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1,205 results on '"CHU Lyon"'

301. Identification clinique par spectrométrie de masse MALDI-TOF des champignons filamenteux : construction de banques de données pour les dermatophytes et les Fusarium

Author: Geraldine Lucchi, David Rageot, Sorez, M., Marc Sautour, Frédéric Dalle, Caillot, D., Ducoroy, P., ProdInra, Migration, Clinical Innovation Proteomic Platform, Partenaires INRAE, Agroécologie [Dijon], 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, Hématologie clinique, CHU Lyon, and Société Française de Spectrométrie de Masse (SFSM). FRA.
Subjects: MALDI-TOF, [SDV] Life Sciences [q-bio], [SDE] Environmental Sciences, dermatophytes, [SDV]Life Sciences [q-bio], [SDE]Environmental Sciences, champignons filamentaux, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, [SDV.BV] Life Sciences [q-bio]/Vegetal Biology, fusarium
Published: 2015

302. The effect of methylphenidate on neurofibromatosis type 1: a randomised, double-blind, placebo-controlled, crossover trial

Author: Stéphane Pinson, Virginie Coutinho, Catherine Mercier, Valentine Bréant, François Gueyffier, Patrick Combemale, Daniel Gérard, Laurence Lion-François, Isabelle Kemlin, Behrouz Kassai, Emeline Peyric, Vania Herbillon, Tiphanie Ginhoux, Vincent des Portes, Diana Rodriguez, Hopital Neurologique , Bron, Département de Neurologie, Hopital Neurologique, Bron-Hopital Neurologique, Bron, Service de neurologie pédiatrique, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Réseau NF1 Rhône alpes Auvergne IHOP, 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 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), Université de Lyon, Dpt psychiatrie de l'enfant [CHU Lyon], Groupement Hospitalier Lyon-Est (GHE), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pharmacologie Clinique (EPICIME), service pharmaceutique, Hospices Civils de Lyon, Laboratoire de génétique humaine [CHU Herriot], Hôpital Edouard Herriot [CHU - HCL], HAL UPMC, Gestionnaire, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Groupement hospitalier Lyon-Est
Subjects: Male, congenital, hereditary, and neonatal diseases and abnormalities, Pediatrics, medicine.medical_specialty, Neurofibromatosis 1, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Randomised controlled trials, Placebo, behavioral disciplines and activities, law.invention, Neurofibromatosis, Double blind, Attention deficit hyperactivity disorder, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, law, mental disorders, medicine, Humans, Genetics(clinical), Pharmacology (medical), 030212 general & internal medicine, Child, Genetics (clinical), Medicine(all), Cross-Over Studies, Dose-Response Relationship, Drug, Methylphenidate, business.industry, Research, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, General Medicine, medicine.disease, Crossover study, Treatment Outcome, Learning disability, Female, medicine.symptom, business, 030217 neurology & neurosurgery, medicine.drug, Follow-Up Studies
Abstract: et Réseau NF1 Rhône Alpes Auvergne-France; International audience; Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with an estimated prevalence of about 1/3000, independent of ethnicity, race, or gender. Attention Deficit Hyperactivity like Disorder (ADHD)-like characteristics are often reported in patients with NF1. We hypothesised that learning disabilities in NF1 children were related to ADHD symptoms. Treatment with methylphenidate (MPD) has improved learning disabilities in ADHD by acting on neurotransmitters. Our objective was to evaluate its efficacy on ADHD-like symptoms in neurofibromatosis type 1 children (7–12 years).Methods: This was a randomised, double blind, placebo controlled, and crossover trial comparing 0.5 to 0.8 mg/kg/d of MPD as it is indicated for ADHD to placebo in NF1 children with ADHD-like symptoms. Children aged 7 to 12 years were eligible when their IQ was between 80 and 120. The total follow-up was 9 weeks including 4 weeks for each period and 1 week wash out. Fifty subjects (25 for each period) were required for testing the primary study hypothesis. The main outcome was an improvement in scores on the simplified Conners' Parent Rating Scale.Results: Thirty-nine patients were included between April 2004 and December 2010. Twenty participants received MPD and 19 placebo during the first period. They all completed the trial. MPD decreased the simplified Conners by 3.9 points (±1.1, p = 0. 0003).Conclusions: This is the first randomised controlled trial showing the short-term benefit of MPD on simplified Conners scores in NF1 children.
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303. Concordance Rate Differences of 3 Noninvasive Imaging Techniques to Measure Carotid Stenosis in Clinical Routine Practice

Author: Philippe Douek, Bernard Langella, Michel Lamure, Bruno Guias, Carmen Rotaru, Pierre Gouny, Norbert Nighoghossian, Valérie Buthion, Pierre Chirossel, Jean François Heautot, Jean Michel Serfaty, Michel Nonent, Chahin Pachai, Laurent Derex, Jean-Yves Gauvrit, Charles Veyret, Isabelle Jars, François Rouhart, 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), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Cerebrovascular Unit [Lyon], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Neurologie [Brest], Service de Neurologie [Lyon], CHU Lyon, Service de Radiologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Service de radiologie et imagerie médicale [Rennes] = Radiology [Rennes], CHU Pontchaillou [Rennes], Service de chirurgie thoracique et cardio vasculaire [Brest] (CCTV - Brest), COACTIS (COACTIS), Université Jean Monnet [Saint-Étienne] (UJM)-Université Lumière - Lyon 2 (UL2), Laboratoire d'analyse des systèmes de santé (LASS), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon, Theralys [Lyon], Theralys, Service de radiologie [Saint-Etienne], CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM), Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Plateforme neurinfo [Rennes], Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), Université Claude Bernard Lyon 1 (UCBL), 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)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), COnception de l'ACTIon en Situation (COACTIS), Université Lumière - Lyon 2 (UL2)-Université Jean Monnet - Saint-Étienne (UJM), Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de Radiologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_treatment, MESH: Magnetic Resonance Angiography, MESH: Ultrasonics, Carotid endarterectomy, Magnetic resonance angiography, 030218 nuclear medicine & medical imaging, MESH: Aged, 80 and over, 0302 clinical medicine, MESH: Carotid Stenosis, Carotid Stenosis, Ultrasonics, Prospective Studies, Stroke, Ultrasonography, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, medicine.diagnostic_test, Middle Aged, MESH: Predictive Value of Tests, MESH: Reproducibility of Results, Predictive value of tests, Female, Radiology, MESH: Image Enhancement, MESH: Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, psychological phenomena and processes, medicine.medical_specialty, Concordance, 03 medical and health sciences, Predictive Value of Tests, medicine, Humans, cardiovascular diseases, Aged, Advanced and Specialized Nursing, MESH: Humans, business.industry, Reproducibility of Results, Digital subtraction angiography, Image Enhancement, medicine.disease, MESH: Prospective Studies, MESH: Male, Stenosis, Angiography, Neurology (clinical), Tomography, X-Ray Computed, business, MESH: Female, Magnetic Resonance Angiography, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: Background and Purpose— To replace digital subtraction angiography (DSA) in carotid stenosis evaluation, noninvasive imaging techniques have to reach a high concordance rate. Our purpose is to compare the concordance rates of contrast-enhanced MR angiography (CEMRA) and CT angiography (CTA) with Doppler ultrasound (DUS) in clinical routine practice. Methods— We evaluated prospectively with DUS, CEMRA, and CTA 150 patients suspected of carotid stenosis. The overall concordance rates of the 3 techniques were calculated for symptomatic stenosis ≥50% and ≥70%, for asymptomatic stenosis ≥60%, and for occlusion. For the carotid arteries treated by surgery (n=97), the results of each method and combined techniques were recorded, and misclassification rates were evaluated from surgical reports. Results— The overall concordance rates of DUS-CEMRA, DUS-CTA, and CEMRA-CTA were not statistically different. However, the concordance rate of DUS-CEMRA (92.53%) was significantly higher than that for DUS-CTA (79.10%) in the surgical asymptomatic stenosis group ( P =0.0258). CTA considered alone would misclassify the stenosis in a significant number of cases (11 of 64) in the surgical asymptomatic group compared with CEMRA (3 of 67) and DUS (1 of 66) ( P =0.0186 versus MRA, P =0.0020 versus DUS). Conclusions— With the techniques as utilized in our study, the overall concordance rates of combined noninvasive methods are similar for measuring carotid stenosis in clinical routine practice, but in asymptomatic carotid stenosis, the decision making for surgery is significantly altered if DUS and CTA are considered in place of DUS and CEMRA.
Published: 2004
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304. Mathematical model of T-cell lymphoblastic lymphoma: disease, treatment, cure or relapse of a virtual cohort of patients

Author: N, Eymard, V, Volpert, P, Kurbatova, N, Bessonov, K, Ogungbenro, L, Aarons, P, Janiaud, P, Nony, A, Bajard, S, Chabaud, Y, Bertrand, B, Kassaï, C, Cornu, Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Multi-scale modelling of cell dynamics : application to hematopoiesis (DRACULA), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Camille Jordan [Villeurbanne] (ICJ), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Modélisation mathématique, calcul scientifique (MMCS), 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), Institute of Mechanical Engineering Problems, Centre for Applied Pharmacokinetic Research, University of Manchester [Manchester], Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [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), Unité de Biostatistique et d'Evaluation des Thérapeutiques (UBET), Centre Léon Bérard [Lyon], Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-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), Institut Camille Jordan (ICJ), 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)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Camille Jordan (ICJ), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut Camille Jordan [Villeurbanne] ( ICJ ), École Centrale de Lyon ( ECL ), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 ( UCBL ), 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 ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Centre National de la Recherche Scientifique ( CNRS ), Multi-scale modelling of cell dynamics : application to hematopoiesis ( DRACULA ), Centre de génétique et de physiologie moléculaire et cellulaire ( CGPhiMC ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut Camille Jordan [Villeurbanne] ( ICJ ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Centre National de la Recherche Scientifique ( CNRS ) -École Centrale de Lyon ( ECL ), 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 ), Unité de Biostatistique et d'Evaluation des Thérapeutiques ( UBET ), Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] ( ICMUB ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Volpert, Vitaly
Subjects: 0301 basic medicine, Pediatrics, medicine.medical_specialty, medicine.medical_treatment, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, chemotherapy, General Biochemistry, Genetics and Molecular Biology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, [ MATH.MATH-AP ] Mathematics [math]/Analysis of PDEs [math.AP], [SDV.CAN] Life Sciences [q-bio]/Cancer, Maintenance therapy, thymus, T-cell lymphoblastic lymphoma, medicine, Humans, cancer, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], Computer Simulation, mathematical modelling, [MATH.MATH-AP] Mathematics [math]/Analysis of PDEs [math.AP], education, randomized controlled clinical trial, General Environmental Science, Pharmacology, Chemotherapy, education.field_of_study, General Immunology and Microbiology, business.industry, Applied Mathematics, General Neuroscience, Lymphoblastic lymphoma, Cancer, General Medicine, Models, Theoretical, medicine.disease, 3. Good health, Lymphoma, Surgery, Clinical trial, 030104 developmental biology, Modeling and Simulation, Cohort, Disease Progression, business
Abstract: International audience; T lymphoblastic lymphoma (T-LBL) is a rare type of lymphoma with a good prognosis with a remission rate of 85%. Patients can be completely cured or can relapse during or after a 2-year treatment. Relapses usually occur early after the remission of the acute phase. The median time of relapse is equal to 1 year, after the occurrence of complete remission (range 0.2–5.9 years) (Uyttebroeck et al., 2008). It can be assumed that patients may be treated longer than necessary with undue toxicity. The aim of our model was to investigate whether the duration of the maintenance therapy could be reduced without increasing the risk of relapses and to determine the minimum treatment duration that could be tested in a future clinical trial. We developed a mathematical model of virtual patients with T-LBL in order to obtain a proportion of virtual relapses close to the one observed in the real population of patients from the EuroLB database. Our simulations reproduced a 2-year follow-up required to study the onset of the disease, the treatment of the acute phase and the maintenance treatment phase.
Published: 2017
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305. OFSEP, a nationwide cohort of people with multiple sclerosis: Consensus minimal MRI protocol

Author: Amélie, Roxana, Anxionnat, René, Armspach, Jean-Paul, Audoin, Bertrand, Barillot, Christian, Berry, Isabelle, Bonneville, Fabrice, Boutet, Claire, Castelnovo, Giovanni, Cervenansky, Frédéric, Cohen, Mikael, Commowick, Olivier, Cotton, François, de Seze, Jérôme, Dousset, Vincent, Durand-Dubief, Françoise, Edan, Gilles, Ferre, Jean-Christophe, Galanaud, Damien, Glattard, Tristan, Grand, Sylvie, Guillaumont, Justine, Guillevin, Rémy, Guttmann, Charles, Hannoun, Salem, Heitz, Fabrice, Krainik, Alexandre, Kremer, Stéphane, Labauge, Pierre, Menjot de Champfleur, Nicolas, Ranjeva, Jean-Philippe, Roch, Jean-Amédée, Sappey-Marinier, Dominique, Savatovsky, Julien, Stankoff, Bruno, Tourdias, Thomas, Tourbah, Ayman, Vukusic, Sandra, Département de Neuroradiologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Visual Augmentation of Complex Environments (MAGRIT), INRIA Lorraine, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université Henri Poincaré - Nancy 1 (UHP)-Université Nancy 2-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS)-Université Henri Poincaré - Nancy 1 (UHP)-Université Nancy 2-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neuroimagerie in Vivo (LNV), CHU Strasbourg-Centre National de la Recherche Scientifique (CNRS), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris 1 Panthéon-Sorbonne (UP1), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-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)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Euromov (EuroMov), Université de Montpellier (UM), Service Informatique et développements, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), 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)-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 Claude Bernard Lyon 1 (UCBL), 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), Espaces, Nature et Culture (ENeC), Université Paris-Sorbonne (UP4)-Centre National de la Recherche Scientifique (CNRS), RMN et optique : De la mesure au biomarqueur, Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [Lyon], CHU Lyon, Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Service de radiologie et imagerie médicale [Rennes] = Radiology [Rennes], Neuro-imagerie fonctionnelle et métabolique (ANTE-INSERM U836, équipe 5), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Center for Neurological Imaging, Departments of Radiology and Neurology, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Département de neuro-radiologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de Neuroradiologie[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Service de Radiologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), 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), Fondation Ophtalmologique Adolphe de Rothschild [Paris], CHU Saint-Antoine [AP-HP], Service Hospitalier Frédéric Joliot (SHFJ), 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), Neurocentre Magendie-U862, Institut François Magendie, and Université de Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), [GIN] Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), CHU Toulouse [Toulouse], 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)-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), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neuroradiologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-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)-Inria de Paris, 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)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), 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), 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, Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique de Lorraine (INPL)-Université Nancy 2-Université Henri Poincaré - Nancy 1 (UHP)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique de Lorraine (INPL)-Université Nancy 2-Université Henri Poincaré - Nancy 1 (UHP), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Inria de Paris, 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 Claude Bernard Lyon 1 (UCBL), 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), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: medicine.medical_specialty, Consensus, Multiple Sclerosis, Population, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Medical physics, education, Protocol (science), education.field_of_study, Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, Multiple sclerosis, Consensus development conferences as topic, Brain, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Workflow, Spinal Cord, Cohort, Physical therapy, Cohort studies, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, Working group, 030217 neurology & neurosurgery, Cohort study
Abstract: International audience; Multiple sclerosis (MS) is most generally considered as a severe disease with high physical and mental risks of disability. Since the end of the 1990s, several high cost long-term disease-modifying treatments provided some clinical efficiency. However, patient's follow-up was needed for the detection and the assessment of their side-effects. The “Observatoire français de la sclérose en plaques” (OFSEP) project aims to improve the clinical, biological and imaging systematic longitudinal follow-up of patients. It should increase the quality, efficiency and safety of patients’ care, with a unique opportunity of large scale, about 41,000 patients followed in 62 French centers using the European Database for Multiple Sclerosis (EDMUS) software. OFSEP is divided into three working groups (clinical, biological and imaging). The imaging working group defines standards for routine MRI follow-up in the whole cohort and contains three subgroups: acquisition, workflow, and data processing. A common and feasible brain and spinal cord acquisition protocol has been defined by the acquisition group, and accepted by the OFSEP steering and scientific committees. This protocol can be implemented in all French MRI centers. The major MRI manufacturers have agreed to provide the dedicated collection of sequences as an “OFSEP box” with every software upgrade or new MRI machine. The new OFSEP protocol will provide a unique opportunity to study a population-based collection of data from people with MS.
Published: 2014
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306. A Phase I Study of Clofarabine With Multiagent Chemotherapy in Childhood High Risk Relapse of Acute Lymphoblastic Leukemia (VANDEVOL Study of the French SFCE Acute Leukemia Committee)

