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Robot-assisted hepatobiliary surgery has been steadily growing in recent years. It represents an alternative to the open and laparoscopic approaches in selected patients. Endowristed instruments and enhanced visualization provide important advantages in terms of selective bleeding control, microsuturing, and dissection. Cholecystectomies and minor hepatectomies are being performed with comparable results to open and laparoscopic surgery. Even complex procedures, such as major and extended hepatectomies, can have excellent outcomes, in expert hands. The addition of indocyanine green fluorescence provides an additional advantage for recognition of the vascular and biliary anatomy. Future innovations will allow for expanding its use and indications. Robotic surgery has become a very important component of modern minimally invasive surgery and the development of new robotic technology will facilitate a broader adoption of this technique. [ABSTRACT FROM AUTHOR]

Robot-assisted hepatobiliary surgery has been steadily growing in recent years. It represents an alternative to the open and laparoscopic approaches in selected patients. Endowristed instruments and enhanced visualization provide important advantages in terms of selective bleeding control, microsuturing, and dissection. Cholecystectomies and minor hepatectomies are being performed with comparable results to open and laparoscopic surgery. Even complex procedures, such as major and extended hepatectomies, can have excellent outcomes, in expert hands. The addition of indocyanine green fluorescence provides an additional advantage for recognition of the vascular and biliary anatomy. Future innovations will allow for expanding its use and indications. Robotic surgery has become a very important component of modern minimally invasive surgery and the development of new robotic technology will facilitate a broader adoption of this technique. [ABSTRACT FROM AUTHOR]

Reports on a decoder-based interconnect structure for multi-context field programmable gate arrays (FPGA). Interconnect structure; Performance analysis; Estimation of the latency associated to memories and decoder.

Background: Monitoring adverse events during chemotherapy by clinicians is a standard practice but clinicians may report fewer side-effects or lower symptom severity than patients. Our aim was to compare symptoms self-reported by patients with symptoms registered by clinicians and nurses, to assess validity of a nurse reporting. [ABSTRACT FROM PUBLISHER]

Background: When choosing an antihypertensive drug for patients with hypertension and diabetes mellitus (DM), the metabolic side effects, possibility of improving some metabolic parameters, and need for adequate blood pressure control must all be considered.Objective: The goal of this study was to compare the impacts of perindopril and candesartan on blood pressure, glucose metabolism, serum lipid profile, and metabolic parameters in patients with mild hypertension and type 2 DM during therapy and after a 1-month washout period.Methods: Type 2 DM patients with mild hypertension and good glucose control who were not taking hypercholesterolemic drugs were enrolled. Perindopril 4 mg QD or candesartan 16 mg QD was administered for 12 months in this randomized, double-blind, controlled, parallel-group clinical trial. Fasting plasma glucose (FPG), fasting plasma insulin (FPI), glycosylated hemoglobin, homeostasis model assessment (HOMA) index, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, lipoprotein(a) (Lp[a]), plasminogen activator inhibitor 1 (PAI-1), homocysteine, body mass index (BMI), and albumin excretion rate (AER) were assessed.Results: Ninety-six patients (49 women and 47 men; mean [SD] ages, 53 [10] years [perindopril] and 55 [9] years [candesartan]) were enrolled. Mean (SD) body weight, height, and BMI were 78.2 (9.4) kg, 1.69 (0.05) m, and 27.2 (2.0) kg/m2 in the perindopril group and 77.5 (8.6) kg, 1.70 (0.06) m, and 26.8 (2.5) kg/m2 in the candesartan group. A significant change occurred from baseline to month 12 during treatment with perindopril in SBP and DBP (both P < 0.01), FPG (P < 0.05), FPI (P < 0.05), TC (P < 0.05), LDL-C (P < 0.05), Lp(a) (P < 0.05), PAM (P < 0.05), and AER (P < 0.05). Significant changes from baseline to month 12 occurred with candesartan in SBP and DBP (both P < 0.01) and AER (P < 0.05). The HOMA index was significantly lower at month 12 in the perindopril group than in the candesartan group (P < 0.05). When we interrupted perindopril and candesartan therapy for a 1-month washout period, changes in SBP and DBP values were significant compared with month 12 in both groups (all P < 0.05). Changes in TC and LDL-C from month 12 to the end of washout were significant only in the perindopril group (both P < 0.05).Conclusions: Perindopril and candesartan both effectively lowered blood pressure in this group of patients with mild hypertension and type 2 DM. Perindopril showed an improvement on some metabolic parameters compared with candesartan. However, the inclusion/exclusion criteria could limit the ability to extrapolate the results to a general population. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to assess obese patients with hypercholesterolemia whom were prescribed a standardized diet, comparing the action of orlistat, fluvastatin, orlistat with fluvastatin, and placebo on anthropometric measurements, blood pressure (BP), and lipid profile. METHODS: This was a 1-year, randomized, double-blind, placebo-controlled trial. The patients were prescribed a controlled-energy diet and were randomly allocated to receive placebo, orlistat 120 mg TID (O group), fluvastatin 80 mg/d (F group), or olistat 120 mg TID with fluvastatin 80 mg/d (OF group). Clinical measurements (body weight, body mass index [BMI], waist circumference, and BP) and lipid profile assessment (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides [TGs]) were performed at baseline and after 6 months and 1 year of treatment. RESULTS: The study included 99 obese patients with hypercholesterolemia (48 men and 51 women; mean [SD] age, 51 [9] years). There were no significant differences between groups in baseline demographic, BP, or plasma lipid values. Three patients dropped out (2 women in the O group and 1 man in the OF group) due to adverse events related to orlistat treatment, including gastrointestinal events (oily spotting and fecal urgency). Ninety-six patients completed the study. There were significant differences from baseline (mean [SD]) in BMI, waist circumference reduction (WCR), and body weight loss (BWL) at 6 months in the OF group (29.9 [1.1] kg/m(2), 2.7 [0.8] cm, and 7.4 [0.9] kg, respectively; all P < 0.05), and BMI, WCR, and BWL at 1 year in the O group (29.0 [1.0] kg/m(2), 3.0 [1.0] cm, and 8.6 [1.0] kg, respectively; all P < 0.02), the F group (29.3 [1.6] kg/m(2), 2.4 [1.0] cm, and 8/0 [1.0] kg, respectively; all P < 0.05), and the OF group (28.4 [0.6] kg/m(2), 4.0 [0.6] cm, and 11.4 [1.0] kg, respectively; all P < 0.01). Significant reductions from baseline in systolic and diastolic BP were observed at 1 year in the O and F groups (all P < 0.05) and the OF group (both P < 0.01). At 6 months, there were significant reductions from baseline in TC and LDL-C in the F group (both P < 0.05) and in TC, LDL-C, and TGs in the OF group (P < 0.02, P < 0.02, and P < 0.05, respectively), as well as a significant increase in HDL-C in the OF group (P < 0.02). At 1 year, there were significant reduction from baseline in TC in the O, F, and OF groups (P < 0.05 and P < 0.01, respectively), LDL-C (P < 0.05, P < 0.02, and P < 0.01, respectively), and TGs (P < 0.02, P < 0.05, and P < 0.02, respectively). Also at 1 year, HDL-C was significantly higher than baseline in the F and OF groups (P < 0.02 and P < 0.01, respectively). CONCLUSION: Improvements in clinical and lipid-profile parameters were found at 1 year with all 3 treatments. [ABSTRACT FROM AUTHOR]

