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

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Title: Physiotherapy as part of multidisciplinary care for patients following a lung transplant operation Objective: To evaluate the mobility of patients in the first days after lung transplantation. To compare the quality of life according to Karnofsky index and Jones dyspnea index. To relate spirometric values FVC and FEV1 of patients in the period prior to lung transplantation with the values in the first year after lung transplantation. Check the link between the development of quality of life and development of spirometric values. Methods: It is a pilot study, which was attended by 18 probands (13 men and 5 women), aged between 14 and 68 years. The data were collected on regular intervals using questionnaires on quality of life (Karnofsky index and Jones dyspnea index) and spirometric examinations taking place at the Motol University Hospital. The data were statistically analyzed using MS EXCEL, mostly using correlations and pair T - test. Results: Results showed substantial changes in the level of significance of p <0,01 both in the development of the quality of life, and in the development of spirometric values compared during the first year after lung transplantation with values before the transpantion. Another important result was the negative effect of a prolonged stay at intensive care...

The Human Organ Transplantation Act - moral and ethical problems of its application This thesis deals with issues related to the applications of the Human Organ Transplantation Act. It is focused on the assessment of existing legislation regarding transplantation, the identification of problematical areas of transplantation law and the possibility of their correction. The thesis is divided into several parts. At the beginning it deals with the history and development of transplant medicine. It also contains a description of the current legislation and a brief summary of an international regulation. The main focus of the thesis is to analyze the deficiencies in Czech legislation and to emphasize the interdisciplinary nature of the transplant law. Finally, it analyzes the forthcoming amendment to The Human Organ Transplantation Act prepared by the Ministry of Health. The Human Organ Transplantation Act is a modern legislation respecting international commitments of the Czech Republic. Nature of the transplant legislation is given by its fundamental aspects  the principle of presumed consent in connection with legally provided guarantee to respect disagreement expressed in accordance with law, the preference of a deceased donor prior to a living one, the principle of fairness in the allocation of...

Hematologic malignancies are among the most often diagnosed forms of cancers. Treatment regimens often utilise various combination of cytostatic drugs and total body irradiation and subsequent transplantation of hematopoietic stem cells. One of the most common combinations includes ionising radiation with the antineoplastic alkylating agent cyclophosphamide. In this study we used congenic Ly5.2 and L5.1 mouse strains that express different isoforms of CD45 antigen to evaluate the effects of various time interval between cyclophosphamide and irradiation treatments on the viability of hematopoietic stem cells and their viability. This was done by competitive repopulation assay. The results revealed that level of engraftment and subsequent reconstitution of hematopoiesis can significantly vary and depend on the time interval between cyclophosphamide and total body irradiation administrations. The results indicate that patients with hematologic malignancies could possibly benefit from the treatment especially if they received transplants after being irradiated five or seven days after cyclophosphamide because at that time point their own stem cells would be least competitive. Key words: bone marrow transplantation, cyclophosphamide, chimerism, hematopoietic stem cells, ionising radiation

Currently there is a critical shortage of transplantable organs in the UK. The existing evidence base highlights that cultural and religious norms can hinder familial consent and uptake of registration as an organ donor, particularly within ethnic minority groups. There is a dearth of information relating to the Polish community in the UK. Since the expansion of the European Union and the potential and consequent economic migration of Poles to the UK, this community presents a potential significant contribution to the active transplant waiting list, NHS Organ Donor Register and requests made for organs for donation on behalf of a relative. The aim of the study was to examine in depth, the perceptions of the relationship between deceased organ donation, gift exchange and religion. Due to the exploratory nature of the study, grounded theory methodology was used and one to one interviews were carried out with 31 participants who were recruited using a purposive convenience sampling strategy. This approach allowed for the collection of rich and deep data in a hitherto under-researched issue with the Polish community in the UK. To contextualise the key findings of the relationship, an in-depth analysis of settlement patterns, helping behaviour and experiences of and attitudes toward religion was conducted. The relationship between religion and gift-exchange was perceived to interact in different ways with deceased organ donation depending on the context. For the individual making an end-of-life choice, gift exchange impacted on the perception of the organ as a gift and whether reciprocity was expected, religion shaped views of the need for the body after death and social and cultural norms influenced the view of the 'typical' donor and family discussion of donation. For the relatives, social, religious and cultural norms impacted on death rituals and the conceptualisation of the dead body and experiences of a relative's death. This study contributes to an understanding of the social, cultural and religious norms toward deceased organ donation from a Polish perspective and the implications for policy, health promotion and clinical practice.

