, MESH : Tibia, MESH : Osteoarthritis, Knee, Aged, 030203 arthritis & rheumatology, MESH: Humans, business.industry, Gold standard, MESH : Humans, MESH: Adult, Prevalence survey, medicine.disease, MESH: Male, Population based study, Radiography, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Osteoarthritis, Hip, business, MESH: Female
Abstract

International audience; OBJECTIVE:Our objective was to compare the use of both anteroposterior (AP) extended-knee X-ray and semi-flexed X-ray (current gold standard) versus the use of semi-flexed X-ray alone to detect femoro-tibial osteoarthritis (OA).METHODS:Individuals 40 to 75 years of age with symptomatic hip and/or knee OA (Kellgren/Lawrence [KL] score≥2) were recruited using a multiregional prevalence survey in France. Both AP and schuss X-rays were performed and read; two years later, the same examiner, blinded to the results of the first reading, performed a second reading of the schuss X-ray. We compared the KL stages of each knee and analyzed osteophyte detection and localization, joint space narrowing (JSN), and the relationship to obesity.RESULTS:The analysis included 350 participants with OA of various stages. Comparing the two readings showed that a higher proportion of patients had KL≥2 when the two X-ray views were combined (right knee: P

Published
2016
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22. Clinical epidemiology and resistance mechanisms of carbapenem-resistant Acinetobacter baumannii, French Guiana, 2008-2014

Author

Magalie Demar, Pierre Couppié, Hatem Kallel, Mathieu Nacher, Christine Simonnet, Didier Hommel, Félix Djossou, Aba Mahamat, Xavier Bertrand, B. Moreau, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Institut de l’Élevage, Centre Hospitalier Andrée-Rosemond, Epidemiologie des Parasitoses Tropicales ( EPaT Team ), Université des Antilles et de la Guyane ( UAG ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Département de Biologie, Unité de Biochimie des Lipides et des Protéines, Faculté des Sciences de Tunis, Ecosystemes Amazoniens et Pathologie Tropicale ( EPat ), Université de Guyane ( UG ) -Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire Hospitalo-Universitaire de Parasitologie-Mycologie, Coordination Régionale de la lutte contre le Virus de L'Immunodéficience Humaine (COREVIH)-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Université des Antilles ( UA ), Unité des Maladies Infectieuses et Tropicales [Cayenne, Guyanne Française], Centre d'investigation clinique Antilles-Guyane ( CIC - Antilles Guyane ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Coordination Régionale de la lutte contre le Virus de L'Immunodéficience Humaine ( COREVIH Guyane ), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Ecosystemes Amazoniens et Pathologie Tropicale (EPat), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Guyane (UG), Faculté des Sciences Mathématiques, Physiques et Naturelles de Tunis (FST), Université de Tunis El Manar (UTM)-Université de Tunis El Manar (UTM), Coordination Régionale de la lutte contre le Virus de L'Immunodéficience Humaine (COREVIH)-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Université des Antilles (UA), Centre d'investigation clinique Antilles-Guyane (CIC - Antilles Guyane), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de la Martinique [Fort de France]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], and Coordination Régionale de la lutte contre le Virus de L'Immunodéficience Humaine (COREVIH Guyane)

Subjects
0301 basic medicine, Male, Acinetobacter baumannii, Imipenem, MESH : Retrospective Studies, Epidemiology, MESH : Multilocus Sequence Typing, MESH: beta-Lactamases, MESH : Carbapenems, Disease Outbreaks, MESH: Carbapenems, Disk Diffusion Antimicrobial Tests, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, polycyclic compounds, MESH : Bacterial Proteins, Pharmacology (medical), MESH : Female, MESH: Disease Outbreaks, MESH: Bacterial Proteins, Cross Infection, Molecular Epidemiology, MESH: Middle Aged, biology, MESH : beta-Lactamases, General Medicine, Middle Aged, MESH : Adult, MESH: Hospitals, Hospitals, 3. Good health, Electrophoresis, Gel, Pulsed-Field, French Guiana, MESH : Hospitals, Infectious Diseases, MESH: Multilocus Sequence Typing, MESH: Electrophoresis, Gel, Pulsed-Field, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Amikacin, MESH: Young Adult, MESH: Disk Diffusion Antimicrobial Tests, Female, MESH: Acinetobacter Infections, MESH : Cross Infection, medicine.drug, Acinetobacter Infections, Microbiology (medical), Adult, MESH : French Guiana, MESH : Male, 030106 microbiology, MESH : Molecular Epidemiology, MESH : Young Adult, Tazobactam, beta-Lactam Resistance, beta-Lactamases, Microbiology, Carbapenem-resistant, 03 medical and health sciences, Young Adult, Bacterial Proteins, MESH : beta-Lactam Resistance, MESH: French Guiana, medicine, Humans, MESH: Molecular Epidemiology, MESH : Acinetobacter Infections, Intensive care unit, MESH : Middle Aged, MESH : Disease Outbreaks, MESH : Disk Diffusion Antimicrobial Tests, MESH : Acinetobacter baumannii, Retrospective Studies, MESH : Electrophoresis, Gel, Pulsed-Field, MESH: Humans, Molecular epidemiology, business.industry, MESH: Acinetobacter baumannii, MESH : Humans, Outbreak, MESH: Cross Infection, MESH: Retrospective Studies, MESH: Adult, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, bacterial infections and mycoses, MESH: Male, MESH: beta-Lactam Resistance, Carbapenems, Colistin, Nosocomial, business, MESH: Female, Piperacillin, Multilocus Sequence Typing
Abstract

International audience; This study investigated the clinical epidemiology and resistance mechanisms of Acinetobacter baumannii and characterised the clonal diversity of carbapenem-resistant A. baumannii (CRAB) during an ICU-associated outbreak at Cayenne Hospital, French Guiana. All non-duplicate A. baumannii isolates from 2008 to 2014 were tested for antibiotic susceptibility by disk diffusion. Multilocus sequence typing, pulsed-field gel electrophoresis (PFGE) and characterisation of carbapenemase-encoding genes were performed on CRAB. Of the 441 A. baumannii isolates, most were from males (54.0%) and were detected mainly from the ICU (30.8%) and medicine wards (21.8%). In the ICU, strains were mainly isolated from the respiratory tract (44.1%) and bloodstream (14.0%), whereas in medicine wards they mainly were from wound/drainage (36.5%) and bloodstream (25.0%). A. baumannii showed the greatest susceptibility to piperacillin/tazobactam (92.7%), imipenem (92.5%), colistin (95.6%) and amikacin (97.2%), being lower in the ICU and medicine wards compared with other wards. An outbreak of OXA-23-producing CRAB occurred in the 13-bed ICU in 2010. CRAB strains were more co-resistant to other antimicrobials compared with non-CRAB. Molecular genetics analysis revealed five sequence types [ST78, ST107 and ST642 and two new STs (ST830 and ST831)]. Analysis of PFGE profiles indicated cross-transmissions of CRAB within the ICU, between the ICU and one medicine ward during transfer of patients, and within that medicine ward. This study provides the first clinical and molecular data of A. baumannii from French Guiana and the Amazon basin. The ICU was the highest risk unit of this nosocomial outbreak of OXA-23-producing CRAB, which could subsequently disseminate within the hospital.

Published
2016

23. Who are the patients with early arthritis with worse than death scores on the EQ-5D? Results from the ESPOIR cohort

Author

Bruno Fautrel, Anne Christine Rat, C. Gaujoux-Viala, Francis Guillemin, Pierre Bourgeois, René Marc Flipo, Service de Rhumatologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Rhumatologie, Université Paris Diderot - Paris 7 ( UPD7 ), Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département de Rhumatologie ( LILLE - Rhumatologie ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Station de Technologie des Produits Végétaux (URTPV), Institut National de la Recherche Agronomique (INRA), Service de Rhumatologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie[Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Paris Diderot - Paris 7 (UPD7), Département de Rhumatologie (LILLE - Rhumatologie), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and CHU Pitié-Salpêtrière [AP-HP]

Subjects
Male, MESH: Antirheumatic Agents, [SDV]Life Sciences [q-bio], MESH: Logistic Models, MESH: Illness Behavior, MESH: Pain Measurement, MESH: Risk Assessment, Logistic regression, Severity of Illness Index, MESH : Early Diagnosis, Arthritis, Rheumatoid, Cohort Studies, Disability Evaluation, 0302 clinical medicine, MESH: Early Diagnosis, Sickness Impact Profile, Surveys and Questionnaires, MESH : Pain Measurement, MESH : Female, MESH : Illness Behavior, Pharmacology (medical), Longitudinal Studies, MESH : Risk Assessment, MESH: Longitudinal Studies, MESH: Cohort Studies, ComputingMilieux_MISCELLANEOUS, MESH : Adaptation, Physiological, Depression (differential diagnoses), Illness Behavior, Pain Measurement, MESH : Longitudinal Studies, MESH: Arthritis, Rheumatoid, MESH: Middle Aged, MESH : Prognosis, 030503 health policy & services, MESH: Disability Evaluation, MESH : Questionnaires, MESH : Adult, Middle Aged, Prognosis, MESH : Antirheumatic Agents, Adaptation, Physiological, MESH: Quality-Adjusted Life Years, MESH: Sickness Impact Profile, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Antirheumatic Agents, Cohort, Anxiety, MESH : Severity of Illness Index, Female, Quality-Adjusted Life Years, medicine.symptom, 0305 other medical science, Adult, medicine.medical_specialty, SF-36, MESH : Male, MESH : Cohort Studies, Mixed anxiety-depressive disorder, MESH : Disability Evaluation, Risk Assessment, MESH: Multivariate Analysis, MESH: Prognosis, 03 medical and health sciences, Rheumatology, EQ-5D, MESH: Severity of Illness Index, Internal medicine, medicine, Humans, MESH : Middle Aged, 030203 arthritis & rheumatology, MESH: Humans, [ SDV ] Life Sciences [q-bio], business.industry, MESH: Questionnaires, MESH : Humans, MESH : Multivariate Analysis, MESH: Adult, MESH : Quality-Adjusted Life Years, medicine.disease, MESH: Adaptation, Physiological, MESH: Male, Quality-adjusted life year, Early Diagnosis, Logistic Models, MESH : Sickness Impact Profile, MESH : Arthritis, Rheumatoid, Multivariate Analysis, Physical therapy, business, MESH: Female, MESH : Logistic Models
Abstract

International audience; OBJECTIVES: The EQ-5D is a five-dimension multi-attribute questionnaire widely used to calculate quality-adjusted life-year scores. We aimed to describe patients with early arthritis (EA) and EQ-5D < 0, a state worse than death, at baseline and over 2 years and determine aspects of EA associated with a negative score. METHODS: EQ-5D scores for 813 patients were longitudinally assessed over 24 months. Characteristics and health status of patients with EQ-5D < 0 were analysed. Multivariate logistic regression was used to determine aspects of EA associated with a negative score. RESULTS: At baseline, 90 (11%) patients had a negative EQ-5D score (median EQ-5D -0.052; range -0.530 to -0.011). Almost all patients had extreme pain/discomfort and at least moderate problems in anxiety/depression domain. These patients had lower educational level, greater disease activity, higher HAQ score (greater functional disability), greater pain and fatigue, lower Short Form 36 (SF-36) mental component scores and higher CRP levels than patients with EQ-5D ≥ 0 (all P < 0.001). In the logistic regression model, worse HAQ and SF-36 mental component scores were associated with EQ-5D < 0. Results were similar at 6, 12 and 24 months, with 25, 23 and 24 patients, respectively, in a state worse than death. CONCLUSION: Pain or discomfort, often severe, is a key domain of the EQ-5D for patients with EA in a health state worse than death, and poor HAQ and SF-36 mental component scores were always independently associated with a state worse than death. EA patients may have specific needs necessitating better management of pain and psychological state.

Published
2012
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24. Incidence, Medical and Socio-Behavioural Predictors of Psychiatric Events in An 11-Year Follow-Up of HIV-Infected Patients on Antiretroviral Therapy

Author

Protopopescu, Camelia, Raffi, François, Brunet-François, Cécile, Salmon, Dominique, Verdon, Renaud, Reboud, Philippe, Carrieri, Maria Patrizia, Leport, Catherine, Spire, Bruno, Michel, Laurent, Michelet, Christian, Aix Marseille Université (AMU), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Maladies infectieuses et tropicales, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Maladies Infectieuses et Tropicales [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Troubles du comportement alimentaire de l'adolescent (UMR_S 669), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), APROCO-COPILOTE (ANRS CO8) Study Group, Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Aix Marseille Université ( AMU ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale ( SESSTIM - U912 INSERM - AMU - IRD ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Service des maladies infectieuses et tropicales, CHU Caen, Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Troubles du comportement alimentaire de l'adolescent ( UMR_S 669 ), Université Paris-Sud - Paris 11 ( UP11 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de recherche, santé, environnement et travail ( Irset ), Université d'Angers ( UA ) -Université de Rennes 1 ( UR1 ), and Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -École des Hautes Études en Santé Publique [EHESP] ( EHESP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université des Antilles ( UA )

Subjects
Male, MESH: CD4 Lymphocyte Count, Epidemiology, HIV Infections, MESH : Viral Load, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Surveys and Questionnaires, Immunopathology, Hiv infected patients, Pharmacology (medical), Longitudinal Studies, MESH: Incidence, MESH: Treatment Outcome, MESH: Middle Aged, Depression, MESH: HIV, Incidence, MESH : HIV Protease Inhibitors, MESH: Follow-Up Studies, MESH: HIV Infections, MESH : Incidence, 3. Good health, Suicide, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Therapy, Combination, Viral disease, Infection, 0305 other medical science, MESH: Social Behavior, medicine.medical_specialty, 03 medical and health sciences, MESH : HIV Infections, Humans, MESH : Middle Aged, Antiviral, Social Behavior, Pharmacology, MESH: Humans, MESH: Questionnaires, MESH : Humans, MESH : Follow-Up Studies, MESH: Adult, MESH : Proportional Hazards Models, medicine.disease, Antiretroviral agent, MESH: Female, Immune deficiency, MESH : Social Behavior, MESH : HIV, MESH: Proportional Hazards Models, Risk Factors, MESH : Depression, MESH: Risk Factors, MESH : Female, 030212 general & internal medicine, MESH: Longitudinal Studies, MESH : Longitudinal Studies, MESH : Suicide, Incidence (epidemiology), MESH : Questionnaires, Middle Aged, Viral Load, MESH : Adult, MESH : Risk Factors, AIDS, Treatment Outcome, Infectious Diseases, Female, France, MESH: Viral Load, Adult, MESH: Depression, MESH : Male, MESH : Treatment Outcome, Acquired immunodeficiency syndrome (AIDS), MESH : CD4 Lymphocyte Count, medicine, Chemotherapy, MESH : France, Psychiatry, Proportional Hazards Models, MESH: HIV Protease Inhibitors, 030505 public health, Potential risk, business.industry, MESH : Drug Therapy, Combination, HIV, HIV Protease Inhibitors, Antiretroviral therapy, MESH: Male, CD4 Lymphocyte Count, Treatment, MESH: France, MESH: Drug Therapy, Combination, MESH: Suicide, Predictive factor, business, Follow-Up Studies
Abstract

Background Psychiatric disorders are relatively common among HIV-infected patients. However, there are few studies about their potential risk factors. This analysis aimed to measure the incidence of severe psychiatric events (PE) among patients receiving combination antiretroviral therapy (cART) of the French APROCO-COPILOTE (ANRS CO8) cohort, and to identify the medical and socio-behavioural correlates of their first episode of depression, suicide or suicide attempt (D/S/SA). Methods APROCO-COPILOTE is a cohort of patients started on a protease inhibitor regimen between 1997 and 1999, with prospective medical standardized records and self-administered questionnaires collecting socio-demographic and socio-behavioural data. This analysis included all 11-year follow-up visits for 1,095 patients having completed baseline self-administered questionnaires. A proportional hazard Cox model was used to identify the correlates of a first D/S/SA event. Results The overall prevalence of severe PE remained low: 50 patients experienced 67 events (incidence rate [95% CI] =1.04 [0.82, 1.32] per 100 person-years). Depression ( n=16), suicides ( n=5) and suicide attempts ( n=14) were the most frequently diagnosed PE (0.54 [0.39, 0.76] per 100 person-years) among 25 patients. Multivariate results showed that unemployment, unstable housing, detectable viral load and smoking more than 20 cigarettes/day were independently associated with D/S/SA. Conclusions Although the incidence of severe PE remained relatively low among the patients of APROCO-COPILOTE cohort, this study's results underline a clinically important problem in HIV-infected patients receiving cART. Furthermore, our findings not only emphasize the importance of comprehensive care, especially for socially vulnerable patients, but may also help future studies designed to assess the effectiveness of interventions in reducing the risk of PE during cART.

