Radionuclide Imaging of Viable Myocardium: Is it Underutilized?

Coronary artery disease is the major cause of heart failure in North America. Viability assessment is important as it aims to identify patients who stand to benefit from coronary revascularization. Radionuclide modalities currently used in the assessment of viability include 201Tl SPECT, 99mTc-based SPECT imaging, and 18F-fluorodexoyglucose (18F-FDG)-PET imaging. Different advances have been made in the last year to improve the sensitivity and specificity of these modalities. In addition, the optimum amount of viable (yet dysfunctional) myocardium is important to identify in patients, as a risk–benefit ratio must be considered. Patients with predominantly viable/hibernating myocardium can benefit from revascularization from a mortality and morbidity standpoint. However, in patients with minimal viability (predominantly scarred myocardium), revascularization risk may certainly be too high to justify revascularization without expected benefit. Understanding different radionuclide modalities and new developments in the assessment of viability in ischemic heart failure patients is the focus of this discussion

Combined Effect of Hemostatic Gene Polymorphisms and the Risk of Myocardial Infarction in Patients with Advanced Coronary Atherosclerosis

BACKGROUND: Relative little attention has been devoted until now to the combined effects of gene polymorphisms of the hemostatic pathway as risk factors for Myocardial Infarction (MI), the main thrombotic complication of Coronary Artery Disease (CAD). The aim of this study was to evaluate the combined effect of ten common prothrombotic polymorphisms as a determinant of MI. METHODOLOGY/PRINCIPAL FINDINGS: We studied a total of 804 subjects, 489 of whom with angiographically proven severe CAD, with or without MI (n = 307; n = 182; respectively). An additive model considering ten common polymorphisms [Prothrombin 20210G>A, PAI-1 4G/5G, Fibrinogen beta -455G>A, FV Leiden and "R2", FVII -402G>A and -323 del/ins, Platelet ADP Receptor P2Y12 -744T>C, Platelet Glycoproteins Ia (873G>A), and IIIa (1565T>C)] was tested. The prevalence of MI increased linearly with an increasing number of unfavorable alleles (chi(2) for trend = 10.68; P = 0.001). In a multiple logistic regression model, the number of unfavorable alleles remained significantly associated with MI after adjustment for classical risk factors. As compared to subjects with 3-7 alleles, those with few (/=8) alleles had an increased MI risk (OR 2.49, 95%CIs 1.03-6.01). The number of procoagulant alleles correlated directly (r = 0.49, P = 0.006) with endogenous thrombin potential. CONCLUSIONS: The combination of prothrombotic polymorphisms may help to predict MI in patients with advanced CAD

Smad phosphoisoform signals in acute and chronic liver injury: similarities and differences between epithelial and mesenchymal cells

Hepatocellular carcinoma (HCC) usually arises from hepatic fibrosis caused by chronic inflammation. In chronic liver damage, hepatic stellate cells undergo progressive activation to myofibroblasts (MFB), which are important extracellular-matrix-producing mesenchymal cells. Concomitantly, perturbation of transforming growth factor (TGF)-β signaling by pro-inflammatory cytokines in the epithelial cells of the liver (hepatocytes) promotes both fibrogenesis and carcinogenesis (fibro-carcinogenesis). Insights into fibro-carcinogenic effects on chronically damaged hepatocytes have come from recent detailed analyses of the TGF-β signaling process. Smad proteins, which convey signals from TGF-β receptors to the nucleus, have intermediate linker regions between conserved Mad homology (MH) 1 and MH2 domains. TGF-β type I receptor and pro-inflammatory cytokine-activated kinases differentially phosphorylate Smad2 and Smad3 to create phosphoisoforms phosphorylated at the COOH-terminal, linker, or both (L/C) regions. After acute liver injury, TGF-β-mediated pSmad3C signaling terminates hepatocytic proliferation induced by the pro-inflammatory cytokine-mediated mitogenic pSmad3L pathway; TGF-β and pro-inflammatory cytokines synergistically enhance collagen synthesis by activated hepatic stellate cells via pSmad2L/C and pSmad3L/C pathways. During chronic liver disease progression, pre-neoplastic hepatocytes persistently affected by TGF-β together with pro-inflammatory cytokines come to exhibit the same carcinogenic (mitogenic) pSmad3L and fibrogenic pSmad2L/C signaling as do MFB, thereby accelerating liver fibrosis while increasing risk of HCC. This review of Smad phosphoisoform-mediated signals examines similarities and differences between epithelial and mesenchymal cells in acute and chronic liver injuries and considers Smad linker phosphorylation as a potential target for the chemoprevention of fibro-carcinogenesis

