48 results on '"D. Touchard"'
Search Results
2. Chronic Viral Hepatitis Is Associated With Low Bone Mineral Density in HIV-Infected Patients, ANRS CO 3 Aquitaine Cohort
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Sylvie, Lawson-Ayayi, Charles, Cazanave, Alphonse, Kpozehouen, Nicole, Barthe, Nadia, Mehsen, Mojgan, Hessamfar, Michel, Dupon, François, Dabis, Didier, Neau, and D, Touchard
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Adult ,Male ,medicine.medical_specialty ,Hepatitis, Viral, Human ,Bone density ,Osteoporosis ,HIV Infections ,Cohort Studies ,Bone Density ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Hepatitis ,business.industry ,Odds ratio ,Middle Aged ,Hepatitis B ,medicine.disease ,Virology ,Osteopenia ,Infectious Diseases ,Chronic Disease ,Coinfection ,Female ,Viral hepatitis ,business - Abstract
BACKGROUND High prevalence rates of low bone mineral density (BMD) have been reported in people living with HIV infection. We aimed to investigate the association of chronic viral hepatitis with low BMD in HIV-infected patients. METHODS A hospital-based cohort of HIV-infected patients was screened for hepatitis B and C coinfection. BMD was measured by dual energy x-ray absorptiometry. T-score was used to define bone status according to the World Health Organization's classification; moreover, each observed BMD value was compared with reference to an average person of the same age and gender as a Z-score
- Published
- 2013
3. Prevalence and factors associated with renal impairment in HIV-infected patients, ANRS C03 Aquitaine Cohort, France
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E K, Déti, R, Thiébaut, F, Bonnet, S, Lawson-Ayayi, M, Dupon, D, Neau, J L, Pellegrin, D, Malvy, S, Tchamgoué, F, Dabis, P, Morlat, and D, Touchard
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Adult ,Male ,medicine.medical_specialty ,Anti-HIV Agents ,Organophosphonates ,Prevalence ,Renal function ,HIV Infections ,Indinavir ,Kidney ,Kidney Function Tests ,Body Mass Index ,chemistry.chemical_compound ,Pharmacotherapy ,Internal medicine ,Epidemiology ,Humans ,Medicine ,Pharmacology (medical) ,Renal Insufficiency ,Stage (cooking) ,Tenofovir ,Creatinine ,business.industry ,Adenine ,Health Policy ,Middle Aged ,CD4 Lymphocyte Count ,Infectious Diseases ,chemistry ,Hypertension ,Cohort ,Immunology ,Female ,France ,Epidemiologic Methods ,business ,Body mass index - Abstract
The aims of the present study were to estimate the prevalence of renal impairment (RI) among HIV-infected adult patients and to investigate the associated factors.A cross-sectional survey was conducted in a French hospital-based cohort. Clearance of creatinine (CC) was calculated using the Cockcroft-Gault formula. Four stages of RI were defined: mild (60-90 mL/min), moderate (30-60), severe (15-30) and end stage (15). Logistic regression models were used to investigate factors associated with RI.The male/female ratio of the 2588 patients enrolled was 3:1 and the median age was 42 years. At the time of assessment of CC, the median CD4 count was 430 cells/microL and HIV plasma viral load (VL) was50 copies/mL in 60%. The overall prevalence of RI was 39.0%: 34.2% mild, 4.4% moderate, 0.3% severe and 0.2% end-stage. Mild RI was associated with female gender [odds ratio (OR)=3.3: 95% CI 2.6-4.3)], age50 years (OR=9.8: 7.4-13.0) and 40-50 years (OR=1.9: 1.5-2.4), body mass index (BMI)22 kg/m(2) (OR=3.3: 2.7-4.3) and tenofovir exposure (OR=1.4: 1.0-1.9 for1 year and OR=1.5: 1.2-2.0 for1 year). Advanced RI (CC60 mL/min) was associated with age50 years (OR=5.6: 2.9-10.9) and 40-50 years (OR=2.2: 1.1-1.4), BMI22 kg/m(2) (OR=1.5: 1.0-2.4), hypertension (OR=2.5: 1.4-2.5) and indinavir (IDV) exposure1 year (OR=2.3: 1.5-3.6).This survey confirms the high prevalence of RI in HIV-infected patients and indicates the importance of the investigation of renal function especially in women, older patients, those with a low BMI or treated with tenofovir or IDV.
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- 2010
4. Virological and immunological response in HIV-1-infected patients with multiple treatment failures receiving raltegravir and optimized background therapy, ANRS CO3 Aquitaine Cohort
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Linda, Wittkop, Dominique, Breilh, Daniel, Da Silva, Pierre, Duffau, Patrick, Mercié, Isabelle, Raymond, Guerric, Anies, Hervé, Fleury, Marie-Claude, Saux, Francois, Dabis, Catherine, Fagard, Rodolphe, Thiébaut, Bernard, Masquelier, Isabelle, Pellegrin, D, Touchard, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Département de pharmacocinétique et pharmacologie clinique, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Variabilité génomique des virus, Université Bordeaux Segalen - Bordeaux 2-IFR66, Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de médecine interne et maladies infectieuses [Bordeaux], and CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André
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Male ,MESH: CD4 Lymphocyte Count ,Integrase inhibitor ,HIV Infections ,MESH: Antiretroviral Therapy, Highly Active ,Raltegravir Potassium ,Cohort Studies ,MESH: HIV-1 ,0302 clinical medicine ,Antiretroviral Therapy, Highly Active ,Pharmacology (medical) ,030212 general & internal medicine ,MESH: Anti-HIV Agents ,MESH: Cohort Studies ,MESH: Treatment Outcome ,0303 health sciences ,MESH: Middle Aged ,MESH: Drug Resistance, Viral ,MESH: HIV Infections ,Middle Aged ,Viral Load ,Pyrrolidinones ,3. Good health ,Treatment Outcome ,Infectious Diseases ,Cohort ,Female ,MESH: Viral Load ,Viral load ,medicine.drug ,Cohort study ,Adult ,Microbiology (medical) ,medicine.medical_specialty ,Anti-HIV Agents ,MESH: Pyrrolidinones ,Article ,03 medical and health sciences ,Internal medicine ,Drug Resistance, Viral ,medicine ,Humans ,Pharmacology ,MESH: Humans ,030306 microbiology ,business.industry ,MESH: Adult ,Odds ratio ,Raltegravir ,MESH: Male ,CD4 Lymphocyte Count ,Surgery ,Regimen ,HIV-1 ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business ,MESH: Female - Abstract
International audience; BACKGROUND: The efficacy of raltegravir plus optimized background therapy (OBT) has been demonstrated for antiretroviral (ARV)-experienced HIV-1-infected patients in randomized clinical trials. We studied viro-immunological response, pharmacokinetic parameters and genotypic test results in an observational cohort of multiple ARV class-experienced patients starting a raltegravir-based regimen. METHODS: Already enrolled ANRS CO3 Aquitaine Cohort patients with virological failure were included in this study after starting a raltegravir-based regimen (400 mg twice a day, week 0). Virological success was defined by the plasma HIV-1 RNA level [viral load (VL)] or =1 and or =2 (P = 0.02), respectively. Raltegravir-related mutations emerged in 9 of 11 failing patients (82%): Q148H/R (n = 5), N155S/H (n = 3) and S230N (n = 1). Median CD4 increases from week 0 to week 4 and week 24 were 28 (-4, 85) and 57 (0, 156) cells/mm(3), respectively. A poor immune response was independently associated with a lower VL decline (week 0 to week 12) [odds ratio (OR): 3.5, 95% confidence interval (CI): 1.4, 8.4, for 1 log(10) less] and CD4+% at baseline (OR: 2.6, 95% CI: 0.97, 8.3, for 10% lower). CONCLUSIONS: Raltegravir plus OBT provided a good virological success rate in highly pre-treated patients under clinical routine conditions.
