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.     

Die Ausübung medizinischer Berufe im Lichte des EG-Vertrages

Ohne Zusammenfassung Rechtsreferendar Mario Kaufmann, Wiss. Hilfskraft am Lehrstuhl für V?lkerrecht, Europarecht, Europ?isches und Internationales Wirtschaftsrecht (Prof. Dr. Stephan Hobe) an der Universit?t zu K?ln, Neusser Stra?e 285, D-50733 K?ln     

Percutaneous biopsy in evaluation of lung nodules.

Management of an indeterminate pulmonary nodule is a diagnostic challenge that commonly confronts primary care physicians and specialists. Patients often present with this radiographic finding in the course of an unrelated medical evaluation. We examined our institution's experience with percutaneous biopsy of lung nodules to determine the impact of this procedure on overall patient care. Although significant complications are uncommon, the expedience of percutaneous lung biopsy often supplants a surgical opinion prior to initiation of therapy without added diagnostic benefit or cost-savings. Hence, we caution practitioners to use this technique as an adjunct to diagnosis and not a substitute for multidisciplinary care.     

Outcome Following Bariatric Surgery in Super versus Morbidly Obese Patients: Does Weight Matter?

Background: Numerous investigators have attempted to identify prognostic indicators for successful outcome following bariatric surgery. The purpose of this study was to determine whether degree of obesity affects outcome in super obese [>225% ideal body weight (IBW)] versus morbidly obese patients (160-225% IBW) undergoing gastric restrictive/bypass procedures. Methods: Since 1984, 157 patients underwent either gastric bypass or vertical banded gastroplasty. Super obese (78) and morbidly obese (79) patients were followed prospectively, documenting outcome and complications. Results: Super obese patients reached maximum weight loss 3 years following bariatric surgery, exhibiting a decrease in body mass index (BMI) from 61 to 39 kg/m² and an average loss of 42% excess body weight (EBW). Morbidly obese patients had a decrease in BMI from 44 to 31 kg/m² and carried 39% EBW at 1 year. After their respective nadirs, each group began to regain the lost weight with the super obese exhibiting a current BMI of 45 kg/m² (61% EBW) versus 34 kg/m² (52% EBW) in the morbidly obese at 72 months cumulative follow-up. Currently, loss of 50% or more of EBW occurred in 53% of super obese patients versus 72% of morbidly obese (P < 0.01). Twenty-six percent of super obese patients returned to within 50% of ideal body weight (IBW) while 71% of morbidly obese were able to reach this goal (P < 0.01). Co-morbidities and complications related to surgery were similar in each group. Conclusions: Super obese patients have a greater absolute weight loss after bariatric surgery than do morbidly obese patients. Using commonly utilized measures of success based on weight, morbidly obese patients tend to have better outcomes following bariatric surgery.     

Effect of low dietary calcium on bone metabolism in the SENCAR mouse

The SENCAR (sensitive to carcinogenesis) mouse is a unique tool for investigating the interaction between a specific defect in intracellular signaling, dietary calcium, and metabolic bone disease. The SENCAR mouse was developed by selective breeding for enhanced sensitivity to two-stage carcinogenesis. Its major genetic defect, which renders it exquisitely sensitive to stimulation with diacylglycerol or phorbol esters, is in the regulatory domain of protein kinase C, one of the primary intracellular mediators of hormonal effects. At sexual maturity, SENCAR mice are large and have big bones, but our previous pharmacokinetic studies showed that they accumulate lesscalcium under normal conditions and lose more calcium under adverse conditions than do other, standard strains of mice. To histologically define the effect of low dietary calcium on bone metabolism, we performed histomorphometric analysis of tetracycline-labeled sections of femoral bone from male SENCAR mice maintained on calcium-sufficient and calcium-deficient diets during the critical period from 10 to 14 weeks of age. The bone volume, absolute osteoid volume, and mineral apposition rate were lower at 14 than at 10 weeks of age in SENCAR mice fed 0.02 or 0.6% calcium diets. Calcium deficiency increased the architectural disarray and the probability of observing focal discontinuities in the growth plate. Thus, characteristic features of impaired bone metabolism (low bone volume and apposition rate) develop early in SENCAR mice and are exacerbated by low dietary calcium. Detailed examinations of the histology and biochemistry of SENCAR mouse bone will provide insights into the mechanisms by which specific defects in the signal transduction of protein kinase C contribute to impaired bone metabolism.     

Methylmercury poisoning: Long-term clinical,radiological, toxicological,and pathological studies of an affected family

For 3 months in 1969 a family in the United States that included a pregnant mother consumed pork containing methylmercury. Children, aged 20, 13, and 8 years and a neonate, developed severe neurological signs. Twenty-two years later, the 2 oldest had cortical blindness or constricted visual fields, diminished hand proprioception, choreoathetosis, and atentional deficits. Magnetic resonance images showed tissue loss in the calcarine and parietal cortices and cerebellar folia. The youngest had quadriplegia, blindness, and severe mental retradation until their deaths. The brain of the 8-year-old who died at age 30 showed cortical atrophy, neuronal loss, and gliosis, most pronounced in the paracentral and parietooccipital regions. The total mercury level in formalin-fixed, left occipital cortex was 1,974 ng/gm as measured by atomic absorption. Regional brain mercury levels correlated with extent of brain damage. A control patient had 38.5 ng of mercury/gm in the occipital cortex. Systemic organs in the patient and a control subject had comparable mercury levels. In mercury-intoxicated rats, we found that only 5 to 10% of total brain mercury was lost by formalin fixation. Brain inorganic mercury in the patient ranged from 82 to 100%. Since inorganic mercury crosses the blood-brain barrier poorly, biotransformation of methyl to inorganic mercury may have occurred after methylmercury crossed the blood-brain barrier, accounting for its persistence in brain and causing part of the brain damage.