36 results on '"Hirschberg Y"'
Search Results
2. 718P A phase II study of patients with advanced or metastatic renal cell carcinoma (mRCC) receiving pazopanib after previous checkpoint inhibitor treatment
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Powles, T.B., primary, Oudard, S., additional, Grünwald, V., additional, Calvo, E., additional, Michaelson, M.D., additional, Burotto, M., additional, Melichar, B., additional, Tyagi, R., additional, Hilmi, F., additional, Gaur, A., additional, Hirschberg, Y., additional, and Heng, D., additional
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- 2020
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3. Real-world Effectiveness and Safety of Pazopanib in Patients With Intermediate Prognostic Risk Advanced Renal Cell Carcinoma
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Procopio, G. Bamias, A. Schmidinger, M. Hawkins, R. Sánchez, A.R. Estevez, S.V. Srihari, N. Kalofonos, H. Bono, P. Pisal, C.B. Hirschberg, Y. Dezzani, L. Ahmad, Q. Rodriguez, C.S. Jonasch, E.
- Abstract
Introduction: The objective of this study was to determine the effectiveness and safety of pazopanib in patients with intermediate-risk advanced/metastatic renal cell carcinoma in the PRINCIPAL study (NCT01649778). Patients and Methods: Patients had clear-cell advanced/metastatic renal cell carcinoma and met intermediate-risk International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Assessments included progression-free survival, overall survival, objective response rate, and safety. We also evaluated effectiveness based on number of risk factors, age, and performance status (PS), as well as safety in older and younger patients. Results: Three hundred sixty three and 343 intermediate-risk MSKCC and IMDC patients were included, respectively. The median progression-free survival was 13.8 months (95% confidence interval [CI], 10.7-18.1 months) and 7.4 months (95% CI, 6.2-10.3 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 13.1 months (95% CI, 10.7-18.1 months) and 8.1 months (95% CI, 6.4-10.7 months) for patients with 1 and 2 IMDC risk factors, respectively. The median overall survival was not reached and was 15.2 months (95% CI, 12.3-26.5 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 33.9 months (95% CI, 33.9 months to not estimable) and 19.4 months (95% CI, 14.3 months to not estimable) with 1 and 2 IMDC risk factors, respectively. A lower overall response rate was observed with Eastern Cooperative Oncology Group PS ≥ 2 (vs. PS < 2). All-grade treatment-related adverse events occurred in approximately 63% of patients, and the safety profile among older and younger patients was similar. Conclusions: Outcomes with pazopanib in intermediate-risk patients suggest that patients can be further stratified by number of risk factors (1 vs. 2) and Eastern Cooperative Oncology Group PS (< 2 vs. ≥ 2) to more accurately predict outcomes. © 2019 Patients with intermediate-risk advanced renal cell carcinoma are a heterogeneous population, having either 1 or 2 risk factors. It is unclear whether all patients in this risk category should be treated similarly. A secondary analysis of the PRINCIPAL study of pazopanib found that patients can be stratified by number of risk factors and Eastern Cooperative Oncology Group performance status to more accurately predict outcomes. © 2019
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- 2019
4. Prospective Observational Study of Pazopanib in Patients with Advanced Renal Cell Carcinoma (PRINCIPAL Study)
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Schmidinger, M. Bamias, A. Procopio, G. Hawkins, R. Sanchez, A.R. Vázquez, S. Srihari, N. Kalofonos, H. Bono, P. Pisal, C.B. Hirschberg, Y. Dezzani, L. Ahmad, Q. Jonasch, E. Gimeno, R.A. Herranz, U.A. Ardavanis, A. Ashraf, S.A. Bamias, A. Barone, C. Bella, S.R. Belz, H. Companario, E.B. Bolling, C. Bono, P. Bothe, K. Carteni, G. Espinosa, J.C. Clausse, M. Confente, C. Coskun, H. Herrero, G.C. Demey, W. D'hondt, R. Santasusana, M.D. Doshi, G. Elkiran, E. Facchini, G. Fein, L. Calvo, O.F. Flaherty, A. Fountzilas, G. Fruehauf, J. Díaz, E.G. Garcia, R. Domínguez, R.G. Ghosn, M. Glorieux, P. Goebell, P.J. Gutierrez, L.G.-A. Gonzalez, M. Green, N.B. Arnau, M.G. Harich, H.-D. Hawkins, R. Hegele, A. Pérez, C.H. Herrmann, E. Horniniger, W.J. Hutson, T.E. Janetschek, G. Kalantari, H. Kalofonos, H. Klausmann, M. Kolin, M. Krause, S. Kroening, H. Sorrosal, J.J.L. Lázaro, M. Lema, M. Lema, M.L. Lin, J. Lueck, A. Lybaert, W. Magi, A. Marina, V.A. Rey, J.P.M. Matus, G. Melear, J. Gonzalez, B.M. Milella, M. Montalar, J. Ferrandis, J.M. Nathan, P. Nechushtan, H. Nusch, A. Ojamaa, K. Oksuzoglu, B. Ozkan, M. Papazisis, K. Passalacqua, R. Pe'er, A. Gracia, J.L.P. Pichler, A. Pokker, H. Porta, C. Rauchenwald, M. Richardet, M.E. Richey, S.L. Garcia, J.M.R. Sánchez, A.R. Rudolph, R. Sabbatini, R. Salmon, J.-P. Lobera, C.S. Sarid, D.L. Saylors, G.B. Schmidinger, M. Schrijvers, D. Schulze, M. Sevilay, A. Shumaker, G.G. Siemer, S. de Prado y Otero, D.S. Srihari, N. Stoiber, F. Rodriguez, C.S. Varela, M.S. Vasanthan, S. Estevez, S.V. Vehling-Kaiser, U. Vogelzang, N. Weiss, H. Whenham, N. Wyendaele, W. Yildiz, R. Yucel, I. Zarba, J.J. Zarkar, A. Zhong, W. Ziem, P. the PRINCIPAL Study Group
- Abstract
Background: Real-world data are essential to accurately assessing efficacy and toxicity of approved agents in everyday practice. PRINCIPAL, a prospective, observational study, was designed to confirm the real-world safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC). Subjects, Materials, and Methods: Patients with clear cell advanced/metastatic RCC and a clinical decision to initiate pazopanib treatment within 30 days of enrollment were eligible. Primary objectives included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), relative dose intensity (RDI) and its effect on treatment outcomes, change in health-related quality of life (HRQoL), and safety. We also compared characteristics and outcomes of clinical-trial-eligible (CTE) patients, defined using COMPARZ trial eligibility criteria, with those of non-clinical-trial-eligible (NCTE) patients. Secondary study objectives were to evaluate clinical efficacy, safety, and RDI in patient subgroups. Results: Six hundred fifty-seven patients were enrolled and received ≥1 dose of pazopanib. Median PFS and OS were 10.3 months (95% confidence interval [CI], 9.2–12.0) and 29.9 months (95% CI, 24.7 to not reached), respectively, and the ORR was 30.3%. HRQoL showed no or little deterioration over time. Treatment-related serious adverse events (AEs) and AEs of special interest occurred in 64 (9.7%), and 399 (60.7%) patients, respectively. More patients were classified NCTE than CTE (85.2% vs. 14.8%). Efficacy of pazopanib was similar between the two groups. Conclusion: PRINCIPAL confirms the efficacy and safety of pazopanib in patients with advanced/metastatic RCC in a real-world clinical setting. Implications for Practice: PRINCIPAL is the largest (n = 657) prospective, observational study of pazopanib in patients with advanced/metastatic renal cell carcinoma, to the authors’ knowledge. Consistent with clinical trial results that often contain specific patient types, the PRINCIPAL study demonstrated that the effectiveness and safety of pazopanib is similarly safe and effective in patients with advanced kidney cancer in a real-world clinical setting. The PRINCIPAL study showed that patients with advanced kidney cancer who are treated with first-line pazopanib generally do not show disease progression for approximately 10 months and generally survive for nearly 30 months. © AlphaMed Press 2019
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- 2019
5. Multiple-dose pharmacokinetics confirm no accumulation and dose proportionality of the novel promotile drug tegaserod (HTF 919)
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Appel-Dingemanse, S., Hirschberg, Y., Osborne, S., Pommier, F., and McLeod, J.
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- 2001
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6. SINGLE- AND MULTIPLE-DOSE PHARMACOKINETICS OF SDZ HTF 919 IN HEALTHY SUBJECTS
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Appel-Dingemanse, S., Guerret, M., Hirschberg, Y., and McLeod, J.
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- 1999
7. Efficacy and safety of pazopanib in patients with advanced and/or metastatic renal cell carcinoma (mRCC) after previous checkpoint inhibitor treatment
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Powles, T., primary, Calvo, E., additional, Grünwald, V., additional, Heng, D., additional, Michaelson, D., additional, Dezzani, L., additional, Hirschberg, Y., additional, Acharya, S., additional, and Oudard, S., additional
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- 2018
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8. Real-world effectiveness of pazopanib in patients with intermediate prognostic risk advanced renal cell carcinoma (PRINCIPAL study)
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Procopio, G., primary, Bamias, A., additional, Schmidinger, M., additional, Hawkins, R., additional, Rodriguez Sanchez, A., additional, Vazquez, S., additional, Srihari, N., additional, Kalofonos, H., additional, Bono, P., additional, Pisal, C., additional, Hirschberg, Y., additional, Dezzani, L., additional, Ahmad, Q., additional, Suarez Rodriguez, C., additional, and Jonasch, E., additional
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- 2018
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9. 884P - Real-world effectiveness of pazopanib in patients with intermediate prognostic risk advanced renal cell carcinoma (PRINCIPAL study)
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Procopio, G., Bamias, A., Schmidinger, M., Hawkins, R., Rodriguez Sanchez, A., Vazquez, S., Srihari, N., Kalofonos, H., Bono, P., Pisal, C., Hirschberg, Y., Dezzani, L., Ahmad, Q., Suarez Rodriguez, C., and Jonasch, E.
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- 2018
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10. Improved control of mealtime glucose excursions with coadministration of nateglinide and metformin.
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Hirschberg, Y, primary, Karara, A H, additional, Pietri, A O, additional, and McLeod, J F, additional
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- 2000
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11. Molecular basis of cardiac troponin T isoform heterogeneity in rabbit heart.
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Greig, A, primary, Hirschberg, Y, additional, Anderson, P A, additional, Hainsworth, C, additional, Malouf, N N, additional, Oakeley, A E, additional, and Kay, B K, additional
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- 1994
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12. Short-term TPN containing n-3 fatty acids ameliorate lactic acidosis induced by endotoxin in guinea pigs
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Pomposelli, JJ, primary, Flores, E, additional, Hirschberg, Y, additional, Teo, TC, additional, Blackburn, GL, additional, Zeisel, SH, additional, and Bistrian, BR, additional
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- 1990
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13. Effect of tracer and intravenous fat emulsion on the measurement of reticuloendothelial system function.
