Effects of bromazepam in frontal theta activity on the performance of a sensorimotor integration task: A quantitative electroencephalography study

Our objective is to verify the modulatory effects of bromazepam on EEG theta absolute power when subjects were submitted to a visuomotor task (i.e., car driver task). Sample was composed of 14 students (9 males and 5 females), right handed, with ages varying between 23 and 42 years (mean = 32.5 +/- 9.5), absence of mental or physical impairments, no psychoactive or psychotropic substance use and no neuromuscular disorders (screened by a clinical examination). The results showed an interaction between condition and electrodes (p=0.034) in favor of F8 electrode compared with F7 in both experimental conditions (t-test; p=0.001). Additionally, main effects were observed for condition (p=0.001), period (p=0.001) and electrodes (p=0.031) in favor of F4 electrode compared with F3. In conclusion, Br 6 mg of bromazepam may interfere in sensorimotor processes in the task performance in an unpredictable scenario allowing that certain visuospatial factors were predominant. Therefore, the results may reflect that bromazepam effects influence the performance of the involved areas because of the acquisition and integration of sensory stimuli processes until the development of a motor behavior based on the same stimuli. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Use of cholesterol-rich nanoparticles that bind to lipoprotein receptors as a vehicle to paclitaxel in the treatment of breast cancer: pharmacokinetics, tumor uptake and a pilot clinical study

Purpose In animal experiments paclitaxel oleate associated with a cholesterol-rich nanoemulsion concentrated in the neoplastic tissues and showed reduced toxicity and increased antitumor activity compared with paclitaxel-Cremophor EL. Here, a clinical study was performed in breast cancer patients to evaluate the tumoral uptake, pharmacokinetics and toxicity of paclitaxel associated to nanoemulsions. Methods Twenty-four hours before mastectomy [(3)H]paclitaxel oleate associated with [(14)C]-cholesteryl oleatenanoemulsion or [(3)H]- paclitaxel in Cremophor EL were injected into five patients for collection of blood samples and fragments of tumor and normal breast tissue. A pilot clinical study of paclitaxel-nanoemulsion administered at 3-week intervals was performed in four breast cancer patients with refractory advanced disease at 175 and 220 mg/m(2) dose levels. Results T(1/2) of paclitaxel oleate associated to the nanoemulsion was greater than that of paclitaxel (t(1/2) = 15.4 +/- 4.7 and 3.5 +/- 0.80 h). Uptake of the [(14)C]-cholesteryl ester nanoemulsion and [(3)H]- paclitaxel oleate by breast malignant tissue was threefold greater than the normal breast tissue and toxicity was minimal at the two dose levels. Conclusions Our results suggest that the paclitaxel-nanoemulsion preparation can be advantageous for use in the treatment of breast cancer because the pharmacokinetic parameters are improved, the drug is concentrated in the neoplastic tissue and the toxicity of paclitaxel is reduced.

Quantitative Ventricular Neuroendoscopy Performed on the Third Ventriculostomy: Anatomic Study

BACKGROUND: One of the key elements for a successful endoscopic intervention in the ventricular system is the ability to recognize the anatomic structures and use them as a reference. OBJECTIVE: To measure the choroid plexus with endoscopy in the interventricular foramen, together with the structures on the third ventricle floor, and to compare these variables. METHODS: An observational prospective study was carried out on 37 brains of cadavers for which the cause of death was assessed at the Death Check Unit of the University of Sao Paulo in April 2008. This study was done on adults of both sexes with a rigid neuroendoscope. Endoscopic images were recorded, submitted for correction of distortion, and then measured. RESULTS: The measurements of the choroid plexus in the interventricular foramen, laterolateral distance of mammillary bodies, distance from the infundibular recess to the mammillary bodies, and area of the triangle in the tuber cinereum were 1.71 +/- 0.77 mm, 2.23 +/- 0.74 mm, 3.22 +/- 0.82 mm, and 3.69 +/- 2.09 mm(2), respectively. The ventricle floor was opaque in 84% of cases. The internal distance of mammillary bodies was absent in 89%. Associations between the translucent floor of the third ventricle and laterolateral distance of mammillary bodies, internal distance of mammillary bodies, and age were identified. CONCLUSION: Before this research, there was no record of the measurements of the choroid plexus in the interventricular foramen. The remaining variables of the present study show a greater number in normal brains compared with others.

