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2. Immunovirological status in people with perinatal and adult-acquired HIV-1 infection: a multi-cohort analysis from FranceResearch in context

Author

Rémonie Seng, Pierre Frange, Albert Faye, Catherine Dollfus, Jérôme le Chenadec, Faroudy Boufassa, Asma Essat, Tessa Goetghebuer, Elisa Arezes, Véronique Avettand-Fènoël, Jean-Joël Bigna, Stéphane Blanche, Cécile Goujard, Laurence Meyer, Josiane Warszawski, Jean-Paul Viard, H. Aumaitre, E. Froguel, F. Caby, S. Dellion, L. Gerard, F. Lucht, C. Chirouze, M. Dupon, Jl Schmit, C. Goujard, T. Allegre, B. Cazenave, G. Hittinger, P. De Truchis, J. Cailhol, C. Duvivier, A. Canestri, O. Bouchaud, M. Karmochkine, D. Salmon-Ceron, D. Zucman, E. Mortier, R. Tubiana, P.M. Girard, C. Pintado, A. Cabie, V. Rabier, P. Morlat, D. Neau, C. Genet, D. Makhloufi, S Bregigeon Ronot, J. Ghosn, V. Reliquet, P. Perré, Jl Pellegrin, C. Arvieux, C. Cheneau, L. Bernard, P. Delobel, R. Verdon, C. Jacomet, L. Piroth, F. Ajana, S. Bevilacqua, Y. Debab, A.L. Lecapitaine, L. Cotte, S. Mokhtari, P. Mercie, P. Poubeau, V. Garrait, Ma Khuong, G. Beck-Wirth, L. Blum, S. Blanche, F. Boccara, T. Prazuck, C. Barbuat, J.P. Viard, S. Stegmann-Planchard, B. Martha, J.M. Treluyer, E. Dore, C. Gaud, M. Niault, E. Fernandes, H. Hitoto, A. Compagnucci, N. Elenga, A. Faye, C. Dollfus, A. Chace, M. Levine, S.A. Martha, C. Floch-Tudal, K. Kebaïli, N. Entz-Werle, J. Tricoire, F. Mazingue, P. Bolot, P. Brazille, T. Goetghebuer, A.F. Gennotte, D. Van Der Linden, V. Schmitz, M. Moutschen, C. Crenn-Hebert, F. Habibi, A. Coursol, E. Guesdon, P.F. Ceccaldi, M. Dehlinger – Paul, E. Pannier, V. Marcou, C. Elleau, M. Achkar, M.O. Vareil, S. Couderc, C. Routier, M.A. Bouldouyre, L. Selleret, A. Chabrol, C. Bellahcene, C. Pluchart, A. Yangui, D. Vignes, A. Alissa, A. Johnson, E. Lachassinne, A. Benbara, L. Karaoui, A. Bongain, B. Yakeu, J.L. Schmit, L. Cravello, C. Hubert, P. Faucher, D. Pinquier, C. Borie, D. Rocchi, C. Brunet-Cartier, C. Briandet, J. Brouard, A. Chalvon-Demersay, M. Rajguru, K. Billiemaz, A. Fresard, A. Moulin, P. Fialaire, L. Mesnard, E. Werner, E. Vintejoux, J. Marian, S. Ranaivojaona, F. Bissuel, M. Abdelhadi, Y. Hammou, C. Genet-Villeger, Y. Hatchuel, G. Bachelard, M. Medus, J. Dendale – Nguyen, T.S. Guimard, A. Martha, M. Rouha, P. Perfezou, L. De Saint Martin, S. Jaffuel, R. Buzele, M. Gousseff, C. Cudeville, V. Vitrat, C. Michau, G. Palenzuela, M. Driessen, B. Heller-Roussin, J.M. Labaune, B. Muanza, J. Massardier, M. Partisani, I. Hau, C. Runel-Belliard, C. Brehin, K. Kebaili, M. Lalande, M. Lagree, K. Lacombe, J.-M. Molina, J. Reynes, O. Robineau, F. Raffi, A. Becker, L. Weiss, T. Allègre, G. Pialoux, F. Souala, A. Rami, C. Katlama, A. Cabié, J.-P. Viard, F. Bastides, C. Michel, D. Salmon, J-D Le Lièvre, A. Sotto, E. Rouveix, A. Naqvi, S. Brégigeon, R. Rodet, A. Simon-Coutelier, J.-L. Esnault, R. Buzelé, A. Stein, C. Godin-Colet, G. Pichancourt, P. Caraux-Paz, M Mohseni Zadeh, L. Gérard, C. Lascaux-Cametz, L. Bodard, J.-L. Pellegrin, N. Ettahar, A. Uludag, E. Rosenthal, F. Prevoteau du Clary, S. Jaureguiberry, P. Philibert, A.-L. Lecapitaine, E. Chakvetadze, H. Champagne, V. Daneluzzi, J. Goupil de Bouillé, A. Leprêtre, I. Lamaury, I. Darasteanu, B. Abraham, D. Garipuy, J.-L. Berger, J.-L. Schmit, K. Diallo, F. Gourdon, O. Vaillant, V. Gaborieau, J. Doll, D. Quinsat, L. Geffray, J.-J. Girard, D. Houlbert, V. Perronne, E. Klement, O. Antioniotti, C. Rouzioux, V. Avettand-Fenoel, O. Lortholary, S. Boucly, A. Maignan, R. Thiebaut, L. Meyer, F. Boufassa, M.A. Charles, R. Dray-Spira, C. Legeai, V. Amon, N. Benammar, R. Seng, L. Slama, P. Bonnard, C. Chakvetadze, T. L’Yavanc, J. Capeau, C. Vigouroux, S. Fellahi, J.P. Bastard, E. Oksenhendler, J.F. Bourge, V. Bajzik, D. Sereni, C. Lascoux-Combe, O. Taulera, L.V. Dien, J. Delgado, J.M. Molina, T. Saint-Marc, S. Ferret, J. Pavie, J.F. Bergmann, M. Parrinello, BLefebvre, C. Boudraa, B. Diallo, C. Lupin, S. Herson, A. Simon, N. Edeb, L. Guillevin, T. Tahi, M.P. Pietri, D. Tisne-Dessus, C. Jalbert, P. Yeni, S. Matheron, G. Pahlavan, B. Phung, N. El-Alami Talbi, Z. Ramani, G. Catalano, C. Godard, F. Boue, V. Chambrin, D. Bornarel, H. Schoen, R. Carlier, B. Fantin, C. Poder, R. Dhote, M. Bentata, P. Honore, Xuan Tuyet, J.F. Delfraissy, F. Chaix, M.T. Rannou, Y. Levy, A. Sobel, C. Dumont, S. Abel, S. Pierre-François, V. Beaujolais, I. Poizot-Martin, O. Zaegel-Faucher, C. Debreux, J. Moreau, E. Van Der Gheynst, M.C. Thiebaut-Drobacheff, A. Foltzer, B. Hoen, J.F. Faucher, H. Gil, J.M. Ragnaud, I. Raymond, I. Louis, M. Hessamfar, V. Baillat, C Merle De Boever, C. Tramoni, A. Soufflet, P. Guadagnin, P. Choutet, O. Mounoury, D. Brosseau, H. Hue, T. May, S. Wassoumbou, M. Stenzel, M.P. Bouillon, Y. Yazdanpanah, T. Huleux, E. Aissi, S. Pavel, D. Rey, P. Fischer, G. Blaison, M. Martinot, A. Pachart, F. Jeanblanc, J.L. Touraine, C. Trepo, P. Miailhes, K. Kouadjo, V. Thoirain, C. Brochier, P. Perre, S. Leautez, J.L. Esnault, and I. Suaud

