LICAVAL: combination therapy in acute and maintenance treatment of bipolar disorder

Background: The challenge of Bipolar Disorder (BD) treatment is due to the complexity of the disease. Current guidelines represent an effort to help clinicians in their everyday practice but still have limitations, specially concerning to long term treatment. LICAVAL (efficacy and tolerability of the combination of LIthium and CArbamazepine compared to lithium and VALproic acid in the treatment of young bipolar patients) study aim to evaluate acute and maintenance phase of BD treatment with two combined drugs. Methods: LICAVAL is a single site, parallel group, randomized, outcome assessor blinded trial. BD I patients according to the DSM-IV-TR, in depressive, manic,/hypomanic or mixed episode, aged 18 to 35 years are eligible. After the diagnostic assessments, the patients are allocated for one of the groups of treatment (lithium + valproic acid or lithium + carbamazepine). Patients will be followed up for 8 weeks in phase I (acute treatment), 6 months in phase II (continuation treatment) and 12 months in phase III (maintenance treatment). Outcome assessors are blind to the treatment. The main outcome is the evaluation of changes in mean scores on CGI-BP-M between baseline and endpoint at the end of each phase of the study. Results: LICAVAL is currently in progress, with patients in phase I, II or III. It will extended until august 2012. Conclusions: Trials comparing specific treatments efficacy in BD (head to head) can show relevant information in clinical practice. Long term treatment is an issue of great important and should be evaluated carefully in more studies as long as BD is a chronic disease.

Neuropsychological Outcome of Ventral Capsular/Ventral Striatal Gamma Capsulotomy for Refractory Obsessive-Compulsive Disorder: A Pilot Study

Five refractory obsessive-compulsive patients were assessed using a neuropsychological battery after a modified gamma knife capsulotomy. The surgical technique was not associated with profound cognitive deficits. The authors found improvements in attention, vocabulary, learning, abstract reasoning, and memory. (The journal of Neuropsychiatry and Clinical Neurosciences 2009; 21:393-397)

Executive dysfunction in children and adolescents with temporal lobe epilepsy: Is the Wisconsin Card Sorting Test enough?

The Wisconsin Card Sorting Test (WCST) is the gold standard in the evaluation of executive dysfunction (ED) in patients with temporal lobe epilepsy (TLE). We evaluated 35 children with TLE and 25 healthy controls with the WCST and with a more comprehensive battery. Among the children with TLE, 77.14% showed impairment on the WCST. On other tests (Wechsler Intelligence Scale for Children-Digit Forward, Matching Familiar Figures Test, Trail Making Test, Word Fluency, Finger Windows, and Number-Letter Memory), impairment was demonstrated in 94.29%. The authors concluded that the WCST is a good paradigm to measure executive impairment in children with TLE: however, it may be not enough. Evaluation performed only with the WCST not only underestimated the number of patients with ED, but also missed relevant information regarding the type of ED. (C) 2009 Elsevier Inc. All rights reserved.

Orbitofrontal cortex gray matter volumes in bipolar disorder patients: a region-of-interest MRI study

Objectives: Functional and postmortem studies suggest that the orbitofrontal cortex (OFC) is involved in the pathophysiology of bipolar disorder (BD). This anatomical magnetic resonance imaging (MRI) study examined whether BD patients have smaller OFC gray matter volumes compared to healthy comparison subjects (HC). Methods: Twenty-eight BD patients were compared to 28 age- and gender-matched HC. Subjects underwent a 1.5T MRI with 3D spoiled gradient recalled acquisition. Total OFC and medial and lateral subdivisions were manually traced by a blinded examiner. Images were segmented and gray matter volumes were calculated using an automated method. Results: Analysis of covariance, with intracranial volume as covariate, showed that BD patients and HC did not differ in gray matter volumes of total OFC or its subdivisions. However, total OFC gray matter volume was significantly smaller in depressed patients (n = 10) compared to euthymic patients (n = 18). Moreover, total OFC gray matter volumes were inversely correlated with depressive symptom intensity, as assessed by the Hamilton Depression Rating Scale. OFC gray matter volumes were not related to lithium treatment, age at disease onset, number of episodes, or family history of mood disorders. Conclusions: Our results suggest that abnormal OFC gray matter volumes are not a pervasive characteristic of BD, but may be associated with specific clinical features of the disorder.