- Published
- 2009
5. Effect of cytomegalovirus-induced immune response, self antigen-induced immune response, and microbial translocation on chronic immune activation in successfully treated HIV type 1-infected patients: the ANRS CO3 Aquitaine Cohort
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Linda, Wittkop, Juliette, Bitard, Estibaliz, Lazaro, Didier, Neau, Fabrice, Bonnet, Patrick, Mercie, Michel, Dupon, Mojgan, Hessamfar, Michel, Ventura, Denis, Malvy, François, Dabis, Jean-Luc, Pellegrin, Jean-François, Moreau, Rodolphe, Thiébaut, Isabelle, Pellegrin, D, Touchard, Statistics In System biology and Translational Medicine ( SISTM ), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ), Service d'immunologie et d'immunogénétique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Service de médecine interne et maladies infectieuses, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service des Maladies Infectieuses et Tropicales A [Bordeaux], Université Panthéon-Sorbonne - UFR d'Économie ( UP1 UFR02 ), Université Panthéon-Sorbonne ( UP1 ), Service de médecine interne et maladies infectieuses [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, CNRS-UMR 5234, Microbiologie fondamentale et Pathogénicité, University of Bordeaux 2, Bordeaux, France, Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Biogéosciences [Dijon] ( BGS ), AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'information médicale, Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Composantes innées de la réponse immunitaire et différenciation (CIRID), Groupe d'Epidémiologie Clinique du SIDA en Aquitaine, Wittkop, Linda, Statistics In System biology and Translational Medicine (SISTM), Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université Paris 1 Panthéon-Sorbonne - UFR d'Économie (UP1 UFR02), Université Paris 1 Panthéon-Sorbonne (UP1), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Biogéosciences [UMR 6282] [Dijon] (BGS), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Dewor, Isabelle, Biogéosciences [UMR 6282] (BGS), and Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
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Male ,Cytomegalovirus ,Autoimmunity ,HIV Infections ,CD8-Positive T-Lymphocytes ,CD38 ,Lymphocyte Activation ,medicine.disease_cause ,Cohort Studies ,0302 clinical medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology ,Antiretroviral Therapy, Highly Active ,Immunology and Allergy ,030212 general & internal medicine ,MESH: Cytomegalovirus Infections/immunology ,MESH: HLA-DR Antigens/metabolism ,MESH: Cohort Studies ,0303 health sciences ,MESH: HIV Infections/drug therapy ,virus diseases ,Viral Load ,3. Good health ,Infectious Diseases ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,MESH: CD8-Positive T-Lymphocytes/immunology ,Cytomegalovirus Infections ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,France ,MESH: Cytomegalovirus/immunology ,MESH: Viral Load ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,Congenital cytomegalovirus infection ,Human leukocyte antigen ,Biology ,QuantiFERON ,Viral Matrix Proteins ,03 medical and health sciences ,Immune system ,MESH: Cross-Sectional Studies ,Antigen ,MESH: Autoimmunity ,medicine ,Humans ,MESH: Phosphoproteins/immunology ,[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology ,MESH: Viral Matrix Proteins/immunology ,030304 developmental biology ,MESH: Humans ,MESH: HIV-1/genetics ,MESH: HIV-1/physiology ,MESH: HIV Infections/immunology ,HLA-DR Antigens ,Phosphoproteins ,medicine.disease ,Virology ,MESH: Male ,MESH: Lymphocyte Activation/immunology ,MESH: France ,Cross-Sectional Studies ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Immunology ,HIV-1 ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,MESH: HIV-1/drug effects ,MESH: Female ,CD8 - Abstract
International audience; We evaluated the impact of cytomegalovirus (CMV)-induced immune responses, autoimmune-induced immune responses, and microbial translocation on immune activation in 191 human immunodeficiency virus type 1-infected patients from the ANRS CO3 Aquitaine Cohort. All enrolled subjects had achieved long-term virological suppression during receipt of combination antiretroviral therapy (cART). HLA-DR(+)/CD38(+) expression was 16.8% among CD8(+) T cells. Independent of age, CD4(+) T-cell count, 16S ribosomal DNA load, and regulatory T-cell count, positive results of Quantiferon CMV analysis (P = .02), positive results of CMV-pp65 enzyme-linked immunosorbent spot analysis (P = .01), positive results of CMV-pp65-specific CD8(+) T-cell analysis (P = .05), and CMV seropositivity (P = .01) were associated with a higher percentage of CD8+ T cells that expressed HLA-DR+/CD38+. Autoimmune response and microbial translocation were not associated with immune activation. Therefore, the CMV-induced immune response seems to be associated with chronic immune activation in cART recipients with sustained virological suppression.
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- 2013
6. THE SPIRAL2 RADIOFREQUENCY COMMAND CONTROL
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D Touchard, C Berthe, P Gillette, M Lechartier, E Lécorché, and Ganil, Normand
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- 2011
- Full Text
- View/download PDF
7. ChemInform Abstract: Metallacumulenes: New Allenylidene-Ruthenium Complexes. Crystal Structure of a Cationic ((Ph2PCH2PPh2)2(Cl)Ru=C=C=CR1R2)+ Derivative
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D. Touchard, Loïc Toupet, Nadine Pirio, and Pierre H. Dixneuf
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chemistry.chemical_compound ,Chemistry ,Polymer chemistry ,Cationic polymerization ,chemistry.chemical_element ,General Medicine ,Crystal structure ,Derivative (chemistry) ,Ruthenium - Published
- 2010
8. Acute/Chronic respiratory failure
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A. Carneiro, A. Harf, D. Touchard, H. Zar, F. Chamieh, E. Chiner, E. Servera, S. Bouchouha, Michael R. Pinsky, M. Simó, A. Ferretti, J. Blanco, F. Marcier, M. Denis, O. Sychev, G. Conti, E. Salazar, R. Boiteou, M. Belghith, C. Tormo, A. Durocher, H. Hmouda, C. Frostell, C. Aldecoa, M. Tejeda, R. Chacornac, L. Di Chiara, G. Schlag, P. Hernandez, I. Cabezas, S. Iribarren, L. Fakhfakh, J. R. Lancaster, E. Valente, Michael Georgieff, F. Staikowsky, L. Gregorakos, A. Amau, Stewart B. Gottfried, F. Beaufils, C. Santré, S. Nouira, F. Ruiz, A. Bchir, L. Behr, S. Tixier, M. T. Martín, F. Bouvet, C. Núñez, V. Lacueva, N. Bloch, C. Beuscart, C. Katsanos, G. Beaucaire, J. Dall’ava, A. Fatrane, V. Malessios, A. Gursahanev, Michel Aubier, F. Lemaire, L. Tsaldari, L. Brochard, C. Gires, Ph. Dewailly, A. J. Schneider, F. Maltais, R. Traversa, J. Nicoiopoulos, F. Abroug, R. Schiener, J. H. Boix, Yu. Sirenko, D. Dell’Utri, C. Truchero, M. Narváez, Cl. Chastang, A. Peloux, D. Pavlovic, T. Lherm, B. Guidet, A. B. J. Groeneveld, V. Lópes, J. M. Gabillet, V. Cayrel, B. Huet, B. Renaud, A. Fernández, D. Perrin-Gachadoat, A. Herrejón, A. Tenaillon, H. Medaoui, Y. Furet, A. M. Durocher, I. Gültuna, L. Firestone, J. Marin, R. Calvo, H. Romo, M. Sovili, S. Bahrami, J. F. Vaxelaire, H Wiedeck, Apostolos Armaganidis, D. Perrin, J. A. Romand, M. Dambrosio, D. Olivares, B. Lafon, B. Rousset, G. Boussignac, M. Dojat, R. I. C. Wesdorp, V. Parra, N. Gueteau, D. Perrotin, W. Erdmann, Paolo Navalesi, J. Kesecioĝlu, M. Högman, S. Elatrous, G. Diaz-Regañón, J. C. Raphael, O. Leroy, P. Amstutz, F. Brunet, L. G. Thijs, H. Arnberg, F. Pochard, H. Georges, F. Boileau, F. Konrad, H. A. Bruining, J. L. Maravall, T. Vassal, Jean-Paul Mira, C. Mayaud, L. Babiy, J. C. Pompe, C. Ince, J. J. Lanore, P. Marino, G. Hedenstierna, H. Redl, J. Muñoz, A. Diaz-Prieto, Y. Yu, A. Cogliati, P. F. Dequin, F. J. Santos, M. Shchupak, S. Chevret, Ch Martínez, J. Moya, F. Saulnier, H. Hedenström, J. Blanquer, C. Lemaire, I. Hamy, G. Offenstadt, D. Pinquier, R. Boiteau, M. Kountouri, J. F. Dhainaut, F. Salord, C. Brun-Buisson, T. Boulain, J. Castañeda, A. Legras, J. Kilian, M. Jaafoura, and L. Gruez
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Acute/chronic respiratory failure ,medicine.medical_specialty ,Continuous Positive Airway Pressure ,Severe Acute Pancreatitis ,business.industry ,Pain medicine ,Critical Care and Intensive Care Medicine ,Pressure Support Ventilation ,Anesthesiology ,Poster Presentation ,Emergency medicine ,Medicine ,business ,Peak Inspiratory Pressure ,Acute Respiratory Failure - Published
- 1992
9. Acute/Chronic respiratory failure II
