Metoprolol prevents sodium retention induced by lower body negative pressure in healthy men.

BACKGROUND: Lower body negative pressure (LBNP) has been shown to induce a progressive activation of neurohormonal systems, and a renal tubular and hemodynamic response that mimics the renal adaptation observed in congestive heart failure (CHF). As beta-blockers play an important role in the management of CHF patients, the effects of metoprolol on the renal response were examined in healthy subjects during sustained LBNP. METHODS: Twenty healthy male subjects were randomized in this double blind, placebo versus metoprolol 200 mg once daily, study. After 10 days of treatment, each subject was exposed to 3 levels of LBNP (0, -10, and -20 mbar) for 1 hour, each level of LBNP being separated by 2 days. Neurohormonal profiles, systemic and renal hemodynamics, as well as renal sodium handling were measured before, during, and after LBNP. RESULTS: Blood pressure and heart rate were significantly lower in the metoprolol group throughout the study (P < 0.01). GFR and RPF were similar in both groups at baseline, and no change in renal hemodynamic values was detected at any level of LBNP. However, a reduction in sodium excretion was observed in the placebo group at -20 mbar, whereas no change was detected in the metoprolol group. An increase in plasma renin activity was also observed at -20 mbar in the placebo group that was not observed with metoprolol. CONCLUSION: The beta-blocker metoprolol prevents the sodium retention induced by lower body negative pressure in healthy subjects despite a lower blood pressure. The prevention of sodium retention may be due to a blunting of the neurohormonal response. These effects of metoprolol on the renal response to LBNP may in part explain the beneficial effects of this agent in heart failure patients.

HCV infection after liver transplantation is associated with lower levels of alloreactive CD4+CD25+CD45RO+IL-7R+high+ T cells

Aim: Expression of IL-7R discriminates alloreactive CD4 T cells (Foxp3 negative), from IL-7Rlow regulatory CD4 T cells (Foxp3 positive). Chronic hepatitis C virus infection (HCV) reduces expression of IL-7R on T cells thus promoting persistence of infection. The aim of this study was to analyze the effect of HCV infection on the expression of IL-7R of activated CD4+ T cells in liver transplant patients. Patients and methods: We analyzed PBMC from liver transplant recipients for the expression of CD4, CD25, FoxP3, IL-7R (24 HCV negative and 29 HCV-chronically infected). We compared these data with non-transplanted individuals (52 HCV-chronically infected patients and 38 healthy donors). Results: In HCV-infected liver transplant recipients, levels of CD4+CD25+CD45RO+IL-7R+ T cells were significantly reduced (10.5+/-0.9%) when compared to non-HCV-infected liver transplant recipients (17.6+/-1.4%) (P<0.001), while both groups (HCV-infected and negative transplant recipients) had significantly higher levels than healthy individuals (6.6+/-0.9%) (P<0.0001). After successful antiviral therapy (sustained antiviral response), 6 HCV-infected transplant recipients showed an increase of CD4+CD25+CD45RO+IL-7R+ T cells, reaching levels similar to that of non-HCVinfected recipients (10.73+/-2.63% prior therapy versus 21.7+/-6.3% after clearance of HCV). (P<0.05) In 4 non-responders (i.e. HCVRNA remaining present in serum), levels of CD4+CD25+CD45RO+IL-7R+ T cells remained unmodified during and after antiviral treatment (11.8+/- 3.3% versus 11.3+/-3.3% respectively). Conclusions: Overall, these data indicate that CD4+CD25+CD45RO+IL-7R+ T cells appear to be modulated by chronic HCV infection after liver transplantation. Whether lower levels of alloreactive T cells in HCV-infected liver transplant recipients are associated with a tolerogenic profile remains to be studied.

Obese and fit adolescents have lower blood pressure levels than obese and unfit counterparts.

