Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Background Organ donation may occur after death determination by neurological criteria or by circulatory criteria (DCC). This thesis evaluates two controversial practices specific to DCC: (1) antemortem heparin administration to DCC donors with the aim of improving organ function, and (2) cardiac donation after DCC, which has not yet been adopted in Canada. Objectives (1) Describe antemortem heparin practices in DCC and explore its effects on transplant outcomes. (2) Describe the opinions, concerns, and insights of Canadian healthcare providers and the public regarding cardiac DCC. Methods Project 1: Systematic review and meta-regression analysis of published studies examining antemortem heparin in DCC donation. Projects 2 and 3: A qualitative interview study to evaluate the perspectives of healthcare providers and a mixed methods study involving focus groups with members of the Canadian public. Results Project 1: We found broad variability in the dosing and timing of heparin administration in DCC. While there were no clinical trials, meta-regression analysis detected no benefit to antemortem heparin in liver transplantation. Projects 2 and 3: Among healthcare providers, we found broad support for cardiac DCC but concerns about potential lack of support by the public. Among members of the public, we found majority support for cardiac DCC with priorities including respect for the wishes of dying individuals and ensuring that they are treated with dignity. Conclusions While preliminary results failed to demonstrate the benefit of antemortem heparin administration to DCC donors, high-quality clinical trials are needed to better evaluate the risks and benefits. Regarding cardiac DCC, despite healthcare providers’ concerns about lack of public support, most public stakeholders engaged in our study were supportive. The multi-modal approach of this thesis may serve as a model for evaluating other controversial practices in deceased organ donation. / Thesis / Candidate in Philosophy / Organs that are donated and transplanted from deceased individuals save thousands of lives every year. Some organs are donated after death by circulatory criteria (i.e., after the heart has stopped beating). We evaluated two controversial practices in organ donation after death is determined by circulatory criteria: (1) giving heparin, a blood thinner, just before death, and (2) heart donation after death is determined by circulatory criteria. In Project 1, our review of existing literature showed broad differences in heparin use around the time of death and heparin had no benefits on liver transplant outcomes. In Project 2, we found that healthcare providers and members of the public supported heart donation after death is determined by circulatory criteria but expressed concerns that are important to consider when establishing heart donation programs. Our approach of using multiple methods to evaluate practices in organ donation can serve as one model for evaluating other controversial practices in organ donation.

Thesis (DScMedSc (Medical Sciences)--University of Stellenbosch, 2010. / Bibliography / ENGLISH ABSTRACT: See full text for abstract / AFRIKAANSE OPSOMMING: Geen opsomming was ingehandig met tesis

published_or_final_version / Surgery / Doctoral / Doctor of Philosophy

Bakgrund: Antalet patienter som väntar på en organ transplantation har ökat stadigt under de senaste årtiondena. En förutsättning till att väntetiderna skall förkortas är att efterfrågan av organ blir mättat. Efterfrågan av organ är större än tillgången, detta medför förlängda väntetider inför en organ transplantation. Patienter som väntar på en organ transplantation blir lidande och detta bidrar till erfarenheter av fysiskt och psykiskt ohälsa. Syfte: Syftet var att beskriva erfarenheterna hos patienter som väntar på en organ transplantation samt att göra en metodologisk granskning av de valda artiklarnas datainsamlingsmetod. Metod: En beskrivande litteraturstudie som har undersökt 13 artiklar, majoriteten av artiklar var av kvalitativ design. Resultat: Patienters erfarenheter av att vänta på en organ transplantation förknippas ofta med känslor som ångest och depression. Patienter upplever att väntetiderna på att få en organ transplantation är långa och erfarenheter är att livet står på paus. Erfarenheter som patienterna upplever är att stöd från närstående och sjukvården har stor betydelse. Även att träffa andra patienter som väntar på en organ transplantation ansågs som ett stöd för patienterna. Patienterna beskrev att erfarenheterna av att få information från sjukvårdspersonalen om sin hälsosituation var av stor betydelse. De valda artiklarnas datainsamlingsmetod bestod av 11 kvalitativa intervjustudier. Två av artiklarna hade kvantitativ ansats där enkäter använts. Slutsats: Patienter som väntar på att genomgå en organ transplantation har ofta erfarenheter av att väntetiderna är långa och med tiden blir patienterna oroliga och rädda. Patienternas erfarenheter av stöd från sjukvårdpersonalen är viktiga för vårdprocessen och att sjuksköterskor därför har ett stort ansvar att anpassa vården efter patientens individuella behov. / Background: The number of patients waiting for an organ transplant has increased steadily for the past decades. A prerequisite for a successful transplantation program is of course that the demand for organs gets saturated by a steady supply of the same. This is unfortunately not the case as the gap between supply and demand is increasing, hence prolonging waiting times and negatively effecting the patients’ health and overall prognosis. Aim: Portrait the experiences of patients waiting for an organ transplant as well as conducting a methodological examination of the data collection method used in a selection of articles. Method: A descriptive literature that has examined 13 articles, the majority of articles were qualitative design. Results: Patients' experiences when waiting for an organ transplant is often associated with feelings such as anxiety and depression. Patients experiencing the waiting time to get an organ transplant as long and the experience is that the patient’s life is paused. Experiences which patients describes is that support from family and healthcare professionals are of great importance. Even to meet with other patients waiting for an organ transplant was considered as a support for patients. Patients described that experience of getting information from medical staff about his health situation was important for the patients. The articles selected data collection method consisted of 11 qualitative interview study. Two of the articles had quantitative design where surveys have been used. Conclusion: Patients waiting to undergo an organ transplant often have experience of waiting times are long and with time these patients are anxious and fearful. The patients experienced the support from medical staff is important to the care process and that nurses therefore have an important responsibility to adapt care to individual patient needs.

