Organ Transplantation Essay

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Organ TransplantationOver the past 50 years organ transplantation has become established worldwide with ever-improving results, conferring immense benefit to hundreds of thousands of patients. The general principles of the surgical procedures and organ preservation have been accepted for all organ transplants, but the biology of graft rejection is still only partly understood. The discovery of natural acquired immunological tolerance and experimental methods of producing tolerance by Billingham, Brent, and Medawar raised the hopes of clinicians that there might be a way of inducing in the recipient at the time of organ grafting a state of temporary immunological plasticity similar to the stage that occurs in fetal development. In 1959 mercaptopurine, which is used in the treatment of leukaemia, was shown by Schwarz and Damechek to prevent antibody formation in rabbits challenged with foreign protein. They called this observation drug-induced immunological tolerance. Studies in the UK on kidney-grafted animals treated with mercaptopurine produced a moderate extension of graft survival and led to a practical clinical regimen of treatment with the mercaptopurine analogue azathioprine plus corticosteroids. At 1 year, graft function was around 50%. Kidney transplantation remained confined to about ten centres worldwide, and the procedure was viewed with suspicion because of the poor overall results. Then, in the late 1970s, Borel and colleagues discovered the immunosuppressive properties of the fungal cyclic peptide ciclosporin, which prolonged survival of skin grafts in mice. Further studies of this drug in the UK showed prolonged survival of cardiac allografts in rats and pigs and renal transplants in dogs. When ciclosporin was first used in people, based on the dose given to animals, it was severely nephrotoxic. After a worrying learning curve of dose adjustments,

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