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2. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
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Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ, Novo S, Krum H, Varigos J, Siostrzonek P, Sinnaeve P, Gotcheva N, Yong H, Urina-Triana M, Milicic D, Vettus R, Manolis AJ, Wyss F, Sigurdsson A, Fucili A, Veze I, Petrauskiene B, Salvador L, Klemsdal TO, Medina F, Budaj A, Otasevic P, Lainscak M, Seung KB, Commerford P, Donath M, Hwang JJ, Kultursay H, Bilazarian S, East C, Forgosh L, Harris B, Ligueros M, Bohula E, Charmarthi B, Cheng S, Chou S, Danik J, McMahon G, Maron B, Ning M, Olenchock B, Pande R, Perlstein T, Pradhan A, Rost N, Singhal A, Taqueti V, Wei N, Burris H, Cioffi A, Dalseg AM, Ghosh N, Gralow J, Mayer T, Rugo H, Fowler V, Limaye AP, Cosgrove S, Levine D, Lopes R, Scott J, Hilkert R, Tamesby G, Mickel C, Manning B, Woelcke J, Tan M, Manfreda S, Ponce T, Kam J, Saini R, Banker K, Salko T, Nandy P, Tawfik R, O’Neil G, Manne S, Jirvankar P, Lal S, Nema D, Jose J, Collins R, Bailey K, Blumenthal R, Colhoun H, Gersh B, Abreu M, Actis MV, Aiub J, Aiub F, Albisu J, Alvarisqueta A, Avalos V, Barreto M, Berli MA, Blumberg C, Bocanera M, Botta C, Bowen L, Budassi N, Buhlman S, Westberg JC, Carabajal T, Caruso G, Casala J, Cendali G, Coloma G, Berra FC, Cuneo C, Degennaro N, Dellasa M, Diaz M, Dos Santos P, Espinosa V, Facello A, Facello M, Farias E, Fernandez AA, Ferrari V, Pacora FF, Flores GS, Franco M, Gabito A, Viola HG, Garcia F, Garcia Duran R, Garcia Pinna J, Glenny J, Godoy Sanchez M, Grosse A, Guzman P, Hasbani E, Hominal M, Ibañez J, Jure H, Jure D, Vico ML, Liniado G, Luciardi H, Luquez H, Maehara G, Maffei L, Majul C, Mallagray M, Marinaro S, Martinez J, Massaccesi R, De Los Milagros Had M, Azize GM, Montana O, Montenegro E, Morell Y, Muntaner J, Navarrete S, Olmedo M, Paganini M, 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Winkelmann B, Winkler J, Wistuba T, Woehrle J, Wohnlich T, Wolf S, Woyczak D, Wrage P, Zirlik A, Anadiotis A, Chachalis G, Dermitzakis A, Kafarakis P, Kaldara E, Kolokathis F, Kostakou P, Lekakis J, Manolis A, Mantas I, Megalou A, Milkas A, Nanas J, Olympios CD, Patsilinakos S, Perperis A, Poulimenos L, Saloustros I, Tsioufis K, Tsorbatzoglou K, Vardas P, Zarifis I, Aguilar M, Arango JL, Borrayo NA, Corona V, Guerrero A, Guzman I, Haase F, De Krumbach L, Montenegro P, Munoz R, Munoz N, Paniagua A, Solares A, Vogel M, Anita S, Blazsek Z, Decsi K, Fulop T, Hangyal T, Hegedus V, Kalina A, Karakai H, Katona A, Kiss RG, Kovacs A, Laszlo Z, Lupkovics G, Medvegy M, Merkely B, Mihaly N, Nagy AC, Dékány JN, Nikoletta P, Noori E, Penzes J, Poor F, Sarszegi Z, Simay A, Simon J, Szakal I, Szatmarine V, Szocs A, Zilahi Z, Karsai XZ, Andersen K, Sigurdadottir E, Skuladottir F, Abdullakutty J, Abhaichand R, Abhyankar A, Agarwal DK, Aggarwal RK, Ahire N, Awasthi AK, Babu R, Bai A, Bali HK, Banker D, 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Bergholtz T, Blom KB, Boman K, Boström PÅ, Curiac D, Jensen ED, Dahlen G, Davidsson K, Duckert A, Hansson A, Härstedt N, Henriksson A, Olsson GH, Johansson K, Jonsson JE, Knutsson A, Lindholm CJ, Lönnberg I, Lundqvist M, Mellberg L, Moodh J, Mooe T, Olofsson M, Risenfors M, Rönndahl M, Sundelin R, Suorra I, Torgersruud M, Torstensson I, Chang KC, Chen CP, Chen ZC, Chen MH, Cheng SM, Cheng JJ, Fang CY, Ho CJ, Hsieh IC, Huang PH, Huang A, Kuo JY, Lai WT, Lee SC, Li YH, Lin T, Liu HM, Tsai MC, Tsao HM, Tzong L, Ueng KC, Wang YL, Wang HC, Wang CP, Yang CC, Abaci F, Birdane A, Yilmaz MB, Asim Oktay AO, Kan G, Koldas N, Ozcan IT, Sahin M, Sahin T, Saka B, Tekten T, Ucar N, Uresin S, Yigit Z, Arif I, Bakhai A, Baksi A, Blagdon M, Brickman T, Brown N, Burton M, Burton J, Chaggar S, Chung A, Collier D, Covell W, Crawford G, Davies N, Davies M, Dayer M, Doughty A, Duff J, Dwenger E, Fisher J, Fitzpatrick L, Garner K, Glover J, Haughton G, Ilsley M, Ivan P, Voyzey EJ, Keenan S, Kelt T, Knight J, Kondagunta V, Lang C, Lee K, Lim L, Macdonald J, Mathew A, Mckenzie A, Mckibbin A, Michalska A, Pagett K, Pogson A, Price R, Price D, Procter K, Pye M, Redfearn H, Rewbury J, Ryding A, Sattar N, Sharp A, Shaw P, Simpson H, Smith W, Squire I, Storey R, Teenan M, Thomas H, Townend J, Trevelyan J, Wakeling J, Walukiewicz P, Wilkinson S, Zaman A, Acevedo L, Benton J, Abbate A, Aboufakher R, Acampora M, Acampora D, Aceto L, Acevedo B, Acheatel R, Adams M, Adams A, Ahmad I, Ahmed SH, Aish B, Akyea-Djamson A, Al Joundi T, Alcide P, Alfieri A, Alfonso T, Alfrey A, Allen J, Alllison DC, Almaliky T, Amos A, Angiolillo D, Antolick A, Ara M, Aragorn L, Arevalo S, Armas E, Arthur A, Asafu-Adjaye N, Ashcom T, Ashford M, Aslam A, Ather N, Atieh M, Aull L, Ayala M, Azizad M, Backer T, Baehl S, Bailey S, Bair S, Baker C, Ballmajo M, Pieretti HB, Baquero A, Barnett S, Baron S, Bartkowiak A, Bashir K, Beall K, Beauregard LA, Sarah S, Beckett L, Belejchak P, Bendelow T, Bender D, Benjamin S, Berdoff R, 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Lee J, Lee HN, Lee JH, Lee KR, Moon K, Park B, Park C, Tahk S, Yim KH, Yim S, Tase T, Andor M, Aron G, Badea C, Casoinic F, Clocotan M, Coman S, Emil B, Imre BS, Istratoaie O, Liviu C, Maximov D, Militaru C, Minescu B, Istvan KP, Parepa I, Petrescu L, Podoleanu C, Pop CF, Popa V, Popescu E, Radoi M, Sarbu I, Socoteanu E, Socoteanu G, Sorodoc L, Spiridon M, Stanciulescu G, Stefanescu M, Tanaseanu C, Tudoran M, Zdrenghea D, Agafina A, Akatova E, Avdonina N, Balukova E, Barbarash OL, Bartosh L, Boyarkin M, Bulashova