Published
2012
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25. Monotonous consumption of fibre-enriched bread at breakfast increases satiety and influences subsequent food intake

Author

Sylvie Issanchou, Aude Gagnaire, Laurent Brondel, Claire Sulmont-Rossé, Peio Touyarou, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), and Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS )

Subjects
Dietary Fiber, Male, Food intake, Hunger, 030309 nutrition & dietetics, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, MESH: Energy Intake, MESH: Eating, Eating, 0302 clinical medicine, Weight loss, MESH: Food, Fortified, MESH : Female, Food science, General Psychology, Mathematics, 2. Zero hunger, 0303 health sciences, MESH : Food Preferences, Cross-Over Studies, Nutrition and Dietetics, digestive, oral, and skin physiology, food and beverages, Bread, MESH : Adult, MESH: Hunger, Food, Fortified, Female, MESH : Food, Fortified, medicine.symptom, Adult, MESH : Eating, MESH : Male, 030209 endocrinology & metabolism, Satiation, MESH: Cross-Over Studies, MESH: Bread, Food Preferences, 03 medical and health sciences, MESH : Hunger, Decreased energy, medicine, Humans, MESH: Food Preferences, Consumption (economics), MESH: Humans, MESH: Satiation, MESH : Humans, Dietary fibre, MESH : Energy Intake, MESH: Adult, MESH : Cross-Over Studies, MESH: Male, Normal weight, MESH: Dietary Fiber, MESH : Dietary Fiber, Energy Intake, MESH : Bread, MESH: Female, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH : Satiation
Abstract

Research report; International audience; This study aimed to observe the influence of the monotonous consumption of two types of fibre-enriched bread at breakfast on hedonic liking for the bread, subsequent hunger and energy intake. Two groups of unrestrained normal weight participants were given either white sandwich bread (WS) or multigrain sandwich bread (MG) at breakfast (the sensory properties of the WS were more similar to the usual bread eaten by the participants than those of the MG). In each group, two 15-day cross-over conditions were set up. During the experimental condition the usual breakfast of each participant was replaced by an isocaloric portion of plain bread (WS or MG). During the control condition, participants consumed only 10 g of the corresponding bread and completed their breakfast with other foods they wanted. The results showed that bread appreciation did not change over exposure even in the experimental condition. Hunger was lower in the experimental condition than in the control condition. The consumption of WS decreased energy intake while the consumption of MG did not in the experimental condition compared to the corresponding control one. In conclusion, a monotonous breakfast composed solely of a fibre-enriched bread may decrease subsequent hunger and, when similar to a familiar bread, food intake.

Published
2012
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26. Bronchoalveolar Lavage in Hypersensitivity Pneumonitis: A Series of 139 Patients

Author

Caillaud, Denis M, Vergnon, Jean M, Madroszyk, Anne, Melloni, Boris M, Murris, Marlene, Dalphin, Jean-Charles, Renseigné, Non, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire Chrono-environnement ( LCE ), and Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC )

Subjects
Male, Pathology, Lymphocyte, MESH : Aged, Bronchoalveolar Lavage, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH : Farmer's Lung, MESH: Aged, 80 and over, Immunology and Allergy, Eosinophilia, MESH : Female, Aged, 80 and over, MESH: Aged, MESH : Bronchoalveolar Lavage Fluid, MESH: Middle Aged, MESH: Bronchoalveolar Lavage, medicine.diagnostic_test, General Medicine, Middle Aged, MESH : Adult, respiratory system, medicine.anatomical_structure, MESH: Young Adult, Female, medicine.symptom, Bronchoalveolar Lavage Fluid, MESH : Bronchoalveolar Lavage, Hypersensitivity pneumonitis, Alveolitis, Extrinsic Allergic, Adult, medicine.medical_specialty, Adolescent, MESH : Male, MESH : Alveolitis, Extrinsic Allergic, Immunology, CD4-CD8 Ratio, MESH : Young Adult, MESH: Alveolitis, Extrinsic Allergic, Young Adult, Antigen, MESH : Adolescent, medicine, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, Aged, MESH: Adolescent, MESH: Farmer's Lung, Pharmacology, MESH: Humans, Lung, MESH: Bronchoalveolar Lavage Fluid, business.industry, MESH : Humans, MESH: Adult, medicine.disease, MESH: Male, Neutrophilia, respiratory tract diseases, Bronchoalveolar lavage, MESH : CD4-CD8 Ratio, Farmer's Lung, MESH: CD4-CD8 Ratio, business, MESH: Female, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, CD8
Abstract

International audience; Hypersensitivity pneumonitis (HP) is characterized by a lymphocytic alveolitis, classically delineated by an increase of CD8+ lymphocytes, with an inversion of the CD4+/CD8+ ratio. The aim of this study is both to describe the yield and cell bronchoalveolar lavage (BAL) profile and to revisit the assumption of low BAL CD4/CD8 ratio in the diagnosis of HP. A multicentric study was conducted on 139 patients who fulfilled the standardized diagnostic criteria of HP, mainly affected by farmer's lung. Mean total cell count in BAL fluid was 594 ± 401.10(3) cells /ml. Prominent absolute lymphocytic alveolitis, moderate neutrophilia, and mild eosinophilia and mastocytosis were found. Mean CD4/CD8 ratio was 3.8 ± 6.1 (median 2.1). Thirty four percent of the patients showed lymphocytic CD8 alveolitis (ratio < 1). The CD4/CD8 ratio was not different between forms, etiologies of HP, and time elapsed since last antigen exposure, but was higher in women (p=0.02). BAL in HP shows high total cell and lymphocyte counts, moderate neutrophilia, and mild eosinophilia and mastocytosis. An absence of low CD4/CD8 ratio should not at all exclude diagnosis.

Published
2012
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27. Oncogenic Alterations in Papillary Thyroid Cancers of Young Patients

Author

G. Sassolas, Z. Hafdi Nejjari, A. Ferraro, M. S. Gandhi, C. Kwon Jung, E. Borbone, M. Decaussin Petrucci, B. Rousset, F. Borson Chazot, N. Berger, FUSCO, ALFREDO, registre rhone-alpin du cancer de la thyroide, Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-registre rhone-alpins du cancer de la thyroide, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), departement de pathologie, Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -registre rhone-alpins du cancer de la thyroide, Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), G., Sassola, Z., Hafdi Nejjari, A., Ferraro, M. S., Gandhi, C., Kwon Jung, E., Borbone, M., Decaussin Petrucci, B., Rousset, F., Borson Chazot, N., Berger, and Fusco, Alfredo

Subjects
Male, Oncology, Pathology, Oncogene Proteins, Fusion, endocrine system diseases, MESH: Carcinoma, Papillary, Endocrinology, Diabetes and Metabolism, Disease, MESH : Oncogene Proteins, Fusion, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Endocrinology, MESH : Child, MESH: Child, MESH : Female, Young adult, Child, Lymph node, education.field_of_study, MESH : Prognosis, MESH : Genes, ras, Thyroid, Age Factors, Protein-Tyrosine Kinases, MESH : Adult, Prognosis, 3. Good health, medicine.anatomical_structure, Thyroid Cancer, Papillary, MESH: Thyroid Neoplasms, MESH: Young Adult, 030220 oncology & carcinogenesis, Female, Mitogen-Activated Protein Kinases, MESH : Mutation, Adult, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, MESH: Mutation, Adolescent, MESH : Male, Population, MESH : Young Adult, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030209 endocrinology & metabolism, MESH: Protein-Tyrosine Kinases, MESH: Prognosis, MESH : Carcinoma, Papillary, Thyroid carcinoma, Young Adult, 03 medical and health sciences, Median follow-up, MESH : Adolescent, Internal medicine, MESH : Protein-Tyrosine Kinases, medicine, Humans, Thyroid Neoplasms, education, MESH : Proto-Oncogene Proteins B-raf, MESH: Adolescent, MESH: Age Factors, MESH: Proto-Oncogene Proteins B-raf, MESH: Humans, business.industry, Carcinoma, MESH : Humans, MESH : Mitogen-Activated Protein Kinases, MESH: Adult, MESH: Mitogen-Activated Protein Kinases, Carcinoma, Papillary, MESH : Thyroid Neoplasms, MESH: Male, MESH: Genes, ras, Genes, ras, Mutation, MESH : Age Factors, business, MESH: Female, V600E, MESH: Oncogene Proteins, Fusion
Abstract

International audience; BACKGROUND: Papillary thyroid carcinoma (PTC) in young people usually has an aggressive initial presentation, though a good general prognosis despite recurrences in 10%-20% of patients. A number of genetic alterations that activate the mitogen-activated protein kinase (MAPK) pathway have been found in PTC. Some of these alterations have been identified as prognostic factors of PTC in adults. The objective of the current study was to comprehensively characterize all known oncogenic alterations of the MAPK pathway in young people. METHODS: One hundred three PTCs removed from 9 children, 19 adolescents, and 75 young adults were submitted to molecular analyses. RESULTS: Altogether, 57 alterations were found in 56 PTCs (55%) corresponding to V600E BRAF in 20.3%, RAS mutations in 12.6%, RET/PTC 1 in 11.6%, RET/PTC 3 in 8.7%, and rearrangement of NTRK in 1.9%. The prevalence of all alterations increased with age (22.2% in children; 52.6% in adolescents, 51.4% in adults 20-25 years, and 55.1% in adults 25-35 years). Prevalence increased from 39.2% earlier to 61.3% after 20 years mainly due to BRAF mutations. Classic-type PTC was associated with a larger prevalence of alterations, predominantly BRAF and RET/PTC, whereas the follicular variant was chiefly associated with RAS. RET/PTC (1 and 3) was significantly associated with extrathyroid extension (ET) and lymph node metastasis (es) (LNM). This association was found in the adult group. There were no associations of BRAF or RAS mutations with ET or LNM. A 3-year median follow up was available for 90 patients. RET/PTC 1 and 3 was associated with short-term disease dissemination (cervical lymph node recurrences and distant metastases) in young adults (p=0.001). Persistent illness was more prevalent in patients with (15%) than in patients without (7%) genetic alterations. CONCLUSION: PTCs in young patients display a low prevalence of the already identified oncogenic alterations. The increasing prevalence with age is mainly due to V600E BRAF mutation. There is no relation between tumor aggressiveness and BRAF mutation. There is a relation between the presence of RET/PTC (1 and 3) and the histological and clinical short-term aggressiveness of PTC in the population of young adults. Such a relation is not found in children and adolescents.

Published
2012
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28. Influenza vaccine effectiveness among adult patients in a University of Lyon hospital (2004–2009)

Author

Brigitte Coppéré, Bruno Lina, Sélilah Amour, Corinne Régis, Brigitte Comte, Philippe Vanhems, Nicolas Voirin, M. Bouscambert-Duchamp, Silène Pires-Cronenberger, Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'Hygiène, Epidémiologie et Prévention [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Virologie et pathologie humaine ( VirPath ), Université de Lyon-Université de Lyon, Service de médecine gériatrique, Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Virologie et pathologie humaine (VirPath), Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], and Hospices Civils de Lyon (HCL)

Subjects
Male, Hospitalized patients, [SDV]Life Sciences [q-bio], MESH : Aged, MESH : Prospective Studies, Hospitals, University, MESH: Influenza Vaccines, MESH: Aged, 80 and over, 0302 clinical medicine, Medicine, MESH : Female, Prospective Studies, MESH : Influenza, Human, 030212 general & internal medicine, Aged, 80 and over, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH: Influenza, Human, virus diseases, Middle Aged, MESH : Adult, MESH: Case-Control Studies, 3. Good health, Infectious Diseases, Influenza Vaccines, Molecular Medicine, Female, France, Adult, MESH : Case-Control Studies, medicine.medical_specialty, Influenza vaccine, MESH : Male, Virus, 03 medical and health sciences, Age groups, Internal medicine, Influenza, Human, Flu season, Humans, MESH : Middle Aged, MESH : France, MESH : Aged, 80 and over, MESH : Hospitals, University, Aged, 030304 developmental biology, MESH: Hospitals, University, MESH: Humans, [ SDV ] Life Sciences [q-bio], General Veterinary, General Immunology and Microbiology, Adult patients, business.industry, MESH : Humans, Public Health, Environmental and Occupational Health, MESH: Adult, MESH: Male, MESH: Prospective Studies, MESH : Influenza Vaccines, Confidence interval, MESH: France, Case-Control Studies, Immunology, business, MESH: Female
Abstract

International audience; The aim of this study was to estimate influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza among hospitalized patients. A case-control investigation was based on the prospective surveillance of influenza-like illness (ILI) during five flu seasons. We compared influenza-positive cases and influenza-negative controls. Unadjusted overall IVE was 62% (95% confidence interval 24% to 81%). We found that IVE was lower during the 2004-05 flu season (11%; 95% CI -232% to 76%) when the vaccine and circulating viruses were mismatched. Expansion of the study to other hospitals could provide IVE estimates earlier in the season, for different age groups and emerging virus strains.

Published
2012
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29. Differential item functioning (DIF) of SF-12 and Q-LES-Q-SF items among french substance users

Author

Stéphanie Bourion-Bédès, Cédric Baumann, Alex Bédès, Vincent Laprevote, Jean Louis Bonnet, Raymund Schwan, Service médico-psychologique régional - Metz, Centre d'Addictovigilance de Nancy [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Centre de soin, d'accompagnement et de prévention en addictologie - Cantal ( C.S.A.P.A. 15 Aurillac ), ESPRI-Biobase [CHRU Nancy] ( Unité fonctionnelle de la plateforme d’aide à la recherche clinique ), Centre d'Addictovigilance de Nancy [CHRU Nancy] (CEIP-A Nancy), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Centre de soin, d'accompagnement et de prévention en addictologie - Cantal (C.S.A.P.A. 15 Aurillac), and ESPRI-Biobase [CHRU Nancy] (Unité fonctionnelle de la plateforme d’aide à la recherche clinique)

Subjects
Male, Psychometrics, Cross-sectional study, Opiate dependence, MESH : Mental Health, Developmental psychology, MESH : Cross-Sectional Studies, Quality of life, Surveys and Questionnaires, MESH : Female, MESH: Middle Aged, Substance dependence, MESH: Mental Health, MESH : Psychometrics, Alcohol dependence, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, Middle Aged, MESH : Adult, humanities, 3. Good health, MESH: Reproducibility of Results, Mental Health, MESH: Young Adult, MESH: Substance-Related Disorders, Female, France, Psychology, MESH : Surveys and Questionnaires, Adult, MESH : Substance-Related Disorders, Substance-Related Disorders, MESH : Male, MESH: Factor Analysis, Statistical, MESH : Young Adult, MESH : Factor Analysis, Statistical, Differential Item Functioning, behavioral disciplines and activities, Young Adult, MESH: Cross-Sectional Studies, MESH: Psychometrics, medicine, Humans, MESH : Middle Aged, MESH: Surveys and Questionnaires, MESH : France, Rasch model, MESH: Humans, Self-reported health status, Research, MESH : Reproducibility of Results, MESH : Humans, Public Health, Environmental and Occupational Health, Reproducibility of Results, MESH: Quality of Life, MESH: Adult, MESH : Quality of Life, medicine.disease, Mental health, Differential item functioning, Q-LES-Q-SF, MESH: Male, MESH: France, Cross-Sectional Studies, Quality of Life, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Factor Analysis, Statistical, MESH: Female
Abstract

International audience; BackgroundDifferential Item Functioning (DIF) is investigated to ensure that each item displays a consistent pattern of responses irrespective of the characteristics of the respondents. Assessing DIF helps to understand the nature of instruments, to assess the quality of a measure and to interpret results. This study aimed to examine whether the items of the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Short-Form 12 (SF-12) exhibit DIF.MethodA total of 124 outpatients diagnosed with substance dependence participated in a cross-sectional, multicenter study. In addition to the Q-LES-Q-SF and SF-12 results, demographic data such as age, sex, type of substance dependence and education level were collected. Rasch analysis was conducted (using RUMM2020 software) to assess DIF of the Q-LES-Q-SF and SF-12 items.ResultsFor SF-12, significant age-related uniform DIF was found in two of the 12 items, and sex-related DIF was found in one of the 12 items. All of the observed DIF effects in SF-12 were found among the mental health items. Three items showed DIF on the Q-LES-Q-SF; however, the impact of DIF item on the delta score calculation for the comparisons of self-reported health status between the groups was minimal in the SF-12 and small in the Q-LES-Q-SF.ConclusionThese results indicated that no major measurement bias affects the validity of the self-reported health status assessed using the Q-LES-Q-SF or SF-12. Thus, these questionnaires are largely robust measures of self-reported health status among substance users.

