Prognostic value of stress-gated 99m-technetium SPECT myocardial perfusion imaging: Risk stratification of patients with multivessel coronary artery disease and prior coronary revascularization

BACKGROUND: This study assessed the prognostic value of stress-gated 99mTc-sestamibi myocardial perfusion SPECT (MPS) in patients with multivessel coronary artery disease (CAD) and prior revascularization according to the presence and severity of ischemia. METHODS AND RESULTS: We studied the outcome of 472 patients with multivessel CAD and prior revascularization (coronary angioplasty, 290 patients; bypass surgery, 182 patients), who underwent exercise or dipyridamole 99mTc-sestamibi MPS for evaluation of ischemia. Visual scoring of perfusion images used 20 segments and a 5-point scale. Gated post-stress EF was automatically calculated. Endpoints included hard events: cardiac death (CD) and nonfatal myocardial infarction (MI). During a mean follow-up of 3.0 ± 1.0 years, 37 hard events occurred, including CD in 15 (3%) and MI in 22 (5%) patients. In a risk-adjusted multivariable Cox model, a history of prior MI, diabetes, abnormal MPS, moderate-to-severe ischemia, and post-stress EF <35% were important predictors of cardiac events. Four-year risk-adjusted survival was 97.9% for normal MPS, 87.3% for abnormal MPS with ischemia, and 82.1% for moderate-to-severe ischemia. CONCLUSIONS: Among patients with previous coronary revascularization, stress-gated 99mTc-sestamibi MPS provides prognostic information for the prediction of cardiac events. A normal perfusion scan confers an excellent prognosis and an exceedingly low hard event rate (<1%/year). The presence of moderate-to-severe ischemia or a post-stress EF <35% identifies patients at highest risk of subsequent cardiac events

Laminin Mediates Tissue-specific Gene Expression

Abstract. Tissue-specific gene expression in mammary epithelium is dependent on the extracellular matrix as well as hormones. There is good evidence that the basement membrane provides signals for regulating H-casein expression, and that integrins are involved in this process. Here, we demonstrate that in the presence of lactogenic hormones, laminin can direct expression of the/~-casein gene. Mouse mammary epithelial cells plated on gels of native laminin or laminin-entactin undergo functional differentiation. On tissue culture plastic, mammary cells respond to soluble basement membrane or purified laminin, but not other extracellular matrix components, by synthesizing T o understand how cell function is maintained withi

Characterization of BCE-1, a Transcriptional Enhancer Regulated by Prolactin and Extracellular Matrix and Modulated by the State of Histone Acetylation

We have previously described a 160-bp enhancer (BCE-1) in the bovine β-casein gene that is activated in the presence of prolactin and extracellular matrix (ECM). Here we report the characterization of the enhancer by deletion and site-directed mutagenesis, electrophoretic mobility shift analysis, and in vivo footprinting. Two essential regions were identified by analysis of mutant constructions: one binds C/EBP-β and the other binds MGF/STAT5 and an as-yet-unidentified binding protein. However, no qualitative or quantitative differences in the binding of these proteins were observed in electrophoretic mobility shift analysis using nuclear extracts derived from cells cultured in the presence or absence of ECM with or without prolactin, indicating that prolactin- and ECM-induced transcription was not dependent on the availability of these factors in the functional cell lines employed. An in vivo footprinting analysis of the factors bound to nuclear chromatin in the presence or absence of ECM and/or prolactin found no differences in the binding of C/EBP-β but did not provide definitive results for the other factors. Neither ECM nor prolactin activated BCE-1 in transient transfections, suggesting that the chromosomal structure of the integrated template may be required for ECM-induced transcription. Further evidence is that treatment of cells with inhibitors of histone deacetylase was sufficient to induce transcription of integrated BCE-1 in the absence of ECM. Together, these results suggest that the ECM induces a complex interaction between the enhancer-bound transcription factors, the basal transcriptional machinery, and a chromosomally integrated template responsive to the acetylation state of the histones

Prognostic value of stress-gated 99m-technetium SPECT myocardial perfusion imaging: Risk stratification of patients with multivessel coronary artery disease and prior coronary revascularization

BACKGROUND: This study assessed the prognostic value of stress-gated 99mTc-sestamibi myocardial perfusion SPECT (MPS) in patients with multivessel coronary artery disease (CAD) and prior revascularization according to the presence and severity of ischemia. METHODS AND RESULTS: We studied the outcome of 472 patients with multivessel CAD and prior revascularization (coronary angioplasty, 290 patients; bypass surgery, 182 patients), who underwent exercise or dipyridamole 99mTc-sestamibi MPS for evaluation of ischemia. Visual scoring of perfusion images used 20 segments and a 5-point scale. Gated post-stress EF was automatically calculated. Endpoints included hard events: cardiac death (CD) and nonfatal myocardial infarction (MI). During a mean follow-up of 3.0 ± 1.0 years, 37 hard events occurred, including CD in 15 (3%) and MI in 22 (5%) patients. In a risk-adjusted multivariable Cox model, a history of prior MI, diabetes, abnormal MPS, moderate-to-severe ischemia, and post-stress EF <35% were important predictors of cardiac events. Four-year risk-adjusted survival was 97.9% for normal MPS, 87.3% for abnormal MPS with ischemia, and 82.1% for moderate-to-severe ischemia. CONCLUSIONS: Among patients with previous coronary revascularization, stress-gated 99mTc-sestamibi MPS provides prognostic information for the prediction of cardiac events. A normal perfusion scan confers an excellent prognosis and an exceedingly low hard event rate (<1%/year). The presence of moderate-to-severe ischemia or a post-stress EF <35% identifies patients at highest risk of subsequent cardiac events

Micro- and meso-level influences on obesity in the former Soviet Union: a multi-level analysis

BACKGROUND: Limited evidence exists on obesity in the former Soviet Union (fSU), particularly its micro- and meso-level determinants. The objectives of this study were to determine age- and gender-adjusted prevalence of self-reported overweight and obesity in nine fSU countries; explore the relationship between individual and household (micro-level) factors and obesity; and explore the relationship between features of nutritional and physical environments (meso-level) and obesity. METHODS: Data were collected from 18?000 adults using household surveys and from 333 communities using community profiles in Azerbaijan, Armenia, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia and Ukraine in 2010. Individual- and community-level determinants of self-reported obesity (body mass index =30?kg/m(2)) were analysed using multi-level random intercept logistic regression models. RESULTS: A total of 13% of the males and 18% of the females were categorized as obese. Factors associated with obesity in males were older age, increasing educational achievement, declining self-reported health, alcohol consumption and automobile ownership. Males who were current smokers, not married and perceived physical activity to be important were less likely to be obese. For females, obesity was associated with older age, completion of secondary-level education, declining self-reported health and average household financial situation. Unmarried women were less likely to be obese. Multi-level analysis indicated that individuals living in communities with higher presence of garbage were more likely to be obese. CONCLUSIONS: This is the first study to examine both micro- and meso-level influences on obesity in fSU using multi-level analysis. Findings indicate a similar obesity risk profile to countries in Western Europe and North America