O, Burova N, Churina S, Demidova M, Dorogova I, Dovgalevskiy Y, Dovgolis S, Dudarev M, Fitilev S, Gapon L, Gazizianova V, Gordeev I, Ivanov I, Izmozherova N, Kazanskay E, Khirmanov V, Khromtsova O, Konradi A, Kosmacheva E, Kozlova S, Kulibaba E, Kuzin A, Libov I, Lipchenko A, Lozhkina N, Malchikova S, Morozov E, Myslyaeva L, Onuchina E, Palatkina T, Panov A, Parmon E, Petelina T, Repin A, Reznik I, Sazonova E, Sergienko T, Shaposhnik I, Shapovalova Y, Shustov S, Shvarts Y, Skopets I, Skuratova M, Smolenskaya O, Solovev O, Trofimov V, Vasiliev M, Vezikova N, Vozzhaev A, Yakushin S, Zadionchenko V, Apostolovic S, Adjic NC, Ilic I, Ilic S, Nikolic L, Pupic L, Stokuca-Korac N, Antalik L, Bugan V, Csala L, Dokupilova A, Dzupina A, Forgon T, Fulop P, Gonsorcik J, Gyorgyova E, Holoubek D, Horvat P, Kamensky G, Kolikova V, Krupciakova B, Lenner E, Lennerova J, Lukac J, Majercak I, Mancikova I, Micko K, Nociar J, Pales J, Palka J Jr, Poliacik P, Ruffini L, Sabo L, Skubova K, Slanina M, Smik R, Srdos V, Stitova M, Stofkova D, Strbova J, Such S, Toth P, Urgeova L, Vinanska D, Zareczky P, Flezar M, Kovacic D, Marcun R, Zagozen P, Bolsmann C, Commerford P, Conradie C, Dawood SY, Decsi KL, Ebrahim I, Henley L, Horak A, Kapp I, Komati S, Lock E, Maboyi S, Makotoko E, Manga P, Page A, Ramdas S, Ranjith N, Roos J, Talliard C, Ajax K, Al-Khalili F, Assarsson E, Bergholtz T, Blom KB, Boman K, Boström PÅ, Curiac D, Jensen ED, Dahlen G, Davidsson K, Duckert A, Hansson A, Härstedt N, Henriksson A, Olsson GH, Johansson K, Jonsson JE, Knutsson A, Lindholm CJ, Liu B, Lönnberg I, Lundqvist M, Mellberg L, Moodh J, Mooe T, Olofsson M, Risenfors M, Rönndahl M, Sundelin R, Suorra I, Torgersruud M, Torstensson I, Chang KC, Chen CP, Chen ZC, Chen MH, Cheng SM, Cheng JJ, Fang CY, Ho CJ, Hsieh IC, Huang PH, Huang A, Hwang JJ, Kuo JY, Lai WT, Lee SC, Li YH, Lin T, Liu HM, Tsai MC, Tsao HM, Tzong L, Ueng KC, Wang YL, Wang HC, Wang CP, Yang CC, Abaci F, Birdane A, Yilmaz MB, Asim Oktay AO, Kan G, Koldas N, Ozcan IT, Sahin M, Sahin T, Saka B, Tekten T, Ucar N, Uresin S, Yigit Z, Arif I, Bakhai A, Baksi A, Blagdon M, Brickman T, Brown N, Burton M, Burton J, Chaggar S, Chung A, Collier D, Covell W, Crawford G, Davies N, Davies M, Dayer M, Doughty A, Duff J, Dwenger E, Fisher J, Fitzpatrick L, Garner K, Glover J, Haughton G, Ilsley M, Ivan P, Voyzey EJ, Keenan S, Kelt T, Knight J, Kondagunta V, Lang C, Lee K, Lim L, Macdonald J, Mathew A, Mckenzie A, Mckibbin A, Michalska A, Pagett K, Pogson A, Price R, Price D, Procter K, Pye M, Redfearn H, Rewbury J, Ryding A, Sattar N, Sharp A, Shaw P, Simpson H, Smith W, Squire I, Storey R, Teenan M, Thomas H, Townend J, Trevelyan J, Wakeling J, Walukiewicz P, Wilkinson S, Zaman A, Acevedo L, Benton J, Abbate A, Aboufakher R, Acampora M, Acampora D, Aceto L, Acevedo B, Acheatel R, Adams M, Adams A, Ahmad I, Ahmed SH, Aish B, Akyea-Djamson A, Al Joundi T, Alcide P, Alfieri A, Alfonso T, Alfrey A, Allen J, Alllison DC, Almaliky T, Amos A, Angiolillo D, Antolick A, Ara M, Aragorn L, Arevalo S, Armas E, Arthur A, Asafu-Adjaye N, Ashcom T, Ashford M, Aslam A, Ather N, Atieh M, Aull L, Ayala M, Azizad M, Backer T, Baehl S, Bailey S, Bair S, Baker C, Ballmajo M, Pieretti HB, Baquero A, Barnett S, Baron S, Bartkowiak A, Bashir K, Beall K, Beauregard LA, Sarah S, Beckett L, Belejchak P, Bendelow T, Bender D, Benjamin S, Berdoff R, Berger V, Bergeron P, Berk M, Bernstein M, Binns Y, Bitzer V, Blahey M, Bloch S, Bluemel J, Boffetti P, Boley K, Bonner J, Boudreaux R, Boulanger K, Bradley A, Bramlet D, Bredlau C, Briggs S, Brousalis L, Brown S, Brown C, Buchannan C, Burke W, Burley T, Burton C, Burtt D, Byars W, Caballero-Valiente B, Carr K, Halliwell TC, Castillo J, Cei L, Cerda L, Chambers J, Chamblee T, Chattin W, Chee L, Chen YC, Cherlin R, Cheung D, Chiodi L, Christensen L, Christenson S, Cislowski D, Clavier-Firmin C, Colfer H, Colvin T, Cosgrove N, Covert C, Cox B, Cox R, Craig W, Crandall L, Crepps K, Cromer M, Cruz H, Cruz H, Cruz M, Cucher F, Damron M, Dave K, Dave B, Davis M, Davis B, Dawkins-Hughes S, Dean J, Debnam S, Defosse C, Dehning M, Dela Llana A, Dellorso M, Denham D, Desalle D, Dettmer M, Dhawan M, Diago M, Dicken T, Diederich C, Diederich M, Diehl R, Digangi D, Diller P, Dimattia M, Dodds G, Doggett J, Donahue K, Doughty L, Dragutksy B, Dreese M, Dunhurst F, Dunn D, Dutka C, Earl J, Eaton C, Eaves W, Ebeling K, Eder F, Edgerton L, Edillo C, Edwards J, Edwards T, Einhorn D, El Hafi S, Ellis M, Erickson B, Ervin W, Eskridge L, Fail P, Falcon D, Fang C, Fattal P, Fawson A, Felix L, Ferdinand K, Fien E, Fintel D, Firek C, Fitz-Patrick D, Flores E, Flores E, Flores H, Floro T, Forker A, Foster M, Foucauld J, Lehman KF, Fox B, Francoeur L, Frandsen B, Frandsen B, Frivold G, Fruchter G, Fullerton D, Gabriel J, Gacioch G, Garas S, Garcia N, Garcia Rinaldi R, Garcia-Fragoso V, Garcia-Portela M, Gelb R, George F, Ghali J, Gilbert J, Gilley J, Glancy R, Goff R, Goldberg N, Gonzales D, Gonzales V, Gonzalez E, Gorges R, Gould R, Grabeau R, Grable M, Graham JA, Graif J, Green E, Greener R, Greenway F, Grieshaber V, Griffin S, Gros C, Gudipati RVC, Guillinta P, Gupta V, Gutmann J, Gwyn M, El Hachem M, Hage F, Hageman T, Haidar A, Hakas J, Haldis T, Hall L, Hall C, Hall S, Halpern S, Hamud-Socoro A, Hardee L, Harrell W, Harrington A, Hartwell J, Hasan F, Hattler B, Haught H, Haynes E, Haywood A, Heaney L, Hecht J, Hernandez I, Herzog W, Hess E, Hill H, Hilton T, Hinderaker P, Hodnett P, Hoffman M, Hogan C, Holmes Z, Rees DH, Hotchkiss D, Huang P, Humbert J, Hutchens E, Iachini K, Ibarra