Angiotensin II Receptor Subtypes and Cardiac Function

All the components of the renin-angiotensin system have been identified in the heart including the angiotensin II receptor subtypes AT1 and AT2 In the normal human heart, there is a decreasing receptor density from the right atrium to the left ventricle. In right atrial membranes prepared from pathological hearts, the percentage of AT1 receptor decreases with the severity of cardiac dysfunction whereas that of AT2 receptor increases. Treatment of hypertrophic rats with AT1 receptor antagonists inhibits cardiac hypertrophy and reverses the increase receptor density, indicating involvement of this Ang II receptor subtype. The role of the AT2 receptor is still largely unknown but it may be involved in cell growth and proliferation. The cloning of both AT1 and AT2 receptors as well as the availability of potent and selective antagonists will help us to understand better the functional role of Angiotensin II in cardiovascular disorder

Selective loss of myelin-associated glycoprotein from myelin correlates with anti-MAG antibody titre in demyelinating paraproteinaemic polyneuropathy

Summary The IgM monoclonal autoantibodies of patients with demyelinating paraproteinaemic polyneuropathy recognize a carbohydrate structure present on both myelin-associated glycoprotein (MAG) and protein zero (Po). These autoantibodies are sufficient to cause the disease but the mechanism of demyelination remains unclear. We have analysed nerve biopsies from eight patients with polyneuropathy and anti-MAG antibodies by quantitative immunohistochemistry and find a concordant pattern of reduced expression of myelin markers with the loss of myelinated fibres. We report here novel features of this disease, in particular a selective lack of detectable MAG in a large proportion of myelinated fibres containing Po, myelin basic protein (MBP) and periaxin. There is also an inverse correlation of the distribution of MAG in peripheral never myelin with the serum anti-MAG antibody titres but no correlation of these titres with the loss of myelinated fibres. Double immunofluorescence staining of paraproteinaemic polyneuropathy (PPN) nerves shows anti-MAG IgM deposited on the periphery of myelinated fibres associated with or lacking MAG staining. These data suggest that the binding of anti-MAG antibodies to MAG and/or other myelin component(s) results in MAG downregulation and may have an essential role in the molecular mechanisms leading to demyelination and partial regeneration in this diseas

Reproducibility and its confounders of CMR feature tracking myocardial strain analysis in patients with suspected myocarditis.

OBJECTIVES Cardiovascular magnetic resonance feature tracking (CMR-FT) is an emerging technique for assessing myocardial strain with valuable diagnostic and prognostic potential. However, the reproducibility of biventricular CMR-FT analysis in a large cardiovascular population has not been assessed. Also, evidence of confounders impacting reader reproducibility for CMR-FT in patients is unknown and currently limits the clinical implementation of this technique. METHODS From a dual-center database of patients referred to CMR for suspected myocarditis, 125 patients were randomly selected to undergo biventricular CMR-FT analysis for 2-dimensional systolic and diastolic measures, with additional 3-dimensional analysis for the left ventricle. All image analysis was replicated by a single reader and by a second reader for intra- and inter-reader analysis (Circle Cardiovascular Imaging). Reliability was tested with intraclass correlation (ICC) tests, and the impact of imaging confounders on agreement was assessed through multivariable analysis. RESULTS Left and right ventricular ejection fractions were reduced in 34% and 37% of the patients, respectively. Good to excellent reliability was shown for 2D (all ICC > 0.85) and 3D (all ICC > 0.70) peak strain and early diastolic strain rate for both ventricles in longitudinal orientation as well as circumferential orientations for the left ventricle. An increased slice number improved agreement while the presence of pericardial effusion compromised diastolic strain rate agreement, and arrhythmia compromised right ventricular agreement. CONCLUSION In a large clinical cohort, we could show CMR-FT yields excellent inter-reader and intra-reader reproducibility. Multi-parametric CMR-FT of the right and left ventricles appears to be a robust tool in cardiovascular patients referred to CMR. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03470571, NCT04774549. Key Points • Cardiovascular magnetic resonance feature tracking (CMR-FT) is an emerging technique to measure myocardial strain in cardiovascular patients referred for CMR; however, the evaluation of its reproducibility in a large cohort has not yet been performed. • In a large clinical cohort, CMR-FT yields excellent inter-reader and intra-reader reproducibility for both left and right ventricular systolic and diastolic parameters. • Arrhythmia and pericardial effusion compromise agreement of select FT parameters, but poor ejection fraction does not

Prevalence and determinants of chronic kidney disease in the Swiss population.

