Peter Mandeville

Arsenite-induced formation of hydroxyl radical in the striatum of awake rats

Recent studies on the mechanisms of arsenite toxicity report that some of its effects have been traced to the generation of reactive oxygen species during oxidative stress. In this study we analyze the formation of hydroxyl radicals in the brain of awake, freely moving rats, in order to obtain direct evidence of arsenic-induced oxidative stress in this tissue. We examined the time-course of hydroxyl radical formation in the striatum of both female and male rats who underwent a direct infusion during 60 min of different concentrations of arsenite in that structure through a microdialysis probe. We report here that basal levels of hydroxyl radical production in female rats are significantly higher than those in male rats (91.9+/-16.1 vs. 59.2+/-18.1 pmol/ml, P<0.001) and that the treatment with arsenite induced significant increases of hydroxyl radical formation over basal levels at 50, 100, 200 and 400 microM (95, 98, 98 and 99% increases, respectively, P<0.05 in all cases). The maximal response to 100 microM arsenite is significantly higher in female than in male rats (194.6+/-50.1 female rats and 88.1+/-11.6 pmol/ml male rats, P=0.036). These results support the participation of hydroxyl radicals in arsenic-induced disturbances in the central nervous system.

Comparison of equivalence and determination of diagnostic utility of min-mod and clamp methods for insulin resistance in diabetes free subjects : A meta-analysis ()

The gold standard for quantifying insulin sensitivity (IS) is the hyperinsulinemic-euglycemic clamp (Clamp) with a cut-off point of 5 × 10−2 (dL/min)/(µU/mL) or less to indicate insulin resistance. Bergman’s minimal model (Min-Mod) is also being used to estimate IS, but there are doubts as to its equivalence with Clamp. The objective of the present study is to determine if Clamp and the tolbutamide and insulin techniques of Min-Mod are equivalent. Meta-analysis based on a bibliographic search from 1970 until the present was made for the MeSH terms: insulin resistance, hyperglycemic-clamp, euglycemic-clamp, Min-Mod, minimal model approach. Concordance was determined with both simple and intraclass correlation and Bland and Altman’s concordance limits using R. Three of the 109 articles found were included. The concordance limits indicate that Clamp and Min-Mod are not equivalent, which could result in diagnostic errors if the accepted cut-off point is used for both methods. Given this lack of equivalence, a ROC analysis was performed and new diagnostic cut-off points of 2.4 and 4.6 × 10−2 (dL/min)/(µU/mL) for insulin and tolbutamide techniques of Min-Mod, respectively, are proposed, with adequate sensitivity, specificity, and predictive value. These values should be prospectively validated.

Association of KIR3DL1/S1 and HLA-Bw4 with CD4 T cell counts in HIV-infected Mexican mestizos

Certain genotypic combinations of killer-cell immunoglobulin-like receptors (KIR) and human leukocyte antigens (HLA) have been associated with favourable outcomes after exposure to human immunodeficiency virus in Caucasoid and African populations. Human immunodeficiency virus (HIV) infection is characterized by a rapid exhaustion of CD4 cells, which results in impaired cellular immunity. During this early phase of infection, it is thought that the natural killer (NK) cells represent the main effector arm of the host immune response to HIV. This study investigates whether KIR and HLA factors are associated to CD4 T cell numbers after HIV infection in Mexican mestizos as assessed at the time of initial medical evaluation and subsequent clinical follow-up. KIR and HLA-B gene carrier frequency differences were compared between groups of patients stratified by CD4 T cell numbers as assessed during their first medical evaluation (a point in time at which all patients were anti-retroviral therapy naïve). In addition, the influence that these genetic factors have on averaged historical CD4 cell counts in patients subjected to follow-up (mostly therapy-experienced) was also evaluated. Our results suggest a protective role for the HLA-Bw4 and KIR3D + Bw4 combination in both therapy-naïve and therapy-experienced patients. This report furthers our understanding on the way that immune genes modulate HIV disease progression in less-studied human populations such as the Mexican mestizos with a special focus on CD4 T cell number and behaviour.

Prognostic indications of the failure to treat amoebic liver abscesses

Abstract Objectives: To identify the variables that predict the failure to treat amoebic liver abscesses. Methods: We prospectively carried out a case–control study on a cohort of patients who had been diagnosed with amoebic liver abscesses using clinical, ultrasonic, and serologic methods. Patients with pyogenic abscesses, negative ELISA tests for amoebiasis, immunosuppression status, or previous abdominal surgery were excluded. All patients received metronidazole, and those who demonstrated 4 days of unfavorable clinical responses received percutaneous or surgical draining of the abscess. Demographic, laboratory, and ultrasonographic characteristics were assessed as prognostic indications of failure. Results: Of 40 patients with amoebic liver abscess, 24 (mean age: 36·7±11·2 years) responded to medical treatment and 16 (41·8±11·6 years) required drainage, including 14 patients who underwent percutaneous drainage and two patients who required surgery. The albumin level, abscess volume, abscess diameter, and alkaline phosphatase level were all statistically significant (P<0·05) on the bivariate analysis. The highest (>99%) sensitivity and negative predictive value were observed for an abscess volume >500 ml and diameter >10 cm, while the best specificity and positive predictive value were achieved with the combination of low serum albumin level, high alkaline phosphatase level, and large abscess volume or diameter. Conclusions: The prognostic indications of the failure to treat amoebic liver abscesses include low albumin, high alkaline phosphatase, and large abscess volume or diameter. The combination of these variables is a useful and easy tool for determining appropriate therapy.