M, Igbokidi O, Ilahi T, Imbrognio M, Ipp E, Iteld B, Jacques G, Jafri A, Jafry B, Jardula M, Jefferson D, Jenkins R, Johnson E, Johnson J, Jones S, Kawahara M, Kelehan S, Kelly R, Kendall T, Kereiakes D, Khan M, Khan S, Kick J, Kimmel M, King T, King A, Kirkland S, Kissel S, Kitchens D, Klein P, Klugherz B, Korban E, Koren M, Korte M, Kostis J, Kotek L, Kozak M, Kreutter F, Kusnick B, Labovitz R, Lail J, Lamance J, Lamas G, Lambert J, Lambert C, Landzberg J, Langdon J, Lavoie W, Ledger G, Lee T, Lee K, Lehman R, Leimbach W, Lennard M, Lepor N, Lester F, Levin P, Levinson L, Lewis D, Lillo J, Link L, Long C, Longaker R, Lorch G, Lucksinger G, Lynd S, Rhudy JM, Madder R, Magness K, Maheshwari A, Alan A, Malek M, Maletz L, Malhotra V, Malhotra S, Mandviwala M, Mani CK, Manuel J, Marchelletta N, Marshall L, Marsters M, Martin L, Martinez E, Mavromatis K, Maynard R, Mays M, Mays B, Mbulaiteye A, Mcalister R, Mccoy C, Mccrary D Jr, Mccullough-O'Brien H, Mcdonald M, Mcgill J, Mcgrew F, Mckenzie C, Mclaurin B, Mclellan BA, Mcneil D, Mcneill R, Mehrle A, Melbie K, Melliza T, Messina T, Meyer R, Michel K, Mikdadi G, Miller C, Miller R, Miller A, Miller G, Miller W, Mitchell J, Moats DJR, Mody F, Moffat J, Molk B, Molter D, Monroe T, Montero H, Montgomery R, Mookherjee D, Moran J, Moriarty P, Morrison J, Morton D, Moshayedi P, Mosley J, Moustafa M, Munshi K, Murray A, Mustafa J, Nadar V, Naidu R, Nalley J, Navy S, Neil L, Neutel JM, Niblack P, Nicely V, Nicolai M, Nijmeh G, Nikas A, Nikyar A, Nixon S, Norman L, Noto G, Nour K, Nugent A, Ocman B, Odegard A, Olsen S, Ortiz-Carrasquillo R, Ossino N, Paez H, Palchick B, Paliwal Y, Pannell R, Parfait V, Partridge J, Patel B, Patel R, Patel M, Patel S, Paysor C, Pena A, Pereira S, Perez M, Perez A, Perkins H, Perry B, Peters P, Phillippi C, Phillips A, Phillips A, Piacente R, Pintado M, Pish R, Pitt W, Poling T, Pomposini D, Poock J, Potts J, Poudrier R, Prior J, Pritchard C, Purighalla R, Quddusi K, Quinones J, Quinton D, Radin M, Radojcsics B, Rajput B, Rama B, Ramos M, Rauch R, Raynes K, Reber AM, Reddy J, Reeves M, Reilly K, Renaud K, Resnick H, Reyes R, Richardson M, Riethof M, Riser J, Rodero M, Rodriguez Araya E, Roper L, Rozeman P, Ruder D, Runquist L, Sack G, Saint-Jacques H, Salfity M, Sall N, Sam K, Samal A, Sanchez D, Santiago J Jr, Savignano C, Saylor R, Scheffel M, Schifferdecker B, Schindler E, Schneider P, Schneider R, Schnitzler R, Schrager B, Schwartz A, Scott R, Seals A, Shah AV, Shah A, Shatsky K, Shayani S, Shealy N, Sheets L, Shelley J, Shepard P, Shetty S, Silver K, Simon M, Singh K, Singh N, Sizemore BC, Skatrud L, Slayton C, Slimak V, Sloane G, Smallwood B, Smith P, Smith M, Smith T, Smith G, Smith B, Smith W, Smith M, Smith J, Smith J, Soca Y, Sofley C, Sopko K, Sosa-Padilla M, Sotolongo R, Sprinkle B, Srivastava S, Starzec M, Steinhoff J, Stelly L, Stinson J, Stoddard M, Stoltz S, Stone B, Stover T, Strain J, Strugatsky S, Stys T, Suleman A, Sullivan P, Tamez W, Tandon N, Teltser M, Terry PS, Terry K, Tessmar C, Thekkoott D, Thomas D, Thomas DM, Thompson E, Thompson J, Thornton A, Tjaden T, Tobias C, Topper J, Tran A, Treasure C, Trenkamp P, Trevino M, Tsou L, Tuholske C, Uy W, Vahtel M, Vaid B, Valenzuela M, Vance A, Vandam J, Vanhecke T, Vanness WC III, Vargas R, Vaz S, Vazquez Tanus J, Veerina K, Vega J, Vento A, Vijay N, Voelker F, Vogt E, Vold D, Vora K, Wade RD, Wadell C, Waksman R, Walker K, Walker K, Wallace K, Warren M, Washam M, Watson B, Webel R, Wells T, West M, Whitaker J, White J, White C, White A, White A, Wilhoit G, Wilkins M, Willingham K, Wilson S, Wilson V, Wise J, Woodall S, Woods A, Wright J, Wu J, Xu ZJ, Yarows S, Young A, Younis L, Zarate J, Zebrack J, Zhang W, Zieve F, Zineldine A, Ridker, P. M., Everett, B. M., Thuren, T., Macfadyen, J. G., Chang, W. H., Ballantyne, C., FONSECA E PIRES, CARLOS EDUARDO, Nicolau, J., Koenig, W., Anker, S. D., Kastelein, J. J. P., Cornel, J. H., Pais, P., Pella, D., Genest, J., Cifkova, R., Lorenzatti, A., Forster, T., Kobalava, Z., Vida-Simiti, L., Flather, M., Shimokawa, H., Ogawa, H., Dellborg, M., Rossi, P. R. F., Troquay, R. P. T., Libby, P., Glynn R., J, CANTOS Trial, Group, Perrone, Filardi, P, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, and ACS - Atherosclerosis & ischemic syndromes
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0301 basic medicine ,030204 cardiovascular system & hematology ,law.invention ,0302 clinical medicine ,c-reactive protein ,Randomized controlled trial ,law ,Cardiovascular Disease ,middle aged ,double-blind method ,antibodies ,Myocardial infarction ,humans ,Stroke ,interleukin-1beta ,biology ,Antibodies, Monoclonal ,drug ,General Medicine ,Lipid ,Aged ,anti-inflammatory agents ,monoclonal ,humanized ,atherosclerosis ,cardiovascular diseases ,dose-response relationship ,female ,incidence ,infections ,lipids ,male ,myocardial infarction ,neutropenia ,secondary prevention ,stroke ,Anti-Inflammatory Agent ,aged ,Editorial ,Atherosclerosi ,Monoclonal ,Human ,medicine.drug ,medicine.medical_specialty ,Neutropenia ,Antibodies, Monoclonal, Humanized ,Infections ,Placebo ,antibodies, monoclonal ,dose-response relationship, drug ,infection ,medicine (all) ,03 medical and health sciences ,Internal medicine ,medicine ,Dose-Response Relationship, Drug ,business.industry ,Antiinflammatory Therapy, Canakinumab, for Atherosclerotic Disease ,C-reactive protein ,medicine.disease ,Surgery ,Canakinumab ,030104 developmental biology ,biology.protein ,business - Abstract
Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.)
