70 results on '"A. Linka"'
Search Results
2. Functional MRI Mapping of Human Meniscus Functionality and its Relation to Degeneration
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Nebelung, Sven, D��tsch, Lisa, Shah, Dhaval, Abrar, Daniel Benjamin, Linka, Kevin, Knobe, Matthias, Sewerin, Philipp, Th��ring, Johannes, Kuhl, Christiane, and Truhn, Daniel
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Adult ,Aged, 80 and over ,Male ,Compressive Strength ,600: Technik ,lcsh:R ,lcsh:Medicine ,Diagnostic markers ,Translational research ,Middle Aged ,musculoskeletal system ,Magnetic Resonance Imaging ,Article ,Cartilage ,Osteoarthritis ,Humans ,Female ,Meniscus ,lcsh:Q ,Arthroplasty, Replacement, Knee ,lcsh:Science ,ddc:600 ,Technik [600] ,Biomedical engineering ,Aged - Abstract
Scientific reports 10, 2499 (2020). doi:10.1038/s41598-020-59573-4, Published by Macmillan Publishers Limited, part of Springer Nature, [London]
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- 2020
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3. OSIEshort: A small stimulus set can reliably estimate individual differences in semantic salience
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Linka, Marcel and de Haas, Benjamin
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Adult ,Male ,saliency ,Fixation, Ocular ,Article ,Semantics ,eye movements ,Young Adult ,free-viewing ,Visual Perception ,Humans ,Attention ,Female ,Eye-Tracking Technology ,individual differences - Abstract
Recent findings revealed consistent individual differences in fixation tendencies among observers free-viewing complex scenes. The present study aimed at (1) replicating these differences, and (2) testing whether they can be estimated using a shorter test. In total, 103 participants completed two eye-tracking sessions. The first session was a direct replication of the original study, but the second session used a smaller subset of images, optimized to capture individual differences efficiently. The first session replicated the large and consistent individual differences along five semantic dimensions observed in the original study. The second session showed that these differences can be estimated using about 40 to 100 images (depending on the tested dimension). Additional analyses revealed that only the first 2 seconds of viewing duration seem to be informative regarding these differences. Taken together, our findings suggest that reliable individual differences in semantic salience can be estimated with a test totaling less than 2 minutes of viewing duration.
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- 2020
4. Machine learning-augmented and microspectroscopy-informed multiparametric MRI for the non-invasive prediction of articular cartilage composition
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Sven Nebelung, Roland C. Aydin, Daniel Truhn, Christian J. Cyron, Dorit Merhof, Kevin Linka, Lassi Rieppo, Christiane K. Kuhl, and Johannes Thüring
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0301 basic medicine ,Adult ,Cartilage, Articular ,Male ,Biomedical Engineering ,Articular cartilage ,Osteoarthritis ,Degeneration (medical) ,Diagnostic tools ,Machine learning ,computer.software_genre ,Machine Learning ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Spectroscopy, Fourier Transform Infrared ,medicine ,Humans ,Orthopedics and Sports Medicine ,Multiparametric Magnetic Resonance Imaging ,Aged ,030203 arthritis & rheumatology ,Aged, 80 and over ,Artificial neural network ,business.industry ,Cartilage ,Non invasive ,Multiparametric MRI ,Middle Aged ,Osteoarthritis, Knee ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Female ,Artificial intelligence ,business ,computer - Abstract
Summary Background Articular cartilage degeneration is the hallmark change of osteoarthritis, a severely disabling disease with high prevalence and considerable socioeconomic and individual burden. Early, potentially reversible cartilage degeneration is characterized by distinct changes in cartilage composition and ultrastructure, while the tissue’s morphology remains largely unaltered. Hence, early degenerative changes may not be diagnosed by clinical standard diagnostic tools. Methods Against this background, this study introduces a novel method to determine the tissue composition non-invasively. Our method involves quantitative MRI parameters (i.e., T1, T1ρ, T2 and T 2 ∗ maps), compositional reference measurements (i.e., microspectroscopically determined local proteoglycan [PG] and collagen [CO] contents) and machine learning techniques (i.e., artificial neural networks [ANNs] and multivariate linear models [MLMs]) on 17 histologically grossly intact human cartilage samples. Results Accuracy and precision were higher in ANN-based predictions than in MLM-based predictions and moderate-to-strong correlations were found between measured and predicted compositional parameters. Conclusion Once trained for the clinical setting, advanced machine learning techniques, in particular ANNs, may be used to non-invasively determine compositional features of cartilage based on quantitative MRI parameters with potential implications for the diagnosis of (early) degeneration and for the monitoring of therapeutic outcomes.
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- 2020
5. Experiences and views of different key stakeholders on the feasibility of treating cancer-related fatigue
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Sarah Stoll, Michael Mikolasek, Claudia Six, Roger Stupp, Josef Jenewein, Claudia M. Witt, Matthias Rostock, Matthias Guckenberger, Esther Linka, Claudia Canella, University of Zurich, and Canella, Claudia
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Male ,Cancer Research ,Stakeholder engagement ,0302 clinical medicine ,Neoplasms ,Health care ,1306 Cancer Research ,030212 general & internal medicine ,Cancer-related fatigue ,Fatigue ,Qualitative Research ,Cancer ,Oncologists ,related fatigue ,Feasibility ,Focus Groups ,Middle Aged ,Prognosis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,10044 Clinic for Radiation Oncology ,Combined Modality Therapy ,Oncology ,030220 oncology & carcinogenesis ,2730 Oncology ,Female ,medicine.symptom ,Psychology ,Research Article ,Adult ,Health Personnel ,610 Medicine & health ,Context (language use) ,lcsh:RC254-282 ,03 medical and health sciences ,1311 Genetics ,Nursing ,Genetics ,medicine ,Humans ,Integrative treatment program ,Family ,Aged ,business.industry ,Focus group ,10034 Institute of Complementary Medicine ,Family member ,10032 Clinic for Oncology and Hematology ,Key (cryptography) ,Feasibility Studies ,Patient Participation ,Qualitative study ,business ,Delivery of Health Care ,Complementary medicine ,Follow-Up Studies ,Qualitative research - Abstract
Background Although cancer-related fatigue (CRF) has gained increased attention in the past decade, therapy remains a challenge. Treatment programs are more likely to be effective if the needs and interests of the persons involved are well represented. This can be achieved by stakeholder engagement. In this paper, different key stakeholders’ experiences and views on the feasibility of treating CRF in the context of supportive care in hospital environments are analyzed. Method In a qualitative study with the aim of developing an integrative treatment program for CRF, a total of 22 stakeholders (6 medical oncologists, 5 nurses, 9 patients, 1 patient family member, 1 representative of the Swiss Cancer League) were interviewed either in a face-to-face (n = 12) or focus group setting (n = 2). For data analyses, the method of qualitative content analysis was used. Results The stakeholders referred to different contextual factors when talking about the feasibility of treating CRF in the context of supportive care in hospital environments. These included: assessment, reporting and information; treatability; attitude; infrastructure, time-management, costs and affordability; and integrative approach. Conclusions Key factors of a feasible treatment approach to CRF are a coherent, cost effective integrative treatment program facilitated by an interdisciplinary team of health care providers. Furthermore, the treatment approach should be patient orientated, adopting an individualized approach. The major challenges of making the integrative treatment program feasible for CRF are resources and interprofessional collaboration.
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- 2020
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6. High Circulating Caspase-Cleaved Keratin 18 Fragments (M30) Indicate Short-Term Mortality in Critically Ill Patients
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Alexander Koch, Janine Linka, Christian Trautwein, Ulf Herbers, Ralf Weiskirchen, Jan Bruensing, Lukas Buendgens, Frank Tacke, Eray Yagmur, Fabienne Schumacher, Ger H. Koek, Interne Geneeskunde, MUMC+: MA Maag Darm Lever (9), and RS: NUTRIM - R2 - Liver and digestive health
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Male ,0301 basic medicine ,LIVER ,PATHOGENESIS ,Clinical Biochemistry ,Gastroenterology ,Keratin 18 ,0302 clinical medicine ,Keratin ,PREDICTS MORTALITY ,Caspase ,chemistry.chemical_classification ,lcsh:R5-920 ,biology ,General Medicine ,Middle Aged ,APOPTOSIS ,Caspases ,SURVIVAL ,SHOCK ,Biomarker (medicine) ,Female ,medicine.symptom ,lcsh:Medicine (General) ,Research Article ,Adult ,medicine.medical_specialty ,Article Subject ,Adolescent ,Inflammation ,Sepsis ,03 medical and health sciences ,Internal medicine ,Genetics ,medicine ,Humans ,Molecular Biology ,Aged ,Keratin-18 ,THERAPEUTIC TARGET ,SEPSIS ,business.industry ,Biochemistry (medical) ,Case-control study ,030208 emergency & critical care medicine ,medicine.disease ,Peptide Fragments ,030104 developmental biology ,CELL-DEATH ,chemistry ,Apoptosis ,Case-Control Studies ,biology.protein ,CRITICAL ILLNESS ,business ,Biomarkers - Abstract
Caspase-cleaved fragments of the intermediate filament protein keratin 18 (cytokeratin-18 (CK18)) can be detected in serum as M30 levels and may serve as a circulating biomarker indicating apoptosis of epithelial and parenchymal cells. In order to evaluate M30 as a biomarker in critical illness, we analyzed circulating M30 levels in 243 critically ill patients (156 with sepsis, 87 without sepsis) at admission to the medical intensive care unit (ICU), in comparison to healthy controls (n=32). M30 levels were significantly elevated in ICU patients compared with healthy controls. Circulating M30 was closely associated with disease severity but did not differ between patients with sepsis and ICU patients without sepsis. M30 serum levels were correlated with biomarkers of inflammation, cell injury, renal failure, and liver failure in critically ill patients. Patients that died at the ICU showed increased M30 levels at admission, compared with surviving patients. A similar trend was observed for the overall survival. Regression analyses confirmed that M30 levels are associated with mortality, and patients with M30 levels above 250.8 U/L displayed an excessive short-term mortality. Thus, our data support the utility of circulating levels of the apoptosis-related keratin fragment M30 as a prognostic biomarker at ICU admission.
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- 2018
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7. Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe
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Moutschen, M., Hofstra, Laura Marije Arije, Sauvageot, Nicolas, Albert, Jan, Alexiev, Ivailo, Garcia, Federico, Struck, Daniel, Van, de Vijver, Åsjö, Birgitta, Beshkov, Danail, Coughlan, Suzie, Descamps, Diane, Griskevicius, Algirdas, Hamouda, Osamah, Horban, Andrzej, Van Kasteren, Marjo, Kolupajeva, Tatjana, Kostrikis, Leontios G., Liitsola, Kirsi, Linka, Marek, Mor, Orna, Nielsen, Claus, Otelea, Dan, Paraskevis, Dimitrios N., Paredes, Roger, Poljak, Mario, Puchhammer-Stöckl, Elisabeth, Sönnerborg, Anders, Staneková, Danica, Stanojevic, Maja, Van Laethem, Kristel, Zazzi, Maurizio, Zidovec Lepej, Snjezana, Boucher, Charles A. B., Schmit, Jean-Claude, Wensing, Annemarie M. J., Puchhammer-Stockl, E., Sarcletti, M., Schmied, B., Geit, M., Balluch, G., Vandamme, A. M., Vercauteren, J., Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., De Wit, S., Echahidi, F., Fransen, K., Goffard, J. -C, Goubau, P., Goudeseune, E., Yombi, J. -C, Lacor, P., Liesnard, C., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Vandekerckhove, L. P. R., Van, den Heuvel, Van, Der Gucht, Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Van Laethem, K., Lepej, S. Z., Begovac, J., Demetriades, Ioannis, Kousiappa, Ioanna, Demetriou, Victoria L., Hezka, Johana, Linka, M., Maly, M., Machala, L., Nielsen, C., Jørgensen, L. B., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Liitsola, K., Ristola, M., Suni, J., Sutinen, J., Descamps, D., Assoumou, L., Castor, G., Grude, M., Flandre, P., Storto, A., Hamouda, O., Kücherer, C., Berg, T., Braun, P., Poggensee, G., Däumer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Korn, K., Müller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Hatzakis, Angelos E., Zavitsanou, Assimina, Vassilakis, A., Lazanas, Marios C., Chini, Maria C., Lioni, A., Sakka, V., Kourkounti, Sofia, Paparizos, Vassilios A., Antoniadou, Anastasia C., Papadopoulos, Antonios I., Poulakou, Garyphallia G., Katsarolis, I., Protopapas, K., Chryssos, Georgios, Drimis, Stylianos, Gargalianos, Panagiotis, Xylomenos, Georgios, Lourida, G., Psichogiou, Mina A., Daikos, George L., Sipsas, N. V., Kontos, Athanasios N., Gamaletsou, M. N., Koratzanis, Georgios, Sambatakou, H., Mariolis, H., Skoutelis, A., Papastamopoulos, V., Georgiou, O., Panagopoulos, Periklis, Maltezos, E., Coughlan, S., De Gascun, C., Byrne, C., Duffy, M., Bergin, C., Reidy, D., Farrell, G., Lambert, J., O'Connor, E., Rochford, A., Low, J., Coakely, P., O'Dea, S., Hall, W., Mor, O., Levi, I., Chemtob, D., Grossman, Z., Zazzi, M., de Luca, A., Balotta, Claudia, Riva, C., Mussini, C., Caramma, I., Capetti, A., Colombo, M. C., Rossi, C., Prati, F., Tramuto, F., Vitale, F., Ciccozzi, M., Angarano, G., Rezza, G., Kolupajeva, T., Vasins, O., Griskevicius, A., Lipnickiene, V., Schmit, J. C., Struck, D., Hemmer, R., Arendt, V., Michaux, C., Staub, T., Sequin-Devaux, C., Wensing, A. M. J., Boucher, C. A. B., van, de Vijver, van Kessel, A., van Bentum, P. H. M., Brinkman, K., Connell, B. J., van, der Ende, Hoepelman, I. M., van Kasteren, M., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M. W. J., Schrijnders-Gudde, L., Schuurman, R., van, de Ven, Kran, A. -M B., Ormaasen, V., Aavitsland, P., Horban, A., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Maolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Camacho, Ricardo J., Palma, C., Borges, F., Paixão, T., Duque, V., Araújo, F., Otelea, D., Paraschiv, S., Tudor, A. M., Cernat, R., Chiriac, C., Dumitrescu, F., Prisecariu, L. J., Stanojevic, M., Jevtovic, Dj, Salemovic, D., Stanekova, D., Habekova, M., Chabadová, Z., Drobkova, T., Bukovinova, P., Shunnar, A., Truska, P., Poljak, M., Lunar, M., Babic, Dunja Z., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Garcia, F., Paredes, R., Monge, S., Moreno, S., del Amo, J., Asensi, V., Sirvent, J. L., de Mendoza, C., Delgado, R., Gutiérrez, F., Berenguer, J., Garcia-Bujalance, S., Stella, Natalia C., de, los Santos, Blanco, J. R., Dalmau, D., Rivero, M., Segura, F., Elıás, Marıá Jesús Pérez, Alvarez, M., Chueca, N., Rodríguez-Martín, C., Vidal, C., Palomares, J. C., Viciana, I., Viciana, P., Cordoba, J., Aguilera, A., Domingo, P., Galindo, M. J., Miralles, C., del Pozo, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., de, la Torre, Vidal, F., Clotet, B., Heidarian, A., Aperia-Peipke, K., Axelsson, M., Mild, M., Karlsson, A., Sönnerborg, A., Thalme, A., Navér, L., Bratt, G., Blaxhult, A., Gisslén, M., Svennerholm, B., Bergbrant, I., Björkman, Per, Säll, C., Mellgren, Å., Lindholm, A., Kuylenstierna, N., Montelius, R., Azimi, F., Johansson, B., Carlsson, M., Johansson, E., Ljungberg, B., Ekvall, H., Strand, A., Mäkitalo, S., Öberg, S., Holmblad, P., Höfer, M., Holmberg, H., Josefson, P., Ryding, U., Van Kessel, A., Clinical sciences, Microbiology and Infection Control, Supporting clinical sciences, Clinicum, Department of Medicine, Virology, Cohorte de Adultos de la Red de Investigación en SIDA, Spain., SPREAD Program, [Hofstra,LM, Sauvageot,N, Struck,D, Schmit,JC ] Luxembourg Institute of Health, Luxembourg. [Hofstra,LM, Wensing,AMJ] Department of Virology, University Medical Center Utrecht, The Netherlands. [Albert,J, Sönnerborg,A] Karolinska Institute, Solna. Karolinska University Hospital, Stockholm, Sweden. [Alexiev,I, Beshkov,D] National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria. [Garcia,F] Complejo Hospitalario Universitario de Granada. Instituto de Investigación IBS Granada, Spain. [Van de Vijver,DAMC, Boucher,CAB] Erasmus MC, University Medical Center, Rotterdam, The Netherlands. [Åsjö,B] University of Bergen, Norway. [Coughlan,S] University College Dublin, Ireland. [Descamps,D] AP-HP Groupe hospitalier Bichat-Claude Bernard. IAME INSERM UMR 1137. Université Paris Diderot Sorbonne Paris Cité, Paris, France. [Griskevicius,A] Lithuanian AIDS Center, Vilnius, Lithuania. [Hamouda,O] Robert Koch Institute, Berlin, Germany. [Horban,A] Hospital of Infectious Diseases, Warsaw, Poland. [Van Kasteren,M] St Elisabeth Hospital, Tilburg, The Netherlands. [Kolupajeva,T] Infectiology Center of Latvia, Riga. [Kostrikis,LG] University of Cyprus, Nicosia. [Liitsola,K] Department of Infectious Diseases, National Institute for Health and Welfare, Helsinki, Finland. [Linka,M] National Reference Laboratory for HIV/AIDS, National Institute of Public Health, Prague, Czech Republic. [Mor,O] National HIV Reference Laboratory, Chaim Sheba Medical Center, Tel-Hashomer, Israel. [Nielsen,C] Statens Serum Institut, Copenhagen, Denmark. [Otelea,D] National Institute for Infectious Diseases 'Prof. dr. Matei Bals', Bucharest, Romania. [Paraskevis,D] National Retrovirus Reference Center, University of Athens, Greece. [Paredes,R] IrsiCaixa Foundation, Badalona, Spain. [Poljak,M] Faculty of Medicine, Slovenian HIV/AIDS Reference Centre, University of Ljubljana, Slovenia. [Puchhammer-Stöckl,E] Medical University Vienna, Austria. [Staneková,D] Slovak Medical University, Bratislava, Slovakia. [Stanojevic,M] Faculty of Medicine, University of Belgrade, Serbia. [Van Laethem,K] Rega Institute for Medical Research, KU Leuven, Belgium. [Zazzi,M] University of Siena, Italy. [Zidovec Lepej,S] University Hospital for Infectious Diseases 'Dr. Fran Mihaljevic', Zagreb, Croatia., This work was supported by a CORE grant of Fond National de la Recherche Luxembourg (grant number C12/BM/4011111–HIV molecular epidemiology in Europe). This work has been partially supported by the European Commission (fifth framework, grant number QLK2-CT-2001-01344, sixth framework, grant number LSHP-CT-2006-518211, DynaNets grant number 233847, seventh framework, CHAIN grant number 223131), Belgium: Belgian AIDS Reference Laboratory Fund, Belgian Fonds voor Wetenschappelijk Onderzoek (grant number G.0692.14), Cyprus: Cyprus Research Promotion Foundation (grant number Health/0104/22), Denmark: Danish AIDS Foundation, France: Agence Nationale de Recherches sur le SIDA et les Hepatites Virales, Germany: Ministry of Health (grant number 1502-686-18), Ministry of Education and Research (grant number 01KI501), Italy: Fifth National Program on HIV/AIDS, Instituto Superiore di Sanità (grant numbers 40F.56 and 20D.1.6), Luxembourg: Fondation Recherche sur le SiDA and Ministry of Health, Republic of Serbia: Ministry of Education and Science (grant number 175024), Slovakia: project 'Center of Excellence of Environmental Health,' ITMS number 26240120033, based on supporting operational research and development program financed from the European Regional Development Fund, and Sweden: Swedish Research Council and Swedish Civil Contingencies Agency., APH - Health Behaviors & Chronic Diseases, Graduate School, Hofstra, LM, Sauvageot, N, Albert, J, Alexiev, I, Garcia, F, Struck, D, Van de Vijver, DA, Åsjö, B, Beshkov, D, Coughlan, S, Descamps, D, Griskevicius, A, Hamouda, O, Horban, A, Van Kasteren, M, Kolupajeva, T, Kostrikis, LG, Liitsola, K, Linka, M, Mor, O, Nielsen, C, Otelea, D, Paraskevis, D, Paredes, R, Poljak, M, Puchhammer-Stöckl, E, Sönnerborg, A, Staneková, D, Stanojevic, M, Van Laethem, K, Zazzi, M, Lepej, SZ, Boucher, CA, Schmit, JC, Wensing, AM, SPREAD program investigators, including Vitale F and Tramuto, F, Vandamme, Annemie, Vercauteren, Jurgen, Schrooten, Yoeri, Van Ranst, Marc, Van Wijngaerden, Eric, Derdelinckx, Inge, Camacho, Ricardo Jorge, Kostrikis, Leontios G. [0000-0002-5340-7109], and Paraskevis, Dimitrios [0000-0001-6167-7152]
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Male ,Human immunodeficiency virus 1 ,Etravirine ,RNA directed DNA polymerase inhibitor ,darunavir ,HIV Infections ,Settore MED/42 - Igiene Generale E Applicata ,Disciplines and Occupations::Health Occupations::Medicine::Public Health [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Salud pública ,genetics ,Inhibidores de proteasas ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Prevalence [Medical Subject Headings] ,atazanavir ,media_common ,transmission ,Geographicals::Geographic Locations::Europe [Medical Subject Headings] ,3. Good health ,microbial sensitivity test ,priority journal ,Europe ,HIV-1 ,antiretroviral therapy ,drug resistance ,HIV/AIDS ,lamivudine ,Reverse Transcriptase Inhibitors/pharmacology ,anti human immunodeficiency virus agent ,Drug ,Microbiology (medical) ,medicine.medical_specialty ,antiviral susceptibility ,Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings] ,media_common.quotation_subject ,030106 microbiology ,HIV Infections/drug therapy ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Reverse Transcriptase Inhibitors [Medical Subject Headings] ,Microbial Sensitivity Tests ,RILPIVIRINE ,Article ,EFAVIRENZ ,03 medical and health sciences ,transmitted drug resistance ,SDG 3 - Good Health and Well-being ,Humans ,Transmission ,human ,Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Drug Resistance [Medical Subject Headings] ,REVERSE-TRANSCRIPTASE INHIBITORS ,Rilpivirina ,INTEGRASE ,MUTATIONS ,abacavir ,major clinical study ,Virology ,Infecciones por VIH ,Regimen ,Antiretroviral therapy ,Drug resistance ,Medicine (all) ,Infectious Diseases ,chemistry ,Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Oxazines::Benzoxazines [Medical Subject Headings] ,Mutation ,0301 basic medicine ,nevirapine ,Communicable diseases ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Confidence Intervals [Medical Subject Headings] ,chemistry.chemical_compound ,antiviral therapy ,INFECTION ,Medicine and Health Sciences ,Prevalence ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Surveys and Questionnaires [Medical Subject Headings] ,Viral ,Non-U.S. Gov't ,Reverse-transcriptase inhibitor ,antiretrovirus agent ,Research Support, Non-U.S. Gov't ,Human immunodeficiency virus infected patient ,Middle Aged ,virology ,PREVALENCE ,Encuestas y Cuestionarios ,ANTIRETROVIRAL TREATMENT ,HIV-1/drug effects ,HIV Protease Inhibitors/pharmacology ,Rilpivirine ,Reverse Transcriptase Inhibitors ,Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [Medical Subject Headings] ,Female ,HIV drug resistance ,medicine.drug ,Adult ,Human immunodeficiency virus proteinase inhibitor ,Chemicals and Drugs::Organic Chemicals::Nitriles::Rilpivirine [Medical Subject Headings] ,Efavirenz ,Anti-HIV Agents ,Research Support ,Resistencia a medicamentos ,Settore MED/17 - MALATTIE INFETTIVE ,antiviral resistance ,Internal medicine ,Anti-HIV Agents/pharmacology ,Drug Resistance, Viral ,Journal Article ,medicine ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors [Medical Subject Headings] ,abacavir plus lamivudine ,Europa (Continente) ,HIV Protease Inhibitors ,emtricitabine ,nonhuman ,Intervalos de confianza ,Mutación ,business.industry ,HIV ,prediction ,Inhibidores de la transcriptasa inversa ,Human immunodeficiency virus 1 infection ,tenofovir ,INDIVIDUALS ,Drug Resistance, Viral/genetics ,Benzoxazinas ,ETRAVIRINE ,drug effects ,3121 General medicine, internal medicine and other clinical medicine ,Prevalencia ,business - Abstract
Transmitted human immunodeficiency virus drug resistance in Europe is stable at around 8%. The impact of baseline mutation patterns on susceptibility to antiretroviral drugs should be addressed using clinical guidelines. The impact on baseline susceptibility is largest for nonnucleoside reverse transcriptase inhibitors., Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. Methods. Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)–infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. Results. The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%–9.5%) in 2008–2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. Conclusions. Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected.
