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The use of organs from donors after circulatory death (DCD) has been recommended as one strategy to enlarge the donor pool and raise the transplant rate. However, DCD allografts had higher incidence of early post-transplant dysfunction. The general aim of this research project was to develop clinical and experimental strategies to reduce the incidence of early post-transplant dysfunction of kidney and liver allografts from DCD. First the ability of a clinical scoring system based on donor data for identifying DCD kidneys with high-risk of post-transplant dysfunction was evaluated using the Oxford and the UK National DCD kidney transplant cohorts. This works suggest that stratification of DCD kidneys before transplantation might allow early identification of kidneys in which lower graft function and survival could be expected if any additional therapeutic intervention is implemented. Second, as it has been suggested that hypothermic machine perfusion (HMP) may protect DCD kidneys from additional preservation injury and improve their outcome after transplantation, this work explored the benefit of HMP as preservation technique fo DCD kidneys in Oxford and discusses the potential of this technique for reducing the incidence of post-transplant dysfunction in DCD kidneys. The Oxford. Liver Group has provided evidence of the benefit of preservation with normothermic machine perfusion (NMP) on post-transplant function and survival of DCD liver allografts. In this work, the molecular mechanisms associated with this benefit were characterized using micro array technology. This analysis suggests that the beneficial effect ofNMP may be associated with the induction of the ischaemic preconditioning phenomenon and highlights a group of genes with potential for gene therapy. Finally, this works provides the "proof-of-concept" that the use of a non-mammalian viral vector for gene transfer of kidneys and livers during conventional cold preservation is feasible and is not associated with additional tissue injury.

Orientador: Luís Gustavo Modelli de Andrade / Banca: André Luíz Balbi / Banca: Silvana Molina / Banca: Lilian Monteiro Pereira / Banca: Marilda Mazzali / Resumo: Introdução: Os receptores de transplante de órgãos sólidos apresentam elevada incidência de não adesão medicamentosa. Existem poucos estudos de intervenção com abordagens visando o aumento da adesão. Objetivo: Avaliar o impacto da estratégia educacional e comportamental na adesão de transplantados renais no período dos três primeiros meses após o transplante. Métodos: Estudo prospectivo de pacientes incidentes em transplante renal. Os pacientes foram randomizados em dois grupos: Grupo controle de orientações usuais da equipe médica e grupo intervenção de orientações usuais somadas à educação complementar (orientações sobre a importância dos imunossupressores e modificações comportamentais com duração de 30 minutos). A adesão foi avaliada pelo questionário de adesão ITAS ao fim de três meses. Foram avaliadas a função renal aos 3, 6 e 12 meses e a incidência de rejeição. Resultados: A não adesão foi de 46,4% no grupo controle e 14,5% no grupo de tratamento (p=0,001). O razão de chance para não adesão foi 2,59 (IC: 1,38 - 4,88) vezes maior no grupo controle. A análise multivariada mostrou que pertencer ao grupo controle aumentou o risco de não adesão em 5,84 vezes (IC: 1,8 - 18,8, p=0,003). Não houve diferenças na função renal e nas taxas de rejeição entre os grupos. Conclusão: A não adesão é elevada nos três primeiros meses do transplante. A estratégia comportamental e educativa objetivando maior esclarecimento da importância do uso dos imunossupressores aumentou significantemente à adesão a terapia imunossupressora / Abstract: Not available / Doutor

