Risk of Clostridium difficile-associated disease among patients receiving proton-pump inhibitors in a Quebec medical intensive care unit.

Our study was conducted to determine whether use of gastric acid-suppressive agents increased the risk of Clostridium difficile-associated disease (CDAD) in a medical intensive care unit of one of the first hospitals to be threatened by the current CDAD epidemic in Quebec, Canada. Our findings suggest that efforts to determine risk factors for CDAD should focus on other areas, such as older age and antibiotic use.     

Presence of specific 11C-meta-Hydroxyephedrine retention in heart, lung, pancreas, and brown adipose tissue.

(11)C-meta-Hydroxyephedrine (HED) is used in cardiac PET as an index of norepinephrine (NE) reuptake transporter (NET) density and synaptic NE levels. Whereas cardiac uptake is well documented, tracer retention in other tissues with rich noradrenergic innervation is unclear. Dysfunctional sympathetic nervous system (SNS) function in extracardiac metabolic storage tissues (i.e., adipose tissue and skeletal muscle) and endocrine organs contributes to several disorders. The aim of this study was to determine the potential of HED as an index of NE function in brown adipose tissue, lung, pancreas, skeletal muscle, and kidney by identifying NET-specific retention and determining the presence of radiolabeled metabolites. METHODS: Male Sprague-Dawley rats were administered HED and sacrificed at 30 min after tracer injection. Tissues were rapidly excised and counted for radioactivity, and relative tracer retention was quantified. Pretreatment with NET inhibitors established specific HED accumulation. The effect of elevated NE was tested by subcutaneous minipump NE infusion or inhibition of monoamine oxidase. Column-switch high-performance liquid chromatography (HPLC) was used to analyze the presence of radiolabeled metabolites in heart, brown adipose tissue, pancreas, and plasma. RESULTS: NET-specific retention was observed in heart, brown adipose tissue, lung, and pancreas but not in liver, skeletal muscle, or kidney. A dose-dependent response of HED accumulation to treatments elevating NE levels was established in tissues exhibiting specific uptake. At 30 min after tracer administration, HPLC analysis revealed 93%-95% of total radioactivity signal derived from unchanged HED in heart, pancreas, and brown adipose tissue compared with 61% +/- 8% unchanged HED in plasma. CONCLUSION: In addition to the heart, lung, pancreas, and brown adipose tissue exhibit specific and NE-responsive uptake of HED, supporting the potential for novel PET studies of SNS integrity in these tissues.     

Prospective, Double-Blind, Randomized, Parallel-Group, Dose-Ranging Study of Botulinum Toxin Type A in Men with Glabellar Rhytids

BACKGROUND: The effective dose for treating glabellar lines with botulinum toxin type A in men has not been studied adequately. OBJECTIVE: To compare the safety, efficacy, and duration of response of four doses of botulinum toxin type A on glabellar rhytids in men. METHODS: Eighty men were randomized to receive a total dose of either 20, 40, 60, or 80 U of botulinum toxin type A (BOTOX, BOTOX Cosmetic, or Vistabel, Allergan, Inc., Irvine, CA, USA) in the glabellar area. Glabellar lines were assessed at rest and maximum frown by a trained observer at baseline, 2 and 4 weeks, and monthly thereafter. Patients provided self-evaluations at the same visits. Adverse events were monitored throughout. RESULTS: The 40, 60, and 80 U doses of botulinum toxin type A were consistently more effective in reducing glabellar lines than the 20 U dose (duration, peak response rate, improvement from baseline). There was a dose-dependent increase in both the response rate at maximum frown and the duration of effect assessed by the trained observer. In addition, the participants reported a dose-dependent reduction in the ability to frown, improvement in their global assessment, and increased feelings of attractiveness, self-confidence, and satisfaction. The incidence of adverse events was not increased with higher doses. CONCLUSION: Male participants with glabellar rhytids benefit from starting doses of at least 40 U of botulinum toxin type A.     

Relationship between oxidative stress and essential hypertension.