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Hirschberg, Yulia, Pomposelli, James J., Mascioli, Edward A., Bistrian, Bruce R., Blackburn, George L., Hirschberg, Y, Pomposelli, J J, Mascioli, E A, Bistrian, B R, and Blackburn, G L
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- 1990
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14. 35th Annual Meeting of the European Association for the Study of Diabetes
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Melander, A., Olsson, J., Lindberg, G., Salzman, A., Howard, T., Stang, P., Lydick, E., Emslie-Smith, A., Boyle, D. I. R., Evans, J. M. M., Macdonald, T. M., Bain, J., Sullivan, F., Juhl, C., Pørksen, N., Sturis, J., Hollingdal, M., Pincus, S., Veldhuis, J., Dejgaard, A., Schmitz, O., Kristensen, J. S., Frandsen, K. B., Bayer, Th., Müller, P., Dunning, B. E., Paladini, S., Gutierrez, C., Deacon, R., Valentin, M., Grunberger, G., Weston, W. M., Patwardhan, R., Rappaport, E. B., Sargeant, L. A., Wareham, N. J., Khaw, K. T., Zethelius, Björn, Lithell, Hans, Hales, C. Nicholas, Berne, Christian, Lakka, H.-M., Oksanen, L., Tuomainen, T.-P., Kontula, K., Salonen, J. T., Dekker, J. M., de Boks, P., de Vegt, F., Stehouwer, C. D. A., Nijpels, G., Bouter, L. M., Heine, R. J., Bruno, G., Cavallo-Perin, P., Bargero, G., D’Errico, N., Borra, M., Macchia, G., Pagano, G., Newton, R. W., Ruta, D. A., New, J. P., Wallace, C., Roxburgh, M. A., Young, R. J., Vaughan, N. J. A., Elliott, P., Brennan, G., Devers, M., MacAlpine, R., Steinke, D., Lawson, D. H., Decallonne, B., Casteels, K., Gysemans, C., Bouillon, R., Mathieu, C., Linn, Thomas, Strate, Christine, Schneider, Kerstin, Funda, D. P., Jirsa, M., Kozáková, H., Kaas, A., Kofronová, O., Tlaskalová-Hogenová, H., Buschard, K., Wanka, H., Hartmann, A., Kuttler, B., Rasmussen, S. B., Sørensen, T. S., Markholst, H., Petersen, J. S., Karounos, D., Dyrberg, T., Mabley, J. G., Haskó, G., Szabó, C., Seissler, J., Nguyen, T. B. T., Steinbrenner, H., Scherbaum, W. A., Cipriani, R., Gabriele, A., Sensi, M., Guidobaldi, L., Pantellini, F., Cerrito, M. G., Scarpa, S., Di Mario, U., Morano, S., Ceolotto, G., Iori, E., Baritono, E., Del Prato, S., Semplicini, A., Trevisan, R., Zerbini, G., Meregalli, G., Asnaghi, V., Tentori, F., Maestroni, A., Mangili, R., Marescotti, C., Vedovato, M., Tiengo, A., Tadjieva, J., Mankovsky, B. N., Van Aken, S., Raes, A., Vande Walle, J., Matthys, D., Craen, M., Hansen, H. P., Lund, S. S., Rossing, P., Jensen, T., Parving, H.-H., Andersen, S., Tarnow, L., Hansen, B. V., Trautner, C., Haastert, B., Ennenbach, N., Willich, S., Tabák, Á. Gy., Orchard, T. J., Spranger, J., Preissner, K. T., Schatz, H., Pfeiffer, A., Cantón, A., Burgos, R., Hernández, C., Lecube, A., Mesa, J., Segura, R. M., Mateo, C., Simó, R., Fathallah, L., Greene, D. A., Obrosova, I., Gilbert, R. E., Kelly, D. J., Cox, A. J., Berka-Wilkinson, J. L., Taylor, H. R., Panagiotopoulos, S., Lee, V., Jerums, G., Cooper, M. E., Hitman, G. A., Aganna, E., Ogunkolade, W. B., Rema, M., Deepa, R., Shanthi-Rani, C. S., Barakat, K., Kumarajeewa, T. R., Cassell, P. G., McDermott, M. F., Mohan, V., Ways, K., Bursell, S., Devries, T., Woodworth, J., Alatorre, C., King, G., Aiello, L. P., Karisen, A. E., Pavlovic, D., Nielsen, K., Jensen, J., Andersen, H. U., Pociot, F., Mandrup-Poulsen, T., Eizirik, D. L., Nerup, J., Lortz, S., Tiedge, M., Lenzen, S., Lally, F. J., Bone, A. J., Darville, M. I., Ho, Y.-S., Sternesjö, J., Sandler, S., Chen, M.-C., Schuit, F., Pipeleers, D. G., Merezak, S., Hardikar, A., Hoet, J. J., Remacle, C., Reusens, B., Bréant, B., Garofano, A., Czernichow, P., Kubota, N., Terauchi, Y., Miki, H., Tamemoto, H., Yamauchi, T., Nakano, R., Komeda, K., Eto, K., Tobe, K., Kimura, S., Kadowaki, T., Ide, T., Murakami, K., Tsunoda, M., Mochizuki, T., Ozanne, S. E., Nave, B. T., Wang, C. L., Dorling, M. W., Petry, C. J., Koopmans, S. J., van der Bent, C., Que, I., Radder, J. K., Sebokova, E., Sana, A. K., Klimes, I., Ruderman, N., Morviducci, L., Pastore, L., Morelli, S., Sagratella, E., Zorretta, D., Buongiomo, A., Tamburrano, G., Giaccari, A., Martinenghi, Sabina, De Angelis, Gabriella Cusella, Ravasi, Flavio, Bifari, Francesco, Bordignon, Claudio, Falqui, Luca, Kessler, A., Dransfeld, O., Sasson, S., Tomas, E., Zorzano, A., Eckel, J., Thorsby, P., Rosenfalck, A. M., Kjems, L., Hanssen, K. F., Madsbad, S., Birkeland, K. I., Hamilton-Wessler, M., Markussen, J., Bergman, R. N., Melki, V., Hanaire-Broutin, H., Bessières-Lacombe, S., Tauber, J.-P., Home, P. D., Lindholm, A., Riis, A., Rosenstock, J., Schwartz, S., Clark, C., Edwards, M., Donley, D., Swift, P., Mortensen, H. B., Lynggaard, H., Hougaard, P., Cull, C. A., Neil, H. A. W., Frighi, V., Manley, S. E., Holman, R. R., Turner, R. C., Steiner, G., Davis, W. A., Weeraratna, T., Bruce, D. G., Davis, T. M. E., Vergès, B., Duvillard, L., Pont, F., Florentin, E., Gambert, Ph., Benko, B., Ljubić, S., Turk, Z., Granić, M., März, W., Wollschläger, H., Klein, G., Neiss, A., Wehling, M., Huxtable, S. J., Saker, P. J., Walker, M., Frayling, T. M., Levy, J. C., O’Rahilly, S., Hattersley, A. T., McCarthy, M. I., Orecchio, A., Giacchini, A., Dominici, R., Canettieri, G., Trinti, B., Zani, M., Andreoli, M., Sciacchitano, S., de Silva, A. M., Whitecross, K., Pasco, J., Kotowicz, M., Nicholson, G., Zimmet, P., Boyko, E. J., Collier, G. R., Frittitta, L., Pizzuti, A., Argiolas, A., Graci, S., Goldfine, I. D., Bozzali, M., Ercolino, T., Costanzo, B., Iacoviello, L., Tassi, V., Trischitta, V., Wauters, M., Rankinen, T., Mertens, I., Chagnon, M., Bouchard, C., Van Gaal, L., Sivenius, K., Valve, R., Hakkarainen, V., Niskanen, L., Laakso, M., Uusitupa, M., Beridze, N., Japaridze, M., Kurashvili, R., Dundua, M., Kebuladze, G., Kazakhashvili, N., Offley-Shore, B., Thomas, B., Ghebremeskel, K., Crawford, M., Lowy, C., Eriksson, Ulf J., Martin Simán, C., Wisse, Bert, Gittenberger-de Groot, Adriana C., Wentzel, P., Eriksson, U. J., Wender-Ożegowska, E., Drews, K., Biczysko, R., Bronisz, A., Rość, D., Graczykowska-Koczorowska, A., Kotschy, M., Sokup, A., Kohnert, K. D., Besch, W., Strese, J., Frick, U., Zander, E., Kemer, W., Škrha, J., Kvasnička, J., Kalvodová, B., Hilgertová, J., Schatteman, K., Goossens, F., Scharpé, S., De Leeuw, I., Hendriks, D., Legakis, I. N., Panayiotou, D., Mountokalakis, Th. D., Enderle, M. D., Beckmann, P., Balletshofer, B., Rittig, K., Maerker, E., Volk, A., Meisner, C., Jacob, S., Matthaei, S., Häring, H. U., Rett, K., Ueda, K., Nakagawa, T., Shimajiri, Y., Kokawa, M., Matsumoto, E., Sasaki, H., Sanke, T., Nanjo, K., McKinnon, Caroline M., Macfarlane, Wendy M., Docherty, Kevin, Furukawa, N., Shirotani, T., Kishikawa, H., Kaneko, K., Araki, E., Shichiri, M., Prentki, M., Roduit, R., Susini, S., Buteau, J., Ejrnæs, A. M., Andersen, N. Aa., Osterhoff, M., Möhlig, M., Ortmann, J., Bikashaghi, F., Mayer, C., Bikashagi, F., Ackermans, M. T., Pereira Arias, A. M., Bisschop, P. H. L. T., Endert, E., Sauerwein, H. P., Romijn, J. A., Gastaldelli, A., Baldi, S., Pettiti, M., Natali, A., Frascerra, S., Camastra, S., Toschi, E., Ferrannini, E., Stingl, H., Krssak, M., Bischof, M. G., Krebs, M., Fürnsinn, C., Nowotny, P., Waldhäusl, W., Roden, M., Neeft, M., Meijer, A. J., Båvenholm, P., Pigon, J., Efendic, S., Kästenbauer, T., Sauseng, S., Sokol, G., Auinger, M., Irsigler, K., Abbott, C. A., Carrington, A. L., Faragher, B., Kulkarni, J., Van Ross, E. R. E., Boulton, A. J. M., Armstrong, D. G., Hadi, S., Nguyen, H. C., Harkless, L. B., Jirkovská, A., Kasalicky, P., Hosová, J., Skibova, J., Uccioli, L., Caselli, A., Giacomozzi, C., Macellari, V., Giurato, L., Lardieri, L., Menzinger, G., Pham, H. T., Rosenblum, B. I., Lyons, T. E., Giurini, J. M., Smakowski, P., Chrzan, J. S., Habershaw, G. M., Veves, A., Foster, A. M., Bates, M., Doxford, M., Edmonds, M. E., Kecha, O., Winkler, R., Martens, H., Collette, J., Lefèbvre, P. J., Greiner, D., Geenen, V., Atlan-Gepner, C., Naspetti, M., Valéro, R., Barad, M., Lepault, F., Vialettes, B., Naquet, P., de Galan, B., Netea, M. G., Hancu, N., Smits, P., Van der Meer, J. W. M., Osterbye, T., Jørgensen, K. H., Tranum-Jensen, J., Fredman, P., Høy, M., Bokvist, K., Olsen, H. L., Horn, T., Gromada, J., Laub, R., Lohmann, T., Hahn, H. J., Adler, T., Emmrich, F., Rabuazzo, A. M., Lupi, R., Dotta, F., Patanè, G., Marselli, L., Realacci, M., Piro, S., Del Guerra, S., Santangelo, C., Navalesi, R., Purrello, F., Marchetti, P., de Vos, P., Visser, L., de Haan, B. J., Klok, P., van Schilfgaarde, R., Poppema, S., Juang, J.