Submitted in partial compliance with the requirements for the Master’s Degree in Technology: Chiropractic, Durban University of Technology, Durban, South Africa, 2015. / Background: The 19th Iteration of the World Transplant Games was hosted in Durban, South Africa in 2013. This biennial, international, multisport event showcases the talents of transplant athletes, whilst demonstrating the benefits of organ transplantation. To date, limited research is available on transplant athletes. This study aimed to determine the injury profile of transplant athletes who presented to the Durban University of Technology Chiropractic Treatment Facilities during the 2013 World Transplant Games. Methods: This retrospective, descriptive cohort study analysed the data collected at the Chiropractic Treatment Facilities at the 2013 World Transplant Games. For inclusion, each WTG Form required completion, reflecting all the elements of that participant’s chiropractic consultation. The data recorded on the World Transplant Games Form generated the data analysed in this study. The data described the frequency (frequency tables), nature and management of injuries treated at the Chiropractic Treatment Facilities during the 2013 World Transplant Games. In order to determine relationships cross tabulations were used. Results: There were 964 athletes registered for the 2013 World Transplant Games, of which 153 presented to the Chiropractic Treatment Facilities (an utilisation rate of 15.9%). A total of 259 consultations by the athletes (n = 223; 86.1%) and non-athletes (n = 36; 13.9%) were recorded. The majority of the treated athletes were White (n = 91; 59.5%), males (n = 109; 71.2%), in which kidney transplant recipients accounted for 37.3% (n = 58) of the total number. Track athletics had the highest injury rate (34.5% of all reported injuries). Athletes sustained injuries to 14 different anatomical regions, with the thigh (26.9%) and shin/calf (20.5%) being the most frequently injured. The majority of injuries (n = 164; 66.4%) were “overuse” injuries, with myofasciitis, muscle strains and thoracic facet syndrome being the most frequently obtained diagnoses (25.5%, 16.6% and 6.5% respectively). The most frequently employed treatment modalities were those of massage (32.1%), ischemic compression (16.3%) and manipulation (13.4%). It was noted that the most injuries sustained (88.3%) were not severe enough to result in an inability to continue current or future participation. Conclusions and Recommendations: Transplant recipient athletes injuries concur with the literature on non-transplant athletes, indicating that solid organ transplantation does not predispose the athlete to different or more serious injuries which would require different management protocols by health care personnel treating these athletes. Further investigation into individual sports is encouraged, to develop accurate, effective injury management and preventative strategies to more appropriately diagnose and treat injuries incurred by transplant athletes and then to prevent them from recurring. An informed healthcare approach towards event organising and athlete treatment will improve preventative strategies and athlete management.

General Abstract Objective: In April 2006, the Scottish Liver Transplant Unit (SLTU) became the first NHS transplant unit in the UK to offer the option of Living Donor Liver Transplantation (LDLT). This represented a unique opportunity to evaluate the functional and psychosocial impact of LDLT upon healthy donors and their recipients. Subsequent aims were to investigate the challenge of introducing LDLT in Scotland and to establish the perceived deterrents and attractions of the procedure. An additional aim was to evaluate the impact of Living Donor Kidney Transplantation (LDKT) upon donors and recipients. Design: A series of cross sectional and longitudinal studies were designed for the purpose of this thesis (3 quantitative, 2 qualitative, and 1 mixed methods). Method: Self report questionnaires were used in each of the quantitative studies, with the addition of neuropsychological computerized tests in two studies. Semi-structured interviews were employed in the qualitative studies. Main Findings: •Prior to its introduction general support for the option of LDLT was found, although it was highlighted that the risk involved was not well understood by the general public. •Since becoming available LDLT has not been a readily acceptable treatment option from the perspective of patients due to the perceived risk for the donor, but it may be considered as a “last option”. Family members were motivated to save their loved one’s life but the personal implications of donating resulted in reconsideration of LDLT. • Staff at the SLTU perceived a lack of family commitment in relation to LDLT, which is explained as a cultural factor contributing to the slow uptake of LDLT. In Scotland, a donation from a younger to an older generation is not easily accepted. This, in addition to patients’ optimism that a deceased donation will arrive, and the poor health of potential donors, is thought to have affected the uptake of LDLT. As has the unit’s conservative approach to the promotion of LDLT. This approach is the result of a perceived reduction in the need for LDLT and a preference to avoid the risk to a healthy donor and conduct transplants with deceased donations. • In over 3 years, only one couple completed LDLT. The recipient showed functional and psychosocial improvement from pre to post procedure, whilst the donor showed slight deterioration in aspects of quality of life 6 weeks post donation, which did not always completely return to a baseline level by 6 months. The donor made sacrifices to provide her husband with a fresh start to life and unmet expectations were found to effect quality of life. •Willingness to become a liver donor is not thought to be influenced by the frame of the information provided. •Like the LDLT donor, LDKT donors experience some functional and psychosocial deterioration at 6 weeks post donation, but donors largely recover by 6 months post donation. However, the anticipated benefit to recipients was not evident and may not be quantifiable until after 6 months post operation. Conclusion: This thesis has added to current knowledge on living organ donation and specifically represents the first psychological evaluation of a UK LDLT programme. The slow uptake of LDLT was unexpected and has resulted in informative, novel research.

