Maintenance Immunosuppressive Drug Therapy and Potential Major Complications

  • K. L. Tyndall
  • D. K. C. Cooper


The various pharmacological immunosuppressive agents available to those involved in organ transplantation have been discussed by a number of authors, and detailed accounts of their structure and mode of action can be found elsewhere. A comprehensive review of the newer agents presently in early clinical use, or in clinical or experimental development, is presented elsewhere in this volume (Chapter 70). The vast majority of centers today, however, utilize triple-drug maintenance therapy with cyclosporin (CsA), azathioprine (AZA), and corticosteroids. CsA-Neoral is beginning to take the place of CsA, and will eventually supersede it. Tacrolimus (FK506) has been introduced in place of CsA in a few centers (Chapters 10 and 70). (It is important to note that CsA and tacrolimus should not be given in combination, due to their severe nephrotoxic effect.) Cyclophosphamide is sometimes used to replace AZA, and mycophenolate mofetil is beginning to replace AZA in a small number of centers (Chapter 70). In addition, some centers include induction cytolytic therapy with an anti-T-cell polyclonal (an antithymocyte (ATG)/antilymphocyte (ALG) globulin) or monoclonal (OKT3) antibody.


Transplant Patient Acute Rejection Transplant Proc Heart Transplant Recipient Heart Lung Transplant 
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  1. 1.
    Borel JF, Feurer C, Gubler HU, Stahelin H. Biological effects of cyclosporin-A: a new antilymphocytic agent. Agents Actions. 1976;6:468.PubMedCrossRefGoogle Scholar
  2. 2.
    Dreyfuss M, Harri E, Hofmann H el al. Cyclosporin-A and C. New metabolites from Trichoderma polysporum. Eur J Appl Microbiol. 1976;3: 125.CrossRefGoogle Scholar
  3. 3.
    White DJG (editor). Cyclosporin-A. (Amsterdam: Elsevier). 1982.Google Scholar
  4. 4.
    Morris PJ. Cyclosporin-A. Transplantation. 1981;32:349.Google Scholar
  5. 5.
    Borel JF. Immunological properties of cyclosporin-A. Heart Transplant. 1982;1:237.Google Scholar
  6. 6.
    White DJG, Calne RY. Chemical immunosuppression. In: Calne RY (editor). Transplantation immunology — clinical and experimental. (Oxford: Oxford University Press), 1984;254.Google Scholar
  7. 7.
    Andreone PA, Olivari MT, Elick B et al. Reduction of infectious complications following heart transplantation with triple-drug immunotherapy. J Heart Transplant. 1986;5:13.PubMedGoogle Scholar
  8. 8.
    Jazzar A, Fagiuoli S, Sisson S, Zuhdi N, Cooper DKC. Induction therapy with cyclosporin and without cytolytic agents result in a low incidence of acute rejection without significant renal impairment in heart transplant patients. Clin Transplant. 1995;9:334.PubMedGoogle Scholar
  9. 9.
    Sisson S, Jazzar A, Mischke L, Cooper DKC, Zuhdi N. How many endomyocardial biopsies (EMBs) are necessary in the first year after heart transplantation? Transplant Int. (In press).Google Scholar
  10. 10.
    Donatsch P, Abisch E, Hornberger M et al. A radioimmunoassay to measure cyclosporin-A in plasma and scrum samples. J Immunoassay. 1981;2:19.PubMedCrossRefGoogle Scholar
  11. 11.
    Sgoutas DS, Hammarstrom M. Comparison of specific radioimmunoassays for cyclosporin. Transplantation. 1989;47:668.PubMedCrossRefGoogle Scholar
  12. 12.
    Schroeder TJ, Brunson ME, Pesce AJ et al. A comparison of the clinical utility of the radioimmunoassay, high-performance liquid chromatography, and TDx cyclosporin assays in outpatient renal transplant recipients. Transplantation. 1989;47:262.PubMedCrossRefGoogle Scholar
  13. 13.
    Gmur DJ. Modified column-switching high-performance liquid Chromatographic method for measurement of cyclosporin in serum. J Chromatogr. 1985;344:422.PubMedCrossRefGoogle Scholar
  14. 14.
    Speck RF, Frey FJ, Frey BM. Cyclosporine kinetics in renal transplant patients as assessed by high-performance liquid chromatography and radioimmunoassay using monoclonal and polyclonal antibodies. Transplantation. 1989;47:802.PubMedCrossRefGoogle Scholar
  15. 15.