Author: Nelken, Brigitte, Cavé, Hélène, Leverger, Guy, Galambrun, Claire, Plat, Genevieve, Schmitt, Claudine, Thomas, Caroline, Vérité, Cecile, Brethon, Benoit, Gandemer, Virginie, Bertrand, Yves, Baruchel, André, Rohrlich, Pierre, Pôle Enfant, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille Nord (France), Département de génétique [Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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 [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Pellegrin Tripode, Pediatric Onco-Hematology Unit, CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hématologie et immunologie pédiatrique, Hospices Civils de Lyon (HCL)-CHU Lyon-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hôpital Femme-Mère-Enfant (HFME), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Direction de la Recherche Clinique du CHRU de Lille, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, and Jonchère, Laurent
Subjects: Male, Salvage Therapy, Adolescent, Dose-Response Relationship, Drug, Maximum Tolerated Dose, Adenine Nucleotides, [SDV]Life Sciences [q-bio], acute lymphoblastic leukemia, phase I, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Dexamethasone, [SDV] Life Sciences [q-bio], Young Adult, resistant disease, Child, Preschool, Antineoplastic Combined Chemotherapy Protocols, Asparaginase, Humans, Female, Arabinonucleosides, Mitoxantrone, Neoplasm Recurrence, Local, Child, Clofarabine, Etoposide
Abstract: International audience; BACKGROUND: Current outcome of very early relapse of acute lymphoblastic leukemia (ALL) in children remains poor. As a single agent, clofarabine provided a response rate of 26% in childhood ALL second relapse and, in combination with cyclophosphamide and etoposide, a 44% complete remission and complete remission without platelet recovery (CR+CRp) rate. Further multi-drug combinations need to be investigated. We used the VANDA regimen as a template, cytarabine being replaced by clofarabine. PATIENTS AND METHODS: A phase I study combining escalating doses of clofarabine (25% increments from 20 to 40 mg/m(2) /d) with fixed doses of mitoxantrone, etoposide, asparaginase, and dexamethasone was undertaken in children presenting with very early or second or post-transplant ALL relapse. RESULTS: Twenty patients were enrolled, 19 were evaluable. Four patients had previously been allografted. Dose-limiting toxicity (DLT) appeared at dose level 3 (32 mg/m(2) ), one out of six patients experienced a liver DLT. At dose level 4 (40 mg/m(2) ), four DLT occurred (two fungal infection and two liver DLT). The maximum tolerated dose (MTD) of clofarabine was thus determined to be 32 mg/m(2) . There was no toxic death. Eleven (57.9%) patients achieved a CR. Six patients proceeded to allogeneic stem cell transplantation. CONCLUSION: Clofarabine MTD was 32 mg/m(2) /d in this combination which appeared feasible and effective in this population. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc
Published: 2014
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307. A methodological framework for drug development in rare diseases

Author: Polina Kurbatova, Charlotte Castellan, Salma Malik, Patrice Nony, Agathe Bajard, Behrouz Kassai, Nathalie Eymard, Sylvie Chabaud, Catherine Cornu, Vitaly Volpert, CCSD, Accord Elsevier, 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 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), Unité de Biostatistique et d'Evaluation des Thérapeutiques (UBET), Centre Léon Bérard [Lyon], CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Multi-scale modelling of cell dynamics : application to hematopoiesis (DRACULA), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), 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)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Modélisation mathématique, calcul scientifique (MMCS), Institut Camille Jordan [Villeurbanne] (ICJ), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Camille Jordan (ICJ), Institut Camille Jordan (ICJ), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Inria Grenoble - Rhône-Alpes, Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Research design, medicine.medical_specialty, Orphan Drug Production, Computer science, education, Drug development, Translational research, Review, Pharmacology, Clinical trial simulation, law.invention, Orphan drug, 03 medical and health sciences, Rare Diseases, 0302 clinical medicine, Randomized controlled trial, law, medicine, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], Humans, Genetics(clinical), Pharmacology (medical), Medical physics, 030212 general & internal medicine, [MATH.MATH-AP] Mathematics [math]/Analysis of PDEs [math.AP], Genetics (clinical), 030304 developmental biology, Medicine(all), Clinical Trials as Topic, 0303 health sciences, business.industry, General Medicine, 3. Good health, Integrative modeling, Clinical trial, Research Design, Personalized medicine, business
Abstract: Introduction Developing orphan drugs is challenging because of their severity and the requisite for effective drugs. The small number of patients does not allow conducting adequately powered randomized controlled trials (RCTs). There is a need to develop high quality, ethically investigated, and appropriately authorized medicines, without subjecting patients to unnecessary trials. Aims and Objectives The main aim is to develop generalizable framework for choosing the best-performing drug/endpoint/design combinations in orphan drug development using an in silico modeling and trial simulation approach. The two main objectives were (i) to provide a global strategy for each disease to identify the most relevant drugs to be evaluated in specific patients during phase III RCTs, (ii) and select the best design for each drug to be used in future RCTs. Methodological approach In silico phase III RCT simulation will be used to find the optimal trial design and was carried out in two steps: (i) statistical analysis of available clinical databases and (ii) integrative modeling that combines mathematical models for diseases with pharmacokinetic-pharmacodynamics models for the selected drug candidates. Conclusion There is a need to speed up the process of orphan drug development, develop new methods for translational research and personalized medicine, and contribute to European Medicines Agency guidelines. The approach presented here offers many perspectives in clinical trial conception.
Published: 2014
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308. The importance of EN ISO 15189 accreditation of allergen-specific IgE determination for reliable in vitro allergy diagnosis

Author: C. Lainé, Thierry Tabary, Marie-Hélène Vivinus, D. Mariotte, E. Treiner, Remy Couderc, C. Capron, Béatrice Uring-Lambert, D. Jaby, Brigitte Evrard, Claude Lambert, Caroline Hémont, Françoise Bienvenu, Pascale Nicaise-Roland, Marie-Alexandra Alyanakian, Séverine Brabant, Jean Martinet, Joana Vitte, Gilles Renier, P.A. Apoil, F. Witthuhn, M. Lelong, C. Vigneron, J. Sainte-Laudy, Anne Sarrat, CHU Saint-Etienne, Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], CHU Toulouse [Toulouse], Hôpital Ambroise Paré [AP-HP], CHU Clermont-Ferrand, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pontchaillou [Rennes], Centre Hospitalier Le Mans (CH Le Mans), Centre Hospitalier Universitaire Clémenceau (CHU Clémenceau ), CHU Rouen, Normandie Université (NU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Dupuytren [CHU Limoges], Hôpital Robert Debré, CHU Amiens-Picardie, CHU Strasbourg, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital l'Archet, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Médecine interne et immunologie clinique [Hôpital de la Conception - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux [Bordeaux], CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), and Université d'Angers (UA)
Subjects: MESH: Fluoroimmunoassay / standards, Analyte, Allergy, [SDV]Life Sciences [q-bio], Immunology, Fluoroimmunoassay, allergen-specific serum IgE, medicine.disease_cause, Immunoglobulin E, Sensitivity and Specificity, accreditation, MESH: Fluoroimmunoassay / methods, Allergen, immune system diseases, medicine, Hypersensitivity, Immunology and Allergy, Humans, MESH: Hypersensitivity / immunology, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Allergen specific IgE, Accreditation, MESH: Hypersensitivity / epidemiology, Reproducibility, MESH: Immunoglobulin E / immunology, MESH: Humans, biology, business.industry, Reproducibility of Results, Repeatability, MESH: Allergens / immunology, Allergens, medicine.disease, EN ISO 15189, MESH: Sensitivity and Specificity, 3. Good health, respiratory tract diseases, MESH: Reproducibility of Results, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, MESH: Hypersensitivity / diagnosis
Abstract: Background Allergen-specific serum immunoglobulin E detection and quantification have become an important step in allergy diagnosis and follow-up. In line with the current trend of laboratory test accreditation to international standards, we set out to design and assess an accreditation procedure for allergen-specific serum IgE. Methods Method validation according to the accreditation procedure under the EN ISO 15189 standard was carried out for allergen-specific immunoglobulin E determination using the fluoroimmunoenzymatic method ImmunoCAP® (ThermoFisher). Data were produced by 25 hospital laboratories in France. A total of 29 allergen specificities including mixes, extracts, and molecular allergens were assayed. Allergen-specific serum immunoglobulin E concentrations ranged from 0.1 to 100 kUA/l. Results Repeatability, reproducibility, and accuracy results fulfilled method validation criteria for automated laboratory tests and proved similar irrespective of the allergen specificity, allergen-specific serum immunoglobulin E concentration, or individual laboratory. Conclusion Allergen-specific serum immunoglobulin E determination with the fluoroimmunoenzymatic method ImmunoCAP® is a highly repeatable, reproducible, and accurate method which may be considered as a single analyte assay in view of the EN ISO 15189 accreditation procedure.
Published: 2014
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309. Pathophysiology of urticaria

Author: Nosbaum, Audrey, Augey, F., Nicolas, Jean-François, Bérard, Frédéric, Immunologie de l'allergie cutanée et vaccination – Immunology of skin allergy and vaccination, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS 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), Département d'allergie et d'immunologie clinique [CHU Lyon Sud], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-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)-École normale supérieure de Lyon (ENS de Lyon)-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: Hypersensitivity, Immediate, Leukotrienes, Immediate, Urticaria, T-Lymphocytes, Histamine Release, Pathophysiology, Antibodies, Cell Degranulation, Mast cell, Xenobiotics, immune system diseases, Models, Hypersensitivity, Humans, Immune Complex Diseases, Innate, Mast Cells, skin and connective tissue diseases, Autoantibodies, Physiopathologie, Models, Immunological, Hypersensibilité, Immunity, Immunoglobulin E, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Immunity, Innate, Antibodies, Anti-Idiotypic, Urticaire, Anti-Idiotypic, Immunological, Immunoglobulin G, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Prostaglandins, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Mastocyte, Histamine
Abstract: International audience; Urticaria is a dermal edema resulting from vascular dilatation and leakage of fluid into the skin in response to molecules released from mast cells. The major mediator responsible for urticaria is histamine. However, the clinical spectrum and pattern of lesions indicate that other molecules, including prostaglandins, leukotrienes, cytokines, and chemokines, produced at different times after mast cell activation contribute to the polymorphism of this symptom and the variable evolution of this disease. It is a common practice to distinguish immunological and nonimmunological urticaria. Immunological urticaria is a hypersensitivity reaction mediated by antibodies and/or T-cells that results in mast cell activation. Although immunoglobulin (Ig) E-mediated type I hypersensitivity (HS) was long postulated to be the major immunological pathway associated with mast cell activation, interaction between IgEbound mast cells and allergens is unlikely to be the mechanism by which urticaria develops in most patients. It is now well established that urticaria may result from the binding of IgG auto-antibodies to IgE and/or to the receptor for IgE molecules on mast cells, thus corresponding to a type II HS reaction. These auto-immune urticarias represent up to 50 % of patients with chronic urticaria. Mast cell activation can also result from type III HS through the binding of circulating immune complexes to mast cell-expressing Fc receptors for IgG and IgM. Finally, under certain circumstances, T-cells can induce activation of mast cells, as well as histamine release (type IV HS). Nonimmunological urticarias result from mast cell activation through membrane receptors involved in innate immunity (e.g., complement, Toll-like, cytokine/chemokine, opioid) or by direct toxicity of xenobiotics (haptens, drugs). In conclusion, urticaria may result from different pathophysiological mechanisms that explain the great heterogeneity of clinical symptoms and the variable responses to treatment.
Published: 2014
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310. Vestibular responses to direct stimulation of the human insular cortex

Author: Mazzola, Laure, Lopez, Christophe, Faillenot, Isabelle, Chouchou, Florian, Mauguière, François, Isnard, Jean, Centre de recherche en neurosciences de Lyon (CRNL), 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), Laboratoire de Neurosciences intégratives et adaptatives (LNIA), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie Fonctionnelle et d'Épileptologie, Hospices Civils de Lyon (HCL), CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Lopez, Christophe, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), 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), Service de neurologie fonctionnelle et d'épileptologie, Hospices Civils de Lyon (HCL)-Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], and Hospices Civils de Lyon (HCL)-Université de Lyon
Subjects: nervous system, otorhinolaryngologic diseases, behavior and behavior mechanisms, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], behavioral disciplines and activities, psychological phenomena and processes, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; Objective: The present study provides a functional mapping of vestibular responses in the human insular cortex. Methods: A total of 642 electrical stimulations of the insula were performed in 219 patients, using stereotactically implanted depth electrodes, during the presurgical evaluation of drug-refractory partial epilepsy. We retrospectively identified 41 contacts where stimulation elicited vestibular sensations (VSs) and analyzed their location with respect to (1) their stereotactic coordinates (for all contacts), (2) the anatomy of insula gyri (for 20 vestibular sites), and (3) the probabilistic cytoarchitectonic maps of the insula (for 9 vestibular sites). Results: VSs occurred in 7.6% of the 541 evoked sensations after electrical stimulations of the insula. VSs were mostly obtained after stimulation of the posterior insula, that is, in the granular insular cortex and the postcentral insular gyrus. The data also suggest a spatial segregation of the responses in the insula, with the rotatory and translational VSs being evoked at more posterior stimulation sites than other less definable VSs. No left-right differences were observed. Interpretation: These results demonstrate vestibular sensory processing in the insula that is centered on its posterior part. The present data add to the understanding of the multiple sensory functions of the insular cortex and of the cortical processing of vestibular signals. The data also indicate that lesion or dysfunction in the posterior insula should be considered during the evaluation of vestibular epileptic seizures.
Published: 2014
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311. Exposure of Staphylococcus aureus to subinhibitory concentrations of β-lactam antibiotics induces heterogeneous vancomycin-intermediate Staphylococcus aureus

Author: Philippe Reix, Adriana Renzoni, A. M. Freydière, Frédéric Laurent, Michèle Bes, Mélanie Roch, Perrine Clair, Annie Martra, François Vandenesch, Reverdy Me, Olivier Dauwalder, Oana Dumitrescu, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-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)-École normale supérieure de Lyon (ENS de Lyon)-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), Centre National de Reference des Staphylocoques, Université de Lyon, Service of Infectious Diseases [Geneva, Switzerland], Geneva University Hospital (HUG), Centre de Ressources et de Compétences en Mucoviscidose [Lyon] (CRCM [Lyon]), Hospices Civils de Lyon (HCL)-CHU Lyon-Hôpital Renée Sabran [CHU - HCL], Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Imipenem, Staphylococcus aureus, medicine.drug_class, Antibiotics, Population, Drug Resistance, Ceftazidime, Drug resistance, Microbial Sensitivity Tests, Biology, medicine.disease_cause, beta-Lactams, Electron, Microbiology, 03 medical and health sciences, Microscopy, Electron, Transmission, Mechanisms of Resistance, Vancomycin, Drug Resistance, Bacterial, medicine, Transmission, Pharmacology (medical), education, 030304 developmental biology, Pharmacology, 0303 health sciences, education.field_of_study, Microscopy, 030306 microbiology, Ceftriaxone, Bacterial, Vancomycin Resistance, biochemical phenomena, metabolism, and nutrition, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Glycopeptide, 3. Good health, Anti-Bacterial Agents, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Methicillin Resistance, medicine.drug
Abstract: Glycopeptides are known to select for heterogeneous vancomycin-intermediate Staphylococcus aureus (h-VISA) from susceptible strains. In certain clinical situations, h-VISA strains have been isolated from patients without previous exposure to glycopeptides, such as cystic fibrosis patients, who frequently receive repeated treatments with beta-lactam antibiotics. Our objective was to determine whether prolonged exposure to beta-lactam antibiotics can induce h-VISA. We exposed 3 clinical vancomycin-susceptible methicillin-resistant Staphylococcus aureus (MRSA) strains to ceftazidime, ceftriaxone, imipenem, and vancomycin (as a control) at subinhibitory concentrations for 18 days in vitro . Population analyses showed progressive increases in vancomycin resistance; seven of the 12 derived strains obtained after induction were classified as h-VISA according to the following criteria: area under the curve (AUC) on day 18/AUC of Mu3 of ≥90% and/or growth on brain heart infusion (BHI) agar with 4 mg/liter vancomycin. The derived isolates had thickened cell walls proportional to the level of glycopeptide resistance. Genes known to be associated with glycopeptide resistance ( vraSR , yvqF , SA1703, graRS , walKR , and rpoB ) were PCR sequenced; no de novo mutations were observed upon beta-lactam exposure. To determine whether trfA , a gene encoding a glycopeptide resistance factor, was essential in the selection of h-VISA upon beta-lactam pressure, a trfA -knockout strain was generated by allelic replacement. Indeed, beta-lactam exposure of this mutated strain showed no capacity to induce vancomycin resistance. In conclusion, these results showed that beta-lactam antibiotics at subinhibitory concentrations can induce intermediate vancomycin resistance in vitro . This induction required an intact trfA locus. Our results suggest that prior use of beta-lactam antibiotics can compromise vancomycin efficacy in the treatment of MRSA infections.
Published: 2014
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312. Large national series of patients with Xq28 duplication involving MECP2: Delineation of brain MRI abnormalities in 30 affected patients