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H. Georges, N. Gueteau, O. Leroy, C. Santré, C. Beuscart, H. Medaoui, C. Lemaire, G. Beaucaire, I. Cabezas, H. Romo, E. Salazar, M. Narváez, D. Pinquier, G. Boussignac, D. Pavlovic, M. Aubier, F. Beaufils, J. C. Raphael, F. Bouvet, S. Chevret, Cl. Chastang, R. Boiteou, T. Lherm, F. Marcier, F. Chamieh, D. Perrin, A. Tenaillon, J. M. Gabillet, B. Guidet, F. Staikowsky, G. Offenstadt, P. Amstutz, C. Truchero, J. Moya, A. Diaz-Prieto, F. Konrad, R. Schiener, J. Kilian, M. Georgieff, F. Salord, V. Cayrel, A. Peloux, S. Tixier, R. Chacornac, A. Durocher, A. M. Durocher, C. Gires, L. Behr, F. Saulnier, L. Gruez, F. Boileau, Ph. Dewailly, H. Wiedeck, R. Boiteau, D. Perrin-Gachadoat, E. Valente, H. Hmouda, A. Fatrane, L. Fakhfakh, N. Bloch, B. Rousset, J. H. Boix, J. Marin, A. Amau, M. Tejeda, D. Olivares, E. Servera, M. Dambrosio, M. Dojat, D. Touchard, A. Harf, F. Lemaire, L. Brochard, C. Tormo, V. Lópes, V. Parra, R. Calvo, V. Lacueva, J. L. Maravall, A. Carneiro, B. Huet, C. Brun-Buisson, A. J. Schneider, A. B. J. Groeneveld, L. G. Thijs, R. I. C. Wesdorp, B. Lafon, M. Denis, T. Vassal, C. Mayaud, M. Högman, H. Hedenström, C. Frostell, H. Arnberg, G. Hedenstierna, J. -A. Romand, M. R. Pinsky, L. Firestone, J. R. Lancaster, H. Zar, F. Brunet, M. Belghith, J. P. Mira, J. J. Lanore, B. Renaud, F. Pochard, J. F. Vaxelaire, I. Hamy, A. Armaganidis, J. Dall’ava, J. F. Dhainaut, P. Navalesi, F. Maltais, A. Gursahanev, P. Hernandez, M. Sovili, S. Gottfried, L. Gregorakos, C. Katsanos, V. Malessios, J. Nicoiopoulos, L. Tsaldari, M. Kountouri, M. T. Martín, F. J. Santos, S. Iribarren, A. Fernández, G. Diaz-Regañón, Ch Martínez, Yu. Sirenko, O. Sychev, M. Shchupak, L. Babiy, J. Muñoz, F. Ruiz, J. Blanquer, M. Simó, A. Herrejón, C. Núñez, E. Chiner, S. Nouira, S. Elatrous, A. Bchir, M. Jaafoura, F. Abroug, S. Bouchouha, S. Bahrami, Y. Yu, H. Redl, G. Schlag, G. Conti, A. Cogliati, D. Dell’Utri, A. Ferretti, R. Traversa, L. Di Chiara, P. Marino, J. Kesecioĝlu, J. C. Pompe, I. Gültuna, C. Ince, W. Erdmann, H. A. Bruining, J. Castañeda, J. Blanco, C. Aldecoa, T. Boulain, Y. Furet, P. F. Dequin, A. Legras, and D. Perrotin
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Critical Care and Intensive Care Medicine - Published
- 1992
10. Effect of chronic administration of cyclosporin A on hepatic uptake and biliary secretion of bromosulfophthalein in rat
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Jean-François Cadranel, V. A. Mesa, Dumont M, D. Touchard, Serge Erlinger, and Claude Degott
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Male ,Taurocholic Acid ,medicine.medical_specialty ,Physiology ,Cyclosporins ,Biology ,Sulfobromophthalein ,Bile flow ,fluids and secretions ,stomatognathic system ,Internal medicine ,Cyclosporin a ,medicine ,Animals ,Bile ,Secretion ,Liver histology ,Inhibitory effect ,Gastroenterology ,Biliary secretion ,Rats, Inbred Strains ,Biological activity ,Hepatology ,Rats ,Endocrinology ,Liver - Abstract
Cyclosporin A (CyA) decreases bile flow and bile salt secretion in the rat. The purpose of this study was to examine the influence of CyA on the hepatic transport of bromosulfophthalein (BSP). Male Sprague-Dawley rats were injected with CyA at the daily dose of 10 mg/kg (treated animals) or solvent (controls) during three weeks. Hepatic uptake of BSP (assessed by the plasma disappearance curve of the dye) and biliary secretion during infusions (95.5 and 178 nmol/min/100 g) were examined in both groups. Administration of CyA resulted in a decrease in both bile flow and BSP biliary secretion at the two infusion rates used. BSP plasma disappearance rate was significantly lower in treated animals than in controls. Conjugation of the dye was unaffected by CyA. There was no modification in ALT activity or in liver histology. These data show that chronic administration of CyA in rats decreases both hepatic uptake and biliary secretion of BSP. Thus, the inhibitory effect of CyA on biliary secretion is not limited to bile salts but also is observed with other cholephilic substances.
- Published
- 1991
11. Transmission of HIV-1 minority-resistant variants and response to first-line antiretroviral therapy
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Olivia, Peuchant, Rodolphe, Thiébaut, Sophie, Capdepont, Valérie, Lavignolle-Aurillac, Didier, Neau, Philippe, Morlat, François, Dabis, Hervé, Fleury, Bernard, Masquelier, D, Touchard, Variabilité génomique des virus, Université Bordeaux Segalen - Bordeaux 2-IFR66, Biostatistique, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses, and CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin
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Male ,Genotype ,Anti-HIV Agents ,Immunology ,Population ,antiretroviral therapy ,HIV Infections ,Polymerase Chain Reaction ,03 medical and health sciences ,0302 clinical medicine ,HIV Protease ,Drug Resistance, Viral ,Humans ,Immunology and Allergy ,Medicine ,030212 general & internal medicine ,Seroconversion ,Sida ,education ,Retrospective Studies ,0303 health sciences ,education.field_of_study ,biology ,030306 microbiology ,business.industry ,minority variants ,transmission ,Viral Load ,Resistance mutation ,biology.organism_classification ,Virology ,HIV Reverse Transcriptase ,Reverse transcriptase ,CD4 Lymphocyte Count ,3. Good health ,Infectious Diseases ,Mutation ,Lentivirus ,HIV-1 ,RNA, Viral ,Female ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Viral disease ,business ,Viral load ,HIV-1 drug resistance - Abstract
International audience; BACKGROUND: The transmission of drug-resistant HIV-1 can impair the virological response to antiretroviral therapy. Minority-resistant variants have been detected in acute seroconverters. We investigated the clinical relevance of the detection of majority and minority-resistant variants in an observational study in antiretroviral therapy naive, recently infected patients. METHODS: We included patients infected between 1996 and 2005, with a plasma sample obtained less than 18 months after seroconversion and prior to antiretroviral therapy initiation. Majority-resistant variants were determined by direct population sequencing. Minority-resistant variants were searched by allele-specific PCR for the mutations K103N and M184V in reverse transcriptase and L90M in protease. The association between resistance and viroimmunological response to antiretroviral therapy was estimated by using a piecewise linear mixed model. RESULTS: Majority-resistant variants were detected in 23/172 (13.4%) patients. Patients with majority-resistant variants had a lower mean plasma viral load and higher mean CD4 cell count at baseline compared with those without resistance. The decrease in viral load between 1 and 6 months on antiretroviral therapy was significantly steeper in patients with sensitive viruses compared with those with majority-resistant variants (P = 0.029). Minority-resistant variants were detected in 21/73 (29%) patients with wild-type viruses at sequencing analysis. The presence of minority-resistant variants did not modify baseline viral load and CD4 cell count and did not affect the changes in viral load and CD4 cell count. CONCLUSION: The transmission of majority-resistant variants, but not minority-resistant variants, influenced the response to antiretroviral therapy in this prospective study. The detection of the transmission of minority-resistant variants warrants further clinical validation.
- Published
- 2008
12. ChemInform Abstract: Monoelectronic Processes in Iron Complexes and Controlled Reactions by Ancillary PR3 Ligands
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D. TOUCHARD, J. L. FILLAUT, H. LE BOZEC, C. MOINET, and P. H. DIXNEUF
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General Medicine - Published
- 1990
13. Changes in the Work of Breathing Induced by Tracheotomy in Ventilator-dependent Patients
- Author
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S El Atrous, D Touchard, Laurent Brochard, François Lemaire, and Jean Luc Diehl
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,Artificial ventilation ,medicine.medical_treatment ,Vital Capacity ,Physical Therapy, Sports Therapy and Rehabilitation ,Respiratory physiology ,Critical Care and Intensive Care Medicine ,Catheterization ,Work of breathing ,Tracheostomy ,Tracheotomy ,Intubation, Intratracheal ,Pressure ,Respiratory muscle ,medicine ,Humans ,Prospective Studies ,Respiratory system ,Aged ,Work of Breathing ,Aged, 80 and over ,Mechanical ventilation ,business.industry ,Middle Aged ,Respiration, Artificial ,Cannula ,Respiratory Muscles ,Anesthesia ,Breathing ,Female ,Respiratory Insufficiency ,Airway ,business ,Follow-Up Studies ,Transpulmonary pressure - Abstract
Tracheotomy is widely performed on ventilator-dependent patients, but its effects on respiratory mechanics have not been studied. We measured the work of breathing (WOB) in eight patients before and after tracheotomy during breathing at three identical levels of pressure support (PS): baseline level (PS-B), PS + 5 cm H2O (PS+5), and PS - 5 cm H2O (PS-5). After the procedure, we also compared the resistive work induced by the patients' endotracheal tubes (ETTs) and by a new tracheotomy cannula in an in vitro bench study. A significant reduction in the WOB was observed after tracheotomy for PS-B (from 0.9 +/- 0.4 to 0.4 +/- 0.2 J/L, p < 0.05), and for PS-5 (1.4 +/- 0.6 to 0.6 +/- 0.3 J/L, p < 0.05), with a near-significant reduction for PS+5 (0.5 +/- 0.5 to 0.2 +/- 0.1 J/L, p = 0.05). A significant reduction was also observed in the pressure-time index of the respiratory muscles (181 +/- 92 to 80 +/- 56 cm H2O. s/min for PS-B, p < 0.05). Resistive and elastic work computed from transpulmonary pressure measurements decreased significantly at PS-B and PS-5. A significant reduction in occlusion pressure and intrinsic positive end-expiratory pressure (PEEP) was also observed for all conditions, with no significant change in breathing pattern. Three patients had ineffective breathing efforts before tracheotomy, and all had improved synchrony with the ventilator after the procedure. In vitro measurements made with ETTs removed from the patients, with new ETTs, and with the tracheotomy cannula showed that the cannula reduced the resistive work induced by the artificial airway. Part of these results was explained by a slight, subtle reduction of the inner diameter of used ETTs. We conclude that tracheotomy can substantially reduce the mechanical workload of ventilator-dependent patients.