Subjects
Perinatal HIV infection, Cohort, Viral failure, Immunological outcome, Epidemiology, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: No study has compared the virological and immunological status of young people with perinatally-acquired HIV infection (P-HIV) with that of people with HIV adulthood (A-HIV) having a similar duration of infection. Methods: 5 French cohorts of P-HIV and A-HIV patients with a known date of HIV-infection and receiving antiretroviral treatment (ART), were used to compare the following proportions of: virological failure (VF) defined as plasma HIV RNA ≥ 50 copies/mL, CD4 cell percentages and CD4:CD8 ratios, at the time of the most recent visit since 2012. The analysis was stratified on time since infection, and multivariate models were adjusted for demographics and treatment history. Findings: 310 P-HIV were compared to 1515 A-HIV (median current ages 20.9 [IQR:14.4–25.5] and 45.9 [IQR:37.9–53.5] respectively). VF at the time of the most recent evaluation was significantly higher among P-HIV (22.6%, 69/306) than A-HIV (3.3%, 50/1514); p ≤ 0.0001. The risk of VF was particularly high among the youngest children (2–5 years), adolescents (13–17 years) and young adults (18–24 years), compared to A-HIV with a similar duration of infection: adjusted Odds-Ratio (aOR) 7.0 [95% CI: 1.7; 30.0], 11.4 [4.2; 31.2] and 3.3 [1.0; 10.8] respectively. The level of CD4 cell percentages did not differ between P-HIV and A-HIV. P-HIV aged 6–12 and 13–17 were more likely than A-HIV to have a CD4:CD8 ratio ≥ 1: 84.1% vs. 58.8% (aOR = 3.5 [1.5; 8.3]), and 60.9% vs. 54.7% (aOR = 1.9 [0.9; 4.2]) respectively. Interpretation: P-HIV were at a higher risk of VF than A-HIV with a similar duration of infection, even after adjusting for treatment history, whereas they were not at a higher risk of immunological impairment. Exposure to viral replication among young patients living with HIV since birth or a very early age, probably because of lower adherence, could have an impact on health, raising major concerns about the selection of resistance mutations and the risk of HIV transmission. Funding: Inserm - ANRS MIE.

