Endoscopy and implantable electronic devices.

The increasing use of implantable electronic devices such as cardiac pacemakers and neurostimulators means that they are being increasingly encountered in endoscopy departments. The electromagnetic fields generated during electrosurgery and with magnetic imaging systems have the potential to interfere with such devices. The authors present a case that highlights some of the steps necessary for minimising risk, review the evidence and summarise the currently available guidance.

Increased incidence of interatrial block in younger adults with cryptogenic stroke and patent foramen ovale.

BACKGROUND: Stroke is often unexplained in younger adults, although it is often associated with a patent foramen ovale (PFO). The reason for the association is not fully explained, and mechanisms other than paradoxical embolism may be involved. Young stroke patients with PFO have more atrial vulnerability than those without PFO. It is plausible that stretching of the interatrial septum may disrupt the interatrial conduction pathways causing interatrial block (IAB). IAB is associated with atrial fibrillation, dysfunctional left atria and stroke. METHODS: Electrocardiogram (ECG) characteristics of prospectively recruited young patients (≤55 years of age) with unexplained stroke (TOAST and A-S-C-O) were compared with control data. All stroke cases underwent bubble contrast transthoracic and transoesophageal echography. IAB was defined as a P-wave duration of ≥110 ms. ECG data were converted to electronic format and analysed in a blind manner. RESULTS: Fifty-five patients and 23 datasets were analysed. Patients with unexplained stroke had longer P-wave duration (p = 0.013) and a greater prevalence of IAB (p = 0.02) than healthy controls. Case status was an independent predictor of P-wave duration in a significant multivariate model. There was a significant increase in the proportion of cases with a PFO with IAB compared with cases without PFO and with controls (p = 0.005). CONCLUSIONS: Young patients with unexplained stroke, particularly those with PFO, exhibit abnormal atrial electrical characteristics suggesting atrial arrhythmia or atrial dysfunction as a possible mechanism of stroke.

Testosterone acts as an efficacious vasodilator in isolated human pulmonary arteries and veins: evidence for a biphasic effect at physiological and supra-physiological concentrations.

BACKGROUND: Testosterone is recognized to elicit vasodilatation in numerous vascular beds, however to date no study has investigated whether testosterone has this effect in the human pulmonary vasculature. AIM: To determine whether isolated human pulmonary arteries and veins dilate in response to testosterone and whether the response differs in relation to gender, endothelial function or location with the pulmonary vasculature. METHODS: Intralobar pulmonary arteries [no.=44, diameter =581 (349) microm] and veins [no.=27, diameter =573 (302) microm] were dissected from lobectomy samples obtained from male and female patients [no.=40, age =69 (8) yr]. Vessels were mounted in an automated wire myograph, bathed in physiological saline at 37 C and pH 7.4, and loaded to their in vivo pressure. Vessels were preconstricted with noradrenaline (10 microM) and exposed to acetylcholine (1 microM) to assess endothelial function, washed and then preconstricted with potassium chloride (1-100 mM) followed by either cumulative concentrations of testosterone (1 nM-100 microM) or ethanol vehicle (<0.1%). RESULTS: Significant marked vasodilatation was seen in all vessels, irrespective of size, gender and endothelial function at micromolar concentrations. Testosterone triggered significant vasodilatation at concentrations > or = 10 nM in pulmonary arteries obtained from males, a response which was not observed in vessels from females. The maximal response at 100 microM was also significantly greater in male pulmonary arteries. Significant vasodilatation was only observed at physiological (nM) concentrations in pulmonary resistance arteries and pulmonary arteries with good endothelial function. CONCLUSION: Testosterone acts as an efficacious vasodilator in the human pulmonary vasculature, with dilatation observed at physiological concentrations in the male arterial resistance bed, dependent on the presence of an intact endothelium.

Inverse relationship between serum levels of interleukin-1beta and testosterone in men with stable coronary artery disease.

OBJECTIVES: To examine the relationship between serum levels of inflammatory cytokines and testosterone in men with stable coronary artery disease (CAD). Evidence supports a beneficial effect of testosterone upon objective measures of myocardial ischaemia in men with CAD, and in animal models of atherosclerosis. Inflammatory cytokines are involved in many stages of the atherosclerotic process, however, the effect of testosterone upon inflammatory cytokines within the cardiovascular system is largely unknown. METHODS: Serum was collected from 69 men (59+/-1 years) having >75% occlusion of 1, 2, or 3 coronary arteries. Levels of total testosterone (TT), bioavailable testosterone (BT), tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-1-beta (IL-1beta), IL-6 and IL-10 were measured and analysis made between men with 1, 2, or 3 vessel CAD, and between men with hypogonadal, borderline hypogonadal and eugonadal serum levels of testosterone. RESULTS: In patients with 1, 2, or 3 vessel CAD, significant stepwise increases were observed in levels of IL-1beta: 0.16+/-0.03, 0.22+/-0.06, and 0.41+/-0.08 pg/ml (p=0.035), and IL-10: 0.93+/-0.11, 1.17+/-0.14, and 2.94+/-0.65 pg/ml (p=0.008). A significant stepwise increase in levels of IL-1beta was also observed in eugonadal, borderline hypogonadal, and hypogonadal men: 0.19+/-0.05, 0.29+/-0.05, and 0.46+/-0.13 pg/ml (p=0.047). CONCLUSION: Consequently this data implicates IL-1beta and IL-10 in the pathogenesis of CAD and suggests that testosterone may regulate IL-1beta activity in men with CAD.

Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life.

BACKGROUND: Low serum testosterone is associated with several cardiovascular risk factors including dyslipidaemia, adverse clotting profiles, obesity, and insulin resistance. Testosterone has been reported to improve symptoms of angina and delay time to ischaemic threshold in unselected men with coronary disease. OBJECTIVE: This randomised single blind placebo controlled crossover study compared testosterone replacement therapy (Sustanon 100) with placebo in 10 men with ischaemic heart disease and hypogonadism. RESULTS: Baseline total testosterone and bioavailable testosterone were respectively 4.2 (0.5) nmol/l and 1.7 (0.4) nmol/l. After a month of testosterone, delta value analysis between testosterone and placebo phase showed that mean (SD) trough testosterone concentrations increased significantly by 4.8 (6.6) nmol/l (total testosterone) (p = 0.05) and 3.8 (4.5) nmol/l (bioavailable testosterone) (p = 0.025), time to 1 mm ST segment depression assessed by Bruce protocol exercise treadmill testing increased by 74 (54) seconds (p = 0.002), and mood scores assessed with validated questionnaires all improved. Compared with placebo, testosterone therapy was also associated with a significant reduction of total cholesterol and serum tumour necrosis factor alpha with delta values of -0.41 (0.54) mmol/l (p = 0.04) and -1.8 (2.4) pg/ml (p = 0.05) respectively. CONCLUSION: Testosterone replacement therapy in hypogonadal men delays time to ischaemia, improves mood, and is associated with potentially beneficial reductions of total cholesterol and serum tumour necrosis factor alpha.

Testosterone as a protective factor against atherosclerosis--immunomodulation and influence upon plaque development and stability.

Inflammation plays a central pathogenic role in the initiation and progression of coronary atheroma and its clinical consequences. Cytokines are the mediators of cellular inflammation and promote local inflammation in the arterial wall, which may lead to vascular smooth muscle apoptosis, degradation of the fibrin cap and plaque rupture. Platelet adhesion and thrombus formation then occur, resulting clinically in unstable angina or myocardial infarction. Recent studies have suggested that cytokines are pathogenic, contributing directly to the disease process. 'Anti-cytokine' therapy may, therefore, be of benefit in preventing or slowing the progression of cardiovascular disease. Both oestrogens and testosterone have been shown to have immune-modulating effects; testosterone in particular appears to suppress activation of pro-inflammatory cytokines. Men with low testosterone levels are at increased risk of coronary artery disease. An anti-inflammatory effect of normal physiological levels of sex hormones may, therefore, be important in atheroprotection. In this Article, we discuss some of the mechanisms involved in atherosclerotic coronary artery disease and the putative link between testosterone deficiency and atheroma formation. We present the hypothesis that the immune-modulating properties of testosterone may be important in inhibiting atheroma formation and progression to acute coronary syndrome.

Effect of cigarette smoking on levels of bioavailable testosterone in healthy men.

The effect of smoking on androgen levels is important given the recent interest in the link between low levels of androgens and the development of cardiovascular disease. Numerous studies examining the effects of cigarette smoking on the levels of total and free testosterone have reported conflicting findings, but there has been no accurate assessment of the effects of cigarette smoking on the levels of bioavailable testosterone [not bound to sex hormone-binding globulin (SHBG)]. We attempted to determine whether smoking affects the level of bioavailable testosterone. We undertook a case-control study of 25 healthy male smokers and 25 healthy never-smokers, matched by age and body mass index. Early morning levels of total, free and bioavailable testosterone, 17beta-oestradiol, SHBG and cotinine were determined and compared between the two groups. Levels of total (18.5+/-4.6 nM versus 15.1+/-4.9 nM, P=0.01) and free testosterone (462+/-91 pM versus 402+/-93 pM, P=0.03) were found to be higher in smokers compared with non-smokers respectively, as was SHBG (34.1+/-12.8 versus 28.1+/-9.0 nM, P=0.06). There were no significant differences in the levels of bioavailable testosterone (3.78+/-1.59 versus 3.51+/-1.26 nM, P=0.49) or 17beta-oestradiol (44.5+/-11.4 versus 42.3+/-11.5 pM, P=0.50) between smokers and non-smokers respectively. These data suggest that cigarette smoking has no significant effect on the biologically active fraction of testosterone, but may influence the levels of total and free testosterone through changes in the levels of SHBG.