BACKGROUND: Repaglinide and glimepiride are relatively new oral hypoglycemic agents. Few data are available concerning their effects on metabolic parameters other than measures of glycemic control. OBJECTIVES: In addition to assessing the effects of repaglinide and glimepiride on glycemic control in patients with type 2 diabetes mellitus, this study also examined the effects of these agents on 3 metabolic parameters known to be cardiovascular risk factors--lipoprotein(a) (Lp[a]), plasminogen activator inhibitor-1 (PAI-1), and homocysteine (Hcy). METHODS: This randomized, placebo-controlled, double-blind trial was conducted at a single center in Italy. Eligible patients were nonsmokers; had no hypertension or coronary heart disease; were taking no hypolipidemic drugs, diuretics, beta-blockers, or thyroxin; and had normal renal function. After an initial 4-week placebo washout period, patients were randomized to receive repaglinide 1 mg/d or glimepiride 1 mg/d. The dose of study drug was optimized over an 8-week titration period, which was followed by a 12-month treatment period. Measures of glycemic control (glycated hemoglobin [HbA1c], fasting plasma glucose [FPG], postprandial plasma glucose [PPG], fasting plasma insulin [FPI], postprandial plasma insulin [PPI]) and the other metabolic parameters of interest were assessed after 6 and 12 months of treatment. RESULTS: One hundred twenty-four patients (63 women, 61 men) completed the study, 62 in each treatment group. There were no significant differences in demographic characteristics between groups. After 6 and 12 months of treatment, FPG levels and HbA1c values were significantly reduced from baseline in both groups (6 months, P < 0.05; 12 months, P < 0.01). After 6 months, PPG levels were significantly decreased only in the repaglinide group (P < 0.05 vs baseline); at 12 months, however, PPG levels were significantly reduced from baseline in both groups (P < 0.01 repaglinide, P < 0.05 glimepiride). No significant changes from baseline in FPI or PPI levels were seen in either group at 6 months, although FPI levels were significantly increased in the repaglinide group at 12 months (P < 0.05). Repaglinide significantly lowered levels of Lp(a), PAI-1, and Hcy after 12 months (all, P < 0.05 vs baseline). Glimepiride significantly lowered levels of Lp(a) and Hcy after 6 months (both, P < 0.05 vs baseline) and levels of Lp(a) (P < 0.01 vs baseline), Hcy (P < 0.01 vs baseline), and PAI-1 (P < 0.05 vs baseline) after 12 months. CONCLUSIONS: Repaglinide and glimepiride improved glycemic control and reduced levels of other metabolic parameters of interest in this population of patients with type 2 diabetes. It is possible that the reductions in Lp(a), PAI-1, and Hcy were the result of improved glucose metabolism; however, the possibility that repaglinide and glimepiride may have a direct effect on these parameters should not be excluded. [ABSTRACT FROM AUTHOR]