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- 2017
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3. G257 A biopsychosocial model of care for children and young people (CYP) with persistent, unexplained, physical symptoms (PUPS)
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Pales, J, primary, Street, K, additional, Howells, R, additional, Lee, A, additional, Burrows, J, additional, Boyd, A, additional, Bloomfield, T, additional, and Palfrey, V, additional
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- 2020
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4. 8 A biopsychosocial model of care for children and young people (CYP) with persistent, unexplained, physical symptoms (PUPS)
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Pales, J, primary, Street, K, additional, Howells, R, additional, Lee, A, additional, Burrows, J, additional, Boyd, A, additional, Bloomfield, T, additional, and Palfrey, V, additional
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- 2019
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5. G119 A pilot multi agency approach to young people with persistent physical symptoms
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Street, K, primary, Pales, J, additional, Lee, A, additional, Burrows, J, additional, Bowman, P, additional, Jones, H, additional, and O’Brien, E, additional
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- 2017
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6. High conservation value areas as a strategic approach for protected area management in the Philippines
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Alban, J. D., Acay, J., Gaschick, F., Rai Kristie Salve Gomez, Guinto, A. F., Ledesma, M., Mallari, N. A., Masigan, J. P., Monzon, A. K., Pales, J. R., Parinas, M., Reyes, S. R., Rico, E. L., Supsup, C., Tablazon, D., Tumaneng, R., Weerd, M., Veridiano, R. K., and Wenceslao, J.
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- 2015
7. Predictors of blood pressure control in patients with resistant hypertension
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Pales, J., primary, Kamensky, G., additional, and Payer, J., additional
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- 2017
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8. Identification of Kir2.1 channel activity in cultured trabecular meshwork cells
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Llobet, A., Gasull, X., Pales, J., Eulalia Marti, and Gual, A.
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Patch-Clamp Techniques ,Potassium Channels ,Dose-Response Relationship, Drug ,Blotting, Western ,8-Bromo Cyclic Adenosine Monophosphate ,Cesium ,Barium ,Trabecular Meshwork ,Potassium ,Potassium Channel Blockers ,Animals ,Humans ,Calcium ,Cattle ,Potassium Channels, Inwardly Rectifying ,Cells, Cultured - Abstract
To study the presence of inwardly rectifying K(+) (Kir) channels in cultured bovine (BTM) and human (HTM) trabecular meshwork cells.Cultures of BTM and HTM cells were obtained by an extracellular matrix digestion technique. Whole-cell patch-clamp recordings of BTM cells were performed with the appropriate solutions to detect K(+) currents. Also, Western blot analysis of Kir2.1 protein expression was performed on both cultured BTM and HTM cells.A strong inwardly rectifying current at negative potentials to the equilibrium potential for K(+) (E(K+)) and highly selective for K(+) was detected in 60% of cultured BTM cells. The slope conductance of the inward rectification was more pronounced when the extracellular [K(+)] was increased and was proportional to [K(+)](0.45). The current was blocked by Ba(2+) and Cs(+) in a voltage- and concentration-dependent manner, with K(d) at 0 mV, of 74.7 microM and 45.6 mM, respectively. Current amplitude was reduced by increasing extracellular [Ca(2+)]. The current was insensitive to 10 microM glibenclamide and 10 nM tertiapin. The application of 100 microM 8-Br-cAMP reduced the current by 50%. Kir2.1 channel expression was detected in confluent monolayers of BTM and HTM cells by Western blot analysis.A population of cultured BTM cells expressed an inwardly rectifying K(+) current that illustrates the biophysical and pharmacologic characteristics of the detected Kir2.1 channel protein. Kir2.1 channels are also thought to be present in HTM cells. Kir2.1 channels could be related to TM physiology, because they are involved in contractile and cell volume regulatory responses, two mechanisms that modify TM permeability.
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- 2001
9. Real-Time 3D Simulation of a Pressurized Water Nuclear Reactor.
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Janosy, J.S., Kereszturi, A., Hazi, G., Pales, J., and Vegh, E.
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- 2010
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10. Active and problem-based learning: two years' experience in physiology at the Medical School of the University of Barcelona
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PALES, J., primary and GUAL, A., additional
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- 1992
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11. An experimental analysis of the effect of air pollution on the conductivity and ion balance of the atmosphere.
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Phillips, B. B., Allee, P. A., Pales, J. C., and Woessner, R. H.
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- 1955
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12. The effects of exogenous testosterone on spatial memory in rats
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Hodosy Július, Páleš Ján, Ostatníková Daniela, and Celec Peter
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testosterone ,androgens ,spatial abilities ,sex differences ,water maze ,Biology (General) ,QH301-705.5 - Published
- 2010
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13. Use of transduction proteins to target trabecular meshwork cells: outflow modulation by profilin I
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Gómez-Cabrero, A., Nuria Comes, González-Linares, J., Lapuente, J., Borras, M., Pales, J., Gual, A., Gasull, X., and Morales, M.
