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No description available.

In this study we have reproduced the prolongation of graft survival by ITI in a rat heart transplant model in which an ITI of an optimal number of donor bone-marrow cells (BMC) was given together with 1ml ALS IP 14 days before transplant. The efficacy of this protocol was critically dependent on the donor-recipient haplotype and influenced by antigenic strength and MHC disparity but not by non-MHC background genes. In strain disparities where ITI was unsuccessful, this was caused by alloreactive recent thymic emigrant cells. In a high responder strain combination the effect was highly dependent on the dose of BMC in the intrathymic injection. Moreover it was readily reproduced with injection of antigen by the intravenous route, even at a lower dose than that required via the intrathymic route. This was in contrast to the other strain combinations tested in which the beneficial effect of donor antigen injection was specific to the intrathymic route, and it suggested that the effect in this group might be at least partly dependent on peripheral mechanisms. The polyclonal ALS can easily be demonstrated to be non-specific in its depletion of peripheral lymphocytes at the dose used in these studies, and we have shown that it also penetrates the thymus. Therefore treatment with ALS may have more effects that mere disablement of peripheral alloreactive T cells, thus complicating the interpretation of the experiments. We have therefore refined our model by recruiting in place of ALS a more specific agent, the partially depleting anti-CD4 monoclonal antibody MRC-OX38, which is equally effective as an adjunct to ITI. We have shown using flow cytometry and immunohistochemistry, that this and certain other monoclonal antibodies, at a therapeutic dose, do not cross the "blood-thymus barrier", and therefore do not complicate the model as ALS potentially does. We would recommend this approach in further studies.

Bone marrow transplantation (BMT) is the treatment of choice for many malignancies and other childhood disorders. Acknowledging that the entire family is affected when a child undergoes a BMT, increasing research attention has been given to understanding this experience from the perspectives of recipients, parents and the family as a whole. Yet, minimal attention has been directed at understanding the experience of healthy siblings as they transition through the BMT experience. Before intervention studies can be undertaken that will help healthy siblings transition through the BMT experience, knowledge about the impact of the experience on siblings is needed. Accordingly, a qualitative study guided by the philosophy of hermeneutic phenomenology was conducted to elicit detailed descriptions of the lived experience of siblings. Participants were children, adolescents and young adults with a sibling who had undergone a BMT during childhood. Participants were recruited from a pediatric BMT clinic in Western Canada. Semi-structured, open-ended interviews that explored siblings’ memories about what it is like to be a sibling of a child who has had a BMT were conducted with each participant. Demographic data and field notes were recorded. All interviews and field notes were transcribed. The transcripts were reviewed repeatedly for significant statements in an attempt to find meaning and understanding through themes. The data analysis revealed the essence of siblings’ lived experience of transitioning through the BMT trajectory as an interruption in family life. Four themes communicated the essence of siblings’ lived experience: (1) life goes on, (2) feeling more or less a part of a family, (3) faith in God that things will be okay, and (4) feelings around families. Differences between donor and non-donor siblings are highlighted. Siblings’ recommendations for health care professionals are also provided. Results from this study will help health professionals better anticipate the diverse and shifting needs and demands of siblings of pediatric BMT patients. Recommendations for future research and innovations in nursing interventions are provided.

