eNOS Tag SNP Haplotypes in Hypertensive Disorders of Pregnancy

Haplotypes formed by polymorphisms (T-786C, rs2070744; a variable number of tandem repeats in intron 4, and Glu298Asp, rs1799983) of the eNOS gene were associated previously with gestational hypertension (GH) and preeclampsia (PE). However, no study has explored the Tag SNPs rs743506 and rs7830 in these disorders. The aim of the current study was to compare the distribution of the genotypes and haplotypes formed by the five eNOS polymorphisms mentioned among healthy pregnant (HP, n = 122), GH (n = 138), and PE (n = 157). The haplotype formed by "C b G G C" was more frequent in HP compared to GH and PE (p = 0.0071), which is supported by previous findings that demonstrated the association of the combination "C b G" with a higher level of nitrite (NO marker). Our results suggest a protective effect of the haplotype "C b G G C" against the development of hypertensive disorders of pregnancy.

Diltiazem como alternativa ao betabloqueador na angiotomografia de artérias coronárias

FUNDAMENTO: A redução da frequência cardíaca (FC) na angiografia por tomografia das artérias coronarianas (ATCCor) é fundamental para a qualidade de imagem. A eficácia dos bloqueadores de cálcio como alternativas para pacientes com contraindicações aos betabloqueadores não foi definida. OBJETIVOS: Comparar a eficácia na redução da FC e variabilidade RR do metoprolol e diltiazem na ATCCor. MÉTODOS: Estudo prospectivo, randomizado, aberto, incluiu pacientes com indicação clínica de ATCCor, em ritmo sinusal, com FC>70bpm e sem uso de agentes que interferissem com a FC. Cinquenta pacientes foram randomizados para grupos: metoprolol IV 5-15 mg ou até FC≤60 bpm(M), e diltiazem IV 0,25-0,60mg/kg ou até FC≤60 bpm (D). Pressão arterial (PA) e FC foram aferidas na condição basal, 1min, 3min e 5min após agentes, na aquisição e após ATCCor. RESULTADOS: A redução da FC em valores absolutos foi maior no grupo M que no grupo D (1, 3, 5min, aquisição e pós-exame). A redução percentual da FC foi significativamente maior no grupo M apenas no 1 min e 3 min após início dos agentes. Não houve diferença no 5 min, durante a aquisição e após exame. A variabilidade RR percentual do grupo D foi estatisticamente menor do que a do grupo M durante a aquisição (variabilidade RR/ FC média da aquisição). Um único caso de BAV, 2:1 Mobitz I, revertido espontaneamente ocorreu (grupo D). CONCLUSÃO: Concluímos que o diltiazem é uma alternativa eficaz e segura aos betabloqueadores na redução da FC na realização de angiografia por tomografia computadorizada das artérias coronarianas. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0)

Do muscle strengthening exercises improve performance in the 6-minute walk test in postmenopausal women?

Background: Walking speed seems to be related to aerobic capacity, lower limb strength, and functional mobility, however it is not clear whether there is a direct relationship between improvement in muscle strength and gait performance in early postmenopausal women. Objective: To evaluate the effect of muscle strengthening exercises on the performance of the 6-minute walk test in women within 5 years of menopause. Methods: The women were randomized into control group (n=31), which performed no exercise, and exercise group (n=27), which performed muscle strengthening exercises. The exercises were performed twice a week for 3 months. The exercise protocol consisted of warm-up, stretching, and strengthening of the quadriceps, hamstring, calf, tibialis anterior, gluteus maximus, and abdominal muscles, followed by relaxation. Muscular strength training started with 60% of 1MR (2 series of 10-15 repetitions), reaching 85% until the end of the 3-month period (4 series of 6 repetitions each). Results: The between-group comparisons pre- and post-intervention did not show any difference in distance walked, heart rate or blood pressure (p>0.05), but showed differences in muscle strength post-intervention, with the exercise group showing greater strength (p<0.05). In the within-group comparison, there were differences in final heart rate and quadriceps and hamstring strength pre- and post-intervention in the exercise group (p<0.05). Conclusion: The results suggest that muscle strengthening of the lower limbs did not improve performance in the 6-minute walk test in this population of postmenopausal women. Trial registration ACTRN12609001053213.

Differentiating between tuberculosis-related and lymphoma-related lymphocytic pleural effusions by measuring clinical and laboratory variables: Is it possible?

