16 results on '"Chiossi E"'
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Ferrie, J., Shipley, M., Cappuccio, F., Brunner, E., Miller, M., Kumari, M., Marmot, M., Coenen, A., Castillo, J. L., Araya, F., Bustamante, G., Montecino, L., Torres, C., Oporto, S., Gronli, J., Fiske, E., Murison, R., Bjorvatn, B., Sorensen, E., Ursin, R., Portas, C. M., Rajaraman, S., Gribok, A., Wesensten, N., Balkin, T., Reifman, J., Dursunoglu, N., Ozkurt, S., Baser, S., Delen, O., Sarikaya, S., Sadler, P., Mitchell, P., Françon, D., Decobert, M., Herve, B., Richard, A., Griebel, G., Avenet, P., Scatton, B., Fur, G. L., Eckert, D., Jordan, A., Wellman, A., Smith, S., Malhotra, A., White, D., Bruck, D., Thomas, I., Kritikos, A., Oertel, W., Stiasny-Kolster, K., Garcia-Borreguero, D., Poewe, W., Hoegl, B., Kohnen, R., Schollmayer, E., Keffel, J., Trenkwalder, C., Valle, A., Roizenblatt, S., Fregni, F., Boggio, P., Tufik, S., Ward, K., Robertson, L., Palmer, L., Eastwood, P., Hillman, D., Lee, J., Mukherjee, S., de Padova, V., Barbato, G., Ficca, G., Zilli, I., Salzarulo, P., Veldi, M., Hion, T., Vasar, V., Kull, M., Nowak, L., Davis, J., Latzer, Y., Tzischinsky, O., Crowley, S., Carskadon, M., Anca-Herschkovitsch, M., Frey, D., Ortega, J., Wiseman, C., Farley, C., Wright, K., Campbell, A., Neill, A., Spiegel, K., Leproult, R., Tasali, E., Scherberg, N., van Cauter, E., Noradina, A. T., Karim, N. A., Norlinah, I., Raymond, A. A., Sahathevan, R., Hamidon, B., Werth, E., Poryazova, R., Khatami, R., Bassetti, C., Beran, R. G., Ainley, L., Holand, G., Duncan, J., Kinney, H., Davis, B., Hood, B., Frey, S., Schmidt, C., Hofstetter, M., Peigneux, P., Cajochen, C., Hu, W.-P., Li, J.-D., Zhang, C., Boehmer, L., Siegel, J., Zhou, Q.-Y., Sagawa, Y., Kondo, H., Takemura, T., Kanayama, H., Kaneko, Y., Sato, M., Kanbayashi, T., Hishikawa, Y., Shimizu, T., Viola, A., James, L., Schlangen, L., Dijk, D.-J., Andretic, R., Kim, Y.-C., Han, K.-A., Jones, F., Greenspan, R., Sanford, L., Yang, L., Tang, X., Dieter, K., Uta, E., Sven, H., Richard, M., Oyane, N., Pallesen, S., Holsten, F., Inoue, Y., Fujita, M., Emura, N., Kuroda, K., Uchimura, N., Johnston, A., Astbury, J., Kennedy, G., Hoedlmoser, K., Schabus, M., Pecherstorfer, T., Moser, S., Gruber, G., Anderer, P., Klimesch, W., Naidoo, N., Ferber, M., Pack, A., Neu, D., Mairesse, O., Hoffmann, G., Dris, A., Lambrecht, L., Linkowski, P., Verbanck, P., Le Bon, O., Matsuura, N., Yamao, M., Adachi, N., Aritomi, R., Komada, Y., Tanaka, H., Shirakawa, S., Kondoh, H., Takemura, F., Ohnuma, S., Suzuki, M., Uemura, S., Iskra-Golec, I., Smith, L., Thanh, D.-V., Boly, M., Phillips, C., Steven, L., Luxen, A., Maquet, M., Jay, S., Dawson, D., Lamond, N., Basner, M., Fomberstein, K., Dinges, D., Ogawa, K., Nittono, H., Yamazaki, K., Hori, T., Glamann, C., Hornung, O., Hansen, M.-L, Danker-Hopfe, H., Jung, C., Kecklund, G., Anund, A., Peters, B., Åkerstedt, T., Verster, J., Roehrs, T., Mets, M., de Senerpont Domis, L., Olivier, B., Volkerts, E., Knutson, K., Lauderdale, D., Rathouz, P., Christie, M., Chen, L., Bolortuya, Y., Lee, E., Mckenna, J., Mccarley, R., Strecker, R., Tamaki, M., Matsuoka, T., Aritake, S., Suzuki, H., Kuriyama, K., Ozaki, A., Abe, Y., Enomoto, M., Tagaya, H., Mishima, K., Matsuura, M., Uchiyama, M., Lima-Pacheco, E., Davis, K., Sabourin, C., Lortie-Lussier, M., de Koninck, J., van Der Werf, Y., van Der Helm, E., Schoonheim, M., van Someren, E., Tokley, M., Ball, M., Sato, T., Ghilardi, M. F., Moisello, C., Bove, M., Busi, M., Pelosin, E., Tononi, G., Eguchi, N., Sakata, M., Urade, Y., Doe, N., Yoshihara, K., Abe, K., Manabe, Y., Iwatsuki, K., Hayashi, T., Shoji, M., Kamiya, T., Gooley, J., Brainard, G., Rajaratnam, S., Kronauer, R., Czeisler, C., Lockley, S., Phillips, A., Robinson, P., Burgess, H., Revell, V., Eastman, C., Bihari, S., Ramakrishnan, N., Camerino, D., Conway, P. M., Costa, G., Vandewalle, G., Albouy, G., Sterpenich, V., Darsaud, A., Rauchs, G., Berken, P.-Y, Balteau, E., Maquet, P., Tendero, J. A., Domenech, M. P., Isern, F. S., Martínez, C., Roure, N., Sancho, E. E., Moreno, C. R., Silva, M., Marqueze, E. C., Waage, S., Bobko, N., Chernyuk, V., Yavorskiy, Y., Saxvig, I., Sørensen, E., de Mello, M. T., Esteves, A., Teixeira, C., Bittencourt, L. R., Silva, R., Pires, M. L., Mottram, V., Middelton, B., Arendt, J., Amaral, O., Rodrigues, M., Pereira, C., Tavares, I., Baba, K., Honma, S., Honma, K.-I., Yamanaka, Y., Hashimoto, S., Tanahashi, Y., Nishide, S.-Y, Honma, K.-I, Sletten, T., Middleton, B., Lederle, K., Skene, D., Roth, T., Walsh, J., Hogben, A., Ellis, J., Archer, S., von Schantz, M., Chen, N.-H., Wang, P.-C., Chen, C.-W., Lin, Y., Shih, T.-S., Armstrong, S., Redman, J., Stephan, E., David, M., Delanaud, S., Chardon, K., Libert, J.-P., Bach, V., Telliez, F., Reid, K., Jaksa, A., Eisengart, J., Kane, P., Naylor, E., Zee, P., Viola, A. U., de Valck, E., Hofmans, J., Theuns, P., Cluydts, R., Alexander, G., Karel, M., Christina, R., Sohn, I.-K., Cho, I. H., Kim, S. J., Yu, S.-H., Kim, H., Yoo, S. Y., Koh, S.-H., Cho, S.