-H., Kuo, C.-H., Hsu, B. R.-S., Nacher, V., Pérez, M., Biarnés, M., Raurell, M., Soler, J., Montanya, E., Ritzel, R., Maubach, J., Büsing, M., Becker, T., Klempnauer, J., Hücking, K., Schmiegel, W. H., Nauck, M. A., Bouček, P., Saudek, F., Adamec, M., Kožitarová, R., Jedináková, T., Vlasáková, Z., Skibová, J., Bartoš, V., Maffi, P., Bertuzzi, F., Aldrighetti, L., Taglietti, M. V., Castelnuovo, A., Pozza, G., Di Carlo, V., Secchi, A., Renier, G., Mamputu, J.-C., Gillespie, J. S., McMaster, D., Mercer, C., Trimble, E. R., Lecomte, M., Véricel, E., Paget, C., Ruggiero, D., Lagarde, M., Wiernsperger, N., Pricci, F., Leto, G., Amadio, L., Cordone, S., Iacobini, C., Catalano, S., Violi, F., Rotella, C. M., Pugliese, G., Zicari, A., Gradini, R., Sale, P., Pala, L., Cresci, B., Giannini, S., Manuelli, C., Dahlfors, G., Arnqvist, H. J., Gonelle-Gispert, C., Halnan, P. A., Sadoul, K., Wolter, S., Lang, J., Niwa, T., Yu, W., Hidaka, H., Senda, T., Niki, I., Fukasawa, T., Renstrom, E., Barg, S., Seward, E., Rorsman, P., Rutter, G. A., Molinete, M., Lilla, V., Ravazzola, M., Halban, P. A., Efanov, A. M., Bertorello, A. M., Zaitsev, S. V., Zwiller, J., Berggren, P.-O., MŞengül, A., Salman, F., Sargrn, M., Özer, E., Karşidaǧ, K., Salman, S., Gedik, S., Satman, İ., Dinççaǧ, N., Yılmaz, M. T., Lloyd, A., Hopkinson, P. K., Testa, M. A., Blonde, L., Turner, R. R., Hayes, J., Simonson, D. C., van der Ven, N. C. W., Lubach, C. H. C., Snoek, F. J., Mollema, E. D., van der Ploeg, H. M., Danne, T., Hoey, H., McGee, H., Fitzgerald, H., Lernmark, B., Thernlund, G., Fredin, K., Hägglöf, B., Lugari, R., Dell’Anna, C., Ugolotti, D., Dei Cas, A., Barilli, A. L., Sard, L., Marani, B., Iotti, M., Zandomeneghi, R., Gnudi, A., Kjems, L. L., Volund, Aa., Toft-Nielsen, M., Damholt, M. B., Hilsted, L., Hughes, T. E., Krarup, T., Holst, J. J., Young, A., Gottlieb, A., Fineman, M., Kolterman, O., Cancelas, J., García-Martínez, J. A., Villanueva-Peñacarrillo, M. L., Valverde, I., Malaisse, W. J., Filipsson, K., Ahrén, B., Balkan, B., Kwasnik, L., Battle, B., Li, X., Egan, J. M., Clocquet, A. R., Elahi, D., Petrella, E., Pricket, K., Petersen, K. F., Sullivan, J. T., Amatruda, J. M., Livingston, J. N., Shulman, G. I., Freyse, E.-J., Knospe, S., Glund, K., Demuth, H.-U., Walker, D., Malik, R. A., Reljanovic, M., Barada, A., Milicevic, Z., Tack, Cees J., Goldstein, David S., Van Huysen, C., Stevens, M. 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I., Witek, P., Geraldes, Elizabete, Rodrigues, D., Pereira, L., Doménech, A., Leitão, P., Anagnostopoulos, D., Foster, A. V. M., Nag, S., Barsoum, M., Lewis, G., Dunlop, N., Connolly, V., Bilous, R., Kelly, W., Chantelau, E., Gede, A., Sharman, D., O’Halloran, D., Best, C., Abbas, Z. G., Lutale, J., Gill, G. V., Jarvis, W. R., Archibald, L. K., Corcoran, S., Mansell, J., Pibworth, L., Terada, H., Shiba, T., Utugi, N., Utugi, T., Blum, M., Strobel, J., Höffken, K., Razvi, F. M., Kritzinger, E. E., Taylor, K., Jones, S., Illahi, W., Grüβer, M., Hartmann, P., Hoffstadt, K., van Leiden, H. A., Moll, A. C., Polak, B. C. P., Pietragalla, G. B., Maurino, M., Montanaro, M., Karadeniz, Ş., Tommasini, P., Quadrini, C., Demiraj, V., Rispoli, E., Ota, A., Takama, H., Saito, N., Hemández, C., Lepore, D., Antico, L., Giardina, B., Franconi, F., Michoud, E., Chamot, S., Riva, Ch., Hammes, H.-P., Renner, O., Breier, G., Lin, J., Alt, A., Betzholtz, C., Bretzel, R. 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M., Cases, A., Clària, J., Iñigo, P., Esmatjcs, E., Sármán, B., Tóth, M., Kocsis, I., Somogyi, A., Bumbure, A., Jachimowicz, K., Samson, J., Tomasiak, M., Sobol, A., Stańczyk, L., Watala, C., Stradina, P., Wiśniewska-Jarosińska, M., Marciniak, D., Więcławska, B., Watała, C., Golański, J., Zinnat, R., Mahmud, I., Büyükasik, Yahya, Demiroğlu, H., Szczepanik, A., Skowroński, M., Murawska, A., Meeking, D. R., Allard, S., Munday, J., Chowienczyk, P., Shaw, K. M., Cummings, M. H., Šimková, R., Jirsa, M., Hadoke, P. W. F., McIntyre, C. A., Jones, G. C., Williams, B. C., Elliott, A. I., McKnight, J. A., Pernow, J., Bombonato, G. C., Finucci, G. F., Zotta, L., Senses, V., Ozyazgan, S., Ince, E., Tunçdemir, M., Oztürk, M., Sultuybek, G., Akkan, A. G., Özyazgan, S., Unlücerci, Y., Bekpınar, S., Meyer, M. F., Lee, B. C., Shore, A. C., Humphreys, J. M., Tooke, J. E., Dell’Omo, G., Giovannitti, G., Caricato, F., Mariani, M., Pedrinelli, R., Kiviet-Boehm, C., Schwelling, V., Matthäei, S., Pfohl, M., McInerney, D., Itoh, H., Ohno, T., Katoh, N., Baumgartner-Parzer, S., Artwohl, M., Graier, W., Ludwig, C., Tachi, Y., Bannai, C., Shinohara, M., Shimpuku, H., Ohura, K., Bertacca, A., Sasvári, M., Szaleczki, E., Pusztai, P., Boes, U., Klaus, E., Dittrich, P., Wagner, Z., Wittmann, I., Pótó, L., Wagner, L., Mazák, I., Nagy, J., Feletto, F., Taboga, C., Tonutti, L., Lizzio, S., Russo, A., Selmo, V., Ceriello, A., Lekakis, J., Papamichael, C. M., Stamatelopoulos, K., Stamatelopoulos, S., Yillar, D. O., Gay, M., Lillaz, E., Passaro, A., Vanini, A., Calzoni, F., D’Elia, K., Carantoni, M., Zuliani, G., Fellin, R., Solini, A., Chwatko, G., Bald, E., Dramais, A.-S., Wallemacq, P. E., Vandeleene, B., Ciaria, M. V., Ariano, M., Strom, R., Gibney, J., Weiss, U., Turner, B., O’Gorman, P., Watts, G., Powrie, J., Crook, M., Shaw, K., and Cummings, M.
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- 1999
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15. 35th Annual Meeting of the European Association for the Study of Diabetes : Brussels, Belgium, 28 September-2 October 1999
- Author
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Melander, A., Olsson, J., Lindberg, G., Salzman, A., Howard, T., Stang, P., Lydick, E., Emslie-Smith, A., Boyle, D. I. R., Evans, J. M. M., Macdonald, T. M., Bain, J., Sullivan, F., Ad Darts Memo, Morris For The Collaboration, Juhl, C., Porksen, N., Sturis, J., Hollingdal, M., Pincus, S., Veldhuis, J., Dejgaard, A., Schmitz, O., Kristensen, J. S., Frandsen, K. B., Bayer, Th, Muller, P., Dunning, B. E., Paladini, S., Gutierrez, C., Deacon, R., Valentin, M., Grunberger, G., Weston, W. M., Patwardhan, R., Rappaport, E. B., Sargeant, L. A., Wareham, N. J., Khaw, K. T., Zethelius, Bjorn, Lithell, Hans, Hales, C. Nicholas, Berne, Christian, Lakka, H-M, Oksanen, L., Tuomainen, T-P, Kontula, K., Salonen, J. T., Dekker, J. M., Boks, P., Vegt, F., Stehouwer, C. D. A., Nijpels, G., Bouter, L. M., Heine, R. J., Bruno, G., Cavallo-Perin, P., Bargero, G., D Errico, N., Borra, M., Macchia, G., Pagano, G., Newton, R. W., Ruta, D. A., New, J. P., Wallace, C., Roxburgh, M. A., Young, R. J., Vaughan, N. J. A., Elliott, P., Brennan, G., Devers, M., Macalpine, R., Steinke, D., Lawson, D. H., Decallonne, B., Casteels, K., Gysemans, C., Bouillon, R., Mathieu, C., Linn, Thomas, Strate, Christine, Schneider, Kerstin, Funda, D. P., Jirsa, M. Jr, Kozakova, H., Kaas, A., Kofronova, O., Tlaskalova-Hogenova, H., Buschard, K., Wanka, H., Hartmann, A., Kuttler, B., Rasmussen, S. B., Sorensen, T. S., Markholst, H., Petersen, J. S., Karounos, D., Dyrberg, T., Mabley, J. G., Hasko, G., Szabo, C., Seissler, J., Nguyen, T. B. T., Steinbrenner, H., Scherbaum, W. A., Cipriani, R., Gabriele, A., Sensi, M., Guidobaldi, L., Pantellini, F., Cerrito, M. G., Scarpa, S., Di Mario, U., Morano, S., Ceolotto, G., Iori, E., Baritono, E., Del Prato, S., Semplicini, A., Trevisan, R., Zerbini, G., Meregalli, G., Asnaghi, V., Tentori, F., Maestroni, A., Mangili, R., Marescotti, C., Vedovato, M., Tiengo, A., Tadjieva, J., Mankovsky, B. N., Aken, S., Raes, A., Vande Walle, J., Matthys, D., Craen, M., Hansen, H. P., Lund, S. S., Rossing, P., Jensen, T., Parving, H-H, Genediab, Study