Prevalence and Correlates of Ischemic ECG Findings among Adults With and Without HIV in Tanzania

Introduction:HIV confers increased risk of myocardial infarction (MI), but there has been little study of ischemic electrocardiogram (ECG) findings among people with HIV in sub-Saharan Africa.Objectives:To compare the prevalence of ischemic ECG findings among Tanzanians with and without HIV and to identify correlates of ischemic ECG changes among Tanzanians with HIV.Methods:Consecutive adults presenting for routine HIV care at a Tanzanian clinic were enrolled. Age- and sex-matched HIV-uninfected controls were enrolled from a nearby general clinic. All participants completed a standardized health questionnaire and underwent 12-lead resting ECG testing, which was adjudicated by independent physicians. Prior MI was defined as pathologic Q-waves in contiguous leads, and myocardial ischemia was defined as ST-segment depression or T-wave inversion in contiguous leads. Pearson’s chi-squared test was used to compare the prevalence of ECG findings among those with and without HIV and multivariate logistic regression was performed to identify correlates of prior MI among all participants.Results:Of 497 participants with HIV and 497 without HIV, 272 (27.8%) were males and mean (sd) age was 45.2(12.0) years. ECG findings suggestive of prior MI (11.1% vs 2.4%, OR 4.97, 95% CI: 2.71–9.89, p < 0.001), and myocardial ischemia (18.7% vs 12.1% OR 1.67, 95% CI: 1.18–2.39, p = 0.004) were significantly more common among participants with HIV. On multivariate analysis, ECG findings suggestive of prior MI among all participants were associated with HIV infection (OR 4.73, 95% CI: 2.51–9.63, p = 0.030) and self-reported family history of MI or stroke (OR 1.96, 95% CI: 1.08–3.46, p = 0.023).Conclusions:There may be a large burden of ischemic heart disease among adults with HIV in Tanzania, and ECG findings suggestive of coronary artery disease are significantly more common among Tanzanians with HIV than those without HIV.     

Diabetes,plasma insulin,and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT)

BACKGROUND: Diabetes mellitus, impaired fasting glucose level, or insulin resistance are associated with increased risk of cardiovascular disease. OBJECTIVES: To determine the efficacy of gemfibrozil in subjects with varying levels of glucose tolerance or hyperinsulinemia and to examine the association between diabetes status and glucose and insulin levels and risk of cardiovascular outcomes. METHODS: Subgroup analyses from the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial, a randomized controlled trial that enrolled 2531 men with coronary heart disease (CHD), a high-density lipoprotein cholesterol level of 40 mg/dL or less (/=271 pmol/L) was associated with a 31% increased risk of events (P =.03). Gemfibrozil was effective in persons with diabetes (risk reduction for composite end point, 32%; P =.004). The reduction in CHD death was 41% (HR, 0.59; 95% CI, 0.39-0.91; P =.02). Among individuals without diabetes, gemfibrozil was most efficacious for those in the highest fasting plasma insulin level quartile (risk reduction, 35%; P =.04). CONCLUSION: In men with CHD and a low high-density lipoprotein cholesterol level, gemfibrozil use was associated with a reduction in major cardiovascular events in persons with diabetes and in nondiabetic subjects with a high fasting plasma insulin level.     

Hypocellular acute leukemia

We examined the clinical features and therapeutic response of a group of patients with acute leukemia and hypocellular bone marrow. Therapists have generally avoided, delayed or modified therapy because of hypocellularity. We demonstrated not only that aggressive therapy is possible, but also that the remission rate is high (complete remission = 73 percent) and survival prolonged (x? > 40 months).     

Spectral turbulence analysis of the signal-averaged electrocardiogram and its predictive accuracy for inducible sustained monomorphic ventricular tachycardia