-J., Rotenberg, L., Silva-Costa, A., Griep, R. H., Amely, T., Kennedy, G. A., Pavlis, A., Thompson, B., Pierce, R., Howard, M., Briellmann, R., Venkateswaran, S., Blunden, S., Krawczyk, E., Blake, J., Gururajan, R., Kerr, D., Matuisi, T., Iwasaki, M., Yamasita, N., Iemura, A., Ohya, T., Yanagawa, T., Misa, R., Coleman, G., Conduit, R., Duce, B., Hukins, C., Nyandaiti, Y. W., Bamaki, S., Mohammed, A., Kwajarfa, S., Veeramachaneni, S. P., Murthy, A., Wilson, A., Maul, J., Hall, G., Stick, S., Moseley, L., Gradisar, M., Kurihara, T., Yamamoto, M., Yamamoto, S., Kuranari, M., Sparks, C. B., Bartle, A., Beckert, L., Latham-Smith, F. B., Hilton, J., Whitehead, B., Gulliver, T., Salvini, A., Grahame, S., Swift, M., Laybutt, N., Sharon, D., Mack, C., Hymell, B., Perrine, B., Ideshita, K., Taira, M., Matuo, A., Furutani, M., van Dongen, H., Mott, C., Huang, J.-K., Mollicone, D. J., Mckenzie, F., Dinges, David, Barnes, M., Rochford, P., Churchward, T., O’Donoghue, F., Penzel, T., Fietze, I., Canisius, S., Bekiaris, E., Terrill, P. I., Wilson, S., Suresh, S., Cooper, D., Suzuki, T., Ouchi, K., Moriya, A., Kameyama, K., Takahashi, M., Büttner, A., Rühle, K.-H., Wang, D., Wong, K., Dungan, II, G., Grunstein, R., Davidson, P., Jones, R., Gergely, V., Mashima, K., Miyazaki, S., Tanaka, T., Okawa, M., Yamada, N., Wyner, A., Raizen, D., Galante, R., Ng, A. K., Koh, T. S., Lim, L. L., Puvanendran, K., Peiris, M., Bones, P., Roebuck, T., Ho, S., Szollosi, I., Naughton, M., Williams, G., Parsley, C., Harris, M.-A., Thornton, A., Ruehland, W., Banks, S., Arroyo, S., Carroll, K., Pilmore, J., Stewart, C., Hamilton, G., van Acker, F., Cvetkovic, D., Holland, G., Cosic, I., Tolson, J., Worsnop, C., Cresswell, P., Hart, I., Bouarab, M., Delechelle, E., Drouot, X., Acebo, C., Singh, P., Lakey, T., Schachter, L., Rand, J., Collin, H., Snyder, E., Ma, J., Svetnick, V., Deacon, S., Dana, B., Konstanze, D., Uwe, M., Ingo, F., Thomas, P., Ivar, R., Mackiewicz, M., Shockley, K., Romer, M., Zimmerman, J., Baldwin, D., Jensen, S., Churchill, G., Paigen, B., Imeri, L., Ferrari, L., Bianchi, S., Dossena, S., Garofoli, A., Mangieri, M., Tagliavini, F., Forloni, G., Chiesa, R., Pedrazzoli, M., Pereira, D., Veauny, M., Bodenmann, S., Hohoff, C., Freitag, C., Deckert, J., Rétey, J., Landolt, H.-P., Strohl, K., Price, E., Yamauchi, M., Dostal, J., Feng, P., Han, F., Havekes, R., Novati, A., Hagewoud, R., Barf, P., van Der Borght, K., van Der Zee, E., Meerlo, P., Ruby, P., Caclin, A., Boulet, S., Delpuech, C., Morlet, D., Veasey, S., Aton, S., Jha, S., Coleman, T., Seibt, J., Frank, M., Lack, L., Churches, O., Feng, S. Y. S., Cassaglia, P., Yu, V. Y. H., Walker, A. M., Kohler, M., Kennedy, D., Martin, J., van Den Heuvel, C., Lushington, K., Herron, K., Khurana, C., Sterr, A., Olivadoti, M., Toth, L., Opp, M., Dang-Vu, T., Degueldre, C., Gais, S., Dang-Vu, T. T., Desseilles, M., Philips, C., Chijavadze, E., Babilodze, M., Chkhartishvili, E., Nachkebia, N., Mchedlidze, O., Dzadzamia, S., Griffiths, R., Walker, A., Horovitz, S., Fukunaga, M., Carr, W., Picchioni, D., de Zwart, J., van Gelderen, P., Braun, A., Duyn, J., Hanlon, E. H., Faraguna, U., Vyazovskiy, V., Cirelli, C., Ocampo-Garcés, A., Ibáñez, F., López, S., Vivaldi, E., Torrealba, F., Romanowski, C. P. N., Fenzl, T., Flachskamm, C., Deussing, J., Kimura, M., Tarokh, L., van Reen, E., Dorn, H., Velluti, R., Qu, W.-M., Huang, Z.-L., Hayaishi, O., Pedemonte, M., Drexler, D., Pol-Fernández, D., Bernhardt, V., Lopez, C., Rodriguez-Servetti, Z., Romanowski, C., Polta, S., Yassouridis, A., Abe, T., Takahashi, K., Koyama, Y., Kayama, Y., Lin, J.-S., Sakai, K., Gulia, K., Karashima, A., Shimazaki, M., Katayama, N., Nakao, M., Winsky-Sommerer, R., Knapman, A., Tobler, I., Altena, E., Sanz-Arigita, E., Chang, F.-C., Lu, C.-Y., Yi, P.-L., Hsiao, Y.-Z., Lowden, A., Nilsson, J., Hillert, L., Wiholm, C., Kuster, N., Arnetz, B., Szameitat, A., Shen, S., Daurat, A., Tiberge, M., Sok, N., D’Ortho, M. P. I. A., Karasinsky, P., Kohlmeier, K., Wess, J., Leonard, C., Kristensen, M., Kalinchuk, A., Porkka-Heiskanen, T., Mccarley, R. W., Basheer, R., Aizawa, R., Sunahara, H., Abe, S.-I., Iwaki, S., Houjyou, M., Satoh, M., Suda, H., Kheirandish-Gozal, L., Gozal, D., Walker, P., Noa, A., O’Driscoll, D., Ng, M., Yang, J., Davey, M., Anderson, V., Trinder, J., Horne, R., Sands, S., Kelly, V., Sia, K., Edwards, B., Skuza, E., Davidson, M., Berger, P. H. I. L. I. P., Wilkinson, M., Sánchez-Narváez, F., Gutiérrez, R., Camacho, L., Anaya, E., García-Campos, E., Labra, A., Domínguez, G., García-Polo, L., Haro, R., Verginis, N., Nixon, G., Baumert, M., Pamula, Y., Mihai, R., Wawurszak, M., Smith, N., Yiallourou, S., Andrew Ramsden, C., Williamson, B., Blecher, G., Teng, A., Dakin, C. Y. N., Yuil, M., Harris, M., Sadasivam, S., Bennison, J., Galland, B., Dawes, P., Taylor, B., Norman, M., Edwards, N., Harrison, H., Kol, C., Sullivan, C., Valladares, E., Macey, P., Kumar, R., Woo, M., Harper, R., Alger, J., Mcnamara, D., Tang, J., Goh, A., Teoh, O. H., Chiang, W. C., Chay, O. M., Marie Salvini, A., Riben, C., Blanck, A.-S., Marklund, M., Tourneux, P., Cardot, V., Leke, A., Iqbal, S. M., (Gus) Cooper, D., Witmans, M., Rodger, K., Thevasagayam, R., El-Hakim, H., Hill, C. M., Baya, A., Bucks, R., Kirkham, F., Virues-Ortega, J., Baldeweg, T., Paul, A., Hogan, A., Goodwin, J., Silva, G., Kaemingk, K., Sherrill, D., Morgan, W., Fregosi, R., Quan, S., Evans, C., Maclean, J., Waters, K., Fitzsimmons, D., Hayward, P., Fitzgerald, D., Terrill, G., O’Connell, A., Vannan, K., Richardson, H., Poluektov, M., Levin, I., Snegodskaya, M., Kolosova, N., Geppe, N., Nixon, G. Michelle, Thompson, J., Yhan, D., Becroft, D., Clark, P., Robinson, E., Waldie, K., Wild, C., Black, P., Stone, K., Britton, W., Chaves, Claudia, Tinoco, C., Goncalves, C., Ferreira, E., Santos, H., Boloto, J., Duarte, L., Paine, S., Wright, H., Slater, A., Rosen, G., Telliez, Frédéric, Djeddi, D., Kongolo, G., Degrugilliers, L., Horton, J., Buscemi, N., Vandermeer, B., Owens, J., Klassen, T., Gordon, J., King, N., Tripp, G., Oka, Y., Suzuki, S., de Lemos, M. C., Gonzaga, F. G., Shah, M. L., Bittencourt, L., Oliveira, L. V. Franco, Elshoff, J.