Group, Andersen, S., Tarnow, L., Hansen, B. V., Trautner, C., Haastert, B., Ennenbach, N., Willich, S., Tabak, A. Gy, Orchard, T. J., Spranger, J., Preissner, K. T., Schatz, H., Pfeiffer, A., Canton, A., Burgos, R., Hernandez, C., Lecube, A., Mesa, J., Segura, R. M., Mateo, C., Simo, R., Fathallah, L., Greene, D. A., Obrosova, I., Gilbert, R. E., Kelly, D. J., Cox, A. J., Berka-Wilkinson, J. L., Taylor, H. R., Panagiotopoulos, S., Lee, V., Jerums, G., Cooper, M. E., Hitman, G. A., Aganna, E., Ogunkolade, W. B., Rema, M., Deepa, R., Shanthi-Rani, C. S., Barakat, K., Kumarajeewa, T. R., Cassell, P. G., Mcdermott, M. F., Mohan, V., Ways, K., Bursell, S., Devries, T., Woodworth, J., Alatorre, C., King, G., Aiello, L. P., Karisen, A. E., Pavlovic, D., Nielsen, K., Jensen, J., Andersen, H. U., Pociot, F., Mandrup-Poulsen, T., Eizirik, D. L., Nerup, J., Lortz, S., Tiedge, M., Lenzen, S., Lally, F. J., Bone, A. J., Darville, M. I., Ho, Y-S, Sternesjo, J., Sandler, S., Chen, M-C, Schuit, F., Pipeleers, D. G., Merezak, S., Hardikar, A., Hoet, J. J., Remacle, C., Reusens, B., Breant, B., Garofano, A., Czernichow, P., Kubota, N., Terauchi, Y., Miki, H., Tamemoto, H., Yamauchi, T., Nakano, R., Komeda, K., Eto, K., Tobe, K., Kimura, S., Kadowaki, T., Ide, T., Murakami, K., Tsunoda, M., Mochizuki, T., Ozanne, S. E., Nave, B. T., Wang, C. L., Dorling, M. W., Petry, C. J., Koopmans, S. J., Bent, C., Que, I., Radder, J. K., Sebokova, E., Sana, A. K., Klimes, I., Ruderman, N., Morviducci, L., Pastore, L., Morelli, S., Sagratella, E., Zorretta, D., Buongiomo, A., Tamburrano, G., Giaccari, A., Martinenghi, Sabina, Angelis, Gabriella Cusella, Ravasi, Flavio, Bifari, Francesco, Bordignon, Claudio, Falqui, Luca, Kessler, A., Dransfeld, O., Sasson, S., Tomas, E., Zorzano, A., Eckel, J., Thorsby, P., Rosenfalck, A. M., Kjems, L., Hanssen, K. F., Madsbad, S., Birkeland, K. I., Hamilton-Wessler, M., Markussen, J., Bergman, R. N., Melki, V., Hanaire-Broutin, H., Bessieres-Lacombe, S., Gedec, Study Group, Tauber, J-P, Home, P. D., Lindholm, A., Riis, A., European Insulin Aspart Study Group, Rosenstock, J., Schwartz, S., Clark, C., Edwards, M., Donley, D., Us Dm, Study Group Of Insulin Glargine In Type, Swift, P., Mortensen, H. B., Lynggaard, H., Hougaard, P., Hvidore Study group on Childhood Diabetes, Cull, C. A., Neil, H. A. W., Frighi, V., Manley, S. E., Holman, R. R., Turner, R. C., Ukpds, Group, Steiner, G., Dais, Project Group, Davis, W. A., Weeraratna, T., Bruce, D. G., Davis, T. M. E., Verges, B., Duvillard, L., Pont, F., Florentin, E., Gambert, Ph, Benko, B., Ljubic, S., Turk, Z., Granic, M., Marz, W., Wollschlager, H., Klein, G., Neiss, A., Wehling, M., Huxtable, S. J., Saker, P. J., Walker, M., Frayling, T. M., Levy, J. C., O Rahilly, S., Hattersley, A. T., Mccarthy, M. I., Orecchio, A., Giacchini, A., Dominici, R., Canettieri, G., Trinti, B., Zani, M., Andreoli, M., Sciacchitano, S., Silva, A. M., Whitecross, K., Pasco, J., Kotowicz, M., Nicholson, G., Zimmet, P., Boyko, E. J., Collier, G. R., Frittitta, L., Pizzuti, A., Argiolas, A., Graci, S., Goldfine, I. D., Bozzali, M., Ercolino, T., Costanzo, B., Iacoviello, L., Tassi, V., Trischitta, V., Wauters, M., Rankinen, T., Mertens, I., Chagnon, M., Bouchard, C., Gaal, L., Sivenius, K., Valve, R., Hakkarainen, V., Niskanen, L., Laakso, M., Uusitupa, M., Beridze, N., Japaridze, M., Kurashvili, R., Dundua, M., Kebuladze, G., Kazakhashvili, N., Offley-Shore, B., Thomas, B., Ghebremeskel, K., Crawford, M., Lowy, C., Eriksson, Ulf J., Martin Siman, C., Wisse, Bert, Gittenberger-De Groot, Adriana C., Wentzel, P., Eriksson, U. J., Wender-Ozegowska, E., Drews, K., Biczysko, R., Bronisz, A., Rosc, D., Graczykowska-Koczorowska, A., Kotschy, M., Sokup, A., Kohnert, K. D., Besch, W., Strese, J., Frick, U., Zander, E., Kemer, W., Skrha, J., Kvasnicka, J., Kalvodova, B., Hilgertova, J., Schatteman, K., Goossens, F., Scharpe, S., Leeuw, I., Hendriks, D., Legakis, I. N., Panayiotou, D., Mountokalakis, Th D., Enderle, M. D., Beckmann, P., Balletshofer, B., Rittig, K., Maerker, E., Volk, A., Meisner, C., Jacob, S., Matthaei, S., Haring, H. U., Rett, K., Ueda, K., Nakagawa, T., Shimajiri, Y., Kokawa, M., Matsumoto, E., Sasaki, H., Sanke, T., Nanjo, K., Mckinnon, Caroline M., Macfarlane, Wendy M., Docherty, Kevin, Furukawa, N., Shirotani, T., Kishikawa, H., Kaneko, K., Araki, E., Shichiri, M., Prentki, M., Roduit, R., Susini, S., Buteau, J., Ejrnas, A. M., Andersen, N. Aa, Osterhoff, M., Mohlig, M., Ortmann, J., Bikashaghi, F., Mayer, C., Bikashagi, F., Ackermans, M. T., Pereira Arias, A. M., Bisschop, P. H. L. T., Endert, E., Sauerwein, H. P., Romijn, J. A., Gastaldelli, A., Baldi, S., Pettiti, M., Natali, A., Frascerra, S., Camastra, S., Toschi, E., Ferrannini, E., Stingl, H., Krssak, M., Bischof, M. G., Krebs, M., Furnsinn, C., Nowotny, P., Waldhausl, W., Roden, M., Neeft, M., Meijer, A. J., Bavenholm, P., Pigon, J., Efendic, S., Kastenbauer, T., Sauseng, S., Sokol, G., Auinger, M., Irsigler, K., Abbott, C. A., Carrington, A. L., Faragher, B., Kulkarni, J., Ross, E. R. E., Boulton, A. J. M., Armstrong, D. G., Hadi, S., Nguyen, H. C., Harkless, L. B., Jirkovska, A., Kasalicky, P., Hosova, J., Skibova, J., Uccioli, L., Caselli, A., Giacomozzi, C., Macellari, V., Giurato, L., Lardieri, L., Menzinger, G., Pham, H. T., Rosenblum, B. I., Lyons, T. E., Giurini, J. M., Smakowski, P., Chrzan, J. S., Habershaw, G. M., Veves, A., Foster, A. M., Bates, M., Doxford, M., Edmonds, M. E., Kecha, O., Winkler, R., Martens, H., Collette, J., Lefebvre, P. J., Greiner, D., Geenen, V., Atlan-Gepner, C., Naspetti, M., Valero, R., Barad, M., Lepault, F., Vialettes, B., Naquet, P., Galan, B., Netea, M. G., Hancu, N., Smits, P., Meer, J. W. M., Osterbye, T., Jorgensen, K. H., Tranum-Jensen, J., Fredman, P., Hoy, M., Bokvist, K., Olsen, H. L., Horn, T., Gromada, J., Laub, R., Lohmann, T., Hahn, H. J., Adler, T., Emmrich, F., Rabuazzo, A. M., Lupi, R., Dotta, F., Patane, G., Marselli, L., Realacci, M., Piro, S., Del Guerra, S., Santangelo, C., Navalesi, R., Purrello, F., Marchetti, P., Vos, P., Visser, L., Haan, B. J., Klok, P., Schilfgaarde, R., Poppema, S., Juang, J-H, Kuo, C-H, Hsu, B. R-S, Nacher, V., Perez, M., Biarnes, M., Raurell, M., Soler, J., Montanya, E., Ritzel, R., Maubach, J., Busing, M., Becker, T., Klempnauer, J., Hucking, K., Schmiegel, W. H., Nauck, M. A., Boucek, P., Saudek, F., Adamec, M., Kozitarova, R., Jedinakova, T., Vlasakova, Z., Bartos, V., Maffi, P., Bertuzzi, F., Aldrighetti, L., Taglietti, M. V., Castelnuovo, A., Pozza, G., Di Carlo, V., Secchi, A., Renier, G., Mamputu, J-C, Gillespie, J. S., Mcmaster, D., Mercer, C., Trimble, E. R., Lecomte, M., Vericel, E., Paget, C., Ruggiero, D., Lagarde, M., Wiernsperger, N., Pricci, F., Leto, G., Amadio, L., Cordone, S., Iacobini, C., Catalano, S., Violi, F., Rotella, C. M., Pugliese, G., Zicari, A., Gradini, R., Sale, P., Pala, L., Cresci, B., Giannini, S., Manuelli, C., Dahlfors, G., Arnqvist, H. J., Gonelle-Gispert, C., Halnan, P. A., Sadoul, K., Wolter, S., Lang, J., Niwa, T., Yu, W., Hidaka, H., Senda, T., Niki, I., Fukasawa, T., Renstrom, E., Barg, S., Seward, E., Rorsman, P., Rutter, G. A., Molinete, M., Lilla, V., Ravazzola, M., Halban, P. A., Efanov, A. M., Bertorello, A. M., Zaitsev, S. V., Zwiller, J., Berggren, P-O, Msengul, A., Salman, F., Sargrn, M., Ozer, E., Karsidaǧ, K., Salman, S., Gedik, S., Satman, I., Dinccaǧ, N., Yilmaz, M. T., Lloyd, A., Hopkinson, P. K., Testa, M. A., Blonde, L., Turner, R. 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S., Leonhardt, W., Konstadelou, E., Gurlek, Alper, Soedamah-Muthu, S., Taskinen, M. R., Ehnholm, C., Wagner, A., Bayen, Laia, Rigla, M., Ortega, E., Caixas, A., Mestron, A., Ordonez, J., Perez, A., Sotiropoulou, G., Servais, P. L., Bertolotto, A., Pilo, M., Suchankova, G., Andratschke, S., Tschop, M., Strasburger, C-J, Rizzo, L., Aerts, P., Vinckx, M., Ansquer, J. C., Ryan, M., Buter, H., Navis, G. J., Jong, P. E., Zeeuw, D., Carreras, G., Gimenez, G., Pou, J. M., Howorka, K., Gabriel, M., Pumprla, J., Koves, A., Bhowmik, N. B., Haque, A., Rahman, A., Paleari, F., Gamba, P., Mauri, G., Rovaris, G., Giannattasio, C., Piatti, M. L., Zincone, A., Cavaletti, G., Mancia, G., Lan, S., Arezzo, J., Gerber, R. A., Klioze, S. S., Saponara, C., Tartaglione, T., Cercone, S., Caputo, S., Meloni, T., Brunetti, D., Di Lazzaro, V., Xu, G., Jiang, H. Y., Shy, M. E., Sugimoto, K., Zhang, W-X, Kuchmerovskaya, T., Donchenko, G., Shymansky, I., Kuchmerovsky, N., Pakyrbaeva, L., Cameron, N. E., Keegan, A., Cotter, M. A., Mirrlees, D., Smale, S. E., Biessels, G. J., Duis, S. E. J., Kamal, A., Gispen, W. H., Carrington, A., Carman, S., Smiarowski, H., Lavoie, D., Sawicki, D., Sabetta, A., Litchfield, J., Zandt, M., Sredy, J., Smirnova, V., Strokov, I., Ivanova, L., Ichunina, A., Nakamura, J., Nakayama, M., Hamada, Y., Chaya, S., Kato, K., Kasuya, Y., Mizubayashi, R., Miwa, K., Yasuda, Y., Kamiya, H., Hotta, N., Biro, K., Kukorelli, T., Szilagyi, N., Kurthy, M., Komaromy, A., Mogyorosi, T., Nagy, K., Cakir, M., Baskal, N., Gullu, S., Elhan, A. H., Erdogan, G., Ziegler, D., Piolot, R., Neubauer, J., Senesi, B., Bonetti, R., Napolitano, A., Canepa, F., Ottonello, P., Schabmann, A., Gimenez-Perez, G., Arroyo, J. A., Lopez, T., Ponz, E., Mauricio, D., Diem, P., Zanchin, L., Suter, S. L., Lefrandt, J. D., Smit, A., Roon, A. M., Dullaart, R., Voita, D., Mackevics, V., Vitols, A., Lengyel, Cs, Farkas, Gy, Torok, T., Legrady, P., Varkonyi, T. T., Kardos, A., Gingl, Z., Kempler, P., Rudas, L., Lonovics, J., Marchand, M., Stevens, L. K., Tarnas, Gy, Eurodiab