Monocyte chemoattractant protein-1: plasma concentrations and A(-2518)G promoter polymorphism of its gene in systemic lupus erythematosus

OBJECTIVE: To determine (1) whether the A(-2518)G polymorphism of CCL-2, the gene encoding monocyte chemoattractant protein-1 (MCP-1), is associated with disease, MCP-1 concentration, nephritis, or coronary artery calcification (CAC) in systemic lupus erythematosus (SLE); and (2) whether MCP-1 and homocysteine (Hcy) concentrations are correlated. METHODS: Statistical tests were applied to determine the relationships between CCL-2 A(-2518)G genotypes, plasma MCP-1 concentrations, and clinical variables in Caucasian and African American patients with SLE and controls. RESULTS: The CCL-2 (-2518)G allele was not significantly associated with SLE in the whole study sample (p = 0.07). Among Caucasians, but not African Americans, G allele carriers had significantly increased risk of SLE (OR 4.2, 95% CI 1.8-9.6, p < 0.0001). Genotype was not associated with nephritis, CAC, or MCP-1 concentrations when all patients or all controls were considered; however, among recently diagnosed patients, G allele carriers had significantly higher MCP-1 concentrations than AA homozygotes (p = 0.02). SLE patients had higher MCP-1 concentrations than controls (p < 0.0001), African American patients had higher concentrations than Caucasian patients (p = 0.006), and patients with nephritis had higher concentrations than those without nephritis (p = 0.02). Although not associated with CAC, MCP-1 concentrations were significantly positively correlated with Hcy. CONCLUSION. CCL-2 A(-2518)G genotype is a significant risk factor for SLE among Caucasians but not African Americans, suggesting that genetically mandated differences in MCP-1 expression contribute to SLE etiology in the former. The positive correlation between MCP-1 and Hcy concentrations is consistent with the hypothesis that active inflammation and hyperhomocysteinemia are etiologically linked.     

Body mass and fat-free mass indices in COPD: relation with variables expressing disease severity

BACKGROUND: COPD primarily affects the lungs but also produces systemic consequences that are not reflected by the recent staging according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Body mass index (BMI) and fat-free mass index (FFMI) represent different aspects of nutrition abnormalities in COPD. We investigated whether BMI and FFMI could be related to parameters expressing airflow obstruction and limitation, exercise capacity, airway inflammation, and quality of life, and whether they would reflect the GOLD staging of the disease. METHODS: One hundred patients with clinically stable COPD equally classified into the five stages of the disease were evaluated for BMI, FFMI (measured by bioelectrical impedance analysis), airway obstruction and hyperinflation (FEV(1), FEV(1)/FVC, inspiratory capacity), exercise capacity (6-min walk distance [6MWD], Borg scale before and after 6MWD]), chronic dyspnea using the Medical Research Council (MRC) scale, airway inflammation (sputum differential cell counts, leukotriene B(4) in supernatant), and quality of life (emotional part of the chronic respiratory disease questionnaire). RESULTS: 6MWD was significantly associated with both BMI and FFMI values, while FFMI additionally presented significant correlations with MRC scale, percentage of predicted FEV(1), and FEV(1)/FVC ratio. No association was observed between the two nutritional indexes. BMI was not statistically different among patients in the five stages of COPD, while FFMI reflected the staging of the disease, presenting the highest values in stage 0. CONCLUSIONS: Nutritional status is mainly related to exercise capacity. FFMI seems to be more accurate in expressing variables of disease severity, as well as the current staging compared to BMI.     

