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11. Effect of methylprednisolone on acute kidney injury in patients undergoing cardiac surgery with a cardiopulmonary bypass pump: a randomized controlled trial

Author

Garg, Amit X, Chan, Matthew TV, Cuerden, Meaghan S, Devereaux, PJ, Abbasi, Seyed Hesameddin, Hildebrand, Ainslie, Lamontagne, Francois, Lamy, Andre, Noiseux, Nicolas, Parikh, Chirag R, Perkovic, Vlado, Quantz, Mackenzie, Rochon, Antoine, Royse, Alistair, Sessler, Daniel I, Shah, Pallav J, Sontrop, Jessica M, Tagarakis, Georgios I, Teoh, Kevin H, Vincent, Jessica, Walsh, Michael, Yared, Jean-Pierre, Yusuf, Salim, Whitlock, Richard P, Whitlock, R, Semelhago, L, Chu, V, Dyub, A, Cybulsky, I, Van Oosteen, R, Cordova, G, Quantz, MA, McKenzie, FN, Fox, S, Chase, L, Stevens, LM, Prieto, I, Basile, F, Finegan, BA, Bryden, C, Meyer, S, Chappell, A, Mazer, CD, Dixon, J, Yagnik, S, Crescini, C, Verma, S, Legare, JF, Greentree, D, Coutu, M, Teijeira, J, Wiley, W, Peniston, C, Teng, C, Rochon, AG, Lamarche, Y, Deschamps, A, Voisine, P, Dagenais, F, Singal, RK, Brown, CD, Kieser, TM, Robinson, R, Fremes, SE, Christakis, GT, Melvin, KN, Parsons, M, Zheng, H, Yu, J, Xu, W, Zhang, Q, Chen, C, Yu, H, Zeng, J, Zuo, Y, Liu, J, Zhang, T, Sun, Y, Song, D, Dong, H, Chen, M, Zhao, J, Tao, L, Huang, W, Cheng, Y, Long, YS, Lei, W, Zhang, W, Xu, MY, Qing, E, Xiao, YB, Karunakaran, J, Pillai, VV, Reddy, PB, Kundan, S, Jain, AR, Mallya, SS, Mehta, CB, Shukla, V, Kuruvila, K, Karthikeyan, G, Devagourou, V, Hote, MP, Airan, B, Padmanabhan, C, Srinivasan, M, Agarwal, SK, Pande, S, Rao, P Simha Mohan, Math, R, Shankar, BPR, Vaijyanath, PH, Nair, SK, Ayapati, DR, Kurz, A, Awais, A, Panjasawatwong, K, Kashy, BK, Huffmyer, JL, Scalzo, DC, Kazemi, A, Huang, KF, Parvathaneni, SV, Gardner, JC, Malik, MR, Eshraghi, Y, Kramer, RS, Essandoh, MK, Portillo, J, Ayad, SS, Akhtar, Z, Castresana, MR, Collard, CD, Rodriguez-Blanco, YF, Eaton, MP, Villar, JC, Umana, JP, Dominguez, CL, Alvarado, PA, Zuluaga, D, Abello, M, Sarquis, T, Vaquiro, E, Oliveros, CA, Manrique, EJ, Vasquez, S, Ortiz, LM, Holliday, J, Griffin, R, Royse, AG, Royse, CF, Williams, Z, Paparella, D, Rotunno, C, De Palo, M, Margari, V, Alfieri, O, Ferrara, D, Schiavi, D, Parolari, A, Myasoedova, VA, Daprati, A, De Feo, M, Bancone, C, Di Bartolomeo, R, Pacini, D, Ribezzo, M, Karimi, A, Salehiomran, A, Hajighasemi, A, Bina, P, Straka, Z, Hlavicka, J, Lukac, P, Vik, K, Mosna, F, Tsilimingas, NB, Simopoulos, VN, Tsolaki, F, Rivilla, MT, Galan, J, Nunez, JAF, Gonzalez, A, Ruiz, D, Orts Rodriguez, M, Issa, M, Vila Nova, DC, Maia, LN, Nakazone, MA, Lico e Cividanes, GV, Hajjar, LA, Neto, V Avila, Lucchese, FA, Stolf, NA, Hutschala, D, Ruetzler, K, Sima, B, Engelen, S, Borms, S, Van De Velde, M, Rex, S, De Hert, SG, Ho, AMH, Chan, MTV, Underwood, MJ, Deluca Bisurgi, D, Torres, D, and Buggy, DJ

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Anti-Inflammatory Agents, 030204 cardiovascular system & hematology, Methylprednisolone, Drug Administration Schedule, law.invention, 03 medical and health sciences, Medicine, General & Internal, 0302 clinical medicine, Postoperative Complications, Randomized controlled trial, law, General & Internal Medicine, Cardiopulmonary bypass, SIRS, Medicine, Humans, 030212 general & internal medicine, Cardiac Surgical Procedures, Glucocorticoids, Dialysis, Aged, Science & Technology, Cardiopulmonary Bypass, business.industry, STEROIDS, Research, Acute kidney injury, General Medicine, Perioperative, Acute Kidney Injury, Middle Aged, medicine.disease, Cardiac surgery, HIGH-DOSE DEXAMETHASONE, Anesthesia, Female, business, Life Sciences & Biomedicine, Kidney disease, medicine.drug
Abstract

BACKGROUND: Perioperative corticosteroid use may reduce acute kidney injury. We sought to test whether methylprednisolone reduces the risk of acute kidney injury after cardiac surgery. METHODS: We conducted a prespecified substudy of a randomized controlled trial involving patients undergoing cardiac surgery with cardiopulmonary bypass (2007-2014); patients were recruited from 79 centres in 18 countries. Eligibility criteria included a moderate-to-high risk of perioperative death based on a preoperative score of 6 or greater on the European System for Cardiac Operative Risk Evaluation I. Patients (n = 7286) were randomly assigned (1:1) to receive intravenous methylprednisolone (250 mg at anesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients, caregivers, data collectors and outcome adjudicators were unaware of the assigned intervention. The primary outcome was postoperative acute kidney injury, defined as an increase in the serum creatinine concentration (from the preoperative value) of 0.3 mg/dL or greater (≥ 26.5 μmol/L) or 50% or greater in the 14-day period after surgery, or use of dialysis within 30 days after surgery. RESULTS: Acute kidney injury occurred in 1479/3647 patients (40.6%) in the methylprednisolone group and in 1426/3639 patients (39.2%) in the placebo group (adjusted relative risk 1.04, 95% confidence interval 0.96 to 1.11). Results were consistent across several definitions of acute kidney injury and in patients with preoperative chronic kidney disease. INTERPRETATION: Intraoperative corticosteroid use did not reduce the risk of acute kidney injury in patients with a moderate-to-high risk of perioperative death who had cardiac surgery with cardiopulmonary bypass. Our results do not support the prophylactic use of steroids during cardiopulmonary bypass surgery. Trial registration: ClinicalTrials.gov, no. NCT00427388. ispartof: CANADIAN MEDICAL ASSOCIATION JOURNAL vol:191 issue:9 pages:E247-E256 ispartof: location:Canada status: published