This study investigated the association of blood pressure with blood oxidative stress-related parameters in normotensive and hypertensive subjects. A cross-sectional design was applied to 31 hypertensive patients and 35 healthy normotensive subjects. All subjects were men between the ages of 35 and 60 years. Exclusion criteria were obesity, dyslipidemia, diabetes mellitus, smoking and current use of any medication. All patients underwent 24-h ambulatory blood pressure monitoring and sampling of blood and urine. Antioxidant enzymes activity, reduced/oxidized glutathione ratio (GSH/GSSG), and lipid peroxidation (malondialdehyde) were determined in erythrocytes. Parameters measured in the plasma of test subjects were plasma antioxidant status, lipid peroxidation (8-isoprostane), plasma vitamin C and E, and the blood pressure modulators renin, aldosterone, endothelin-1 and homocysteine. Daytime systolic and diastolic blood pressures of hypertensives were negatively correlated with plasma antioxidant capacity (r=-0.46, p<0.009 and r=-0.48, p<0.007), plasma vitamin C levels (r=-0.53, p<0.003 and r=-0.44, p<0.02), erythrocyte activity of antioxidant enzymes, and erythrocyte GSH/GSSG ratio, with hypertensives showing higher levels of oxidative stress. Blood pressures showed a positive correlation with both plasma and urine 8-isoprostane. Neither plasma vitamin E nor the assessed blood pressure modulator levels showed significant differences between the groups or correlation with blood pressures. These findings demonstrate a strong association between blood pressure and some oxidative stress-related parameters and suggest a possible role of oxidative stress in the pathophysiology of essential hypertension.     

Microcrack frequency and bone remodeling in postmenopausal osteoporotic women on long-term bisphosphonates: a bone biopsy study.

We sought whether microdamage could rise in postmenopausal osteoporotic women on long-term bisphosphonates, as suggested by recent animal studies. We found few microcracks in iliac bone biopsies, despite a marked reduction in bone turnover. INTRODUCTION: Animal studies suggest that bisphosphonates (BPs) could increase microdamage frequency in a dose-dependent manner, caused by excessively suppressed bone turnover. However, there is limited data in humans receiving BP therapeutic doses for >3 yr. MATERIALS AND METHODS: We measured microcrack frequency and histomorphometry parameters on transiliac bone biopsies in 50 postmenopausal osteoporotic women (mean age = 68 yr) who had received BP therapy (3 on intravenous pamidronate, 37 on oral alendronate, and 10 on oral risedronate) for at least 3 yr (mean treatment duration = 6.5 yr). We compared these results with transiliac bone biopsies obtained from 12 cadavers. We used bulk staining with green calcein as a fluorochrome. The microcracks were quantified in three 100-microm-thick sections using optic microscopy and were confirmed by laser confocal microscopy. Microcrack frequency (number of microcracks/mm2 of bone tissue) was compared between treated women and controls using nonparametric tests. We also explored predictors of microcrack frequency, including age, duration of BP therapy, and activation frequency. RESULTS: Among treated women, cancellous bone microcrack frequency was low (mean, 0.13 microcracks/mm2) and did not differ significantly from that observed in controls (0.05 microcracks/mm2; p = 0.59). Of note, 54% of the treated women and 58% of the controls had no observable microcracks. There was no association between microcrack frequency and the duration of BP therapy (for microcracks/mm2 and duration, Spearman r = 0.04, p = 0.80) and between patients' ages and the number of microcracks (Spearman r = -0.09, p = 0.61). Although bone remodeling parameters were suppressed in treated women, we found no relationship between microcrack density and activation frequency (Spearman r = -0.003, p = 0.99). Also, microcrack frequency was not increased in women with prevalent vertebral fracture compared with those without fractures. CONCLUSIONS: Among postmenopausal osteoporotic women on long-term BPs, microcrack frequency in the iliac bone is low, despite a marked reduction of bone turnover.     

CASPER, a Computer ASsisted PERicardial puncture system: first clinical results.

Pericardial puncture is the percutaneous insertion of a needle into the pericardial space to drain a pathological pericardial effusion. The challenge for the operating surgeon is to reach percutaneously a target zone in the vicinity of the mobile heart, in a soft-tissue environment. The surgeon's ability to accomplish this depends on his own mental picture of the effusion. CASPER is a navigation software using an optical localizer which assists the surgeon by enhancing the representation of the effusion and guiding the needle's progress. Using a localized and calibrated echographic probe, the surgeon acquires a set of images in the region of interest. This zone is then manually segmented on each image, a common zone is computed, and the surgeon defines a trajectory for the needle. During the puncture procedure, the surgeon follows the position of the localized needle on a computer monitor. After initial validation on an experimental phantom, a feasibility study was performed using canine and porcine models. The optical localization device was changed from an Optotrak to a Polaris device for easier use in the clinical setting. Prior to clinical application, various tests were performed concerning the mobility of the thoracic cage, the reproducibility of the thoracic position over several apneas, and the stability of anatomic structures relative to the thoracic cage. Finally, a first clinical application was successfully performed using this system. The present paper reports on these last two stages.