The cyclic opeptide Cyclosporinee A (CsA) is best known as the immunosuppressive drug which has revoulutionized organ transplantation. It selectively suppresses T cell activation by blocking the transcription of cytokine genes such as IL‐2 at the level of transxcription factor modulation. The structurally unrelated immuniusuppressant FK 506 acts on the same pathway and blocks cytokine gene expression. In contrast, rapamycin, a structural analoguwe of FK 506, interferes with the immune response at a different level, by blocking the response induced by (...) ctytokines such as IL‐2.Although these drugs have been most studied for their immunosuppressive activities, it is clear that their effects on cytokine pathways extend far beyond the scole IL‐2.‐mediated responses involved in the immune response. IFor instance, CsA and FK 506 inhibit the transcription of IL‐3, IL‐4, IFNγ, TNFα or GM‐CSF by activated T cells, and rapamycin has been shown to blcock the response to various growth factors such as IL‐3, IL‐4 or IL‐6.Here, we receap what is known about the effects of CsA, FK 506 and rapamycin on hematopoiesis in vitro and in vivo and extrapolate on what these drugs can teach us aboput the physiological role of cytokines for hematopoiesis. (shrink)

Transplantation continues to push the frontiers of medicine into domains that summon forth troublesome ethical questions. Looming on the frontier today is human facial transplantation. We develop criteria that, we maintain, must be satisfied in order to ethically undertake this as-yet-untried transplant procedure. We draw on the criteria advanced by Dr. Francis Moore in the late 1980s for introducing innovative procedures in transplant surgery. In addition to these we also insist that human face transplantation must meet all the ethical requirements (...) usually applied to health care research. We summarize the achievements of transplant surgery to date, focusing in particular on the safety and efficacy of immunosuppressive medications. We also emphasize the importance of risk/benefit assessments that take into account the physical, aesthetic, psychological, and social dimensions of facial disfiguration, reconstruction, and transplantation. Finally, we maintain that the time has come to move facial transplantation research into the clinical phase. (shrink)

As innovations in the field of vascular composite allotransplantation (VCA) progress, whole-eye transplantation (WET) is poised to transition from non-human mammalian models to living human recipients. Present treatment options for vision loss are generally considered suboptimal, and attendant concerns ranging from aesthetics and prosthesis maintenance to social stigma may be mitigated by WET. Potential benefits to WET recipients may also include partial vision restoration, psychosocial benefits related to identity and social integration, improvements in physical comfort and function, and reduced surgical (...) risk associated with a biologic eye compared to a prosthesis. Perioperative and postoperative risks of WET are expected to be comparable to those of facial transplantation (FT), and may be similarly mitigated by immunosuppressive protocols, adequate psychosocial support, and a thorough selection process for both the recipient and donor. To minimize the risks associated with immunosuppressive medications, the first attempts in human recipients will likely be performed in conjunction with a FT. If first-in-human attempts at combined FT-WET prove successful and the biologic eye survives, this opens the door for further advancement in the field of vision restoration by means of a viable surgical option. This analysis integrates recent innovations in WET research with the existing discourse on the ethics of surgical innovation and offers preliminary guidance to VCA programs considering undertaking WET in human recipients. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:A Semi-Personal Story from a Ukrainian NGO Professional (or a Semi-Professional Story from a Ukrainian Person) Living through the WarYuliya NogovitsynaI live in Kyiv with my husband and two daughters. On 24 February 2022, my husband woke me up at 5 am tapping me on the shoulder and saying, “Yulia, wake up. There are bombings outside. The war started”. [End Page 160]That day was our younger daughter’s birthday. She (...) turned six. We had planned a birthday party for her with friends, cake, candles and birthday gifts. Instead, we had to move both daughters to the bathroom where there are no windows so that broken glass did not hurt them if a missile hit.I am the Program Director at Tabletochki Charity Foundation, Ukraine’s largest childhood cancer NGO (https://tabletochki.org/en/). For 11 years before the war, we have been fostering childhood cancer care in Ukraine—through our direct assistance to families, support of pediatric oncology units, professional development of medical personnel, and advocacy.The Russian invasion of Ukraine in February 2022 dramatically changed the healthcare system landscape in Ukraine. The physical threat, treatment disruption, exposure of immunosuppressed patients to improper conditions in bomb shelters and cellars, interruption in supplies, infrastructure damage, logistics failure, and funding constraints have been among the most manifested immediate and deferred implications of the war for the health-care system in Ukraine.That said, the biggest professional challenge was uncertainty and inability to plan. You have nothing to rely on in developing at least a short-term strategy. This may sound speculative and unimportant—who bothers about uncertainty when there is a physical threat to your life? But this is a wrong perception—uncertainty paralyzes and disables long before a bullet or missile reaches you.War also brings the collapse of relationships, partnerships, and coalitions. It depletes and limits resources, whether human, financial, or emotional. Scarce resources make hospitals, healthcare professionals, and NGOs compete for patients, donors, and financing. The war and the external threat unite only for a short period of emergency response. Once the situation transitions to a protracted conflict, people and institutions start fighting for their own survival.My family stayed in Ukraine but moved to Lviv, a city in Western Ukraine, which turned into an evacuation hub for children with cancer. More than 1,000 children with cancer were evacuated and referred for treatment abroad through the SAFER Ukraine collaborative initiative by St. Jude Global, Tabletochki, West-Ukrainian Specialized Children’s Medical Center (WUSCMC), and other international and local partners.During the first months of the war, we worked hand-in-hand day and night to bring critically ill children to safety and treatment. We sent evacuation convoys from Lviv to Poland twice a week, the largest one with 71 families, included four buses and 11 ambulances. We slept 4-5 hours per day. Within two weeks, my hands and legs were trembling from constant tension, concentration, and tiredness.And even this extremely fast-responding and effective evacuation may be questioned. We have been facing an ethical dilemma—whether the safety needs of the existing patients prevail over the needs of future patients in diagnostics and treatment in Ukraine. We discussed more than once whether we should stop evacuation and referral of children to European hospitals to sustain the Ukrainian childhood cancer care system and prevent it from degradation. It is very uncomfortable to confront such questions. Could our heroic efforts to evacuate as many Ukrainian children with cancer as possible turn into an evil for future patients to come? By evacuating patients, we left pediatric oncology units empty, without work for Ukrainian pediatric oncologists, and the usual pathways for diagnostics and treatment were disrupted. A healthcare system without patients is like a cardiovascular system without blood.My family returned to Kyiv in August 2022 for our daughters to continue their schooling. There were (and still are) only five to seven kids in a class; other children left Ukraine or switched to online studies. My husband and I decided that our children will attend school offline—despite the regular missile attacks. This is a private school; we pay for it. In such a way... (shrink)

