Cellular cholesterol efflux mediated by HDL isolated from subjects with low HDL levels and coronary artery disease

OBJECTIVE: The aim of this study was to verify whether HDL particles isolated from patients with coronary artery disease (CAD) and low HDL-C had diminished ability to promote cholesterol efflux from cultured cells compared with HDL isolated from subjects without CAD and with normal HDL-C. METHODS: Smooth muscle cells isolated from human aortas cultured and radiolabeled with ³H-cholesterol were loaded with cholesterol and incubated with increasing concentrations of HDL isolated from 13 CAD patients with low HDL-C (CAD group) or from 5 controls without CAD (C group). Efflux of cellular cholesterol was measured by cellular depletion of radiolabeled cholesterol and by the appearance of ³H-cholesterol into experimental medium expressed as a percentage of total labeled cholesterol. RESULTS: Cholesterol efflux increased with the amount of HDL present in the medium, and no difference was found between groups at various HDL protein concentrations: efflux was 28 ± 6.3% (C) and 25.5 ± 8.9% (CAD) with 25 mg/mL; 34 ± 4.3% (C) and 31.9 ± 6.6% (CD) with 50 mg/mL and 39.5 ± 3.5% (C) and 37.1 ± 4.4% (CAD) with 100 mg/mL, HDL. CONCLUSION: Because the HDL fraction of CAD patients with low HDL-C have normal ability to extract cholesterol from cells of the vessel wall, it is suggested that low HDL-C atherogenicity should be ascribed to diminished concentrations of HDL particles rather than to the qualitative properties of the HDL fraction.

Depression as a Clinical Determinant of Dependence and Low Quality of Life in Elderly Patients with Cardiovascular Disease

Background:The aging process promotes a progressive increase in chronic-degenerative diseases. The effect of these diseases on the functional capacity has been well recognized. Another health parameter concerns “quality of life related to health”. Among the elderly population, cardiovascular diseases stand out due to the epidemiological and clinical impact. Usually, these diseases have been associated with others. This set of problems may compromise both independence and quality of life in elderly patients who seek cardiologic treatment. These health parameters have not been well contemplated by cardiologists.Objective:Evaluating, among the elderly population with cardiovascular disease, which are the most relevant clinical determinants regarding dependence and quality of life.Methods:This group was randomly and consecutively selected and four questionnaires were applied: HAQ, SF-36, PRIME-MD e Mini Mental State.Results:The study included 1,020 elderly patients, 63.3% women. The group had been between 60 and 97 years-old (mean: 75.56 ± 6.62 years-old). 61.4% were independent or mild dependence. The quality of life total score was high (HAQ: 88.66 ± 2.68). 87.8% of patients had a SF-36 total score > 66. In the multivariate analysis, the association between diagnoses and high degrees of dependence was significant only for previous stroke (p = 0.014), obesity (p < 0.001), lack of physical activity (p = 0.016), osteoarthritis (p < 0.001), cognitive impairment (p < 0.001), and major depression (p < 0.001). Analyzing the quality of life, major depression and physical illness for depression was significantly associated with all domains of the SF-36.Conclusion:Among an elderly outpatient cardiology population, dependence and quality of life clinical determinants are not cardiovascular comorbidities, especially the depression.

Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe

Abstract Background: The effect of statins on the endothelial function in humans remains under discussion. Particularly, it is still unclear if the improvement in endothelial function is due to a reduction in LDL-cholesterol or to an arterial pleiotropic effect. Objective: To test the hypothesis that modulation of the endothelial function promoted by statins is primarily mediated by the degree of reduction in LDL-cholesterol, independent of the dose of statin administered. Methods: Randomized clinical trial with two groups of lipid-lowering treatment (16 patients/each) and one placebo group (14 patients). The two active groups were designed to promote a similar degree of reduction in LDL-cholesterol: the first used statin at a high dose (80 mg, simvastatin 80 group) and the second used statin at a low dose (10 mg) associated with ezetimibe (10 mg, simvastatin 10/ezetimibe group) to optimize the hypolipidemic effect. The endothelial function was assessed by flow-mediated vasodilation (FMV) before and 8 weeks after treatment. Results: The decrease in LDL-cholesterol was similar between the groups simvastatin 80 and simvastatin 10/ezetimibe (27% ± 31% and 30% ± 29%, respectively, p = 0.75). The simvastatin 80 group presented an increase in FMV from 8.4% ± 4.3% at baseline to 11% ± 4.2% after 8 weeks (p = 0.02). Similarly, the group simvastatin 10/ezetimibe showed improvement in FMV from 7.3% ± 3.9% to 12% ± 4.4% (p = 0.001). The placebo group showed no variation in LDL-cholesterol level or endothelial function. Conclusion: The improvement in endothelial function with statin seems to depend more on a reduction in LDL-cholesterol levels, independent of the dose of statin administered, than on pleiotropic mechanisms.