-P., Braun, M., Andreas, J.-O., Strauss, B., Horstmann, R., Ahrweiler, S., Goldammer, N., Wada, M., Matsumoto, N., Rahman, M. D., Xu, X.-H., Makino, Y., Hashimoto, K., Zhang, M., Sastre, J.-P., Buda, C., Anaclet, C., Ohtsu, H., Danober, L., Desos, P., Cordi, A., Roger, A., Jacquet, A., Rogez, N., Thomas, J.-Y., Krentner, M., Boutin, J., Audinot-Bouchez, V., Baumann, C., Valko, P., Uhl, M., Hersberger, M., Rupp, T., Uchiyama, N., Nakamura, N., Konishi, T., Mcgrath, P., Fujiki, N., Tokunaga, J., Iijima, S., Nishino, S., Catherine, B.-R., Lely, F., Ralf, K., Oliver, N., François, J., Francois, J., Cedric, F., Changbin, Q., Patrick, H., Homanics, G., Heussler, H., Norris, R., Pache, D., Charles, B., Mcguire, T., Shelton, J., Bonaventure, P., Kelly, L., Aluisio, L., Lovenberg, T., Atack, J., Dugovic, C., Shapiro, C., Shen, J., Trajanovic, N., Chien, J., Verma, M., Fish, V., Wheatley, J., Amis, T., Alexiou, T., Wild, J., Bjursell, A., Solin, P., Sato, S., Matsubuchi, N., Gingras, M.-A., Labrosse, M., Chevrier, É, Lageix, P., Guay, M.-C., Braun, C., Godbout, R., Fatim, E. H., Loic, D., Stephane, D., Nathalie, L., Stéphane, D., Alain, G., Wiâm, R., Koabyashi, T., Tomita, S., Ishikawa, T., Manadai, O., Arakawa, K., Siato, Y., Bassi, A., Ocampo, A., Estrada, J., Blyton, D., O’Keeffe, K., Galletly, D., Larsen, P., Amatoury, J., Bilston, L., Kairaitis, K., Stephenson, R., Chu, K., Sekiguchi, Y., Suzuki, N., Yasuda, Y., Kodama, T., Honda, Y., Hsieh, K.-C., Lai, Y.-Y., Bannai, M., Kawai, N., Amici, R., Baracchi, F., Cerri, M., Del Sindaco, E., Dentico, D., Jones, C. A., Luppi, M., Martelli, D., Perez, E., Tazaki, M., Katayose, Y., Yasuda, K., Tokuyama, K., Maddison, K., Platt, P., Kirkness, J., Ware, J. C., May, J., Rosenthal, T., Park, G., Guibert, M., Allen, R. W., Cetin, T., Roman, V., Mollicone, D., Crummy, F., Cameron, P., Swann, P., Kossman, T., Taggart, F., Kandala, N.-B., Currie, A., Peile, E., Stranges, S., Marshall, N., Peltonen, M., Stenlof, K., Hedner, J., Sjostrom, L., Anderson, C., Platten, C., Jordan, K., Horne, J., Bjorkum, A., Kluge, B., Braseth, T., Gurvin, I., Kristensen, T., Nybo, R., Rosendahl, K., Nygaard, I., Biggs, S., Dollman, J., Kennedy, J. D., Martin, A. J., Haghighi, K. S., Bakht, N., Hyde, M., Harris, E., Zerouali, Y., Hosein, A., Jemel, B., Dodd, M., Rogers, N., Andersen, M., Martins, R., Alvarenga, T., Antunes, I., Papale, L., Killgore, W. S., Axelsson, J., Lekander, M., Ingre, M., Brismar, K., Dorrian, J., Ferguson, S., Jones, C., Buxton, O., Marcelli, E., Phipps-Nelson, J. O., Teixeira, L. R., de Castro Moreno, C., Turte, S. L., Nagai, R., do Rosário Dias De Oliveira Latorre, M., Marina, F., Paterson, J., Jackson, M., Johnston, P., Papafotiou, K., Croft, R., Dawson, S., Leenaars, C., Sandberg, H., Joosten, R., Dematteis, M., Feenstra, M., Wehrle, R., Rieger, M., Widmann, A., Dietl, T., Philipp, S., Wetter, T., Drummond, S., Czisch, M., Cairns, A., Lebourgeois, M., Harsh, J., Baulk, S., Vakulin, A., Catcheside, P., Antic, N., Mcevoy, D., Orff, H., Salamat, J., Meloy, M. J., Caron, A., Kostela, J., Purnell, M., Feyer, A.-M., Herbison, P., Saaresranta, T., Aittokallio, J., Karppinen, N., Toikka, J., Polo, O., Sallinen, M., Haavisto, M.-L., Hublin, C., Kiti, M., Jussi, V., Mikko, H., Chuah, L., Chee, M., Borges, F., Fischer, F., Moreno, C., Soares, N., Fonseca, M., Smolensky, M., Sackett-Lundeen, L., Haus, E., Nagata, N., Michael, N., Siccoli, M., Rogers, A., Hwang, W.-T., Scott, L., Dean, G., Geissler, E., Ametamey, S., Treyer, V., Wyss, M., Achermann, P., Schubiger, P., Theorell-Haglöw, J., Berne, C., Janson, C., Svensson, M., Lindberg, E., Caruso, H., Avinash, D., Minkel, J., Thompson, C., Wisor, J., Gerashchenko, D., Smith, K., Kuan, L., Pathak, S., Hawrylycz, M., Jones, A., Kilduff, T., Bergamo, C., Ecker, A., William, J., Niyogi, S., Coble, M., Goel, N., Lakhtman, L., Horswill, M., Whetton, M., Chambers, B., Signal, L., van Den Berg, M., Gander, P., Polotsky, V., Savransky, V., Bevans, S., Nanayakkara, A., Li, J.-G., Smith, P., Torbenson, M., Stockx, E., Brodecky, V., Berger, P., Chung-Mei Lam, J., Rial, R., Roca, C., Garau, C., Akaarir, M., Mccoy, J., Ward, C., Connolly, N., Tartar, J., Brown, R., Carberry, J., Bradford, A., O’Halloran, K., Mcguire, M., Nacher, M., Serrano-Mollar, A., Navajas, D., Farre, R., Montserrat, J., Fenik, V., Rukhadze, I., Kubin, L., Sivertsen, B., Overland, S., Mykletun, A., Czira, M., Fornádi, K., Lindner, A., Szeifert, L., Szentkirályi, A., Mucsi, I., Molnár, M., Novák, M., Zoller, R., Chin, K., Takegami, M., Oga, T., Nakayama-Asida, Y., Wakamura, T., Mishima, M., Fukuhara, S., Shepherd, K., Keir, G., Rixon, K., Makarie-Rofail, L., Unger, G., Svanborg, E., Harder, L., Sarberg, M., Broström, A., Josefsson, A., Herrera, A., Aguilera, L., Diaz, M., Fedson, A., Hung, J., Williams, C., Love, G., Middleton, S., Vermeulen, W., Middleton, P., Steinfort, D., Goldin, J., Eritaia, J., Dionysopoulos, P., Irving, L., Ciftci, T. U., Kokturk, O., Demirtas, S., Kanbay, A., Tavil, Y., Bukan, N., Demritas, S., Olsen, S., Douglas, J., Oei, T., Williams, S., Leung, S., Starmer, G., Lee, R., Chan, A., Dungan, G., Cistulli, P., Zeng, B., Bansal, A., Patial, K., Vijayan, V. K., Sonka, K., Fialova, L., Svarcova, J., Volna, J., Jiroutek, P., Pretl, M., Bartos, A., Hasegawa, R. A., Sasanabe, R., Nomura, A., Morita, M., Hori, R., Ohkura, Y., Shiomi, T. T., Collins, A., Jerums, G., Hare, D., Panagiotopoulos, S., Weatherhead, B., Bailey, M., Neil, C., Goldsworthy, U., Hill, C., Valencia-Flores, M., Resendiz, M., Juarez, S., Castano, A., Santiago, V., Aguilar, C., Ostrosky, F., Krum, H., Kaye, D., Neves, C., Decio, M., Monteiro, M., Cintra, F., Poyares, D., Viegas, C., Silva, C., Oliveira, H., Peixoto, T., Mikami, A., Watanabe, T., Kumano-Go, T., Adachi, H., Sugita, Y., Takeda, M., Oktay, B., Firat, H., Akbal, E., Ardic, S., Paim, S., Santos, R., Barrreto, A., Whitmore, H., Imperial, J., Temple, K., Rue, A., Hoffman, L., Liljenquist, D., Kazsa, K., Pavasovic, M., Copland, J., Ho, M., Jayamaha, J., Peverill, R., Hii, S., Hensley, M., Rowland, S., Windler, S., Johansson, M., Eriksson, P., Peker, Y., Råstam, L., Lindblad, U., Grote, L., Zou, D., Radlinski, J., Eder, D., Plens, C. M., Garcia Gonzaga, F. M., Farias Sa, P., Franco Oliveira, L. V., Faria Sa, P., Yoon, I.-Y., Chung, S., Hee Lee, C., Kim, J.-W., Faludi, B., Wang, X., Li, Q., Wan, H., Li, M., Pallayova, M., Donic, V., Tomori, Z., Ioacara, S., Olech, T., Mccallum, C., Bowes, M., Bowes, J., Chia, M., Gilbert, S. S., Sajkov, D., Teichtahl, H., Stevenson, I., Cunnington, D., Kalman, J., Szaboova, E., Higami, S., Kryger, M., Higami, Y., Suzuki, C., Kitano, H., Carin, S., Olof, S., Yngve, G., Gösta, B., Carlberg, B., Stenlund, H., Franklin, K. A., Oliveira, A., Vasconcelos, L., Martinez, D., Goncalves, S. C., Gus, M., Silva, E. O. A., Fuchs, S. C., Fuchs, F. D., Li, A., Au, J., Ho, C., Sung, R., Wing, Y., Tada, H., Terada, N., Togawa, K., Nakagawa, Y., Kishida, K., Kihara, S., Hirata, A., Sonoda, M., Nishizawa, H., Nakamura, T., Shimomura, I., Funahashi, T., Andrewartha, P., Sasse, A., Becker, M., Troester, N., Olschewski, H., Lisamayerkard, L., Glos, M., Blau, A., Peter, J.-G., Chesworth, W., Wilson, G., Piper, A., Chuang, L.-P., Lin, S.-W., Wang, C.-J., Li, H.-Y., Chou, Y.-T., Fu, J.-Y., Liao, Y.-F., Tsai, Y.-H., Chan, K., Laks, L., Nishibayashi, M., Miyamoto, M., Miyamoto, T., Hirata, K., Hoever, P., De Haas, S., Chiossi, E., Van Gerven, J., Dingemanse, J., Winkler, J., Cavallaro, M., Narui, K., Kasai, T., Dohl, T., Takaya, H., Kawana, F., Ueno, K., Panjwani, U., Thakur, L., Anand, J. P., Banerjee, P. K., Leigh, M., Paduch, A., Armstrong, J., Sampson, D., Kotajima, F., Mochizuki, T., Lorr, D., Harder, H., Chesworth, M., Becker, H., Abd-Elaty, N. M., Elprince, M., Ismail, N., Elserogi, W., Yeo, A., George, K., Thomson, K., Stadler, D., Bradley, J., Paul, D., Schwartz, A., Hagander, L., Harlid, R., Hultcrantz, E., Haraldsson, P., Cho, J.-G., Narayan, J., Nagarajah, M., Perri, R., Johnson, P., Burgess, K., Chau, N., Mcevoy, R. D., Arnardottir, E. S., Thorleifsdottir, B., Olafsson, I., Gislason, T., Tsuiki, S., Fujimatsu, S., Munezawa, T., Sato, Y., Subedi, P., Ainslie, P., Topor, Z., Whitelaw, W., Chan, M., So, H., Lam, H., Ng, S., Chan, I., Lam, C., Saigusa, H., Higurashi, N., He, Z. M., Cui, X. C., Li, J., Dong, X., Lv, Y., Zhou, M., Han, X., An, P., Wang, L., Macey, P. M., Serber, S., Cross, R., Yan-Go, F., Marshall, M., Rees, D., Lee, S. H., Ho Cho, J. I., Shin, C., Lee, J. Y., Kwon, S. Y., Kim, T.-H., Vedam, H., Barnes, D., Walter, H., Karin, J., Hermann, P., Belyavskiy, E., Galitsyn, P., Arbolishvili, G., Litvin, A., Chazova, I., Mareev, V., Ramar, K., Khan, A., Gay, P., Strömberg, A., Ulander, M., Fridlund, B., Mårtensson, J., Yee, B., Desai, A., Buchanan, P., Crompton, R., Melehan, K., Wong, P., Tee, A., Ng, A., Darendeliler, M. A., Ye, L., Maislin, G., Hurley, S., Mccluskey, S., Weaver, T., Yun, C.-H., Ji, K.-H., Ahn, J. Y., Lee, H.-W., Zhang, X., Yin, K., Zhaofang, G., Chong, L., Navailles, B., Zenou, E., Cheze, L., Pignat, J.-C., Tang, T., Remmers, J., Vasilakos, K., Denotti, A., Gilholme, J., Castronovo, V., Marelli, S., Aloia, M., Fantini, M. L., Kuo, T., Manconi, M., Zucconi, M., Ferini-Strambi, L., Livia Fantini, M., Giarolli, L., Oldani, A., Lee, Y., Trenell, M., Berend, N., Wang, M., Liang, Z., Lei, F., Komada, I., Nishikawa, M., Sriram, K., Mignone, L., Antic, R., Fujiwara, K., Beaudry, M., Gauthier, L., Laforte, M., Lavigne, G., Wylie, P., Orr, W., Grover, S., Geisler, P., Engelke, E., Cossa, G., Veitch, E., Brillante, R., Mcardle, N., Murphy, M., Singh, B., Gain, K., Maguire, C., Mutch, S., Brown, S., Asciuto, T., Newsam, C., Fransson, A., Ísacsson, G., Tsou, M.-C., Hsu, S.-P., Almendros, I., Acerbi, I., Vilaseca, I., Dcruz, O., Vaughn, B., Muenzer, J., Lacassagne, L., Montemayor, T., Roch-Paoli, J., Qian, J., Petocz, P., Chan, M. R., Munro, J., Zimmerman, M., Stanchina, M., Millman, R., Cassel, W., Ploch, T., Loh, A., Koehler, U., Jerrentrup, A., Greulich, T., Doyle, G., Pascoe, T., Jorgensen, G., Baglioni, C., Lombardo, C., Espie, C., Violani, C., Edell-Gustafsson, U., Swahn, E., Ejdeback, J., Tygesen, H., Johansson, A., Neckelmann, D., Hilde Nordhus, I., Zs-Kovács, Á., Vámos, E., Zs-Molnár, M., Maisuradze, L., Gugushvili, J., Darchia, N., Gvilia, I., Lortkipanidze, N., Oniani, N., Wang-Weigand, S., Mayer, G., Roth-Schechter, B., Hsu, S.-C., Yang, C.-M., Liu, C.