The objective of the current study was to examine the efficacy and tolerability of the β-blocker metoprolol succinate controlled release/extended release (CR/XL) in patients with diabetes in the ...Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF).
The Cox proportional hazards model was used to calculate hazard ratios (HR) for convenience expressed as relative risks (risk reduction = 1-HR), and 95% confidence intervals (CI).
The risk of hospitalization for heart failure was 76% higher in diabetics compared to non-diabetics (95% CI 38% to 123%). Metoprolol CR/XL was well tolerated and reduced the risk of hospitalization for heart failure by 37% in the diabetic group (95% CI 53% to 15%), and by 35% in the non-diabetic group (95% CI 48% to 19%). Pooling of mortality data from the Cardiac Insufficiency Bisoprolol Study II (CIBIS II), MERIT-HF, and the Carvedilol Prospective Randomized Cumulative Survival Study (COPERNICUS) showed similar survival benefits in patients with diabetes (25%; 95% CI 40% to 4%) and without diabetes (36%; 95% CI 44% to 27%); test of diabetes by treatment interaction was non-significant. Adverse events were reported more often on placebo than on metoprolol CR/XL.
Patients with heart failure and diabetes have a much higher risk of hospitalization than patients without diabetes. Regardless of diabetic status, a highly significant reduction in hospitalizations for heart failure was observed with metoprolol CR/XL therapy, which was very well tolerated also by patients with diabetes. Furthermore, the pooled data showed a statistically significant survival benefit in patients with diabetes.
Oral mucosal wound-healing is characterized by rapid re-epithelialization and remodeling, with minimal scar formation. This may be attributed to the distinct phenotypic characteristics of the ...resident fibroblasts. To test this hypothesis, we investigated patient-matched oral mucosal and skin fibroblasts. Compared with skin fibroblasts, oral mucosal fibroblasts had longer proliferative lifespans, underwent more population doublings, and experienced senescence later, which was directly related to longer telomere lengths within oral mucosal fibroblasts. The presence of these longer telomeres was independent of telomerase expression, since both oral oral mucosal fibroblasts and skin fibroblasts were negative for active telomerase, as assessed according to the Telomeric Repeat Amplification Protocol. This study has demonstrated that, compared with skin fibroblasts, oral mucosal fibroblasts are ‘younger’, with a more embryonic/fetal-like phenotype that may provide a notable advantage for their ability to repair wounds in a scarless fashion.
Cardiovascular abnormalities are frequently the cause, as well as the effect, of elevated blood pressure. As such, early cardiovascular disease (CVD) may be established before identifiable blood ...pressure thresholds are crossed. To identify individuals at risk for CVD at an earlier point in the disease process, as well as to avoid labeling persons as hypertensive who are at low risk for CVD, the Hypertension Writing Group proposes incorporating the presence or absence of cardiovascular risk factors, early disease markers, and target organ damage into the definition and classification scheme of hypertension. To describe both the complexity and progressive nature of hypertension, the following definition is proposed: “Hypertension is a progressive cardiovascular syndrome arising from complex and interrelated etiologies. Early markers of the syndrome are often present before blood pressure elevation is observed; therefore, hypertension cannot be classified solely by discrete blood pressure thresholds. Progression is strongly associated with functional and structural cardiac and vascular abnormalities that damage the heart, kidneys, brain, vasculature, and other organs and lead to premature morbidity and death.” Classification of hypertension must involve assessing global cardiovascular risk to situate an individual's risk for CVD and events along a continuum. As knowledge of early CVD continues to evolve, the approach to classifying individuals along that continuum can be expected to evolve accordingly. The four categories currently used to classify hypertension are normal, prehypertension, and stages 1 and 2 hypertension. The population identified with prehypertension includes a subgroup with early CVD. We believe it would be preferable to classify all individuals as either normal or hypertensive, based on their cardiovascular evaluation, using the four categories of normal and stages 1, 2, and 3 hypertension.
Background: Recombinant interleukin (IL)-11 is a thrombopoietic growth factor. The purpose of this study was to assess the toxicity, safety and efficacy of low-dose recombinant IL-11 in patients with ...bone marrow failure (BMF). Patients and methods: Patients with BMF due to myelodysplastic syndromes (MDS), graft failure, chemotherapy or aplastic anemia (AA) were treated. Patients were required to have a platelet count of <20 × 109/l, or a platelet count of <50 × 109/l with an absolute neutrophil count <1 × 109/l, or a hemoglobin value <10 g/dl. Treatment consisted of daily IL-11 at a dose of 10 μg/kg subcutaneously followed by a 2-week rest period. Two induction courses were given. Responders could receive maintenance therapy. Results: Thirty-three patients (MDS, n=14; AA, n=16; prolonged thrombocytopenia following stem cell transplantation or chemotherapy, n=3) were evaluable. Their median age was 58 years (range 5–85). Three patients (9%) had poor risk cytogenetics. Nine patients (27%) responded to IL-11 (six MDS, three AA). Of these, three patients treated with IL-11 alone (n=1) or IL-11 together with other growth factors (n=2) showed multilineage recovery. The median time to response was 0.9 months (range 0.3–11). Factors associated with higher response rates in univariate analysis were age >50 years (P=0.008), diagnosis of MDS versus AA (P=0.025) and creatinine level >1 mg/dl (P=0.0004). The median response duration was 3 months (range 1.4–34.5+). Amongst responders, the median increment in platelet count was 111 × 109/l (range 43–165). The most common side-effects were grade 1–2 lower extremity edema, conjunctival injections and fatigue. Grade 3 toxicities included arrhythmia (n=1) and transient ischemic attack (n=1). Ten patients (30%) had no side-effects. Conclusions: Low-dose IL-11 has activity in patients with BMF and is generally well tolerated.
The Genetics of Hypertension—Where to Look? Giles, Thomas D.
The journal of clinical hypertension (Greenwich, Conn.),
December 2011, Letnik:
13, Številka:
12
Journal Article
Resistant hypertension (RH), defined simply, is blood pressure (BP) requiring the use of four or more antihypertensive agents, whether controlled or uncontrolled. RH is an increasingly common problem ...in elderly patients and may affect as many as 20% of the hypertensive population. Unfortunately, at least 30% of patients evaluated for RH are actually adequately controlled when more carefully assessed by home BP monitoring or ambulatory BP monitoring, thus representing a white coat effect. It is also essential to exclude pseudoresistance resulting from improper BP recording techniques or failure of the patient to adhere to the prescribed treatment regimen. Concurrent use of drugs that may interfere with prescribed antihypertensive agents, including many over the counter herbal preparations, must also be excluded. The underlying mechanisms principally driving true RH include pathophysiologic abnormalities of aldosterone signaling, sodium and water retention, excessive sympathetic nervous system activity, and obstructive sleep apnea. Appropriate treatment regimens will usually include an inhibitor of the renin-angiotensin-aldosterone system, a calcium channel blocker, and a diuretic. An aldosterone receptor blocker can be instituted at any step, and is very effective as a fourth drug. Beta-blockers can also be integrated into these treatment plans and may be especially helpful when excessive sympathetic nervous system activity is suspected. Novel device therapies that interrupt sympathetic nerve stimulation at the carotid sinus and kidney are under investigation, and may add entirely new directions in the management of RH. What is most important is that treatment regimens should be targeted to specific patient profiles.
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