    Lake KD. Cyclosporine drug interactions: a review. Cardiac Surgery: State of the Art Reviews. 1988;2:617.Google Scholar
  16. 16.
    Valentine H, Keogh A, Mclntosh N et al. Cost containment: coadministration of diltiazem with cyclosporin after heart transplantation. J Heart Lung Transplant. 1992;11:1.Google Scholar
  17. 17.
    Schroeder JS, Gao SZ, Alderman EL et al. A preliminary study of diltiazem in the prevention of coronary artery disease in heart transplant recipients. N Engl J Med. 1993;328:164.PubMedCrossRefGoogle Scholar
  18. 18.
    Vazquez De Prada JA, Martin-Duran R, Garcia-Monco C et al. Cyclosporine neu rotoxicity in heart transplantation. J Heart Transplant. 1990;9:581.Google Scholar
  19. 19.
    Hughes RL. Cyclosporine-related central nervous system toxicity in cardiac transplantation. N Engl J Med. 1990;323:420.PubMedCrossRefGoogle Scholar
  20. 20.
    Andrews BT. The neurological complications of cardiac transplantation (editorial). Surg Neurol. 1991;35:248.PubMedCrossRefGoogle Scholar
  21. 21.
    McManus RP, O’Hair DP, Schweiger J, Beitzinger J, Siegel R. Cyclosporine associated central neurotoxicity after heart transplantation. Ann Thorac Surg. 1992;53:326.PubMedCrossRefGoogle Scholar
  22. 22.
    Thompson CB, June CH, Sullivan KM, Thomas ED. Association between cyclosporin neurotoxicity and hypomagnesaemia. Lancet. 1984;2:1116.PubMedCrossRefGoogle Scholar
  23. 23.
    Schmitz N, Eulen HH, Loffler H. Hypomagnesaemia and cyclosporin toxicity (Letter). Lancet. 1985;1:103.Google Scholar
  24. 24.
    de Groen FC, Aksamit AJ, Rakela J, Forbes GS, Krom RAF. Central nervous system toxicity after liver transplantation: the role of cyclosporine and cholesterol. N Engl J Med. 1987;317:861.PubMedCrossRefGoogle Scholar
  25. 25.
    Cooper DKC, Novitzky D, Davis L et al. Does central nervous system toxicity occur in hypocholesterolemic transplant patients receiving cyclosporin? J Heart Transplant. 1989;8:221.PubMedGoogle Scholar
  26. 26.
    Becker DM, Markakis M, Sension M et al. Prevalence of hyperlipidemia in heart transplant recipients. Transplantation. 1987;44:323.PubMedCrossRefGoogle Scholar
  27. 27.
    Ballantyne CM, Jones PH, Payton-Ross C et al. Hyperlipidemia following heart transplantation: natural history and intervention with mebinolin (lovastatin). Transplant Proc. 1987;19:60.PubMedGoogle Scholar
  28. 28.
    Norman DJ, Illingworth DR, Munson J, Hosenpud J. Myolysis and acute renal failure in a heart-transplant recipient receiving lovastalin (Letter). N Engl J Med. 1988;318:46.PubMedCrossRefGoogle Scholar
  29. 29.
    East C, Alivazatos PA, Grundy SM, Jones PH, Farmer JA. Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation (Letter). N Engl J Med. 1988;318:47.PubMedCrossRefGoogle Scholar
  30. 30.
    Kobashigawa JA, Murphy FL, Stevenson LW et al. Low-dose lovastalin safely lowers cholesterol after cardiac transplantation. Circulation. 1990;82(Suppl. 5):281.Google Scholar
  31. 31.
    Movsowitz C, Epstein S, Fallon M el al. Cyclosporin A in vivo produces severe osteopenia in the rat; effect of dose and duration of administration. Endocrinology. 1988;123:2571.PubMedCrossRefGoogle Scholar
  32. 32.
    Voncerscher J, Meinzer A. Rationale for the development of Sandimmun neoral. Transplant Proc. 1994;26:2925.Google Scholar
  33. 33.
    Lemaire M, Fahr A, Maurer G. Pharmacokinetics of cyclosporin: inter-and intra-individual variations and metabolic pathways. Transplant Proc. 1990;22:1110.PubMedGoogle Scholar
  34. 34.
