ADHD in a representative sample of the Brazilian population: estimated prevalence and comparative adequacy of criteria between adolescents and adults according to the item response theory

Background: Attention deficit hyperactivity disorder (ADHD) is a clinically significant disorder in adulthood, but current diagnostic criteria and instruments do not seem to adequately capture the complexity of the disorder in this developmental phase. Accordingly, there are limited data on the proportion of adults affected by the disorder, specially in developing countries. Method: We assessed a representative household sample of the Brazilian population for ADHD with the Adult ADHD Self-report Scale (ASRS) Screener, and evaluated the instrument according to the Rasch model of item response theory. Results: The sample was comprised by 3007 individuals, and the overal prevalence of positive screeners for ADHD was 5.8% [95% confidence interval (CI), 4.8-7.0]. Rasch analyses revealed the misfitt of the overall sample to expectations of the model. The evaluation of the sample stratified by age revealed that data for adolescents showed a signficant fittnes to the model expectations, while items completed by adults were not adequated. Conclusions: The lack of fitness to the model for adult respondents challenges the possibility of a linear transformation of the ordinal data into interval measures and the utilization of parametric analyses of data. This result suggests that diagnostic criteria and instruments for adult ADHD must take into account a developmental perspective. Moreover, it calls for further evaluation of currently employed research methods in light of modern theories of psychometrics. Copyright (C) 2010 John Wiley & Sons, Ltd.

The Alzheimer`s Association external quality control program for cerebrospinal fluid biomarkers

Background: The cerebrospinal fluid (CSF) biomarkers amyloid beta (A beta)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer`s disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer`s Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods: The program is open for laboratories using commercially available kits for A beta, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Molndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results: Forty laboratories participated. Twenty-six used INNOTEST enzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure A beta-(1-42), P-tau(181P), and T-tau), and 5 used Mesa Scale Discovery with the A beta triplex (A beta N-42, A beta N-40, and A beta N-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions: Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers. (C) 2011 The Alzheimer`s Association. All rights reserved.

Implications of Extending the ADHD Age-of-Onset Criterion to Age 12: Results from a Prospectively Studied Birth Cohort

Objective: To evaluate whether including children with onset of symptoms between ages 7 and 12 years in the ADHD diagnostic category would: (a) increase the prevalence of the disorder at age 12, and (b) change the clinical and cognitive features, impairment profile, and risk factors for ADHD compared with findings in the literature based on the DSM-IV definition of the disorder. Method: A birth cohort of 2,232 British children was prospectively evaluated at ages 7 and 12 years for ADHD using information from mothers and teachers. The prevalence of diagnosed ADHD at age 12 was evaluated with and without the inclusion of individuals who met DSM-IV age-of-onset criterion through mothers` or teachers` reports of symptoms at age 7. Children with onset of ADHD symptoms before versus after age 7 were compared on their clinical and cognitive features, impairment profile, and risk factors for ADHD. Results: Extending the age-of-onset criterion to age 12 resulted in a negligible increase in ADHD prevalence by age 12 years of 0.1%. Children who first manifested ADHD symptoms between ages 7 and 12 did not present correlates or risk factors that were significantly different from children who manifested symptoms before age 7. Conclusions: Results from this prospective birth cohort might suggest that adults who are able to report symptom onset by age 12 also had symptoms by age 7, even if they are not able to report them. The data suggest that the prevalence estimate, correlates and risk factors of ADHD will not be affected if the new diagnostic scheme extends the age-of-onset criterion to age 12. J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(3):210-216.

Association between symptom severity and internal capsule volume in obsessive-compulsive disorder

Neurobiological models support an involvement of white matter tracts in the pathophysiology of obsessive-compulsive disorder (OCD), but there has been little systematic evaluation of white matter volumes in OCD using magnetic resonance imaging (MRI). We investigated potential differences in the volume of the cingulum bundle (CB) and anterior limb of internal capsule (ALIC) in OCD patients (n = 19) relative to asymptomatic control subjects (n = 15). White matter volumes were assessed using a 1.5T MRI scanner. Between-group comparisons were carried out after spatial normalization and image segmentation using optimized voxel-based morphometry. Correlations between regional white matter volumes in OCD subjects and symptom severity ratings were also investigated. We found significant global white matter reductions in OCD patients compared to control subjects. The voxel-based search for regional abnormalities (with covariance for total white matter volumes) showed no specific white matter volume deficits in brain portions predicted a priori to be affected in OCD (CB and ALIC). However, large clusters of significant positive correlation with OCD severity scores were found bilaterally on the ALIC. These findings provide evidence of OCD-related ALIC abnormalities and suggest a connectivity dysfunction within frontal-striatal-thalamic-cortical circuits. Further studies are warranted to better define the role of such white matter alterations in the pathophysiology of OCD, and may provide clues for a more effectively targeting of neurosurgical treatments for OCD. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Do Phenotypic Characteristics, Parental Psychopathology, Family Functioning, and Environmental Stressors Have a Role in the Response to Methylphenidate in Children With Attention-Deficit/Hyperactivity Disorder? A Naturalistic Study From a Developing Country