Mycophenolate mofetil (MMF) is widely used to minimise acute rejection following solid organ transplantation as it inhibits inosine monophosphate dehydrogenase (IMPDH) and thereby reduces lymphocyte activation. The effects of MMF and azathioprine on renal allograft outcome were examined by analysis of the national transplant database held at National Health Service (NHS) Blood and Transplant, Stoke Gifford, Bristol, UK. In a paired kidney analysis, MMF treated patients had a 3 year death censored graft survival of 91% (n=217) contrasts to 97% (n=231) in azathioprine treated patients (p=0.07) with an increased acute rejection rate in the first year after transplantation (44 v 31%, n=105 v 74, p<0.01). In a further study, 13% (n=71) of patients were found to be taking less than 1 g of MMF which was associated with a 3-fold increased risk of graft failure and inferior graft function up to 36 months. One strategy to improve graft outcome would entail targeting MMF dose according to pre-transplant IMPDH activity, which is known to display wide variability between patients, in order to maximize efficacy and minimize toxicity. Therefore, it was decided to measure pre-transplant IMPDH activity and to investigate associations with renal allograft outcome and MMF dose tolerated after transplantation. IMPDH activity was measured by detection of generated XMP by a validated HPLC method in the peripheral mononuclear cells of 55 patients waiting for renal transplantation and was found to exhibit a 4-fold variation of IMPDH activity. Black males had significantly increased IMPDH activity contrasts to Black females (p=0.01). Within the first year of transplantation, 71% (n=12) patients required a reduction in MMF dose. There was no association between pre-transplant IMPDH activity and MMF dose achieved at 1 year or MMF associated side effects or eGFR up to 36 months. It was proposed that the inter-individual variability of IMPDH activity may be associated with genetic polymorphisms and therefore sequencing of the exons of IMPDH I and II was undertaken. Two novel single nucleotide polymorphisms (SNPs), Leu244Leu and Ala285Thr, were identified in the IMPDH I gene. Patients with these variants did not exhibit differential IMPDH activity. Genotyping for established intronic SNPs was undertaken in our patient cohort as well as a random sample of 1040 recipients from the Collaborative Transplant Study DNA bank based at the University of Heidelberg, Germany. The presence of these SNPs did not increase the risk of rejection or affect graft function or MMF dose tolerated at 1 year after transplantation and there was no association between pre-transplant IMPDH activity, 5 year graft and patient survival and genotype. In our study, MMF treatment did not result in improved renal allograft outcomes in comparison to azathioprine therapy. Furthermore, we suggest that measurement of pre-transplant IMPDH activity or genotyping of the IMPDH enzymes is unlikely to assist in optimizing MMF dose and renal allograft outcome.

Ping-kuen Lam. / "May 1998." / Thesis (Ph.D.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (p. 109-121). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

by Henry Yurianto. / "18 September 1998." / Thesis (Ph.D.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (p. 138-149). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

published_or_final_version / Surgery / Doctoral / Doctor of Philosophy

published_or_final_version / Surgery / Master / Master of Surgery