Objective-The aim of this study was to determine whether macrophages dispersed throughout perivascular fat are crucial to the loss of anticontractile function when healthy adipose tissue becomes inflamed and to gain an understanding of the mechanisms involved. Methods and Results-Pharmacological studies on in vitro small arterial segments from a mouse model of inducible macrophage ablation and on wild-type animals were carried out with and without perivascular fat using 2 physiological stimuli of inflammation: aldosterone and hypoxia. Both inflammatory insults caused a similar loss of anticontractile capacity of perivascular fat and increased macrophage activation. Aldosterone receptor antagonism and free radical scavengers were able to restore this capacity and reduce macrophage activation. However, in a mouse deficient of macrophages CD11b-diptheria toxin receptor (CD11b-DTR), there was no increase in contractility of arteries following aldosterone incubation or hypoxia. Conclusion-The presence and activation of macrophages in adipose tissue is the key modulator of the increase in contractility in arteries with perivascular fat following induction of inflammation. Despite multiple factors that may be involved in bringing about the vascular consequences of obesity, the ability of eplerenone to ameliorate the inflammatory effects of both aldosterone and hypoxia may be of potential therapeutic interest. Key Words: hypoxia Ⅲ microcirculation Ⅲ obesity Ⅲ inflammation O besity is set to reach epidemic levels in many countries, 1 predisposing individuals to an increased risk of type II diabetes, hypertension, and the inevitable consequences of circulatory disease. 2 The hallmark of this phenotype is an increase in the size of individual adipocytes as excess energy is stored, together with the recruitment and activation of macrophages and the release of cytokines as local inflammation ensues. 3,4 The effect on the vasculature can be profound, with loss of vasodilator adipokine bioavailability, increased tone, 5,6 and the development of the metabolic syndrome. 7

Background: Chest x-ray (CXR) is the first line investigation for lung cancer in many countries. Previous research has suggested that lung cancer is not detected by CXR in approximately 20% of patients. The risk of lung cancer, with particular symptoms, following a negative CXR is not known. Aims: 1) To establish the sensitivity and specificity of CXR requested by symptomatic patients 2) To determine the positive predictive values (PPVs) of each presenting symptom of lung cancer following a negative CXR. Design & Setting: A prospective cohort study based on routinely collected data from a service which allowed patients with symptoms to request CXR. Methods: Symptom data was combined with a diagnostic category (positive or negative) for each CXR. Sensitivity and specificity of CXR for lung cancer was calculated. The positive predictive values (PPVs) of lung cancer associated with each symptom was estimated for those with negative CXR. Results: 114 (1.3%) out of 8996 patients were diagnosed with lung cancer within one year. Sensitivity was 75.4% and specificity was 90.2%. Risk of lung cancer following a negative CXR was low for all symptoms with the exception of haemoptysis, which had a positive predictive value of 2.9%. Conclusion: CXR has limited sensitivity. However, in a low prevalence population, its high specificity and negative predictive value means that lung cancer is very unlikely to be present following a negative result. The study also provides further evidence that supports guidance that unexplained haemoptysis warrants urgent referral, regardless of CXR result.

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