Search

Your search keyword '"Ancona, E"' showing total 822 results
Start Over Author "Ancona, E"
822 results on '"Ancona, E"'

57. Oesophagus

Author

Ismail, T., Bancewicz, J., Barlow, J., Gillen, P., Thornton, J., Byrne, P. J., Lawlor, P., Walsh, T. N., Hennessy, T. P. J., Baker, S. R., Soo, K. S., Michie, C. A., Wyllie, J. H., Edwards, D. A. W., Hakhamaneshi, D., Zaninotto, G., Costantini, M., Polo, R., Bagolin, F., Ancona, E., Anselmino, M., Baessalo, M., Bonavina, L., Ruol, A., Peracchia, A., Sidhu, P., O’Donnell, A. F., Luke, D. A., Wood, A. E., Goldberg, P. A., Krige, J. E. J., Bomman, P. C., and Terblanche, J.

Published
1992
Full Text
View/download PDF

59. LAPAROSCOPIC ANTIREFLUX SURGERY VS ESOMEPRAZOLE TREATMENT FOR CHRONIC GERD – THE LOTUS RANDOMIZED CLINICAL TRIAL

Author

Miholic J, Hubmann R, Danis J, Tack J, Lerut T, Piessevaux H, Devière J, Buset M, Chioccioli C, De Looze D, Demoulin JC, Louis E, Ghilain JM, Maisin JM, Funch Jensen P, Nielsen J, Christensen L, Antonsen H, Lauritsen K, Jess P, Wallin L, Naver L, Galmiche JP, Letessier E, Zerbib F, Bonaz B, Bost R, Delchier JC, Fein M, Maroske J, Ell C, Hölscher A, Zornig C, Schneider JH, Hüttl T, Büchler M, Wehrmann U, Kemen M, Layer P, Fuchs KH, Kemen S, Hüppe D, Oddsdóttir M, Thjodleifsson B, Bonavina L, Ancona E, Morino M, Pignata G, Giurissa A, Rossi M, Cestari R, Gooszen H, Hatlebakk J, Tefera S, Johnsen G, Jahnsen J, Sandstad O, Stallemo A, Florholmen J, Tollåli G, Engström C, Liedman B, Lundell L, Babbs C, Attwood S., ROSATI , RICCARDO, Miholic, J, Hubmann, R, Danis, J, Tack, J, Lerut, T, Piessevaux, H, Devière, J, Buset, M, Chioccioli, C, De Looze, D, Demoulin, Jc, Louis, E, Ghilain, Jm, Maisin, Jm, Funch Jensen, P, Nielsen, J, Christensen, L, Antonsen, H, Lauritsen, K, Jess, P, Wallin, L, Naver, L, Galmiche, Jp, Letessier, E, Zerbib, F, Bonaz, B, Bost, R, Delchier, Jc, Fein, M, Maroske, J, Ell, C, Hölscher, A, Zornig, C, Schneider, Jh, Hüttl, T, Büchler, M, Wehrmann, U, Kemen, M, Layer, P, Fuchs, Kh, Kemen, S, Hüppe, D, Oddsdóttir, M, Thjodleifsson, B, Bonavina, L, Ancona, E, Morino, M, Pignata, G, Giurissa, A, Rossi, M, Rosati, Riccardo, Cestari, R, Gooszen, H, Hatlebakk, J, Tefera, S, Johnsen, G, Jahnsen, J, Sandstad, O, Stallemo, A, Florholmen, J, Tollåli, G, Engström, C, Liedman, B, Lundell, L, Babbs, C, and Attwood, S.

Published
2011

62. Anti-inflammatory responses and tolerability following the in vivo administration of a carbon monoxide-releasing molecule in primates

Author

Seveso, M, Vadori, M, Besenzon, F, Bosio, E, Fante, F, Ravarotto, L, Bedendo, S, Baldan, N, Lavitrano, M, Johnson, T, Mann, B, Motterlini, R, Cozzi, E, Ancona, E, Johnson, TR, Mann, BEM, Ancona, E., LAVITRANO, MARIALUISA, Seveso, M, Vadori, M, Besenzon, F, Bosio, E, Fante, F, Ravarotto, L, Bedendo, S, Baldan, N, Lavitrano, M, Johnson, T, Mann, B, Motterlini, R, Cozzi, E, Ancona, E, Johnson, TR, Mann, BEM, Ancona, E., and LAVITRANO, MARIALUISA