Thesis (Ph. D.)--University of Lund, 1994. / Published dissertation. Includes bibliographical references.

Thesis (Ph. D.)--University of Lund, 1994. / Published dissertation. Includes bibliographical references.

Orientador: Newton Kara-Jose / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-13T21:12:46Z (GMT). No. of bitstreams: 1 Costa_DacioCarvalho_D.pdf: 11382661 bytes, checksum: a5c3e2c591c002085753bfe5397e34f3 (MD5) Previous issue date: 2009 / Resumo: Objetivo: Comparar a eficácia da injeção subconjuntival de 20 mg de triancinolona associada a prednisolona 1% tópica com a injeção intravenosa de 500 mg de metilprednisolona associada a prednisolona 1% tópica no tratamento da rejeição endotelial de transplante de córnea. Métodos: Estudo caso-controle realizado no Hospital das Clínicas da UNICAMP. Os pacientes submetidos a transplante penetrante de córnea que apresentaram primeiro episódio de rejeição endotelial com até 15 dias do início dos sintomas durante o período de novembro de 2005 a outubro de 2006 foram tratados com injeção subconjuntival de 20 mg de acetonido de triancinolona associado a acetato de prednisolona 1% tópico. Estes pacientes foram pareados por idade e diagnóstico com pacientes submetidos a tratamento com injeção intravenosa de 500 mg de succinato sódico de metilprednisolona associado a acetato de prednisolona 1% tópico e analisados quanto à capacidade de reversão do episódio de rejeição, pressão intraocular aos 30 dias e acuidade visual ao final de 1 ano. Resultados: 16 pacientes foram tratados com 20 mg de triancinolona subconjuntival e prednisolona 1% tópica durante o período de recrutamento e foram pareados com 16 pacientes tratados com 500 mg de metilprednisolona intravenosa e prednisolona 1% tópica. Ao final de 1 ano, o grupo tratado com triancinolona obteve melhores resultados do que o grupo tratado com metilprednisolona (p=0,025), obtendo 15 pacientes com córnea transparente enquanto o grupo tratado com metilprednisolona obteve 10 pacientes. 3 pacientes do grupo tratado com triancinolona apresentaram segundo episódio de rejeição durante o seguimento e foram retratados com sucesso enquanto no grupo da metilprednisolona, 4 pacientes apresentaram segunda rejeição, com 2 pacientes apresentando falência com o retratamento e 2 obtendo sucesso. A pressão intraocular subiu nos dois grupos (p=0,002) após 30 dias, porém não houve diferença entre os grupos (p=0,433). A acuidade visual melhorou após 1 ano em ambos os grupos (p=0,049) e o grupo tratado com triancinolona obteve melhor acuidade visual (p=0,002). Conclusão: A injeção subconjuntival de 20 mg de triancinolona combinada com prednisolona 1% tópica mostrou-se mais eficaz em reverter episódios de rejeição de transplante de córnea neste estudo caso-controle do que a aplicação intravenosa de 500 mg de metilprednisolona. Estudos adicionais necessitam ser realizados para verificar a segurança e eficácia deste tratamento em grandes populações / Abstract: Purpose: To compare the efficacy of 20 mg subconjunctival triamcinolone in association with topical prednisolone 1% to 500 mg intravenous methylprednisolone in association with topical prednisolone 1% in the treatment of cornea endothelial graft rejection. Methods: Case-control study carried out at State University of Campinas Hospital. Patients submitted to penetrating keratoplasty that presented first episode of corneal endothelial rejection within 15 days of symptoms onset between November 2005 and October 2006 were treated with 20 mg subconjunctival injection of triamcinolone acetate in association with topical prednisolone acetate 1%. These patients were matched for age and diagnosis to patients that were submitted to a single 500 mg intravenous injection of methylprednisolone sodium succinate in association with topical prednisolone acetate 1% and analyzed regarding the reversion of the rejection episode, intraocular pressure at day 30 and visual acuity at the end of 1 year. Results: 16 patients were treated with 20 mg subconjunctival triamcinolone and topical prednisolone 1% during the period of recruitment and were matched to 16 patients treated with 500 mg intravenous methylprednisolone and topical prednisolone 1%. At the end of 1 year, the group treated with triamcinolone had a better outcome than the group treated with methylprednisolone (p=0.025), having 15 patients with clear grafts as the group treated with methylprednisolone had 10 patients. 3 patients from the group treated with triamcinolone had new rejection episodes during follow-up and were retreated successfully as in the group treated with methylprednisolone 4 patients had a new rejection episode, with 2 progressing to failure and 2 to success with retreatment. Intraocular pressure rose in both groups (p=0.002) at day 30 but there were no statistically significant differences between the groups (p=0.433). Visual acuity improved after 1 year in both groups (p=0.049) and the group treated with triamcinolone had better visual acuities (p=0.002). Conclusions: 20 mg subconjunctival injection of triamcinolone acetonide associated with topical prednisolone acetate 1% showed to be more effective than 500 mg intravenous methylprednisolone associated with prednisolone acetate 1% in this case-control study. Further studies need to be accomplished to verify its safety and effectiveness in larger populations / Doutorado / Oftalmologia / Doutor em Ciências Médicas