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- 2016
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8. Developing an Integrative Treatment Program for Cancer-Related Fatigue Using Stakeholder Engagement – A Qualitative Study
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Sarah Stoll, Claudia M. Witt, Esther Linka, Claudia Six, Matthias Guckenberger, Michael Mikolasek, Matthias Rostock, Josef Jenewein, Jörg Beyer, Claudia Canella, Roger Stupp, University of Zurich, and Canella, Claudia
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Adult ,Male ,Patients ,Psychological intervention ,Nurses ,Stakeholder engagement ,610 Medicine & health ,03 medical and health sciences ,0302 clinical medicine ,Nursing ,Neoplasms ,medicine ,Humans ,030212 general & internal medicine ,Cancer-related fatigue ,RC254-282 ,Fatigue ,Aged ,Oncologists ,Integrative Medicine ,2707 Complementary and Alternative Medicine ,Stakeholder ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Guideline ,Middle Aged ,10044 Clinic for Radiation Oncology ,Focus group ,10034 Institute of Complementary Medicine ,Complementary and alternative medicine ,Oncology ,Evaluation Studies as Topic ,030220 oncology & carcinogenesis ,10032 Clinic for Oncology and Hematology ,2730 Oncology ,Female ,Integrative medicine ,medicine.symptom ,Psychology ,Qualitative research - Abstract
Background: Although cancer-related fatigue (CRF) has gained increased attention in the past decade, it remains difficult to treat. An integrative approach combining conventional and complementary medicine interventions seems highly promising. Treatment programs are more likely to be effective if the needs and interests of the people involved are well represented. This can be achieved through stakeholder engagement. Objectives: The aim of the study was to develop an integrative CRF treatment program using stakeholder engagement and to compare it to an expert version. Method: In a qualitative study, a total of 22 stakeholders (4 oncologists, 1 radiation-oncologist, 1 psycho-oncologist, 5 nurses/nurse experts, 9 patients, 1 patient family member, 1 representative of a local Swiss Cancer League) were interviewed either face-to-face or in a focus group setting. For data analysis, qualitative content analysis was used. Results: With stakeholder engagement, the integrative CRF treatment program was adapted to usual care using a prioritizing approach and allowing more patient choice. Unlike the expert version, in which all intervention options were on the same level, the stakeholder engagement process resulted in a program with 3 different levels. The first level includes mandatory nonpharmacological interventions, the second includes nonpharmacological choice-based interventions, and the third includes pharmacological interventions for severe CRF. The resulting stakeholder based integrative CRF treatment program was implemented as clinical practice guideline at our clinic (Institute for Complementary and Integrative Medicine, University Hospital Zurich). Conclusion: Through the stakeholder engagement approach, we integrated the needs and preferences of people who are directly affected by CRF. This resulted in an integrative CRF treatment program with graded recommendations for interventions and therefore potentially greater sustainability in a usual care setting.
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- 2017
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9. Evolocumab and clinical outcomes in patients with cardiovascular disease
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Tahirkheli, N, Delgado, E, Derian, W, Greenwald, J, Harris, M, Jackson, R, Marhefka, G, Mcelveen, W, Mooss, A, Morris, P, Murray, J, Pearlstein, P, Raisinghani, A, Rezkalla, S, Sakhrani, L, Schreibman, D, Shaoulian, E, Steinsapir, J, Yataco, A, De La Cruz, A, Fredrick, M, Goldenberg, E, Lee, D, Mccullum, K, Mclellan, B, Stephens, L, Wilson, S, Alfieri, A, Mandviwala, M, Orourke, D, Samal, A, Schmedtje, J, Waxman, F, Carhart, R, Clements, B, Dyke, C, Ghali, J, Gruberg, L, Hack, T, Jehle, A, Pogue, B, Schooley, C, and Shifrin, G
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Male ,STATIN THERAPY ,2700 General Medicine ,Disease ,Cardiovascular ,PLACEBO-CONTROLLED TRIAL ,Gastroenterology ,0302 clinical medicine ,Anticholesteremic Agent ,Medicine ,Myocardial infarction ,11 Medical and Health Sciences ,ddc:616 ,Incidence ,Antibodies, Monoclonal ,General Medicine ,Cholesterol ,Cardiovascular Diseases ,Monoclonal ,Drug Therapy, Combination ,Proprotein Convertase 9 ,Antibody ,Aged ,Anticholesteremic Agents ,Atherosclerosis ,Cholesterol, LDL ,Double-Blind Method ,Female ,Follow-Up Studies ,Humans ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Hypercholesterolemia ,Least-Squares Analysis ,Middle Aged ,Medicine (all) ,REDUCING LIPIDS ,Human ,medicine.medical_specialty ,Evinacumab ,Clinical Trials and Supportive Activities ,PCSK9 INHIBITION ,Follow-Up Studie ,LDL ,03 medical and health sciences ,Drug Therapy ,Clinical Research ,LDL-C ,Least-Squares Analysi ,Science & Technology ,Unstable angina ,PCSK9 ,medicine.disease ,chemistry ,Clinical Biochemistry ,030204 cardiovascular system & hematology ,Bococizumab ,FOURIER Steering Committee and Investigators ,Medical and Health Sciences ,chemistry.chemical_compound ,Antibodies monoclonal ,Cardiovascular Disease ,030212 general & internal medicine ,Stroke ,Humanized ,RISK ,biology ,PCSK9 Inhibitors ,10051 Rheumatology Clinic and Institute of Physical Medicine ,Heart Disease ,Atherosclerosi ,6.1 Pharmaceuticals ,Combination ,Cardiology ,Life Sciences & Biomedicine ,Antibodies, Monoclonal, Humanized ,EZETIMIBE ,610 Medicine & health ,Antibodies ,Medicine, General & Internal ,General & Internal Medicine ,Internal medicine ,CORONARY-HEART-DISEASE ,In patient ,Heart Disease - Coronary Heart Disease ,Alirocumab ,Ldl cholesterol ,business.industry ,Evaluation of treatments and therapeutic interventions ,Evolocumab ,Good Health and Well Being ,Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE ,biology.protein ,MODERATE ,Hydroxymethylglutaryl-CoA Reductase Inhibitor ,business - Abstract
Background Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. Methods We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. Results At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P
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- 2017
10. Preoperative platelet to lymphocyte ratio is a valuable prognostic biomarker in patients with colorectal cancer
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Martin Braddock, Gui-Long Guo, Gui-Qi Zhu, Linka Xie, Zonghai Huang, Ouchen Wang, Liang Shi, Wen-Yue Liu, Ming-Hua Zheng, and Jie You
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0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Multivariate analysis ,disease-free survival ,Colorectal cancer ,overall survival ,colorectal cancer ,Kaplan-Meier Estimate ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,Lymphocyte Count ,Risk factor ,prognostic biomarker ,Aged ,Proportional Hazards Models ,business.industry ,Proportional hazards model ,Platelet Count ,platelet to lymphocyte ratio ,Hazard ratio ,Cancer ,Hepatology ,Middle Aged ,medicine.disease ,Prognosis ,Surgery ,body regions ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Female ,business ,Colorectal Neoplasms ,Body mass index ,Research Paper - Abstract
// Jie You 1, 2, * , Gui-Qi Zhu 3, 4, * , Linka Xie 5, * , Wen-Yue Liu 6 , Liang Shi 7 , Ou-Chen Wang 1 , Zong-Hai Huang 2 , Martin Braddock 8 , Gui-Long Guo 1 , Ming-Hua Zheng 3, 9 1 Department of Oncological Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China 2 Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China 3 Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China 4 School of The First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou 325000, China 5 Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China 6 Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China 7 Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China 8 Global Medicines Development, AstraZeneca R & D, Alderley Park, United Kingdom 9 Institute of Hepatology, Wenzhou Medical University, Wenzhou 325000, China * Co-first authors, the author contributed equally to this work Correspondence to: Ming-Hua Zheng, e-mail: zhengmh@wmu.edu.cn Gui-Long Guo, e-mail: wzguoguilong@163.com Keywords: colorectal cancer, platelet to lymphocyte ratio, overall survival, disease-free survival, prognostic biomarker Received: December 04, 2015 Accepted: March 07, 2016 Published: March 24, 2016 ABSTRACT Objectives: Recent studies suggest that an elevated preoperative platelet to lymphocyte ratio (PLR) may be considered a poor prognostic biomarker in patients with colorectal cancer (CRC). The aim of this study was to evaluate the prognostic impact of PLR in patients with CRC. Methods: We enrolled 1314 patients who underwent surgery for CRC between 2005 and 2011. Preoperative PLR level was stratified into quintiles for Kaplan-Meier analysis and multivariable Cox proportional hazard regression models. Results: Higher PLR quintiles were significantly associated with poorer overall survival ( P = 0.002). Multivariate analysis showed that PLR was an independent risk factor for overall survival (OS) ( P = 0.034). Patients in PLR quintile 5 had lower overall survival than in quintile 1 (hazard ratio (HR) = 1.701, 95% confidence interval (CI): 1.267–2.282, P 65 years) and body mass index (≤ 25) ( P < 0.05 for all measurements). The results remained unchanged when the PLR was analyzed as a dichotomous variable by applying different cut-off values of 150, 185, 220. Conclusions: Elevated preoperative PLR was independently associated with an increased risk of mortality in patients with CRC. The utility of PLR may help to improve prognostic predictors.
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- 2016
11. Effect of the use of a model with peer instruction for the teaching of membrane potential and action potential
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Rachel Linka Beniz Gouveia, Maria Regina de Freitas, Juliany Santiago de Araújo, Rita de Cássia da Silveira e Sá, Nattan Almeida e Sousa, Larissa Suelen da Silva Lins, Francisco Antônio de Oliveira Junior, Temilce Simões de Assis, Fabiola da Silva Albuquerque, and Vinícius José Baccin Martins
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Male ,Students, Health Occupations ,020205 medical informatics ,Physiology ,Action Potentials ,Northeast brazil ,02 engineering and technology ,Models, Biological ,Peer Group ,Education ,Membrane Potentials ,Young Adult ,0202 electrical engineering, electronic engineering, information engineering ,Mathematics education ,Humans ,Membrane potential ,Teaching ,05 social sciences ,Undergraduate education ,050301 education ,General Medicine ,Peer instruction ,Action (philosophy) ,Health Occupations ,Active learning ,Female ,Educational Measurement ,Psychology ,0503 education - Abstract
A group of teachers from Northeast Brazil developed a model of membrane potentials and action potential and tested the hypothesis that using the peer-instruction model would provide a better performance for students in reading traditional texts and lectures. The results were obtained from 357 students from 20 different courses in 9 different undergraduate programs. All students attended two 100-min theoretical lecture and, at the end of the second lecture, were asked to answer a multiple-choice question (a pretest). In the following lecture, students were divided into three groups: control, text, and model. At the end of the lecture, everyone responded to a posttest. Student performance in the pretest did not differ significantly between groups. In the comparison between the pretest and the posttest, students in the model and text groups significantly improved their performance, but there was no improvement in the control group. In the posttest, the model group presented a better performance than the control group. In the evaluation of the strategies used, 46% of the students indicated that the text would be very useful to remind them about the subject in the future, whereas 80% of those who used the model indicated that it would be very useful or extremely useful. useful. Although it was not possible to support the hypothesis conclusively, the performance model group, at least in part, was due to the use of active methodologies that constitute a differential in the teaching-learning process.
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- 2018
12. Towards Patient-Specific Computational Modelling of Articular Cartilage on the Basis of Advanced Multiparametric MRI Techniques
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Markus Hillgärtner, Kevin Linka, Mikhail Itskov, Lea Hitpass, Matthias Knobe, Johannes Thuering, Christiane K. Kuhl, Sven Nebelung, Amelie Schäfer, and Daniel Truhn
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0301 basic medicine ,Adult ,Cartilage, Articular ,Male ,Materials science ,Compressive Strength ,lcsh:Medicine ,Context (language use) ,Osteoarthritis ,Models, Biological ,Article ,03 medical and health sciences ,0302 clinical medicine ,Medical research ,medicine ,Image Processing, Computer-Assisted ,Humans ,Prospective Studies ,Multiparametric Magnetic Resonance Imaging ,lcsh:Science ,Aged ,Multidisciplinary ,Basis (linear algebra) ,Cartilage ,lcsh:R ,Biomechanics ,Multiparametric MRI ,Patient specific ,Middle Aged ,medicine.disease ,Tissue Degeneration ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Q ,Female ,Cartilage Diseases ,Biomedical engineering ,030217 neurology & neurosurgery ,Algorithms - Abstract
Scientific reports 9, 7172 (2019). doi:10.1038/s41598-019-43389-y, Published by Macmillan Publishers Limited, part of Springer Nature, [London]
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- 2018
13. Crushed dolutegravir/abacavir/lamivudine given via nasogastric tube in gastric outlet obstruction caused by cancer resulted in rapid viral load suppression
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Zdeňka Jerhotová, Václav Chmelík, Aleš Chrdle, Michal Vacík, and Marek Linka
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Male ,medicine.medical_specialty ,Parenteral Nutrition ,Sustained Virologic Response ,Pyridones ,HIV Infections ,Dermatology ,Adenocarcinoma ,Gastroenterology ,Piperazines ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Abacavir ,Stomach Neoplasms ,Internal medicine ,Oxazines ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Intubation, Gastrointestinal ,030505 public health ,business.industry ,Gastric Outlet Obstruction ,Stomach ,Public Health, Environmental and Occupational Health ,Lamivudine ,Gastric outlet obstruction ,Abacavir/Lamivudine ,Middle Aged ,medicine.disease ,Dideoxynucleosides ,Infectious Diseases ,medicine.anatomical_structure ,Parenteral nutrition ,Treatment Outcome ,chemistry ,Anti-Retroviral Agents ,Dolutegravir ,0305 other medical science ,business ,Viral load ,Heterocyclic Compounds, 3-Ring ,medicine.drug - Abstract
Alternative modes of antiretroviral administration are sought for people with impaired intestinal passage and/or absorption. We present a case of late HIV diagnosis (CD4+ count 160 cells/µL) with gastric outlet obstruction due to stomach adenocarcinoma. Co-morbidities included oesophageal candidiasis, Helicobacter pylori-positive duodenal ulcers and cytomegalovirus duodenitis. The gastric outlet obstruction required total parenteral nutrition and parenteral medication during four weeks of diagnostic work-up leading to pyloric resection. Crushed dolutegravir, abacavir and lamivudine were administered during this time in the evening via nasogastric tube, which was kept clamped overnight. The tube was unclamped in the morning and stomach content was drained during the daytime. This mode of administration resulted in rapid and sustained viral load suppression (from 300,000 to 115 copies per mL in 28 days, 81 copies/mL after 42 days of treatment and less than 40 copies/mL thereafter). Therapeutic drug monitoring confirmed sufficient antiretroviral plasma levels during this mode of administration. The absorption of crushed dolutegravir, abacavir and lamivudine in the stomach may be considered in people with questionable gastrointestinal passage or impaired gastric emptying to achieve viral load suppression.
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- 2018
14. Right atrial epithelioid angiosarcoma with multiple pulmonary metastasis confirmed by multimodality imaging-guided pulmonary biopsy
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Liu, Cuiwei, Zhao, Yanxia, Yin, Zhongyuan, Hu, Ting, Ren, Jinghua, Wei, Jielin, Xie, Linka, Xiong, Jie, Wu, Hongge, Dai, Xiaofang, and Fei, Shihong
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Adult ,Male ,Lung Neoplasms ,Biopsy ,Hemangiosarcoma ,imaging-guided biopsy ,Heart Neoplasms ,atrial angiosarcoma ,Dyspnea ,Fluorodeoxyglucose F18 ,Positron Emission Tomography Computed Tomography ,case report ,Hemangioendothelioma, Epithelioid ,Humans ,Clinical Case Report ,Heart Atria ,pulmonary metastasis ,Lung ,Research Article - Abstract
Rationale: Primary cardiac tumors are very rare, and angiosarcoma accounts for about 33% of all primary malignant cardiac tumors. Primary cardiac epithelioid angiosarcoma is a highly aggressive and difficult to diagnose tumor, with early systemic metastasis and poor prognosis. Patient concerns: A 35-year-old Han male experienced sudden severe palpitation and moderate dyspnea. The patient received a whole body F-18 fluoro-deoxyglucose positron emission tomography (18F-FDG PET)/computed tomography (CT) scan, the scan showed a large mass in the right atrium (RA) and numerous pulmonary nodules in both lungs. Diagnoses: The patient was diagnosed as right atrial epithelioid angiosarcoma with multiple pulmonary metastasis by pulmonary biopsy through CT-guided percutaneous transthoracic fine needle aspiration. Interventions: The patient received a cycle of chemotherapy with docetaxel and gemcitabine, followed by another cycle with epirubicin and ifosfamide. Outcomes: The chemotherapy was ineffective. After the two cycles, the bilateral pleural effusion steadily increased, the patient had severe dyspnea and palpitation, and died three weeks later, with an overall survival of 2.5 months. Lessons: Primary angiosarcoma of heart is a very rare and aggressive disease, and its diagnosis and treatment are difficult. Most patients may have systemic metastasis at diagnosis, and have a very short survival without surgical resection. Hence, early diagnosis and surgical resection is extremely important to treat this disease.
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- 2018
15. Loss-of-function mutations within the IL-2 inducible kinase ITK in patients with EBV-associated lymphoproliferative diseases
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Radovan Dvorsky, Mohammad Reza Ahmadian, Hassan Jumaa, Werner M, René M. Linka, F. Krux, Sylvain Latour, Cindy Synaeve, Yvonne Linka, Michael Gombert, René Deenen, Bernhard Fleckenstein, Sarah L. Risse, Sebastian Ginzel, Burkhart Schraven, Polina Stepensky, Roland Hartig, Arndt Borkhardt, Alain Fischer, Mika Helminen, Anne Halenius, Hans-Jürgen Laws, Kim Vettenranta, Karl Köhrer, and Kirsten Bienemann
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Male ,Herpesvirus 4, Human ,Cancer Research ,Mutation, Missense ,Biology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,ITK Deficiency ,Calcium flux ,medicine ,Humans ,Phosphorylation ,Child ,Germ-Line Mutation ,030304 developmental biology ,0303 health sciences ,Mutation ,Binding Sites ,Kinase ,Hematology ,Protein-Tyrosine Kinases ,Lymphoproliferative Disorders ,Pedigree ,3. Good health ,XIAP ,Pleckstrin homology domain ,Oncology ,Child, Preschool ,Cancer research ,Female ,Tyrosine kinase ,030215 immunology - Abstract
The purpose of this study was the appraisal of the clinical and functional consequences of germline mutations within the gene for the IL-2 inducible T-cell kinase, ITK. Among patients with Epstein-Barr virus-driven lymphoproliferative disorders (EBV-LPD), negative for mutations in SH2D1A and XIAP (n=46), we identified two patients with R29H or D500T,F501L,M503X mutations, respectively. Human wild-type (wt) ITK, but none of the mutants, was able to rescue defective calcium flux in murine Itk(-/-) T cells. Pulse-chase experiments showed that ITK mutations lead to varying reductions of protein half-life from 25 to 69% as compared with wt ITK (107 min). The pleckstrin homology domain of wt ITK binds most prominently to phosphatidylinositol monophosphates (PI(3)P, PI(4)P, PI(5)P) and to lesser extend to its double or triple phosphorylated derivates (PIP2, PIP3), interactions which were dramatically reduced in the patient with the ITK(R29H) mutant. ITK mutations are distributed over the entire protein and include missense, nonsense and indel mutations, reminiscent of the situation in its sister kinase in B cells, Bruton's tyrosine kinase.
