Nebivolol, a vasodilatory β1‐blocker, may be well suited for the hemodynamics of the younger hypertensive patient. In this 8‐week trial, 18‐ to 54‐year‐olds with a diastolic blood pressure (DBP) of ...95 mm Hg to 109 mm Hg who completed a 4‐week placebo‐only phase were randomized to receive nebivolol (5 mg/d, titrated to 10–20 mg/d based on achievement of blood pressure <140/90 mm Hg n=427) or placebo (n=214). Primary and secondary efficacy parameters were changes in trough seated DBP and systolic blood pressure (SBP), respectively. Safety parameters included adverse events (AEs). The baseline mean age was 45.3 years; SBP/DBP, 154/100 mm Hg; and heart rate, 78 beats per minute. Completion rates were 91.3% (nebivolol) and 88.3% (placebo). At endpoint, there was a significant effect of nebivolol over placebo for DBP (−11.8 mm Hg vs −5.5 mm Hg, P<.001) and SBP (−13.7 mm Hg vs −5.5 mm Hg, P<.001). Total AE rates were 34.7% (nebivolol) and 32.2% (placebo). Nebivolol monotherapy is efficacious and well tolerated in adults younger than 55 years of age with increased DBP.
Stable organic nitroxide radicals have been shown to exhibit similar cell biology signaling properties as the well-known but short-lived small molecule nitric oxide, such as affecting intracellular ...redox states and cell proliferation behavior. Biological processes might thus be amenable to biointerfacial regulation via release of stable nitroxide molecules from coatings applied onto biomedical devices. In this study, we utilized the facile and technologically attractive process of plasma polymerization for the deposition of thin layers containing stable nitroxide radicals, using TEMPO (2,2,6,6-tetramethylpiperidin-1-yl)oxyl as the “monomer” for creating a thin polymeric film. Coatings (TEMPOpps) produced under various conditions were characterized by ellipsometry, XPS, ToF-SIMS, and EPR as well as in vitro biological effects on bacteria (Staphylococcus epidermidis), fungi (Candida albicans), and human cancer cells (KG1a). TEMPOpps were compared with plasma coatings from three structurally related precursors that lack nitroxide groups. Surface characterization by XPS and ToF-SIMS confirmed the similarity of atomic composition and molecular fragments of the TEMPOpp films to the precursor molecule. Thin (241–312 nm) films were shown by EPR to contain stable nitroxide radicals, with a G-factor of 17 G typical of TEMPO. The plasma conditions modulated the density of radicals included in the films. On TEMPOpp surfaces, the microbial pathogens Staphylococcus epidermidis and Candida albicans exhibited reduced capacity to form biofilm, and fungal cells did not transition to hyphal forms. In addition, for the nonadherent human cancer cell line KG1a, we found that TEMPOpp coatings upregulated the cells’ intracellular reactive oxygen species (ROS) but were not cytotoxic. Thus, we demonstrate that TEMPOpp films with nitroxide radicals possess versatile promising biological activities, such as for coating biomedical devices to prevent infections.
The prevalence of individuals with increased blood pressure (BP) is growing. A greater understanding of the various pathogenetic mechanisms of hypertension and associated BP increases would provide a ...better strategy for preventing and treating this condition. Hypertension is strongly associated with other cardiovascular risk factors. Additionally, there is no threshold of BP >115/70 mm Hg that identifies cardiovascular risk (i.e., risk is linear and doubles for each 20/10‐mm Hg BP rise). These insights have led a group of hypertension experts to propose a new definition of hypertension as “a progressive cardiovascular syndrome arising from complex and interrelated etiologies,” which features early markers that are “often present before blood pressure elevation is sustained.” Early cardiovascular markers include widened pulse pressure, left ventricular hypertrophy, increased arterial stiffness, endothelial dysfunction, and microalbuminuria. Importantly, antihypertensive treatment for patients with prehypertension (systolic BP of 120–139 mm Hg or diastolic BP of 80–89 mm Hg) has recently been shown to prevent the development of frank hypertension. This revision of the definition of hypertension and the need to assess BP levels in the context of global cardiovascular risk should lead to earlier detection of at‐risk patients.
The efficacy, toxicity, and tolerability of chemoimmunotherapy with the combination of fludarabine, cyclophosphamide, and rituximab (FCR) were evaluated in previously treated patients with chronic ...lymphocytic leukemia (CLL). The purpose of this study was to improve the complete remission (CR) rate for previously treated patients and evaluate the quality of bone marrow response.