Diagnosis of Mild Cognitive Impairment Revisited after One Year Preliminary Results of a Prospective Study

Background/Aims: The diagnostic stability of mild cognitive impairment (MCI) on short-term follow- up is a key issue in the characterization of this clinical syndrome. We aim to determine the cognitive outcome after 1 year of follow- up in a cohort of older adults. Methods: Baseline clinical and neuropsychological assessments were carried out in older subjects recruited at a tertiary memory clinic. The subjects were reassessed after 1 year of follow- up with the same clinical and neuropsychological protocol. Results: A total of 115 older adults, including MCI (n = 54) and controls (n = 61), underwent baseline and follow- up evaluation. Ten subjects classified as MCI at baseline (23%) resumed normal cognitive function and 13 controls (21%) progressed to MCI upon follow-up (chi(2) = 0.015, d.f. = 1, p = 0.90). The subjects diagnosed as having MCI on both assessments were older (p = 0.002) and had a worse global cognitive performance according to the Cambridge Cognitive Test (p = 0.014). Conclusion: The subjects who maintain the MCI status are older and have a worse baseline cognitive performance as well as multiple cognitive deficits. Copyright (C) 2009 S. Karger AG, Basel

The effects of bromazepam over the temporo-parietal areas during the performance of a visuomotor task: A qEEG study

This study investigated the effects of bromazepam on qEEG when 14 healthy subjects were asked to perform a visuomotor task (i.e., motor vehicle driving task). The subjects were exposed to two experimental conditions: the placebo (PL) and 6 mg of bromazepam (Br 6 mg), following a randomized, double-blind design on different days. Specifically, we observe absolute power extracted from qEEG data for theta band. We expected to see a decrease in absolute theta power in the temporal and parietal areas due to the influence of bromazepam for the experimental group when compared with the placebo group. We found a main effect for the condition factor for electrodes T3, T4, P3 and P4. We also observed a main effect for the period factor for electrodes P3 and P4. We observed that the ingestion of 6 mg of bromazepam induces different patterns in theta power at the temporal and parietal sites. We concluded that 6 mg of bromazepam was an important factor in the fluctuation of the activities in the temporal and parietal areas. We then hypothesize about the specific role of this drug during the execution of a visuomotor task and within the sensorimotor integration process. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

The epidemiology of acute respiratory failure in hospitalized patients: A Brazilian prospective cohort study

Purpose: The purpose of this study was to assess risk factors associated with the development of acute respiratory failure (ARF) and death in a general intensive care unit (ICU). Materials and Methods: Adults who were hospitalized at 12 surgical and nonsurgical ICUs were prospectively followed up. Multivariable analyses were realized to determine the risk factors for ARF and point out the prognostic factors for mortality in these patients. Results: A total of 1732 patients were evaluated, with an ARF prevalence of 57%. Of the 889 patients who were admitted without ARF, 141 (16%) developed this syndrome in the ICU. The independent risk factors for developing ARF were 64 years of age or older, longer time between hospital and ICU admission, unscheduled surgical or clinical reason for ICU admission, and severity of illness. Of the 984 patients with ARF, 475 (48%) died during the ICU stay. Independent prognostic factors for death were age older than 64 years, time between hospital and ICU admission of more than 4 days, history of hematologic malignancy or AIDS, the development of ARF in ICU, acute lung injury, and severity of illness. Conclusions: Acute respiratory failure represents a large percentage of all ICU patients, and the high mortality is related to some preventable factors such as the time to ICU admission. (C) 2011 Elsevier Inc. All rights reserved.

Genetic Analysis of Age-at-Onset for Cardiovascular Risk Factors in a Brazilian Family Study

Background/Aims: Statistical analysis of age-at-onset involving family data is particularly complicated because there is a correlation pattern that needs to be modeled and also because there are measurements that are censored. In this paper, our main purpose was to evaluate the effect of genetic and shared family environmental factors on age-at-onset of three cardiovascular risk factors: hypertension, diabetes and high cholesterol. Methods: The mixed-effects Cox model proposed by Pankratz et al. [2005] was used to analyze the data from 81 families, involving 1,675 individuals from the village of Baependi, in the state of Minas Gerais, Brazil. Results: The analyses performed showed that the polygenic effect plays a greater role than the shared family environmental effect in explaining the variability of the age-at-onset of hypertension, diabetes and high cholesterol. The model which simultaneously evaluated both effects indicated that there are individuals which may have risk of hypertension due to polygenic effects 130% higher than the overall average risk for the entire sample. For diabetes and high cholesterol the risks of some individuals were 115 and 45%, respectively, higher than the overall average risk for the entire population. Conclusions: Results showed evidence of significant polygenic effects indicating that age-at-onset is a useful trait for gene mapping of the common complex diseases analyzed. In addition, we found that the polygenic random component might absorb the effects of some covariates usually considered in the risk evaluation, such as gender, age and BMI. Copyright (C) 2008 S. Karger AG, Basel