This study was designed to assess the accuracy of a new noninvasive frequency analysis method for predicting patients with inducible sustained monomorphic ventricular tachycardia (VT) at electrophysiologic study and hence the risk of spontaneous ventricular tachyarrhythmias. Signal-averaged electrocardiograms from 3 orthogonal bipolar surface leads were evaluated using a microcomputer-based frequency analysis system that performs analysis of conventional time-domain late potentials as well as incorporating a new technique for spectral analysis of relatively short, overlapping signal segments spanning the whole QRS complex. The spectral analysis technique measured abnormalities anywhere in the entire QRS complex and did so without dependence on any arbitrarily defined frequency, duration or amplitude cutoffs. The hallmark of arrhythmogenic abnormality was hypothesized to be frequent and abrupt changes in the frequency signature of the QRS wave front velocity as it propagates throughout the ventricle around areas of abnormal conduction, resulting in a high degree of spectral turbulence. One-hundred forty-two subjects were studied, including 71 totally normal control subjects ("true negatives"), 33 with both late potentials by time-domain analysis and inducible sustained monomorphic VT ("true positives"), 28 with late potentials but no evidence of spontaneous or inducible sustained monomorphic VT ("false positives") and 10 with inducible sustained monomorphic VT but absence of time-domain late potentials ("false negatives"). The frequency analysis technique correctly classified 100% of the true negatives, 97% of the true positives, 86% of the late potentials false positives and 60% of the late potentials false negatives. The total predictive accuracy of frequency analysis for all groups was 94%, compared with 73% for time-domain late potential analysis. The results suggest that a high degree of spectral turbulence of the overall QRS signal during sinus rhythm may provide a more accurate marker for the anatomic-electrophysiologic substrate of reentrant tachyarrhythmias than detection of late potentials in the terminal QRS region by either time- or frequency-domain analysis. Spectral turbulence analysis is applicable to patients irrespective of the QRS duration and the presence or absence of bundle branch block.     

New recurrent balanced translocations in acute myeloid leukemia and myelodysplastic syndromes: Cancer and leukemia group B 8461

Acquired chromosome abnormalities in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are among the most valuable determinants of diagnosis and prognosis. In search of new recurrent balanced translocations, we reviewed the Cancer and Leukemia Group B (CALGB) cytogenetics database containing pretreatment and relapse karyotypes of 4,701 adults with AML and 565 with MDS who were treated on CALGB trials. We identified all cases with balanced structural rearrangements occurring as a sole abnormality or in addition to one other abnormality, excluded abnormalities known to be recurrent, and then reviewed the literature to determine whether any of what we considered unique, previously unknown abnormalities had been reported. As a result, we identified seven new recurrent balanced translocations in AML or MDS: t(7;11)(q22;p15.5), t(10;11)(q23;p15), t(2;12)(p13;p13), t(12;17)(p13;q12), t(2;3)(p21;p21), t(5;21)(q31;q22), and t(8;14)(q24.1;q32.2), and additionally, t(10;12)(p11;q15), a new translocation in AML previously reported in a case of acute lymphoblastic leukemia. Herein, we report hematologic and clinical characteristics and treatment outcomes of patients with these newly recognized recurrent translocations. We also report 52 unique balanced translocations, together with the clinical data of patients harboring them, which to our knowledge have not been previously published. We hope that once the awareness of their existence is increased, some of these translocations may become recognized as novel recurring abnormalities. Identification of additional cases with both the new recurrent and the unique balanced translocations will enable determination of their prognostic significance and help to provide insights into the mechanisms of disease pathogenesis in patients with these rare abnormalities. © 2012 Wiley Periodicals, Inc.     

Brief undernutrition in late-gestation sheep programs the hypothalamic-pituitary-adrenal axis in adult offspring

Reduced size at birth in humans has been associated with altered function of the hypothalamic-pituitary-adrenal (HPA) axis in childhood and adult life. Experimentally, maternal undernutrition has also been associated with altered fetal HPA function. However, the relationship between birth size, fetal nutrition, and adult pathophysiology is not clear. We recently have reported that glucose tolerance, blood pressure, and IGF-I levels in adult sheep were more closely associated with birth weight than with nutritional insult in late gestation or with current weight. Here, we report adult HPA function in the same group of animals. Pregnant ewes were severely undernourished for 10 d (UN10) or 20 d (UN20) from 105 d gestation (term, 146 d), or were ad libitum-fed controls. At 30 months, female offspring were subjected to an insulin tolerance test and a CRH plus arginine vasopressin (AVP) challenge. UN20 lambs were lighter at birth, but there were no significant differences in weight at 30 months. Adult UN10 ewes had an increased ACTH response to both CRH+AVP challenge and insulin tolerance test, but no differences in cortisol response. UN10 ewes also demonstrated elevated 11-deoxycortisol concentrations, but lower progesterone concentrations, in response to CRH+AVP challenge. In contrast, the responses of UN20 ewes to these challenges were not different from ad libitum controls. Protein levels of P450(c17) and P450(11beta1) were not significantly different among groups. We conclude that brief maternal undernutrition for 10 d, but not 20 d, in late gestation alters HPA function in adult offspring. In contrast to our previous findings, these HPA effects are independent of birth weight and current weight, suggesting that different mechanisms may be involved in programming different physiological axes.