    Naoumov NV, Tredger JM, Steward CM et al. Cyclosporin A pharmacokinetics in liver transplant recipients in relation to biliary T-tube clamping and liver dysfunction. Gut. 1989;30:391.PubMedGoogle Scholar
  35. 35.
    Venkataramanan R, Burckhart GJ, Ptachcinski RJ. Pharmacokinetics and monitoring of cyclosporin following orthotopic liver transplantation. Sem Liver Dis. 1985;5:357.Google Scholar
  36. 36.
    Ritshcel WA, Adolph S, Ritsheel GB, Schroeder T. Improvement of peroral absorption of cyclosporin A by microcmulsions. Exp Clin Pharmcol. 1990;12:127.Google Scholar
  37. 37.
    Mueller EA, Kovarik JM, Vanbree JB et al. Influence of a fat-rich meal on the pharmacokinetics of a new oral formulation of cyclosporin in a new oral formulation of cyclosporin in a crossover comparison with the market formulation. Pharmaceut Res. 1994;11:151.CrossRefGoogle Scholar
  38. 38.
    Korvarik JM, Mueller EA, Vanbree JB, Tetzloff W, Kulz K. Reduced inter and intra-individual variability in cyclosporin pharmacokinetics from a microemulsion formulation. J Pharmaceut Sci. 1994;83:444.CrossRefGoogle Scholar
  39. 39.
    Trull AK, Tan KK, Uttridge J et al. Cyclosporin absorption from microemulsion formulation in liver transplant recipients. Lancet. 1993;341:433.PubMedCrossRefGoogle Scholar
  40. 40.
    Kahan BD, Dunn J, Fitts D et al. The neoral formulation: improved correlation between cyclosporin trough levels and exposure in stable renal transplant recipients. Transplant Proc. 1994;26:2940.PubMedGoogle Scholar
  41. 41.
    Holt DW, Mueller EA, Kovarik JM, Van Bree JB, Kulz K. The pharmacokinetics of Sandimmun neoral: a new oral formulation of cyclosporin. Transplant Proc. 1994;26:2935.PubMedGoogle Scholar
  42. 42.
    Reymond JP, Steimer JL, Niederberger W. On the dose dependency of cyclosporin A absorption and disposition in healthy volunteers. J Pharmacokinet Biopharm. 1988;16:331.PubMedCrossRefGoogle Scholar
  43. 43.
    Fiocchi R, Mamprin F, Gamba A et al. Pharmacokinetics profile of cyclosporin in long-term heart transplanted patients treated with a new oral formulation. Transplant Proc. 1994;26:2994.PubMedGoogle Scholar
  44. 44.
    Farber L, Maibucher A, Geissler F et al. Favorable clinical results of Sandimmun neoral in malabsorbing liver and heart transplant recipients. Transplant Proc. 1994;26:1988.Google Scholar
  45. 45.
    Mikhail G, Eadon H, Leaver N, Yacoub M. Use of neoral in heart transplant recipients. Transplant Proc. 1994;26:2985.PubMedGoogle Scholar
  46. 46.
    Trull AK, Tan KKC, Tan L, Alexander GJM, Jamieson NV. Enhanced absorption of new oral cyclosporin microemulsion formulation, neoral, in liver transplant recipients with external biliary diversion. Transplant Proc. 1994;26:2977.PubMedGoogle Scholar
  47. 47.
    Mueller EA, Kovarik JM, Vanbree JB, Lison AE, Kutz K. Pharmacokinetics and tolerability of a microemulsion formulation of cyclosporin in renal allograft recipients: a concentration-controlled comparison with the commercial formulation. Transplantation. 1994;57:1178.PubMedCrossRefGoogle Scholar
  48. 48.
    Goto T, Kino T, Halanaka H et al. Discovery of FK506. a novel immunosuppressant isolated from streptomyces tsukubaensis. Transplant Proc. 1987;19(Suppl. 6):4.PubMedGoogle Scholar
  49. 49.
    Tanaka H, Kuroda A, Marusawa H et ul. Physicochemical properties of FK506, a novel immunosuppressant isolated from streptomyces tsukubaensis. Transplant Proc. 1987;19(Suppl. 6):11.PubMedGoogle Scholar
  50. 50.
    Kino T, Hatanaka H, Hashimoto M et al. FK506, a novel immunosuppressant isolated from a streptomyces. I. Fermentation, isolation, and physicochemical and biological characteristics. J Antibiot. 1987;40:1249.PubMedGoogle Scholar
  51. 51.