Study of the Extent of the Information of Cardiologists from Sao Paulo City, Brazil, Regarding a Low-Prevalence Entity: Brugada Syndrome

Objective: To determine the degree of knowledge that cardiologists from Sao Paulo, Brazil, have regarding a low-prevalent entity associated with a high rate of sudden death-Brugada syndrome. Methods: Two hundred forty-four cardiologists were interviewed by an instrument divided in two parts: in the first, we recorded gender, age, and data related to academic profile. The second-answered only by the professionals that manifested having some degree of knowledge on the syndrome-had 28 questions that evaluated their knowledge. The answers were spontaneous and they did not have a chance to consult. We used uni- and multivariate analysis on the average percentage of right and wrong answers, and the influence of the academic profile. Results: The predominant gender was the male gender (61.1%), the average age was 44.32 +/- 10.83 years, 40% with more than 20 years after obtaining their degree, 44% were educated in public institutions, 69% had a residency in cardiology, 20% had overseas practice, 12% had postdegree, 41% were linked to an educational institution, 24% with publication(s) in an indexed journal, 17.2% were authors of chapters in books, 2.5% had edited books, and 10% were linked to the Brazilian Society of Cardiac Arrhythmias. The average percentage of right answers was 45.7%. Conclusion: The sample studied revealed a little knowledge on the entity. A residency in cardiology was the factor of greater significance in the percentage of right answers. Other significant factors were the link of the interviewed person to an educational institution, or the Brazilian Society of Cardiac Arrhythmias, and having a specialist degree.

Trigger performance of mid-level ICU mechanical ventilators during assisted ventilation: a bench study

Objective: To compare the triggering performance of mid-level ICU mechanical ventilators with a standard ICU mechanical ventilator. Design: Experimental bench study. Setting: The respiratory care laboratory of a university-affiliated teaching hospital. Subject: A computerized mechanical lung model, the IngMar ASL5000. Interventions: Ten mid-level ICU ventilators were compared to an ICU ventilator at two levels of lung model effort, three combinations of respiratory mechanics (normal, COPD and ARDS) and two modes of ventilation, volume and pressure assist/control. A total of 12 conditions were compared. Measurements and main results: Performance varied widely among ventilators. Mean inspiratory trigger time was < 100 ms for only half of the tested ventilators. The mean inspiratory delay time (time from initiation of the breath to return of airway pressure to baseline) was longer than that for the ICU ventilator for all tested ventilators except one. The pressure drop during triggering (Ptrig) was comparable with that of the ICU ventilator for only two ventilators. Expiratory Settling Time (time for pressure to return to baseline) had the greatest variability among ventilators. Conclusions: Triggering differences among these mid-level ICU ventilators and with the ICU ventilator were identified. Some of these ventilators had a much poorer triggering response with high inspiratory effort than the ICU ventilator. These ventilators do not perform as well as ICU ventilators in patients with high ventilatory demand.

Impact of metabolic syndrome on the outcome of patients with stable coronary artery disease: 2-year follow-up of the MASS II study

Objective We characterized the impact of the metabolic syndrome (MetS) and its components on cardiovascular adverse events in patients with symptomatic chronic multivessel coronary artery disease, which have been followed prospectively for 2 years. Methods Patients enrolled in the MASS II study were evaluated for each component of the MetS, as well as the full syndrome. Results The criteria for MetS were fulfilled in 52% of patients. The presence of MetS (P < 0.05), glucose intolerance (P=0.007), and diabetes (P=0.04) was associated with an increased mortality in our studied population. Moreover, despite a clear tendency for each of its components to increase the mortality risk, only the presence of the MetS significantly increased the risk of mortality among nondiabetic study participants in a multivariate model (P=0.03, relative risk 3.5, 95% confidence interval 1.1-6). Finally, MetS was still associated with increased mortality even after adjustment for diabetes status. These results indicate a strong and consistent relationship of the MetS with mortality in patients with stable coronary artery disease. Conclusion Although glucose homeostasis seems to be the major force driving the increased risk of MetS, the operational diagnosis of MetS still has information for stratifying patients when diabetes information is taken into account.