Iddm, Study Group, Estrella, F., Christensen, N. J., Keresztes, K., Barna, I., Hermanyi, Zs, Vargha, P., Bonnevie, L., Chanudet, X., Larroque, P., Tutuncu, N. Bascil, Deger, A., Batur, M. K., Yildirir, A., Onalan, O., Aksoyek, S., Kabakciota, G., Erbas, T., Galicka-Latala, D., Surdacki, A., Gerritsen, J., Tenvoorde, B. J., Heethaar, R. M., Tagawa, T. S., Kodama, M., Yoshioka, R., Yamasaki, Y., Didangelos, T., Athyros, V., Kontopoulos, A., Papageorgiou, A., Karamitsos, D., Lacigova, S., Rusavy, Z., Karova, R., Perrild, H., Kay, L., Jorgensen, T., Bien, A. I., Witek, P., Geraldes, Elizabete, Rodrigues, D., Pereira, L., Domenech, A., Leitao, P., Anagnostopoulos, D., Foster, A. V. M., Nag, S., Barsoum, M., Lewis, G., Dunlop, N., Connolly, V., Bilous, R., Kelly, W., Chantelau, E., Gede, A., Sharman, D., O Halloran, D., Best, C., Abbas, Z. G., Lutale, J., Gill, G. V., Jarvis, W. R., Archibald, L. K., Corcoran, S., Mansell, J., Pibworth, L., Terada, H., Shiba, T., Utugi, N., Utugi, T., Blum, M., Strobel, J., Hoffken, K., Razvi, F. M., Kritzinger, E. E., Taylor, K., Jones, S., Illahi, W., Grubetaer, M., Hartmann, P., Hoffstadt, K., Leiden, H. A., Moll, A. C., Polak, B. C. P., Pietragalla, G. B., Maurino, M., Montanaro, M., Karadeniz, S., Tommasini, P., Quadrini, C., Demiraj, V., Rispoli, E., Ota, A., Takama, H., Saito, N., Hemandez, C., Lepore, D., Antico, L., Giardina, B., Franconi, F., Michoud, E., Chamot, S., Riva, Ch, Hammes, H-P, Renner, O., Breier, G., Lin, J., Alt, A., Betzholtz, C., Bretzel, R. G. Rd, Manti, R., Gallo, M., Molinar Hin, A., Brignardello, E., Boccuzzi, G., Li, Shanfang, Xiang, Kunsan, Zhang, Rugeng, Shangguan, Xinhong, Wu, Jianrong, Donnan, P. T., Broomhall, J., Hunter, K., Morris, A. D., Darts Memo, Collaboration, Ioannidis, G., Peppa, M., Rontogianni, E., Kallifronas, M., Lekatsas, I., Chrysanthopoulou, G., Anthopoulos, L., Kesse, M., Thalassinos, N., Neves, C., Medina, J. L., Lopes, F., Guvener, N., Guvener, M., Kocagoz, T., Boke, E., Pasaoglu, I., Bascil Tutuncu, N., Oto, A., Karvonen, M. K., Koulu, M., Pesonen, U., Mercuri, M., Rauramaa, R., Pittsburgh Epidemiology of Diabetes Complications (EDC) Study, Rutter, M. K., Kestevan, P., Mccomb, J. M., Marshall, S. M., Sobieska, M., Wiktorowicz, K., Kanters, S. D. J. M., Banga, J. D., Algra, A., Frijns, C. J. M., Beutler, J. J., Fijnheer, R., Nicoloff, G., Baydanoff, S., Stanimirova, N., Petrova, Ch, Lario, S., Campistol, J. M., Cases, A., Claria, J., Inigo, P., Esmatjcs, E., Sarman, B., Toth, M., Kocsis, I., Somogyi, A., Bumbure, A., Jachimowicz, K., Samson, J., Tomasiak, M., Sobol, A., Stanczyk, L., Watala, C., Stradina, P., Wisniewska-Jarosinska, M., Marciniak, D., Wieclawska, B., Golanski, J., Zinnat, R., Mahmud, I., Buyukasik, Yahya, Demiroglu, H., Szczepanik, A., Skowronski, M., Murawska, A., Meeking, D. R., Allard, S., Munday, J., Chowienczyk, P., Shaw, K. M., Cummings, M. H., Simkova, R., Jirsa, M., Hadoke, P. W. F., Mcintyre, C. A., Jones, G. C., Williams, B. C., Elliott, A. I., Mcknight, J. A., Pernow, J., Bombonato, G. C., Finucci, G. F., Zotta, L., Senses, V., Ozyazgan, S., Ince, E., Tuncdemir, M., Sultuybek, G., Akkan, A. G., Unlucerci, Y., Bekpinar, S., Meyer, M. F., Lee, B. C., Shore, A. C., Humphreys, J. M., Tooke, J. E., Omo, G., Giovannitti, G., Caricato, F., Mariani, M., Pedrinelli, R., Kiviet-Boehm, C., Schwelling, V., Pfohl, M., Mcinerney, D., Itoh, H., Ohno, T., Katoh, N., Baumgartner-Parzer, S., Artwohl, M., Graier, W., Ludwig, C., Tachi, Y., Bannai, C., Shinohara, M., Shimpuku, H., Ohura, K., Bertacca, A., Sasvari, M., Szaleczki, E., Pusztai, P., Boes, U., Klaus, E., Dittrich, P., Wagner, Z., Wittmann, I., Poto, L., Wagner, L., Mazak, I., Nagy, J., Feletto, F., Taboga, C., Tonutti, L., Lizzio, S., Russo, A., Selmo, V., Ceriello, A., Lekakis, J., Papamichael, C. M., Stamatelopoulos, K., Stamatelopoulos, S., Yillar, D. O., Gay, M., Lillaz, E., Passaro, A., Vanini, A., Calzoni, F., D Elia, K., Carantoni, M., Zuliani, G., Fellin, R., Solini, A., Chwatko, G., Bald, E., Dramais, A-S, Wallemacq, P. E., Vandeleene, B., Ciaria, M. V., Ariano, M., Strom, R., Gibney, J., Weiss, U., Turner, B., O Gorman, P., Watts, G., Powrie, J., Crook, M., Shaw, K., and Cummings, M.
16. The Influence of Substituents on the Ultraviolet Absorption Spectrum of Styrene
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Hirschberg, Y., primary
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- 1949
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17. Short-term TPN containing n-3 fatty acids ameliorate lactic acidosisinduced by endotoxin in guinea pigs
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Blackburn, G.L., Flores, E., Zeisel, S. H., Bistrian, B. R., Hirschberg, Y., Pomposelli, J. J., and Teo, T. C.
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ENDOTOXINS ,FATTY acids ,GUINEA pigs ,NUTRITION - Published
- 1990
18. P121 - Efficacy and safety of pazopanib in patients with advanced and/or metastatic renal cell carcinoma (mRCC) after previous checkpoint inhibitor treatment.
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Powles, T., Calvo, E., Grünwald, V., Heng, D., Michaelson, D., Dezzani, L., Hirschberg, Y., Acharya, S., and Oudard, S.
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- *
RENAL cell carcinoma , *VASCULAR endothelial growth factors , *HEMOSTASIS , *BLOOD coagulation , *MEDICAL care - Published
- 2018
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19. Assessment of brain-derived extracellular vesicle enrichment for blood biomarker analysis in age-related neurodegenerative diseases: An international overview.
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Badhwar A, Hirschberg Y, Valle-Tamayo N, Iulita MF, Udeh-Momoh CT, Matton A, Tarawneh RM, Rissman RA, Ledreux A, Winston CN, and Haqqani AS
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- Humans, Extracellular Vesicles metabolism, Neurodegenerative Diseases blood, Biomarkers blood, Brain
- Abstract
Introduction: Brain-derived extracellular vesicles (BEVs) in blood allows for minimally-invasive investigations of central nervous system (CNS) -specific markers of age-related neurodegenerative diseases (NDDs). Polymer-based EV- and immunoprecipitation (IP)-based BEV-enrichment protocols from blood have gained popularity. We systematically investigated protocol consistency across studies, and determined CNS-specificity of proteins associated with these protocols., Methods: NDD articles investigating BEVs in blood using polymer-based and/or IP-based BEV enrichment protocols were systematically identified, and protocols compared. Proteins used for BEV-enrichment and/or post-enrichment were assessed for CNS- and brain-cell-type-specificity, extracellular domains (ECD+), and presence in EV-databases., Results: A total of 82.1% of studies used polymer-based (ExoQuick) EV-enrichment, and 92.3% used L1CAM for IP-based BEV-enrichment. Centrifugation times differed across studies. A total of 26.8% of 82 proteins systematically identified were CNS-specific: 50% ECD+, 77.3% were listed in EV-databases., Conclusions: We identified protocol steps requiring standardization, and recommend additional CNS-specific proteins that can be used for BEV-enrichment or as BEV-biomarkers., Highlights: Across NDDs, we identified protocols commonly used for EV/BEV enrichment from blood. We identified protocol steps showing variability that require harmonization. We assessed CNS-specificity of proteins used for BEV-enrichment or found in BEV cargo. CNS-specific EV proteins with ECD+ or without were identified. We recommend evaluation of blood-BEV enrichment using these additional ECD+ proteins., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
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- 2024
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20. Proteomic comparison between non-purified cerebrospinal fluid and cerebrospinal fluid-derived extracellular vesicles from patients with Alzheimer's, Parkinson's and Lewy body dementia.