    Kino T, Hatanaka H, Miyata S et al. FK506, a novel immunosuppressanl isolated from a streptomyces. II. Immunosuppressive effect of FK506 in vitro. J Antibiot. 1987;40:2256.Google Scholar
  52. 52.
    Inamura N, Nakahara K, Kino T et al. Prolongation of skin allograft survival in rats by a novel immunosuppressive agent, FK506. Transplantation. 1988;45: 106.CrossRefGoogle Scholar
  53. 53.
    Ochiai T, Nagata M, Nakajima K et al. Effect of a new immunosuppressive agent, FK506. on hcterotopic cardiac allotransplantation in the rat. Transplant Proc. 1987;19:1284.PubMedGoogle Scholar
  54. 54.
    Ochiai T, Nakajima K, Nagata M et al. Studies of the induction and maintenance of long-term graft acceptance by treatment with FK506 in heterotopic cardiac allotransplantation in rats. Transplantation. 1987;44:734.PubMedCrossRefGoogle Scholar
  55. 55.
    Sewing K-Fr. Pharmacokinetics, dosing principles, and blood level monitoring of FK506. Transplanl Proc. 1994;26:3267.Google Scholar
  56. 56.
    Venkataramanan R, Jain A, Varty VW et al. Pharmacokinetics of FK506 following oral administration: a comparison of FK506 and cyclosporin. Transplant Proc. 1991;23:931.PubMedGoogle Scholar
  57. 57.
    Warty V, Venkataramanan R, Zendehrough P et al. Distribution of FK506 in plasma lipoproteins in transplant patients. Transplanl Proc. 1991;23:954.Google Scholar
  58. 58.
    Honbo T, Kobayashi M, Haue K, Hata T, Ueda Y. The oral dosage form of FK506. Transplant Proc. 1987; 19:17.PubMedGoogle Scholar
  59. 59.
    Zeevi A, Duquesnoy R, Eiras G et al. Immunosuppressive effect of FK506 on in vitro lymphocyte alloactivation: synergism with cyclosporin A. Transplant Proc. 1987;19(Suppl.6):40.PubMedGoogle Scholar
  60. 60.
    Ochiai T. A novel Immunosuppressive agent: FK506. (Letter) Transplant Immunol. 1990;8:3.Google Scholar
  61. 61.
    Morris R. Modes of action of FK506. cyclosporin A, and rapamycin. Transplant Proc. 1994;26:3272.PubMedGoogle Scholar
  62. 62.
    Kino T, Inamura N, Sakai F et al. Effect of FK506 on human mixed lymphocyte reaction in vitro. Transplant Proc. 1987;19(Suppl. 61):36.PubMedGoogle Scholar
  63. 63.
    Yoshimura N, Matsui S, Hamashima T, Oka T. Effect of a new immunosuppressive agent. FK506, on human lymphocyte responses in vitro. II. Inhibition of the production of IL-2 and gamma-INF. but not B cell stimulating factor 2. Transplantation. 1989;47:356.PubMedCrossRefGoogle Scholar
  64. 64.
    Eirus G, Shimizu Y, Vanseventer GA, Duquesnoy RLJ, Zeevi A. Effects of FK506 and cyclosporin on T cell activation: integrin-mediated adhesion of T cells, proliferation and maturation ol cytotoxic T cells. Transplant Proc. 1991;23:936.Google Scholar
  65. 65.
    Tocci MJ, Matkovich DA, Collier KA et al. The immunosuppressant FK506 seleclively inhibits expression of early T cell activation genes. J Immunol. 1989;143:718.PubMedGoogle Scholar
  66. 66.
    Sawada S, Suzuki G, Kawase Y, Takaku F. Novel immunosuppressive agent, FK506. in vitro effects on the cloned T cell activation. J Immunol. 1987;139:1797.PubMedGoogle Scholar
  67. 67.
    Lagodzinski Z, Gorski A, Stepien-Sopniewska B, Wasik M. Effect of FK506 on B cell responses. Transplant Proc. 1991;23:942.PubMedGoogle Scholar
  68. 68.
    McMichael J, Irish W, McCauley J et al. Evaluation of a novel ‘intelligent’ dosing system for optimizing FK506 therapy. Transplant Proc. 1991;23:2780.PubMedGoogle Scholar
  69. 69.
