l-Arginine supplementation in severe asthma.

BACKGROUNDDysregulation of l-arginine metabolism has been proposed to occur in patients with severe asthma. The effects of l-arginine supplementation on l-arginine metabolite profiles in these patients are unknown. We hypothesized that individuals with severe asthma with low fractional exhaled nitric oxide (FeNO) would have fewer exacerbations with the addition of l-arginine to their standard asthma medications compared with placebo and would demonstrate the greatest changes in metabolite profiles.METHODSParticipants were enrolled in a single-center, crossover, double-blind l-arginine intervention trial at UCD. Subjects received placebo or l-arginine, dosed orally at 0.05 mg/kg (ideal body weight) twice daily. The primary end point was moderate asthma exacerbations. Longitudinal plasma metabolite levels were measured using mass spectrometry. A linear mixed-effect model with subject-specific intercepts was used for testing treatment effects.RESULTSA cohort of 50 subjects was included in the final analysis. l-Arginine did not significantly decrease asthma exacerbations in the overall cohort. Higher citrulline levels and a lower arginine availability index (AAI) were associated with higher FeNO (P = 0.005 and P = 2.51 × 10-9, respectively). Higher AAI was associated with lower exacerbation events. The eicosanoid prostaglandin H2 (PGH2) and Nα-acetyl-l-arginine were found to be good predictors for differentiating clinical responders and nonresponders.CONCLUSIONSThere was no statistically significant decrease in asthma exacerbations in the overall cohort with l-arginine intervention. PGH2, Nα-acetyl-l-arginine, and the AAI could serve as predictive biomarkers in future clinical trials that intervene in the arginine metabolome.TRIAL REGISTRATIONClinicalTrials.gov NCT01841281.FUNDINGThis study was supported by NIH grants R01HL105573, DK097154, UL1 TR001861, and K08HL114882. Metabolomics analysis was supported in part by a grant from the University of California Tobacco-Related Disease Research Program program (TRDRP)

Proliferating cell nuclear antigen expression in mucoepidermoid carcinoma of salivary glands

CONTEXT: Among the cytological and morphological properties of mucoepidermoid carcinoma, one of the most important criteria for measuring its biological behavior and aggressiveness is cell proliferation. In this way, immunohistochemical markers of cell proliferation have been found to be useful in tumor classification and have formed part of the prognostic and therapeutic studies of these pathologies. OBJECTIVE: To analyze 11 cases of mucoepidermoid carcinoma (MEC) using the proliferation activity marker (PCNA) and to determine its relationship to the grade of malignancy of these tumors. DESIGN: Correlation study. SETTING: Head and Neck Surgery Service of Heliópolis Hospital, São Paulo, Brazil. SAMPLE: Slides of 11 cases of primary mucoepidermoid carcinomas of salivary glands were prepared according to routine techniques employed in the Oral Pathology Department of the Dentistry Faculty of São Paulo University, Brazil. They were fixed in a 10% formaldehyde solution and stained with hematoxylin and eosin. After this preparation the tumors were classified as low, intermediate and high grade of malignancy, according to the criteria established by Seifert & Sobin and Auclair, Goode & Ellis. The slides were sent for immunohistochemical processing to evaluate the positivity of proliferating cell nuclear antigen using the streptavidin biotin technique. MAIN MEASUREMENT: The correlation between proliferating cell nuclear antigen expression and the histological malignancy grade in mucoepidermoid carcinoma of salivary glands. RESULTS: there were 4 cases (36%) of low grade, 4 cases (36%) of intermediate grade and 3 cases (27%) of high grade of malignancy. After a comparative study between histological features and immunohistochemical analysis, significant differences were observed (P < 0.01) for low, intermediate and high grades: 16.04%, 26.98% and 56.98% of proliferating cell nuclear antigen expression in mucoepidermoid carcinoma , respectively. CONCLUSION: The proliferating cell nuclear antigen expression increases with the grade of malignancy in mucoepidermoid carcinoma of salivary glands

A quality improvement plan for hypertension control: the INCOTECA Project (INterventions for COntrol of hyperTEnsion in CAtalonia)

<p>Abstract</p> <p>Background</p> <p>Different studies have shown insufficient blood pressure (BP) control in hypertensive patients. Multiple factors influence hypertension management, and the quality of primary care is one of them. We decided therefore to evaluate the effectiveness of a quality improvement plan directed at professionals of Primary Health Care Teams (PHCT) with the aim to achieve a better control of hypertension. The hypothesis of the study is that the implementation of a quality improvement plan will improve the control of hypertension. The primary aim of this study will be to evaluate the effectiveness of this plan.</p> <p>Methods and design</p> <p><it>Design</it>: multicentric study quasi-experimental before – after with control group. The non-randomised allocation of the intervention will be done at PHCT level. </p> <p><it>Setting</it>: 18 PHCT in the Barcelona province (Spain). </p> <p><it>Sample</it>: all patients with a diagnosis of hypertension (population based study). Exclusion criteria: patients with a diagnosis of hypertension made later than 01/01/2006 and patients younger than 18 years. </p> <p><it>Intervention</it>: a quality improvement plan, which targets primary health care professionals and includes educational sessions, feedback to health professionals, audit and implementation of recommended clinical practice guidelines for the management of hypertensive patients. </p> <p><it>Measurements</it>: age, sex, associated co-morbidity (diabetes mellitus type I and II, heart failure and renal failure). The following variables will be recorded: BP measurement, cardiovascular risk and antihypertensive drugs used. Results will be measured before the start of the intervention and twelve months after the start of the study. </p> <p><it>Dependent variable</it>: prevalence of hypertensive patients with poor BP control. </p> <p><it>Analysis</it>: Chi-square test and Student's t-test will be used to measure the association between independent qualitative and quantitative variables, respectively. Non-parametric tests will be used for the analysis of non-normally distributed variables. Significance level (α) will be set at < 0.05. Outcomes will be analysed on an intention-to-treat basis.</p> <p>Discussion</p> <p>The implementation of a quality improvement plan might benefit the coordination of different professionals of PHCTs and may also improve blood pressure control.</p> <p>Trial Registration</p> <p>This protocol has been registered at clinicaltrials.gov with the ID number MS: 1998275938244441.</p