First reported cases: renal denervation with secondgeneration multi-electrode catheter via brachial and radial access

Renal denervation is a minimally invasive procedure that aims to reduce brain–kidney sympathetic cross-talk. Despite the negative results of the recent SYMPLICITY HTN-3 trial, the procedure is considered safe and has been associated with many beneficial effects, including the reversal of hypertensive heart disease substrate and the prevention of cardiac arrhythmia. The first-generation radiofrequency catheter system featured a monopolar catheter that required sequential singlepoint energy application, followed by rotation, partial withdrawal of the catheter and re-application of energy. The latest generation device features four electrodes configured in a helical arrangement that can simultaneously ablate in four quadrants of the vessel circumference. Renal denervation via brachial or radial arterial access with the second-generation system has not been described before.     

Inter- and intra-rater reliability of diffusion tensor imaging parameters in the normal pediatric spinal cord

AIM: To assess inter- and intra-rater reliability (agreement) between two region of interest (ROI) methods in pediatric spinal cord diffusion tensor imaging (DTI).METHODS: Inner-Field-of-View DTI data previously acquired from ten pediatric healthy subjects (mean age = 12.10 years) was used to assess for reliability. ROIs were drawn by two neuroradiologists on each subject data twice within a 3-mo interval. ROIs were placed on axial B₀ maps along the cervical spine using free-hand and fixed-size ROIs. Agreement analyses for fractional anisotropy (FA), axial diffusivity, radial diffusivity and mean diffusivity were performed using intra-class-correlation (ICC) and Cronbach’s alpha statistical methods.RESULTS: Inter- and intra-rater agreement between the two ROI methods showed moderate (ICC = 0.5) to strong (ICC = 0.84). There were significant differences between raters in the number of pixels selected using free-hand ROIs (P < 0.05). However, no significant differences were observed in DTI parameter values. FA showed highest variability in ICC values (0.10-0.87). Cronbach’s alpha showed moderate-high values for raters and ROI methods.CONCLUSION: The study showed that high reproducibility in spinal cord DTI can be achieved, and demonstrated the importance of setting detailed methodology for post-processing DTI data, specifically the placement of ROIs.     

Redefining heart failure: the utility of genomics

In this era of genomics, new technologies and the information that they generate have a wide range of potential applications to heart failure. Though there has not been widespread practical use of genomic information in everyday practice, there are many examples of how this information is beginning to transform the way we look at disease states in terms of diagnosis, prognosis, and treatment. The experience of oncology and other fields helps inform the heart failure field of not only the use of this information in investigating diagnosis, prognosis, and treatment response, but the reciprocal nature of this information. This information can be clinically useful (for instance, predicting treatment response) as well as further drive laboratory investigation (teasing out the biological pathways in non-responders to treatment can be a focus of new drug discovery); this is the essence of translational medicine. We believe that this is a good time to review where new technologies and information they generate can be placed into our classic understanding of heart failure: that is how we might redefine cardiomyopathy given our new information. Here we will review genomic evidence to date and how it can and may be considered in the evaluation and management of cardiomyopathies.     

Clinical trial issues in weight-loss therapy

BACKGROUND: Overweight and obesity rates continue to increase nationally, generating significant interest in weight-loss therapies to address both the burden of obesity-associated chronic disease and individual concerns about appearance. Effective obesity therapies also have the potential for off-label use and unintended consequences. METHODS: The behavioral, pharmacologic, and surgical therapies for obesity are reviewed. Clinical trial issues common to chronic disease states and issues specific to obesity trials are examined. Finally, study designs for obesity therapy, including populations, control arms, sample size, and duration of therapy, are discussed.     

Growth hormone administration to aged animals reduces disulfide glutathione levels in hippocampus

Systemic growth hormone (GH) and insulin-like growth factor-1 (IGF-1), potent anabolic hormones, decrease with age. In humans and animal models, administration of growth hormone or IGF-1 to aged subjects improves learning and memory, suggesting that the age-related decline in cognitive performance results, in part, from peripheral GH/IGF-1 deficiency. However, the cellular mechanisms by which GH/IGF-1 effect cognitive function are unknown. We propose that the effects of these hormones may be mediated by increasing cellular redox potential resulting in reduced oxidative stress. Because the most abundant endogenous antioxidant is glutathione (GSH), we assessed GSH and disulfide glutathione (GSSH) levels in hippocampus and frontal cortex of young (4-month-old) and aged (30-month-old) male Fisher 344xBrown Norway rats treated with porcine growth hormone (200microg/animal, twice/daily) or vehicle. We report that hippocampal levels of GSSG increase with age (0.54+/-0.08 to 1.55+/-0.24nmolGSSG/mgprotein, p<0.05) and growth hormone treatment ameliorates both the age-related rise in GSSG (1.55+/-0.24 to 0.87+/-0.24nmolGSSG/mgprotein, p<0.05) and the decline in GSH/GSSG ratios. Analysis of GSSG reductase activity in aged animals indicated no effect of either age or growth hormone treatment (p=0.81). Although similar age-related increases in GSSG and decreases in GSH/GSSG ratios were evident in frontal cortex, growth hormone had no effect. Subsequently, we assessed whether the effects of age and growth hormone treatment result from modulating trace metal accumulation. Thirteen metals were analyzed in hippocampus and frontal cortex by inductive coupled plasma mass spectrometry. Aluminum, copper, iron, manganese and zinc levels increased with age (p<0.05 each) but growth hormone replacement had no effect on metal accumulation. Our results indicate that growth hormone replacement attenuates the age-related increase in oxidative stress in hippocampus without effects on glutathione reductase or trace metal accumulation. We conclude that the age-related decline in circulating growth hormone and IGF-1 contribute to increased oxidative stress in hippocampus with age.