Rita Bottino,1 Santosh Nagaraju,2 Vikas Satyananda,2 Hidetaka Hara,2 Martin Wijkstrom,2 Massimo Trucco,1 David KC Cooper2 1Institute of Cellular Therapeutics, Allegheny Health Network, 2Thomas E Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA: Diabetes mellitus is increasing worldwide. Type 1 diabetes can be treated successfully by islet allotransplantation, the results of which are steadily improving. However, the number of islets that can be obtained from deceased human donors will never be sufficient to cure more than a very (...) small percentage of patients who might benefit from transplantation. Although there are some differences in glucose metabolism between pigs and humans, the use of pigs could provide an unlimited supply of islets, and the insulin produced would undoubtedly control glucose levels. Transplantation of islets into the portal vein results in islets residing in the liver; however, an early inflammatory response and rejection remain problematic, even when the recipient is receiving immunosuppressive therapy. In the long term, immunosuppressive drugs may exhibit toxicities to patients and specifically harm the islet cells. In contrast, encapsulation techniques provide islets with a physical barrier that prevents antibodies binding to the islet graft while still allowing insulin to be released into the recipient's circulation; in theory, patients receiving encapsulated grafts might not require exogenous immunosuppressive therapy. Nonhuman primates with encapsulated pig islet transplants have remained insulin-independent for several weeks, but long-term efficacy remains uncertain. Furthermore, techniques are now available to knock out genes from the pig and/or insert human genes, thus rendering the antigenic structure of pigs closer to that of humans, and providing protection from the human immune response. Islet transplantation from genetically engineered pigs has been followed by insulin independence in a small number of nonhuman primates for greater than 1 year. Neonatal islets have some advantages over adult islets in that they are easier to isolate and culture, and have the ability to proliferate during the first few months after transplantation. In 2009, the International Xenotransplantation Association set up a group to encourage and advise on clinical trials of pig islet xenotransplantation; this group's guidelines are discussed. Clinical trials of encapsulated pig islets are already under way. Keywords: diabetes, islets, pancreatic, pig, xenotransplantation. (shrink)

In the late summer and fall of 1983 articles appeared in such publications as the New York Times, Fortune Magazine, and Science News telling of attempts to set up an agency for the selling of kidneys from living donors. The shortage of organs, especially of kidneys where the transplantation success has increased quite markedly over the past decade, has become something of a crisis. A situation of increased need and inadequate supply is also becoming a problem for such substances as (...) human bone marrow, for use in the treatment of immune and blood diseases, and large quantities of human plasma for use by hemophiliacs. Obtaining a kidney for a patient in renal failure was difficult in the past because adequate matching is likely only between very close relatives. Now with new immunosuppressant drugs such as cyclosporine, close matches have become less important. Cadaver organs or marrow from unrelated living donors can be used with far greater success. The supply problem is still immense and the literature is filled with suggestions for appropriate and efficient means of organ acquisition. One of the latest suggestions involves a system of salvaging based on implied consent of deceased donors. The organs would be taken without asking directly for permission from family. The relatives would have the right to object to the organ removal, but unless they did so, the organ would be taken when needed. (shrink)

Norway provides total social welfare coverage for organ transplantations, including free immunosuppressive medication and prepaid life-long follow up for both recipients and donors. Despite these benefits the proportion of living kidney donors has in recent years declined from around 40% of all kidney transplantations to 24%. This study suggests harnessing patient- and donor-narratives as a tool for addressing the current fall in donation rates. The hospital records of 18 recipient/donor dyads were compared with patient and donor accounts elicited in semi-structured (...) interviews. Narratives afford a pertinent supplement to the primarily biomedical and technical information stored in medical records. Even in condensed form, the messages embedded in narratives contribute to a ‘thicker’ understanding of the complexity of living kidney donation -decisions. Narratives represent a source of education for referring-nephrologists wishing to deepen their evaluation skills and avoid making decisions based on insufficient insight into patients’ and potential donors’ values and life-situation. Recipients’ and donors’ unedited accounts of their motivations, worries, doubts and expectations afford a revealing and edifying supplement to the primarily biomedical and technical information stored in medical records. In narratives, the predicaments and dilemmas surrounding LKD become visible and debatable and can serve as support for future donors, recipients and the nephrologists responsible for evaluation–conclusions. Generating narratives raises a number of practical, epistemic and normative challenges. (shrink)

The history of Western foreign policy in the Middle East has long assimilated Arab culture to sickness. Specifically, the biological episteme of “contamination” has shaped American foreign policy in the Gulf for decades. In so doing, the US Government continually borrowed references from the natural sciences to frame its foreign policy, leading some commentators to claim that biology supplanted philosophy and religion as the primary political category. The article analyses the semantics of Iraqnophobic metaphors, from the British experience of “nursing” (...) Arabs at the close of the First World War to the recent “shock doctrine” of American therapists. First, the paper will concentrate its attention on the metaphors of disinfection and surgical resection. Second, it will address the metaphors of lustration, State-rearing and scientific recovery. Finally, it will explore Iraqis’ rebellion against their self-appointed tutors and doctors. Elaborating on the belligerents’ nursing and biomedical metaphors, the following pages address the life cycle of foreign “legal transplantation”, “antibody” resistance and “immunosuppressant” counterinsurgency in Iraq. (shrink)

Amit Sharma, Rajesh Ramanathan, Marc Posner, Robert A Fisher Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, VA, USA: Pediatric kidney transplantation is the preferred treatment for children with end-stage renal disease. The most common indications for transplantation in children are renal developmental anomalies, obstructive uropathy, and focal segmental glomerulosclerosis. Living donor kidney transplants are often performed pre-emptively and offer excellent graft function. Policy changes in deceased-donor kidney allocation have increased the proportion of such transplants in pediatric recipients. Adequate pretransplant workup (...) along with evaluation of urologic abnormalities is imperative in achieving good outcomes. Overall, patient and graft outcomes after kidney transplantation have improved, with five-year deceased donor and living donor graft survivals of 78.8% and 84.3%, respectively. Improvements in induction and maintenance immunosuppression have contributed to the gradual improvement in outcomes. Unique challenges in pediatric recipients include increased graft thrombosis, adverse growth, and abnormal development relating to immunosuppression, increased rejection due to nonadherence, increased susceptibility to opportunistic infections, and post-transplant malignancy. This review focuses on the current practices and outcomes in pediatric kidney transplantation in North America. We discuss the indications for transplantation, the evaluation process, some key surgical and immunologic considerations, and the common risk factors for graft dysfunction. Keywords: pediatric kidney transplantation, end-stage renal disease, dialysis, organ donors, immunosuppression. (shrink)