Published
2015
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30. Epidemiological trends in invasive aspergillosis in France: the SAIF network (2005–2007)

Author

Stéphane Bretagne, B. Lebeau, F. de Monbrison, Olivier Lortholary, Karine Sitbon, Françoise Dromer, Jean-Pierre Gangneux, Bruno Coignard, Y. Le Strat, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris], Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Parasitologie-Mycologie [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Laboratoire de parasitologie-mycologie, CHU Grenoble, Laboratoire de Parasitologie-Mycologie, Centre Hospitalo-Universitaire de Lyon, Département des maladies infectieuses, Institut de Veille Sanitaire (INVS), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Biologie moléculaire et immunologie parasitaires et fongiques (BIPAR), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Veille Sanitaire, Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire d'Alfort (ENVA)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Université de Rennes (UR), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire ( CNRMA ), Signalisation et Réponses aux Agents Infectieux et Chimiques ( SeRAIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Biologie moléculaire et immunologie parasitaires et fongiques ( BIPAR ), Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -AFSSA-Ecole Nationale Vétérinaire d'Alfort-Institut National de la Recherche Agronomique ( INRA ), CHU Necker - Enfants Malades [AP-HP], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)

Subjects
Male, Epidemiology, MESH : Prospective Studies, MESH : Aged, Aspergillosis, Mannans, 0302 clinical medicine, MESH: Immunocompromised Host, Prospective Studies, MESH: Incidence, Aged, 80 and over, Invasive Pulmonary Aspergillosis, 0303 health sciences, MESH: Middle Aged, Incidence, General Medicine, MESH : Incidence, 3. Good health, Aspergillus, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Young Adult, Drug Therapy, Combination, Microbiology (medical), MESH: Invasive Pulmonary Aspergillosis, medicine.medical_specialty, MESH : Young Adult, 03 medical and health sciences, Galactomannan, Pharmacotherapy, MESH: Mannans, MESH : Adolescent, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, Aged, MESH: Adolescent, MESH: Humans, MESH : Seasons, 030306 microbiology, MESH : Humans, MESH: Adult, MESH: Antifungal Agents, medicine.disease, chemistry, galactomannan, Immunology, MESH: Female, Antifungal Agents, chemistry.chemical_compound, MESH: Aged, 80 and over, Risk Factors, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Risk Factors, MESH : Female, 030212 general & internal medicine, Prospective cohort study, MESH: Aged, Incidence (epidemiology), MESH : Aspergillus, MESH : Immunocompromised Host, Middle Aged, MESH : Adult, MESH: Hospitals, MESH : Risk Factors, Hospitals, MESH : Hospitals, Infectious Diseases, MESH: Aspergillus, outcome, Female, France, Seasons, medicine.drug, Adult, Adolescent, MESH : Male, MESH : Antifungal Agents, Immunocompromised Host, Young Adult, Internal medicine, voriconazole, medicine, MESH : France, Voriconazole, invasive aspergillosis, business.industry, MESH : Drug Therapy, Combination, Galactose, MESH: Male, MESH: Prospective Studies, MESH: France, Transplantation, MESH: Drug Therapy, Combination, MESH : Invasive Pulmonary Aspergillosis, Caspofungin, business, MESH : Mannans, MESH: Seasons
Abstract

International audience; A prospective (2005-2007) hospital-based multicentre surveillance of EORTC/MSG-proven or probable invasive aspergillosis (IA) cases whatever the underlying diseases was implemented in 12 French academic hospitals. Admissions per hospital and transplantation procedures were obtained. Cox regression models were used to determine risk factors associated with the 12-week overall mortality. With 424 case-patients included, the median incidence/hospital was 0.271/10(3) admissions (range 0.072-0.910) without significant alteration of incidence and seasonality over time. Among the 393 adults (62% men, 56 years (16-84 years)), 15% had proven IA, 78% haematological conditions, and 92.9% had lung involvement. Acute leukaemia (34.6%) and allogeneic stem cell transplantation (21.4%) were major host factors, together with chronic lymphoproliferative disorders (21.6%), which emerged as a new high-risk group. The other risk host factors consisted of solid organ transplantation (8.7%), solid tumours (4.3%), systemic inflammatory diseases (4.6%) and chronic respiratory diseases (2.3%). Serum galactomannan tests were more often positive (≥69%) for acute leukaemia and allogeneic stem cell transplantation than for the others (

Published
2011
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31. The DESIR cohort: A 10-year follow-up of early inflammatory back pain in France: Study design and baseline characteristics of the 708 recruited patients

Author

Christian Roux, Isabelle Logeart, Alain Saraux, Maxime Dougados, Joelle Benessiano, Francis Berenbaum, Maria Antonietta D'Agostino, Jean-Marc Tréluyer, Pascal Claudepierre, Patricia Dargent-Molina, Véronique Leblanc, Philippe Goupille, Pascal Richette, Antoine Feydy, Martin Rudwaleit, Jean-Pierre Daurès, Maxime Breban, D. Wendling, Désirée van der Heijde, Bruno Fautrel, Bernard Combe, Thao Pham, Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Service de Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor, Laboratoire d'Investigation Clinique ( LIC ), Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Hôpital Lapeyronie [Montpellier] ( CHU ), Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants ( UMR_S 953 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris-Sud - Paris 11 ( UP11 ), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 ( AIDMP ), Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Rhumatologie, Université Paris Diderot - Paris 7 ( UPD7 ), Service de radiologie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Service de rhumatologie [Tours], CHU Trousseau [APHP], Laboratoire Merck Sharp & Dhome, Service de rhumatologie, Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 ( UPD7 ), Optimisation continue des actions thérapeutiques par l'intégration d'informations, Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Investigation Clinique ( CIC - Brest ), CHRU Brest - Service de Rhumatologie ( CHU - BREST - Rhumato ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Epilepsies de l'Enfant et Plasticité Cérébrale ( U1129 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Pharmacologie Clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Hôpital Saint-Vincent de Paul-Université Paris Descartes - Paris 5 ( UPD5 ), Department of Rheumatology, University Hospital Maastricht, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Laboratoire d'Investigation Clinique (LIC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Lapeyronie [Montpellier] (CHU), Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants (UMR_S 953), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Merck & Co. Inc, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique (CIC - Brest), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Saint-Vincent de Paul-Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Hôpital Saint-Vincent de Paul-Université Paris Descartes - Paris 5 (UPD5), and Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz

Subjects
Male, Ankylosing spondlyitis, Settore MED/16 - REUMATOLOGIA, MESH : Retrospective Studies, MESH : Prospective Studies, MESH: Comorbidity, Comorbidity, MESH: Magnetic Resonance Imaging, Cohort Studies, MESH : Back Pain, 0302 clinical medicine, Bone Density, Epidemiology, MESH : Female, Longitudinal Studies, Prospective Studies, MESH : Bone Density, MESH: Longitudinal Studies, Prospective cohort study, MESH: Bone Density, MESH: Cohort Studies, Case report form, BASDAI, Ultrasonography, MESH : Longitudinal Studies, MESH : Prognosis, MESH: Pelvic Bones, Cohort, MESH: Follow-Up Studies, MESH : Spondylarthritis, MESH : Adult, Prognosis, Magnetic Resonance Imaging, 3. Good health, MESH : Comorbidity, Female, France, MESH: Spine, Cohort study, Adult, medicine.medical_specialty, MESH: Spondylarthritis, MESH : Male, MESH : Cohort Studies, MESH : Pelvic Bones, MESH: Prognosis, MESH: Social Class, 03 medical and health sciences, Rheumatology, MESH : Magnetic Resonance Imaging, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Internal medicine, Spondylarthritis, Spondyloarthritis, MESH : Social Class, MESH : Spine, medicine, Humans, Pelvic Bones, MESH : France, Retrospective Studies, 030203 arthritis & rheumatology, MESH: Humans, business.industry, MESH : Humans, MESH: Adult, MESH: Retrospective Studies, MESH : Follow-Up Studies, Retrospective cohort study, medicine.disease, Spine, MESH: Male, MESH: Prospective Studies, MESH: France, Social Class, Back Pain, MESH: Back Pain, Physical therapy, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies, 030215 immunology
Abstract

Objectives The French Society of Rheumatology has initiated a large national multicenter, longitudinal, prospective follow-up of patients presenting with early inflammatory back pain in order to set up a database to facilitate several investigations on diagnosis, prognosis, epidemiology, pathogenesis and medico-economics in the field of early inflammatory back pain and spondyloarthritis. Methods Patients were recruited if they had inflammatory back pain of more than 3 months and less than 3 years. Patients will be followed every 6 months during the first 2 years then every year during at least 5 years. Apart from information collected on a Case Report Form (demographics, disease activity, severity, co-morbidities, socio-economics, treatments, radiological and MRI evaluation of the spine and the pelvis according to the local investigators, and for some centers bone densitometry and ultrasonography of entheses), the digital X-rays and MRI of the spine and pelvis are stored using a specific software (Carestream) and the biological samples (DNA, RNA, sera, urines) are centralized at the Biological Resources Center (Bichat Hospital). Results The recruitment period of the 708 patients (mean age: 34 ± 9 years, female 54%, HLA-B27 positive: 57%) in the 25 centers was 26 months (from December 2007 to April 2010). The modified New York criteria, Amor criteria, ESSG criteria and axial ASAS criteria were fulfilled by 26%, 77%, 76% and 67% of the patients at entry, respectively. A history or current symptoms suggestive of peripheral arthritis, acute anterior uveitis and inflammatory bowel disease were observed in 21%, 9% and 4% of the patients, respectively. The disease was active (BASDAI: 45 ± 20) despite an NSAID intake in 66% of the patients. Conclusion This large cohort should facilitate the conduct of researches in different areas (clinical, medico-economics, translational) in order to improve our knowledge on the pathogenesis and natural history of axial spondyloarthritis.

Published
2011
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32. Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial

Author

Didier Debieuvre, Jean-Marc Limacher, Elisabeth Quoix, A. Madroszyk, Marc Buyse, Jean-Yves Bonnefoy, Z. Papai, Erich Stoelben, Gisèle Lacoste, Piotr Koralewski, Hervé Lena, Denis Braun, Alain Rivière, Marie-Pierre Chenard, Bérangère Bastien, Jean-Luc Breton, Annette Tavernaro, Rodryg Ramlau, Bruce Acres, Nadine Bizouarne, Virginie Westeel, Service de pneumologie, CHU Strasbourg-Hopital Civil, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Laboratoire d'Ingénierie des Systèmes Mécaniques et des MAtériaux ( LISMMA ), Université Paris 8 Vincennes-Saint-Denis ( UP8 ) -SUPMECA - Institut supérieur de mécanique de Paris, Centre Hospitalier de Belfort-Montbéliard, Service de Pneumologie, CHI de la Haute-Saône, International Drug Development Institute ( IDDI ), Service d'Anatomie Pathologique Générale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire d'Ingénierie des Systèmes Mécaniques et des MAtériaux (LISMMA), Université Paris 8 Vincennes-Saint-Denis (UP8)-SUPMECA - Institut supérieur de mécanique de Paris (SUPMECA), CH Belfort-Montbéliard, and International Drug Development Institute (IDDI)

Subjects
Male, Lung Neoplasms, MESH: Chi-Square Distribution, MESH : Antineoplastic Combined Chemotherapy Protocols, medicine.medical_treatment, MESH: Membrane Glycoproteins, MESH : Aged, MESH: Risk Assessment, Deoxycytidine, Gastroenterology, MESH: Cancer Vaccines, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, MESH: Vaccinia virus, Clinical endpoint, MESH : Neoplasm Staging, MESH: Treatment Outcome, Vaccines, Synthetic, 0303 health sciences, Membrane Glycoproteins, MESH: Middle Aged, MESH : Vaccinia virus, MESH : Antimetabolites, Antineoplastic, MESH : Chemotherapy, Adjuvant, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, Oncology, 030220 oncology & carcinogenesis, Antimetabolites, Antineoplastic, medicine.medical_specialty, MESH: Vaccines, Synthetic, Risk Assessment, Disease-Free Survival, MESH : Cisplatin, 03 medical and health sciences, Humans, MESH : Middle Aged, MESH : Lung Neoplasms, MESH : Vaccines, Synthetic, Adverse effect, MESH: Kaplan-Meier Estimate, Aged, Chi-Square Distribution, MESH: Humans, MESH : Carcinoma, Non-Small-Cell Lung, MESH : Chi-Square Distribution, MESH: Deoxycytidine, MESH : Humans, MESH: Adult, MESH: Interleukin-2, MESH : Proportional Hazards Models, medicine.disease, MESH: Lung Neoplasms, MESH: Disease-Free Survival, Cisplatin, MESH: Female, MESH: Mucin-1, Time Factors, MESH : Membrane Glycoproteins, Kaplan-Meier Estimate, MESH: Proportional Hazards Models, Risk Factors, MESH: Risk Factors, Carcinoma, Non-Small-Cell Lung, MESH : Female, MESH : Risk Assessment, MESH: Aged, MESH: Antimetabolites, Antineoplastic, MESH : Cancer Vaccines, MESH: Neoplasm Staging, Middle Aged, MESH : Adult, MESH : Risk Factors, Europe, Treatment Outcome, Chemotherapy, Adjuvant, MESH: Chemotherapy, Adjuvant, MESH : Mucin-1, MESH : Disease-Free Survival, Female, MESH : Time Factors, medicine.drug, Adult, Combination therapy, MESH : Male, MESH : Europe, Vaccinia virus, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Treatment Outcome, Neutropenia, Cancer Vaccines, MESH : Interleukin-2, MESH : Kaplan-Meier Estimate, MESH : Deoxycytidine, Internal medicine, medicine, Lung cancer, Neoplasm Staging, Proportional Hazards Models, 030304 developmental biology, Chemotherapy, Performance status, business.industry, Mucin-1, MESH: Time Factors, Gemcitabine, MESH: Male, Surgery, MESH: Cisplatin, Interleukin-2, MESH: Europe, business, MESH: Carcinoma, Non-Small-Cell Lung
Abstract

International audience; BACKGROUND: Chemotherapy is the standard of care for advanced stages of non-small-cell lung cancer (NSCLC). TG4010 is a targeted immunotherapy based on a poxvirus (modified vaccinia virus Ankara) that codes for MUC1 tumour-associated antigen and interleukin 2. This study assessed TG4010 in combination with first-line chemotherapy in advanced NSCLC. METHODS: 148 patients with advanced (stage IIIB [wet] or IV) NSCLC expressing MUC1 by immunohistochemistry, and with performance status 0 or 1, were enrolled in parallel groups in this open-label, phase 2B study. 74 patients were allocated to the combination therapy group, and received TG4010 (10(8) plaque forming units) plus cisplatin (75 mg/m(2) on day 1) and gemcitabine (1250 mg/m(2) on days 1 and 8) repeated every 3 weeks for up to six cycles. 74 patients allocated to the control group received the same chemotherapy alone. Patients were allocated using a dynamic minimisation procedure stratified by centre, performance status, and disease stage. The primary endpoint was 6-month progression-free survival (PFS), with a target rate of 40% or higher in the experimental group. Analyses were done on an intention-to-treat basis. This study is completed and is registered with ClinicalTrials.gov, number NCT00415818. FINDINGS: 6-month PFS was 43*2% (32 of 74; 95% CI 33*4-53*5) in the TG4010 plus chemotherapy group, and 35*1% (26 of 74; 25*9-45*3) in the chemotherapy alone group. Fever, abdominal pain, and injection-site pain of any grade according to National Cancer Institute Common Toxicity Criteria were more common in the TG4010 group than in the chemotherapy alone group: 17 of 73 patients (23*3%) versus six of 72 (8*3%), 12 (16*4%) versus two (2*8%), and four (5*5%) versus zero (0%), respectively. The most common grade 3-4 adverse events were neutropenia (33 [45*2%] of patients in the TG4010 plus chemotherapy group vs 31 [43*1%] in the chemotherapy alone group) and fatigue (18 [24*7%] vs 13 [18*1%]); the only grade 3-4 events that differed significantly between groups were anorexia (three [4*1%] vs 10 [13*9%]) and pleural effusion (none vs four [5*6%]). 38 of 73 patients (52*1%) in the TG4010 plus chemotherapy group and 34 of 72 (47*2%) in the chemotherapy alone group had at least one serious adverse event. INTERPRETATION: This phase 2B study suggests that TG4010 enhances the effect of chemotherapy in advanced NSCLC. A confirmatory phase 2B-3 trial has been initiated. FUNDING: Transgene SA, Advanced Diagnostics for New Therapeutic Approaches (ADNA)/OSEO.