    Jain AB, Fung JJ, Venkataramanan R et al. FK506 dosage in human organ transplantation. Transplant Proc. 1990;22(Suppl. 1):23.PubMedGoogle Scholar
  70. 70.
    Armitage JM, Kormos RL, Fung J, Lavee J, Fricker FJ. Preliminary experience with FK506 in thoracic transplantation. Transplantation. 1991;52:164.PubMedCrossRefGoogle Scholar
  71. 71.
    Armitage JM, Kormos RL, Fung J, Starzl TE. The clinical trial of FK506 as primary and rescue immunosuppression in adult cardiac transplantation. Transplant Proc. 1991;23:3054.PubMedGoogle Scholar
  72. 72.
    Armitage JM, Kormos RL, Morita S et al. Clinical trial of FK506 immunosuppression in adult cardiac transplantation. Ann Thorac Surg. 1992;54:205.PubMedCrossRefGoogle Scholar
  73. 73.
    Griffith GP, Bando K, Hardesty RI. et al. A prospective randomized trial of FK506 versus cyclosporin alter human pulmonary transplantation. Transplantation. 1994;57:848.PubMedCrossRefGoogle Scholar
  74. 74.
    Venkataramanan R, Jain A, Warty VS. Pharmacokinetics of FK506 following oral administration. A comparison of FK506 and cyclosporin. Transplant Proc. 1991;23:931.PubMedGoogle Scholar
  75. 75.
    Venkataramanan R, Jain A, Warty VS. Pharmacokinetics of FK506 in transplant patients. Transplant Proc. 1991;23:2736.PubMedGoogle Scholar
  76. 76.
    Beysens AJ, Wijnen RMH, Beuman GH et al. FK506: monitoring in plasma or in whole blood? Transplant Proc. 1991;23:2745.PubMedGoogle Scholar
  77. 77.
    Ericzon BG, Ekqvist B, Groth CG, Sawe J. Pharmacokinetics of FK506 during maintenance therapy in liver transplant patients. Transplant Proc. 1991;23:1775.Google Scholar
  78. 78.
    Tamura K, Kobayashi M, Hashimoto K et al. A highly sensitive method to assay FK506 levels in plasma. Transplant Proc. 1987;19(Suppl. 6):23.PubMedGoogle Scholar
  79. 79.
    Murthy JN, Chen Y, Warty VS et al. Radioreceptor assay for quantifying FK506 immunosuppressant in whole blood. Clin Chem. 1992;38:1307.PubMedGoogle Scholar
  80. 80.
    Christians U, Kruse C, Kownatzki R et al. Measurement of FK506 by HPLC and isolation and characterization of its metabolites. Transplant Proc. 1991;23:940.PubMedGoogle Scholar
  81. 81.
    Grenier FC, Luczkiw J, Bergmann M et al. A whole blood FK506 assay for the IMs analyzer. Transplant Proc. 1991;23:2748.PubMedGoogle Scholar
  82. 82.
    Friob MC, Hassoun A, Latinne D el al. A combined HPLC-ELISA evaluation of FK506 in transplant patients. Transplant Proc. 1991;23:2750.PubMedGoogle Scholar
  83. 83.
    Warty V, Zuckerman S, Venkataramanan R et al. FK506 measurement: comparison of different analytical methods. Ther Drug Monitor. 1993; 15:204.CrossRefGoogle Scholar
  84. 84.
    Nielsen FT, Leyssac PP, Kemp E, Starklint H, Dicperink H. Nephrotoxicity of FK506: a preliminary study on comparative aspects of FK506 and cyclosporin nephrotoxocity. Transplant Proc. 1994;26:31.Google Scholar
  85. 85.
    Sumpio BE, Phan S. Nephrotoxic potential of FK506. Transplant Proc. 1991;23:2789.PubMedGoogle Scholar
  86. 86.
    Cillo V, Allessiani M, Fung J et al. Major adverse effect of FK506 used as an immunosuppressive agent after liver transplantation. XIV International Congress of the Transplantation Society, Paris. 1992, p. 68 (abstract).Google Scholar
  87. 87.
    Tabasco-Minguillan J, Mieles L, Carroll P et al. Long-term insulin requirement after liver transplantation with FK506 in American veterans. Transplant Proc. 1993;25:677.PubMedGoogle Scholar
  88. 88.