This project is a pilot study to assess the viability of transplantation as a technique to establish reindeer lichens on reclaimed areas of oil sands surface mines in the Athabasca region of Alberta. There were two components to this study: a) a lichen transplant trial, where I investigated which commonly available substrates found in reclaimed forest sites would promote the best lichen fragment survival and vigour for a lichen ‘seeding’ program; and b) a diversity assessment of the reclaimed site to compare the existing cryptogam community with the expected community for the target ecosite based on published descriptions from the surrounding native forests and documented chronosequences for terrestrial lichen communities. In July 2009, Cladonia mitis was transplanted into 54 plots on three sites that were planted with jack pine or spruce 12 or 24 years ago, respectively, on the Suncor Millenium/Steepbank Mine (Suncor Mine). This trial was designed to investigate possible short-term indicators of successful lichen establishment and the effect of substrate (moss, litter, or soil) on the establishment of transplanted lichen thallus fragments. The indicators of lichen establishment evaluated were vigour, movement from plots, photographic areal cover, and microscopic growth (hyphal growth, annual growth and lateral branching). After two growing seasons, the effect of substrate on lichen transplant survival varied by site; there was no significant difference in lichen fragment retention in plots by substrate on the 24-year old sites, but median fragment retention was significantly higher on moss and litter substrates than soil on the 12-year old site. There was also no significant difference in fragment vigour between substrates on each site, except on the south-facing 24-year-old forest site where average vigour was significantly higher on moss plots than on soil plots. Photographic areal measurement is not recommended as a short-term lichen establishment monitoring tool for transplanted fragments based on the difficulties encountered using the method for this trial. Forty-one percent of the fragments collected for microscopic assessment after the first growing season had grown hyphae, 23 percent of the fragments collected during September 2009 and September 2010 had formed apothecia, and 31 percent of the fragments collected in September 2010 had grown lateral branches. The results of the biodiversity assessment were compared with the successional communities previously described for spruce- and pine-lichen boreal forests. There were no lichens found on the 12-year-old site, though the cup lichens were common to abundant on the 24-year-old sites, which is consistent with the cryptogammic community expected for a regenerating natural site of that age. Cladonia mitis was also present but rare to uncommon on the 24-year-old site, while Cladonia stellaris, Cladonia rangiferina and Cladonia stygia that, together with C. mitis, are indicative of the al and c1 ecosites of the Central Mixedwood Boreal forest, were not present. / Graduate

Bone marrow transplantation (BMT) is the treatment of choice for many malignancies and other childhood disorders. Acknowledging that the entire family is affected when a child undergoes a BMT, increasing research attention has been given to understanding this experience from the perspectives of recipients, parents and the family as a whole. Yet, minimal attention has been directed at understanding the experience of healthy siblings as they transition through the BMT experience. Before intervention studies can be undertaken that will help healthy siblings transition through the BMT experience, knowledge about the impact of the experience on siblings is needed. Accordingly, a qualitative study guided by the philosophy of hermeneutic phenomenology was conducted to elicit detailed descriptions of the lived experience of siblings. Participants were children, adolescents and young adults with a sibling who had undergone a BMT during childhood. Participants were recruited from a pediatric BMT clinic in Western Canada. Semi-structured, open-ended interviews that explored siblings’ memories about what it is like to be a sibling of a child who has had a BMT were conducted with each participant. Demographic data and field notes were recorded. All interviews and field notes were transcribed. The transcripts were reviewed repeatedly for significant statements in an attempt to find meaning and understanding through themes. The data analysis revealed the essence of siblings’ lived experience of transitioning through the BMT trajectory as an interruption in family life. Four themes communicated the essence of siblings’ lived experience: (1) life goes on, (2) feeling more or less a part of a family, (3) faith in God that things will be okay, and (4) feelings around families. Differences between donor and non-donor siblings are highlighted. Siblings’ recommendations for health care professionals are also provided. Results from this study will help health professionals better anticipate the diverse and shifting needs and demands of siblings of pediatric BMT patients. Recommendations for future research and innovations in nursing interventions are provided.

