The long-term success of transplantation is limited by the need for immunosuppression; thus, tolerance induction is an important therapeutic goal. A 16-day treatment with rapamycin in mice led to indefinite graft survival of fully mismatched cardiac allografts, whereas untreated hearts were rejected after 8-10 days. Specific tolerance was confirmed through subsequent skin grafts and in vitro lymphocyte assays that showed recipient mice remained immunocompetent towards 3rd party antigens but were impaired in responding to donor antigens. Mechanisms that account for this tolerant state were then investigated. Splenic CD8+CD44+ memory T-cells were reduced in tolerant mice but had increased frequencies of the CD62LLO population. CD4+CD25+Foxp3+ regulatory T-cells were increased in tolerant mice. Through multiplex PCR, 4 regulatory T-cell related genes were found up-regulated and 2 proinflammatory genes were down-regulated in accepted hearts. This expression pattern may serve as a putative biomarker of tolerance in patients undergoing transplantation.

Human leukocyte antigen-G (HLA-G), a non-classical MHC I protein, plays an essential role in immune tolerance and is associated with a lower incidence of graft rejection and cardiac allograft vasculopathy (CAV). To examine the pattern of HLA-G expression post-transplantation we determined that HLA-G can be up-regulated in smooth muscle cells (SMCs) following exposure to everolimus. We also determined that HLA-G at 500 and 1000 ng/ml reduces SMC proliferation. In further studies, treatment with HLA-G inhibited TNFα-stimulated neutrophil adhesion to endothelial cells (ECs) at all concentrations tested (0.1-1 ng/ml), suggesting a role in inflammation. The expression of HLA-G is influenced by a polymorphism in the HLA-G gene. We sought to determine if the 14bp insertion/deletion polymorphism can predict the development of CAV. There was no association between this polymorphism and CAV; however, this study had a small number of patients; therefore further investigations are needed to confirm these findings.

No description available.

No description available.

Entwicklungen im Bereich der Medizin führen immer wieder zu einer Neuformulierung der Grenze zwischen Leben und Tod. Jüngere Skandale um die Vergabe von Spenderorganen sorgen für Diskussionen um die ethischen Grundlagen der Transplantationspraxis, zu denen die Definition des Hirntodes gehört. Zur Auseinandersetzung mit ethischen Fragen gehört, den eigenen Kulturraum näher zu betrachten und zu analysieren. Der chinesische Kulturraum soll dabei als Vergleichsebene dienen, sich mit einem anderen Zugang zu und einem anderen Verständnis von Bioethik zu beschäftigen. Die Disziplin der Bioethik im chinesischen Kulturraum ist zwar noch eine sehr junge, kann aber auf eine eigenständige Medizintradition (Traditionelle Chinesische Medizin) zurückgreifen. Dieser bioethischen Analyse liegen entsprechend alte Denktraditionen des Konfuzianismus, Buddhismus und Daoismus zugrunde. Die vorliegende Arbeit beinhaltet den ethisch-kulturellen Vergleich zwischen Deutschland und der Volksrepublik China, die Suche nach Unterschieden und Gemeinsamkeiten im Umgang mit Organtransplantation und Hirntodkonzept. Dabei geht es zum einen um die direkte Gegenüberstellung der gesetzlichen Regelungen, zum anderen erfolgt eine deskriptive-ethische Analyse auf Grundlage der vier Diskussionsebenen – diagnostische Tests, Todeskriterium, Todesdefinition, Menschenbild – um das Hirntodkonzept in beiden Ländern