Appropriateness criteria for surgery improve clinical outcomes in patients with low back pain and/or sciatica.

STUDY DESIGN: Prospective, controlled, observational outcome study using clinical, radiographic, and patient/physician-based questionnaire data, with patient outcomes at 12 months follow-up. OBJECTIVE: To validate appropriateness criteria for low back surgery. SUMMARY OF BACKGROUND DATA: Most surgical treatment failures are attributed to poor patient selection, but no widely accepted consensus exists on detailed indications for appropriate surgery. METHODS: Appropriateness criteria for low back surgery have been developed by a multispecialty panel using the RAND appropriateness method. Based on panel criteria, a prospective study compared outcomes of patients appropriately and inappropriately treated at a single institution with 12 months follow-up assessment. Included were patients with low back pain and/or sciatica referred to the neurosurgical department. Information about symptoms, neurologic signs, the health-related quality of life (SF-36), disability status (Roland-Morris), and pain intensity (VAS) was assessed at baseline, at 6 months, and at 12 months follow-up. The appropriateness criteria were administered prospectively to each clinical situation and outside of the clinical setting, with the surgeon and patients blinded to the results of the panel decision. The patients were further stratified into 2 groups: appropriate treatment group (ATG) and inappropriate treatment group (ITG). RESULTS: Overall, 398 patients completed all forms at 12 months. Treatment was considered appropriate for 365 participants and inappropriate for 33 participants. The mean improvement in the SF-36 physical component score at 12 months was significantly higher in the ATG (mean: 12.3 points) than in the ITG (mean: 6.8 points) (P = 0.01), as well as the mean improvement in the SF-36 mental component score (ATG mean: 5.0 points; ITG mean: -0.5 points) (P = 0.02). Improvement was also significantly higher in the ATG for the mean VAS back pain (ATG mean: 2.3 points; ITG mean: 0.8 points; P = 0.02) and Roland-Morris disability score (ATG mean: 7.7 points; ITG mean: 4.2 points; P = 0.004). The ATG also had a higher improvement in mean VAS for sciatica (4.0 points) than the ITG (2.8 points), but the difference was not significant (P = 0.08). The SF-36 General Health score declined in both groups after 12 months, however, the decline was worse in the ITG (mean decline: 8.2 points) than in the ATG (mean decline: 1.2 points) (P = 0.04). Overall, in comparison to ITG patients, ATG patients had significantly higher improvement at 12 months, both statistically and clinically. CONCLUSION: In comparison to previously reported literature, our study is the first to assess the utility of appropriateness criteria for low back surgery at 1-year follow-up with multiple outcome dimensions. Our results confirm the hypothesis that application of appropriateness criteria can significantly improve patient outcomes.

First-line chemotherapy with local treatment can prevent external-beam irradiation and enucleation in low-stage intraocular retinoblastoma.