Little is known about the effect of clinical characteristics, parental psychopathology, family functioning, and environmental stressors in the response to methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD) followed up in a naturalistic setting. Data from cultures outside the United States are extremely scarce. This is a longitudinal study using a nonrandom assignment, quasi-experimental design. One hundred twenty-five children with ADHD were treated with methylphenidate according to standard clinical procedures, and followed up for 6 months. The severity of ADHD symptoms was assessed by the Swanson, Nolan, and Pelham rating scale. In the final multivariate model, ADHD combined subtype (P < 0.001) and comorbidity with oppositional defiant disorder (P = 0.03) were both predictors of a worse clinical response. In addition, the levels of maternal ADHD symptoms were also associated with worse prognosis (P < 0.001). In the context of several adverse psychosocial factors assessed, only undesired pregnancy was associated with poorer response to methylphenidate in the final comprehensive-model (P = 0.02). Our study provides evidence for the involvement of clinical characteristics, maternal psychopathology, and environmental stressors in the response to methylphenidate. Clinicians may consider adjuvant strategies when negative predictors are present to increase the chances of success with methylphenidate treatment.

Gamma ventral capsulotomy for treatment of resistant obsessive-compulsive disorder: A structural MRI pilot prospective study

Objective: The purpose of this study was to investigate regional structural abnormalities in the brains of five patients with refractory obsessive-compulsive disorder (OCD) submitted to gamma ventral capsulotomy. Methods: We acquired morphometric magnetic resonance imaging (MRI) data before and after 1 year of radiosurgery using a 1.5-T MRI scanner. Images were spatially normalized and segmented using optimized voxel-based morphometry (VBM) methods. Voxelwise statistical comparisons between pre- and post-surgery MRI scans were performed using a general linear model. Findings in regions predicted a priori to show volumetric changes (orbitofrontal cortex, anterior cingulate gyrus, basal ganglia and thalamus) were reported as significant if surpassing a statistical threshold of p<0.001 (uncorrected for multiple comparisons). Results: We detected a significant regional postoperative increase in gray matter volume in the right inferior frontal gyri (Brodmann area 47, BA47) when comparing all patients pre and postoperatively. Conclusions: Our results support the current theory of frontal-striatal-thalamic-cortical (FSTC) circuitry involvement in OCD pathogenesis. Gamma ventral capsulotomy is associated with neurobiological changes in the inferior orbitofrontal cortex in refractory OCD patients. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Effects of Tityus serrulatus scorpion venom on lung mechanics and inflammation in mice

The present study evaluated the effects of an intramuscular injection of Tityus serrulatus venom (TsV) (0.67 mu g/g) on lung mechanics and lung inflammation at 15, 30, 60 and 180 min after inoculation. TsV inoculation resulted in increased lung elastance when compared with the control group (p < 0.001): these values were significantly higher at 60 min than at 15 and 180 min (p < 0.05). Resistive pressure (Delta P(1)) values decreased significantly at 30, 60 and 180 min after TsV injection (p < 0.001). TsV inoculation resulted in increased lung inflammation, characterised by an increased density of mononuclear cells at 15, 30, 60 and 180 min after TsV injection when compared with the control group (p < 0.001). TsV inoculation also resulted in an increased pulmonary density of polymorphonuclear cells at 15, 30 and 60 min following injection when compared to the control group (p < 0.001). In conclusion, T serrulatus venom leads to acute lung injury, characterised by altered lung mechanics and increased pulmonary inflammation. (C) 2009 Elsevier Ltd. All rights reserved.