Mr. F. is a fifty‐year‐old father of two school‐aged daughters. Six years ago, he received a double lung transplant because he was suffering from interstitial lung disease, a fatal illness that causes suffocation by progressive scarring of the lungs. He is now experiencing chronic rejection of the transplant and is being considered to receive another. Without it, he is expected to survive only a year and a half. With it, his prognosis will improve, but the numbers are still not good. (...) Three years after his lung transplant, Mr. F. stopped attending his office visits. For a period of sixteen months he went without the studies and attention essential to posttransplant care. He stopped performing the required daily self‐monitoring of his lung function about eight months after his transplant, but he has maintained a regular exercise regimen. While lost to follow‐up, he continued to take his immunosuppressant medications, but he stopped taking medicine to control his high blood pressure because of its expense. (shrink)

For decades The People’s Republic of China has been expanding its capacity to perform organ transplants, primarily kidneys and livers but also hearts, lungs and multiorgan transplants. The annual number of organ transplants performed is estimated to be over 30 000. The number is expected to grow with a projected market for immunosuppressants expected to be over ¥30 billion/$4.3 billion by 2024.1 China is second only to the USA and is expected to become the country with the largest number of (...) organ transplants by 2021 or 2022. Many transplants are performed on Chinese citizens but an active market in transplants for ‘tourists’ is ongoing.2 The source of the supply of organs to fuel this rapid growth has long been suspect.3 China had no system for obtaining organs for many years from cadaver sources making it impossible to credit claims that gifts from the newly dead were the sole or even majority source of transplantable organs. Critics, including myself, have long alleged that the only possible source of organs for both Chinese citizens and transplant tourists are executed prisoners. Many accounts, commissions and investigations have confirmed an immoral reliance on this vulnerable …. (shrink)

No one has the right to say what should be done to their body after deathIn my opinion any concept of property in the human body either during life or after death is biologically inaccurate and morally wrong. The body should be regarded as on loan to the individual from the biomass, to which the cadaver will inevitably return. Development of immunosuppressive drugs has resulted in the cadaver becoming a unique and invaluable resource to those who will benefit from organ (...) donation. Faced with the biological reality, the moral error of any concept of property in the body, and the quantitative failure of voluntary organ donation, I believe that the right of control over the cadaver should be vested in the state as representative of those who may benefit from organ donation.How one regards the dead human body, the cadaver, is in part governed by one’s familiarity with it. At the present time, very few people ever see a cadaver which has not in some way been altered after death, and even fewer touch, handle, deal in any way with the dead human body. In developed countries, death itself most frequently occurs away from the home, in an institution, under the supervision of professional caregivers. For most people, ideas concerning the cadaver, its nature, the proper way to deal with it, are formed under these conditions.As a pathologist specialising in forensic pathology, for 50 years I have been at the other end of the spectrum of experience. In my daily work I have been privileged to examine the cadaver in all its stages after death from the immediate postmortem moments through all the stages of decomposition to bare bones. Working in a relatively small community, I have sometimes been charged with examining the body of someone I …. (shrink)

Mass vaccination has been a successful public health strategy for many contagious diseases. The immunity of the vaccinated also protects others who cannot be safely or effectively vaccinated—including infants and the immunosuppressed. When vaccination rates fall, diseases like measles can rapidly resurge in a population. Those who cannot be vaccinated for medical reasons are at the highest risk of severe disease and death. They thus may bear the burden of others' freedom to opt out of vaccination. It is often asked (...) whether it is legitimate for states to adopt and enforce mandatory universal vaccination. Yet this neglects a related question: are those who opt out, where it is permitted, morally responsible when others are harmed or die as a result of their decision? In this article, we argue that individuals who opt out of vaccination are morally responsible for resultant harms to others. Using measles as our main example, we demonstrate the ways in which opting out of vaccination can result in a significant risk of harm and death to others, especially infants and the immunosuppressed. We argue that imposing these risks without good justification is blameworthy and examine ways of reaching a coherent understanding of individual moral responsibility for harms in the context of the collective action required for disease transmission. Finally, we consider several objections to this view, provide counterarguments and suggest morally permissible alternatives to mandatory universal vaccination including controlled infection, self-imposed social isolation and financial penalties for refusal to vaccinate. (shrink)

One day soon it may be possible to replace a failing heart, liver, or kidney with a long-lasting mechanical replacement or perhaps even with a 3-D printed version based on the patient's own tissue. Such artificial organs could make transplant waiting lists and immunosuppression a thing of the past. Supposing that this happens, what will the ongoing care of people with these implants involve? In particular, how will the need to maintain the functioning of artificial organs over an extended (...) period affect patients and their doctors and the responsibilities of those who manufacture such devices? Drawing on lessons from the history of the cardiac pacemaker, this article offers an initial survey of the ethical issues posed by the need to maintain and service artificial organs. We briefly outline the nature and history of cardiac pacemakers, with a particular focus on the need for technical support, maintenance, and replacement of these devices. Drawing on the existing medical literature and on our conversations and correspondence with cardiologists, regulators, and manufacturers, we describe five sources of ethical issues associated with pacemaker maintenance: the location of the devices inside the human body, such that maintenance generates surgical risks; the complexity of the devices, which increases the risk of harms to patients as well as introducing potential injustices in access to treatment; the role of software—particularly software that can be remotely accessed—in the functioning of the devices, which generates privacy and security issues; the impact of continual development and improvement of the device; and the influence of commercial interests in the context of a medical device market in which there are several competing products. Finally, we offer some initial suggestions as to how these questions should be answered. (shrink)