Published
2011
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33. Sex differences in the GSK3β-mediated survival of adherent leukemic progenitors

Author

Jessica Bertrand, Bernard Payrastre, N Gallay, Nathalie Vergnolle, Véronique Maguer-Satta, Mathieu Despeaux, Cécile Demur, Ezzeddine Bourogaa, S Joly, P Bonnevialle, F Louache, Claire Racaud-Sultan, ANDRA, Laboratoire d'Hématologie [Purpan], Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Equipe 11, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Physiopathologie Toulouse Purpan, Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Departement /u563 : Oncogenèse, Signalisation et Innovation thérapeutique, Université Paul Sabatier - Toulouse 3 ( UPS ) -Institut Claudius Regaud-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Claudius Regaud

Subjects
Male, MESH : Aged, Antigens, CD34, MESH : Blotting, Western, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Glycogen Synthase Kinase 3, 0302 clinical medicine, MESH : Indoles, MESH : Tumor Cells, Cultured, GSK-3, Tumor Cells, Cultured, Protein Phosphatase 2, MESH : GTP-Binding Proteins, Cells, Cultured, MESH: Glycogen Synthase Kinase 3, MESH: Etoposide, Etoposide, MESH: Indoles, MESH : Maleimides, Aged, 80 and over, MESH : Cell Survival, 0303 health sciences, education.field_of_study, MESH: Middle Aged, MESH: Protein Phosphatase 2, Neoplasm Proteins, MESH: Cell Survival, MESH: Young Adult, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, RNA Interference, MESH: Cells, Cultured, MESH : Protein Phosphatase 2, MESH : Glycogen Synthase Kinase 3, MESH: Antineoplastic Agents, Phytogenic, Blotting, Western, MESH : Young Adult, Receptors, Cell Surface, MESH: Cell Adhesion, 03 medical and health sciences, MESH : Neoplasm Proteins, MESH: Sex Factors, Genetics, MESH: Blotting, Western, Humans, MESH : Middle Aged, MESH: Tumor Cells, Cultured, Progenitor cell, MESH : Aged, 80 and over, Clonogenic assay, education, Molecular Biology, Aged, MESH: Interleukin-3 Receptor alpha Subunit, MESH: Humans, Glycogen Synthase Kinase 3 beta, MESH : Hematopoietic Stem Cells, MESH : Humans, MESH : Leukemia, MESH: Adult, MESH: Antigens, CD34, Protein phosphatase 2, Hematopoietic Stem Cells, MESH: Neoplastic Stem Cells, Immunology, MESH: Female, MESH: Neoplasm Proteins, Cancer Research, Indoles, MESH : Receptors, Cell Surface, MESH : Interleukin-3 Receptor alpha Subunit, MESH : Antineoplastic Agents, Phytogenic, MESH: Hematopoietic Stem Cells, Maleimides, MESH: Aged, 80 and over, MESH : Female, MESH: Maleimides, MESH: Receptors, Cell Surface, MESH: Aged, Leukemia, Myeloid leukemia, MESH : Adult, Middle Aged, medicine.anatomical_structure, MESH : Antigens, CD34, Female, Stem cell, Adult, MESH: GTP-Binding Proteins, Cell Survival, MESH : Male, MESH : Sex Factors, MESH: RNA Interference, Population, Interleukin-3 Receptor alpha Subunit, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Etoposide, Biology, Receptors for Activated C Kinase, Young Adult, MESH : Neoplastic Stem Cells, Sex Factors, GTP-Binding Proteins, MESH: Leukemia, MESH : Cells, Cultured, Cell Adhesion, medicine, 030304 developmental biology, Antineoplastic Agents, Phytogenic, MESH: Male, MESH : Cell Adhesion, Cancer research, Bone marrow, MESH : RNA Interference
Abstract

International audience; Therapeutic resistance of acute myeloid leukemia stem cells, enriched in the CD34(+)38(-)123(+) progenitor population, is supported by extrinsic factors such as the bone marrow niche. Here, we report that when adherent onto fibronectin or osteoblast components, CD34(+)38(-)123(+) progenitors survive through an integrin-dependent activation of glycogen synthase kinase 3β (GSK3β) by serine 9-dephosphorylation. Strikingly, GSK3β-mediated survival was restricted to leukemic progenitors from female patients. GSK3β inhibition restored sensitivity to etoposide, and impaired the clonogenic capacities of adherent leukemic progenitors from female patients. In leukemic progenitors from female but not male patients, the scaffolding protein RACK1, activated downstream of α(5)β(1)-integrin engagement, was specifically upregulated and controlled GSK3β activation through the phosphatase protein phosphatase 2A (PP2A). In a mirrored manner, survival of adherent progenitors (CD34(+)38(-)) from male but not female healthy donors was partially dependent on this pathway. We conclude that the GSK3β-dependent survival pathway might be sex-specific in normal immature population and flip-flopped upon leukemogenesis. Taken together, our results strengthen GSK3β as a promising target for leukemic stem cell therapy and reveal gender differences as a new parameter in anti-leukemia therapy.

Published
2011
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34. Increased Levels of Circulating Endothelial-Derived Microparticles and Small-Size Platelet-Derived Microparticles in Psoriasis

Author

Philippe Humbert, Chrystelle Vidal, Sabeha Biichle, Estelle Seilles, Fabien Pelletier, Francine Garnache-Ottou, Fanny Angelot, François Aubin, Philippe Saas, Département de dermatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Clinical Investigation Centre, Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Plateforme de Biomonitoring, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques-Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Franche-Comté ( UFC ), Centre d'Investigation Clinique de Besançon ( CICB ), Etablissement Français du Sang Bourgogne Franche-Comté-Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Franche-Comté ( UFC ), Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), and Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC )

Subjects
Male, MESH: Platelet Membrane Glycoprotein IIb, MESH : Psoriasis, MESH : Aged, MESH : Cell-Derived Microparticles, 030204 cardiovascular system & hematology, Biochemistry, MESH : Platelet Membrane Glycoprotein IIb, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Cell-Derived Microparticles, MESH: Cell-Derived Microparticles, Medicine, MESH : Female, MESH: Endothelial Cells, Platelet, ComputingMilieux_MISCELLANEOUS, MESH: Blood Platelets, MESH: Aged, MESH: Psoriasis, 0303 health sciences, MESH: Middle Aged, Middle Aged, MESH : Adult, humanities, 3. Good health, Platelet Endothelial Cell Adhesion Molecule-1, MESH : Antigens, CD31, Female, Adult, Blood Platelets, Platelet Membrane Glycoprotein IIb, Adolescent, MESH : Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, 03 medical and health sciences, Text mining, MESH : Adolescent, Psoriasis, Humans, MESH : Middle Aged, Molecular Biology, Aged, 030304 developmental biology, MESH: Adolescent, MESH: Humans, MESH : Endothelial Cells, business.industry, MESH : Humans, Endothelial Cells, MESH : Blood Platelets, MESH: Adult, MESH: Antigens, CD31, Cell Biology, medicine.disease, MESH: Male, Immunology, business, MESH: Female
Abstract

International audience

Published
2011
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35. Somatic mutations activating STAT3 in human inflammatory hepatocellular adenomas. : Activating STAT3 mutations in hepatocellular adenoma

Author

Jeanne Tran Van Nhieu, Michel Bihl, Karine Poussin, Mohamed Amessou, Paulette Bioulac-Sage, Jessica Zucman-Rossi, Charles Balabaud, Camilla Pilati, Jean-Charles Nault, Tina Izard, Valérie Paradis, Gabrielle Couchy, Genomique Fonctionnelle des Tumeurs Solides, Université Paris Diderot - Paris 7 ( UPD7 ) -IFR105-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Labex Immuno-oncology, Centre de Recherche des Cordeliers ( CRC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -PRES Sorbonne Paris Cité-Faculté de Médecine, Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service de Pathologie [Clichy], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Beaujon, Department of Cancer Biology, The Scripps Research Institute, Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service d'Hépato-Gastro Entérologie et Oncologie Digestive, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), and This work was supported by the association pour la recherche Contre le Cancer (ARC, grant n°3194), Inserm (Réseaux de recherche clinique et réseaux de recherche en santé des populations), Collection Nationale des Carcinomes Hépatocellulaires, the Ligue Nationale Contre le Cancer ('Cartes d'identité des tumeurs' program) and the BioIntelligence collaborative program. C.P., M.A. and J-C.N. are supported by a fellowship from the MENRT, Inca and ARC, respectively. T.I. is supported by the National Institutes of Health grants GM071596, AI055894, and AI067949.

Subjects
MESH : Tyrosine, Male, Models, Molecular, MESH : Liver Neoplasms, MESH : Mutant Proteins, MESH : Aged, MESH : RNA, Small Interfering, SH2 domain, medicine.disease_cause, HNF1A, STAT3, MESH : Phosphorylation, 0302 clinical medicine, MESH : STAT3 Transcription Factor, Cytokine Receptor gp130, Immunology and Allergy, CTNNB1, MESH : Female, SOCS3, Phosphorylation, RNA, Small Interfering, 0303 health sciences, Mutation, Liver Neoplasms, DNA, Neoplasm, MESH : Adult, Middle Aged, SAA, 3. Good health, MESH : Cytokine Receptor gp130, JAK1, src-Family Kinases, JAK2, MESH : Dimerization, 030220 oncology & carcinogenesis, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Female, MESH : DNA, Neoplasm, MESH : Mutation, CRP, IL6ST, Dimerization, Tyrosine kinase, Src, Signal Transduction, Proto-oncogene tyrosine-protein kinase Src, MESH : Carcinoma, Hepatocellular, Adult, STAT3 Transcription Factor, Carcinoma, Hepatocellular, MESH : Interleukin-6, MESH : Models, Molecular, MESH : Male, Immunology, Active Transport, Cell Nucleus, Biology, IFN, Adenoma, Liver Cell, gp130, 03 medical and health sciences, MESH : Adenoma, Liver Cell, MESH : Protein Structure, Quaternary, Cell Line, Tumor, medicine, Humans, MESH : Middle Aged, Protein Structure, Quaternary, MESH : Active Transport, Cell Nucleus, Aged, 030304 developmental biology, MESH : Signal Transduction, IL-6, Base Sequence, MESH : Cell Line, Tumor, Interleukin-6, MESH : Humans, Brief Definitive Report, beta-catenin, digestive system diseases, STAT protein, Inflammatory Hepatocellular Adenoma, Cancer research, Tyrosine, MESH : src-Family Kinases, MESH : Base Sequence, Mutant Proteins, Carcinogenesis
Abstract

Somatic STAT3 mutations present in a subset of inflammatory hepatocellular adenomas result in the generation of constitutively active STAT3 proteins that homodimerize independently of IL-6 stimulation., Inflammatory hepatocellular adenomas (IHCAs) are benign liver tumors. 60% of these tumors have IL-6 signal transducer (IL6ST; gp130) mutations that activate interleukin 6 (IL-6) signaling. Here, we report that 12% of IHCA subsets lacking IL6ST mutations harbor somatic signal transducer and activator of transcription 3 (STAT3) mutations (6/49). Most of these mutations are amino acid substitutions in the SH2 domain that directs STAT3 dimerization. In contrast to wild-type STAT3, IHCA STAT3 mutants constitutively activated the IL-6 signaling pathway independent of ligand in hepatocellular cells. Indeed, the IHCA STAT3 Y640 mutant homodimerized independent of IL-6 and was hypersensitive to IL-6 stimulation. This was associated with phosphorylation of tyrosine 705, a residue required for IL-6–induced STAT3 activation. Silencing or inhibiting the tyrosine kinases JAK1 or Src, which phosphorylate STAT3, impaired constitutive activity of IHCA STAT3 mutants in hepatocellular cells. Thus, we identified for the first time somatic STAT3 mutations in human tumors, revealing a new mechanism of recurrent STAT3 activation and underscoring the role of the IL-6–STAT3 pathway in benign hepatocellular tumorigenesis.

Published
2011
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36. Physiological and Pharmacological Mechanisms through which the DPP-4 Inhibitor Sitagliptin Regulates Glycemia in Mice

Author

Pierre Cattan, Julien Castel, Rémy Burcelin, Aurélie Waget, Daniel J. Drucker, Mattieu Armanet, Melis Karaca, Christophe Magnan, Jens J. Holst, Céline Garret, Thierry Sulpice, Gaëlle Payros, Myriam Masseboeuf, Adriano Maida, Cendrine Cabou, Institut des Maladies Métaboliques et Cardiovasculaires ( I2MC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Cell Therapy Unit, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Biologie Fonctionnelle et Adaptative ( BFA ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Medicine, University of Toronto-Samuel Lunenfeld Research Institute-Mount Sinai Hospital ( MSH ), Physiogenex SAS, Prologue Biotech, PHYSIOGENEX S.A.S, Department of Biomedical Sciences, The panum Institute-University of Copenhagen ( KU ), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Toronto-Samuel Lunenfeld Research Institute-Mount Sinai Hospital [Toronto, Canada] (MSH), Physiogenex, Department of Biomedical Sciences [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Toronto-Mount Sinai Hospital [Toronto, Canada] (MSH)-Samuel Lunenfeld Research Institute, and University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)

Subjects
MESH : Insulin, medicine.medical_treatment, MESH : Vagus Nerve, MESH : Receptors, Glucagon, 0302 clinical medicine, Endocrinology, MESH: Dipeptides, MESH: Vagus Nerve, Glucose homeostasis, MESH: Animals, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH : Dipeptidyl-Peptidase IV Inhibitors, 0303 health sciences, Glucose tolerance test, MESH: Middle Aged, MESH: Dipeptidyl-Peptidase IV Inhibitors, medicine.diagnostic_test, MESH : Glucagon, MESH: Glucagon, digestive, oral, and skin physiology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH : Adult, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Glucagon-like peptide-1, 3. Good health, MESH : Pyrazines, MESH: Pyrazines, Sitagliptin, hormones, hormone substitutes, and hormone antagonists, medicine.drug, endocrine system, medicine.medical_specialty, MESH: Glucose Tolerance Test, MESH : Male, MESH : Dipeptides, MESH : Receptors, Gastrointestinal Hormone, Incretin, 030209 endocrinology & metabolism, MESH: Insulin, MESH : Mice, Inbred C57BL, Biology, Sitagliptin Phosphate, MESH : Glucose Tolerance Test, MESH: Receptors, Glucagon, 03 medical and health sciences, MESH: Mice, Inbred C57BL, Internal medicine, MESH : Mice, MESH : Triazoles, medicine, MESH : Middle Aged, MESH: Mice, Dipeptidyl peptidase-4, 030304 developmental biology, MESH: Humans, MESH: Receptors, Gastrointestinal Hormone, Insulin, MESH : Humans, MESH: Adult, MESH: Dipeptidyl Peptidase 4, MESH : Blood Glucose, MESH: Male, MESH: Triazoles, MESH : Dipeptidyl Peptidase 4, MESH: Blood Glucose, MESH : Animals
Abstract

International audience; Inhibition of dipeptidyl peptidase-4 (DPP-4) activity improves glucose homeostasis through a mode of action related to the stabilization of the active forms of DPP-4-sensitive hormones such as the incretins that enhance glucose-induced insulin secretion. However, the DPP-4 enzyme is highly expressed on the surface of intestinal epithelial cells; hence, the role of intestinal vs. systemic DPP-4 remains unclear. To analyze mechanisms through which the DPP-4 inhibitor sitagliptin regulates glycemia in mice, we administered low oral doses of the DPP-4 inhibitor sitagliptin that selectively reduced DPP-4 activity in the intestine. Glp1r(-/-) and Gipr(-/-) mice were studied and glucagon-like peptide (GLP)-1 receptor (GLP-1R) signaling was blocked by an i.v. infusion of the corresponding receptor antagonist exendin (9-39). The role of the dipeptides His-Ala and Tyr-Ala as DPP-4-generated GLP-1 and glucose-dependent insulinotropic peptide (GIP) degradation products was studied in vivo and in vitro on isolated islets. We demonstrate that very low doses of oral sitagliptin improve glucose tolerance and plasma insulin levels with selective reduction of intestinal but not systemic DPP-4 activity. The glucoregulatory action of sitagliptin was associated with increased vagus nerve activity and was diminished in wild-type mice treated with the GLP-1R antagonist exendin (9-39) and in Glp1r(-/-) and Gipr(-/-) mice. Furthermore, the dipeptides liberated from GLP-1 (His-Ala) and GIP (Tyr-Ala) deteriorated glucose tolerance, reduced insulin, and increased portal glucagon levels. The predominant mechanism through which DPP-4 inhibitors regulate glycemia involves local inhibition of intestinal DPP-4 activity, activation of incretin receptors, reduced liberation of bioactive dipeptides, and activation of the gut-to-pancreas neural axis.