Neuropsychological Profile of Brazilian Older Adults with Heterogeneous Educational Backgrounds

Education significantly impacts cognitive performance of older adults even in the absence of dementia. Some cognitive tests seem less vulnerable to the influence of education and thus may be more suitable for cognitive assessment of older adults with heterogeneous backgrounds. The objective of this study was to investigate which tests in a cognitive battery were less influenced by educational levels in a sample of cognitively unimpaired older Brazilians. In addition, we evaluated the impact of very high educational levels on cognitive performance. The cognitive battery consisted of the Mini Mental State Examination (MMSE), Cambridge Cognitive Test (CAMCOG), Clock Drawing Test, Short Cognitive Performance Test (SKT), Rivermead Behavioural Memory Test (RBMT), Fuld Object Memory Evaluation (FOME), Verbal Fluency Test (VF) fruit category, Trail Making Test A and B, WAIS-R Vocabulary, and Block Design. Education did not exert a significant influence on the RBMT, FOME, and VF (p < .05). Subjects with very high educational levels had similar performance on the latter tests when compared with those with intermediate and low levels of education. In conclusion, the RBMT, FOME, and VF fruit category seem to be appropriate tools for the assessment of cognitive function in elderly Brazilians with varying degrees of educational attainment.

CAMCOG as a screening tool for diagnosis of Mild Cognitive Impairment and Dementia in a Brazilian clinical sample of moderate to high education

Background The CAMCOG is a brief neuropsychological battery designed to assess global cognitive function and ascertain the impairments that are required for the diagnosis of dementia. To date, the cut-off scores for mild cognitive impairment (MCI) have not been determined. Given the need for an earlier diagnosis of mild dementia, new cut-off values are also necessary, taking into account cultural and educational effects. Methods One hundred and fifty-seven older adults (mean age: 69.6 +/- 7.4 years) with 8 or more years of formal education (mean years of schooling 14.2 +/- 3.8) attending a memory clinic at the Institute of Psychiatry University of Sao Paulo were included. Subjects were divided into three groups according to their cognitive status, established through clinical and neuropsychological assessment: normal controls, n = 62; MCI, n = 65; and mild or moderate dementia, n = 30. ROC curve analyses were performed for dementia vs controls, MCI vs controls and MCI vs dementia. Results The cut-off values were: 92/93 for dementia is controls (AUC = 0.99: sensitivity: 100%, specificity: 95%); 95/96 for MCI vs controls (AUC = 0.83, sensitivity: 64%, specificity: 88%), and 85/86 for MCI vs dementia (AUC = 0.91, sensitivity: 81%, specificity: 88%). The total CAMCOG score was more accurate than its subtests Mini-mental State Examination, Verbal Fluency Test and Clock Drawing Test when used separately. Conclusions The CAMCOG discriminated controls and MCI from demented patients, but was less accurate to discriminate MCI from controls. The best cut-off value to differentiate controls and demented was higher than suggested in the original publication, probably because only cases of mild to moderate dementia were included. This is important given the need for a diagnostic at earlier stages of Alzheimer`s disease. Copyright (C) 2008 John Wiley & Sons, Ltd.