Objective: To describe clinical and laboratory characteristics in patients with tuberculosis-related or lymphoma-related lymphocytic pleural effusions, in order to identify the variables that might contribute to differentiating between these diseases. Methods: This was a retrospective study involving 159 adult HIV-negative patients with tuberculosis-related or lymphoma-related lymphocytic effusions (130 and 29 patients, respectively), treated between October of 2008 and March of 2010 at the Pleural Diseases Outpatient Clinic of the University of Sao Paulo School of Medicine Hospital das Clinicas Heart Institute, in the city of Sao Paulo, Brazil. Results: Mean age and the mean duration of symptoms were lower in the tuberculosis group than in the lymphoma group. The levels of proteins, albumin, cholesterol, amylase, and adenosine deaminase (ADA) in pleural fluid, as well as the serum levels of proteins, albumin, and amylase, were higher in the tuberculosis group, whereas serum cholesterol and triglycerides were higher in the lymphoma group. Pleural fluid leukocyte and lymphocyte counts were higher in the tuberculosis group. Of the tuberculosis group patients, none showed malignant cells; however, 4 showed atypical lymphocytes. Among the lymphoma group patients, cytology for neoplastic cells was positive, suspicious, and negative in 51.8%, 24.1%, and 24.1%, respectively. Immunophenotyping of pleural fluid was conclusive in most of the lymphoma patients. Conclusions: Our results demonstrate clinical and laboratory similarities among the patients with tuberculosis or lymphoma. Although protein and ADA levels in pleural fluid tended to be higher in the tuberculosis group than in the lymphoma group, even these variables showed an overlap. However, none of the tuberculosis group patients had pleural fluid ADA levels below the 40-U/L cut-off point.

Effects of Gastric Bypass Surgery in Patients With Type 2 Diabetes and Only Mild Obesity

OBJECTIVE-Roux-en-Y gastric bypass (RYGB) ameliorates type 2 diabetes in severely obese patients through mechanisms beyond just weight loss, and it may benefit less obese diabetic patients. We determined the long-term impact of RYGB on patients with diabetes and only class 1 obesity. RESEARCH DESIGN AND METHODS-Sixty-six consecutively selected diabetic patients with BMI 30-35 kg/m(2) underwent RYGB in a tertiary-care hospital and were prospectively studied for up to 6 years (median 5 years [range 1-6]), with 100% follow-up. Main outcome measures were safety and the percentage of patients experiencing diabetes remission (HbA(1c) <6.5% without diabetes medication). RESULTS-Participants had severe, longstanding diabetes, with disease duration 12.5 +/- 7.4 years and HbA(1c) 9.7 +/- 1.5%, despite insulin and/or oral diabetes medication usage in everyone. For up to 6 years following RYGB, durable diabetes remission occurred in 88% of cases, with glycemic improvement in 11%. Mean HbA(1c) fell from 9.7 +/- 1.5 to 5.9 +/- 0.1% (P < 0.001), despite diabetes medication cessation in the majority. Weight loss failed to correlate with several measures of improved glucose homeostasis, consistent with weight-independent antidiabetes mechanisms of RYGB. C-peptide responses to glucose increased substantially, suggesting improved beta-cell function. There was no mortality, major surgical morbidity, or excessive weight loss. Hypertension and dyslipidemia also improved, yielding 50-84% reductions in predicted 10-year cardiovascular disease risks of fatal and nonfatal coronary heart disease and stroke. CONCLUSIONS-This is the largest, longest-term study examining RYGB for diabetic patients without severe obesity. RYGB safely and effectively ameliorated diabetes and associated comorbidities, reducing cardiovascular risk, in patients with a BMI of only 30-35 kg/m(2).

Duration of dual antiplatelet therapy and outcomes after coronary stenting with the genous (TM) bio-engineered R stent (TM) in patients from the e-healing registry

Objective: We investigated the relation between duration of dual antiplatelet therapy (DAPT) and clinical outcomes up to 12 months after Genous (TM) endothelial progenitor cell capturing R stent (TM) placement in patients from the e-HEALING registry. Background: Cessation of (DAPT) has been shown to be associated with the occurrence of stent thrombosis (ST). After Genous placement, 1 month of DAPT is recommended. Methods: Patients were analyzed according to continuation or discontinuation of DAPT at a 30-day and 6-month landmark, excluding patients with events before the landmark. Each landmark was a new baseline, and outcomes were followed up to 12 months after stenting. The main outcome for our current analysis was target vessel failure (TVF), defined as target vessel-related cardiac death or myocardial infarction and target vessel revascularization. Secondary outcomes included ST. (Un)adjusted hazard ratios (HR) for TVF were calculated with Cox regression. Results: No difference was observed in the incidence of TVF [HR: 1.03; 95% confidence intervals (CI): 0.651.65, P = 0.89] in patients continuing DAPT (n = 4,249) at 30 days versus patients stopped (n = 309), and HR: 0.82 (95% CI: 0.551.23, P = 0.34) in patients continuing DAPT (n = 2,654) at 6 months versus patients stopped [n = 1,408] DAPT). Furthermore, no differences were observed in ST. Even after addition of identified independent predictors for TVF, adjusted TVF hazards were comparable. Conclusions: In a post-hoc analysis of e-HEALING, duration of DAPT was not associated with the occurrence of the outcomes TVF or ST. The Genous stent may be an attractive treatment especially in patients at increased risk for (temporary) cessation of DAPT or bleeding. (C) 2011 Wiley Periodicals, Inc.

