Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.     

The relationship between blood pressure and C-reactive protein in the Multi-Ethnic Study of Atherosclerosis (MESA).

OBJECTIVES: The goal of this study was to determine the relationship between resting blood pressure (BP) and C-reactive protein (CRP) in a multi-ethnic cohort of men and women from the Multi-Ethnic Study of Atherosclerosis (MESA). BACKGROUND: Several investigators have observed elevated levels of CRP in individuals with hypertension. Hypertension prevalence varies considerably across ethnic groups. Important questions remain regarding whether the relationship between hypertension and CRP is similar across ethnic and gender subgroups. METHODS: The MESA participants had CRP levels determined at the baseline clinical examination (N = 6,814). Hypertension, treated as a dichotomous variable (yes/no), was defined as a systolic or diastolic BP > or =140/90 mm Hg or a self-reported history of hypertension and use of antihypertensive medications. RESULTS: The geometric mean CRP in hypertensive participants was 2.3 +/- 0.07 mg/l compared with 1.6 +/- 0.07 mg/l among normotensive participants (p < 0.0001). The relative difference in CRP levels in hypertensives compared with normotensives was similar regardless of gender (13% in men and 13% in women). Ethnic comparisons showed that Chinese participants had the lowest CRP concentration but the largest difference in CRP by hypertension status (24%). Caucasians and African Americans had 10% to 15% higher CRP levels with hypertension, whereas Hispanics had no significant difference in CRP by hypertension status. CONCLUSIONS: This study confirms the existence of an independent association between hypertension and inflammation in both men and women. Ethnic group differences were evident, with the strongest association observed in Chinese participants and no difference in CRP levels by hypertension status in Hispanics.     

Lipid-altering therapy and atrial fibrillation

Atrial fibrillation (AF) is a common cardiac arrhythmia with significant morbidity and public health cost. Because of limitations of efficacy and safety of conventional antiarrhythmic agents, alternative therapies for AF are needed. The potential antiarrhythmic properties of lipid-altering therapy, including the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and fish oils, are increasingly recognized, particularly in light of their potential anti-inflammatory properties. This review examines the known effects of lipid-altering therapy on atrial arrhythmias in both experimental and clinical settings. Inflammatory states, such as post-cardiac surgery and AF of recent onset, show promise as targets. In contrast, lipid-lowering therapy is less likely to affect longstanding persistent AF. Current recommendations for the use of lipid-altering therapy for prevention and treatment of AF are summarized.     

Life's Simple 7 and Nonalcoholic Fatty Liver Disease: The Multiethnic Study of Atherosclerosis

BackgroundThe American Heart Association (AHA) has defined Life's Simple 7 (LS7) as a measure of overall cardiovascular health . Nonalcoholic fatty liver disease (NAFLD) has been involved as a risk factor for cardiovascular disease. We evaluated the association between LS7 and NAFLD.MethodsWe evaluated participants form the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Cardiovascular health score was calculated from the Life's Simple 7 metrics. A score of 0-8 was considered inadequate, 9-10 average, and 11-14 optimal. NAFLD was defined using noncontrast cardiac computed tomography (CT) and a liver/spleen attenuation ratio (L/S) < 1. Multivariable regression were performed to evaluate the association.ResultsOur cross-sectional analysis of 3901 participants showed 19% (n = 747) had optimal cardiovascular health, 33% (n = 1270) had average, and 48% (n = 1884) had inadequate. White participants were most likely to have an optimal score (51%, n = 378), whereas African American participants had the lowest proportion with optimal scores (16%, n = 120; P < 0.001). The overall prevalence of NAFLD was 18% with a distribution of 7%, 14%, and 25% in the optimal, average, and inadequate score categories, respectively (P < 0.001). Adjusted for risk factors, average and optimal health categories had lower odds of NAFLD compared to those with inadequate scores: odds ratio for average, 0.44 (95% confidence interval 0.36-0.54); optimal, odds ratio 0.19 (95% confidence interval 0.14-0.26). This association was similar across gender, race and age groups.ConclusionA more favorable cardiovascular health score was associated with a lower prevalence of NAFLD. This study may suggest a potential of Life's Simple 7 in the prevention of liver disease.     

