Catabolism of newly synthesized decorin in vitro by human peritoneal mesothelial cells.

OBJECTIVE: Previous studies have shown that decorin and biglycan account for over 70% of the proteoglycans (PGs) synthesized by human peritoneal mesothelial cells (HPMCs). Since these PGs are involved in the control of cell growth, cell differentiation, and matrix assembly, we investigated their turnover in cultured HPMCs. METHODS: Confluent HPMCs were metabolically labeled with [35S]-sulfate and the labeled products isolated from the cell medium and the cell layer characterized by sensitivity to bacterial eliminases. Experiments were undertaken with exogenous labeled decorin, and its metabolic state was studied. RESULTS: In a 24-hour labeling period, 75% of the newly synthesized chondroitin sulfate/dermatan sulfate (CS/DS) PGs appeared in the culture medium, the majority of which (90%) was decorin. In the cell layer, protein-free glycosaminoglycan (GAG) chains accounted for 21% of the total CS/DS at 24 hours and exhibited constant specific activity at 12-16 hours. The latter material was turned over with a half-life of approximately 2.5 hours. Exogenous decorin underwent receptor-mediated endocytosis and subsequent intracellular degradation. Uptake but not degradation could be inhibited by heparin. CONCLUSIONS: HPMCs are distinguished by a rapid turnover of decorin. A characteristic metabolic feature is the existence of a large intracellular pool of protein-free DS-GAGs. Understanding the control of decorin turnover in HPMCs might lead to delineation of its potential role in both the physiology and pathophysiology of the membrane in PD patients.     

Evaluating the effectiveness of interventions: exploration of two statistical methods.

Repeated measures designs are often used to evaluate the effectiveness of interventions. In these designs, the outcomes are measured on several occasions before and after implementation of the intervention. Two statistical methods, the repeated measures analysis of variance (RM-ANOVA) and hierarchical linear models (HLM), can be used to analyze the data. The authors provide an overview of the statistical models underlying RM-ANOVA and HLM and discuss the strengths and limitations of each. They propose that the 2 methods are complementary in determining the effectiveness of interventions.     

Insulin resistance Type A and short 5th metacarpals.

BACKGROUND/AIMS: Insulin resistance is associated with a number genetic syndromes and a variety of defects of insulin action. METHODS: We describe three members of an extended family spanning two generations with insulin resistance Type A and short 5th metacarpals. The proband had secondary amenorrhoea, male pattern hair distribution, acne, hirsutism, deep voice, acanthosis nigricans, polycystic ovaries, diabetes, features of acromegaly, raised creatine kinase and triglyceride levels and short 5th metacarpals. Her growth hormone, adrenal steroid and testosterone levels were normal. The proband's daughter had severe acne, hirsutism, acanthosis nigricans, polycystic ovaries, raised triglyceride, glucose and testosterone level short metacarpals and normal insulin receptor gene. The proband's son had a muscular build, raised creatine kinase, hypertriglyceridaemia and short 5th metacarpals. His fasting insulin levels were normal but pro-insulin was raised. RESULT/CONCLUSION: There are many familial and genetic syndromes associated with insulin resistance. This family was diagnosed as having insulin resistance Type A. This family does not conform entirely to any of the previously described syndromes and a number of family members have the phenotype of short 5th metacarpals, which appears to be associated with the features of insulin resistance Type A.     

Reproducibility of the measurement of submucous fibroid protrusion into the uterine cavity using three-dimensional saline contrast sonohysterography.

OBJECTIVE: To determine the intraobserver and interobserver reproducibility of measurement of the percentage of protrusion of submucous fibroids into the uterine cavity using three-dimensional saline contrast sonohysterography (3D-SCSH). METHODS: Women diagnosed with submucous uterine fibroids on B-mode two-dimensional (2D) ultrasound scan were invited to join the study and 3D-SCSH was carried out. 3D volume datasets were stored digitally and were examined later using the technique of planar reformatted sections. The reproducibilities of the measurement of fibroid diameter and protrusion ratio into the uterine cavity (ratio of the size of the segment of the fibroid protruding into the cavity to the total diameter of the fibroid) were examined by two independent observers who were unaware of the initial 2D scan findings. Interobserver reproducibility was assessed by calculating the difference between measurements taken by the two operators (limits of agreement) and interclass correlation coefficient. Intraobserver repeatability was assessed by calculating the difference between two measurements for each variable (limits of agreement) and further expressed as an intraclass correlation coefficient. RESULTS: Thirty-three 3D ultrasound volumes were examined. There was a good agreement between the observers in classifying the fibroids as greater or less than 50% confined to the myometrium (Cohen's kappa 0.81). There was no bias in measurements for both variables either between observers or with repeated measurements by each observer. For fibroid diameter and protrusion ratio the inter- and intraclass correlation coefficients were high (0.984-0.995), with narrow limits of agreement. CONCLUSION: 3D-SCSH is a reproducible method for the quantification of the percentage of a submucous fibroid protruding into the uterine cavity.     

