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This book is addressed to researchers, practicing physicians, and surgeons in the field of organ transplantation, as well as the medical students, residents, and fellows. The topics covered include the religious concepts in organ transplantation, embryonic organ transplantation, tolerance, normothermic graft perfusion, pharmacogenetics of immunosuppressors, viral transmission in organ transplantation, pediatric and split-liver transplantation, portopulmonary hypertension, mechanical circulatory support, ex vivo lung perfusion, and ABO-incompatible kidney transplantation.
In Defying the Gods, Scott McCartney takes the reader inside the world of organ transplants, focusing on four patients at the Baylor University Medical Center in Dallas. Baylor is home to one of the top three leading transplant teams in the country - a pair of "Top Gun" cutters who have stretched the boundaries of science to save lives. Defying the Gods shows not only what goes on inside the operating room, but also details the circumstances that brought the patients and the organs to the operating table - because for every triumphant successful transplant, there is the death of the person who donated the organ. McCartney follows the four patients on this difficult journey, from the weeks or even months of anguished waiting on the list of potential recipients, to the stressful recovery period when both doctors and patients watch tensely to see if the organ will be rejected by the patient's body - which in some cases means death. McCartney also profiles the transplant surgeons, who consider themselves on the cutting edge of medicine as they constantly push back the borders of death, and explains and critiques the transplant system: Who decides who gets one of the small number of available organs, and how is that decision made? Are doctors' and hospitals' hands tied by the laws regulating the collection and allocation of organs, or do they manipulate those laws? How important is it for patients to pass what doctors call the "wallet biopsy"? What can we do to assure an adequate supply of organs in the future? Defying the Gods is the definitive account of the history, science, and ethics that make transplants possible, covering the terrible choices transplantation presents for families, themoral dilemmas facing doctors, and the ongoing debate over how best to allocate the limited organs to those who need them. It is both suspenseful and moving, addressing important medical issues on a most human level.
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The first real major breakthrough that laid the basis of HLA antibody detection in the field of solid organ transplantation, came with the introduction of the complement dependent cytotoxicity (CDC) test in 1964 by Terasaki and McClelland. Since then, methods for antibody detection have evolved remarkably from conventional cell-based assays to the current advanced solid phase systems on the Luminex platform, with increasing degree of sensitivity and specificity. The latter have been indispensable for more accurate identification of donor specific HLA antibodies in broadly reactive allo antisera, and to guide donor selection and kidney paired exchange programs through virtual crossmatching, in addition to serving as excellent tools for initiating pre-transplant desensitization and post- transplant antibody monitoring. Consensus is evolving on the optimal routine employment of these methods in donor selection strategies along with an understanding of the clinical relevance of antibodies detected by each of them. The immunoassays based on the Luminex platform and flow cytometric beads are however unable to discriminate complement fixing from non-complement fixing HLA antibodies. This is important because the former are considered clinically more pertinent in the peri-transplant period. The C1q assay which is a modification of the solid phase assay based on Luminex single antigen beads, which can be used effectively to monitor high dose IVIG desensitization is essentially a surrogate complement fixing assay, retaining the exquisite sensitivity and specificity of the Luminex platform. Currently, information obtained from these assays is preliminary and much needs to be done to standardize technologies and set a consensus ‘MFI cut off’ for antibody positivity. Besides the overriding influence of anti-HLA antibodies on overall solid organ graft survival, immune response to non-HLA antigens has become a topic of substantial interest in recent years. An ever expanding list of non-HLA antigens has been implicated in graft rejection for various organs, of which the most noted are the Major Histocompatibility Complex class I chain-related molecule A (MICA), Vimentin, Myosin, Angiotensin II type 1 receptor (AT1R), Tubulin and Collagen. MICA is one of the most polymorphic and extensively studied non-HLA antigenic targets especially in renal transplantation. Although there are clear indications of MICA antibodies being associated with adverse graft outcome, to date a definitive consensus on this relationship has not been agreed. Because MICA molecules are not expressed constitutively on immunocompetent cells such as T and B lymphocytes, it is of utmost importance to address the impact of MICA donor specific antibodies (DSA) as compared to those that are non- donor specific (NDSA) on graft outcome. The soluble isoform of MICA molecule (sMICA) that is derived from the proteolytic shedding of membrane bound molecules has the potential to engage the NK-cell activating receptor NKG2D and down-regulate its expression. Consequent to the interaction of NKG2D by sMICA, the receptor ligand complex is endocytosed and degraded and thus suppresses NKG2D mediated lysis of the target by NK cells. Thus interaction between NKG2D and sMICA leads to expansion of immunosuppressive/anergic T cells thereby resulting in suppression of NKG2D mediated host innate immunity. These concept support the possible involvement of an immunosuppressive role for sMICA during allotransplantation as shown recently for heart transplantation. This research topic focusses on the clinical utility of investigating the complete antibody repertoire in solid organ transplantation.
The replacement of a diseased liver with a healthy liver is known as liver transplantation. Liver transplantation is used as a treatment option for acute liver failure and end-stage liver disease. Orthotopic transplantation is a common and effective technique used for liver transplantation. The transplantation surgery usually takes 4 to 18 hours. The common requirements for a liver donor include good health, a blood type which is compatible with the recipient, having an age of 20-60 years, and being of similar or larger size than the recipient. Liver transplantation involves a few complications, such as infection, bleeding, possibility of blood clots, painful incision and prolonged recovery. This book brings forth some of the most innovative concepts and elucidates the unexplored aspects of liver transplantation. It studies, analyzes and upholds the pillars of liver transplantation and its utmost significance in modern times. The extensive content of this book provides the readers with a thorough understanding of the subject.
Previously, ABO-incompatible kidney transplantation (KTx) was believed to be a "taboo" for immunological reasons. In Japan, the Tokyo Women's Medical University reported the first successful case of such transplantation, performed on January 19, 1989. Since then, we have been striving to improve the outcome of ABO-incompatible transplantation for a quarter of a century.
- Donation refusal is high in all the regions of Argentina. - The deficient operative structure is a negative reality that allows inadequate donor maintenance and organ procurement. - In more developed regions, there are a high number of organs which are not utilized. This is true for heart, liver and lungs. Small waiting lists for these organs probably reflect an inadequate economic coverage for these organ transplant activities. - There is a long waiting list for cadaveric kidney transplants, which reflect poor procurement and transplant activity. - Lack of awareness by many physicians leads to the denouncing of brain deaths. In spite of these factors, we can say that there has been a significant growth in organ procuration and transplantation in 1993, after the regionalization of the INCUCAI. Conclusions Is there a shortage of organs in Argentina? There may be. But the situation in Argentina differs from that in Europe, as we have a pool of organs which are not utilized (donation refusal, operational deficits, lack of denouncing of brain deaths). Perhaps, in the future, when we are able to make good use of all the organs submitted for transplantation, we will be able to say objectively whether the number of organs is sufficient or not. Acknowledgements I would like to thank the University of Lyon and the Merieux Foundation, especially Professors Traeger, Touraine and Dr. Dupuy for the honour of being invited to talk about the issue of organ procurement.