Experience with a new design of endoretractor for gasless laparoscopic cholecystectomy.

Background Cholecystectomy has replaced open surgery and is regarded as the standard procedure today. The pneumoperitoneum needed to create working space can induce cardiovascular changes. Gasless laparoscopic surgery is effective; we evaluate a new retractor design. Methods Patients older than 15 years with elective cholecystectomy and American Society of Anesthesiology I-II were consequently assigned to conventional or gasless surgery. We evaluated surgical time, hemodynamic stability, hours of hospital stay, and days of recuperation. Results We analyzed 22 cholecystectomies, 10 by the gasless technique and 12 by gas laparoscopy. We did not observe significant differences in surgical time, length of hospital stay, or days of recuperation. However, surgical exposition time was longer in the retractor group than was expected by chance (P<0.05). Hemodynamic stability was similar between the groups. Conclusions Similar surgical and recuperation times and length of hospital stay were observed. Our design is comparable with conventional laparoscopic surgery despite longer surgical exposition time.

Urinary sediment suggests lupus nephritis histology

Objectives The objective of this paper was to evaluate correlations between kidney biopsy indexes (activity and chronicity) and urinary sediment findings; the secondary objective was to find which components of urinary sediment can discriminate proliferative from other classes of lupus nephritis. Methods Lupus nephritis patients scheduled for a kidney biopsy were included in our study. The morning before the kidney biopsy, we took urine samples from each patient. Receiver operating characteristic (ROC) curves were plotted to determine the area under the curve (AUC) of each test for detecting proliferative lupus nephritis; a classification tree was calculated to select a set of values that best-predicted lupus nephritis classes. Results We included 51 patients, 36 of whom were women (70.6%). Correlations of lupus nephritis activity index with the counts in the urinary sediment of erythrocytes (isomorphic and dysmorphic), acanthocytes, and leukocytes were 0.65 (p < 0.0001) 0.62 (p < 0.0001) and 0.22 (p = 0.1228), respectively. Correlations of lupus nephritis chronicity index with the counts of erythrocytes, acanthocytes, and leukocytes were 0.60 (p ≤ 0.0001), 0.52 (p = 0.0001) and 0.17 (p = 0.2300), respectively. Our classification tree had an accuracy of 84.3%. Conclusions Evaluation of urine sediment reflects lupus nephritis histology.

Effect of Silver Nanoparticle-Added Pit and Fissure Sealant in the Prevention of Dental Caries in Children

OBJECTIVE The objective of this study was to evaluate the effects of pit and fissure sealant mixed with silver nanoparticles on dental caries, by means of monthly measurement of fluorescence with DIAGNOdent over six months. STUDY DESIGN This study was divided in two phases: experimental and clinical. In the experimental phase, the adhesion and microleakage of the pit and fissure sealant experiment were evaluated. Two groups of 10 teeth, without serious carious lesions, were included. Conventional (group A) and silver nanoparticles (group B) were added to the pit and fissure sealant. For the clinical phase, a split-mouth study was performed on 40 children aged 6-10 years old with healthy, erupted permanent first molars. A conventional pit and fissure sealant or a silver nanoparticle-mixed sealant was randomly placed. Repeated measures analysis was performed. RESULTS Conventional sealant presented an average microleakage of 30.6%, and the silver nanoparticle-mixed sealant showed 33.6% (P=NS). A three times greater reduction in fluorescence was found in the silver nanoparticles group compared to the conventional group (P<0.05). No sex- or age-based associations were found. CONCLUSIONS The silver nanoparticle-mixed sealant reduced tooth demineralization significantly and likely increased remineralization, compared to the conventional sealant.

Clinical and Echocardiographic Factors Associated with Right Ventricular Systolic Dysfunction in Hemodialysis Patients

Background: Chronic kidney disease is a disorder of epidemic proportions that impairs cardiac function. Cardiovascular diseases are the leading cause of death in hemodialysis patients, and the understanding of new nontraditional predictors of mortality could improve their outcomes. Right ventricular systolic dysfunction (RVSD) has recently been recognized as a predictor of cardiovascular death in heart failure and hemodialysis patients. However, the factors contributing to RVSD in hemodialysis patients remain unknown. The aim of this study was to evaluate the clinical and echocardiographic factors associated with RVSD in hemodialysis patients. Methods: A cross-sectional study was conducted in which 100 outpatients with end-stage renal disease on chronic hemodialysis were evaluated. A transthoracic echocardiographic examination was performed at optimal dry weight. Right ventricular systolic function was evaluated using tricuspid annular plane systolic excursion (TAPSE). Clinical and echocardiographic data were recorded for each patient. A multivariate linear logistic regression was created using RVSD (TAPSE <14 mm) as the dependent variable. Results: Fifteen patients with RVSD and 85 patients without RVSD were analyzed. TAPSE had a positive correlation with left ventricular ejection fraction (LVEF) and myocardial relaxation velocity. Independent contributors to RVSD were LVEF (OR 1.14, 95% CI 1.05-1.26), left ventricular mass index (OR 1.02, 95% CI 1.00-1.04), and myocardial relaxation velocity (OR 1.81, 95% CI 1.18-3.19). Conclusions: Echocardiographic factors were significant contributors to RVSD. These measurements could be included as part of the routine workup in all end-stage renal disease patients on hemodialysis.