Therapy of idiopathic dilated cardiomyopathy with chronic β-adrenergic blockade

Conventional therapy of patients with idiopathic dilated cardiomyopathy is currently directed at the control of heart failure. However, the morbidity and mortality of idiopathic dilated cardiomyopathy remains very high despite such interventions. One promising new approach to therapy of idiopathic dilated cardiomyopathy is -blockade. The potential mechanisms for benefit from -blockade include protection from catecholamine cardiotoxicity, upregulation of myocardial -adrenergic receptors, reduction in sudden death, reduction in heart rate, improved ventricular diastolic function, and reduction in afterload. Several reports have suggested that longterm -blockade may improve hemodynamic function, clinical symptoms, and survival in patients with idiopathic dilated cardiomyopathy. However, data from controlled trials are limited and some reports have been negative. This paper will summarize the rationale for the use of -blocker therapy in idiopathic dilated cardiomyopathy and review the clinical experience with this therapy.Address for reprints: Edward M. Gilbert, M.D., Division of Cardiology 4A-100, University of Utah Medical Center, 50 North Medical Drive, Salt Lake City, UT 84132, USA     

Compliance with Deferoxamine Therapy and Thyroid Dysfunction of Patients with β-Thalassemia Major in Syria

Abstract

Hypothyroidism is one of the common endocrine complications described in patients with β-thalassemia major (β-TM). Studies have reported its incidence and severity depending on the region, quality of management and treatment protocols. The reported thyroid dysfunction includes overt hypothyroidism, subclinical hypothyroidism and rarely, central hypothyroidism. The main aims of this study were to identify the incidence of hypothyroidism in 82 patients with β-TM in Syria, and also to evaluate the effect of compliance with deferoxamine (DFO) therapy on the patients’ thyroid function. Out of the 82 patients included in this study, 24 had subclinical hypothyroidism (29.27%) and one patient had overt hypothyroidism (1.22%). It was demonstrated by this study that noncompliance with DFO therapy increases the risk of thyroid dysfunction 6.38-times compared to compliance with DFO [risk ratio (RR) = 6.385; 95% confidence interval (95% CI) 2.40-16.95)]. These results emphasize the importance of compliance with chelation therapy to minimize the burden of thyropathy on patients’ quality of life, and also augment the rationale for a routine follow-up and endocrine evaluation for early detection and management of these complications.     

Do Persons with Diabetes Benefit from Combination Statin and Fibrate Therapy?

Combination fibrate-statin therapy favorably modifies the atherogenic, triglyceride-rich lipoprotein environment, common to insulin resistance, diabetes, and higher cardiovascular disease (CVD) risk. Five major fibrate randomized clinical trial (RCT) results (HHS, VA-HIT, BIP, FIELD, and ACCORD-Lipid) demonstrated four consistent features: 1) the highest CVD event rates occurred in the placebo subgroups possessing atherogenic “moderate” dyslipidemia (triglycerides, > 200 mg/dL, and low high-density lipoprotein cholesterol [HDL-C], < 35–40 mg/dL); 2) with this subgroup having the greatest “hypothesis-generating” fibrate benefit (27% to 65% relative risk reduction, variable significance [P values ranging 0.057–0.005]); 3) those subgroups without moderate dyslipidemia had relatively lower CVD event rates; and 4) little or no benefit from fibrates. The ACCORD-Lipid results, specifically, demonstrated benefits against the background of statin therapy. Three independent meta-analyses combining the five RCTs, which provided a large sample of moderate dyslipidemia participants (i.e., 2401 on fibrates; 2270 on placebo), demonstrated a fibrate benefit with significant heterogeneity of effect across lipid subgroups (P = 0.0002). The fibrate benefit was observed in “low HDL-C only” patients, reducing CVD events by 17% (P < 0.001) or “hypertriglyceridemia-only” patients, reducing CVD events by 28% (P < 0.001), or “atherogenic (moderate) dyslipidemia” phenotype, reducing CVD events by 30% (P < 0.0001), compared with a nonsignificant 6% reduction (P = 0.13) in nonatherogenic dyslipidemia patients. Fibrate RCTs in patients with diabetes (FIELD and ACCORD-Lipid) also demonstrated significant microvascular (ie, retinopathy and nephropathy) outcome benefit possibly independent of lipid levels.     

No Benefit of Continuing 5-Aminosalicylates in Patients with Crohn’s Disease Treated with Anti-metabolite Therapy

Digestive Diseases and Sciences - 5-aminosalicylates (5-ASA) are frequently used in the management of Crohn’s disease (CD). We used a de-identified administrative claims database to compare...     