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- 2012
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16. HIV-1 Infection in Cyprus, the Eastern Mediterranean European Frontier: A Densely Sampled Transmission Dynamics Analysis from 1986 to 2012
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Pineda-Peña, Andrea-Clemencia, Theys, Kristof, Stylianou, Dora C., Demetriades, Ioannis, Puchhammer, Elisabeth, Vandamme, Anne-Mieke, Aleksiev, Ivailo, Zidovec Lepej, Snjezana, Linka, Marek, Fonage, Jannik, Liitsola, Kirsi, Kaiser, Rolf, Hamouda, Osamah, Paraskevis, Dimitrios, Coughlan, Suzie, Grossman, Zehava, Mor, Orna, Zazzi, Maurizio, Griskevicius, Algirdas, Lipnickiene, Vilnele, Devaux, Carole, Boucher, Charles, Hofstra, Marije, Wensing, Annemarie, Bakken-Kran, Anne-Marte, Horban, Andrzej, Camacho, Ricardo, Paraschiv, Simona, Otelea, Dan, Stanojevic, Maja, Stanekova, Danika, Poljak, Mario, Garcia, Federico, Paredes, Roger, Albert, Jan, Abecasis, Ana, Kostrikis, Leondios G., Virology, Kostrikis, Leondios G. [0000-0002-5340-7109], Stylianou, Dora C. [0000-0003-4167-1380], Vandamme, Anne-Mieke, and Camacho, Ricardo
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0301 basic medicine ,Male ,Genotyping Techniques ,Human immunodeficiency virus (HIV) ,HIV Infections ,medicine.disease_cause ,law.invention ,0302 clinical medicine ,law ,Epidemiology ,Prevalence ,Cluster Analysis ,030212 general & internal medicine ,Ofhivinfected Individuals ,Molecular Epidemiology ,Multidisciplinary ,Infectious ,virus diseases ,Middle Aged ,Infection Cyprus ,Subtyping ,3. Good health ,Transmission (mechanics) ,Geography ,Cohort ,Síndromes de inmunodeficiencia ,Medicine ,Female ,Adult ,medicine.medical_specialty ,Science ,Sida ,Disease cluster ,Article ,03 medical and health sciences ,Frontier ,Young Adult ,Disease Transmission ,SDG 3 - Good Health and Well-being ,Environmental health ,medicine ,Disease Transmission, Infectious ,Humans ,Cyprus ,HIV-1 ,VIH ,Enfermedades ,Eastern mediterranean ,030104 developmental biology - Abstract
Since HIV-1 treatment is increasingly considered an effective preventionstrategy, it is important to study local HIV-1 epidemics to formulate tailored preventionpolicies. The prevalence of HIV-1 in Cyprus was historically low until 2005. To investigatethe shift in epidemiological trends, we studied the transmission dynamics of HIV-1 in Cyprususing a densely sampled Cypriot HIV-1 transmission cohort that included 85 percent ofHIV-1-infected individuals linked to clinical care between 1986 and 2012 based on detailedclinical, epidemiological, behavioral and HIV-1 genetic information. Subtyping andtransmission cluster reconstruction were performed using maximum likelihood and Bayesianmethods, and the transmission chain network was linked to the clinical, epidemiological andbehavioral data. The results reveal that for the main HIV-1 subtype A1 and B sub-epidemics,young and drug-naïve HIV-1-infected individuals in Cyprus are driving the dynamics of thelocal HIV-1 epidemic. The results of this study provide a better understanding of thedynamics of the HIV-1 infection in Cyprus, which may impact the development of preventionstrategies. Furthermore, this methodology for analyzing densely sampled transmissiondynamics is applicable to other geographic regions to implement effective HIV-1 preventionstrategies in local settings. ispartof: Scientific Reports vol:8 issue:1 ispartof: location:England status: Published online
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- 2017
17. Infection Exposure Promotes
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Guillermo, Rodríguez-Hernández, Julia, Hauer, Alberto, Martín-Lorenzo, Daniel, Schäfer, Christoph, Bartenhagen, Idoia, García-Ramírez, Franziska, Auer, Inés, González-Herrero, Lucia, Ruiz-Roca, Michael, Gombert, Vera, Okpanyi, Ute, Fischer, Cai, Chen, Martin, Dugas, Sanil, Bhatia, René Martin, Linka, Marta, Garcia-Suquia, María Victoria, Rascón-Trincado, Angel, Garcia-Sanchez, Oscar, Blanco, Maria Begoña, García-Cenador, Francisco Javier, García-Criado, César, Cobaleda, Diego, Alonso-López, Javier, De Las Rivas, Markus, Müschen, Carolina, Vicente-Dueñas, Isidro, Sánchez-García, and Arndt, Borkhardt
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Histone Demethylases ,Male ,Mice, Inbred C57BL ,Disease Models, Animal ,Mice ,Oncogene Proteins, Fusion ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,Core Binding Factor Alpha 2 Subunit ,Mice, Inbred CBA ,Animals ,Humans ,Mice, Transgenic ,Hematopoietic Stem Cells - Published
- 2017
18. Anabolic–Androgenic Steroid Use Among Brazilian Bodybuilders
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Aline de Freitas Brito, Rachel Linka Beniz Gouveia, Fabiana Ranielle de Siqueira Nogueira, Thaiza Isidro Vieira, and Caio Victor Coutinho de Oliveira
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Adult ,Male ,medicine.medical_specialty ,Health (social science) ,Adolescent ,Weight Lifting ,Anabolism ,Substance-Related Disorders ,Low education ,Exploratory research ,Medicine (miscellaneous) ,Convenience sample ,Anabolic Agents ,Sustanon ,Young Adult ,Environmental health ,Prevalence ,medicine ,Humans ,Socioeconomic status ,Doping in Sports ,business.industry ,Public Health, Environmental and Occupational Health ,Middle Aged ,Psychiatry and Mental health ,Cross-Sectional Studies ,Steroid use ,Androgens ,Physical therapy ,Female ,business ,Brazil ,medicine.drug - Abstract
This cross-sectional, quantitative, exploratory study investigated the prevalence and profile of anabolic-androgenic steroids (AAS) users amongst a convenience sample of 510 bodybuilders from 52 gyms, in João Pessoa, Brazil, with a structured questionnaire containing selected questions about socioeconomic and training variables on the use of AAS. Data were analyzed using frequency and chi-square tests. AAS prevalence use was 20.6%; mostly young men (98.1%), of a low education level (46.7%), who trained for more than 4 years (49.5%). The use of AAS was related to the use of dietary supplements. About 81% of consumed AAS consisted of Deca-Durabolin, Winstrol, and Sustanon. Study's limitations are noted.
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- 2014
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19. Ezetimibe added to statin therapy after acute coronary syndromes
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Cannon, Christopher P., Blazing, Michael A., Giugliano, Robert P., Mccagg, Amy, White, Jennifer A., Theroux, Pierre, Darius, Harald, Lewis, Basil S., Ophuis, Ton Oude, Jukema, J. Wouter, De Ferrari, Gaetano M., Ruzyllo, Witold, De Lucca, Paul, Kyungah, Im, Bohula, Erin A., Reist, Craig, Wiviott, Stephen D., Tershakovec, Andrew M., Musliner, Thomas A., Braunwald, Eugene, Califf, Musliner T, Robert M., Tershakovec, A, Gurfinkel, E, Aylward, P, Tonkin, A, Maurer, G, Van de Werf, F, Nicolau, Jc, Theroux, P, Genest, J, Armstrong, P, Corbalan, R, Isaza, D, Spinar, J, Grande, P, Voitk, J, Kesaniemi, A, Bassand, Jp, Farnier, M, Darius, H, Keltai, M, Mathur, A, Mittal, S, Reddy, K, Lewis, B, De Ferrari GM, Ophuis, To, Jukema, J, White, H, Pedersen, T, Britto, F, Ruzyllo, W, Carrageta, M, Duris, T, Dalby, A, Seung, Kb, Lopez-Sendon, J, Dellborg, M, Mach, F, Guneri, S, Parkhomenko, A, Brady, A, Cannon, C, Blazing, M, Ballantyne, C, de Lemos, J, Kleiman, N, Mcguire, Dk, Centeno, E, Casalins, M, Cartasegna, L, Beltrano, Mc, Guerrero, R, Fanuele, M, Berra, F, Egido, J, Colombo, H, Dellatorre, M, Terns, P, Blumberg, E, Reges, P, Azize, G, Ramos, H, Fernandez, R, Carlessi, C, Milesi, R, Schmuck, R, Duronto, E, Procopio, G, Carlevaro, O, Maffeo, H, Beloscar, J, Viso, M, Hominal, M, Castoldi, M, Bluguermann, J, Mauro, D, Macin, S, Cocco, N, Ruiz, N, Ricart, J, Lozada, A, Nani, S, Turri, D, Fernandez, H, Caruso, O, Zarandon, R, Bono, J, Arias, V, Allall, O, Marino, J, Cusimano, S, Schygiel, P, Buzetti, C, Penaloza, N, Berli, M, Worthley, S, Roach, A, Chew, D, Wright, T, Leitch, J, Hicks, E, Rankin, J, Venn-Edmonds, C, Lehman, R, Morrison, H, Shaw, J, Mak, V, Hii, C, Smith, K, Cross, D, Lilwall, L, Nelson, G, Loxton, A, Horowitz, J, Rose, J, Steinwender, C, Leisch, F, Kammler, J, Brussee, H, Zweiker, R, Niederl, E, Weihs, W, Giorgio, G, Lang, I, Drexel, H, Zanolin, D, Hoppe, U, Atzenhofer-Baumgartner, K, Pichler, M, Hainzer, D, Eber, B, Pichler, F, Foeger, B, Wechselberger, T, Mayr, H, Hofer, J, Stockenhuber, F, Warlits, B, Huber, K, Egger, F, Weidinger, F, Ziegler, B, Jirak, P, Metzler, B, Pachinger, O, Wanitschek, M, Auer, J, Grabscheit, G, Podczeck-Schweighofer, A, Priesnitz, T, Frank, H, El Allaf, D, Marechal, P, Roosen, J, Joly, E, Lefebvre, P, Arend, C, Sinnaeve, P, De Velder, L, Hellemans, S, Vanhauwaert, B, Van Dorpe, A, Heyse, A, Vantomme, C, Striekwold, H, Van Den Broeck, D, Lancellotti, P, Schoors, D, Lemoine, I, Taeymans, Y, De Wolf, L, Brike, C, Vercauteren, S, Tahon, S, Vervoort, G, Mestdagh, I, Pirenne, B, Cardinal, F, Lips, S, Dujardin, K, Debrouwer, K, Dhooghe, G, Holvoet, G, van de Borne, P, Renard, M, De Clippel, M, Lesseliers, H, Van Miert, N, Saraiva, J, Vicente, C, Rossi, P, Dos Santos LB, Duda, N, Tognon, Ap, Serrano, C, Gomes, Fl, Manenti, Er, Silveira, Ds, Maia, L, Mouco, Om, Paiva, M, Antonangelo, A, de Souza, J, Lino, Ea, Leães, P, Blacher, Mg, Kormann, A, Ultramari, Ft, Dutra, O, Mendelski, Am, Morgado, S, Ardito, W, Greque, G, Ardito, Rv, Pimentel Filho, P, Zucchetti, C, Alves, A, Seabra, Am, Mattos, M, Miranda, Lf, Silva, D, Uehara, Rm, Marin Neto, J, Schmidt, A, Braga, J, Rodrigues, A, 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Chian-Yi, W., Yeh, H., Mei-Juan, C., Hsieh, I., Wang, Y., Ural, E., Sahin, T., Yildiz, Z., Kayikcioglu, M., Kultursay, H., Yigit, Z., Calpar, I., Ata, N., Goktekin, O., Senol, U., Yalcin, R., Timurkaynak, T., Kaya, U., Yildirir, A., Karacaglar, E., Faynyk, A., Sorokivskyy, M., Koval, O., Kaplan, P., Kraiz, I., Popova, K., Kyyak, Y., Barnett, O., Karpenko, O., Todoriuk, L., Tseluyko, V., Kopytsya, M., Petyunina, O., Kovalskyy, I., Zhukova, Y., Katerenchuk, I., M'yakinkova, L., Lutay, Y., Syvolap, V., Kyselov, S., Vakaliuk, I., Nesterak, R., Nikonov, V., Feskov, O., Goloborodko, B., Golovtsev, Y., Berezniakov, I., Lebedynska, M., Rudenko, L., Tutov, I., Ahsan, A., Burton, J., Levy, T., Lakeman, N., Spratt, J., Langford, E., Sutcliffe, S., Khwanda, A., Davis, G., Rodrigues, E., Dickinson, D., Been, M., Trouton, T., Riddell, J., Moriarty, A., McEneaney, D., Squire, I., Narayan, H., Goode, G., Helliwell, L., Boos, C., Greaves, K., Knops, K., Pegge, N., Signy, M., Wong, Y., Moore, S., Fluck, 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Alexander, J., Genova, E., MacDonell, A., Broadwater, S., Kereiakes, D., White, D., Lopez, M., Schenks, R., Lui, H., Gibbons, P., Davis, B., Thornton, K., Daley, P., Budzon, S., McCullum, K., Delio-Cox, B., Nadar, V., Keim, S., McLaurin, B., Davis, C., Betzu, R., Al-Jumaily, J., Bolli, R., Alshaher, M., Leesar, M., Collins, T., Akkad, H., Bilazarian, S., Marsters, M., Kennett, J., Melegrito, K., Mostel, E., Harris, R., Chang, M., Hatfield, G., Makam, S., Garvey, M., Levite, H., White, J., Abdel-Latief, A., Pelletier, L., Carr, K., Mckenna, K., De Lemos, J., Soto, G., Kozina, J., Harris, D., Vlastaris, A., Bittel, B., Riba, A., Gugudis, J., Singh, N., Qureshi, I., Doty, W., Lehmann, J., Lieber, I., Martin, S., Nicu, M., Bhalodkar, N., Ravi, P., Canto, J., Bass, M., Campbell, C., Steinhubl, S., Moles, K., Harjai, K., Stapleton, D.D., Hoey, K., Erwin, J., Fikes, W., Stein, B., Sabatino, K., Teklinski, A., Colfer, H., Ward, P., Langevin, E., Faucett, S., Mamdani, S., DeSimone, L., Tuohy, E., Cullen, T., Eisenberg, S., Chronos, N., Allen, R.P., Erickson, B., Mahon, K., Kirby, A., Siegel, C., Stroud, L., Johnson, J., Panchal, V., Pearson, A., Abell, T., De Gregorio, M., Boomer, L., Vahdat, O., VanNatta, B., Long, P., Chalavarya, G., Skatrud, L., Carey, C., Wright, W., Mechem, C., Matthews, B., Adams, A., Vora, K., Wead, J., Koren, M., Gregory, D., El Khadra, M., Peacock, G., Kieval, J., Barron, M., Lewis, D., Grice, R., Bobek, M., Moore, C., Nygaard, T., Fischell, T., Salman, W., Schneider, C., Muhlestein, B., Peeler, D., Chang, D., Todd, A., Chilakamarri, V., Hanley, P., Gelormini, J., Iacona, M.A., Effron, B., Mazzurco, S., Mazzella, M., Wyman, P., Orchard, R., Battin, D., Rezkalla, S., Bishop, C., Sharp, S., Gredler, F., Knap, P., Fadel, M., Saucedo, J., Keng, A., Imburgia, M., Blank, E., Effat, M., Khoury, S., Mardis, R., Baldari, D., Tafuri, L., Mascolo, R., Taylor, D., Mandviwala, M., Khan, W., Mumford, T., Mayer, N., Mitchell, B., Oliver, T., Lombardi, W., Zimmerman, T., Rohrbeck, S., Cooke, L., Craig, M., Mego, D., Griffin, B., Perez, J., LeClerc, K., Addington, J., Aboufakher, R., Ahmed, A., Westecott, B., Steel, K., Hawkins, K., Shah, A., Ward, U., McGreevy, M., Goldberg, R., Prashad, R., McDonough, C., Silver, K., Josephson, R., Witsaman, S., Labib, S., Woodhead, G., Schrank, J., Bell, K., Chandna, H., Holly, D., Bethea, C., Fife, B., Gruberg, L., Singer, A., Ramgadoo, M., Lalonde, T., Morin, R., French, W., Barillas, O., Gradner, G., Kahn, Z., Gress, J., Rocco, D., Thew, S., Stifter, W., Fisher, M., McNamara, J., Kupfer, J., Agocha, A., Cush, S., Jones, S., Whitaker, T., Stover, T., Kumkumian, G., Kent, K., Greenberg, A., Pandey, P., Pytlewski, G., Matsumura, M., Kai, W., Sameshima, S., Thomas, J., MacNicholas, D., Pillai, K., Jones, D., Navas, J.P., Laskoe, B., Patel, P., Fini, G., Minor, S., Shipwash, T., Cabrera-Santamaria, A., Rivera, E., Mincher, L., Jafar, M., Yen, M., Finkle, C., Rahimtoola, A., Severson, L., Labroo, A., Jinich, D., Tam, K., Vogel, C., Aggarwal, R., Zakhary, B., Curtis, S., Lyster, M., Humphrey, K., Lavine, P., Fujise, K., Birnbaum, Y., Allen, J., Kesselbrenner, M., Michel, K., Staniloae, C., Liu, M., Sonel, A., Macioce-Caffas, A., Amidon, T., Leggett, J., Yedinak, S., Gudmundsson, G., Sabharwal, J., Dagefoerde, N., Wu, W., Meyerrose, G., Roongsritong, C., Jenkins, L., Lieberman, S., Sokol, S., Gutierrez, C., Nelson, C., Barrett, J., Hotchkiss, D., Farley, A., Atassi, K., Christy, L., Baig, M., Di Fazio, J., Meengs, M., Thomas, K., Surmitis, J., DeVault, S., Farhat, N., Hulyalkar, A., Riddell, L., Rivera, W., Sheynberg, B., Kobayashi, J., Katsaropoulos, J., Jan, M., Krucoff, M., Paterno, C., Chandrasekaran, S., Curry, R., Cassavar, D., Wheeler, M., McGarvey, J., Schwarz, L., Miller, E., Andrea, B., Carswell, B.S., Lurie, M., Patti, J., Bowden, W., Vasiliauskas, T., Latham, R., Schwartz, B., Bradford, L., Mattleman, S., Wertheimer, J., Goulden, D., Khan, M., Hawkins, B., Ostfeld, R., Mueller, H., Ash, Y., Wilson, V., Bayer, M., Marshall, J., Dobies, D., Dawson, G., Osman, A., Saba, F., Costello, T., Fuentes, F., Underwood, C., Vijay, N., Washam, M., Dietz, W., Glasgow, B., Mukherjee, S., Hinchion, N., Speirs, S., Thornley, A., Lee, K., Movahed, M., Strootman, D., Chernick, R., Parrott, C., Flock, C., Marques, V., Syzmanski, E., Rama, P., Domingo, D., Wu, L., Bauer, B., Dionisopoulos, P., Aggarwal, A., Holcomb, R., Foster, R., Hancock, T., Hargrove, J., Fletcher, A., Stine, R., Bullivant, M., Adams, K., Lohman, J., Klepper, V., Kabour, A., Neidhardt, J., Phillips, W., Tardiff, S., Aji, J., Corut, S., Foster, G., Firek, C., St Goar, F., Sumner, R., Davis, T., Schneider, R., Schneider, W., Villa, A., Desai, V., Chhabra, A., Banks, K., Herzog, W., Burley, T., Quyyumi, A., Smiley, W., Manocha, P., Fishbein, G., Weller, C., Coffman, A., Kim, C., Kedia, A., Firth, B., Rizvi, M., Dahiya, R., Foster, B., Balcells, E., Metzger, D.C., Lester, J., Bissett, J., Fahdi, I., Sides, E.A., Azrin, M., Martin, C., Quick, A., Conaway, D., Garg, M., Schallert, G., Lancaster, L., Mckissick, S., Atieh, M., Garbarino, J., Eisenberg, D., Uusinarkaus, K., Wirtemburg, P., Ellis, J., Cristaldi, J., Berglund, R., Negus, B., Pappas, J., Rocha, R., Nguyen, T., Stone, J., Janosik, D., Labovitz, A., Elmore, N., Dave, R., Loffredo, K., Gabriel, G., Snyder, C., Ahmed, O., Stone, H., Kelley, M., Diffenback, M., Friedman, B., Zirkle, J., Severa, L., Sample, S., Dignen, K., Raisinghani, A., Ben-Yehuda, O., Ghannadian, B., Moscoso, R., Mankowski, J., Boliek, W., Rukavina, M., Davis, W., Ledbetter, S., Handel, F., Mastouri, R., Mahenthiran, J., Foltz, J., Malhotra, V., Jonas, J., Berk, M., Singh, V., Nelson, M., Elsner, G., Gall, J., Kondo, N., Frank, S., Chandraratna, P., Ranasinghe, S., Ebrahimi, R., Treadwell, M., Walters, B., Hughes, L., Kramer, J., Kumar, K., Mente, T., Lachterman, B., Schifferdecker, B., Munshi, K., Sease, D., Waldo, D., Chandler, G., Manns, D., Nahhas, A., Kamalesh, M., Williams, V., Reich, D., Desalca, M., Sharma, S., Liston, M., Gupta, K., Costa, M., Altschuller, A., Lemmertz, K., Shanes, J., Hansen, C., Therrien, M., Mendelson, R., Ramnarine, R., Myers, G., Donovan, C., Klein, M., Fine, D., Owens, S., Murray, C., Ketroser, R., Heifetz, S., Darnell, Z., Touchon, R., Taghizadeh, B., Bohle, D., Norwood, D., Forrest, T., Jackson, S., Shumate, K., Bayles, A., Masroor, M., North, W.K., Fishberg, R., Merveil-Ceneus, B., Butcher, R., Menapace, F., Kilbride, S., Ramabadran, R.S., Loukinen, K., Khalil, J., Ramabadran, R., Walsh, S., Gill, S., Cyncar, R., McLachlan, J., Surakanti, V., Rusterholtz, L., Shoukfeh, F., Stephenson, L., Tsang, M., Nolan, V., Gilchrist, I., Jefferson, D., Feldman, T., Reyes, L., Santos, R., Little, W., Wesley, D., Gharib, W., Mendell, A., Esham, G., Kakavas, P., Whitcomb, C., Book, K., Bazzi, A., Alvarez, J., Cohen, Y., Ayres, T., Rhule, V., Labib, A., Schuler, P., Zughaib, M., Telck, K., Bikkina, M., Turnbull, K., Sharma, T., Orosz, S., Shah, R., Petrino, M., Hughes, M., Hershey, J., Hudock, D., Hui, P., Von Bakonyi, A., Arnold, A., Kappel, D., Pennock, G., Cloud, B., Tucker, K., Harp, L., Hoover, C., Eisenhauer, M., Roth, J., Young, C., Thai, H., Escalante, A., Bautista, J., Gazmuri, R., Nyland, J., Cubeddu, L., DeFranco, A., Dias, D., Fielding, M., Reeves, R., Hermany, P., Meissner-Dengler, S., Evans, M., Flores, E., Tannenbaum, A., McGarr, K., Moran, J., Stout, E., Allred, S., Henderson, D., Crandall, L., Strote, J., Voyles, W., Robeson, D., Bedoya, R., Omar, B., Pettyjohn, F., Revere, C., Coy, K., Margolis, J., Sotolongo, C., Scheffel, M., Munir, A., Shirwany, A., Douglas, L., Girala, R., Humphreys, R., Agarwal, J., Bankowski, D., Watson, R., Bishop, B., Klementowicz, P., Blais, D., Cohen, B., Lobur, E., Dimenna, J., Dempsey, K., Izzo, M., Bondi, L., Carell, E., Eaton, C., Saltiel, F., Grewal, G., Connolly, T., Little, T., Wiegman, P., Gips, S., Held, J., Paraschos, A., Quesada, R., Goudreau, E., Sears, M., Istfan, P., Holt, S., McClung, J., Nguyen, N., Quintana, O., Gottlieb, D., Knutson, T., Barringhaus, K., Lester, F., Sullivan, P., Rodriguez-Ospina, L., Cannon, Cp, Blazing, Ma, Giugliano, Rp, Mccagg, A, White, Ja, Theroux, P, Darius, H, Lewis, B, Ophuis, To, Jukema, Jw, De Ferrari, Gm, Ruzyllo, W, De Lucca, P, Im, K, Bohula, Ea, Reist, C, Wiviott, Sd, Tershakovec, Am, Musliner, Ta, Braunwald, E, Califf, Rm, for the IMPROVE-IT, Investigator, Cianflone, D, Cardiovascular Division (SZG), Brigham and Women's Hospital [Boston], College of Information Science and Engineering, Ritsumeikan University, Montreal Heart Institute (MONTREAL HEART INSTITUTE), Laboratoire des Micro-algues toxiques, Institut Louis Malardé [Papeete] (ILM), Institut de Recherche pour le Développement (IRD)-Institut de Recherche pour le Développement (IRD), Interuniversity Cardiology Institute Netherlands, Institute of Cardiology (WARSAW - Cardiology), Institute of Cardiology, Merck Sharp & Dohme Corp., Merck & Co. Inc, DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, Facolta' di MEDICINA e CHIRURGIA, AREA MIN. 06 - Scienze mediche, Cannon, C.P., Blazing, M.A., Giugliano, R.P., Mccagg, A., White, J.A., Lewis, B.S., Jukema, J.W., De Lucca, P., Im, K., Bohula, E.A., Reist, C., Wiviott, S.D., Tershakovec, A.M., Musliner, T.A., Braunwald, E., Califf, R.M., for the IMPROVE-IT Investigators [.., C. Rapezzi, ], Other departments, Cannon, Christopher P, Blazing, Michael A., Giugliano, Robert P., Mccagg, Amy, White, Jennifer A., Theroux, Pierre, Darius, Harald, Lewis, Basil S., Ophuis, Ton Oude, Jukema, J. Wouter, De Ferrari, Gaetano M., Ruzyllo, Witold, De Lucca, Paul, Kyungah, Im, Bohula, Erin A., Reist, Craig, Wiviott, Stephen D., Tershakovec, Andrew M., Musliner, Thomas A., Braunwald, Eugene, and Califf, Robert M.