The active state of plasminogen activator inhibitor type-1 (PAI-1) is prolonged when it forms a complex with vitronectin (VN), a major serum protein. Active PAI-1 in the PAI-1:VN complex serves many functions related to fibrinolysis and cell migration but key to these effects is its extracellular distribution. PAI-1:VN complexes can bind to exposed vimentin (VIM) on activated platelet and platelet microparticles, resulting in the assembly of PAI-1:VN:VIM ternary complexes. However, the manner in which the vimentin cytoskeleton is presented extracellularlyi s not well understood. I hypothesized that PAI-1:VN:VIM ternary complex assembly occurs on cell surfaces when microparticle release leads to exposure of vimentin cytoskeleton which can lead to either assembly of the ternary complex or become involved in an autoimmune response specific for vimentin. To follow the intracellular and extracellular fate of PAI-1, I constructed an expression vector encoding PAI-1-dsRed, a fluorescent form of PAI-1, which would permit live cell tracking of PAI-1 in megakaryocytes and endothelial cells. Secondly, to study how vimentin is expressed on platelets and platelet microparticles, flow cytometry was used to isolate vimentin positive platelets or PMP's and atomic force microscopy was performed to image platelets or PMP's at nanoscale resolution. From these studies, I propose a model of vimentin expression in which the junction of microparticle release results in the exposure of cytoskeletal vimentin on both the cell and the microparticle. This exposed vimentin could potentially induce VN multimerization on the same cell surface leading to incorporation of multiple PAI-1:VN complexes. Finally, I investigated how anti-vimentin antibodies can induce platelet:leukocyte conjugate formation. To achieve this, in vitro tests were performed to determine the binding site of anti-vimentin antibodies (AVA's) and how they induce blood cell activation. Overall, my results suggest that vimentin exposure in our model of microparticle release can lead to ternary complex assembly if suitable quantities of PAI-1 are released during platelet activation. In the setting of transplant vasculopathy with high titres of AVA's, vimentin-positive granulocytes can bind these autoantibodies, which then leads to platelet activation and the formation of platelet:leukocyte conjugates.

Solid organ transplantation is the gold standard treatment for a variety of conditions that result in organ failure. However, despite considerable advances in clinical transplantation in recent decades, the almost ubiquitous requirement of life-long immunosuppression of transplant recipients persists and is complicated by graft loss to rejection in the long term and multiple serious adverse effects that are frequently life limiting. Helminths currently infect more than one quarter of the world’s population and it is now well established that their success as parasites is the result of active immunomodulation of the host immune response. Whilst this primarily secures ongoing survival of the parasites, in some cases helminth-induced immunomodulation can be beneficial to the infected host and is not associated with the adverse sequelae of pharmacological immunosuppression. An emerging body of evidence suggests that harmful immune responses to alloantigens can be suppressed by helminths, but little mechanistic data exists and the active immunomodulators involved have remained hitherto unidentified. The hypothesis behind this thesis is that the model intestinal nematode, Heligmosomoides polygyrus, produces immunomodulatory molecules that can suppress responses to allo- and auto-antigens in animal models of transplantation and autoimmunity, and that some of these molecules could potentially be exploited as novel therapeutic agents. Full-thickness skin grafting was performed between fully-allogeneic mouse strains (BALB/c to C57BL/6). Recipient mice infected with H. polygyrus immediately prior to transplantation showed significantly prolonged allograft survival. Likewise, protection from allograft rejection could be replicated in recipient mice in which H. polygyrus excretory-secretory products (HES) (isolated from culture of adult worms) were delivered by continuous infusion via surgically implanted osmotic minipumps. A number of potential mechanisms underlying allograft protection were identified including induction of CD4+CD25+Foxp3+ regulatory T cells (Treg) and suppression of Th1 and Th17 effector CD4+ T cell phenotypes. H. polygyrus and HES were further shown to ameliorate disease in murine (pMOG) experimental autoimmune encephalomyelitis and colitis induced by T cell transfer. In addition to expansion of Treg, H. polygyrus-mediated protection against EAE was found to be almost completely lost in IL-4 receptor deficient mice, indicating a protective role of Th2 immune responses in this context. Finally, the mechanisms of action of the newly-identified TGF-β mimic, TGM, contained within HES were investigated. Despite bearing no sequence homology or structural resemblance to TGF-β, TGM was shown to act through the TGF-β receptor complex to induce Treg in human and mouse CD4+ T cells in vitro and to suppress murine allogeneic skin graft rejection in vivo. TGM may represent the origin of a safe, effective and long-overdue novel alternative to current immunosuppression therapy.