- Published
- 1999
14. Reaction de stobbe en serie ferrocenique. Mise en evidence de reactions specifiques
- Author
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R. Dabard and D. Touchard
- Subjects
Chemistry ,Organic Chemistry ,Drug Discovery ,Biochemistry ,Medicinal chemistry - Published
- 1972
15. ChemInform Abstract: THE INFLUENCE OF TEMPERATURE ON THE COURSE OF THE PHOTODECOMPOSITION OF N-HALOACETAMIDES IN THE PRESENCE OF OLEFINS
- Author
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D. TOUCHARD and J. LESSARD
- Subjects
General Medicine - Published
- 1973
16. ChemInform Abstract: NOVEL ROUTE TO CATIONIC NITROSYL COMPLEXES. DISPLACEMENT OF CARBON DISULFIDE COORDINATED TO IRON
- Author
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D. TOUCHARD, H. LE BOZEC, and P. DIXNEUF
- Subjects
General Medicine - Published
- 1979
17. ChemInform Abstract: SULFUR-CONTAINING CARBENE-METAL COMPOUNDS: GENERAL ROUTE FROM CARBON DISULFIDE MANGANESE COMPLEXES; X-RAY STRUCTURE OF 1,3-DITHIOL-2-YLIDENEMANGANESE(I DERIVATIVE
- Author
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J. Y. LE MAROUILLE, C. LELAY, A. BENOIT, D. GRANDJEAN, D. TOUCHARD, H. LE BOZEC, and P. DIXNEUF
- Subjects
General Medicine - Published
- 1980
18. ChemInform Abstract: NEUTRAL AND CATIONIC (η2-DITHIOALKYL ESTER)IRON(II) COMPLEXES. SYNTHESIS, SPECTROSCOPIC STUDIES, AND X-RAY STRUCTURE OF (FE(η2-CS2CH2PH)(CO)2(PME3)2)PF6
- Author
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D. TOUCHARD, H. LE BOZEC, P. H. DIXNEUF, A. J. CARTY, and N. J. TAYLOR
- Subjects
General Medicine - Published
- 1981
19. ChemInform Abstract: DIE ADDITION VON OLEFINEN AN ACYLAMINORADIKALE AUS DER PHOTOCHEMISCHEN ZERS. HALOGENIERTER N-CHLOR- UND N-BROM-ACETAMIDE
- Author
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J. Lessard and D. Touchard
- Subjects
Chemistry ,General Medicine ,Medicinal chemistry - Published
- 1972
20. ChemInform Abstract: STOBBE-KONDENSATION IN DER FERROCEN-REIHE, BEWEIS VON SPEZIFISCHEN RK
- Author
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D. Touchard and R. Dabard
- Subjects
Chemistry ,General Medicine ,Medicinal chemistry - Published
- 1973
21. Effect of chronic administration of cyclosporin a on hepatic uptake and biliary secretion of bromosulfophthalein in the rat
- Author
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Claude Degott, D. Touchard, V. A. Mesa, Serge Erlinger, Dumont M, and Jean-François Cadranel
- Subjects
Hepatology ,business.industry ,Cyclosporin a ,Biliary secretion ,Medicine ,Pharmacology ,business - Published
- 1989
22. Functional Mapping of Adhesiveness on Live Cells Reveals How Guidance Phenotypes Can Emerge From Complex Spatiotemporal Integrin Regulation.
- Author
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Robert P, Biarnes-Pelicot M, Garcia-Seyda N, Hatoum P, Touchard D, Brustlein S, Nicolas P, Malissen B, Valignat MP, and Theodoly O
- Abstract
Immune cells have the ubiquitous capability to migrate disregarding the adhesion properties of the environment, which requires a versatile adaptation of their adhesiveness mediated by integrins, a family of specialized adhesion proteins. Each subtype of integrins has several ligands and several affinity states controlled by internal and external stimuli. However, probing cell adhesion properties on live cells without perturbing cell motility is highly challenging, especially in vivo . Here, we developed a novel in vitro method using micron-size beads pulled by flow to functionally probe the local surface adhesiveness of live and motile cells. This method allowed a functional mapping of the adhesiveness mediated by VLA-4 and LFA-1 integrins on the trailing and leading edges of live human T lymphocytes. We show that cell polarization processes enhance integrin-mediated adhesiveness toward cell rear for VLA-4 and cell front for LFA-1. Furthermore, an inhibiting crosstalk of LFA-1 toward VLA-4 and an activating crosstalk of VLA-4 toward LFA-1 were found to modulate cell adhesiveness with a long-distance effect across the cell. These combined signaling processes directly support the bistable model that explains the emergence of the versatile guidance of lymphocyte under flow. Molecularly, Sharpin, an LFA-1 inhibitor in lymphocyte uropod, was found involved in the LFA-1 deadhesion of lymphocytes; however, both Sharpin and Myosin inhibition had a rather modest impact on adhesiveness. Quantitative 3D immunostaining identified high-affinity LFA-1 and VLA-4 densities at around 50 and 100 molecules/μm
2 in basal adherent zones, respectively. Interestingly, a latent adhesiveness of dorsal zones was not grasped by immunostaining but assessed by direct functional assays with beads. The combination of live functional assays, molecular imaging, and genome editing is instrumental to characterizing the spatiotemporal regulation of integrin-mediated adhesiveness at molecular and cell scales, which opens a new perspective to decipher sophisticated phenotypes of motility and guidance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Robert, Biarnes-Pelicot, Garcia-Seyda, Hatoum, Touchard, Brustlein, Nicolas, Malissen, Valignat and Theodoly.)- Published
- 2021
- Full Text
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23. Leishmania infection modulates beta-1 integrin activation and alters the kinetics of monocyte spreading over fibronectin.
- Author
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Figueira CP, Carvalhal DG, Almeida RA, Hermida Md, Touchard D, Robert P, Pierres A, Bongrand P, and dos-Santos WL
- Subjects
- Cell Adhesion physiology, Humans, Integrin alpha4beta1 metabolism, Kinetics, Leukocytes metabolism, Leukocytes parasitology, Fibronectins metabolism, Integrin beta1 metabolism, Leishmania metabolism, Leishmaniasis metabolism, Leishmaniasis parasitology, Monocytes metabolism, Monocytes parasitology
- Abstract
Contact with Leishmania leads to a decreases in mononuclear phagocyte adherence to connective tissue. In this work, we studied the early stages of bond formation between VLA4 and fibronectin, measured the kinetics of membrane alignment and the monocyte cytoplasm spreading area over a fibronectin-coated surface, and studied the expression of high affinity integrin epitope in uninfected and Leishmania-infected human monocytes. Our results show that the initial VLA4-mediated interaction of Leishmania-infected monocyte with a fibronectin-coated surface is preserved, however, the later stage, leukocyte spreading over the substrate is abrogated in Leishmania-infected cells. The median of spreading area was 72 [55-89] μm(2) for uninfected and 41 [34-51] μm(2) for Leishmania-infected monocyte. This cytoplasm spread was inhibited using an anti-VLA4 blocking antibody. After the initial contact with the fibronectrin-coated surface, uninfected monocyte quickly spread the cytoplasm at a 15 μm(2) s(-1) ratio whilst Leishmania-infected monocytes only made small contacts at a 5.5 μm(2) s(-1) ratio. The expression of high affinity epitope by VLA4 (from 39 ± 21% to 14 ± 3%); and LFA1 (from 37 ± 32% to 18 ± 16%) molecules was reduced in Leishmania-infected monocytes. These changes in phagocyte function may be important for parasite dissemination and distribution of lesions in leishmaniasis.
- Published
- 2015
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24. Biophysical description of multiple events contributing blood leukocyte arrest on endothelium.
- Author
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Robert P, Touchard D, Bongrand P, and Pierres A
- Abstract
Blood leukocytes have a remarkable capacity to bind to and stop on specific blood vessel areas. Many studies have disclosed a key role of integrin structural changes following the interaction of rolling leukocytes with surface-bound chemoattractants. However, the functional significance of structural data and mechanisms of cell arrest are incompletely understood. Recent experiments revealed the unexpected complexity of several key steps of cell-surface interaction: (i) ligand-receptor binding requires a minimum amount of time to proceed and this is influenced by forces. (ii) Also, molecular interactions at interfaces are not fully accounted for by the interaction properties of soluble molecules. (iii) Cell arrest depends on nanoscale topography and mechanical properties of the cell membrane, and these properties are highly dynamic. Here, we summarize these results and we discuss their relevance to recent functional studies of integrin-receptor association in cells from a patient with type III leukocyte adhesion deficiency. It is concluded that an accurate understanding of all physical events listed in this review is needed to unravel the precise role of the multiple molecules and biochemical pathway involved in arrest triggering.
- Published
- 2013
- Full Text
- View/download PDF
25. A new method for rapid detection of T lymphocyte decision to proliferate after encountering activating surfaces.
- Author
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Cretel E, Touchard D, Bongrand P, and Pierres A
- Subjects
- Antibodies, Monoclonal immunology, CD3 Complex immunology, Cell Proliferation, Cell Separation, Cell Surface Extensions immunology, Cells, Cultured, Extracellular Signal-Regulated MAP Kinases immunology, Extracellular Signal-Regulated MAP Kinases metabolism, Flow Cytometry, Fluoresceins metabolism, Focal Adhesions immunology, Humans, Microscopy, Interference, Signal Transduction immunology, Succinimides metabolism, T-Lymphocytes immunology, T-Lymphocytes pathology, Antibodies, Monoclonal metabolism, Cell Surface Extensions pathology, Focal Adhesions pathology, Lymphocyte Activation, T-Lymphocytes metabolism
- Abstract
A critical step of the adaptive response is the detection of foreign peptides on antigen presenting cells by T lymphocytes. It is a major challenge for a T lymphocyte to detect the presence of a few tens of cognate ligands or less on the membrane of a cell exposing millions of protein molecules. Detection is followed by the cell decision to undergo full or partial activation or even to start an inhibitory program. While the measurement of cell proliferation or cytokine synthesis is accepted as a reliable means of monitoring T lymphocyte activation, this requires hours or days to complete, which is a significant drawback to relate decision to particular signaling events or to assess lymphocyte reactivity in patients. Here we show that the contact area formed between T lymphocytes and potentially activating surfaces is exquisitely correlated to the proliferative response measured with the standard CFSE technique. Correlation is even better than the Erk activation that was reported as a digital reporter of cell activation. The simple and accurate method of assessing lymphocyte-to-surface contact extension that we describe might be very useful both to monitor lymphocyte reactivity for clinical purposes and to identify early steps of lymphocyte activation., (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Published
- 2011
- Full Text
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26. Early contacts between T lymphocytes and activating surfaces.
