Evaluation of neuropsychomotor development in first grade children and its relation with nutrition

OBJECTIVE: To investigate the neurological performance of elementary school students from the city of Porto Alegre, state of Rio Grande do Sul, Brazil, in order to assess the association of neurological development and nutritional status. METHODS: We carried out an observational, analytical, and crosssectional study on a random and proportional population sample selected out of all first-grade students (n=35,521) in the city of Porto Alegre for a total of 484 children, out of which 64.7% were enrolled in state public schools, 11.9% in city public schools, and 23.4% in private schools. Our sample size allowed for a precision of -/+ 3% (95% confidence interval) for an estimated prevalence of 10% of cortical dysfunction. Children were submitted to individual examinations at the school. We collected data regarding sex, age, color of skin, nutritional status, and school of origin. An informed consent was obtained from the State and City Departments of Education and from the principals of the private schools. Statistical analysis was carried out using the chi-square test and ANOVA. RESULTS: From 11.4% to 38.2% of children presented ENE results lower than expected according to their age. The most affected factors were sensory activity and gnosia (38.2%), and the least affected factor was motor persistence (11.4%). There were no statistically significant differences between boys and girls. We observed an association of children with low height-for-age and weight-for-age and cortical dysfunction. CONCLUSIONS: Chronic malnutrition is a risk factor for brain function performance.     

Irritable bowel syndrome: attrition rates of patients identified at primary care centers during a 50-week period versus those identified in hospitals in a phase II clinical trial

Although most irritable bowel syndrome (IBS) patients are managed in primary care centers, most trials are performed in the hospital setting. A successful recruitment strategy is important for trial completeness and its external validity. To this end, it was important to assess the attrition rates of patients identified at primary care centers and hospitals in this phase II trial conducted in the outpatient clinics of 16 hospitals. IBS patients were identified through review of the centers' files (prescreening). After a 2-week single-blind placebo screening phase, the patients were randomized to receive an investigational drug or a matched placebo for 24 weeks (dose-ranging study). Thereafter, the patients were invited to participate in a 24-week, double-blind extension study. The attrition rates among patients identified at hospitals (group A) and at primary care centers (group B) were compared in each study phase and during the 50-week period by bivariate and multivariate regression analyses. Group A and B patients were identified in 13 hospitals and 51 primary care centers, respectively. Of 1,001 prescreened patients, 302 started the screening phase with attrition rates of 35% (of 132 patients) and 25% (of 170) for groups A and B, respectively (p = 0.054). The attrition rate during the double-blind phase was 14%. Of the 184 patients who completed the dose-ranging study, 39 (group A: 32%; group B: 14%; p = 0.005) did not wish to participate in the extension study. The attrition rate in the extension study was 15%. The overall attrition rates during the 50-week period were 67% and 53% (p = 0.016) for groups A and B, respectively. The multivariate regression analysis showed that the screening phases (p = 0.000) and unwillingness to participate in the extension study (p = 0.007) had the highest impact on attrition rates. We conclude that referring patients identified in primary care centers to hospitals seems appropriate to ensure potentially eligible patients for IBS trials. Patients identified in primary care centers are more likely than those identified in hospitals to participate in a 24-week extension study, which may be due to their positive feelings about being treated in a hospital rather than being referred back to their original primary care center. This strategy may be considered in future trials since, with a reasonably low attrition rate, it would enhance the external validity of the results obtained.     

Clinical prognostic factors for patients with recurrent head and neck cancer: implications for randomized trials

The purpose of our study was to determine the clinical prognostic factors for the duration of the overall survival from recurrence (OSR) in patients with recurrent head and neck squamous-cell carcinoma. We performed a retrospective analysis on 496 patients treated between 1982 and 1993 at the Antoine Lacassagne Center. The significant favorable prognostic factors for the OSR were: initial T(1-2) (p = 0.008), no initial nodal involvement (p = 0.002), no initial chemotherapy exposure (p = 0.002), induction chemotherapy response (p = 0.001), duration of disease-free interval (DFI; p = 0.0001), performance status (PS) 0-1 (p = 0.004) and local-regional recurrence (p = 0.001). In the multivariate analysis, the apparent nonsignificance of all factors apart from the DFI suggested that relevant prognostic factors could be embedded in the DFI. Multivariate analysis was performed after excluding the DFI. The results indicated that local-regional recurrence, PS 0-1 and no initial chemotherapy exposure remained significant favorable prognostic factors for the OSR. The advantages of taking into account such prognostic factors are to eliminate the patient selection bias and to ensure a fairer comparative evaluation of new or already existing agents in recurrent head and neck cancer.     