Background: Patients with type 2 diabetes mellitus often have other cardiovascular risk factors, and alterations in lipid profile play an important role. The angiotensin-converting enzyme inhibitors are often used in these patients, particularly those with type 2 diabetes and proteinuria.Objective: This study evaluated the effects of fosinopril therapy on fasting plasma glucose (FPG), lipid profile, and lipoprotein(a), or Lp(a), levels in normotensive patients with type 2 diabetes mellitus and microalbuminuria.Methods: Normotensive (systolic blood pressure [SBP] <130 mm Hg and diastolic blood pressure [DBP] <85 mm Hg) patients with type 2 diabetes and microalbuminuria and a normal lipid profile were enrolled. Patients had their diabetes controlled by diet alone or diet plus oral hypoglycemic agents. Fosinopril 10 mg/d was administered for 6 months and then interrupted for 1 month. FPG, glycosylated hemoglobin, SBP, DBP, lipid profile (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides), Lp(a), albumin excretion rate (AER), and creatinine levels were evaluated at baseline; 1, 3, and 6 months after initiation of treatment; and 1 month after interruption of treatment.Results: A total of 120 patients were enrolled (63 men, 57 women; mean age +/- SD, 54 +/- 10 years; duration of diabetes, 7 +/- 2 years). Significant decreases versus baseline were observed in the following parameters at month 6: SBP (122 +/- 7 vs 117 +/- 9.1 mm Hg, P < 0.01), DBP (80 +/- 4.8 vs 74 +/- 4.5 mm Hg, P < 0.05), TC (186 +/- 11 vs 176 +/- 10 mg/dL, P < 0.05), LDL-C (124 +/- 10 vs 114 +/- 11 mg/dL, P < 0.05), Lp(a) (24 +/- 10 vs 19 +/- 7.5 mg/dL, P < 0.05), and AER (103 +/- 45 vs 48 +/- 21 mg/24 hours, P < 0.01). When fosinopril therapy was interrupted for 1 month, the values for all these parameters tended to return to baseline values; SBP, TC, and Lp(a) values were significantly different from month 6 values, whereas DBP, LDL-C, and AER did not change significantly during the washout period.Conclusions: Fosinopril therapy for 6 months resulted in a reduction of microalbuminuria and an improvement in lipid profile and Lp(a) levels in patients with type 2 diabetes. This suggests that fosinopril may improve lipid profile and reduce Lp(a) levels by lowering proteinuria or by other more direct actions on lipid and Lp(a) metabolism. Additional controlled studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, 1515-1523 (2012) Abstract Aim To quantify how much exenatide added to metformin improves β-cell function, and to evaluate the impact on glycaemic control, insulin resistance and inflammation compared with metformin alone. Methods A total of 174 patients with Type 2 diabetes with poor glycaemic control were instructed to take metformin for 8 ± 2 months, then they were randomly assigned to exenatide (5 μg twice a day for the first 4 weeks and forced titration to 10 μg twice a day thereafter) or placebo for 12 months. At 12 months we evaluated anthropometric measurements, glycaemic control, insulin resistance and β-cell function variables, glucagon, adiponectin, high sensitivity-C reactive protein and tumour necrosis factor-α. Before and after 12 months, patients underwent a combined euglycaemic hyperinsulinaemic and hyperglycaemic clamp, with subsequent arginine stimulation. Results Exenatide + metformin gave a greater decrease in body weight, glycaemic control, fasting plasma proinsulin and insulin and their ratio, homeostasis model assessment for insulin resistance (HOMA-IR), and glucagon values and a greater increase in C-peptide levels, homeostasis model assessment β-cell function index (HOMA-β) and adiponectin compared with placebo + metformin. Exenatide + metformin decreased waist and hip circumference, and reduced concentrations of high sensitivity-C reactive protein and tumour necrosis factor-α. Exenatide + metformin gave a greater increase in M value (+34%), and disposition index (+55%) compared with placebo + metformin; first (+21%) and second phase (+34%) C-peptide response to glucose and C-peptide response to arginine (+25%) were also improved by exenatide + metformin treatment, but not by placebo + metformin. Conclusion Exenatide is effective not only on glycaemic control, but also in protecting β-cells and in reducing inflammation. [ABSTRACT FROM AUTHOR]

Background and objective: One of the problems associated with reaching the low-density lipoprotein cholesterol (LDL-C) target during statin treatment is the emergence of laboratory or clinical side effects. The aim of our study was to evaluate the prevalence of statin-associated adverse events in diabetic and non-diabetic patients affected by polygenic hypercholesterolemia or combined hyperlipidemia and the efficacy and tolerability of treatment with ezetimibe/simvastatin 10/10 mg/day on the same subjects experiencing the adverse events. Methods: Consecutively enrolment of patients affected by polygenic hypercholesterolemia or combined hyperlipidemia with or without type 2 diabetes mellitus. Each Centre used any of the available statins on the basis of current clinical judgement and monitored enrolled patients for adverse events during the following 2 years. Those patients with moderate adverse events suspended the current statin therapy for 1 month (washout period), and then were shifted to treatment with ezetimibe/simvastatin 10/10 mg/day and again monitored for adverse events in the following 6 months. We assessed body mass index, glycated haemoglobin, fasting plasma glucose, total cholesterol, LDL-C, high-density lipoprotein cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, creatinine phosphokinase and monitored adverse events such as asthenia and myalgia. Results and discussion: All 1170 Caucasian patients affected by polygenic hypercholesterolemia obtained a significant reduction in LDL-C during the observation period ( P < 0·05), while those with combined hyperlipidemia also showed a reduction in TG plasma level ( P < 0·05) and a significant increase in HDL-C ( P < 0·05). Patients affected by polygenic hypercholesterolemia experiencing adverse event under statin treatment obtained a significantly lower reduction than those tolerating the treatment ( P < 0·001). The prevalence of adverse events under statin treatment was 4·9% in non-diabetic patients with polygenic hypercholesterolemia, 8·6% in those with combined hyperlipidemia, 7·1% in diabetic patients with polygenic hypercholesterolemia and 7·6% in those with combined hyperlipidemia. Six months after the shift to treatment with ezetimibe/simvastatin 10/10 mg, all patients experienced a significant improvement in LDL-C, TG and HDL-C plasma level. No adverse event was registered during the ezetimibe/simvastatin 10/10 mg treatment period. It seems that previous side effects observed with statins did not re-appear with the administration of ezetimibe/simvastatin 10/10 mg/day. Conclusions: The efficacy and adverse effect profile of the ezetimibe and simvastatin combination appear to be good for both diabetic and non-diabetic patients, and in both conditions. [ABSTRACT FROM AUTHOR]