Pulmonary mechanic and lung histology injury induced by Crotalus durissus terrificus snake venom

In the present work we investigated the effects of Crotalus durissus terrificus venom (CdtV) on the pulmonary mechanic events [static and dynamic elastance, resistive (Delta P1) and viscoelastic pressures (Delta P2)] and histology after intramuscular injection of saline solution (control) or venom (0.6 mu g/g). The static and dynamic elastance values were increased significantly after 3 It of venom inoculation, but were reduced at control values in the other periods studied. The Delta P1 values that correspond to the resistive properties of lung tissue presented a significant increase after 6 h of CdtV injection, reducing to basal levels 12 h after the venom injection. In Delta P2 analysis, correspondent to viscoelastic components, an increase occurred 12 h after the venom injection, returning to control values at 24 h. CdtV also caused an increase of leukocytes recruitment (3-24 h) to the airways wall as well as to the lung parenchyma. In conclusion, C. durissus terrificus rattlesnake venom leads to lung injury which is reverted, after 24 h of inoculation. (c) 2008 Elsevier Ltd. All rights reserved.

Coordinated expression of ER, PR and HER2 define different prognostic subtypes among poorly differentiated breast carcinomas

Aims: Histological grade is one of the most important prognostic factors in breast carcinomas, but poorly differentiated neoplasms still have quite heterogeneous biological behaviour, since they can be genetically classified as basal-like, HER2+ or even luminal. The aim was to analyse the frequency of oestrogen receptor (ER), progesterone receptor (PR) and HER2 expression profiles among breast carcinomas with < 10% tubular formation, and their correlation with classic prognostic factors. Methods and results: One hundred and thirty-four samples of paraffin-embedded tumours were studied retrospectively. The tumours were classified in to four groups by their ER/PR/HER2 profile: (i) ER+ and/or PR+ but HER2-; (ii) ER+ and/or PR+ and HER2+; (iii) ER- and/or PR- but HER2+; and (iv) ER-, PR- and HER2- (triple-negative). The histological features of triple-negative and HER2+ carcinomas overlap. The only difference was the expression of basal cytokeratins (basal CK), which was more frequent among triple-negative carcinomas. Basal-CK expression defined a more aggressive group of tumours, according to the pathological features, regardless of the immunohistochemical profile. Conclusions: Group 1 and 2 tumours (ER+ and/or PR+ tumours with or without HER2 expression) were not statistically different, suggesting that poorly differentiated carcinomas with hormone receptors correspond to the luminal B type of tumour. Among poorly differentiated breast carcinomas, the classic profile associated with basal-CK identifies distinct subtypes equivalent to those seen by genetic classification.

Hormonal Contraceptives and the Length of Their Use Are Not Independent Risk Factors for High-Risk HPV Infections or High-Grade CIN

Aims: To evaluate the role of hormonal contraceptives as a risk factor of high-risk human papillomavirus (HR-HPV), cervical intraepithelial lesions (CIN) and cervical cancer in our multi-center population-based LAMS (Latin American Screening) study. Methods: A cohort study with >12,000 women from Brazil and Argentina using logistic regression to analyze the covariates of hormonal contraception (HOC - oral, injections, patches, implants, vaginal ring and progesterone intrauterine system) use followed by multivariate modeling for predictors of HR-HPV and CIN2+. Results: HR-HPV infection was a consistent risk factor of high-grade CIN in all three groups of women. The length of HOC use was not significantly related to high-grade squamous intraepithelial lesions (HSIL)+ Pap (p = 0.069), LSIL+ Pap (p = 0.781) or ASCUS+ (p = 0.231). The same was true with the length of HOC use and histology CIN3+ (p = 0.115) and CIN2+ (p = 0.515). Frequently, HOC users have previously shown more HPV-related lesions, as well as lower HPV prevalence if they were current smokers. But HOC use and time of usage were not independent risk factors of either HR-HPV infection or high-grade CIN using multiple logistic regressions. Conclusions: No evidence was found for an association between the use of HOC with an increased risk for HR-HPV infection or high-grade CIN in this cohort. Copyright (C) 2010 S. Karger AG, Basel

Negative Anti-C1q Antibody Titers May Influence Therapeutic Decisions and Reduce the Number of Renal Biopsies in Systemic Lupus Erythematosus

