Treating mild hypercholesterolemia in the absence of overt cardiovascular disease: If,when, and why?

Summary Cohort data define a range of cholesterol concentrations (160–200 mg/dl), which is desirable in terms of public health. Cholesterol-lowering treatment leading to a serum cholesterol in this range is favorable for coronary heart disease prevention and safe in terms of noncardiovascular mortality. In individuals with moderate cholesterol elevation and without other coronary risk factors, the physician should encourage a healthy lifestyle and give prudent nutritional advice. Detection of asymptomatic cardiovascular disease by noninvasive methods might be used to identify individuals with mild hypercholesterolemia, but nevertheless at high risk for ischemic accidents. The aim of lipid-lowering treatment is to improve life expectancy through reduction of a major cause of premature death.     

Mobilization of early hematopoietic progenitor cells with BB-10010: a genetically engineered variant of human macrophage inflammatory protein- 1 alpha

BB-10010 is a genetically engineered variant of human macrophage inflammatory protein-1 alpha with improved solution properties. We show here that it mobilizes stem cells into the peripheral blood. We investigated the mobilizing effects of BB-10010 on the numbers of circulating 8-day spleen colony-forming units (CFU-S8), CFU-S12, and progenitors with marrow repopulating ability (MRA). A single subcutaneous dose of BB-10010 caused a twofold increase in circulating numbers of CFU-S8, CFU-S12, and MRA 30 minutes after dosing. We also investigated the effects of granulocyte colony-stimulating factor (G- CSF) and the combination of G-CSF with BB-10010 on progenitor mobilization. Two days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA progenitors by 25.7-, 19.8-, and 27.7-fold. A single administration of BB-10010 after 2 days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA even further to 38-, 33-, and 100- fold. Splenectomy resulted in increased circulating progenitor numbers but did not change the pattern of mobilization. Two days of treatment with G-CSF then increased circulating CFU-S8, CFU-S12, and MRA by 64-, 69-, and 32-fold. A single BB-10010 administration after G-CSF treatment further increased them to 85-, 117-, and 140-fold, respectively, compared with control. We conclude that BB-10010 causes a rapid increase in the number of circulating hematopoietic progenitors and further enhances the numbers induced by pretreatment with G-CSF. BB- 10010 preferentially mobilized the more primitive progenitors with marrow repopulating activity, releasing four times the number achieved with G-CSF alone. Translated into a clinical setting, this improvement in progenitor cell mobilization may enhance the efficiency of harvest and the quality of grafts for peripheral blood stem cell transplantation.     

Relation between maximum time-varying elastance pressure-volume areas and myocardial oxygen consumption in dogs

To establish whether pressure-volume areas (PVAs) calculated using the maximum time-varying elastance (Emax) have a relation with myocardial oxygen consumption (MVO2) that improves on other indexes of myocardial oxygen demand, we studied nine dogs of either sex weighing 19-39 kg, which were instrumented with a micromanometer left ventricular (LV) catheter and a Wilton-Webster coronary sinus flow catheter and had red blood cells tagged with technetium-99m for radionuclide angiography. Hemodynamics, coronary sinus flow determinations, and radionuclide angiograms were obtained under control conditions and during three to five steady-state loading conditions (mean +/- SD, 5.6 +/- 0.7). Isochronal pressure-volume data points from each pressure-volume loop were subjected to linear regression analysis to calculate Emax. The Emax relations, diastolic curves, and systolic portions of each pressure-volume loop were used to obtain calibrated PVAs. The Emax PVA (mm Hg.ml.beat-1.100 g-1) and MVO2 (ml O2.beat-1.100 g-1) values correlated in each animal (r = 0.77 to 0.99). Their slopes averaged (3.48 +/- 1.68) x 10(-5) ml O2.mm Hg-1.ml-1, and their y-axis intercepts averaged 0.07 +/- 0.04 ml O2.beat-1.100 g-1. When the MVO2 relations were compared with Emax PVA, LV systolic pressure-rate product, LV stroke work, and a modification of the LV pressure-work index, the Emax PVA, LV systolic pressure-rate product, and LV pressure-work index had similar relations with MVO2, whereas LV stroke work was a weaker index of MVO2 (p less than 0.05 versus Emax PVA). This occurred because the Emax PVA:MVO2 slopes and y-axis intercepts differed in each dog, which was due to differences in basal LV contractility. The Emax PVA:MVO2 slopes correlated with Emax (r = 0.73, p less than 0.05), and the y-axis intercepts were also weakly related to Emax (r = 0.48, p = 0.19). We conclude that the Emax PVAs calculated using data acquisition techniques that are clinically applicable have relations with MVO2 that in general do not improve on other indexes of myocardial oxygen demand in this animal preparation.     