The data reported in literature revealed a novel function for matrix metalloproteinases (MMPs) as modulators of adipogenesis. However, their expression profile and role in the cellular microenvironment during obesity-mediated adipose tissue development remain poorly defined. The authors hypothesized that MMP-2 and MMP-9 levels might be abnormal in obesity, reflecting alterations in extracellular matrix (ECM) turnover. One hundred and sixty three obese patients and 165 controls were enrolled. The following were measured: body mass index (BMI), waist circumference (WC), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment (HOMA) index, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (Tg), lipoprotein(a) (Lp(a)), and plasma levels of MMP-2 and MMP-9. A significant increase of BMI and WC (p< .0001) was observed in obese patients. No FPG change was present in obese group, whereas FPI and HOMA index increases (p< .0001) were obtained in obese patients compared to control subjects. No SBP and DBP variations were observed in obese group. Significant TC and LDL-C increases (p< .0001) were present in obese patients, whereas no HDL-C, Tg, and Lp(a) changes were obtained in both groups. MMP-2 and MMP-9 levels were significantly higher in obese group (p< .0001). Plasma levels of MMP-2 and MMP-9 are increased in obese patients which may reflect abnormal ECM metabolism. [ABSTRACT FROM AUTHOR]

Background: Metformin is considered the gold standard for type 2 diabetes treatment as monotherapy and in combination with sulphonylureas and insulin, whereas the combination of metformin with thiazolidinediones is relatively less studied. The aim of the present study was to assess the differential effect on glycaemic metabolism and lipid variables of the combination of metformin plus pioglitazone or metformin plus rosiglitazone in diabetic patients with metabolic syndrome. Methods: All patients began metformin and were randomized to receive pioglitazone or rosiglitazone for 12 months. We assessed body mass index, glycated haemoglobin, fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, postprandial plasma insulin, homeostasis model assessment index, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, and apolipoprotein B. Results: Significant decreases in glycated haemoglobin, fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, and postprandial plasma insulin were seen after 9 and 12 months in both groups. Homeostasis model assessment index improved at 12 months in both groups. Significant total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, and apolipoprotein B improvement was observed in pioglitazone group after 12 months, but not in the rosiglitazone group. These variations were significant between groups. Conclusion: The combination of metformin plus thiazolidinediones was able to improve glycaemic control compared with previous therapy. Pioglitazone was associated with a significant improvement in lipid and lipoprotein variables. [ABSTRACT FROM AUTHOR]

