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.     

Genetic abnormalities and CNS tumors: report of two cases of ependymoma associated with Klinefelter’s Syndrome (KS)

Objects Genetic syndromes associated with ependymoma are uncommon, with the exception of NF2. We describe two cases of ependymoma presenting with Klinefelter’s Syndrome (KS) as co-morbid condition. Materials and methods The first patient was diagnosed for KS during pregnancy; he also presented a thyroid agenesis and a deficit of methyltetrahydrofolate reductase (MTHFR); at 30 months of age he was operated on for a grade II ependymoma of IV ventricle; after a multiple-stage surgery, he underwent oral chemotherapy and stereotactic radiotherapy, but after 15 months he presented a local recurrence and died. The second patient was diagnosed for KS at the age of 16 months; at 10 years of age, due to back pain, he underwent an MRI, which showed a cauda equine tumor. He underwent surgery and radiotherapy. Histology was of mixopapillary ependymoma. Conclusion In a review of literature, various neoplasms have been described in association with KS. To our knowledge, these are the first two cases reported of ependymoma associated to KS. A retrospective study of 44 monoinstitutional ependymoma cases demonstrated association with genetic syndromes in 22%.     

Management of bowel obstruction in advanced and terminal cancer patients

Background: Bowel obstruction is a common and distressing outcomein patients with abdominal or pelvic cancer. Patients and methods: Patients may develop bowel obstructionat any time in their clinical history, with an incidence rangingfrom 5.5% to 42% in ovarian carcinoma and from 10% to 28.4%in colorectal cancer. The causes of the obstruction may be benignpostoperative adhesions, a focal malignant or benign deposit,relapse or diffuse carcinomatosis. The symptoms which are almostalways present are intestinal colic (reported in 72%–76%of patients), abdominal pain due to distension, hepatomegalyor tumor masses (in 92% of patients) and vomiting (68%–100%)of cases. Conclusion: While surgery must remain the primary treatmentfor malignant obstruction, it is now recognised that there isa group of patients with advanced disease or poor general conditionwho are unfit for surgery and require alternative managementto relieve distressing symptoms. A number of treatment optionsare now available for the patient with advanced cancer who developsintestinal obstruction. In this review of the literature, theindications for surgery will be examined, the use of nasogastrictube and percutaneous gastrostomy evaluated and the place ofdrugs for symptom control described. bowel obstruction, advanced and terminal cancer patients     

Clinical epidemiology and survival of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy: Data from the Italian Registry Investigative Neuro AIDS (IRINA)

Human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML) remains a relevant clinical problem even in the era of highly active antiretroviral therapy (HAART). Aims of the study were to analyze clinical and treatment-related features and the survival probability of PML patients observed within the Italian Registry Investigative Neuro AIDS (IRINA) during a 29-month period of HAART. Intravenous drug use, the presence of focal signs, and the involvement of white matter at neuroradiology increased the risk of having PML. A reduced probability of PML was observed when meningeal signs were reported. Patients starting HAART at PML diagnosis and previously naïve for antiretrovirals showed significantly higher 1-year probability of survival (.58), compared to those continuing HAART (.24), or never receiving HAART (.00). Higher CD4 cell count were associated with a higher survival probability (.45). At multivariate analysis, a younger age, higher CD4, starting HAART at PML diagnosis, the absence of previous acquired immunodeficiency syndrome (AIDS)-defining events, and the absence of a severe neurologic impairment were all associated with a reduced hazard of death. The use of cidofovir showed a trend towards a reduced risk of death.     

Acetaldehyde, ethanol and acetone concentrations in blood of alcohol-treated mice receiving aldehyde dehydrogenase-loaded erythrocytes.