Relation of Uric Acid to Serum Levels of High-Sensitivity C-Reactive Protein, Triglycerides, and High-Density Lipoprotein Cholesterol and to Hepatic Steatosis

Increased uric acid (UA) is strongly linked to cardiovascular disease. However, the independent role of UA is still debated because it is associated with several cardiovascular risk factors including obesity and metabolic syndrome. This study assessed the association of UA with increased high-sensitivity C-reactive protein (hs-CRP), increased ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL), sonographically detected hepatic steatosis, and their clustering in the presence and absence of obesity and metabolic syndrome. We evaluated 3,518 employed subjects without clinical cardiovascular disease from November 2008 through July 2010. Prevalence of tis-CRP >= 3 mg/L was 19%, that of TG/HDL >= 3 was 44%, and that of hepatic steatosis was 43%. In multivariable logistic regression after adjusting for traditional cardiovascular risk factors and confounders, highest versus lowest UA quartile was associated with hs-CRP >= 3 mg/L (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.01 to 2.28, p = 0.04), TG/HDL >= 3 (OR 3.29, 95% CI 2.36 to 4.60, p <0.001), and hepatic steatosis (OR 3.10, 95% CI 2.22 to 4.32, p <0.001) independently of obesity and metabolic syndrome. Association of UA with hs-CRP >= 3 mg/L became nonsignificant in analyses stratified by obesity. Ascending UA quartiles compared to the lowest UA quartile demonstrated a graded increase in the odds of having 2 or 3 of these risk conditions and a successive decrease in the odds of having none. In conclusion, high UA levels were associated with increased TG/HDL and hepatic steatosis independently of metabolic syndrome and obesity and with increased hs-CRP independently of metabolic syndrome. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110:1787-1792)

A combined oral contraceptive containing drospirenone changes neither endothelial function nor hemodynamic parameters in healthy young women: a prospective clinical trial

Background: Combined oral contraceptives (COCs) may lead to a rise in cardiovascular disease risk, possibly associated with changes in blood pressure and endothelial function. Study Design: The objective was to evaluate the impact of COC containing 20 mcg of ethinylestradiol (EE) and 3 mg of drospirenone (DRSP) on the arterial endothelial function, systolic and diastolic blood pressure (SBP and DBP, respectively), heart rate (HR), cardiac output (CO) and total peripheral resistance (TPR) of healthy young women. Of the 71 women in the study, 43 were evaluated before the introduction of COC and after 6 months of its use (case group) and 28, COC nonusers, were assessed for the same parameters at the same time interval (control group). Results: No significant changes in endothelium-dependent and endothelium-independent functions or in measures of SBP, DBP, HR, CO and TPR caused by COC use were observed in the case group (p>.05 for all variables) or in the control group. Conclusion: These data suggest COC with 20 mcg EE and 3 mg DRSP does not alter arterial endothelial function or hemodynamic parameters in healthy young women. (C) 2012 Elsevier Inc. All rights reserved.

Angiotensin II Facilitates Breast Cancer Cell Migration and Metastasis

Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. In this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis. We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN) were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites. Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. In vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix. At the molecular level, a total of 102 genes differentially expressed following angiotensin II pretreatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen. Among those, up-regulated MMP2/MMP9 and ICAM1 stand at the crossroad of a network of genes involved in cell adhesion, migration and invasion. Our data suggest that targeting angiotensin II production or action may represent a valuable therapeutic option to prevent metastatic progression of invasive breast tumors.