Published
2005

63. Effect of preoperative chemoradiotherapy on outcome of patients with locally advanced esophagogastric junction adenocarcinoma&mdash

Author

Orditura, M., Galizia, G., Martino, N. Di, Ancona, E., Castoro, C., Pacelli, R., Morgillo, F., Rossetti, S., Gambardella, V., Farella, A., Laterza, M.M., Ruol, A., Fabozzi, A., Napolitano, V., Iovino, F., Lieto, E., Fei, L., Conzo, G., Ciardiello, F., and Vita, F. De

Subjects
genetic structures, gastroesophageal junction cancer, folfox4, Preoperative chemoradiotherapy
Abstract

To date, few studies of preoperative chemotherapy or chemoradiotherapy (crt) in gastroesophageal junction (gej) cancer have been statistically powered, indeed, gej tumours have thus far been grouped with esophageal or gastric cancer in phase iii trials, thereby generating conflicting results. We studied 41 patients affected by locally advanced Siewert type i and ii gej adenocarcinoma who were treated with a neoadjuvant crt regimen [folfox4 (leucovorin&ndash, 5-fluorouracil&ndash, oxaliplatin) for 4 cycles, and concurrent computed tomography&ndash, based three-dimensional conformal radiotherapy delivered using 5 daily fractions of 1.8 Gy per week for a total dose of 45 Gy], followed by surgery. Completeness of tumour resection (performed approximately 6 weeks after completion of crt), clinical and pathologic response rates, and safety and outcome of the treatment were the main endpoints of the study. All 41 patients completed preoperative treatment. Combined therapy was well tolerated, with no treatment-related deaths. Dose reduction was necessary in 8 patients (19.5%). After crt, 78% of the patients showed a partial clinical response, 17% were stable, and 5% experienced disease progression. Pathology examination of surgical specimens demonstrated a 10% complete response rate. The median and mean survival times were 26 and 36 months respectively (95% confidence interval: 14 to 37 months and 30 to 41 months respectively). On multivariate analysis, TNM staging and clinical response were demonstrated to be the only independent variables related to long-term survival. In our experience, preoperative chemoradiotherapy with folfox4 is feasible in locally advanced gej adenocarcinoma, but shows mild efficacy, as suggested by the low rate of pathologic complete response.

Published
2014
Full Text
View/download PDF

64. Carbon monoxide significantly reduces the apoptotic events associated with ischemia-reperfusion injury: Observations in a renal pig-to-primate model

Author

Cozzi, E, Seveso, M, Calabrese, F, De Benedictis, G, Baldan, N, Boldrin, M, Castagnaro, M, Ravarotto, L, Carraro, P, Busetto, R, Otterbein, L, Lavitrano, M, Bernardini, D, Thiene, G, Bach, F, Ancona, E, Otterbein, LE, Bach, FH, Ancona, E., LAVITRANO, MARIALUISA, Cozzi, E, Seveso, M, Calabrese, F, De Benedictis, G, Baldan, N, Boldrin, M, Castagnaro, M, Ravarotto, L, Carraro, P, Busetto, R, Otterbein, L, Lavitrano, M, Bernardini, D, Thiene, G, Bach, F, Ancona, E, Otterbein, LE, Bach, FH, Ancona, E., and LAVITRANO, MARIALUISA

Published
2004

65. Carbon monoxide (CO) prevents apoptotic events related to ischemia/reperfusion (IR) injury in an hDAF pig-to-primate xenotransplantation model

Author

Calabrese, F, Seveso, M, Iacopetti, I, Ferrari, V, Boldrin, M, Mattiazzo, G, Rigotti, P, Busetto, R, Bernardini, D, Lavitrano, M, Thiene, G, Cozzi, E, Bach, F, Ancona, E, Bach, FH, Ancona, E., LAVITRANO, MARIALUISA, Calabrese, F, Seveso, M, Iacopetti, I, Ferrari, V, Boldrin, M, Mattiazzo, G, Rigotti, P, Busetto, R, Bernardini, D, Lavitrano, M, Thiene, G, Cozzi, E, Bach, F, Ancona, E, Bach, FH, Ancona, E., and LAVITRANO, MARIALUISA