In the atavistic model of cancer progression, tumor cell dedifferentiation is interpreted as a reversion to phylogenetically earlier capabilities. The more recently evolved capabilities are compromised first during cancer progression. This suggests a therapeutic strategy for targeting cancer: design challenges to cancer that can only be met by the recently evolved capabilities no longer functional in cancer cells. We describe several examples of this target‐the‐weakness strategy. Our most detailed example involves the immune system. The absence of adaptive immunity in immunosuppressed (...) tumor environments is an irreversible weakness of cancer that can be exploited by creating a challenge that only the presence of adaptive immunity can meet. This leaves tumor cells more vulnerable than healthy tissue to pathogenic attack. Such a target‐the‐weakness therapeutic strategy has broad applications, and contrasts with current therapies that target the main strength of cancer: cell proliferation. (shrink)

Although it is commonly believed that the concept of brain death was developed to benefit organ transplants, it evolved independently. Transplantation owed its development to advances in surgery and immunosuppressive treatment; BD owed its origin to the development of intensive care. The first autotransplant was achieved in the early 1900s, when studies of increased intracranial pressure causing respiratory arrest with preserved heartbeat were reported. Between 1902 and 1950, the BD concept was supported by the discovery of EEG, Crile’s definition of (...) death, the use of EEG to demonstrate abolition of brain potentials after ischaemia, and Crafoord’s statement that death was due to cessation of blood flow. Transplantation saw the first xenotransplant in humans and the first unsuccessful kidney transplant from a cadaver. In the 1950s, circulatory arrest in coma was identified by angiography, and the death of the nervous system and coma dépassé were described. Murray performed the first successful kidney transplant. In the 1960s, the BD concept and organ transplants were instantly linked when the first kidney transplant using a brain-dead donor was performed; Schwab proposed to use EEG in BD; the Harvard Committee report and the Sydney Declaration appeared; the first successful kidney, lung and pancreas transplants using cadaveric donors were achieved; Barnard performed the first human heart transplant. This historical review demonstrates that the BD concept and organ transplantation arose separately and advanced in parallel, and only began to progress together in the late 1960s. Therefore, the BD concept did not evolve to benefit transplantation. (shrink)

There is a nationwide resurgence of tuberculosis in the country’s urban centers; New York City stands at the forefront of this resurgence. The root causes are increased homelessness, drug addiction and poverty, all symbols of deteriorating social and economic conditions in the city. The inadequate level of public health resources devoted to TB has also contributed to its spread. Still, even with these factors, it is questionable whether the escalating number of TB cases in this country would have occurred without (...) the reservoir of immunosuppressed persons, who are less resistant to the disease, created by the AIDS epidemic. The fear and urgency of this public health crisis, which has been emerging since the beginning of the last decade, are fueled by the rise of TB strains resistant to the first-line drugs and by the disease’s contagiousness. (shrink)

There is a nationwide resurgence of tuberculosis in the country’s urban centers; New York City stands at the forefront of this resurgence. The root causes are increased homelessness, drug addiction and poverty, all symbols of deteriorating social and economic conditions in the city. The inadequate level of public health resources devoted to TB has also contributed to its spread. Still, even with these factors, it is questionable whether the escalating number of TB cases in this country would have occurred without (...) the reservoir of immunosuppressed persons, who are less resistant to the disease, created by the AIDS epidemic. The fear and urgency of this public health crisis, which has been emerging since the beginning of the last decade, are fueled by the rise of TB strains resistant to the first-line drugs and by the disease’s contagiousness. (shrink)

Social analysis of transplant organ demand often focuses on either small-scale (familial) tyrannies of the gift or large-scale (global) markets. Media accounts of the scandalous in transplant medicine stress the latter, a homogeneous model of flows of biovalue down gradients of economic and social capital. This article examines particular globalizations of tissue demand organized as much around claims of social similarity as gradients of social difference. To engage apparent ‘diasporic’ networks of organ purchase — Non-Resident Indians traveling to India and (...) Overseas Chinese to China — I elaborate a concept of bodily supplementarity. Supplementarity in this account is the ability of an individual or population to secure longevity through the mobilization or acquisition of the organic form of others. Diasporic tissue circuits are analyzed in the context of ‘experiments’ in supplementarity that proliferate with the transformation of the molecular conditions for supplementarity. The emergence of powerful immunosuppressants renders the scale of tissue recruitment flexible and contingent, and allows clinics to develop alternatives to brain death. These circuits emerge as situations that reorder the relation of the familial and the global in transplantation, in the service not only of migrant supplementarity but also efforts to reimagine the challenges of emigrant belonging within particular configurations of racialized life and its government. (shrink)

Resource constraints in developing countries compel policy makers to ration the provision of healthcare services. This article examines one such set of Guidelines: A patient dialysing in the state sector in South Africa may not refuse renal transplantation when a kidney becomes available. Refusal of transplantation can lead to exclusion from the state-funded dialysis programme. This Guideline is legally acceptable as related to Constitutional stipulations which allow for rationing healthcare resources in South Africa. Evaluating the ethical merit of the Guideline, (...) and exploring the ethical dilemma it poses, proves a more complex task. We examine the actions of healthcare professionals as constrained by the Guideline. From a best interests framework, we argue that in these circumstances directing patient decision making is not necessarily unethical or unacceptably paternalistic. We then scrutinise the guideline itself through several different ethical ‘lenses’. Here, we argue that bioethics does not provide a definitive answer as to the moral merit of rationing dialysis under these circumstances, however it can be considered just in this context. We conclude by examining a potential pitfall of the Guideline: Unwilling transplant recipients may not comply with immunosuppressive medication, which raises questions for policies based on resource management and rationing. (shrink)

