Use of a monoclonal antibody against human heart ferritin for evaluating acidic ferritin concentration in human serum

Immunoassays for acidic ferritins rich in H subunits have shown that these isoferritins are predominant in some cells such as monocytes and red blood cells but have provided conflicting results about their presence in human serum. We have used an immunoradiometric assay based on a monoclonal antibody against human heart ferritin (monoclonal 2A4) for evaluating acidic ferritin concentration in human serum. This assay proved to be highly specific for acidic isoferritins having more than 60% H subunits. Heart-type ferritin was detected in only one fifth of normal sera and sera from patients with iron overload; values were very low compared with those for basic ferritin. Acidic ferritin was found in relatively high concentrations in most patients with iron deficiency anaemia. In other disease states characterized by increased serum concentrations of basic ferritin, acidic ferritin was always less than 21% of the total ferritin. Dialysis in low-ionic-strength buffer showed that both normal and pathological sera had binding factors for human heart ferritin. We conclude that: (i) human serum contains low concentrations of acidic isoferritins which, at variance with basic ferritin, do not appear to be directly related to the amount of storage iron; (ii) the findings of the present study reinforce the opinion that basic and acidic ferritins have different functional behaviours.     

Metabolic effects and disposition of sebacate, an alternate dicarboxylic fuel substrate.

Disodium sebacate is a 10-carbon-atom dicarboxylic acid, proposed as substrate for parenteral nutrition. We investigated its pharmacokinetic profile and thermogenic effect during a short-time infusion (5 h at 10 g/h) in 7 male volunteers. Sebacate in serum and urine was measured by high-performance liquid chromatography. A single-compartment model with two linear elimination routes was fitted. Metabolic measurements (VO2, VCO2, respiratory quotient, metabolic rate) were continuously performed for 8 h (5 h during and 3 h after the infusion) by a canopy indirect calorimeter. The apparent volume of distribution of sebacate was 8.39 +/- 0.69 liters, and the plasma fractional removal rate constant was 0.0086 +/- 0.00077 min-1. The average half-life and plasma clearance were 80.6 min and 72 ml/min, respectively. The increase in metabolic rate, the decrease in respiratory quotient and the changes in ketone body, glucagon and insulin levels during the infusion were not significant. 24-hour catecholamine excretion was within normal limits. Calories administered by sebacate seem to be available for utilization without relevant metabolic side effects.     

Favourable effects of heart rate reduction with intravenous administration of ivabradine in patients with advanced heart failure

BACKGROUND: Heart rate (HR) reduction may be useful in treatment of patients with heart failure (HF). There are no data on the haemodynamic effects of ivabradine (a selective I(f) current inhibitor) in advanced HF patients. AIMS: To assess the haemodynamic effects of ivabradine in patients with advanced HF and markedly depressed left ventricular (LV) function. METHODS AND RESULTS: Ten NYHA class III patients (50+/-12 years, LV ejection fraction 21+/-7%) underwent 24-h haemodynamic monitoring. Ivabradine 0.1 mg/kg was infused over 90', followed by 0.05-0.075 mg/kg in the subsequent 90'. Baseline HR was 93+/-8 bpm, cardiac index (CI) 2.2+/-0.6 l/min*m2; LV stroke volume 44+/-11 ml and systolic work 39+/-13 g. Ivabradine significantly reduced HR, by a maximum of 27% (to 68+/-9 bpm) at 4 h, without decreasing CI. Ivabradine increased stroke volume and LV systolic work by a maximum of 51% (to 66+/-17 ml) and 53% (to 58+/-20 g) at 4 h. No serious adverse events occurred. CONCLUSION: In patients with advanced HF and markedly depressed LV function, the acute administration of ivabradine is well tolerated, effectively reduces HR, markedly increases stroke volume and preserves cardiac output. Ivabradine appears a promising approach for the treatment of patients with moderate and advanced heart failure.     

HCV chronic hepatitis in patients with HIV: clinical management issues

HIV-hepatitis C virus (HCV) coinfection is common and affects more than one-third of all HIV infected persons worldwide. Prevalence among risk categories varies according to shared risk factors for transmission, mainly intravenous drug use (IDU) and hemophiliacs. Chronic HCV infection seems to accelerate the course of HIV disease, resulting in a worsened clinical and immunological progression. At the same time, several studies suggest that HIV disease modifies the natural history of HCV infection, leading to a faster course of progression from active hepatitis to cirrhosis, to end stage liver disease and death. HCV infection mimics opportunistic diseases because its natural history is significantly accelerated in HIV patients. Since highly active antiretroviral therapy (HAART) has slowed the progression of HIV disease and decreased the rate of HIV associated mortality, the prognosis of HIV disease has been modified, and the need to treat HCV coinfection become a significant issue. Because of the poor response rate obtained by either interferon alone or interferon thrice weekly plus ribavirin, the combination of pegylated interferon and ribavirin will probably become the standard of care, although the clinicians should be aware of the overlapping toxicity of nucleoside analogues and ribavirin. Many selected categories of patients pose particular challenges to physicians treating HCV infection: nonresponders to interferon, cirrhotic patients, and patients infected with both HCV and HBV. Liver transplantation in HIV patients is currently under evaluation, but should become the rescue therapy for HIV patients with end stage liver disease.     