Severe injury may result in disconnection between the peripheral and central nervous system. Regeneration of the central portion of sensory neurons into the spinal cord is notoriously poor in adult mammals, with low regenerative drive and an unpermissive central environment, most likely resulting in persistent loss of sensory function. A variety of strategies have been addressedto augment regeneration, including application of growth promoting factors, counteraction of inhibitory molecules, and provision of growth permissive substrates. Stem cells have been investigated in these contexts, as well as for the possibility of providing new neurons to act as a relay between the periphery and spinal cord. Here we have investigated different sources of neural stem cells for their ability to form neurons and glia after transplantation to the periphery; to project axons into the spinal cord; and to assist regeneration of surviving sensory neurons. These have been performed at two locations: the "dorsal root ganglion cavity", and the transitional zone following dorsal root avulsion. Neurons and glia were generated form mouse boundary cap neural crest stem cells and embryonic stem cell derived ventral spinal cord progenitors, and in addition to this, regeneration of sensory fibers was observed after transplantation of human fetal spinal cord derived progenitors and human embryonic stem cell derived ventral spinal cord progenitors. Further, delivery of neurotrophic factor mimetics via mesoporous silica nanoparticles proved a valuable tool for stem cell survival and differentiation. While technological advances make in vivo differentiation a realistic goal, our findings indicate that so far assisting regeneration of host sensory fibers to reconnect with the spinal cord by transplantation of stem cells is a more reliable strategy.

Through the recruitment of immunologic mechanisms, allogeneic hematopoeitic cell transplantation (HCT) has been establiched as a curative treatment for various hematologic diseases. The most convenient source to obtain hematopoietic progenitor cells are peripheral blood stem cells (PBSCs) which are harvested from the donor via leukapheresis after mobilization with granulocyte-colony stimulating factors. With the introduction of reduced intensity condition (RIC), the curative potential of allogeneic HCT became accessible to older and/or frail patients otherwise ineligible for HCT. However, new challenges arise as the increasing age of patients is inevitably accompanied by a comparable increase in the age of donors. Safety considerations of collecting PBSCs might attain new dimensions. Data to potential risks in elderly donors are lacking. Moreover, the impact of donor’s age on the feasibility of PBSCs collection and on the quality of the harvest in terms of stem cells (CD34+) and natural killer (NK)-cells has not been studied. It is also unknown whether PBSCs obtained from donors above 50 years would negatively influence engraftment or the incidence of graft-versus-host disease (GVHD) in the recipient. These questions were explored in a retrospective study including 167 recipients of an allogeneic HCT (52.7% after RIC) from a matched related sibling. Median donors’ age was 47 years [67 (40%) donors were > 50 years including 34 donors > 60 years]. Safety of mobilization and leukapheresis was age independent. Adequate PBSCs were collected from all donors though a higher CD34+-cell count was seen in donors < 50 years (p<0.0005), whereas harvests from donors > 60 years contained a higher NK-cell count (p=0.003). Engraftment in the recipient occurred after a median of 12 days and was not affected by an advanced donor age. Similarly, a higher incidence of GVHD was not seen in recipients of harvests from older donors. For the first time, we show that donor’s age, even beyond 60 years, does not preclude successful collection of PBSCs from siblings, does not jeopardize the short-term safety of the donor, and is not associated with deleterious sequels for the recipient in terms of engraftment or GVHD. As NK-cells have been implicated in the suppression of GVHD, and the mediation of a graft versus leukemia effect, the impact of the higher number of NK-cells in harvests from elderly donors on relapse of hematologic malignancies in the recipient warrants further studies.

A qualitative phenomenological study using van Manen’s human science method was conducted to gain insight into the lived experience of patients and their family members transitioning through one hundred days post haematopoietic stem cell transplantation (HSCT). Three families between zero and five years post HSCT were recruited from a bone marrow transplant unit in central Canada. Multiple in-depth open-ended interviews and field notes were employed to arrive at a detailed description of the lived experience of patients and family members. Awakening from the cocoon emerged as the main essence of patient’s and family members’ experiences, supported by three themes: the disruptions, the chrysalis, and new beginnings. The results from this study provide evidence that the families viewed the HSCT in a positive perspective and highlight the importance of supporting families throughout the acute phase of transplantation.