A phase II study of UFT with leucovorin administered as a twice daily schedule in the treatment of patients with metastatic colorectal cancer

Prolonged infusions have been shown to be safer and potentially more effective than bolus regimens of 5-fluorouracil (5-FU) as treatment for metastatic colorectal cancer (mCRC). However, infusional 5-FU requires central venous access and costly infusion pumps. Oral fluoropyrimidines enable longer exposures to 5-FU with increased convenience. Tegafur - uracil (UFT) with leucovorin (LV) given thrice daily has improved safety plus comparable survival and response rates to bolus 5-FU/LV. We conducted a phase II clinical study in 98 patients with mCRC to evaluate if UFT with LV given twice daily provided comparable time to progression ( TTP), efficacy and tolerability to that reported for thrice daily in two phase III clinical studies. Secondary objectives included overall response rate ( ORR) and overall survival ( OS). Median TTP was 3.8 months, when compared with 3.5 months for thrice daily. The ORR ( 11%) and median OS ( 12.8 months) with twice daily administration were similar to that of thrice daily administration ( 12% and 12.4 months). The incidence of grade 3/4 treatment-related diarrhoea was 30% on the twice daily and 21% on the thrice daily schedule. These results suggest that twice daily administration has similar efficacy and tolerability to thrice daily administration and is an acceptable alternative for patients who would benefit from UFT with LV therapy.

The role played by the parietoocciptal cortex in the process of sensory-motor integration: An electroencephalographic study

Introduction. A fundamental aspect of planning future actions is the performance and control of motor tasks. This behaviour is done through sensory-motor integration. Aim. To explain the electrophysiological mechanisms in the cortex (modifications to the alpha band) that are involved in anticipatory actions when individuals have to catch a free-falling object. Subjects and methods. The sample was made up of 20 healthy subjects of both sexes (11 males and 9 females) with ages ranging between 25 and 40 years (32.5 +/- 7.5) who were free of mental or physical diseases (previous medical history); the subjects were right-handed (Edinburgh Inventory) and were not taking any psychoactive or psychotropic substances at the time of the study. The experiment consisted in a task in which subjects had to catch freely falling objects. The experiment was made up of six blocks of 15 tests, each of which lasted 2 minutes and 30 seconds before and two seconds after each ball was dropped. Results. An interaction of the factors moment and position was only observed for the right parietooccipital cortex, in the combination of electrodes P4-O2. Conclusion. These findings suggest that the right parietooccipital cortex plays an important role in increasing expectation and swiftness in the process of preparing for a motor task.

Risk factors across the life course and dementia in a Brazilian population: results from the Sao Paulo Ageing & Health Study (SPAH)

Background Several mechanisms have been suggested to explain the association between adversities across life and dementia. This study aimed to investigate the association between indicators of socioeconomic disadvantages throughout the life-course and dementia among older adults in Sao Paulo, Brazil and to explore possible causal pathways. Methods We used baseline data from the SPAH study which involved participants aged 65 years and older (n = 2005). The outcome of interest was prevalent dementia. Exposures included in the analyses were socioeconomic position (SEP) indicators in childhood (place of birth and literacy) and adulthood (occupation and income), anthropometric measurements as markers of intrauterine and childhood environment (head circumference and leg length), smoking, diabetes and hypertension. Logistic regression models were used to test the hypothesized pathways and to assess whether there was an association between cumulative adversities across the life course and prevalent dementia. Results Indicators of socioeconomic disadvantage in early life were associated with increased prevalence of dementia. This association was partially mediated through adulthood SEP. Head circumference and leg length were also clearly associated with dementia but there was no evidence that this association was mediated by early life socioeconomic disadvantage. There was an association between cumulative unfavourable conditions across the life course and dementia. Conclusions Early life disadvantages seem to operate through biological mechanisms associated with passive brain reserve and opportunities in life representing active cognitive reserve. Prevention of dementia should start early in life and continue through life span as seen with many other chronic diseases.