Race, Kidney Transplants, Immunosuppression Research, and White Supremacy under Apartheid, 1960-80.

This paper uses the history of kidney transplantation in South Africa as a lens through which to write a racialized, micro history that illustrates the politics of medical discoveries and medical research at one of South Africa's most prestigious medical research universities, the University of the Witwatersrand (Wits) in Johannesburg. Between 1966 and the 1980s, the Wits team became the most advanced and prolific kidney transplant unit in the country. Yet the racist, oppressive Apartheid system fundamentally shaped these developments. Transplantation, as this paper shows, became an elite medical procedure, performed by a select group of white doctors on mostly white patients. For these doctors, transplantation showed their medical prowess and displayed the technical advancements they were able to make in research and clinical practice as they strove to position South Africa as a significant international player in medical research, despite academic boycotts and increasing sanctions. Transplantation became a symbol of white supremacy in a country where the black majority were excluded from anything but the most basic health care.

The Untold Story of the First Hand Transplant: Dedicated to the Memory of one of the Great Minds of the Ecuadorian Medical Community and the World.

BACKGROUND: In 1964, faced with the challenge of traumatic amputation, a team of surgeons at Clinica Guayaquil was convinced that the transplantation of a hand could significantly improve function and quality of life for the recipient. With a current but basic understanding of immunosuppression, the surgeons identified a recipient and waited for the correct donor. A human hand transplant had never been performed to date. METHODS: The surgeons' criteria for the recipient included a young healthy individual who had sustained a traumatic amputation at the distal forearm level with full motion of the proximal joints. Communication with receiving hospitals and military facilities identified what they perceived to be a feasible donor for an allograft transplantation. Consent was obtained from the family in conjunction with the local military medical authorities and the clergy. Iced saline solution and Heparin irrigation were to be used to prepare the donor extremity. The immunosuppression regimen, limited at the time, consisted only of intravenous cortisone, Imuran, and a single dose of radiation. RESULTS: A member of the Ecuadorian marine sustained a limited blast injury that amputated his dominant hand but spared the forearm. He was transferred to the emergency department of Clinica Guayaquil. A donor who had recently died in a nearby hospital was identified not long after. A successful technical surgical transplantation was achieved. Consultants from major hospitals around the world (including Peter Bent Brigham Hospital) convened at the patient's bedside to observe the results. Despite all efforts, the patient suffered an irreversible rejection at 21 days post-transplant. CONCLUSION: This was the first allograft transplantation of a hand. The surgeons embarked on an intervention never tried before, firmly believing that better function and quality of life would result. The bravery of this surgical team was commendable. This early surgical endeavor opened the way for future successes in transplant surgery today.

Historical perspectives in kidney transplantation: an updated review.

The present state of success in kidney transplantation, including its benefits to patients with end-stage renal failure, was achieved through relentless research, both in experimental animal models and human volunteers. Kidney transplantation has evolved during the past century thanks to various milestones in surgical techniques, immunology, immunosuppressive drugs, expansion of donor sources, organ preservation, transplant against immunological barriers (ABO blood group-incompatible and positive crossmatch transplants), and research on induction of tolerance, xenotransplants, and stem cell technology. Despite significant improvements in graft and patient survival, several issues still must be addressed to reduce the growing number of patients with kidney failure waiting to receive organs. This article provides an up-to-date review of the milestones in the history of kidney transplantation and highlights strategies to resolve current problems faced by patients and the transplant community.

Ischemia-reperfusion injury in vascularized composite allotransplantation.

Vascularized composite allotransplantation may now be considered a viable treatment option in patients with complex craniofacial and limb defects. However, the field is still in its infancy, and challenges continue to exist. These challenges, most notably the adverse effects of lifelong immunosuppression, must be weighed against the benefits of the procedure. Improvements in this risk-benefit ratio can be achieved by achieving tolerance and preventing rejection. Five decades after Dr. Joseph E. Murray introduced the field of transplantation to the world, we now have a better understanding of the immunologic factors that may contribute to rejection and inhibit tolerance. In this article, we review emerging evidence that suggests that "danger signals" associated with ischemia-reperfusion injury contribute to innate immune activation, promoting rejection, and inhibiting tolerance. Based on this understanding, we also describe several strategies that may ameliorate the damaging effects of ischemia-reperfusion and the clinical implications of ischemia-reperfusion on the vascularized composite tissue allotransplantation outcome.

Immunosuppressive therapies in the management of immune-mediated marrow failures in adults: where we stand and where we are going.

Immunosuppression is a key treatment strategy for aplastic anaemia (AA) and the related immune-mediated bone marrow failure syndromes (BMFS). For the last 20 years the standard immunosuppressive regimen for AA patients has been anti-thymocyte globulin (ATG) plus ciclosporin A (CyA), which results in response rates ranging between 50% and 70%, and even higher overall survival. However, primary and secondary failures after immunosuppressive therapy remain frequent, and to date all attempts aiming to overcome this problem have been unfruitful. This article reviews the state of the art of current immunosuppressive therapies for AA, focusing on open questions linked to standard immunosuppressive treatment, and on experimental immunosuppressive strategies which could lead to future improvement of current treatments. Specific immunosuppressive strategies employed for other BMFS, such as lineage-restricted marrow failures, myelodysplastic syndromes and large granular lymphocyte leukaemia-associated cytopenias, are also briefly discussed.

