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Buenos Aires, Argentina

Sposato L.A.,University of Buenos Aires | Sposato L.A.,Neurovascular Center | Klein F.R.,University of Buenos Aires | Jauregui A.,University of Buenos Aires | And 5 more authors.
Journal of Stroke and Cerebrovascular Diseases

Atrial fibrillation (AF) is the major cause of cardioembolic stroke. It often remains occult when asymptomatic and paroxysmal. We hypothesized that the detection of AF after acute ischemic stroke (AIS) or transient ischemic attack (TIA) could be improved by using continuous cardiac monitoring (CCM) immediately after admission. We sought to determine the detection rate of AF by immediate in-hospital CCM after cryptogenic and noncryptogenic AIS or TIA in patients without a previous diagnosis of AF. We retrospectively studied a cohort of 155 patients with cryptogenic and noncryptogenic AIS or TIA without known AF. We compared the detection rates of newly diagnosed AF (NDAF) in patients admitted to areas with CCM and those never admitted to these areas. We developed a multiple logistic regression model for identifying predictors of NDAF. We characterized NDAF episodes and analyzed how the availability of CCM data changed secondary prevention strategies. We detected NDAF in 21 patients (13.5%). Diagnostic rates of NDAF in patients who underwent CCM and those who did not undergo CCM were 18.2% and 2.2%, respectively (P =.005). The median time from admission to recognition of NDAF was 2.0 days. Most NDAFs were paroxysmal (95.2%) and lasted less than 1 hour (85.7%). Diabetes mellitus and infarct size were predictors of NDAF. Detection of NDAF prompted the initiation of anticoagulation therapy in 8.2% of the patients admitted to areas with CCM availability. Our findings suggest that immediate and prolonged CCM significantly improves the detection of NDAF after cryptogenic and noncryptogenic AIS or TIA, and that diabetes mellitus and infarct size are significantly associated with NDAF. © 2012 by National Stroke Association. Source

Feldstein C.A.,Hospital de Clinicas Jose de San Martin
Journal of the American Society of Hypertension

Hypertension is the leading risk factor for ischemic and intracerebral hemorrhagic subtypes of stroke. Additionally, high blood pressure (BP) in the acute cerebrovascular event is associated with poor outcome, and a high percentage of stroke survivors have inadequate control of hypertension. The present is a systematic review of prospective, randomized, and controlled trials carried out on safety and efficacy of antihypertensive treatment of both subtypes of acute stroke. Six trials involving 7512 patients were included, which revealed controversies on the speed and the goals of treatment. These controversies could be due at least in part, from the fact that some studies analyzed the results of antihypertensive treatment in ischemic and intracerebral hemorrhagic subtypes of acute stroke together, and from a different prevalence of past-stroke in the randomized groups. Further research is necessary to establish whether standard antihypertensive treatment provides greater benefit than simple observation in patients with ischemic acute stroke and Stage 2 hypertension of JNC 7, albeit they were not candidates for acute reperfusion. In that case, the target reduction in BP could be 10% to 15% within 24 hours. The recently published INTERACT 2 has provided evidence that patients with hemorrhagic stroke may receive intensive antihypertensive treatment safely with the goal of reducing systolic BP to levels no lower than 130 mm Hg. It is important to take into account that marked BP lowering in acute stroke increases the risk of poor outcome by worsening cerebral ischemia from deterioration of cerebral blood flow autoregulation. © 2014 American Society of Hypertension. All rights reserved. Source

Ricci A.G.,CONICET | Olivares C.N.,CONICET | Bilotas M.A.,CONICET | Baston J.I.,CONICET | And 3 more authors.
Human Reproduction

Study Question Can resveratrol and epigallocatechin-3-gallate (EGCG) inhibit the growth and survival of endometriotic-like lesions in vivo in a BALB/c model of endometriosis, and in vitro in primary cultures of human endometrial epithelial cells (EECs)? Summary Answer Resveratrol and EGCG exerted a potent inhibitory effect on the development of endometriosis in a BALB/c murine model and on the survival of EECs. What is Known Already Endometriosis is a common condition associated with infertility and pelvic pain in women of reproductive age. Resveratrol and EGCG are two polyphenols with anticarcinogenic and antioxidant properties that have been proposed as natural therapies to treat endometriosis. Study Design, Size, Duration Fifty-six 2-month-old female BALB/c mice underwent surgical induction of endometriosis. Treatments with resveratrol or EGCG started 15 days post-surgery and continued for 4 weeks. Human biopsies were taken with a metal Novak curette from the posterior uterine wall from 16 patients with untreated endometriosis and 15 controls who underwent diagnostic laparoscopy for infertility. Materials, Setting, Methods after the treatments, animals were sacrificed and lesions were counted, measured, excised and fixed. Immunohistochemistry for proliferating cell nuclear antigen and CD34 was performed for cell proliferation and vascularization assessment in the lesions. The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) technique was performed for apoptosis evaluation. Peritoneal fluid was collected to analyze vascular endothelial growth factor levels. Human EECs were purified from proliferative-phase endometrial biopsies and cultured. The effect of both polyphenols on cell proliferation was determined by a colorimetric assay using the CellTiter 96®AQueous One Solution Cell Proliferation Assay kit and on apoptosis by the TUNEL technique, using an In Situ Cell Death Detection Kit with Fluorescein. Main Results In the mouse model, both treatments significantly reduced the mean number (P < 0.05 versus control) and the volume of established lesions (P < 0.05 versus control). Treatments consistently statistically significantly diminished cell proliferation (resveratrol P < 0.01 and EGCG P < 0.05, versus control), reduced vascular density (resveratrol P < 0.01 and EGCG P < 0.001, versus control) and increased apoptosis within the lesions (resveratrol P < 0.01 and EGCG P < 0.05, versus control). Both compounds induced reduction in human EEC proliferation (P < 0.05 versus basal) and increased apoptosis (P < 0.05 versus basal) in primary cultures. Limitations In vitro studies were only carried out in epithelial cells from human eutopic endometrium. Wider Implications of the Findings The present findings are promising and will assist the development of novel natural treatments for endometriosis. Study Funding This study was supported by ANPCYT (PICT 6384 BID 1201 OC-AR) and CONICET (PIP 5471), Argentina. None of the authors has any conflict of interest to declare. © 2012 The Author. Source