Telmisartan and irbesartan therapy in type 2 diabetic patients treated with rosiglitazone: effects on insulin-resistance, leptin and tumor necrosis factor-alpha.

The aim of our study was to investigate the metabolic effect of telmisartan and irbesartan in subjects treated with rosiglitazone, a well-known insulin-sensitizing drug, in order to clarify the direct metabolic effects of the two former drugs. Patients were enrolled, evaluated, and followed at 3 Italian centers. We evaluated 188 type 2 diabetic patients with metabolic syndrome (94 males and 94 females in total; 49 males and 46 females, aged 56+/-5, treated with telmisartan; and 45 males and 48 females, aged 55+/-4, treated with irbesartan). All had been diabetic for at least 6 months, and glycemic control by the maximum tolerated dietary changes and maximum tolerated dose of oral hypoglycemic agents had been attempted and failed in all cases. All patients took a fixed dose of rosiglitazone, 4 mg/day. We administered telmisartan (40 mg/day) or irbesartan (150 mg/day) in a randomized, controlled, double-blind clinical manner. We evaluated body mass index (BMI), glycemic control (HbA1c fasting plasma glucose and insulin levels [FPG, and FPI, respectively], and homeostasis model assessment [HOMA] index), lipid profile (total cholesterol [TC], low density lipoprotein-cholesterol [LDL-C], high density lipoprotein-cholesterol [HDL-C], and triglycerides [TG]), systolic and diastolic blood pressure (SBP and DBP), tumor necrosis factor-alpha (TNF-alpha), and leptin during the 12 months of this treatment. No BMI change was observed after 6 or 12 months in either group. Significant decreases in HbAlc and FPG were observed after 6 months in the telmisartan group, and after 12 months in both groups. The decrease in HbA1c and FPG at 12 months was statistically significant only in the telmisartan group. A significant decrease in FPI was observed at 12 months in both groups, and this decrease was significantly greater in the telmisartan group. Significant decreases in the HOMA index were observed at 6 and 12 months in both groups, and the decrease in the HOMA index after 12 months was significantly greater in the telmisartan group than in the irbesartan group. Significant changes in SBP, DBP, TC, and LDL-C were observed after 6 and 12 months in both groups. Significant decreases in TNF-alpha and leptin levels were observed after 6 months in the telmisartan group, and after 12 months in both groups. In conclusion, in this study of patients with type 2 diabetes mellitus and metabolic syndrome, telmisartan seemed to result in a greater improvement in glycemic and lipid control and metabolic parameters related to metabolic syndrome compared to irbesartan. These observed metabolic effects of different angiotensin type 1 receptor blockers could be relevant when choosing a therapy to correct metabolic derangement of patients affected by metabolic syndrome and diabetes.     

对慢性心力衰竭患者的心肺运动试验采用非线性分析可提高预测价值：摄氧效率斜率

目的:次极量运动过程中摄氧量(VO2)的降低,妨碍了对慢性心力衰竭(CH F)患者依据峰值运动VO2预测生存情况。摄氧效率斜率(OUES)是对运动的通气反应的非线性描绘,甚至在运动早期就可能反映出异常。作者评价了OUES的生理学意义及其对CH F患者预后信息的潜在价值。方法和结果:243例     

Allergen avoidance in the secondary and tertiary prevention of allergic diseases: does it work?

Although allergen avoidance is widely recommended as part of a secondary and tertiary prevention strategy for allergic diseases, a clear-cut demonstration of its effectiveness is still lacking. Ongoing observational secondary prevention cohorts show that sensitisation to mite can be prevented in the short term by allergen avoidance measures, but further follow-up of these children is needed to show if this effect can be sustained, as well as to ascertain its impact on allergic disease. More well-designed trials are still required before we can give any conclusive advice to our patients. Considering the management of allergy, current evidence suggests that interventions in children (either single or multifaceted) may be associated with some beneficial effect on asthma control, but no conclusive evidence exists regarding rhinitis or eczema. Conversely, there is little evidence to support the recommendation of allergen avoidance methods in adults with asthma and rhinitis. There is a need for an adequately designed trial assessing the effects of a multifaceted intervention in this age group.