- Author
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Cretel E, Touchard D, Benoliel AM, Bongrand P, and Pierres A
- Subjects
- Cells, Cultured, Humans, Cell Adhesion physiology, Focal Adhesions physiology, T-Lymphocytes physiology
- Abstract
Cells continually probe their environment to adapt their behaviour. A current challenge is to determine how they analyse nearby surfaces and how they process information to take decisions. We addressed this problem by monitoring human T lymphocyte attachment to surfaces coated with activating anti-CD3 or control anti-HLA antibodies. Interference reflection microscopy allowed us to monitor cell-to-surface apposition with a few nanometre vertical resolution during the first minutes following contact. We found that (i) when a cell fell on a surface, contact extension was preceded by a lag of several tens of seconds. (ii) During this lag, vertical membrane undulations seemed to generate transient contacts with underlying surfaces. (iii) After the lag period, the contact area started increasing linearly with a rate of about 1.5 µm(2) s(-1) on activating surfaces and about 0.2 µm(2) s(-1) on control surfaces. (iv) Concomitantly with lateral surface extension, the apparent distance between cell membranes and surfaces steadily decreased. These results are consistent with the hypothesis that the cell decision to spread rapidly on activating surfaces resulted from the integration of information yielded by transient contacts with these surfaces generated by membrane undulations during a period of about 1 min.
- Published
- 2010
- Full Text
- View/download PDF
27. "Chain-like" trimetallic ruthenium complexes with C7 carbon-rich bridges: experimental and theoretical investigations of electronic communication tuning in five distinct oxidation states.
- Author
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Olivier C, Costuas K, Choua S, Maurel V, Turek P, Saillard JY, Touchard D, and Rigaut S
- Abstract
In this work, we report the synthesis and the electronic properties of the unique highly conjugated molecular wires trans-[Cl-(dppe)(2)Ru=C=C=(Ph)C-CH=(CH(3))C-C[triple bond]C-(X)(2)Ru-C=C-C(CH(3))=CH-C(Ph)=C=C=Ru(dppe)(2)Cl](n+) (n = 2, X = dppe ([3a](OTf)(2)) and dppm ([3b](OTf)(2)) with three similar metal centers spanned by two odd-numbered unsaturated C(7) chains providing a 28 A long conjugated path and displaying five well-separated redox states (n = 0-4). Successive one-electron transfer steps were studied by means of cyclic voltammetry, EPR and UV-vis-NIR-IR spectroelectrochemistry. The electronic and physical properties of the different states were further rationalized with the help of DFT-based calculations. Upon one-electron reduction (n = 1), the single electron is delocalized over the two carbon chains through the central metal atom to an extent driven by the rotations within and between the chains. The second reduction (n = 0) involves the whole carbon-rich conjugated path of the molecule in a spin polarized scheme: one electron is delocalized over each chain, and the two electrons are antiferromagnetically coupled with a coupling on the order of kT. Interestingly, oxidation processes strongly involve both the metal atoms and the bridging ligands. The combined investigations reveal that the mono-oxidized system (n = 3) presents a spin density uniformly distributed between the metal atoms and the carbon atoms of the chains, whereas in the second oxidation state (n = 4) the compounds show a strong antiferromagnetic coupling on the order of 4 kT between the two single electrons localized in two distinct delocalized spin orbitals implying all the carbon atoms of the bridges and the three metal atoms. Thus, for the first time, electronic communication was fully evidenced and tuned in homonuclear trimetallic oligomeric carbon-rich systems in either an oxidation or a reduction process.
- Published
- 2010
- Full Text
- View/download PDF
28. How cells tiptoe on adhesive surfaces before sticking.
- Author
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Pierres A, Benoliel AM, Touchard D, and Bongrand P
- Subjects
- Cell Line, Computer Simulation, Humans, Cell Adhesion physiology, Cell Membrane physiology, Cell Movement physiology, Membrane Fluidity physiology, Models, Biological, Monocytes cytology, Monocytes physiology
- Abstract
Cell membranes are studded with protrusions that were thoroughly analyzed with electron microscopy. However, the nanometer-scale three-dimensional motions generated by cell membranes to fit the topography of foreign surfaces and initiate adhesion remain poorly understood. Here, we describe the dynamics of surface deformations displayed by monocytic cells bumping against fibronectin-coated surfaces. We observed membrane undulations with typically 5 nm amplitude and 5-10 s lifetime. Cell membranes behaved as independent units of micrometer size. Cells detected the presence of foreign surfaces at 50 nm separation, resulting in time-dependent amplification of membrane undulations. Molecular contact then ensued with apparent cell-membrane separation of 30-40 nm, and this distance steadily decreased during the following tens of seconds. Contact maturation was associated with in-plane egress of bulky molecules and robust membrane fluctuations. Thus, membrane undulations may be the major determinant of cell sensitivity to substrate topography, outcome of interaction, and initial kinetics of contact extension.
- Published
- 2008
- Full Text
- View/download PDF
29. Electronic communication in "chain-like" trimetallic ruthenium complexes with two C7 carbon-rich conjugated bridges.
- Author
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Olivier C, Choua S, Turek P, Touchard D, and Rigaut S
- Subjects
- Electrochemistry, Electron Spin Resonance Spectroscopy, Carbon chemistry, Ruthenium Compounds chemistry
- Abstract
This paper describes the synthesis and properties of the first homotrinuclear metal complexes with large carbon-rich ligands that provide unique extended conduits for electron mobility.
- Published
- 2007
- Full Text
- View/download PDF
30. Dissecting subsecond cadherin bound states reveals an efficient way for cells to achieve ultrafast probing of their environment.
- Author
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Pierres A, Prakasam A, Touchard D, Benoliel AM, Bongrand P, and Leckband D
- Subjects
- Animals, Environment, Models, Theoretical, Protein Binding, Time Factors, Cadherins metabolism, Cell Communication physiology
- Abstract
Cells continuously probe their environment with membrane receptors, achieving subsecond adaptation of their behaviour [Diez, G., Gerisch, G., Anderson, K., Müller-Taubenberger, A. and Bretschneider, T. (2006) Subsecond reorganization of the actin network in cell motility and chemotaxis. Proc. Natl. Acad. Sci. USA 102, 7601-7606, Shamri, R., Grabovsky, V., Gauguet, J.M., Feigelson, S., Manevich, E., Kolanus, W., Robinson, M.K., Staunton, D.E., von Andrian, U.H. and Alon, R. (2005) Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endothelium-bound chemokines. Nat. Immunol. 6, 497-606, Jiang, G., Huang, A.H., Cai, Y., Tanase, M. and Sheetz, M.P. (2006) Rigidity sensing at the leading edge through alpha(V)beta(3) integrins and RPTPalpha. Biophys. J. 90, 1804-2006]. Recently, several receptors, including cadherins, were found to bind ligands with a lifetime of order of one second. Here we show at the single molecule level that homotypic C-cadherin association involves transient intermediates lasting less than a few tens of milliseconds. Further, these intermediates transitionned towards more stable states with a kinetic rate displaying exponential decrease with piconewton forces. These features enable cells to detect ligands or measure surrounding mechanical behaviour within a fraction of a second, much more rapidly than was previously thought.
- Published
- 2007
- Full Text
- View/download PDF
31. C7 and C9 carbon-rich bridges in diruthenium systems: synthesis, spectroscopic, and theoretical investigations of different oxidation States.
- Author
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Rigaut S, Olivier C, Costuas K, Choua S, Fadhel O, Massue J, Turek P, Saillard JY, Dixneuf PH, and Touchard D
- Subjects
- Models, Molecular, Oxidation-Reduction, Spectrum Analysis methods, Carbon chemistry, Ruthenium chemistry
- Abstract
Two methodologies of C-C bond formation to achieve organometallic complexes with 7 or 9 conjugated carbon atoms are described. A C7 annelated trans-[Cl(dppe)2Ru=C=C=C-CH=C(CH2)-C[triple bond]C-Ru(dppe)2Cl][X] (X = PF6, OTf) complex is obtained from the diyne trans-[Cl(dppe)2Ru-(C[triple bond]C)2-R] (R = H, SiMe3) in the presence of [FeCp2][PF6] or HOTf, and C7 or C9 complexes trans-[Cl(dppe)2Ru-(C[triple bond]C)n-C(CH3)=C(R1)-C(R2)=C=C=Ru(dppe)2Cl][X] (n = 1, 2; R1 = Me, Ph, R2 = H, Me; X = BF4, OTf) are formed in the presence of a polyyne trans-[Cl(dppe)2Ru-(C[triple bond]C)n-R] (n = 2, 3; R = H, SiMe3) with a ruthenium allenylidene trans-[Cl(dppe)2Ru=C=C=C(CH2R1)R2][X]. These reactions proceed under mild conditions and involve cumulenic intermediates [M+]=(C=)nCHR (n = 3, 5), including a hexapentaenylidene. A combination of chemical, electrochemical, spectroscopic (UV-vis, IR, NIR, EPR), and theoretical (DFT) techniques is used to show the influence of the nature and conformation of the bridge on the properties of the complexes and to give a picture of the electron delocalization in the reduced and oxidized states. These studies demonstrate that the C7 bridging ligand spanning the metal centers by almost 12 angstroms is implicated in both redox processes and serves as a molecular wire to convey the unpaired electron with no tendency for spin localization on one of the halves of the molecules. The reactivity of the C7 complexes toward protonation and deprotonation led to original bis(acetylides), vinylidene-allenylidene, or carbyne-vinylidene species such as trans-[Cl(dppe)2Ru[triple bond]C-CH=C(CH3)-CH=C(CH3)-HC=C=Ru(dppe)2Cl][BF4]3.