14. Antiinflammatory therapy with canakinumab for atherosclerotic disease
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Ridker P.M., Everett B.M., Thuren T., MacFadyen J.G., Chang W.H., Ballantyne C., Fonseca F., Nicolau J., Koenig W., Anker S.D., Kastelein J.J.P., Cornel J.H., Pais P., Pella D., Genest J., Cifkova R., Lorenzatti A., Forster T., Kobalava Z., Vida-Simiti L., Flather M., Shimokawa H., Ogawa H., Dellborg M., Rossi P.R.F., Troquay R.P.T., Libby P., Glynn R.J., Krum H., Varigos J., Siostrzonek P., Sinnaeve P., Gotcheva N., Yong H., Urina-Triana M., Milicic D., Vettus R., Manolis A.J., Wyss F., Sigurdsson A., Fucili A., Veze I., Petrauskiene B., Salvador L., Klemsdal T.O., Medina F., Budaj A., Otasevic P., Lainscak M., Seung K.B., Commerford P., Donath M., Hwang J.J., Kultursay H., Bilazarian S., East C., Forgosh L., Harris B., Ligueros M., Bohula E., Charmarthi B., Cheng S., Chou S., Danik J., McMahon G., Maron B., Ning M., Olenchock B., Pande R., Perlstein T., Pradhan A., Rost N., Singhal A., Taqueti V., Wei N., Burris H., Cioffi A., Dalseg A.M., Ghosh N., Gralow J., Mayer T., Rugo H., 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Siemann M., Stern M., Toom M., Vahula V., Apel T., Axthelm C., Ayasse D., Ayasse M., Baar M., Baeumer A., Bagi E.S., Becker B., Binder A., Blankenberg S., Braun P., Johansen B.B., Contzen C., Delfonso F., Denecke C., Dengler T., Donaubauer T., Eichinger G., Englmann E., Erhard M., Faghih M., Foerster A., Frankenstein L., Fuchs R., Furch G., Gaeb-Strasas B., Germann H., Giese C., Goette A., Gravenhorst-Muenter U., Haege R., Haenel T., Hagemann D., Hagenow A., Hanefeld M., Heider J., Heisters J., Hennig D., Hielscher S., Himpel-Boenninghoff A., Holscher A., Hornig M., Jeserich M., Kaczmarek N., Kanitz S., Kara Y.D., Khariouzov A., Kiefer R., Kiroglu K., Klamm M., Klein C., Korth-Wiemann B., Krapivsky A., Kuenzler J., Kuntzsch A., Landers B., Lappo M., Laube S., Leggewie S., Lehmann D., Lepp H., Lierse T., Lindner C., Luecke-Uzar M., Luedemann J., Marschke T., Maruzzo S., Mauersberger K., Maus O., Meinrich M., Meissner A., Moehring B., Muehlhaus J., Mueller S., Muenter K.C., Muenzel T., 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Bevilacqua M.T., Bolognesi M.G., Dessalvi C.C., Calabrese A., Campanale E.G., Candusso R., Caso P., Cosmi F., Crea F., Crocamo A., De Caterina R., De Rosa S., Destro M., Di Biase M., Dognini G.P., Eleuteri E., Fedele F., Ferrario M., Gabrielli D., Gamba C., Ganau A., Gravellone M., Iannopollo G., Indolfi C., Infusino F., Invitti C., Landolfi A., Lembo G., Liberato N.L., Mannucci E., Marino P., Mariottoni B., Marziali A., Mercuro G., Monti L., Mos L., Mureddu V., Musumeci M.B., Novo S., Panzarino C., Parente A., Perotti M., Filardi P.P., Petrillo C., Piatti P., Priori S., Racca V., Ragghianti B., Renda G., Righini V., Sarcone M., Senni M., Soro E., Tamburrini P., Vallone L., Villani G.Q., Volpe M., Ajioka M., Akai Y., Ashino K., Baden M., Doi M., Eki Y., Endo T., Fukuike C., Hagiwara Y., Hasegawa K., Higuchi Y., Higuchi T., Hioki M., Hirayama A., Hiroma J., Hosokawa S., Ichisawa M., Iijima T., Inada T., Inagaki M., Ito K., Kaigawa K., Kajihara S., Kamiya H., Kamiya J., Kaneno Y., Katahira K., Kataoka M., Kawai M., Kawasaki T., Kojima E., Komura Y., Kuramochi T., Kuruma T., Kyo E., Mani H., Miyamoto T., Morii I., Morinaga Y., Morisawa T., Nagai Y., Naka T., Nakamura Y., Nakamura S., Nakayoshi K., Nishibe A., Ogawa M., Okada Y., Okawa M., Sakamoto Y., Sakurada M., Sasaki S., Seki S., Shimomura H., Shinozaki T., Sugimoto N., Suzuki A., Taguchi S., Takahashi J., Takase S., Tanabe K., Tanaka A., Tani S., Tomioka J., Tsuboi H., Tsuji M., Tsujita K., Tsujiyama S., Umesu A., Yamada T., Yamaguchi E., Yamamoto H., Yamamoto T., Yamane M., Yanase T., Yasuoka S., Yasutake M., Yokoyama M., Yoshida M., Yoshimoto E., Yunoki C., Balode A., Dormidontova G., Flaksa I., Nagele-Luse I., Rancane G., Sime I., Bartuseviciene S., Cepinskiene L., Dobilas V., Grigaraviciene I., Marcinkeviciene J., Mazutavicius R., Miliuniene R., Motiejuniene R., Norkiene S., Norkute-Macijauske U., Rudys A., Slapikas R., Stonkute K., Strazdiene D., Tijuneliene E., Urbonas G., Vanagiene S., Viezelis M., 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W., Caballero-Valiente B., Carr K., Halliwell T.C., Castillo J., Cei L., Cerda L., Chambers J., Chamblee T., Chattin W., Chee L., Chen Y.C., Cherlin R., Cheung D., Chiodi L., Christensen L., Christenson S., Cislowski D., Clavier-Firmin C., Colfer H., Colvin T., Cosgrove N., Covert C., Cox B., Cox R., Craig W., Crandall L., Crepps K., Cromer M., Cruz H., Cruz M., Cucher F., Damron M., Dave K., Dave B., Davis M., Davis B., Dawkins-Hughes S., Dean J., Debnam S., Defosse C., Dehning M., Dela Llana A., Dellorso M., Denham D., Desalle D., Dettmer M., Dhawan M., Diago M., Dicken T., Diederich C., Diederich M., Diehl R., Digangi D., Diller P., Dimattia M., Dodds G., Doggett J., Donahue K., Doughty L., Dragutksy B., Dreese M., Dunhurst F., Dunn D., Dutka C., Earl J., Eaton C., Eaves W., Ebeling K., Eder F., Edgerton L., Edillo C., Edwards J., Edwards T., Einhorn D., El Hafi S., Ellis M., Erickson B., Ervin W., Eskridge L., Fail P., Falcon D., Fang C., Fattal P., Fawson A., Felix L., Ferdinand 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D.H., Hotchkiss D., Huang P., Humbert J., Hutchens E., Iachini K., Ibarra M., Igbokidi O., Ilahi T., Imbrognio M., Ipp E., Iteld B., Jacques G., Jafri A., Jafry B., Jardula M., Jefferson D., Jenkins R., Johnson E., Johnson J., Jones S., Kawahara M., Kelehan S., Kelly R., Kendall T., Kereiakes D., Khan M., Khan S., Kick J., Kimmel M., King T., King A., Kirkland S., Kissel S., Kitchens D., Klein P., Klugherz B., Korban E., Koren M., Korte M., Kostis J., Kotek L., Kozak M., Kreutter F., Kusnick B., Labovitz R., Lail J., Lamance J., Lamas G., Lambert J., Lambert C., Landzberg J., Langdon J., Lavoie W., Ledger G., Lee T., Lehman R., Leimbach W., Lennard M., Lepor N., Lester F., Levin P., Levinson L., Lewis D., Lillo J., Link L., Long C., Longaker R., Lorch G., Lucksinger G., Lynd S., Rhudy J.M., Madder R., Magness K., Maheshwari A., Alan A., Malek M., Maletz L., Malhotra V., Malhotra