Calcineurin is a Ca2+/calmodulin‐activated protein phosphatase that is conserved in eukaryotes, from yeast to humans, and is the conserved target of the immunosuppressive drugs cyclosporin A (CsA) and FK506. Genetic studies in yeast and fungi established the molecular basis of calcineurin inhibition by the cyclophilin A–CsA and FKBP12–FK506 complexes. Calcineurin also functions in fungi to control a myriad of physiological processes including cell cycle progression, cation homeostasis, and morphogenesis. Recent investigations into the molecular mechanisms of pathogenesis in Candida albicans and (...) Cryptococcus neoformans, two fungi that cause life‐threatening infections in humans, have revealed an essential role for calcineurin in morphogenesis, virulence, and antifungal drug action. Novel non‐immunosuppressive analogs of the calcineurin inhibitors CsA and FK506 that retain antifungal activity have been identified and hold promise as candidate antifungal drugs. In addition, comparisons of calcineurin function in both fungi and humans may identify fungal‐specific components of calcineurin‐signaling pathways that could be targeted for therapy, as well as conserved elements of calcium signaling events. BioEssays 24:894–903, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Brock Macdonald1, Evi Vakiani2, Rhonda K Yantiss3, Jun Lee4, Robert S Brown Jr5, Samuel H Sigal61Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco, CA, 2Department of Pathology, Memorial Sloan–Kettering Cancer Center, New York, NY, 3Department of Pathology and Laboratory Medicine, New York Weill Cornell Medical College, New York, NY, 4Division of Nephrology, Department of Medicine, Weill Cornell Medical College, New York, NY, 5Division of Gastroenterology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, (...) NY, 6Division of Gastroenterology and Hepatology, Department of Medicine, New York University, New York, NY, USA: The use of sirolimus as an alternative to calcineurin inhibitors for posttransplant immunosuppression is associated with a variety of inflammatory conditions. In this report, we describe the case of a 34-year-old man who developed abnormal liver tests 6 years after live-donor kidney transplantation and 5 years after initiation of sirolimus-based immunosuppression. Elevated aminotransferase levels persisted after withdrawal of potentially hepatotoxic medications, and serologic evaluation for viral hepatitis, autoimmune disease, and genetic disorders was unrevealing. Liver biopsy revealed prominent hepatocellular injury associated with a mixed inflammatory infiltrate and liver tests normalized within 2 weeks of discontinuation of sirolimus. In this report, we review previous reports of sirolimus hepatotoxicity and propose a unifying hypothesis for the various inflammatory conditions that have been attributed to sirolimus.Keywords: sirolimus, immunosuppression, transplant, inflammatory conditions, hepatotoxicity. (shrink)

Wana Manitpisitkul1, Sabrina Lee2, Matthew Cooper31Department of Pharmacy, University of Maryland Medical Center, Baltimore, MD, USA; 2Solid Organ Transplant Program, University of Utah Health Care, Salt Lake City, UT, USA; 3Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA: Addition of mycophenolate mofetil to calcineurin-based immunosuppressive therapy has led to a significant improvement in graft survival and reduction of acute rejection in renal transplant recipients. However, in clinical practice, MMF dose reduction, interruption, or discontinuation due to hematological (...) and gastrointestinal side-effects occurred in up to 50% of the patients. Large retrospective analyses have demonstrated that patients requiring MMF dose manipulation due to adverse events experienced a higher rate of rejection and graft loss. Enteric-coated mycophenolate sodium was developed with the goal of improving upper GI side-effects. Here, we review the efficacy and safety of EC-MPS in de novo kidney transplant recipient, and in stable renal transplant patients who were converted from MMF. The changes in GI-related adverse events using patient-reported outcome instruments are also reviewed.Keywords: enteric-coated mycophenolate sodium, mycophenolate mofetil, kidney transplant, efficacy, gastrointestinal tolerability. (shrink)

HIV/AIDS is the leading cause of morbidity and mortality in the southern African country of Malawi. At the largest referral health facility in Blantyre, the Queen Elizabeth Central Hospital, the majority of patients hospitalized in medical wards and up to a third of those in the maternity unit are infected with HIV. Many patients in the surgical wards also have HIV/AIDS. Health professionals in Blantyre, however, often choose not to write down the diagnosis of HIV or AIDS; rather, they prefer (...) to use ‘SGOT’, ‘ELISA’ and ‘spot test’ to represent the HIV test, while ‘immunosuppression’, ‘↓ CD4 disease’ and ‘ARC’ are preferred instead of ‘AIDS’. It is possible that health professionals’ belief that mentioning HIV and/or AIDS will harm patients is encouraging them to use these euphemisms. The use of less than exact terms to label HIV and AIDS may not be without cost. For instance, future attempts to conduct retrospective case study research may be hampered by this practice, which is not in accordance with the international classification of diseases. It is suggested that, although stigmatization and discrimination could be important driving factors in the use of cryptic language, it may be more worthy to fight discrimination and stigmatization head-on, rather than create avenues where these reactions may be perpetuated. (shrink)

The exact process that leads to the eruption of autoimmune reactions against β cells and the evolution of diabetes is not fully understood. Macrophages and T cells may launch an initial immune reaction against the pancreatic islets of Langerhans, provoking inflammation and destructive insulitis. The information on the molecular mechanisms of the emergence of β cell injury is controversial and points to possibly important roles for the perforin–granzyme, Fas–Fas-ligand (FasL) and tumor-necrosis-factor-mediated apoptotic pathways. FasL has several unique features that make (...) it a potentially ideal immunomodulatory tool. Most important, FasL is selectively toxic to cytotoxic T cells and less harmful to regulatory T cells. This review discusses the intrinsic sensitivity of β cells to FasL-mediated apoptosis, the conditions that underlie this β cell sensitivity, and the feasibility of using FasL to arrest autoimmunity and prevent islet allograft rejection. In both the autoimmune and transplant settings, it is imperative to progress from the administration of nonspecific immunosuppressive therapy to the concept of β-cell-specific immunomodulation. FasL evolves as a prime candidate for antigen-specific immunomodulation. BioEssays 28: 211–222, 2006. © 2006 Wiley periodicals, Inc. (shrink)

The exact process that leads to the eruption of autoimmune reactions against β cells and the evolution of diabetes is not fully understood. Macrophages and T cells may launch an initial immune reaction against the pancreatic islets of Langerhans, provoking inflammation and destructive insulitis. The information on the molecular mechanisms of the emergence of β cell injury is controversial and points to possibly important roles for the perforin–granzyme, Fas–Fas-ligand (FasL) and tumor-necrosis-factor-mediated apoptotic pathways. FasL has several unique features that make (...) it a potentially ideal immunomodulatory tool. Most important, FasL is selectively toxic to cytotoxic T cells and less harmful to regulatory T cells. This review discusses the intrinsic sensitivity of β cells to FasL-mediated apoptosis, the conditions that underlie this β cell sensitivity, and the feasibility of using FasL to arrest autoimmunity and prevent islet allograft rejection. In both the autoimmune and transplant settings, it is imperative to progress from the administration of nonspecific immunosuppressive therapy to the concept of β-cell-specific immunomodulation. FasL evolves as a prime candidate for antigen-specific immunomodulation. BioEssays 28: 211–222, 2006. © 2006 Wiley periodicals, Inc. (shrink)