- Published
- 2006
- Full Text
- View/download PDF
32. Health promotion for socially disadvantaged groups: the case of homeless older men in Australia.
- Author
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Quine S, Kendig H, Russell C, and Touchard D
- Subjects
- Aged, Aged, 80 and over, Health Status Indicators, Humans, Male, Middle Aged, New South Wales epidemiology, Poverty, Urban Population, Health Promotion organization & administration, Ill-Housed Persons, Life Style
- Abstract
There is extensive evidence that health promotion routinely benefits those who are already most socioeconomically advantaged. While the government's healthy ageing policy recognizes that improving health outcomes will require a range of strategies involving different target groups, recommendations focus on the issues and needs of the comfortable majority. This paper examines the scope and relevance of health promotion for one disadvantaged minority with extensive health needs: homeless older men. In an ethnographic study of older men (> or = 50 years of age) living alone in the inner city (Sydney), 32 men were identified as homeless and are the focus of this paper. Face to face semi-structured interviews were used to record the men's accounts of their everyday lives, including their health and use of services. The conditions in which these men were living were observed and recorded, and the researchers were aware of health and other services available in the geographic area. All informants were living on or below the poverty line. They reported a range of health conditions, for which many accessed available mainstream and specialist health services. Some obstacles to accessing services were noted. Information relevant to widely endorsed prescriptions for 'healthy ageing' also emerged. These included physical activity (especially walking), healthy eating, social activity and adopting healthy lifestyle habits. Findings highlight the extent to which these men lack the basic requirements for healthy ageing, notably adequate incomes and housing. At the same time, within the constraints of the lifestyle they lead, they are motivated to maintain their health and independence. While there are limits to what can be achieved for such people at a local level of service delivery, it is possible to identify feasible health promotion goals and service strategies.
- Published
- 2004
- Full Text
- View/download PDF
33. Bis-allenylidene metal complex and unique related radical with delocalization of one electron over both trans carbon-rich chains.
- Author
-
Rigaut S, Costuas K, Touchard D, Saillard JY, Golhen S, and Dixneuf PH
- Abstract
We report the preparation of the first real bis(allenylidene) metal complex trans-[Ph2C=C=C=Ru=C=C=CPh2(dppe)2]2+, and its one electron reduction that gives a stable radical with the unpaired electron delocalized over both trans carbon-rich chains linked by the ruthenium atom, on the basis of spectroscopic and DFT, QM(DFT)/MM computational studies.
- Published
- 2004
- Full Text
- View/download PDF
34. Cell membrane alignment along adhesive surfaces: contribution of active and passive cell processes.
- Author
-
Pierres A, Eymeric P, Baloche E, Touchard D, Benoliel AM, and Bongrand P
- Subjects
- Cell Adhesion physiology, Cell Polarity physiology, Cell Size, Cells, Cultured, Coated Materials, Biocompatible chemistry, Elasticity, Humans, Microscopy, Interference methods, Monocytes chemistry, Stress, Mechanical, Cell Membrane chemistry, Cell Membrane physiology, Membrane Fluidity physiology, Membrane Fusion physiology, Monocytes cytology, Monocytes physiology, Polylysine chemistry
- Abstract
Cell adhesion requires nanometer scale membrane alignment to allow contact between adhesion receptors. Little quantitative information is presently available on this important biological process. Here we present an interference reflection microscopic study of the initial interaction between monocytic THP-1 cells and adhesive surfaces, with concomitant determination of cell deformability, using micropipette aspiration, and adhesiveness, using a laminar flow assay. We report that 1), during the first few minutes after contact, cells form irregular-shaped interaction zones reaching approximately 100 micro m(2) with a margin extension velocity of 0.01-0.02 micro m/s. This happens before the overall cell deformations usually defined as spreading. 2), These interference reflection microscopic-detected zones represent bona fide adhesion inasmuch as cells are not released by hydrodynamic forces. 3), Alignment is markedly decreased but not abolished by microfilament blockade with cytochalasin or even cell fixation with paraformaldehyde. 4), In contrast, exposing cells to hypotonic medium increased the rate of contact extension. 5), Contacts formed in presence of cytochalasin, after paraformaldehyde fixation or in hypotonic medium, were much more regular-shaped than controls and their extension matched cell deformability. 6), None of the aforementioned treatments altered adhesiveness to the surface. It is concluded that adhesive forces and passive membrane deformations are sufficient to generate initial cell alignment to adhesive surfaces, and this process is accelerated by spontaneous cytoskeletally-driven membrane motion.
- Published
- 2003
- Full Text
- View/download PDF
35. Unprecedented coupling of allenylidene and diynyl metal complexes: a bimetallic ruthenium system with a C7 conjugated bridge.
- Author
-
Rigaut S, Massue J, Touchard D, Fillaut JL, Golhen S, and Dixneuf PH
- Published
- 2002
- Full Text
- View/download PDF
36. Dissecting streptavidin-biotin interaction with a laminar flow chamber.
- Author
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Pierres A, Touchard D, Benoliel AM, and Bongrand P
- Subjects
- Adsorption, Aluminum Silicates, Binding Sites, Biophysical Phenomena, Biophysics, Ligands, Microspheres, Rheology instrumentation, Surface Properties, Biotin chemistry, Streptavidin chemistry
- Abstract
A laminar flow chamber was used to study single molecule interactions between biotinylated surfaces and streptavidin-coated spheres subjected to a hydrodynamic drag lower than a piconewton. Spheres were tracked with 20 ms and 40 nm resolution. They displayed multiple arrests lasting between a few tens of milliseconds and several minutes or more. Analysis of about 500,000 positions revealed that streptavidin-biotin interaction was multiphasic: transient bound states displayed a rupture frequency of 5.3 s(-1) and a rate of transition toward a more stable configuration of 1.3 s(-1). These parameters did not display any significant change when the force exerted on bonds varied between 3.5 and 11 pN. However, the apparent rate of streptavidin-biotin association exhibited about 10-fold decrease when the wall shear rate was increased from 7 to 22 s(-1), which supports the existence of an energy barrier opposing the formation of the transient binding state. It is concluded that a laminar flow chamber can yield new and useful information on the formation of molecular bonds, and especially on the structure of the external part of the energy landscape of ligand-receptor complexes.
- Published
- 2002
- Full Text
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37. Airway occlusion pressure to titrate positive end-expiratory pressure in patients with dynamic hyperinflation.
- Author
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Mancebo J, Albaladejo P, Touchard D, Bak E, Subirana M, Lemaire F, Harf A, and Brochard L
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Lung Diseases, Obstructive mortality, Lung Diseases, Obstructive physiopathology, Male, Middle Aged, Positive-Pressure Respiration, Intrinsic physiopathology, Positive-Pressure Respiration, Intrinsic therapy, Pressure, Lung Diseases, Obstructive therapy, Positive-Pressure Respiration methods, Work of Breathing physiology
- Abstract
Background: Although the use of external positive end-expiratory pressure (PEEP) is recommended for patients with intrinsic PEEP, no simple method exists for bedside titration. We hypothesized that the occlusion pressure, measured from airway pressure during the phase of ventilator triggering (P0.1t), could help to indicate the effects of PEEP on the work of breathing (WOB)., Methods: Twenty patients under assisted ventilation with chronic obstructive pulmonary disease were studied with 0, 5, and 10 cm H2O of PEEP while ventilated with a fixed level of pressure support., Results: PEEP 5 significantly reduced intrinsic PEEP (mean +/- SD, 5.2 +/- 2.4 cm H2O at PEEP 0 to 3.6 +/- 1.9 at PEEP 5; P < 0.001), WOB per min (12. 6 +/- 6.7 J/min to 9.1 +/- 5.9 J/min; P = 0.003), WOB per liter (1.2 +/- 0.4 J/l to 0.8 +/- 0.4 J/l; P < 0.001), pressure time product of the diaphragm (216 +/- 86 cm H2O. s-1. min-1 to 155 +/- 179 cm H2O. s-1. min-1; P = 0.001) and P0.1t (3.3 +/- 1.5 cm H2O to 2.3 +/- 1.4 cm H2O; P = 0.002). At PEEP 10, no further significant reduction in muscle effort nor in P0.1t (2.5 +/- 2.1 cm H2O) occurred, and transpulmonary pressure indicated an increase in end-expiratory lung volume. Significant correlations were found between WOB per min and P0.1t at the three levels of PEEP (P < 0.001), and between the changes in P0.1t versus the changes in WOB per min (P < 0.005), indicating that P0.1t and WOB changed in the same direction. A decrease in P0.1 with PEEP indicated a decrease in intrinsic PEEP with a specificity of 71% and a sensitivity of 88% and a decrease in WOB with a specificity of 86% and a sensitivity of 91%., Conclusion: These results show that P0.1t may help to assess the effects of PEEP in patients with intrinsic PEEP.