One hundred seventy-seven previously treated patients with CLL were evaluated. Treatment consisted of rituximab 375 mg/m(2) day 1 of course 1 and 500 mg/m(2) day 1 of courses 2 to 6; fludarabine 25 mg/m(2)/d days 2 to 4 of course 1 and days 1 to 3 of courses 2 to 6; and cyclophosphamide 250 mg/m(2)/d days 2 to 4 of course 1 and days 1 to 3 of courses 2 to 6. Courses were repeated every 4 weeks.
CR was achieved in 25% of 177 patients, and nodular partial remission and partial remission were achieved in 16% and 32% of patients, respectively; the overall response rate was 73%. Twelve (32%) of 37 complete responders tested achieved molecular remission in bone marrow. Univariate and multivariate analyses were used to identify pretreatment patient characteristics associated with CR and overall remission, longer time to progression, and overall survival.
The FCR regimen was an active and well-tolerated treatment for previously treated patients with CLL. Myelosuppression was the most common toxicity. FCR induced the highest CR rate reported in a clinical trial of previously treated patients with CLL. Furthermore, molecular remissions were achieved in a third of patients achieving CR.
Great Expectations Fulfilled Giles, Thomas D.
The journal of clinical hypertension (Greenwich, Conn.),
February 2010, Letnik:
12, Številka:
2
Journal Article
Cardiovascular disease accounts for the majority of deaths in patients with type 2 diabetes mellitus. Lifestyle interventions aimed at weight loss and increased physical activity and therapy with ...antidiabetic drugs have proven effective in reducing the risk of new‐onset diabetes in high‐risk individuals. Substantial evidence also suggests that drugs that inhibit the renin‐angiotensin system, namely angiotensin‐converting enzyme inhibitors and angiotensin II receptor blockers, also prolong the time to onset of clinical diabetes. An open question is whether delay of new‐onset diabetes with antidiabetic or antihypertensive agents reduces cardiovascular morbidity and mortality. A large ongoing study is investigating whether therapy with an oral antidiabetic drug or an angiotensin II receptor blocker reduces the incidence of new‐onset diabetes and cardiovascular events in high‐risk patients.
Peroxisome-proliferator-activated receptor-gamma (PPAR-gamma) agonists (known as thiazolidinediones; TDZs) activate nuclear receptors that regulate gene expression; they were developed as ...insulin-sensitizing drugs to treat type 2 diabetes mellitus. Although the prototypic TZD troglitazone was withdrawn from the market due to hepatic toxicity, rosiglitazone and pioglitazone are mainstays in managing type 2 diabetes mellitus. TZDs exert their hypoglycemic effect by reducing insulin resistance, hence improving insulin sensitivity. However, TZDs also exhibit a broad range of cardiovascular actions, with the clinical consequence of reduction in blood pressure (BP), observed in animal models and human diabetic subjects. The magnitude of reduction appears to be about 4 to 5 mm Hg in systolic and 2 to 4 mm Hg in diastolic BP--sufficient to significantly reduce subsequent cardiovascular event rates. But these BP-reducing properties, which are not present with metformin or sulfonylureas, are particularly important when viewed in conjunction with hypoglycemic effects. A significant proportion of patients with type 2 diabetes mellitus and BP mildly above target range might be successfully treated for both processes with a single drug.
ABSTRACT
We present the MARD-Y3 catalogue of between 1086 and 2171 galaxy clusters (52 per cent and 65 per cent new) produced using multicomponent matched filter (MCMF) follow-up in 5000 deg2 of ...DES-Y3 optical data of the ∼20 000 overlapping ROSAT All-Sky Survey source catalogue (2RXS) X-ray sources. Optical counterparts are identified as peaks in galaxy richness as a function of redshift along the line of sight towards each 2RXS source within a search region informed by an X-ray prior. All peaks are assigned a probability fcont of being a random superposition. The clusters lie at 0.02 < z < 1.1 with more than 100 clusters at z > 0.5. Residual contamination is 2.6 per cent and 9.6 per cent for the cuts adopted here. For each cluster we present the optical centre, redshift, rest frame X-ray luminosity, M500 mass, coincidence with NWAY infrared sources, and estimators of dynamical state. About 2 per cent of MARD-Y3 clusters have multiple possible counterparts, the photo-z’s are high quality with σΔz/(1 + z) = 0.0046, and ∼1 per cent of clusters exhibit evidence of X-ray luminosity boosting from emission by cluster active galactic nuclei. Comparison with other catalogues (MCXC, RM, SPT-SZ, Planck) is performed to test consistency of richness, luminosity, and mass estimates. We measure the MARD-Y3 X-ray luminosity function and compare it to the expectation from a fiducial cosmology and externally calibrated luminosity- and richness–mass relations. Agreement is good, providing evidence that MARD-Y3 has low contamination and can be understood as a simple two step selection – X-ray and then optical – of an underlying cluster population described by the halo mass function.
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