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Background & Aims Hepatitis C virus (HCV) associates with lipoproteins to form “lipoviral particles” (LVPs) that can facilitate viral entry into hepatocytes. Initial attachment occurs via heparan sulphate proteoglycans and low-density lipoprotein receptor (LDLR); CD81 then mediates a post-attachment event. Proprotein convertase subtilisin kexin type 9 (PCSK9) enhances the degradation of the LDLR and modulates liver CD81 levels. We measured LVP and PCSK9 in patients chronically infected with HCV genotype (G)3. PCSK9 concentrations were also measured in HCV-G1 to indirectly examine the role of LDLR in LVP clearance. Methods HCV RNA, LVP ( d <1.07 g/ml) and non-LVP ( d >1.07 g/ml) fractions, were quantified in patients with HCV-G3 (n = 39) by real time RT-PCR and LVP ratios (LVPr; LVP/(LVP + non-LVP)) were calculated. Insulin resistance (IR) was assessed using the homeostasis model assessment of IR (HOMA-IR). Plasma PCSK9 concentrations were measured by ELISA in HCV-G3 and HCV-G1 (n = 51). Results In HCV-G3 LVP load correlated inversely with HDL-C (r = −0.421; p = 0.008), and apoE (r = −0.428; p = 0.013). The LVPr varied more than 35-fold (median 0.286; range 0.027 to 0.969); PCSK9 was the strongest negative predictor of LVPr (R 2 = 16.2%; p = 0.012). HOMA-IR was not associated with LVP load or LVPr. PCSK9 concentrations were significantly lower in HCV-G3 compared to HCV-G1 ( p <0.001). PCSK9 did not correlate with LDL-C in HCV-G3 or G1. Conclusions The inverse correlation of LVP with apoE in HCV-G3, compared to the reverse in HCV-G1 suggests HCV genotype-specific differences in apoE mediated viral entry. Lower PCSK9 and LDL concentrations imply upregulated LDLR activity in HCV-G3. [ABSTRACT FROM AUTHOR]

Chest pain (CP) in children/adolescents is a common referral for the pediatric cardiologist. A group of 263 patients (141 males/122 females, mean age = 13.4 years, range = 5–22 years) with the primary complaint of CP underwent evaluation in the cardiac stress lab at Children’s Hospital of Wisconsin. Echocardiograms at rest were obtained in 70% of patients with no significant cardiac abnormalities identified. Endurance time (EXT) and oxygen consumption (VO2/kg) were below predicted in 26% and 46%, respectively. Reactive airway disease (RAD) as a preexisting condition was reported in 19% of patients, but abnormal resting pulmonary function (PFTs) were found in 26% ( n = 68), with 48/68 never having the diagnosis of RAD. At risk of overweight (BMI >85th percentile), was seen in 28% of the cohort, with 16% identified as being overweight (BMI >95th percentile). A significant difference in RAD ( p < 0.01) was seen in African Americans (AA) and decreased EXT ( p = 0.01) was seen in Hispanics (H). VO2/kg was significantly reduced in both AA and H ( p < 0.01). These results identify both racial and age-related differences in the etiology of CP in children. Most importantly, true cardiac pathology is extremely rare. AOW, deconditioning, and respiratory compromise play important roles in CP. The need for comprehensive cardiopulmonary monitoring is emphasized by these findings. [ABSTRACT FROM AUTHOR]

Objectives: To assess the effects of intravenous magnesium on converting acute onset atrial fibrillation to sinus rhythm, reducing ventricular response and risk of bradycardia. Design and data sources: Randomised controlled trials evaluating intravenous magnesium to treat acute onset atrial fibrillation from MEDLINE (1966 to 2006), EMBASE (1990 to 2006) and Cochrane Controlled Trials Register without language restrictions. Review methods: Two researchers independently performed the literature search and data extraction. Results: 10 randomised controlled trials, including a total of 515 patients with acute onset atrial fibrillation, were considered. Intravenous magnesium was not effective in converting acute onset atrial fibrillation to sinus rhythm when compared to placebo or an alternative antiarrhythmic drug. When compared to placebo, adding intravenous magnesium to digoxin increased the proportion of patients with a ventricular response <100 beats/min (58.8% vs 32.6%; OR 3.2, 95% CI 1.93 to 5.42; p<0.001). When compared to calcium antagonists or amiodarone, intravenous magnesium was less effective in reducing the ventricular response (21.4% vs 58.5%; OR 0.19, 95% CI 0.09 to 0.44; p<0.001) but also less likely to induce significant bradycardia or atrioventricular block (0% vs 9.2%; OR 0.13, 95% CI 0.02 to 0.76; p=0.02). The use of intravenous magnesium was associated with transient minor symptoms of flushing, tingling and dizziness in about 17% of the patients (OR 14.5, 95% CI 3.7 to 56.7; p<0.001). Conclusions: Adding intravenous magnesium to digoxin reduces fast ventricular response in acute onset atrial fibrillation. The effect of intravenous magnesium on the ventricular rate and its cardiovascular side effects are less significant than other calcium antagonists or amiodarone. Intravenous magnesium can be considered as a safe adjunct to digoxin in controlling the ventricular response in atrial fibrillation. [ABSTRACT FROM AUTHOR]