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OBJECTIVE Cytokines and other inflammatory mediators are involved in the pathogenesis of otitis media. We hypothesized that polymorphisms in inflammatory response genes contribute to the increased susceptibility to acute otitis media in otitis-prone children. PATIENTS AND METHODS DNA samples from 348 children with > or = 2 acute otitis media episodes, who(More)
Macrophages infiltrate peripheral nerves and may contribute to neural damage in the Guillain-Barré syndrome (GBS). We determined whether single nucleotide polymorphisms (SNP) in genes encoding macrophage-mediators are related to the susceptibility and severity of GBS. The frequencies of SNP in the TNFA, MMP9, IL10, and NOS2a genes did not differ between 263(More)
Meningococcal disease is an infection caused by Neisseria meningitidis. Genetic factors contribute to host susceptibility and progression to disease, but the genes responsible for disease development are largely unknown. We report here a genome-wide association study for host susceptibility to meningococcal disease using 475 individuals with meningococcal(More)
The clinical presentation of infections caused by Neisseria meningitidis is highly diverse. Some patients develop meningitis, and others present with sepsis or even septic shock. After invasion of the bloodstream by the bacteria, three main cascade pathways are activated. These are the complement system, the inflammatory response, and the coagulation and(More)
BACKGROUND Identification of new therapeutic targets remains an imperative goal to improve the morbidity and mortality associated with severe sepsis and septic shock. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine and counterregulator of glucocorticoids, has recently emerged as a critical mediator of innate immunity and(More)
BACKGROUND To gain insight into factors that might affect results of future case-control studies, we performed an analysis of children with sepsis and purpura admitted to the paediatric intensive care unit (PICU) of Erasmus MC-Sophia Children's Hospital (Rotterdam, The Netherlands). METHODS Between 1988 and 2006, all 287 children consecutively admitted(More)
BACKGROUND Staphylococcus aureus is capable of persistently colonizing the vestibulum nasi. We hypothesized that polymorphisms in host inflammatory response genes and genetic variation in S. aureus contribute to susceptibility to S. aureus carriage and infection. METHODS The prevalence of persistent nasal carriage of S. aureus in 3851 participants aged(More)
OBJECTIVE Cell death leading to circulating nucleosomes and histones is a critical step in the pathogenesis of sepsis and contributes to lethality. Activated protein C was demonstrated to attenuate the harmful effects of histones. The objective of this retrospective study was to evaluate whether nucleosomes correlate with the severity of the inflammatory(More)
BACKGROUND Various cytokines and inflammatory mediators are known to be involved in the pathogenesis of rheumatoid arthritis (RA). We hypothesized that polymorphisms in selected inflammatory response and tissue repair genes contribute to the susceptibility to and severity of RA. METHODS Polymorphisms in TNFA, IL1B, IL4, IL6, IL8, IL10, PAI1, NOS2a, C1INH,(More)
INTRODUCTION The glucocorticoid receptor (GR) plays an important regulatory role in the immune system. Four polymorphisms in the GR gene are associated with differences in glucocorticoid (GC) sensitivity; the minor alleles of the polymorphisms N363 S and BclI are associated with relative hypersensitivity to GCs, while those of the polymorphisms ER22/23EK(More)