Thesis (doctoral)--Westfälische Wilhelms-Universität zu Münster. / Includes bibliographical references (p. [25]-27).

Rheumatic heart disease is an inflammatory heart disease that affects millions of people around the world. Especially high rates of the disease can be found in Oceania, including the island nation of Samoa. Genetic studies of immune response genes have provided insight into a possible genetic link to increased susceptibility to rheumatic heart disease, including the genes that code for the toll-like receptor (TLR) protein family. One of the functions of TLR proteins is to recognize the presence of bacteria via identification of bacterial flagella. My evaluation of a Samoan family identified a variant in the TLR-5 gene that would inhibit this ability. However, further study showed this variant to not be statistically significant in relation to rheumatic heart disease susceptibility. My contribution to a regional genome-wide association study of Oceania resulted in the discovery of a variant in the IGHV4-61 gene affecting the ability of antibodies to properly bind to bacterial antigens. This variant was associated with a 1.4-fold increased risk of rheumatic heart disease development. The success of this study warrants further investigation of the IGHV4-61 variant in other populations and illustrates the benefits of utilizing a genome-wide association study to study rheumatic heart disease.

Thesis (M.P.H.)--University of Michigan, 1950.

Thesis (M.P.H.)--University of Michigan, 1950.

No description available.

No description available.

No description available.

Orientador: Julio Defaveri / Resumo: O presente trabalho teve como objetivo principal padronizar o teste de contraimunoeletroforese (CIE) para detecção dos autoanticorpos contra os antígenos SS-A/Ro e SS-B/La. Como complementação, realizou-se a padronização da obtenção dos antígenos Ro e La à partir de baço de cão. Para consecução dos objetivos, foram realizadas as seguintes etapas: 1. Extração dos antígenos Ro e La à partir de baço de cão 2. Padronização da CIE com os antígenos obtidos: 2.1 Padronização da técnica CIE propriamente dita; 2.2 Teste qualitativo dos antígenos Ro e La obtidos com padrão USP-SP e ELISA-kit comercial para esses antígenos. 3. Escolha dos casos de doença reumática (diagnosticados por biópsia - 40 pacientes) e controles (soro de doadores de sangue - 10 doadores). As doenças selecionadas tiveram a seguinte distribuição: 3.1 Lúpus Eritematoso Sistêmico = 29 casos 3.2 Lúpus Eritematoso Discóide = 4 casos 3.3 Esclerodermia = 3 casos 3.4 Síndrome de Sjögren = 4 casos 4. Realização dos testes CIE e ELISA-kit. 5. Obtenção dos resultados dos testes de imunofluorescência indireta (IFI) para fator anti-núcleo (FAN) e anti-DNA, ELISA- RNP e ELISA- Sm, realizados na rotina diagnóstica de doenças autoimunes no Laboratório de Imunopatologia do Departamento de Patologia- FMB-UNESP. 6. Comparação e estatística dos resultados obtidos pela CIE com os demais testes. Os resultados e as conclusões obtidas foram as seguintes: 1. Na padronização e nos testes dos soros dos pacientes reumáticos, a CIE apresentou, em geral, apenas uma linha de precipitação bem definida. Somente em dois casos ocorreram duas linhas de precipitação. A presença de uma linha de precipitação impossibilitou a caracterização da presença de anticorpos anti-Ro e anti-La. A detecção de apenas uma linha de precipitação pode ter sido devida: a) aos baixos níveis de ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The main objective of the present work was to standardize the counterimmunoelectrophoresis assay for the detection of autoantibodies to the SS-A/Ro and SS-B/La autoantigens. As a complementary objective, the extraction of both antigens from dog's spleen was also standardized. To accomplish these objectives, the following steps was performed: 1. Extraction of the Ro e La antigens from dog's spleen. 2. CIE standardization with the extracted antigens: 2.1 Standardization of CIE test; 2.2 Qualitative and quantitative analysis of the Ro e La antigens present in the extract of the spleens with a gold-standard (positive serum against Ro and La antigens + Ro and La antigens obtained from spleen dog) obtained from the University of São Paulo-SP and with a commercial ELISA-kit for detection of autoantibodies against these antigens. 3. Selection of the cases with rheumatic disease (diagnosed by biopsys - 40 patients) and normal individual for control serum (blood donors - 10 donors). The diseases and the number of each one in the forty selected cases was distributed as follow: 3.1 Systemic erithematous lupus = 29 cases 3.2 Discoid erithematous lupus = 4 cases 3.3 Scleroderma = 3 cases 3.4 Sjögren syndrome = 4 cases 4. Performance of the CIE e the ELISA-kit tests. 5. Obtaining the results of the following tests: IFI , AAN anti-DNA, ELISA- RNP and ELISA- Sm, registered in the files of the service of autoimmune diseases of the Laboratory of Immunopathology, Department of Pathology - UNESP University - Botucatu Medical School. 6. Statistical analysis and comparison of the results of CIE and other tests. The results and conclusions were the following: 1. In the standardization for the Ro and La antigens in the extract of the spleens and in the tests performed in the serum of rheumatic patients, the CIE in general expressed only one well-defined line of precipitation. Only... (Complete abstract, click electronic access below) / Mestre

Background: Despite Rheumatic Heart Disease (RHD) contributing to an estimated disease burden in 2019 of 40 million people and 285 500 deaths, few studies document the characteristics and outcomes in children. We undertook a sub-analysis of children from the multi-centre prospective two-year global Rheumatic Heart Disease Registry (REMEDY) to document their presentation, clinical characteristics and outcomes. Methods: Nine-hundred and twenty-one children were enrolled into the REMEDY registry among the 3,343 symptomatic RHD patients from 25 hospitals in 12 African countries, India and Yemen and followed up over 24 months to assess characteristics, complications and outcome. Results: More than half of the children enrolled in the REMEDY study presented with severe valvular heart disease; 60% had more than one valve involved, 30% were classified as NYHA class III/IV and 17.7% died within 24 months. Just over 20% of children were not on penicillin prophylaxis. Although 20% met criteria for surgery, only less than 9% (n=78, 8.5%) had had percutaneous or surgical intervention with half from upper-middle-income countries. The major risk factors associated with mortality included older age (Hazard Ratio (HR): 1.01, p=0.001) and atrial fibrillation or flutter (HR: 2.3, p=0.028). Female gender(HR: 0.68, p=0.062) and education level above primary school (HR: 0.88, p=0.68) did not confer significant protection. However, a past medical history of ARF conferred some protection against mortality (HR: 0.61, p=0.031). In follow-up, 30% (n=238, 29.6%) of children experienced an adverse cardiovascular event, nearly 15% (n=114, 14.1%) were hospitalised and six young women became pregnant during the study period. Conclusion: Children with RHD in low- and middle-income countries are severely affected, with significant mortality and morbidity. The use of penicillin was suboptimal and the substantial need for surgery is evident. Our findings support the recommendations of the World Health Assembly (WHA) Resolution 71.14 passed in May 2018 for consistent provision of penicillin, integrated collaborative efforts focused on children and adolescent health as well as access to specialised services including cardiac surgery.

Dissertation submitted to the University of the Witwatersrand, in partial fulfilment of an MSc in Child Health. Johannesburg 1997 / AC2017