Improved Risk Stratification for Ventricular Arrhythmias and Sudden Death in Patients With Nonischemic Dilated Cardiomyopathy

BackgroundRisk stratification for ventricular arrhythmias (VA) and sudden death in nonischemic dilated cardiomyopathy (DCM) remains suboptimal.ObjectivesThe goal of this study was to provide an improved risk stratification algorithm for VA and sudden death in DCM.MethodsThis was a retrospective cohort study of consecutive patients with DCM who underwent cardiac magnetic resonance with late gadolinium enhancement (LGE) at 2 tertiary referral centers. The combined arrhythmic endpoint included appropriate implantable cardioverter-defibrillator therapies, sustained ventricular tachycardia, resuscitated cardiac arrest, and sudden death.ResultsIn 1,165 patients with a median follow-up of 36 months, LGE was an independent and strong predictor of the arrhythmic endpoint (hazard ratio: 9.7; p < 0.001). This association was consistent across all strata of left ventricular ejection fraction (LVEF). Epicardial LGE, transmural LGE, and combined septal and free-wall LGE were all associated with heightened risk. A simple algorithm combining LGE and 3 LVEF strata (i.e., ≤20%, 21% to 35%, >35%) was significantly superior to LVEF with the 35% cutoff (Harrell’s C statistic: 0.8 vs. 0.69; area under the curve: 0.82 vs. 0.7; p < 0.001) and reclassified the arrhythmic risk of 34% of patients with DCM. LGE-negative patients with LVEF 21% to 35% had low risk (annual event rate 0.7%), whereas those with high-risk LGE distributions and LVEF >35% had significantly higher risk (annual event rate 3%; p = 0.007).ConclusionsIn a large cohort of patients with DCM, LGE was found to be a significant, consistent, and strong predictor of VA or sudden death. Specific high-risk LGE distributions were identified. A new clinical algorithm integrating LGE and LVEF significantly improved the risk stratification for VA and sudden death, with relevant implications for implantable cardioverter-defibrillator allocation.     

Bicuspid aortic valve: abnormal aortic elastic properties

BACKGROUND AND AIMS OF THE STUDY: Bicuspid aortic valve (BAV) is frequently associated with clinically relevant abnormalities of the aorta, suggesting the existence of a common underlying developmental defect involving the aortic valve and wall of the ascending aorta. The study aim was to evaluate noninvasively the elastic properties of the aortic root in young males with BAV, to discover whether structural abnormalities of the aorta might be manifested by impairment in elasticity. METHODS: Forty-nine young male subjects with isolated BAV were consecutively detected during preenrollment military screening, and studied using transthoracic echocardiography. Data were compared with those obtained in 45 normal subjects, matched for gender and age. RESULTS: Patients and controls were comparable for body size, and systolic and diastolic blood pressures. BAVs were normally functioning in 18 patients (37%), and mildly regurgitant in 31 (63%). Measurements made by two-dimensional echocardiography showed that BAV patients had significantly larger aortic root dimensions at the annulus (2.4+/-0.2 versus 2.2+/-0.2 cm, p <0.001), at the sinus of Valsalva (3.3+/-0.4 versus 2.6+/-0.3 cm, p <0.001), at the sinotubular junction (2.9+/-0.3 versus 2.5+/-0.2 cm, p <0.001), and at the proximal ascending aorta (2.8+/-0.3 versus 2.5+/-0.2 cm, p <0.001). Measurements made using M-mode echocardiography at 3 cm from the annulus, showed the difference between systolic and diastolic diameters of the aortic root to be significantly smaller in patients than in controls (2.1+/-1.2 versus 3.0+/-1.1 mm, respectively, p <0.001). In patients and in controls, both aortic distensibility (2.7+/-1.5 versus 4.8+/-2.2 x 10(-6) cm2 dyne(-1), respectively, p <0.001) and aortic stiffness index (10.2+/-5.3 versus 5.03+/-1.97, respectively, p <0.001) were significantly different. CONCLUSION: Young male subjects with BAV and no or mild aortic regurgitation display large aortic size and abnormal elastic properties of the ascending aorta compared with controls. These findings confirm the notion that, in these patients, aortic root dilatation is a morphological correlate of intrinsic structural aortic abnormality.