    Bertino JR. Chemical action and pharmacology of methotrexate, azathioprine. and cyclophosphamide in man. Arthritis Rheum. 1973;16:79.PubMedCrossRefGoogle Scholar
  89. 89.
    Calne RY. Inhibition of the rejection of renal homografts in dogs by purine analogues. Transplant Bull. 1961;28:65.PubMedGoogle Scholar
  90. 90.
    Gleason RE, Murray JE. Report from Kidney Transplant Registry: analysis of variables in the function of human kidney transplants. Transplantation. 1967;5:360.Google Scholar
  91. 91.
    Kries H, Lacombe M, Noel LH et al. Kidney graft rejection: has the need for steroids to be re-evaluated? Lancet. 1978;2:1169.CrossRefGoogle Scholar
  92. 92.
    Jazzar A, Fagiuoli S, Caraceni P et al. Incidence and etiology of hepatic dysfunction in heart transplant recipients receiving a cyclosporin-based triple immunosuppressive therapy. Transplant Proc. 1994;26:2654.PubMedGoogle Scholar
  93. 93.
    Cooper DKC, Novitzky D. Diagnosis and management of acute rejection. In: Cooper DKC, Lanza RP. editors. Heart Transplantation. (Lancaster. MTP), 1984:177.Google Scholar
  94. 94.
    Williams HJ, Wilkens RF, Samuelson CO et al. Comparison of low-dose oral methotrexate and placebo in the treatment of rheumatoid arthritis: a controlled clinical trial. Arthritis Rheum. 1985;28:721.PubMedCrossRefGoogle Scholar
  95. 95.
    Thompson RN, Watts C, Edelman J, Esdaile J, Russell AS. A controlled two-center trial ol parenteral methotrexate therapy for refractory rheumatoid arthritis. J Rheumatol. 1984;11:760.PubMedGoogle Scholar
  96. 96.
    Andersen PA, West SG, O’Dell JR et al. Weekly pulse methotrexate in rheumatoid arthritis: clinical and immunologic effects in a randomized double-blind study. Ann Intern Med. 1985;103:489.PubMedGoogle Scholar
  97. 97.
    Storb R, Deeg J, Whitehead J et al. Methotrexate and cyelosporin compared with cyclosporin alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med. 1986;314:729.PubMedCrossRefGoogle Scholar
  98. 98.
    Sokoloff MC, Goldberg LS, Perason CM. Treatment of corticosteroid-resistant polymyositis with methotrexate. Lancet. 1971;1:14.PubMedCrossRefGoogle Scholar
  99. 99.
    Rosenthal GJ, Weigand GW, Germolec DR. Suppression of B cell function by methotrexate and trimetrexate: evidence of inhibition of purine biosynthesis as a major mechanism of action. J Immunol. 1988;141:410.PubMedGoogle Scholar
  100. 100.
    Costanzo-Nordin MR, Grusk BB, Silver MA et al. Reversal of recalcitrant cardiac allograft rejection with methotrexate. Circulation. 1988;78:111.47.Google Scholar
  101. 101.
    Bouchart F, Gundry SR, Vanschaack-Gonzales J et al. Methotrexale as rescue/ adjunctive immunotherapy in infant and adult heart transplantation. J Heart Lung Transplant. 1993;12:427.PubMedGoogle Scholar
  102. 102.
    Olsen SL, O’Connell JB, Bristow MR, Renlund DG. Methotrexate as an adjunct in the treatment of persistent mild cardiac allograft rejection. Transplantation. 1990;50:773.PubMedCrossRefGoogle Scholar
  103. 103.
    Shaddy RE, Bullock EA, Tani LY et al. Melhotrexate therapy in pediatric heart transplantation as treatment of recurrent mild to moderate acute cellular rejection. J Heart Lung Transplant. 1994;13:1009.PubMedGoogle Scholar
  104. 104.
    Pizarro TT, Malinowska K, Kovacs EJ et al. Diminished cytotoxic gene expression in rat cardiac transplants with low-dose cyclosporin/methotrexate combination therapy. Transplantation. 1994;58:223.PubMedGoogle Scholar
  105. 105.
    Kahn DR, Forrest DE, Otto DA. Prolonged survival of rat cardiac allografts by donor pretreatment with methotrexate. Transplantation. 1991;51:697.PubMedCrossRefGoogle Scholar
  106. 106.