Steady state crossflow microfiltration (CMF) is an important and often necessary means for varying sized particle separation. It has been widely used in both industrial and biomedical processes, including a wearable water removal device intended to maintain end stage renal disease (ESRD) patients euvolemic. For kidney replacement therapies, there are few options available. Kidney transplantation still represents the optimal treatment for ESRD patients, even though it often requires daily post-transplant medication including immunosuppressant drugs to avoid rejection of the transplanted organ. The transplanted kidney itself has an average lifespan of only 10 years. The biggest engineering contribution to the cited problem was made about 60 years ago with the invention of dialysis machines (or some variation thereof). Dialysis still represents the optimal and most widely used therapeutic approach to renal replacement during long waits on a transplant list. The present-day dialysis system is bulky, totally mechanical, and extracorporeal, leading to a widely used therapy that is only effective in extracting water and toxins out of the blood-stream, but still with major drawbacks (i.e. intermittent treatments, 5-hours thrice-weekly, and forcing clinic-centered therapy) that are permanently costly. These drawbacks pose a major impediment to rehabilitation or any other lifestyle activity such as working or studying. Of all the vital organs, the kidney is both the most subtle in its homeostatic action and the most complex in terms of the structures it uses to accomplish its action. This thesis proposes a single facet of the multiple complexity of this vital organ: filtration. To that effect, CMF of blood suspensions through a microsieve were studied. Experiments, reported here, have correlated macroscopic measurements - filtration rates, transmembrane pressures (TMP), shear rates - during filtration through a photolithographically pored semiconductor membrane with direct observation of erythrocyte behavior at the filtering surface. Erythrocytes, the preponderant particles in blood, are believed to dominate filtration resistance. At low filtration rates (low TMP), erythrocytes roll along the filter, but at higher rates (higher TMP), there is an increasing probability of their sticking to the sieve. The design of membrane separation processes requires quantitative expressions relating the separation performance to material properties. The factors controlling the performance of CMF have been and continue to be extensively reviewed. There have been a number of influential approaches in CMF. Most have been based on the rate limiting effects of the concentration polarization of rejectate at the sieving surface. Various empirical and intuitive models exist which have been critically assessed in terms of their predictive capability and applicability to CMF from a microfluidic channel. Chapter 1 summarizes this assessment. Chapter 2 takes a closer look at how erythrocytes behave in a microfiltration environment. Maximum steady-state filtration flux has been observed to be a function of wall shear rate, as predicted by any conventional cross-flow filtration theory, but to show weak dependence on erythrocyte concentration, contrary to theory based on convective diffusion. Flux is known to be directly proportional to the TMP; however, since the pressure drop across a channel decreases along the direction of flow, TMP must modulate along the channel (highest at the leading edge of the membrane and lowest at the trailing edge). As a consequence, an area of stuck particles growing from the inlet (regimen of high TMP) has been observed, leading to a “fouling cascade.” Post-filtration scanning electron micrographs revealed significant capture and deformation of erythrocytes in all filter pores in the range 0.25 to 2 m diameter. This was then found to form a self-assembled partially complete monolayer. Filtration rates through these filters were reported and a largely unrecognized mechanism was proposed, which allows for stable filtration in the presence of substantial cell layering. Chapter 3 proposes a microfiltration model that pertains to non-deformable particles that are large enough to intrude significantly into the shear layer of a microchannel. A stable, stationary multilayer of particles was studied, whose thickness is shear-limited. The structure and parameters in that limit of steady filtration in this environment was then identified. A steady cake-layer thickness was observed and because of the simple geometry afforded by uniform spheres, the force balance, cake resistance, and filtration rate were derived from first principles. The good fit of the data to the proposed mechanism, provides a firm basis for the semi-quantitative analysis of the behavior of more complex suspensions. Finally, in Chapter 4, a design methodology was imposed to maintain the TMP constant throughout the whole sieving surface by introducing a flow chamber beneath and parallel to the sieve’s main flow. Co-current filtration was found to allow the TMP to remain stable along the membrane surface, enabling the entire sieve to perform optimally, and thus allowing greater stable filtration rates to be achieved. Co-current flow conditions allowed for twice as much filtration flux compared to a conventional CMF modality.

Thesis--Auburn University, 2009. / Abstract. Vita. Includes bibliographical references (p. 38).

Made available in DSpace on 2016-06-07T17:12:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-02-06. Added 1 bitstream(s) on 2016-06-07T17:16:33Z : No. of bitstreams: 1 000864048.pdf: 1351667 bytes, checksum: 796481e4e6af079db8e1da7cbec4de0f (MD5) / Introdução: Os receptores de transplante de órgãos sólidos apresentam elevada incidência de não adesão medicamentosa. Existem poucos estudos de intervenção com abordagens visando o aumento da adesão. Objetivo: Avaliar o impacto da estratégia educacional e comportamental na adesão de transplantados renais no período dos três primeiros meses após o transplante. Métodos: Estudo prospectivo de pacientes incidentes em transplante renal. Os pacientes foram randomizados em dois grupos: Grupo controle de orientações usuais da equipe médica e grupo intervenção de orientações usuais somadas à educação complementar (orientações sobre a importância dos imunossupressores e modificações comportamentais com duração de 30 minutos). A adesão foi avaliada pelo questionário de adesão ITAS ao fim de três meses. Foram avaliadas a função renal aos 3, 6 e 12 meses e a incidência de rejeição. Resultados: A não adesão foi de 46,4% no grupo controle e 14,5% no grupo de tratamento (p=0,001). O razão de chance para não adesão foi 2,59 (IC: 1,38 - 4,88) vezes maior no grupo controle. A análise multivariada mostrou que pertencer ao grupo controle aumentou o risco de não adesão em 5,84 vezes (IC: 1,8 - 18,8, p=0,003). Não houve diferenças na função renal e nas taxas de rejeição entre os grupos. Conclusão: A não adesão é elevada nos três primeiros meses do transplante. A estratégia comportamental e educativa objetivando maior esclarecimento da importância do uso dos imunossupressores aumentou significantemente à adesão a terapia imunossupressora

