In reply to Swain et al.: Re-evaluation of updated meta-analysis including trials RTOG 1016 and De-ESCALaTE

European Archives of Oto-Rhino-Laryngology -     

Vascular calcification and atherosclerosis in hemodialysis patients: what can we learn from the routine clinical practice?

BACKGROUND: Hemodialysis (HD) patients are at increased risk for arterial intimal (AIC) and medial calcification (AMC). METHODS: In a cross-sectional study on 153 HD patients we evaluated the presence of AIC and AMC using plain radiography of the pelvis and the presence of atherosclerotic lesions using high-resolution B-mode ultrasonography of the common carotid arteries (CCA). RESULTS: The radiography of the pelvis confirmed the frequent presence of AIC (35.3%) and AMC (35.9%) in our HD patients. Arterial calcification was absent (non calcified-NC) in a minority of patients (28.8%). Patients with AIC had significantly higher prevalence of atherosclerotic plaques on CCA (78.6%) compared with both other groups and a higher number of documented atherosclerotic complications, such as cardiovascular (85.2%), cerebrovascular (33.3%) and peripheral arterial disease (38.9%) in comparison with the NC patients. According to the 1-year calculated data from patient records, there were no significant differences in the specific HD risks, such as the dose of prescribed calcium carbonate and vitamin D3, serum levels of calcium, phosphate, calcium-phosphate product and intact parathyroid hormone. All four bone metabolism markers within the range proposed by K/DOQI guidelines were achieved in 9.3%, 14.5% and 20.4% in the AIC, AMC and NC group, respectively. CONCLUSIONS: Patients with AIC and AMC are frequently found in the HD population. Screening for arterial calcifications in chronic kidney disease patients is suggested even in the early pre-dialysis period. The highest proportion of patients within the guidelines proposed range for bone and mineral metabolism markers was observed in the NC group. A longer period of data analysis is required in order to evaluate the possible role of some traditional and HD-specific risk factors for the development of arterial calcifications. The achievement of the K/DOQI guidelines is an important issue in the prevention of those conditions.     

Atypical presentation of distal renal tubular acidosis in two siblings

Primary distal renal tubular acidosis (dRTA) is an inherited disease characterized by the inability of the distal tubule to lower urine pH <5.50 during systemic acidosis. We report two male siblings who presented with severe hyperchloremic metabolic acidosis, high urinary pH, nephrocalcinosis, growth retardation, sensorineural hearing loss, and hypokalemic paralysis. Laboratory investigations revealed proximal tubular dysfunction (low molecular weight proteinuria, generalized hyperaminoaciduria, hypophosphatemia with hyperphosphaturia, and hypouricemia with hyperuricosuria). There was significant hyperoxaluria and laboratory evidence for mild rhabdomyolysis. Under potassium and alkali therapy, proximal tubular abnormalities, muscular enzymes, and oxaluria normalized. A homozygous mutation in the ATP6V1B1 gene, which is responsible for dRTA with early hearing loss, was detected in both siblings. In conclusion, proximal tubular dysfunction and hyperoxaluria may be found in children with dRTA and are reversible under appropriate therapy.     

Voxel‐wise quantification of myocardial perfusion by cardiac magnetic resonance. Feasibility and methods comparison

The purpose of this study is to enable high spatial resolution voxel‐wise quantitative analysis of myocardial perfusion in dynamic contrast‐enhanced cardiovascular MR, in particular by finding the most favorable quantification algorithm in this context. Four deconvolution algorithms—Fermi function modeling, deconvolution using B‐spline basis, deconvolution using exponential basis, and autoregressive moving average modeling —were tested to calculate voxel‐wise perfusion estimates. The algorithms were developed on synthetic data and validated against a true gold‐standard using a hardware perfusion phantom. The accuracy of each method was assessed for different levels of spatial averaging and perfusion rate. Finally, voxel‐wise analysis was used to generate high resolution perfusion maps on real data acquired from five patients with suspected coronary artery disease and two healthy volunteers. On both synthetic and perfusion phantom data, the B‐spline method had the highest error in estimation of myocardial blood flow. The autoregressive moving average modeling and exponential methods gave accurate estimates of myocardial blood flow. The Fermi model was the most robust method to noise. Both simulations and maps in the patients and hardware phantom showed that voxel‐wise quantification of myocardium perfusion is feasible and can be used to detect abnormal regions. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

Effects of Chair-Based,Low–Load Elastic Band Resistance Training on Functional Fitness and Metabolic Biomarkers in Older Women

