Prevalence of silent myocardial ischemia in asymptomatic individuals with subclinical atherosclerosis detected by electron beam tomography

BACKGROUND: Electron beam tomography coronary calcium imaging is an evolving technique for the early detection of coronary atherosclerosis, and recent studies have established its prognostic value in asymptomatic individuals. The relationship of coronary artery calcium scores (CAC) to obstructive coronary artery disease (CAD) has been poorly studied but is clinically relevant because it determines which individuals are likely to benefit from revascularization procedures. Hence, we prospectively evaluated the prevalence of myocardial ischemia in asymptomatic patients with cardiovascular risk factors and subclinical atherosclerosis. METHODS AND RESULTS: We studied 864 asymptomatic patients with no previous CAD but with cardiovascular risk factors, referred for electron beam tomography coronary calcium imaging to our institution over an 18-month period. From this group, 220 consecutive patients (85% men; mean age, 61 +/- 9 years; age range, 31-84 years) with moderate to severe atherosclerotic disease (coronary calcium score > or =100 Agatston units) were prospectively evaluated by technetium 99m sestamibi single photon emission computed tomography (SPECT). Patients were followed up (mean follow-up, 14 months) and data regarding their subsequent clinical management recorded. Of the 220 patients, 119 had moderate atherosclerosis (CAC score of 100-400 Agatston units) and 101 had severe atherosclerosis (CAC score > or =400 Agatston units). Abnormal SPECT findings were seen in 18% of patients with moderate atherosclerosis (n = 21) and 45% of patients with severe atherosclerosis (n = 45). Increasing severity of atherosclerosis was related to increasing ischemic burden (summed difference score = 1 +/- 0.2 for CAC score of 100-400 Agatston units and 3.2 +/- 0.5 for CAC score > or =400 Agatston units). In a multivariate linear regression model incorporating risk factors, CAC was the only predictor of silent ischemia. CONCLUSION: In comparison to previously published data, we detected a higher prevalence of silent ischemia even in patients with moderate coronary atherosclerosis (18%). This may reflect the differing risk factor profile of our patient population. When coronary calcium screening is used to preselect asymptomatic patients with cardiovascular risk factors for myocardial perfusion imaging, the optimum coronary calcium score threshold will depend on the population prevalence of risk factors and asymptomatic obstructive CAD.     

Fidgetin-like 1 gene inhibited by basic fibroblast growth factor regulates the proliferation and differentiation of osteoblasts.

The FIGNL1 gene was proven to be a new subfamily member of ATPases associated with diverse cellular activities (AAA proteins). In this in vitro study, the AAA proteins inhibited osteoblast proliferation and stimulated osteoblast differentiation. We showed that FIGNL1 may play some regulatory role in osteoblastogenesis. INTRODUCTION: The fidgetin-like 1 (FIGNL1) gene encodes a new subfamily member of ATPases associated with diverse cellular activities (AAA proteins). Although the FIGNL1 protein localizes to both the nucleus and cytoplasm, the function of FIGNL1 remains unknown. In a previous study, we identified several genes that mediate the anabolic effects of basic fibroblast growth factor (bFGF) on bone by using microarray data. FIGNL1 was one of the genes that downregulated >2-fold in MC3T3-E1 cells after treatment with bFGF. Therefore, this study was aimed to identify and confirm the function of FIGNL1 on osteoblastogenesis. MATERIALS AND METHODS: We examined the effect of the FIGNL1 gene on proliferation, differentiation, and apoptosis in mouse osteoblast cells (MC3T3-E1 and mouse primary calvarial cells) using flow cytometry, RT-PCR, cell proliferation assay, and cell death assay. MC3T3-E1 cells and mouse calvarial cells were transfected with small interfering RNA (siRNA) directed against the FIGNL1 or nontargeting control siRNA and examined by cell proliferation and cell death assays. Also, FIGNL1 was fused to enhance green fluorescent protein (EGFP), and the EGFP-fused protein was transiently expressed in MC3T3-E1 cells. RESULTS: Reduced expression of FIGNL1 by bFGF and TGF-beta1 treatment was verified by RT-PCR analysis. Overexpression of FIGNL1 reduced the proliferation of MC3T3-E1 and calvarial cells, more than the mock transfected control cells did. In contrast, siFIGNL1 transfection significantly increased the proliferation of osteoblasts, whereas overexpression of FIGNL1 did not seem to alter apoptosis in osteoblasts. Meanwhile, overexpression of FIGNL1 enhanced the mRNA expression of alkaline phosphatase (ALP) and osteocalcin (OCN) in osteoblasts. In contrast, siFIGNL1 decreased the expression of ALP and OCN. A pEGFP-FIGNL1 transfected into MCT3-E1 cells had an initially ubiquitous distribution and rapidly translocated to the nucleus 1 h after bFGF treatment. CONCLUSIONS: From these results, we proposed that FIGNL1, a subfamily member of the AAA family of proteins, might play some regulatory role in osteoblast proliferation and differentiation. Further analyses of FIGNL1 will be needed to better delineate the mechanisms contributing to the inhibition of proliferation and stimulation of osteoblast differentiation.     