S., Mandviwala M., Mani C.K., Manuel J., Marchelletta N., Marshall L., Marsters M., Martin L., Martinez E., Mavromatis K., Maynard R., Mays M., Mays B., Mbulaiteye A., Mcalister R., Mccoy C., Mccrary D.Jr., Mccullough-O'Brien H., Mcdonald M., Mcgill J., Mcgrew F., Mckenzie C., Mclaurin B., Mclellan B.A., Mcneil D., Mcneill R., Mehrle A., Melbie K., Melliza T., Messina T., Meyer R., Michel K., Mikdadi G., Miller C., Miller R., Miller A., Miller G., Miller W., Mitchell J., Moats DJR., Mody F., Moffat J., Molk B., Molter D., Monroe T., Montero H., Montgomery R., Mookherjee D., Moran J., Moriarty P., Morrison J., Morton D., Moshayedi P., Mosley J., Moustafa M., Munshi K., Murray A., Mustafa J., Nadar V., Naidu R., Nalley J., Navy S., Neil L., Neutel J.M., Niblack P., Nicely V., Nicolai M., Nijmeh G., Nikas A., Nikyar A., Nixon S., Norman L., Noto G., Nour K., Nugent A., Ocman B., Odegard A., Olsen S., Ortiz-Carrasquillo R., Ossino N., Paez H., Palchick B., Paliwal Y., Pannell R., Parfait V., Partridge J., Patel B., Patel M., Patel S., Paysor C., Pena A., Pereira S., Perez M., Perez A., Perkins H., Perry B., Peters P., Phillippi C., Phillips A., Piacente R., Pintado M., Pish R., Pitt W., Poling T., Pomposini D., Poock J., Potts J., Poudrier R., Prior J., Pritchard C., Purighalla R., Quddusi K., Quinones J., Quinton D., Radin M., Radojcsics B., Rajput B., Rama B., Ramos M., Rauch R., Raynes K., Reber A.M., Reddy J., Reeves M., Reilly K., Renaud K., Resnick H., Reyes R., Richardson M., Riethof M., Riser J., Rodero M., Rodriguez Araya E., Roper L., Rozeman P., Ruder D., Runquist L., Sack G., Saint-Jacques H., Salfity M., Sall N., Sam K., Samal A., Sanchez D., Santiago J.Jr., Savignano C., Saylor R., Scheffel M., Schifferdecker B., Schindler E., Schneider P., Schneider R., Schnitzler R., Schrager B., Schwartz A., Scott R., Seals A., Shah A.V., Shah A., Shatsky K., Shayani S., Shealy N., Sheets L., Shelley J., Shepard P., Shetty S., Silver K., Simon M., Singh K., Singh N., Sizemore B.C., Skatrud L., Slayton C., Slimak V., Sloane G., Smallwood B., Smith P., Smith M., Smith T., Smith G., Smith B., Smith J., Soca Y., Sofley C., Sopko K., Sosa-Padilla M., Sotolongo R., Sprinkle B., Srivastava S., Starzec M., Steinhoff J., Stelly L., Stinson J., Stoddard M., Stoltz S., Stone B., Stover T., Strain J., Strugatsky S., Stys T., Suleman A., Sullivan P., Tamez W., Tandon N., Teltser M., Terry P.S., Terry K., Tessmar C., Thekkoott D., Thomas D., Thomas D.M., Thompson E., Thompson J., Thornton A., Tjaden T., Tobias C., Topper J., Tran A., Treasure C., Trenkamp P., Trevino M., Tsou L., Tuholske C., Uy W., Vahtel M., Vaid B., Valenzuela M., Vance A., Vandam J., Vanhecke T., Vanness WC III., Vargas R., Vaz S., Vazquez Tanus J., Veerina K., Vega J., Vento A., Vijay N., Voelker F., Vogt E., Vold D., Vora K., Wade R.D., Wadell C., Waksman R., Walker K., Wallace K., Warren M., Washam M., Watson B., Webel R., Wells T., West M., Whitaker J., White J., White C., White A., Wilhoit G., Wilkins M., Willingham K., Wilson S., Wilson V., Wise J., Woodall S., Woods A., Wright J., Xu 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Taqueti V., Wei N., Burris H., Cioffi A., Dalseg A.M., Ghosh N., Gralow J., Mayer T., Rugo H., Fowler V., Limaye A.P., Cosgrove S., Levine D., Lopes R., Scott J., Hilkert R., Tamesby G., Mickel C., Manning B., Woelcke J., Tan M., Manfreda S., Ponce T., Kam J., Saini R., Banker K., Salko T., Nandy P., Tawfik R., O’Neil G., Manne S., Jirvankar P., Lal S., Nema D., Jose J., Collins R., Bailey K., Blumenthal R., Colhoun H., Gersh B., Abreu M., Actis M.V., Aiub J., Aiub F., Albisu J., Alvarisqueta A., Avalos V., Barreto M., Berli M.A., Blumberg C., Bocanera M., Botta C., Bowen L., Budassi N., Buhlman S., Westberg J.C., Carabajal T., Caruso G., Casala J., Cendali G., Coloma G., Berra F.C., Cuneo C., Degennaro N., Dellasa M., Diaz M., Dos Santos P., Espinosa V., Facello A., Facello M., Farias E., Fernandez A.A., Ferrari V., Pacora F.F., Flores G.S., Franco M., Gabito A., Viola H.G., Garcia F., Garcia Duran R., Garcia Pinna J., Glenny J., Godoy Sanchez M., Grosse A., Guzman P., Hasbani E., Hominal M., Ibañez J., Jure H., Jure D., Vico M.L., Liniado G., Luciardi H., Luquez H., Maehara G., Maffei L., Majul C., Mallagray M., Marinaro S., Martinez J., Massaccesi R., De Los Milagros Had M., Azize G.M., Montana O., Montenegro E., Morell Y., Muntaner J., Navarrete S., Olmedo M., Paganini M., Paz S., Perez Manghi F., Piskorz D., Polato C., Recoaro R., Romano A., Salinger M., Sanchez A., Saravia M.A., Sarjanovich R., Scaro G., Schiavi L.B., Soler J., Tinnirello V., Tomassi A., Valle M., Vallejo M.A., Venturini C., Marcela Wenetz L.M., Yossen M., Zaidman C., Zalazar L., Zangroniz P., Amerena J., Brady L., Colquhoun D., Eccleston D., Ferreira-Jardim A., French J., Jayasinghe R., Mcintosh C., Ord M., Plotz M., Purnell P., Roberts-Thomson P., Schultz C., Shanahan T., Tan R., Taverner P., Turner F., Vibert J., Vorster M., William M., Youssef G., Bergler-Klein J., Brath H., Brodmann M., Fliesser-Goerzer E., Haider K., Heeren G., Hiden C., Mandic L., Paulweber B., Ploechl A., Prenner A., Steringer-Mascherbauer R., Strohner-Kaestenbauer H., Barbato E., Bouvy C., Briké C., Charlier F., Cools F., De Knijf K., De Wolf L., Delforge M., Deweerdt N., Gits F., Goffinet C., Hermans K., Hollanders G., Mestdagh I., Pirenne B., Servaes V., Simons N., Tahon S., Theunissen E., Van Genechten G., Vervoort G., Vissers C., Vranckx P., Vrolix M., Abib E.Jr., Abrantes J., Araujo Fonseca M., Barbosa E., Barroso W., Barroso A., Bodanese L., Botelho R., Costa Amorim R., Da Costa F., Da Silva A., Da Silva O.Jr., Da Silva D.Jr., Ferreira Dos Santos T., Dos Santos F., Dos Santos A., Duda N., Feitosa G., Felario Junior GA., Ferraz R., Filho P., Fonseca A., Wanderley F.F., Freitas E., Fucci F., Marengo Garcia De Carvalho L., Hernandez M., Hettwer Magedanz E., Julião K., Kormann A., Lameira A., Lima F., Lino E., Maia L., Manenti E., Marchi A.L., Fischer S.M., Michalaros Y., Moraes J.Jr., Moreira L., Pagnan M., Pesce F., Pinheiro L., Rassi S., Reis G., Reis H., Resende I., Roel A., Ruschel K., Saporito W., Saraiva J.F., Seroqui M., Silva R., Unterkircher