Being inherently different from any other lifesaving organ transplant, uterine transplantation does not aim at saving lives but supporting the possibility to generate life. Unlike the kidneys or the liver, the uterus is not specifically a vital organ. Given the non-lifesaving nature of this procedure, questions have been raised about its feasibility. The ethical dilemma revolves around whether it is worth placing two lives at risk related to surgery and immunosuppression, amongst others, to enable a woman with absolute uterine (...) factor infertility to experience the presence of an organ enabling childbirth. In the year 2000, the first uterine transplantation, albeit unsuccessful, was performed in Saudi Arabia from where it has spread to the rest of the world including Sweden, the United States and now recently India. The procedure is, however, still in the preclinical stages and several ethical, legal, social and religious concerns are yet to be addressed before it can be integrated into the clinical setting as standard of care for women with absolute uterine factor infertility. (shrink)

This book covers lymphoproliferative disorders in patients with congenital or acquired immunodeficiencies. Acquired immunodeficiencies are caused by infections with the human immunodeficiency virus or arise following immunosuppressive therapy administered after organ transplantation or to treat connective tissue diseases such as rheumatoid arthritis. It was recently discovered that various diseases or therapeutic modalities that induce a state of immunosuppression may cause virally driven lymphoproliferations. This book summarizes for the first time this group of immunodeficiency-associated lymphoproliferations.

Although it is commonly believed that the concept of brain death was developed to benefit organ transplants, it evolved independently. Transplantation owed its development to advances in surgery and immunosuppressive treatment; BD owed its origin to the development of intensive care. The first autotransplant was achieved in the early 1900s, when studies of increased intracranial pressure causing respiratory arrest with preserved heartbeat were reported. Between 1902 and 1950, the BD concept was supported by the discovery of EEG, Crile’s definition of (...) death, the use of EEG to demonstrate abolition of brain potentials after ischaemia, and Crafoord’s statement that death was due to cessation of blood flow. Transplantation saw the first xenotransplant in humans and the first unsuccessful kidney transplant from a cadaver. In the 1950s, circulatory arrest in coma was identified by angiography, and the death of the nervous system and coma dépassé were described. Murray performed the first successful kidney transplant. In the 1960s, the BD concept and organ transplants were instantly linked when the first kidney transplant using a brain-dead donor was performed; Schwab proposed to use EEG in BD; the Harvard Committee report and the Sydney Declaration appeared; the first successful kidney, lung and pancreas transplants using cadaveric donors were achieved; Barnard performed the first human heart transplant. This historical review demonstrates that the BD concept and organ transplantation arose separately and advanced in parallel, and only began to progress together in the late 1960s. Therefore, the BD concept did not evolve to benefit transplantation. (shrink)

Although it is commonly believed that the concept of brain death was developed to benefit organ transplants, it evolved independently. Transplantation owed its development to advances in surgery and immunosuppressive treatment; BD owed its origin to the development of intensive care. The first autotransplant was achieved in the early 1900s, when studies of increased intracranial pressure causing respiratory arrest with preserved heartbeat were reported. Between 1902 and 1950, the BD concept was supported by the discovery of EEG, Crile’s definition of (...) death, the use of EEG to demonstrate abolition of brain potentials after ischaemia, and Crafoord’s statement that death was due to cessation of blood flow. Transplantation saw the first xenotransplant in humans and the first unsuccessful kidney transplant from a cadaver. In the 1950s, circulatory arrest in coma was identified by angiography, and the death of the nervous system and coma dépassé were described. Murray performed the first successful kidney transplant. In the 1960s, the BD concept and organ transplants were instantly linked when the first kidney transplant using a brain-dead donor was performed; Schwab proposed to use EEG in BD; the Harvard Committee report and the Sydney Declaration appeared; the first successful kidney, lung and pancreas transplants using cadaveric donors were achieved; Barnard performed the first human heart transplant. This historical review demonstrates that the BD concept and organ transplantation arose separately and advanced in parallel, and only began to progress together in the late 1960s. Therefore, the BD concept did not evolve to benefit transplantation. (shrink)

Human allografts for life-threatening organ failure have been demonstrated to be lifesaving and are now considered to be standard of care for many conditions. Transplantation of non-vital anatomic body parts has also been accomplished. Hand transplantation after limb loss in adults has been shown to offer some promising benefits in both functional and psychological measures in preliminary studies. It has been suggested to expand eligibility criteria to include minors, with one such operation having already been performed. With this in mind, (...) we examine the current state of hand transplantation research in the context of available alternatives. We examine the ethics of carrying out these operations in minors, including under the protections of clinical research. We argue that children should not be considered for this surgery due to the substantial risks of immunosuppressive medication, the likelihood that the graft will need to be replaced during the patient’s lifetime and the lack of significant compensatory advantages over modern prosthetics. (shrink)

Given the increasing need for solid organ and tissue transplants and the decreasing supply of suitable allographic organs and tissue to meet this need, it is understandable that the hope for successful xenotransplantation has resurfaced in recent years. The biomedical obstacles to xenotransplantation encountered in previous attempts could be mitigated or overcome by developments in immunosuppression and especially by genetic manipulation of organ source animals. In this essay we consider the history of xenotransplantation, discuss the biomedical obstacles to success, (...) explore recent developments in transgenic sourcing of organs and tissues, and analyze the problem of infectious disease resulting from xenotransplantation (xenosis). We then apply a model of risk analysis to these risks. The conclusions of this risk analysis are used in an ethical evaluation of informed consent in xenotransplantation, with an ethical foundation in Kantian autonomy and Levinasian heteronomic alterity. Our conclusion is that individual and collective informed consent to the infectious disease risks of xenotransplantation requires an open, participatory and dialogical public policy process not yet seen in the United States and Europe. Until that process is created, we propose caution in xenotransplantation in general and a postponement of solid organ xenotransplants in particular. (shrink)