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Hirschberg Y, Valle-Tamayo N, Dols-Icardo O, Engelborghs S, Buelens B, Vandenbroucke RE, Vermeiren Y, Boonen K, and Mertens I
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- Humans, Proteomics, Biomarkers, Alzheimer Disease diagnosis, Lewy Body Disease diagnosis, Lewy Body Disease cerebrospinal fluid, Lewy Body Disease complications, Parkinson Disease diagnosis, Parkinson Disease cerebrospinal fluid, Parkinson Disease complications, Dementia diagnosis, Dementia cerebrospinal fluid, Dementia etiology, Extracellular Vesicles
- Abstract
Dementia is a leading cause of death worldwide, with increasing prevalence as global life expectancy increases. The most common neurodegenerative disorders are Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). With this study, we took an in-depth look at the proteome of the (non-purified) cerebrospinal fluid (CSF) and the CSF-derived extracellular vesicles (EVs) of AD, PD, PD-MCI (Parkinson's disease with mild cognitive impairment), PDD and DLB patients analysed by label-free mass spectrometry. This has led to the discovery of differentially expressed proteins that may be helpful for differential diagnosis. We observed a greater number of differentially expressed proteins in CSF-derived EV samples (N = 276) compared to non-purified CSF (N = 169), with minimal overlap between both datasets. This finding suggests that CSF-derived EV samples may be more suitable for the discovery phase of a biomarker study, due to the removal of more abundant proteins, resulting in a narrower dynamic range. As disease-specific markers, we selected a total of 39 biomarker candidates identified in non-purified CSF, and 37 biomarker candidates across the different diseases under investigation in the CSF-derived EV data. After further exploration and validation of these proteins, they can be used to further differentiate between the included dementias and may offer new avenues for research into more disease-specific pharmacological therapeutics., (© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)
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- 2023
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21. Assessment of brain-derived extracellular vesicle enrichment for blood biomarker analysis in age-related neurodegenerative diseases: An international overview.
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Badhwar A, Hirschberg Y, Tamayo NV, Iulita MF, Udeh-Momoh CT, Matton A, Tarawneh RM, Rissman RA, Ledreux A, Winston CN, and Haqqani AS
- Abstract
Introduction: Brain-derived extracellular vesicles (BEVs) in blood allows for minimally- invasive investigations of CNS-specific markers of age-related neurodegenerative diseases (NDDs). Polymer-based EV- and immunoprecipitation (IP)-based BEV-enrichment protocols from blood have gained popularity. We systematically investigated protocol consistency across studies, and determined CNS-specificity of proteins associated with these protocols., Methods: NDD articles investigating BEVs in blood using polymer-based and/or IP-based BEV enrichment protocols were systematically identified, and protocols compared. Proteins used for BEV-enrichment and/or post-enrichment were assessed for CNS- and brain-cell-type- specificity; extracellular domains (ECD+); and presence in EV-databases., Results: 82.1% of studies used polymer-based (ExoQuick) EV-enrichment, and 92.3% used L1CAM for IP-based BEV-enrichment. Centrifugation times differed across studies. 26.8% of 82 proteins systematically identified were CNS-specific: 50% ECD+, 77.3% were listed in EV- databases., Discussion: We identified protocol steps requiring standardization, and recommend additional CNS-specific proteins that can be used for BEV-enrichment or as BEV-biomarkers.
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- 2023
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22. Characterising extracellular vesicles from individual low volume cerebrospinal fluid samples, isolated by SmartSEC.
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Hirschberg Y, Boonen K, Schildermans K, van Dam A, Pintelon I, Vandendriessche C, Velimirovic M, Jacobs A, Vandenbroucke RE, Nelissen I, Vermeiren Y, and Mertens I
- Abstract
Extracellular vesicles (EVs) are suggested to have a role in the progression of neurodegeneration, and are able to transmit pathological proteins from one cell to another. One of the biofluids from which EVs can be isolated is cerebrospinal fluid (CSF). However, so far, few studies have been performed on small volumes of CSF. Since pooling of patient samples possibly leads to the loss of essential individual patient information, and CSF samples are precious, it is important to have efficient techniques for the isolation of EVs from smaller volumes. In this study, the SmartSEC HT isolation kit from System Biosciences has been evaluated for this purpose. The SmartSEC HT isolation kit was used for isolation of EVs from 500 μL starting volumes of CSF, resulting in two possible EV fractions of 500 μL. Both fractions were characterised and compared to one another using a whole range of characterisation techniques. Results indicated the presence of EVs in both fractions, albeit fraction 1 showed more reproducible results over the different characterisation methods. For example, CMG (CellMask Green membrane stain) fluorescence nanotracking analysis (NTA), ExoView, and the particles/μg ratio demonstrated a clear difference between fraction 1 and 2, where fraction 1 came out as the one where most EVs were eluted with the least contamination. In the other methods, this difference was less noticeable. We successfully performed complementary characterisation tests using only 500 μL of CSF starting volume, and, conclude that fraction 1 consisted of sufficiently pure EVs for further biomarker studies. This means that future EV extractions may be based upon smaller CSF quantities, such as from individual patients. In that way, patient samples do not have to be pooled and individual patient information can be included in forthcoming studies, potentially linking EV content, size and distribution to individualised neurological diagnoses., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Journal of Extracellular Biology published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)
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- 2022
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23. Real-World Evidence Study on the Long-Term Safety of Everolimus in Patients With Tuberous Sclerosis Complex: Final Analysis Results.
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Ruiz-Falcó Rojas ML, Feucht M, Macaya A, Wilken B, Hahn A, Maamari R, Hirschberg Y, Ridolfi A, and Kingswood JC
- Abstract
The TuberOus SClerosis registry to increase disease Awareness (TOSCA) Post-Authorization Safety Study (PASS) was a non-interventional, multicenter, safety substudy that assessed the long-term safety of everolimus in patients with tuberous sclerosis complex (TSC) receiving everolimus for its licensed indications in the European Union (EU). This substudy also aimed to address TSC-associated neuropsychiatric disorders (TAND), sexual development, and male infertility. Eligible patients were enrolled from 39 sites across 11 countries in the EU. Outcomes of interest included the incidence of adverse events (AEs), serious adverse events (SAEs), treatment-related AEs (TRAEs), AEs leading to everolimus discontinuation, AEs of special interest (AESIs), the observed relationship between everolimus blood levels and incidence of AESIs, TAND, and reproductive clinical features. Herein, we present the final analysis results from this substudy (data cutoff date: 22 January 2020). At data cutoff, 179 patients were enrolled (female, 59.2%; age ≥18 years, 65.9%), of which the majority completed the study (76%). Overall, 121 patients (67.6%) had AEs regardless of causality. The most frequent TRAEs (≥5%) were stomatitis (7.8%), aphthous ulcer (6.7%), and hypercholesterolemia (6.1%). The most common treatment-related SAEs (>1%) were pneumonia (3.4%), influenza, pyelonephritis, aphthous ulcer, stomatitis, dyslipidemia, and hypercholesterolemia (1.1% each). Ten patients (5.6%) reported AEs leading to everolimus discontinuation. The common psychiatric disorders ( N = 179) were autism spectrum disorder (21.8%), anxiety disorder (12.8%), "other" psychiatric disorders (8.9%), attention-deficit hyperactivity disorder, and depressive disorder (7.8% each). Of 179 patients, 88 (49.2%) had ≥1 behavioral problem. Of these ( n = 88), the most common (>20%) were sleep difficulties (47.7%), anxiety (43.2%), mood swings (37.5%), depression mood (35.2%), impulsivity (30.7%), severe aggression (23.9%), and overactivity (22.7%). Of 179 patients, four (2.2%) reported abnormal puberty onset, and three (1.7%) reported other reproductive disorders. Of 106 females, 23 (21.7%) reported menstrual cycle disorders and 10 (9.4%) reported amenorrhea. Available data did not show delays in sexual maturation or an association between sexual development and infertility. The results demonstrate that everolimus has a manageable long-term safety profile in the TSC treatment setting. No new safety signals emerged. This substudy also contributed to the mapping of TAND and reproductive clinical features in patients with TSC., Competing Interests: Authors RM and YH are employees at Novartis and report stock ownership at Novartis. Author AR is an employee at Novartis. MF reports consulting fees for being part of the scientific advisory board and TOSCA working committee; received speaker honoraria, support for travel, and payment for expert testimony from Novartis; and reports leadership or fiduciary role in the following: ILAE task force epilepsy surgery, ERN EpiCARE, ÖGKN, and ÖGfE. AM received honoraria and support for travel from Novartis. BW reports honoraria for a lecture from Takeda. JK received honoraria, support for travel, and research grant from Novartis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ruiz-Falcó Rojas, Feucht, Macaya, Wilken, Hahn, Maamari, Hirschberg, Ridolfi and Kingswood.)
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- 2022
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24. Biofluid Markers for Prodromal Parkinson's Disease: Evidence From a Catecholaminergic Perspective.
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Vermeiren Y, Hirschberg Y, Mertens I, and De Deyn PP
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Parkinson's disease (PD) is the most frequent of all Lewy body diseases, a family of progressive neurodegenerative disorders characterized by intra-neuronal cytoplasmic inclusions of α-synuclein. Its most defining features are bradykinesia, tremor, rigidity and postural instability. By the time PD manifests with motor signs, 70% of dopaminergic midbrain neurons are lost, and the disease is already in the middle or late stage. However, there are various non-motor symptoms occurring up to 20 years before the actual parkinsonism that are closely associated with profound deficiency of myocardial noradrenaline content and peripheral sympathetic denervation, as evidenced by neuroimaging experiments in recent years. Additionally, there is an inherent autotoxicity of catecholamines in the neuronal cells in which they are produced, forming toxic catecholaldehyde intermediates that make α-synuclein prone to aggregation, initiating a cascade of events that ultimately leads to neuronal death. The etiopathogenesis of PD and related synucleinopathies thus may well be a prototypical example of a catecholamine-regulated neurodegeneration, given that the synucleinopathy in PD spreads in synergy with central and peripheral catecholaminergic dysfunction from the earliest phases onward. That is why catecholamines and their metabolites, precursors, or derivatives in cerebrospinal fluid or plasma could be of particular interest as biomarkers for prodromal and de novo PD. Because there is great demand for such markers, this mini-review summarizes all catecholamine-related studies to date, in addition to providing profound neurochemical evidence on a systemic and cellular level to further emphasize this hypothesis and with emphasis on extracellular vesicles as a novel diagnostic and therapeutic incentive., (Copyright © 2020 Vermeiren, Hirschberg, Mertens and De Deyn.)
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- 2020
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25. Altered age-linked regulation of plasma DYRK1A in elderly cognitive complainers (INSIGHT-preAD study) with high brain amyloid load.
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Delabar JM, Ortner M, Simon S, Wijkhuisen A, Feraudet-Tarisse C, Pegon J, Vidal E, Hirschberg Y, Dubois B, and Potier MC
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Introduction: An effective therapy has not yet been developed for Alzheimer's disease (AD), in part because pathological changes occur years before clinical symptoms manifest. We recently showed that decreased plasma DYRK1A identifies individuals with mild cognitive impairment (MCI) or AD, and that aged mice have higher DYRK1A levels., Methods: We assessed DYRK1A in plasma in young/aged controls and in elderly cognitive complainers with low (L) and high (H) brain amyloid load., Results: DYRK1A level increases with age in humans. However, plasma from elderly individuals reporting cognitive complaints showed that the H group had the same DYRK1A level as young adults, suggesting that the age-associated DYRK1A increase is blocked in this group. L and H groups had similar levels of clusterin., Discussion: These results are reflective of early changes in the brain. These observations suggest that plasma DYRK1A and not clusterin could be used to classify elderly memory complainers for risk for amyloid beta pathology., Competing Interests: Bruno Dubois has received consultancy fees from Biogen, Boehringer Ingelheim and Eli Lilly, and grants for his institution from Merck, Pfizer, and Roche. The other authors declare no competing interests., (© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)
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- 2020
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26. Real-world Effectiveness and Safety of Pazopanib in Patients With Intermediate Prognostic Risk Advanced Renal Cell Carcinoma.