- Published
- 2000
- Full Text
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38. Cationic ruthenium allenylidene complexes as catalysts for ring closing olefin metathesis
- Author
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Furstner A, Liebl M, Lehmann CW, Picquet M, Kunz R, Bruneau C, Touchard D, and Dixneuf PH
- Abstract
A series of well accessible cationic ruthenium allenylidene complexes of the general type [(eta6-arene)(R3P)RuCl(=C=CR'2)]+ X- is described which constitute a new class of pre-catalysts for ring closing olefin metathesis reactions (RCM) and provide an unprecedented example for the involvement of metal allenylidenes in catalysis. They effect the cyclization of various functionalized dienes and enynes with good to excellent yields and show a great tolerance towards an array of functional groups. Systematic variations of their basic structural motif have provided insights into the essential parameters responsible for catalytic activity which can be enhanced further by addition of Lewis or Bronsted acids, by irradiation with UV light, or by the adequate choice of the "non-coordinating" counterion X-. The latter turned out to play a particularly important role in determining the rate and selectivity of the reaction. A similarly pronounced influence is exerted by remote substituents on the allenylidene residue which indicates that this ligand (or a ligand derived thereof) may remain attached to the metal throughout the catalytic process. X-ray crystal structures of the catalytically active allenylidene complexes 3b.PF6 and 15.OTf as well as of the chelate complex 10 required for the preparation of the latter catalyst are reported.
- Published
- 2000
- Full Text
- View/download PDF
39. Clinical evaluation of a computer-controlled pressure support mode.
- Author
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Dojat M, Harf A, Touchard D, Lemaire F, and Brochard L
- Subjects
- Aged, Female, Humans, Male, Monitoring, Physiologic, Respiratory Insufficiency therapy, Ventilator Weaning, Ventilators, Mechanical, Computers, Respiration, Artificial methods
- Abstract
We have designed a computerized system providing closed-loop control of the level of pressure support ventilation (PSV). The system sets itself at the lowest level of PSV that maintains respiratory rate (RR), tidal volume (VT), and end-tidal CO(2) pressure (PET(CO(2))) within predetermined ranges defining acceptable ventilation (i.e., 12 < RR < 28 cycles/min, VT > 300 ml [> 250 if weight < 55 kg], and PET(CO(2)) < 55 mm Hg [< 65 mm Hg if chronic CO(2) retention]). Ten patients received computer-controlled (automatic) PSV and physician-controlled (standard) PSV, in random order, during 24 h for each mode. An estimation of occlusion pressure (P(0.1)) was recorded continuously. The average time spent with acceptable ventilation as previously defined was 66 +/- 24% of the total ventilation time with standard PSV versus 93 +/- 8% with automatic PSV (p < 0.05), whereas the level of PSV was similar during the two periods (17 +/- 4 cm H(2)O versus 19 +/- 6 cm H(2)O). The time spent with an estimated P(0.1) above 4 cm H(2)O was 34 +/- 35% of the standard PSV time versus only 11 +/- 17% of the automatic PSV time (p < 0.01). Automatic PSV increased the time spent within desired ventilation parameter ranges and apparently reduced periods of excessive workload.
- Published
- 2000
- Full Text
- View/download PDF
40. Changes in the work of breathing induced by tracheotomy in ventilator-dependent patients.
- Author
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Diehl JL, El Atrous S, Touchard D, Lemaire F, and Brochard L
- Subjects
- Adult, Aged, Aged, 80 and over, Catheterization instrumentation, Female, Follow-Up Studies, Humans, Intubation, Intratracheal instrumentation, Male, Middle Aged, Pressure, Prospective Studies, Respiratory Insufficiency etiology, Respiratory Insufficiency therapy, Respiratory Muscles physiopathology, Vital Capacity, Respiration, Artificial, Respiratory Insufficiency physiopathology, Tracheostomy, Work of Breathing physiology
- Abstract
Tracheotomy is widely performed on ventilator-dependent patients, but its effects on respiratory mechanics have not been studied. We measured the work of breathing (WOB) in eight patients before and after tracheotomy during breathing at three identical levels of pressure support (PS): baseline level (PS-B), PS + 5 cm H2O (PS+5), and PS - 5 cm H2O (PS-5). After the procedure, we also compared the resistive work induced by the patients' endotracheal tubes (ETTs) and by a new tracheotomy cannula in an in vitro bench study. A significant reduction in the WOB was observed after tracheotomy for PS-B (from 0.9 +/- 0.4 to 0.4 +/- 0.2 J/L, p < 0.05), and for PS-5 (1.4 +/- 0.6 to 0.6 +/- 0.3 J/L, p < 0.05), with a near-significant reduction for PS+5 (0.5 +/- 0.5 to 0.2 +/- 0.1 J/L, p = 0.05). A significant reduction was also observed in the pressure-time index of the respiratory muscles (181 +/- 92 to 80 +/- 56 cm H2O. s/min for PS-B, p < 0.05). Resistive and elastic work computed from transpulmonary pressure measurements decreased significantly at PS-B and PS-5. A significant reduction in occlusion pressure and intrinsic positive end-expiratory pressure (PEEP) was also observed for all conditions, with no significant change in breathing pattern. Three patients had ineffective breathing efforts before tracheotomy, and all had improved synchrony with the ventilator after the procedure. In vitro measurements made with ETTs removed from the patients, with new ETTs, and with the tracheotomy cannula showed that the cannula reduced the resistive work induced by the artificial airway. Part of these results was explained by a slight, subtle reduction of the inner diameter of used ETTs. We conclude that tracheotomy can substantially reduce the mechanical workload of ventilator-dependent patients.
- Published
- 1999
- Full Text
- View/download PDF
41. Gravity effects on upper airway area and lung volumes during parabolic flight.
- Author
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Beaumont M, Fodil R, Isabey D, Lofaso F, Touchard D, Harf A, and Louis B
- Subjects
- Adult, Female, Forced Expiratory Volume physiology, Humans, Hypergravity, Larynx physiology, Lung Volume Measurements, Male, Pharynx physiology, Plethysmography, Posture physiology, Tidal Volume physiology, Weightlessness, Gravitation, Lung physiology
- Abstract
We measured upper airway caliber and lung volumes in six normal subjects in the sitting and supine positions during 20-s periods in normogravity, hypergravity [1.8 + head-to-foot acceleration (Gz)], and microgravity ( approximately 0 Gz) induced by parabolic flights. Airway caliber and lung volumes were inferred by the acoustic reflection method and inductance plethysmography, respectively. In subjects in the sitting position, an increase in gravity from 0 to 1. 8 +Gz was associated with increases in the calibers of the retrobasitongue and palatopharyngeal regions (+20 and +30%, respectively) and with a concomitant 0.5-liter increase in end-expiratory lung volume (functional residual capacity, FRC). In subjects in the supine position, no changes in the areas of these regions were observed, despite significant decreases in FRC from microgravity to normogravity (-0.6 liter) and from microgravity to hypergravity (-0.5 liter). Laryngeal narrowing also occurred in both positions (about -15%) when gravity increased from 0 to 1.8 +Gz. We concluded that variation in lung volume is insufficient to explain all upper airway caliber variation but that direct gravity effects on tissues surrounding the upper airway should be taken into account.
- Published
- 1998
- Full Text
- View/download PDF
42. NéoGanesh: a working system for the automated control of assisted ventilation in ICUs.
- Author
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Dojat M, Pachet F, Guessoum Z, Touchard D, Harf A, and Brochard L
- Subjects
- Humans, Monitoring, Physiologic, Ventilator Weaning, Artificial Intelligence, Decision Support Systems, Clinical, Respiration, Artificial, Therapy, Computer-Assisted
- Abstract
Automating the control of therapy administered to a patient requires systems which integrate the knowledge of experienced physicians. This paper describes NéoGanesh, a knowledge-based system which controls, in closed-loop, the mechanical assistance provided to patients hospitalized in intensive care units. We report on how new advances in knowledge representation techniques have been used to model medical expertise. The clinical evaluation shows that such a system relieves the medical staff of routine tasks, improves patient care, and efficiently supports medical decisions regarding weaning. To be able to work in closed-loop and to be tested in real medical situations, NéoGanesh deals with a voluntarily limited problem. However, embedded in a powerful distributed environment, it is intended to support future extensions and refinements and to support reuse of knowledge bases.
- Published
- 1997
- Full Text
- View/download PDF
43. Evaluation of a knowledge-based system providing ventilatory management and decision for extubation.
- Author
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Dojat M, Harf A, Touchard D, Laforest M, Lemaire F, and Brochard L
- Subjects
- Adult, Aged, Aged, 80 and over, Evaluation Studies as Topic, Female, Follow-Up Studies, Forecasting, Humans, Male, Middle Aged, Respiration, Sensitivity and Specificity, Treatment Outcome, Artificial Intelligence, Decision Making, Respiration, Artificial instrumentation, Ventilator Weaning
- Abstract
We evaluated whether a knowledge-based system (KBS) connected to a ventilator in pressure support mode could correctly predict the ability of patients to tolerate total withdrawal from ventilatory support. The KBS was designed to continuously adapt ventilatory assistance to the needs of the patient, to manage a strategy of gradually decreasing ventilatory assistance, and to indicate when the patient was able to breathe without assistance. Thirty-eight patients for whom weaning was being considered were evaluated using a conventional battery of parameters, including weaning criteria, tolerance of a T-piece trial, and outcome 48h after permanent withdrawal of ventilation. The results of this evaluation were compared with the suggestions made by the KBS at the end of a period of KBS-driven mechanical ventilation inserted in the conventional weaning procedure. The positive predictive value of the KBS was 89%, versus 77% for the conventional procedure and 81% for the rapid shallow breathing index alone. The KBS correctly predicted the course of five patients who tolerated a T-piece trial but required ventilation within 48 h. We conclude that our KBS ensured appropriate patient management during the weaning period and improved our ability to predict responses to weaning.