    Bourge RC, Kirklin JK, White-Williams C et al. Methotrexate pulse therapy in the treatment of recurrent acute heart rejection. J Heart Lung Transplant. 1992;11:1116.PubMedGoogle Scholar
  107. 107.
    Hosenpud JD, Hershberger RE, Ratkovec RR et al. Methotrexate for the treatment of patients with multiple episodes of acute cardiac allograft rejection. J Heart Lung Transplant. 1992; 11:739.PubMedGoogle Scholar
  108. 108.
    Whiting-O’Keefe QE, Fye KH, Sack KD. Methotrexate histologic hepatic abnormalities: a meta-analysis. Am J Med. 1991;90:711.PubMedGoogle Scholar
  109. 109.
    Roenigk HH, Aucrbach R, Maibach HI, Weinstein GD. Methotrexate guidelines revised. J Am Acad Dermatol. 1982;6:145.PubMedCrossRefGoogle Scholar
  110. 110.
    Chan G, Weinstein S, Vijayanagar R et al. Treatment of recalcitrant cardiac allograft rejection with methotrexate. Clin Transplant. 1995;9:106.PubMedGoogle Scholar
  111. 111.
    Goodwin WH, Kaufman JJ, Minis MM et al. Human renal transplantation. I. Clinical experiences with six cases of renal homotransplantation. J Urol. 1963;89:13.PubMedGoogle Scholar
  112. 112.
    Copeland J, Fuller J, Sailor MJ, McAleer MJ. Heart transplantation at the Health Sciences Center of the University of Arizona. Heart Transplanl. 1983;2:246.Google Scholar
  113. 113.
    Kirkman RL, Strom TB, Weir MR, Tilney NL. Late mortality and morbidity in recipients of long-term renal allografts. Transplantation. 1982;34:347.PubMedCrossRefGoogle Scholar
  114. 114.
    Crosnier J, Leski M, Kreis H, Descamps D. Non-renal complications of kidney allotransplantation. In: Alwall N. et al., editors. Proceedings of the Fourth International Congress of Nephrology, Stockholm, vol. 3. (Basel: Karger). 1969:270.Google Scholar
  115. 115.
    Abele R, Novick AC, Braun WE et al. Long-term results of renal transplantation in recipients with a functioning graft for two years. Transplantation. 1982;34:264.PubMedCrossRefGoogle Scholar
  116. 116.
    Bourne MS, Dawson H. Acute pancreatitis complicating prednisolone therapy. Lancet. 1958;2:1209.PubMedCrossRefGoogle Scholar
  117. 117.
    Kawanishi H, Rudolph E, Bull FE. Azathioprine-induced acute pancreatitis. N Engl J Med. 1973;289:357.PubMedCrossRefGoogle Scholar
  118. 118.
    Jones PF, Oelbaum MH. Furosemide-induced pancreatitis. Br Med J. 1975; 1:133.PubMedGoogle Scholar
  119. 119.
    Nakashima Y, Howard JM. Drug-induced acute pancreatitis. Surg Gynecol Obstet. 1977; 145:105.PubMedGoogle Scholar
  120. 120.
    Mallory A, Kern F. Drug-induced pancreatitis: a critical review. Gastroenterology. 1980;78:813.PubMedGoogle Scholar
  121. 121.
    Tilney NL, Collins JJ, Wilson RE. Hemorrhagic pancreatitis: a fatal complication of renal transplantation. N Engl J Med. 1966;275:1051.CrossRefGoogle Scholar
  122. 122.
    Hume DM. Kidney transplantation. In: Rappaport FT, Dausset J, editors. Human transplantation. (New York: Grune & Stratton). 1968;110.Google Scholar
  123. 123.
    Werbitt W, Mohsenifar Z. Mononucleosis pancreatitis. South Med J. 1980;73:1094.PubMedGoogle Scholar
  124. 124.
    Imrie CW, Ferguson JC, Sommerville RG. Coxsackie and mumps virus infection in a prospective study of acute pancreatitis. Gut. 1977;18:53.PubMedGoogle Scholar
  125. 125.
    Fujii G, Nelson RA. The cross-reactivity and transfer of antibody in transplantation immunity. J Exp Med. 1963;118:1037.PubMedCrossRefGoogle Scholar
  126. 126.
    Amos DB, Stickel DL. Human transplantation antigens. Adv Intern Med. 1968;14:15.PubMedGoogle Scholar
  127. 127.