Hauser R.A.,University of South Florida | Cantillon M.,Merck | Cantillon M.,Critical Path Institute | Pourcher E.,Laval University | And 5 more authors.
The Lancet Neurology

Background: Preladenant is an adenosine 2A (A2A) receptor antagonist. In animal models of Parkinson's disease, preladenant monotherapy improves motor function without causing dyskinesia and, as an adjunct to levodopa, it improves motor function without worsening dyskinesia. We aimed to assess the efficacy and safety of preladenant in patients with Parkinson's disease and motor fluctuations who were receiving levodopa and other antiparkinsonian drugs. Methods: In this phase 2, dose-finding trial, patients with Parkinson's disease who were receiving levodopa were enrolled and treated at 44 sites in 15 countries between December, 2006, and November, 2008. Assignment to treatment was done centrally with an interactive voice response system, according to a block randomisation schedule that was computer generated by the sponsor. Patients were assigned to receive 1, 2, 5, or 10 mg oral preladenant twice daily, or matching placebo for 12 weeks. Patients, study staff, investigators, and all sponsor personnel were masked to treatment assignment. The primary outcome was change in mean daily off time from baseline to week 12, as assessed by home diaries. Efficacy analysis included all patients who received at least one dose of study drug and had data for assessments after baseline. This trial is registered with ClinicalTrials.gov, number NCT00406029. Findings: 253 patients were randomised to receive preladenant (1 mg [n=49], 2 mg [n=49], 5 mg [n=49], 10 mg [n=57]) or placebo (n=49), of whom 234 on preladenant (1 mg [n=47], 2 mg [n=48], 5 mg [n=45], 10 mg [n=49]) and placebo (n=45) were eligible for the efficacy analysis. Mean daily off time from baseline to week 12 was reduced versus placebo in patients on 5 mg preladenant (difference -1·0 h, 95% CI -2·1 to 0·0; p=0·0486) and 10 mg preladenant (-1·2 h, -2·2 to -0·2; p=0·019). Changes in mean daily off time versus placebo were not significant for 1 mg preladenant (0·2 h, -0·9 to 1·2; p=0·753) or 2 mg preladenant (-0·7 h, -1·7 to 0·3; p=0·162). The most common adverse events in the combined preladenant group versus placebo were worsening of Parkinson's disease (22 [11%] vs 4 [9%]), somnolence (20 [10%] vs 3 [6%]), dyskinesia (18 [9%] vs 6 [13%]), nausea (17 [9%] vs 5 [11%]), constipation (15 [8%] vs 1 [2%]), and insomnia (15 [8%] vs 4 [9%]). Interpretation: 5 and 10 mg preladenant twice daily might be clinically useful to reduce off time in patients with Parkinson's disease and motor fluctuations. Funding: Schering-Plough, a subsidiary of Merck. © 2011 Elsevier Ltd. Source

Correale J.,Institute For Neurological Research Dr Raul Carrea | Balbuena Aguirre M.E.,Hospital de Clinicas Jose de San Martin | Farez M.F.,Institute For Neurological Research Dr Raul Carrea
Clinical Immunology

Vitamin D status, smoking, and Epstein-Barr virus infection (EBV) may all contribute to explain differences in disease prevalence and incidence of Multiple Sclerosis (MS). MS affects women more often than men, and recent cross-sectional study assessments provide evidence of increased female to male prevalence in relapsing remitting MS patients, suggesting that sex hormones may exert an active role in disease pathogenesis. Studies in both humans and animal disease models demonstrate a functional synergy for the immunomodulatory effects of Vitamin D3 and 17-β estradiol. Both smoking and EBV infection clearly increase MS risk, and smoking history has also been associated with poorer disease prognosis. However, neither factor can explain the recent trend indicating greater female prevalence. Therefore, large population-based case-control studies from well defined geographic areas with homogeneous populations should be performed, in order to define environmental factor effects, and sex hormone influences, to better understand prevalence and incidence gender differences observed. © 2013 Elsevier Inc. Source

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