Vitamin or mineral supplement intake and the risk of head and neck cancer: pooled analysis in the INHANCE consortium

To investigate the potential role of vitamin or mineral supplementation on the risk of head and neck cancer (HNC), we analyzed individual-level pooled data from 12 casecontrol studies (7,002 HNC cases and 8,383 controls) participating in the International Head and Neck Cancer Epidemiology consortium. There were a total of 2,028 oral cavity cancer, 2,465 pharyngeal cancer, 874 unspecified oral/pharynx cancer, 1,329 laryngeal cancer and 306 overlapping HNC cases. Odds ratios (OR) and 95% confidence intervals (CIs) for self reported ever use of any vitamins, multivitamins, vitamin A, vitamin C, vitamin E, and calcium, beta-carotene, iron, selenium and zinc supplements were assessed. We further examined frequency, duration and cumulative exposure of each vitamin or mineral when possible and stratified by smoking and drinking status. All ORs were adjusted for age, sex, race/ethnicity, study center, education level, pack-years of smoking, frequency of alcohol drinking and fruit/vegetable intake. A decreased risk of HNC was observed with ever use of vitamin C (OR = 0.76, 95% CI = 0.590.96) and with ever use of calcium supplement (OR = 0.64, 95% CI = 0.420.97). The inverse association with HNC risk was also observed for 10 or more years of vitamin C use (OR = 0.72, 95% CI = 0.540.97) and more than 365 tablets of cumulative calcium intake (OR = 0.36, 95% CI = 0.160.83), but linear trends were not observed for the frequency or duration of any supplement intake. We did not observe any strong associations between vitamin or mineral supplement intake and the risk of HNC.

Trends, drivers and impacts of changes in swidden cultivation in tropical forest-agriculture frontiers: A global assessment

This meta-analysis of land-cover transformations of the past 10-15 years in tropical forest-agriculture frontiers world-wide shows that swidden agriculture decreases in landscapes with access to local, national and international markets that encourage cattle production and cash cropping, including biofuels. Conservation policies and practices also accelerate changes in swidden by restricting forest clearing and encouraging commercial agriculture. However, swidden remains important in many frontier areas where farmers have unequal or insecure access to investment and market opportunities, or where multi-functionality of land uses has been preserved as a strategy to adapt to current ecological, economic and political circumstances. In some areas swidden remains important simply because intensification is not a viable choice, for example when population densities and/or food market demands are low. The transformation of swidden landscapes into more intensive land uses has generally increased household incomes, but has also led to negative effects on the social and human capital of local communities to varying degrees. From an environmental perspective, the transition from swidden to other land uses often contributes to permanent deforestation, loss of biodiversity, increased weed pressure, declines in soil fertility, and accelerated soil erosion. Our prognosis is that, despite the global trend towards land use intensification, in many areas swidden will remain part of rural landscapes as the safety component of diversified systems, particularly in response to risks and uncertainties associated with more intensive land use systems. (C) 2011 Elsevier Ltd. All rights reserved.

Sonothrombolysis for acute ischemic stroke: a systematic review of randomized controlled trials

Object. Sonothrombolysis has recently been considered an emerging modality for the treatment of stroke. The purpose of the present paper was to review randomized clinical studies concerning the effects of sonothrombolysis associated with tissue plasminogen activator (tPA) on acute ischemic stroke. Methods. Systematic searches for literature published between January 1996 and July 2011 were performed for studies regarding sonothrombolysis combined with tPA for acute ischemic stroke. Only randomized controlled trials were included. Data extraction was based on ultrasound variables, patient characteristics, and outcome variables (rate of intracranial hemorrhages and arterial recanalization). Results. Four trials were included in this study; 2 trials evaluated the effect of transcranial Doppler (TCD) ultrasonography on sonothrombolysis, and 2 addressed transcranial color-coded duplex (TCCD) ultrasonography. The frequency of ultrasound waves varied from 1.8 to 2 MHz. The duration of thrombus exposure to ultrasound energy ranged from 60 to 120 minutes. Sample sizes were small, recanalization was evaluated at different time points (60 and 120 minutes), and inclusion criteria were heterogeneous. Sonothrombolysis combined with tPA did not lead to an increase in symptomatic intracranial hemorrhagic complications. Two studies demonstrated that patients treated with ultrasound combined with tPA had statistically significant higher rates of recanalization than patients treated with tPA alone. Conclusions. Despite the heterogeneity and the limitations of the reviewed studies, there is evidence that sonothrombolysis associated with tPA is a safe procedure and results in an increased rate of recanalization in the setting of acute ischemic stroke when wave frequencies and energy intensities of diagnostic ultrasound systems are used. (http://thejns.org/doi/abs/10.3171/2011.10.FOCUS11251)

Are Multiple Cryoprobes Additive or Synergistic in Renal Cryotherapy?