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Male ,Simvastatin ,acute coronary syndrome ,aged ,anticholesteremic agents ,azetidines ,cardiovascular diseases ,cholesterol, ldl ,double-blind method ,drug therapy, combination ,ezetimibe ,female ,humans ,hydroxymethylglutaryl-coa reductase inhibitors ,kaplan-meier estimate ,male ,middle aged ,simvastatin ,triglycerides ,medicine (all ,[SDV]Life Sciences [q-bio] ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Bococizumab ,Triglyceride ,chemistry.chemical_compound ,0302 clinical medicine ,Azetidine ,Cardiovascular Disease ,Anticholesteremic Agent ,Acute Coronary Syndrome ,Aged ,Anticholesteremic Agents ,Azetidines ,Cardiovascular Diseases ,Cholesterol, LDL ,Double-Blind Method ,Drug Therapy, Combination ,Female ,Humans ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Middle Aged ,Triglycerides ,030212 general & internal medicine ,Medicine (all) ,Research Support, Non-U.S. Gov't ,Hazard ratio ,General Medicine ,Acute Coronary Syndrome, Aged ,Anticholesteremic Agents, Azetidines, Cardiovascular Diseases ,Ezetimibe, Female, Humans ,Male, Middle Aged ,3. Good health ,Multicenter Study ,Editorial ,Cholesterol ,Randomized Controlled Trial ,Combination ,Ezetimibe ,lipids (amino acids, peptides, and proteins) ,Human ,medicine.drug ,medicine.medical_specialty ,Acute Coronary Syndroms ,Urology ,Acute Coronary Syndrome/drug therapy ,Anticholesteremic Agents/adverse effects ,Anticholesteremic Agents/therapeutic use ,Azetidines/adverse effects ,Azetidines/therapeutic use ,Cardiovascular Diseases/epidemiology ,Cardiovascular Diseases/mortality ,Cardiovascular Diseases/prevention & control ,Cholesterol, LDL/blood ,Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ,Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ,Simvastatin/therapeutic use ,Triglycerides/blood ,NO ,LDL ,03 medical and health sciences ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Drug Therapy ,Internal medicine ,Journal Article ,medicine ,Comparative Study ,Alirocumab ,business.industry ,PCSK9 ,ta3121 ,Lomitapide ,DOENÇAS CARDIOVASCULARES ,Endocrinology ,chemistry ,Statin Therapy ,Hydroxymethylglutaryl-CoA Reductase Inhibitor ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
BACKGROUND: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known.METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years.RESULTS: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (PCONCLUSIONS: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit. (Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878.).
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- 2015
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20. Patterns of transmitted HIV drug resistance in Europe vary by risk group
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Frentz, D., Van De Vijver, D., Abecasis, A. B., Albert, Jan, Hamouda, O., Jørgensen, L., Kücherer, C., Struck, D., Schmit, J. -C, Vercauteren, J., Åsjö, Birgitta, Balotta, Claudia, Bergin, C., Beshkov, Danail, Camacho, Ricardo J., Clotet, B., Griskevicius, A., Grossman, Z., Horban, A., Kolupajeva, T., Korn, K., Kostrikis, Leontios G., Linka, K. L. M., Nielsen, C., Otelea, D., Paraskevis, Dimitrios N., Paredes, R., Poljak, M., Puchhammer-Stöckl, E., Sönnerborg, A., Stanekova, D., Stanojevic, M., Vandamme, A. -M, Boucher, C., Wensing, A., Kostrikis, Leontios G. [0000-0002-5340-7109], Paraskevis, Dimitrios [0000-0001-6167-7152], Frentz, D., van de Vijver, D., Abecasis, A., Albert, J., Hamouda, O., Jørgensen, L., Kücherer, C., Struck, D., Schmit, J., Vercauteren, J., Asjö, B., Balotta, C., Bergin, C., Beshkov, D., Camacho, R., Clotet, B., Griskevicius, A., Grossman, Z., Horban, A., Kolupajeva, T., Korn, K., Kostrikis, L., Linka, K., Nielsen, C., Otelea, D., Paraskevis, D., Paredes, R., Poljak, M., Puchhammer-Stöckl, E., Sönnerborg, A., Stanekova, D., Stanojevic, M., Vandamme, A., Wensing, A., and Tramuto, F. among SPREAD Programme investigators, Graduate School, Sluis-Cremer, Nicolas, Van Wijngaerden, Eric, Virology, and Erasmus MC other
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Male ,Epidemiology ,genotype ,Human immunodeficiency virus 1 ,HIV Infections ,RNA directed DNA polymerase inhibitor ,high risk patient ,Logistic regression ,Settore MED/42 - Igiene Generale E Applicata ,Men who have sex with men ,0302 clinical medicine ,Immunodeficiency Viruses ,middle aged ,statistics and numerical data ,10. No inequality ,Substance Abuse, Intravenous ,0303 health sciences ,adult ,transmission ,virus diseases ,virus transmission ,highly active antiretroviral therapy ,HIV immunopathogenesis ,3. Good health ,Medical Microbiology ,Viral Pathogens ,high risk behavior ,Medicine ,Science & Technology - Other Topics ,POPULATIONS ,health program ,anti human immunodeficiency virus agent ,USERS ,medicine.medical_specialty ,Science ,Sexual Behavior ,Immunology ,Sexually Transmitted Diseases ,intravenous drug abuse ,Microbiology ,03 medical and health sciences ,Antibiotic resistance ,SDG 3 - Good Health and Well-being ,Human immunodeficiency virus infection ,proteinase inhibitor ,Humans ,Protease Inhibitors ,human ,Heterosexuality ,Microbial Pathogens ,seroconversion ,Medicine and health sciences ,Science & Technology ,Genitourinary Infections ,MUTATIONS ,Virology ,major clinical study ,Logistic Models ,transmitted drug resistance mutation ,HIV-1 ,Viral Diseases ,Medical sciences: 700::Basic medical, dental and veterinary sciences: 710::Medical immunology: 716 [VDP] ,drug response ,men who have sex with men ,Drug resistance ,Clinical immunology ,geography ,APPEARANCE ,male homosexuality ,Medizinische Fakultät ,immune system diseases ,INFECTION ,Medicine and Health Sciences ,substance abuse ,030212 general & internal medicine ,risk ,Multidisciplinary ,ACTIVE ANTIRETROVIRAL THERAPY ,Transmission (medicine) ,virus mutation ,article ,Obstetrics and Gynecology ,HIV diagnosis and management ,Middle Aged ,virology ,Multidisciplinary Sciences ,Europe ,Infectious Diseases ,female ,Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk immunologi: 716 [VDP] ,Reverse Transcriptase Inhibitors ,HIV clinical manifestations ,Female ,epidemiology ,blood sampling ,HIV drug resistance ,Research Article ,Adult ,Risk ,risk-group ,Anti-HIV Agents ,Urology ,prevalence ,Infectious Disease Epidemiology ,sexual behavior ,Risk-Taking ,male ,antiviral resistance ,Internal medicine ,Drug Resistance, Viral ,medicine ,controlled study ,ddc:610 ,Homosexuality, Male ,030304 developmental biology ,drug resistance ,Biology and life sciences ,business.industry ,statistical model ,HIV ,CD4 lymphocyte count ,heterosexuality ,nonnucleoside reverse transcriptase inhibitor ,Human immunodeficiency virus 1 infection ,Diagnostic medicine ,INDIVIDUALS ,drug effects ,Women's Health ,business ,trend study - Abstract
BACKGROUND: In Europe, a continuous programme (SPREAD) has been in place for ten years to study transmission of drug resistant HIV. We analysed time trends of transmitted drug resistance mutations (TDRM) in relation to the risk behaviour reported. METHODS: HIV-1 patients newly diagnosed in 27 countries from 2002 through 2007 were included. Inclusion was representative for risk group and geographical distribution in the participating countries in Europe. Trends over time were calculated by logistic regression. RESULTS: From the 4317 patients included, the majority was men-having-sex-with-men -MSM (2084, 48%), followed by heterosexuals (1501, 35%) and injection drug users (IDU) (355, 8%). MSM were more often from Western Europe origin, infected with subtype B virus, and recently infected (
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- 2014
21. Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe
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Moutschen, M., Frentz, D., Van de Vijver, D. A. M. C., Abecasis, A. B., Albert, Jan, Hamouda, O., Jørgensen, L. B., Ku¨cherer, C., Struck, D., Schmit, J. -C, Vercauteren, J., A˚sjo¨, B., Balotta, Claudia, Beshkov, Danail, Camacho, Ricardo J., Clotet, B., Coughlan, S., Griskevicius, A., Grossman, Z., Horban, A., Kolupajeva, T., Korn, K., Kostrikis, Leontios G., Liitsola, K., Linka, M., Nielsen, C., Otelea, D., Paraskevis, Dimitrios N., Paredes, R., Poljak, M., Puchhammer, Stockl E., So¨nnerborg, A., Stanekova, D., Stanojevic, M., Van Wijngaerden, E., Wensing, A. M. J., Boucher, C. A. B., Sarcletti, M., Schmied, B., Geit, M., Balluch, G., Vandamme, A. -M, Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., De Wit, S., Echahidi, F., Fransen, K., Goffard, J. -C, Goubau, P., Goudeseune, E., Yombi, J. -C, Lacor, P., Liesnard, C., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Vandekerckhove, L. P. R., Van den Heuvel, A., Van Der Gucht, B., Van Ranst, M., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Van Laethem, K., Demetriades, Ioannis, Kousiappa, Ioanna, Demetriou, Victoria L., Hezka, Johana, Bruckova, M., Machala, L., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Salminen, M., Ristola, M., Suni, J., Sutinen, J., Berg, T., Braun, P., Poggensee, G., Da¨umer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Mu¨ller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Hatzakis, Angelos E., Magiorkinis, Emmanouil N., Hatzitheodorou, Eleni, Haida, Catherine, Zavitsanou, Assimina, Magiorkinis, Gkikas, Lazanas, Marios C., Chini, Maria C., Magafas, N., Tsogas, Nickolaos, Paparizos, Vassilios A., Kourkounti, Sofia, Antoniadou, Anastasia C., Papadopoulos, Antonios I., Panagopoulos, Periklis, Poulakou, Garyphallia G., Sakka, V., Chryssos, Georgios, Drimis, Stylianos, Gargalianos, Panagiotis, Lelekis, Moyssis I., Chilomenos, G., Psichogiou, Mina A., Daikos, George L., Panos, George, Haratsis, G., Kordossis, Theodore, Kontos, Athanasios N., Koratzanis, Georgios, Theodoridou, Maria C., Mostrou, Glykeria J., Spoulou, Vana I., De Gascun, C., Byrne, C., Duffy, M., Bergin, C., Reidy, D., Farrell, G., Lambert, J., O'Connor, E., Rochford, A., Low, J., Coakely, P., O'Dea, S., Hall, W., Levi, I., Chemtob, D., Riva, C., Mussini, C., Caramma, I., Capetti, A., Colombo, M. C., Rossi, C., Prati, F., Tramuto, F., Vitale, F., Ciccozzi, M., Angarano, G., Rezza, G., Schmit, J. C., Hemmer, R., Arendt, V., Staub, T., Schneider, F., Roman, F., van Kessel, A., van Bentum, P. H. M., Brinkman, K., op de Coul, E. L., van der Ende, M. E., Hoepelman, I., van Kasteren, M., Juttmann, J., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R., Schrijnders-Gudde, L., Schuurman, R., van de Ven, B. J. M., Ormaasen, V., Aavitsland, P., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Malolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Palma, C., Borges, F., Paixa&tild, o, T., Duque, V., Araújo, F., Jevtovic, D., Salemovic, D., Habekova, M., Mokráš, Miloš, Truska, P., Lunar, M., Babic, Dunja Z., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Domingo, P., Galindo, M. J., Miralles, C., del Pozo, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., de la Torre, J., Vidal, F., Garcia, F., Heidarian, A., Aperia-Peipke, K., Axelsson, M., Mild, M., Karlsson, A., Thalme, A., Nave´r, L., Bratt, G., Blaxhult, A., Gissle´n, M., Svennerholm, B., Bergbrant, I., Björkman, Per, Sa¨ll, C., Mellgren, A˚, Lindholm, A., Kuylenstierna, N., Montelius, R., Azimi, F., Johansson, B., Carlsson, M., Johansson, E., Ljungberg, B., Ekvall, H., Strand, A., Ma¨kitalo, S., o¨berg, S., Holmblad, P., Ho¨fer, M., Holmberg, H., Josefson, P., Ryding, U., Van Kessel, A., Kostrikis, Leontios G. [0000-0002-5340-7109], Paraskevis, Dimitrios [0000-0001-6167-7152], Virology, Erasmus MC other, Frentz, Dineke, Van de Vijver, David A.M.C., Abecasis, Ana B., Albert, Jan, Hamouda, Osamah, Jørgensen, Louise B., Ku¨cherer, Claudia, Struck, Daniel, Schmit, Jean-Claude, Vercauteren, Jurgen, A˚sjo¨, Birgitta, Balotta, Claudia, Beshkov, Danail, Camacho, Ricardo J., Clotet, Bonaventura, Coughlan, Suzie, Griskevicius, Algirda, Grossman, Zehava, Horban, Andrzej, Kolupajeva, Tatjana, Korn, Klau, Kostrikis, Leondios G., Liitsola, Kirsi, Linka, Marek, Nielsen, Clau, Otelea, Dan, Paraskevis, Dimitrio, Paredes, Roger, Poljak, Mario, Puchhammer-Sto¨ckl, Elisabeth, So¨nnerborg, Ander, Stanekova, Danica, Stanojevic, Maja, Van Wijngaerden, Eric, Wensing, Annemarie M.J., Boucher, Charles A.B., SPREAD programme investigators, including Vitale F and Tramuto F., Graduate School, UCL - SSS/IREC/MBLG - Pôle de Microbiologie médicale, UCL - (SLuc) Service de microbiologie, UCL - (SLuc) Service de médecine interne générale, UCL - (SLuc) Service d'hématologie, Clinicum, and Department of Medicine
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Male ,virus strain ,Resistance ,HIV Infections ,Drug resistance ,THERAPY ,Nucleoside Reverse Transcriptase Inhibitor ,ANTIRETROVIRAL DRUG-RESISTANCE ,0302 clinical medicine ,Medical microbiology ,Genotype ,Medicine and Health Sciences ,Prevalence ,HIV Infection ,030212 general & internal medicine ,UNITED-KINGDOM ,Phylogeny ,0303 health sciences ,Communicable disease ,Transmission (medicine) ,adult ,virus mutation ,UPDATED RECOMMENDATIONS ,virus transmission ,3. Good health ,Europe ,Infectious Diseases ,female ,risk factor ,virus resistance ,Female ,NAIVE PATIENTS ,SOCIETY-USA PANEL ,Research Article ,Human ,Adult ,medicine.medical_specialty ,Anti-HIV Agents ,Virus ,Article ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,male ,MOLECULAR EPIDEMIOLOGY ,Drug Resistance, Viral ,medicine ,proteinase inhibitor ,Humans ,Transmission ,controlled study ,human ,molecular phylogeny ,030304 developmental biology ,nonhuman ,MUTATIONS ,business.industry ,Anti-HIV Agent ,nucleotide sequence ,nonnucleoside reverse transcriptase inhibitor ,Human immunodeficiency virus 1 infection ,Virology ,major clinical study ,unindexed sequence ,Parasitology ,3121 General medicine, internal medicine and other clinical medicine ,Mutation ,HIV-1 ,business - Abstract
Background: One out of ten newly diagnosed patients in Europe was infected with a virus carrying a drug resistant mutation. We analysed the patterns over time for transmitted drug resistance mutations (TDRM) using data from the European Spread program.Methods: Clinical, epidemiological and virological data from 4317 patients newly diagnosed with HIV-1 infection between 2002 and 2007 were analysed. Patients were enrolled using a pre-defined sampling strategy.Results: The overall prevalence of TDRM in this period was 8.9% (95% CI: 8.1-9.8). Interestingly, significant changes over time in TDRM caused by the different drug classes were found. Whereas nucleoside resistance mutations remained constant at 5%, a significant decline in protease inhibitors resistance mutations was observed, from 3.9% in 2002 to 1.6% in 2007 (p = 0.001). In contrast, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) doubled from 2.0% in 2002 to 4.1% in 2007 (p = 0.004) with 58% of viral strains carrying a K103N mutation. Phylogenetic analysis showed that these temporal changes could not be explained by large clusters of TDRM.Conclusion: During the years 2002 to 2007 transmitted resistance to NNRTI has doubled to 4% in Europe. The frequent use of NNRTI in first-line regimens and the clinical impact of NNRTI mutations warrants continued monitoring. © 2014 Frentz et al. licensee BioMed Central Ltd. 14 Cited By :16
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- 2014
22. IL-2-inducible T-cell kinase deficiency: clinical presentation and therapeutic approach
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Igor B. Resnick, Polina Stepensky, René M. Linka, Kirsten Huck, Avraham Shaag, Michael Weintraub, Orly Elpeleg, Shoshana Revel-Vilk, Frank Krux, Asaf Yanir, and Arndt Borkhardt
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Male ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Nonsense mutation ,Lymphoproliferative disorders ,Antineoplastic Agents ,Biology ,Lymphocyte Activation ,medicine.disease_cause ,Disease-Free Survival ,Lymphohistiocytosis, Hemophagocytic ,ITK Deficiency ,medicine ,Humans ,Transplantation, Homologous ,Bone Marrow Transplantation ,B-Lymphocytes ,Hemophagocytic lymphohistiocytosis ,Brief Report ,Homozygote ,Remission Induction ,Hematology ,Protein-Tyrosine Kinases ,medicine.disease ,Hodgkin Disease ,Epstein–Barr virus ,Pedigree ,Lymphoma ,Death ,Transplantation ,medicine.anatomical_structure ,Codon, Nonsense ,Child, Preschool ,Immunology ,Female ,Bone marrow - Abstract
Mutations in the IL-2-inducible T-cell kinase gene have recently been shown to cause an autosomal recessive fatal Epstein Barr virus (EBV) associated lymphoproliferation. We report 3 cases from a single family who presented with EBV-positive B-cell proliferation diagnosed as Hodgkin’s lymphoma. Single nucleotide polymorphism array-based genome-wide linkage analysis revealed IL-2-inducible T-cell kinase as a candidate gene for this disorder. All 3 patients harbored the same novel homozygous nonsense mutation C1764G which causes a premature stop-codon in the kinase domain. All cases were initially treated with chemotherapy. One patient remains in durable remission, the second patient subsequently developed severe hemophagocytic lymphohistiocytosis with multi-organ failure and died, and the third patient underwent a successful allogeneic bone marrow transplantation. IL-2-inducible T-cell kinase deficiency underlies a new primary immune deficiency which may account for part of the spectrum of Epstein Barr virus related lymphoproliferative disorders which can be successfully corrected by bone marrow transplantation.
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- 2010
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23. Pharmacokinetics and Pharmacodynamics of Sildenafil in a Patient Treated With Human Immunodeficiency Virus Protease Inhibitors
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Markus R. Wenk, Manuel Haschke, Yvonne Zysset Aschmann, Andrea Azzola, Michael Bodmer, Oliver Kummer, André Linka, and Stephan Krähenbühl
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Adult ,Male ,medicine.medical_specialty ,medicine.drug_mechanism_of_action ,Sildenafil ,Hypertension, Pulmonary ,Vasodilator Agents ,Cmax ,HIV Infections ,Pharmacology ,Piperazines ,Sildenafil Citrate ,chemistry.chemical_compound ,Pharmacokinetics ,Reference Values ,Internal medicine ,medicine ,Humans ,Drug Interactions ,Pharmacology (medical) ,Protease inhibitor (pharmacology) ,Sulfones ,business.industry ,Area under the curve ,HIV Protease Inhibitors ,medicine.disease ,Pulmonary hypertension ,respiratory tract diseases ,Endocrinology ,chemistry ,Purines ,Area Under Curve ,Pharmacodynamics ,cardiovascular system ,business ,Phosphodiesterase 5 inhibitor ,Half-Life - Abstract
We describe a 44-year-old male patient with human immunodeficiency virus (HIV) infection and pulmonary arterial hypertension who was treated with several protease inhibitors and with sildenafil. In order to guide treatment with sildenafil, the pharmacokinetics and dynamics of sildenafil were monitored at various time points. In comparison with healthy subjects, the maximal concentration in plasma (Cmax), area under the curve (AUC), and elimination half-life of sildenafil were approximately doubled in the patient. After increasing the sildenafil dose to ensure therapeutic drug levels over 24 hours, the pulmonary arterial hypertension and physical performance of the patient improved significantly. We conclude that the elimination of sildenafil is impaired in patients treated with protease inhibitors, but to a lesser extent than predicted from single-dose studies reported in the literature. Patients treated concomitantly with protease inhibitors and sildenafil need close monitoring of plasma levels, pharmacodynamics, and toxicity of sildenafil in order to be treated optimally.
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- 2008
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24. The intensity dependence of auditory ERP components in unmedicated patients with major depression and healthy controls. An analysis of group differences
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Bernhard W. Müller, Markus Gastpar, Gudrun Sartory, Stefan Bender, and Thomas Linka
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Adult ,Male ,Serotonin ,medicine.medical_specialty ,Sound Spectrography ,Multivariate analysis ,Loudness Perception ,Audiology ,Serotonergic ,Reference Values ,Event-related potential ,medicine ,Humans ,Psychiatry ,Major depressive episode ,Depression (differential diagnoses) ,Ovum ,Cerebral Cortex ,Depressive Disorder, Major ,Cognition ,Middle Aged ,Psychiatry and Mental health ,Clinical Psychology ,Acoustic Stimulation ,Multivariate Analysis ,Evoked Potentials, Auditory ,Antidepressant ,Female ,Abnormality ,medicine.symptom ,Psychology - Abstract
Background The intensity dependent amplitude change (IDAP) of auditory evoked Event Related Potential (ERP) components has been found to correlate with the level of central serotonergic neurotransmission and to be associated with response to certain antidepressants. However, it is currently unknown whether there is a general abnormality of the IDAP in patients with major depression. Therefore, the purpose of the present study was to compare the IDAP in unmedicated depressed patients with that of healthy control subjects. Methods We report the results of a study evaluating the change of auditory evoked P1, N1, P2 as well as P1/N1 and N1/P2 peak to peak amplitudes in 34 in-patients with major depressive episode prior to antidepressant treatment, and 44 healthy control subjects. Clinical symptoms of depression were assessed by means of standardized psychiatric rating scales (CGI, HDRS, HAMA and BDI). Results In multivariate analyses of variance we found no group differences in the intensity dependent increase neither of the P1, N1, and P2 nor of the P1/N1 and N1/P2 peak to peak amplitudes between patients and controls. Conclusions Our data revealed no general abnormality of the IDAP in patients with major depression in comparison to healthy control subjects. This result suggests that specific alterations of the IDAP are not to be expected in major depression in general, these may be confined to subgroups of depressed patients.