QUESTIONS UNDER STUDY: The prevalence of chronic kidney disease (CKD) is increasing worldwide, corresponding to an increased risk of cardiovascular disease. The latest study on prevalence of CKD involving the three linguistic regions of Switzerland dates back to 2002-2003 and definitions have changed since then. We aimed to assess the current prevalence and determinants of CKD in the Swiss general population. METHODS: We analysed the data of 1353 participants from a cross-sectional population-based survey performed in 2010-2012 in the three linguistic regions of Switzerland. The prevalence of CKD and the derived cardiovascular risk categories were assessed according to the Kidney Disease - Improving Global Outcomes (KDIGO) 2012 classification, using estimated glomerular filtration rate (GFR; CKD-Epidemiological Collaboration equation) and albuminuria level. Multivariate logistic regression was used to analyse factors associated with CKD. RESULTS: We included 660 men and 693 women, equally distributed in four age categories (15-29, 30-44, 45-59 and over 60 years). The overall prevalence of CKD was 10.4%. The prevalence in the low, moderate, high and very high risk KDIGO categories were 89.6%, 8.4%, 1.6% and 0.5%, respectively. The prevalence of CKD was similar in all linguistic regions. In multivariate analysis, female gender, older age, diabetes and uric acid were independently associated with CKD in persons ≥45 y. In younger participants, diabetes and lower educational level were associated with CKD. CONCLUSIONS: In the general Swiss population, CKD affects one in ten adults. Subjects older than 60 years, as well as patients with diabetes and hypertension, show a high prevalence of CKD. Systematic screening may be recommended in this population

Associations of sodium, potassium and protein intake with blood pressure and hypertension in Switzerland.

Nutritional factors play an important role in the regulation of blood pressure and in the development of hypertension. In this analysis, we explored the associations of 24-hour urinary Na+, K+ and urea excretion with blood pressure levels and the risk of hypertension in the Swiss population, taking regional linguistic differences into account. The Swiss Survey on Salt is a population based cross-sectional study that included 1336 subjects from the three main linguistic regions (French, German and Italian) of Switzerland. Blood pressure was measured with a validated oscillometric Omron HEM 907 device. Hypertension was defined as current antihypertensive treatment or a mean systolic blood pressure >140 mm Hg and/or diastolic >90 mm Hg, based on eight blood pressure measurements performed at two visits. Na+, K+ and urea excretion were assessed in 24-hour urine collections. We use multiple logistic/linear regressions to explore the associations of urine Na+, K+ and urea with blood pressure / hypertension, taking into account potential confounders and effect modifiers. The prevalence of hypertension was 30%, 26% and 17% in the German-, French- and Italian- speaking regions respectively, (p-value across regions <0.001). In the Swiss adult population, besides age, sex, and body mass index, urinary Na+ excretion was positively associated with systolic blood pressure and hypertension. Urinary K+ excretion tended to be negatively associated with blood pressure but this was not significant (p = 0.08). Hypertensive people had a higher 24-hour urinary Na+/K+ ratio than normotensive people (p = 0.003). Urinary urea excretion was associated with neither blood pressure nor hypertension. Participants from the German-speaking region had a higher likelihood of having a high systolic blood pressure. We confirm a high prevalence of elevated blood pressure in Swiss adults, including regional differences. In Switzerland, urinary Na+ excretion is associated positively with blood pressure and hypertension, independently of urinary K+ and urea excretion. The observed differences in blood pressure levels across linguistic regions are independent of the urinary Na+, K+ and urea excretion

Design of the Swiss Atrial Fibrillation Cohort Study (Swiss-AF): structural brain damage and cognitive decline among patients with atrial fibrillation.