Background and objective: Metformin is considered the gold standard for type 2 diabetes treatment as monotherapy and in combination with sulphonylureas and insulin. The combination of metformin with thiazolidinediones is less well studied. The aim of the present study was to assess the differential effect, and tolerability, of metformin combined with pioglitazone or rosiglitazone on glucose, coagulation and fibrinolysis parameters in patients with type 2 diabetes mellitus and metabolic syndrome. Methods: This 12-month, multicentre, double-blind, randomized, controlled, parallel-group trial was conducted at three study sites in Italy. We assessed patients with type 2 diabetes mellitus (duration ≥6 months) and with metabolic syndrome. All patients were required to have poor glycaemic control with diet, or experienced adverse effects with diet and metformin, administered up to the maximum tolerated dose. Patients were randomized to receive either pioglitazone or rosiglitazone self-administered for 12 months. We assessed body mass index (BMI), glycaemic control [glycosylated haemoglobin (HbA1c), fasting and postprandial plasma glucose and insulin levels (FPG, PPG, FPI, and PPI respectively), 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)], lipoprotein (a) [Lp(a)] and homocysteine (HCT) at baseline and at 3, 6, 9 and 12 months of treatment. Results and discussion: No BMI change was observed at 3, 6, 9 and 12 months in either group. Significant HbA1c decreases were observed at 9 and 12 months in both groups. After 9 and 12 months, mean FPG and PPG levels decreased in both groups. Decreases in FPI and PPI were observed at 9 and 12 months compared with the baseline in both groups. Furthermore, in both groups, the HOMA index improved but only at 12 months. Significant TC, LDL-C, HDL-C, TG improvement was present in the pioglitazone group at 12 months compared with the baseline values, and these variations were significantly different between groups. No TC, LDL-C, TG improvement was present in the rosiglitazone group after 12 months. Significant Lp(a) and HCT improvement was present in the pioglitazone group at 12 months compared with the baseline values, and Lp(a) change was significant compared with the rosiglitazone group. Significant HCT decrease was observed in the rosiglitazone group at the end of the study. In our type 2 diabetic patients, both drugs were safe and effective for glycaemic control and improving HCT plasma levels. However, long-term treatment with metformin plus pioglitazone significantly reduced Lp(a) plasma levels, whereas metformin + rosiglitazone did not. Conclusion: For patients with type 2 diabetes mellitus and metabolic syndrome, combined treatment with metformin and rosiglitazone or pioglitazone is safe and effective, However, the pioglitazone combination also reduced the plasma Lp(a) levels whereas the rosiglitazone combination did not. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although the metabolic effects of the thiazolidinediones have been well studied, there is a lack of comparative data on their effects on certain cardiovascular risk factors, such as elevated plasma levels of lipoprotein (a) (Lp[a]) and homocysteine (Hcy). OBJECTIVE: This study compared the effects of pioglitazone or rosiglitazone added to glimepiride on a range of lipid parameters, focusing on Lp(a) and Hcy, in patients with type 2 diabetes mellitus and the metabolic syndrome. METHODS: This was a multicenter, randomized, controlled, double-blind study in patients with type 2 diabetes and the metabolic syndrome (hypertension [>or=130/85 mm Hg]) and triglyceridemia (>or=150 mg/dL). In addition to glimepiride 4 mg/d, patients received pioglitazone 15 mg QD or rosiglitazone 4 mg QD for 1 year. The primary efficacy variables were change from baseline in body mass index (BMI), glycosylated hemoglobin (HbA(1c)), Lp(a), and Hey. Secondary efficacy measures were changes in fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) concentrations, fasting and postprandial insulin concentrations (FPI and PPI, respectively), the Homeostasis Model Assessment index, and the lipid profile (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides). All these parameters were measured after a 12-hour fast every 3 months for 1 year. Tolerability was assessed based on reported adverse events and laboratory abnormalities at each study visit. RESULTS: Ninety-one white patients with type 2 diabetes and the metabolic syndrome were enrolled, and 87 completed the study (43 men, 44 women; mean [SD] age, 53 [6] years; mean weight, 68.4 [3.3] kg). Mean baseline values for BMI and HbA(1c) were 24.3 (0.8) kg/m(2) and 8.1% (0.8%), respectively. At the end of 1 year, both treatment groups had significant increases from baseline in BMI (4.9% glimepiride + pio glitazone, 6.2% glimepiride + rosiglitazone; P < 0.05). Glimepiride + pioglitazone was associated with the following percent improvements from baseline in measures of glycemic control: -17.1% in HbA(1c), -19.3% in FPG, -17.8% in PPG, -40.1% in FPI, and -22.6% in PPI (all, P < 0.01). The corresponding percent improvements from baseline with glimepiride + rosiglitazone were -16.3%, -19.9%, -15.0%, -44.8%, and -22.1% (all, P < 0.01). There were no significant differences between treatment groups in any of these parameters. The pioglitazone group had significant improvements from baseline in TC (-11.1%), LDL-C (-12.0%), HDL-C (15.0%), and triglycerides (-22.4%) [corrected] (all, P < 0.05), whereas the rosiglitazone group had significant increases in TC (14.9%), LDL-C (16.5%), and triglycerides (17.9%) (all, P < 0.05); the difference between pioglitazone and rosiglitazone was statistically significant (P < 0.05). The change from baseline in Lp(a) was significant in the pioglitazone group, both relative to baseline and compared with the rosiglitazone group (-19.7% vs 0.5%, respectively; P < 0.05 vs baseline and vs rosiglitazone). Changes from baseline in Hey were significant in both the pioglitazone and rosiglitazone groups (-20.2% and -25.0%, respectively; P < 0.05), with no significant difference between groups. Both treatments were well tolerated, and no patients had significant changes in transaminases. CONCLUSIONS: In these patients with type 2 diabetes and the metabolic syndrome, the combinations of glimepiride with pioglitazone and glimepiride with rosiglitazone produced significant improvements in measures of glycemic control, plasma lipids, and homocysteinemia. One year of treatment with the pioglitazone combination was associated with significantly reduced plasma Lp(a) levels compared with the rosiglitazone combination. [ABSTRACT FROM AUTHOR]

Aim: Accumulating evidence suggests that combination therapy using oral antidiabetic agents with different mechanisms of action may be highly effective in achieving and maintaining target blood glucose levels. The aim of our study is to evaluate the differential effect on glucose and lipid parameters of the association between glimepiride plus metformin and rosiglitazone plus metformin in patients affected by type 2 diabetes and metabolic syndrome. Methods: Patients were enroled, evaluated and followed at two Italian centres. We evaluated 99 type 2 diabetic patients with metabolic syndrome (48 males and 47 females; 23 males and 24 females, aged 52 ± 5 with glimepiride; 25 males and 23 females, aged 54 ± 4 with cglitazone). All were required to have been diagnosed as being diabetic for at least 6 months and did not have glycaemic control with diet and oral hypoglycaemic agents such as sulphonylureas or metformin, both to the maximum tolerated dose. All patients took a fixed dose of metformin, 1500 mg/day. We administered glimepiride (2 mg/day) or rosiglitazone (4 mg/day) in a randomized, controlled, double-blind clinical study. We evaluated body mass index (BMI), glycaemic control, lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol and triglycerides] and lipoprotein parameters [apolipoprotein A-I and apolipoprotein B (Apo B)] during 12 months of this treatment. Results: A total of 95 patients completed the study. Significant BMI decrease was observed at 12 months in glimepiride and rosiglitazone group (p < 0.05 and p < 0.01 respectively) as well as of glycated haemoglobin decrease (p < 0.05 and p < 0.01 respectively), mean fasting plasma glucose and postprandial plasma glucose levels (p < 0.05 and p < 0.01 respectively). A decrease in fasting plasma insulin and postprandial plasma insulin at 12 months (p < 0.05 and p < 0.01 respectively) compared with the baseline value in rosiglitazone group was observed. Furthermore, homeostasis model assessment index improvement was obtained only at 9 and 12 months (p < 0.05 and p < 0.01 respectively) compared with the baseline value in rosiglitazone group. Significant TC, LDL-C and Apo B improvement (p < 0.05 respectively) was present in glimepiride group after 12 months compared with the baseline values, and these variations were significant (p < 0.05) between groups. Of the 95 patients who completed the study, 8.5% of patients in glimepiride group and 12.5% of patients in rosiglitazone group had side-effects (p = not significant). Four patients had transient side-effects in glimepiride group and six patients in rosiglitazone group. Altogether, we did not have statistically significant changes in transaminases. Conclusions: The rosiglitazone–metformin association significantly improve the long-term control of all insulin-resistance-related parameters in comparison with the glimepiride–metformin-treated group. On the other side, glimepiride treatment is associated to a slight improvement in cholesterolaemia, not observed in the rosiglitazone-treated patients. [ABSTRACT FROM AUTHOR]