Effects of fibroblast growth factor-4 (k-FGF) on long-term cultures of human bone marrow cells

Fibroblast growth factor-4 (FGF-4), a highly mitogenic protein encoded by the k-fgf/hst oncogene, stimulates the growth of a variety of cells of mesenchymal and neuroectodermal origin. Addition of FGF-4 to human long-term bone marrow cultures increased both the cell density of the stromal layer and the number of hematopoietic colony forming cells in the cultures in a dose-dependent manner. Hematopoiesis in the stromal layer persisted for up to 8 months. Erythropoiesis was maintained for up to 4 weeks, but granulocytes were the predominant nonadherent cell type. Cultures treated with FGF had increased numbers of monocytes compared with control cultures and some CD14+, CD45+ monocytes could still be detected after 8 months of continuous culture. The addition of the growth factor increased the rate of growth of the stromal layer and appeared to delay its senescence. Subcultures made in the presence of FGF-4 had up to 10-fold increases in plating efficiency and grew as relatively uniform monolayers. These subcultures retained the capacity to support hematopoiesis for several months, while untreated subcultures, made without FGF-4, grew erratically and generally lost the capacity to support hematopoiesis within 4 to 6 weeks. The improved growth after subculture greatly enhanced the reliability of limit- dilution assays of multipotential hematopoietic stem cells that use stromal cell monolayers. The primary effect of FGF-4 appeared to be on the stromal cells of the long-term bone marrow cultures, but a direct effect on hematopoietic progenitors could not be ruled out.     

Cardiovascular effects of raloxifene: the arterial and venous systems

Background

Cardiovascular disease caused by atherosclerosis is the largest single killer of women. Prior observational data had suggested that hormone therapy may have cardioprotective effects.

Methods

Data from clinical trials and basic science studies were evaluated to assess the cardiovascular effects of hormone therapy and selective estrogen replacement modulators.

Results

Hormone therapy does not appear to lower the risk of cardiovascular events in older postmenopausal women. Selective estrogen receptor modulators (SERMS) have been approved for human use; tamoxifen is used for treatment and prevention of breast cancer and raloxifene is used for the treatment and prevention of osteoporosis. Raloxifene is the only SERM being specifically studied for its effects on coronary heart disease events in a prospective, randomized, controlled trial.

Conclusions

Although raloxifene does increase venous thromboembolic events, there is suggestive data that it may have favorable effects on the arterial systems in women. Only compelling positive data from the Raloxifene Use for The Heart (RUTH) trial will lead to greater use of SERMS to potentially lower the risk of atherosclerotic vascular disease.     

The implications of the ezetimibe and simvastatin in hypercholesterolemia enhances atherosclerosis regression trial: a return to first principles

To outward appearances, the publication of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial has led to a monolithic backlash against the use of ezetimibe by cardiologists for the treatment of hyperlipidemia. Rather than be swayed by popular opinion, we should each put the results of ENHANCE into context and ask the questions: should I put my trust in an imaging surrogate or in low‐density lipoprotein (LDL) cholesterol (LDL‐C), and how do the safety and efficacy of ezetimibe compare with other nonstatin lipid‐lowering agents? Copyright © 2008 Wiley Periodicals, Inc.     

Long-term effects of exercise on psychological functioning in older men and women

The purpose of this study was to determine the psychological, behavioral, and cognitive changes associated with up to 14 months of aerobic exercise training. For the first 4 months of the study, 101 older (greater than 60 years) men and women were randomly assigned to one of three conditions: Aerobic exercise, Yoga, or a Waiting List control group. Before and following the intervention, all subjects completed a comprehensive assessment battery, including measures of mood and cognitive functioning. A semi-crossover design was employed such that, following completion of the second assessment, all subjects completed 4 months of aerobic exercise and underwent a third assessment. Subjects were given the option of participating in 6 additional months of supervised aerobic exercise (14 months total), and all subjects, regardless of their exercise status, completed a fourth assessment. Results indicated that subjects experienced a 10-15% improvement in aerobic capacity. In general, there were relatively few improvements in cognitive performance associated with aerobic exercise, although subjects who maintained their exercise participation for 14 months experienced improvements in some psychiatric symptoms. However, the healthy subjects in this study were functioning at a relatively high level to begin with, and exercise training may produce greater improvements among elderly with concomitant physical or emotional impairments.