-Y., Ito, H., Omvik, S., Nordhus, I. H., Farber, R., Scharf, M., Harris-Collazo, R., Pereira, J., Andras, S., Ohayon, M., David, B., Morgan, K., Voorn, T., Vis, J., Kuijer, J., Fortier-Brochu, E., Beaulieu-Bonneau, S., Ivers, H., Morin, C., Beaulieu-Benneau, S., Harris, J., Bartlett, D., Paisley, L., Moncada, S., Toelle, B., Bonnet, M. H., Arand, D., Bonnet, J., Bonnet, M., Doi, Y., Edéll-Gustafsson, U., Strijers, R., Fernando, A., Arroll, B., Warman, G., Funakura, M., Shikano, S., Unemoto, Y., Fujisawa, M., Hong, S.-C., Jeong, J.-H., Shin, Y.-K., Han, J.-H., Lee, S.-P., Lee, J.-H., Mignot, E., Nakajima, T., Hayashida, K., Honda, M., Ardestani, P., Etemadifar, M., Nejadnik, H., Maghzi, A. H., Basiri, K., Ebrahimi, A., Davoodi, M., Peraita-Adrados, R., Vicario, J. L., Shin, H.-B., Marti, I., Carriero, L., Fulda, S., Beitinger, P., Pollmacher, T., Lam, J. S. P., Fong, S. Y. Y., Tang, N. L. S., Ho, C. K. W., Li, A. M. C., Wing, Y. K., Guilleminault, C., Black, J., Wells, C., Kantor, S., Janisiewicz, A., Scammell, T., Tanaka, S., Smith, A., Neufing, P., Gordon, T., Fuller, P., Gompf, H., Pedersen, N., Saper, C., Lu, J., Sasai, T., Donjacour, C., Fronczek, R., Le Cessie, S., Lammers, G. J., van Dijk, J. G., Hayashi-Ogawa, Y., Okuda, M., Lam, V. K.-H., Chen, A. L., Ho, C. K.-W., Wing, Y.-K., Lehrhaft, B., Brilliante, R., van Der Zande, W., Overeem, S., van Dijk, G., Lammers, J. G., Opazo, C. J., Jeong, D.-U., Sung, Y. H., Lyoo, I. K., Takahashi, Y., Murasaki, M., Bloch, K., Jung, H., Dahab, M. M., Campos, T. F., Mccabe, S., Maravic, K., Wiggs, L., Connelly, V., Barnes, J., Saito, Y., Ogawa, M., Murata, M., Nadig, U., Rahman, A., Aritake, K., D’Cruz, O., Suzuki, K., Kaji, Y., Takekawa, H., Nomura, T., Yasui, K., Nakashima, K., Bahammam, A., Rab, M. G., Owais, S., Alsuwat, K., Hamam, K., Zs, M., Boroojerdi, B., Giladi, N., Wood, D., Sherman, D., Chaudhuri, R., Partinen, M., Abdo, F., Bloem, B., Kremer, B., Verbeek, M., Cronlein, T., Mueller, U., Hajak, G., Zulley, J., Namba, K., Li, L., Mtsuura, M., Kaneita, Y., Ohida, T., Cappeliez, B., Moutrier, R., De, S., Dwivedi, S., Chambers, D., Gabbay, E., Watanabe, A., Valle, C., Kauati, A., Watanabe, R., Chediek, F., Botte, S., Azevedo, E., Kempf, J., Cizza, G., Torvik, S., Brancati, G., Smirne, N., Bruni, A., Goff, E., Freilich, S., Malaweera, A., Simonds, A., Mathias, C., Morrell, M., Rinsky, B., Fonarow, G., Gradinger, F. P., Boldt, C., Geyh, S., Stucki, A., Dahlberg, A., Michel, F., Savard, M.-H., Savard, J., Quesnel, C., Hirose, K., Takahara, M., Mizuno, K., Sadachi, H., Nagashima, Y., Yada, Y., Cheung, C.-F., Lau, C., Lai, W., Sin, K., Tam, C., Hellgren, J., Omenaas, E., Gíslason, T., Jögi, R., Franklin, K., Torén, K., Wang, F., Kadono, M., Shigeta, M., Nakazawa, A., Ueda, M., Fukui, M., Hasegawa, G., Yoshikawa, T., de Niet, G., Tiemens, B., Lendemeijer, B., Hutschemaekers, G., Gauthier, A.-K., Chevrette, T., Chevrier, E., Bouvier, H., Parry, B., Meliska, C., Nowakowski, S., Lopez, A., Martinez, F., Sorenson, D., Lien, M. L., Lattova, Z., Maurovich-Horvat, E., Nia, S., Pollmächer, T., Poulin, J., Chouinard, S., Stip, E., Guillem, F., Venne, D., Caouette, M., Lamont, M.-E., Lázár, A., Lázár, Z., Bíró, A., Gyõri, M., Tárnok, Z., Prekop, C., Gádoros, J., Halász, P., Bódizs, R., Okun, M., Hanusa, B., Hall, M., Wisner, K., Pereira, M., Kumar, R. A. J. E. S. H., Macey, P. A. U. L., Woo, M. A. R. Y., Serber, S. T. A. C. Y., Valladares, E. D. W. I. N., Harper, R. E. B. E. C. C. A., Harper, R. O. N. A. L. D., Puttonen, S., Härmä, M., Vahtera, J., Kivimäki, M., Lamarche, L., Hemmeter, U. M., Thum, A., Rocamora, R., Giesler, M., Haag, A., Dodel, R., Krieg, J. C., Shechter, A., L’Esperance, P., Boivin, D. B., Vu, M.-T., and Richards, H.
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- 2007
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3. Orexin Receptor Antagonism, a New Sleep-Enabling Paradigm: A Proof-of-Concept Clinical Trial
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Hoever, P, Dorffner, G, Beneš, H, Penzel, T, Danker-Hopfe, H, Barbanoj, M J, Pillar, G, Saletu, B, Polo, O, Kunz, D, Zeitlhofer, J, Berg, S, Partinen, M, Bassetti, C L, Högl, B, Ebrahim, I O, Holsboer-Trachsler, E, Bengtsson, H, Peker, Y, Hemmeter, U-M, Chiossi, E, Hajak, G, and Dingemanse, J
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- 2012
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4. Orexin Receptor Antagonism, a New Sleep-Promoting Paradigm: An Ascending Single-Dose Study With Almorexant
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Hoever, P, de Haas, S, Winkler, J, Schoemaker, R C, Chiossi, E, van Gerven, J, and Dingemanse, J
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- 2010
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5. Family study of epilepsy in first degree relatives: data from the Italian Episcreen Study
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BIANCHI, A., VIAGGI, S., and CHIOSSI, E.
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- 2003
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6. Bosentan shows persistent benefit in functional class and exercise capacity amongst Eisenmenger patients in the BREATHE-5 open label extension study
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Gatzoulis MA, Beghetti m, Granton J, Berger R, Lauer A, Chiossi E, Landzberg M.J., GALIE', NAZZARENO, Gatzoulis MA, Beghetti m, Galie N, Granton J, Berger R, Lauer A, Chiossi E, and Landzberg MJ.