The aim of our study was to comparatively evaluate the efficacy and safety of orlistat and sibutramine treatment in obese hypertensive patients, with a specific attention to cardiovascular effects and to side effects because of this treatment.Patients were enrolled, evaluated and followed at three Italian Centres of Internal Medicine. We evaluated 115 obese and hypertensive patients. (55 males and 60 females; 26 males and 29 females, aged 50 ± 4 with orlistat; 28 males and 30 females, aged 51 ± 5 with sibutramine). All patients took antihypertensive therapy for at least 6 months before the study. We administered orlistat or sibutramine in a randomized, controlled, double-blind clinical study. We evaluated anthropometric variables, blood pressure and heart rate (HR) during 12 months of this treatment.A total of 113 completed the 4 weeks with controlled energy diet and were randomized to double-blind treatment with orlistat (n = 55) or sibutramine (n = 58). Significant body mass index (BMI) improvement was present after 6 (p < 0.05), 9 (p < 0.02), and 12 (p < 0.01) months in both groups, and body weight (BW) improvement was obtained after 9 (p < 0.05) and 12 (p < 0.02) months in both groups. Significant waist circumference (WC), hip circumference (HC) and waist/hip ratio (W/H ratio) improvement was observed after 12 months (p < 0.05, respectively) in both groups. Significant systolic blood pressure (SBP) and diastolic blood pressure (DBP) improvement (p < 0.05) was present in orlistat group after 12 months. Lipid profile[total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and triglycerides] reduction (p < 0.05, respectively) was observed in orlistat group and triglyceride reduction (p < 0.05) in sibutramine group after 12 months. No significant change was observed in sibutramine group during the study. No significant HR variation was obtained during the study in both groups. Of the 109 patients who completed the study, 48.1% of patients in the orlistat group and 17.5% of patients in the sibutramine group had side effects (p < 0.05 vs. orlistat group). Side-effect profiles were different in the two treatment groups. All orlistat side effects were gastrointestinal events. Sibutramine caused an increase in blood pressure (both SBP and DBP) in two patients, but it has been controlled by antihypertensive treatment. The vitamin changes were small and all mean vitamin andβ-carotene values stayed within reference ranges. No patients required vitamin supplementation.Both orlistat and sibutramine are effective on anthropometric variables during the 12-month treatment; in our sample, orlistat has been associated to a mild reduction in blood pressure, while sibutramine assumption has not be associated to any cardiovascular effect and was generically better tolerated than orlistat. [ABSTRACT FROM AUTHOR]