- Published
- 1996
- Full Text
- View/download PDF
44. Evaluation of carbon dioxide rebreathing during pressure support ventilation with airway management system (BiPAP) devices.
- Author
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Lofaso F, Brochard L, Touchard D, Hang T, Harf A, and Isabey D
- Subjects
- Adult, Aged, Cross-Over Studies, Female, Humans, Lung physiology, Male, Middle Aged, Models, Biological, Ventilator Weaning, Work of Breathing, Carbon Dioxide adverse effects, Carbon Dioxide analysis, Positive-Pressure Respiration instrumentation, Positive-Pressure Respiration methods, Respiratory Insufficiency therapy, Ventilators, Mechanical
- Abstract
The purpose of this study was to evaluate whether carbon dioxide (CO2) rebreathing occurs in acute respiratory failure patients ventilated using the standard airway management system (BiPAP pressure support ventilator; Respironics; Murrysville, Pa) with positive inspiratory airway pressure and a minimal level of positive end-expiratory pressure (PEEP) and whether any CO2 rebreathing may be efficiently prevented by the addition of a nonrebreathing valve to the BiPAP system circuit. In the first part of the study, the standard device was tested on a lung model with a nonrebreathing valve (BiPAP-NRV) and with the usual Whisper Swivel connector (BiPAP-uc). With the BiPAP-uc device, the resident volume of expired air in the inspiratory circuit at the end of expiration (RVEA) was 55% of the tidal volume (VT) when the inspiratory pressure was 10 cm H2O and the frequency was at 15 cycles per minute. The BiPAP-NRV device efficiently prevented CO2 rebreathing but resulted in a slight decrease in VT, which was due to a significant increase in external PEEP (2.4 vs 1.3 cm H2O) caused by the additional expiratory valve resistance. For similar reasons, both the pressure swing necessary to trigger pressure support and the imposed expiratory work were increased in the lung model when the nonrebreathing valve was used. In the second part of the study, seven patients weaned from mechanical ventilation were investigated using a randomized crossover design to compare three situations: pressure support ventilation with a conventional intensive care ventilator (CIPS), BiPAP system use, and BiPAP-NRV. When we compared the BiPAP system use with the other two systems, we observed no significant effect on blood gases but found significant increases in VT, minute ventilation, and work of breathing. These findings are experimental and are clinical evidence that significant CO2 rebreathing occurs with the standard BiPAP system. This drawback can be overcome by using a non-rebreathing valve, but only at the expense of greater expiratory resistance.
- Published
- 1995
- Full Text
- View/download PDF
45. Effect of chronic administration of cyclosporin A on hepatic uptake and biliary secretion of bromosulfophthalein in rat.
- Author
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Cadranel JF, Dumont M, Mesa VA, Degott C, Touchard D, and Erlinger S
- Subjects
- Animals, Bile metabolism, Cyclosporins administration & dosage, Liver metabolism, Male, Rats, Rats, Inbred Strains, Taurocholic Acid administration & dosage, Taurocholic Acid pharmacology, Bile drug effects, Cyclosporins pharmacology, Liver drug effects, Sulfobromophthalein pharmacokinetics
- Abstract
Cyclosporin A (CyA) decreases bile flow and bile salt secretion in the rat. The purpose of this study was to examine the influence of CyA on the hepatic transport of bromosulfophthalein (BSP). Male Sprague-Dawley rats were injected with CyA at the daily dose of 10 mg/kg (treated animals) or solvent (controls) during three weeks. Hepatic uptake of BSP (assessed by the plasma disappearance curve of the dye) and biliary secretion during infusions (95.5 and 178 nmol/min/100 g) were examined in both groups. Administration of CyA resulted in a decrease in both bile flow and BSP biliary secretion at the two infusion rates used. BSP plasma disappearance rate was significantly lower in treated animals than in controls. Conjugation of the dye was unaffected by CyA. There was no modification in ALT activity or in liver histology. These data show that chronic administration of CyA in rats decreases both hepatic uptake and biliary secretion of BSP. Thus, the inhibitory effect of CyA on biliary secretion is not limited to bile salts but also is observed with other cholephilic substances.
- Published
- 1991
- Full Text
- View/download PDF
46. Inhibition of liver glutathione S-transferase activity in rats by hypolipidemic drugs related or unrelated to clofibrate.
- Author
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Foliot A, Touchard D, and Mallet L
- Subjects
- Animals, Bile metabolism, Cell Division drug effects, Clofibric Acid analogs & derivatives, Clofibric Acid pharmacology, Fibric Acids, Male, Microbodies drug effects, Rats, Rats, Inbred Strains, Sulfobromophthalein metabolism, Clofibrate pharmacology, Glutathione Transferase antagonists & inhibitors, Hypolipidemic Agents pharmacology, Liver enzymology
- Abstract
The effects of in vivo administration of six hypolipidemic drugs on rat liver glutathione S-transferase activity were compared. This activity was measured with sulfobromophthalein (BSP), 1,2-dichloro-4-nitrobenzene (DCNB) or 1-chloro-2,4-dinitrobenzene (CDNB) as substrate. Except for the nicotinic acid derivative ethanolamine oxiniacate, all the compounds tested significantly reduced it, whether or not they were related to clofibrate. The hepatic glutathione concentration either remained unchanged or only increased slightly after treatment with the various drugs. When measured, the maximal excretion rate of bile BSP dropped significantly, but not that of phenol-3,6-dibromophthalein (DBSP). Hepatic dye uptake and storage were not impaired. These results show that hypolipidemic drugs of the peroxisome proliferator type inhibit rat liver glutathione S-transferase activity and may reduce transport of anions conjugated with glutathione before excretion.
- Published
- 1986
- Full Text
- View/download PDF
47. Impairment of hepatic glutathione S-transferase activity as a cause of reduced biliary sulfobromophthalein excretion in clofibrate-treated rats.
- Author
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Foliot A, Touchard D, and Celier C
- Subjects
- Animals, Bile metabolism, Biological Transport drug effects, Biotransformation drug effects, Liver enzymology, Liver metabolism, Male, Rats, Sulfobromophthalein analogs & derivatives, Clofibrate pharmacology, Glutathione Transferase antagonists & inhibitors, Liver drug effects, Sulfobromophthalein metabolism
- Abstract
Administration of clofibrate reduced the maximal excretion rate of bile sulfobromophthalein (BSP) in rats but left that of phenol-3,6-dibromophthalein (DBSP) unchanged. This decrease in liver transport of BSP was due to reduced bile excretion of conjugated BSP. Hepatic uptake and storage of this dye were not impaired. Liver glutathione S-transferase activity in vitro, measured with BSP, 1,2-dichloro-4-nitrobenzene (DCNB) or 1-chloro-2, 4-dinitrobenzene (CDNB) was significantly reduced. This alteration in liver conjugating activity was probably not related to a modification of the hepatic GSH pool, since the GSH level was unchanged or only increased slightly after clofibrate treatment. Detection of this inhibition required at least two daily doses of clofibrate. Inhibition was dose-related and lasted for several days after cessation of the drug. In clofibrate-treated rats, Lineweaver-Burk plots showed a reduced Vmax for both the BSP and GSH substrates. These results suggest that clofibrate decreases hepatobiliary transport of BSP by lowering glutathione S-transferase activity in the liver.
- Published
- 1984
- Full Text
- View/download PDF
48. Deficient induction of sulfobromophthalein conjugating activity by phenobarbital in hamster liver.
- Author
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Foliot A, Touchard D, Myara A, Trivin F, and Chauffert M
- Subjects
- Animals, Cricetinae, Dinitrochlorobenzene metabolism, Enzyme Induction, Epoxy Compounds metabolism, Glutathione analogs & derivatives, Glutathione metabolism, Glutathione Disulfide, Glutathione Transferase biosynthesis, Liver metabolism, Male, Mesocricetus, Nitrophenols metabolism, Liver drug effects, Phenobarbital pharmacology, Sulfobromophthalein metabolism
- Abstract
Administration of phenobarbital, a known inducer of glutathione S-transferase activity in rat liver, failed to stimulate sulfobromophthalein (BSP) conjugation by liver cytosol in hamsters. The latter displayed poor ability to conjugate this substrate, despite very high glutathione-conjugating activity with the broad-spectrum substrate 1-chloro-2,4-dinitrobenzene (CDNB). Of the six substrates tested, in this species, 1,2-epoxy-3-(4-nitrophenoxy)propane (ENPP) was the only one whose conjugation was greatly enhanced by phenobarbital (+172%). Nevertheless, hamsters proved as responsive to phenobarbital induction as rats, since it increased their relative liver weight and microsomal enzyme activity. The deficient induction of liver BSP-conjugating activity observed with phenobarbital is consistent with the finding that it did not affect the hepatic transport of this substrate in hamsters.
- Published
- 1987
- Full Text
- View/download PDF
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