Published
2019

12. Optimizing the Safety Profile of Everolimus by Delayed Initiation in De Novo Heart Transplant Recipients: Results of the Prospective Randomized Study EVERHEART

Author

Potena, L., Pellegrini, C., Grigioni, F., Amarelli, C., Livi, U., Maccherini, M., Masciocco, G., Faggian, G., Lilla Della Monica, P., Gerosa, G., Marraudino, N., Corda, M., Boffini, M., De Santo, L. S., Tona, F., Poggio, D., Savini, C., Ambrogi, F., Bernazzali, S., D'Armini, A. M., Mattiucci, G., Rinaldi, M., Ribezzo, M., Porcu, M., Musumeci, F., Gambino, A., Maiello, C., Frigerio, M., Guzzi, G., Forni, A., and Capone, G.

Subjects
Male, medicine.medical_specialty, Pleural effusion, medicine.medical_treatment, 030204 cardiovascular system & hematology, 030230 surgery, Pericardial effusion, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Cumulative incidence, Everolimus, Prospective Studies, Prospective cohort study, Heart transplantation, Transplantation, business.industry, Original Clinical Science—General, medicine.disease, Surgery, Discontinuation, Heart Transplantation, Female, Immunosuppressive Agents, business, medicine.drug
Abstract

Background Although everolimus potentially improves long-term heart transplantation (HTx) outcomes, its early postoperative safety profile had raised concerns and needs optimization. Methods This 6-month, open-label, multicenter randomized trial was designed to compare the cumulative incidence of a primary composite safety endpoint comprising wound healing delays, pericardial effusion, pleural effusion needing drainage, and renal insufficiency events (estimated glomerular filtration rate ≤30/mL/min per 1.73 m2) in de novo HTx recipients receiving immediate everolimus (EVR-I) (≤144 hours post-HTx) or delayed everolimus (EVR-D) (4-6 weeks post-HTx with mycophenolate mofetil as a bridge) with reduced-dose cyclosporine A. Cumulative incidence of biopsy-proven rejection ≥ 2R, rejection with hemodynamic compromise, graft loss, or death was the secondary composite efficacy endpoint. Results Overall, 181 patients were randomized to the EVR-I (n = 89) or EVR-D (n = 92) arms. Incidence of primary safety endpoint was higher for EVR-I than EVR-D arm (44.9% vs 32.6%; P = 0.191), mainly driven by a higher rate of pericardial effusion (33.7% vs 19.6%; P = 0.04); wound healing delays, acute renal insufficiency events, and pleural effusion occurred at similar frequencies in the study arms. Efficacy failure was not significantly different in EVR-I arm versus EVR-D arm (37.1% vs 28.3%; P = 0.191). Three patients in the EVR-I arm and 1 in the EVR-D arm died. Incidence of clinically significant adverse events leading to discontinuation was higher in EVR-I arm versus EVR-D arm (P = 0.02). Conclusions Compared with immediate initiation, delayed everolimus initiation appeared to provide a clinically relevant early safety benefit in de novo HTx recipients, without compromising efficacy., The 6-month, open-label, multicenter randomized trial is designed to compare primary safety endpoints in de novo heart transplantation and delayed everolimus initiation seems to provide a clinically relevant early safety benefit compared to immediate initiation without compromising efficacy. Supplemental digital content is available in the text.