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- 2006
7. Breathe-5: Bosentan improves hemodynamics and exercise capacity in the first randomized placebo-controlled trial in Eisenmenger physiology
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GALIE', NAZZARENO, Beghetti M, Gatzonlis N, Granton J, Berger R, Lauer A, Chiossi E, Landzberg M., IRWIN RS, Galie N, Beghetti M, Gatzonlis N, Granton J, Berger R, Lauer A, Chiossi E, and Landzberg M
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- 2005
8. Bosentan therapy in patients with eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study.
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Galiè N, Beghetti M, Gatzoulis MA, Granton J, Berger RM, Lauer A, Chiossi E, Landzberg M, and Bosentan Randomized Trial of Endothelin Antagonist Therapy-5 (BREATHE-5) Investigators
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- 2006
9. Longer-term bosentan therapy improves functional capacity in Eisenmenger syndrome: Results of the BREATHE-5 open-label extension study
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Michael A, Gatzoulis, Maurice, Beghetti, Nazzareno, Galiè, John, Granton, Rolf M F, Berger, Andrea, Lauer, Eleonora, Chiossi, Michael, Landzberg, Dorothy D, Pearson, Faculteit Medische Wetenschappen/UMCG, Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), Gatzoulis MA., Beghetti M., Galiè N., Granton J., Berger RM., Lauer A., Chiossi E., and Landzberg M.
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Male ,Eisenmenger Complex/drug therapy/physiopathology ,Placebo-controlled study ,Hemodynamics ,PLACEBO-CONTROLLED TRIAL ,PULMONARY-ARTERIAL-HYPERTENSION ,law.invention ,DOUBLE-BLIND ,Randomized controlled trial ,law ,pulmonary arterial hypertension ,Sulfonamides ,ddc:618 ,Exercise Tolerance ,DEATH ,Middle Aged ,Treatment Outcome ,Anesthesia ,SURVIVAL ,Arterial blood ,Female ,Cardiology and Cardiovascular Medicine ,PROSTACYCLIN ANALOG ,medicine.drug ,Adult ,RECEPTOR ANTAGONIST BOSENTAN ,endothelin receptor antagonism ,Drug Administration Schedule ,Double-Blind Method ,medicine ,Humans ,PHYSIOLOGY ,Antihypertensive Agents ,Aged ,Sulfonamides/administration & dosage ,Vascular disease ,business.industry ,Vascular Resistance/drug effects ,Eisenmenger syndrome ,Bosentan ,ADULTS ,Eisenmenger Complex ,medicine.disease ,Pulmonary hypertension ,respiratory tract diseases ,Vascular Resistance ,Antihypertensive Agents/administration & dosage ,business - Abstract
BACKGROUND: Bosentan, an oral endothelin ET(A)/ET(B) receptor antagonist, improves hemodynamics and exercise capacity in patients with Eisenmenger syndrome but longer-term effects are unknown. This study investigated the efficacy and safety of bosentan up to 40 weeks in these patients.METHODS: Following the 16-week, double blind, placebo-controlled BREATHE-5 study of bosentan in patients with Eisenmenger syndrome, an open-label extension (OLE) was performed. Patients who completed BREATHE-5 received bosentan for an additional 24 weeks (62.5 mg b.i.d. for 4 weeks, then 125 mg b.i.d.) and were analyzed in two groups; ex-placebo and ex-bosentan, according to BREATHE-5 treatment.RESULTS: Thirty-seven patients with Eisenmenger syndrome who participated in BREATHE-5 were included in the OLE. At week 24, the 6-minute walk distance (mean+/-SE) increased from OLE baseline for the ex-placebo (+33.2+/-23.9 m) and ex-bosentan group (+6.7+/-10.0 m). The overall improvement from baseline of BREATHE-5 was +61.3+/-8.1 m (95% confidence interval: [44.7, 78.0]) for the ex-bosentan group. WHO functional class was improved in both groups. Bosentan did not reduce systemic arterial blood oxygen saturation; safety profile was comparable to previous trials.CONCLUSIONS: In conclusion, these longer follow-up data support the efficacy and safety profile reported in the preceding BREATHE-5 study of bosentan treatment of Eisenmenger syndrome, challenging the notion that pulmonary vascular disease and severe functional impairment in these patients are not amenable to therapy.
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- 2008
10. Atrial septal defects versus ventricular septal defects in BREATHE-5, a placebo-controlled study of pulmonary arterial hypertension related to Eisenmenger's syndrome: a subgroup analysis
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Rolf M. F. Berger, Michael J. Landzberg, Michael A. Gatzoulis, Maurice Beghetti, Andrea Lauer, Eleonora Chiossi, Nazzareno Galiè, John Granton, Faculteit Medische Wetenschappen/UMCG, Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), Berger RM, Beghetti M, Galiè N, Gatzoulis MA, Granton J, Lauer A, Chiossi E, and Landzberg M.
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Heart Septal Defects, Ventricular ,Male ,Pulmonary Circulation ,Ventricular septal defect ,Pulmonary arterial hypertension ,Heart Septal Defects, Atrial ,ENDOTHELIN ,Oximetry ,Netherlands ,Ontario ,Heart septal defect ,Sulfonamides ,Eisenmenger's syndrome ,VASCULAR-DISEASE ,Middle Aged ,CONGENITAL HEART-DISEASE ,medicine.anatomical_structure ,Treatment Outcome ,Italy ,Anesthesia ,Cardiology ,Atrial septal defect ,SURVIVAL ,Female ,Cardiology and Cardiovascular Medicine ,Switzerland ,medicine.drug ,Adult ,medicine.medical_specialty ,Canada ,Hypertension, Pulmonary ,Atrial septal defects ,Double-Blind Method ,Internal medicine ,BREATHE-5 ,medicine ,Humans ,Pulmonary Wedge Pressure ,Pulmonary wedge pressure ,Exercise ,ANTAGONIST BOSENTAN ,Antihypertensive Agents ,business.industry ,Hemodynamics ,Bosentan ,ADULTS ,Eisenmenger Complex ,medicine.disease ,Pulmonary hypertension ,United Kingdom ,Eisenmenger syndrome ,Vascular resistance ,Vascular Resistance ,business ,Boston - Abstract
BACKGROUND: Eisenmenger's syndrome (ES) is the most advanced form of pulmonary arterial hypertension related to congenital heart disease. Evolution of pulmonary vascular disease differs markedly between patients with atrial septal defects (ASD) versus ventricular septal defects (VSD), potentially affecting response to treatment. We compared the effects of bosentan and placebo in patients with isolated ASD (ASD subgroup) versus patients with isolated VSD or both defects (VSD subgroup).METHODS: Post-hoc analysis of a 16-week, multicenter, randomized, double-blind, placebo-controlled trial was performed. Fifty-four patients (13: ASDs, 36: VSDs, 5: VSD+ASD) were randomized to bosentan 62.5 mg bid for four weeks (uptitrated to 125 mg bid thereafter) or placebo. Main outcome measures were: indexed pulmonary vascular resistance (PVRi), exercise capacity, mean pulmonary artery pressure (mPAP), pulmonary blood flow index (Qpi), and changes in oxygen saturation (SpO₂).RESULTS: Placebo-corrected median (95% CI) treatment effects on PVRi were -544.0 dyn·s·cm⁻⁵ (-1593.8, 344.7) and -436.4 dyn·s·cm⁻⁵ (-960.0, 167.0) in the ASD and VSD subgroups, respectively. Effects of bosentan on exercise capacity and mPAP were similar in both subgroups. No changes in SpO₂ or Qpi were observed in either bosentan or placebo subgroups.CONCLUSIONS: Improvements in exercise capacity and cardiopulmonary hemodynamics, without desaturation, were observed in ES patients with both ASDs and VSDs. Although not reaching statistical significance, improvements were similar to those in the BREATHE-5 analyses, suggesting that the location of septal defects is not a key determinant of treatment response. These data further support the use of bosentan for the treatment of ES, independent of shunt location.
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- 2008
11. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial
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Hikmet Al-Hiti, Marius M. Hoeper, Pavel Jansa, Gmb Meyer, Gérald Simonneau, Lewis J. Rubin, Andjela Kusic-Pajic, Nazzareno Galiè, Eleonora Chiossi, Galiè N, Rubin Lj, Hoeper M, Jansa P, Al-Hiti H, Meyer G, Chiossi E, Kusic-Pajic A, and Simonneau G.