Involvement of dorsal raphe nucleus and dorsal periaqueductal gray 5-HT receptors in the modulation of mouse defensive behaviors

Previous findings point to the involvement of the dorsal raphe nucleus (DRN) and dorsal periaqueductal gray (dPAG) serotonergic receptors in the mediation of defensive responses that are associated with specific subtypes of anxiety disorders. These studies have mostly been conducted with rats tested in the elevated T-maze, an experimental model of anxiety that was developed to allow the measurement, in the same animal, of two behaviors mentioned: inhibitory avoidance and one-way escape. Such behavioral responses have been respectively related to generalized anxiety disorder (GAD) and panic disorder (PD). In order to assess the generality of these findings, in the current study we investigated the effects of the injection of 5-HT-related drugs into the DRN and dPAG of another rodent species, mouse, on the mouse defense test battery (MDTB), a test of a range of defensive behaviors to an unconditioned threat, a predator. Male CD-1 mice were tested in the MDTB after intra-DRN administration of the 5-HT(1A) receptor antagonist WAY-100635 or after intra-dPAG injection of two serotonergic agonists, the 5-HT1A receptor agonist 8-OH-DPAT and the 5-HT(2A/2C) receptor agonist DOI. Intra-DRN injection of WAY-100635 did not change behavioral responses of mice confronted with a rat in the MDTB. In the dPAG, both 8-OH-DPAT and DOI consistently impaired mouse escape behavior assessed in the MDTB. Intra-dPAG infusion of 8-OH-DPAT also decreased measures of mouse risk assessment in the rat exposure test. In conclusion, the current findings are in partial agreement with previous results obtained with rats tested in the elevated T-maze. Although there is a high level of similarity between the behavioral effects obtained in rats (elevated T-maze) and mice (MDTB and RET) with the infusion of 5-HT agonists into the dPAG, the same is not true regarding the effects of blockade of DRN 5-HT(1A) receptors in these rodent species. These data suggest that there may be differences between mice and rats regarding the involvement of the DRN in the mediation of defensive behaviors. (C) 2010 Elsevier B.V. and ECNP. All rights reserved.

Saccadic Movements in subjects with cerebellar disorders

Saccades are part of the electrooculography tests battery. The cerebellum has important connections with the brainstem and thalamic structures involved in the generation of saccades. Aim: to study saccadic movements in subjects with cerebellar disorders. Study Method: Prospective clinical study. Materials and Methods: 11 subjects with cerebellar disorders were selected, together with a control group with 27 normal subjects. The patients of both groups had their saccadic movements registered (fixed and randomized). We compared and quantitatively analyzed the responses from both groups. Results: We did not find any differences among the quantitative parameters between the two. Age and gender did not influence these values. Despite these findings, the morphologies of the saccadic curves were very different between the two groups. Conclusion: Quantitative parameters of horizontal saccades from individuals with cerebellar diseases do not differ from those presented by normal subjects. Gender and age also did not influence these parameters.

Brazilian Version of the Addenbrooke Cognitive Examination-revised in the Diagnosis of Mild Alzheimer Disease

Objective: To investigate the accuracy of the Brazilian version of the Addenbrooke Cognitive Examination-revised (ACE-R) in the diagnosis of mild Alzheimer disease (AD). Background: The ACE-R is an accurate and brief cognitive battery for the detection of mild dementia, especially for the discrimination between AD and frontotemporal dementia. Methods: The battery was administered to 31 patients with mild AD and 62 age-matched and education-matched cognitively healthy controls. Both groups were selected using the Dementia Rating Scale and were submitted to the ACE-R. Depression was ruled out in both groups by the Cornell Scale for Depression in Dementia. The performance of patients and controls in the ACE-R was compared and receiver operator characteristic curve analysis was undertaken to ascertain the accuracy of the instrument for the diagnosis of mild AD. Results: The mean scores at the ACE-R were 63.10 +/- 10.22 points for patients with AD and 83.63 +/- 7.90 points for controls. The cut-off score < 78 yielded high diagnostic accuracy (receiver operator characteristic area under the curve = 0.947), with 100% sensitivity, 82.26% specificity, 73.8% positive predictive value, and 100% negative predictive value. Conclusions: The Brazilian version of the ACE-R displayed high diagnostic accuracy for the identification of mild AD in the studied sample.