nÃo hà / O transplante cardÃaco à uma modalidade terapÃutica de alta complexidade e exige do enfermeiro uma assistÃncia especÃfica, com qualidade, tendo como foco o autocuidado, uma vez que possibilita o envolvimento do paciente de maneira participativa no tratamento. Teve-se como objetivo geral avaliar o autocuidado de pacientes que realizaram transplante cardÃaco, baseado no Modelo do Autocuidado de Orem. E como especÃficos: identificar os fatores condicionantes que interferem na prÃtica do autocuidado de paciente transplantado cardÃaco apÃs a alta hospitalar; verificar os dÃficits de autocuidado de pacientes adultos que realizaram transplante cardÃaco; e correlacionar os fatores condicionantes com o Perfil de Engajamento do Autocuidado. Trata-se de um estudo descritivo-analÃtico, com delineamento transversal e natureza quantitativa, desenvolvido na Unidade de Transplante e InsuficiÃncia CardÃaca de um hospital pÃblico terciÃrio da cidade de Fortaleza-CearÃ-Brasil. A amostra foi composta por 63 pacientes transplantados cardÃacos, que atenderam aos critÃrios de inclusÃo. A coleta de dados foi realizada mediante uma entrevista individualizada, no perÃodo de outubro a dezembro de 2011. O projeto foi aprovado pelo Comità de Ãtica e Pesquisa, sob protocolo do CEP/HM: 109/11. Como resultados dos fatores condicionantes, obteve-se: sexo masculino (88,9%); a idade variou de 23 a 72 anos, predominando de 40 a 59 anos (68,3%); cor da pele nÃo-branca (74,6%), catÃlico (81,0%); casado (77,8%); procedentes do interior do estado (49,2%); nÃvel de escolaridade-ensino fundamental (71,4%); aposentado ou nÃo trabalha (82,5%); renda de atà um salÃrio mÃnimo (47,6%); miocardiopatia chagÃsica (28,6%); tempo pÃs-transplante entre um e trÃs anos (39,7%). Em relaÃÃo ao autocuidado do requisito universal, tÃm-se como dÃficit os seguintes dados: oxigenaÃÃo/respiraÃÃo (26,9%); higiene pessoal (31,7%); higiene do ambiente domiciliar (47,6%); ingestÃo de lÃquidos (39,6%); ingestÃo de alimentos (68,8%); eliminaÃÃes (20,6%); prÃtica de exercÃcio fÃsico (87,3%); sono e repouso (79,3%); interaÃÃo social (90,4%); comportamento emocional (58,7%); prevenÃÃo de doenÃa/promoÃÃo da saÃde (77,7%); tabagismo (1,58%); etilismo (3,17%); prÃtica sexual (61,9%); prevenÃÃo do cÃncer (60,3%). Quanto ao autocuidado do requisito desenvolvimental, apresentou os seguintes dÃficits: participaÃÃo das atividades educativas (39,6%); adaptaÃÃo Ãs mudanÃas apÃs transplante cardÃaco (34,9%). E ao requisito desvio de saÃde, tÃm-se os seguintes dÃficits: comparecimento Ãs consultas da equipe de saÃde (41,2%); imunizaÃÃo bÃsica (100%); uso de mÃscara descartÃvel (46%); contato com pessoas e animais domÃsticos (38%); e conhecimento (20,6%). O Perfil de Engajamento do Autocuidado variou de 88 a 113, constatando-se que a maioria dos pacientes apresentou algum dÃficit de autocuidado, pois 57,1% estavam na classe que âfrequentemente realizava autocuidadoâ. No entanto, embora nenhum paciente realizasse 100% das prÃticas de autocuidado recomendadas para o transplantado cardÃaco, 42,9% sempre realizavam o autocuidado. Conclui-se que os pacientes transplantados cardÃacos apresentam dÃficit de autocuidado para manutenÃÃo e promoÃÃo da saÃde. Portanto, à necessÃrio que os profissionais da equipe de transplante cardÃaco estejam atentos para os fatores condicionantes do autocuidado dos pacientes transplantados cardÃacos, visando estabelecer estratÃgias para reduÃÃo do dÃficit de autocuidado.