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Hypertension, Pulmonary ,Walking ,Placebo ,Severity of Illness Index ,law.invention ,Double-Blind Method ,Randomized controlled trial ,law ,Internal medicine ,Humans ,Medicine ,Antihypertensive Agents ,Sulfonamides ,business.industry ,Endothelin receptor antagonist ,Respiratory disease ,Bosentan ,General Medicine ,Middle Aged ,medicine.disease ,Pulmonary hypertension ,Surgery ,Clinical trial ,Treatment Outcome ,medicine.anatomical_structure ,Vascular resistance ,Cardiology ,Female ,Vascular Resistance ,business ,medicine.drug - Abstract
Treatments for pulmonary arterial hypertension have been mainly studied in patients with advanced disease (WHO functional class [FC] III and IV). This study was designed to assess the effect of the dual endothelin receptor antagonist bosentan in patients with WHO FC II pulmonary arterial hypertension.Patients with WHO FC II pulmonary arterial hypertension aged 12 years or over with 6-min walk distance of less than 80% of the normal predicted value or less than 500 m associated with a Borg dyspnoea index of 2 or greater were enrolled in this double-blind, placebo-controlled, multicentre trial. 185 patients were randomly assigned to receive bosentan (n=93) or placebo (n=92) for the 6-month double-blind treatment period via a centralised integrated voice recognition system. Primary endpoints were pulmonary vascular resistance at month 6 expressed as percentage of baseline and change from baseline to month 6 in 6-min walk distance. Analyses of the primary endpoints were done with all randomised patients who had a valid baseline assessment and an assessment or an imputed value for month 6. This trial was registered with ClinicalTrials.gov, number NCT00091715.Analyses were done with 168 patients (80 in the bosentan group, 88 in the placebo group) for pulmonary vascular resistance and with 177 (86 and 91) for 6-min walking distance. At month 6, geometric mean pulmonary vascular resistance was 83.2% (95% CI 73.8-93.7) of the baseline value in the bosentan group and 107.5% (97.6-118.4) of the baseline value in the placebo group (treatment effect -22.6%, 95% CI -33.5 to -10.0; p0.0001). Mean 6-min walk distance increased from baseline in the bosentan group (11.2 m, 95% CI -4.6 to 27.0) and decreased in the placebo group (-7.9 m, -24.3 to 8.5), with a mean treatment effect of 19.1 m (95% CI 3.6-41.8; p=0.0758). 12 (13%) patients in the bosentan group and eight (9%) in the placebo group reported serious adverse events, the most common of which were syncope in the bosentan group and right ventricular failure in the placebo group.Bosentan treatment could be beneficial for patients with WHO FC II pulmonary arterial hypertension.
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- 2008
12. Orexin receptor antagonism: an ascending multiple-dose study with almorexant.
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Hoever P, de Haas SL, Dorffner G, Chiossi E, van Gerven JM, and Dingemanse J
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- Adolescent, Adult, Brain Waves drug effects, Dose-Response Relationship, Drug, Double-Blind Method, Electroencephalography drug effects, Female, Humans, Male, Orexin Receptors, Polysomnography drug effects, Psychomotor Performance drug effects, Sleep Stages drug effects, Acetamides adverse effects, Acetamides pharmacokinetics, Acetamides pharmacology, Hypnotics and Sedatives adverse effects, Hypnotics and Sedatives pharmacokinetics, Hypnotics and Sedatives pharmacology, Isoquinolines adverse effects, Isoquinolines pharmacokinetics, Isoquinolines pharmacology, Receptors, G-Protein-Coupled antagonists & inhibitors, Receptors, Neuropeptide antagonists & inhibitors
- Abstract
The objectives of this study were to investigate the multiple-dose tolerability, safety, pharmacokinetics, and pharmacodynamics of the dual orexin receptor antagonist almorexant. Healthy subjects received daily doses of almorexant (100, 200, 400 or 1000 mg) or placebo in the morning for four days followed by two days with evening administration (Days 5-6). Each dose level was investigated in a new group of 10 subjects (eight active, two placebo, 1:1 sex). Dose-dependent increases in frequency and intensity were observed for somnolence and other adverse events. Pharmacokinetics at steady state showed rapid absorption, low concentrations eight hours post-dose, and minimal accumulation. Following evening, administration absorption was delayed and C(max) decreased. Almorexant at 400 and 1000 mg administered in the morning reduced vigilance, alertness, visuomotor coordination, and motor coordination assessed in a psychometric test battery. Polysomnography recordings following evening administration showed a trend towards shorter latency to sleep stages 3 and 4, and shorter latency to, and longer time in, rapid-eye-movement sleep at higher doses when compared to placebo. Whether these findings in healthy subjects translate into relevant sleep-enabling effects in insomnia patients needs to be investigated in future studies.
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- 2012
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13. Hemodynamics and pharmacokinetics of tezosentan, a dual endothelin receptor antagonist, in patients with cirrhosis.
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Lebrec D, Bosch J, Jalan R, Dudley FJ, Jessic R, Moreau R, Garcia-Pagan JC, Mookerjee RP, Chiossi E, Van Giersbergen PL, Kusic-Pajic A, and Dingemanse J
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- Antihypertensive Agents adverse effects, Antihypertensive Agents blood, Antihypertensive Agents pharmacokinetics, Antihypertensive Agents therapeutic use, Double-Blind Method, Endothelin-1 blood, Female, Heart Rate drug effects, Humans, Hypertension, Portal etiology, Infusions, Parenteral, Liver blood supply, Liver drug effects, Liver physiopathology, Liver Cirrhosis blood, Liver Cirrhosis virology, Liver Cirrhosis, Alcoholic drug therapy, Liver Cirrhosis, Alcoholic physiopathology, Male, Metabolic Clearance Rate, Middle Aged, Pyridines adverse effects, Pyridines blood, Pyridines pharmacokinetics, Severity of Illness Index, Splanchnic Circulation drug effects, Tetrazoles adverse effects, Tetrazoles blood, Tetrazoles pharmacokinetics, Vasodilator Agents adverse effects, Vasodilator Agents blood, Vasodilator Agents pharmacokinetics, Endothelin Receptor Antagonists, Hemodynamics drug effects, Hypertension, Portal drug therapy, Liver Cirrhosis physiopathology, Pyridines therapeutic use, Tetrazoles therapeutic use, Vasodilator Agents therapeutic use
- Abstract
Purpose: To assess the effect of tezosentan, a parenteral dual ET receptor antagonist, on splanchnic and systemic hemodynamics in patients with cirrhosis. In addition, the safety, pharmacokinetics, and pharmacodynamics of tezosentan were evaluated., Methods: The population consisted of patients with cirrhosis with clinically significant portal hypertension. This was a randomized, double-blind, multicenter study. The patients were randomized 3:1 to tezosentan (3 mg/h for 2-3 h) or placebo. HVPG, hepatic blood flow (HBF, ICG method), and systemic arterial pressures were measured before and after tezosentan administration. Plasma concentrations of tezosentan and ET-1 were determined peripherally and in the hepatic vein., Results: Eighteen patients received tezosentan and six placebo. Baseline clinical, biochemical, and hemodynamic characteristics were balanced between the two groups. There was no significant treatment effect on HVPG. The extraction ratio (0.31), the plasma clearance of ICG (280 ml/min), and the HBF (1,430 ml/min) did not show any relevant changes during the infusion of tezosentan, and there were no differences between placebo- and tezosentan-treated patients. A linear relationship was observed between the maximum-fold increase in ET-1 concentration and the steady-state tezosentan plasma concentration (r = 0.82). There was a strong correlation (r = 0.88) between plasma clearance of ICG and that of tezosentan (10.2 l/h). Arterial pressure and heart rate did not significantly change in either group., Conclusion: In patients with cirrhosis, a 2- to 3-h tezosentan infusion was safe and well tolerated but did not change the HVPG. Tezosentan infusion had no influence on the extraction ratio and plasma clearance of ICG and did not change HBF.
