Organ transplantations

It has been over 50 years since the first successful human organ 

After the surgery, new antibodies and killer lymphocytes that cause rejection may develop within days. To prevent this from happening, or at least reduce the chances of it, scientists have discovered and developed a number of immunosuppressive drugs that help extend the life of the transplanted organ and, thus, the life of its recipient. Corticosteroids and the cancer chemotherapy drug azathioprine were the first drugs used to suppress the immune system for organ 

Because the transplant waiting list continues to grow, scientists have explored nonhuman animals as a possible source of organs. Despite the shock and repulsion it sometimes causes, the idea of xenotransplantation, or transplantation of an organ from one species to another, deserves some serious consideration. 

At first, it seemed reasonable to look toward nonhuman primates, such as chimpanzees and baboons, as organ donors. With experience. 

What factors have led researchers to explore xenotransplantation  

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Adrenocortical insufficiency Organ transplants Liver disease Adrenogenital syndrome Nephrotic syndrome Acute spinal cord injury Hyp ere alemia Hematologic disorders Myasthenia gravis Neoplastic disease... 

Although there is no rehable method as of this writing for induction of Ag-speciftc unresponsiveness, some degree of tolerance has been observed by use of nonspecific immunosuppressive therapy. This conclusion is supported by a decrease in the frequency of precursor T-ceUs reactive with graft HLA Ags in long-term recipients of organ transplants. 

Chemokines have been shown to be associated with a number of autoinflammatory diseases including multiple sclerosis, rheumatoid arthritis, atherosclerosis, dermatitis, and organ transplant rejection. Evidence, reviewed below, is mounting that chemokines may play a major role in the pathophysiology of these diseases and thus chemokine receptor antagonists could prove to be useful therapeutics in treating these and other proinflammatory diseases. 

Basiliximab Anti-IL-2 CD25 Allogeneic organ transplantation... 

Immune defense mechanisms can become deleterious for an individual when they are not controlled properly. Then they can cause disease. In such situations therapy is aimed to dampen immune reactions. Important examples are sqttic shock, allergy, autoimmune diseases, and chronic inflammatory diseases such as rheumatoid arthritis. Also, the success of organ transplantation... 

Anticytokine receptor antibodies Basiliximab, Da-cluzimab Both are humanized monoclonal antibodies against the IL-2 receptor that block T-cell proliferation by inhibiting IL-2 and thus decrease the T-cell mediated frequency of rejection episodes in organ transplantation. 

Based upon theoretical considerations of the mechanisms of hypothermic-induced cellular injury, we developed the University of Wisconsin organ preservation solution (UW solution) that has had a widespread and dramatic effect on organ preservation (Table 2). Prior to the development of this solution, the liver and pancreas could be preserved for only four to six hours. Thus, there was a large time constraint on liver and pancreas transplantation and many cadaveric organs were wasted. However, the UW solution increased preservation duration to 48 to 72 hours, and dramatically increased the quality and numbers of these organs transplanted. Furthermore, this solution appears effective for the preservation of the kidney for three days and the heart for at least 15 hours. 

Inflammatory-immune injury Rheumatoid arthritis Organ transplantation... 

Describe common reasons for the various solid-organ transplants. 

Differentiate between the functions of cell-mediated and humoral immunity and how they relate to organ transplantation. 

The earliest recorded attempts at organ transplant date back thousands of years.1 More than a few apocryphal descriptions exist from ancient Egypt, China, India, and Rome documenting experimentation with transplantation. For example, an Indian text from the second century bc describes a procedure for nasal reconstruction surgery with the use of autografted skin. Also, Roman Catholic lore has saints Damian and Cosmas replacing the gangrenous leg of a man with the leg of a recently deceased man in the third century ad.1... 

Joseph Murray performed the first successful organ transplant in 1954, a kidney transplant between identical twins.1 This was a success in large part because no immunosuppression was necessary since the donor and recipient were genetically identical. Murray s success led to attempts with other organs over the next 20 years (Table 52-1). 

Transplant of a pancreas may involve either the entire organ or a pancreas segment. Currently, whole-organ transplant is the most common procedure, with a portion of the duodenum often transplanted along with the pancreas. Living donors are often the source of segmental transplants. In recent years, isolation and transplantation of beta islet cells alone have been completed, although at the time of this publication this procedure is still considered experimental. 

Regulatory T cells, or suppressor T cells, suppress the activation of an immune response. The activity of these cells in organ transplant is not well elucidated. 

The induction agents are highly immunosuppressive and, when given prior to some organ transplants (e.g., kidney transplant), allow for significant reductions in acute rejection... 

SCr, serum creatinine SRL, sirolimus TAC, tacrolimus. (Reprinted from Johnson HJ, Schonder KS. Solid-organ transplantation. 

MPA derivatives have replaced azathioprine as the antiproliferative agent of choice in most organ transplant centers. The MPA derivatives generally are considered to provide a more specific immunosuppressive effect compared with azathioprine. Mycophenolate mofetil and enteric-coated mycophe-nolic acid have similar safety and efficacy data in renal transplant recipients. 

The most commonly used corticosteroids are methylpred-nisolone (IV and oral) and prednisone (oral), although prednisolone and dexamethasone also have been shown to be effective for organ transplantation. Corticosteroid doses vary by center-specific protocols, organ type, and patient characteristics. A typical taper would include an IV 100 to 500 mg bolus of methylprednisolone at the time of transplant and then a taper over 5 to 7 days to a maintenance dose of prednisone 20 mg/day or complete cessation.2,7 It is important for practitioners to know that approximately 4 mg methylprednisolone is equivalent to 5 mg prednisone and 0.75 mg dexamethasone.11 At most transplant centers, therapeutic drug monitoring of corticosteroids is not employed. Corticosteroids are associated with a variety of acute and chronic toxicides. The most common adverse events have been summarized in Table 52-5. 

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