Author: Vincent des Portes, Salima El Chehadeh, Odile Boespflug-Tanguy, Nathalie Marle, Charles Coutton, Didier Lacombe, Patrick Callier, Anne Moncla, Mathilde Nizon, Christine Francannet, Marlène Rio, Valérie Cormier-Daire, Jean-Paul Bonnefont, Pierre-Simon Jouk, Anne-Laure Mosca-Boidron, Christophe Philippe, Alice Goldenberg, Hubert Journel, Mathilde Lefebvre, Bertrand Isidor, Bernard Echenne, Séverine Drunat, Françoise Devillard, Sébastien Lebon, Jeanne Amiel, Nicole Philip, Jean-Marie Cuisset, Nathalie Perreton, Marie-Claude Addor, Fabienne Prieur, Christel Thauvin-Robinet, Laurent Pasquier, Sophie Julia, Christèle Dubourg, Danièle Martinet, Laurent Guibaud, Laetitia Lambert, Jeanne Andrieux, Cédric Le Caignec, Catherine Badens, Catherine Sarret, Alice Masurel, Julien Thevenon, Renaud Touraine, Ghislaine Plessis, Fanny Laffargue, Lydie Burglen, Laurence Perrin, Bruno Leheup, Thierry Bienvenu, Valérie Malan, Alexandra Afenjar, Albert David, Clarisse Baumann, Marie-Ange Delrue, Jacqueline Vigneron, Annick Toutain, Laurence Faivre, Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de cytogénétique (CHU de Dijon), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne-Hôpital Nord - Saint-Etienne, CHU Saint-Etienne, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Service de biologie moléculaire, Hôpital Pontchaillou, Service Génétique Médicale [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Génétique Médicale, CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de neuropédiatrie [Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Department of pediatrics, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de Génétique Clinique, Hôpital Jeanne de Flandre [Lille]-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Génétique [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), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de génétique médicale, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Génétique Médicale [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), Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA)-Hôpital Chubert, Unité Fonctionnelle de Génétique Clinique [CHU Pitié Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Biochimie et biologie moléculaire, Hôpital Cochin [AP-HP], Département Génétique Médicale-Maternité, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Département de Génétique Médicale, Département de génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Centre de génétique et Centre de référence maladies rares et anomalies du développement et syndromes malformatifs du Centre Est, Département de Génétique et Procréation UF-Hôpital Couple Enfant de Grenoble-CHU Grenoble, Dynamiques Cellulaire et Tissulaire - Interdisciplinarité, Modélisation & Microscopie (TIMC-IMAG-DyCTiM2), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Département de génétique et procréation, Université Joseph Fourier - Grenoble 1 (UJF)-Hôpital Couple-Enfant, Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), AGeing and IMagery (AGIM), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Maladies Rares - Génétique et Métabolisme (MRGM), Université Bordeaux Segalen - Bordeaux 2-Hôpital Pellegrin-Service de Génétique Médicale du CHU de Bordeaux, Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Génétique Chromosomique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Référence ' Anomalies du Développement et Syndromes Malformatifs Sud - Est PACA ', Centre de référence maladie rare Thalassémie, CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Regional Council of Burgundy (PARI 2012), Association Xtraordinaire, Jonchère, Laurent, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de génétique médicale [Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Dynamique Cellulaire et Tissulaire- Interdisciplinarité, Modèles & Microscopies (TIMC-IMAG-DyCTiM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École Pratique des Hautes Études (EPHE), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Génétique des Anomalies du Développement ( GAD ), Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Génétique, reproduction et développement ( GReD ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR79-Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ), Department of Genetics and Cytogenetics, CHU Clermont-Ferrand-Hôpital d'Estaing, Service de Génétique Médical, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Promoting Research Oriented Towards Early Cns Therapies ( PROTECT ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Université de Nantes ( UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hôpital Jeanne de Flandre [Lille]-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), CHU Caen-Hôpital Clémenceau, Hôpital Bretonneau-CHRU Tours, CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Centre Hospitalier Bretagne Atlantique-Hôpital Chubert, Unité Fonctionnelle de Génétique Clinique, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP]-Centre de référence 'Déficiences Intellectuelles de Causes Rares' - Paris-Groupe de Recherche Clinique 'Déficience Intellectuelle et Autisme' - Paris, Service de Neuropédiatrie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Service de Génétique et d'Embryologie Médicale, Service de neuropédiatrie et pathologie du développement, CHU Cochin [AP-HP], Centre Hospitalier Universitaire Vaudois [Lausanne] ( CHUV ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), 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 ) -Hôpital Couple-Enfant, AGeing and IMagery ( AGIM ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -École pratique des hautes études ( EPHE ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Bordeaux ( UB ) -CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Maladies Rares - Génétique et Métabolisme ( MRGM ), Génétique Médicale et Génomique Fonctionnelle ( GMGF ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) -Aix Marseille Université ( AMU ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Hôpital Femme Mère Enfant [CHU - HCL] ( HFME ), Hospices Civils de Lyon ( HCL ), Service de Génétique [Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: 0301 basic medicine, Male, Pathology, Methyl-CpG-Binding Protein 2, [SDV]Life Sciences [q-bio], 030105 genetics & heredity, Corpus callosum, Lateral ventricles, 0302 clinical medicine, Gene Duplication, IKBKG, FLNA, Child, Genetics (clinical), Genetics, Brain Diseases, medicine.diagnostic_test, Middle Aged, Prognosis, Magnetic Resonance Imaging, Hypotonia, 3. Good health, Pedigree, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Phenotype, Xq28 duplication, Child, Preschool, Female, medicine.symptom, Adult, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Adolescent, Genotype, Biology, genotype-phenotype correlation, White matter, 03 medical and health sciences, Young Adult, medicine, Humans, Genetic Association Studies, Chromosomes, Human, X, [ SDV ] Life Sciences [q-bio], Infant, Newborn, Infant, Magnetic resonance imaging, Hyperintensity, nervous system diseases, Mental Retardation, X-Linked, MECP2 gene, 030217 neurology & neurosurgery
Abstract: International audience; Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability, stereotyped movements, and recurrent pulmonary infections. We report on standardized brain magnetic resonance imaging (MRI) data of 30 affected patients carrying an Xq28 duplication involving MECP2 of various sizes (228 kb to 11.7 Mb). The aim of this study was to seek recurrent malformations and attempt to determine whether variations in imaging features could be explained by differences in the size of the duplications. We showed that 93% of patients had brain MRI abnormalities such as corpus callosum abnormalities (n = 20), reduced volume of the white matter (WM) (n = 12), ventricular dilatation (n = 9), abnormal increased hyperintensities on T2-weighted images involving posterior periventricular WM (n = 6), and vermis hypoplasia (n = 5). The occipitofrontal circumference varied considerably between \textgreater+2SD in five patients and \textless-2SD in four patients. Among the nine patients with dilatation of the lateral ventricles, six had a duplication involving L1CAM. The only patient harboring bilateral posterior subependymal nodular heterotopia also carried an FLNA gene duplication. We could not demonstrate a correlation between periventricular WM hyperintensities/delayed myelination and duplication of the IKBKG gene. We thus conclude that patients with an Xq28 duplication involving MECP2 share some similar but non-specific brain abnormalities. These imaging features, therefore, could not constitute a diagnostic clue. The genotype-phenotype correlation failed to demonstrate a relationship between the presence of nodular heterotopia, ventricular dilatation, WM abnormalities, and the presence of FLNA, L1CAM, or IKBKG, respectively, in the duplicated segment. © 2015 Wiley Periodicals, Inc
Published: 2014
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313. UV Radiation Induces the Epidermal Recruitment of Dendritic Cells that Compensate for the Depletion of Langerhans Cells in Human Skin

Author: Sophie Grande, Josette Péguet-Navarro, Philippe Bastien, Amine Achachi, Catherine Goujon, Audrey Gueniche, Lionel Breton, Marc Vocanson, Isabelle Castiel-Higounenc, Jean-François Nicolas, Immunologie de l'allergie cutanée et vaccination – Immunology of skin allergy and vaccination, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-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)-École normale supérieure de Lyon (ENS de Lyon)-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), L'Oréal Recherche France (L'Oréal Recherche), L'OREAL, Department of Dermatology, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département d'allergie et d'immunologie clinique [CHU Lyon Sud], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Adolescent, Ultraviolet Rays, CD14, Biopsy, Inflammation, Human skin, Dermatology, Biology, Biochemistry, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Immune system, Transforming Growth Factor beta, Cell Movement, Receptors, medicine, Humans, Receptor, Molecular Biology, 030304 developmental biology, Skin, 0303 health sciences, integumentary system, Epidermis (botany), Cell Biology, Dendritic cell, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Interleukin-10, Phenotype, 030220 oncology & carcinogenesis, Case-Control Studies, Langerhans Cells, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytokines, Female, Skin cancer, medicine.symptom, Epidermis, Receptors, Transforming Growth Factor beta
Abstract: International audience; UVR causes skin injury and inflammation, resulting in impaired immune function and increased skin cancer risk. Langerhans cells (LCs), the immune sentinels of the epidermis, are depleted for several days following a single UVR exposure and can be reconstituted from circulating monocytes. However, the differentiation pathways leading to the recovery of a normal pool of LCs is still unclear. To study the dynamic changes in human skin with UV injury, we exposed a cohort of 29 healthy human volunteers to a clinically relevant dose of UVR and analyzed sequential epidermal biopsies for changes in leukocyte and dendritic cell (DC) subsets. UV-induced depletion of CD1a(high) LC was compensated by sequential appearance of various epidermal leukocytes. CD14(+) monocytes were recruited as early as D1 post exposure, followed by recruitment of two inflammatory DC subsets that may represent precursors of LCs. These CD1a(low) CD207(-) and the heretofore unknown CD1a(low) CD207(+) DCs appeared at day 1 and day 4 post UVR, respectively, and were endowed with T-cell-activating properties similar to those of LCs. We conclude that recruitment of monocytes and inflammatory DCs appear as a physiological response of the epidermis in order to repair UVR-induced LC depletion associated with immune suppression.
Published: 2014
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314. Synovial sarcoma relapses in children and adolescents: prognostic factors, treatment, and outcome

Author: Frederick, Soole, Carole, Maupain, Anne-Sophie, Defachelles, Sophie, Taque, Veronique, Minard-Colin, Christophe, Bergeron, Yann, De Rycke, Daniel, Orbach, Département de Pédiatrie, Institut Curie [Paris], Service d'Hématologie et d'Oncologie pédiatrique, CHU Pontchaillou [Rennes], Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Hématologie et immunologie pédiatrique, Hospices Civils de Lyon (HCL)-CHU Lyon-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hôpital Femme-Mère-Enfant (HFME), and Department of Biostatistics
Subjects: Male, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Neoplasm Recurrence Local/mortality/pathology/therapy, Child Preschool, [SDV]Life Sciences [q-bio], Age Factors, Sarcoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, Synovial/mortality/pathology/therapy, Survival Rate, Sarcoma, Synovial, Child, Preschool, Humans, Female, Neoplasm Recurrence, Local, Child, Retrospective Studies
Abstract: International audience; Twenty-five to 32% of patients with synovial sarcoma (SS) relapse after appropriate treatment, and experience a poor outcome. Patients who can be salvaged by second-line therapy need to be more clearly identified. Data of patients treated in SFCE (Société Française des Cancers de l'Enfant) centers with an initial diagnosis of localized SS before the age of 18 years and treated from 1/1988 to 12/2008, and who experienced at least one relapse, were retrieved. After descriptive analysis, statistical analysis was performed to determine prognostic factors. Thirty-seven patients were identified. First relapse occurred after a median interval of 24 months and was localized in 73.0% of cases and metastatic in 24.3% of cases. Treatment of relapse consisted of new surgery in 75.7% of cases, second-line chemotherapy in 73.0% of cases and radiotherapy in 48.6% of cases. Response rate to ifosfamide-based regimens was 36.4%. Overall, 70.3% patients achieved a second complete remission. Median 5-year-event-free survival was 32.8% and 5-year overall survival was 42.1%. Factors significantly correlated with better survival were primary tumor involving the limbs, age less than 12 years at diagnosis, absence of chemotherapy or radiotherapy as initial treatment and local relapse. Despite its poor overall outcome, relapse of synovial sarcoma sometimes remains curable. Aggressive surgery, when possible, in combination with chemotherapy and radiotherapy is the recommended treatment. Ifosfamide-based regimens may remain effective in patients with relapsed SS. However, alternative therapies should be proposed in patients with poor prognostic factors.
Published: 2014
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315. Recurrent angioedema: diagnosis strategy and biological aspects

Author: Isabelle Boccon-Gibod, Laurence Bouillet, Frédéric Bérard, Jean-François Nicolas, Centre de référence des angioedèmes à kinines (CREAK), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Département d'allergie et d'immunologie clinique [CHU Lyon Sud], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Immunologie de l'allergie cutanée et vaccination – Immunology of skin allergy and vaccination, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-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)-École normale supérieure de Lyon (ENS de Lyon)-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), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Biological test, medicine.medical_specialty, diagnosis, Bradykinin, Dermatology, chemistry.chemical_compound, urticaria, Recurrence, medicine, Humans, Angioedema, Short duration, business.industry, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Clinical Practice, chemistry, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, C1Inh, medicine.symptom, business, Histamine
Abstract: International audience; The aetiologies of recurrent angioedema (AE) comprise the frequent histaminergic AE and the rare bradykinin-mediated AE. Diagnosis must be done carefully because they do not have the same treatment. Diagnosis strategy is clinical. The most specific symptoms for bradykinin AE are: isolated AE without wheals, long duration of the attack, abdominal localisation. The unique useful biological tests for the diagnosis of bradykinin AE are C1Inh exploration which is altered in hereditary AE (HAE) types I and II. No other biological test is useful in clinical practice at present. In case of suspicion of bradykinin AE with normal C1Inh, physicians must think of drug-induced AE. Hereditary AE with normal C1Inh may be associated with a mutation on gene F12 in 20% of cases. For 80% of patients without mutation, the diagnosis must be done very carefully.
Published: 2014
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316. Disseminated porokeratosis transiently healed by cancer chemotherapy

Author: Jean-François Nicolas, Pauline Pralong, Frédéric Bérard, Véronique Trillet-Lenoir, Anne Laure Breton, Brigitte Balme, Département d'allergie et d'immunologie clinique [CHU Lyon Sud], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Hospices Civils de Lyon (HCL), Immunologie de l'allergie cutanée et vaccination – Immunology of skin allergy and vaccination, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS 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 International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-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)-École normale supérieure de Lyon (ENS de Lyon)-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: Pathology, medicine.medical_specialty, Cancer chemotherapy, Antineoplastic Agents, Dermatology, Disseminated superficial actinic porokeratosis, Medicine, Humans, Heterogeneous group, business.industry, Remission Induction, Histological feature, Papule, Middle Aged, Primary lesion, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Porokeratosis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, business, Cornoid lamella
Abstract: International audience; Porokeratosis (PK) is a heterogeneous group of hereditary or acquired cutaneous disorders of epidermal keratinization with various clinical presentations and etiologies. The primary lesion of PK is a superficial annular macule or papule bordered by a peripheral, grooved, keratotic ridge. Common to all PK is the typical histological feature of cornoid lamella, which clinically corresponds to this hyperkeratotic rim. Porokeratosis of Mibelli and disseminated superficial actinic porokeratosis (DSAP) [...]
Published: 2014
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317. Peripheral blood involvement in patients with follicular lymphoma: a rare disease manifestation associated with poor prognosis

Author: Alexandra Traverse-Glehen, Lucile Baseggio, Martine Ffrench, Bertrand Coiffier, Pierre Feugier, Françoise Berger, John F. Seymour, Clémentine Sarkozy, Olivier Dumas, Fritz Offner, Anne-Sophie Michallet, Lionel Karlin, Armando López-Guillermo, Gilles Salles, Laure Lebras, Pascale Felman, Evelyne Callet-Bauchu, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Peter MacCallum Cancer Centre, Peter MacCallum Cancer Center, University of Melbourne, Universiteit Gent = Ghent University [Belgium] (UGENT), Service d’Anatomie et de Cytologie Pathologiques [Louis Pradel - CHU Lyon], Hôpital Louis Pradel [CHU - HCL], Barcelona Centre for International Health Research, Hospital Clinic (CRESIB), and Universitat de Barcelona (UB)
Subjects: Oncology, Male, Pathology, Leukocytosis, [SDV]Life Sciences [q-bio], Follicular lymphoma, Severity of Illness Index, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, International Prognostic Index, Antineoplastic Combined Chemotherapy Protocols, Medicine and Health Sciences, CD44, prognostic factor, Lymphoma, Follicular, biology, LEUKEMIC PHASE, Hematology, Middle Aged, Neoplastic Cells, Circulating, Prognosis, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, SURVIVAL, Disease Progression, Female, Rituximab, medicine.medical_specialty, Antineoplastic Agents, 03 medical and health sciences, Rare Diseases, follicular lymphoma, Internal medicine, medicine, Humans, RESPONSE CRITERIA, Aged, Retrospective Studies, Proportional hazards model, business.industry, medicine.disease, Survival Analysis, Lymphoma, MANTLE-CELL LYMPHOMA, rituximab maintenance, biology.protein, peripheral blood involvement, Mantle cell lymphoma, business, 030215 immunology, Rare disease
Abstract: International audience; Follicular Lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) subtype and its course is heterogeneous. At diagnosis, some patients with FL manifest a detectable leukaemic phase (FL-LP), but this feature has been seldom described and is poorly characterized. Among 499 patients diagnosed with FL in Lyon-Sud hospital, 37 (7·4%) had characteristic FL-LP (by cytological blood smears and flow cytometric analysis). In addition, 91/1135 FL patients from the PRIMA study presented FL-LP at study entry. In order to evaluate the outcome of this Lyon-Sud cohort, FL-LP patients were matched with 111 newly diagnosed FL without LP according to the Follicular Lymphoma International Prognostic Index (FLIPI) score, age and treatment. Presence of FL-LP was associated with shorter progression-free survival (PFS) and overall survival (OS) (P = 0·004 and P = 0·031, respectively). Presence of FL-LP and high FLIPI score remained independent prognostic factors in a Cox model for time to progression (TTP). A number of circulating lymphoma cells (CLC) >4 × 109/l was the most significant predictor for a shorter TTP in this Cox model. The prognostic impact of FL-LP on TTP was validated in the PRIMA cohort (P = 0·0004). In conclusion, FL-LP is a rare event associated with shorter PFS and patients with CLC >4 × 109/l have a poorer outcome. These patients should be monitored carefully to consider alternative therapeutic options.
Published: 2014
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318. Hepatomegaly and fever at the time of neutrophil recovery revealing L-asparaginase toxicity in the treatment of acute lymphoblastic leukemia