Published
2003

66. Two-year follow-up of a once daily modified release Tacrolimus regimen in de novo kidney transplant recipients

Author

Wlodarczyk Z, Squifflet JP, Ostrowski M, Ancona E, Castagneto M, Vanrenterghem Y, Krämer B, Oppenheimer F, Abramowicz D, Pietruck F, Russ G, Neumayer H, Clavien P, Heemann U, Villafruela JJ, STEFONI, SERGIO, Wlodarczyk Z, Squifflet JP, Ostrowski M, Ancona E, Stefoni S, Castagneto M, Vanrenterghem Y, Krämer B, Oppenheimer F, Abramowicz D, Pietruck F, Russ G, Neumayer H, Clavien P, Heemann U, and Villafruela JJ

Published
2007

68. Carbon monoxide (CO) prevents apoptotic events related to ischemia/reperfusion (IR) injury in an hDAF pig-to-primate xenotransplantation model

Author

Calabrese, Fiorella, Seveso, M., Iacopetti, Ilaria, Ferrari, V., Boldrin, M., Mattiazzo, G., Rigotti, Paolo, Busetto, Roberto, Bernardini, Daniele, Lavitrano, M. L., Thiene, Gaetano, Cozzi, E., Bach, Fh, Ancona, E., Calabrese, F, Seveso, M, Iacopetti, I, Ferrari, V, Boldrin, M, Mattiazzo, G, Rigotti, P, Busetto, R, Bernardini, D, Lavitrano, M, Thiene, G, Cozzi, E, Bach, F, and Ancona, E

Subjects
xenotransplantation
Published
2003

70. XXIth International SMIER Congress

Author

Bourbon, P., Rousseau, E., Zarski, J. P., Aubert, H., Martin, G., Rachail, M., Courrier, A., Simonnet, Ph., Arbogast, J., Maffxoli Cl, Delvaux, M., Escourrou, J., Hajjar, A., Rumeau, J. L., Frexinos, J., Ribet, A., Sabben, G., Lambert, R., Chavaillon, A., Bonvoisin, S., Descos, F., Olive, C., Lambert, R., Sabben, G., Descos, F., Al-Watban, F. A. H., Brannon, R. C., King, G. A., Qureshi, A., Altamero, T., Norberto, L., Cusumano, A., Martella, B., Bardini, R., Ancona, E., Peracchia, A., Jung, M., Manegold, B. C., Haguenauer, J. P., Gaillard, J., Pignat, J. C., Leval, J., Catalano, G. B., Serra, A., Arcidiacono, A., Saita, V., La Mantia, I., Morgoii, A., Haguenauer, J. P., Dubreuil, C., Leval, J., Disant, F., Begou, G., Catalano, G. B., Serra, A., Arcidiacono, A., Saita, V., La Mantia, I., Monnier, Ph., Savary, M., Freche, Ch., Pech, A., Piquet, J. J., Berrier, A., Van Ton, J., Vaneecloo, F. M., Gaillard, J., HAGuenauer, J. P., Leval, J., Pignat, J. C., Comptat, P., Cuerin, J. C., Martinat, Y., Picnat, J. C., Hacuenauer, J. P., Personne, C., Colchen, A., Colchen, A., Personne, C., Martinat, Y., Guerin, J. C., Lazib, A., Guerin, J. C., Martinat, Y., Boutin, C., Jullian, H., Convert, G., Velardocchio, J. M., Frangenheim, H., and Frangenheim, Th.

Published
1985
Full Text
View/download PDF

72. A prospective multicenter study on laparoscopic treatment of gastroesophageal reflux disease in Italy: type of surgery, conversions, complications, and early results