Published
2018

19. Poster Session 1: Thursday 8 December 2011, 08:30-12:30 * Location: Poster Area

Author

Vijayan, S., primary, Khanji, M., additional, Ionescu, A., additional, Vijayan, S., additional, Podoleanu, C., additional, Frigy, A., additional, Ugri, A., additional, Varga, A., additional, Podoleanu, D., additional, Incze, A., additional, Carasca, E., additional, Dobreanu, D., additional, Mjolstad, O., additional, Dalen, H., additional, Graven, T., additional, Kleinau, J., additional, Hagen, B., additional, Fu, H., additional, Liu, T., additional, Li, J., additional, Liu, C., additional, Zhou, C., additional, Li, G., additional, Bordese, R., additional, Capriolo, M., additional, Brero, D., additional, Salvetti, I., additional, Cannillo, M., additional, Antolini, M., additional, Grosso Marra, W., additional, Frea, S., additional, Morello, M., additional, Gaita, F., additional, Maffessanti, F., additional, Caiani, E., additional, Muraru, D., additional, Tuveri, F., additional, Dal Bianco, L., additional, Badano, L., additional, Majid, A., additional, Soesanto, A., additional, Ario Suryo Kuncoro, B., additional, Sukmawan, R., additional, Ganesja, M. H., additional, Benedek, T., additional, Chitu, M., additional, Beata, J., additional, Suciu, Z., additional, Kovacs, I., additional, Bucur, O., additional, Benedek, I., additional, Hrynkiewicz-Szymanska, A., additional, Szymanski, F., additional, Karpinski, G., additional, Filipiak, K., additional, Radunovic, Z., additional, Lande Wekre, L., additional, Steine, K., additional, Bech-Hanssen, O., additional, Rundqvist, B., additional, Lindgren, F., additional, Selimovic, N., additional, Jedrzychowska-Baraniak, J., additional, Jozwa, R., additional, Larysz, B., additional, Kasprzak, J., additional, Ripp, T., additional, Mordovin, V., additional, Ripp, E., additional, Ciobanu, A., additional, Dulgheru, R., additional, Dragoi, R., additional, Magda, S., additional, Florescu, M., additional, Mihaila, S., additional, Rimbas, R., additional, Cinteza, M., additional, Vinereanu, D., additional, Benavides-Vallve, C., additional, Pelacho, B., additional, Iglesias, O., additional, Castano, S., additional, Munoz-Barrutia, A., additional, Prosper, F., additional, Ortiz De Solorzano, C., additional, Manouras, A., additional, Sahlen, A., additional, Winter, R., additional, Vardas, P., additional, Brodin, L., additional, Sarvari, S. I., additional, Haugaa, K. H., additional, Zahid, W., additional, Bendz, B., additional, Aaberge, L., additional, Edvardsen, T., additional, Di Bella, G., additional, Pedri, S., additional, Donato, R., additional, Madaffari, A., additional, Zito, C., additional, Stapf, D., additional, Schreckenberg, M., additional, Carerj, S., additional, Yoshikawa, H., additional, Suzuki, M., additional, Kusunose, Y., additional, Hashimoto, G., additional, Otsuka, T., additional, Nakamura, M., additional, Sugi, K., additional, Grapsa, J., additional, Dawson, D., additional, Gin-Sing, W., additional, Howard, L., additional, Gibbs, J., additional, Nihoyannopoulos, P., additional, Smith, B., additional, Coulter, T., additional, Rendon, A., additional, Gorissen, W., additional, Shiran, A., additional, Asmer, I., additional, Adawi, S., additional, Ganaeem, M., additional, Shehadeh, J., additional, Cameli, M., additional, Lisi, M., additional, Righini, F., additional, Maccherini, M., additional, Sani, G., additional, Galderisi, M., additional, Mondillo, S., additional, Kalimanovska-Ostric, D., additional, Nastasovic, T., additional, Jovanovic, I., additional, Milakovic, B., additional, Dostanic, M., additional, Stosic, M., additional, Sasic, I., additional, Sveen, K., additional, Nerdrum, T., additional, Hanssen, K., additional, Dahl-Jorgensen, K., additional, Holte, E., additional, Vegsundvaag, J., additional, Hole, T., additional, Hegbom, K., additional, Wiseth, R., additional, Ikonomidis, I., additional, Lekakis, J., additional, Tritakis, V., additional, Papadakis, I., additional, Kadoglou, N., additional, Tzortzis, S., additional, Trivilou, P., additional, Koukoulis, C., additional, Paraskevaidis, I., additional, Anastasiou-Nana, M., additional, Smedsrud, M. K., additional, Sarvari, S., additional, Gjesdal, O., additional, Beraldo, M., additional, Solda', E., additional, Cucchini, U., additional, Peluso, D., additional, Tuveri, M., additional, Al Mamary, A., additional, Iliceto, S., additional, Dores, H., additional, Abecasis, J., additional, Carvalho, M., additional, Santos, M., additional, Andrade, M., additional, Ribeiras, R., additional, Reis, C., additional, Horta, E., additional, Gouveia, R., additional, Mendes, M., additional, Zaliaduonyte-Peksiene, D., additional, Mizariene, V., additional, Cesnaite, G., additional, Tamuleviciute, E., additional, Jurkevicius, R., additional, Vaskelyte, J., additional, Zaliunas, R., additional, Smarz, K., additional, Zaborska, B., additional, Jaxa-Chamiec, T., additional, Maciejewski, P., additional, Budaj, A., additional, Trifunovic, D., additional, Sobic-Saranovic, D., additional, Stankovic, S., additional, Ostojic, M., additional, Vujisic-Tesic, B., additional, Petrovic, M., additional, Nedeljkovic, I., additional, Banovic, M., additional, Tesic, M., additional, Petrovic, I., additional, Peovska, I., additional, Srbinovska, E., additional, Maksimovic, J., additional, Andova, V., additional, Arnaudova, F., additional, Hristova, E., additional, Otljanska, M., additional, Vavlukis, M., additional, Jovanova, S., additional, Tamborini, G., additional, Fusini, L., additional, Gripari, P., additional, Muratori, M., additional, Pontone, G., additional, Andreini, D., additional, Bertella, E., additional, Ghulam