Indiana University-Purdue University Indianapolis (IUPUI) / Solid organ transplantation is limited by available donor allografts. Pig to human transplantation, xenotransplantation, could potentially solve this problem if physiologic and immunologic incompatibilities are overcome. Genetic modifications of pigs have proven valuable in the study of xenotransplantation by improving pig to human compatibility. More genetic targets must be identified for clinical success. First, this study examines platelet homeostasis incompatibilities leading to acute thrombocytopenia in liver xenotransplantation. Mechanisms for xenogeneic thrombocytopenia were evaluated using liver macrophages, Kupffer cells, leading to identification of CD18, beta-2 integrin, as a potential target for modification. When disruption of CD18 was accomplished, human platelet binding and clearance by pig Kupffer cells was inhibited. Further, human and pig platelet surface carbohydrates were examined demonstrating significant differences in carbohydrates known to be involved with platelet homeostasis. Carbohydrate recognition domains of receptors responsible for platelet clearance Macrophage antigen complex-1 (CD11b/CD18) and Asialoglycoprotein receptor 1 in pigs were found to be different from those in humans, further supporting the involvement of platelet surface carbohydrate differences in xenogeneic thrombocytopenia. Second, immunologic incompatibilities due to antibody recognition of antigens resulting in antibody-mediated rejection were studied. Identification of relevant targets was systematically approached through evaluation of a known xenoantigenic protein fibronectin from genetically modified pigs. N-Glycolylneuraminic acid, a sialic acid not found in humans, was expressed on pig fibronectin and was identified as an antigenic epitope recognized by human IgG. These studies have provided further insight into xenogeneic thrombocytopenia and antibody-mediated rejection, and have identified potential targets to improve pig to human transplant compatibility.

The views of medical doctors regarding organ donation and transplantation in the Durban Metropolitan Region were examined in an exploratory and explanatory study, which included a descriptive, convenience sampled study of 43 graduate and postgraduate professionals, practicing in the private and provincial sectors. Characteristics were obtained from a 1 D6-item questionnaire that were later divided into component contributions according to Fazio's attitude to behavior process model (Fazio, 1989; Fazio & RoskosEewoldson, 1994). Variables which were analysed included personal demographics, personal views, knowledge and skills, practice-related issues, attitudes and perceptions as well as future recommendations. Analysis of the information revealed that most medical doctors approved of organ donation practices and viewed transplantation as a significant roleplayer in both the community and medical sectors. However, a knowledge and skills deficit combined with religious presumptions and general uncertainty regarding issues surrounding the practical, legal and emotional concepts of brain death may be responsible for the relatively low personal dedication and practice participation rate among the sample. Medical doctors from the provincial sector appeared to have considerable concerns which included: time constraints; a perceived lack of support from colleagues, nurses and hospital administrators; a lack of medico-Iegal awareness relating to organ donation and brain death and a scarcity of experience and insight into the transplant process. In order to address the paucity of awareness pertaining to brain death and organ donation activities, the findings indicate that formal and interactive education programs during the undergraduate, postgraduate and medical development phases are required in which issues surrounding death and dying can be explored by a multidisciplinary team. It appears that this team must comprise of doctors, lawyers, religious leaders, psychologists, administrators, nurses, donor families and transplant co-ordinators. This development may serve to emphasize the professional importance of holistic bereavement counseling, improve doctor and patient satisfaction, increase organ donation referrals and transplantation rates as well as diminish medico-Iegal concerns. / Thesis (M.Cur.)-University of Natal, Durban, 2001.