The development of kidney transplant nursing.

An analysis of published literature, interviews with early transplant nurses, and other primary source materials shows how evolving medical treatments for rejection, nurses' ability to learn on the job, and their commitment to patients influenced the development of kidney transplantation as a specialized area of practice. The work of these nurses work is discussed in the context of unfolding nursing specialization at the middle of the twentieth century.

Intestinal transplantation: evolution in immunosuppression protocols.

PURPOSE OF REVIEW: Intestinal transplantation is a treatment for patients with short bowel syndrome and associated severe complications. The intestine has long been seen as a 'forbidden' organ to transplant. This fact is because the first attempts at intestinal transplantation were rapidly defeated by rejection and sepsis. RECENT FINDINGS: Several factors have contributed to improve the results: tacrolimus-based immunosuppression, induction therapy (independent of the type), introduction of ganciclovir and rituximab and subsequent better control of cytomegalovirus and posttransplant lymphoma, better differential diagnosis between rejection versus infection and ischemia (avoiding unnecessary overimmunosuppression), better patient follow-up. Center experience is more important than a particular immunosuppressive protocol. M-TOR inhibitors, infliximab have been used. Mycophenolate mofetil is less frequently used because of its potential gastrointestinal toxicity. Of note, no significant improvement in short-term and long-term (>1 year) survival was observed since 2000 and 1985, respectively. SUMMARY: Intestinal transplantation remains a formidable clinical/immunological challenge. With newer immunosuppression and accumulated experience, intestinal transplantation results have improved and the procedure represents a life-saving option in patients with short bowel syndrome-related complications. Before intestinal transplantation becomes a 'quality of life-improving' procedure (offered to patients who are free of short bowel syndrome-related complications), new strategies focusing on facilitating graft acceptance and reducing the need for immunosuppression will have to be developed.

Immunosuppression and rejection in human hand transplantation.

Avoidance or at least minimization of maintenance immunosuppression represents the key step for promoting wider applicability of reconstructive transplantation. Understanding the mechanisms of composite tissue allograft rejection is essential in working toward that goal. We herein review the current knowledge on acute rejection in reconstructive transplantation and discuss findings in the light of novel immunosuppressive and immunomodulatory strategies.

History of solid organ transplantation and organ donation.

Solid organ transplantation is one of the most remarkable and dramatic therapeutic advances in medicine during the past 60 years. This field has progressed initially from what can accurately be termed a "clinical experiment" to routine and reliable practice, which has proven to be clinically effective, life-saving and cost-effective. This remarkable evolution stems from a serial confluence of: cultural acceptance; legal and political evolution to facilitate organ donation, procurement and allocation; technical and cognitive advances in organ preservation, surgery, immunology, immunosuppression; and management of infectious diseases. Some of the major milestones of this multidisciplinary clinical science are reviewed in this article.

Overcoming the force and power of immunity: a history of immunosuppression in kidney transplantation.

Immunosuppression for organ transplantation is a modern concept. The earliest reports of organ replacement have their roots in mythology and human fantasy. The primacy of overcoming the immunologic barrier for successful transplantation of organs has been influenced by geopolitical conflict, unorthodox ideas, application of knowledge across medical disciplines, and serendipity. The earliest form of chemical immunosuppression had its origin in chemical gas in warfare. Further developments in immunology, cancer therapy and biochemistry helped shape the intellectual basis for the introduction of chemical immunosuppression.

Renal transplantation: the present and the future.

Children receiving kidney transplants in the modern era in developed countries have excellent overall results. Graft survival and patient survival in children is now virtually equal to that in adult organ recipients. Deceased donor source kidneys are no longer associated with significantly inferior outcomes. These advances are in large part due to development in more potent immunosuppressive agents and newer combinations. These advances have also come at a price in the form of increased post-transplant infections. The transplant community is now moving to minimization protocols to reduce the adverse effects of many of the medications and to reduce the incidence of infections. Newer techniques of diagnosis of acute rejection, degree of immunosuppression and DNA-based viral surveillance are changing the face of clinical practice. Newer technologies such as stem cell transplantation, tissue engineering and xenotransplantation promise even more changes in the future.

Twenty years of renal transplantation at Ohio State University: the results of five eras of immunosuppression.

Over the past 20 years, more than 4,000 patients have undergone an abdominal solid organ transplant at Ohio State University. The 20-year period can be divided into five eras, each defined by an immunosuppressive protocol used during that period. With each successful era came a new immunosuppressive protocol that produced an incremental improvement in outcomes of patients and graft survival resulting from the application of the newest and most sophisticated combination of immunosuppressive drugs. The incidence of acute rejection episodes and graft survival from each era are compared and demonstrate the substantial improvement in results that has been achieved over the past 20 years.