Ali, S., additional, Bartorelli, A., additional, Pepi, M., additional, Cusma-Piccione, M., additional, Salvia, J., additional, Antonini-Canterin, F., additional, Lentini, S., additional, Donato, D., additional, Miceli, M., additional, Oreto, G., additional, Sachner, R., additional, Rubinshtein, R., additional, Shnapp, M., additional, Gaspar, T., additional, Marchese, A., additional, Deste, W., additional, Sanfilippo, A., additional, Aruta, P., additional, Patane, M., additional, Millan, G., additional, Ussia, G., additional, Tamburino, C., additional, Kujacic, V., additional, Obradovic, S., additional, Crkvenac, Z., additional, Bernard, A., additional, Piquemal, M., additional, Muller, G., additional, Arbeille, P., additional, Charbonnier, B., additional, Broyd, C., additional, Davies, J., additional, Mikhail, G., additional, Mayet, J., additional, Francis, D., additional, Rosca, M., additional, Magne, J., additional, Szymanski, C., additional, Popescu, B., additional, Ginghina, C., additional, Pierard, L., additional, Lancellotti, P., additional, Gonzalez-Mansilla, A., additional, Solis, J., additional, Angulo, R., additional, Perez-David, E., additional, Madrid, G., additional, Garcia-Robles, J., additional, Yotti, R., additional, Prieto, R., additional, Bermejo, J., additional, Fernandez-Aviles, F., additional, Ishikawa, Y., additional, Ishida, T., additional, Osaki, T., additional, Matsuyama, M., additional, Yamashita, H., additional, Ozaki, S., additional, Stevanella, M., additional, Votta, E., additional, Veronesi, F., additional, Alamanni, F., additional, Redaelli, A., additional, Park, S. D., additional, Lee, J., additional, Shin, S., additional, Woo, S., additional, Kim, D., additional, Park, K., additional, Kwan, J., additional, Tsang, W., additional, Chandra, S., additional, Weinert, L., additional, Gayat, E., additional, Djelassi, M., additional, Balbach, T., additional, Mor-Avi, V., additional, Lang, R., additional, De Meester, P., additional, Van De Bruaene, A., additional, Delcroix, M., additional, Budts, W., additional, Abid, L., additional, Frikha, Z., additional, Makni, K., additional, Rekik, H., additional, Znazen, A., additional, Mourad, H., additional, Kammoun, S., additional, Sargento, L., additional, Satendra, M., additional, Sousa, C., additional, Lopes, S., additional, Longo, S., additional, Lousada, N., additional, Palma Reis, R., additional, Fouad, D., additional, Shams Eldeen, R., additional, Beladan, C., additional, Calin, A., additional, Voinea, F., additional, Enache, R., additional, Jurcut, R., additional, Coman, I., additional, Ghionea, M., additional, Djordjevic-Dikic, A., additional, Petrovic, O., additional, Boricic, M., additional, Giga, V., additional, Pisciella, L., additional, Lanzillo, C., additional, Minati, M., additional, Caselli, S., additional, Di Roma, M., additional, Fratini, S., additional, Romano, S., additional, Calo', L., additional, Lioy, E., additional, Penco, M., additional, Finocchiaro, G., additional, Pinamonti, B., additional, Merlo, M., additional, Barbati, G., additional, Sinagra, G., additional, Dilenarda, A., additional, Comenale Pinto, S., additional, Ancona, R., additional, Caso, P., additional, Cavallaro, C., additional, Vecchione, F., additional, D'onofrio, A., additional, Fero', M., additional, Calabro', R., additional, Gustafsson, S., additional, Ihse, E., additional, Henein, M., additional, Westermark, P., additional, Suhr, O., additional, Lindqvist, P., additional, Oliva Sandoval, M., additional, Gonzalez Carrillo, M., additional, Garcia Navarro, M., additional, Garcia-Molina Saez, E., additional, Sabater Molina, M., additional, Saura Espin, D., additional, Lacunza Ruiz, J., additional, Gimeno Blanes, J., additional, De La Morena Valenzuela, G., additional, Valdes Chavarri, M., additional, Prinz, C., additional, Faber, L., additional, Horstkotte, D., additional, Hoetz, H., additional, Voigt, J., additional, Gandara, F., additional, Correia, M., additional, Rosario, I., additional, Fonseca, C., additional, Arroja, I., additional, Aleixo, A., additional, Martins, A., additional, Radulescu, L., additional, Dan Radulescu, D., additional, Parv Andreea, P., additional, Duncea Caius, D., additional, Ciuleanu T, C., additional, Mitrea Paulina, M., additional, Cali Quaglia, F., additional, Ribezzo, M., additional, Boffini, M., additional, Rinaldi, M., additional, Maceira Gonzalez, A. M., additional, Cosin-Sales, J., additional, Dalli, E., additional, Diago, J., additional, Aguilar, J., additional, Ruvira, J., additional, Goncalves, S., additional, Gomes, A., additional, Pinto, F., additional, Tsai, W.-C., additional, Liu, Y.-W., additional, Shih, J.-Y., additional, Huang, Y.-Y., additional, Chen, J.-Y., additional, Tsai, L.-M., additional, Chen, J.-H., additional, Ribeiro, S., additional, Doroteia, D., additional, Santos, L., additional, David, C., additional, Vinhas De Sousa, G., additional, Almeida, A., additional, Iwase, M., additional, Itou, Y., additional, Yasukochi, S., additional, Shiino, K., additional, Inuzuka, H., additional, Sugimoto, K., additional, Ozaki, Y., additional, Gieszczyk-Strozik, K., additional, Sikora-Puz, A., additional, Mizia, M., additional, Lasota, B., additional, Chmiel, A., additional, Lis-Swiety, A., additional, Michna, J., additional, Brzezinska-Wcislo, L., additional, Mizia-Stec, K., additional, Gasior, Z., additional, Luijendijk, P., additional, De Bruin-Bon, H., additional, Zwiers, C., additional, Vriend, J., additional, Van Den Brink, R., additional, Mulder, B., additional, Bouma, B., additional, Brigido, S., additional, Gianfagna, P., additional, Proclemer, A., additional, Plicht, B., additional, Kahlert, P., additional, Kaelsch, H., additional, Buck, T., additional, Erbel, R., additional, Konorza, T., additional, Yoon, H., additional, Kim, K., additional, Ahn, Y., additional, Jeong, M., additional, Cho, J., additional, Park, J., additional, Kang, J., additional, Rha, W., additional, Jansen Klomp, W. W., additional, Brandon Bravo Bruinsma, G., additional, Van 'T Hof, A., additional, Spanjersberg, S., additional, Nierich, A., additional, Bombardini, T., additional, Gherardi, S., additional, Picano, E., additional, Ciarka, A., additional, Herbots, L., additional, Eroglu, E., additional, Van Cleemput, J., additional, Droogne, W., additional, Jasityte, R., additional, Meyns, B., additional, D'hooge, J., additional, Vanhaecke, J., additional, Al