京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21960号 / 医博第4502号 / 新制||医||1037(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 平井 豊博, 教授 松原 和夫, 教授 湊谷 謙司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22004号 / 医博第4518号 / 新制||医||1038(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 辻川 明孝, 教授 中川 一路, 教授 高橋 淳 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13355号 / 論医博第2201号 / 新制||医||1044(附属図書館) / (主査)教授 妹尾 浩, 教授 羽賀 博典, 教授 武藤 学 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23079号 / 医博第4706号 / 新制||医||1049(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 松田 道行, 教授 稲垣 暢也, 教授 妹尾 浩 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23095号 / 医博第4722号 / 新制||医||1050(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊佐 正, 教授 井上 治久, 教授 渡邉 大 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Background: Cardiovascular disease (CVD) has emerged as a major cause of morbidity and mortality in HIV-infected adults. Research in noninfected populations suggests that knowledge of CVD risk factors significantly influences perception of risk. Understanding the level of risk factor knowledge and risk perception can inform the development of innovative interventions to reduce risk. The purpose of this study was to describe cardiovascular risk factor knowledge and risk perception in a cohort of HIV-infected adults. Specific aims included (a) describing the estimated risk of CVD, the perceived risk of CVD, and the level of CVD risk factor knowledge; (b) describing the relationship between estimated and perceived risk, and (c) examining the influence of risk factor knowledge on perceived risk of CVD. The Health Belief Model was the theoretical framework that guided the study. Methods: A prospective observational cohort; cross-sectional design. A convenience sample of 130 HIV-infected adults was recruited from two hospital-based HIV clinics. Each participant had one study visit in which all data were collected by direct interview. Results: Results: Mean age of enrollees was 48 years (SD 8.4); 62% were male; 41.5% White, 32% Black, 23% Hispanic; 56% current smokers; mean years since HIV diagnosis were 14.7; mean BMI 27 (SD 5.5); 48.5% had prehypertension. Higher scores on the Heart Disease Fact Questionnaire indicate a higher degree of knowledge. In this sample, the Mean was 19, (S.D. 3.5; range 6–25), indicating a fair degree of knowledge. Estimated and perceived risk were significantly, though weakly, correlated r (126) = .24, p = .01. Controlling for age, risk factor knowledge was not predictive of perceived risk (F[1,117] = 0.13, p > .05). Conclusions: HIV-infected adults are at increased risk for cardiovascular disease. Traditional CVD risk factors such as smoking, prehypertension, and being overweight are highly prevalent. Despite having a fair level of risk factor knowledge, knowledge did not influence perception of risk for CVD. Research to improve risk perception and to develop innovative interventions that reduce CVD risk is needed for this population.

La préservation statique à froid (SCS) est l’étalon-or de la préservation des organes après une greffe. En raison de la pénurie d’organes et de l’augmentation du nombre de patients figurant sur la liste d’attente, le recours aux organes provenant des donneurs à critères élargis, lesquels sont très sensibles au syndrome d’ischémie-reperfusion (IRS), ce qui entraîne une non-fonction primaire (PNF) ou un dysfonctionnement précoce (EAD), est de plus en plus fréquent.Cette recherche avait pour but d’étudier et d’identifier de nouvelles stratégies pour améliorer la qualité de la préservation des organes - d'atténuer les séquelles de l'IRS en utilisant la machine de perfusion hépatique à différentes températures et à différentes périodes d'utilisation après le prélèvement de l'organe ou en ajoutant une hémoglobine extracellulaire en tant que transporteur d'oxygène pendant le SCS.Deux modèles différents ex-vivo ont été analysés : L’un chez le petit animal avec des foies de rats normaux et stéatosiques, pour la perfusion hypothermique (HMP) et SCS avec le transporteur d'oxygène et au niveau préclinique, des foies humains stéatosiques récusés, pour la perfusion normothermique (NMP).Les résultats ont confirmé de manière significative l'intérêt de l’HMP dans la phase pré-ischémique du SCS et celui de l'utilisation de l'hémoglobine extracellulaire en améliorant la fonction hépatique, le maintien de l'anatomie des hépatocytes et en réduisant des marqueurs du stress oxydatif, de l'apoptose et de l'inflammation. Egalement, l'utilisation de NMP a permis d'analyser les foies sévèrement stéatosiques pouvant être récupérés pour une transplantation dans un avenir très proche.Cette recherche met en évidence de nouvelles approches en matière de préservation d'organes susceptibles d'augmenter le pool d'organes et d'améliorer les résultats en transplantation hépatique.Mots-clés : greffe de foie, stockage froid dans le froid, perfusion dans une machine à foie, lésion de reperfusion par ischémie, transporteur d'oxygène. / Static cold storage (SCS) is the gold standard of organ preservation after being procured for transplantation. Due to the organ shortage and the increase of number of patients in the waiting list have pushed the use organs from extended criteria donors which are very susceptible to the ischemia reperfusion syndrome (IRS) leading to primary non-function (PNF) or to early allograft dysfunction (EAD).This research was aimed to study and identify new strategies to improve the quality of organ preservation -liver, to attenuate the IRS sequels by using the liver perfusion machine (LPM) at different temperatures and times of usage after the organ procurement or by adding an extracellular hemoglobin as an oxygen carrier during SCS.Two different ex-vivo models were analyzed: small animal -normal and steatotic rat livers, for hypothermic perfusion (HMP) and SCS with the oxygen carrier and preclinical -steatotic discarded human livers, for normothermic perfusion (NMP).The results significantly confirmed the benefit of the HMP in the preischemic phase of SCS and that of the use of the extracellular hemoglobin by improving the liver function, maintenance of the hepatocytes anatomy and by a reduction of the oxidative stress, apoptosis and inflammation markers. Also, the use of NMP permitted to analyze the severely steatotic livers that can be rescued for transplantation in the very near future.This investigation unveils new approaches in organ preservation that could increase the pool of organs and improve the results in liver transplantation. Key words: liver transplantation, static cold storage, liver machine perfusion, ischemia reperfusion injury, oxygen carrier.

Most South Africans die without their organs being harvested for transplantation. In a country where motor vehicle accidents or violent crime are often the cause of death, presumably leaving most of the organs fit for transplantation, it is astounding that the offer of organs doesn’t meet the demand. The aim of this dissertation is to find a practical solution for the current shortage of transplantable human organs in South Africa. This is achieved by critically discussing current South African legislation regulating organ transplantation, considering alternative organ procurement methods, as well as the impact that bioethics and the Constitution might have on the success of an organ procurement system. This dissertation is concluded with the realisation that although the current organ procurement method needs to be changed to required request, relieving the organ shortage will only be achieved by combining several proposed legislative changes, including, but not limited to, creating a national donor as well as a national waiting list; launching an educational campaign; limiting the role of relatives; and expanding the definition of death for the purpose of organ harvesting. KEY TERMS: organ procurement methods; National Health Act; Constitution; organ shortage; bioethics; autonomy; dignity; required request. / Dissertation (LLM)--University of Pretoria, 2013. / gm2014 / Public Law / unrestricted

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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.