Cross-cultural adaptation to Brazilian Portuguese of the Activity Measure for Post-Acute Care (AM-PAC) short forms for outpatients in rehabilitation

Background

The Activity Measure for Post-Acute Care was developed to evaluate the limitations of activities of adult individuals with different health conditions.

Evaluation of dopaminergic tone in hyperprolactinemia. III. Thyroid-stimulating hormone response to metoclopramide in differential diagnosis and postoperative follow-up of prolactinoma patients

Recently, it has been shown that patients with a PRL-secreting pituitary adenoma have a greater thyroid stimulating hormone (TSH) release after dopamine (DA)-receptor blockade than normal subjects. We have compared the TSH and PRL responses to metoclopramide (MCP) in normal and postpartum lactating women with those in 28 patients with hyperprolactinemia of different origin. Patients with a PRL-secreting pituitary adenoma were also tested after transsphenoidal removal of the tumor in order to establish the prognostic value of this test in such patients. Following MCP administration, percent increases in plasma PRL levels were greater in normal female subjects than postpartum lactating women. Plasma TSH levels did not increase in postpartum women and had a modest increment in normal subjects. In patients with hypothalamic tumors and empty sella syndrome plasma PRL and TSH levels showed modest or no increases after MCP administration. In ten patients harboring a microprolactinoma, plasma TSH levels showed an exaggerated increment after DA-receptor blockade. Postoperatively, despite normal or borderline PRL levels in the immediate postoperative period, a TSH response to MCP was present (in five patients one to two weeks after the operation, and in five patients one to three years after the operation), suggesting an increased DA activity even in the absence of hyperprolactinemia. In conclusion, the TSH test can easily detect increased DA-activity in patients with a microprolactinoma both preoperatively and postoperatively. It is possible that some patients with increased DA-activity in presence of normal PRL levels and normal PRL responsiveness to stimulation will experience a recurrence of hyperprolactinemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricular mass and blood pressure during ergometric exercise in primary hypertension

The pathophysiology of left ventricular hypertrophy (LVH) in hypertensive patients is still an intriguing point. The lack of a close relationship between LVH and systolic or diastolic blood pressure at rest, previously observed by other investigators, was confirmed in our group of 45 patients with uncomplicated primary hypertension. The strength of correlation between echocardiographic left ventricular mass (LVMe) and blood pressure, expressed as incremental area (IA = total area under the curve--basal area), however, increased during bicycle exercise testing (r = 0.33, p less than 0.05 for diastolic blood pressure; r = 0.39, p less than 0.01 for systolic blood pressure; r = 0.41, p less than 0.01 for mean arterial pressure). Other echocardiographic parameters of myocardial mass such as LVM index (LVMI) and septal thickness (ST) were also significantly correlated with blood pressure during exercise. These results suggest either that blood pressure during exercise is a better index of the cardiac workload than resting blood pressure or that the pathogenesis of cardiac hypertrophy involves an enhanced reactivity to adrenergic drive, particularly stimulated during ergometric exercise. Increased blood pressure alone, however, only partly accounts (about 20%) for the increase in myocardial mass in hypertensive patients; other factors, therefore, need to be further investigated for a better understanding of the pathophysiology of left ventricular hypertrophy.     

Beer Affects Oxidative Stress due to Ethanol in Rats

The relationship between chronic moderate beerconsumption and oxidative stress was studied in rats.Animals were fed three different isocaloric diets forsix weeks: a beercontaining diet (30% w/w), an ethanol-supplemented diet (1.1 g/100 g, thesame as in the beer diet) and an alcohol-free basaldiet. At the end of the feeding period, rats wereanalyzed for plasma and liver oxidative status. Somelivers were isolated and exposed toischemiareperfusion to assess the additional oxidativestress determined by reperfusion. No significantdifferences in plasma antioxidant status were foundamong the three dietary groups. Lipoproteins from the beer group,however, showed a greater propensity to resist lipidperoxidation. Ischemia caused a decrease in liver energyand antioxidant status in all groups. Nevertheless, ATP was lower in the livers of rats exposed tothe ethanol diet. During reperfusion, lipoperoxidationincreased significantly in all groups. However, liversobtained from ethanoltreated rats showed the higher formation of lipoperoxides. Inconclusion, a moderate consumption of beer in awell-balanced diet did not appear to cause oxidativestress in rats; moreover, probably through its minorcomponents, beer could attenuate the oxidative action ofethanol by itself.