Author: Françoise Berger, Xavier Thomas, Mauricette Michallet, Julien Saison, Fanny Lebosse, Regis Audoual, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS 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), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Département de Pathologie [CHU Lyon-Sud - HCL], Service d'hépatogastroentérologie [Hôpital de la Croix-Rousse, Hospices Civils de Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-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)-École normale supérieure de Lyon (ENS de Lyon)-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), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Vincristine, medicine.medical_specialty, Cyclophosphamide, acute lymphoblastic leukemia, Neutropenia, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, hepatomegaly, Internal medicine, medicine, steatosis, medicine.diagnostic_test, business.industry, Articles, General Medicine, Hepatology, medicine.disease, L-asparaginase, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Elevated alkaline phosphatase, 030220 oncology & carcinogenesis, Liver biopsy, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030211 gastroenterology & hepatology, Steatohepatitis, medicine.symptom, Liver function tests, business, cholestasis, medicine.drug
Abstract: International audience; PATIENT: Male, 52 FINAL DIAGNOSIS: L-asparaginase associated steatohepatitis and pulmonary Pneumocystis Symptoms: Cholestasis \textbullet hepatomegaly MEDICATION: Corticosteroids \textbullet atovaquone \textbullet antioxidant therapy Clinical Procedure: Liver biopsy Specialty: Hematology \textbullet Infectious Disease \textbullet Hepatology. OBJECTIVE: Challenging differential diagnosis. BACKGROUND: L-asparaginase (L-aspa) is an important component of chemotherapy in acute lymphoblastic leukemia (ALL). Main adverse effects of L-aspa include allergic reactions, pancreatitis, thrombosis, and liver disturbances. L-aspa-associated steatohepatitis may be a life-threatening disorder but has very rarely been reported in the literature. CASE REPORT: ALL was diagnosed in a 52-year-old man with a history of cardiovascular disease and obesity. Chemotherapy combining daunorubicin, vincristine, cyclophosphamide, and L-aspa was initiated. At the time of neutrophil recovery, the patient developed hepatomegaly in the context of fever and cough. On day 25, after 6 injections of L-aspa, liver function tests showed elevated alkaline phosphatase and transaminases levels. Although pulmonary Pneumocystis was concomitantly diagnosed, biological hepatic disturbances were attributed to L-aspa-associated toxicity. A liver biopsy revealed severe diffuse micro- and macrovesicular steatosis affecting more than 50% of hepatocytes. Other causes of liver dysfunction were eliminated. L-aspa and other hepatotoxic treatments were stopped, and treatment with antioxidant therapy, atovaquone, and corticosteroids was initiated. The clinical outcome was rapidly favorable. CONCLUSIONS: This case illustrates the necessity of carefully monitoring liver function test results in patients receiving L-aspa. In case of major increase of hepatic enzymes, a hepatic biopsy should rapidly be performed to exclude differential diagnosis in patients with prolonged neutropenia. L-aspa should be stopped and further administration definitively avoided. In the present case, the early administration of systemic corticosteroids as treatment of the concomitant Pneumocystis with hypoxemia could have participated to the favorable clinical evolution.
Published: 2014
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319. De novo mutations in HCN1 cause early infantile epileptic encephalopathy

Author: Nava, Caroline, Dalle, Carine, Rastetter, Agnès, Striano, Pasquale, de Kovel, Carolien G F, Nabbout, Rima, Cancès, Claude, Ville, Dorothée, Brilstra, Eva H, Gobbi, Giuseppe, Raffo, Emmanuel, Bouteiller, Delphine, Marie, Yannick, Trouillard, Oriane, Robbiano, Angela, Keren, Boris, Agher, Dahbia, Roze, Emmanuel, Lesage, Suzanne, Nicolas, Aude, Brice, Alexis, Baulac, Michel, Vogt, Cornelia, El Hajj, Nady, Schneider, Eberhard, Suls, Arvid, Weckhuysen, Sarah, Gormley, Padhraig, Lehesjoki, Anna-Elina, De Jonghe, Peter, Helbig, Ingo, Baulac, Stéphanie, Zara, Federico, Koeleman, Bobby P C, Haaf, Thomas, LeGuern, Eric, Depienne, Christel, Møller, Rikke Steensbjerre, Service de Génétique et Cytogénétique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], 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), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Giannina Gaslini Institute, University Medical Center [Utrecht], Service de neurologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], 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 Neurologie Pédiatrique [Toulouse], CHU Toulouse [Toulouse], Service de Neurologie Pédiatrique [CHU Lyon], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), IRCCS Istituto delle Scienze Neurologiche di Bologna [Bologna, Italy], Ospedale Bellaria [Bologna, Italy], Développement, Adaptation et Handicap. Régulations cardio-respiratoires et de la motricité. (DevAH), Université de Lorraine (UL), Service de Neurologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Institüt für Humangenetik [Würzburg], Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Neurogenetics Group, Institute Born-Bunge, University of Antwerp (UA), The Wellcome Trust Sanger Institute [Cambridge], Department of Medical and Clinical Genetics [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, University of Helsinki, University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Développement, Adaptation et Handicap. Régulations cardio-respiratoires et de la motricité (DevAH), EuroEPINOMICS RES Consortium, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service Neurologie Pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Julius-Maximilians-Universität Würzburg (JMU), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, and Helsingin yliopisto = Helsingfors universitet = University of Helsinki
Subjects: Male, MESH: Sequence Analysis, DNA, Patch-Clamp Techniques, Potassium Channels, MESH: Spasms, Infantile, MESH: Sequence Homology, Amino Acid, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Mutant, DNA Mutational Analysis, Sequence Homology, MESH: Cricetinae, Aicardi Syndrome, Amino Acid Sequence, Animals, CHO Cells, Child, Preschool, Cohort Studies, Cricetinae, Cricetulus, Female, Humans, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Infant, Molecular Sequence Data, Mutation, Missense, Pedigree, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Spasms, Infantile, Point Mutation, Genetics, MESH: Amino Acid Sequence, Bioinformatics, Infantile, Spasms, Epilepsy, 0302 clinical medicine, MESH: Cricetulus, Missense mutation, MESH: Animals, MESH: DNA Mutational Analysis, Child, MESH: Cohort Studies, Exome sequencing, 0303 health sciences, MESH: Potassium Channels, de novo mutation, epileptic encephalopathies, MESH: Infant, 3. Good health, Amino Acid, Sequence Analysis, MESH: Pedigree, Biology, 03 medical and health sciences, Dravet syndrome, MESH: CHO Cells, MESH: Patch-Clamp Techniques, medicine, Homomeric, MESH: Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, MESH: Aicardi Syndrome, Preschool, Gene, 030304 developmental biology, MESH: Point Mutation, MESH: Mutation, Missense, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, MESH: Humans, MESH: Molecular Sequence Data, Point mutation, MESH: Child, Preschool, DNA, medicine.disease, MESH: Male, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, Human medicine, Missense, MESH: Female, 030217 neurology & neurosurgery
Abstract: International audience; Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to cationic Ih current in neurons and regulate the excitability of neuronal networks. Studies in rat models have shown that the Hcn1 gene has a key role in epilepsy, but clinical evidence implicating HCN1 mutations in human epilepsy is lacking. We carried out exome sequencing for parent-offspring trios with fever-sensitive, intractable epileptic encephalopathy, leading to the discovery of two de novo missense HCN1 mutations. Screening of follow-up cohorts comprising 157 cases in total identified 4 additional amino acid substitutions. Patch-clamp recordings of Ih currents in cells expressing wild-type or mutant human HCN1 channels showed that the mutations had striking but divergent effects on homomeric channels. Individuals with mutations had clinical features resembling those of Dravet syndrome with progression toward atypical absences, intellectual disability and autistic traits. These findings provide clear evidence that de novo HCN1 point mutations cause a recognizable early-onset epileptic encephalopathy in humans.
Published: 2014
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320. Computer-aided staging of lymphoma patients with FDG PET/CT imaging based on textural information

Author: Matthieu Rogez, Emilie Niaf, Carole Lartizien, F. Ricard, 2 - Images et Modèles, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), 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 Claude Bernard Lyon 1 ( UCBL ), 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 Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ), Département de médecine nucléaire, Hospices Civils de Lyon ( HCL ), Images et Modèles, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-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 Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-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), and Centre Hospitalier Universitaire de Lyon (CHU Lyon)
Subjects: Adult, Male, Support Vector Machine, Lymphoma, Computer science, Feature selection, [ SPI.SIGNAL ] Engineering Sciences [physics]/Signal and Image processing, Young Adult, [STAT.ML]Statistics [stat]/Machine Learning [stat.ML], Health Information Management, Image texture, Fluorodeoxyglucose F18, medicine, Image Processing, Computer-Assisted, Humans, Diagnosis, Computer-Assisted, Electrical and Electronic Engineering, Aged, Neoplasm Staging, PET-CT, medicine.diagnostic_test, Receiver operating characteristic, Contextual image classification, business.industry, Pattern recognition, Middle Aged, Computer Science Applications, Support vector machine, ROC Curve, Positron emission tomography, Positron-Emission Tomography, Female, Tomography, Artificial intelligence, Nuclear medicine, business, Tomography, X-Ray Computed, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Biotechnology
Abstract: International audience; We have designed a computer-aided diagnosis system to discriminate between hypermetabolic cancer lesions and hypermetabolic inflammatory or physiological but noncancerous processes in FDG PET/CT exams of lymphoma patients. Detection performance of the support vector machine (SVM) classifier was assessed based on feature sets including 105 positron emission tomography (PET) and Computed tomography (CT) characteristics derived from the clinical practice and from more sophisticated texture analysis. An original feature selection method based on combining different filter methods was proposed. The evaluation database consisted of 156 lymphomatous and 32 suspicious but nonlymphomatous regions of interest. Different types of training databases including either the PET and CT features or the PET features only, with or without feature selection, were evaluated to assess the added value of multimodality and texture information on classification performance. An optimization study was conducted for each classifier separately to select the best combination of parameters. Promising classification performance was achieved by the SVM classifier combined with the 12 most discriminant PET and CT features with a value of the area under the receiver operating curve of 0.91.
Published: 2013
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321. Theta signal as the neural signature of social exclusion

Author: Sylvain Harquel, Gianluca Deiana, Angela Sirigu, Irene Cristofori, Andres Posada, Jean Isnard, Laura Moretti, François Mauguière, Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Psychologie et NeuroCognition (LPNC), Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie fonctionnelle et d'épileptologie, Hospices Civils de Lyon (HCL)-Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], and Hospices Civils de Lyon (HCL)-Université de Lyon
Subjects: Adult, Male, Cognitive Neuroscience, media_common.quotation_subject, Electroencephalography Phase Synchronization, Gyrus Cinguli, 050105 experimental psychology, Developmental psychology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, 0302 clinical medicine, Perception, Sensation, medicine, Humans, 0501 psychology and cognitive sciences, Theta Rhythm, 10. No inequality, Anterior cingulate cortex, media_common, [SCCO.NEUR]Cognitive science/Neuroscience, 05 social sciences, Brain, Electroencephalography, Pain Perception, Neurophysiology, Middle Aged, Social relation, medicine.anatomical_structure, Feeling, Psychological Distance, Social exclusion, Female, Psychology, Neuroscience, Insula, 030217 neurology & neurosurgery
Abstract: International audience; The feeling of being excluded from a social interaction triggers social pain, a sensation as intense as actual physical pain. Little is known about the neurophysiological underpinnings of social pain. We addressed this issue using intracranial electroencephalography in 15 patients performing a ball game where inclusion and exclusion blocks were alternated. Time-frequency analyses showed an increase in power of theta-band oscillations during exclusion in the anterior insula (AI) and posterior insula, the subgenual anterior cingulate cortex (sACC), and the fusiform "face area" (FFA). Interestingly, the AI showed an initial fast response to exclusion but the signal rapidly faded out. Activity in the sACC gradually increased and remained significant thereafter. This suggests that the AI may signal social pain by detecting emotional distress caused by the exclusion, whereas the sACC may be linked to the learning aspects of social pain. Theta activity in the FFA was time-locked to the observation of a player poised to exclude the participant, suggesting that the FFA encodes the social value of faces. Taken together, our findings suggest that theta activity represents the neural signature of social pain. The time course of this signal varies across regions important for processing emotional features linked to social information.
Published: 2013
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322. Risk factors for adjacent segment degeneration after adolescent idiopathic scoliosis surgery: the intervertebral disc stability concept

Author: Abelin-Genevois, Kariman, Swider, Pascal, Estivalèzes, Erik, Briot, Jérôme, Accadbled, Franck, Sales de Gauzy, Jérôme, Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Centre Hospitalier Universitaire de Lyon - CHU Lyon (FRANCE), Centre Hospitalier Universitaire de Toulouse - CHU Toulouse (FRANCE), and Laboratoire de Biomécanique (Toulouse, France)
Subjects: Idiopathic scoliosis, Intervertebral disc, Ingénierie biomédicale
Abstract: Ideal surgical management of adolescent idiopathic scoliosis (AIS) aims for an optimal correction of the deformity while preserving mobility. An unbalanced rigid spine puts the mobile segment at higher risk of disk degeneration. The goal of our study is to clarify the long term outcome of AIS after spinal fusion.
Published: 2013

323. Intracranial evaluation of the epileptogenic zone in regional infrasylvian polymicrogyria

Author: Ramantani, Georgia, Koessler, Laurent, Colnat-Coulbois, Sophie, Vignal, Jean-Pierre, Isnard, Jean, Catenoix, Hélène, Jonas, Jacques, Zentner, Josef, Schulze-Bonhage, Andreas, Maillard, Louis, epilepsy center (EC), University of Freiburg [Freiburg], Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Développement, Adaptation et Handicap. Régulations cardio-respiratoires et de la motricité (DevAH), Université de Lorraine (UL), CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie fonctionnelle et d'épileptologie, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Department of Neurosurgery, Epilepsy Centre, and University Hospital Freiburg
Subjects: Adult, Male, Malformations of cortical development, Adolescent, SEEG, Outcomes, Hippocampus, Neurosurgical Procedures, Young Adult, Epilepsy surgery, Image Processing, Computer-Assisted, Intracranial recordings, Schizencephaly, Humans, Child, Epilepsy, Brain, Electroencephalography, Magnetic Resonance Imaging, Temporal Lobe, Treatment Outcome, Polymicrogyria, Positron-Emission Tomography, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Nerve Net, Tomography, X-Ray Computed
Abstract: International audience; Purpose: To define the relationship between the epileptogenic zone and the polymicrogyric area using intracranial electroencephalography (EEG) recordings in patients with structural epilepsy associated with regional infrasylvian polymicrogyria (PMG). Methods: We retrospectively reviewed the medical charts, scalp, and intracranial video-EEG recordings, neuroimaging findings, and neuropsychological evaluations of four patients with refractory temporal lobe epilepsy related to PMG who consequently underwent resective surgery. Key Findings: High-resolution magnetic resonance imaging (MRI) revealed temporal lobe PMG in all cases, accompanied by hippocampal malrotation and closed lip schizencephaly in 3/4 cases, respectively. In intracranial recordings, interictal spike activity was localized within the PMG in only 2/4 and within the amygdala, hippocampus, and entorhinal cortex in all cases. In the first patient, two epileptogenic networks coexisted: the prevailing network initially involved the mesial temporal structures with spread to the anterior PMG; the secondary network successively involved the anterior part of the PMG and later the mesial temporal structures. In the second patient, the epileptogenic network was limited to the mesial temporal structures, fully sparing the PMG. In the third patient, the epileptogenic network first involved the mesial temporal structures and later the PMG. Conversely, in the last case, part of the PMG harbored an epileptogenic network that propagated to the mesial temporal structures. Consistent with these findings a favorable outcome (Engel class I in three of four patients; Engel class II in one of four) at last follow-up was obtained by a resection involving parts of the PMG cortex in three of four and anteromesial temporal lobe structures in another three of four cases. Significance: Infrasylvian PMG displays a heterogeneous epileptogenicity and is occasionally and partially involved in the epileptogenic zone that commonly includes the mesial temporal structures. Our results highlight the intricate interrelations between the MRI-detectable lesion and the epileptogenic zone as delineated by intracranial recordings. Seizure freedom can be accomplished as a result of a meticulous intracranial study guiding a tailored resection that may spare part of the PMG.
Published: 2013
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324. Pandoraea pulmonicola chronic colonization in a cystic fibrosis patient, France