Cannabis use before age 15 and subsequent executive functioning

Background Many studies have suggested that adolescence is a period of particular vulnerability to neurocognitive effects associated with substance misuse. However, few large studies have measured differences in cognitive performance between chronic cannabis users who started in early adolescence (before age 15) with those who started later. Aims To examine the executive functioning of individuals who started chronic cannabis use before age 15 compared with those who started chronic cannabis use after 15 and controls. Method We evaluated the performance of 104 chronic cannabis users (49 early-onset users and 55 late-onset users) and 44 controls who undertook neuropsychological tasks, with a focus on executive functioning. Comparisons involving neuropsychological measures were performed using generalised linear model analysis of variance (ANOVA). Results The early-onset group showed significantly poorer performance compared with the controls and the late-onset group on tasks assessing sustained attention, impulse control and executive functioning. Conclusions Early-onset chronic cannabis users exhibited poorer cognitive performance than controls and late-onset users in executive functioning. Chronic cannabis use, when started before age 15, may have more deleterious effects on neurocognitive functioning.

Processing Speed and Working Memory Span: Their Differential Role in Superficial and Deep Memory Processes in Schizophrenia

Previous work has suggested that decrement in both processing speed and working memory span plays a role in the memory impairment observed in patients with schizophrenia. We undertook a study to examine simultaneously the effect of these two factors. A sample of 49 patients with schizophrenia and 43 healthy controls underwent a battery of verbal and visual memory tasks. Superficial and deep encoding memory measures were tallied. We conducted regression analyses on the various memory measures, using processing speed and working memory span as independent variables. In the patient group, processing speed was a significant predictor of superficial and deep memory measures in verbal and visual memory. Working memory span was an additional significant predictor of the deep memory measures only. Regression analyses involving all participants revealed that the effect of diagnosis on all the deep encoding memory measures was reduced to non-significance when processing speed was entered in the regression. Decreased processing speed is involved in verbal and visual memory deficit in patients, whether the task require superficial or deep encoding. Working memory is involved only insofar as the task requires a certain amount of effort. (JINS, 2011, 17, 485-493)

A note on averting goats to a toxic but palatable plant, Leucaena leucocephala

Conditioned taste aversions are a useful tool to reduce livestock consumption of toxic plants. The forage legume Leucaena leucocephala (leucaena) is both toxic and palatable. The objective of this study was to determine if goats could be aversively conditioned to avoid leucaena. Adult and juvenile female goats, naive to leucaena, were divided into control and averted groups. Animals were exposed to leucaena, and time(s) spent eating leucaena was measured. During initial conditioning with lithium chloride (LiCl), averted goats spent less time eating leucaena (P < 0.05) than did controls. The averted groups maintained their reduced consumption (P < 0.05) of leucaena compared to controls during open field tests when goats could chose between leucaena and sugar cane. In final tests (two tests per week), averted goats reduced (P < 0.05) the amount of time they spent eating leucaena compared to control animals, but the aversion eventually extinguished. Aversive conditioning was successful in greatly reducing, but not entirely eliminating goats` consumption of leucaena. (C) 2007 Elsevier B.V. All rights reserved.