Synchronous Bilateral Breast Carcinoma in a Patient with Cowden Syndrome: A Case Report with Morphologic,Immunohistochemical and Genetic Analysis

Abstract: Synchronous bilateral breast carcinoma (SBBC) and early onset are important characteristics of hereditary cases. The lifetime risk for breast carcinoma in Cowden syndrome (CS) is estimated to be 25–50%. We reported a 44‐year‐old woman presenting SBBC and characteristic mucocutaneous lesions of CS, confirmed by PTEN gene mutation analysis. Bilateral modified mastectomy and axillary dissection were performed. Histopathologic examination revealed a moderate‐differentiated invasive ductal carcinoma with mixed features of luminal A immunophenotype (Estrogen and/or Progesterone Receptors >50% and/or Ki67 < 30% of positive cells). The skin lesions showed the characteristic findings of tricholemmoma. Lack of PTEN expression was observed in all specimens. Sequencing analysis confirmed the presence of PTEN splice‐acceptor site mutation in intron 8 (c.1027‐2A>G), a germline mutation which had not been previously reported in CS. The patient received adjuvant chemotherapy and tamoxifen for 5 years. After 5 years of follow‐up, she persists recurrence‐free. SBBC with early onset suggests a hereditary predisposition. Thus, analysis of PTEN expression abnormality, easily assessed by immunohistochemistry, may be of clinical value to screen those patients with CS.     

Determination of stress-induced degradation products of cetirizine dihydrochloride by a stability-indicating RP-HPLC method

Background

A new, simple and accurate stability-indicating reverse phase high performance liquid chromatography method was developed and validated during the early stage of drug development of an oral lyophilizate dosage form of cetirizine dihydrochloride.

Methods

For RP-HPLC analysis it was used an Eclipse XDB C8 column 150 mm × 4.6 mm, 5 μm (Agilent columns, Barcelona, Spain) as the stationary phase with a mobile phase consisted of a mixture of 0.2 M K₂HPO4 pH 7.00 and acetonitrile (65:35, v/v) at a flow rate of 1 mL min ⁻¹. Detection was performed at 230 nm using diode array detector. The method was validated in accordance with ICH guidelines with respect to linearity, accuracy, precision, specificity, limit of detection and quantification.

Results

The method results in excellent separation between the drug substance and its stress-induced degradation products. The peak purity factor is >950 for the drug substance after all types of stress, which confirms the complete separation of the drug substance peak from its stress induced degradation products.Regression analysis showed r² > 0.999 for cetirizine dihydrochloride in the concentration range of 650 μg mL ⁻¹ to 350 μg mL⁻¹ for drug substance assay and a r² > 0.999 in the concentration range of 0.25 μg mL⁻¹ to 5 μg mL⁻¹ for degradation products. The method presents a limit of detection of 0.056 μg mL ⁻¹ and a limit of quantification of 0.25 μg mL⁻¹. The obtained results for precision and accuracy for drug substance and degradation products are within the specifications established for the validation of the method.

Conclusions

The proposed stability-indicating method developed in the early phase of drug development proved to be a simple, sensitive, accurate, precise, reproducible and therefore useful for the following stages of the cetirizine dihydrochloride oral lyophilizate dosage form development.     

Effects of Wheat Naturally Contaminated with Fusarium Mycotoxins on Growth Performance and Selected Health Indices of Red Tilapia (Oreochromis niloticus × O. mossambicus)

An 8-week feeding trial was conducted to examine effects of wheat naturally contaminated with Fusarium mycotoxins (deoxynivalenol, DON 41 mg·kg⁻¹) on growth performance and selected health indices of red tilapia (Oreochromis niloticus × O. mossambicus; initial weight = 4.3 g/fish). Five experimental diets were formulated by replacement of clean wheat with naturally contaminated wheat resulting in graded levels of DON and zearalenone (ZEN) (Diet 1 0.07/0.01, Diet 2 0.31/0.09, Diet 3 0.50/0.21, Diet 4 0.92/0.37 and Diet 5 1.15/0.98 mg·kg⁻¹). Groups of 50 fish were randomly allocated into each of 20 aquaria and fed to near-satiety for eight weeks. Growth rate, feed intake and feed efficiency of fish fed the experimental diets decreased linearly with increasing levels of Fusarium mycotoxins (p < 0.05). Although growth depression was associated with feeding diets naturally contaminated with Fusarium mycotoxins, especially DON, no biochemical and histopathological parameters measured in blood and liver appeared affected by Fusarium mycotoxin concentrations of diets (p > 0.05). Though there was no clear evidence of overt DON toxicity to red tilapia, it is recommended that feed ingredients should be screened for Fusarium mycotoxin contamination to ensure optimal growth performance.