Bakgrund: Varje år genomförs mer är 50 000 stamcellstransplantationer världen över och antalet ökar. Stamcellstransplantation, är en potentiell terapeutisk behandling för ett flertal olika livshotande blodsjukdomar. Återhämtningen efter behandlingen är lång, genomsnittstiden är ett år innan patienterna är tillbaka till samma livskvalitet de hade innan. Syfte: Syftet med litteraturstudien var att beskriva patienters upplevelse av att genomgå en stamcellstransplantation Metod: En litteraturstudie baserad på 1o kvalitativa studier. Resultat: Resultatet presenterades i fyra kategorier och sammanlagt tolv subkategorier. Att livet hotas innebar osäkerheter och rädslor. Alternativa hanteringsstrategier som användes var optimism, att skjuta ifrån sig, tro på något större, förlita sig på andra och att bli expert på sin sjukdom. Konsekvenser av behandlingen var kroppsligt lidande och att vara nära döden. Nystart innebar en ny tillvaro, förändrad syn på livet och förändrade relationer. Konklusion: Upplevelsen av behandlingen varierar mellan varje patient och osäkerhet och rädslor inför vad som kommer att hända fanns. Hopp gavs av anhöriga och vårdpersonal. För att hantera situationen använde de sig av olika strategier. Bristfällig information bidrog till patienternas osäkerhet och behov av bättre individuellt anpassad information finns. Nyckelord: Livskvalitet, patienters upplevelse, stamcellstransplantation / Title: Patients' experience of undergoing stem cell transplantation. Background: Every year more than 50 000 stem cell transplantations are performed worldwide. Stem cell transplantation is a potential therapeutic treatment for several life-threatening blood diseases. The recovery after treatment is long, the average time is one year before the patients are back to the same quality of life as they had before treatment started. Aim: The aim of this study was to describe patients' experience of undergoing stem cell transplantation. Methods: A literature study based on 10 qualitative articles. Results: The results were presented in four categories and twelve subcategories. Threat on life included both insecurity and fears. Alternative coping strategies used were optimism, distance yourself, believe in something bigger, relying on others and becoming expert on your disease. Consequences of the treatment included bodily suffering and being close to death. The new beginning included a new existence, a changed outlook on life and changed relationships. Conclusion: The experience of the treatment differed between patients and there was uncertainty and fears about what was going to happen. Relatives and health professionals gave hope to the patients. Different coping strategies were used to cope with the situation. Inadequate information contributed to the uncertainty among the patients and there is a need for better individualized information. Keywords: Quality of life, patients experience, stem cell transplantation

