Double-blind, Randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: Results from EFECT

Purpose The third-generation nonsteroidal aromatase inhibitors (AIs) are increasingly used as adjuvant and first-line advanced therapy for postmenopausal, hormone receptor-positive (HR +) breast cancer. Because many patients subsequently experience progression or relapse, it is important to identify agents with efficacy after AI failure. Materials and Methods Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT) is a randomized, double-blind, placebo controlled, multicenter phase III trial of fulvestrant versus exemestane in postmenopausal women with HR + advanced breast cancer (ABC) progressing or recurring after nonsteroidal AI. The primary end point was time to progression (TTP). A fulvestrant loading-dose (LD) regimen was used: 500 mg intramuscularly on day 0, 250 mg on days 14, 28, and 250 mg every 28 days thereafter. Exemestane 25 mg orally was administered once daily. Results A total of 693 women were randomly assigned to fulvestrant (n = 351) or exemestane ( n = 342). Approximately 60% of patients had received at least two prior endocrine therapies. Median TTP was 3.7 months in both groups ( hazard ratio = 0.963; 95% CI, 0.819 to 1.133; P = .6531). The overall response rate ( 7.4% v 6.7%; P = .736) and clinical benefit rate ( 32.2% v 31.5%; P = .853) were similar between fulvestrant and exemestane respectively. Median duration of clinical benefit was 9.3 and 8.3 months, respectively. Both treatments were well tolerated, with no significant differences in the incidence of adverse events or quality of life. Pharmacokinetic data confirm that steady-state was reached within 1 month with the LD schedule of fulvestrant. Conclusion Fulvestrant LD and exemestane are equally active and well-tolerated in a meaningful proportion of postmenopausal women with ABC who have experienced progression or recurrence during treatment with a nonsteroidal AI.

Repetitive transcranial magnetic stimulation improve tinnitus in normal hearing patients: a double-blind controlled, clinical and neuroimaging outcome study

Background and purpose: Tinnitus is a frequent disorder which is very difficult to treat and there is compelling evidence that tinnitus is associated with functional alterations in the central nervous system. Targeted modulation of tinnitus-related cortical activity has been proposed as a promising new treatment approach. We aimed to investigate both immediate and long-term effects of low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) in patients with tinnitus and normal hearing. Methods: Using a parallel design, 20 patients were randomized to receive either active or placebo stimulation over the left temporoparietal cortex for five consecutive days. Treatment results were assessed by using the Tinnitus Handicap Inventory. Ethyl cysteinate dimmer-single photon emission computed tomography (SPECT) imaging was performed before and 14 days after rTMS. Results: After active rTMS there was significant improvement of the tinnitus score as compared to sham rTMS for up to 6 months after stimulation. SPECT measurements demonstrated a reduction of metabolic activity in the inferior left temporal lobe after active rTMS. Conclusion: These results support the potential of rTMS as a new therapeutic tool for the treatment of chronic tinnitus, by demonstrating a significant reduction of tinnitus complaints over a period of at least 6 months and significant reduction of neural activity in the inferior temporal cortex, despite the stimulation applied on the superior temporal cortex.

Safety of oral glutamine in the abbreviation of preoperative fasting; a double-blind, controlled, randomized clinical trial