Barjas, M., additional, Iskreva, R., additional, Morris, R., additional, Davar, J., additional, Zhao, Y., additional, Holmgren, A., additional, Morner, S., additional, Stepanovic, J., additional, Beleslin, B., additional, Nedeljkovic, M., additional, Mazic, S., additional, Stojanov, V., additional, Piatkowski, R., additional, Kochanowski, J., additional, Scislo, P., additional, Grabowski, M., additional, Marchel, M., additional, Roik, M., additional, Kosior, D., additional, Opolski, G., additional, Tomaszewski, A., additional, Kutarski, A., additional, Tomaszewski, M., additional, Eibel, S., additional, Hasheminejad, E., additional, Mukherjee, C., additional, Tschernich, H., additional, Ender, J., additional, Delithanasis, I., additional, Celutkiene, J., additional, Kenny, C., additional, Monaghan, M., additional, Van Den Oord, S., additional, Ten Kate, G., additional, Akkus, Z., additional, Renaud, G., additional, Sijbrands, E., additional, Ten Cate, F., additional, De Jong, N., additional, Bosch, J., additional, Van Der Steen, A., additional, Schinkel, A., additional, Lisowska, A., additional, Knapp, M., additional, Tycinska, A., additional, Sawicki, R., additional, Kralisz, P., additional, Sobkowicz, B., additional, Chang, S.-A., additional, Lee, S.-C., additional, Kim, E.-Y., additional, Hahm, S.-H., additional, Ahn, G.-T., additional, Sohn, M.-K., additional, Park, S.-J., additional, Choi, J.-O., additional, Park, S.-W., additional, Oh, J.-K., additional, Gursoy, M. O., additional, Gokdeniz, T., additional, Astarcioglu, M., additional, Bayram, Z., additional, Cakal, B., additional, Karakoyun, S., additional, Kalcik, M., additional, Kahveci, G., additional, Yildiz, M., additional, Ozkan, M., additional, Skidan, V., additional, Borowski, A., additional, Park, M., additional, Thomas, J., additional, Ranjbar, S., additional, Hassantash, S., additional, Karvandi, M., additional, Foroughi, M., additional, Davidsen, E. S., additional, Cramariuc, D., additional, Bleie, O., additional, Gerdts, E., additional, Matre, K., additional, Cusma' Piccione, M., additional, Bagnato, G., additional, Mohammed, M., additional, Piluso, S., additional, Oreto, L., additional, Bitter, T., additional, Carvalho, S., additional, Canada, M., additional, Santisteban Sanchez De Puerta, M., additional, Mesa Rubio, M. D., additional, Ruiz Ortiz, M., additional, Delgado Ortega, M., additional, Pena Pena, M. L., additional, Puentes Chiachio, M., additional, Suarez De Lezo Cruz-Conde, J., additional, Pan Alvarez-Ossorio, M., additional, Mazuelos Bellido, F., additional, Suarez De Lezo Herreros De Tejada, J., additional, Altekin, E., additional, Yanikoglu, A., additional, Karakas, S., additional, Oncel, C., additional, Akdemir, B., additional, Belgi Yildirim, A., additional, Cilli, A., additional, Yilmaz, H., additional, Lenartowska, L., additional, Furdal, M., additional, Knysz, B., additional, Konieczny, A., additional, Lewczuk, J., additional, Severino, S., additional, Cavallaro, M., additional, Coppola, M., additional, Motoki, H., additional, To, A., additional, Bhargava, M., additional, Wazni, O., additional, Marwick, T., additional, Klein, A., additional, Sinkovskaya, E., additional, Horton, S., additional, Abuhamad, A., additional, Mingo Santos, S., additional, Monivas Palomero, V., additional, Beltran Correas, B., additional, Mitroi, C., additional, Gutierrez Landaluce, C., additional, Garcia Lunar, I., additional, Gonzalez Mirelis, J., additional, Cavero, M., additional, Segovia Cubero, J., additional, Alonso Pulpon, L., additional, Gurel, E., additional, Karaahmet, T., additional, Tigen, K., additional, Kirma, C., additional, Dundar, C., additional, Pala, S., additional, Isiklar, I., additional, Cevik, C., additional, Kilicgedik, A., additional, Basaran, Y., additional, Brambatti, M., additional, Romandini, A., additional, Barbarossa, A., additional, Molini, S., additional, Urbinati, A., additional, Giovagnoli, A., additional, Cipolletta, L., additional, Capucci, A., additional, Park, S., additional, Choi, E., additional, Ahn, C., additional, Hong, S., additional, Kim, M., additional, Lim, D., additional, Shim, W., additional, Xie, J., additional, Fang, F., additional, Zhang, Q., additional, Chan, J., additional, Yip, G., additional, Sanderson, J., additional, Lam, Y., additional, Yan, B., additional, Yu, C., additional, Jorge Perez, P., additional, De La Rosa Hernandez, A., additional, Hernandez Garcia, C., additional, Duque Garcia, A., additional, Barragan Acea, A., additional, Arroyo Ucar, E., additional, Jimenez Rivera, J., additional, Lacalzada Almeida, J., additional, Laynez Cerdena, I., additional, Carminati, C., additional, Capoulade, R., additional, Larose, E., additional, Clavel, M., additional, Dumesnil, J., additional, Arsenault, M., additional, Bedard, E., additional, Mathieu, P., additional, Pibarot, P., additional, Gargani, L., additional, Baldi, G., additional, Forfori, F., additional, Caramella, D., additional, D'errico, L., additional, Abramo, A., additional, Sicari, R., additional, Giunta, F., additional, Lee, W.-N., additional, Larrat, B., additional, Messas, E., additional, Pernot, M., additional, Tanter, M., additional, Velagic, V., additional, Cikes, M., additional, Matasic, R., additional, Skorak, I., additional, Samardzic, J., additional, Puljevic, D., additional, Lovric Bencic, M., additional, Biocina, B., additional, Milicic, D., additional, Roosens, B., additional, Bala, G., additional, Droogmans, S., additional, Hostens, J., additional, Somja, J., additional, Delvenne, E., additional, Schiettecatte, J., additional, Lahoutte, T., additional, Van Camp, G., additional, Cosyns, B., additional, Ghosh, A., additional, Hardy, R., additional, Chaturvedi, N., additional, Deanfield, J., additional, Pellerin, D., additional, Kuh, D., additional, Hughes, A., additional, Malmgren, A., additional, Dencker, M., additional, Stagmo, M., additional, Gudmundsson, P., additional, Seo, Y., additional, Ishizu, T., additional, Aonuma, K., additional, Schuuring, M. J., additional, Vis, J., additional, Van Dijk, A., additional, Van Melle, J., additional, Pieper, P., additional, Vliegen, H., additional, Sieswerda, G., additional, Foukarakis, E., additional, Pitarokilis, A., additional, Kafarakis, P., additional, Kiritsi, A., additional, Klironomos, E., additional, Manousakis, A., additional, Fragiadaki, X., additional, Papadakis, E., additional, and Dermitzakis, A., additional