Rate of change and instability in body mass index, insulin resistance, and lipid metabolism as predictors of atherosclerotic vascular disease

CONTEXT: By definition, levels of metabolic risk factors predict atherosclerotic vascular disease, but the effects of long-term adverse change and instability remain underresearched. OBJECTIVE: Our objective was to quantify long-term rates of change and instability in risk factors and relate these measures to clinical atherosclerotic vascular disease outcomes. DESIGN AND SETTING: We conducted a prospective cohort study with unmatched and age- and follow-up-matched control analyses at a teaching hospital day ward. PARTICIPANTS: Participants included 465 predominantly healthy white males in an occupational cohort who had undergone repeated metabolic risk factor measurements (mean observation period 11.6 yr, range 2-28 yr), 62 of whom developed clinical atherosclerotic vascular disease. MAIN OUTCOME MEASURES: Rate of change and instability in metabolic risk factor levels were quantified in each individual by linear regression with time and evaluated as predictors of atherosclerotic vascular disease and coronary and cerebrovascular disease separately. RESULTS: As expected, baseline and/or mean follow-up measures of established risk factors relating to blood pressure, lipid metabolism, and subclinical inflammation were significant predictors. Predictors independent of baseline and mean follow-up levels, confirmed in matched and unmatched analyses, were 1) for atherosclerotic vascular disease, instability in weight (cases vs. controls: 2.9 vs. +2.5%); 2) for coronary heart disease, instability in body mass index (3.0 vs. +2.3%), a decline (-0.041 vs. -0.011 per decade) and instability (19.1 vs. 14.6%) in the high-density lipoprotein/non-high-density lipoprotein cholesterol ratio, declining erythrocyte sedimentation rate, and increasing uric acid; and 3) for cerebrovascular disease, a decline in insulin sensitivity (-0.394 vs. 0.324 per decade). CONCLUSIONS: Within an individual, long-term change in metabolic risk factors, as well as their absolute levels, can be important in atherosclerotic vascular disease.     

Lamivudine/pegylated interferon alfa-2b sequential combination therapy compared with lamivudine monotherapy in HBeAg-negative chronic hepatitis B

BACKGROUND AND AIM: Monotherapy has been proven insufficient in achieving sustained control of chronic hepatitis B. We aimed to assess the efficacy of combined sequential administration of lamivudine and pegylated interferon alfa-2b in patients with hepatitis Be antigen (HBeAg)-negative chronic hepatitis B. METHODS: Eighteen patients were given sequential combination treatment starting with 3 months of lamivudine monotherapy followed by 9 months of pegylated interferon alfa-2b (after a 3-month period of concomitant administration of the two drugs) and 24 patients received lamivudine monotherapy. RESULTS: At the end of treatment, 88.9% of the patients who received sequential combination treatment and 70.8% of those who received lamivudine monotherapy had hepatitis B virus (HBV) DNA levels below 400 copies/mL (P = not significant). At the end of treatment, 72.2% of the patients who received sequential combination treatment and 70.8% of those who received lamivudine monotherapy achieved alanine aminotransferase normalization (P = not significant). After 12 months of follow up, 33.3% of the patients who received sequential combination treatment and 16.7% of those who received lamivudine monotherapy had HBV-DNA levels below 400 copies/mL (P = 0.4). After 12 months of follow up, 72.2% of the patients who received sequential combination treatment and 25.0% of those who received lamivudine monotherapy had normal alanine aminotransferase levels (P < 0.01). Twenty-five percent of the patients in the lamivudine monotherapy group had virological breakthrough compared to none in the sequential combination treatment group (P = 0.06). CONCLUSIONS: Sequential combination treatment is able to improve sustained biochemical response rates and prevent the emergence of lamivudine-resistant mutants in patients with HBeAg-negative chronic hepatitis B.     

Insulin sensitivity assessment with euglycemic insulin clamp in adult beta-thalassaemia major patients

Objective: To assess insulin sensitivity in young adult normoglycemic β‐thalassaemia major patients. Methods: We measured insulin sensitivity with the euglycemic insulin clamp in 10 young adult (mean age 24.85 ± 2.45 yrs) normoglycemic β‐thalassaemia major patients and 10 sex‐ & age‐ matched controls. Liver iron accumulation was assessed by magnetic resonance imaging (MRI). Results: Glucose infusion rate (M) required to maintain euglycemia was significantly reduced in thalassaemic patients compared to controls (261.5 ± 63.5 mg/m²·min vs. 355.6 ± 35.3 mg/m²·min, P = 0.008). Consequently, significantly reduced in the thalassaemic group were also tissue sensitivity to insulin (M/I_s‐s) and glucose metabolic clearance rate (M/G_s‐s). There was significant negative correlation between ferritin levels and glucose infusion rate (r = ?0.918 P = 0.004). No significant correlations were observed between age, body mass index, daily transfusional iron accumulation, liver iron content and any of the euglycemic clamp parameters. Fasting insulin levels were significantly increased in patients with β‐thalassaemia major compared to controls (P = 0.01), and had significant negative correlation to MRI‐derived liver iron content (r = ?0.733, P = 0.03). Conclusions: Our data indicate that reduced insulin sensitivity resulting in hyperinsulinaemia precedes the manifestation of glucose intolerance in patients with β‐thalassaemia major. Insulin resistance seems to correlate with increased serum ferritin levels.     