Introduction: No study so far has tested a beverage containing glutamine 2 h before anesthesia in patients undergoing surgery. Objectives: The aim of the study was to investigate: 1) the safety of the abbreviation of preoperative fasting to 2 h with a carbohydrate-L-glutamine-rich drink; and 2) the residual gastric volume (RGV) measured after the induction of anesthesia for laparoscopic cholecystectomies. Methods: Randomized controlled trial with 56 women (42 (17-65) years-old) submitted to elective laparoscopic cholecystectomy. Patients were randomized to receive either conventional preoperative fasting of 8 hours (fasted group, n = 12) or one of three different beverages drunk in the evening before surgery (400 mL) and 2 hours before the initiation of anesthesia (200 mL). The beverages were water (placebo group, n = 12), 12.5% (240 mOsm/L) maltodextrine (carbohydrate group, n = 12) or the latter in addition to 50 g (40 g in the evening drink and 10g in the morning drink) of L-glutamine (glutamine group, n = 14). A 20 F nasogastric tube was inserted immediately after the induction of general anesthesia to aspirate and measure the RGV. Results: Fifty patients completed the study. None of the patients had either regurgitation during the induction of anesthesia or postoperative complications. The median (range) of RGV was 6 (0-80) mL. The RGV was similar (p = 0.29) between glutamine group (4.5 [0-15] mL), carbohydrate group (7.0 [0-80] mL), placebo group (8.5 [0-50] mL), and fasted group (5.0 [0-50] mL). Conclusion: The abbreviation of preoperative fasting to 2 h with carbohydrate and L-glutamine is safe and does not increase the RGV during induction of anesthesia. (Nutr Hosp. 2011;26:86-90) DOI:10.3305/nh.2011.26.1.4993

Supplementation of Vitamin E, Vitamin C, and Zinc Attenuates Oxidative Stress in Burned Children: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

The aim of this study was to investigate the effect of supplementation of vitamin E, vitamin C, and zinc on the oxidative stress in burned children. In a prospective double-blind placebo-controlled pilot study, 32 patients were randomized as no supplementation (n = 15) or antioxidant supplementation (n = 17) groups. Supplementation consisted of the antioxidant mixture of vitamin C (1.5 times upper intake level), vitamin E (1.35 times upper intake level), and zinc (2.0 times recommended dietary allowance) administered during 7 days starting on the second day of admittance into the hospital. Energy requirement was calculated by the Curreri equation, and protein input was 3.0 g/kg of ideal body mass index (percentile 50 degrees). Total antioxidant capacity of plasma and malondialdehyde were used to monitor oxidative stress. The time of wound healing was evaluated as the main clinical feature. Patients (age 54.2 +/- 48.9 months, 65.6% males), who exhibited 15.5 +/- 6.7% of total burn area, showed no differences in age and sex, when compared with controls. Intake of the administered antioxidants was obviously higher in treated subjects (P = .005), and serum differences were confirmed for vitamin E and C, but not for zinc (P = .180). There was a decrease in lipid peroxidation (malondialdehyde level) (P = .006) and an increase in vitamin E concentrations in the antioxidant supplementation group (P = .016). The time of wound healing was lower in the supplemented group (P < .001). The antioxidant supplementation through vitamin E and C and the mineral zinc apparently enhanced antioxidant protection against oxidative stress and allowed less time for wound healing. (J Burn Care Res 2009;30:859-866)

Brazilian version of the Functional Assessment Measure: cross-cultural adaptation and reliability evaluation

The objective of this prospective study was to perform a cross-cultural adaptation of the Functional Assessment Measure (FAM) into Brazilian Portuguese, and to assess the test-retest reliability. The instrument was translated, back-translated, pretested, and reviewed by a committee. The Brazilian version was assessed in 61 brain-injury patients. Intrarater and interrater reliability was verified by a test-retest procedure (intraclass correlation). Intrarater reliability was moderate-to-excellent; interrater reliability was moderate-to-excellent, with the exception of one item. The Brazilian version of the FAM has acceptable test-retest reliability. Results suggest the use of the Brazilian version of the FAM in the Brazilian population, for disability evaluation and outcome assessment. Further research is required to evaluate the psychometric properties of the scale. International Journal of Rehabilitation Research 34:89-91 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Neural response telemetry in patients with the double-array cochlear implant

This study aimed to evaluate the neural response in double-array cochlear implant as well as to describe the refractory recovery and the spread of excitation functions. In a prospective study 11 patients were implanted with the double-array cochlear implant. Neural response telemetry (NRT) was performed intra-operatively. NRT threshold could be registered in 6 of the 11 patients, at least in one electrode. The remaining five patients did not show measurable neural response intra-operatively. It was noted that although recovery and spread of excitation functions could be recorded in all the tested electrodes with measurable neural responses, the responses were shown to be different from the usual register in patients with other etiologies.