Platelet dysfunction and coagulopathy in intraventricular hemorrhage in the premature infant

We investigated platelet count, bleeding time, platelet aggregation, prothrombin time, activated partial thromboplastin time, and fibrinogen level in 58 very low-birth-weight infants during the first postnatal day to determine the relationship between hemostatic disorders and intraventricular hemorrhage. Thirty-two of the 58 infants (55%) were found to have periventricular-intraventricular hemorrhage by computerized tomography or autopsy. Nine patients (16%) had subarachnoid hemorrhage only and 17 (29%) had no evidence of intracranial hemorrhage. Infants with IVH had a significantly lower mean platelet count than did infants with no SAH/IVH. However, only five patients with IVH had initial thrombocytopenia. The IVH group had a mean bleeding time which was significantly prolonged compared to that of the group without SAH/IVH. Similarly, patients with IVH had a mean platelet aggregation response which was significantly diminished in comparison to that of patients with no SAH/IVH. Infants with IVH had a significantly longer mean PT than did infants with no SAH/IVH. In addition, babies with IVH had a significantly longer mean APTT compared to that of babies without SAH/IVH. The groups did not differ significantly with respect to fibrinogen levels. Three infants with IVH had disseminated-intravascular coagulation in the early neonatal period. These data suggest that disorders of platelet-capillary interaction and defects in the intrinsic and extrinsic coagulation pathways may play important roles in intraventricular hemorrhage in the premature infant

Valsartan Improves Insulin Sensitivity without Altering Vascular Function in Healthy Overweight Adults without the Metabolic Syndrome

ABSTRACT Background. We investigated hyperactivity of the renin-angiotensin system (RAS) as a cause of endothelial dysfunction in obese humans. Methods. Thirty five healthy overweight (BMI ϭ 33.6 Ϯ 6.6 kg m Ϫ2 ) adults (33 Ϯ 10 years old) without cardiovascular risk factors received valsartan (160 mg) orally daily or a matching placebo for 6 weeks each. Results. Baseline flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) were not altered by placebo or valsartan. However, fasting plasma insulin was significantly decreased by valsartan compared to placebo (Ϫ4.6 Ϯ 16.0 UmL Ϫ1 versus Ϫ0.4 Ϯ 11.6 UmL Ϫ1 , P ϭ 0.032) with no changes in glucose. A secondary analysis in patients with elevated waist to hip ratios (ÿ 0.85, n ϭ 18) showed an increase in FMD with valsartan. Conclusions. Our findings suggest that angiotensin 2 receptor blockade may aid in the prevention of diabetes even at the earliest stages of risk due solely to uncomplicated obesity. The lack of an improvement in FMD does not support a central role of RAS-hyperactivity in the etiology of the vascular dysfunction due solely to obesity. However, it is possible that obese patients with central adiposity may improve FMD with RAS blockade, and future investigation is warranted in this subgroup

Changing blood culture isolates in a referral neonatal intensive care unit.

An analysis was made of all cases of bacteraemia that had occurred in the referral neonatal intensive care unit at Hammersmith Hospital during the years 1976--79. One hundred and thirteen infants had positive blood cultures; 27 were born in the hospital, and 86 admitted from elsewhere. This gave a rate of 5.7/1000 live hospital births, and 165/1000 outborn admissions to the unit. The latter infants were predominantly of very low birthweight or were ill. Thirty-three of the isolates were cultured in the first 48 hours of life (early) and the remaining 80 after that time (later). Staphylococcus epidermidis was the organism most often isolated both early and later. These results were different from those recorded in the previous 9 years (1967--75) from the same unit. Then, group B beta-haemolytic streptococcus was the organism most often isolated early, while Gram-negative bacteria predominated among later isolates. The changing nature of care may contribute to these findings