Author

Zaninotto G, Molena D, Ancona E, Peracchia A, Bonavina L, Costantini M, Nicoletti L, Favretti F, Valletta S, Sartori C, Franzato B, Antonello GB, Di Falco G, Pavanello M, Morino M, Rebecchi F, Melotti G, Lanzani A, Viola G, Procaccini E, Ruggiero R, Basso N, Genco A, Rea S, Croce E, Olmi S, Parini U, Fosson A, Lale Murix E, Del Genio A, Landolfi V, Rosati R, Fumagalli U, Bona S, Bresadola F, Bresadola V, Terrosu G, Corso D, De Bernardinis M, Basile F, Migliore M, Vecchioni R, Saviano M, Picciocchi A, Coppola R, Castrucci G, Botta GC, Contini S, Rossi M, Anselmino M, Zaninotto, G, Molena, D, Ancona, E, Peracchia, A, Bonavina, L, Costantini, M, Nicoletti, L, Favretti, F, Valletta, S, Sartori, C, Franzato, B, Antonello, Gb, Di Falco, G, Pavanello, M, Morino, M, Rebecchi, F, Melotti, G, Lanzani, A, Viola, G, Procaccini, E, Ruggiero, Roberto, Basso, N, Genco, A, Rea, S, Croce, E, Olmi, S, Parini, U, Fosson, A, Lale Muriz, E, Del Genio, A, Landolfi, V, Rosati, R, Fumagalli, U, Bona, S, Bresadola, F, Bresadola, V, Terrosu, G, Corso, D, De Bernardinis, M, Basile, F, Migliore, M, Vecchioni, R, Saviano, M, Picciocchi, A, Coppola, R, Castrucci, R, Botta, Gc, Contini, S, Rossi, M, Anselmino, M., Ruggiero, R, Lale Murix, E, Castrucci, G, and Anselmino, M

Published
2000

73. Emergenze Toraciche

Author

Alamanni F, Ancona E, Anselmino M, Beltrami V, Bergami F, Biglioli P, Boglino C, Bonavina L, Brazzi L, Cappelletti M, Carretta A, Castagnone D, Chiesa G, Ciprandi G, Cortale M, Di Nuzzo D, Donin I, Fedriga E, Floriani M, Gattinoni L, Gherli T, Giulini SM, Grossi A, Guglielmi M, Inserra A, Leggeri A, Liguori G, Lovaria A, Lubatti L, Messineo A, Pelosi P, Peracchia A, Pouchè A, Pozzato C, Rossi P, Sottini A, Stipa S, Tiberio G, Tiberio GAM, Trazzi R, Volterrani F, Ziparo V., DOCIMO, Ludovico, Alamanni, F, Ancona, E, Anselmino, M, Beltrami, V, Bergami, F, Biglioli, P, Boglino, C, Bonavina, L, Brazzi, L, Cappelletti, M, Carretta, A, Castagnone, D, Chiesa, G, Ciprandi, G, Cortale, M, Di Nuzzo, D, Docimo, Ludovico, Donin, I, Fedriga, E, Floriani, M, Gattinoni, L, Gherli, T, Giulini, Sm, Grossi, A, Guglielmi, M, Inserra, A, Leggeri, A, Liguori, G, Lovaria, A, Lubatti, L, Messineo, A, Pelosi, P, Peracchia, A, Pouchè, A, Pozzato, C, Rossi, P, Sottini, A, Stipa, S, Tiberio, G, Tiberio, Gam, Trazzi, R, Volterrani, F, and Ziparo, V.

Published
2000

75. Porcine embryonic xenografts transgenic for CTLA4-Ig enable longterm recovery in parkinsonian macaques

Author

Badin, Ra, Padoan, A., Vadori, M., Boldrin, M., Giulia Maria De Benedictis, Fante, F., Sgarabotto, D., Jan, C., Daguin, V., Naveilhan, P., Neveu, I., Soullilou, Jp, Vanhove, B., Plat, M., Botte, F., Venturi, F., LUCA DENARO, Seveso, M., Manara, R., Zampieri, P., Avella, Domenico D., Rubello, D., Ancona, E., Hantraye, P., Cozzi, E., Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ura2210, Centre National de la Recherche Scientifique (CNRS), Universita di Padova, Consorzio per la Ricerca sul Trapianto di Organi, Partenaires INRAE, Azienda Ospedaliera di Padova, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Unité Expérimentale de Physiologie Animale de l‘Orfrasiére (UE PAO), Institut National de la Recherche Agronomique (INRA), Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), ProdInra, Migration, Università degli Studi di Padova = University of Padua (Unipd), and Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV] Life Sciences [q-bio], XENOGREFFE, [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], HISTOLOGIE, [INFO] Computer Science [cs], EMBRYON TRANSGENIQUE, MACAQUE, ComputingMilieux_MISCELLANEOUS
Abstract