Cross-cultural adaptation and validation of a Quality of Life questionnaire: The Nasal Obstruction Symptom Evaluation questionnaire

Background:The Nasal Obstruction Symptom Evaluation (NOSE) instrument is a disease-specific questionnaire for assessing the outcome of an intervention in nasal obstruction in trials. This instrument is only available in the English language and cross-culturally valid questionnaires are very important for all research, including nasal obstruction. The aim of the current study was to reproduce the cross-cultural adaptation process for the NOSE questionnaire in the Portuguese language (NOSE-p). Methodology: Cross-cultural adaptation and validation of the instrument were divided into two stages. Stage I involved four bilingual professionals, an expert committee and the author of the original instrument. In Stage 2, the NOSE-p was tested on 33 patients undergoing septoplasty for internal consistency, test-retest reliability, construct validity. discriminant validity, criterion validity, and response sensitivity. Results: The cross-cultural adaptation process was completed and the NOSE-p was demonstrated to be a valid instrument with satisfactory construct validity. It showed an adequate internal consistency reliability and adequate test-retest reliability. It could discriminate between patients with and without nasal obstruction and it has a high response sensitivity to change. Conclusions: The cross-cultural adaptation and validation process demonstrated to be valid and the NOSE-p proved to be applicable in Brazil.

The effects of topical isoflavones on postmenopausal skin: Double-blind and randomized clinical trial of efficacy

Objective: The aim of this study was to evaluate the effects of estrogen and isoflavones on postmenopausal skin morphological parameters. Study design: A randomized, double-blind, estrogen-controlled trial was performed on postmenopausal women treated in the Gynecology Department of the Federal University of Sao Paulo. This study was designed to analyze the effects of topical administration of estradiol and isoflavones on facial skin for 24 weeks. The participants were divided into two groups: G1-17-betaestradiol 0.01% (n = 18) and G2-isoflavones 40% (genistein 4%, n = 18). Skin biopsies were performed on each patient before and after the treatment. The skin samples were processed for histological analysis, stained with haematoxylin and eosin, and examined using light microscopy. Results: After 24 weeks of treatment, the estradiol group had a significant increase in skin parameters analyzed compared to the isoflavone group and to the baseline measurements: epidermal thickness (a 75% increase in the estrogen group and 20% in the isoflavone group), number of dermal papillae (a rise of 125% with estrogen, no significant gain with isoflavones), fibroblasts (a 123% accretion with estradiol, no significant gain with isoflavones), and vessels (a 77% increase with estrogen and 36% with isoflavones). Conclusion: Our data suggest that estrogens may have a stronger effect on histomorphometrical parameters than isoflavones. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Cross-cultural adaptation and validation of a Brazilian Portuguese version of the chronic pain grade

To verify the reliability and validity of a Brazilian Portuguese version of the chronic pain grade (CPG-Br). Cultural adaptation was made in accordance with established guidelines, with modifications aiming at improving this process. Adaptations were made based on interviews with 45 chronic pain patients from So Paulo city. Validation was studied by concurrent application of the short-form-36 health survey (SF-36) and other questionnaires to 283 participants with chronic pain from the general population. Temporal stability was verified by a second application to 131 individuals. Factor analysis resulted in a two-factor solution with factors named characteristic pain intensity and activity limitation due to pain. Alpha coefficients of 0.78 and 0.70 and intraclass correlation coefficients of 0.76 and 0.72 for each factor indicated good internal consistency and temporal stability. Significant correlations between CPG-Br and SF-36, Roland-Morris disability questionnaire and neck disability index scores were noted. A consistent linear trend was also observed between pain grades and SF-36 scores. Frequency of use of pain medications and of pain-related medical visits increased with pain grade. This Brazilian Portuguese version of the chronic pain grade, tested on a sample of the Brazilian population, demonstrated good reliability and validity.

