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.     

Evaluation of vertebral volumetric vs. areal bone mineral density during growth

Bone mineral “density” (BMD) measured by dual-energy X-ray absorptiometry (DEXA) does not represent the volumetric density (grams per cubic centimeter), but rather the areal density (grams per square centimeter). This distinction is important during growth. The purpose of this study was to measure vertebral dimensions in cadavers of young pigtail macaques (Macaca nemestrina), and to derive equations to predict the volumetric bone density from noninvasive measurements. We measured the areal bone density by DEXA, vertebral volume by underwater weighing, mineral content by ashing, dimensions of lumbar vertebrae by calipers, and dimensions of vertebrae by radiography. Somatometric measurements of the female lumbar vertebral bodies showed that the shape changed during growth. The bone mineral content from the densitometer correlated significantly with the ash weight (r = 0.99, error 8.7%). The correlation coefficient between the volumetric bone mineral density and areal BMD measurement was significant (r = 0.68, p < 0.0001) with a 9.5% error; this improved significantly to 0.82 (7.2% error) when the BMD was divided by the vertebral depth from the radiograph. Areal BMD showed a strong correlation with age (r = 0.82, p < 0.0001), with an average increase of 7.4%/year. In contrast, volumetric mineral density showed a weak relationship with age (r = 0.43, p < 0.01), for an average increase of 1.5%/year. When studying bone mineral density during growth, the differences between volumetric and areal bone mineral density should be taken into consideration. (     

The combination oral and nutritional treatment of late-onset diabetes mellitus (CONTROL DM) trial results.

OBJECTIVE: To examine the effect of short-term improvements in glycaemic control on brachial artery endothelial function as a marker of cardiovascular health. METHODS: Persons with Type 2 diabetes who were poorly controlled on oral therapy were randomly assigned to monotherapy with repaglinide or combination therapy with repaglinide plus metformin. Brachial artery flow-mediated vasodilation was assessed by ultrasonography at randomization and following 16 weeks of therapy. The primary outcome was change in brachial artery endothelial function from baseline. Comparison of randomized groups was a secondary aim. RESULTS: Eighty-six participants were randomized, and 83 were followed to study completion. Post occlusion brachial artery vasodilation was 3.74% at baseline and 3.82% following 16 weeks of therapy (P = 0.77). The treatment effect was 0.08% (95% CI: -0.48%, 0.64%). No difference was seen between treatment groups (P = 0.69). Overall, A1C was reduced from 8.3% to 7.0%, with a greater reduction in the combination therapy group (from 8.4% to 6.7%) than in the monotherapy group (from 8.3% to 7.3%, p for difference between groups = 0.01). Statistically significant reductions were observed in fasting glucose, and plasminogen activator inhibitor-1. Statistically significant increases were observed for fasting insulin, uric acid, weight and BMI. CONCLUSIONS: Brachial artery endothelial function was not influenced by short-term improvements in glycaemic control. The CONTROL DM group was successful in lowering A1C. Future research should explore more intensive and longer-lasting improvements in glycaemic control on endothelial function. Some data previously published in abstract form (Diabetes 2001; 50 (Suppl. 2): A217).     

Serum markers of bone formation in parenteral nutrition patients

Summary Bone gamma-carboxyglutamic acid containing protein (BGP) has been utilized effectively as a serum marker of bone turnover in healthy normals and in individuals with a variety of metabolic bone disorders including postmenopausal osteoporosis and Paget's disease. The utility of this serum marker in other bone disorders, including that associated with the maintenance of patients on long-term parenteral nutrition, still requires definition. Because of our interest in this clinical syndrome and the availability of serum and of bone formation rates (BFR) measured directly from double tetracycline labeling in 11 long-term parenteral nutrition patients, we measured BGP levels in these patients and attempted to correlate this measure with BFR. Serum vitamin D metabolites, immunoreactive parathyroid hormone (PTH), and alkaline phosphatase (alk phos) were also measured. Serum BGP was only weakly and not significantly correlated (r=0.24, p=NS) with bone formation rate for the group as a whole. However, in a subgroup of 10 patients without hyperparathyroidism, there was strong and significant correlation (r=0.81,P<0.01) between BGP and BFR. There was also a strong correlation between bone formation rate and serum 1,25 dihydroxyvitamin D [1,25(OH)2D] levels (r=0.89,P<0.01, n=11). The mechanism of this association could not be established. A correlation of borderline significance was observed between bone formation rate and serum alk phos (r=0.60,P=0.05, n=11). The current data suggest that additional studies may help to more fully define the utility of serum measurements in quantifying bone dynamics in parenteral nutrition patients, and that measures of vitamin D metabolites, BGP, and alk phos may prove useful.     

The condensation of γ-butyrolactone with ethyl acetate

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 22, No. 12, pp. 1465–1469, December, 1988.     

Exercise physiology and the role of the periphery in cardiac failure

Cardiopulmonary exercise testing remains the standard method of functional assessment in chronic heart failure, and both peak oxygen consumption achieved on progressive maximal exercise testing and anaerobic threshold are widely used endpoints in clinical trials. Peak oxygen consumption achieved on progressive maximal exercise testing may be used in clinical practice to estimate prognosis and aid the prioritization of patients for cardiac transplantation. Anaerobic threshold is a valuable index of submaximal exercise performance, but there are many different criteria used to define anaerobic threshold and careful attention to the methodology is essential. The mechanisms of limitation of exercise capacity and the importance of the peripheral abnormalities in chronic heart failure are still not elucidated. The skeletal muscles are reduced in size, weak, and easily fatigued; in addition, nuclear magnetic resonance spectroscopic studies have shown that high-energy phosphates are depleted and acidosis develops more rapidly during exercise in patients with chronic heart failure than in normal subjects. However, the relationship of these abnormalities to the mechanical performance of the muscles, the differences between treated and untreated heart failure, and the effects of physical training have yet to be clarified.     

Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.      

New strategies for the treatment of type 2 diabetes

This review of current developments in the treatment of type 2 diabetes focuses on the achievement of normoglycemia through appropriately defined goals of diet, exercise, and drug therapy. Clinical nutritionists are central partners in the management of type 2 diabetes, and nutrition therapy is still considered the first-line therapy of choice. A nutritionist's role in the treatment at type 2 diabetes is to ensure an individualized, nutritionally adequate diet for patients, uncomplicated by episodes of hypoglycemia. In this role, clinical nutritionists must be aware of potential drug interactions with diet therapy and may be able to provide essential feedback about possible drug interactions to other members of the health care team, including nurses, pharmacists, and physicians. The role of insulin in treating type 2 diabetes is reexamined in the light of newly available oral antidiabetic agents and increasing awareness of the importance of insulin resistance and hyperinsulinemia in the development of diabetes complications. Because many patients use insulin to reduce blood glucose and glycated hemoglobin (HbA1c) to acceptable levels, management should combine diet therapy with insulin and/or 1 or 2 oral antidiabetic agents to help minimize the dose of exogenous insulin needed for glucose control.