Retinol binding protein 4 expression in humans: relationship to insulin resistance, inflammation, and response to pioglitazone

CONTEXT: Retinol binding protein 4 (RBP4) was recently found to be expressed and secreted by adipose tissue, and was strongly associated with insulin resistance. OBJECTIVE: The aim was to determine the relationship between RBP4 and obesity, insulin resistance, and other markers of insulin resistance in humans. DESIGN AND PATIENTS: RBP4 mRNA levels in adipose tissue and muscle of nondiabetic human subjects with either normal or impaired glucose tolerance (IGT) were studied, along with plasma RBP4. RBP4 gene expression was also measured in adipose tissue fractions, and from visceral and sc adipose tissue (SAT) from surgical patients. SETTING: The study was conducted at University Hospital and General Clinical Research Center. INTERVENTION: Insulin sensitivity (S(I)) was measured, and fat and muscle biopsies were performed. In IGT subjects, these procedures were performed before and after treatment with metformin or pioglitazone. MAIN OUTCOME MEASURES: The relationship between RBP4 expression and obesity, S(I), adipose tissue inflammation, and intramyocellular lipid level, and response to insulin sensitizers was measured. RESULTS: RBP4 was expressed predominantly from the adipocyte fraction of SAT. Although SAT RBP4 expression and the plasma RBP4 level demonstrated no significant relationship with body mass index or S(I), there was a strong positive correlation between RBP4 mRNA and adipose inflammation (monocyte chemoattractant protein-1 and CD68), and glucose transporter 4 mRNA. Treatment of IGT subjects with pioglitazone resulted in an increase in S(I) and an increase in RBP4 gene expression in both adipose tissue and muscle, but not in plasma RBP4 level, and the in vitro treatment of cultured adipocytes with pioglitazone yielded a similar increase in RBP4 mRNA. CONCLUSIONS: RBP4 gene expression in humans is associated with inflammatory markers, but not with insulin resistance. The increase in RBP4 mRNA after pioglitazone treatment is unusual, suggesting a complex regulation of this novel adipokine.     

Thymectomy for myasthenia gravis: prognostic factors in 70 patients

Thymectomy has become increasingly accepted as an efficacious procedure for myasthenia gravis, with high rates of complete clinical remission. Predictors of the response to thymectomy for myasthenia gravis vary in the literature. We retrospectively reviewed the clinical records of 70 patients (63% female; mean age, 38 years) diagnosed with myasthenia gravis from August 1993 to August 2004, to determine the factors predicting outcome. Complications occurred in 20%, but there was no hospital mortality. Complete clinical remission was obtained postoperatively in 47%. Our results indicate that patients with less than 1 year's duration of disease have a better prognosis, and Osserman stages I, IIa, and IIb are also associated with higher clinical remission rates. Female patients have a better prognosis than males, and the younger the patient the better the outcome. Thymectomy is indicated for myasthenia gravis as early as possible in the course of the disease.     

Is Transesophageal Echocardiography Necessary before D.C. Cardioversion in Patients with a Normal Transthoracic Echocardiogram?

PURPOSE: Transesophageal echocardiography has emerged as an accepted approach before D.C. cardioversion for atrial fibrillation. The frequency of atrial thrombi detected on transesophageal echocardiography has varied from 7% to 23%. Many patients undergoing transesophageal echocardiography have had a previous transthoracic echocardiogram. Though transthoracic echocardiography has a low yield for the detection of intracardiac thrombi, it is highly accurate in diagnosing a structurally abnormal heart. The purpose of this study was to assess the frequency of thrombi detected by transesophageal echocardiography in patients with an entirely normal transthoracic echocardiogram and hence the advocacy of a selective approach in performing transesophageal echocardiography in patients undergoing D.C. cardioversion for atrial fibrillation. METHODS: 112 consecutive patients with atrial fibrillation who had undergone transesophageal echocardiography before D.C. cardioversion were evaluated. They all had a transthoracic echocardiogram within the 2 months preceding their transesophageal echocardiogram. Based on their transthoracic echocardiographic study, they were divided into two groups: Group 1 consisted of patients with a normal transthoracic echocardiogram and Group 2, those with an abnormal study. RESULTS: Thrombi or spontaneous echo contrast were found in 14 of 112 patients (16%). All however were detected in Group 2 patients. There was no patient with a normal transthoracic echocardiogram who had thrombus on his/her transesophageal echocardiogram. CONCLUSIONS: Our results suggest that a selective approach may be exercised in the use of transesophageal echocardiography prior to D.C. cardioversion for atrial fibrillation. Patients with an entirely "normal" transthoracic echocardiogram may proceed directly to cardioversion without a precardioversion transesophageal echocardiogram.     

Optical Non-Invasive Glucose Monitoring: Continuous Noninvasive Glucose Monitoring Technology Based on ��Occlusion Spectroscopy��

Background

A truly noninvasive glucose-sensing device could revolutionalize diabetes treatment by leading to improved compliance with recommended glucose levels, thus reducing the long-term complications and cost of diabetes. Herein, we present the technology and evaluate the efficacy of a truly noninvasive device for continuous blood glucose monitoring, the NBM (OrSense Ltd.).

Methods

In vitro analysis was used to validate the technology and algorithms. A clinical study was performed to quantify the in vivo performance of the NBM device. A total of 23 patients with type 1 (n = 12) and type 2 (n = 11) diabetes were enrolled in the clinical study and participated in 111 sessions. Accuracy was assessed by comparing NBM data with paired self-monitoring of blood glucose meter readings.

Results

In vitro experiments showed a strong correlation between calculated and actual glucose concentrations. The clinical trial produced a total of 1690 paired glucose values (NBM vs reference). In the paired data set, the reference glucose range was 40–496 mg/dl. No systematic bias was found at any of the glucose levels examined (70, 100, 150, and 200 mg/dl). The mean relative absolute difference was 17.2%, and a Clarke error grid analysis showed that 95.5% of the measurements fall within the clinically acceptable A&B regions (zone A, 69.7%; and zone B, 25.7%).

Conclusions

This study indicates the potential use of OrSense''s NBM device as a noninvasive sensor for continuous blood glucose evaluation. The device was safe and well tolerated.