    Feiner H. Pancreatitis after cardiac surgery. Am J Surg. 1976; 131:684.PubMedCrossRefGoogle Scholar
  128. 128.
    Karrer FM, Mammana RB, Copeland JG. Survival following pancreatitis and surgical drainage of a pancreatic pseudocyst in a heart transplant recipient. Heart Transplant. 1982;1:325.Google Scholar
  129. 129.
    Uys CJ, Rose AG, Barnard CN. The pathology of human cardiac transplantation. S Air Med J. 1979;56:887.Google Scholar
  130. 130.
    Quarton GC, Clark LD, Cobb S, Bauer W. Mental disturbance associated with ACTH and cortisone: a review of explanatory hypotheses. Medicine. 1955;34:13.PubMedCrossRefGoogle Scholar
  131. 131.
    Ritchie HA. Toxic psychosis under cortisone and corticotropin. J Menl Sci. 1956;102:830.Google Scholar
  132. 132.
    Woodruff MF, Anderson NF. Effects of lymphocyte depletion by thoracic duct fistula and administration of antilymphocytic serum on the survival of skin homografts in rats. Nature (London). 1963;200:702.CrossRefGoogle Scholar
  133. 133.
    Touraine JL, Malik MC, Traeger J. Antilymphocyte globulin and thoracic duct drainage in renal transplantation. In: Salaman JR. editor. Immunosuppressive therapy. (Lancaster: MTP Press). 1981:55.Google Scholar
  134. 134.
    Baumgartner WA, Reitz BA, Over PE, Stinson EB, Shumway NE. Cardiac homotransplantation. Curr Probl Surg. 1979;16:1.PubMedCrossRefGoogle Scholar
  135. 135.
    Jamieson SW, Bieber CP, Over PK, Suppression of immunity for cardiac transplantation. In: Salaman JR, editor. Immunosuppressive therapy. (Lancaster: MTP Press), 1981:177.Google Scholar
  136. 136.
    Jazzar A, Cooper DKC, Muchmore JS et al. A successful regimen to reduce cytomegalovirus disease in heart transplant patients. Transplantology. 1993;4:47.Google Scholar
  137. 137.
    Meuer SC, Acuto O, Hercend T, Schlossman SF, Reinherz EL. The human T cell receptor. Annu Rev Immunol. 1984;2:23.PubMedCrossRefGoogle Scholar
  138. 138.
    Giorgi JV, Burton RC, Barrett LV et al. Immunosuppressive effect and immunogenicity of OKT11A monoclonal antibody in monkey allograft recipients. Transplant Proc. 1983;15:629.Google Scholar
  139. 139.
    Estabrook A, Berger CL, Mittler R et al. Antigenic modulation of human T-iymphocytes by monoclonal anlibodies. Transplant Proc. 1983;15:651.Google Scholar
  140. 140.
    Chang TW, Kung PC, Gingras SP, Goldstein G. Does OKT3 monoclonal antibody react with an antigen-recognition structure on human T cells? Proc Natl Acad Sci USA. 1981;78:1805.PubMedCrossRefGoogle Scholar
  141. 141.
    Bristow MR, Gilbert EM, Renlund EG et al. Use of OKT3 monoclonal antibody in heart transplantation: review of the initial experience. J Heart Transplant. 1988;7:1.Google Scholar
  142. 142.
    Gilbert FM, Dewitt CW, Eiswirth CC et al. Treatment of refractory cardiac allograft rejection with OKT3 monoclonal antibody. Am J Med. 1987;82:203.CrossRefGoogle Scholar
  143. 143.
    Bristow MR, Gilbert EM, O’Connell JB et al. OKT3 monoclonal antibody in heart transplantation. Am J Kidney Dis. 1988;11:135.PubMedGoogle Scholar
  144. 144.
    Kirklin JK, Naftel DC, Levine TB and the Cardiac Transplant Research Database Group. Cytomegalovirus alter heart transplantation. Risk factors for infection and death: a multi-institutional study. J Heart Lung Transplant. 1994;13:394.PubMedGoogle Scholar
  145. 145.
    Jaffers GJ, Fuller TC, Cosimi AB et al. Monoclonal antibody therapy: anti-idiotypic and non-anti-idiotypic antibodies to OKT3 arising despite intense immunosuppression. Transplantation. 1986;41:572.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • K. L. Tyndall
  • D. K. C. Cooper

There are no affiliations available

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