Although in certain contexts judged to be over-rated,1 consistency is generally held to be a virtue in arguments about medical ethics. In everyday life, to be told that you are acting hypocritically, in a manner that is inconsistent with values you profess, is at least embarrassing, and depending on the circumstances can have more serious consequences, not least for politicians. How far complete consistency in thought and action is humanly possible or even desirable is a more doubtful however. In terms (...) of inconsistency over time, certainly, the maxim ‘When the facts change, I change my mind’ can be a reasonable defence: but in order to avoid less defensible forms of inconsistency, changing your mind about one thing may require changing it about others also. To take seriously just such a possibility is the ethical challenge of this month’s feature article: ‘Moral Uncertainty and the Farming of Human-Pig Chimeras’ by Julian Koplin and Dominic Wilkinson.2 In this case, the facts that have or could soon have changed surround the emerging possibility of generating, within human-pig chimeras, human organs for transplantation into patients who need them and of avoiding the need for immunosuppression by generating the organs using stem cells from the patients themselves. The potential benefits of this possible answer to the worldwide shortage of transplantable organs clearly are immense. But, Koplin and Wilkinson point out, there are also serious potential harms. If human-pig chimeras with ‘partly humanised brains’ were to ‘develop morally relevant cognitive capacities’, such as dawning self-awareness, their moral status would make farming and killing them ‘a serious moral wrong’. Yet having said that, the real difficulty is that we cannot be certain, philosophically, ‘precisely what capacities confer what …. (shrink)

Research with enhanced potential pandemic pathogens (ePPP) makes pathogens substantially more lethal, communicable, immunosuppressive or otherwise capable of triggering a pandemic. We briefly relay an existing argument that the benefits of ePPP research do not outweigh its risks and then consider why proponents of these arguments continue to confidently endorse them. We argue that these endorsements may well be the product of common cognitive biases—in which case they would provide no challenge to the argument against ePPP research. If the case (...) against ePPP research is strong, the views of professional experts do little to move the needle in favour of ePPP research. (shrink)

The orderly sequence of events that constitutes the cell cycle is carefully regulated. A part of this regulation depends upon the ubiquitous calcium signalling system. Many growth factors utilize the messenger inositol trisphosphate (InsP3) to set up prolonged calcium signals, often organized in an oscillatory pattern. These repetitive calcium spikes require both the entry of external calcium and its release from internal stores. One function of this calcium signal is to activate the immediate early genes responsible for inducing resting cells (...) (G0) to re‐enter the cell cycle. It may also promote the initiation of DNA synthesis at the G1/S transition. Finally, calcium contributes to the completion of the cell cycle by stimulating events at mitosis. The role of calcium in cell proliferation is highlighted by the increasing number of anticancer therapies and immunosuppressant drugs directed towards this calcium signalling pathway. (shrink)

Mr. F. is a fifty‐year‐old father of two school‐aged daughters. Six years ago, he received a double lung transplant because he was suffering from interstitial lung disease, a fatal illness that causes suffocation by progressive scarring of the lungs. He is now experiencing chronic rejection of the transplant and is being considered to receive another. Without it, he is expected to survive only a year and a half. With it, his prognosis will improve, but the numbers are still not good. (...) Three years after his lung transplant, Mr. F. stopped attending his office visits. For a period of sixteen months he went without the studies and attention essential to posttransplant care. He stopped performing the required daily self‐monitoring of his lung function about eight months after his transplant, but he has maintained a regular exercise regimen. While lost to follow‐up, he continued to take his immunosuppressant medications, but he stopped taking medicine to control his high blood pressure because of its expense. (shrink)

Physical exercise is seen as the main ally for health promotion, preventing and protecting the organism from several diseases. According to WHO, there is a tendency of constant growth in the elderly population in the coming years. The regular practice of exercises by the elderly becomes relevant to minimize the deleterious effects of the aging process and to increase the fitness index. Recently, the world population started a confrontation against Corona Virus Disease (COVID-19), which is the most significant public health (...) challenge globally. Although social isolation is a reasonable measure in an attempt to stop contamination by COVID-19, this measure has limited the ability of individuals to exercise outdoors or in gyms and health clubs, which increased the risk of developing chronic illnesses related to a sedentary lifestyle. The critical point is that the recent recommendations on exercise prescription to combat the potentially harmful effects of COVID-19 failure to adequately address resistance exercise interventions as home-based exercise strategy. Thus, in this paper, we discussed the physical exercise as medicine if the training status is enough to protect the elderly against COVID-19 infection, about the role of physical activity on immunosuppression. Possible risks for COVID-19 infection, and the old training methods, such as no-load resistance training as possible resistance exercise strategies and high-intensity interval training, as new proposals of home-based exercise interventions, could perform during the current COVID-19 pandemic. (shrink)

The mechanical view on the human body may be considered as the context in which the highly technological medicine of these days originated. Organ transplantation is certainly one of the most impressive possibilities of this new evolution in medical technology. It exists by the grace of the paradigm of the body as a “Körper” : this paradigm leads to a self-evident acceptance of transplantation medicine in its most brilliant applications. Refinement of surgical techniques, better preservation of organs, the development of (...) more effective immunosuppressives, better procedures for the establishment of brain death criteria and better criteria for the selection and matching of donors and receptors are immanent goals of this type of medicine. Meanwhile the lives of many thousands of patients are saved and these patients even receive the chance for a new life, with much more quality. The ethical reflection on organ transplantation has followed rather rapidly this technical discourse and sounds as a kind of “moral engineering”. This is certainly connected with the upcoming success of “Principlism” , whereby medical decision making is oriented by applying four major principles to medical cases . It is also connected with the ethical approach of utilitarianism, which fits almost perfectly in this technological atmosphere. The authors question this approach and suggest that a more relational understanding of the human body as “Leib” would be a better paradigm for the promotion of solidarity in the context of organ donation and transplantation. Human beings do not only ‘have’ a body, but ‘are’ also their body. The body of the deceased refers to the life of a loved one. Technical procedures surrounding organ removals sometimes hinder the possibility for the family to bereave adequately around their loved one. The authors are convinced that the urging problem of organ shortage is not only caused by lack of solidarity or laziness, but also by the reductionist discourse of transplantation medicine itself. They suggest that we have to find – eventually with the help of poets and writers – an adequate new language to replace the alienating discourse of current transplantation medicine. They see also in communitarianism and personalist care ethics a better ethical approach for touching the peculiar sensitivities of eventual donors and receptors. (shrink)