Published
2011
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29. The use of CO2 removal devices in patients awaiting lung transplantation: an initial experience

Author

Massimo Boffini, Davide Ricci, S. El Qarra, V. M. Ranieri, M. Ribezzo, Mauro Rinaldi, L Del Sorbo, R. Bonato, Chiara Comoglio, Ricci D, Boffini M, Del Sorbo L, El Qarra S, Comoglio C, Ribezzo M, Bonato R, Ranieri VM, and Rinaldi M.

Subjects
Adult, Graft Rejection, Male, medicine.medical_specialty, Artificial Organs, Blood Gas Analysis, Carbon Dioxide, Cause of Death, Emphysema, Extracorporeal Membrane Oxygenation, Female, Humans, Lung Transplantation, Middle Aged, Pulmonary Fibrosis, Respiratory Insufficiency, Waiting Lists, medicine.medical_treatment, Cystic fibrosis, Extracorporeal, medicine, Lung transplantation, Mechanical ventilation, Transplantation, Lung, business.industry, medicine.disease, Surgery, medicine.anatomical_structure, n/a, Respiratory failure, medicine.symptom, business, Hypercapnia
Abstract

BACKGROUND: Lung transplantation is the treatment of choice for patients with end-stage lung failure. Limitations are presented by the shortage of donors and the long waiting list periods. New techniques, such as extracorporeal membrane ventilator devices with or without pump support, have been developed as bridges to transplantation for patients with severe, unresponsive respiratory insufficiency. METHODS: Between November 2005 and September 2009, 12 patients (7 males and 5 females), of overall mean age of 43.3 +/- 15.5 years underwent decapneization with extracorporeal devices. In 6 cases, a NovaLung system was used; in the remaining 6 patients, it was a Decap device. Causes of respiratory failure that led to implantation of such devices were cystic fibrosis (n = 6), pulmonary emphysema (n = 5), and chronic rejection of a previous double lung transplant (n = 1). RESULTS: Mean time on extracorporeal decapneization was 13.5 +/- 14.2 days. Eight patients died on the device. Three patients were bridged to lung transplantation; 1 recovered and was weaned from the device after 11 days. Mean PaCO(2) on the extracorporeal gas exchanger was significantly lower for both the devices at 24, 48, and 72 hours after implantation (P < .05). No significant difference was observed for the 2 systems. CONCLUSION: In our initial experience, decapneization devices have been simple, efficient methods to support patients with mild hypoxia and severe hypercapnia that is refractory to mechanical ventilation. This could represent a valid bridge to lung transplantation in these patients.

Published
2010

30. Relationship between ventricular pressure and coronary artery disease in asymptomatic adult heart transplant recipients.

Author

Iannaccone M, Meynet I, Omedè P, D'Ascenzo F, Taha S, Bertaina M, Colaci C, Marangoni L, Ribezzo M, Boffini M, Rinaldi M, Moretti C, and Gaita F

Subjects
Adult, Cause of Death, Coronary Angiography, Female, Humans, Italy, Logistic Models, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, Retrospective Studies, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease physiopathology, Heart Transplantation adverse effects, Pulmonary Wedge Pressure, Ventricular Pressure
Abstract

Introduction: The association between data of right heart catheterization and cardiac allograft vasculopathy (CAV) in adult heart transplant (HTx) recipients remains to be determined., Methods and Results: This is an observational, retrospective study, including all consecutive asymptomatic HTx patients undergoing routine right and left catheterization. The independent predictive power of pulmonary capillary wedge pressure (PCWP) to predict CAV (classified according to working formulation of a standardized nomenclature for CAV-2010) was the primary end point. Seventy-one patients were included, with a mean time from HTx to procedure of 19 ± 25 months. At coronary angiography first degree of CAV was found in eight patients (11.2%), second degree of CAV in two patients (2.8%), and third in two (2.8%). PCWP values were significantly higher in patients with CAV compared with patients without CAV (17.5 ± 7.5 vs. 10.4 ± 5.6, P < 0.001) and values of 15 mmHg or greater had an AUC of 0.71 (0.48-0.92), with a sensitivity of 71% and a specificity of 73% in predicting CAV, with an independent relationship confirmed at logistic regression analysis (odds ratio 1.28, IC 1.06-1.53; P = 0.008)., Conclusion: A significantly elevated PCWP at the time of the diagnosis of transplant coronary artery disease may be considered as an early marker of CAV, especially in asymptomatic HTx recipients.

Published
2017
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31. Incidence and severity of primary graft dysfunction after lung transplantation using rejected grafts reconditioned with ex vivo lung perfusion.

Author

Boffini M, Ricci D, Bonato R, Fanelli V, Attisani M, Ribezzo M, Solidoro P, Del Sorbo L, Ranieri VM, and Rinaldi M

Subjects
Adult, Aged, Female, Humans, Incidence, Lung physiology, Lung Transplantation adverse effects, Male, Middle Aged, Perfusion methods, Primary Graft Dysfunction etiology, Primary Graft Dysfunction physiopathology, Risk Factors, Tissue Donors statistics & numerical data, Lung blood supply, Lung surgery, Lung Transplantation methods
Abstract

Objectives: Ex vivo lung perfusion (EVLP) is a novel technique used to evaluate and recondition marginal or rejected grafts. Primary graft dysfunction (PGD) is a major early complication after lung transplantation (LTx). The use of marginal or initially rejected grafts may increase its incidence and severity. The aim of this study is to evaluate the incidence of PGD after LTx using rejected grafts reconditioned with EVLP., Methods: PGD has been evaluated immediately after LTx (t0) and after 72 h (t72) in patients receiving standard (Group A) or reconditioned (Group B) grafts. EVLP was performed using a controlled acellular perfusion according to the Toronto technique., Results: From July 2011 to February 2013, 36 LTxs have been performed: 28 patients (21 M/7 F, mean age 51.7 ± 14.7 years) in Group A and 8 (6 M/2 F, mean age 46.6 ± 9.8 years) in Group B (successful recondition rate of 73%, 8 of 11 cases). Incidence rate of PGD 3 at t0 and at t72 (Group A versus Group B) was 50 vs 37% (P = NS) and 25 vs 0% (P = NS), respectively. Post-transplant extracorporeal membrane oxygenation was required in 5 and 2 patients in Groups A and B, respectively (P = NS)., Conclusions: The use of initially rejected grafts treated with EVLP does not increase the incidence and severity of PGD after LTx. Although comparison of PGD 3 incidence in the two groups did not reach a statistical difference, all EVLP patients suffering from severe PGD early after transplant recovered normal lung function at 72 h, suggesting a protective role of EVLP against PGD occurrence and severity., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Published
2014
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32. Regional mapping of myocardial hibernation phenotype in idiopathic end-stage dilated cardiomyopathy.