Published
2011
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37. Potency, safety, and pharmacokinetics of the NS3/4A protease inhibitor BI201335 in patients with chronic HCV genotype-1 infection

Author

Christian Trepo, Michael P. Manns, David Wright, Jose Luis Calleja, Peter W. White, Chan-Loi Yong, Stanislas Pol, George Kukolj, Jerry O. Stern, Marc Bourlière, Maurizio Bonacini, Thomas Berg, Wulf Otto Boecher, Yves Benhamou, Gerhard G. Steinmann, Joe Scherer, Department of Gastroenterology, Hepatology and Endocrinology (MHH), Hannover Medical School [Hannover] (MHH), Hôpital saint joseph, Service d' Hépato-gastroentérologie, Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), California Pacific medical research center institute, Pacific medical center, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), IFR Laennec (IL), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario]-Offord Centre for Child Studies, University Clinic, University Clinic, Leipzig, Hospital universitano Puerta de Hierro, hospital universitano puerta de hierro, Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Gastroenterology, Hepatology and Endocrinology ( MHH ), Hannover Medical School [Hannover] ( MHH ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), IFR Laennec ( IL ), Institut National de la Recherche Agronomique ( INRA ) -Université Claude Bernard Lyon 1 ( UCBL ), and Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
Male, Aminoisobutyric Acids, Hepacivirus, MESH : Viral Load, Viral Nonstructural Proteins, medicine.disease_cause, Gastroenterology, MESH : Hepacivirus, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Polyethylene Glycols, MESH: Recombinant Proteins, chemistry.chemical_compound, 0302 clinical medicine, MESH : Thiazoles, Pegylated interferon, MESH : Female, MESH: Double-Blind Method, MESH: Hepacivirus, MESH : Viral Nonstructural Proteins, 0303 health sciences, MESH: Middle Aged, MESH: Protease Inhibitors, MESH: Drug Resistance, Viral, biology, MESH : Polyethylene Glycols, Intracellular Signaling Peptides and Proteins, MESH : Adult, Middle Aged, Viral Load, Hepatitis C, Recombinant Proteins, MESH : Antiviral Agents, 3. Good health, MESH : Drug Resistance, Viral, MESH: Oligopeptides, Quinolines, MESH : Interferon-alpha, Female, 030211 gastroenterology & hepatology, MESH : Carrier Proteins, MESH: Interferon-alpha, MESH: Viral Load, Oligopeptides, Viral load, medicine.drug, Pegylated Interferon Alfa, MESH : Oligopeptides, Adult, MESH: Antiviral Agents, medicine.medical_specialty, MESH : Protease Inhibitors, Proline, MESH : Recombinant Proteins, MESH : Male, Hepatitis C virus, MESH: Thiazoles, MESH: Carrier Proteins, [SDV.CAN]Life Sciences [q-bio]/Cancer, Interferon alpha-2, Antiviral Agents, 03 medical and health sciences, Double-Blind Method, Leucine, MESH: Ribavirin, Internal medicine, Drug Resistance, Viral, Ribavirin, medicine, MESH : Double-Blind Method, Humans, MESH : Middle Aged, Protease Inhibitors, Protease inhibitor (pharmacology), 030304 developmental biology, MESH: Hepatitis C, MESH: Humans, Hepatology, business.industry, MESH : Humans, Interferon-alpha, MESH: Adult, MESH : Hepatitis C, biology.organism_classification, MESH: Male, MESH : Ribavirin, Thiazoles, MESH: Polyethylene Glycols, chemistry, Faldaprevir, Immunology, MESH: Viral Nonstructural Proteins, Carrier Proteins, business, MESH: Female
Abstract

International audience; BACKGROUND & AIMS: BI201335 is a highly specific and potent HCV protease inhibitor. This multiple rising dose trial evaluated antiviral activity and safety in chronic HCV genotype-1 patients. METHODS: Thirty-four treatment-naïve patients were randomized to monotherapy with placebo or BI201335 at 20-240 mg once-daily for 14 days, followed by combination with pegylated interferon alfa/ribavirin (PegIFN/RBV) through Day 28. Nineteen treatment-experienced patients received 48-240 mg BI201335 once-daily with PegIFN/RBV for 28 days. HCV-RNA was measured with Roche COBAS TaqMan. RESULTS: In treatment-naïve patients, median maximal viral load (VL) reductions during 14-day monotherapy were -3.0, -3.6, -3.7, and -4.2 log(10) for the 20, 48, 120, and 240 mg groups. VL breakthroughs (≥1 log(10) from nadir) were seen in most patients on monotherapy and were caused by NS3/4A variants (R155K, D168V) conferring in vitro resistance to BI201335. Adding PegIFN/RBV at Days 15-28 led to continuous viral load reductions in most patients. In treatment-experienced patients, treatment with BI201335 and PegIFN/RBV achieved VL

Published
2011
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38. Aberrant DNA methylation distinguishes hepatocellular carcinoma associated with HBV and HCV infection and alcohol intake

Author

Fabien Zoulim, Marie-Pierre Lambert, Massimo Tommasino, Zdenko Herceg, Jörg Tost, Jean-Yves Scoazec, Anupam Paliwal, Pierre Hainaut, Thomas Vaissière, Bakary S. Sylla, Isabelle Chemin, Centre de Recherche en Cancérologie de Lyon (CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions Bactéries-Cellules (UIBC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), International Agency for Cancer Research (IACR), Equipe 16, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Service d'hépatologie et de gastroentérologie, Hospices Civils de Lyon (HCL)-Hôtel-Dieu-Hospices Civils de Lyon (HCL)-Hôtel-Dieu-Centre de Recherche en Cancérologie de Lyon (CRCL), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Sect Mech Carcinogenesis, equipe 4, Laboratoire Central d'Anatomie et de Cytologie Pathologiques [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Cancérologie de Lyon (CRCL), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Interactions Bactéries-Cellules ( UIBC ), Institut National de la Recherche Agronomique ( INRA ) -Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), International Agency for Cancer Research ( IACR ), International Agency for Cancer Research, Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Hospices Civils de Lyon ( HCL ) -Hôtel-Dieu-Hospices Civils de Lyon ( HCL ) -Hôtel-Dieu-Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer ( CIRC - IARC ), Organisation mondiale de la santé (OMS/WHO), international Agency for Research on Cancer - IARC, Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Hospices Civils de Lyon (HCL)-Hôtel-Dieu-Hospices Civils de Lyon (HCL)-Hôtel-Dieu-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), and Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MESH : Liver Neoplasms, MESH : Aged, Receptors, Nicotinic, MESH: Base Sequence, medicine.disease_cause, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: DNA Methylation, 0302 clinical medicine, Risk Factors, MESH: Liver Neoplasms, MESH: Risk Factors, MESH : Female, MESH: Gene Silencing, MESH: Carcinoma, Hepatocellular, MESH: Glutathione S-Transferase pi, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH : Tumor Suppressor Proteins, Liver Neoplasms, RNA-Binding Proteins, DNA, Neoplasm, Hepatitis C, Methylation, Middle Aged, MESH : Adult, Hepatitis B, MESH : Risk Factors, 3. Good health, DNA-Binding Proteins, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, DNA methylation, MESH: Receptors, Nicotinic, Female, MESH : DNA Primers, MESH : DNA, Neoplasm, MESH : DNA-Binding Proteins, Adult, MESH : Carcinoma, Hepatocellular, MESH: DNA Primers, Carcinoma, Hepatocellular, Alcohol Drinking, MESH : Male, Hepatitis C virus, MESH : RNA-Binding Proteins, MESH: DNA, Neoplasm, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MESH: Phosphoproteins, 03 medical and health sciences, MESH : Gene Silencing, medicine, Humans, MESH : Middle Aged, MESH: Tumor Suppressor Proteins, Gene Silencing, neoplasms, Aged, DNA Primers, 030304 developmental biology, MESH: Hepatitis C, Hepatitis B virus, MESH: Humans, Base Sequence, MESH : Receptors, Nicotinic, MESH: Hepatitis B, Hepatology, Tumor Suppressor Proteins, MESH : Humans, MESH : Hepatitis B, Cancer, MESH: Adult, DNA Methylation, MESH : Hepatitis C, Phosphoproteins, medicine.disease, MESH: Male, digestive system diseases, MESH : Alcohol Drinking, MESH: RNA-Binding Proteins, Glutathione S-Transferase pi, MESH : Glutathione S-Transferase pi, Immunology, MESH : Base Sequence, MESH : Phosphoproteins, MESH : DNA Methylation, MESH: Female, MESH: Alcohol Drinking, MESH: DNA-Binding Proteins
Abstract

International audience; BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the most frequent human cancers and a major cause of cancer-related death worldwide. The major risk factors for developing HCC are infection by hepatitis B virus (HBV) and hepatitis C virus (HCV), chronic alcoholism, and aflatoxins; however, critical gene targets remain largely unknown. Herein, we sought to establish DNA methylation patterns in HCC and corresponding cirrhotic tissues and to identify DNA methylation changes associated with major risk factors. METHODS: We have established assays for quantitative analysis of DNA methylation levels in a panel of seven cancer-associated genes and repetitive elements, and combined these assays with a series of HCC tumors, associated with major risk factors, collected from two different geographical areas. RESULTS: We found a high frequency of aberrant hypermethylation of specific genes (RASSF1A, GSTP1, CHRNA3, and DOK1) in HCC tumors as compared to control cirrhotic or normal liver tissues, suggesting that aberrant hypermethylation exhibits non-random and tumor-specific patterns in HCC. Importantly, our analysis revealed an association between alcohol intake and the hypomethylation of MGMT and between hypermethylation of GSTP1 and HBV infection, indicating that hypermethylation of the genes analyzed in HCC tumors exhibits remarkably distinct patterns depending on associated risk factors. CONCLUSIONS: This study identifies aberrant DNA methylation of specific cellular genes in HCC and the major risk factors associated with these changes, providing information that could be exploited for biomarker discovery in clinics and molecular epidemiology.

Published
2011
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39. Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency)

Author

Pierre Bordigoni, Danielle Canioni, Michèle Milili, Nathalie Lambert, Claire Galambrun, Marie Ouachée-Chardin, Filomeen Haerynck, Françoise Le Deist, Despina Moshous, Christelle Lenoir, Stephanie Rigaud, Lionel Galicier, Fabien Touzot, Capucine Picard, Mohamed Hamidou, Hirokazu Kanegane, Ester Mejstrikova, Helen Chapel, Eduardo López-Granados, Stéphane Blanche, Alain Dabadie, Jana Pachlopnik Schmid, Pierre-Simon Rohrlich, Fabian Hauck, Geneviève de Saint Basile, Claudin Schiff, Jean-Louis Stephan, Alain Fischer, Isabelle Pellier, Nizar Mahlaoui, Sylvain Latour, Alain Fourmaintraux, Vincent Barlogis, IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Graduate School of Medicine, University of Toyama, Department of pediatrics, University of Oxford [Oxford], Teaching Hospital Motol and 2nd Medical School, Charles University, Department of Pediatric Hematology and Oncology, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'immuno-hématologie pédiatrique [CHU Necker], Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Groupe Hospitalier Sud Réunion (GHSR), Centre Hospitalier Universitaire [Rennes], Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Department of Paediatric Pulmonology, Ghent University Hospital, Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Département de pédiatrie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, CHU Saint-Etienne, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'étude des Déficits Immunitaires, Assistance Publique-Hôpitaux de Paris, Service d'Immunologie et d'Hématologie Pédiatrique, Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), University of Oxford, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Collège de France - Chaire Médecine expérimentale (A. Fischer), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Groupe Hospitalier Sud Réunion ( GHSR ), Centre de Référence Déficits Immunitaires Héréditaires ( CEREDIH ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Centre d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), and Assistance publique - Hôpitaux de Paris (AP-HP)

Subjects
Male, MESH : Retrospective Studies, MESH: X-Linked Inhibitor of Apoptosis Protein, MESH : Aged, MESH : Child, Preschool, Biochemistry, Cohort Studies, Immunoenzyme Techniques, Hypogammaglobulinemia, MESH: Lymphoproliferative Disorders, 0302 clinical medicine, MESH : Child, MESH: Child, hemic and lymphatic diseases, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, XIAP Deficiency, Signaling Lymphocytic Activation Molecule Associated Protein, X-Linked Lymphoproliferative Syndrome, Child, MESH: Cohort Studies, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH : Lymphoproliferative Disorders, Intracellular Signaling Peptides and Proteins, MESH : Infant, Hematology, MESH : Adult, Middle Aged, MESH : Survival Rate, MESH: Infant, 3. Good health, Survival Rate, MESH : Phenotype, Phenotype, MESH: Young Adult, Child, Preschool, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Mutation, Adult, medicine.medical_specialty, MESH: Mutation, Adolescent, MESH: Survival Rate, MESH : Male, Immunology, MESH : Young Adult, MESH : Cohort Studies, X-Linked Inhibitor of Apoptosis Protein, Biology, MESH: Phenotype, Virus, Young Adult, 03 medical and health sciences, MESH : Intracellular Signaling Peptides and Proteins, MESH : Immunoenzyme Techniques, MESH : Adolescent, MESH: Intracellular Signaling Peptides and Proteins, medicine, Humans, MESH : Middle Aged, MESH: Immunoenzyme Techniques, Aged, Retrospective Studies, 030304 developmental biology, MESH: Adolescent, Hemophagocytic lymphohistiocytosis, Cytopenia, MESH: Humans, MESH : Humans, MESH: Child, Preschool, Infant, X-linked lymphoproliferative disease, MESH: Adult, MESH: Retrospective Studies, Cell Biology, medicine.disease, Lymphoproliferative Disorders, MESH: Male, MESH : X-Linked Inhibitor of Apoptosis Protein, Mutation, Histopathology, MESH: Female, 030215 immunology
Abstract

X-linked lymphoproliferative syndromes (XLP) are primary immunodeficiencies characterized by a particular vulnerability toward Epstein-Barr virus infection, frequently resulting in hemophagocytic lymphohistiocytosis (HLH). XLP type 1 (XLP-1) is caused by mutations in the gene SH2D1A (also named SAP), whereas mutations in the gene XIAP underlie XLP type 2 (XLP-2). Here, a comparison of the clinical phenotypes associated with XLP-1 and XLP-2 was performed in cohorts of 33 and 30 patients, respectively. HLH (XLP-1, 55%; XLP-2, 76%) and hypogammaglobulinemia (XLP-1, 67%; XLP-2, 33%) occurred in both groups. Epstein-Barr virus infection in XLP-1 and XLP-2 was the common trigger of HLH (XLP-1, 92%; XLP-2, 83%). Survival rates and mean ages at the first HLH episode did not differ for both groups, but HLH was more severe with lethal outcome in XLP-1 (XLP-1, 61%; XLP-2, 23%). Although only XLP-1 patients developed lymphomas (30%), XLP-2 patients (17%) had chronic hemorrhagic colitis as documented by histopathology. Recurrent splenomegaly often associated with cytopenia and fever was preferentially observed in XLP-2 (XLP-1, 7%; XLP-2, 87%) and probably represents minimal forms of HLH as documented by histopathology. This first phenotypic comparison of XLP subtypes should help to improve the diagnosis and the care of patients with XLP conditions.