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- 2007
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25. Limited cross-border infections in patients newly diagnosed with HIV in Europe
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Moutschen, M., Frentz, D., Wensing, A. M. J., Albert, Jan, Paraskevis, Dimitrios N., Abecasis, A. B., Hamouda, O., Jørgensen, L. B., Kücherer, C., Struck, D., Schmit, J. -C, Åsjö, Birgitta, Balotta, Claudia, Beshkov, Danail, Camacho, Ricardo J., Clotet, B., Coughlan, S., De Wit, S., Griskevicius, A., Grossman, Z., Horban, A., Kolupajeva, T., Korn, K., Kostrikis, Leontios G., Liitsola, K., Linka, M., Nielsen, C., Otelea, D., Paredes, R., Poljak, M., Puchhammer-Stöckl, E., Sönnerborg, A., Stanekova, D., Stanojevic, M., Vandamme, A. -M, Boucher, C. A. B., Van de Vijver, D. A. M. C., Balluch, G., Vercauteren, J., Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., Echahidi, F., Fransen, K., Goffard, J. -C, Goubau, P., Goudeseune, E., Yombi, J. -C, Lacor, P., Liesnard, C., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Vandekerckhove, L. P. R., Van den Heuvel, A., Van Der Gucht, B., Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Van Laethem, K., Demetriades, Ioannis, Kousiappa, Ioanna, Demetriou, Victoria L., Hezka, Johana, Bruckova, M., Machala, L., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Salminen, M., Ristola, M., Suni, J., Sutinen, J., Berg, T., Braun, P., Poggensee, G., Däumer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Müller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Hatzakis, Angelos E., Magiorkinis, Emmanouil N., Hatzitheodorou, Eleni, Haida, Catherine, Zavitsanou, Assimina, Magiorkinis, Gkikas, Lazanas, Marios C., Chini, Maria C., Magafas, N., Tsogas, Nickolaos, Paparizos, Vassilios A., Kourkounti, Sofia, Antoniadou, Anastasia C., Papadopoulos, Antonios I., Panagopoulos, Periklis, Poulakou, Garyphallia G., Sakka, V., Chryssos, Georgios, Drimis, Stylianos, Gargalianos, Panagiotis, Lelekis, Moyssis I., Chilomenos, G., Psichogiou, Mina A., Daikos, George L., Panos, George, Haratsis, G., Kordossis, Theodore, Kontos, Athanasios N., Koratzanis, Georgios, Theodoridou, Maria C., Mostrou, Glykeria J., Spoulou, Vana I., De Gascun, C., Byrne, C., Duffy, M., Bergin, C., Reidy, D., Farrell, G., Lambert, J., O'Connor, E., Rochford, A., Low, J., Coakely, P., O'Dea, S., Hall, W., Levi, I., Chemtob, D., Franzetti, M., Lai, A., Binda, F., Tramuto, F., Ciccozzi, M., Mussini, C., Angarano, G., Rezza, G., Schmit, J. C., Hemmer, R., Arendt, V., Staub, T., Schneider, F., Roman, F., van Kessel, A., van Bentum, P. H. M., Brinkman, K., de Coul, E. L., van der Ende, M. E., Hoepelman, I. M., van Kasteren, M., Juttmann, J., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M. W. J., Schrijnders-Gudde, L., Schuurman, R., van de Ven, B. J. M., Ormaasen, V., Aavitsland, P., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Malolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Palma, C., Borges, F., Paixão, T., Duque, V., Araújo, F., Jevtovic, D., Salemovic, D., Habekova, M., Mokráš, Miloš, Truska, P., Lunar, M., Babic, Dunja Z., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Domingo, P., Galindo, M. J., Miralles, C., del Pozo, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., de la Torre, J., Vidal, F., Garcia, F., Heidarian, A., Aperia-Peipke, K., Axelsson, M., Mild, M., Karlsson, A., Thalme, A., Navér, L., Bratt, G., Blaxhult, A., Gisslén, M., Svennerholm, B., Bergbrant, I., Björkman, Per, Säll, C., Mellgren, Å., Lindholm, A., Kuylenstierna, N., Montelius, R., Azimi, F., Johansson, B., Carlsson, M., Johansson, E., Ljungberg, B., Ekvall, H., Strand, A., Mäkitalo, S., öberg, S., Holmblad, P., Höfer, M., Holmberg, H., Josefson, P., Ryding, U., Van Kessel, A., Instituto de Higiene e Medicina Tropical (IHMT), Centro de Malária e outras Doenças Tropicais (CMDT), Clinicum, Department of Medicine, Infektiosairauksien yksikkö, Frentz, D, Wensing, AMJ, Albert, J, Paraskevis, D, Abecasis, AB, Hamouda, O, Jørgensen, LB, Kücherer, C, Struck, D, Schmit, JC, Åsjö, B, Balotta, C, Beshkov, D, Camacho, RJ, Clotet, B, Coughlan, S, De Wit, S, Griskevicius, A, Grossman, Z, Horban, A, Kolupajeva, T, Korn, K, Kostrikis, LG, Liitsola, K, Linka, M, Nielsen, C, Otelea, D, Paredes, R, Poljak, M, Puchhammer-Stöckl, E, Sönnerborg, A, Stanekova, D, Stanojevic, M, Vandamme, AM, Boucher, CAB, Van de Vijver, DAMC, Tramuto, F, Van Wijngaerden, Eric, Van Ranst, Marc, Van Laethem, Kristel, Derdelinckx, Inge, Kostrikis, Leontios G. [0000-0002-5340-7109], Paraskevis, Dimitrios [0000-0001-6167-7152], Virology, and Graduate School
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Male ,Epidemiology ,Human immunodeficiency virus (HIV) ,Human immunodeficiency virus 1 ,HIV Infections ,medicine.disease_cause ,Virologie générale ,phylogeny ,Settore MED/42 - Igiene Generale E Applicata ,Men who have sex with men ,EMERGENCE ,0302 clinical medicine ,Medicine and Health Sciences ,Medicine ,Infection control ,Cluster Analysis ,030212 general & internal medicine ,Israel ,Pathologie maladies infectieuses ,travel ,Phylogeny ,0303 health sciences ,Molecular Epidemiology ,Travel ,Transmission (medicine) ,article ,virus transmission ,IMMUNODEFICIENCY-VIRUS TYPE-1 ,3. Good health ,Europe ,female ,Infectious Diseases ,SUBTYPE B ,DRUG-RESISTANT HIV-1 ,RNA, Viral ,male homosexual ,Adult ,structural gene ,Molecular Sequence Data ,Newly diagnosed ,Clusters ,03 medical and health sciences ,male ,SDG 3 - Good Health and Well-being ,MOLECULAR EPIDEMIOLOGY ,SWITZERLAND ,Virology ,geographic distribution ,Humans ,Transmission ,In patient ,human ,030304 developmental biology ,nonhuman ,Molecular epidemiology ,business.industry ,Research ,high risk population ,Virologie médicale ,nucleotide sequence ,Sequence Analysis, DNA ,Human immunodeficiency virus 1 infection ,major clinical study ,unindexed sequence ,3121 General medicine, internal medicine and other clinical medicine ,HIV-1 ,business ,Europe, HIV-1, Transmission, Clusters ,Demography ,cluster analysis - Abstract
Background: International travel plays a role in the spread of HIV-1 across Europe. It is, however, not known whether international travel is more important for spread of the epidemic as compared to endogenous infections within single countries. In this study, phylogenetic associations among HIV of newly diagnosed patients were determined across Europe.Results: Data came from the SPREAD programme which collects samples of newly diagnosed patients that are representative for national HIV epidemics. 4260 pol sequences from 25 European countries and Israel collected in 2002-2007 were included.We identified 457 clusters including 1330 persons (31.2% of all patients). The cluster size ranged between 2 and 28. A number of 987 patients (74.2%) were part of a cluster that consisted only of patients originating from the same country. In addition, 135 patients (10.2%) were in a cluster including only individuals from neighboring countries. Finally, 208 patients (15.6%) clustered with individuals from countries without a common border. Clustering with patients from the same country was less prevalent in patients being infected with B subtype (P-value, SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2013
26. Global dispersal pattern of HIV type 1 subtype CRF01-AE : A genetic trace of human mobility related to heterosexual sexual activities centralized in southeast Asia
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Angelis, Konstantinos, Albert, Jan, Mamais, Ioannis A., Magiorkinis, Gkikas, Hatzakis, Angelos E., Hamouda, O., Struck, D., Vercauteren, J., Wensing, A. M. J., Alexiev, Ivailo, Åsjö, Birgitta, Balotta, Claudia, Camacho, Ricardo J., Coughlan, S., Griskevicius, A., Grossman, Z., Horban, A., Kostrikis, Leontios G., Lepej, S., Liitsola, K., Linka, M., Nielsen, C., Otelea, D., Paredes, R., Poljak, M., Puchhammer-Stöckl, E., Schmit, J. -C, Sönnerborg, A., Staneková, D., Stanojevic, M., Boucher, C. A. B., Kaplan, L., Vandamme, A. -M, Paraskevis, Dimitrios N., Kostrikis, Leontios G. [0000-0002-5340-7109], Paraskevis, Dimitrios [0000-0001-6167-7152], Kostrikis, Leontios G. [0000-0002-5340-7109]|Paraskevis, Dimitrios [0000-0001-6167-7152], and Virology
- Subjects
virus strain ,CRF01_AE ,HIV-1 ,dispersal pattern ,migration ,phylogeography ,maximum likelihood method ,Databases, Factual ,viruses ,Population Dynamics ,Human immunodeficiency virus 1 ,HIV Infections ,Diseases ,genetic analysis ,Communicable diseases ,phylogeny ,0302 clinical medicine ,Japan ,Western world ,Cluster Analysis ,Immunology and Allergy ,030212 general & internal medicine ,Socioeconomics ,Clade ,Asia, Southeastern ,Phylogeny ,cladistics ,0303 health sciences ,Singapore ,SDG 10 - Reduced Inequalities ,Thailand ,Southeast Asia ,3. Good health ,CRF01-AE ,Europe ,Human immunodeficiency virus 1 subtype CRF01_AE ,Geography ,female ,Infectious Diseases ,priority journal ,Viet Nam ,sequence alignment ,Medicine ,Causes and theories of causation ,Electronic journals ,sex tourism ,China ,Taiwan ,gene sequence ,Article ,03 medical and health sciences ,sexual behavior ,male ,SDG 3 - Good Health and Well-being ,parasitic diseases ,Humans ,controlled study ,human ,Heterosexuality ,030304 developmental biology ,Asian ,Exportation ,heterosexuality ,major clinical study ,Emigration ,Phylogeography ,North America ,Africa ,Biological dispersal ,Tourism - Abstract
Background. Human immunodeficiency virus type 1 (HIV-1) subtype CRF01-AE originated in Africa and then passed to Thailand, where it established a major epidemic. Despite the global presence of CRF01-AE, little is known about its subsequent dispersal pattern. Methods. We assembled a global data set of 2736 CRF01-AE sequences by pooling sequences from public databases and patient-cohort studies. We estimated viral dispersal patterns, using statistical phylogeographic analysis run over bootstrap trees estimated by the maximum likelihood method. Results. We show that Thailand has been the source of viral dispersal to most areas worldwide, including 17 of 20 sampled countries in Europe. Japan, Singapore, Vietnam, and other Asian countries have played a secondary role in the viral dissemination. In contrast, China and Taiwan have mainly imported strains from neighboring Asian countries, North America, and Africa without any significant viral exportation. Discussion. The central role of Thailand in the global spread of CRF01-AE can be probably explained by the popularity of Thailand as a vacation destination characterized by sex tourism and by Thai emigration to the Western world. Our study highlights the unique case of CRF01-AE, the only globally distributed non-B clade whose global dispersal did not originate in Africa. © 2014 The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. 211 1735 1744 Cited By :22
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- 2015
27. Primary resistance to integrase strand-transfer inhibitors in Europe
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Casadellà, M, van Ham, P M, Noguera-Julian, M, van Kessel, A, Pou, C, Hofstra, L M, Santos, J R, Garcia, F, Struck, D, Alexiev, I, Bakken Kran, A M, Hoepelman, A I, Kostrikis, L G, Somogyi, S, Liitsola, K, Linka, M, Nielsen, C, Otelea, D, Paraskevis, D, Poljak, M, Puchhammer-Stöckl, E, Staneková, D, Stanojevic, M, Van Laethem, K, Zidovec Lepej, S, Clotet, B, Boucher, C A B, Paredes, R, Wensing, A M J, SPREAD programme, Goubau, Patrick, Yombi, Jean Cyr, Vandercam, Bernard, Vekemans, Marie-Christiane, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service de microbiologie, UCL - (SLuc) Service d'hématologie, and UCL - (SLuc) Service de médecine interne générale
- Subjects
DOLUTEGRAVIR ,Male ,HIV-1 INFECTION ,Genotype ,HIV Infections ,HIV Integrase ,Risk Factors ,Antiretroviral Therapy, Highly Active ,Drug Resistance, Viral ,Humans ,Pharmacology (medical) ,HIV Integrase Inhibitors ,ELVITEGRAVIR ,Pharmacology ,MUTATIONS ,RALTEGRAVIR ,Genetic Variation ,Sequence Analysis, DNA ,Viral Load ,CD4 Lymphocyte Count ,Europe ,Infectious Diseases ,Cross-Sectional Studies ,Population Surveillance ,HIV-1 ,Female - Abstract
Objectives: The objective of this study was to define the natural genotypic variation of the HIV-1 integrase gene across Europe for epidemiological surveillance of integrase strand-transfer inhibitor (InSTI) resistance. Methods: This was a multicentre, cross-sectional study within the European SPREAD HIV resistance surveillance programme. A representative set of 300 samples was selected from 1950 naive HIV-positive subjects newly diagnosed in 2006-07. The prevalence of InSTI resistance was evaluated using quality-controlled baseline population sequencing of integrase. Signature raltegravir, elvitegravir and dolutegravir resistance mutations were defined according to the IAS-USA 2014 list. In addition, all integrase substitutions relative to HXB2 were identified, including those with a Stanford HIVdb score >= 10 to at least one InSTI. To rule out circulation of minority InSTI-resistant HIV, 65 samples were selected for 454 integrase sequencing. Results: For the population sequencing analysis, 278 samples were retrieved and successfully analysed. No signature resistance mutations to any of the InSTIs were detected. Eleven (4%) subjects had mutations at resistance-associated positions with an HIVdb score >= 10. Of the 56 samples successfully analysed with 454 sequencing, no InSTI signature mutations were detected, whereas integrase substitutions with an HIVdb score >= 10 were found in 8 (14.3%) individuals. Conclusions: No signature InSTI-resistant variants were circulating in Europe before the introduction of InSTIs. However, polymorphisms contributing to InSTI resistance were not rare. As InSTI use becomes more widespread, continuous surveillance of primary InSTI resistance is warranted. These data will be key to modelling the kinetics of InSTI resistance transmission in Europe in the coming years.
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- 2015
28. Primary resistance to integrase strand-transfer inhibitors in Europe
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Moutschen, M., Casadellà, M., van Ham, P. M., Noguera-Julian, M., van Kessel, A., Pou, C., Hofstra, Laura Marije Arije, Santos, J. R., Garcia, F., Struck, D., Alexiev, Ivailo, Bakken Kran, A. M., Hoepelman, A. I., Kostrikis, Leontios G., Somogyi, Sybille, Liitsola, K., Linka, M., Nielsen, C., Otelea, D., Paraskevis, Dimitrios N., Poljak, M., Puchhammer-Stöckl, E., Staneková, D., Stanojevic, M., Van Laethem, K., Zidovec Lepej, S., Clotet, B., Boucher, C. A. B., Paredes, R., Wensing, A. M. J., Sarcletti, M., Schmied, B., Geit, M., Balluch, G., Vandamme, A. M., Vercauteren, J., Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., De Wit, S., Echahidi, F., Fransen, K., Goffard, J. C., Goubau, P., Goudeseune, E., Yombi, J. C., Lacor, P., Liesnard, C., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Vandekerckhove, L. P., Van den Heuvel, A., Van Der Gucht, B., Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Beshkov, Danail, Begovac, J., Demetriades, Ioannis, Kousiappa, Ioanna, Demetriou, Victoria L., Hezka, Johana, Machala, L., Maly, M., Jørgensen, L. B., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Ristola, M., Suni, J., Sutinen, J., Hamouda, O., Kücherer, C., Berg, T., Braun, P., Poggensee, G., Däumer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Korn, K., Müller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Hatzakis, Angelos E., Magiorkinis, Emmanouil N., Hatzitheodorou, Eleni, Haida, Catherine, Zavitsanou, Assimina, Magiorkinis, Gkikas, Lazanas, Marios C., Chini, Maria C., Magafas, N., Tsogas, Nickolaos, Paparizos, Vassilios A., Kourkounti, Sofia, Antoniadou, Anastasia C., Papadopoulos, Antonios I., Panagopoulos, Periklis, Poulakou, Garyphallia G., Sakka, V., Chryssos, Georgios, Drimis, Stylianos, Gargalianos, Panagiotis, Lelekis, Moyssis I., Chilomenos, G., Psichogiou, Mina A., Daikos, George L., Sabatakou, H., Panos, George, Haratsis, G., Kordossis, Theodore, Kontos, Athanasios N., Koratzanis, Georgios, Theodoridou, Maria C., Mostrou, Glykeria J., Spoulou, Vana I., Schmit, J. C., Hemmer, R., Arendt, V., Staub, T., Schneider, F., Roman, F., Wensing, A. M., Boucher, C. A., van de Vijver, D. A., van, P. H., Brinkman, K., Op de, E. L., van der Ende, M. E., Hoepelman, I. M., van Kasteren, M., Juttmann, J., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M., Schrijnders-Gudde, L., Schuurman, R., van de Ven, B. J., Åsjö, Birgitta, Bakken, A. M., Ormaasen, V., Aavitsland, P., Paraschiv, S., Tudor, A. M., Jevtovic, D., Salemovic, D., Stanekova, D., Habekova, M., Mokráš, Miloš, Truska, P., Lunar, M., Babic, Dunja Z., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Domingo, P., Galindo, M. J., Miralles, C., Del, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., de la Torre, J., Vidal, F., Kostrikis, Leontios G. [0000-0002-5340-7109], and Paraskevis, Dimitrios [0000-0001-6167-7152]
- Subjects
sequence analysis ,genotype ,Human immunodeficiency virus 1 ,HIV Infections ,RNA directed DNA polymerase inhibitor ,integrase strand transfer inhibitor ,HIV Integrase ,molecular epidemiology ,Human immunodeficiency virus prevalence ,Risk Factors ,Antiretroviral Therapy, Highly Active ,genetic variability ,genetics ,Stanford HIVdb score ,clinical trial ,Human immunodeficiency virus infected patient ,highly active antiretroviral therapy ,Viral Load ,unclassified drug ,virology ,health survey ,dolutegravir ,Europe ,female ,risk factor ,Population Surveillance ,virus gene ,raltegravir ,amino acid substitution ,p31 integrase protein, Human immunodeficiency virus 1 ,DNA sequence ,gene sequence ,Article ,male ,antiviral resistance ,Drug Resistance, Viral ,proteinase inhibitor ,Humans ,cross-sectional study ,controlled study ,human ,HIV Integrase Inhibitors ,quality control ,scoring system ,CD4 lymphocyte count ,integrase inhibitor ,Sequence Analysis, DNA ,virus load ,nonnucleoside reverse transcriptase inhibitor ,Human immunodeficiency virus 1 infection ,major clinical study ,drug efficacy ,Cross-Sectional Studies ,multicenter study ,drug effects ,genetic variation ,HIV-1 ,integrase - Abstract
Objectives: The objective of this study was to define the natural genotypic variation of the HIV-1 integrase gene across Europe for epidemiological surveillance of integrase strand-transfer inhibitor (InSTI) resistance. Methods: This was a multicentre, cross-sectional study within the European SPREAD HIV resistance surveillance programme. A representative set of 300 samples was selected from 1950 naive HIV-positive subjects newly diagnosed in 2006-07. The prevalence of InSTI resistance was evaluated using quality-controlled baseline population sequencing of integrase. Signature raltegravir, elvitegravir and dolutegravir resistance mutations were defined according to the IAS-USA 2014 list. In addition, all integrase substitutions relative to HXB2 were identified, including those with a Stanford HIVdb score=10 to at least one InSTI. To rule out circulation of minority InSTIresistant HIV, 65 samples were selected for 454 integrase sequencing. Results: For the population sequencing analysis, 278 samples were retrieved and successfully analysed. No signature resistance mutations to any of the InSTIswere detected. Eleven (4%) subjects hadmutations at resistance-associated positions with an HIVdb score =10. Of the 56 samples successfully analysed with 454 sequencing, no InSTI signature mutationsweredetected, whereas integrase substitutionswithanHIVdbscore=10were found in8(14.3%) individuals. Conclusions:No signature InSTI-resistant variantswere circulating in Europe before the introduction of InSTIs. However, polymorphisms contributing to InSTI resistancewere not rare. As InSTI use becomes more widespread, continuous surveillance of primary InSTI resistance is warranted. These data will be key to modelling the kinetics of InSTI resistance transmission in Europe in the coming years. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. 70 2885 2888 Cited By :15
- Published
- 2015
29. Diffusion-Weighted Imaging in Stroke Attributable to Patent Foramen Ovale
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Stefan T. Engelter, Arnheid Kessel-Schaefer, Ernst-Wilhelm Radue, Leo H. Bonati, Stephan G. Wetzel, André Linka, Peter Buser, and Philippe Lyrer
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Adult ,Male ,medicine.medical_specialty ,Databases, Factual ,Foramen secundum ,Heart Septal Defects, Atrial ,Persistent fetal circulation ,Brain Ischemia ,Cohort Studies ,Aneurysm ,Coronary Circulation ,Internal medicine ,Heart Septum ,medicine ,Humans ,Heart Atria ,cardiovascular diseases ,Heart Aneurysm ,Stroke ,Retrospective Studies ,Foramen ovale (heart) ,Advanced and Specialized Nursing ,business.industry ,Cerebral infarction ,Middle Aged ,medicine.disease ,Surgery ,Diffusion Magnetic Resonance Imaging ,Logistic Models ,medicine.anatomical_structure ,Intracranial Embolism ,Echocardiography ,Multivariate Analysis ,Patent foramen ovale ,Cardiology ,Female ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,Echocardiography, Transesophageal ,Interatrial septum - Abstract
Background and Purpose— Patent foramen ovale (PFO) is an established cause of stroke in young patients without other determined etiologies (ie, cryptogenic stroke). The additional presence of atrial septum aneurysm (ASA) possibly increases stroke risk, but it remains undetermined which factors best predict thromboembolism in patients with PFO. Diffusion-weighted imaging (DWI) may help to distinguish the characteristics of cerebral embolism associated with different features of the interatrial septum in PFO stroke. Methods— In a stroke databank-based cohort study, DWI and transthoracic/transesophageal echocardiography findings were assessed in 48 consecutive patients with cryptogenic ischemic stroke associated with PFO. The number, size, and distribution of acute ischemic lesions on DWI were correlated with PFO size, degree of interatrial right-to-left shunt (RLS), and the presence of ASA. Results— Patients with PFO plus ASA combined more often had multiple acute DWI lesions (16 of 30, 53%) than those with PFO alone (3 of 18, 17%; P =0.01). This association remained significant after correction for PFO size, degree of RLS, and vascular risk factors in a logistic-regression analysis ( P =0.04). No significant associations between DWI lesion characteristics and PFO size or degree of RLS were found. Conclusions— The presence of concomitant ASA is independently associated with multiple cerebral ischemic lesions in PFO stroke, which may indicate an increased embolic risk.
