To assess the genetic influence on cytokine production and its contribution to fatal outcome, we determined the capacity to produce tumour necrosis factor-α (TNFα) and interleukin-10 (IL-10) in ...families of patients who had had meningococcal disease.
We studied 190 first-degree relatives of 61 patients with meningococcal disease; we also studied 26 monozygotic twins. Production of cytokines was determined during endotoxin stimulation of whole-blood samples ex-vivo. Heritability was estimated in a pedigreebased maximum-likelihood model. DNA was typed for the G to A transition polymorphisms at position −308 and −238 in the TNF gene promoter.
Heritability in monozygotic twins was 0·60 for the production of TNF and 0·75 for the production of IL-10. Families with low TNF production had a tenfold increased risk for fatal outcome (OR 8·9, 95% CI 1·8–45), whereas high IL-10 production increased the risk 20-fold (19·5, 2·3–165). Families with both characteristics had the greatest risk. The transition polymorphisms in the TNF gene promoter were not associated with outcome.
Genetic factors substantially influence production of cytokines. An innate anti-inflammatory cytokine profile may contribute to fatal meningococcal disease.
The purpose of this study was to determine the relative risk of deep vein thrombosis (DVT) during pregnancy and puerperium in a setting that was not influenced by diagnostic suspicion and referral ...bias.
Three hundred ninety-three consecutive females with suspicion of a first episode of venous thrombosis were referred in the same way to diagnostic centers. Medical history was obtained before objective testing for deep vein thrombosis.
Seventy-six of the 393 females were diagnosed as having deep vein thrombosis; the others were used as control subjects. The odds ratios for pregnancy, cesarean section, and puerperium after adjustment for age, center, family history, and calendar time were, respectively, 5.7 (95% CI 2.5-12.9), 4.0 (95% CI 1.3-12.6), and 2.9 (95% CI 1.2-6.9).
In this case-control study, in which patients and control patients were subject to the same referral and diagnostic procedures, we found similar risk estimates for pregnancy and puerperium as in previous studies. Our findings show that previous studies were less affected by diagnostic suspicion and referral bias than presumed.
Addresses the question 'how is medical knowledge being shaped?' and defines the shaping of medical knowledge as the relative role of fact versus opinion, or of empiricism versus theory. Suggests that ...this is a process much more complicated than previously thought, and that the answers may prove unsettling. Discusses what medical journal editors do in the shaping of knowledge. (Quotes from original text)
Cancer of the gastric stump is a classical late complication of gastrectomy for benign lesion. This tumor is defined by various criteria, including a minimal delay of 5 years since the initial ...gastrectomy and the benignity of the initial lesion. Early diagnosis is difficult since suggestive clinical signs are usually associated with advanced tumors. Prognosis is globally bad and theoretically justifies routine endoscopic screening. For tumors which can be radically resected, completion gastrectomy with lymphadenectomy is indicated and allows a 40% 5-year survival. In other cases, palliative treatment remains a major concern.
Human autoimmune gastritis (AIG) is a chronic inflammatory disorder of the gastric corpus. We have defined the antigen repertoire and the functional properties of in vivo activated CD4+ T cells ...derived from the gastric mucosa of patients with AIG. A remarkable proportion of the CD4+ T cell clones proliferated in response to H+,K+-ATPase. Six epitopes identified in the α chain, and 5 in the β chain, of gastric K+,K+-ATPase were recognized by autoreactive gastric T cell clones. The majority of the autoreactive T cell clones secreted IFN-γ and showed a T helper 1 (Th1) profile. All clones produced TNF-α,provided help for B cell immunoglobulin production, expressed perforin-mediated cytotoxicity, and most induced Fas-Fas ligand-mediated apoptosis. Data suggest that activation of gastric H+,K+-ATPase-specific Th1 T cells is crucial in the pathogenesis of human gastric autoimmunity and atrophy.