Author: M. Reynaud-Gaubert, Fadi Bittar, S. Kokcha, Pascal Thomas, Carine Gomez, Laurent Mely, Jean-Marc Rolain, Jean Gaubert, Unité de Recherche sur les Maladies Infectieuses Tropicales Emergentes (URMITE), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Neuropsychologie cognitive et neuroanatomie fonctionnelles de la mémoire humaine, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Nord [CHU - APHM], Centre de Ressources et de Compétences en Mucoviscidose [Lyon] (CRCM [Lyon]), Hospices Civils de Lyon (HCL)-CHU Lyon-Hôpital Renée Sabran [CHU - HCL], Hospices Civils de Lyon (HCL), Institut des Matériaux, de Microélectronique et des Nanosciences de Provence (IM2NP), Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Loughborough University, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Bittar, Fadi, Normandie Université (NU)-Normandie Université (NU)-École Pratique des Hautes Études (EPHE), École pratique des hautes études (EPHE)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'étude des Interactions Sol - Agrosystème - Hydrosystème (UMR LISAH), and Institut de Recherche pour le Développement (IRD)-Institut de Recherche pour le Développement (IRD [ Madagascar])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)
Subjects: Pathology, medicine.medical_specialty, Antibiotic resistance, medicine.medical_treatment, Context (language use), pulmonary infection, Pandoraea pulmonicola, Chronic colonization, Microbiology, Cystic fibrosis, 03 medical and health sciences, 0302 clinical medicine, medicine, lung transplantation, Lung transplantation, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Pandoraea, biology, 030306 microbiology, business.industry, Bilateral lung transplantation, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Infectious Diseases, multi-drug resistant bacteria, New Microbes in Humans-New Resistant Microbes in Humans, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business
Abstract: International audience; Pandoraea are considered emerging multidrug resistant pathogens in the context of cystic fibrosis. We report herein for the first time the case of a 30-year-old woman with cystic fibrosis, living in France, who was chronically infected with Pandoraea pulmonicola and who died of Pseudomonas aeruginosa sepsis 3 weeks after bilateral lung transplantation.
Published: 2013
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325. Individual patient data systematic review and meta-analysis of optic nerve sheath diameter ultrasonography for detecting raised intracranial pressure: protocol of the ONSD research group

Author: Etienne Javouhey, Antonino Gullo, Mahmoud Messerer, Sachita P. Shah, Behrouz Kassai, Julie Dubourg, Carmelo Denaro, Gianluca Cammarata, Gregorios Kouraklis, Roy Thomas Daniel, John Poularas, Alessandro Cammarata, Giuseppe Mannanici, Sybille Merceron, Keith A. Marill, Abderrhammane Hamlat, Emmanuel Douzinas, Giuseppe Ristagno, Dimitrios Karakitsos, Erik Antonsen, Clément Dubost, Thomas Geeraerts, Vicki E. Noble, Heidi H. Kimberly, Venkatakrishna Rajajee, Moncef Berhouma, Riccardo Moretti, Michael Cotton, Muriel Rabilloud, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service de Neurochirurgie, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Department of Intensive Care, General State Hospital of Athens, Departments of Neurosurgery and Neurology, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Harvard Affiliated Emergency Medicine Residency, Brigham and Women's Hospital [Boston], Service de Réanimation Pédiatrique [Hôpital Femme Mère Enfant - HCL], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Medical School, Università degli studi di Catania = University of Catania (Unict), Service des Urgences, Department of Anesthesia and Intensive Care, Cannizzaro Hospital, Third Intensive Care Department, Evgenidion Hospital, Service d'anesthésie et soins intensifs, Hôpital Bégin, Service de Neurochirurgie A, Hospices Civils de Lyon (HCL)-Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pharmacologie Clinique (EPICIME), Département de Biostatistiques, Biostatistiques santé, 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), Catania University Hospital, Service de neurochirurgie [Rennes] = Neurosurgery [Rennes], CHU Pontchaillou [Rennes], Second Department of Propedeutic Surgery, LAIKO General Hospital-National and Kapodistrian University of Athens (NKUA), Department of Emergency Medicine, Massachusetts General Hospital [Boston], Service de soins intensifs, Centre Hospitalier de Versailles André Mignot (CHV), Department of Cardiovascular Research, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Harborview Medical Center, Department of Anesthesia and Critical Care, Ospedale SS Antonio e Biagio e Cesare Arrigo, Pôle Anesthésie Réanimation [CHU de Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Università degli studi di Catania [Catania], Pôle Anesthésie Réanimation, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Service de neurochirurgie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and BMC, Ed.
Subjects: medicine.medical_specialty, Optic nerve sheath, Databases, Factual, Intracranial Pressure, Medicine (miscellaneous), Diagnostic accuracy, Raised intracranial pressure, 03 medical and health sciences, 0302 clinical medicine, Meta-Analysis as Topic, Reference Values, Optic nerve sheath diameter, Protocol, medicine, Humans, 030212 general & internal medicine, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Ultrasonography, Intracranial pressure, Protocol (science), business.industry, Optic Nerve, Patient data, 3. Good health, Surgery, Meta-analysis, Research Design, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Optic nerve, Individual patient data, Intracranial Hypertension/ultrasonography, Optic Nerve/ultrasonography, Review Literature as Topic, Radiology, Intracranial Hypertension, business, 030217 neurology & neurosurgery, Systematic Reviews as Topic
Abstract: International audience; BACKGROUND: The purpose of the optic nerve sheath diameter (ONSD) research group project is to establish an individual patient-level database from high quality studies of ONSD ultrasonography for the detection of raised intracranial pressure (ICP), and to perform a systematic review and an individual patient data meta-analysis (IPDMA), which will provide a cutoff value to help physicians making decisions and encourage further research. Previous meta-analyses were able to assess the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP but failed to determine a precise cutoff value. Thus, the ONSD research group was founded to synthesize data from several recent studies on the subject and to provide evidence on the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP. METHODS: This IPDMA will be conducted in different phases. First, we will systematically search for eligible studies. To be eligible, studies must have compared ONSD ultrasonography to invasive intracranial devices, the current reference standard for diagnosing raised ICP. Subsequently, we will assess the quality of studies included based on the QUADAS-2 tool, and then collect and validate individual patient data. The objectives of the primary analyses will be to assess the diagnostic accuracy of ONSD ultrasonography and to determine a precise cutoff value for detecting raised ICP. Secondly, we will construct a logistic regression model to assess whether patient and study characteristics influence diagnostic accuracy. DISCUSSION: We believe that this IPD MA will provide the most reliable basis for the assessment of diagnostic accuracy of ONSD ultrasonography for detecting raised ICP and to provide a cutoff value. We also hope that the creation of the ONSD research group will encourage further study. TRIAL REGISTRATION: PROSPERO registration number: CRD42012003072.
Published: 2013
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326. Applications de la force de Lorentz en acoustique médicale

Author: Grasland-Mongrain, Pol, STAR, ABES, CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard - Lyon I, Cyril Lafon, and Jean-Yves Chapelon
Subjects: Élastographie, Acoustique médicale, Lorentz Force Electrical Impedance Tomography, Ultrasons Focalisés à Haute Intensité, [PHYS.MECA.ACOU]Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph], Tomographie Magnéto-Acousto-Electrique, Lorentz force, Electrical impedance, Impédance électrique, Medical acoustics, Magneto-Acoustic-Electrical Tomography, High Intensity Focused Ultrasound, Force de Lorentz, Hydrophone, Elastography, [PHYS.MECA.ACOU] Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph], Tomographie d’Impédance Electrique par Force de Lorentz
Abstract: The ability of the Lorentz force to link a mechanical displacement to an electrical current presents a strong interest for medical acoustics, and three applications were studied in this thesis. In the first part of this work, a hydrophone was developed for mapping the particle velocity of an acoustic field. This hydrophone was constructed using a thin copper wire and an external magnetic field. A model was elaborated to determine the relationship between the acoustic pressure and the measured electrical current, which is induced by Lorentz force when the wire vibrates in the acoustic field of an ultrasound transducer. The built prototype was characterized and its spatial resolution, frequency response, sensitivity, robustness and directivity response were investigated. An imaging method called Lorentz Force Electrical Impedance Tomography was also studied. In this method, a biological tissue is vibrated by ultrasound in a magnetic field, which induces an electrical current by Lorentz force. The electrical impedance of the tissue can be deduced from the measurement of the current. This technique was applied for imaging a gelatin phantom, a beef muscle sample, and a thermal lesion in a chicken breast sample. This showed the method may be useful for providing additional contrast to conventional ultrasound imaging. Finally, this thesis demonstrated that shear waves can be generated in soft tissues using Lorentz force. This work was performed by applying an electrical current with two electrodes in a soft solid placed in a magnetic field. Shear waves were observed in gelatin phantom and liver sample. The speed of the shear waves were used to compute elasticity and their source to map the electrical conductivity of the samples, La capacité de la force de Lorentz à relier un déplacement mécanique à un courant électrique présente un intérêt certain pour l'acoustique médicale, et trois applications ont été étudiées dans cette thèse. Dans la première partie de ce travail, un hydrophone a été développé pour effectuer des champs de vitesse acoustique. Cet hydrophone était constitué d'un fil de cuivre vibrant dans un champ magnétique. Un modèle a été élaboré pour déterminer une relation entre la pression acoustique et le courant électrique mesure, qui est induit par force de Lorentz lorsque le fil vibre dans un champ acoustique. Un prototype a ensuite été conçu et sa résolution spatiale, sa réponse fréquentielle, sa sensibilité, sa résistance et sa réponse directionnelle ont été examinées. Une méthode d'imagerie appelée Tomographie d'Impedance Electrique par Force de Lorentz a aussi été étudiée. Dans cette méthode, un tissu biologique est déplacé par ultrasons dans un champ magnétique, ce qui induit un courant électrique par force de Lorentz. L'impédance électrique du tissu peut ensuite être déduite de la mesure du courant. Cette technique a été appliquée pour réaliser des images d'un fantôme de gélatine, d'un muscle de bœuf, et d'une lésion thermique dans un échantillon de poulet. Cela a montré que la méthode est potentiellement utile pour fournir un contraste supplémentaire à des images ultrasonores classiques. Enfin, cette thèse a démontré que des ondes de cisaillement peuvent être générées dans des tissus mous par force de Lorentz. Cela a été réalisé en appliquant un courant électrique par deux électrodes dans un solide mou place dans un champ magnétique. Des ondes de cisaillement ont été observées dans des échantillons de gélatine et de foie. La vitesse des ondes de cisaillement a été utilisée pour calculer l'élasticité et leur source pour cartographier la conductivité électrique des échantillons
Published: 2013

327. Are concomitant treatments confounding factors in randomized controlled trials on intensive blood-glucose control in type 2 diabetes? a systematic review

Author: Theodora Bejan-Angoulvant, Behrouz Kassai, Rémy Boussageon, Michel Cucherat, Irène Supper, Catherine Cornu, Sylvie Erpeldinger, François Gueyffier, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, 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), Service de Pharmacologie Clinique, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL)-Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Service de Pharmacologie Clinique, CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), BMC, Ed., Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université de Tours-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Blinding, Epidemiology, Health Informatics, Type 2 diabetes, Cochrane Library, Observer bias, law.invention, Diabetes Complications, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Diabetes mellitus, Internal medicine, Type 2 diabetes mellitus, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Medicine, Humans, Hypoglycemic Agents, Blood glucose, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030212 general & internal medicine, Antihypertensive Agents, Randomized Controlled Trials as Topic, Observer Variation, Aspirin, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Type 2 Diabetes Mellitus, Confounding Factors, Epidemiologic, medicine.disease, 3. Good health, Treatment Outcome, Concomitant treatment, Diabetes Mellitus, Type 2, 030220 oncology & carcinogenesis, Concomitant, Hypertension, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug, Research Article
Abstract: Background Open-label, randomized controlled trials (RCTs) are subject to observer bias. If patient management is conducted without blinding, a difference between groups may be explained by other factors than study treatment. One factor may come from taking concomitant treatments with an efficacy on the studied outcomes. In type 2 diabetes, some antihypertensive or lipid-lowering drugs are effective against diabetic complications. We wanted to determine if these concomitant treatments were correctly reported in articles of RCTs on type 2 diabetes and if they might have influenced the outcome. Methods We performed a systematic review using Medline, Embase, and the Cochrane Library (from January 1950 to July 2010). Open-label RCTs assessing the effectiveness of intensive blood-glucose control in type 2 diabetes were included. We chose five therapeutic classes with proven efficacy against diabetes complications: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor antagonists (AIIRAs), fibrates, statins, and aspirin. Differences between concomitant treatments were considered statistically significant when p < 0.05. Results A total of eight open-label RCTs were included, but only three (37.5%) of them published concomitant treatments. In two studies (ACCORD and ADVANCE), a statistically significant difference was observed between the two groups for aspirin (p = 0.02) and ACEIs (p = 0.02). Conclusions Few concomitant treatments were published in this sample of open-label RCTs. We cannot completely eliminate an observer bias for these studies. This bias probably influenced the results to an extent that has yet to be determined.
Published: 2013

328. Revising the ECRIN standard requirements for information technology and data management in clinical trials

Author: Enrico Nicolis, Steve Canham, Jochen Dreß, François Gueyffier, Catherine Cornu, Christian Ohmann, Michael Wittenberg, Wolfgang Kuchinke, Coordination Centre for Clinical Trials, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre for Clinical Studies (ZKS), University of Cologne, Service de Pharmacologie Clinique et Essais Thérapeutiques, Hospices Civils de Lyon (HCL)-Faculté de Médecine Laennec, 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), Department of Cardiovascular Research, Mario Negri Institute- IRCCS, Philipps Universität Marburg, Philipps Universität Marburg = Philipps University of Marburg, and BMC, Ed.
Subjects: Research design, Standards, Certification, Data management, Information Storage and Retrieval, Medicine (miscellaneous), Guidelines as Topic, Information technology, European, 030226 pharmacology & pharmacy, Health informatics, Update, Task (project management), 03 medical and health sciences, 0302 clinical medicine, Health Information Management, Terminology as Topic, Controlled vocabulary, Humans, Medicine, Pharmacology (medical), 030212 general & internal medicine, Program Development, Clinical Trials as Topic, business.industry, ECRIN, Clinical trial, Engineering management, Vocabulary, Controlled, Research Design, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Data Interpretation, Statistical, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Guideline Adherence, business, Medical Informatics
Abstract: International audience; The pilot phase of the ECRIN (European Clinical Research Infrastructure Network) certification programme for European data centres, in late 2011, led to a substantial revision of the original ECRIN standards, completed by June 2012. The pilot phase, the conclusions drawn from it and the revised set of standards are described. Issues concerning the further development of standards and related material are discussed, as are the methods available to best support that development. A strategy is outlined based on short-lived specific task groups, established as necessary by a steering group drawn from ECRIN-ERIC. A final section discusses possible future developments.
Published: 2013
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329. Étude structurale et fonctionnelle d'un nouvel ARN non codant, Asgard, contrôlant l'autorenouvellement des cellules souches embryonnaires

Author: Giudice, Vincent, STAR, ABES, CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard - Lyon I, and Pierre Savatier
Subjects: Asgard, Embryonic stem cells, MicroARN, Différenciation, MicroRNA, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Non coding RNA, Cellules souches embryonnaires, Klf4, LIF/STAT3 signalling pathway, Autorenouvellement, Voie de signalisation LIF/STAT3, Differentiation, Self-renewal, ARN non codants, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Abstract: The Leukemia Inhibitory Factor (LIF) activates the transcription factor STAT3, which results in the maintenance of mouse embryonic stem cells in the undifferentiated state by inhibiting mesodermal and endodermal differentiation. We identified several target genes of STAT3 by transcriptomic analysis. Among them, we focused on an unknown gene referred as 1456160_at on Affymetrix array. This gene is highly expressed in embryonic stem cells and its expression level decreases during differentiation. We named this gene Asgard for Another Self-renewal GuARDian. Its characterization and sequencing revealed that Asgard encodes for a microRNA sequence. Several microRNAs have been shown to play key role in the maintenance of self-renewal of mouse ES cells and in the control of differentiation. Inhibition and overexpression assays showed that Asgard inhibits endodermal differentiation in order to maintain self-renewal. Through preliminary analysis, we identified Pbx3, FoxA2 and Sox17 as potential targets of the microRNA Asgard. Our work enables us to identify a new key gene of self-renewal of mouse ES cells, Chez la souris, le Leukemia Inhibitory Factor (LIF) joue un rôle clé dans le maintien des cellules souches embryonnaires (ES) à l’état pluripotent. Le LIF agit en activant le facteur de transcription STAT3 via les kinases Jak. Cette activation est nécessaire et suffisante au maintien des cellules ES en autorenouvellement en présence de sérum. Une étude du transcriptome de STAT3 réalisée au laboratoire a permis d’identifier plusieurs gènes cibles de ce facteur, parmi lesquels plusieurs gènes inconnus. L’un d’eux, le gène 1456160_at, est fortement exprimé dans les cellules ES de souris et son expression diminue après induction de la différenciation. Ce gène a été appelé Asgard pour Another Self-renewal GuARDian. La caractérisation et le séquençage de ce gène ont permis de mettre en évidence qu'Asgard code pour un microARN. De nombreux microARNs jouent un rôle clé dans le maintien de l'autorenouvellement des cellules ES et dans le contrôle de la différenciation. Des expériences d’inhibition et de surexpression ont permis de montrer que Asgard est impliqué dans la régulation de la différenciation endoderme versus mésoderme. Des analyses préliminaires ont permis d’identifier Pbx3, FoxA2 et Sox17 comme cibles potentielles. Bien que les mécanismes d’action du microARN Asgard restent à confirmer, ce travail a permis d’identifier un nouveau gène clé de l'autorenouvellement des cellules ES de souris
Published: 2013

330. Multifaceted intervention to enhance the screening and care of hospitalised malnourished children: study protocol for the PREDIRE cluster randomized controlled trial