B., Vicente C., Vieira N., Xavier J.P., Zucchetti C., Angelova I., Dimitrov G., Genova D., Gospodinov K., Goudev A., Grigorova V., Hristova K., Makedonska J.J., Katova T., Kostov K., Lazov P., Manov E., Manukov I., Manukov D., Milanova M., Kabakchieva V.M., Petrov D., Petrusheva T., Pramatarova I., Raev D., Runev N., Sirakova-Taseva A., Tisheva-Gospodinova S., Todorova A., Tzekova M., Yakovova S., Yanev T., Abulencia K., Arora S., Baker A., Bata I.R., Beaudry M., Belle Isle J., Bilodeau N., Boivin M.C., Bolduc H., Bourgeois S., Brons S., Cantor W., Chaussé I., Chhabra A., Chouinard G., Cleveland T., Dattani D., Deslongchamps F., Diodati J., Drouin K., Duchesne L., Fontaine S., D'Amours D.G., Gervais B., Gosselin G., Graham J., Grover A., Gupta A., Haldane H., Hartleib M., Hickey L., Huynh T., Johnston J., Julien V.E., Lachance P., Lake J., Lamontagne C., Lauzon C., Lepage S., Maheux K., Manyari D., Martin E., McPherson C., Mehta S., Michaud N., Kouz S.M., Murphy G., OKeefe D., Otis R., Ouimet F., Pandey S., Peck C., Perkins L., Richert L., Robbins K., Robinson S., Cabau J.R., Ross B., Roy C., Roy M., Roy A., Rupka D., Affaki G.S., Saunders K., Savard D., Soucy D., St Amour E., Thiessen S., Vertes G., Vezina M., Vincelli G., Weisnagel S.J., Zadra R., Chen J., Chen Y., Dong X., Feng Y., Feng Z., Fu G., Han B., Hao Y., He Y., He Z., Hong T., Jia Z., Jiang T., Jiang J., Jiang X., Ke Y., Li Y., Li Z., Li W., Li X., Liu P., Liu Y., Liu B., Liu S., Liu L., Lu Z., Lv Y., Ma C., Ma G., Peng L., Qing L., Ren L., Sang X., Song M., Sun Z., Wang J., Wang Y., Wei J., Wu W., Wu J., Xu H., Yan J., Yang P., Yang K., Yao Z., Yaoqing H., Yuan Z., Zhai Z., Zhang J., Zhang Y., Zhao R., Zhou H., Accini Mendoza JL., Aparicio C.V., Castillo T., Chaverra I., Conrado Y., Coronel J., Cotes C., Cuentas I., Cuervo A., Dussan M.A., Echeverria L., Hernandez E., Ibarra J., Isaza D., Jimenez D., Lopez P., Manzur F., Mejia I., Mendoza Y., Molina D.I., Patino J.M., Rodriguez D., Rodriguez L.M., Rodriguez S.M., Sanchez Vallejo G., Luz Serrano H., Sotomayor A., Urina M., Vesga B., Yupanqui H., Akrap B., Busic N., Ciglenecki N., Cmrecnjak J., Fucak E., Gabor M., Jeric M., Jutrisa N., Kordic K., Planinc I., Popovic Z., Radeljic V., Sesto I., Sutalo K., Tusek S., Belohlavek J., Budkova J., Busak L., Capova L., Cech V., Cermak O., Coufalova Z., Cyprian R., Dedek V., Dedkova S., Ferkl R., Hanak P., Hanustiakova A., Homza M., Horackova K., Houra M., Iveta H., Kaiserova L., Kala P., Karel I., Kellnerova I., Koleckar P., Kreckova M., Krupicka J., Lorenc Z., Machova V., Malik J., Masarikova L., Matyasek I., Mikus M., Mikusova T., Ondrasik J., Otava M., Palubova L., Pavlickova L., Peterka M., Petrova I., Pokorna B., Povolny P., Radvan M., Reznakova S., Rickova Z., Roszkowska P., Rotreklova M., Samkova D., Skalicka H., Slechticka A., Sternthal P., Telekes P., Tesak M., Vesely P., Vesely J., Vins P., Vitovec M., Vodnansky P., Zidova M., Keba E., Laane E., Pool T., Randvee L., Ratnik E., Reimand M., Reinmets S., Rivis L., Siemann M., Stern M., Toom M., Vahula V., Apel T., Axthelm C., Ayasse D., Ayasse M., Baar M., Baeumer A., Bagi E.S., Becker B., Binder A., Blankenberg S., Braun P., Johansen B.B., Contzen C., Delfonso F., Denecke C., Dengler T., Donaubauer T., Eichinger G., Englmann E., Erhard M., Faghih M., Foerster A., Frankenstein L., Fuchs R., Furch G., Gaeb-Strasas B., Germann H., Giese C., Goette A., Gravenhorst-Muenter U., Haege R., Haenel T., Hagemann D., Hagenow A., Hanefeld M., Heider J., Heisters J., Hennig D., Hielscher S., Himpel-Boenninghoff A., Holscher A., Hornig M., Jeserich M., Kaczmarek N., Kanitz S., Kara Y.D., Khariouzov A., Kiefer R., Kiroglu K., Klamm M., Klein C., Korth-Wiemann B., Krapivsky A., Kuenzler J., Kuntzsch A., Landers B., Lappo M., Laube S., Leggewie S., Lehmann D., Lepp H., Lierse T., Lindner C., Luecke-Uzar M., Luedemann J., Marschke T., Maruzzo S., Mauersberger K., Maus O., Meinrich M., Meissner A., Moehring B., Muehlhaus J., Mueller S., Muenter K.C., Muenzel T., Naumann R., Nebel J., Neumann J., Nuding S., Overhoff U., Papke B., Pencz I., Peter Y., Peukert A.M., Radde I., Rau T., Regner S., Reichenbach D., Reimer D., Rinke A., Roettges R., Romanski A., Rummel R., Samer H., Sanuri M., Sarnighausen H.E., Schäfer B., Scheibner T., Schermaul K.H., Schindler A., Schlundt C., Schmidt E., Schmidt K., Schnabel A., Schoen N., Schorn K., Schroeder T., Schulenburg D., Schulz M., Schulze U., Schulze J., Schumacher M., Schwerin G., Schwerin M., Stadelmeier S., Stahl H.D., Stahl A., Stockhausen J., Stockhausen G., Stoessel J., Stolze K., Stratmann M., Szymanowski N., Teschner A.B., Teske A., Uecker C., Veit S., Voeller H., Walter I., Walter J., Walther I., Weber H.G., Weimer J., Wichterich K., Wiebusch A., Willmerdinger M., Willner C., Winkelmann B., Winkler J., Wistuba T., Woehrle J., Wohnlich T., Wolf S., Woyczak D., Wrage P., Zirlik A., Anadiotis A., Chachalis 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Raghu C., Chauhan D., Chauhan H., Chavada J., Chaware G., Chella S., Chintala P., Dash D., Desai D., Devasia T., Dhanak R., Dobariya H., Dudhatra N., Duhan S., Fulwani M., Ghondale N., Ghosh S., Gohel P., Govindaraj D., Goyal B., Goyal S., Gundala A.K., Gupta M., Hardas S., Iby M., Jagtap P., Jain A., Joshi U., Karpuram M., Kaur H., Khan A., Khan R., Kodem D.R., Koeitti P., Kulkarni L., Kullal P., Kumar K.S., Kumbla M., Latheef K., Lohkare M., Santosh M.J., Makhe B., Mandati M., Mehta A., Minocha G., Mittal A., Modi R., Mohan K., Oomman A., Pai R., Pai V., Palaniswami N., Pansheriya A., Parekh N., Patel J., Patel R., Patole T., Praveen M., Radhakrishnan V., Rajan B A., Rajasekhar D., Rao M., Rao M.B., Rao N.M., Rathnavel S., Rathore A., Rathore SRS., Rawat S., Reddy N.C., Sarma R., Sathe S., Shah J., Shaikh P., Sharma K., Sharma S., Sharma T., Shetty P., Sidhu G., Singh V., Sohi G.S., Srinath V.S., Raju S.S., Taran A., Thakkar B., Velusamy K., Vijan V., Vora V., Vuriya A.K., Agosta 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Willingham K., Wilson S., Wilson V., Wise J., Woodall S., Woods A., Wright J., Xu Z.J., Yarows S., Young A., Younis L., Zarate J., Zebrack J., Zhang W., Zieve F., and Zineldine A.