Acute allograft rejection remains a major problem in solid organ transplantation, because rejection may lead to acute or chronic loss of graft function. The failure of certain anti-rejection prophylactic treatments suggests that several unexpected pathways might be involved in the rejection process.<p>The aim of our experiments was to investigate the effector mechanisms responsible for skin graft rejection in mice. To adress this question, we took advantage of the possibility to restrict the alloimmune response to isolated allogeneic MHC class II molecules or to isolated minor transplantation antigens, combined with the possibility to study separately the response of CD4+ or CD8+ T cells in mice deficient for Th1 or Th2 cytokines or cytotoxic molecules. We used the bm12 skin graft combination (C57BL/6 H2Kbm12 grafted on C57BL/6 H2Kb) as a model of single MHC class II disparity and the b2microglobulin skin graft model (C57BL/6 b2m+/+ grafted on C57BL/6 b2m-/-) as a model of minor transplantation antigen disparity. Our goal was to engage a limited number of effectors, trying in a second time to block each rejection pathway selectively. <p>We showed that Fas/FasL-mediated CD4+ T cells cytotoxicity, eosinophil recruitment, activation and degranulation induced by Th2 derived cytokines, and CD4-derived IFN-g production are involved in the rejection of grafts bearing either a single MHC class II disparity or b2m-derived minor histocompatibilty antigens. In addition, rejection of MHC class II disparate skin grafts also includes the participation of neutrophils, in particular conditions where the occurrence of the Th2/eosinophil pathway was prevented. <p>Altogether, our data show a multiplicity and a redundancy of the effector pathways participating in allograft rejection. Among the different effectors pathways identified, including effectors from both innate and adaptive immune systems, some act synergistically, whereas others act as alternative pathways, depending of the degree of donor-recipient mismatch. / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

Indiana University-Purdue University Indianapolis (IUPUI) / Graft-versus-host disease (GVHD) remains the major complication after allogeneic hematopoietic stem cell transplantation (HSCT), resulting from immunological attack on target organs such as gastrointestinal (GI) tract, liver and skin from donor allogeneic T cells. The most common treatment for GVHD is immunosuppressive drugs such as corticosteroids, which may result in many side effects including the loss of the beneficial graft-versus-leukemia (GVL) effect and increased infection rates. However, GVHD-specific drugs have yet to be implemented. Here we show that by targeting on a novel pathogenic CD4+ T cell subpopulation that our lab previously found in patients with GI GVHD, we can develop new avenues to treat GVHD. This novel population is characterized as CD146+CCR5+ T cells, co-expressing IL-17A and IFN-γ. We found that the inducible T-cell costimulator (ICOS), which has been reported to be important for human Th17 differentiation in vitro, is critical for the development of this nonconventional T Helper 1 (Th1*)-polarized CD146+CCR5+ conventional T cells (Tconvs) population. Furthermore, we found that ICOS can induce the generation of Th1*-polarized CD146+CCR5+ regulatory T cells (Tregs) population, lowering the frequencies of phenotypic markers of functional Tregs. Our data also showed that inhibiting the major transcriptional factor of Th17, RAR-related orphan receptor gamma t (RORγt), could prevent the development of CD146+CCR5+ Tconvs in vitro. Our results demonstrate how pathogenic CD146+CCR5+ T cells are induced through ICOS or RORγt, suggesting new targets for GVHD treatment. We anticipate our assay to be a starting point for the development of novel GVHD-specific drugs. For example, the treatments that focus on inhibiting RORγ would have fewer side effects than general immunosuppressive drugs that GVHD patients use today and inhibit GVHD while sparing the GVL effect. Furthermore, we expect the CD146+CCR5+ Tconvs and/or Tregs can be used as GVHD biomarkers. These biomarkers may guide preemptive treatments such as RORγt inhibitor.

Indiana University-Purdue University Indianapolis (IUPUI) / Living donors have contributed about 6,000 kidneys per year in the past 10 years, but more than 100,000 individuals are still waiting for a kidney transplant. Living kidney donors undergo a major surgical procedure without direct medical benefit to themselves, but comprehensive follow-up information on living donors’ health is unfortunately limited. Expert recommendations suggest capturing clinical information beyond traditional sources to improve surveillance of co-morbid conditions from living kidney donors. Currently the United Network for Organ Sharing is responsible for collecting and reporting follow-up data for all living donors from U.S. transplant centers. Under policy implemented in February of 2013, transplant centers must submit follow-up date for two years after donation, but current processes often yield to incomplete and untimely reporting. This dissertation uses a statewide Health Information Exchange as a new clinical data source to 1) retrospectively identify a cohort of living kidney donors, 2) understand their follow-up care patterns, and 3) observe selected clinical outcomes including hypertension, diabetes and post-donation renal function.