In a cross-sectional study involving 62 patients with systemic lupus erythematosus (SLE), we found that patients with biopsy-proven lupus nephritis (LN) had higher titers of anti-C1q antibodies than active SLE without nephritis patients. Anti-C1q was associated with a negative predictive value of 94.59%, a positive predictive value of 52%, a sensitivity of 86.66% and a specificity of 74.47% for the diagnosis of LN. We conclude that high titers of anti-C1q antibodies are strongly associated with the presence of active LN, and the negative predictive value of this test for diagnosing LN is very high; therefore, it can influence therapeutic decisions and reduce the number of renal biopsies in patients with SLE. Copyright (C) 2011 S. Karger AG, Basel

Evaluation of subclinical atherosclerosis by computed tomography coronary angiography and its association with risk factors in familial hypercholesterolemia

Background: Increasing age and cholesterol levels, male gender, and family history of early coronary heart disease (CHD) are associated with early onset of CHD in familial hypercholesterolemia (FH). Objective: Assess subclinical atherosclerosis by computed tomography coronary angiography (CTCA) and its association with clinical and laboratorial parameters in asymptomatic FH subjects. Methods: 102 FH subjects (36% male, 45 +/- 13 years, LDL-c 280 +/- 54 mg/dL) and 35 controls (40% male, 46 +/- 12 years, LDL-c 103 +/- 18 mg/dL) were submitted to CTCA. Plaques were divided into calcified, mixed and non-calcified; luminal stenosis was characterized as >50% obstruction. Results: FH had a greater atherosclerotic burden represented by higher number of patients with: plaques (48% vs. 14%, p = 0.0005), stenosis (19% vs. 3%, p = 0.015), segments with plaques (2.05 +/- 2.85 vs. 0.43 +/- 1.33, p = 0.0016) and calcium scores (55 perpendicular to 129 vs. 38 perpendicular to 140, p = 0.0028). After multivariate analysis, determinants of plaque presence were increasing age (OR = 2.06, for age change of 10 years, CI95%: 1.38-3.07, p < 0.001) and total cholesterol (OR = 1.86, for cholesterol change by 1 standard deviation, CI95%: 1.09-3.15, p = 0.027). Coronary calcium score was associated with the presence of stenosis (OR = 1.54; CI95%: 1.27-1.86, p < 0.001, for doubling the calcium score). Male gender was directly associated with the presence of non-calcified plaques (OR: 15.45, CI95% 1.72-138.23, p = 0.014) and inversely with calcified plaques (OR = 0.21, CI95%: 0.05-0.84, p = 0.027). Family history of early CHD was associated with the presence of mixed plaques (OR = 4.90, CI95%: 1.32-18.21, p = 0.018). Conclusions: Patients with FH had an increased burden of coronary atherosclerosis by CTCA. The burden of atherosclerosis and individual plaque subtypes differed with the presence of other associated risk factors, with age and cholesterol being most important. A coronary calcium score of zero ruled out obstructive disease in this higher risk population. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Reduced medial prefrontal N-Acetyl-Aspartate levels in pediatric major depressive disorder: A multi-voxel in vivo (1)H spectroscopy study

There is increasing evidence of a reciprocal fronto-limbic network in the pathogenesis of mood disorders. Prior in vivo proton ((1)H) spectroscopy studies provide evidence of abnormal neurochemical levels in the cingulate and dorsolateral prefrontal cortex (DLPFC) of adult subjects with major depressive disorder (MOD). We examined whether similar abnormalities occur in children and adolescents with MDD. We collected two-dimensional multi-voxel in vivo 1H spectroscopy data at 1.5 Tesla to quantify levels of N-acetyl-aspartate (NAA), glycerolphosphocholine plus phosphocholine (GPC + PC), and phosphocreatine plus creatine (PCr + Cr) in the DLPFC, medial prefrontal cortex (MPFC), and anterior cingulate (AC) of children and adolescents aged 8-17 years with MDD (n = 16) compared with healthy control subjects (n = 38). Analysis of covariance with age and gender as covariates was performed. MDD subjects showed significantly lower levels of NAA in the right MPFC and right AC than controls. MDD subjects also had significantly lower levels of GPC + PC in the right AC than control subjects. There were no significant differences in other metabolites in the studied regions. Pediatric patients with MDD exhibit neurochemical alterations in prefrontal cortex regions that are important in the monitoring and regulation of emotional states. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Milia en plaque

Milia en plaque is a rare type of primary milia. Issues related to esthetics and differential diagnoses represent a concern to patients and a challenge for physicians. In this paper, a case of milia en plaque is reported and a review of the literature is described.