PURPOSE: To evaluate the efficacy of first-line chemotherapy (CT) in preventing external-beam radiotherapy (EBR) and/or enucleation in patients with retinoblastoma (Rbl). PATIENTS AND METHODS: Twenty-four patients with newly diagnosed unilateral or bilateral Rbl received CT associated with local treatment (LT). Two to five courses of etoposide and carboplatin were administered at 3- to 4-week intervals, depending on tumor response, and were completed each time by LT. RESULTS: Tumor response was observed in all eyes. Twenty-one of 24 patients showed a complete response (CR) that persisted at a median follow-up (FU) of 31 months (range, 4 to 41 months). Among the three patients who relapsed, two were lost to FU and one died of progressive disease. CR was achieved by CT and LT alone in 15 (71.4%) of 21 patients with less advanced disease (groups I to III). Six other patients with advanced disease (groups IV and V) experienced treatment failure and needed salvage treatment by EBR and/or enucleation. The difference between the two patient groups with regard to disease stage was statistically significant (P <.0001). EBR could be avoided in 13 (68.4%) of 19 patients, who presented with groups I to III (15 eyes) and group V (one eye) disease, whereas enucleation could be avoided in only two (40%) of five. CONCLUSION: CT combined with intensive LT is effective in patients with groups I to III Rbl, permitting the avoidance of EBR in the majority of these young children and, thus, reducing the risk of long-term sequelae. This is in contrast with the disappointing results for patients with groups IV and V Rbl, in whom EBR and/or enucleation was needed.

Parasite and egg burden, hepatic collagen and histologic pattern of liver granulomas in selection III high and low antibody responder mice infected with Schistosoma mansoni

Selection III mice have particular immunological characteristics: they are high (H III) or low (L III) antibody producer animals, yet both lines display similar T cell responses and macrophage activities. We submittedthese mice to infection with Schistosoma mansoni to assess in vivo parasite and egg burden, hepatic collagen and cellular composition of granulomas in both lines. Titration of anti-Schistosoma IgG by ELISA showed remarkably higher values inH III line, at both studied periods (8th and 12th weeks post-infection). Nevertheless, the number of adult worms recovered from the portal system was similar inboth lines, being not associated with anti-Schistosoma antibody levels. There isan increase in hepatic collagen from the 8th to the 12th weeks post-infection, which is paralleled by an increase in the number of eggs in the liver. This association apparently occurs at the same radio in H III and L III animals. The most important difference found between the two lines was the outstanding contrast interms of volume and eosinophil counts in the granulomas, with lesions from H IIImice clearly being larger and containing more of these cells than LIII lesions.

Use of levosimendan as rescue therapy in children with low cardiac output syndrome.

Objective: Aim of post operative treatments after cardiac surgery is to avoid low cardiac output syndrome (LCOS). Levosimendan, a new inotrope agent, has been demonstrated in adult patient to be an effective treatment for this purpose when classical therapy is not effective. It shows a positive effect on cardiac output, with fewer adverse effects and lower mortality than with dopamine. There is very few data on its benefit in the paediatric population. The aim of this study is to evaluate the effect of levosimendan in cardiac children with LCOS.Methods: Retrospective analysis of 25 children hospitalised in our PICU after cardiac surgery that demonstrated LCOS not responding to classical catecholamine therapy and who received levosimendan as rescue. LCOS parameters like urine output, mixed venous oxygen saturation (SvO2), arterio-venous differences in CO2 (AVCO2) and plasmatic lactate were compared before therapy and at 12, 24, 48 and 72 hours after the beginning of the levosimendan infusion. We also analyzed the effect on the utilisation of amines (amine score), adverse events and mortality.Results: After the beginning of levosimendan infusion, urine output (3.1 vs 5.3ml/kg/h, p=0.003) and SVO2 (56 vs 64mmHg, p=0.001) increase significantly during first 72 hours and at the same time plasmatic lactate (2.6 vs 1.4 mmole/l, p<0.001), AVCO2 (11 vs 8 mmHg, p=0.002) and amine score (63 vs 39, p=0.007) decrease significantly. No side effects were noted during administration of levosimendan. In this group of patients, mortality was 0%.Conclusion: Levosimendan is an effective treatment in children after congenital heart surgery. Our study, with a greater sample of patient than other studies, confirms the improvement of cardiac output already shown in other paediatric studies.

Understanding the low-temperature limitations to forest growth through calibration of a forest dynamics model with tree-ring data