OBJECTIVE To investigate the relationship between multiple cryoprobes was investigated to determine whether they work in an additive or synergistic fashion in an in vivo animal model because 1.47 mm (17-gauge) cryoprobes have been introduced to the armamentarium for renal cryotherapy. METHODS Laparoscopic-guided percutaneous cryoablation was performed in both renal poles of 3 pigs using 3 IceRod cryoprobes. These 12 cryolesions were compared with 12 cryolesions using a single IceRod cryoprobe. Each cycle consisted of two 10-minute freeze cycles separated by a 5-minute thaw. The iceball volume was measured using intraoperative ultrasonography. The kidneys were harvested, and cryolesion surface area was calculated. The lesions were fixed and excised to obtain a volume measurement. Statistical analysis was used to compare the single probe results multiplied by 3 to the multiple probe group for iceball volume, cryolesion surface area, and cryolesion volume. RESULTS The iceball volume for the first freeze cycle for the single cryoprobe multiplied by 3 was 8.55 cm(3) compared with 9.79 cm(3) for the multiple cryoprobe group (P = .44) and 10.01 cm(3) versus 16.58 cm(3) for the second freeze (P = .03). The cryolesion volume for the single cryoprobe multiplied by 3 was 11.29 cm(3) versus 14.75 cm(3) for the multiple cyroprobe group (P = .06). The gross cryolesion surface area for the single cryoprobe multiplied by 3 was 13.14 cm(2) versus 13.89 cm(2) for the multiple probe group (P = .52). CONCLUSION The cryolesion created by 3 simultaneously activated 1.47-mm probes appears to be larger than that of an additive effect. The lesions were significantly larger as measured by ultrasonography and nearly so (P = .06) as measured by the gross cryolesion volume. UROLOGY 79: 484.e1-484.e6, 2012. (c) 2012 Elsevier Inc. All rights reserved.

Re-treatment of previous non-responders and relapsers to interferon plus ribavirin with peginterferon alfa-2a (40KD), ribavirin +/- amantadine in patients with chronic hepatitis C: randomized multicentre clinical trial

Introduction. A large number of patients with chronic hepatitis C have not been cured with interferon-based therapy. Therefore, we evaluated the efficacy of amantadine combined with the standard of care (pegylated interferon plus ribavirin) in patients who had not responded to or had relapsed after 24 weeks of treatment with conventional interferon plus ribavirin. Material and methods. Patients stratified by previous response (i.e., non-response or relapse) were randomized to 48 weeks of open-label treatment with peginterferon alfa-2a (401(D) 180 pg/week plus ribavirin 1,000/1,200 mg/day plus amantadine 200 mg/day (triple therapy), or the standard of care (peginterferon alfa-2a [40KD] plus ribavirin). Results. The primary outcome was sustained virological response (SVR), defined as undetectable hepatitis C virus RNA in serum (< 50 IU/mL) at end of follow-up (week 72). Among patients with a previous non-response, 12/53 (22.6%; 95% confidence interval [CI] 12.3-36.2%) randomized to triple therapy achieved an SVR compared with 16/52 (30.8%; 95% CI 18.7-45.1%) randomized to the standard of care. Among patients with a previous relapse 22/39 (56.4%; 95% CI 39.6-72.2%) randomized to triple therapy achieved an SVR compared with 23/38 (60.5%; 95% CI 43.4-76.0%) randomized to the standard of care. Undetectable HCV RNA (< 50 IU/mL) at week 12 had a high positive predictive value for SVR. A substantial proportion of non-responders and relapsers to conventional interferon plus ribavirin achieve an SVR when re-treated with peginterferon alfa-2a (40KD) plus ribavirin. Conclusion. Amantadine does not enhance SVR rates in previously treated patients with chronic hepatitis C and cannot be recommended in this setting.

EVIDENCE-BASED PRACTICES PUBLISHED IN BRAZIL: IDENTIFICATION AND ANALYSIS STUDIES ABOUT HUMAN HEALTH PREVENTION

Integrative review of Brazilian studies about evidence-based practices (EBP) about prevention in human health, published in Web of Science/JCR journals, between October 2010 and April 2011. The aim was to identify the specialties that most accomplished these studies, their foci and methodological approaches. Based on inclusion criteria, 84 studies were selected, mainly published in public health journals, focusing on primary care and also addressing clinical issues and different specialties. Prevention foci and methodological approaches also varied, with a predominance of systematic reviews without meta-analysis. The results indicate that there is no single way to conceptualize and practice EBP in the field of prevention, and that its application may not only serve to obtain indisputable evidence to equip intervention actions. This endless knowledge area is under construction, with a view to the analysis and further understanding of health phenomena.