- Published
- 2012
- Full Text
- View/download PDF
14. Atrial septal defects versus ventricular septal defects in BREATHE-5, a placebo-controlled study of pulmonary arterial hypertension related to Eisenmenger's syndrome: a subgroup analysis.
- Author
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Berger RM, Beghetti M, Galiè N, Gatzoulis MA, Granton J, Lauer A, Chiossi E, and Landzberg M
- Subjects
- Adult, Bosentan, Boston, Canada, Double-Blind Method, Eisenmenger Complex physiopathology, Exercise, Female, Heart Septal Defects, Atrial physiopathology, Heart Septal Defects, Ventricular physiopathology, Hemodynamics drug effects, Humans, Hypertension, Pulmonary physiopathology, Italy, Male, Middle Aged, Netherlands, Ontario, Oximetry, Pulmonary Circulation drug effects, Pulmonary Wedge Pressure drug effects, Switzerland, Treatment Outcome, United Kingdom, Vascular Resistance drug effects, Antihypertensive Agents therapeutic use, Eisenmenger Complex complications, Heart Septal Defects, Atrial complications, Heart Septal Defects, Ventricular complications, Hypertension, Pulmonary drug therapy, Hypertension, Pulmonary etiology, Sulfonamides therapeutic use
- Abstract
Background: Eisenmenger's syndrome (ES) is the most advanced form of pulmonary arterial hypertension related to congenital heart disease. Evolution of pulmonary vascular disease differs markedly between patients with atrial septal defects (ASD) versus ventricular septal defects (VSD), potentially affecting response to treatment. We compared the effects of bosentan and placebo in patients with isolated ASD (ASD subgroup) versus patients with isolated VSD or both defects (VSD subgroup)., Methods: Post-hoc analysis of a 16-week, multicenter, randomized, double-blind, placebo-controlled trial was performed. Fifty-four patients (13: ASDs, 36: VSDs, 5: VSD+ASD) were randomized to bosentan 62.5 mg bid for four weeks (uptitrated to 125 mg bid thereafter) or placebo. Main outcome measures were: indexed pulmonary vascular resistance (PVRi), exercise capacity, mean pulmonary artery pressure (mPAP), pulmonary blood flow index (Qpi), and changes in oxygen saturation (SpO₂)., Results: Placebo-corrected median (95% CI) treatment effects on PVRi were -544.0 dyn·s·cm⁻⁵ (-1593.8, 344.7) and -436.4 dyn·s·cm⁻⁵ (-960.0, 167.0) in the ASD and VSD subgroups, respectively. Effects of bosentan on exercise capacity and mPAP were similar in both subgroups. No changes in SpO₂ or Qpi were observed in either bosentan or placebo subgroups., Conclusions: Improvements in exercise capacity and cardiopulmonary hemodynamics, without desaturation, were observed in ES patients with both ASDs and VSDs. Although not reaching statistical significance, improvements were similar to those in the BREATHE-5 analyses, suggesting that the location of septal defects is not a key determinant of treatment response. These data further support the use of bosentan for the treatment of ES, independent of shunt location., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
15. Effect of the urotensin-II receptor antagonist palosuran on secretion of and sensitivity to insulin in patients with Type 2 diabetes mellitus.
- Author
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Sidharta PN, Rave K, Heinemann L, Chiossi E, Krähenbühl S, and Dingemanse J
- Subjects
- Adult, Aged, Blood Glucose metabolism, Diabetes Mellitus, Type 2 drug therapy, Double-Blind Method, Female, Glucose Clamp Technique, Glucose Tolerance Test, Humans, Insulin blood, Insulin Secretion, Male, Middle Aged, Quinolines therapeutic use, Treatment Outcome, Urea blood, Urea therapeutic use, Blood Glucose drug effects, Diabetes Mellitus, Type 2 blood, Insulin metabolism, Quinolines blood, Receptors, G-Protein-Coupled blood, Urea analogs & derivatives, Urotensins blood
- Abstract
Aims: To investigate the effects of palosuran, a nonpeptidic, potent and selective antagonist of the urotensin-II receptor, on insulin and glucose regulation in 20 diet-treated patients with Type 2 diabetes mellitus in a double-blind, placebo-controlled, randomized, crossover, proof-of-concept study., Methods: After 4 weeks' oral treatment with 125 mg palosuran or placebo b.i.d.,effects on insulin secretion and sensitivity and blood glucose levels were assessed by means of a hyperglycaemic glucose clamp, meal tolerance test, homeostasis model assessment-insulin resistance score, and daily self-monitoring of blood glucose. Plasma concentrations of palosuran were determined for 12 h on the last day of intake., Results: Palosuran did not affect second-phase insulin response (primary end-point) during the hyperglycaemic glucose clamp in comparison with placebo [paired difference of -1.8 microU ml(-1), 95% confidence interval (CI) -7.8, 4.2]. Likewise, no effects of palosuran were detected on the first-phase insulin response, or on insulin secretion and blood glucose levels during the meal tolerance test or on homeostasis model assessment-insulin resistance score. No clinically significant effects on daily blood glucose profiles were observed during the study. Geometric mean C(max) and AUC(tau) (95% CI) and median t(max) (range) in this patient population were 180 ng ml(-1) (125, 260), 581 ng.h ml(-1) (422, 800) and 3.0 h (0.67, 4.3), respectively., Conclusions: The results of this study indicate that antagonism of the urotensin-II system does not influence insulin secretion or sensitivity or daily blood glucose levels in diet-treated patients with Type 2 diabetes.
- Published
- 2009
- Full Text
- View/download PDF
16. Longer-term bosentan therapy improves functional capacity in Eisenmenger syndrome: results of the BREATHE-5 open-label extension study.
- Author
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Gatzoulis MA, Beghetti M, Galiè N, Granton J, Berger RM, Lauer A, Chiossi E, and Landzberg M
- Subjects
- Adult, Aged, Bosentan, Double-Blind Method, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Treatment Outcome, Vascular Resistance drug effects, Antihypertensive Agents administration & dosage, Eisenmenger Complex drug therapy, Eisenmenger Complex physiopathology, Exercise Tolerance, Sulfonamides administration & dosage
- Abstract
Background: Bosentan, an oral endothelin ET(A)/ET(B) receptor antagonist, improves hemodynamics and exercise capacity in patients with Eisenmenger syndrome but longer-term effects are unknown. This study investigated the efficacy and safety of bosentan up to 40 weeks in these patients., Methods: Following the 16-week, double blind, placebo-controlled BREATHE-5 study of bosentan in patients with Eisenmenger syndrome, an open-label extension (OLE) was performed. Patients who completed BREATHE-5 received bosentan for an additional 24 weeks (62.5 mg b.i.d. for 4 weeks, then 125 mg b.i.d.) and were analyzed in two groups; ex-placebo and ex-bosentan, according to BREATHE-5 treatment., Results: Thirty-seven patients with Eisenmenger syndrome who participated in BREATHE-5 were included in the OLE. At week 24, the 6-minute walk distance (mean+/-SE) increased from OLE baseline for the ex-placebo (+33.2+/-23.9 m) and ex-bosentan group (+6.7+/-10.0 m). The overall improvement from baseline of BREATHE-5 was +61.3+/-8.1 m (95% confidence interval: [44.7, 78.0]) for the ex-bosentan group. WHO functional class was improved in both groups. Bosentan did not reduce systemic arterial blood oxygen saturation; safety profile was comparable to previous trials., Conclusions: In conclusion, these longer follow-up data support the efficacy and safety profile reported in the preceding BREATHE-5 study of bosentan treatment of Eisenmenger syndrome, challenging the notion that pulmonary vascular disease and severe functional impairment in these patients are not amenable to therapy.
- Published
- 2008
- Full Text
- View/download PDF
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