Slow crack growth and reliability of dental ceramics

Objective. To determine the slow crack growth (SCG) and Weibull parameters of five dental ceramics: a vitreous porcelain (V), a leucite-based porcelain (D), a leucite-based glass-ceramic (E1), a lithium disilicate glass-ceramic (E2) and a glass-infiltrated alumina composite (IC). Methods. Eighty disks (empty set 12mm x 1.1mm thick) of each material were constructed according to manufacturers` recommendations and polished. The stress corrosion susceptibility coefficient (n) was obtained by dynamic fatigue test, and specimens were tested in biaxial flexure at five stress rates immersed in artificial saliva at 37 degrees C. Weibull parameters were calculated for the 30 specimens tested at 1MPa/s in artificial saliva at 37 degrees C. The 80 specimens were distributed as follows: 10 for each stress rate (10(-2), 10(-1), 10(1), 10(2) MPa/s), 10 for inert strength (10(2) MPa/s, silicon oil) and 30 for 10(0) MPa/s. Fractographic analysis was also performed to investigate the fracture origin. Results. E2 showed the lowest slow crack growth susceptibility coefficient (17.2), followed by D (20.4) and V (26.3). E1 and IC presented the highest n values (30.1 and 31.1, respectively). Porcelain V presented the lowest Weibull modulus (5.2). All other materials showed similar Weibull modulus values, ranging from 9.4 to 11.7. Fractographic analysis indicated that for porcelain D, glass-ceramics E1 and E2, and composite IC crack deflection was the main toughening mechanism. Significance. This study provides a detailed microstructural and slow crack growth characterization of widely used dental ceramics. This is important from a clinical standpoint to assist the clinician in choosing the best ceramic material for each situation as well as predicting its clinical longevity. It also can be helpful in developing new materials for dental prostheses. (c) 2010 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Effect of processing induced particle alignment on the fracture toughness and fracture behavior of multiphase dental ceramics

Objective. To investigate the processing induced particle alignment on fracture behavior of four multiphase dental ceramics (one porcelain, two glass-ceramics and a glass-infiltrated-alumina composite). Methods. Disks (empty set12mm x 1.1 mm-thick) and bars (3 mm x 4 mm x 20 mm) of each material were processed according to manufacturer instructions, machined and polished. Fracture toughness (K(IC)) was determined by the indentation strength method using 3-point bending and biaxial flexure fixtures for the fracture of bars and disks, respectively. Microstructural and fractographic analyses were performed with scanning electron microscopy, energy dispersive spectroscopy and X-ray diffraction. Results. The isotropic microstructure of the porcelain and the leucite-based glass-ceramic resulted in similar fracture toughness values regardless of the specimen geometry. On the other hand, materials containing second-phase particles with high aspect ratio (lithium disilicate glass-ceramic and glass-infiltrated-alumina composite) showed lower fracture toughness for disk specimens compared to bars. For the lithium disilicate glass-ceramic disks, it was demonstrated that the occurrence of particle alignment during the heat-pressing procedure resulted in an unfavorable pattern that created weak microstructural paths during the biaxial test. For the glass-infiltrated-alumina composite, the microstructural analysis showed that the large alumina platelets tended to align their large surfaces perpendicularly to the direction of particle deposition during slip casting of green preforms. Significance. The fracture toughness of dental ceramics with anisotropic microstructure should be determined by means of biaxial testing, since it results in lower values. (C) 2009 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Evaluation of the Frequency of Micronuclei in Exfoliated Cells from Oral Lesions Previously Identified by Toluidine Blue

Objective: Patients using a removable prosthesis are susceptible to a variety of oral lesions that may progress to cancer. Toluidine blue (TB) staining is used to identify premalignant lesions, but the results are still controversial. Since micronuclei (MN) are a biomarker of genetic instability, the objective of this study was to determine the frequency of MN in white lesions of the oral mucosa and to compare the results with those of the TB test. Study Design: The study included 20 removable prosthesis users with white lesions that were previously classified as toluidine positive or negative. The frequency of MN was evaluated in exfoliated cells from lesions and normal mucosa. Nuclear anomalies were also registered. Results: A significant increase (p < 0.05) in the frequency of MN was observed in exfoliated cells from lesions compared to normal mucosal cells, and no relationship was seen with TB staining. Lifestyle factors or gender did not influence the results. Conclusions: The frequency of MN is a sensitive biomarker and can be used to predict genomic instability in white oral lesions. The MN assay may serve as a good parameter in the battery of tests used to identify high-risk individuals, contributing to the identification of the biological conditions of oral lesions. Copyright (C) 2011 S. Karger AG, Basel