Pulse pressure and left ventricular diastolic dysfunction in hypertensive patients

BACKGROUND: Impaired left ventricular diastolic function is a common finding in essential hypertension. METHODS: In order to investigate possible relationships between flow velocity through the mitral valve (E/A; index of left ventricular diastolic function) and 24-hour blood pressure and heart rate variations, 198 patients with mild to moderate essential hypertension were studied by Doppler echocardiography and ambulatory blood pressure monitoring. They were divided according to age into group 1 (n = 88, age 40-54 years) and group 2 (n = 110, age 55-79 years). Each group was divided into subgroups with (1a, 2a) or without (1b, 2b) left ventricular hypertrophy according to the end-diastolic posterior wall thickness and/or the interventricular septum thickness. RESULTS: In a multivariate stepwise regression analysis, age (beta = -0.25, p < 0.0001), posterior wall thickness (beta = -0.31, p < 0.0057) and mean heart rate during the day (beta = -0.34, p < 0.0284) were the independent predictors of E/A in the pooled population. In group 1a (young subjects with left ventricular hypertrophy), mean systolic blood pressure during the night (beta = -0.33, p < 0.041) was the only independent predictor of E/A. In the elderly group without left ventricular hypertrophy (group 2b), the mean heart rate during the day (beta = -0.44, p < 0.0000) and mean pulse pressure during the night (beta = -0.60, p < 0.0007) were the independent predictors of E/A. CONCLUSIONS: The new finding provided by this study is that in elderly hypertensive patients without left ventricular hypertrophy, a large pulse pressure at night may serve as an independent predictor of abnormal left ventricular diastolic filling.     

Joint ESCMID,FEMS, IDSA,ISID and SSI position paper on the fair handling of career breaks among physicians and scientists when assessing eligibility for early-career awards

BackgroundThough women increasingly make up the majority of medical-school and other science graduates, they remain a minority in academic biomedical settings, where they are less likely to hold leadership positions or be awarded research funding. A major factor is the career breaks that women disproportionately take to see to familial duties. They experience a related, but overlooked, hurdle upon their return: they are often too old to be eligible for ‘early-career researcher’ grants and ‘career-development’ awards, which are stepping stones to leadership positions in many institutions and which determine the demographics of their hierarchies for decades to come. Though age limits are imposed to protect young applicants from more experienced seniors, they have an unintended side effect of excluding returning workers, still disproportionately women, from the running.MethodsIn this joint effort by the European Society of Clinical Microbiology and Infectious Diseases, the Federation of European Microbiological Societies, the Infectious Disease Society of America, the International Society for Infectious Diseases and the Swiss Society for Infectious Diseases, we invited all European Congress of Clinical Microbiology and Infectious Diseases-affiliated medical societies and funding bodies to participate in a survey on current ‘early-career’ application restrictions and measures taken to provide protections for career breaks.RecommendationsThe following simple consensus recommendations are geared to funding bodies, academic societies and other organizations for the fair handling of eligibility for early-career awards: 1. Apply a professional, not physiological, age limit to applicants. 2. State clearly in the award announcement that career breaks will be factored into applicants' evaluations such that: ? Time absent is time extended: for every full-time equivalent of career break taken, the same full-time equivalent will be extended to the professional age limit. ? Opportunity costs will also be taken into account: people who take career breaks risk additional opportunity costs, with work that they did before the career break often being forgotten or poorly documented, particularly in bibliometric accounting. Although there is no standardized metric to measure additional opportunity costs, organizations should (a) keep in mind their existence when judging applicants' submissions, and (b) note clearly in the award announcement that opportunity costs of career breaks are also taken into account. 3. State clearly that further considerations can be undertaken, using more individualized criteria that are specific to the applicant population and the award in question.The working group welcomes feedback so that these recommendations can be improved and updated as needed.     

Development and characterization of DNAzyme candidates demonstrating significant efficiency against human rhinoviruses

1. Download high-res image (359KB)
2. Download full-size image

     

Budesonide and formoterol inhibit inflammatory mediator production by bronchial epithelial cells infected with rhinovirus

Background Rhinoviruses (RVs) are responsible for the majority of acute asthma and chronic obstructive pulmonary disease (COPD) exacerbations. RVs infect the lower airways and induce the production of pro-inflammatory and remodelling-associated mediators. Budesonide (BUD) and formoterol (FORM) synergize in controlling asthma and COPD exacerbations; however, their effects on virus-induced inflammation and remodelling are less known.
Objective We investigated whether BUD and FORM synergize in suppressing RV-induced inflammation and remodelling in the airways.
Methods In vitro models of RV infection of BEAS-2B and primary normal human bronchial epithelial (NHBE) cells were used. We assessed the effects of individual and combined drugs administered post-infection, at a clinically relevant concentration range (10⁻⁶–10⁻¹⁰  m ), on the production of CCL5, CXCL10, CXCL8, IL-6 and the remodelling-associated VEGF and bFGF, using ELISA and RT-PCR.
Results BUD effectively suppressed RV-mediated induction of all mediators studied, in a concentration-dependent manner. FORM alone suppressed the production of CXCL8 and bFGF. The combination of BUD and FORM had concentration-dependent, additive or synergistic effects in the suppression of RV-induced CCL5, CXCL8 and CXCL10 in both cell types as well as VEGF in NHBE only. Combination treatment also resulted in an enhanced suppression of RV-induced IL-6, and CCL5 at the mRNA level as compared with BUD or FORM alone.
Conclusion BUD and FORM suppress RV-induced chemokines and growth factors in bronchial epithelial cells in a concentration-dependent, synergistic or additive manner. These data further support the combined use of BUD and FORM in asthma and COPD and intensification of this therapy during exacerbations.