Published
2024
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3. Modalités d'administration de l'insuline par voie intraveineuse chez le nouveau-né prématuré

Author

F. Egrot, C. Farges, Patrick Hubert, D. Mitanchez-Mokhtari, E. Walter-Nicolet, and J.M. Tréluyer

Subjects
Gynecology, medicine.medical_specialty, business.industry, Recien nacido, Pediatrics, Perinatology and Child Health, medicine, Recem nascido, Glucose homeostasis, Professional practice, Insulin pharmacokinetics, business, Infant newborn
Abstract

Resume L'hyperglycemie transitoire est frequente au cours de la premiere semaine de vie chez le grand premature de moins de 30 semaines d'âge gestationnel. L'insuline en perfusion continue est un traitement indique dans cette situation. Objectifs. – Evaluer les pratiques de l'administration de l'insuline chez le nouveau-ne premature de differents centres de neonatologie francais. Materiel et methodes. – Nous avons realise une enquete par questionnaire aupres de 49 equipes. Trente-huit reponses ont ete recueillies (77,5 %). Resultats. – La majorite des centres utilisait l'insuline en perfusion continue (89,5 %). Le seuil de la glycemie indiquant la mise en route du traitement etait tres variable (de 7 a 16,5 mmol/l), de meme que la posologie initiale (de 0,01 a 0,1 U/kg par heure). La concentration minimale en insuline de la solution perfusee variait de 0,01 a 1 U/ml, 57 % des centres utilisant une concentration minimale entre 0,05 et 0,2 U/ml. Le debit minimal de perfusion etait inferieur a 0,3 ml/heure dans 76 % des centres. L'adjonction d'albumine a la solution d'insuline est devenue rare et 57 % des centres preferaient utiliser comme alternative une methode de saturation de la ligne de perfusion. Les techniques de saturation etaient tres differentes selon les centres. Malgre les precautions prises pour eviter l'adsorption de l'insuline perfusee sur la tubulure, des difficultes a type d'hypoglycemie ou de resistance a l'insuline etaient frequemment rapportees (respectivement 30 % des cas et 47 % des cas). Ces differentes pratiques sont discutees en fonction des donnees de la litterature. Conclusion. – Afin d'optimiser l'utilisation de l'insuline, un protocole d'administration de l'insuline chez le nouveau-ne premature est propose a titre indicatif.

Published
2004
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4. Pharmacologie des corticoïdes chez l'enfant et l'adulte

Author

J.M. Tréluyer

Subjects
Pharmacokinetics, Mechanism of action, business.industry, medicine.drug_class, medicine, Corticosteroid, Distribution (pharmacology), Drug interaction, medicine.symptom, Pharmacology, Critical Care and Intensive Care Medicine, business
Published
2000
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5. Quoi de neuf en pharmacologie pédiatrique ?