Author

Lionetti V, Matteucci M, Ribezzo M, Di Silvestre D, Brambilla F, Agostini S, Mauri P, Padeletti L, Pingitore A, Delsedime L, Rinaldi M, Recchia FA, and Pucci A

Subjects
Adult, Apoptosis, Capillaries pathology, Cardiomyopathy, Dilated complications, Cardiomyopathy, Dilated diagnostic imaging, Cardiomyopathy, Dilated physiopathology, Cell Size, Collagen Type I metabolism, Connexin 43 metabolism, Female, Fibronectins metabolism, Heart Failure pathology, Heart Transplantation, Heart Ventricles diagnostic imaging, Heart Ventricles pathology, Heart Ventricles physiopathology, Hemodynamics, Humans, Male, Middle Aged, Myocardial Ischemia pathology, Myocardial Stunning complications, Myocardial Stunning metabolism, Myocytes, Cardiac pathology, Phenotype, Proteomics, Ultrasonography, Vimentin metabolism, Cardiomyopathy, Dilated pathology, Myocardial Stunning pathology
Abstract

Myocardial hibernation (MH) is a well-known feature of human ischaemic cardiomyopathy (ICM), whereas its presence in human idiopathic dilated cardiomyopathy (DCM) is still controversial. We investigated the histological and molecular features of MH in left ventricle (LV) regions of failing DCM or ICM hearts. We examined failing hearts from DCM (n = 11; 41.9 ± 5.45 years; left ventricle-ejection fraction (LV-EF), 18 ± 3.16%) and ICM patients (n = 12; 58.08 ± 1.7 years; LVEF, 21.5 ± 6.08%) undergoing cardiac transplantation, and normal donor hearts (N, n = 8). LV inter-ventricular septum (IVS) and antero-lateral free wall (FW) were transmurally (i.e. sub-epicardial, mesocardial and sub-endocardial layers) analysed. LV glycogen content was shown to be increased in both DCM and ICM as compared with N hearts (P < 0.001), with a U-shaped transmural distribution (lower values in mesocardium). Capillary density was homogenously reduced in both DCM and ICM as compared with N (P < 0.05 versus N), with a lower decrease independent of the extent of fibrosis in sub-endocardial and sub-epicardial layers of DCM as compared with ICM. HIF1-α and nestin, recognized ischaemic molecular hallmarks, were similarly expressed in DCM-LV and ICM-LV myocardium. The proteomic profile was overlapping by ~50% in DCM and ICM groups. Morphological and molecular features of MH were detected in end-stage ICM as well as in end-stage DCM LV, despite epicardial coronary artery patency and lower fibrosis in DCM hearts. Unravelling the presence of MH in the absence of coronary stenosis may be helpful to design a novel approach in the clinical management of DCM., (© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Published
2014
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33. Prognostic role of myocardial performance index on long-term survival after heart transplantation: a prospective study.

Author

Frea S, Capriolo M, Bergamasco L, Iacovino C, Quaglia FC, Ribezzo M, Marra WG, Boffini M, Rinaldi M, Morello M, and Gaita F

Subjects
Death, Sudden, Cardiac prevention & control, Echocardiography methods, Female, Humans, Incidence, Italy epidemiology, Male, Middle Aged, Prognosis, Prospective Studies, Reproducibility of Results, Risk Assessment methods, Sensitivity and Specificity, Survival Analysis, Death, Sudden, Cardiac epidemiology, Echocardiography statistics & numerical data, Heart Failure mortality, Heart Failure surgery, Heart Transplantation mortality, Postoperative Complications mortality, Survivors statistics & numerical data
Abstract

The survival rate of heart transplant patients is increasing, underlying the need for accurate predictors of adverse events during clinical follow-up. Myocardial performance index (MPI) is a Doppler-derived index of combined systolic and diastolic function: we assessed the prognostic role of MPI in survival of patients >1 year after heart transplantation (HT). A total of 152 consecutive HT patients referred to our institution were enrolled in this prospective study. Primary endpoints were cardiac death and a composite of major adverse cardiac events (MACE). During follow-up (69 ± 22 months), 68 (44.7%) patients had an adverse event and 20 (13.15%) patients died. Patients with MACE during follow-up showed lower EF (57.3 ± 9.3 vs. 63 ± 6.1; P < 0.001) and higher MPI (0.45 ± 0.19 vs. 0.31 ± 0.13; P < 0.001) at enrolment. MPI and EF were independently related to MACE (OR = 2.2; 95% confidence interval [CI] = 1.01-5.1; and OR = 6.6; 95% CI = 3.5-11.2, respectively) and showed strong diagnostic power (MPI: receiver operating characteristic [ROC] area = 79%, with 79% sensitivity and 81% specificity; EF: ROC area = 77%, with 54% sensitivity and 91% specificity) in the subsequent year. Patients with EF > 50% and MPI < 0.45 at enrolment showed 75% event-free survival 5 years after HT. In HT patients, MPI combined with EF was an accurate means of predicting long-term adverse events., (© 2013, Wiley Periodicals, Inc.)

Published
2013
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34. Human cardiac progenitor cell grafts as unrestricted source of supernumerary cardiac cells in healthy murine hearts.

Author

Forte G, Pietronave S, Nardone G, Zamperone A, Magnani E, Pagliari S, Pagliari F, Giacinti C, Nicoletti C, Musaró A, Rinaldi M, Ribezzo M, Comoglio C, Traversa E, Okano T, Minieri M, Prat M, and Di Nardo P

Subjects
Aged, Aged, 80 and over, Animals, Cell Differentiation, Cell Movement, Coculture Techniques, Female, Gene Expression Profiling, Heart Ventricles cytology, Heart Ventricles metabolism, Humans, Male, Mice, Mice, Inbred C57BL, Middle Aged, Myocardium cytology, Myocytes, Cardiac physiology, Myocytes, Cardiac transplantation, Phenotype, Tissue Transplantation methods, Heart Ventricles transplantation, Myocardium metabolism, Myocytes, Cardiac cytology, Stem Cells cytology, Tissue Engineering methods
Abstract

Human heart harbors a population of resident progenitor cells that can be isolated by stem cell antigen-1 antibody and expanded in culture. These cells can differentiate into cardiomyocytes in vitro and contribute to cardiac regeneration in vivo. However, when directly injected as single cell suspension, less than 1%-5% survive and differentiate. Among the major causes of this failure are the distressing protocols used to culture in vitro and implant progenitor cells into damaged hearts. Human cardiac progenitors obtained from the auricles of patients were cultured as scaffoldless engineered tissues fabricated using temperature-responsive surfaces. In the engineered tissue, progenitor cells established proper three-dimensional intercellular relationships and were embedded in self-produced extracellular matrix preserving their phenotype and multipotency in the absence of significant apoptosis. After engineered tissues were leant on visceral pericardium, a number of cells migrated into the murine myocardium and in the vascular walls, where they integrated in the respective textures. The study demonstrates the suitability of such an approach to deliver stem cells to the myocardium. Interestingly, the successful delivery of cells in murine healthy hearts suggests that myocardium displays a continued cell cupidity that is strictly regulated by the limited release of progenitor cells by the adopted source. When an unregulated cell source is added to the system, cells are delivered to the myocardium. The exploitation of this novel concept may pave the way to the setup of new protocols in cardiac cell therapy., (Copyright © 2011 AlphaMed Press.)