Orientador: Marcelo Lopes de Lima / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-15T03:07:06Z (GMT). No. of bitstreams: 1 Cotrim_CristianoAugustoCalderaro_M.pdf: 1654250 bytes, checksum: 1d22b5f31344acd1edcaf4646caac447 (MD5) Previous issue date: 2009 / Resumo: Tratamento laparoscópico da linfocele pós-transplante renal. Introdução: O tratamento cirúrgico da linfocele sintomática pós-transplante renal consiste na criação de uma fenestração entre a cavidade abdominal e a linfocele para permitir a drenagem eficiente da linfa. Objetivo: Avaliar os resultados do tratamento cirúrgico laparoscópico da linfocele pós-transplante renal quanto ao índice de sucesso e recidiva. Pacientes e Métodos: Foram avaliados os dados de 25 pacientes que desenvolveram linfocele sintomática pós-transplante renal. Resultados: Entre 1996 e 2008, 991 pacientes foram transplantados na Universidade Estadual de Campinas, São Paulo, Brasil (523 doadores falecidos, 468 doadores vivos). Em 25 pacientes (2,52%) desenvolveu-se linfocele sintomática e a drenagem laparoscópica foi executada. As indicações para a drenagem cirúrgica incluíram disfunção do enxerto (84%), sintomas locais (16%) ou ambos (32%). A média de tempo de diagnóstico da linfocele após o transplante foi de 14,2±6 semanas. A média de internação foi de 1,5±0,2 dias. Dois pacientes (8%) desenvolveram complicações pós-operatórias (uma lesão ureteral e uma hérnia incisional) requerendo tratamento cirúrgico. Depois de uma média de seguimento de 36,2 meses, um paciente apresentou uma recorrência sintomática. Conclusão: A técnica laparoscópica foi efetiva para o tratamento da linfocele pós-transplante renal e pode ser considerada como método de escolha para o seu tratamento cirúrgico / Abstract: Laparoscopic treatment of lymphoceles after kidney transplantation Introduction: The surgical treatment of symptomatic lymphocele after kidney transplantation consists in the creation of a fenestration between the lymphocele and the abdominal cavity to allow efficient drainage of lymph. Objective: To evaluate the results of laparoscopic surgical treatment of lymphocele after kidney transplantation considering the rate of success and recurrence. Materials and Methods: The records of 25 patients who underwent surgical treatment for a symptomatic lymphocele following kidney transplantation were retrospectively reviewed. Results: Between 1996 and 2008, 991 patients received a kidney transplant at the Campinas State University, São Paulo, Brazil (523 cadaveric, 468 living). In 25 patients (2.52%) a symptomatic lymphocele developed and laparoscopic drainage was completed. The indications for surgical drainage were graft dysfunction (84%), local symptoms (16%) or both (32%). The mean time to surgical therapy was 14.2 weeks. Mean hospital stay was 1.5±0.2 days. The average time of appearance of lymphocele after transplantation was 14.2 ± 6 weeks. Postoperative complications occurred in only two patients (8%) (one ureteral injure and one incisional hernia) and required reoperation. After a mean follow up of 36.2 months, 1 patient had a symptomatic recurrence. Conclusions: Laparoscopic technique is effective and can be considered the method of choice to treat lymphocele following kidney transplantation / Mestrado / Cirurgia / Mestre em Cirurgia

M.A. (Psychology) / The purpose of this study was to determine whether psychological factors contribute to the rejection of a transplanted kidney. After a review of existing literature on the relationship between various psychological factors and immunological system of the body, it was hypothesized that psychological factors such as state- and trait anxiety, stress, locus of control as well as hopelessness would affect immune responses, and therefore contribute to the acceptance or rejection of a transplanted kidney. In order to test the hypothesis, patients of the Johannesburg Hospital undergoing haemodialysis and on the waiting list for kidney transplant were tested. Out of the initial sample, 12 of these patients, who had undergone a renal transplant, were used in the study. Out of the 12 patients, 6 patients had accepted the graft, while 6 patients had rejected the graft. The tests used in the study were the Spielberger State-Trait Anxiety Scale, Hopelessness Scale, Health Locus of Control and the Rotter Internal-External Locus of Control Scale. The analysis of the data indicated a significant difference in the mean score for the two groups with relation to state anxiety, trait anxiety and health locus of control. The results indicated that the higher the state and trait anxiety, and the more internal the health locus of control of the patient, the greater the chances that the graft would be accepted. The results of this study indicated that psychological factors do contribute to the immune response of the body to a transplanted kidney. This would imply that more research is necessary to establish influence of various psychological as well as social variables in transplants and medical immunology.

Ph.D. (Psychology) / In this study the illness behavior of people with a life threatening illness was described and the relationship between stress, affect and illness behavior investigated. An overview of the literature shows that the illness behavior patients exhibit is and should be an important consideration in the diagnosis of illness and treatment of patients. This is evident in reports of a high amount of ill people who do not receive treatment and the high amount of patients who seek treatment for minor ailments. It is further evident in the light of findings that illness behavior does not always accurately represent the physical disfunction and that it may even be present in :t- the absence of a physical disfunction. The paucity of research on the illness behavior of specific patient groups, and of information on the relative effects of physical versus psychological factors on illness behavior, indicate a void in the literature. The present study investigates this relationship in a group of patients with a life threatening illness. In the first phase of the study 15 kidney transplant patients were compared to themselves, under normal conditions and conditions of stress, regarding affect, the experiencing of stress and the reporting of physical symptoms. In the second phase of the study 15 kidney transplant patients were compared to 15 patients with acute but minor ailments regarding the reporting of physical symptoms, affect, the experiencing of stress and the psychosocial impact of the illness.