RESUMO
We initiated a program for early detection of diabetes and hypertension, the main causes of kidney failure in Guyana, South America. We trained local high school students with the goal that these students would stay in the villages for long-term, become health advocates and shift the reliance away from physicians. This project involved 7 high school students who were taught to monitor the health of one village of 1000-1500 population each. The program will be implemented for 3 years in which the entire population of seven villages (approximately 10,000 people) will be covered. This represents 1.3% population in Guyana. We present data from the pilot study from the sample of 619 people. The prevalence of diabetes mellitus was 13.9%. Among diabetics, 33.7% were using insulin and 86% oral hypoglycemic agents. Prevalence of hypertension was 29.4%, 63.2% were overweight and 17% were obese. About 9.9% patients were unaware about the existence of hypertension. We have shown in our study that high school students can be used to collect health data and monitor diabetes and hypertension. There was also a significant incidence of undetected diabetes and hypertension.
RESUMO
Vascularized composite allotransplantation (VCA) has emerged as a treatment option for treating nonlife-threatening conditions. Therefore, in order to make VCA a safe reconstruction option, there is a need to minimize immunosuppression, develop tolerance-inducing strategies and elucidate the mechanisms of VCA rejection and tolerance. In this study we explored the effects of hIL-2/Fc (a long-lasting human IL-2 fusion protein), in combination with antilymphocyte serum (ALS) and short-term cyclosporine A (CsA), on graft survival, regulatory T cell (Treg) proliferation and tolerance induction in a rat hind-limb transplant model. We demonstrate that hIL-2/Fc therapy tips the immune balance, increasing Treg proliferation and suppressing effector T cells, and permits VCA tolerance as demonstrated by long-term allograft survival and donor-antigen acceptance. Moreover, we observe two distinct types of acute rejection (AR), progressive and reversible, within hIL-2/Fc plus ALS and CsA treated recipients. Our study shows differential gene expression profiles of FoxP3 versus GzmB, Prf1 or interferon-γ in these two types of AR, with reversible rejection demonstrating higher Treg to Teff gene expression. This correlation of gene expression profile at the first clinical sign of AR with VCA outcomes can provide the basis for further inquiry into the mechanistic aspects of VCA rejection and future drug targets.
Assuntos
Membro Posterior/transplante , Interleucina-2/química , Proteínas Recombinantes de Fusão/química , Tolerância ao Transplante/efeitos dos fármacos , Alotransplante de Tecidos Compostos Vascularizados/métodos , Animais , Proliferação de Células , Ciclosporina/química , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Rejeição de Enxerto , Sobrevivência de Enxerto , Granzimas/metabolismo , Humanos , Sistema Imunitário , Tolerância Imunológica , Masculino , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Ratos , Ratos Endogâmicos Lew , Ratos Wistar , Transplante HomólogoRESUMO
INTRODUCTION: We describe ethical/moral issues in patient selection in a new living donor kidney transplant program in Guyana, South America. CASE REPORTS: Over 3 years, we screened 450 patients with chronic kidney disease among which 70 were suitable for kidney transplantation. There were five patients whose evaluations raised possible ethical dilemmas: one had nonadherence to dialysis; two of Guyanese origin living abroad wished to have the transplant performed in Guyana; a minor wished to donate to her mother; and another subject was considering commercialization of the transplant process. RESULTS: Since inception of the renal replacement program in 2008, we have completed 13 living kidney transplantations, 17 peritoneal dialysis placements, and 20 vascular access procedures. In the five patients wherein faced ethical dilemmas, three were rejected for consideration despite having living donors: one was nonadherent, the second excluded due to an attempt to commercialize the process, and the third, a minor who wished to donate to the mother. The other two patients were considered Guyanese ex-patriots acceptable for the program. DISCUSSION: The consequence of kidney failure in Guyana prior to introduction of renal replacement therapy was a virtual death sentence. These cases illustrate ethical dilemmas serving to throw into stark relief the implications of decisions made in a developing country versus those in a developing country.