Author: Sandrine Touzet, Guillaume Gamba, Noël Peretti, Fleur Cour-Andlauer, Antoine Duclos, Angélique Denis, Daniel Betito, Lioara Restier-Miron, Pauline Occelli, Stéphanie Polazzi, Cyrille Colin, Alain Lachaux, BMC, Ed., Pôle Information Médicale Evaluation Recherche (IMER), Hospices Civils de Lyon (HCL), Santé Individu Société - SIS (SIS), Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition Pédiatrique, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Direction du Système d'Information et de l'Informatique, Hospices Civils de Lyon - Groupement Hospitalier Est, CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), This study was supported by a grant from the Programme de Recherche en Qualité Hospitalière 2008 of the French Ministry of Health (Ministère chargé de la Santé, Direction de l'Hospitalisation et de l'Organisation des Soins)., The PREDIRE Study Group, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université Lumière - Lyon 2 (UL2), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Santé Individu Société (SIS), Université de Lyon-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, Multifaceted intervention, Adolescent, Cluster randomized trial, 030204 cardiovascular system & hematology, Child Nutrition Disorders, Health administration, law.invention, 03 medical and health sciences, Study Protocol, 0302 clinical medicine, Randomized controlled trial, law, Health care, Medical Staff, Hospital, Medicine, Cluster Analysis, Humans, Mass Screening, Nutritional support team, 030212 general & internal medicine, Cluster randomised controlled trial, Intensive care medicine, Child, Mass screening, Patient Care Team, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Computerized clinical decision support system, business.industry, Nursing research, Health Policy, Infant, medicine.disease, Decision Support Systems, Clinical, 3. Good health, Hospitalization, Malnutrition, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Child, Preschool, Observational study, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business, Malnourished children, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; BACKGROUND: Hospital malnutrition is an underestimated problem and as many as half of malnourished patients do not receive appropriate treatment. In order to extend the management of malnutrition in health care facilities, multidisciplinary teams focusing on clinical nutrition were established in France. The establishment of such teams within hospital facilities remains nonetheless difficult. We have consequently developed a multifaceted intervention coordinated by a Nutritional Support Team (NST). Our study aims to evaluate the impact of this multifaceted intervention coordinated by a NST, in adherence to recommended practices for the care of malnourished children, among health care workers of a paediatric university hospital. METHODS/DESIGN: We carried out 1) a six-month observational phase focusing on the medical care procedures relative to malnourished children followed by 2) a cluster randomised controlled trial phase to evaluate the impact of a multidisciplinary nutrition team over an 18 month time frame.Based on power analyses and assuming a conservative intracluster correlation coefficient, 1289 children were needed to detect a 25% difference in rates between the two groups of the cluster trial.The implementation of our intervention was coordinated by the NST and had three major components: a) access to a computerised malnutrition screening system associated with an automatic alert system, b) an awareness campaign directed toward the health care workers and c) a leadership based strategy.Main outcomes included the number of daily weighings during hospitalisation, the investigation of malnutrition etiology and the management of malnutrition by a dietician and/or the NST.Due to the clustered nature of the data with children nested in departments, a generalized estimated equations approach will be used to analyse the impact of the multifaceted intervention on primary and secondary outcomes. DISCUSSION: Our results will provide an overall response regarding the effectiveness of our multifaceted intervention and we should be able to suggest an organization and mode of operation of NST. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01081587.
Published: 2013
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331. Interferon beta 1b following natalizumab discontinuation: one year, randomized, prospective, pilot trial

Author: François Cotton, David Leppert, Charles R.G. Guttmann, Chiara Zecca, Dominik S. Meier, Claudio Gobbi, Martina Sintzel, Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano, Center for Neurological Imaging, Departments of Radiology and Neurology, Laboratoire d'Anatomie de Rockefeller, Université de Lyon-CHU Lyon, Service de Radiologie, Hospices Civils de Lyon (HCL), 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), MCS Medical Communication Services, Neurology, University Hospital Basel [Basel], BMC, Ed., Université Claude Bernard Lyon 1 (UCBL), 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)-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)
Subjects: Male, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Gadolinium, Pilot Projects, Kaplan-Meier Estimate, Disability Evaluation, 0302 clinical medicine, Natalizumab, Clinical endpoint, Young adult, Progressive multifocal leukoencephalopathy, General Medicine, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Magnetic Resonance Imaging, De-escalation, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Female, Interferon beta1b, medicine.drug, Research Article, Interferon beta-1b, Adult, medicine.medical_specialty, Clinical Neurology, Antibodies, Monoclonal, Humanized, Multiple sclerosis, 03 medical and health sciences, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Double-Blind Method, 030225 pediatrics, Internal medicine, parasitic diseases, medicine, Humans, Immunologic Factors, Intention-to-treat analysis, business.industry, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Interferon-beta, medicine.disease, Discontinuation, Surgery, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Background Natalizumab (NTZ) discontinuation leads to multiple sclerosis reactivation. The objective of this study is to compare disease activity in MS patients who continued on NTZ treatment to those who were switched to subcutaneous interferon 1b (IFNB) treatment. Methods 1-year randomized, rater-blinded, parallel-group, pilot study (ClinicalTrial.gov ID: NCT01144052). Relapsing remitting MS patients on NTZ for ≥12 months who had been free of disease activity on this therapy (no relapses and disability progression for ≥6 months, no gadolinium-enhancing lesions on baseline MRI) were randomized to NTZ or IFNB. Primary endpoint was time to first on-study relapse. Additional clinical, MRI and safety parameters were assessed. Analysis was based on intention to treat. Results 19 patients (NTZ n=10; IFNB n=9) with similar baseline characteristics were included. 78% of IFNB treated patients remained relapse free (NTZ group: 100%), and 25% remained free of new T2 lesions (NTZ group: 62.5%). While time to first on-study relapse was not significantly different between groups (p=0.125), many secondary clinical and radiological endpoints (number of relapses, proportion of relapse free patients, number of new T2 lesions) showed a trend, or were significant (new T2 lesions at month 6) in favoring NTZ. Conclusions De-escalation therapy from NTZ to IFNB over 1 year was associated with some clinical and radiological disease recurrence. Overall no major safety concerns were observed.
Published: 2013
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332. Aide au diagnostic du lymphome en imagerie hybride TEP/TDM: distinctions entre fixations cancéreuses et inflammatoires

Author: Lartizien , C., Rogez , M., Niaf , E., Ricard , F., Images et Modèles, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), 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 Claude Bernard Lyon 1 (UCBL), 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), Centre Hospitalier Universitaire de Lyon (CHU Lyon), 2 - Images et Modèles, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), 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 Claude Bernard Lyon 1 ( UCBL ), 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 Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ), Département de médecine nucléaire, and Hospices Civils de Lyon ( HCL )
Subjects: [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, [ SPI.SIGNAL ] Engineering Sciences [physics]/Signal and Image processing, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2012

333. Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial

Author: François Gueyffier, Catherine Cornu, Catherine Mercier, Marie-Françoise Mattei, Bernard Lelong, Michel Redonnet, Agnès Sirinelli, Pascale Boissonnat, Annick Mouly-Bandini, Marc-Alain Billes, L. Sebbag, Ségolène Gaillard, Eric Epailly, Shaida Varnous, Sabine Pattier, René Ecochard, Pôle Médico-Chirurgical de Transplantation Cardiaque Adulte, Hospices Civils de Lyon (HCL)-Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biostatistique, 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 chirurgie cadiovasculaire et thoracique [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Service de Cardiologie et Transplantation [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Chirurgie Cardiaque Adultes, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Département de Cardiologie et Transplantation, Hôpital Guillaume et René Laënnec, Service de Chirurgie Cardiaque, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CHU Strasbourg, Service de Chirurgie cardiaque et thoracique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [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), Evaluation et modélisation des effets thérapeutiques, CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), BMC, Ed., Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Urology, Medicine (miscellaneous), Renal function, Heart transplantation, 030204 cardiovascular system & hematology, 030230 surgery, Kidney, Calcineurin inhibition, Randomised clinical trial, law.invention, Cyclosporine A, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Clinical endpoint, Humans, Medicine, Pharmacology (medical), Prospective Studies, Prospective cohort study, Aged, lcsh:R5-920, Creatinine, business.industry, Research, Middle Aged, Surgery, Clinical trial, medicine.anatomical_structure, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cyclosporine, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, lcsh:Medicine (General), business, Immunosuppressive Agents
Abstract: Background Using reduced doses of Cyclosporine A immediately after heart transplantation in clinical trials may suggest benefits for renal function by reducing serum creatinine levels without a significant change in clinical endpoints. However, these trials were not sufficiently powered to prove clinical outcomes. Methods In a prospective, multicentre, open-label, parallel-group controlled trial, 95 patients aged 18 to 65 years old, undergoing de novo heart transplantation were centrally randomised to receive either a low (130 Results At 12 months, the mean (± SD) creatinine value was 120.7 μmol/L (± 35.8) in the low-dose group and 132.3 μmol/L (± 49.1) in the standard-dose group (P = 0.162). Post hoc analyses suggested that patients with higher creatinine levels at baseline benefited significantly from the lower Cyclosporine A target. The number of patients with at least one rejection episode was not significantly different but one patient in the low-dose group and six in the standard-dose group required dialysis. Conclusions In patients with de novo cardiac transplantation, early Cyclosporine A dose reduction was not associated with renal benefit at 12 months. However, the strategy may benefit patients with high creatinine levels before transplantation. Trial registration ClinicalTrials.gov NCT00159159
Published: 2012
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334. Qualification des émissions d'aérosols radioactifs liées à l'utilisation d'un générateur de technétium en service de médecine nucléaire

Author: Bombardier, P., Gensdarmes, F., Daugeron, D., Roche, A., Veyre, A., Giammarile, F., Houzard, C., Fraysse, M., Quisefit, J.-P., Laboratoire de Physique et de Métrologie des Aérosols (DSU/SERAC/LPMA), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire de Physique et Chimie de l'Environnement et de l'Espace (LPC2E), Observatoire des Sciences de l'Univers en région Centre (OSUC), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National d’Études Spatiales [Paris] (CNES), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Centre Hospitalier Universitaire de Lyon (CHU Lyon), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), and Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: National audience; The objective of this work is to characterize the emission of radioactive particles of 99mTc (technetium-99, a metastable gamma emitter of 6 h half-life) for lung marking in the environment of a nuclear medicine department. We studied the leakage of radioactive particles from the generating system during a lung scan test. This possible source of air contamination has been little studied and a specifically adapted survey methodology remains to be developed. To measure the leakage of radioactive particles from the generator, we designed a transportable test enclosure permitting one to collect and sample particles with a known accuracy, a low background level and the capability of recording short time events. Here, we present the characterization operations for this system and results we obtained with patients. The results show that radioactivity released in the air by the generator leakage is superior to that deposited in the patients' lungs by inhalation, that is, respectively, 5.7% and 3.8% of the total radioactivity initially introduced into the generator. © 2012 EDP Sciences.; L’objectif de ce travail est de caractériser l’émission de particules radioactives de 99mTc (technétium-99 métastable émetteur gamma de demi-vie 6 h) servant au marquage pulmonaire dans l’environnement d’un service de médecine nucléaire. Nous avons étudié les fuites du système générateur de particules radioactives lors d’un examen de scintigraphie pulmonaire. Cette éventuelle source de contamination ambiante a été peu étudiée et une méthodologie de surveillance spécifiquement adaptée reste à développer. Pour mesurer les fuites des générateurs d’aérosols radioactifs étudiés, nous avons conçu une enceinte d’essai transportable permettant de capter les particules et de les échantillonner avec une précision connue, un niveau de bruit de fond très faible et une capacité d’enregistrer les émissions transitoires courtes. Nous présentons les opérations de caractérisation de ce système et les résultats obtenus avec des patients. Ces résultats montrent que l’activité émise en ambiance par les fuites du générateur est supérieure à celle déposée dans les poumons du patient par inhalation, soit respectivement 5,7 % et 3,8 % de l’activité initialement introduite dans le générateur.
Published: 2012
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335. A 4-weekly course of rituximab is safe and improves tumor control for patients with minimal residual disease persisting 3 months after autologous hematopoietic stem-cell transplantation: results of a prospective multicenter phase II study in patients with follicular lymphoma

Author: Corinne Haioun, Gilles Salles, Eric Deconinck, F. Lazreg, Loïc Bergougnoux, Pauline Brice, Christian Recher, Philippe Colombat, Norbert Vey, Michel Attal, Jean-François Rossi, Remy Gressin, Noel Milpied, Franck Morschhauser, Georges Delsol, Service d'hématologie, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], CHU Bordeaux [Bordeaux], CHU Grenoble-Hôpital Michallon, Service d'hématologie/oncologie, CHU Lyon-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'hématologie-oncologie adultes, 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), Service d'Hématologie, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Roche, Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Saas, Philippe, Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Subjects: autologous stem cell transplantation, Neoplasm, Residual, medicine.medical_treatment, Follicular lymphoma, Phases of clinical research, Hematopoietic stem cell transplantation, Gastroenterology, Polymerase Chain Reaction, MESH: Lymphoma, Follicular, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, Autologous stem-cell transplantation, Medicine, Prospective Studies, Lymphoma, Follicular, CD20, MESH: Aged, MESH: Middle Aged, biology, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, 3. Good health, Oncology, MESH: Young Adult, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, medicine.drug, Adult, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Adolescent, Antineoplastic Agents, 03 medical and health sciences, Young Adult, follicular lymphoma, Internal medicine, Humans, MESH: Hematopoietic Stem Cell Transplantation, MESH: Neoplasm, Residual, Aged, MESH: Adolescent, MESH: Humans, business.industry, MESH: Adult, MESH: Polymerase Chain Reaction, medicine.disease, Minimal residual disease, MESH: Prospective Studies, Surgery, Transplantation, MESH: Antibodies, Monoclonal, Murine-Derived, biology.protein, minimal residual disease, MESH: Antineoplastic Agents, business, 030215 immunology
Abstract: International audience; BACKGROUND: This study explored the efficacy and safety of rituximab as treatment of clinical or molecular residual disease after autologous stem-cell transplantation (ASCT) in follicular lymphoma (FL). PATIENTS AND METHODS: Forty patients with CD20+ FL and clinically (group A, n = 14) or clono-specific PCR-detectable (group B, n = 25) residual disease persisting 3 months after ASCT received rituximab 375 mg/m² once weekly for 4 weeks. RESULTS: Response rate at day 50 was 36% [90% confidence interval (CI) 15-61] in group A (World Health Organization criteria) and 52% (90% CI 34-70) in group B (conversion PCR-undetectable status to undetectable status). The best response rate was 71% [nine complete responses (CRs) and one partial response] in group A and 76% in group B. At 36 months, all 10 responses persisted in group A, whereas 46% of patients in group B still had PCR-undetectable disease. Furthermore, 68% of patients in group B were still in clinical CR. Rituximab after ASCT was safe with few grade 3-4 toxic effects (15% patients), mainly acute reactions and infections. CONCLUSION: Rituximab induced a high rate of durable CRs in patients with clinically detectable disease, as well as durable eradication of PCR-detectable disease in patients with FL after ASCT. Continued molecular responses assessed with a highly sensitive and clono-specific PCR technique were correlated with an excellent disease control.
Published: 2012
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336. Correlation and agreement between contrast-enhanced ultrasonography and perfusion computed tomography for assessment of liver metastases from endocrine tumors: normalization enhances correlation

Author: Lefort, T., Pilleul, F., Mule, S., Bridal, S. L., Frouin, F., Lombard-Bohas, C., Walter, T., Lucidarme, O., Guibal, A., Departement d'imagerie Digestive, Hospices Civils de Lyon (HCL), Centre Léon Bérard [Lyon], 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 Universitaire de Reims (CHU Reims), CHU Lyon, Deutsches Elektronen-Synchrotron [Zeuthen] (DESY), Helmholtz-Gemeinschaft = Helmholtz Association, Service de Radiologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2012

337. Computer aided staging of lymphoma patients with FDG PET/CT imaging based on textural information

Author: Matthieu Rogez, Carole Lartizien, F. Ricard, Francesco Giammarile, Adeline Susset, Emilie Niaf, 2 - Images et Modèles, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), 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 Claude Bernard Lyon 1 ( UCBL ), 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 Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ), Département de médecine nucléaire, Hospices Civils de Lyon ( HCL ), Images et Modèles, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), 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 Claude Bernard Lyon 1 (UCBL), 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), and Centre Hospitalier Universitaire de Lyon (CHU Lyon)
Subjects: medicine.diagnostic_test, Computer science, business.industry, Decision tree, Cancer, Feature selection, [ SPI.SIGNAL ] Engineering Sciences [physics]/Signal and Image processing, medicine.disease, Lymphoma, Random forest, Support vector machine, [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], Image texture, Computer-aided diagnosis, Positron emission tomography, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Nuclear medicine, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Classifier (UML)
Abstract: International audience; We have designed a computer aided diagnosis (CADx) system to assess the presence of cancer in FDG PET/CT exams of lymphoma patients. Detection performances of the random decision forest (RDF) and support vector machine (SVM) classifiers were assessed based on a feature set including 115 PET and CT first order and textural parameters. An original feature selection method based on combining different filter methods was proposed. The evaluation database consisted of 156 lymphomatous (M for malignant), 158 physiologic (N for normal) and 32 inflammatory (NS for normal suspicious) regions of interest. An optimization study was performed for each classifier separately to select the best combination of parameters considering the two problems of discriminating the {M} and {NS+N} classes and the {M} and {NS} classes. Promising classification performance was achieved by the SVM combined with the 12 most discriminant features with AUC values of 0.97 and 0.91 for the first and second problem respectively.
Published: 2012
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338. Description and outcome of a cohort of 8 patients with WHIM syndrome from the French Severe Chronic Neutropenia Registry