Blood levels of acetaldehyde (ACh), ethanol and acetone were investigated in mice treated with ethanol for 6 months and receiving compatible erythrocytes (RBCs) overloaded with aldehyde dehydrogenase (AlDH). Following an acute dose of ethanol, ACh levels were significantly lower in these animals than in alcohol-treated mice receiving AlDH-unloaded RBCs, and were similar to the ACh levels of normal mice. The peak ethanol concentration was higher in normal mice than in both groups of alcohol-treated animals, while acetone concentrations were not significantly different in the three groups of animals.     

The pharmacokinetics of lignocaine in humans during a computer-controlled infusion.

Several types of chronic pain syndromes are effectively treated with sodium channel blockers such as lignocaine. Further investigation of this therapeutic modality would be facilitated by refinement of the parameters describing lignocaine distribution and elimination. This would allow precise lignocaine infusion by a computer-controlled infusion to attain and maintain stable target lignocaine concentrations. Arterial blood samples were obtained at frequent intervals during a computer-controlled infusion of lignocaine in 12 adult human volunteers. Plasma lignocaine concentrations of 1, 2, 3, 4 and 5 microg/ml were targeted for 15 min at each concentration. A three-compartment mammillary pharmacokinetic model best described the resulting concentration vs time profile. A population pharmacokinetic analysis was performed using three different techniques; the two-stage, pooled and mixed effects modelling. There was marked overshoot of the plasma concentration above the target prior to refinement of the pharmacokinetic parameters. The best parameters of a three-compartment mammillary model fit to the measured concentration using the pooled data approach were: V(1) = 7.44, V(2) =11.5 and V(3) = 97.71; Cl(1) = 0.585, Cl(2) = 2.23 and Cl(3) =1.64 l/min. Similarly calculated parameters using NONMEM were V(1) = 6.99, V(2) =12.2 and V(3) =1341; Cl(1) = 0.703, Cl(2) =1.24 and Cl(3) =1.49 l/min. The addition of age as a covariate of the pharmacokinetic parameters improved the model in both cases. Height, lean body mass and body surface area as covariates of the pharmacokinetic parameters did not improve the predicted value of the model. Prospective testing of the pharmacokinetic parameters will be required to define whether they function well. The refinement of pharmacokinetic parameters for the computer-controlled intravenous infusion of lignocaine will facilitate further research in pain therapy. Published lignocaine pharmacokinetic values have a relatively large central volume of distribution, and hence, when implemented as a computer-controlled infusion, result in dramatic overshoot shortly after targeting a higher plasma concentration. In light of the long-lasting pain relief provided by sodium channel blockade in neuropathic pain states, overshoot of plasma concentrations must be avoided if the concentration vs effect relationship is to be defined.     

Reducing the Occupational Risk of Infections for the Surgeon: Multicentric National Survey on More Than 15,000 Surgical Procedures

The objective of this study was to find the incidence of accidental exposures to blood and body fluids among surgeons during operations and to describe their dynamics. A probabilistic model was also used to predict the cumulative 30-year risk to the surgeon of contracting hepatitis B and C viruses (HBV, HCV) or human immunodeficiency virus (HIV) infection and estimate the effect of preventive strategies in reducing this risk. A multicentric prospective survey, based on self-administered questionnaires, was conducted during a period of 6 months in 39 Italian hospitals. An accidental exposure to blood or body fluids occurred in 9.2% of 15,375 operations. In about 2% of procedures a parenteral-type injury, such as actual skin puncture or eye contamination, was suffered by the operating surgeon. A needle-stick injury was the commonest accident, and its occurrence was found to vary with the phase of the procedure and its length. The current lifetime risk of acquiring HBV, HCV, and HIV infection in our regions was estimated to be as high as 42.7%, 34.8%, and 0.54%, respectively. The adoption of preventive strategies is expected to reduce this risk to 21% for HBV, 16.6% for HCV, and 0.23% for HIV infection. Active immunization of surgeons against HBV is strongly recommended. The case is also made for the use of a face-shield combined with a permanent change in our surgical practice capable of reducing the current high rate of parenteral injuries.