The sensitivity of altitudinal and latitudinal tree-line ecotones to climate change, particularly that of temperature, has received much attention. To improve our understanding of the factors affecting tree-line position, we used the spatially explicit dynamic forest model TreeMig. Although well-suited because of its landscape dynamics functions, TreeMig features a parabolic temperature growth response curve, which has recently been questioned. and the species parameters are not specifically calibrated for cold temperatures. Our main goals were to improve the theoretical basis of the temperature growth response curve in the model and develop a method for deriving that curve's parameters from tree-ring data. We replaced the parabola with an asymptotic curve, calibrated for the main species at the subalpine (Swiss Alps: Pinus cembra, Larix decidua, Picea abies) and boreal (Fennoscandia: Pinus sylvestris, Betula pubescens, P. abies) tree-lines. After fitting new parameters, the growth curve matched observed tree-ring widths better. For the subalpine species, the minimum degree-day sum allowing, growth (kDDMin) was lowered by around 100 degree-days; in the case of Larix, the maximum potential ring-width was increased to 5.19 mm. At the boreal tree-line, the kDDMin for P. sylvestris was lowered by 210 degree-days and its maximum ring-width increased to 2.943 mm; for Betula (new in the model) kDDMin was set to 325 degree-days and the maximum ring-width to 2.51 mm; the values from the only boreal sample site for Picea were similar to the subalpine ones, so the same parameters were used. However, adjusting the growth response alone did not improve the model's output concerning species' distributions and their relative importance at tree-line. Minimum winter temperature (MinWiT, mean of the coldest winter month), which controls seedling establishment in TreeMig, proved more important for determining distribution. Picea, P. sylvestris and Betula did not previously have minimum winter temperature limits, so these values were set to the 95th percentile of each species' coldest MinWiT site (respectively -7, -11, -13). In a case study for the Alps, the original and newly calibrated versions of TreeMig were compared with biomass data from the National Forest Inventor), (NFI). Both models gave similar, reasonably realistic results. In conclusion, this method of deriving temperature responses from tree-rings works well. However, regeneration and its underlying factors seem more important for controlling species' distributions than previously thought. More research on regeneration ecology, especially at the upper limit of forests. is needed to improve predictions of tree-line responses to climate change further.

Lack of metabolic and behavioral adaptations in rural Gambian men with low body mass index.

Energy expenditure was measured by means of a respiratory chamber in two groups of adult rural Gambian men. The first group (n = 29) had a low body mass index (BMI; in kg/m2) < 18.5), whereas the control group (n = 29) had a higher BMI (> 22). This study shows that the energy expenditure of Gambian men with low BMI is not different from that of Gambian men with normal BMI when the results are normalized for fat-free mass or for weight by analysis of covariance. In Gambian men the nutritional status thus does not seem to affect energy metabolism notably. No differences in respiratory quotient, diet-induced thermogenesis, net work efficiency, spontaneous physical activity, heart rate, or urinary catecholamine excretion were observed between the two groups. It is, however, interesting to note that the basal metabolic rate of Gambian men, regardless of their nutritional status, is approximately 10% (range 4-12% depending on the reference value used) lower than that predicted for individuals living in industrialized countries.

Low occurrence of arthritic manifestations in patients with pulmonary tuberculosis: T cell subsets and humoral studies

Given the suspected role of mycobacteria in the establishment of disorders with an autoimmune background and joint damage, a study was conducted to analize whether rheumatic symptoms were likely to be present in tuberculosis (TB) patients. To this end, 330 patients with a bacteriologic confirmation of tuberculosis were investigated for the presence of arthritic complaints. The latter were recorded in five of them with rheumatic symptoms mostly involving interphalangeal and metacarpophalanged joints, and preceding the clinical manifestations of the TB illness. Three out of these five patients remained arthritic by the time of the bacteriologic conversion and fulfilled the criteria for the diagnosis of rheumatoid arthritis. In the two remaining patients sputum negativization was accompanied by a disappearance of rheumatic manifestations. These patients were also assessed for their peripheral levels of major T cell subsets as well as for the presence of autoantibodies. Comparisons with a series of non-arthritic TB cases, rheumatoid arthritis patients, and controls revealed that presence of rheumatic manifestations was associated with a different profile of autoantibody formation and T cell subset changes. Evidence recorded in the present study indicates that joint affectation in TB is a rare event, being rather the exception than the rule.

Use of a renal-specific oral supplement by haemodialysis patients with low protein intake does not increase the need for phosphate binders and may prevent a decline in nutritional status and quality of life.