Treatment of Indolent Non-Hodgkin’s Lymphoma with Cladribine as Single-Agent Therapy and in Combination with Mitoxantrone

The term indolent in describing a non-Hodgkin's lymphoma (NHL) generally refers to a group of B-cell NHLs composed of predominantly small cells that make up several categories, including follicular lymphoma, small lymphocytic lymphoma, and lymphoma of mucosa-associated lymphoid tissue. Most patients with follicular lymphoma respond to therapy, and the average survival time in large series is approximately 10 years. Patients who achieve a complete remission with initial treatment have an approximately 25% chance of remaining free of disease for 10 years. However, this means that more than 80% of patients will require salvage therapy. Cladribine is a newer purine analogue and is of particular interest because it is resistant to deamination by adenosine deaminase. It is cytotoxic to both proliferating and resting lymphocytes, making it an attractive agent for the treatment of indolent NHL. In this review article, we summarize the current treatment approaches for indolent NHL and the results of cladribine monotherapy studies in Japan and cladribine studies in Germany that have focused on a combination therapy with mitoxantrone. Cladribine is a potent inhibitor of DNA repair. The combination of a DNA-damaging agent with an inhibitor of DNA repair constitutes the rationale for combining cladribine with mitoxantrone. A German study has demonstrated that the combination of reduced-dose cladribine and mitoxantrone is a highly active regimen with favorable toxicity profiles. Cladribine is highly effective as a single agent and in combination with mitoxantrone in the treatment of indolent NHL, and its availability broadens the range of therapeutic options for indolent NHL.     

Outcome Predictors for Thiopurine Maintenance Therapy in Patients with Crohn’s Disease

Background  

Little is known about the factors that predict clinical relapse in Crohn’s disease patients receiving thiopurine therapy to maintain remission. The objective of this study was, therefore, to investigate these factors.     

successful Thrombolytic Therapy in a Child with Kawasaki Disease and Acute Myocardial Infarction

CLINICAL MATERIALSThe patient was 7 year - old boy, body weight 20 kg. He was admitted on May 10th , 2002 because of fever, rashes, enlarged lymphnodes, conjunctivae injection, strawberry tongue, edema and erythema of the hands and feet. Laboratory data as follow: 1. Promine nt increase in white blood cell(WBC) 14. 3 - 22. 7×109 . 2. Anemia, hemoglobin (Hb) 121→103 g/L.     

“Bridging” Therapy with Low Molecular Weight Heparin in Pregnant Patients and Patients with Mechanical Prosthetic Heart Valves

A substantial body of published, peer-reviewed, trial and cohort study-based evidence, institutional data sets and expert clinical experience/opinion supports the safe and effective use of enoxaparin for anticoagulation management of non-pregnant patients with prosthetic mechanical heart valves. A comparable body of data and trial results exists, also supported by a significant and authoritative base of expert opinion, for enoxaparin-based VTE prevention and treatment of at-risk pregnant patients who do not have mechanical heart valves. In pregnant women with prosthetic mechanical heart valves, no recommendations on the use of LMWHs can be made until the availability of more data (Lovenox Injection (package insert). Available at www.aventis-us.com/PIs/lovenox. Accessed July 30, 2003. Aventis Pharmaceuticals 2003).     

What Combination Therapy with a Statin,If Any,Would You Recommend?

The latest recommended goals for blood lipid levels may require multiple lipid drugs. Lower doses in combination may render more efficacy and safety than highest doses of single agents. Except for isolated hypoalphalipoproteinemia (a low level of high-density lipoprotein cholesterol), therapies will start with a statin. All marketed statins are acceptable. The choice may be based on dose- efficacy and patient’s tolerability. High-potency statins (eg, atorvastatin, simvastatin, or rosuvastatin) are often chosen. Currently, generic statins, such as simvastatin, lovastatin, pravastatin, and fluvastatin, offer cost benefits. The choice of added agent depends on the “residual lipoprotein abnormalities” after statin therapy, efficacy, compliance issues, and cost. Approved “combined” preparations improve cost and compliance. To further lower low-density lipoprotein cholesterol, ezetimibe is a safe, efficacious choice, pending resolution of a controversial trial’s results. Colesevelam is moderately effective and the best tolerated bile acids sequestrant. In combined dyslipidemias, extended-release niacin is the best tolerated niacin preparation; other quality-controlled immediate-release preparations have similar safety and efficacy but produce more flushing of the skin. Niacin or fenofibrate is effective in normalizing high-density lipoprotein and triglyceride levels persisting after statin therapy. Agents approved by the US Food and Drug Administration and the latest guidelines of the National Cholesterol Education Program, American Heart Association/American College of Cardiology provide choices and indications of drug combinations.     

Interferon-γ and Granulocyte-Macrophage Colony Stimulating Factor Therapy in Three Patients with Pulmonary Aspergillosis

An immune response mediated by type 2 cytokines is thought to contribute to the development and unfavorable outcome of aspergillosis. Adjuvant therapy with interferon-gamma (IFN-gamma) and granulocyte-macrophage colony stimulating factor (GM-CSF) was added to antifungal treatment in three nonneutropenic patients (one HIV-positive and two HIV-negative patients) with culture proven aspergillosis refractory to classical antifungal therapy. Clinical improvement was observed concomitantly with an increase in peripheral blood leukocyte proliferation and type 1 cytokines production. Our findings suggest an association between the improvement in type 1 cytokine production observed during IFN-gamma and GM-CSF administration and a better control of Aspergillus infection in patients with progressive disease despite adequate antifungal therapy.