Several studies found that patients with atrial fibrillation (AF) have an increased risk of cognitive decline and dementia over time. However, the magnitude of the problem, associated risk factors and underlying mechanisms remain unclear. This article describes the design and methodology of the Swiss Atrial Fibrillation (Swiss-AF) Cohort Study, a prospective multicentre national cohort study of 2400 patients across 13 sites in Switzerland. Eligible patients must have documented AF. Main exclusion criteria are the inability to provide informed consent and the presence of exclusively short episodes of reversible forms of AF. All patients undergo extensive phenotyping and genotyping, including repeated assessment of cognitive functions, quality of life, disability, electrocardiography and cerebral magnetic resonance imaging. We also collect information on health related costs, and we assemble a large biobank. Key clinical outcomes in Swiss-AF are death, stroke, systemic embolism, bleeding, hospitalisation for heart failure and myocardial infarction. Information on outcomes and updates on other characteristics are being collected during yearly follow-up visits. Up to 7 April 2017, we have enrolled 2133 patients into Swiss-AF. With the current recruitment rate of 15 to 20 patients per week, we expect that the target sample size of 2400 patients will be reached by summer 2017. Swiss-AF is a large national prospective cohort of patients with AF in Switzerland. This study will provide important new information on structural and functional brain damage in patients with AF and on other AF related complications, using a large variety of genetic, phenotypic and health economic parameters

Equal pay by gender and by nationality: a comparative analysis of Switzerland's unequal equal pay policy regimes across time

What explains the adoption of two different policies on equal pay by gender (EPG) and by nationality (EPN) in Switzerland? And why is the liberal, litigation-based, equal pay policy regime set up by the Gender Equality Act of 1996 much less effective than the neocorporatist ‘accompanying measures' to the Bilateral European Union-Switzerland Agreement on Free Movement of Persons adopted in 1999 to ensure equal pay for workers of different national origins? The formation of two different policy regimes cannot be explained by different levels of political will. Equally, different ‘varieties of capitalism' cannot explain the setup of the two different equal pay policy regimes within the very same country. Instead, our qualitative comparative analysis across time suggests that the differences can be best explained by a particular constellation of attributes, namely the use of different policy frames—i.e. ‘anti-discrimination' in the EPG and ‘unfair competition' in the EPN case—and the different setting of interest politics epitomised by the opposite stances adopted by Switzerland's employer associations in the two case

Where are the Pots and Pans? Collective Responses in Ireland to Neoliberalization in a Time of Crisis: Learning from Latin America

Since 2008, Ireland has experienced a profound multi-faceted crisis, stemming from the collapse of the financial and property sectors. Despite enduring six years of neoliberal austerity measures in response to this situation, popular protest has been muted. Using Silva's [(2009) Challenging Neoliberalism in Latin America (Cambridge and New York: Cambridge University Press)] framework of analysis of popular responses in Latin America to that region's debt crisis of the 1980s and 1990s, this article seeks to investigate why this has been the case. We assess how the crisis is being framed among popular and civil society groups, and whether increased associational and collective power is developing. In doing so, we look at processes of intra-group cooperation, cross-group cooperation and framing and brokerage mechanisms. We then ask, where such processes exist, if they can lead to a comprehensive challenge to the neoliberal policies currently being implemented, as happened in much of Latin America. We conclude that the crisis has not yet reached sufficient depth or longevity to foster a more robust popular response, but propose that analysis of similar processes in Latin America can help us understand better why this is the case, not just in Ireland, but in other countries of Europe experiencing similar situations

Study of Z Boson Pair Production in e+e- Collisions at LEP at \sqrt{s}=189 GeV

The pair production of Z bosons is studied using the data collected by the L3 detector at LEP in 1998 in e+e- collisions at a centre-of-mass energy of 189 GeV. All the visible final states are considered and the cross section of this process is measured to be 0.74 +0.15 -0.14 (stat.) +/- 0.04 (syst.) pb. Final states containing b quarks are enhanced by a dedicated selection and their production cross section is found to be 0.18 +0.09 -0.07 (stat.) +/- 0.02 (syst.) pb. Both results are in agreement with the Standard Model predictions. Limits on anomalous couplings between neutral gauge bosons are derived from these measurements

Search for Scalar Leptons in e+e- collisions at \sqrt{s}=189 GeV

We report the result of a search for scalar leptons in e+e- collisions at 189 GeV centre-of-mass energy at LEP. No evidence for such particles is found in a data sample of 176 pb^{-1}. Improved upper limits are set on the production cross sections for these new particles. New exclusion contours in the parameter space of the Minimal Supersymmetric Standard Model are derived, as well as new lower limits on the masses of these supersymmetric particles. Under the assumptions of common gaugino and scalar masses at the GUT scale, we set an absolute lower limit on the mass of the lightest scalar electron of 65.5 Ge