Angiotensin II type 1a receptor signals are involved in the progression of heart failure in MLP-deficient mice.

BACKGROUND: Angiotensin II (AT) is implicated in the development of cardiac remodeling, which leads to heart failure, and pharmacological inhibition of the AT type 1 (AT1) receptor has improved mortality and morbidity in patients of heart failure. The aim of this study was to elucidate the role of the AT1 receptor in disease progression in muscle LIM protein (MLP)-deficient mice, which are susceptible to heart failure because of defective function of mechanosensors in cardiomyocytes. METHOD AND RESULTS: Hearts from MLP knockout (MLPKO) mice and MLP-AT1a receptor double knockout (DKO) mice were analyzed. MLPKO hearts showed marked chamber dilatation with cardiac fibrosis and reactivation of the fetal gene program. All of these changes were significantly milder in the DKO hearts. Impaired left ventricular (LV) contractility and filling were alleviated in DKO hearts. However, the impaired relaxation and downregulated expression of sarcoplasmic reticulum calcium-ATPase 2 were unchanged in DKO hearts. CONCLUSIONS: The AT1a receptor is involved in progression of LV remodeling and deterioration of cardiac function in the hearts of MLPKO mice. These results suggest that blockade of the receptor is effective in preventing progression of heart failure in dilated cardiomyopathy.     

Rotationplasty for limb salvage in the treatment of malignant tumors: a report of two cases

Limb salvage is now more common than amputation after radical excision to treat malignant tumors. In a skeletally immature patient who has malignant tumors in a lower extremity, rotationplasty offers a more reliable and durable option than other limb salvage procedures. It is an excellent method of resolving the problem of unequal leg lengths, and preserves best limb function with few complications. Here, we present our experience with rotationplasty for limb salvage in the treatment of malignant tumors, with good functional results seen in follow-up examination 11 years after surgery.     

Rosiglitazone improves insulin sensitivity and glucose tolerance in subjects with impaired glucose tolerance

OBJECTIVE: This study was designed to evaluate the effects of rosiglitazone (ROS) on insulin sensitivity, beta-cell function, and glycaemic response to glucose challenge and meal in subjects with impaired glucose tolerance (IGT). METHODS: Thirty patients with IGT (ages between 30 and 75 years and BMI (body mass index) < or = 27 kg/m2) were randomly assigned to receive either placebo (n = 15) or ROS (4 mg/day) (n = 15). All participants underwent a 75-g oral glucose tolerance test (OGTT), meal test, and frequently sampled intravenous glucose tolerance test (FSIGT) before and after the 12-week treatment. RESULTS: After 12 weeks of ROS treatment, there were significant increases in total cholesterol (TC) (4.25 +/- 0.22 vs 4.80 +/- 0.17 mmol/l, P < 0.001), high-density lipoprotein cholesterol (HDL-C) (1.25 +/- 0.07 vs 1.43 +/- 0.06 mmol/l, P < 0.05), and low-density lipoprotein cholesterol (LDL-C) (2.70 +/- 0.15 vs 3.37 +/- 0.17 mmol/l, P < 0.05) without changes in triglyceride concentration, TC/HDL-C and LDL-C/HDL-C ratio. Although the acute insulin response (AIR) to intravenous glucose and disposition index (measured as the ability of pancreatic beta-cell compensation in the presence of insulin resistance) remained unchanged, the insulin sensitivity (SI) and glucose effectiveness (SG) were remarkably elevated (0.38 +/- 0.06 vs 0.54 +/- 0.09 x 10(-5) min(-1)/pmol, P < 0.05; 0.017 +/- 0.002 vs 0.021 +/- 0.001 min(-1), P < 0.05, respectively) in the ROS group. The glucose, insulin, and c-peptide areas under curve (AUC) in response to OGTT and the glucose and insulin AUC during meal were significantly ameliorated in the ROS group. Five out of 15 (33%) and two out of 15 (13%) subjects treated with ROS and placebo, respectively, reversed to normal response during OGTT (P < 0.05). CONCLUSION: Rosiglitazone treatment significantly improved insulin resistance and reduced postchallenge glucose and insulin concentrations in patients with impaired glucose tolerance without remarkable effects on beta-cell secretory function.     