Profile of Autoantibodies Against Phosphorylcholine and Cross-reactivity to Oxidation-Specific Neoantigens in Selective IgA Deficiency With or Without Autoimmune Diseases

Immunoglobulin A deficiency (IgAD) is considered the most common form of primary immunodeficiency. The majority of IgA-deficient individuals are considered asymptomatic, even though IgAD has been associated with an increased frequency of recurrent infections, allergy, and autoimmune diseases. In this study we evaluate the Natural autoantibodies (NatAbs) reactivity to phosphorylcholine (PC) and to some pro-inflammatory molecules in IgAD with or without autoimmune disorders. We observed that in the absence of IgA there is an enhancement of IgG subclasses functioning as NatAbs against PC. Immunoglobulin G (IgG) against lipopolysaccharide, C-reactive protein, and IgA was found in IgAD, regardless of the autoimmune manifestations. Nonetheless, IgAD patients with autoimmune disease showed significantly higher IgG reactivity against pro-inflammatory molecules, such as cardiolipin, oxidized low-density lipoproteins, and phosphatidylserine, with positive correlation between them. In conclusion, the IgG NatAbs against PC may represent a compensatory defense mechanism against infections and control excess of inflammation, explaining the asymptomatic status in the IgA deficiency.

Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report

Animal and human studies indicate that cannabidiol (CBD), a major constituent of cannabis, has anxiolytic properties. However, no study to date has investigated the effects of this compound on human pathological anxiety and its underlying brain mechanisms. The aim of the present study was to investigate this in patients with generalized social anxiety disorder (SAD) using functional neuroimaging. Regional cerebral blood flow (rCBF) at rest was measured twice using (99m)Tc-ECD SPECT in 10 treatment-naive patients with SAD. In the first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a double-blind procedure. In the second session, the same procedure was performed using the drug that had not been administered in the previous session. Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping. Relative to placebo, CBD was associated with significantly decreased subjective anxiety (p < 0.001), reduced ECD uptake in the left parahippocampal gyrus, hippocampus, and inferior temporal gyrus (p < 0.001, uncorrected), and increased ECD uptake in the right posterior cingulate gyrus (p < 0.001, uncorrected). These results suggest that CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.

Cross-cultural Adaptation, Reliability and Validity of the DAFS-R in a Sample of Brazilian Older Adults

The Direct Assessment of Functional Status-Revised (DAFS-R) is an instrument developed to objectively measure functional capacities required for independent living. The objective of this study was to translate and culturally adapt the DAFS-R for Brazilian Portuguese (DAFS-BR) and to evaluate its reliability and validity. The DAFS-BR was administered to 89 older patients classified previously as normal controls, mild cognitive impairment (MCI) and Alzheimer`s disease (AD). The results indicated good internal consistency (Cronbach`s alpha = 0.78) in the total sample. The DAFS-BR showed high interobserver reliability (0.996; p < .001) as well as test-retest stability over 1-week interval (0.995; p < .001). Correlation between the DAFS-BR total score and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) was moderate and significant (r = -.65, p < .001) in the total sample, whereas it did not reach statistical significance within each diagnostic group. Receiver operating characteristic curve analyses suggested that DAFS-BR has good sensitivity and specificity to identify MCI and AD. Results suggest that DAFS-BR can document degrees of severity of functional impairment among Brazilian older adults.

Self-Esteem, Confidence, and Relationships in Brazilian Men with Erectile Dysfunction Receiving Sildenafil Citrate: A Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Study in Brazil