Author: Philippe Bensaid, Gerard Daltroff, Gilles Devouassoux, Emmanuel Plouvier, Odile Fenneteau, Jean-François Nicolas, Yves Bertrand, Sarah Beaussant Cohen, Pierre Bordigoni, Fanny Fouyssac, Delphine Kerob, Jean Donadieu, Anne-Lise Delezoide, Françoise Bachelerie, Alain Dupuy, Blandine Beaupain, Pierre-Simon Rohrlich, Christine bellanne Chantelot, Karl Balabanian, Isabelle Plantier, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie et Oncologie pédiatrique [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'Hématologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Service de Pédiatrie, CH Belfort-Montbéliard, Service d'hématologie, Centre Hospitalier de Roubaix, Service de Dermatologie [Rennes] = Dermatology [Rennes], CHU Pontchaillou [Rennes], Service de Dermatologie [Saint-Louis], 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), Service de Médecine Infantile II [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Biologie du Développement, Service de Pneumologie, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'immunologie clinique et allergologie, Hématologie et immunologie pédiatrique, Hospices Civils de Lyon (HCL)-CHU Lyon-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hôpital Femme-Mère-Enfant (HFME), Cytokines, chimiokines et immunopathologie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The French registry is supported by grants from Amgen SAS, Chugai SA, GIS Maladies Rares, Institut de Veille Sanitaire and Inserm. This research is a study from the Centre de Référence des Déficits Immunitaires Héréditaires (CEREDIH: the French National Reference Center for Primary Immune Deficiencies, www.ceredih.fr) and has been supported by the Société Française d'Hématologie et d'Immunologie Pédiatrique. The K.B. laboratory is supported by the Agence Nationale de la Recherche, the Université Paris-Sud and Inserm, FB was supported by the ANR, AP-HP and E-rare (07 E-RARE 013-01), and K.B. and F.B. are members of the Laboratory of Excellence LERMIT supported by a grant from ANR (Investissements d'Avenir)., and BMC, Ed.
Subjects: Male, Pediatrics, WHIM, lcsh:Medicine, Monocytopenia, [SDV.GEN] Life Sciences [q-bio]/Genetics, Genital warts, Hypogammaglobulinemia, 0302 clinical medicine, Genetics(clinical), Pharmacology (medical), Registries, Child, Genetics (clinical), Medicine(all), 0303 health sciences, Bacterial Infections, General Medicine, Myelokathexis, Anti-Bacterial Agents, Pedigree, 3. Good health, Child, Preschool, Female, Warts, WHIM syndrome, Adult, Receptors, CXCR4, medicine.medical_specialty, Registry, Neutropenia, Adolescent, Primary Immunodeficiency Diseases, Infections, Young Adult, 03 medical and health sciences, medicine, Humans, Congenital Neutropenia, 030304 developmental biology, CXCR4, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Research, lcsh:R, Immunologic Deficiency Syndromes, Infant, medicine.disease, Immunology, Skin cancer, business, 030215 immunology
Abstract: BackgroundWHIM syndrome (WS), a rare congenital neutropenia due to mutations of the CXCR4 chemokine receptor, is associated with Human Papillomavirus (HPV)-induced Warts, Hypogammaglobulinemia, bacterial Infections and Myelokathexis. The long term follow up of eight patients highlights the clinical heterogeneity of this disease as well as the main therapeutic approaches and remaining challenges in the light of the recent development of new CXCR4 inhibitors.ObjectiveThis study aims to describe the natural history of WS based on a French cohort of 8 patients.MethodsWe have reviewed the clinical, biological and immunological features of patients with WS enrolled into the French Severe Chronic Neutropenia Registry.ResultsWe identified four pedigrees with WS comprised of eight patients and one foetus. Estimated incidence for WS was of 0.23 per million births. Median age at the last visit was 29 years. Three pedigrees encompassing seven patients and the fetus displayed autosomal dominant heterozygous mutations of theCXCR4gene, while one patient presented a wild-typeCXCR4gene. Two subjects exhibited congenital conotruncal heart malformations. In addition to neutropenia and myelokathexis, all patients presented deep monocytopenia and lymphopenia. Seven patients presented repeated bacterial Ears Nose Throat as well as severe bacterial infections that were curable with antibiotics. Four patients with late onset prophylaxis developed chronic obstructive pulmonary disease (COPD). Two patients reported atypical mycobacteria infections which in one case may have been responsible for one patient’s death due to liver failure at the age of 40.6 years. HPV-related disease manifested in five subjects and progressed as invasive vulvar carcinoma with a fatal course in one patient at the age of 39.5 years. In addition, two patients developed T cell lymphoma skin cancer and basal cell carcinoma at the age of 38 and 65 years.ConclusionsContinuous prophylactic anti-infective measures, when started in early childhood, seem to effectively prevent further bacterial infections and the consequent development of COPD. Long-term follow up is needed to evaluate the effect of early anti-HPV targeted prophylaxis on the development of skin and genital warts.
Published: 2012
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339. Hepatic arterial embolization versus chemoembolization in the treatment of liver metastases from well-differentiated midgut endocrine tumors: a prospective randomized study

Author: Anne Laure Pelletier, Vinciane Rebours, Frank Pilleul, Dermot O'Toole, Catherine Lombard-Bohas, Pascal Hammel, Magaly Zappa, Marie-Pierre Vullierme, Frédérique Maire, Philippe Ruszniewski, Anne Couvelard, Olivia Hentic, CHU Lyon, Swiss Federal Research Institute WSL, SWISS FEDERAL RESEARCH INSTITUTE WSL, Departement d'imagerie Digestive, Hospices Civils de Lyon (HCL), Centre Léon Bérard [Lyon], 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), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de gastro-entérologie et assistance nutritive, Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon
Subjects: Oncology, Adult, Male, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Urinary system, Gastroenterology, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Endocrinology, Hepatic Artery, Internal medicine, medicine, Humans, Infusions, Intra-Arterial, Embolization, Progression-free survival, Prospective Studies, Chemoembolization, Therapeutic, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Aged, Gastrointestinal Neoplasms, Chemotherapy, Endocrine and Autonomic Systems, business.industry, Arterial Embolization, Liver Neoplasms, Middle Aged, medicine.disease, Primary tumor, Embolization, Therapeutic, 3. Good health, Neuroendocrine Tumors, Treatment Outcome, Doxorubicin, 030220 oncology & carcinogenesis, Concomitant, Female, business, Follow-Up Studies
Abstract: Background: Liver surgery is the best treatment for endocrine liver metastases, but it is often impossible due to diffuse disease. Systemic chemotherapy is poorly effective. Hepatic arterial embolization (HAE) and chemoembolization (HACE) have shown efficacy but have never been compared. Patients and Methods: Patients with progressive unresectable liver metastases from midgut endocrine tumors were randomly assigned to receive HAE or HACE (two procedures at 3-month interval). The primary end point was the 2-year progression-free survival (PFS) rate. Secondary end points were response rates, overall survival, and safety. Results: Twelve patients were assigned to receive HACE and 14 to receive HAE. The patient characteristics were well matched across the treatment arms. The 2-year PFS rates were 38 and 44% in the HACE and HAE arms, respectively (p = 0.90). Age, gender, previous resection of the primary tumor or liver metastases, extent of liver involvement, and concomitant treatment with somatostatin analogues were not associated with changes in PFS, whereas elevated baseline urinary 5-HIAA and serum chromogranin A levels were associated with shorter PFS. The 2-year overall survival rates were 80 and 100% in the HACE and HAE arms, respectively (p = 0.16). The disease control rate on CT scan was 95%. Grade 3 toxicity occurred in 19% of patients, with no treatment-related deaths and no differences in the treatment arms. Conclusion: HACE and HAE are safe and permit tumor control in 95% of patients with progressive liver metastases from midgut endocrine tumors. The 2-year PFS was not higher among patients receiving HACE, not favoring the hypothesis of an additive efficacy of arterial chemotherapy or embolization alone.
Published: 2012

340. A randomised phase II study of the efficacy, safety and cost-effectiveness of pegfilgrastim and filgrastim after autologous stem cell transplant for lymphoma and myeloma (PALM study)

Author: Lionel Perrier, André Schmidt, Celine Ferlay, Philippe Quittet, Anne Lefranc, Philippe Moreau, Séverine Lissandre, Hervé Ghesquières, Leila Kammoun, Daniel Espinouse, Jacques-Olivier Bay, Catherine Sebban, Mauricette Michallet, David Pérol, Department of Medical Oncology, Centre Léon Bérard [Lyon], Groupe d'analyse et de théorie économique (GATE Lyon Saint-Étienne), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Hématologie et oncologie pédiatrique, Hématologie clinique, CHU Lyon, Département Hématologie (FNCLCC), Unité de transplantation médullaire et laboratoire d'oncologie moléculaire, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER, Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Department of Biostatistics, Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Dao, Taï, Groupe d'Analyse et de Théorie Economique Lyon - Saint-Etienne (GATE Lyon Saint-Étienne), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Oncology, Male, Cancer Research, Lymphoma, Cost effectiveness, Cost-Benefit Analysis, after autologou, Polyethylene Glycols, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Granulocyte Colony-Stimulating Factor, stem, [SHS.ECO] Humanities and Social Sciences/Economics and Finance, ComputingMilieux_MISCELLANEOUS, randomis, Middle Aged, cell transplant, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, autologou stem, Combined Modality Therapy, Recombinant Proteins, 3. Good health, Granulocyte colony-stimulating factor, myeloma, 030220 oncology & carcinogenesis, Absolute neutrophil count, Female, Multiple Myeloma, palm, Pegfilgrastim, medicine.drug, Adult, medicine.medical_specialty, Neutropenia, Fever, Filgrastim, randomis phase, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, transplant, cost-effectiveness, Aged, Peripheral Blood Stem Cell Transplantation, business.industry, medicine.disease, pegfilgrastim, Surgery, Transplantation, stem cell, business, Febrile neutropenia, 030215 immunology
Abstract: Aim To evaluate in a multicentre randomised study the effect on duration of febrile neutropenia (FN), the safety and cost-effectiveness of a single subcutaneous pegfilgrastim injection compared with daily injections of filgrastim after peripheral blood stem cell transplantation in patients receiving high dose chemotherapy for myeloma and lymphoma. Methods Patients were randomly assigned to a single dose of pegfilgrastim at day 5 (D5) or daily filgrastim from D5 to the recovery of absolute neutrophil count (ANC) to 0.5 G/L. Duration of FN, of neutrophil and platelet recovery, transfusion and antibiotic requirements were the main end-points of the study. Costs were calculated from D0 until transplant unit discharge. The incremental cost-effectiveness ratio was expressed as the cost per day of FN prevented. Probabilistic sensitivity analysis was performed by non-parametric bootstrap methods. Results Between October 2008 and September 2009, 10 centres enrolled 151 patients: 80 patients with lymphoma and 71 patients with myeloma. The mean duration of FN was 3.07 days (standard deviation (SD) 1.96) in the pegfilgrastin arm and 3.29 (SD 2.54) in the filgrastim one. Mean total costs were 23,256 and 25,448 euros for pegfilgrastim and filgrastim patients, respectively. There was a 62% probability that pegfilgrastim strictly dominates filgrastim. Concluding statement Pegfilgrastim after PBSC transplantation in myeloma and lymphoma is safe, effective when compared with filgrastim and could represent a cost-effective alternative in this setting.
Published: 2011

341. Diastolic Dysfunction in Patients with Type 2 Diabetes Mellitus: Is It Really the First Marker of Diabetic Cardiomyopathy?

Author: Hélène Thibault, Geneviève Derumeaux, Marc De Buyzere, M. Ovize, L. Groisne, Pierre Gautier Pignon-Blanc, Laura Ernande, Pierre Croisille, Cyrille Bergerot, Philippe Moulin, Ernst Rietzschel, Thierry C. Gillebert, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Hôpital Louis Pradel, Hospices Civils de Lyon (HCL), RMN et optique : De la mesure au biomarqueur, 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)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Claude Bernard Lyon 1 (UCBL), 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 Claude Bernard Lyon 1 (UCBL), and 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)
Subjects: Adult, Male, medicine.medical_specialty, Heart disease, Diabetic Cardiomyopathies, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV]Life Sciences [q-bio], Diastole, 030209 endocrinology & metabolism, Speckle tracking echocardiography, Comorbidity, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Diabetes mellitus, Prevalence, Ventricular Dysfunction, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, ComputingMilieux_MISCELLANEOUS, Ultrasonography, 2. Zero hunger, Ejection fraction, business.industry, Middle Aged, medicine.disease, 3. Good health, Blood pressure, Diabetes Mellitus, Type 2, Heart failure, Multivariate Analysis, Cardiology, Female, Cardiology and Cardiovascular Medicine, Isovolumic relaxation time, business
Abstract: Background Diastolic dysfunction is considered the first marker of diabetic cardiomyopathy. However, preclinical systolic alteration was also recently described by strain, but its association with diastolic dysfunction has never been investigated. Methods One hundred fourteen patients with type 2 diabetes mellitus (DM) with controlled blood pressure and without overt heart disease were prospectively enrolled and compared with 88 age-matched controls. All subjects underwent comprehensive echocardiography, including diastolic evaluation according to current recommendations and speckle-tracking imaging. The prevalence of diastolic dysfunction, the determinants of diastolic parameters, and the association between preclinical systolic and diastolic dysfunctions were studied. Results Diastolic parameters were altered in patients compared with controls, with lower E/A ratios, longer mitral deceleration and isovolumic relaxation times, and higher E/e′ ratio. Diastolic dysfunction occurred in 47% of patients with DM (33% and 14% with grade I and II diastolic dysfunction, respectively) and systolic alteration (longitudinal strain ≥ −18%) in 32% of patients. Whereas longitudinal systolic strain was independently associated with DM and gender, diastolic parameters were influenced by many factors, including age, rate-pressure product, history of hypertension, and body mass index. Systolic alteration occurred in 28% of patients with DM with normal diastolic function and in 35% with diastolic dysfunction. Conclusions Diastolic dysfunction diagnosed according to current recommendations is frequent in patients with DM but is also influenced by other factors. Systolic strain alteration may exist despite normal diastolic function, indicating that diastolic dysfunction should not be considered the first marker of a preclinical form of diabetic cardiomyopathy.
Published: 2011
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342. Is there any relationship between the exposure to mycophenolic acid and the clinical status in children with lupus?

Author: C. Jurado, M Fischbac, Bruno Ranchin, Etienne Bérard, Stéphane Decramer, Franck Saint-Marcoux, Brigitte Bader-Meunier, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges], CHU Limoges, Service d'immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie pédiatrique, CHU Lyon, Service de Pédiatrie - Néphrologie, Médecine interne, Hypertension, CHU Toulouse [Toulouse]-Hôpital des Enfants, CHU Toulouse [Toulouse], Service de pédiatrie, CHU Strasbourg, Service de Néphrologie Pédiatrique, Centre Hospitalier Universitaire de Nice (CHU Nice)-Fondation LENVAL-Hopital pour Enfants, BMC, Ed., and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: medicine.medical_specialty, Pediatrics, lcsh:Diseases of the musculoskeletal system, Logistic regression, Gastroenterology, Mycophenolic acid, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Rheumatology, Pharmacokinetics, Internal medicine, Area under curve, medicine, Immunology and Allergy, Pediatrics, Perinatology, and Child Health, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Systemic lupus erythematosus, medicine.diagnostic_test, business.industry, lcsh:RJ1-570, lcsh:Pediatrics, medicine.disease, 3. Good health, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Therapeutic drug monitoring, Poster Presentation, Pediatrics, Perinatology and Child Health, lcsh:RC925-935, business, medicine.drug
Abstract: Methods We launched a non-interventional study with analysis of clinical, biological and pharmacokinetic information. Full-PK profiles of MPA were modelled using an iterative two-stage approach (1). The clinical status was defined by the SLEDAI, the SLE being considered active for a score ≥6. Relationships between MPA through concentrations (C0), AUC (Area Under Curve) or AUC/ dose values, and the disease’s activity were studied using logistic regression analysis.
Published: 2011
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343. Functional mapping of the A2 domain from human factor VIII

