Objective-To determine whether serum concentrations of the cytokines tumour necrosis factor a (TNFa) and interleukin 6 (IL-6), which regulate C reactive protein, are associated with cardiovascular risk factors and prevalent coronary heart disease. Design--A population based cross sectional study. Subjects and methods-198 men aged 50 to 69 years were part of a random population sample drawn from south London. Serum cytokine and C reactive protein concentrations were determined by enzyme linked immunosorbent assay. The presence of coronary heart disease was determined by Rose angina questionnaire and Minnesota coded electrocardiogram. Results-Serum TNFa concentrations were positively related to body mass index and Helicobacter pylori infection, but inversely related to alcohol consumption. IL-6 concentrations were positively associated with smoking, symptoms of chronic bronchitis, age, and father having a manual occupation. TNFa was associated with increased IL-6 and triglycerides, and reduced high density lipoprotein cholesterol. IL-6 was associated with raised fibrinogen, sialic acid, and triglycerides. ECG abnormalities were independently associated with increases in IL-6 and TNFa, each by approximately 50% (P < 0*05 for TNFa, P < 0 1 for IL-6). The corresponding increases in men with an abnormal ECG or symptomatic coronary heart disease were 28% for TNFa and 36% for IL-6 (P = 0*14 for TNFa and P < 0*05 for IL-6). Conclusions-This study confirms that many of the phenomena with which C reactive protein is associated, are also associated with serum levels of cytokine, which may be the mechanism. (Heart 1997;78:273-277) Keywords: C reactive protein; interleukin 6; TNFa; cardiovascular risk; coronary heart disease Cardiovascular risk factors as established in prospective studies could be considered to fall into two broad groups: endogenous and exogenous (lifestyle) Inflammation may be this mechanism.Most cardiovascular risk factors are changed in an adverse direction by acute inflammation: fibrinogen and the white blood cell count rise, glucose rises, HDL falls, and triglycerides rise.5-7 We have shown recently that low levels of systemic inflammation, as measured by serum C reactive protein in normal subjects, are related to many of these endogenous risk factors and that these levels of inflammatory activity are influenced in turn by many of the exogenous (lifestyle) cardiovascular risk factors.8 C reactive protein production by the liver is regulated by cytokines, principally interleukin 6 (IL-6), and tumour necrosis factor a (TNFa), which is the main trigger for the production of IL-6 by a variety of cells.9 The effect of these cytokines is modulated by cortisol and growth factors such as insulin.'0 In vitro and animal challenge experiments suggest that IL-6 and TNFa play important roles in the regulation of the synthesis of other acute phase proteins which are established risk factors for atherosclerosis, such as fibrinogen and factor VIII.10 These cytokines also have profound effects on lipid meta...

When an economic evaluation incorporates patient-level data, there are two types of uncertainty over the results: uncertainty due to variation in the sampled data, and uncertainty over the choice of modelling parameters and assumptions. Previously statistical methods have been used to estimate the extent of the former, and sensitivity analysis to estimate the extent of the latter. Ideally interval estimates for economic variables should reflect both types of uncertainty. This paper describes a method for combining bootstrapping with probabilistic sensitivity analysis to estimate a total 'uncertainty range' for incremental costs. The approach is illustrated using cost data from a randomized controlled trial of endoscopy for Helicobactor pylori negative young dyspeptic patients. The trial failed to demonstrate any clinical benefit from endoscopy, which was on average pound 395 more costly. The combined 95% uncertainty range for incremental costs (-pound 236 to pound 931) was wider than 95% intervals estimated by either probabilistic sensitivity analysis (pound 43 to pound 592) or the non-parametric bootstrap method (-pound 95 to pound 667) alone. The method can easily be extended to the calculation of uncertainty ranges for incremental cost-effectiveness ratios.

Celiac disease is a common condition that is thought to affect 1 in 200 people throughout Europe and America, with prevalence rates reaching 1:100 in Ireland. Improvements in the sensitivity and specificity of serological testing for celiac disease over the past 15 years have resulted in a larger number of diagnoses being made. Up to 34% of patients with newly diagnosed celiac disease are older than 60 years of age. The symptomatic presentation of celiac disease in elderly patients can be subtle, leading to a considerable delay in diagnosis and potential accumulation of associated secondary complications. Given that celiac disease is associated with significant morbidity and reduced life expectancy, physicians need to be aware of this condition and its occurrence in the current increasingly elderly population. Compliance with a strict gluten-free diet is as easily achieved in elderly patients as in younger patients, and has been reported to reduce the risks of cancer and lymphoma associated with celiac disease. This Review highlights age-related differences in the clinical presentation and investigation of patients with suspected celiac disease.

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