Published
2011
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40. 18F-FLT and 18F-FDG positron emission tomography for the imaging of advanced well-differentiated gastro-entero-pancreatic endocrine tumours

Author

Francesco Giammarile, Valérie Hervieu, Didier Le Bars, Jean-Philippe Vuillez, Catherine Lombard-Bohas, Jean-Yves Scoazec, Catherine Cornu, Claire Houzard, Françoise Borson-Chazot, Claire Bournaud, Sandrine Masson, Thomas Walter, Marc Janier, Claire Billotey, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Laboratoire de Physico-Chimie des Matériaux Luminescents (LPCML), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, E04, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), DOCOMO Euro-Labs, DOCOMO Communications Laboratories Europe GmbH-DOCOMO Communications Laboratories Europe GmbH-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon, Laboratoire Central d'Anatomie et de Cytologie Pathologiques [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Radiopharmaceutiques biocliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Laboratoire de Physico-Chimie des Matériaux Luminescents ( LPCML ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Exploration et de Recherche Médicales par Émission de Positons ( CERMEP ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon ( HCL ) -CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), DOCOMO Communications Laboratories Europe GmbH-DOCOMO Communications Laboratories Europe GmbH-Centre de Recherche en Cancérologie de Lyon ( CRCL ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, MESH : Aged, Neuroendocrine tumors, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 030218 nuclear medicine & medical imaging, 0302 clinical medicine, MESH: Fluorodeoxyglucose F18, MESH : Intestinal Neoplasms, MESH : Stomach Neoplasms, MESH : Neoplasm Staging, MESH : Female, Prospective cohort study, MESH: Aged, MESH: Middle Aged, medicine.diagnostic_test, Ultrasound, MESH : Neuroendocrine Tumors, Cell Differentiation, MESH: Stomach Neoplasms, MESH: Neoplasm Staging, General Medicine, MESH : Adult, Middle Aged, MESH: Positron-Emission Tomography, 3. Good health, Neuroendocrine Tumors, MESH: Dideoxynucleosides, Positron emission tomography, 030220 oncology & carcinogenesis, MESH : Dideoxynucleosides, Female, MESH: Pancreatic Neoplasms, Radiology, MESH : Cell Differentiation, Preclinical imaging, MESH: Cell Differentiation, Adult, medicine.medical_specialty, MESH: Neuroendocrine Tumors, MESH : Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Fluorodeoxyglucose F18, Stomach Neoplasms, Intestinal Neoplasms, Brain positron emission tomography, medicine, Humans, Endocrine system, MESH : Middle Aged, Radiology, Nuclear Medicine and imaging, MESH: Intestinal Neoplasms, Aged, Neoplasm Staging, MESH: Humans, business.industry, MESH : Humans, MESH : Positron-Emission Tomography, MESH: Adult, MESH : Fluorodeoxyglucose F18, medicine.disease, MESH: Male, Dideoxynucleosides, Pancreatic Neoplasms, Positron-Emission Tomography, business, MESH: Female, MESH : Pancreatic Neoplasms, Progressive disease
Abstract

International audience; PURPOSE: Gastro-entero-pancreatic (GEP) endocrine tumours are a heterogenous group of tumours of variable localization and prognosis. It has been suggested that positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) may have a prognostic value and help to identify patients at risk of progression. [18F]fluoro-3'-deoxy-3'-L-fluorothymidine (18F-FLT) has been recently developed as a PET proliferation tracer. At present, there are no studies investigating its role in GEP. The aim of this prospective study was to assess the value of 18F-FLT-PET for the evaluation of GEP. MATERIALS AND METHODS: Ten patients with biopsy-proven locally advanced or metastasized, well-differentiated GEP neuroendocrine tumours were prospectively enrolled and scheduled for 18F-FDG and 18F-FLT-PET. Images were compared with other conventional diagnostic procedures, namely computed tomography, ultrasound, somatostatin receptor scintigraphy and with clinical and diagnostic follow-up. RESULTS: Evaluation criteria were interpreted in terms of assumed presence of tumoral tissue. According to the patient's status, FDG was positive in five out of the seven patients with stable disease and in two out of the three patients with progressive disease. No positive case was identified by 18F-FLT in either the primary or the metastatic tumour site, whatever the status of patients, and this was probably a reflection of the slow proliferation rate of tumours. CONCLUSION: These preliminary data suggest that 18F-FLT-PET is not a suitable tracer for the evaluation of advanced well-differentiated GEP tumours. FDG showed good diagnostic performance but does not help to identify patients at risk of progression.

Published
2011
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41. Liver methylene fraction by dual- and triple-echo gradient-echo imaging at 3.0T: Correlation with proton MR spectroscopy and estimation of robustness after SPIO administration

Author

David Masson, Patrick Hillon, Isabelle Robin, Romaric Loffroy, Boris Guiu, Serge Aho, Jean-Michel Petit, Bruno Vergès, Jean-Pierre Cercueil, Douraied Ben Salem, Denis Krausé, Service de radiologie et d'Imagerie médicale diagnostique et thérapeutique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Unité de Génétique Moléculaire Animale (UGMA), Université de Limoges (UNILIM)-Institut National de la Recherche Agronomique (INRA), Service d'Ophtalmologie (CHU de Dijon), Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Service de Diabétologie, Service d'Hépato-Gastroentérologie, Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Unité de Génétique Moléculaire Animale (UMR GMA), Université de Brest (UBO)-Université de Brest (UBO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Unité de Génétique Moléculaire Animale ( UGMA ), Université de Limoges ( UNILIM ) -Institut National de la Recherche Agronomique ( INRA ), Laboratoire Electronique, Informatique et Image ( Le2i ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Groupe d'Etude de la Thrombose de Bretagne Occidentale ( GETBO ), Université de Brest ( UBO ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon )

Subjects
Male, Magnetic Resonance Spectroscopy, MESH : Fatty Liver, MESH: Echo-Planar Imaging, [SDV]Life Sciences [q-bio], Carbon Compounds, Inorganic, MESH : Statistics as Topic, Statistics as Topic, MESH : Aged, Contrast Media, MESH : Carbon Compounds, Inorganic, MESH : Tissue Distribution, 030218 nuclear medicine & medical imaging, Correlation, chemistry.chemical_compound, 0302 clinical medicine, MESH : Dextrans, Non-alcoholic Fatty Liver Disease, MESH : Female, Tissue Distribution, MESH: Dextrans, Methylene, Magnetite Nanoparticles, MESH: Fatty Liver, MESH: Aged, MESH: Middle Aged, medicine.diagnostic_test, Echo-Planar Imaging, Dextrans, Nuclear magnetic resonance spectroscopy, MESH : Adult, Middle Aged, MESH: Reproducibility of Results, Adipose Tissue, Liver, Female, 030211 gastroenterology & hepatology, MESH : Sensitivity and Specificity, Protons, MESH: Adipose Tissue, Adult, Iron Overload, MESH : Male, MESH: Magnetite Nanoparticles, MESH : Adipose Tissue, Sensitivity and Specificity, MESH: Iron Overload, 03 medical and health sciences, Flip angle, Robustness (computer science), MESH: Contrast Media, Linear regression, medicine, MESH : Protons, Humans, MESH : Middle Aged, Radiology, Nuclear Medicine and imaging, MESH: Tissue Distribution, MESH: Statistics as Topic, Aged, MESH : Contrast Media, MESH : Iron Overload, MESH: Humans, MESH : Echo-Planar Imaging, [ SDV ] Life Sciences [q-bio], MESH: Magnetic Resonance Spectroscopy, business.industry, MESH : Reproducibility of Results, MESH : Humans, MESH: Biological Markers, MESH: Carbon Compounds, Inorganic, MESH : Liver, MESH : Magnetite Nanoparticles, Reproducibility of Results, MESH: Adult, Magnetic resonance imaging, MESH: Male, MESH: Sensitivity and Specificity, Proton mr spectroscopy, MESH : Biological Markers, Fatty Liver, chemistry, MESH : Magnetic Resonance Spectroscopy, MESH: Protons, Nuclear medicine, business, MESH: Female, Biomarkers, MESH: Liver
Abstract

Purpose To assess the systematic errors in liver methylene fraction (LMF) resulting from fat–fat interference effects with dual- and triple-echo gradient-recalled-echo Dual/Triple GRE) sequences and to test the robustness of these sequences after iron overloading. Materials and Methods Forty type-2 diabetic patients underwent LMF measurement by 3.0T 1H magnetic resonance spectroscopy (corrected for T1 and T2 decays) as the reference standard and liver fat fraction (%Fat) measurement by four Dual/Triple GRE sequences with 20° and 60° flip angle (α), corrected for T1 recovery. The same four sequences were repeated in eight patients after ferumoxide injection. Corrections for systematic errors were determined from the linear regressions (spectroscopy LMF values over Dual/Triple GRE %Fat values). Robustness was tested using Wilcoxon's signed-rank test. Results Fat–fat interference effects produced a ∼10% relative systematic error and T2* decay produced a 1.9%–4.2% absolute systematic error in LMF. When comparing before and after ferumoxide, dual-echo imaging with α = 20° and α = 60°, even when corrected, showed absolute differences of 7.23% [2.81%–10.25%] (P = 0.0117) and 5.65% [1.89%–8.216.8%] (P = 0.0117), respectively; compared to only 1.17% [0.08%–2.83%] (P = 0.0251) and 1.15% [0.37%–2.73%] (P = 0.2626) with triple-echo imaging and α = 20° and α = 60°, respectively. Conclusion Triple-echo imaging with α = 60° corrected for both T1 recovery and fat–fat interference effects is robust after superparamagnetic iron oxide (SPIO) administration and can reliably quantify LMF. J. Magn. Reson. Imaging 2011;33:119–127. © 2010 Wiley-Liss, Inc.

Published
2010
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42. Adrenal Cortex Remodeling and Functional Zona Glomerulosa Hyperplasia in Primary Aldosteronism

Author

Arndt Benecke, Xavier Jeunemaitre, Estelle Louiset, José-Felipe Golib Dzib, Pierre-François Plouin, Sheerazed Boulkroun, Tchao Meatchi, Enzo Lalli, Laurence Amar, Benoit Samson-Couterie, Hervé Lefebvre, Maria-Christina Zennaro, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Institut des Hautes Etudes Scientifiques (IHES), IHES, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] (IRI), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé-Université de Lille, Sciences et Technologies, Service de génétique [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Institut des Hautes Etudes Scientifiques ( IHES ), Différenciation et communication neuronale et neuroendocrine ( DC2N ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), UNIROUEN - UFR Santé, Normandie Université ( NU ) -Normandie Université ( NU ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Institut de pharmacologie moléculaire et cellulaire ( IPMC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Université Côte d'Azur ( UCA ), Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] ( IRI ), Université de Lille, Sciences et Technologies-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA), Université de Lille, Sciences et Technologies-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)

Subjects
Male, MESH : Steroid 11-beta-Hydroxylase, MESH : Immunohistochemistry, MESH : Adrenal Cortex Neoplasms, MESH: Adrenal Cortex Neoplasms, MESH : Adrenal Cortex, chemistry.chemical_compound, 0302 clinical medicine, Primary aldosteronism, MESH : Female, Aldosterone, In Situ Hybridization, 0303 health sciences, MESH: Middle Aged, Adrenal cortex, MESH : In Situ Hybridization, Middle Aged, MESH : Adult, Hyperplasia, Immunohistochemistry, MESH : Hyperaldosteronism, MESH: Hyperaldosteronism, medicine.anatomical_structure, Female, Zona Glomerulosa, Adenoma, Adult, medicine.medical_specialty, MESH: Zona Glomerulosa, medicine.drug_class, MESH : Male, 030209 endocrinology & metabolism, Biology, MESH: Aldosterone Synthase, 03 medical and health sciences, MESH: In Situ Hybridization, MESH : Hyperplasia, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Internal medicine, Hyperaldosteronism, Internal Medicine, medicine, Cytochrome P-450 CYP11B2, Humans, MESH : Middle Aged, Steroid 11-beta-hydroxylase, 030304 developmental biology, MESH : Aldosterone Synthase, MESH: Adenoma, MESH: Humans, MESH : Aldosterone, MESH: Hyperplasia, MESH : Humans, MESH: Aldosterone, MESH: Immunohistochemistry, MESH: Adult, medicine.disease, Adrenal Cortex Neoplasms, MESH: Male, Endocrinology, MESH : Adenoma, chemistry, Mineralocorticoid, Zona glomerulosa, Adrenal Cortex, Steroid 11-beta-Hydroxylase, MESH: Adrenal Cortex, MESH : Zona Glomerulosa, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH: Steroid 11-beta-Hydroxylase
Abstract

International audience; Primary aldosteronism is the most common form of secondary hypertension with hypokalemia and suppressed renin-angiotensin system caused by autonomous aldosterone production. Our aim was to compare zona glomerulosa (ZG) structure and function between control adrenals and the peritumoral tissue from patients operated on for aldosterone-producing adenoma. ZG morphology and CYP11B1, CYP11B2, and disabled 2 expression were studied in 15 control adrenals and 25 adrenals with aldosterone-producing adenoma. A transcriptome analysis was done using publicly available data sets. In control adrenals, ZG was discontinuous, and CYP11B2 expression was focal or partly continuous and localized to 3 structures, foci, megafoci, and aldosterone-producing cell clusters. CYP11B2 expression was restricted to a limited number of ZG cells expressing Dab2 but not CYP11B1; aldosterone-producing cell clusters were composed of cells with an intermediate phenotype expressing CYP11B2 but not disabled 2 or CYP11B1. In peritumoral tissue, large remodeling of the adrenal cortex was observed with increased nodulation and decreased vascularization that were not correlated with CYP11B2 expression. In 17 out of 25 adrenals, hyperplasia of adjacent ZG was observed with persistent expression of CYP11B2 that was extended to the entire ZG. In all of the adrenals from patients with aldosterone-producing adenoma, CYP11B2 expression was present in foci, megafoci, and aldosterone-producing cell clusters. Transcriptome profiling indicates a close relationship between peritumoral and control adrenal cortex. In conclusion, adrenal cortex remodeling, reduced vascularization, and ZG hyperplasia are major features of adrenals with aldosterone-producing adenoma. Transcriptional phenotyping is not in favor of this being an intermediate step toward the formation of aldosterone-producing adenoma.