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Procopio G, Bamias A, Schmidinger M, Hawkins R, Sánchez AR, Estevez SV, Srihari N, Kalofonos H, Bono P, Pisal CB, Hirschberg Y, Dezzani L, Ahmad Q, Rodriguez CS, and Jonasch E
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- Adult, Aged, Aged, 80 and over, Carcinoma, Renal Cell secondary, Female, Follow-Up Studies, Humans, Indazoles, Kidney Neoplasms pathology, Male, Middle Aged, Neoplasm Metastasis, Patient Safety, Prognosis, Prospective Studies, Risk Factors, Survival Rate, Young Adult, Angiogenesis Inhibitors therapeutic use, Carcinoma, Renal Cell drug therapy, Kidney Neoplasms drug therapy, Pyrimidines therapeutic use, Sulfonamides therapeutic use
- Abstract
Introduction: The objective of this study was to determine the effectiveness and safety of pazopanib in patients with intermediate-risk advanced/metastatic renal cell carcinoma in the PRINCIPAL study (NCT01649778)., Patients and Methods: Patients had clear-cell advanced/metastatic renal cell carcinoma and met intermediate-risk International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Assessments included progression-free survival, overall survival, objective response rate, and safety. We also evaluated effectiveness based on number of risk factors, age, and performance status (PS), as well as safety in older and younger patients., Results: Three hundred sixty three and 343 intermediate-risk MSKCC and IMDC patients were included, respectively. The median progression-free survival was 13.8 months (95% confidence interval [CI], 10.7-18.1 months) and 7.4 months (95% CI, 6.2-10.3 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 13.1 months (95% CI, 10.7-18.1 months) and 8.1 months (95% CI, 6.4-10.7 months) for patients with 1 and 2 IMDC risk factors, respectively. The median overall survival was not reached and was 15.2 months (95% CI, 12.3-26.5 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 33.9 months (95% CI, 33.9 months to not estimable) and 19.4 months (95% CI, 14.3 months to not estimable) with 1 and 2 IMDC risk factors, respectively. A lower overall response rate was observed with Eastern Cooperative Oncology Group PS ≥ 2 (vs. PS < 2). All-grade treatment-related adverse events occurred in approximately 63% of patients, and the safety profile among older and younger patients was similar., Conclusions: Outcomes with pazopanib in intermediate-risk patients suggest that patients can be further stratified by number of risk factors (1 vs. 2) and Eastern Cooperative Oncology Group PS (< 2 vs. ≥ 2) to more accurately predict outcomes., (Copyright © 2019. Published by Elsevier Inc.)
- Published
- 2019
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27. Prospective Observational Study of Pazopanib in Patients with Advanced Renal Cell Carcinoma (PRINCIPAL Study).
- Author
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Schmidinger M, Bamias A, Procopio G, Hawkins R, Sanchez AR, Vázquez S, Srihari N, Kalofonos H, Bono P, Pisal CB, Hirschberg Y, Dezzani L, Ahmad Q, and Jonasch E
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Renal Cell secondary, Female, Follow-Up Studies, Humans, Indazoles, Kidney Neoplasms pathology, Male, Middle Aged, Prognosis, Prospective Studies, Quality of Life, Survival Rate, Treatment Outcome, Young Adult, Angiogenesis Inhibitors therapeutic use, Carcinoma, Renal Cell drug therapy, Kidney Neoplasms drug therapy, Pyrimidines therapeutic use, Sulfonamides therapeutic use
- Abstract
Background: Real-world data are essential to accurately assessing efficacy and toxicity of approved agents in everyday practice. PRINCIPAL, a prospective, observational study, was designed to confirm the real-world safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC)., Subjects, Materials, and Methods: Patients with clear cell advanced/metastatic RCC and a clinical decision to initiate pazopanib treatment within 30 days of enrollment were eligible. Primary objectives included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), relative dose intensity (RDI) and its effect on treatment outcomes, change in health-related quality of life (HRQoL), and safety. We also compared characteristics and outcomes of clinical-trial-eligible (CTE) patients, defined using COMPARZ trial eligibility criteria, with those of non-clinical-trial-eligible (NCTE) patients. Secondary study objectives were to evaluate clinical efficacy, safety, and RDI in patient subgroups., Results: Six hundred fifty-seven patients were enrolled and received ≥1 dose of pazopanib. Median PFS and OS were 10.3 months (95% confidence interval [CI], 9.2-12.0) and 29.9 months (95% CI, 24.7 to not reached), respectively, and the ORR was 30.3%. HRQoL showed no or little deterioration over time. Treatment-related serious adverse events (AEs) and AEs of special interest occurred in 64 (9.7%), and 399 (60.7%) patients, respectively. More patients were classified NCTE than CTE (85.2% vs. 14.8%). Efficacy of pazopanib was similar between the two groups., Conclusion: PRINCIPAL confirms the efficacy and safety of pazopanib in patients with advanced/metastatic RCC in a real-world clinical setting., Implications for Practice: PRINCIPAL is the largest ( n = 657) prospective, observational study of pazopanib in patients with advanced/metastatic renal cell carcinoma, to the authors' knowledge. Consistent with clinical trial results that often contain specific patient types, the PRINCIPAL study demonstrated that the effectiveness and safety of pazopanib is similarly safe and effective in patients with advanced kidney cancer in a real-world clinical setting. The PRINCIPAL study showed that patients with advanced kidney cancer who are treated with first-line pazopanib generally do not show disease progression for approximately 10 months and generally survive for nearly 30 months., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)
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- 2019
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28. Single-dose pharmacokinetics of nateglinide in subjects with hepatic cirrhosis.
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Choudhury S, Hirschberg Y, Filipek R, Lasseter K, and McLeod JF
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- Adult, Aged, Cyclohexanes administration & dosage, Cyclohexanes adverse effects, Female, Humans, Male, Middle Aged, Nateglinide, Phenylalanine administration & dosage, Phenylalanine adverse effects, Phenylalanine pharmacokinetics, Cyclohexanes pharmacokinetics, Hypoglycemic Agents pharmacokinetics, Liver Cirrhosis metabolism, Phenylalanine analogs & derivatives
- Abstract
This single-dose, open-label, parallel-group study compared the pharmacokinetics and tolerability of 120 mg doses of nateglinide, a physiologic mealtime glucose regulator for type 2 diabetes, in 8 subjects with cirrhosis and 8 matched healthy subjects. In both groups, plasma concentration peaked in a median of 0.5 hours, and mean terminal elimination half-lives were comparable. Mean +/- SD pharmacokinetic parameters in cirrhotic versus healthy subjects were slightly different (Cmax, 7.7 +/- 4.9 vs. 5.6 +/- 1.3 micrograms/ml; AUC(0-t), 18.5 +/- 7.5 vs. 14.2 +/- 2.1 micrograms.h/ml, respectively). Mean apparent total clearance and mean renal clearance in both groups were comparable. Mean protein-bound fractions were equivalent; binding appeared unaltered by metabolites. One cirrhotic and 2 healthy subjects each reported one adverse event. No statistically significant or clinically relevant alteration in pharmacokinetic parameters of nateglinide resulted from hepatic dysfunction, and it was well tolerated; therefore, adjustment of nateglinide dosage is not required in subjects with mild to moderate cirrhosis.
- Published
- 2000
29. In vitro and in situ permeability of a 'second generation' hydroxypyridinone oral iron chelator: correlation with physico-chemical properties and oral activity.
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Lowther N, Fox R, Faller B, Nick H, Jin Y, Sergejew T, Hirschberg Y, Oberle R, and Donnelly H
- Subjects
- Administration, Oral, Animals, Caco-2 Cells, Callithrix, Carbon Radioisotopes, Humans, In Vitro Techniques, Intestinal Absorption, Iron Chelating Agents chemistry, Male, Mannitol metabolism, Perfusion, Permeability, Pyridines chemistry, Rats, Rats, Inbred F344, Iron Chelating Agents pharmacokinetics, Jejunum metabolism, Pyridines pharmacokinetics
- Abstract
Purpose: The in vitro and in situ transport of CGP 65015 ((+)-3-hydroxy-1-(2-hydroxyethyl)-2-hydroxyphenyl-methyl-1H-pyridin-4-on e), a novel oral iron chelator, is described. The predictive power of these data in assessing intestinal absorption in man is described., Methods: Caco-2 epithelial monolayer and in situ rat jejunum perfusion intestinal permeability models were utilized. In vivo iron excretion and preliminary animal pharmacokinetic experiments were described. Ionization constants and octanol/aqueous partition coefficients were measured potentiometrically. Solubilities and intrinsic dissolution rates were determined using standard procedures., Results: Caco-2 cell (Papp approximately 0.25 x 10(-6) cm x s(-1)) and rat jejunum (Pw approximately 0.4) permeabilities of CGP 65015 were determined. The log D(pH 7.4) of CGP 65015 was 0.58 and its aqueous solubility was < 0.5 mg x ml(-1) (pH 3-9). The intrinsic dissolution rate of CGP 65015 in USP simulated intestinal fluid was 0.012 mg x min(-1) x cm(-2). CGP 65015 promotes iron excretion effectively and dose dependently in animals., Conclusions: Caco-2 and rat intestinal permeabilities predict incomplete oral absorption of CGP 65015 in man. Preliminary rat pharmacokinetics support this. Physico-chemical data are, also, in line and suggest that CGP 65015 may, in addition, be solubility/dissolution rate limited in vivo. Nevertheless, early animal pharmacological data demonstrate that CGP 65015 is a viable oral iron chelator candidate.
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- 1999
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30. Oral absorption of CGS-20625, an insoluble drug, in dogs and man.
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Hirschberg Y, Oberle RL, Ortiz M, Lau H, and Markowska M
- Subjects
- Absorption, Administration, Oral, Adult, Animals, Biological Availability, Dogs, Female, Humans, Male, Metabolic Clearance Rate, Anti-Anxiety Agents pharmacokinetics, Pyrazoles pharmacokinetics
- Abstract
Oral bioavailability of highly water-insoluble drugs is often quite limited and variable, requiring the development of improved formulations. Animal models are an essential aspect of the design and testing of such formulations designed to improve absorption in man. The present report compares the absorption of CGS-20625, an insoluble drug, in dog and man after oral administration of the drug as a powder, a solid dispersion capsule, and after gastric and duodenal administration in PEG 400 solution. CGS-20625 powder (20 mg) given orally exhibited slow, delayed absorption in both dog and man, with a Cmax of 0.26 +/- 0.07 microgram/ml at Tmax of 3 hr in dog, and 0.01 +/- 0.004 microgram/ml at 2 hr in man. Administration of CGS-20625 in PEG 400 solution improved absorption in dog and man, with a Cmax of 1.2 +/- 0.10 microgram/ml at Tmax of 0.25 hr in dog, and a Cmax of 0.10 +/- 0.04 microgram/ml at 0.5 hr in man. Tmax after administration of the hard gelatin capsule formulation was 0.9 and 1.0 hr in dog and man, with Cmax of 0.89 +/- 0.16 and 0.052 +/- 0.014 microgram/ml, respectively. Absolute bioavailability of CGS-20625 powder in the dog was 0.67 +/- 0.21, whereas the bioavailabilities of the powder and the capsule relative to the PEG 400 solution were 0.84 and 1.1, respectively, in dog, and 0.41 and 0.85 respectively, in man. No significant benefits of duodenal administration were observed. Plasma levels were approximately 10-fold greater and oral clearance was approximately 5-fold less in the dog than in man. Furthermore, pharmacokinetic data were less variable and relative bioavailability was greater in dogs than in humans. Physiological factors in the gastrointestinal tract or greater first-pass metabolism in man may account for these species differences. The relative rate and extent of CGS-20625 absorption were similar between dog and man, in the order of powder < capsule < PEG 400 solution. In addition, in vivo absorption rates in both species reflect in vitro dissolution differences between the powder and the capsule. These data strongly support the use of the dog as a model for developing improved formulations of CGS-20625. Further investigation of the dog as a model to evaluate insoluble drug absorption is warranted.