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- 2006
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30. Incremental cost-effectiveness of drug-eluting stents compared with a third-generation bare-metal stent in a real-world setting: randomised Basel Stent Kosten Effektivitäts Trial (BASKET)
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M Pfisterer, Michael J. Zellweger, Stefan Osswald, Leticia Grize, P. Buser, Alain Bernheim, Hans-Peter Brunner-La Rocca, André Linka, Piero O. Bonetti, Christoph Kaiser, and Andreas W Zutter
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Adult ,Male ,Bare-metal stent ,medicine.medical_specialty ,Paclitaxel ,Cost-Benefit Analysis ,medicine.medical_treatment ,Myocardial Ischemia ,Coronary Disease ,Coronary Restenosis ,Angioplasty ,Clinical endpoint ,medicine ,Humans ,Myocardial infarction ,Angioplasty, Balloon, Coronary ,Aged ,Aged, 80 and over ,Sirolimus ,business.industry ,Stent ,General Medicine ,Odds ratio ,Middle Aged ,medicine.disease ,Surgery ,Clinical trial ,Drug-eluting stent ,Female ,Stents ,Chromium Alloys ,business - Abstract
No prospective trial-based data are available for incremental cost-effectiveness of drug-eluting stents (DES) compared with bare-metal stents (BMS) in unselected patients, as treated in everyday practice.The Basel stent cost-effectiveness trial (BASKET) included 826 consecutive patients treated with angioplasty and stenting for 1281 de-novo lesions, irrespective of indication for angioplasty. Patients were randomised to one of two DES (Cypher, n=264; Taxus, n=281) or to a cobalt-chromium-based BMS (Vision, n=281) and followed up for 6 months for occurrence of major adverse cardiac events and costs. Analysis was by intention-to-treat. The primary endpoint was cost-effectiveness after 6 months, with effectiveness defined as reduction of major adverse cardiac events.Cardiac death, myocardial infarction, or target vessel revascularisation occurred in 39 of 544 (7.2%) patients with DES and 34 of 280 (12.1%) with BMS (odds ratio 0.56, 95% CI 0.35-0.91; p=0.02), without significant differences between the two DES. Total costs at 6 months were higher with DES (mean 10,544, SD 6849) than with BMS (9639, 9067; p0.0001); higher stent costs of DES were not compensated for by lower follow-up costs. Incremental cost-effectiveness ratio of DES compared with BMS to avoid one major event was 18,311, and costs per quality-adjusted life-year gained were more than 50 000. Subgroup analyses showed that DES were more cost-effective for elderly patients in specific high-risk groups.In a real-world setting, use of DES in all patients is less cost effective than in studies with selected patients. Use of these stents could be restricted to patients in high-risk groups.
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- 2005
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31. Safety and efficacy of combined clozapine–lithium pharmacotherapy
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Markus Gastpar, Thomas Linka, Hermann-Josef Paulus, Jörg Wolstein, Susanne Gehendges, Ulrich Schall, and Stefan Bender
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Adult ,Male ,Myoclonus ,Dyskinesia, Drug-Induced ,Lithium (medication) ,Lithium ,Serotonergic ,Pharmacotherapy ,Therapeutic index ,Antimanic Agents ,medicine ,Humans ,Pharmacology (medical) ,Adverse effect ,Clozapine ,Aged ,Psychiatric Status Rating Scales ,Pharmacology ,business.industry ,Medical record ,Middle Aged ,Psychiatry and Mental health ,Psychotic Disorders ,Anesthesia ,Schizophrenia ,Antidepressant ,Drug Therapy, Combination ,Female ,Schizophrenic Psychology ,business ,Antipsychotic Agents ,medicine.drug - Abstract
Several case reports described neurotoxic side-effects in the course of a combined clozapine-lithium treatment. Here we report on the safety and efficacy of this combination in a sample of 44 hospital patients. Medical records were retrospectively audited and a subsample of 23 patients was re-assessed. Mean total duration of combined treatment was 23.5 months. The combination (indications: prophylaxis; treatment of affective symptoms or aggression/excitement; augmentation of neuroleptic efficacy) was rated effective in 84% and adverse events were reported in 64% of the patients. Notably, most of the adverse events were benign and transient. However, 8 patients (18%) developed transient neurological adverse events that were genuinely novel in only 3 patients (7%) and coincided with high dosage of medication or high plasma levels or serotonergic (antidepressant) co-medication. Our data suggest that combined clozapine-lithium treatment may appear to be safe and effective when administered within a moderate therapeutic dose range and without serotonergic co-medication or other substances interfering with clozapine metabolism.
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- 2004
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32. Effects of Newer Atypical Antipsychotics on Autonomic Neurocardiac Function: A Comparison Between Amisulpride, Olanzapine, Sertindole, and Clozapine
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T. Majewski, K. Lukas, E. Klieser, Marcus W. Agelink, T. Linka, Heiko Ullrich, and Cornelius Wurthmann
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Adult ,Male ,Olanzapine ,Psychosis ,Indoles ,Autonomic Nervous System ,QT interval ,Benzodiazepines ,Electrocardiography ,Sertindole ,Heart Rate ,Heart rate ,medicine ,Humans ,Pharmacology (medical) ,Prospective Studies ,Amisulpride ,Clozapine ,Imidazoles ,Heart ,Pirenzepine ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,Schizophrenia ,Anesthesia ,Female ,Sulpiride ,Psychology ,Antipsychotic Agents ,medicine.drug - Abstract
As part of a prospective clinical study investigating the effects of atypical neuroleptics on autonomic neurocardiac function (ANF), serial standardized recordings of conventional electrocardiograms and computer-calculated measurements of 5-minute resting heart rate variability (HRV) were obtained from 51 medication-free inpatients with schizophrenia (DSM-III-R-diagnosed) before and after an average of 14.1 days of treatment with amisulpride 400 mg/day (N = 12), olanzapine 20 mg/day (N = 13), sertindole 12 mg/day (N = 13), or clozapine 100 mg/day (N = 13). Reference values for the HRV data were obtained from a large group of well-matched healthy controls (N = 70). The most important findings were the following: (1) clozapine, olanzapine, and sertindole all prolonged mean frequency-corrected QTc times, which, in the case of sertindole, proved to be significant (Wilcoxon test p
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- 2001
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33. A Study of HIV-1 Genetic Diversity in the Czech Republic: 1986-2007
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Jana Vandasova, Marek Malý, Brůcková M, Marie Stankova, Milan Reinis, and Marek Linka
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Male ,Czech ,Molecular Sequence Data ,HIV Infections ,Genome, Viral ,Biology ,Genetic analysis ,Acquired immunodeficiency syndrome (AIDS) ,HIV Seroprevalence ,HIV Seropositivity ,medicine ,Humans ,Czech Republic ,Genetics ,Molecular Epidemiology ,Genetic diversity ,Base Sequence ,Phylogenetic tree ,Molecular epidemiology ,Reverse Transcriptase Polymerase Chain Reaction ,Public Health, Environmental and Occupational Health ,Genetic Variation ,virus diseases ,General Medicine ,Emigration and Immigration ,medicine.disease ,Genes, pol ,Subtyping ,language.human_language ,Eastern european ,Phenotype ,HIV-1 ,language ,RNA, Viral ,Female - Abstract
SUMMARY Background: The global HIV/AIDS epidemic consists of a number of regional epidemics caused by different HIV-1 subtypes prevailing in different regions. Objectives: To study changes in genetic diversity of HIV-1 strains isolated in the Czech Republic (CR) over a more than twenty-year period (1986–2007). Study Design: HIV-1 strains isolated in CR from 1986 to 2007 were subtyped by pol gene sequencing followed by phylogenetic analysis. The role of HIV-1 subtyping in molecular epidemiology was considered. Results: A wide range of HIV-1 subtypes were found, with subtype B, into which 76.6 % of 534 HIV-1 isolates were classified, being predo minant during the whole study period. An increasing number of non-B subtypes A1, C, D, F1, G and some recombinant forms (CRF 01_AE, CR F 02_AG and CRF 06_cpx) were identified after 1990. Conclusions: The absolute predominance of subtype B among HIV-1 strains in the Czech Republic ended in 1991 when different non-B subtypes had been introduced into the country. The East-West migration is responsible for the introduction of HIV-1 subtypes prevalent i n Eastern European and some Asian countries. Genetic analysis of HIV-1 isolates from a given region can be helpful in tracing the course of the HIV/AIDS epidemic.
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- 2008
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34. Randomized, Double-Blind Crossover Study to Investigate the Effects of Amlodipine and Isosorbide Mononitrate on the Time Course and Severity of Exercise-Induced Myocardial Stunning
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Helen Saunders, Andre Linka, Philip Avery, Navroz Masani, Christopher A. Rinaldi, Elizabeth C. Jones, and Roger Hall
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Male ,Isosorbide Dinitrate ,Angina Pectoris ,Double-Blind Method ,Physiology (medical) ,Isosorbide mononitrate ,medicine ,Humans ,Amlodipine ,Aged ,Myocardial Stunning ,Tomography, Emission-Computed, Single-Photon ,ST depression ,Myocardial stunning ,Cross-Over Studies ,medicine.diagnostic_test ,business.industry ,Stunning ,Middle Aged ,Calcium Channel Blockers ,medicine.disease ,Crossover study ,Echocardiography ,Anesthesia ,Exercise Test ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Perfusion ,Emission computed tomography ,medicine.drug - Abstract
Background —Myocardial stunning may cause prolonged left ventricular dysfunction after exercise-induced ischemia that can be attenuated by calcium antagonists in animal models. To assess their effects in humans, we performed a randomized, double-blind crossover study comparing the calcium antagonist amlodipine (10 mg once daily) versus isosorbide mononitrate (ISMN, 50 mg once daily) on postexercise stunning. Methods and Results —Twenty-four men with chronic stable angina and normal left ventricular function underwent serial quantitative exercise stress echocardiography after 3 weeks on each treatment to assess the degree of postexercise stunning with simultaneous sestamibi single-photon emission computed tomography perfusion scans at peak stress to quantify the ischemic burden. Exercise time ( P =1), maximum ST depression ( P =0.48), and sestamibi single-photon emission computed tomography scores ( P =0.17) were unchanged between treatments. Stunning occurred more often with ISMN than amlodipine (82% versus 48%). The global and segmental stress echocardiography parameters of stunning were attenuated in patients while taking amlodipine compared with ISMN. Shortening fractions and ejection fractions were less impaired 30 minutes after exercise in patients receiving amlodipine (3.5±1.4% versus 2.5±1.4%, P =0.014, and 59.7±5.4% versus 54.5±8%, P P =0.018). Conclusions —Despite comparable levels of ischemia, amlodipine attenuated stunning when compared with ISMN. This beneficial effect may relate to a prevention of the calcium overload implicated in the pathogenesis of stunning.
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- 1998
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35. Right ventricle best predicts the race performance in amateur ironman athletes
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Beat Knechtle, Alain Bernheim, Anja Faeh-Gunz, Christine H. Attenhofer Jost, Argelia Medeiros-Domingo, Monica Pfyffer, André Linka, Gabriella De Pasquale, Michel Zuber, and Burkhardt Seifert
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Adult ,Male ,medicine.medical_specialty ,Heart Ventricles ,Physical Therapy, Sports Therapy and Rehabilitation ,Athletic Performance ,Race (biology) ,Endurance training ,Internal medicine ,medicine ,Humans ,Orthopedics and Sports Medicine ,Exercise ,Ultrasonography ,biology ,Anthropometry ,business.industry ,Athletes ,Middle Aged ,biology.organism_classification ,Confidence interval ,Weak correlation ,medicine.anatomical_structure ,Fractional area change ,Ventricle ,Cardiology ,Body Composition ,Physical Endurance ,Female ,business ,Switzerland - Abstract
PURPOSE The ironman (IM) triathlon is a popular ultraendurance competition, consisting of 3.8 km of swimming, 180.2 km of cycling, and 42.2 km of running. The aim of this study was to investigate the predictors of IM race time, comparing echocardiographic findings, anthropometric measures, and training characteristics. METHODS Amateur IM athletes (ATHL) participating in the Zurich IM race in 2010 were included. Participants were examined the day before the race by a comprehensive echocardiographic examination. Moreover, anthropometric measurements were obtained the same day. During the 3 months before the race, each IM-ATHL maintained a detailed training diary. Recorded data were related to total IM race time. RESULTS Thirty-eight IM finishers (mean ± SD age = 38 ± 9 yr, 32 men [84%]) were evaluated. Total race time was 684 ± 89 min (mean ± SD). For right ventricular fractional area change (45% ± 7%, Spearman ρ = -0.33, P = 0.05), a weak correlation with race time was observed. Race performance exhibited stronger associations with percent body fat (15.2 ± 5.6%, ρ = 0.56, P = 0.001), speed in running training (11.7 ± 1.2 km · h(-1), ρ = -0.52, P = 0.002), and left ventricular myocardial mass index (98 ± 24 g · m(-2), ρ = -0.42, P = 0.009). The strongest association was found between race time and right ventricular end-diastolic area (22 ± 4 cm2, ρ = -0.64, P < 0.0001). In multivariate analysis, right ventricular end-diastolic area (β = -16.7, 95% confidence interval = -27.3 to -6.1, P = 0.003) and percent body fat (β = 6.8, 95% confidence interval = 1.1-12.6, P = 0.02) were independently predictive of IM race time. CONCLUSIONS In amateur IM-ATHL, RV end-diastolic area and percent body fat were independently related to race performance. RV end-diastolic area was the strongest predictor of race time. The role of the RV in endurance exercise may thus be more important than previously thought and needs to be further studied.
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- 2013
36. Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients
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Moutschen, M., Theys, K., Deforche, K., Vercauteren, J., Libin, P., van de Vijver, D. A. M. C., Albert, Jan, Åsjö, Birgitta, Balotta, Claudia, Bruckova, M., Camacho, Ricardo J., Clotet, B., Coughlan, S., Grossman, Z., Hamouda, O., Horban, A., Korn, K., Kostrikis, Leontios G., Kücherer, C., Nielsen, C., Paraskevis, Dimitrios N., Poljak, M., Puchhammer-Stockl, E., Riva, C., Ruiz, L., Liitsola, K., Schmit, J. -C, Schuurman, R., Sönnerborg, A., Stanekova, D., Stanojevic, M., Struck, D., Van Laethem, K., Wensing, A. M. J., Boucher, C. A. B., Vandamme, A. M., Sarcletti, M., Schmied, B., Geit, M., Balluch, G., Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., De Wit, S., Echahidi, F., Fransen, K., Goffard, J. -C, Goubau, P., Goudeseune, E., Yombi, J. -C, Lacor, P., Liesnard, C., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Van den Heuvel, A., Van Der Gucht, B., Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Demetriades, Ioannis, Kousiappa, Ioanna, Demetriou, Victoria L., Hezka, Johana, Linka, M., Machala, L., Jrgensen, L. B., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Ristola, M., Suni, J., Sutinen, J., K̈ucherer, C., Berg, T., Braun, P., Poggensee, G., Däumer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Müller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Hatzakis, Angelos E., Magiorkinis, Emmanouil N., Hatzitheodorou, Eleni, Issaris, C., Haida, Catherine, Zavitsanou, Assimina, Magiorkinis, Gkikas, Lazanas, Marios C., Chini, Maria C., Magafas, N., Tsogas, Nickolaos, Paparizos, Vassilios A., Kourkounti, Sofia, Antoniadou, Anastasia C., Papadopoulos, Antonios I., Panagopoulos, Periklis, Poulakou, Garyphallia G., Sakka, V., Chryssos, Georgios, Drimis, Stylianos, Gargalianos, Panagiotis, Lelekis, Moyssis I., Xilomenos, G., Psichogiou, Mina A., Daikos, George L., Panos, George, Haratsis, G., Kordossis, Theodore, Kontos, Athanasios N., Koratzanis, Georgios, Theodoridou, Maria C., Mostrou, Glykeria J., Spoulou, Vana I., Hall, W., De Gascun, C., Byrne, C., Duffy, M., Bergin, C., Reidy, D., Farrell, G., Lambert, J., O'Connor, E., Rochford, A., Low, J., Coakely, P., Levi, I., Chemtob, D., Mussini, C., Caramma, I., Capetti, A., Colombo, M. C., Rossi, C., Prati, F., Tramuto, F., Vitale, F., Ciccozzi, M., Angarano, G., Rezza, G., Schmit, J. C., Hemmer, R., Arendt, V., Staub, T., Schneider, F., Roman, F., van Bentum, P. H. M., Brinkman, K., op de Coul, E. L., van der Ende, M. E., Hoepelman, I. M., van Kasteren, M., Juttmann, J., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M. W. J., Schrijnders-Gudde, L., van de Ven, B. J. M., Ormaasen, V., Aavitsland, P., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Malolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Palma, C., Borges, F., Paix̃ao, T., Duque, V., Araújo, F., Jevtovic, D. J., Salemovic, D., Habekova, M., Mokráš, Miloš, Truska, P., Babic, Dunja Z., Tomazic, J., Vidmar, L., Karner, P., Gutíerrez, C., deMendoza, C., Erkicia, I., Domingo, P., Camino, X., Galindo, M. J., Blanco, J. L., Leal, M., Masabeu, A., Guelar, A., Llibre, J. M., Margall, N., Iribarren, J. A., Gutierrez, S., Baldov́i, J. F., Pedreira, J. D., Gatell, J. M., Moreno, S., de Mendoza, C., Soriano, V., Blaxhult, A., Heidarian, A., Karlsson, A., Aperia-Peipke, K., Bergbrant, I. -M, Gissĺen, M., Svennerholm, M., Björkman, Per, Bratt, G., Carlsson, M., Ekvall, H., Ericsson, M., Ḧofer, M., Johansson, B., Sonnerb̈org, A., Kuylenstierna, N., Ljungberg, B., Mäkitalo, S., Strand, A., Öberg, S., Virology, Erasmus MC other, Van Wijngaerden, Eric, Clinicum, Department of Medicine, Infektiosairauksien yksikkö, Centro de Malária e outras Doenças Tropicais (CMDT), Graduate School, Kostrikis, Leontios G. [0000-0002-5340-7109], Paraskevis, Dimitrios [0000-0001-6167-7152], UCL - SSS/IREC/MBLG - Pôle de Microbiologie médicale, UCL - (SLuc) Service de microbiologie, UCL - (SLuc) Service de médecine interne générale, Theys, K, Deforche, K, Vercauteren, J, Libin, P, van de Vijver, DA, Albert, J, Asjö, B, Balotta, C, Bruckova, M, Camacho, RJ, Clotet, B, Coughlan, S, Grossman, Z, Hamouda, O, Horban, A, Korn, K, Kostrikis, LG, Kücherer, C, Nielsen, C, Paraskevis, D, Poljak, M, Puchhammer Stockl, E, Riva, C, Ruiz, L, Liitsola, K, Schmit, JC, Schuurman, R, Sönnerborg, A, Stanekova, D, Stanojevic, M, Struck, D, Van Laethem, K, Wensing, AM, Boucher, CA, Vandamme, AM, Tramuto, F, and Vitale, F
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Adult ,Male ,lcsh:Immunologic diseases. Allergy ,Anti-HIV Agents ,education ,Virulence ,HIV Infections ,Drug resistance ,Biology ,Settore MED/42 - Igiene Generale E Applicata ,Virus ,polymorphism ,03 medical and health sciences ,Viral Proteins ,SDG 3 - Good Health and Well-being ,Virology ,Genotype ,Drug Resistance, Viral ,drug-naive ,medicine ,Humans ,Prospective Studies ,030304 developmental biology ,0303 health sciences ,Polymorphism, Genetic ,030306 microbiology ,Research ,protease ,Viral Load ,Reverse transcriptase ,3. Good health ,CD4 Lymphocyte Count ,Drug-naïve ,Infectious Diseases ,3121 General medicine, internal medicine and other clinical medicine ,Immunology ,biology.protein ,HIV-1 ,Female ,Antibody ,lcsh:RC581-607 ,Viral load ,HIV-1 infected patient ,medicine.drug ,Peptide Hydrolases - Abstract