Published
2010
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43. Adaptive Differentiation ofPlasmodium falciparumPopulations Inferred from Single‐Nucleotide Polymorphisms (SNPs) Conferring Drug Resistance and from Neutral SNPs

Author

Rabia Mazmouz, Agnès Aubouy, Emmanuelle Renard, Sabah A. Omar, Jérôme Clain, Sarah Falcão, Emeline Broussier, Abdoulaye Djimde, Vély Jean-François, Jean-François Lepère, Jacques Le Bras, Dorina G. Bustos, Oumou Maïga-Ascofaré, Milijaona Randrianarivelojosia, Mère et enfant face aux infections tropicales (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5), Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy, and Odontostomatology, Université de Bamako, Centre de consultations de Bandraboua, Research Institute for Tropical Medicine, Institut Pasteur de Madagascar, Institut Pasteur de Madagascar - Réseau International des Instituts Pasteur (RIIP), Kenya Medical Research Institute, Unité de Recherche 010, IRD, Service National de Lutte Antipaludique, Financial support: French Ministry of Health (grant to the Centre National de Réference du Paludisme), Institut de Médecine et d'Epidémiologie Appliquée/Fondation Léon Mba (grant 5988CLN90PFGO), French Ministry of Foreign Affairs for the France-Philippine Technical Cooperation Project on Malaria (grant), Bio-MalPar Network of Excellence., Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Réseau International des Instituts Pasteur (RIIP), and Kenya Medical Research Institute (KEMRI)

Subjects
Male, MESH: Philippines, MESH: Geography, Philippines, [SDV]Life Sciences [q-bio], Genes, Protozoan, Adaptation, Biological, Drug Resistance, MESH : Aged, Drug resistance, MESH: Africa, MESH : Child, Preschool, MESH : Malaria, Falciparum, MESH: Aged, 80 and over, 0302 clinical medicine, MESH : Child, Polymorphism (computer science), MESH: Child, MESH : Haiti, MESH : Philippines, MESH : Plasmodium falciparum, Immunology and Allergy, MESH : Female, MESH : Adaptation, Biological, Malaria, Falciparum, Child, MESH : DNA, Protozoan, MESH: Plasmodium falciparum, Aged, 80 and over, MESH: Aged, Genetics, 0303 health sciences, MESH: Middle Aged, Geography, biology, MESH: Polymorphism, Single Nucleotide, MESH: Malaria, Falciparum, MESH: Infant, Newborn, MESH : Polymorphism, Single Nucleotide, MESH : Geography, MESH : Infant, Middle Aged, MESH : Adult, MESH: Infant, 3. Good health, [SDV] Life Sciences [q-bio], MESH: Haiti, Infectious Diseases, MESH: Genes, Protozoan, MESH: Young Adult, Child, Preschool, MESH : Genes, Protozoan, MESH: Drug Resistance, Female, Adult, Adolescent, MESH : Africa, MESH : Male, Plasmodium falciparum, 030231 tropical medicine, MESH : Young Adult, MESH: DNA, Protozoan, Context (language use), Single-nucleotide polymorphism, MESH : Infant, Newborn, Polymorphism, Single Nucleotide, Young Adult, 03 medical and health sciences, MESH : Adolescent, parasitic diseases, Humans, MESH : Middle Aged, Allele, MESH : Aged, 80 and over, Gene, Allele frequency, Aged, 030304 developmental biology, MESH: Adolescent, MESH : Drug Resistance, MESH: Humans, MESH: Adaptation, Biological, MESH: Child, Preschool, MESH : Humans, Infant, Newborn, Infant, MESH: Adult, DNA, Protozoan, biology.organism_classification, Haiti, MESH: Male, Africa, MESH: Female
Abstract

International audience; BACKGROUND: Theoretical and experimental data support the geographic differentiation strategy as a valuable tool for detecting loci under selection. In the context of Plasmodium falciparum malaria, few populations have been studied, with limited genomic coverage. METHODS: We examined geographic differentiation in P. falciparum populations on the basis of 12 single-nucleotide polymorphisms (SNPs) in 4 genes encoding drug resistance determinants, 5 SNPs in 2 genes encoding antigens, and a set of 17 putatively neutral SNPs dispersed on 13 chromosomes. We sampled 326 parasite isolates representing 7 P. falciparum populations from regions with varied levels of malaria transmission (Gabon, Kenya, Madagascar, Mali, Mayotte, Haiti, and the Philippines). RESULTS: Frequencies of drug resistance alleles varied considerably among populations (mean F(ST), 0.52). In contrast, allele frequencies varied significantly less for antigenic and neutral SNPs (mean F(ST), 0.16 and 0.24, respectively). This contrasting pattern was more pronounced when only the African populations were considered. Signature of selection was detected for most of the resistant SNPs but not for the antigenic SNPs. CONCLUSION: These data further validate the utility of geographic differentiation for identifying loci under strong positive selection, such as drug resistance loci. This study also provides frequencies of molecular makers of resistance in some overlooked populations.

Published
2010
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44. Antithymocyte globulins and chronic graft-vs-host disease after myeloablative allogeneic stem cell transplantation from HLA-matched unrelated donors: a report from the Sociéte Française de Greffe de Moelle et de Thérapie Cellulaire

Author

Colette Raffoux, Mohamad Mohty, R. Tabrizi, J.Y. Cahn, Ibrahim Yakoub-Agha, J. H. Bourhis, Yosr Hicheri, Norbert Ifrah, Mauricette Michallet, Agnès Buzyn, Nathalie Dhedin, Myriam Labopin, Marie-Lorraine Balere, Didier Blaise, Gérard Socié, Helene Esperou, Noel Milpied, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Université Bordeaux Segalen - Bordeaux 2, Service des maladies du sang, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, Centre Léon Bérard [Lyon], Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut Gustave Roussy (IGR), Service greffe de moelle osseuse, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, Centre hospitalier universitaire de Nantes ( CHU Nantes ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Institut Gustave Roussy ( IGR ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]

Subjects
Male, MESH: Tissue Donors, Cancer Research, MESH : Retrospective Studies, MESH : Aged, MESH: Rabbits, Graft vs Host Disease, Gastroenterology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH : HLA Antigens, MESH: Antilymphocyte Serum, HLA Antigens, MESH : Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH : Female, MESH: Animals, Cumulative incidence, MESH: Incidence, MESH: HLA Antigens, MESH : Tissue Donors, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, Hematology, Histocompatibility Testing, Incidence, Incidence (epidemiology), MESH : Graft vs Host Disease, MESH : Histocompatibility Testing, MESH : Adult, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH : Incidence, Tissue Donors, 3. Good health, Leukemia, Myeloid, Acute, Leukemia, Treatment Outcome, surgical procedures, operative, Oncology, 030220 oncology & carcinogenesis, Female, Rabbits, MESH: Stem Cell Transplantation, MESH: Leukemia, Myeloid, Acute, MESH: Myelodysplastic Syndromes, Adult, endocrine system, medicine.medical_specialty, Adolescent, MESH : Transplantation, Homologous, MESH : Male, MESH : Leukemia, Myeloid, Acute, MESH : Antilymphocyte Serum, MESH: Graft vs Host Disease, MESH : Myelodysplastic Syndromes, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Treatment Outcome, MESH: Histocompatibility Testing, MESH : Stem Cell Transplantation, 03 medical and health sciences, MESH : Adolescent, Internal medicine, MESH: Transplantation, Homologous, medicine, Animals, Humans, Transplantation, Homologous, MESH : Middle Aged, MESH : Rabbits, Aged, Antilymphocyte Serum, Retrospective Studies, MESH: Adolescent, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Humans, business.industry, Myelodysplastic syndromes, MESH : Humans, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH: Male, Histocompatibility, Transplantation, Graft-versus-host disease, Myelodysplastic Syndromes, Immunology, MESH : Animals, business, MESH: Female, Stem Cell Transplantation, 030215 immunology
Abstract

International audience; This retrospective report assessed the impact of rabbit antithymocyte globulins (ATG), incorporated within a standard myeloablative conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT) using human leukocyte antigen-matched unrelated donors (HLA-MUD), on the incidence of acute and chronic graft-vs-host disease (GVHD). In this series of leukemia patients, 120 patients (70%) did not receive ATG ('no-ATG' group), whereas 51 patients received ATG ('ATG' group). With a median follow-up of 30.3 months, the cumulative incidence of grade 3-4 acute GVHD was 36% in the no-ATG group and 20% in the ATG group (P = 0.11). The cumulative incidence of extensive chronic GVHD was significantly lower in the ATG group as compared to the no-ATG group (4 vs 32%, respectively; P = 0.0017). In multivariate analysis, the absence of use of ATG was the strongest parameter associated with an increased risk of extensive chronic GVHD (relative risk) = 7.14, 95% CI: 1.7-33.3, P = 0.008). At 2 years, the probability of nonrelapse mortality, relapse, overall and leukemia-free survivals was not significantly different between the no-ATG and ATG groups. We conclude that the addition of ATG to GVHD prophylaxis resulted in decreased incidence of extensive chronic GVHD without an increase in relapse or nonrelapse mortality, and without compromising survival after myeloablative allo-SCT from HLA-MUD.

Published
2010
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45. Self-rated residual symptoms do not predict 1-year recurrence of depression

Author

Guido Bondolfi, D. Marra, Jean-Michel Aubry, Christian Osiek, Nicola Gérard Gervasoni, Gilles Bertschy, Marianne Gex-Fabry, Emmanuel Haffen, Laboratoire de Neurosciences Intégratives et Cliniques - UFC ( NEURO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)

Subjects
Male, Time Factors, Psychometrics, MESH : Recurrence, MESH : Aged, Test validity, ddc:616.89, 0302 clinical medicine, Recurrence, Surveys and Questionnaires, Depressive Disorder, Major/*diagnosis/*epidemiology, MESH : Female, Major depressive episode, Depression (differential diagnoses), MESH: Aged, MESH: Middle Aged, Questionnaires, MESH : Questionnaires, MESH: Follow-Up Studies, Middle Aged, MESH : Adult, MESH: Predictive Value of Tests, Psychiatry and Mental health, Convergent validity, MESH: Young Adult, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, medicine.symptom, Psychology, MESH : Depressive Disorder, Major, MESH : Time Factors, Adult, Predictive validity, medicine.medical_specialty, MESH : Male, MESH: Depressive Disorder, Major, MESH : Young Adult, Young Adult, 03 medical and health sciences, Predictive Value of Tests, Rating scale, Internal medicine, medicine, Humans, MESH : Middle Aged, MESH : Predictive Value of Tests, Risk factor, Psychiatry, Aged, Depressive Disorder, Major, MESH: Humans, MESH: Questionnaires, MESH: Time Factors, MESH : Humans, MESH: Adult, MESH : Follow-Up Studies, MESH: Male, MESH: Recurrence, 030227 psychiatry, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Female, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

BackgroundResidual depressive symptoms are generally documented as a risk factor for recurrence. In the absence of a specific instrument for the assessment of residual symptoms, a new 25-item Depression Residual Symptom Scale (DRSS) was elaborated and tested for recurrence prediction over a 1-year follow-up.Sampling and methodsFifty-nine patients in remission after a major depressive episode (MDE) were recruited in two centres. They were assessed with the DRSS and the Montgomery-Asberg Depression Rating Scale (MADRS) at inclusion and followed for 1 year according to a seminaturalistic design. The DRSS included specific depressive symptoms and subjective symptoms of vulnerability, lack of return to usual self and premorbid level of functioning.ResultsSeverity of residual symptoms was not significantly associated with increased risk of recurrence. However, DRSS score was significantly higher among patients with three or more episodes than one to two episodes. Number of previous episodes and treatment interruption were not identified as significant predictors of recurrence.ConclusionThe proposed instrument is not predictive of depressive recurrence, but is sensitive to increased perception of vulnerability associated with consecutive episodes. Limitations include small sample size, seminaturalistic design (no standardisation of treatment) and content of the instrument.

Published
2010
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46. Detection of alpha- and beta-human papillomavirus (HPV) in cutaneous melanoma: a matched and controlled study using specific multiplex PCR combined with DNA microarray primer extension

Author

Jean Luc Prétet, Bernadette Kantelip, Christiane Mougin, Tarik Gheit, Jean Baptiste Ruer, Line Pépin, François Aubin, Chrystelle Vidal, Massimo Tommasino, Laboratoire d'anatomie pathologique [Besancon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Université Libre de Bruxelles [Bruxelles] ( ULB ), Service d'Anatomie pathologique [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Université libre de Bruxelles (ULB)

Subjects
Male, Oncology, Skin Neoplasms, Microarray, Gammapapillomavirus, MESH : Aged, MESH : Gammapapillomavirus, Alphapapillomavirus, Polymerase Chain Reaction, Biochemistry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Aged, 80 and over, 0302 clinical medicine, MESH : Alphapapillomavirus, MESH : Neoplasm Staging, MESH : Female, MESH : DNA, Viral, Melanoma, MESH : Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Skin, MESH: Human papillomavirus 16, Aged, 80 and over, MESH: Aged, Human papillomavirus 16, 0303 health sciences, education.field_of_study, MESH: Middle Aged, MESH : Prognosis, HPV infection, virus diseases, MESH: Neoplasm Staging, Middle Aged, MESH : Adult, Prognosis, female genital diseases and pregnancy complications, 3. Good health, MESH : Oligonucleotide Array Sequence Analysis, MESH: Young Adult, 030220 oncology & carcinogenesis, Female, Adult, medicine.medical_specialty, MESH: Melanoma, MESH : Male, Population, MESH : Melanoma, MESH : Young Adult, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, Biology, MESH: Betapapillomavirus, MESH: Prognosis, Young Adult, 03 medical and health sciences, MESH: Skin, Internal medicine, Multiplex polymerase chain reaction, MESH : Skin, medicine, Betapapillomavirus, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, education, MESH: Alphapapillomavirus, Molecular Biology, Aged, Neoplasm Staging, 030304 developmental biology, MESH: Humans, MESH : Betapapillomavirus, MESH: Skin Neoplasms, MESH : Skin Neoplasms, MESH : Humans, MESH : Human papillomavirus 16, Cancer, MESH: Adult, MESH: Polymerase Chain Reaction, medicine.disease, DNA extraction, MESH: Male, MESH: DNA, Viral, DNA, Viral, MESH: Oligonucleotide Array Sequence Analysis, Cutaneous melanoma, Immunology, MESH: Female, MESH: Gammapapillomavirus
Abstract

International audience; There are few contradictory studies investigating the involvement of HPV in melanoma. We designed a controlled study to evaluate the HPV DNA prevalence in melanoma. One hundred patients with cutaneous malignant melanoma diagnosed between 2002 and 2006 were included. Complementary wide excision (healthy skin) was performed in 85 patients and was used as internal control. After DNA extraction, 68 different HPV types were studied using a multiplex PCR combined with microarray primer extension. We did not observe any statistical significant difference in terms of HPV DNA prevalence in melanoma (38.8%) and in healthy skin from wide excision (42.4%). Twenty-one different HPV types were detected but only one type was present in the majority of our samples (80/85 melanoma vs 59/66 HS). The distribution of HPV genera and types was similar in melanoma and HS, and beta-HPV was predominant (30.6% and 31.8%). Among alpha-HPV (10.6%), high-risk mucosal HPV16 was predominant. Among beta-HPV, melanoma harboured significantly more type 22 than control normal skin from the same patients and significantly less type 21 than paired control normal skin. No correlation between clinical and pathological melanoma characteristics and HPV DNA prevalence was found. Our data do not support a role of HPV infection in melanocarcinogenesis, but confirm the previous data suggesting that HPV DNA is widely distributed among the population and that occult HPV infections are frequent. Furthermore, specific HPV types, such as a-HPV16 and beta-HPV species 2 may be involved in a sub-group of melanoma.

