Effects of Vasopressin on Sweat Rate and Composition in Patients with Diabetes Insipidus and Normal Controls

Baseline sweat rate and concentrations of sodium, chloride, and potassium, and the effect of exogenous vasopressin on these parameters were determined in 13 patients with acquired diabetes insipidus (ADI), four patients with nephrogenic diabetes insipidus (NDI), three subjects with cystic fibrosis, and age- and sex-matched controls. The four patients with NDI did not differ from the controls with respect to baseline sweat rate, but baseline sodium, chloride, and potassium concentrations were significantly elevated. In addition, parenteral vasopressin caused a significant decrease in sweat rate (p < .01) while the electrolyte concentrations remained unchanged. This indicates that vasopressin may also have an effect on electrolyte reabsorption in NDI patients. Alternatively, the amount of sweat precursor fluid may have been reduced. The patients with ADI did not differ from the controls with respect to baseline data, and parenteral vasopressin had no effect on their sweat rate and composition. Likewise, vasopressin had no effect in controls or patients with cystic fibrosis. We conclude that, except in patients with NDI, vasopressin does not play a significant role in the regulation of human eccrine sweating. Sweat gland physiology appears to be different in patients with NDI and in them vasopressin may have a significant effect on sweat

Global clinical response in C ushing's syndrome patients treated with mifepristone

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106755/1/cen12332.pd

Belinostat and panobinostat (HDACI): in vitro and in vivo studies in thyroid cancer

PurposeAdvanced thyroid cancer responds poorly to most therapies. New therapies and combinations are needed. The aim of this study was to examine both in vitro and in vivo activity of two relatively new histone deacetylase inhibitors (HDACIs), belinostat and panobinostat, and a variety of tyrosine kinase inhibitors (TKIs) against a panel of nine human thyroid cancer cell lines.MethodsThe anti-proliferative activity and the effects of HDACIs, TKIs and their combinations on thyroid cancer cells were determined by cytotoxicity assays, microarray and immunoblot analyses. Synergism between HDACIs and TKIs was assessed by the median effects model of Chou-Talalay (Calcusyn(®)).ResultsBelinostat and panobinostat were active against the thyroid cancer cell lines irrespective of their mutational composition, and belinostat was effective in preventing growth of human thyroid cancer xenografts in immunodeficient mice. Further studies showed that both HDACIs induced apoptosis. HDACI also elevated acetylated histone 3, p21(Waf), and PARP, and decreased levels of phosphorylated ERK and AKT (Ser473). RNA assay analysis suggested both HDACIs modulated genes associated with the cell cycle, DNA damage and apoptosis. Most of the TKI (pazopanib, motesanib, sorafenib and dasatinib) were either inactive in vitro or were active only at high doses. However, the novel combinations of either pazopanib or dasatinib TKIs with either belinostat or panobinostat synergistically inhibited cell growth of thyroid cancer cells in vitro.ConclusionsIn summary, these HDACIs either alone or combined with selected TKIs may have a role in treatment of aggressive thyroid cancer

Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial.

Background: Oophorectomy reduces serum testosterone levels. We studied the efficacy and safety of transdermal testosterone in treating hypoactive sexual desire disorder in surgically menopausal women

Diet and exercise changes following direct-to-consumer personal genomic testing

Background: The impacts of direct-to-consumer personal genomic testing (PGT) on health behaviors such as diet and exercise are poorly understood. Our investigation aimed to evaluate diet and exercise changes following PGT and to determine if changes were associated with genetic test results obtained from PGT. Methods: Customers of 23andMe and Pathway Genomics completed a web-based survey prior to receiving PGT results (baseline) and 6 months post-results. Fruit and vegetable intake (servings/day), and light, vigorous and strength exercise frequency (days/week) were assessed. Changes in diet and exercise were examined using paired t-tests and linear regressions. Additional analyses examined whether outcomes differed by baseline self-reported health (SRH) or content of PGT results. Results: Longitudinal data were available for 1,002 participants. Significant increases were observed for vegetable intake (mean Δ = 0.11 (95% CI = 0.05, 0.17), p = 0.0003) and strength exercise (Δ = 0.14 (0.03, 0.25), p = 0.0153). When stratified by SRH, significant increases were observed for all outcomes among lower SRH participants: fruit intake, Δ = 0.11 (0.02, 0.21), p = 0.0148; vegetable intake, Δ = 0.16 (0.07, 0.25), p = 0.0005; light exercise, Δ = 0.25 (0.03, 0.47), p = 0.0263; vigorous exercise, Δ = 0.23 (0.06, 0.41), p = 0.0097; strength exercise, Δ = 0.19 (0.01, 0.37), p = 0.0369. A significant change among higher SRH participants was only observed for light exercise, and in the opposite direction: Δ = -0.2468 (-0.06, -0.44), p = 0.0111. Genetic results were not consistently associated with any diet or exercise changes. Conclusions: The experience of PGT was associated with modest, mostly positive changes in diet and exercise. Associations were independent of genetic results from PGT

Pharmacoeconomics of genotyping-based treatment decisions in patients with chronic pain

Abstract. Introduction:. Genotyping-based treatment decisions may optimize treatment response and minimize adverse drug events (ADEs) in patients with chronic pain. Objectives:. To estimate the financial impact of genotyping-based treatment decisions in patients with moderate to severe chronic pain in a managed care setting. Methods:. A budget impact model was built with a 1-year time horizon to estimate costs of genotyping-based treatment decisions in a 1000-patient cohort. The model includes drug costs, type and cost of ADEs, distribution of treatments used, and genotyping costs. Event rates and health care costs were derived from primary literature. Three patient cohorts were assessed with and without genotyping-based treatment decisions: no genetic testing; 50% genetic testing; and 100% genetic testing. Sensitivity analysis was performed varying costs, adherence, and the percentage of patients treated according to genotyping results. Results:. Medical and ADE costs varied by patient severity and genotyping rates. Without genotyping, drug and ADE costs ranged from $1,544,377 to$24,313,844. With genotyping-based treatment, total costs ranged from $1,780,922 to$18,868,032. Sensitivity analysis, varying costs, adherence, and genotyping rates suggested genotyping improves outcomes and is cost saving in patients with chronic pain. Conclusion:. Genotyping-based treatment costs are offset by reduced medication utilization and adverse event costs. Genotyping should be considered for patients with chronic pain in clinical practice and within clinical trials