LB01; International audience

Published
2010

77. Transgenic porcine embryonic xenografts as a treatment for Parkinson's disease in non-human primates

Author

Aron, B.R., Padoan, A., Vadori, M., Boldrin, M., Cavicchioli, Lionel, de Benedictis, G.M., Fante, F., Seveso, M., Sgarabotto, D., Jan, Charlie, Daguin, V., Naveilhan, P., Neveu, I., Soulillou, J.P., Vanhove, B., Plat, Martine, Botté, Françoise, Venturi, Eric, Denaro, L., Manara, R., Zampieri, P., d'Avella, D., Rubello, D., Ancona, E., Hantraye, P., Cozzi, Elena, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ura2210, Centre National de la Recherche Scientifique (CNRS), Universita di Padova, Consortium for Research in Organ Transplantation (CORIT), Azienda Ospedaliera di Padova, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Centre hospitalier universitaire de Nantes (CHU Nantes), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Unité Expérimentale de Physiologie Animale de l‘Orfrasiére (UE PAO), Institut National de la Recherche Agronomique (INRA), Università degli Studi di Perugia (UNIPG), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Padova = University of Padua (Unipd), Consorzio per la Ricerca sul Trapianto d'Organ = Consortium for Research in Organ Transplantation (CORIT), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Perugia = University of Perugia (UNIPG), and ProdInra, Migration

Subjects
[SDV] Life Sciences [q-bio], XENOGREFFE, EMBRYON PORCIN TRANSGENIQUE, [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], [INFO] Computer Science [cs], ComputingMilieux_MISCELLANEOUS
Abstract

Communication orale LB IXA O-1; International audience

Published
2009

81. De novo anti-HLA antibody responses after renal transplantation: detection and clinical impact

Author

Seveso, M., Bosio, E., Ancona, E., and Cozzi, E.

Subjects
Graft Rejection, Antibody Specificity, HLA Antigens, Isoantibodies, Complement C4b, Humans, Kidney, Kidney Transplantation, Peptide Fragments, Tissue Donors
Abstract

Numerous retrospective and prospective studies have been conducted to determine the prevalence and significance on long-term graft survival of de novo post-transplant donor-specific antibodies (DSA), directed against both HLA and non-HLA molecules. Moreover, it has been postulated that the development of anti-HLA antibodies may precede the clinical manifestation of chronic rejection, therefore being considered a predictive marker. In this context, the detection of C4d deposition in the failing kidney in patients presenting de novo DSA supports the hypothesis that antibody production and complement deposition could be involved in the pathogenesis of graft failure. Due to the development of more sensitive meth-ods to detect alloantibodies, the number of transplanted patients which show the appearance of DSA at different times following transplantation has increased. Nevertheless, this increased sensitivity has allowed the identification of circulating donor-specific anti-HLA antibodies in many patients with otherwise good graft function. Such findings are worthy of discussion, as it has yet to be determined whether these circulating antibodies can only be considered an early marker of humoral rejection or whether they could play a protective role. The possible relevance of the post-transplant appearance of non-DSA should also be mentioned. This review will focus primarily on de novo anti-donor HLA antibody responses in kidney transplant patients and will only briefly deal with anti-non HLA and non-DSA that will be discussed elsewhere in this issue.

Published
2008

95. [How to prevent saphenous nerve injury. A personal modified technique for the stripping of the long saphenous vein]

Author

Sorrentino P, Renier M, Coppa F, Sarzo G, Tiziana Morbin, Scappin S, Baccaglini U, and Ancona E

Subjects
Adult, Postoperative Complications, Ambulatory Surgical Procedures, Venous Insufficiency, Peripheral Nerve Injuries, Humans, Saphenous Vein, Prospective Studies, Middle Aged, Intraoperative Complications, Follow-Up Studies
Abstract

In literature the incidence of paresthesia caused by long stripping (LS) of the saphenous vein (SV) varies widely. Best results have been reported with the invagination technique by Van Der Stricht. However, this technique is associated with a high incidence of vein rupture and incomplete stripping. The aim of this study is to test a personal technique to avoid the SV rupture and to reduce the incidence of saphenous nerve injury.Sixty-eight patients underwent LS of the SV from groin to ankle under monolateral spinal anesthesia on a one-day surgery basis using a personal technique combining external and invaginated saphenous stripping. All patients underwent a clinical re-evalutation 1, 3, 6, 12, 24 and 48 months after the operation.No intraoperative complications were recorded. Stripping of the long saphenous vein was complete in all cases without any rupture of the veins. Only one postoperative hematoma of the leg (1.5%) which was naturally reabsorbed, was recorded; four patients (5.9%) had transitory saphenous nerve injury. Permanent saphenous nerve damage was found in only one of 68 patients (1.5%). All the patients were discharged on the day of operation and we did not register any prolonged hospitalization.The result of our approach was a very low postoperative complication rate (1.5% of permanent neurological damage) without any rupture of the vein.

