Osteoarthritis (OA) refers to a heterogeneous group of conditions. This thesis focuses on OA with a hereditary background; Familial OA at multiple joint sites and radiological hand OA at middle age... Show moreOsteoarthritis (OA) refers to a heterogeneous group of conditions. This thesis focuses on OA with a hereditary background; Familial OA at multiple joint sites and radiological hand OA at middle age. The main objective is to identify risk factors that play a role in the development of OA in order to gain further insight in the aetiology of OA. The secondary objective is to investigate factors that determine the outcome in OA. This thesis provides evidence that familial clustering of symptomatic OA is most prominent for hand and hip OA. In search for genetic risk factors, we present data suggesting that a proportion of the genetic susceptibility for OA at multiple sites is encoded by variation in innate cytokine activity. Further, we find HLA-DR antigens to be associated with radiological hand OA. In addition to genetic risk factors, this thesis demonstrates that other systemic risk factors such as hormonal status and local factors, to be important in the susceptibility of familial OA at multiple sites, underscoring the multicausal etioliology of this phenotype. Finally, this thesis addresses the resulting disability from OA. Using the International Classification of Functioning, Disability and Health as framework, we show illness perceptions and mental health to be important modifying factors in OA in the hands and lower extremities. Show less
In a surveillance study in Jakarta, Indonesia, 88 typhoid and 26 paratyphoid fever patients were identified by blood culture. Risk factors for transmission of typhoid fever were mainly intra... Show moreIn a surveillance study in Jakarta, Indonesia, 88 typhoid and 26 paratyphoid fever patients were identified by blood culture. Risk factors for transmission of typhoid fever were mainly intra-household factors (poor hand-washing hygiene, recent household contacts), whereas paratyphoid was mainly contracted through street food. In an additional study, street vendors observed poorer hand-washing and food-handling hygiene compared to food handlers in restaurants, and had higher bacterial loads in dishwater. Further host factor-studies in (para)typhoid patients revealed that polymorphisms in genes encoding pro-inflammatory cytokines (IFN-_, IL1A/B, IL1R1, TNFRSF1A, CASP1 and CRP) were not associated with susceptibility to typhoid fever, and might therefore at most be associated with severity of disease. An association was found of typhoid fever and a polymorphism in the PARK2/PACRG proteasome-mediated protein degradation pathway through ubiquitination, similar to infection with Mycobacterium leprae. Also an association between genotypes in the Cystic Fibrosis Transmembrane Conductance Regulator (the affected protein in Cystic Fibrosis) and susceptibility to typhoid fever was found, suggesting a decreased adherence potential of S. typhi to intestinal mucosal cells with these polymorphisms. Finally, bacterial characteristics were compared by use of AFLP and biochemical/antibiotic susceptibility profiles, showing very homogeneous S. typhi and S. paratyphi A strains circulating in the study area. Show less
The role of the multifunctional cytokine Transforming Growth Factor-beta 1 in cervical carcinoma on the formation of tumor stroma, tumor infiltrate, PAI-1 and alpha v beta 6 is investigated.