BACKGROUND: Diabetes risk is often complicated by a mixed hyperlipoproteinemia not sufficiently controlled by a single antihyperlipidemic drug; however, there are some concerns about the safety of combined statin and fibrate treatments. OBJECTIVE: The aim of this study was to compare the efficacy and safety profile of fluvastatin + fenofibrate combination therapy and those of fluvastatin monotherapy in the treatment of combined hyperlipidemia, type 2 diabetes mellitus (DM), and coronary heart disease (CHD) (ie, high risk for cardiovascular disease [CVD]). METHODS: This 12-month, randomized, double-blind, controlled trial was conducted at the University of Pavia, Pavia, Italy. Patients aged 18 to 80 years with combined hyperlipidemia, type 2 DM, and CHD were randomly assigned to receive combination therapy with extended-release fluvastatin 80 mg + micronized fenofibrate 200 mg or monotherapy with extended-release fluvastatin 80 mg. All treatments were given in tablet form, once daily with the evening meal, for 12 months. Lipid variables (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) at 6 and 12 months were the primary efficacy variables, and glycemic status (glycosylated hemoglobin [HbA(1c)], fasting plasma glucose, and postprandial plasma glucose levels) at 6 and 12 months was the secondary efficacy variable. Tolerability was assessed using physical examination, including vital-sign assessment, body-weight measurement, electrocardiography, adverse events, and laboratory tests. A pharmacoeconomic analysis of both treatment regimens was also carried out using the incremental cost-effectiveness ratio (ICER). RESULTS: A total of 48 patients (24 men, 24 women; mean [SD] age, 60 [5] years) were enrolled. After 6 months, all primary efficacy variables, except for TG level, showed significant improvements from baseline only in the combination-therapy group (changes: LDL-C, -25%; HDL-C, +12%; and TC, -19%; all, P < 0.05 vs baseline). After 12 months, lipid variables showed significant improvements over baseline in both groups (all, P < 0.05), except for TG in the monotherapy group. Significant changes in LDL-C, HDL-C, and TG were found in the combination-therapy group (-35%, +34%, -32%, respectively) versus the monotherapy group (-25%, +14%, -17%, respectively; all, P < 0.05 between groups). The change from baseline in HbA(1c) level was significant with combination therapy (-12% vs -7%; P < 0.05). Both treatments were well tolerated, with no significant differences in the incidences of adverse events between the 2 groups. The ICER showed that each 1% decrease in LDL-C level achieved with the fenofibrate + fluvastatin combination added a cost of 14.97 Euros/y (US 12.25 US dollars/y), and each 1% increase in HDL-C level added a cost of 7.48 Euros/y (6.12/y US dollars), over the cost of monotherapy. CONCLUSIONS: In this selected sample of patients with combined hyperlipidemia, type 2 DM, and CHD, the combination of extended-release fluvastatin + micronized fenofibrate was associated with a more improved lipid profile than fluvastatin monotherapy, and was a well-tolerated and cost-effective therapeutic choice to treat these patients at high risk for CVD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Angiotensin receptor blockers (ARBs) provide effective blood pressure control. Whereas none of the ARBs appear to affect glucose homeostasis, some ARBs have been associated with a decrease in cholesterolemia. OBJECTIVE: This study was conducted to evaluate blood pressure control glucose homeostasis, and the plasma lipid profile in patients with type 2 diabetes mellitus and mild hypertension during 12 months of treatment with the ARB telmisartan or nifedipine gastrointestinal therapeutic system (GITS). METHODS: In this double-blind trial, patients taking oral hypoglycemic agents were randomized to receive telmisartan 40 mg or nifedipine GITS 20 mg once daily for 12 months. At the time of enrollment, patients were given advice on diet (1400-1600 kcal/d) and exercise (stationary bicycle for > or =30 min, 4 d/wk). Assessments of systolic blood pressure (SBP), diastolic blood pressure, body mass index (BMI), fasting plasma glucose concentrations, glycosylated hemoglobin, fasting plasma insulin concentrations, the homeostasis model assessment of insulin resistance, and the lipid profile were performed at baseline and after 6 and 12 months of treatment. RESULTS: One hundred sixteen patients were divided into 2 age- and sex-matched treatment groups (58 men, 58 women; mean [SD] age, 52.5 [5] years). All patients were in good general health at baseline; had achieved adequate glycemic control with diet and oral hypoglycemic agents; were taking antihypercholesterolemic drugs; and had no evidence of macroangiopathy, microalbuminuria, or neuropathy. There were significant reductions from baseline in seated trough SBP after 12 months of treatment with both telmisartan and nifedipine GITS (from 139 [4] to 132 [4] mm Hg and from 140 [4] to 130 [4] mm Hg, respectively; both, P < 0.01). No change in BMI or glucose metabolism was observed with either treatment. After 12 months, there were significant improvements in concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) with telmisartan (-9% and -11.5%, respectively; both, P < 0.01) compared with nifedipine GITS (-2% and -1.5%). CONCLUSIONS: In this selected sample of patients with type 2 diabetes and mild hypertension, both telmisartan and nifedipine GITS produced significant reductions in blood pressure. Telmisartan was associated with a slight but statistically significant improvement in plasma TC and LDL-C concentrations compared with nifedipine GITS. [ABSTRACT FROM AUTHOR]

BACKGROUND: Glimepiride is approved as monotherapy and in combination with metformin or with insulin, whereas the combination of glimepiride with other antihyperglycemic drugs is under investigation. OBJECTIVE: The aim of this study was to assess the differential effect on glucose and lipid variables and tolerability of the combination of glimepiride plus pioglitazone or rosiglitazone in patients with type 2 diabetes mellitus (DM) and metabolic syndrome. METHODS: This 12-month, multicenter, double-blind, randomized, controlled, parallel-group trial was conducted at 3 study sites in Italy. We assessed patients with type 2 DM (duration, > or =6 months) and with metabolic syndrome. All patients were required to have poor glycemic control with, or to have experienced > or =1 adverse effect (AE) with, diet and oral hypoglycemic agents such as sulfonylureas or metformin, both given up to the maximum tolerated dose. All patients received a fixed oral dose of glimepiride, 4 mg/d divided into 2 doses, self-administered for 12 months. Patients also were randomized to receive oral pioglitazone (15 mg once daily) (G + P group) or oral rosiglitazone (4 mg once daily) (G + R group), self-administered for 12 months. We assessed body mass index (BMI), glycemic control (glycosylated hemoglobin [HbA(1c)], fasting and postprandial plasma glucose and insulin levels [FPG, PPG, FPI, and PPI, respectively], and homeostasis model assessment index), lipid profile (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides [TG]), and lipoprotein variables (apolipoprotein [apo] A-I and apo B) at baseline and at 3, 6, 9, and 12 months of treatment. Treatment tolerability was assessed at each study visit using a thorough interview of patients, and comparisons of clinical and laboratory values to baseline levels. RESULTS: A total of 91 patients were enrolled in the study; 87 patients completed it (G + P group: 24 women, 21 men; mean [SD] age, 53 [6] years; G + R group: 20 women, 22 men; mean [SD] age, 54 [5] years). Patients in the G + P and G + R groups experienced significant increases in mean BMI at 12 months compared with baseline (4.92% and 6.17%, respectively; both, P < 0.05). The combination of glimepiride with pioglitazone or rosiglitazone significantly improved glycemic control in the study patients. At 12 months, we observed a 1.3% improvement in mean values for plasma HbA(1c) concentration (P < 0.01) 19.3% in FPG (P < 0.01), 16.3% in PPG (P < 0.01), 42.4% in FPI ), and 23.3% in PPI (P <0.05); no significant differences were found between treatment groups. Although the G + P group experienced a significant improvement at 12 months in almost all variables of lipid metabolism from baseline (TC, - 11%; LDL-C, -12%; HDL-C, 15%; and apo B, - 10.6% [all, P , 0.05]), the G + R group experienced a significant increase in mostly the lipid risk factors for cardiovascular disease (TC, 14.9%; LDL-C, 16.5%; TG, 17.9%; and apo B, 10.3% [all, P , 0.05]). Overall, no statistically significant changes in plasma aminotransferase activities were observed. Of the 87 patients who completed the study, 6.7% (3/45) of patients in the G + P group and 11.9% (5/42) of patients in the G + R group had transient, mild to moderate AEs that did not cause withdrawal from the trial. CONCLUSION: In this study of patients with type 2 DM and metabolic syndrome who did not respond adequately to, or experienced AEs with, diet and either a sulfonylurea or metformin previously, the combination of glimepiride plus pioglitazone was associated with a significant improvement in lipid and lipoprotein variables, whereas the combination of glimepiride plus rosiglitazone appears to not have had any clinically significant effect on lipid metabolism. [ABSTRACT FROM AUTHOR]