Published
2009
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47. From prenatal HIV testing of the mother to prevention of sexual HIV transmission within the couple

Author

Annick Tijou Traoré, Hermann Brou, Annabel Desgrées-du-Loû, Gérard Djohan, Valériane Leroy, Renaud Becquet, Mouillet, Evelyne, Centre population et développement (CEPED - UMR_D 196), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Ecole nationale supérieure de statistique et d'économie appliquée [Abidjan] (ENSEA), Aménagement, Développement, Environnement, Santé et Sociétés (ADES), Université Bordeaux Segalen - Bordeaux 2-Université Bordeaux Montaigne-Centre National de la Recherche Scientifique (CNRS), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, for the ANRS 1201/1202/1253 Ditrame Plus Group, Université Bordeaux Segalen - Bordeaux 2-Université Bordeaux Montaigne (UBM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Bordeaux Montaigne, Centre Population et Développement (CEPED), Institut national d'études démographiques (INED)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Centre Population et Développement, the ANRS 1201/1202/1253 Ditrame Plus Group, Centre population et développement ( CEPED - UMR_D 196 ), Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ), Ecole nationale supérieure de statistique et d'économie appliquée [Abidjan] ( ENSEA ), Aménagement, Développement, Environnement, Santé et Sociétés ( ADES ), Université Bordeaux Segalen - Bordeaux 2-Université Bordeaux Montaigne-Centre National de la Recherche Scientifique ( CNRS ), Institut de Santé Publique, d'Epidémiologie et de Développement ( ISPED ), and Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR99-ISPED

Subjects
Counseling, Male, Sexually transmitted disease, MESH: Sexual Behavior, MESH: Chi-Square Distribution, Health (social science), HIV Infections, MESH : Sexual Partners, COMMUNICATION, MESH : Interpersonal Relations, law.invention, MESH: Pregnancy, MESH : Sexual Behavior, GROSSESSE, Pregnancy, Risk Factors, MESH: Risk Factors, law, Prenatal Diagnosis, MESH: Sexual Partners, MESH : Female, Pregnancy Complications, Infectious, MESH : Infectious Disease Transmission, Vertical, SIDA, COUPLE, MESH: Counseling, virus diseases, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Follow-Up Studies, MESH: HIV Infections, MESH : Adult, MESH: Interpersonal Relations, MESH: Interviews as Topic, MESH : Risk Factors, MESH : Truth Disclosure, MESH : Counseling, MESH: Infectious Disease Transmission, Vertical, ENFANT, Sexual Partners, SANTE DE LA REPRODUCTION, Cohort, Female, MESH: Truth Disclosure, PRESERVATIF, EDUCATION SANITAIRE, Adult, MESH : Disease Transmission, Infectious, medicine.medical_specialty, Sexual transmission, MESH: Cote d'Ivoire, MESH : Male, SEROPOSITIVITE, Sexual Behavior, Context (language use), MESH: Disease Transmission, Infectious, Truth Disclosure, Interviews as Topic, History and Philosophy of Science, Condom, Acquired immunodeficiency syndrome (AIDS), MESH : HIV Infections, Disease Transmission, Infectious, medicine, Humans, Interpersonal Relations, MESH: Pregnancy Complications, Infectious, MESH: Prenatal Diagnosis, MESH : Prenatal Diagnosis, Gynecology, Chi-Square Distribution, MESH: Humans, MESH : Chi-Square Distribution, business.industry, Public health, MESH : Humans, MESH : Follow-Up Studies, MESH: Adult, MESH : Cote d'Ivoire, PREVENTION SANITAIRE, medicine.disease, Infectious Disease Transmission, Vertical, MESH: Male, MESH : Pregnancy, Cote d'Ivoire, MESH : Pregnancy Complications, Infectious, FEMME, DEPISTAGE, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Interviews as Topic, Family medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Serostatus, MESH: Female, Follow-Up Studies
Abstract

International audience; The first step in preventing mother-to-child HIV transmission (PMTCT) programmes is offering HIV counselling and testing to pregnant women. In developing countries where HIV testing remains rare, it represents a unique opportunity for many women to learn their HIV status. This prenatal HIV testing is not only the entry point to prevention of mother-to-child HIV transmission, but also an occasion for women to sensitize their male partner to sexual risks. Here we explore if these women, HIV-tested as mothers, apply the prevention recommendations they also receive as women. In the Ditrame Plus PMTCT program in Abidjan, Côte d'Ivoire, two cohorts of women (475 HIV-infected women and 400 HIV-negative women) were followed up two years after the pregnancy when they were offered prenatal HIV testing. In each cohort, we compared the proportion of women who communicated with their regular partner on sexual risks, prior to and after prenatal HIV testing. We analysed socio-demographic factors related to this communication. We measured two potential conjugal outcomes of women HIV testing: the level of condom use at sex resumption after delivery and the risk of union break-up. Prenatal HIV testing increased conjugal communication regarding sexual risks, whatever the woman's serostatus. This communication was less frequent for women in a polygamous union or not residing with their partner. Around 30% of women systematically used condoms at sex resumption. Among HIV infected ones, conjugal talk on sexual risks was related to improved condom use. After HIV testing, more HIV-infected women separated from their partners than HIV-uninfected women, despite very few negative reactions from the notified partners. In conclusion, offering prenatal HIV counselling and testing is an efficient tool for sensitizing women and their partners to HIV prevention. But sexual prevention in a conjugal context remains difficult and need to be specifically addressed.

Published
2009
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48. Couples, PMTCT programs and infant feeding decision-making in Ivory Coast

Author

Madina Querre, Valériane Leroy, Annabel Desgrées-du-Loû, Hermann Brou, Alice Desclaux, Annick Tijou Traoré, Aménagement, Développement, Environnement, Santé et Sociétés ( ADES ), Université Bordeaux Segalen - Bordeaux 2-Université Bordeaux Montaigne-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche Cultures, Santé, Sociétés (JE 2424) ( CReCSS ), Université Paul Cézanne - Aix-Marseille 3-JE2424, Ecole nationale supérieure de statistique et d'économie appliquée [Abidjan] ( ENSEA ), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre population et développement ( CEPED - UMR_D 196 ), Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ), Aménagement, Développement, Environnement, Santé et Sociétés (ADES), Université Bordeaux Segalen - Bordeaux 2-Université Bordeaux Montaigne (UBM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Cultures, Santé, Sociétés (JE 2424) (CReCSS), Ecole nationale supérieure de statistique et d'économie appliquée [Abidjan] (ENSEA), Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre population et développement (CEPED - UMR_D 196), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Bordeaux Montaigne, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Université Bordeaux Segalen - Bordeaux 2, Université Bordeaux Segalen - Bordeaux 2-Université Bordeaux Montaigne-Centre National de la Recherche Scientifique (CNRS), and Mouillet, Evelyne

Subjects
Male, MESH: Decision Making, Health (social science), MESH : Infant Nutritional Physiological Phenomena, HIV Infections, 0302 clinical medicine, ACTION SANITAIRE, Medicine, education.field_of_study, MESH: Middle Aged, SIDA, COUPLE, MESH: Sex Distribution, MESH : Infant, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: HIV Infections, MESH: Interviews as Topic, MESH: Infant, Project team, 3. Good health, Breast Feeding, ENFANT, SANTE DE LA REPRODUCTION, MESH: Young Adult, Spouse, MESH: Breast Feeding, MESH: Truth Disclosure, 0305 other medical science, Attitude to Health, medicine.medical_specialty, MESH: Cote d'Ivoire, MESH: Attitude to Health, MESH : Young Adult, Developing country, Truth Disclosure, Feeding Methods, 03 medical and health sciences, History and Philosophy of Science, MESH : HIV Infections, Humans, Interpersonal Relations, MESH : Middle Aged, education, MESH: Age Distribution, MESH: Humans, Public health, MESH : Humans, Infant, MESH : Feeding Methods, ALLAITEMENT MATERNEL, MESH: Adult, PREVENTION SANITAIRE, medicine.disease, Infectious Disease Transmission, Vertical, MESH : Attitude to Health, MESH : Interviews as Topic, MESH : Breast Feeding, ENQUETE, MESH: Female, Pediatrics, TRANSMISSION MERE ENFANT, MESH: Infant Nutritional Physiological Phenomena, MESH : Age Distribution, Breastfeeding, MESH : Interpersonal Relations, 5. Gender equality, MESH : Socioeconomic Factors, MESH : Female, 030212 general & internal medicine, Infant Nutritional Physiological Phenomena, MESH : Infectious Disease Transmission, Vertical, MESH : Sex Distribution, Family Characteristics, MESH: Feeding Methods, Middle Aged, MESH: Interpersonal Relations, MESH : Adult, MESH : Truth Disclosure, MESH: Infectious Disease Transmission, Vertical, Female, Adult, MESH: Socioeconomic Factors, TRANSMISSION, MESH : Male, Decision Making, Population, Interviews as Topic, SYSTEME DE REPRESENTATIONS, Young Adult, Age Distribution, Acquired immunodeficiency syndrome (AIDS), MESH: Family Characteristics, Sex Distribution, MESH : Family Characteristics, 030505 public health, business.industry, PARENT, MESH : Cote d'Ivoire, MESH: Male, MESH : Decision Making, Cote d'Ivoire, Socioeconomic Factors, FEMME, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Family medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Breast feeding
Abstract

International audience; In Sub-Saharan Africa, prevention of HIV pediatric infection due to breastfeeding requires turning to alternatives to prolonged breastfeeding: artificial feeding or exclusive breastfeeding with early weaning. Choosing a preventive option and applying it does not only depend upon the mother but also on the father and more specifically on couple interactions. To date, not enough studies have considered this question. In Abidjan, Ivory Coast, HIV-positive women and their infants were followed over two years in Ditrame Plus, a prevention of mother-to-child transmission (PMTCT) project. Using data from this project and from interviews conducted with couples and women, we analyzed the construction of decisions and practices concerning the application of preventive infant feeding options. Differences may be found between women and men in discourses regarding their attitudes, which are in part related to their conceptions of motherhood and fatherhood. We found that when men know their wife is HIV positive and are involved in the PMTCT project, they play an active role in applying the advice received. However, women do not always need the support of their spouse to undertake preventative behaviour. The project team also plays an important role in the adoption of such by women and men. The implementation of preventive options is a complex process in which three groups of actors (women, men and the project team) interact. In order to optimize PMTCT programs for couples, it is essential that this dynamic be taken into account.

Published
2009
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49. Coexpression of major histocompatibility complex class II with chemokines and nuclear NFκB p50 in melanoma: a rational for their association with poor prognosis

Author

Olivier Verola, Manuelle Viguier, Frédérique Deshayes, Jessica Lauriol, Dominique Charron, Isabelle Martins, Khaoussou Sylla, Catherine Alcaide-Loridan, Marie-Caroline Dieu-Nosjean, Reem Al-Daccak, Stephanie Ghislin, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Réponses immunes : régulation et développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Dermatologie, Université Paris, Service d'anatomo-pathologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIB-HOG, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)

Subjects
Male, MESH: NF-kappa B p50 Subunit, Cancer Research, Chemokine, Skin Neoplasms, MESH : Aged, MESH: NF-kappa B, MESH : Neoplasm Invasiveness, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Aged, 80 and over, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, Extracellular Signal-Regulated MAP Kinases, Melanoma, MESH: Extracellular Signal-Regulated MAP Kinases, Aged, 80 and over, MESH: Aged, Regulation of gene expression, MESH : Trans-Activators, 0303 health sciences, MESH : Prognosis, MESH: Middle Aged, Kinase, NF-kappa B, Nuclear Proteins, MESH: Gene Expression Regulation, Neoplastic, MESH : Adult, Middle Aged, Prognosis, MESH: Chemokines, MESH : Extracellular Signal-Regulated MAP Kinases, Gene Expression Regulation, Neoplastic, Oncology, MESH : NF-kappa B, 030220 oncology & carcinogenesis, Disease Progression, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Disease Progression, Chemokines, Matrix Metalloproteinase 1, Adult, Proto-Oncogene Proteins B-raf, MESH: Cell Line, Tumor, P50, MESH : Gene Expression Regulation, Neoplastic, MESH: Melanoma, MESH: Trans-Activators, MESH : Male, MESH : Melanoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, Biology, MESH: Prognosis, 03 medical and health sciences, MESH : HLA-DR Antigens, Cell Line, Tumor, Extracellular, medicine, Humans, MESH : Middle Aged, MESH : Chemokines, Neoplasm Invasiveness, MESH : Aged, 80 and over, Protein kinase A, MESH : Proto-Oncogene Proteins B-raf, Aged, 030304 developmental biology, MESH: Proto-Oncogene Proteins B-raf, MESH: Humans, MESH : Matrix Metalloproteinase 1, MESH : Cell Line, Tumor, MESH: Skin Neoplasms, MESH : Humans, MESH : Skin Neoplasms, MESH: Biological Markers, MESH : Nuclear Proteins, NF-kappa B p50 Subunit, MESH: Adult, MESH : Disease Progression, HLA-DR Antigens, MESH: Neoplasm Invasiveness, MESH: HLA-DR Antigens, medicine.disease, MESH: Male, MESH : Biological Markers, MESH: Matrix Metalloproteinase 1, MESH : NF-kappa B p50 Subunit, Tumor progression, Immunology, Trans-Activators, biology.protein, MESH: Nuclear Proteins, MESH: Female, Biomarkers
Abstract

International audience; The constitutive expression of major histocompatibility complex class II (MHC II) molecules in melanoma is highly unusual and has been associated with unfavorable clinical outcome and higher metastatic dissemination. This association remains poorly understood and therefore, in this study we looked to whether it is caused by intracellular events that promote tumor progression. We previously reported that MHC II expression in melanoma cells requires active mitogen-activated protein kinase/extracellular signal-related kinase. However, our comparative and molecular analyses of a panel of melanoma cell lines herein provide clear evidence that mitogen-activated protein kinase/extracellular signal-related kinase is not sufficient for HLA-DR expression. We found that the expression of HLA-DR in these tumors rather coincides with the expression of CXCL-1 and CXCL-8 chemokines, both known to be expressed in tumors that invade early and are related to invasive stages of melanoma. The expression of HLA-DR also nicely paralleled that of the nuclear NFkappaB p50 subunit, regulating the expression of these chemokines in melanoma and previously correlated with poor prognosis of melanoma patients, although we provide evidence that NFkappaB is not directly regulating MHC II expression level. The molecular basis for class II transactivator and HLA-DR expression in melanoma therefore remains unsolved, but our findings linking together the expression of HLA-DR, of chemokines involved in invasiveness, and of nuclear NFkappaB p50 strongly support the content that MHC II may be a marker of invasive primary melanoma, and could explain the long-standing association of MHC II expression with overall poor prognosis and unfavorable clinical outcome.

Published
2009
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50. Epidemiology of ischemic stroke from atrial fibrillation in Dijon, France, from 1985 to 2006

Author

Thibault Moreau, Yves Cottin, Guy-Victor Osseby, Christine Marie, Jérôme Durier, M. Giroud, Yannick Béjot, D. Ben Salem, G. Couvreur, Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Département de radiologie [Brest] (DR - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Département de radiologie [Brest] ( DR - Brest ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Groupe d'Etude de la Thrombose de Bretagne Occidentale ( GETBO ), Université de Brest ( UBO ), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] ( IBMM ), and Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
Male, MESH : Stroke, MESH: Registries, [SDV]Life Sciences [q-bio], MESH : Aged, MESH : Prospective Studies, 030204 cardiovascular system & hematology, Rate ratio, Brain Ischemia, MESH: Aged, 80 and over, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Atrial Fibrillation, MESH: Fibrinolytic Agents, MESH : Female, Prospective Studies, Registries, Myocardial infarction, Prospective cohort study, Stroke, MESH: Aged, Aged, 80 and over, education.field_of_study, MESH: Middle Aged, Cerebral infarction, Incidence (epidemiology), MESH: Brain Ischemia, Atrial fibrillation, MESH : Adult, Middle Aged, MESH : Survival Rate, MESH : Risk Factors, 3. Good health, Survival Rate, MESH: Atrial Fibrillation, Cardiology, Female, France, Adult, medicine.medical_specialty, MESH: Survival Rate, MESH : Male, Population, MESH: Stroke, 03 medical and health sciences, Fibrinolytic Agents, Internal medicine, medicine, Humans, MESH : Middle Aged, cardiovascular diseases, MESH : Aged, 80 and over, MESH : France, education, Aged, MESH: Humans, [ SDV ] Life Sciences [q-bio], business.industry, MESH : Humans, MESH : Fibrinolytic Agents, MESH: Adult, medicine.disease, MESH: Male, MESH: Prospective Studies, Surgery, MESH: France, MESH : Atrial Fibrillation, MESH : Brain Ischemia, Neurology (clinical), business, MESH: Female, MESH : Registries, 030217 neurology & neurosurgery
Abstract

Background: Atrial fibrillation (AF) is strongly associated with age, and epidemiologic studies are needed to evaluate the impact of both aging of the population and the use of anticoagulant therapy in patients with AF on the incidence of cardioembolic stroke with AF (CE/AF stroke). Methods: We evaluated trends in incidence rates, risk factors, prestroke therapy, and survival in CE/AF stroke from a prospective population-based registry, from 1985 to 2006. Results: A total of 3,064 ischemic strokes, including 572 (18.7%) CE/AF strokes, were recorded. Over the 22 years, a decrease in the incidence of overall CE/AF stroke was noted (incidence rate ratio 0.9858, 95% confidence interval [CI] 0.9731–0.9986; p = 0.03). We observed a higher prevalence of previous AF, previous myocardial infarction, and patients aged >70 years in CE/AF stroke ( p p = 0.003). A significant increase in the use of anticoagulants and antiplatelet agents was noted, and was particularly pronounced for CE/AF stroke with previous AF. For CE/AF stroke, survival rates were 72% at 1 month (95% CI 0.68–0.76), 52% at 1 year (95% CI 0.48–0.56), and 43% at 2 years (95% CI 0.39–0.48), and remained lower than those of other ischemic stroke. Conclusions: The decrease in the incidence of cardioembolic/atrial fibrillation stroke in our study was probably due to a slight increase in the utilization of antithrombotic therapy in patients with atrial fibrillation, but the use of such therapies will have to increase further because of the expected aging of the population in coming years. AF = atrial fibrillation; CE = cardioembolic; CI = confidence interval; IRR = incidence rate ratios.

Published
2009
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