Published
2003

96. Xenotransplantation, where do we stand?

Author

Emanuele Cozzi and Ancona, E.

Subjects
Animals, Genetically Modified, Graft Rejection, Primates, Transplantation, Heterologous, Swine, Transplantation, Heterologous, Animals, Humans, Genetic Engineering, Genetically Modified
Abstract

Xenotransplantation is currently being investigated as a possible solution to the world-wide shortage of human organs. Several major advances have unquestionably been accomplished in the last decade in this field. These include an elucidation of the immunological mechanisms underlying the rejection of pig organs transplanted into primates, the generation of novel lines of genetically-engineered pigs that are more "compatible" with man and a better understanding of the risk of zoonosis related to the transmission of porcine endogenous retroviruses to primates. Though very encouraging, the existing preclinical data do not entitle clinical trials with pig organs to begin as yet and, for the time being, the use of human organs remains the only viable option for patients with terminal organ failure.

Published
2003

99. Methotrexate for immunosuppression in life-supporting pig-to-cynomolgus monkey renal xenotransplantation

Author

Cozzi, E., Cadrobbi, R., Baldan, N., Dedja, A., Calabrese, F., Castagnaro, M., Fante, F., Boldrin, M., Iacopetti, I., Ravarotto, L., Carraro, P., Bronte, Vincenzo, Santo, C. D., Busetto, R., Plebani, M., Cancellotti, F. M., Rigotti, P., Thiene, G., and Ancona, E.

Subjects
Diarrhea, Graft Rejection, Male, Transplantation, Heterologous, CD55 Antigens, Swine, Graft Survival, Transplantation, Heterologous, Genetically Modified, Animals, Antigens, CD55, Female, Humans, Immunosuppressive Agents, Intestine, Small, Kidney Transplantation, Macaca fascicularis, Methotrexate, Animals, Genetically Modified, Intestine, Small
Abstract

Methotrexate (MTX) has been used successfully as an immunosuppressant in rodent xenotransplantation models, but the data generated so far with MTX in pig-to-baboon cardiac transplantation studies have been disappointing. The potential of this agent was consequently explored in a life-supporting pig-to-primate renal model using the cynomolgus monkey as the recipient species. Introductory in vitro and in vivo pharmacokinetic and pharmacodynamic studies with MTX were conducted in three cynomolgus monkeys. Subsequently, 10 cynomolgus monkey recipients of a life-supporting kidney from human decay-accelerating factor transgenic pigs were administered MTX intravenously according to three different regimens. All the animals also received cyclosporine A and steroids. In addition, mycophenolate sodium (MPS) was administered post-operatively in two of the three groups of transplanted animals. At clinically relevant concentrations, MTX is able in vitro to inhibit the mixed lymphocyte reactions (MLR) in cynomolgus monkeys. After intravenous administration, moreover, exposure of cynomolgus monkeys to MTX appeared to be higher than had been previously reported in baboons. Graft function was observed in the transplanted animals, which survived from 0 to 41 days. All but two animals revealed acute humoral rejection in the explanted graft and developed diarrhea. Diarrhea was the cause of euthanasia in five cases. It was unrelated to the administration of MPS and associated with severe histopathological signs of enteritis. This study demonstrates that the pharmacokinetic and pharmacodynamic profiles if MTX vary substantially between non-human primate species. In vitro, MTX has immunosuppressive properties in the cynomolgus monkey at clinically relevant concentrations. In vivo, MTX has a very narrow therapeutic window in cynomolgus monkeys, however, as it does in baboons. We conclude that MTX is scarcely effective as an immunosuppressant, be it for induction or maintenance, in pig-to-cynomolgus monkey renal xenotransplantation.

Published
2003

Catalog

Books, media, physical & digital resources
See catalog results