Study protocol to investigate the effects of testosterone therapy as an adjunct to exercise rehabilitation in hypogonadal males with chronic heart failure

BACKGROUND: Testosterone deficiency is a common occurrence in men with chronic heart failure (CHF) and may underpin features of advanced disease, including reduced skeletal muscle mass and fatigue. It is positively correlated with cardiac output and exercise capacity in patients with CHF, whereas a significant improvement in both these parameters has been observed following testosterone replacement therapy. Testosterone therapy has also been shown to reduce circulating levels of inflammatory markers, (TNF-α, sICAM-1 and sVCAM-1) in patients with established coronary artery disease and testosterone deficiency. This pilot study will assess the feasibility of a combined exercise rehabilitation and adjunctive testosterone therapy intervention for evoking improvements in exercise capacity, circulating inflammatory markers, cardiac and skeletal muscle function, indices of psychological health status and quality of life in hypogonadal males with chronic heart failure. METHODS/DESIGN: Following ethical approval, 36 patients will be randomly allocated to one of two groups: testosterone or placebo therapy during exercise rehabilitation. A combined programme of moderate intensity aerobic exercise and resistance (strength) training will be used. The primary outcome measure is exercise capacity, assessed using an incremental shuttle walk test. Secondary outcome measures include measures of peak oxygen uptake, cardiac function, lower-limb skeletal muscle contractile function and oxygenation during exercise, circulating inflammatory markers, psychological health status and quality of life. DISCUSSION: Exercise rehabilitation can safely increase exercise capacity in stable CHF patients but there is a need for studies which are aimed at evaluating the long-term effects of physical training on functional status, morbidity and mortality. This pilot study will provide valuable preliminary data on the efficacy of testosterone therapy as an adjunct to exercise rehabilitation on a range of functional, physiological and health-related outcomes in this patient population. Preliminary data will be used in the design of a large-scale randomised controlled trial, aimed at informing clinical practice with respect to optimisation of exercise rehabilitation in this patient group

Telling stories about European Union Health Law: The emergence of a new field of law

The ideational narrative power of law has now solidified, and continues to solidify, ‘European Union health law’, into an entity with a distinctive legal identity. EU health law was previously seen as either non-existent, or so broad as to be meaningless, or as existing only in relations between EU law and health (the ‘and’ approach), or as consisting of a body of barely or loosely connected policy domains (the ‘patchwork’ approach). The process of bringing EU health law into being is a process of narration. The ways in which EU health law is narrated (and continues to be narrated) involve three main groups of actors: the legislature, courts and the academy

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Comparison of deposition images obtained by use of an ultrafine 99m-technetium-labeled carbon dry aerosol with ventilation images obtained by use of 81m-krypton gas for evaluation of pulmonary dysfunction in calves.

OBJECTIVE: To characterize the accuracy of an ultrafine 99m-technetium-labeled carbon dry aerosol for use in assessment of regional ventilation in calves with pulmonary dysfunction. ANIMALS: 7 Belgian White and Blue calves. PROCEDURE: The ultrafine aerosol was assessed by comparing deposition (D) images with ventilation (V) images obtained by use of 81 m-krypton (81mKr) gas via D-to-V ratio (D:V) image analysis in calves during spontaneous breathing (SB) and during experimentally induced pulmonary dysfunction (ePD). RESULTS: Mismatching index (LrTot) calculated on the D:V images revealed a good match (LrTot, 0.96 +/- 0.01) between D and V distribution patterns in calves during SB. Calculation of the ultrafine aerosol penetration index relative to 81mKr (PIRel) revealed preferential distribution of the ultrafine aerosol in lung parenchyma (PIRel, 1.13 +/- 0.11). In ePD, heterogeneity in the D:V distribution was observed (LrTot, 0.78 +/- 0.10) as a result of ultrafine aerosol particles impaction in airways as indicated by PIRel (0.66 +/- 0.16) and a proportion of pixels more radioactive in D images, compared with V images, that was located in the central part of the lung (475 +/- 77% in ePD vs 32.8 +/- 5.7% in SB). However, this central deposition did not prevent visual examination of the entire ventilated lung. CONCLUSIONS AND CLINICAL RELEVANCE: The ultrafine aerosol appears suitable for use in examination of ventilated parts of lungs of cattle, even those with impaired pulmonary function. However, airway impaction of ultrafine aerosol particles impedes the quantification of regional ventilation in cattle with abnormal lung function