Strength training can improve myriad health parameters in elderly cohorts. Although potentially more appropriate for the elderly, low-load resistance training protocols have been less investigated. We aimed to examine the effects of 12 weeks of chair-based, low-load resistance training with elastic band (EBT) on functional fitness and metabolic biomarkers in older women. One hundred sixty-eight women were allocated randomly to an elastic band resistance training (EBT, n = 86, 75.7 ± 8.9 years, 71.3 ± 12.2 kg) or a control group (CON, n = 82, 74.5 ± 8.2years, 70.6 ± 12.0 kg). RT protocol consisted of periodized chair-based, low-load whole-body resistance exercises (2 sets, 12-15 repetitions, 40-60% of one repetition maximum-1RM) using an elastic band, twice weekly for 12 weeks. The resistance training program was generally designed to maintain internal load over time, provided with increasing intensity using various elastic bands (Thera-Band). Functional fitness (30-s Chair Stand,30-s Arm Curl, 2-min Step Test, Chair Sit-and-Reach, Back Scratch, 8-Foot Up-and-Go, Handgrip Strength) and metabolic markers (Fasting blood glucose, triglycerides, total cholesterol, high (HDL) and low (LDL) density lipoprotein) were measured before and after the training period. To detect pre/post intervention changes and between group- differences 2x2 repeated measures ANOVA was applied. Significant improvements over time for all fitness variables for EBT comparing to CON were obtained (F = 12.78, p < 0.05 for 30-s Chair Stand; F = 14.04, p < 0.05 for 30-s Arm Curl; F = 5.18, p < 0.05 for 2-min Step Test; F = 10.90, p < 0.05 for Chair Sit-and-Reach; F = 16.57, p < 0.05 for Back Scratch; F = 11.79, p < 0.05 for 8-foot Up-and-Go; and F = 29.25, p < 0.05 for Handgrip Strength). In addition, significant improvements over time for all but one (triglycerides) biomarkers for EBT comparing to CON were obtained (F = 7.30, p < 0.05 for blood sugar levels; F = 13.36, p < 0.05 for total cholesterol; F = 8.61, p < 0.05 for HDL; and F = 11.53, p < 0.05 for LDL). Furthermore, the participants’ adherence to training sessions of over 90% was reported. In conclusion, 12 weeks of EBT is safe and beneficial for improving health-related fitness and metabolic biomarkers in older women and seems to be viable model to ensure a high training adherence rate.Key points

• EBT lead to a significant improvement in glucose, total cholesterol, HDL and LDL in older women.
• EBT lead to a significant increase in cardiorespiratory fitness, handgrip strength, lower- body strength and flexibility, upper-body strength and flexibility and agility in older women.
• EBT seems to be viable model to ensure high training adherence rate.

Key words: Aging, lipoproteins, low-intensity strength training, physical function     

Partial Left Ventriculectomy and Limited Heart Transplantation Availability

BACKGROUND AND AIM: Partial left ventriculectomy, a novel cardiac volume reduction operation, is applied in countries without a developed heart transplantation program. We sought to determine its impact in our population of patients. METHODS: Partial left ventriculectomy was performed in 38 patients during the last 4 years. Basic inclusion criteria were nonischemic dilated cardiomyopathy and poor response to medical therapy for heart failure. Hemodynamic evaluation was carried out before and after operation. A modified surgical technique of mitral valve repair and ventricle suturing was applied. RESULTS: Thirty-day, 6-month, and 2-year survival rates were 82% +/- 7%, 65% +/- 8%, and 61% +/- 9%, respectively. Duration of heart failure symptoms was the only predictor of survival (p = 0.042). A high proportion of noncardiac causes of death was noted. Functional capacity in surviving patients improved at every successive measurement up to 1 year postoperatively. CONCLUSIONS: The introduction of partial left ventriculectomy in a country with limited heart transplantation availability had a great impact on the management of end-stage heart failure and may represent the only surgical option for some patients. The average cost per patient was substantially lower when compared to heart transplantation.     

Mutant androgen receptors in prostatic tumors distinguish between amino-acid-sequence requirements for transactivation and ligand binding

Mutant androgen receptors are thought to contribute to hormone resistance in prostate carcinoma. The part they play in this process, however, is ill-defined. Here we report on transactivation by 2 mutant androgen receptors from prostatic tumors with single amino-acid exchanges in their hormone-binding domains. These exchanges enhance the transactivation property of the receptors, particularly to androsterone and androstanediol, 2 metabolized derivatives of testosterone present in the prostate. Additionally, they enhance the transactivation potential of the mutant receptors to hydroxyflutamide, an anti-androgen frequently used in hormone ablation therapy. The increased transactivation by the mutant receptors did not result from altered affinity of the receptors to the inducing ligands nor from measurable changes in conformation of the liganded receptors. Thus the single amino-acid exchanges identify differences in amino-acid-sequence requirements for transactivation and ligand binding in the hormone-binding domain of the androgen receptor. These results provide new insights into ligand-dependent transactivation, and form a framework for the search for effective antagonists to be used in prostate-cancer therapy.