Psychosocial manifestations of erectile dysfunction (ED) differ across cultures. Understanding the treatment response to ED medications within cultural groups can aid in resource allocation and in developing treatment strategies. Evaluate the effect of sildenafil treatment on self-esteem, confidence, and sexual relationship satisfaction in Brazilian men with ED. The Self-Esteem and Relationship (SEAR) questionnaire, a validated, 14-question instrument developed to specifically address self-esteem and relationship issues within the context of ED. Men aged 18 years or older with a clinical diagnosis of ED (<= 21 on the Sexual Health Inventory for Men) and in a stable relationship with a partner during the study were eligible. The primary end point was a change from baseline in the self-esteem subscale of the SEAR questionnaire. Thirteen Brazilian sites participated in a randomized, double-blind, placebo-controlled trial of sildenafil treatment for ED. Patients were randomized to receive either 50 mg of sildenafil (adjustable to 25 mg or 100 mg based on patient response) or matching placebo approximately 1 hour before anticipated sexual activity but not more than once a day. At the end of double-blind treatment, 63 and 66 patients in the placebo and sildenafil groups, respectively, from 13 Brazilian sites were assessed for efficacy. Brazilian patients receiving sildenafil had significantly greater improvements in their scores on the SEAR self-esteem subscale (42.9 [95% confidence interval 35.7-50.0]) compared with placebo (21.1 [95% confidence interval 13.7-28.6]; P < 0.0001). Effect sizes ranged from 0.91 to 1.25 for individual SEAR components. The psychosocial parameters in Brazilian men with ED assessed by the SEAR questionnaire showed significant improvements in self-esteem, confidence, and relationships after treatment with sildenafil. Glina S, Damiao R, Abdo C, Afif-Abdo J, Tseng L-J, and Stecher V. Self-esteem, confidence, and relationships in Brazilian men with erectile dysfunction receiving sildenafil citrate: A randomized, parallel-group, double-blind, placebo-controlled study in Brazil. J Sex Med 2009;6:268-275.

A cross-sectional study on the clinical and immunological spectrum of human Leishmania (L.) infantum chagasi infection in the Brazilian Amazon region

The objectives of this study were to identify individuals with symptomatic and/or asymptomatic infection due to Leishmania (L.) infantum chagasi; to study the two types of infection, both clinically and immunologically, and to determine the prevalence rate of infection at the beginning of the study. This was a cross-sectional study with a cohort of 946 individuals, of both genders, from the age of 1 year, living in the municipality of Barcarena, PA, Brazil, an area endemic for American visceral leishmaniasis (AVL). The leishmanin skin test (LST) and the indirect fluorescent test (IFAT), were used for the diagnosis of infection. One hundred and twenty cases of infection were diagnosed, with a prevalence rate of 12.6%; eight cases showed high seroreactivity (1280-10240, IgG) in IFAT and no LST reaction; four of these cases were typical AVL and four had subclinical oligosymptomatic infection. Using two immunological methods with a clinical examination of the infected individuals enabled the identification of five clinical-immunological profiles which may promote a better understanding of the interaction between L. (L.) i. chagasi and the human immune response: asymptomatic infection (AI) 73.4%; subclinical resistant infection (SRI) 15%; subclinicat oligosymptomatic infection (SOI) 3%; symptomatic infection (AVL) 3% and indeterminate initial infection (III) 5%. (C) 2009 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Similar Intracellular Peptide Profile of TAP1/beta 2 Microglobulin Double-Knockout Mice and C57BL/6 Wild-Type Mice as Revealed by Peptidomic Analysis

Cells produce and use peptides in distinctive ways. In the present report, using isotope labeling plus semi-quantitative mass spectrometry, we evaluated the intracellular peptide profile of TAP1/beta 2m(-/-) (transporter associated with antigen-processing 1/beta 2 microglobulin) double-knockout mice and compared it with that of C57BL/6 wild-type animals. Overall, 92 distinctive peptides were identified, and most were shown to have a similar concentration in both mouse strains. However, some peptides showed a modest increase or decrease (similar to 2-fold), whereas a glycine-rich peptide derived from the C-terminal of neurogranin (KGPGPGGPGGAGGARGGAGGGPSGD) showed a substantial increase (6-fold) in TAP1/beta 2m(-/-) mice. Thus, TAP1 and beta 2microglobulin have a small influence on the peptide profile of neuronal tissue, suggesting that the presence of peptides derived from intracellular proteins in neuronal tissue is not associated with antigens of the class I major histocompatibility complex. Therefore, it is possible that these intracellular peptides play a physiological role.