Author: Marc Delcourt, Jean-Luc Plantier, Jean-Luc Pellequer, Claude Negrier, Didier Saboulard, Laboratoire d’hémobiologie, Université Catholique de Lyon (UCLy) (UCLy), BIOMETHODES, Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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)-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), Laboratoire des Intéractions et Reconnaissances Moléculaires (LIRM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Universitaire de Lyon (CHU Lyon), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Mutant, MESH: Cricetinae, MESH: Amino Acid Sequence, 030204 cardiovascular system & hematology, MESH: Mutant Proteins, MESH: Protein Structure, Tertiary, 0302 clinical medicine, MESH: Chlorocebus aethiops, Cricetinae, Chlorocebus aethiops, MESH: Animals, MESH: Peptide Fragments, Alanine, chemistry.chemical_classification, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, Hematology, MESH: Factor VIII, MESH: COS Cells, MESH: Mutagenesis, Site-Directed, Coagulation, Biochemistry, MESH: Blood Coagulation, Domain (ring theory), COS Cells, MESH: Mutation, Molecular Sequence Data, Hemophilia A, Cofactor, 03 medical and health sciences, Animals, Humans, Amino Acid Sequence, Blood Coagulation, MESH: Humans, MESH: Molecular Sequence Data, Factor VIII, MESH: Hemophilia A, Peptide Fragments, Protein Structure, Tertiary, Functional mapping, 030104 developmental biology, Mutation, biology.protein, Mutagenesis, Site-Directed, Mutant Proteins, Glycoprotein, Function (biology)
Abstract: SummaryCoagulation factor VIII (FVIII) is a multidomain glycoprotein in which the FVIII A2 domain is a key structural element. We aimed at identifying residues within FVIII A2 domain that are crucial for the maintenance of the cofactor function. A high number (n=206) of mutants were generated by substituting original residues with alanine. The mutants were expressed in COS-1 cells and their antigen levels and procoagulant activities were measured. The residues were classified in three categories: those with a non-detrimental alteration of their activities (activity >50 % of control FVIII; n=98), those with a moderate alteration (15 %
Published: 2011
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344. Pegfilgrastim versus Filgrastim after high-dose chemotherapy and autologous stem cell transplantation in adult patients with lymphoma and myeloma: cost-effectiveness evaluation alongside a randomized controlled trial

Author: Perrier, Lionel, Lefranc, Anne, Quittet, Philippe, Ghesquières, Hervé, Favier, Bertrand, Espinouse, Daniel, de Peretti, Christian, Moles, Marie Pierre, Cacheux, Victoria, Leprêtre, Stéphane, Renaud, Marc, Pérol, David, Sylvestre-Baron, Patrick, Sebban, Catherine, Groupe d'analyse et de théorie économique (GATE Lyon Saint-Étienne), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Centre Léon Bérard [Lyon], Service d'hématologie et oncologie médicale, Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Département Hématologie (FNCLCC), Department of Pharmacy, Hématologie clinique, CHU Lyon, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), HEMATOLOGIE, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Département d'Hématologie et Oncologie Médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Biostatistics, Department of Medical Oncology, Dao, Taï, Groupe d'Analyse et de Théorie Economique Lyon - Saint-Etienne (GATE Lyon Saint-Étienne), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), and Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM)
Subjects: JEL: I - Health, Education, and Welfare/I.I1 - Health/I.I1.I11 - Analysis of Health Care Markets, Filgrastim, JEL: I - Health, Education, and Welfare/I.I1 - Health, Cost-effectiveness, [SHS.ECO] Humanities and Social Sciences/Economics and Finance, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Pegfilgrastim, JEL: I - Health, Education, and Welfare/I.I1 - Health/I.I1.I18 - Government Policy • Regulation • Public Health
Published: 2011

345. l-asparaginase loaded red blood cells in refractory or relapsing acute lymphoblastic leukaemia in children and adults: results of the GRASPALL 2005-01 randomized trial

Author: Carine, Domenech, Xavier, Thomas, Sylvie, Chabaud, Andre, Baruchel, François, Gueyffier, Françoise, Mazingue, Anne, Auvrignon, Selim, Corm, Herve, Dombret, Patrice, Chevallier, Claire, Galambrun, Françoise, Huguet, Faezeh, Legrand, Françoise, Mechinaud, Norbert, Vey, Irène, Philip, David, Liens, Yann, Godfrin, Dominique, Rigal, Yves, Bertrand, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), equipe 14, 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)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), 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 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), CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire d'Hématologie [Purpan], 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], Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Children's Cancer Center, The Royal Children's Hospital, Hematology (IPC-Marseille), Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC), Centre Léon Bérard [Lyon], Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Adult, Male, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Erythrocytes, Adolescent, MESH: Drug Delivery Systems, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Drug Administration Schedule, Drug Administration Schedule, MESH: Dose-Response Relationship, Drug, Young Adult, MESH: Bioreactors, Bioreactors, Drug Delivery Systems, MESH: Child, Asparaginase, Humans, MESH: Asparaginase, Child, MESH: Adolescent, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, Drug Carriers, MESH: Humans, MESH: Middle Aged, Dose-Response Relationship, Drug, MESH: Erythrocytes, MESH: Child, Preschool, Infant, MESH: Adult, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Infant, MESH: Male, MESH: Drug Carriers, MESH: Young Adult, Child, Preschool, MESH: Antineoplastic Agents
Abstract: International audience; l-asparaginase encapsulated within erythrocytes (GRASPA(®) ) should allow serum asparagine depletion over a longer period than the native form of the enzyme, using lower doses and allowing better tolerance. The GRASPALL 2005-01 study, a multicentre randomized controlled trial, investigated three doses of GRASPA(®) for the duration of asparagine depletion in a phase I/II study in adults and children with acute lymphoblastic leukaemia (ALL) in first relapse. Between February 2006 and April 2008, 18 patients received GRASPA(®) (50 iu/kg: n = 6,100 iu/kg: n = 6, 150 iu/kg: n = 6) after randomization, and six patients were assigned to the Escherichia coli native l-asparaginase (E. colil-ASNase) control group. GRASPA(®) was effective at depleting l-asparagine. One single injection of 150 iu/kg of GRASPA(®) provided similar results to 8 × 10,000 iu/m(2) intravenous injections of E. colil-ASNase. The safety profile of GRASPA(®) showed a reduction in the number and severity of allergic reactions and a trend towards less coagulation disorders. Other expected adverse events were comparable to those observed with E. colil-ASNase and there was also no difference between the three doses of GRASPA(®) .
Published: 2011
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346. Safe, efficient, and reproductible gene therapy of the brain in the dog models of Sanfilippo and Hurler syndromes

Author: Sylvie Raoul, Yan Cherel, Béatrice Joussemet, Stéphanie Bigou, Jean-Michel Heard, Karen L. Kline, Philippe Moullier, Jérôme Ausseil, Song Liu, Monique Piraud, Eman E.A. Mohammed, Irène Maire, Christopher B. Thomson, N. Matthew Ellinwood, Marie-Thérèse Vanier, Jackie K. Jens, Nathalie Desmaris, Harald Petry, Jennifer D. Parkes, Stephan Hermening, Elizabeth M. Snella, Rachid Benchaouir, Roseline Froissart, Yaouen Lajat, Marie-Anne Colle, Marc Tardieu, Carine Ciron, Françoise A. Roux, Iowa State University (ISU), Rétrovirus et Transfert Génétique, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurochirurgie, Centre hospitalier universitaire de Nantes (CHU Nantes), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Développement et Pathologie du Tissu Musculaire (DPTM), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Nantes, Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal [CHU Lyon] (Centre de Biologie et Pathologie Est), Hospices Civils de Lyon (HCL)-Groupement Hospitalier Est, Amsterdam Molecular Therapeutics, Partenaires INRAE, Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Vecteurs viraux et transfert de gènes in vivo, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Veterinary Clinical Science, University Estadual Paulista, Métabolomique et maladies métaboliques, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), ProdInra, Migration, Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Mucopolysaccharidosis I, Genetic enhancement, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Genetic Vectors, Biology, Polymerase Chain Reaction, MODELE SOURIS, Mucopolysaccharidosis III, 03 medical and health sciences, Dogs, 0302 clinical medicine, Acetylglucosaminidase, Drug Discovery, Genetics, medicine, Lysosomal storage disease, Animals, Vector (molecular biology), Hurler syndrome, Molecular Biology, Neuroinflammation, 030304 developmental biology, Sanfilippo syndrome, Pharmacology, 0303 health sciences, Brain, Immunosuppression, Genetic Therapy, Dependovirus, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Disease Models, Animal, Immunology, Molecular Medicine, Original Article, 030217 neurology & neurosurgery
Abstract: International audience; Recent trials in patients with neurodegenerative diseases documented the safety of gene therapy based on adeno-associated virus (AAV) vectors deposited into the brain. Inborn errors of the metabolism are the most frequent causes of neurodegeneration in pre-adulthood. In Sanfilippo syndrome, a lysosomal storage disease in which heparan sulfate oligosaccharides accumulate, the onset of clinical manifestation is before 5 years. Studies in the mouse model showed that gene therapy providing the missing enzyme alpha-N-acetyl-glucosaminidase to brain cells prevents neurodegeneration and improves behavior. We now document safety and efficacy in affected dogs. Animals received eight deposits of a serotype 5 AAV vector, including vector prepared in insect Sf9 cells. As shown previously in dogs with the closely related Hurler syndrome, immunosuppression was necessary to prevent neuroinflammation and elimination of transduced cells. In immunosuppressed dogs, vector was efficiently delivered throughout the brain, induced alpha-N-acetyl-glucosaminidase production, cleared stored compounds and storage lesions. The suitability of the procedure for clinical application was further assessed in Hurler dogs, providing information on reproducibility, tolerance, appropriate vector type and dosage, and optimal age for treatment in a total number of 25 treated dogs. Results strongly support projects of human trials aimed at assessing this treatment in Sanfilippo syndrome.
Published: 2011
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347. Neuroendocrine tumors of Meckel's diverticulum: lessons from a single institution study of eight cases

Author: Poncet, G., Hervieu, V., Walter, T., Lepinasse, F., Chardon, L., Pilleul, F., Lombard-Bohas, C., Chayvialle, J. A., Partensky, C., Scoazec, J. Y., Deutsches Elektronen-Synchrotron [Zeuthen] (DESY), Helmholtz-Gemeinschaft = Helmholtz Association, Departement d'imagerie Digestive, Hospices Civils de Lyon (HCL), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), 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), CHU Lyon, Université de Lyon, Tumeurs endocrines digestives : mécanismes de la tumorigenèse et de la progression tumorale, and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2011

348. Coagulation dynamics of a blood sample by multiple scattering analysis

Author: Marie-Line Cosnier, Anne Planat-Chrétien, Philippe Peltie, Magalie Faivre, Christophe Nougier, Claude Negrier, Myriam Cubizolles, Patrick Pouteau, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Centre Hospitalier Universitaire de Lyon (CHU Lyon)
Subjects: speckle correlation Paper 10311RR, Whole Blood Coagulation Time, Materials science, Light, Coagulation time, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Biomedical Engineering, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Light scattering, law.invention, Photometry, Biomaterials, Speckle pattern, Optics, law, Humans, Scattering, Radiation, Coagulation (water treatment), [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, International Normalized Ratio, coagulation, Blood Coagulation, Scattering, business.industry, Lasers, Dynamics (mechanics), Equipment Design, Laser, Sample (graphics), prothrombin time, Atomic and Molecular Physics, and Optics, Electronic, Optical and Magnetic Materials, multiple scattering analysis, Equipment Failure Analysis, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Refractometry, Biophysics, blood dynamics, business
Abstract: International audience; We report a new technique to measure coagulation dynamics on whole-blood samples. The method relies on the analysis of the speckle figure resulting from a whole-blood sample mixed with coagulation reagent and introduced in a thin chamber illuminated with a coherent light. A dynamic study of the speckle reveals a typical behavior due to coagulation. We compare our measured coagulation times to a reference method obtained in a medical laboratory. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).
Published: 2011
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349. Version française des questionnaires de dépistage de l'autisme de haut niveau ou du syndrome d'Asperger chez l'adolescent : Quotient du spectre de l'autisme Quotient d'Empathie et Quotient de Systématisation. Protocole et traduction des questionnaires

Author: Sandrine, Sonié, Behrouz, Kassai, Elodie, Pirat, Sandrine, Masson, Paul, Bain, Janine, Robinson, Anne, Reboul, Bruno, Wicker, Coralie, Chevallier, Véronique, Beaude-Chervet, Marie-Hélène, Deleage, Dorothée, Charvet, Catherine, Barthélémy, Thierry, Rochet, Mohamed, Tatou, Valérie, Arnaud, Sabine, Manificat, Centre Hospitalier le Vinatier [Bron], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), University of Cambridge [UK] (CAM), Laboratoire sur le langage, le cerveau et la cognition (L2C2), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Cognitives (ISC), Institut de neurosciences cognitives de la méditerranée - UMR 6193 (INCM), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), King‘s College London, Clinique Saint Jean de Dieu, Hôpital Bretonneau, and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Cross-Cultural Comparison, Male, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Adolescent, Mental Disorders, Intelligence, Reproducibility of Results, Translating, Personality Assessment, Cross-Sectional Studies, Reference Values, Surveys and Questionnaires, Humans, Mass Screening, Female, France, Asperger Syndrome, Autistic Disorder, Empathy, Child
Abstract: Objectif: Aucun outil n’est disponible en France pour le dépistage des troubles du spectre de l’autisme sans déficience intellectuelle (« Autisme de Haut Niveau » ou Syndrome d’Asperger, ici nommés « TED SDI »). L’utilisation de test de dépistage par des cliniciens « de première ligne » permettrait de mieux détecter les enfants susceptibles d’avoir de tels troubles et d’améliorer leur prise en charge. Au Royaume-Uni, 3 questionnaires ont été évalués : Quotient du spectre de l’autisme (AQ), Quotient d’empathie (EQ), et Quotient de systématisation (SQ). Nous avons traduit ces 3 questionnaires et proposons leur méthode d’évaluation en France auprès d’adolescents TED SDI et d’adolescents témoins.Méthode. La traduction du questionnaire en français a nécessité deux traductions simultanées, deux rétro-traductions et deux réunions d’harmonisation. Il s’agit d’une étude transversale comparant les scores obtenus avec les trois questionnaires AQ, EQ et SQ remplis par les parents de 4 groupes d’adolescents : 100 adolescents TED SDI (50 avec QI ≥ 85 et 50 avec 70 ≤ QI < 85), 50 adolescents ayant un autre trouble psychiatrique (TP), et 200 adolescents témoins (T).Résultats. Au total, 580 questionnaires ont été envoyés à 40 centres recruteurs en date du 28/02/2010 et 277 questionnaires ont été reçus : TED SDI : 70 (70 %) ; TP : 25 (50 %) et T : 182 (91 %). Dans le groupe témoin, 92 filles (moyenne 14,4 ± 1,7 ans) et 66 garçons (14,5 ± 1,7 ans) ont été enregistrés avec des données validées et saisies. Dans le groupe TED SDI, 4 filles (14,3 ± 2,4 ans) et 42 garçons (14,5 ± 1,7 ans) ont été recrutés. Une fille (81) et 6 garçons (72,2 ± 7,7) ont un QI compris entre 70 et 85 et 3 filles (95,3 ± 4,2) et 36 garçons (102,9 ± 12) ont un QI supérieur à 85. Dans le groupe TP, 9 filles (15,9 ± 1,7 ans) et 4 garçons (15,8 ± 1,9 ans) ont été recrutés.Conclusion. L’objectif de cette étude est de mettre à disposition en français les questionnaires AQ, EQ et SQ pour les cliniciens francophones. Cette étude permettra d’évaluer avec rigueur l’intérêt du questionnaire AQ pour le dépistage des TED SDI chez les adolescents.
Published: 2011
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350. Perfusion characterization of liver metastases from endocrine tumors: Computed tomography perfusion

Author: Aurélie Guyennon, Marius Mihaila, John Palma, Catherine Lombard-Bohas, Frank Pilleul, Jean-Alain Chayvialle, CHU Lyon, Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), Université Claude Bernard Lyon 1 (UCBL), 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)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Ratiney, Helene
Subjects: Aorta, medicine.medical_specialty, Brief Article, business.industry, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Blood volume, Blood flow, Neuroendocrine tumors, medicine.disease, Contrast medium, Vascularity, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, medicine.artery, Endocrine system, Medicine, Radiology, medicine.symptom, business, Perfusion, ComputingMilieux_MISCELLANEOUS
Abstract: AIM: To assess prospectively parameters of computed tomography perfusion (CT p) for evaluation of vascularity of liver metastases from neuroendocrine tumors. METHODS: This study was approved by the hospital’s institutional review board. All 18 patients provided informed consent. There were 30 liver metastases from neuroendocrine tumors. Patients were divided into three groups depending on the appearance of the liver metastases at the arterial phase of morphological CT (hyperdense, hypodense and necrotic). Sequential acquisition of the liver was performed before and for 2 min after intravenous injection of 0.5 mg/kg contrast medium, at 4 mL/s. Data were analyzed using deconvolution analysis to calculate blood flow (BF), blood volume (BV), mean transit time (MTT), hepatic arterial perfusion index (HAPI) and a bi-compartmental analysis was performed to obtain vascular permeability-surface area product (PS). Post-treatment analysis was performed by a radiologist and regions of interest were plotted on the metastases, normal liver, aorta and portal vein. RESULTS: At the arterial phase of the morphological CT scan, the aspects of liver metastases were hyperdense (n = 21), hypodense (n = 7), and necrotic (n = 2). In cases of necrotic metastases, none of the CT p parameters were changed. Compared to normal liver, a significant difference in all CT p parameters was found in cases of hyperdense metastases, and only for HAPI and MTT in cases of hypodense metastases. No significant difference was found for MTT and HAPI between hypo- and hyperdense metastases. A significant decrease of PS, BV and BF was demonstrated in cases of patients with hypodense lesions PS (23 ± 11.6 mL/100 g per minute) compared to patients with hyperdense lesions; PS (13.5 ± 10.4 mL/100 g per minute), BF (93.7 ± 75.4 vs 196.0 ± 115.6 mL/100 g per minute) and BV (9.7 ± 5.9 vs 24.5 ± 10.9 mL/100 g). CONCLUSION: CT p provides additional information compared to the morphological appearance of liver metastases.
Published: 2010

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