Background: The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase fitness during treatment, their presence may also modulate viral fitness and virulence in absence of therapy and major resistance mutations. We previously designed a modeling technique that quantifies genotypic footprints of in vivo treatment selective pressure, including both drug resistance mutations and polymorphic compensatory mutations, through the quantitative description of a fitness landscape from virus genetic sequences. Results: Genotypic correlates of viral load and CD4 cell count were evaluated in subtype B sequences from recently diagnosed treatment-naive patients enrolled in the SPREAD programme. The association of surveillance drug resistance mutations, reported compensatory mutations and fitness estimated from drug selective pressure fitness landscapes with baseline viral load and CD4 cell count was evaluated using regression techniques. Protease genotypic variability estimated to increase fitness during treatment was associated with higher viral load and lower CD4 cell counts also in treatment-naive patients, which could primarily be attributed to well-known compensatory mutations at highly polymorphic positions. By contrast, treatment-related mutations in reverse transcriptase could not explain viral load or CD4 cell count variability. Conclusions: These results suggest that polymorphic compensatory mutations in protease, reported to be selected during treatment, may improve the replicative capacity of HIV-1 even in absence of drug selective pressure or major resistance mutations. The presence of this polymorphic variation may either reflect a history of drug selective pressure, i.e. transmission from a treated patient, or merely be a result of diversity in wild-type virus. Our findings suggest that transmitted drug resistance has the potential to contribute to faster disease progression in the newly infected host and to shape the HIV-1 epidemic at a population level. ispartof: Retrovirology vol:9 issue:1 ispartof: location:England status: published
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- 2012
37. Structural and functional cardiac alterations in Ironman athletes: new insights into athlete's heart remodeling
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Barbara Naegeli, Anja Faeh-Gunz, André Linka, Alain Bernheim, Monica Pfyffer, G. De Pasquale, C.H. Attenhofer Jost, Beat Knechtle, Michel Zuber, Burkhardt Seifert, University of Zurich, and Bernheim, A M
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11035 Institute of General Practice ,Adult ,Male ,medicine.medical_specialty ,biology ,Ventricular Remodeling ,business.industry ,Athletes ,Athlete's heart ,Cardiomyopathy ,610 Medicine & health ,Heart ,10060 Epidemiology, Biostatistics and Prevention Institute (EBPI) ,medicine.disease ,biology.organism_classification ,2705 Cardiology and Cardiovascular Medicine ,Echocardiography ,Physical therapy ,medicine ,Physical Endurance ,Humans ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
athlete's heart remodeling☆ A.M. Bernheim ⁎, M. Zuber , B. Knechtle , A. Linka , A. Faeh-Gunz , G. De Pasquale , B. Seifert , M. Pfyffer , B. Naegeli , C.H. Attenhofer Jost e,1 a Department of Cardiology, Stadtspital Triemli, Zurich, Switzerland b Department of Cardiology, Kantonsspital Lucerne, Lucerne, Switzerland c Gesundheitszentrum, St. Gallen, Switzerland d Department of Cardiology, Kantonsspital Winterthur,Winterthur, Switzerland e Cardiovascular Center, Klinik Im Park, Zurich, Switzerland f Division of Biostatistics, ISPM, University of Zurich, Zurich, Switzerland
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- 2012
38. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization
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L. Wang, T. Stys, William E. Boden, R. H. Urbano, D. M. Olinic, Karen S. Pieper, A. Kuijper, E. Soh, J. Nicolau, Jadwiga Nessler, William J. Rogers, Ernesto Rivera, R. Braam, H. Kadr, J. Csikasz, B. Boichev, Prafulla Kerkar, I. Kraiz, R. Babu, Ali Aydinlar, D. Safley, O. Nguyen-Khac, P. Chua, W. Buchanan, C. A. Morales, A. Abyankar, A. Srinivas, S. Genth-Zotz, J. Rocha Faria Neto, D. Drenning, L. Moretti, S. Varma, D. Roth, C. Matei, Jane E. Onken, H. Tumbev, P. Keeling, Xian Li, N. Ciglenecki, Shahyar M. Gharacholou, P. P. Goh, D. Sporn, M. Chang, Marcin Gruchała, R. Foreman, Bogdan Minescu, S. Nawaz, N. Alexeeva, Y. Shalev, C. Fastabend, L. van Zyl, J. F. Certic, J. Longo, J. Wang, K. Dave, Olivier Morel, F. Maatouk, Y. El Rakshy, J. Giacomini, P. Lazov, R. Marino, Dimitar Raev, M. Y. Chan, L. Z. Dextre, Y. Hao, P. Sepulveda, K. Ramshev, C. Bayron, Ameer Kabour, Alon Marmor, Luciano Moreira Baracioli, H. Marais, Rajendra H. Mehta, R. Breedveld, A. Ben Khalfallah, Kurtulus Ozdemir, I. Westendorp, J. A. Quion, Daniel J. George, D. F. Garcia, J.-P Bassand, G. Szalai, Huw Griffiths, O. Ushakov, M. Tzekova, E. Suprun, A. Mowafy, N. El Mansour, Gail V.W. Johnson, Tereshchenko Sn, W. T. Lai, Petr Widimsky, Hany Ragy, V. R. Castillo, M. Padour, Gilles Montalescot, Louie Tirador, Deepak L. Bhatt, M. Marrinan, S. Promisloff, A. Nambiar, Reginald G.E.J. Groutars, S. R. Lee, J. Cabrera, S. Zhang, András Jánosi, K. Wita, R. Sciborski, Annabelle Rodriguez, P. Sedlon, Jaroslaw D. Kasprzak, A. Faynyk, A. Romero Acuña, M. C. Ramirez, Rakesh Gupta, R. Saligrama, Jacek Gniot, Y. Ke, John H. Alexander, X. Liu, E. Baranov, R. Grzywna, Mukul Sharma, A. Linka, Jarosław Wójcik, Haroon Rashid, M. S. Sanchez, M. Gadkari, B. Rao, James S. Zebrack, Paul W. Armstrong, Francois Schiele, Gracita O. Topacio, Peter J. Casterella, A. Belhassane, P. Golino, F. Plat, P. Roberts-Thomson, K. S. Kim, Stephen D. Wiviott, Mathew T. Roe, Y. D. Chen, I. A. Khan, S. Thanvi, S. Isserman, G. Falck, R. M. Coching, S. C. Stamate, M. Ogorek, K. Danisa, Poul Anders Hansen, M. Medvegy, Amos Katz, R. K. Seerangachar, B. Farah, V. Kale, B. Kusnick, Maurice Pye, M. Mosseri, M. Vatutin, D. Weinstein, Norma Keller, A. Mihov, Ewa Mirek-Bryniarska, N. Adjei, S. Sethi, A. Irimpen, M. Broeders, T. Huynh, K. Niezgoda, P. Samardzic, D. Ziperman, Stuart J. Pocock, T. Arad, J. Lewczuk, M. Amuchastegui, R. Moscoso, B. Dimov, W. A. Ahmad, E. Dalli, P. Laothavorn, S. Shaikh, Helmut U. Klein, J. Menon, H. Colombo, L. Fattore, G. Zarrella, Dorairaj Prabhakaran, N. Viboolkitvarakul, Judith D. Goldberg, Neetika Garg, Y. Hasin, F. Rossi Dos Santos, S. J. Vigo, L. Horbach, O. Prokhorov, H. Moellmann, T. R. Vera, C. E. Botta, Domitilla Russo, M. Rossovskaya, David C. Henderson, Rebecca B. Costello, V. Shcherbak, C. J.P.J. Werter, W. Kus, I. Dobre, P. Marechal, T. Nair, H. Nielsen, J. Waites, J. B. Moraes Junior, T. Römer, J. Senior, P. Ionescu, S. Kalashetti, R. N. Ortega, Gail E. Hafley, G. A. Dan, Apur R. Kamdar, Ruth Ann Greenfield, David F. Kong, J. Bergallo, O. Barnum, Antonis S. Manolis, Sumeet Subherwal, S. Schaefer, A. Figueredo, Habib Gamra, S. Bandyopadhyay, V. Miloradovic, Imran Arif, Peter R. Carroll, M. Demirtas, S. Guidera, G. Rogelio, Naseem Jaffrani, N. Mulvihill, Marvin J. Slepian, Darren K. McGuire, Rohit Kalra, Luís A. Providência, F. Van de Werf, Andras Vertes, J. Xu, C. F. Gamio, R. G. Xuereb, R. F. Ramos, E. Kis, N. Bustros, M. De Luca, S. Zhurba, T. Connelly, S. Singhi, F. Gredler, Serdar Kucukoglu, Francesco Fedele, C. Chavez, Christoph Kadel, Antônio Carlos Sobral Sousa, S. Srimahachota, Igor Kaidashev, J. H. Garcia, I. Teodorescu, Birute Petrauskiene, O. Kracoff, Liwa T. Younis, Alain Bouchard, P. Osmancik, Y. Sun, C. Hammett, S. Sabri, William Wallace, Mehmet Yazici, L. Ermoshkina, Harish Chandna, G. Ramos-Lopez, M. Bronisz, Sergio Luiz Zimmermann, Giuseppe Ambrosio, V. Hergeldjieva, César A. Jardim, A. Rifai, H. Lui, A. Lee, J. Scholz Issa, A. Blenkhorn, P. Micale, V. Barbarich, C. Maccallum, Peter J. Grant, G. Topacio, N. Budassi, J. Yan, Keith A.A. Fox, Y. Xia, Jan H. Cornel, A. Rafael, Paul Hermany, S. Potthoff, Mohsin A.F. Khan, Pierre Coste, Neal Ready, N. T. Duda, M. Reyes, A. Chandran, I. G. Gordeev, Anne W. Beaven, B. J.B. Hamer, C. Treasure, Pravin Manga, M. R. Babarskiene, T. Devedzhiev, Alberto Menozzi, L. Lenarz, N. Llerena, Thomas F. Lüscher, Giovânio Vieira da Silva, Y. Malynovsky, L. Ramanathan, M. Belicova, M. O. Ibarra, D. Chew, R. Castillo, M. Kesselbrenner, A. H. Li, E. Baldjiev, M. El-Harari, S. H. Hur, S. Chiaramida, C. E. Chiang, Viliam Fridrich, L. R. Cartasegna, A. Yagensky, Steven E. Hearne, Gregory Pavlides, Witold Rużyłło, Y. Chandrashekhar, S. Welka, H. Petijean, Jose L. Leiva-Pons, Shaul Atar, Andrzej Lubiński, S. Zhao, János Tomcsányi, Narinder Singh, D. Banker, T. Boyek, H. Ebinc, N. Calambur, A. Mouhaffel, M. Creteanu, H. Huang, J. O. Jeong, E. Goudreau, D. Alexopoulos, E. Duronto, S. Car, O. Bashkirtsev, J. Mandak, V. Papademetriou, David O. Williams, Oscar Pereira Dutra, R. Baman, T. J. Hong, J. O. Ibañez, D. L. Gomez, R. K. Jain, R. Jozwa, L. Di Lorenzo, Matthew Wilson, Christian W. Hamm, A. Buakhamsri, Nikitas Moschos, Ashok Kumar, A. Kadiiski, C. Y. Lee, M. Opazo, J. Tang, E. Ferrari, P. Colon-Hernandez, Jean-Pierre Déry, B. Goloborodko, L. Gimple, Diego Ardissino, M. Bergovec, S. Thew, Dariusz Dudek, K. Tang, P. A.G. Zwart, A. Deshpande, S. Sathe, Yves Cottin, V. Pai, O. Koval, J. Lesnik, Pavan S. Reddy, A. Espinoza, Rungroj Krittayaphong, Carisi Anne Polanczyk, E. Kukuy, L. Tejada, J. Nobel, Renato D. Lopes, J. Bagatin, A. Manolova, E. Boudriot, A. Godoy, N. Perepech, Christopher D. Olympios, A. E. Guimarães, James Harris, Aref Rahman, D. Foley, H. J. Kruik, J. Bruguera I Cortada, I. Fotiadis, A. Bharani, Petar Otasevic, Eileen Brown, N. Gratsiansky, J. E. Poulard, Vladimir Gašparović, Habib Haouala, A. de Belder, J. Schmedtje, Lilia Nigro Maia, J. Cobos, Werner Benzer, E. Korban, A. U. Quraishi, X. Hong, A. Bazzi, P. Kotha, L. Gubolino, H. Ingersoll, Debra Marshall, Udo Sechtem, Sandipan Dutta, G. Frago, Anthony Mathur, Shaun G. Goodman, William Bachinsky, A. Hamer, Jaime Gomez, Patrizio Lancellotti, Vance Wilson, L. White, P.P. Mohanan, Aleksandar Knezevic, Sorin J. Brener, Susanna R. Stevens, H. Luquez, S. K. Lee, P. E. Leaes, P. Benjarge, T. Tu, Z. Coufal, N. Koliopoulos, Mahmut Şahin, X. Huang, S. Boldueva, J. De Souza, N. Chidambaram, S. Zolyomi, K. G. Shyu, H. Montecinos, A. Piombo, Wladmir Faustino Saporito, R. L. Kulkarni, I. Szakal, G. Arminio, M. Elbaz, Samir Pancholy, Jang Ho Bae, Giuseppe Musumeci, S. B. Zouari, A. Chois, D. Wojciechowski, A. Bakbak, E. Bozkurt, Kenneth J. Winters, R. Raugaliene, D. Sarkar, J. M. Alegret, Hubertus Heuer, E. Bobescu, E. Roncallo, R. Carlsson, R. Craig McLendon, L K Newby, K. Zrazhevskiy, João Pedro Ferreira, A. Haidar, D. Tellez, Robert Olszewski, Shmuel Gottlieb, H. Jure, A. Garcia Escudero, S. Sengupta, V. Ochean, W. Kostuk, G. Range, F. Leroy, G. Parale, R. Fernandez, M. Fulwani, M. Padovan, Y. Dovgalevskiy, Kreton Mavromatis, H. Hart, Y. G. Ko, F. Seixo, V. Bisne, J. McGarvey, Kimberly L. Blackwell, John H. Strickler, Sanjay Kumar, A. Bordonava, L. Egorova, C. Patocchi, A. Karczmarczyk, Chiara Melloni, Piyamitr Sritara, M. Anastasiou-Nana, Roman Szełemej, K. Penchev, D. Morales, M. Tokmakova, Krzysztof Zmudka, Rakesh Yadav, E. Bressollette, D. Nul, A. L. Astesiano, M. Urban, Abdulhay Albirini, C. T. Chin, F. Moulin, I. M. Coman, R. Watkin, J. Abanilla, J. Brønnum-Schou, J. Anusauskiene, P. Andrade Lotufo, Joseph G. Rogers, M. Bessen, P. C. Sartori, Paulo Roberto Ferreira Rossi, K. Atassi, H. V. Anderson, B. Klugherz, Bateshwar Prasad Singh, Mirza S. Baig, Z. Yusof, J. H. Geertman, A. Labroo, P. Nash, Freek W.A. Verheugt, Nancy J. Brown, M. A. Alcocer, A. Neskovic, L. Francek, Judith S. Hochman, A. Hoffmann, R. Dran, A. Podczeck-Schweighofer, Jeffry Katz, Josh Roberts, Roger E. McLendon, Ronald Rodriguez, T. Downes, A. Roth, L. E. Mayorga, Armagan Altun, José-Luis López-Sendón, M. Krotin, N. van der Merwe, O. Gigliotti, C. Park, G. Brigden, M. Kumbla, D. C G Basart, D. Erdogan, R. van Kranen, J. Beloscar, Johny Joseph, Pierluigi Tricoci, J. Marino, N. Mahon, S. Dani, I. Kovalskyy, Ioannis Nanas, V. Volkov, M. I. Edmilao, J. Kruells-Muench, F. Alamgir, R. Rinaldi, W. E. Mogrovejo, J. Mirat, C. Staniloae, S. Borromeo, H. Kozman, H. Zhang, Y. Zhou, S. Shurmur, A. Manari, M. A. Barrera, A. Vasylenko, D. Keedy, Paul A. Gurbel, Ali Oto, Charles R. Lambert, V. G. Ribeiro, A. Quintero, H. Joshi, L. Tang, J. Allan, C. S. Díaz, F. Carvalho Neuenschwander, Mircea Cintezǎ, M. Kokles, G. Piovaccari, Z. Kovacs, W. Li, C. Beauloye, E. J. Ramos, D. Bertolim Precoma, J. Burstein, G. Covelli, E. C. Zambrano, Assen Goudev, A. Tang, F. Henriquez, S. Tangsuntornwiwat, C. Kirma, GR Aycock, Kenneth W. Mahaffey, M. Ardnt, Jose C. Nicolau, O. Barbarash, E. K. Shin, P. Potapenko, T. Supryadkina, Asok Venkataraman, W. Mogrovejo, M. Acikel, R. Bohorquez, M. Syvänne, M. Chan, H. Mardikar, H. Berlin, O. Quintana, K. Heintz, J. M. Bastos, Guillermo Llamas Esperon, G. Aroney, J. Chen, Nancy H. Collins, C. Ahsan, G. Heins, F. Baer, V. Kondle, Nicholas Danchin, G. Shetty, Sergio Berti, Philip E. Aylward, James Cotton, G. S. Vallejo, Massimo Volpe, Z. Vasiljevic-Pokrajcic, C. Bugueño, Seung Woon Rha, S. Ilic, G. E. Stanciulescu, Z. Li, D. Nassiacos, R. Sciberras, S. Kuanprasert, Denilson Campos de Albuquerque, M. Pavlovic, Craig S. Barr, Mohammed R. Essop, John G. Canto, David T. Roberts, M. Ozdemir, Jacquelyn Miller, T. K. Ong, Sian E. Harding, V. Bose, J. Yoon, R. Syan, M. A. Paz, O. Maskon, Dennis V. Cokkinos, L. Kraus, Z. Masud, K. Amosova, M. Boyarkin, L. Mos, Dmitry Zamoryakhin, Arif Anis Khan, Jeffrey A. Breall, A. Gallino, Ivo Petrov, F. A. Alves da Cost, Saul Vizel, Hugo Vargas Filho, P. Kaewsuwanna, G. Antonelli, Chuen Den Tseng, I. Vakaliuk, J. Miklin, A. El Hawary, Ashok Jacob, D. Gumm, Kurt Huber, G. Pajes, N. Jathappa, Stanislaw Bartus, P. V. Lavhe, C. Romero, J. Balkin, T. Gould, R. Durgaprasad, Felipe Martinez, Henning Ebelt, A. Puri, D. K. Agarwal, E. E. Buyukoner, R. Mora Junior, P. Poliacik, A. Dande, X. Zhao, J. Floro, A. Bagriy, Yuliya Lokhnygina, M. Atieh, V. Batushkin, Valentin Markov, O. Karpenko, Peter Clemmensen, P. Castro, L. Paloscia, F. Florenzano, J. L. Accini, Tony Schibler, J. Arneja, W. Wu, B. Andruszkiewicz, Michael A. Morse, P. Vojtisek, D. Sadler, S. Frischwasser, M. Cayli, W N Leimbach, E. Flores, B. Wang, A Sosa Liprandi, Y. Michalaros, H. C. Finimundi, Raul D. Santos, N. Vijay, E. Magnus Ohman, Y. Karpenko, J. Sirotiakova, Z. Shogenov, D A Zateyshchikov, Eric P. Viergever, R. Bach, Gary S. Niess, D. C. Acosta, G. Piegari, J. B. Gupta, J. Shanes, E. Ronner, J. Arter, Claudio Cavallini, M. A. Hominal, V. Bugan, S. D. Varini, K. Nyman, B. G. Castillo, Sinan Aydoğdu, N. Novikova, D. Wang, P. Simpson, Y. Huang, Taral Patel, Gabriel Tatu-Chitoiu, D. Silva Junior, H. Theron, C. Alvarez, Anikó Ilona Nagy, T. Chua, P. Georgiev, D. Rittoo, G. De Luca, R. Blonder, Alberto Caccavo, D. Koganti, E. Manenti, N. Ghaisas, G. Letcher, D. Platogiannis, Arshed A. Quyyumi, J. Dy, Z. Ples, W. Kunz Sebba Barroso de Souza, Hamid Taheri, S. Kammoun, A. Salvioni, B. Stockins, K. Sutalo, J. C. Post, Merih Kutlu, Vijay K. Chopra, C. Mathis, Stephen M. Schwartz, Manish Jain, D. Coisne, A. Goudev, A. Dalby, João Morais, P. van Kalmthout, Andrzej Budaj, I. Dotani, L. Mircoli, R. Vicari, J. P. Herrman, M. Moran, G. Lupkovics, Alexander Parkhomenko, J. Heath, Andrew Moriarty, C. Pop, J. Y. Hwang, S. Kassam, R. Martingano, I. Nikolskaya, Z. Zheng, Johann S. de Bono, M. Izzo, R. Labonte, E. H. Forte, W. Moleerergpoom, Piera Angelica Merlini, D. Lee, W. Macias, G. Syan, S. Zhou, S. W. Kim, T. Duris, E. Shaoulian, Andreas U. Wali, Marco Antonio Mota Gomes, Pritibha Singh, M. Ovize, M. Del Core, W. Bowden, B. Xu, Ravi Bhagwat, C. Wongvipaporn, J. Vojacek, Steven Lindsay, F. McGrew, J. Gorny, J. D. Pappas, R. Vuyyuru, J. Chahin, Ashraf Reda, T. Lau, E. Conn, J. Meisner, S. Meymandi, A. D. Hrabar, M. Slanina, D. Jarasuniene, C. Lang, A. Vo, Christian Hamm, H. Gogia, Z. Yuan, T. Mathew, A. Van Dorpe, J. Kettner, M. Barbiero, Harvey D. White, L. Rudenko, V. Jain, M. Carter, David Erlinge, G. Ma, V. Sierkova, D. K. Kim, Steven O. Smith, R. K. Premchand, P. Jetty, J. Y. Hou, V. Simanenkov, T. Kaelsch, David P. Foley, A. Francis, Piotr Ponikowski, Ramón Corbalán, D. Connolly, J. Tuma, R. Zambahari, Miodrag Ostojic, R. Lamich, A. Rabelo Alves, V. Tseluyko, G. Moises Azize, L. Khaisheva, G. Pencheva, C. Ingram, J. Cooke, A. Prado, M. De Tollenaere, M. Kim, Alan Rees, Melanie B. Turner, Mark B. Abelson, H. L. Luciardi, L. Illyes, R. Sarma, L. Manriquez, J. A. Marin Neto, D. Iordachescu-Petica, G. Hoedemaker, Victor S. Gurevich, F. Ridocci, J. Grman, F. Waxman, Jorge F. Saucedo, E. Boughzala, B. S. Jagadesa, Heba Abdullah, A. Weiss, N. Bichan, L. Tami, Y. Bouzid, N. I. Gomez, Zafar Sy, Béla Merkely, J. P. Albisu, L. Rodriguez-Ospina, John C. Chambers, L. L. Lobo Marquez, R. Guan, Steven Georgeson, M. K. Sarna, L. Nogueira Liberato de Sousa, Mika Laine, P. Pimentel Filho, Teresa Kawka-Urbanek, G P Arutyunov, S. Elhadad, A. Dambrauskaite, R. Leon de la Fuente, Audes D. M. Feitosa, P. Baetslé, Abraham Al Ahmad, José Francisco Kerr Saraiva, Roland P.T. Troquay, J. Berlingieri, Margaret Arstall, J. L. Coronado, K. Yang, S. V. Shalaev, Bernard J. Gersh, A. El-Etreby, Elżbieta Zinka, F. De Valais, John E.A. Blair, P. Fajardo, M. Rodriguez, R. Boujnah, H. Hammerman, Y. S. Chong, Stigi Joseph, M. H. Jeong, J. Ge, Q. He, Robert S Iwaoka, Bimal R. Shah, J. Sawhney, T. Sakulsaengprapha, G. Werner, Jill Anderson, M. Hondl, Meinrad Gawaz, Gilmar Reis, M. Dalkowski, Tomáš Janota, M. Damiao Gomes Seabra, A. Dharmadhikari, Aleš Linhart, John Elliott, Kodangudi B. Ramanathan, Doron Zahger, Dilek Ural, L. Regos, F. R. Bolohan, Marcello Galvani, B. Zakhary, N. Qureshi, D. Deac, Maria Emília Figueiredo Teixeira, T. Venter, Santosh Gupta, W. Wright, P. Telekes, A. Furber, V. Nykonov, Zhu Junren, M. Cinteza, I. Lang, S. Junejo, D. Martins, Mauro Esteves Hernandes, G. Ishmurzin, Anthony J. Dalby, R. Scioli, P. Babu, R. Habaluyas, V. Mendoza, G. B. Scaro, Matthew T. Roe, M. Senaratne, D. J. van der Heijden, T. Pillay, Yoav Turgeman, J. Moreira, C. Cuccia, C. Astarita, S. De Servi, Robert G. Wilcox, M. C. Constantinescu, Kardiyoloji, Roe Matthew, T., Armstrong Paul, W., Fox Keith, A. A., White Harvey, D., Prabhakaran, Dorairaj, Goodman Shaun, G., Cornel Jan, H., Bhatt Deepak, L., Clemmensen, Peter, Martinez, Felipe, Ardissino, Diego, Nicolau Jose, C., Boden William, E., Gurbel Paul, A., Ruzyllo, Witold, Dalby Anthony, J., McGuire Darren, K., Leiva Pons Jose, L., Parkhomenko, Alexander, Gottlieb, Shmuel, Topacio Gracita, O., Hamm, Christian, Pavlides, Gregory, Goudev Assen, R., Oto, Ali, Tseng Chuen, Den, Merkely, Bela, Gasparovic, Vladimir, Corbalan, Ramon, Cinteza, Mircea, McLendon R., Craig, Winters Kenneth, J., Brown Eileen, B., Lokhnygina, Yuliya, Aylward Philip, E., Huber, Kurt, Hochman Judith, S., Ohman E., Magnu, and Golino, Paolo
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Male ,Prasugrel ,Myocardial Infarction ,Kaplan-Meier Estimate ,Piperazines ,Purinergic P2 Receptor Antagonists ,Myocardial infarction ,education.field_of_study ,Cardiovascular diseases [NCEBP 14] ,Acute Coronary Syndrome ,Aged ,Angina, Unstable ,Aspirin ,Cardiovascular Diseases ,Double-Blind Method ,Drug Therapy, Combination ,Female ,Follow-Up Studies ,Humans ,Middle Aged ,Platelet Aggregation Inhibitors ,Prasugrel Hydrochloride ,Stroke ,Thiophenes ,Ticlopidine ,Medicine (all) ,Hazard ratio ,Clopidogrel ,Acute Coronary Syndromes ,General Medicine ,Angina ,Combination ,Cardiology ,medicine.drug ,medicine.medical_specialty ,Acute coronary syndrome ,Population ,Unstable ,Drug Therapy ,General & Internal Medicine ,Internal medicine ,medicine ,cardiovascular diseases ,education ,Acute coronary syndromes ,Revascularisation ,Unstable angina ,business.industry ,medicine.disease ,REVASCULARIZAÇÃO MIOCÁRDICA ,business - Abstract
Item does not contain fulltext BACKGROUND: The effect of intensified platelet inhibition for patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization has not been delineated. METHODS: In this double-blind, randomized trial, in a primary analysis involving 7243 patients under the age of 75 years receiving aspirin, we evaluated up to 30 months of treatment with prasugrel (10 mg daily) versus clopidogrel (75 mg daily). In a secondary analysis involving 2083 patients 75 years of age or older, we evaluated 5 mg of prasugrel versus 75 mg of clopidogrel. RESULTS: At a median follow-up of 17 months, the primary end point of death from cardiovascular causes, myocardial infarction, or stroke among patients under the age of 75 years occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (hazard ratio in the prasugrel group, 0.91; 95% confidence interval [CI], 0.79 to 1.05; P=0.21). Similar results were observed in the overall population. The prespecified analysis of multiple recurrent ischemic events (all components of the primary end point) suggested a lower risk for prasugrel among patients under the age of 75 years (hazard ratio, 0.85; 95% CI, 0.72 to 1.00; P=0.04). Rates of severe and intracranial bleeding were similar in the two groups in all age groups. There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events, except for a higher frequency of heart failure in the clopidogrel group. CONCLUSIONS: Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).