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / O transplante hepÃtico à o tratamento padrÃo para os portadores de doenÃa hepÃtica terminal. Com o refinamento da tÃcnica cirÃrgica, melhoria da eficÃcia dos imunossupressores, o entendimento da lesÃo de isquemia-reperfusÃo e o uso de soluÃÃes de preservaÃÃo mais fisiolÃgicas, houve um aumento considerÃvel da sobrevida do enxerto hepÃtico, e consequentemente, da sobrevida do paciente. A soluÃÃo de preservaÃÃo de Collins à a mais simples e a mais econÃmica, sendo utilizada desde 1969 principalmente no transplante renal. A soluÃÃo de Belzer à a mais utilizada mundialmente e preserva o enxerto hepÃtico por um perÃodo maior, entretanto com um custo mais elevado. O presente estudo compara 2 esquemas de perfusÃo hepÃtica utilizando a soluÃÃo de Collins e Belzer. A diferenÃa entre os dois grupos à que a soluÃÃo de Belzer infundida pela veia porta à substituÃda pela soluÃÃo de Collins. Foram avaliados 49 pacientes submetidos a transplante hepÃtico com doador falecido no Hospital UniversitÃrio Walter CantÃdio da Universidade Federal do CearÃ. A funÃÃo hepÃtica apÃs o transplante foi avaliada atravÃs das concentraÃÃes sÃricas de AST, ALT, Bilirrubinas e valores de INR (RelaÃÃo Normatizada Internacional do tempo de protrombina) no primeiro e sÃtimo dia pÃs-operatÃrio. O tempo de isquemia fria foi menor que 10 horas em todos os pacientes. NÃo houve diferenÃa entre os dois grupos nos parÃmetros analisados, exceto no INR do grupo em que foi infundida soluÃÃo de Collins na veia porta, que foi maior no 1 PO. Os dois esquemas de preservaÃÃo hepÃtica podem ser utilizados com seguranÃa, desde que observado um tempo de isquemia fria menor que 10 horas. Houve uma reduÃÃo do custo do transplante no grupo que utilizou um menor volume da soluÃÃo de Belzer / The hepatic transplant is the standard treatment for terminal hepatic illness. With the refinement of the surgical technique, improvement of the effectiveness of the immunosuppressive drugs, the better knowledge of the reperfusion injury and the use of more physiological solutions of preservation, had a considerable increase of the survival of hepatic graft. The Collinsâ preservation solution used since 1969 , in renal transplant, is simplest and most economic preservation solution. The Belzerâs solution is used world wide and preserves hepatic graft for a longer period, although more expensive. The present study it compares 2 projects of hepatic perfusion using the Collins and Belzerâs solution. The difference between the two groups is that the Belzerâs solution perfused for the portal vein is substituted by the solution of Collins. At Walter CantÃdio Hospital of the Federal University of the Cearà 49 patients submitted to hepatic transplant of deceased donors graft were evaluated. The hepatic function after the transplant was evaluated through parameters AST, ALT, INR and Bilirubin in first and the seventh postoperative day. The time of cold ischemia was less than 10 hours in all the patients. There was no difference between the two groups in the analyzed parameters, except in the INR of the group where Collinsâ solution in the portal vein was perfused, which was greater in the 1 postoperative day. The two projects of hepatic preservation can be used with security, as the cold ischemia time is less than 10 hours, however, it had a reduction of the cost of the liver transplant in the group that used a lesser volume of the solution of Belzer.