The aim of the study was to assess the effects of physical fitness on the relationships between body mass index (BMI) and body fat (BF) on blood pressure (BP) levels. Cross-sectional study conducted in 25 schools of Lisbon (Portugal), including 2041 boys and 1995 girls aged 10-18. BF was assessed by bioimpedance. Cardiovascular fitness was assessed by the 20-meter shuttle run and classified as fit/unfit. Obesity (BMI or BF defined) was defined according to international criteria. In both sexes, BMI was positively related with systolic and diastolic BP, while BF was only positively related with diastolic BP z-scores. No interaction was found between fitness and BMI categories regarding BP levels, while for BF a significant interaction was found. Being fit reduced the BF-induced increase in the Odds ratio (OR) of presenting with high BP: OR (95% confidence interval) 1.01 (0.73-1.40) and 0.99 (0.70-1.38) for overweight and obese fit boys, respectively, the corresponding values for unfit overweight and obese boys being 1.33 (0.94-1.90) and 1.75 (1.34-2.28), respectively. The values were 0.88 (0.57-1.35) and 1.66 (0.98-2.80) for overweight and obese fit girls, respectively, the corresponding values for unfit overweight and obese being 1.63 (1.12-2.37) and 1.90 (1.32-2.73) respectively. No interaction was found between fitness and BMI-defined overweight and obesity. Being fit reduces the negative impact of BF on BP levels and high BP status in adolescents. This protective effect was not found with BMI.

Treatment of genital mycoplasma in colonized pregnant women in late pregnancy is associated with a lower rate of premature labour and neonatal complications.

Mycoplasma hominis and Ureaplasma spp. may colonize the human genital tract and have been associated with adverse pregnancy outcomes such as preterm labour and preterm premature rupture of membranes. However, as these bacteria can reside in the normal vaginal flora, there are controversies regarding their true role during pregnancy and so the need to treat these organisms. We therefore conducted a retrospective analysis to evaluate the treatment of genital mycoplasma in 5377 pregnant patients showing symptoms of potential obstetric complications at 25-37 weeks of gestation. Women presenting with symptoms were routinely screened by culture for the presence of these bacteria and treated with clindamycin when positive. Compared with uninfected untreated patients, women treated for genital mycoplasma demonstrated lower rates of premature labour. Indeed preterm birth rates were, respectively, 40.9% and 37.7% in women colonized with Ureaplasma spp. and M. hominis, compared with 44.1% in uncolonized women (Ureaplasma spp., p 0.024; M. hominis, p 0.001). Moreover, a reduction of neonatal complications rates was observed, with 10.9% of newborns developing respiratory diseases in case of Ureaplasma spp. colonization and 5.9% in the presence of M. hominis, compared with 12.8% in the absence of those bacteria (Ureaplasma spp., p 0.050; M. hominis, p <0.001). Microbiological screening of Ureaplasma spp. and/or M. hominis and pre-emptive antibiotic therapy of symptomatic pregnant women in late pregnancy might represent a beneficial strategy to reduce premature labour and neonatal complications.

Global surveillance of cancer survival 1995-2009 : analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75 000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems. FUNDING: Canadian Partnership Against Cancer (Toronto, Canada), Cancer Focus Northern Ireland (Belfast, UK), Cancer Institute New South Wales (Sydney, Australia), Cancer Research UK (London, UK), Centers for Disease Control and Prevention (Atlanta, GA, USA), Swiss Re (London, UK), Swiss Cancer Research foundation (Bern, Switzerland), Swiss Cancer League (Bern, Switzerland), and University of Kentucky (Lexington, KY, USA).

Soft tissue artifact distribution on lower limbs during treadmill gait: Influence of skin markers' location on cluster design.

Segment poses and joint kinematics estimated from skin markers are highly affected by soft tissue artifact (STA) and its rigid motion component (STARM). While four marker-clusters could decrease the STA non-rigid motion during gait activity, other data, such as marker location or STARM patterns, would be crucial to compensate for STA in clinical gait analysis. The present study proposed 1) to devise a comprehensive average map illustrating the spatial distribution of STA for the lower limb during treadmill gait and 2) to analyze STARM from four marker-clusters assigned to areas extracted from spatial distribution. All experiments were realized using a stereophotogrammetric system to track the skin markers and a bi-plane fluoroscopic system to track the knee prosthesis. Computation of the spatial distribution of STA was realized on 19 subjects using 80 markers apposed on the lower limb. Three different areas were extracted from the distribution map of the thigh. The marker displacement reached a maximum of 24.9mm and 15.3mm in the proximal areas of thigh and shank, respectively. STARM was larger on thigh than the shank with RMS error in cluster orientations between 1.2° and 8.1°. The translation RMS errors were also large (3.0mm to 16.2mm). No marker-cluster correctly compensated for STARM. However, the coefficient of multiple correlations exhibited excellent scores between skin and bone kinematics, as well as for STARM between subjects. These correlations highlight dependencies between STARM and the kinematic components. This study provides new insights for modeling STARM for gait activity.