Despite having paved the way for face, womb and penis transplants, hand transplantation today remains a small hybrid of reconstructive microsurgery and transplant immunology. An exceptionally limited patient population internationally complicates medical researchers’ efforts to parse outcomes “objectively.” Presumed functional and psychosocial benefits of gaining a transplant hand must be weighed in both patient decisions and bioethical discussions against the difficulty of adhering to post-transplant medications, the physical demands of hand transplant recovery on the patient, and the serious long-term health (...) risks of immunosuppressant drugs. This paper relates five narratives of hand transplantation drawn from an oral history project to show how narrative methods can and should inform ethical evaluations and the clinical process of hand transplantation. The interviews with patients and their partners analyzed here lead us to suggest that qualitative accounts of patient experiences should be used to complement clinical case studies reported in medical journals and to help develop instruments to assess outcomes more systematically. (shrink)

Bulang He,1,2 Jeffrey M Hamdorf2 1Liver and Kidney Transplant Unit, Sir Charles Gairdner Hospital, Perth, WA, Australia; 2School of Surgery, The University of Western Australia, Perth, WA, Australia Aims: The aim of this paper was to review the current status of laparoscopic/robotic kidney transplant and evaluate its feasibility and safety in comparison with conventional standard "open" kidney transplant. Methods: An electronic search of PubMed, Embase, and the Cochrane library database was performed to identify the papers between January 1980 and June (...) 2013 that reported on laparoscopic/robotic kidney transplantation. The terms "laparoscopic kidney/renal transplant" and "robotic kidney/renal transplant " were used. Cross-referencing was also used to find the further publications. Only English language reports were selected and accepted for descriptive analysis. Results: A total of 17 papers and abstracts were retrieved. There were two case-control studies of small volume. High-level evidence comparing the safety and efficacy of laparoscopic/robotic kidney transplant with conventional open kidney transplant was not available at the time of this review. Conclusion: The limited published data have suggested that laparoscopic/robotic kidney transplant may offer the advantages of less pain, better cosmesis, possible shorter hospital stay, and fewer wound complications, without compromising graft function. Accordingly, some immunosuppressive agents, such as sirolimus, might be able to be commenced earlier, after laparoscopic/robotic kidney transplant. The techniques are various at this early stage. A uniformed operative technique may be established in the near future. With refinement of laparoscopic devices, this technique may be widely employed. Further studies will be needed to demonstrate the advantages of laparoscopic/robotic kidney transplant over the conventional open kidney transplant. Keywords: laparoscopic surgery, robotic surgery. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:When Is Enough, Enough?Megan HomsyThis was a case that stuck with many members of our transplant team for a long time. The patient was a 44-year-old Caucasian male evaluated for a liver transplant with a diagnosis of hepatitis C virus (HCV), originally diagnosed 11 years before the transplant evaluation. The patient met the criteria for the following substance use diagnoses: alcohol use disorder moderate in sustained remission, in a (...) controlled environment, opioid use disorder, severe, in sustained remission, on maintenance therapy, in a controlled environment, stimulant use disorder, amphetamine-type, severe, in early remission, in a controlled environment and stimulant use disorder, cocaine-type, severe in early remission, in a controlled environment.The patient had been living in a sober living housing program for approximately ten months prior to his transplant evaluation with me, his social worker. He had also been diagnosed with depression and bipolar disorder. He had been intermittently linked with mental health services and had participated in numerous detox and substance abuse programs over the last ten years, with varying degrees of success. He was in dual diagnosis treatment (i.e., treatment for co-occurring substance use and mental health disorders) through his Suboxone clinic and was completing toxicology screenings on a biweekly basis.After concluding the minimum three months of drug and alcohol treatment set forth by the state's Organ Transplantation Consortium, the patient graduated from his sober living program, moved in with his sister, and was listed for a liver transplant.The patient was transplanted five months after his clinic evaluation. At the time of the surgery, the patient's Suboxone was abruptly discontinued and replaced with IV Dilaudid. Within days of his transplant, the patient frequently expressed concerns about his pain. Several medical services attempted to manage the pain medications, resulting in his pain management plan being changed repeatedly and much confusion over his current medication regimen. During his liver transplant hospitalization, the RN found the patient with a needle in his arm, and after a search of the patient's hospital room, the hospital police found drug paraphernalia and illicit substances. The patient was eventually discharged to an inpatient substance abuse program, which he left before completing the program and against medical advice.During his first year post-transplant, I attempted to arrange other various treatment programs for him (most of which he did not follow through with) and to find housing for him (as he had been forced to leave his sister's home after his relapse). Eventually, the patient was incarcerated on drug-related charges. Numerous times, the patient missed completing his labs and his post-transplant appointments. He did not refill his immunosuppressant medications, and for lengthy periods of time, he was unreachable by the transplant care team, which resulted in my team members and I calling the patient's family, other providers, and the police for safety checks.In the aftermath of these issues, my colleagues and I had to reckon with the realization that we had failed the patient. As a team, our transplant center created a task force to review this case and what to do in the future to prevent such breakdowns in patient care. We created protocols for managing patients who, at the time of their transplant, are on Medication Assisted Treatment (MAT) such as Suboxone and methadone. Staff across the multidisciplinary team attended trainings regarding addiction, pain management, and best practices for MAT services. Additionally, our transplant center collaborated with our hospital's addiction treatment program for a streamlined referral process for transplant patients to addiction services.This patient's case and its sensational nature resulted in many conversations, both professional and unprofessional. Members of the social worker department became aware that personnel within transplant, though not involved in patient care, were inappropriately discussing this patient's case and engaging in unprofessional behavior. Said actions led to the termination of a member of the transplant team. I was placed in the unenviable [End Page E3] position of having to report this behavior to hospital management and legal teams to protect a vulnerable patient.The ethical challenge behind this case really stems from the transplant team attempting to balance two... (shrink)

The recent advances in assisted reproductive technology, such as hormonal stimulation, IVF, and intracytoplasmic sperm injection (ICSI), have made it possible to circumvent many causes of male and female factor infertility. However, uterine infertility is still considered an ‘‘unconditionally infertile’’ condition. Owing to the continued advances in organ transplantation, microvascular anastomosis techniques, and immunosuppressive medicine, the transplantation of organs is no longer restricted to the ones necessary for continued life. Quality-of-life enhancing types of transplantation, such as uterine transplantation, in recent (...) years, have also entered the clinical arena. This undoubtedly brings new hope to such women, but also creates ethical challenges. Selection of the donor, the impact on the recipient and offspring, as well as challenges to moral and social norms are issues that cannot be ignored. In the present review, the ethical issues of transplantation of the uterus will be discussed in light of recent progress in the procedure. (shrink)