Cardiac transplant rejection

Frist, W. Yasuda, T. SegaU, G. Khaw, B.A. Strauss, H.W. Gold, H.K. Stinson, E. Oyer, P. Baldwin, J. BiUingham, M. McDougall, R. Haber, E. Non-invasive detection of human cardiac transplant rejection with in antimyosin (Fab) imaging. Circulation 1987, 76, V81-85. 

Weller, G. E., Ln, E., Csikari, M. M., Klibanov, A. L., Fischer, D., Wagner, W. R., and Villanueva, F. S. (2003). Ultrasound imaging of acute cardiac transplant rejection with microbub-bles targeted to intercellular adhesion molecule-1. Circulation 108, 218-24. 

Calcineurin is involved in cardiac hypertrophy and in cognitive and behavioral defects in the brain. Inhibitors of calcineurin such as cyclosporine A and FK 506 are used clinically in transplant rejection and autoimmune diseases. 

Neutropenia Up to 2% of renal transplant patients, up to 3.6% of hepatic transplant patients, and up to 2.8% of cardiac transplant patients receiving mycophenolate developed severe neutropenia. Neutropenia has been observed most frequently in the period from 31 to 180 days posttransplant in patients treated for prevention of rejection. 

Nephrotoxicity Nephrotoxicity has been noted in 25% of cases of renal transplantation, 38% of cases of cardiac transplantation, and 37% of cases of liver transplantation. Mild nephrotoxicity was generally noted 2 to 3 months after transplant and consisted of an arrest in the fall of the preoperative elevations of BUN and creatinine at a range of 35 to 45 mg/dL and 2 to 2.5 mg/dL, respectively. These elevations are often responsive to dosage reductions. More overt nephrotoxicity was seen early after transplantation and was characterized by a rapidly rising BUN and creatinine. Because these events are similar to rejection episodes, care must be taken to differentiate between them. This form of toxicity is usually responsive to cyclosporine dosage reduction. 

Eisen HJ, Tuzcu EM, Dorent R, Kobashigawa J, Mancini D, Valantine-von Kaeppler HA et al. Everohmus for the prevention of allograft rejection and vasculopa-thy in cardiac-transplant recipients. N Engl J Med 2003 349(9) 847-58. 

Mycophenolate mofetil (CdlCept), in conjunction with cyclosporine and corticosteroids, has clinical applications in the prevention of organ rejection in patients receiving allogeneic renal and cardiac transplants. By effectively inhibiting de novo purine synthesis, it can impair the proliferation of both T and B lymphocytes. Following oral administration, mycophenolate mofetil is almost completely absorbed from the GI tract, metabolized in the liver first to the active compound my-cophenolic acid, and then further metabolized to an inactive glucuronide. 

Muromonab-(CD3) Orthoclone OKT3) is a mouse monoclonal antibody that is a purified IgG. It is used for the prevention of acute allograft rejection in kidney and hepatic transplants and as prophylaxis in cardiac transplantation. It is also used to deplete T cells in marrow from donors before bone marrow transplantation. 

Muromonoab-CD3 is used for the treatment of acute organ transplant rejection. It is effective in preventing graft rejection after kidney, heart or liver transplantation. Muromonoab-CD3 is effective in patients who after acute cardiac or liver allograft rejection do not respond to steroid therapy. It is administered intravenously and with a dose of 5 mg/day, a general concentration range of 400-1500 ng/ml can be achieved. A serum concentration of 600-1150 ng/ml in renal transplant patients produces desirable immunosuppressive effects. The levels of CD3 expression, their production and antibodies to the drug determine its rate of clearance. In the absence of antibodies to muromonoab-CD3, its half-life is about 18 h. 

Hershberger RE, Randall SC, Eisen HJ, Bergh C-H, et al. 2005. Daclizumab to prevent rejection after cardiac transplantation. NEJM. 352 2705-2713. 

Bishop DK, Shelby J, Eichwald EJ. 1992. Mobilization of T lymphocytes following cardiac transplantation. Evidence that CD4- positive cells are required for cytotoxic T lymphocyte activation, inflammatory endothelial development, graft infiltration and acute allograft rejection. Transplantation. 53 849-857. 

Schofield RS, Hill JA, McGinn CJ, Aranda JM. Hormone therapy in men and risk of cardiac allograft rejection. J Heart Lung Transplant 2002 21(4) 493-5. 

Poston RS, Mann MJ, Hoyt EG, Ennen M, Dzau VJ, Robbins RC. Antisense oligodeoxynucleotides prevent acute cardiac allograft rejection via a novel, non-toxic, highly efficient transfection method. Transplantation 1999 68 825-832. 

Suppression of organ graft rejection. Mouse to rat cardiac transplantation was performed. One group of rats was exposed to 400 ppm CO in air for 2 days following the operation and survived for 50 days. The other group breathed air, and survived only 5-7 days [16]. 

Prolongs the survival rate of transplanted hearts using a model of cardiac allograft rejection in mice [142]... 

Influenza infection has been a significant problem in cardiac transplant patients immunization of such patients could therefore be beneficial. However, its use has been limited by concern that stimulation of the immune system might in principle cause an increased risk of cardiac rejection. In the renal transplant experience, influenza infection itself can trigger an immunological response to cause graft rejection, as well as predisposing to other infections. Another concern is whether an immunosuppressed cardiac transplant recipient could seroconvert sufficiently. In a case-control study in 18 cardiac transplant recipients and 18 control patients 6 months or more beyond transplant surgery, there were no differences in the incidence of cardiac rejection or immune responses (28). 

Kobashigawa JA, Warner-Stevenson L, Johnson BL, Moriguchi JD, Kawata N, Drinkwater DC, Laks H. Influenza vaccine does not cause rejection after cardiac transplantation. Transplant Proc 1993 25(4) 2738-9. 

Cyclophosphamide is used in human medicine as an antineoplastic (anticancer) agent in a variety of applications. Cyclophosphamide is a potent immunosuppressive agent and is used to prevent rejection episodes following renal, hepatic, and cardiac transplantation and in non-neoplastic disorders in which... 

Gene-expression profiling for rejection surveillance after cardiac transplantation. N Engl J Med 362 1890-1900... 

Michaels PJ, Espejo ML, Kobashigawa J, et al. Humoral rejection in cardiac transplantation Risk factors, hemodynamic consequences and relationship to transplant coronary artery disease. J Heart Limg Transplant 2003 22 58-69. 

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