INTRODUÇÃO: O Transplante de fígado evoluiu nas últimas décadas, sempre em busca de melhorar a sobrevida do paciente e do enxerto. Importante causa de morbi-mortalidade é a disfunção precoce do enxerto (DPE) e o não funcionamento primário do enxerto (NFP). Diversos biomarcadores vem sendo estudados, porém ainda não há um consenso. Com isso tivemos a hipótese científica de avaliar e quantificar a função hepática avaliada pele verde de indocianina (VI) após o transplante de fígado. OBJETIVO: Avaliar a disfunção precoce do enxerto pela taxa de depuração plasmática do (VI) no pós-operatório imediato de transplante hepático. MÉTODO: Estudo clinico, de julho de 2014 a junho de 2015, prospectivo e observacional. Um total de 40 pacientes fizeram parte desta análise pela pulso-densitometria, usando o sistema de Limon (Impulse Medical System, Munique, Alemanha). Foram avaliados também o índice de risco de doadores (DRI), os critérios de Wagener e de Olthoff e preditores prognósticos pós-transplante de fígado. Todos os testes realizados levaram em consideração um alfa bidirecional de 0,05 e intervalo de confiança (IC) de 95% e foram realizados com apoio computacional dos softwares IBM SPSS 25 (Statistical Package for the Social Sciences) e Excel 2016® (Microsoft Office). RESULTADOS: Um total de 40 pacientes foram avaliados. A idade média foi de 53 anos e a maioria do sexo masculino (70%). A etiologia da cirrose mais comum foi hepatite por vírus C (42,5%). Os pacientes eram Child C em 45% dos casos. A taxa de retenção o verde de indocianina em 15 minutos (R15) permaneceu aumentada nos dias 1 e 3 de pós operatório ( > 10%) e normalizou no 7º dia de pós operatório ( < 10%). A taxa de depuração manteve valores normais, com 18,5% no 1º dia; 20,3 no 3º e 20,4 no 7º dia pós operatório. A comparação com os critérios de Olthoff e Wagener não mostrou diferença estatística (p=0,467 e p=0,178). Na comparação com DRI > 1,5 encontrou-se p=0,066, e com desfecho negativo (Perda do enxerto ou óbito) em p=0,063. A depuração do verde de indocianina mostrou relação significativa com o grau de lesão histológica pós isquemia e reperfusão (p=0,030). CONCLUSÃO: A reserva funcional hepática apresenta-se diminuída no pós operatório recente de transplante de fígado com melhora ao final da primeira semana. A depuração hepática do verde de indocianina não relaciona-se com a disfunção precoce do enxerto avaliada pelos critérios de Oltoff e Wagener. Por outro lado ela tem uma relação significativa inversamente proporcional ao grau da lesão hepática pós isquemia e reperfusão / INTRODUCTION: Liver transplantation has evolved in the last decades, alway seeking to improve patient and graft survival. Important cause of morbidity and mortality is early graft dysfunction (EGD) and primary non-graft function (NGF). Several biomarkers have been studied, but there is still no consensus. With this we had the scientific hypothesis to evaluate and quantify the hepatic function evaluated by indocyanine green (IG) after liver transplantation. OBJECTIVE: To evaluate the early graft dysfunction by the plasma clearance rate of (IG) in the immediate postoperative period of liver transplantation. METHOD: Clinical study, from July 2014 to June 2015, prospective and observational. A total of 40 patients were part of this analysis by pulse-densitometry, using the Limon system (Impulse Medical System, Munich, Germany). Donor risk index (DRI), Wagener and Olthoff criteria, and prognostic predictors after liver transplantation were also evaluated. All the tests performed into account a bidirectional Alpha of 0.05 and a 95% confidence interval (CI) and were performed with computational support of the software IBM SPSS 25 (Statistical Package for the Social Sciences) and Excel 2016 (Microsoft Office). RESULTS: A total of 40 patients were evaluated. The mean age was 53 years and the majority of them was male (70%). The most common etiology of cirrhosis was C virus hepatitis (42.5%). The patients were Child C in 45% of cases. The indocyanine green retention rate in 15 minutes (R15) was increased on days 1 and 3 postoperatively ( > 10%) and normalized on the 7th postoperative day ( < 10%). The ICG clearance rate maintained normal values, with 18.5% in the 1st day; 20.3 in the 3rd and 20.4 in the 7th postoperative day. The comparison with Olthoff and Wagener criteria showed no statistical difference (p=0,467 e p=0,178). In the comparison with DRI > 1.5 a p = 0.066 was found; and with negative outcome (Loss of graft or death) a p = 0.063 was found. The clearance of indocyanine green showed a significant relation with the degree of histological lesion after ischemia and reperfusion (p = 0.030). CONCLUSION: The liver functional reserve is decreased in the recent postoperative period of liver transplantation with improvement at the end of the first week. Hepatic clearance of indocyanine green is not related to early graft dysfunction assessed by Oltoff and Wagener criteria. On the other hand, it has a significant relationship inversely proportional to the degree of ischemia and reperfusion hepatic injury

Die Forschung um die Optimierung der Insel-Transplantation nimmt in der Behandlung des Typ I Diabetes eine Vorreiterstellung ein. Nachdem im Zeitraum von drei Jahrzehnten Fortschritte im Bereich der Insel-Isolierung und Immunosuppression gemacht wurden, stehen wir heute am Beginn des klinischen Einsatzes dieser Technik an ausgewählten Patientengruppen. Ziel der vorliegenden Arbeit ist die umfassende Funktionsdiagnostik isolierter porziner mikroverkapselter Inseln. Mit Hilfe einer miniaturisierten Mikroperifusionskammer wurde der Einfluss des Kulturmediums, der IEQ-Zahl sowie der Mikroverkapselung auf die Insulinsekretion untersucht. Zusätzlich wurde die Insel-Vitalität den Perifusions- Parametern gegenübergestellt. Untersucht wurden zudem die dosisabhängige Stimulierbarkeit der Inseln mit Nährstoffen, Hormonen und Neuromediatoren unter normo- und hyperglykämischen Bedingungen und ihre Aktivierbarkeit bei anhaltender In-Vitro-Kultur. / The research towards an optimized transplantation of islet cells takes an outrider position in the future treatment of the typ I diabetes. After three decades of progress in the field of island isolation and immunosuppression, we face the beginning of the clinical application of this technology at selected groups of patients. A goal of this study was a comprehensive functional diagnostic of isolated microencapsulated porcine Islets of Langerhans. With a new miniaturized microperifusion chamber we studied the influence of the culture medium, IEQ numbers as well as the microencapsulation on the insulin secretion of the islet cells. Additionally the island vitality was correlated to functional parameters received during microperifusion. Besides this we qualitatively and quantitatively examined the dose-dependent stimulation of the islands with nutrients, hormones and neuromediators under normo and hyperglycaemic conditions as well as their function under prolonged in-vitro-culture.