BACKGROUND: Protein-energy wasting is a frequent and debilitating condition in maintenance dialysis. We randomly tested if an energy-dense, phosphate-restricted, renal-specific oral supplement could maintain adequate nutritional intake and prevent malnutrition in maintenance haemodialysis patients with insufficient intake. METHODS: Eighty-six patients were assigned to a standard care (CTRL) group or were prescribed two 125-ml packs of Renilon 7.5(R) daily for 3 months (SUPP). Dietary intake, serum (S) albumin, prealbumin, protein nitrogen appearance (nPNA), C-reactive protein, subjective global assessment (SGA) and quality of life (QOL) were recorded at baseline and after 3 months. RESULTS: While intention to treat analysis (ITT) did not reveal strong statistically significant changes in dietary intake between groups, per protocol (PP) analysis showed that the SUPP group increased protein (P < 0.01) and energy (P < 0.01) intakes. In contrast, protein and energy intakes further deteriorated in the CTRL group (PP). Although there was no difference in serum albumin and prealbumin changes between groups, in the total population serum albumin and prealbumin changes were positively associated with the increment in protein intake (r = 0.29, P = 0.01 and r = 0.27, P = 0.02, respectively). The SUPP group did not increase phosphate intake, phosphataemia remained unaffected, and the use of phosphate binders remained stable or decreased. The SUPP group exhibited improved SGA and QOL (P < 0.05). CONCLUSION: This study shows that providing maintenance haemodialysis patients with insufficient intake with a renal-specific oral supplement may prevent deterioration in nutritional indices and QOL without increasing the need for phosphate binders.

Subjective Memory Deficits in People with and without Dementia: Findings from the 10/66 Dementia Research Group Pilot Studies in Low- and Middle-Income Countries

OBJECTIVES To compare subjective memory deficit (SMD) in older adults with and without dementia or depression across multiple centers in low- and middle-income countries (LAMICs). DESIGN Secondary analysis of data from 23 case control studies. SETTING Twenty-three centers in India, Southeast Asia (including China), Latin America and the Caribbean, Nigeria, and Russia. PARTICIPANTS Two thousand six hundred ninety-two community-dwelling people aged 60 and older in one of three groups: people with dementia, people with depression, and controls free of dementia and depression. MEASUREMENTS SMD was derived from the Geriatric Mental State examination. RESULTS Median SMD frequency was lowest in participants without dementia (26.2%) and higher in those with depression (50.0%) and dementia (66.7%). Frequency of SMD varied between centers. Depression and dementia were consistently associated with SMD. Older age and hypochondriasis were associated with SMD only in subjects without dementia. In those with dementia, SMD was associated with better cognitive function, whereas the reverse was the case in controls. CONCLUSION Associations with SMD may differ between subjects with and without dementia living in LAMICs.

Confounding effects of heart rate on pulse wave velocity in paced patients with a low degree of atherosclerosis.

BACKGROUND: Pulse wave velocity (PWV), an index of arterial wall stiffness, is modulated by blood pressure (BP). Whether heart rate (HR) is also a modulator of PWV is controversial. Recent research involving mainly patients with high aortic PWV have found either no change or a positive correlation between the two. Given that PWV is increasingly being measured in cardiovascular studies, the relationship between HR and PWV should be known in patients with preserved arterial wall elasticity. OBJECTIVE: The aim of this study was to evaluate the importance of HR as a determinant of the variability in PWV in patients with a low degree of atherosclerosis. DESIGN AND METHODS: Fourteen patients (five female, nine male; aged 68 +/- 8 years) were evaluated post pacemaker implantation due to sick sinus or carotid hypersensitivity syndromes. Carotid-femoral PWV was measured at rest and during atrial pacing at 80, 90 and 100 bpm (paced HR). Arterial femoral blood flow (AFBF) was measured by echodoppler. RESULTS: PWV increased from 6.2 +/- 1.5 m/s (mean +/- SD) during resting sinus rhythm (HR 62 +/- 8 bpm; mean +/- SD) to 6.8 +/- 1.0, 7.0 +/- 0.9, and 7.6 +/- 1.1 m/s at pacing rates of 80, 90 and 100 bpm, respectively (P < 0.0001). Systolic (SBP) and mean blood pressure (MBP) remained constant at all HR levels, whereas AFBF increased in a linear fashion. CONCLUSIONS: These results demonstrate that even in patients with a low degree of atherosclerosis, HR is a potential modulator of carotid-femoral PWV.