Mild Gestational Diabetes Mellitus and Long-Term Child Health

OBJECTIVETo evaluate whether treatment of mild gestational diabetes mellitus (GDM) confers sustained offspring health benefits, including a lower frequency of obesity.RESULTSFive hundred of 905 eligible offspring (55%) were enrolled. Maternal baseline characteristics were similar between the follow-up treated and untreated groups. The frequencies of BMI ≥95th (20.8% and 22.9%) and 85th (32.6% and 38.6%) percentiles were not significantly different in treated versus untreated offspring (P = 0.69 and P = 0.26). No associations were observed for BMI z score, log waist circumference, log triglycerides, HDL cholesterol, blood pressure, or log HOMA-estimated insulin resistance (HOMA-IR). The effect of treatment was different by sex for fasting glucose and log HOMA-IR (P for interaction = 0.002 and 0.02, respectively) but not by age-group (5–6 and 7–10 years) for any outcomes. Female offspring of treated women had significantly lower fasting glucose levels.CONCLUSIONSAlthough treatment for mild GDM has been associated with neonatal benefits, no reduction in childhood obesity or metabolic dysfunction in the offspring of treated women was found. However, only female offspring of women treated for mild GDM had lower fasting glucose.     

The predictors of successful percutaneous coronary intervention in ostial left anterior descending artery chronic total occlusion

Background: Percutaneous coronary intervention (PCI) to chronic total occlusion (CTO) has become one of the treatment strategies in recent era. The ostium of the left anterior descending artery (LAD) is one of the most difficult positions for CTO revascularization. Until now, limited data has been made available for the prediction of successful ostial LAD CTO PCI. Objective: The aim of the study was to compare the differences between ostial LAD and all other CTOs and to identify the predictors of successful ostial LAD CTO PCI. Methods: This retrospective analysis included consecutive patients referred for CTO PCI between January 2001 and September 2013. Ostial LAD CTO was defined as CTO at the position whose distance between lesion and left main bifurcation was less than 1 mm. Baseline demographics, lesion characteristics, interventional procedure details, and devices were compared between the ostial LAD group and the all other CTOs group. The predictors of successful ostial LAD CTO PCI were also evaluated. Results: 621 patients who underwent CTO PCI were enrolled retrospectively to this study. A total of 70 patients of ostial LAD CTO were compared with 551 patients of all other CTOs group in this study. Ostial LAD CTO was found to have more bridging and better collaterals than all other CTOs. Procedure time, fluoroscopic time, contrast volumes, the use of contralateral injection, and the use of the retrograde approach were significantly greater in the ostial LAD CTO group. The ostial LAD CTO group also had significantly higher J‐CTO scores (2.7 ± 0.8 vs. 2.2 ± 1.1, P = 0.011) and higher Syntax Scores (28.3 ± 6.5 vs. 20.9 ± 9.7, P < 0.001). A slightly lower final success rate, but statistically non‐significant, was observed in the ostial LAD CTO group (80.0% vs. 81.9%, P = 0.706). Univariate and multivariate logistic regression revealed that without antegrade failure and with retrograde success were predictors of the success of ostial LAD CTO PCI. Syntax Score was also capable of predicting the ostial LAD CTO PCI outcome. J‐CTO score was not found to be associated with final success for ostial LAD CTO patients. Conclusions: Ostial LAD CTO resulted in higher lesion complexity in J‐CTO scores and Syntax Scores. Ostial LAD CTO PCI had a slightly lower final success rate than that of all other CTOs PCI with longer procedure duration, fluoroscopic time and larger contrast volume. Without antegrade failure, with retrograde success, and lower Syntax Score were found to predict the success of ostial LAD CTO PCI. © 2014 Wiley Periodicals, Inc.