Author

J.M. Tréluyer and Gérard Pons

Subjects
Pediatrics, medicine.medical_specialty, business.industry, Legislation, medicine.disease, Clinical trial, Investigation methods, Incentive, Clinical investigation, Recien nacido, Pediatrics, Perinatology and Child Health, medicine, Medical emergency, Dosing, business
Abstract

Only a minority of the drugs administered to children and infants have a pediatric labeling and have been sufficiently tested for efficacy, safety and correct pediatric dosing, which cannot necessarily be extrapolated from adult data. This situation is scientifically and ethically unacceptable. To address this problem, the suggestion is being made in several countries that more formal legal requirements should be introduced. In the United States, in 1997, a new legislation encouraged pharmaceutical companies to study medicines in children (for example, by offering the financial incentive of a six-month extension to patent exclusivity). However, there are undeniable difficulties in pediatric and neonatal studies. To minimize the risks of clinical investigation in children, appropriate methodologies should be used. New in vitro and in vivo methods are now available, taking into account pediatric characteristics.

Published
2000
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7. Pharmacokinetics and toxicity of docetaxel: role of CYP3A, MDR1, and GST polymorphisms

Author

François Goldwasser, J.M. Tréluyer, A. Tran, G. Pons, E. Rey, V. Dieras, V. Girre, F. Rabillon, V. Jullien, and Jérôme Alexandre

Subjects
Male, medicine.medical_treatment, Organic Anion Transporters, Docetaxel, Pharmacology, Biology, Neutropenia, Polymerase Chain Reaction, Pharmacokinetics, Cytochrome P-450 Enzyme System, medicine, Cytochrome P-450 CYP3A, Humans, Pharmacology (medical), ATP Binding Cassette Transporter, Subfamily B, Member 1, Infusions, Intravenous, neoplasms, Aged, DNA Primers, Chemotherapy, Polymorphism, Genetic, Area under the curve, DNA, Middle Aged, medicine.disease, Antineoplastic Agents, Phytogenic, Area Under Curve, Toxicity, Absolute neutrophil count, Female, Taxoids, Febrile neutropenia, medicine.drug
Abstract

Objective Patients initiating docetaxel chemotherapy were genotyped for CYP3A4, CYP3A5, MDR1, GSTM1, GSTT1, GSTM3, and GSTP1 to identify variability factors of docetaxel pharmacokinetics and toxicity. Methods Genotyping was performed by direct sequencing (CYP3A4), real-time polymerase chain reaction (CYP3A5), and polymerase chain reaction–restriction fragment length polymorphism (MDR1 and GST). The clearance and area under the curve of docetaxel were calculated by use of a Bayesian approach. Absolute neutrophil count was recorded twice weekly. Results With regard to the pharmacokinetic analysis, 58 patients were included. CYP3A4*1B carriers (*1A/*1B, n=4), who are also CYP3A5*1/*3 carriers, had a significantly higher clearance and lower dose-normalized area under the curve of docetaxel than those with the wild genotype (*1A/*1A, n=53): 55.2 ± 13.5 L/h versus 37.3 ± 11.7 L/h (P=.01) and 31.4 ± 6.2 (μg · h/L)/(mg/m2) versus 52.7 ± 18.2 (μg · h/L)/(mg/m2) (P=.005), respectively. No influence of MDR1 was evidenced. With regard to the pharmacodynamic analysis, febrile neutropenia occurred more frequently in GSTP1*A/*B carriers (31.6% versus 3.7% in *A/*A carriers and 0% in *A/*C, *B/*B, and *B/*C carriers) (P=.037). Grade 3 neutropenia occurred more frequently in 3435TT MDR1 genotype carriers: TT, 100%; CT, 77.3%; and CC, 54.5% (P=.046). No influence of GSTM1, GSTT1, or GSTM3 polymorphisms was evidenced on docetaxel toxicity. Conclusions Patients carrying the CYP3A*1B allele may have enhanced docetaxel clearance and may be underexposed, whereas those carrying GSTP1*A/*B and 3435TT genotypes may have excessive hematologic toxicity. Further studies are warranted to determine the usefulness of genotyping before docetaxel treatment. Clinical Pharmacology & Therapeutics (2006) 79, 366–366; doi: 10.1016/j.clpt.2006.02.003

Published
2005

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