BACKGROUND: A previous study has demonstrated that L-carnitine reduces plasma lipoprotein(a) (Lp[a]) levels in patients with hypercholesterolemia. OBJECTIVE: To test a tolerable Lp(a)-reducing agent in diabetic patients, we assessed the effect of a dietary supplementation of L-carnitine on plasma lipid levels, particularly Lp(a), of patients with type 2 diabetes mellitus (DM) and hypercholesterolemia. METHODS: In this 6-month, randomized, double-masked, placebo-controlled clinical trial, patients were enrolled, assessed, and followed up at the Diabetic and Metabolic Diseases Center of the Department of Internal Medicine and Therapeutics at the University of Pavia, Pavia, Italy. All study patients had newly diagnosed type 2 DM that was managed through dietary restriction alone throughout the study, as well as hypercholesterolemia. Patients were randomized to 1 of 2 groups. One group received L-carnitine, one 1-g tablet BID. The other group received a corresponding placebo. We assessed body mass index, fasting plasma glucose, postprandial plasma glucose, glycosylated hemoglobin, fasting plasma insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein (apo) A-I, apo B, and Lp(a) at baseline and at 1, 3, and 6 months of treatment. RESULTS: This study included 94 patients. The treatment group included 24 men and 22 women (mean [SD] age, 52 [6] years). The placebo group included 23 men and 25 women (mean [SD] age, 50 [7] years). The baseline characteristics of the groups did not differ significantly. The mean (SD) body weight, height, and body mass index were 78.2 (5.8) kg, 1.70 (0.04) m, and 27.3 (2.5) kg/m(2), respectively, in the L-carnitine group and 77.6 (6.4) kg, 1.71 (0.05) m, and 26.8 (2.2) kg/m(2), respectively, in the placebo group. In the treatment group, Lp(a) was significantly reduced at 3 and 6 months compared with baseline (P < 0.05) and P < 0.01, respectively). We observed a significant improvement after 6 months (P < 0.05) in the Lp(a) value in patients taking L-carnitine compared with those taking placebo. Between-group differences in other variables did not reach a level of significance at months 3 and 6. No drug-related adverse events were reported or observed. CONCLUSION: In this preliminary study, after 3 and 6 months, L-carnitine significantly lowered the plasma Lp(a) level compared with placebo in selected hypercholesterolemic patients with newly diagnosed type 2 DM. [ABSTRACT FROM AUTHOR]

A reading time and an ERP experiment conducted in Italian investigated the parser's responses to a syntactic violation (subject-verb number agreement) and to a semantic violation (subject-verb selectional restriction), examining the time course of comprehension processes until sentence end. The reading-time data showed that the syntactic violation was detected earlier than the semantic one and that the two violations differed in the time-course. The ERP data fully supported the reading time data: Syntactic anomalies elicited a left anterior negativity (LAN) and a P600. Semantic anomalies elicited a N400 centred on the parietal sites which started 90 ms later (latency 430 ms) than the LAN. Furthermore, the N400 evoked by the words that followed the target word continued and increased until sentence end. The results are discussed with respect to the hypotheses that the parser constructs distinct syntactic and semantic analyses of a sentence and that this characteristic holds cross-linguistically. The appropriateness of different methodologies to the study of sentence processing is also evaluated. [ABSTRACT FROM AUTHOR]

Cardiovascular and cerebrovascular disease risks are almost doubled when the hypertensive patient is also affected by diabetes mellitus. Lowering of blood pressure markedly decreases the rate of cardiovascular events and renal deterioration in these patients. The aim of this study is to compare glucose homeostasis, serum lipid profile, fibrinolytic activity, albumin excretion rate, and homocysteine in patients with mild hypertension and type II diabetes, during therapy with perindopril and candesartan. A total of 96 patients with type II diabetes according to the American Diabetes Association criteria, who had been diagnosed within the last 6 months and with mild essential hypertension according to the World Health Organization criteria on repeated measurements in the absence of any antihypertensive treatment, were recruited for the study. No subject experienced adverse effects serious enough to warrant discontinuing either drug, but some side effects were manifested: dry cough, abnormal taste, or epigastric discomfort in five patients of the perindopril group and headache, dizziness, or nausea in three patients of the candesartan group.