Effectiveness of an intensive nutritional intervention in patients with type 2 diabetes mellitus: results from a pilot study

The aim of this pilot study was to compare the effects of an intensive nutritional intervention with usual care conditions on dropout rate, body weight, lifestyle changes and glycemic control in patients with type 2 diabetes mellitus (T2DM). Thirty outpatients with T2DM but without insulin treatment (mean age: 57 +/- 9 yr) were randomly assigned to one of the two intervention groups: intensive care (IC) or usual care (UC). Patients in the UC group were given advice about dietary and physical activity goals in one consultation session at baseline, while patients in the IC group attended five goal-oriented consultation sessions held approximately every two weeks from baseline onwards. Changes in body weight, T2DM knowledge, dietary intake, physical activity, HbA1c, and percentage of dropouts were evaluated at 1-year follow-up post-intervention. Fifty percent of patients quitted the program and were classified as "dropouts". Program completers were older and included a lower percentage of newly diagnosed T2DM compared with dropouts. A tendency to a negative association between attendance of the IC group and the likelihood of dropping out was found (p = 0.08). No difference was detected between UC and IC groups regarding changes in body weight, HbA1c or other outcome measures, at post-intervention or 1-year follow-up. This pilot study did not confirm advantages of intensive nutritional intervention in T2DM patients in terms of glycemic control, body weight, diet and physical activity. However, the high dropout rate may have hampered its effectiveness.     

Saving space for less invasive direct-vision, mitral valve surgery with altered cannulation protocol

Saving vital space in less invasive cardiac surgery is of great importance, especially in mitral valve surgery which is sometimes difficult, even with the full sternotomy approach. We present a modification of the venous cannulation protocol we use in less invasive, direct-vision mitral valve surgery through a half-lower partial sternotomy. The superior vena cava is drained with a right jugular vein cannula. For inferior vena cava drainage we use an oval venous cannula which is exteriorized through another small skin incision. These modifications, together with the use of a smaller diameter aortic cannula, provide vital space for surgical maneuvers through a small (810 cm) skin incision.     

Lipoprotein profile,glycemic control and physical fitness after strength and aerobic training in post-menopausal women with type 2 diabetes

We studied the effects on blood lipids and physical fitness after a training program that combined strength and aerobic exercise in postmenopausal women with type 2 diabetes. Ten patients (55.0 ± 5.2 years) followed four exercise sessions per week, two strength and two aerobic, and ten (59.4 ± 3.2 years) served as a control group. Lipid profile, glycated hemoglobin (HbA_1c), HOMA2 index, exercise stress and muscular testing were assessed at the beginning and after 16 weeks of training program. Exercise training increased significantly HDL-C (17.2%; P < 0.001) and decreased triglycerides (18.9%), HbA_1c (15.0%), fasting plasma glucose (5.4%), insulin resistance (HOMA2 25.2%) and resting blood pressure (P < 0.01). After 16 weeks of training, exercise time (17.8%) and muscular strength increased significantly (P < 0.001). The results indicated that a combined strength and aerobic training program could induce positive adaptations on lipid profile, glycemic control, insulin resistance, cardiovascular function, and physical fitness in post-menopausal women with type 2 diabetes. An erratum to this article can be found at     

Hat,shade, long sleeves,or sunscreen? Rethinking US sun protection messages based on their relative effectiveness

Background  

Sun protection messages in the United States emphasize sunscreen use, although its efficacy in skin cancer prevention remains controversial.