- Abstract
BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83
15. G119 A pilot multi agency approach to young people with persistent physical symptoms
- Author
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Street, K, Pales, J, Lee, A, Burrows, J, Bowman, P, Jones, H, and O’Brien, E
- Abstract
Background/aimsYoung people with Persistent Physical Symptoms (PPS) that reduce function and school attendance are worrying. Many have repeat admissions/appointments, unnecessary investigations/treatments. Local data showed 4% of inpatients/ outpatients<18 years in our district general hospital have PPS. Data from education welfare services (EWS) showed 10% of <85% school attenders known to local paediatricians with PPS. Paediatrics, Child and Adolescent Mental Health Services (CAMHS) and EWS committed to a 12 month pilot of joint working cases to assess impact and inform service development.MethodsSince June 2016 a weekly, hour long meeting with psychiatrist, CAMHS worker, psychologist and EWS inclusion officer, facilitated by paediatrician. Allied health professionals join where appropriate. Cases presented by managing paediatrician. All planned input provided within existing resource plus additional 3 hr/week of CAMHS therapist and paediatric staff grade providing joint appointments where appropriate. Databases, case studies, questionnaires (SDQ, RCADS, DAWBA, session rating scales), focus groups provided outcome data.Results32 cases discussed in 5 months. Symptoms included abdominal/joint/muscle pains, headache, fatigue, acute behavioural disturbance, breathing difficulty. Median age 15 (4–18), girls: boys 2:1. 5 were repeat attending inpatients, 27 outpatients. Previous investigation included bloods, neurophysiology, medical imaging. 4 were out of school, 13<85% attendance. Outcomes ranged from further information gathering and rediscussion (6), signposting school/community services (4), joint paediatric/ CAMHS appointments (9), CAMHS assessment/input (10), allied health professional input (3). 18 were discharged from medical follow up, no further admissions. 2 education referrals for out of school provision reversed and successfully reintegrated, overall improved school attendance in cohort. Qualitative feedback from professionals involved showed better understanding of PPS and mental health comorbidities. Paediatricians reported change in practise to reduce investigations/follow up and raising psychological aspects of symptoms earlier. Feedback from young people/ families was positive.ConclusionJoint working between physical/mental health/education services is an acceptable and effective way of managing young people with PPS and can reduce hospital admissions/ appointments, investigations, improve school attendance/reintegration. Mental health comorbidity is common. Poor school attendance/attainment and mental illness is associated with long term burden on public services. Additional resource is needed to provide joined up services offering assessment/support for PPS in young people and needs to be recognised by commissioners as investment to save.
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- 2017
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16. Facility Changes Mediated by cAMP in the Bovine Anterior Segment In Vitro
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GILABERT, R., GASULL, X., PALÉS, J., BELMONTE, C., BERGAMINI, M.V.M., and GUAL, A.
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- 1997
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17. Regulacion de la respiracion
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Gual, A., Palés, J., Obeso, A., and González, C.
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- 1991
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18. Predictors of blood pressure control in patients with resistant hypertension.
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Pales J, Kamensky G, and Payer J
- Subjects
- Aged, Aged, 80 and over, Antihypertensive Agents adverse effects, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Prognosis, Risk Factors, Antihypertensive Agents therapeutic use, Blood Pressure drug effects, Blood Pressure Monitoring, Ambulatory, Coronary Vasospasm drug therapy, Hypertension drug therapy
- Abstract
Background: Uncontrolled resistant hypertension (RH) defined by the mean 24-hour ambulatory blood pressure (ABPM) represents an independent risk factor in hypertensive patients. Predictors of blood pressure (BP) control in RH are not yet clearly defined., Objectives: To evaluate the predictors of BP control in RH patients with repeated ABPM measurements., Methods: 114 consecutive patients from outpatient cardiology office fulfilling criteria for RH (office BP ≥ 140 and/or 90 mmHg, with treatment of ≥ 3 antihypertensive drugs, including diuretic, or controlled BP with > 3 drugs), with two consecutive ABPM studies were compared in clinical characteristics according to BP control assessed by ABPM RESULTS: After the second ABPM, BP was controlled in 25.4 % of patients; the remaining 74.6 % were classified as uncontrolled. In the uncontrolled BP group, systolic office BP was 140.91±16.71 mmHg, diastolic 81.26 ± 10.92 mmHg. In ABPM, systolic was 145.11 ± 13.65 mmHg, diastolic 81.26 ± 10.92 mmHg. Compared to the controlled BP group, in the uncontrolled group the age was higher 72.32 ±10.89 years (p = 0.047), baseline average real variability of systolic BP was lower 12.66 ± 3.08 vs. 14.52 ± 3.53 (p = 0.013), no significant difference in baseline standard deviation of systolic BP changes was found., Conclusion: Higher office BP, older age, and increased short term BP variability were associated with an uncontrolled hypertension. Stronger association was found with baseline average real variability rather than standard deviation. No significant differences were found in the dipping status and other clinical characteristics (Tab. 6, Fig. 1, Ref. 28).
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- 2016
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19. Use of transduction proteins to target trabecular meshwork cells: outflow modulation by profilin I.
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Gomez-Cabrero A, Comes N, Gonzalez-Linares J, de Lapuente J, Borras M, Pales J, Gual A, Gasull X, and Morales M
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- Actins metabolism, Animals, Aqueous Humor metabolism, Blotting, Western, Cattle, Cells, Cultured, Cloning, Molecular, Genetic Vectors, Membrane Transport Proteins physiology, Microscopy, Confocal, Oligopeptides metabolism, Protein Transport physiology, Recombinant Fusion Proteins metabolism, Trabecular Meshwork cytology, Anterior Eye Segment metabolism, Gene Products, tat metabolism, Profilins metabolism, Trabecular Meshwork metabolism
- Abstract
Purpose: Fusion proteins containing a protein transduction domain (PTD4) are able to cross biological membranes. We tested the applicability of the protein transduction method for study of the aqueous humor trabecular outflow pathway by targeting the actin cytoskeleton, which is known to be involved in outflow facility regulation., Methods: Expression vectors useful for generating fusion proteins with the PTD4 domain and the actin-binding protein Profilin I were constructed. The transductional and functional properties of these proteins were tested in bovine trabecular meshwork cells in culture. The effects of PTD4-Profilin I on outflow facility were evaluated in perfused bovine anterior segments. PTD4-beta-galactosidase was used to visually check correct delivery of fusion proteins to trabecular meshwork cells., Results: The fusion proteins generated were characterized by western blot. Immunocytochemistry experiments showed intracellular staining for PTD4-Profilin I in trabecular meshwork cells in culture. The fusion protein was found in the cytoplasm associated with actin filaments and in the leading edge of the cellular membrane. In contrast, control Profilin I, without the PTD4 domain, was unable to cross the cell membrane. In perfused anterior segments, 2 microM PTD4-Profilin I increased trabecular outflow facility in a reversible manner, while Profilin I had no significant effect. Anterior segments perfused with PTD4-beta-galactosidase showed positive staining in the trabecular meshwork tissue., Conclusions: Protein transduction technology is a valuable tool for targeting trabecular meshwork tissue, not only for performing physiological studies, but also as a potential drug-delivery method. Profilin I action on the actin cytoskeleton further reinforces the importance of this structure in outflow facility regulation.
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- 2005
20. Effects of polyamines on platelet aggregation.
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Pales JL, Lopez A, and Vidal S
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- Adenosine Diphosphate pharmacology, Adolescent, Adult, Epinephrine pharmacology, Female, Humans, Male, Stimulation, Chemical, Platelet Aggregation drug effects, Spermidine pharmacology, Spermine pharmacology
- Abstract
Polyamines, spermine and spermidine in the micromolar range (1-100 mumol/l) increase ADP and epinephrine-induced platelet aggregation in vitro. The possible rôle of polyamines as regulating factors of platelet aggregation in physiological and pathological states is discussed.
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- 1984
- Full Text
- View/download PDF
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