Published
2011
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35. PPARγ in coronary atherosclerosis: in vivo expression pattern and correlations with hyperlipidemic status and statin treatment.

Author

Pucci A, Formato L, Muscio M, Brscic E, Pizzimenti S, Ferroni F, Ribezzo M, Toaldo C, Pettazzoni P, Ciamporcero E, Barrera G, Rinaldi M, Bergamasco L, Sheiban I, and Spinnler MT

Subjects
Adult, Aged, Arteries metabolism, Coronary Artery Disease drug therapy, Female, Humans, Hyperlipidemias drug therapy, Immunohistochemistry methods, Inflammation, Macrophages metabolism, Male, Middle Aged, Plaque, Atherosclerotic drug therapy, Plaque, Atherosclerotic metabolism, U937 Cells, Coronary Artery Disease metabolism, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology, Hyperlipidemias metabolism, PPAR gamma metabolism
Abstract

Objective: Peroxisome proliferator-activated receptor-γ (PPARγ) is involved in regulation of macrophage inflammation and in atherosclerosis. Herein we investigate the influence of statin treatment on PPARγ expression in coronary artery disease., Method: PPARγ expression was investigated in coronary atherosclerotic atherectomies (N=48) and arteries (N=12) from patients with stable or unstable coronary syndromes or undergoing cardiac transplantation for end-stage ischemic cardiomyopathy, respectively, by immunohistochemistry. Plaque components and tissue factor immunoreactivity were also investigated. Atherectomies were obtained from de novo culprit lesions of hypercholesterolemic (16 statin-treated and 16 untreated) and normolipidemic (N=16) patients. Furthermore, PPARγ expression was evaluated in patients peripheral blood monocytes and in monocytic U937 cells after atorvastatin incubation, by Western blot analysis., Result: PPARγ expression was higher in coronary plaques and peripheral blood monocytes of statin-treated patients, and it significantly increased in monocytes after 24h atorvastatin incubation (p<0.05). Intra-plaque macrophage content, atheroma, neoangiogenesis and hemorrhage, and circulating CRP levels were lower in statin-treated than untreated hypercholesterolemic patients and comparable with normolipidemic subjects. PPARγ immunoreactivity was localized to neointima and media, its distribution pattern being different from that of tissue factor., Conclusion: PPARγ expression was enhanced in statin-treated patients with different distribution and behavior as compared to atheroma, macrophage content, tissue factor immunoreactivity and serum CRP. In vitro studies showed increased PPARγ expression in monocytes after atorvastatin incubation. These findings provide further evidence as to the protective role of statins in coronary artery disease and their influence on PPARγ expression in coronary plaques and on the inflammatory status of patients., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Published
2011
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36. Nail gun penetrating injury of the heart mimicking an acute coronary syndrome.

Author

Comoglio C, Sansone F, Boffini M, Ribezzo M, and Rinaldi M

Abstract

We describe the case of a 75-year-old man admitted to hospital for chest pain and syncope. Physical examination was normal with evidence of a very small wound on the left chest. Considering the presence of multiple coronary risk factors, an acute coronary syndrome was initially suspected, but the electrocardiogram (EKG) was normal and only a slight increase of cardiac enzymes was detected. The hypothesis of aortic dissection was also considered and in order to discriminate between the aortic and coronary syndrome, a thoracic and coronary computed tomography (CT) scan was performed. The CT scan showed a metallic structure, suggestive of a nail, about 6 cm in length, in the deep layers of the left ventricular wall and a small pneumothorax due to a lung lesion. The patient was therefore transferred to our department for urgent cardiac surgery that was performed without complications.

Published
2010
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37. Emergent coronary artery bypass grafting for cardiogenic shock caused by very late drug-eluting stent thrombosis.

Author

Boffini M, Ceresa F, Sansone F, Ribezzo M, Comoglio C, and Rinaldi M

Subjects
Angioplasty, Balloon, Coronary instrumentation, Coronary Angiography, Emergency Treatment, Humans, Male, Middle Aged, Platelet Aggregation Inhibitors therapeutic use, Shock, Cardiogenic diagnostic imaging, Shock, Cardiogenic etiology, Thrombosis diagnostic imaging, Thrombosis etiology, Time Factors, Treatment Outcome, Angioplasty, Balloon, Coronary adverse effects, Coronary Artery Bypass, Coronary Artery Disease therapy, Drug-Eluting Stents adverse effects, Shock, Cardiogenic surgery, Thrombosis surgery
Abstract

We describe a case of cardiogenic shock caused by a very late drug-eluting stent (DES) thrombosis. The patient underwent emergent coronary artery bypass grafting (CABG) and was discharged home 15 days after the operation. The incidence of stent restenosis had been reduced by the use of DES, but the Achilles' heel of DES is represented by a higher rate of stent thrombosis. In our case, the DES thrombosis occurred 5 years after its implantation, underlining the importance of prolonged dual antiplatelet therapy. Even though rare, this complication may be life-threatening. We believe that CABG provides better event-free survival than percutaneous coronary intervention in patients with multivessel coronary disease despite the use of DES.

Published
2009
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38. [A biological marker in drug dependence: microcirculatory homeostasis].

Author

Marconi G, Labate M, Catalucci F, Sergio G, Ribezzo MG, and Proietti MG

Subjects
Humans, Substance Withdrawal Syndrome etiology, Biological Clocks, Heroin Dependence physiopathology, Homeostasis, Microcirculation
Abstract

In 25 heroin addicts examined an initial alteration in microcirculatory homeostasis was found ond held to be responsible for the addiction. As in other cases it is thought possible to use the chronobiological course of haemodynamic balance and imbalance as a biological marker for prevention and treatment.

Published
1986

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