O antígeno leucocitário humano (HLA)-G corresponde a uma molécula não clássica de classe I do complexo principal de histocompatibilidade. Segundo a literatura, tal molécula pode ser expressa em ambos os contextos patológico e fisiológico. Diversos autores têm apresentado evidências acerca do papel do HLA-G na tolerância imune do feto durante a gestação, bem como para o sucesso de alotransplantes. No entanto, até o momento, há poucas informações publicadas a respeito da expressão fisiológica dessa molécula nos diferentes órgãos humanos. Em acréscimo a isso, a participação do HLA-G em eventos fisiológicos é ainda um assunto controverso entre cientistas. Tendo em vista o exposto, o objetivo desse estudo foi investigar a expressão da proteína HLA-G em órgãos fetais durante o progredir da gestação, bem como em órgãos adultos. Trata-se de um estudo descritivo, comparativo, transversal e retrospectivo realizado com base na revisão de prontuários e análise de necropsias/biópsias de diferentes órgãos de fetos e adultos através do método de imunohistoquímica. Os resultados demonstraram a existência de diferença estatística significativa na imunomarcação da proteína HLA-G em glândulas adrenais (p= 0,0003), baço (p= 0,0276), coração (p= 0,0474), fígado (p= 0,0052), pulmões (p = 0,0367), rins (p = 0,0377) e timo (p= 0,0336) na comparação entre o primeiro e segundo trimestre gestacional; em glândulas adrenais (p= 0,0329), baço (p= 0,0095), pâncreas (p= 0,0009) e placenta (p= 0,0285) na comparação entre o segundo e terceiro trimestre gestacional; e no coração (p= 0,0304), fígado (p= 0,0055), pulmões (p= 0,0150) e rins (p= 0,0312) na comparação entre o terceiro trimestre gestacional e a fase adulta. Foi verificado um aumento na expressão do HLA-G fetal a partir do segundo trimestre gestacional em órgãos como glândulas adrenais, coração, fígado, rins, timo e pulmões. Entretanto, isso não foi uma constante, pois em outros, a exemplo do baço, pâncreas e placenta, não observouse essa tendência durante o mesmo período. Durante o terceiro trimestre gestacional e a fase adulta evidenciou-se valores mais elevados para a expressão do HLA-G nos rins, e valores bastante inferiores no fígado. A expressão fisiológica do HLA-G embora positiva em todos os órgãos avaliados, nos três trimestres gestacionais e/ou na fase adulta, apresentou diferenças na intensidade e localização nos diferentes órgãos e períodos. Os achados a partir dessa pesquisa certamente representam uma importante contribuição para um melhor entendimento do mecanismo gestacional, assim como da fisiologia do HLA-G em adultos, sobretudo no que concerne o estabelecimento da tolerância imunológica em transplante de órgãos / Human leukocyte antigen (HLA)-G is a nonclassical class I major histocompatibility complex molecule. According to the literature, this molecule can be expressed in both pathological and physiological contexts. Several authors have presented evidence about the role of HLA-G in the immune tolerance of the fetus during pregnancy, as well as for the success of allotransplants. However, until now, there are very few published data regarding the physiological expression of this molecule in different human organs. Moreover, the role of HLA-G in physiological events is still a controversial subject among scientists. In view of the above, the objective of this study was to investigate the expression of HLA-G protein in fetal organs during the progression of gestation, as well as in adult organs. This was a descriptive, comparative, cross-sectional and retrospective study based on the review of medical records and immunohistochemical analysis of different organs of fetuses and adult people. The results showed a statistically significant difference in the immunostaining of HLA-G protein in adrenal glands (p = 0.0003), spleen (p = 0.0276), heart (p = 0.0474), liver (p = 0.0367), kidneys (p = 0.0377) and thymus (p = 0.0336) in the comparison between the first and second gestational trimesters; in adrenal glands (p = 0.0329), spleen (p = 0.0095), pancreas (p = 0.0009) and placenta (p = 0.0285) in the comparison between the second and third gestational trimesters; and in the heart (p = 0.0304), liver (p = 0.0055), lungs (p = 0.0150) and kidneys (p = 0.0312) in the comparison between the third gestational trimester and the adult phase. An increase of fetal HLA-G expression was observed from the second gestational trimester in organs such as adrenal glands, heart, liver, kidneys, thymus and lungs. However, this was not a constant finding, since in other organs including spleen, pancreas and placenta, this trend was not observed during the same period. During the third gestational trimester and the adult phase, higher values for HLA-G expression in the kidneys and much lower values in the liver were observed. Although the physiological expression of HLA-G has been positive in all evaluated organs (in the three gestational trimesters and/or in adulthood), it showed differences in its intensity and location in the different organs and periods. The findings from this research certainly represent an important contribution to a better understanding of the gestational mechanism, as well as on the physiology of HLA-G in adults, especially regarding the establishment of immunological tolerance in organ transplantation