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- 2012
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39. Retrograde ascending aortic dissection: a diagnostic and therapeutic challenge
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Rolf Jenni, L. K. Von Segesser, Manfred Ritter, Miralem Pasic, Pierre Vogt, André Linka, M. I. Turina, and Thierry Carrel
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Adult ,Male ,Pulmonary and Respiratory Medicine ,Aortic arch ,medicine.medical_specialty ,Dissection (medical) ,Sensitivity and Specificity ,Aortic aneurysm ,Aneurysm ,Internal medicine ,medicine.artery ,Ascending aorta ,medicine ,Humans ,Prospective Studies ,Aged ,Aortic dissection ,Analysis of Variance ,Aortic Aneurysm, Thoracic ,business.industry ,Vascular disease ,General Medicine ,Middle Aged ,medicine.disease ,Echocardiography, Doppler ,Aortic Aneurysm ,Surgery ,Aortic Dissection ,Treatment Outcome ,cardiovascular system ,Deep hypothermic circulatory arrest ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Aortic dissection with an entrance tear in the transverse aorta is generally considered to have the highest acute fatality rate of any type of dissection and the direction of its extension is the most difficult to predict. In a prospective study, we evaluated 61 consecutive patients (mean age 56.7 years, ranging from 21 to 75 years), presenting with ascending aortic dissection during a 36-month-period and tried to clarify the incidence of retrograde ascending aortic dissection. In 49 patients (80.3%), the intimal tear was located in the ascending aorta, whereas the dissection originated in the transverse aorta in 12 patients (19.7%); in this latter group, extension was strictly retrograde in 5 patients and in both directions in 7 patients. Three patients died before operation; 58 patients underwent aortic replacement/repair under moderate hypothermia; if the primary tear extended into the transverse aorta or was not found in the ascending aorta, the aortic arch was explored during a brief period of deep hypothermic circulatory arrest. The overall operative mortality was 12.1% (7/58); it was 10.4% (5/48) in ascending aortic dissection and 20% (2/10) in dissection of the transverse aorta. Age (P < 0.005), concomitant coronary artery disease (P < 0.01) and the site of intimal tear (P < 0.01) were significant predictive factors of operative risk. A tear in the transverse aorta is almost always associated with retrograde dissection and may simulate dissection with the entrance tear in the ascending aorta. Localization of the entrance tear remains a diagnostic challenge in aortic dissection but Doppler-echocardiography had a high sensitivity in this series (96.7%).(ABSTRACT TRUNCATED AT 250 WORDS)
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- 1993
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40. Acute tricuspid papillary muscle rupture following blunt chest trauma
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M. I. Turina, Andre Linka, Rolf Jenni, and Manfred Ritter
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Adult ,Male ,Thorax ,medicine.medical_specialty ,Thoracic Injuries ,Heart disease ,Wounds, Nonpenetrating ,Blunt ,medicine ,Humans ,Papillary muscle ,Tricuspid valve ,business.industry ,Papillary Muscles ,Papillary muscle rupture ,medicine.disease ,Tricuspid Valve Insufficiency ,Surgery ,medicine.anatomical_structure ,Heart Injuries ,Echocardiography ,Acute Disease ,Tricuspid Valve ,Radiology ,Cardiology and Cardiovascular Medicine ,business ,Complication - Published
- 1992
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41. Treatment effects of serotonergic and noradrenergic antidepressants on the intensity dependence of auditory ERP components in major depression
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Gudrun Sartory, Thomas Linka, Bernhard W. Müller, and Jens Wiltfang
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Adult ,Male ,medicine.medical_specialty ,Serotonin reuptake inhibitor ,Morpholines ,Audiology ,Citalopram ,Serotonergic ,behavioral disciplines and activities ,chemistry.chemical_compound ,Reboxetine ,mental disorders ,medicine ,Humans ,Neurotransmitter ,Depressive Disorder, Major ,Adrenergic Uptake Inhibitors ,General Neuroscience ,Middle Aged ,medicine.disease ,Antidepressive Agents ,chemistry ,Evoked Potentials, Auditory ,Antidepressant ,Major depressive disorder ,Female ,Serotonin ,Psychology ,Selective Serotonin Reuptake Inhibitors ,medicine.drug ,Clinical psychology - Abstract
The intensity dependent amplitude change of auditory evoked potentials (IDAP), an assumed indicator of the level of central nervous serotonergic neurotransmission, was measured in major depressive disorder (MDD, DSM-IV: 296.2, 296.3; APA 1994) before and after treatment with either a selective serotonin reuptake inhibitor or a selective noradrenaline reuptake inhibitor antidepressant and compared with the results of a healthy control group. Auditory evoked P1, N1, P2, P1/N1 and N1/P2 peak-to-peak amplitudes were evaluated in 26 in-patients with MDD prior to and after antidepressant treatment with citalopram (24 days, n=14) or reboxetine (25 days, n=12), and in 43 healthy control subjects. Clinical symptoms of MDD were assessed by means of standardized psychiatric rating scales (CGI, HDRS, HAMA and BDI). The IDAP within the control group remained stable over 24 days (N1 amplitude slope retest ANOVA p=.79). Neither applied antidepressants nor decrease of HDRS total score during treatment had a significant effect on the IDAP in the patients' sample. The conclusion that the IDAP does not reflect the temporary depressive state in MDD is discussed.
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- 2009
42. A randomised, controlled trial of bosentan in severe COPD
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Michael Tamm, Martin Brutsche, M Di Valentino, H Rasch, André Linka, Anja Meyer, and D. Stolz
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Pulmonary and Respiratory Medicine ,Male ,medicine.medical_specialty ,Hypertension, Pulmonary ,Vasodilator Agents ,Physical exercise ,Pulmonary Disease, Chronic Obstructive ,Double-Blind Method ,Internal medicine ,medicine ,Humans ,Hypoxia ,Aged ,COPD ,Sulfonamides ,Exercise Tolerance ,business.industry ,Endothelin receptor antagonist ,Respiratory disease ,VO2 max ,Bosentan ,Hypoxia (medical) ,Middle Aged ,medicine.disease ,Pulmonary hypertension ,respiratory tract diseases ,Surgery ,Cardiology ,Quality of Life ,Female ,medicine.symptom ,business ,medicine.drug - Abstract
Pulmonary hypertension during exercise is common in severe chronic obstructive pulmonary disease (COPD). It was hypothesised that the use of the endothelin-receptor antagonist bosentan can improve cardiopulmonary haemodynamics during exercise, thus increasing exercise tolerance in patients with severe COPD. In the present double-blind, placebo-controlled study, 30 patients with severe or very severe COPD were randomly assigned in a 2:1 ratio to receive either bosentan or placebo for 12 weeks. The primary end-point was change in the 6-min walking distance. Secondary end-points included changes in health-related quality of life, lung function, cardiac haemodynamics, maximal oxygen uptake and pulmonary perfusion patterns. Compared with placebo, patients treated with bosentan during 12 weeks showed no significant improvement in exercise capacity as measured by the 6-min walking distance (mean+/-SD 331+/-123 versus 329+/-94 m). There was no change in lung function, pulmonary arterial pressure, maximal oxygen uptake or regional pulmonary perfusion pattern. In contrast, arterial oxygen pressure dropped, the alveolar-arterial gradient increased and quality of life deteriorated significantly in patients assigned bosentan. The oral administration of the endothelin receptor antagonist bosentan not only failed to improve exercise capacity but also deteriorated hypoxaemia and functional status in severe chronic obstructive pulmonary disease patients without severe pulmonary hypertension at rest.
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- 2008
43. Hypomorphic mutations in the gene encoding a key fanconi anemia protein, fancd2, sustain a significant group of fa-d2 patients with severe phenotype
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Johan P. de Winter, Holger Hoehn, Elsa Callen, Rosalina van Spaendonk, Yvonne Linka, Reinhard Kalb, Juan A. Bueren, H Joenje, Hildegard Schneider, Curtis Hunt, Arleen D. Auerbach, Angeles Dasí, Kornelia Neveling, Jean Soulier, Gerard Pals, Eliane Gluckman, Detlev Schindler, Sat Dev Batish, Markus Grompe, C. Michel Zwaan, Marianne Berwick, José A. Casado, Helmut Hanenberg, Jordi Surrallés, Pediatrics, Clinical Genetics, Developmental Biology, Pediatric surgery, and Human genetics
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Male ,Fanconi anemia, complementation group C ,Pseudogene ,RNA Splicing ,Biology ,medicine.disease_cause ,Article ,Cell Line ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Fanconi anemia ,Pregnancy ,hemic and lymphatic diseases ,FANCD2 ,medicine ,Ethnicity ,RNA Precursors ,Genetics ,Humans ,Genetics(clinical) ,Child ,Genetics (clinical) ,Alleles ,030304 developmental biology ,DNA Primers ,0303 health sciences ,Mutation ,Base Sequence ,Mosaicism ,Fanconi Anemia Complementation Group D2 Protein ,Haplotype ,Genetic Complementation Test ,Exons ,medicine.disease ,Introns ,3. Good health ,Complementation ,Fanconi Anemia ,Phenotype ,030220 oncology & carcinogenesis ,Child, Preschool ,Female ,Pseudogenes - Abstract
FANCD2 is an evolutionarily conserved Fanconi anemia (FA) gene that plays a key role in DNA double-strand-type damage responses. Using complementation assays and immunoblotting, a consortium of American and European groups assigned 29 patients with FA from 23 families and 4 additional unrelated patients to complementation group FA-D2. This amounts to 3%-6% of FA-affected patients registered in various data sets. Malformations are frequent in FA-D2 patients, and hematological manifestations appear earlier and progress more rapidly when compared with all other patients combined (FA-non-D2) in the International Fanconi Anemia Registry. FANCD2 is flanked by two pseudogenes. Mutation analysis revealed the expected total of 66 mutated alleles, 34 of which result in aberrant splicing patterns. Many mutations are recurrent and have ethnic associations and shared allelic haplotypes. There were no biallelic null mutations; residual FANCD2 protein of both isotypes was observed in all available patient cell lines. These analyses suggest that, unlike the knockout mouse model, total absence of FANCD2 does not exist in FA-D2 patients, because of constraints on viable combinations of FANCD2 mutations. Although hypomorphic mutations arie involved, clinically, these patients have a relatively severe form of FA.
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- 2007
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44. Value of repeated cardiac magnetic resonance imaging in patients with suspected arrhythmogenic right ventricular cardiomyopathy
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Thomas A. Cron, Stefan Osswald, André Linka, Matthias Pfisterer, Peter Buser, Jens Bremerich, Dagmar I. Keller, and David Conen
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Male ,medicine.medical_specialty ,Right ventricular cardiomyopathy ,Electrocardiography ,Cardiac magnetic resonance imaging ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,In patient ,cardiovascular diseases ,Prospective Studies ,Prospective cohort study ,Arrhythmogenic Right Ventricular Dysplasia ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Disease progression ,Follow up studies ,Magnetic Resonance Imaging ,Echocardiography ,Ambulatory ,cardiovascular system ,Cardiology ,Disease Progression ,Electrocardiography, Ambulatory ,Female ,Radiology ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Diagnosis of early stages of arrhythmogenic right ventricular cardiomyopathy (ARVC) with minimal structural abnormalities is challenging. The purpose of this study was to assess the value of repeated cardiac magnetic resonance imaging (CMR) in patients referred for right ventricular arrhythmias and clinical suspicion of ARVC.Prospective follow-up study of 18 patients (8 females) studied with CMR for suspected ARVC. Patients with implanted defibrillators (ICD) were excluded. Mean follow-up was 37 +/- 16 (12-59) months. Patients were assigned to 2 categories (ARVC likely or ARVC unlikely) according to a CMR-score based on right ventricular abnormalities. Clinical follow-up revealed no disease progression in 17 patients (94%). In 1 patient, an ICD was implanted because of disease progression. Of 9 patients with initial findings suggestive of ARVC, follow-up CMR remained positive in 3 and was diagnosed as normal in 6, mainly due to the inability to confirm the presence of fatty infiltrates at follow-up (5 of 6 patients). Initially, 9 patients had a normal CMR and 8 of those remained normal during follow-up.Repeated CMR after an average follow-up of 3 years was normal in 6 of 9 patients with clinical findings consistent with early stages of ARVC at the time of baseline CMR. Thus, CMR diagnosis of early stage ARVC is difficult and should be made with caution.
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- 2006
45. Adenosine myocardial contrast echo in intermediate severity coronary stenoses: a prospective two-center study
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Raymonde Busch, Stefan Martinoff, André Linka, Christian Firschke, and Peter Andrássy
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Male ,Technetium Tc 99m Sestamibi ,medicine.medical_specialty ,Adenosine ,Vasodilator Agents ,Contrast Media ,Blood volume ,Coronary stenosis ,Coronary Angiography ,Statistics, Nonparametric ,Internal medicine ,Albumins ,Image Processing, Computer-Assisted ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Stage (cooking) ,Prospective cohort study ,Cardiac imaging ,Tomography, Emission-Computed, Single-Photon ,Fluorocarbons ,business.industry ,Coronary Stenosis ,Middle Aged ,Echocardiography ,Cardiology ,Exercise Test ,Female ,Radiopharmaceuticals ,Cardiology and Cardiovascular Medicine ,business ,Perfusion ,medicine.drug - Abstract
We sought to evaluate the role of adenosine myocardial contrast echocardiography (MCE) for the determination of functional relevance of coronary stenoses with intermediate angiographic severity and compared the results to single photon imaging (SPECT). We hypothezised that sole assessment of myocardial blood volume changes during adenosine on MCE would indicate functional stensosis relevance when accompanied by increased myocardial oxygen consumption (MVO2).Fifty-seven patients withor=1 coronary stenosis underwent adenosine MCE (ultraharmonic imaging) and exercise SPECT. On MCE, myocardial blood volume was assessed and constant or increased myocardial opacification during adenosine coupled with increased MVO2 was defined as normal and decreased opacification as abnormal.Rate-pressure product significantly increased during adenosine in all patients due to reflex tachycardia following mild hypotension, indicative of increased MVO2. Concordance between MCE and SPECT for the detection of reversible myocardial perfusion defects was 89% (kappa = 0.83). Comparison of regions between rest and during adenosine as opposed to comparison to remote regions of the same stage was important for accurate assessment because concordance betweenn MCE and SPECT was less on separate assessment at rest (73%, kappa = 0.40) compared to stress (91%, kappa = 0.81, P0.05) mainly due to territories scored normal on SPECT and abnormal on MCE.Assessment of myocardial blood volume changes during adenosine using MCE can be used for the determination of the functional relevance of coronary stenoses of intermediate angiographic severity if MVO2 is increased during adenosine.
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- 2006
46. Long-term analysis of the resistance development in HIV-1 positive patients treated with protease and reverse transcriptase inhibitors: correlation of the genotype and disease progression
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J, Václavíková, J, Weber, L, Machala, M, Reinis, M, Linka, M, Brůcková, J, Vandasová, M, Stanková, and J, Konvalinka
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Male ,Genotype ,Anti-HIV Agents ,Reverse Transcriptase Polymerase Chain Reaction ,HIV Infections ,HIV Protease Inhibitors ,Viral Load ,HIV Reverse Transcriptase ,CD4 Lymphocyte Count ,Amino Acid Substitution ,HIV Protease ,Antiretroviral Therapy, Highly Active ,Drug Resistance, Viral ,Mutation ,Disease Progression ,HIV-1 ,Humans ,RNA, Viral ,Reverse Transcriptase Inhibitors ,Female ,Czech Republic - Abstract
In this study, 27 HIV-1-positive patients on long-term highly active antiretroviral therapy (HAART) in the Czech Republic were followed for a period of up to 7 years. Variability of the HIV-1 protease (PR) sequence common in the Czech Republic was observed. Under the pressure of inhibitors of protease (PRIs) and reverse transcriptase (RTIs) mutations in PR were detected. Development of resistance to PRIs was followed by a decrease in CD4 count and increase in viral load. The dynamics of viral load closely corresponded to the accumulation of specific primary mutations in PR and RT. Out of 27 patients 18 developed resistance to PRIs and the prolonged therapy led to the accumulation of a higher number of amino acid changes associated with the resistance and, consequently, cross-resistance to several PRIs was observed. These multi-resistant variants of HIV-1 with mutations in PR could not be inhibited sufficiently with PRIs that are currently available in clinical practice. Efficient yet temporary suppression of viral replication was achieved by a lopinavir (LPV) treatment.
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- 2005
47. [Asymptomatic myocarditis after infection of the upper respiratory tract]
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C, Ramazzina, J, Bremerich, A, Linka, and U, Eriksson
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Adult ,Male ,Arthritis, Infectious ,Anti-Inflammatory Agents, Non-Steroidal ,Troponin I ,Rheumatic Heart Disease ,Subtalar Joint ,Amoxicillin-Potassium Clavulanate Combination ,Magnetic Resonance Imaging ,Antistreptolysin ,Anti-Bacterial Agents ,Electrocardiography ,Myocarditis ,Tonsillitis ,Echocardiography ,Humans ,Drug Therapy, Combination - Abstract
A 20-year-old patient was hospitalized with persistent high fever after tonsillitis and swelling of the talocalcanean joint.The ECG showed a partial right bundle branch block pattern and pathological T inversions on the left precordial leads. Cardiac Troponin I levels were slightly elevated and echocardiography revealed a dyscinetic area at the right ventricular apex. The anti-streptolysin titer was elevated.Post-streptococcal rheumatic myocarditis. THERAPY AND FOLLOW-UP: Antibiotic therapy for 2 weeks. The patient showed subjective full recovery after 6 weeks. The anti-streptolysin titer further increases. Nuclear spin tomography of the heart reveal postinflammatory alterations at the apex of the right ventricle.Rheumatoid fever is a rare diagnosis in developed countries. This case, however, illustrates that the true prevalence of rheumatoid carditis might be underestimated in the presence of only minimal heart-and joint-specific symptoms.
- Published
- 2005
48. The intensity dependence of auditory evoked ERP components predicts responsiveness to reboxetine treatment in major depression
- Author
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Bernhard W. Müller, Stefan Bender, Gudrun Sartory, Thomas Linka, and Markus Gastpar
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Morpholines ,Statistics as Topic ,Audiology ,Electroencephalography ,Serotonergic ,Loudness ,Reboxetine ,Predictive Value of Tests ,medicine ,Humans ,Pharmacology (medical) ,Major depressive episode ,Psychiatry ,Electrodes ,Depressive Disorder, Major ,medicine.diagnostic_test ,Dose-Response Relationship, Radiation ,General Medicine ,Middle Aged ,Antidepressive Agents ,Intensity (physics) ,Psychiatry and Mental health ,Treatment Outcome ,Acoustic Stimulation ,Predictive value of tests ,Evoked Potentials, Auditory ,Antidepressant ,Female ,medicine.symptom ,Psychology ,medicine.drug - Abstract
Introduction: The intensity (loudness)-dependent amplitude change (IDAP) of auditory evoked event-related potential (ERP) components has been suggested as an indicator of central serotonergic neurotransmission. In patients with major depression, associations of high IDAP with favorable SSRI treatment outcome have been reported. This is the first study to assess the predictive value of the IDAP in SNRI treatment. Methods: We evaluated the pre-treatment intensity-dependent change of auditory evoked P1, N1, P2, and P1/N1 and N1/P2 peak-to-peak amplitudes in 14 inpatients with major depressive episode (DSM IV) in the course of 24 days of treatment with the SNRI reboxetine (6-12 mg/d). Results: Our data revealed a highly significant correlation between lower intensity-dependent N1 amplitude slopes prior to reboxetine treatment and stronger decrease of HDRS total score at Fz (r = 0.86, P < 0.001), Fcz (r = 0.91, P < 0.001), and Cz (r = 0.93, P < 0.001). Conclusion: This result corroborates the hypothesis of the IDAP as a differential indicator of serotonergic versus noradrenergic antidepressant psychopharmacotherapy.
- Published
- 2005
49. Right atrial pacing impairs cardiac function during resynchronization therapy: acute effects of DDD pacing compared to VDD pacing
- Author
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Alain, Bernheim, Peter, Ammann, Christian, Sticherling, Peter, Burger, Beat, Schaer, Hans Peter, Brunner-La Rocca, Jens, Eckstein, Stephanie, Kiencke, Christoph, Kaiser, Andre, Linka, Peter, Buser, Matthias, Pfisterer, and Stefan, Osswald
- Subjects
Cardiomyopathy, Dilated ,Male ,Electrocardiography ,Pacemaker, Artificial ,Treatment Outcome ,Atrial Fibrillation ,Cardiac Pacing, Artificial ,Hemodynamics ,Humans ,Female ,Heart Atria ,Middle Aged ,Echocardiography, Doppler - Abstract
We aimed to compare the hemodynamic effects of right-atrial-paced (DDD) and right-atrial-sensed (VDD) biventricular paced rhythm on cardiac resynchronization therapy (CRT).Cardiac resynchronization therapy improves hemodynamics in patients with severe heart failure and left ventricular (LV) dyssynchrony. However, the impact of active right atrial pacing on resynchronization therapy is unknown.Seventeen CRT patients were studied 10 months (range: 1 to 46 months) after implantation. At baseline, the programmed atrioventricular delay was optimized by timing LV contraction properly at the end of atrial contraction. In both modes the acute hemodynamic effects were assessed by multiple Doppler echocardiographic parameters.Compared to DDD pacing, VDD pacing resulted in much better improvement of intraventricular dyssynchrony assessed by the septal-to-posterior wall motion delay (VDD 106 +/- 83 ms vs. DDD 145 +/- 95 ms; p = 0.001), whereas the interventricular mechanical delay (difference between onset of pulmonary and aortic outflow) did not differ (VDD 20 +/- 21 ms vs. DDD 18 +/- 17 ms; p = NS). Furthermore, VDD pacing significantly prolonged the rate-corrected LV filling period (VDD 458 +/- 123 ms vs. DDD 371 +/- 94 ms; p = 0.0001) and improved the myocardial performance index (VDD 0.60 +/- 0.18 vs. DDD 0.71 +/- 0.23; p0.01).Our findings suggest that avoidance of right atrial pacing results in a higher degree of LV resynchronization, in a substantial prolongation of the LV filling period, and in an improved myocardial performance. Thus, the VDD mode seems to be superior to the DDD mode in CRT patients.
- Published
- 2004
50. Response of HIV positive patients to the long-term salvage therapy by lopinavir/ritonavir
- Author
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Jan Konvalinka, Marek Linka, Jana Vandasová, Jana Václavíková, Brůcková M, Marie Staňková, and Ladislav Machala
- Subjects
Adult ,Male ,medicine.medical_specialty ,Efavirenz ,Time Factors ,Salvage therapy ,Lopinavir/ritonavir ,Pyrimidinones ,Gastroenterology ,Lopinavir ,chemistry.chemical_compound ,Indinavir ,Abacavir ,Virology ,Internal medicine ,HIV Seropositivity ,medicine ,Humans ,Salvage Therapy ,Ritonavir ,business.industry ,HIV Protease Inhibitors ,Middle Aged ,CD4 Lymphocyte Count ,Infectious Diseases ,Treatment Outcome ,chemistry ,Immunology ,HIV-1 ,RNA, Viral ,Female ,business ,Saquinavir ,medicine.drug - Abstract
Background: The cohort of 19 patients on LPV/r salvage regimen was followed for the period of up to 37.5 months. Patient's virologic response was evaluated with regard to the various baseline characteristics. Results: A 73.7% of patients (14 out of 19) achieved viral suppression during the first three months of treatment, either complete (47.4%) or partial (26.3%). This effect was only transient in five cases (virologic rebound emerged after 9 months of treatment on average) and in nine cases the treatment was successful in the long-term analysis (HIV RNA plasma level still undetectable at 31st month of the therapy on average with maximum of 36 months). We analyzed the link between the virologic response and possible predictive factors of treatment efficiency, such as lopinavir mutation score, various individual mutations, previous PI exposure, etc. We also describe changes in the PR sequence associated with poor response to the salvage therapy to LPV/r. Conclusions: The results of LPV/r salvage therapy were encouraging. About 47% of patients from our study achieved stable suppression of viral replication for 31 months on average. LPV/r proved to be potent inhibitor despite unfavourable prognosis.
- Published
- 2004
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