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.     

Effects of captopril on hemodynamics and blood gases in chronic obstructive lung disease with pulmonary hypertension

The effects of Captopril, an angiotensin-converting enzyme inhibitor, on pulmonary hemodynamics and blood gases were studied in 9 patients with chronic obstructive lung disease (COLD) and pulmonary hypertension (PA-P greater than 20 mm Hg). Hemodynamic data were recorded prior to Captopril administration (50 mg per os) and for the next 60 min. Following Captopril administration, significant reductions in mean pulmonary artery pressure (PA-P) (p less than 0.05), in mean pulmonary wedge pressure (PW-P) (p less than 0.05), and in total pulmonary resistance (TPR) were noted; significant reductions in mean brachial artery pressure (BA-P) and systemic vascular resistance (SVR) were also recorded, while cardiac output, heart rate and blood gas tensions showed no significant changes. Furthermore, the higher the hypoxemia, the greater was the reduction in BA-P (p less than 0.05). We therefore feel that Captopril, when administered to COLD patients with pulmonary hypertension, may protect the pulmonary circulation from hypoxic pulmonary vasoconstriction.     

Incidence of fever of difficult diagnosis observed from January 1990 to August 1998

Design: We evalueted incidence, period and etiology of the fever of difficult diagnosis (FDD) among 169 cases of fever of unknown origin (FUO) observed from 1-90 to 8-98. Materials and methods: we used the general and orientative diagnostic criteria useful for identifying some pathologies and also for distinguishing between infectious and non infectious fevers. Only as last attempt to solve the problem did we adopt ex-adiuvantibus treatments. Results: FDD incidence was 29.58%; we identified four main categories after detailed diagnostic work up:1) Fictitious fevers and abitual hyperthermia; 2) Systemic vasculitis with atypical clinical features; 3) Rheumatic polymyalgia; 4) Steroid-responder fevers. Conclusion: FDD is not a rare event, but of complicated resolution, some remaining unsolved. Our experience suggests that we consider only a few elements at first to distinguish organic from sine materia fevers: age, history of recent surgery, general clinical picture and aspecific indexes of inflammation.     

Action of vitamin D and E on the erythrocyte membrane. II. Morphological changes in the erythrocytes studied by transmission electron microscopy]

Man, rabbit, guinea-pig erythrocytes treated "in vitro" with high doses of cholecalcipherol or alpha-tocopherol release K+ and haemoglobin and show ultrastructural damages. These damages consist in a change of the red cells profile as well as in the desappearance of the glycocalix, in alterations of the membrane and of the cortical cytoplasm structure. These ultrastructural alterations are of a different degree, depending on the animal species; they partly resemble the erythrocyte changes induced by retinol. Our results are in partial agreement with the Dingle and Lucy's hypothesis on the common action of liposoluble vitamines on the erythrocyte membrane.     

Microdiscectomy in the treatment of lumbar disc herniation

The authors report their experience with short- and medium-term microdiskectomy for the treatment of lumbar disc herniation. It is based on 760 operations performed between 1985 and July 1999: expulsed hernias and those of large size with intense pain symptoms and/or neurologic deficit were treated. During the same period of time, the authors used enzymatic and percutaneous nucleolysis according to Onik for smaller hernias. The incidence of satisfactory results was high (90.1%), in agreement with the results published in the literature. There was a low incidence of complications (4.6%), and of these 2.8% had a benign spontaneous evolution; 1% was prevented during surgery, 0.5% was prevented with subsequent surgery, while only 0.2% was the cause of definitive failure. Unsatisfactory results were constituted by the sequelae of complications (1 discitis, 4 liquoral cysts, 1 error in level not diagnosed intraoperatively), stenosis of the lateral recess not diagnosed pre- or intraoperatively, and thus not treated; in 6.1% of cases there was no plausible justification. The microsurgical technique above all reduces the duration of hospitalization (5 days on the average, but with 91% of cases dismissed on day 3), and allows for a rapid return to work activity (after 63 days for patients who are not employees, but with a return after 20 days in 95% of cases).     

Gastrointestinal haemorrhage due to erosion of the duodenal wall by a biliary stent

Complications from improperly placed biliary stents are not uncommon. Free loose wires from the ends of an uncovered stent can irritate and damage adjacent mucosal surfaces. Effective management can be achieved via percutaneous placement of a second stent to alter the orientation of the original stent.     

Informant ratings of cognitive decline of elderly people: relationship to longitudinal change on cognitive tests

Formal assessment of cognitive decline with cognitive tests can be difficult, requiring either two measurement points or a comparison of 'hold' with 'don't hold' tests. Informant-based assessment provides an alternative approach because informants can adopt a longitudinal perspective and directly rate cognitive change. A study was carried out to assess the validity of informant ratings collected by means of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). A community sample of 500 subjects aged 74 or over underwent four cognitive tests on two occasions 3½ years apart. On the second occasion, informants filled out the IQCODE. Subjects rated as having moderate or severe decline were found to have greater change on the cognitive tests. These findings support the validity of informant ratings of cognitive decline.     

Restriction of cell lysis by homologous complement: II. Protection of erythrocytes against lysis by newly activated complement

Our previous work revealed that homologous complement (C) was ineffective in lysing antibody-sensitized erythrocytes (EA) even at high concentrations. It was also shown that activation of complement on homologous EA resulted in the binding of C9 and the formation of EA bearing complement proteins C1 through C9 (EAC1-9), yet few hemolytic sites were formed. Instead, as shown here, the formation of homologous EAC1-9 caused the cells to become resistant to lysis even by heterologous complement during a second incubation. In contrast, when homologous EAC1-8 were produced by incubating EA with C9-depleted serum, such intermediates were not protected against lysis by heterologous complement during a second incubation. Furthermore, homologous C9 on EAC1-9 was able to reduce the hemolytic efficiency of heterologous complement without blocking C activation and the formation of new C5b-9 complexes. Protection was not modified when homologous EAC1-9 were produced in one step, by incubation of EA with serum, or sequentially by adding C9 to EAC1-8. The minimum number of 9-sites required to confer a protective effect on EAC1-9 was less than 200 per cell. Thus, in addition to its known effect in heterologous cell killing, homologous C9 is capable of protecting homologous cells against inadvertent complement lysis.