- Published
- 1995
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31. The response to endotoxin in guinea pigs after intravenous black currant seed oil.
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Hirschberg Y, Shackelford A, Mascioli EA, Babayan VK, Bistrian BR, and Blackburn GL
- Subjects
- 8,11,14-Eicosatrienoic Acid blood, Animals, Bicarbonates blood, Blood, Dietary Fats, Unsaturated administration & dosage, Endotoxins, Fatty Acids blood, Guinea Pigs, Hydrogen-Ion Concentration, Lactates blood, Lactic Acid, Linolenic Acids administration & dosage, Linolenic Acids blood, Male, Parenteral Nutrition, Total, gamma-Linolenic Acid, Dietary Fats, Unsaturated therapeutic use, Linolenic Acids therapeutic use, Shock, Septic therapy
- Abstract
The influence on the metabolic response to endotoxin of three days of total parenteral nutrition with lipids high in gammalinolenic acid (18:3 omega 6, GLA) compared to soy oil (SO) was examined in acute operatively stressed guinea pigs. GLA is the precursor of dihomogammalinolenic acid (DHLA), the substrate for synthesis of "1" series prostaglandins such as PGE1, which have previously been shown to be protective in endotoxin lung injury and traumatic shock. Guinea pigs fed an intravenous diet containing black currant seed oil (BCO) emulsion (20% GLA) or soy oil emulsion (0% GLA) for 2.5 days had their arterial pH, pCO2, pO2, and bicarbonate measured at baseline and hourly during a 7-hr infusion of endotoxin (lipopolysaccharide (LPS), 2mg/kg) or saline. Plasma lactate and fatty acid profile analyses were performed at the end of the LPS infusion. Increased levels of GLA and DHLA were present in the plasma phospholipid fraction of animals fed the black currant seed oil diet, while soy-fed animals had only trace amounts of GLA. In addition, the ratio of DHLA to arachidonate was higher in animals receiving the black currant seed oil total parenteral nutrition (TPN). After 2 hr of LPS infusion, all animals exhibited the typical shock response resulting in metabolic acidosis characterized by a significant (p less than 0.05) drop in pH from 7.34 +/- .02 (SO) and 7.39 +/- .02 (BCO) at baseline to 7.14 +/- .05 and 7.22 +/- .04 by 7 hr for SO and BCO groups, respectively. Plasma lactate values at the end of the infusion were significantly elevated compared to saline in both groups (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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- 1990
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32. The effects of chronic fish oil feeding in rats on protein catabolism induced by recombinant mediators.
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Hirschberg Y, Pomposelli JJ, Blackburn GL, Istfan NW, Babayan V, and Bistrian BR
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- Animals, Body Weight drug effects, Liver anatomy & histology, Liver drug effects, Male, Organ Size drug effects, Rats, Rats, Inbred Strains, Recombinant Proteins pharmacology, Reference Values, Fish Oils pharmacology, Interleukin-1 pharmacology, Plant Oils pharmacology, Proteins metabolism, Safflower Oil pharmacology, Tumor Necrosis Factor-alpha pharmacology
- Abstract
The influence of dietary lipid manipulation with menhaden or safflower oil on changes in protein metabolism in rats receiving recombinant interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha/cachectin (TNF), or both combined (COINF) was examined. Whole-body protein kinetics, energy expenditure, nitrogen excretion, and liver and muscle protein synthesis were studied using tracer quantities of L-[1-14C]-leucine. Rats fed menhaden oil, high in omega-3 fatty acids, had significantly lower rates of leucine oxidation compared to safflower-fed rats after monokine infusion (P less than .05). However, muscle protein synthetic rates and the specific activity of free leucine in plasma and muscle indicated greater net muscle-protein breakdown in animals fed fish oil or receiving monokines. Rats fed omega-3 fatty acids had significantly larger livers as percent of body weight and more total liver protein than safflower oil controls (P less than .0001). Liver weight was further increased by monokines, particularly TNF and COINF (P less than .001) in both diet groups, suggesting that net hepatic anabolism occurred at the expense of net skeletal protein catabolism. Monokines as a group and COINF significantly decreased whole-body leucine flux and incorporation into protein; no effect of menhaden oil was noted. In addition, monokines increased nitrogen excretion during the 24-hour experimental period (P less than .05), and total energy expenditure rose significantly in all groups receiving IL-1 beta and COINF. The recombinant monokines IL-1 beta and TNF, particularly when coinfused, are able to reproduce many of the protein anabolic and catabolic consequences seen following infection and injury.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1990
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33. Decreased loss of liver nucleotides and energy charge during hypothermic preservation by donor pretreatment with glucose--a preliminary report.
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Palombo JD, Hirschberg Y, Pomposelli JJ, Blackburn GL, Zeisel SH, and Bistrian BR
- Subjects
- Animals, Cold Temperature, Liver cytology, Liver metabolism, Male, Rats, Rats, Inbred Strains, Reference Values, Energy Metabolism drug effects, Glucose pharmacology, Liver Transplantation, Ribonucleotides metabolism, Tissue Preservation methods
- Published
- 1989
34. Glycolytic support of adenine nucleotides in rat liver flush-preserved with UW or Collins' II. Importance of donor nutritional status.
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Palombo JD, Pomposelli JJ, Hirschberg Y, Blackburn GL, and Bistrian BR
- Subjects
- Adenosine, Allopurinol, Animals, Glutathione, Insulin, Lactates metabolism, Lactic Acid, Liver metabolism, Male, Organ Size, Raffinose, Rats, Rats, Inbred Strains, Adenine Nucleotides metabolism, Glycolysis, Hypertonic Solutions pharmacology, Liver Transplantation, Nutritional Status, Organ Preservation methods, Organ Preservation Solutions, Solutions pharmacology
- Abstract
Correlation of hepatocellular adenine nucleotides in donor liver with clinical posttransplant outcome has recently been reported. Our earlier work with rats has shown that pretreatment of donors with glucose effectively retards hepatocellular ATP losses in livers preserved in Collins' II solution through potentiation of their glycolytic capacity. The primary substrate--i.e., endogenous or exogenous glucose--was not identified. The current study was undertaken to compare the relative efficacy of the University of Wisconsin (UW) solution, which is devoid of glucose, with Collins' II in the support of adenine nucleotides through anaerobic glycolysis in flush-preserved rat liver. Adult rats were either pretreated with 25% dextrose or fasted prior to liver harvesting and preservation in either UW or Collins' II. Adenine nucleotide degradation and lactate production during preservation were assessed. For a given dietary pretreatment, losses of ATP and adenylate energy charge and lactate production were similar for UW- and Collins' II-preserved livers. Donor pretreatment with dextrose resulted in significantly higher ex vivo liver ATP, energy charge, and lactate regardless of the preservation solution. Salvageable nucleotide degradates were increased significantly in UW livers, presumably through the effects of allopurinol. These results demonstrate that effective support of adenine nucleotides by glycolysis in flush-preserved liver is independent of the presence of exogenous glucose but dependent upon the nutritional status of the donor prior to liver procurement.
- Published
- 1989
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35. Serum fatty acid profiles after intravenous medium chain triglyceride administration.
- Author
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Mascioli EA, Lopes S, Randall S, Porter KA, Kater G, Hirschberg Y, Babayan VK, Bistrian BR, and Blackburn GL
- Subjects
- Adult, Aged, Arachidonic Acids blood, Cholesterol Esters blood, Decanoic Acids blood, Diet, Female, Humans, Injections, Intravenous, Linoleic Acids blood, Linolenic Acids blood, Male, Middle Aged, Oleic Acids blood, Palmitic Acids blood, Phospholipids blood, Stearic Acids blood, Time Factors, Fatty Acids blood, Triglycerides administration & dosage
- Abstract
The serum fatty acid profiles of patients receiving either intravenous medium or long chain triglycerides were studied. Seventeen hospitalized patients, dependent on total parenteral nutrition, were randomly enrolled into a prospective study. The total parenteral nutrition (TPN) delivered amino acids and glucose and either a 75% medium chain triglyceride and 25% long chain triglyceride (MCT group) physical mixture or all long chain triglyceride (LCT group), as the respective fat sources. The amino acids and glucose were given continuously, and the lipid was given for 10 hours each day over five days. Fatty acid profiles on serum triglycerides and free fatty acids were done in the morning before any lipid was given and also later in the afternoon, near the end of the lipid administration, on days 1, 3 and 5. Medium chain fatty acids rose quickly in the triglyceride fraction in patients given MCT. Rapid MCT hydrolysis occurred as evidenced by the appearance of medium chain fatty acids in the free fatty acid fraction in the afternoon sampling. Clearance of the hydrolyzed medium chain free fatty acids (MCFFA) occurred so that little, if any, were present in the morning sampling one day later. Long chain fatty acids, as either triglycerides or free fatty acids, showed expected increases during the daily infusion, but not of such relative magnitude as the medium chain fatty acids. Medium chain fatty acid incorporation into the phospholipid or cholesterol ester fractions by the end of the five-day feeding period was present but minimal.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1989
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36. Decreased loss of liver adenosine triphosphate during hypothermic preservation in rats pretreated with glucose: implications for organ donor management.
- Author
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Palombo JD, Hirschberg Y, Pomposelli JJ, Blackburn GL, Zeisel SH, and Bistrian BR
- Subjects
- Animals, Aspartate Aminotransferases metabolism, Choline metabolism, Energy Metabolism, Fasting, Germ-Free Life, Hypothermia, Induced, Lactates metabolism, Liver Glycogen metabolism, Male, Rats, Rats, Inbred Strains, Adenosine Triphosphate metabolism, Glucose administration & dosage, Liver metabolism, Organ Preservation methods
- Abstract
Recent studies of human donor livers indicate an association between ex vivo hepatocellular adenosine triphosphate and posttransplant graft function. To test the hypothesis that prior glucose loading of donor liver would optimize its adenosine triphosphate production and adenylate energy charge during ex vivo organ preservation, adult male rats were randomized to receive either intravenous dextrose or saline for 44 h. After this infusion, a liver lobe was exposed and freeze-clamped (time 0). The remaining liver was quickly flushed, excised, and stored in Collins' II solution at 2 degrees C for 8 h. Additional lobes were freeze-clamped at 1, 4, and 8 h. Liver adenosine triphosphate, total nucleoside triphosphates, and energy charge losses were significantly reduced in the dextrose-treated rats in comparison with saline-treated rats during the first 4 h of preservation. Although the livers from rats receiving intravenous dextrose were able to generate lactate, their glycogen stores were not utilized appreciably, suggesting that exogenous glucose served as a substrate for anaerobic glycolysis. Unesterified choline levels of the fasted rat livers were significantly higher than those from the rats receiving intravenous dextrose by the first hour, indicative of increased membrane breakdown. These results indicate that prior infusion of glucose enhances the capacity of the ex vivo liver, presumably through the induction and stabilization of key glycolytic enzymes, to anaerobically generate adenosine triphosphate. Administration of glucose to liver donors before organ procurement may improve post-transplant graft function by reducing the loss of hepatocellular energy, retarding membrane damage, and fostering glycogen storage for use in the early postoperative period.
- Published
- 1988
- Full Text
- View/download PDF
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