BACKGROUND: Organ transplantation is one of the best modalities for treating fatal organ failure. Despite the success of this procedure, an increasing incidence of cancer in this population has drawn the attention of public health officials in recent years. OBJECTIVES: The overall objective of this study is to conduct a detailed examination of adverse health outcomes among Canadian organ transplant recipients, with an emphasis on cancer incidence and mortality. METHODS: This project employed a retrospective cohort follow-up study design, whereby Canadian Organ Replacement Registry records were linked to the Canadian Mortality Database and the Canadian Cancer Registry Database. The study population consisted of more than 16,000 solid organ transplant recipients registered between January 1, 1981 and December 31, 1998. This study was designed to assess the risks of developing cancer, overall and site-specific, in transplant recipients in comparison to the general Canadian population using Standardized Incidence Ratios (SIR), Standardized Mortality Ratios (SMR), and Proportionate Mortality Ratios (PMR). In addition, Cox and logistic models were used to assess the effects of various risk factors on cancer incidence and mortality in transplant sub-populations, while cumulative incidence was used to study the patient survival pattern. Lastly, Population Attributable Risk (PAR) was used to quantify the impact of organ transplantation on cancer incidence and mortality. RESULTS: Among major causes of death, the highest PMRs are due to genitourinary diseases, followed by endocrine, nutritional and metabolic diseases, and infectious diseases. SIRs indicate that cancer incidence and mortality were relatively lower than that observed for other major causes of death, and slightly higher than that observed in the general Canadian population. Lastly, logistic regression results indicate that age, year of surgery, and smoking status were significant risk factors in mortality due to all causes, while the Cox regression model shows that age, sex and year of surgery were significant risk factors for cancer incidence. Overall, the PAR in this cohort was very minimal, indicating that the risk in mortality and cancer incidence due to organ transplantation is negligible. CONCLUSION: Life threatening diseases such as those of the genitourinary system, as well as endocrine, nutritional and metabolic diseases and infectious diseases are leading causes of death. Future research should be directed at ways of reducing incidence and subsequent mortality due to these causes.

ABSTRAKT Bakgrund: Ett nytt organ är livräddande behandling för patienter med kroniska hjärt- eller leversjukdomar. För den som blir transplanterad innebär det en stor omställning i livet, från att ha varit kronisk sjuk till att leva med ett nytt organ. Efter en transplantation är målet att personen ska kunna återgå till ett normalt liv. Syfte: Syftet med litteraturstudien var att belysa den transplanterades perspektiv på att leva med ett nytt organ. Metod: I litteraturstudien har tio kvalitativa studier granskats och analyserats med inspiration av innehållsanalys. Artikelsökning gjordes i Cinahl, PubMed och PsycInfo. Resultat: I resultatet framkom tre huvudkategorier: ”Förändrad kropp”, ”Känslomässig berg- och dalbana” och ”Att leva vidare”. Under dessa framkom åtta underkategorier. Slutsats: Att genomgå en organtransplantation är en livsomvälvande upplevelse som förändrar livet för alltid. För sjuksköterskan är det viktigt att vara medveten om patientens perspektiv för att kunna ge god och anpassad omvårdnad. Trots att transplantationen följs av en påfrestande återhämtning både fysiskt och psykiskt så ges man genom ett nytt organ en andra chans i livet och hopp om en bättre framtid.   Nyckelord: Organtransplantation, patientperspektiv, omvårdnad / ABSTRACT Background: A new organ is a lifesaving treatment for patients living with chronicle illness in heart or liver. To be transplanted implicates a big change in life, from living with a chronicle illness to be living with a new organ. After the transplantation the aim for the patient is to go back to living a normal life again. Aim: The aim of this literature review was to elucidate the transplanted patient perspective of living with a new organ. Method: In this literature review ten qualitative studies were viewed and analysed. The articles were searched in CINAHL, PubMed and PsycInfo.  Result: The result identified three main categories: ”Changed body”, ”Emotional rollercoaster” and ”To manage to keep living”. From these categories eight sub categorize were identified. Conclusion: To be transplanted is a life changing experience that changes the life forever. It is important for the nurse to be aware of the patient perspective to be able to offer a good and suitable care for the patient. Though the transplantation is followed by a difficult recovery, both physical and psychological, to be transplanted gives you a second chance in life and hope of a better future. Keywords: Organ transplantation, patient perspective, nursing