An association between plastic mattress covers and sheepskin underbedding use in infancy and house dust mite sensitization in childhood: a prospective study

BACKGROUND: Higher house dust mite (HDM) allergen exposure during infancy has been associated with increased HDM sensitization. Infant bedding has been associated with the accumulation of varying levels of HDM. Prospective data on the relationship between infant bedding and the development of HDM sensitization has not been previously examined. OBJECTIVES: To determine if particular types of bedding used in infancy are associated with increased risk of house dust mite sensitization in childhood. METHODS: A population-based sample (n = 498) of children born in 1988 or 1989, and who were resident in Northern Tasmania in 1997, participated in this study. These children were part of a birth cohort study (1988-95), the Tasmanian Infant Health Survey. Data on infant underbedding and mattresses was available on 460 and 457 children, respectively. The main outcome measure was HDM sensitization defined as a skin prick test (SPT) reaction of 3 mm or more to the allergens of Dermatophagoides pteronyssinus and/or Dermatophagoides farinae. RESULTS: The use of either sheepskin underbedding or plastic mattress covers in infancy was associated with an increased risk of sensitization to HDM allergens at age 8 years. The adjusted risk ratio (RR) for sensitization to HDM with sheepskin in infancy was 2.27 (95% CI: 1.14, 4.55), P = 0.020. The adjusted RR for sensitization to HDM with the use of plastic mattress covers in infancy was 2.06 (95% CI: 1.22, 3.51), P = 0.007. The use of a foam mattress in infancy was not related to subsequent HDM sensitization. CONCLUSION: Infant's bedding plays a role in the development of HDM sensitization in childhood. Intervention studies to examine mite allergen levels and the role of underbedding on the development of HDM sensitization are required.     

Quantitative assessment of variables that influence soft-tissue electrovaporization in a fluid environment

Objectives. To evaluate the process of soft-tissue electrovaporization and to study variables that affect tissue clearance rates in a laboratory setting, in order to identify parameters that can optimize transurethral electrovaporization of the prostate.Methods. Fresh bovine skeletal muscle, equivalent in impedance and surface properties to the human prostate, was submerged in 3.3% sorbitol solution and electrovaporized with a grooved monopolar electrode attached to the weighted arm of a linear actuator. The effects of excursion rate, applied mechanical load, power setting, electrode configuration, and generator performance on the volume of tissue removed, were assessed.Results. Tissue removal increased significantly when electrode excursion rate was slowed from 25 to 15 mm/s (P <0.05) and then to 10 mm/s (P <0.05); when the load was increased from 20 to 50 g (P <0.005); and when dial power was increased from 120 to 150 W (P <0.01). Tissue removal was generator dependent. There was no significant difference between the Force 40 and the Force 2 (P > 0.4), but a new computer-controlled constant power output generator (Force FX) did significantly improve tissue vaporization at an equivalent power setting (P <0.005 and P <0.01, respectively). Tissue removal was also dependent upon electrode configuration, with the VaporTrode-Grooved Bar removing significantly more tissue than either an ungrooved roller bar of equivalent size or 2-mm smooth roller ball, respectively, both after a single pass (P <0.001 and P <0.05) and after five repeated passes (P <0.05 and P <0.005). The histologic depth of tissue thermal effect was less than 1 mm, but it was 38% greater for the VaporTrode-Grooved Bar (0.68 mm) than for the standard cutting loop (0.5 mm, P <0.01).Conclusions. Using a novel method to quantify tissue removal, we have demonstrated that electrode configuration, excursion rate, applied load, power setting, and generator performance are interdependent factors that influence the efficacy of the electrovaporization process in a fluid environment.