Trypan blue staining for capsulorhexis: Ultrastructural effect on lens epithelial cells and capsules

PURPOSE: To evaluate the ultrastructural effect of trypan blue 0.1% staining for capsulorhexis on lens epithelial cells (LECs) and capsules SETTING: Division of Ophthalmology. University of Sao Paulo, Sao Paulo, Brazil METHODS: Before capsulorhexis, patients were randomly assigned to 1 of 2 groups Trypan blue 0 1% staining was performed in the treatment group No trypan blue was used in the control group Samples of capsules with LECs were fixed and analyzed with routine optical microscopy techniques. immunohistochemistry for beclin-1 expression (a marker of autophagy), terminal deoxynucleotidyl transf erase-mediated dUTP-biotin nick-end labeling to detect apoptosis, and transmission electron microscopy (TEM) Morphometric analyses were performed. and the 2 sets of data were compared. RESULTS: Each group comprised 15 patients Cell death by autophagy and apoptosis was observed in the treatment group but not in the control group The TEM images of subcapsular epithelium cells showed mitochondria` rupture, dilation of the cisterns of the endoplasmic reticulum, increased cytoplasmic and nuclear electron density, and abnormalities in the nuclear profile of trypan blue-stained cells. Morphometric analysis showed statistically significant differences between the 2 groups in the longest nuclear axes and the ratio between the total nuclear perimeter and the cell area (P = .03) The difference in capsule thickness between groups was not significant. CONCLUSION: Trypan blue caused LEC death, which supports the hypothesis that staining with trypan blue 0 1% can help reduce the incidence of posterior capsule pacification after cataract surgery

Marijuana Smoking and the Risk of Head and Neck Cancer: Pooled Analysis in the INHANCE Consortium

Background: Marijuana contains carcinogens similar to tobacco smoke and has been suggested by relatively small studies to increase the risk of head and neck cancer (HNC). Because tobacco is a major risk factor for HNC, large studies with substantial numbers of never tobacco users could help to clarify whether marijuana smoking is independently associated with HNC risk. Methods: We pooled self-reported interview data on marijuana smoking and known HNC risk factors on 4,029 HNC cases and 5,015 controls from five case-control studies within the INHANCE Consortium. Subanalyses were conducted among never tobacco users (493 cases and 1,813 controls) and among individuals who did not consume alcohol or smoke tobacco (237 cases and 887 controls). Results: The risk of HNC was not elevated by ever marijuana smoking [odds ratio (OR), 0.88; 95% confidence intervals (95% Cl), 0.67-1.16], and there was no increasing risk associated with increasing frequency, duration, or cumulative consumption of marijuana smoking. An increased risk of HNC associated with marijuana use was not detected among never tobacco users (OR, 0.93; 95% Cl, 0.63-1.37; three studies) nor among individuals who did not drink alcohol and smoke tobacco (OR, 1.06; 95% Cl, 0.47-2.38; two studies). Conclusion: Our results are consistent with the notion that infrequent marijuana smoking does not confer a risk of these malignancies. Nonetheless, because the prevalence of frequent marijuana smoking was low in most of the contributing studies, we could not rule out a moderately increased risk, particularly among subgroups without exposure to tobacco and alcohol. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1544-51)

The awareness of chronic fatigue syndrome: A comparative study in Brazil and the United Kingdom

Objective: While in many Western affluent countries there is widespread awareness of chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), little is known about the awareness of CFS/ME in low- and middle-income countries. We compared the awareness of CFS in Brazil and the United Kingdom. Methods: Recognition and knowledge of CFS were assessed among 120 Brazilian specialist doctors in two major university hospitals using a typical case vignette of CFS. We also surveyed 3914 and 2435 consecutive attenders in Brazilian and British primary care clinics, respectively, concerning their awareness of CFS. Results: When given a typical case vignette of CFS, only 30.8% [95% confidence interval (CI), 22.7-39.9%] of Brazilian specialist doctors mentioned chronic fatigue or CFS as a possible diagnosis, a proportion substantially lower than that observed in Western affluent countries. Similarly, only 16.2% (95% CI, 15.1-17.4%) of Brazilian primary care attenders were aware of CFS, in contrast to 55.1% (95% CI, 53.1-57.1%) of their British counterparts (P <.001). This difference remained highly significant after controlling for patients` sociodemographic and socioeconomic characteristics (P <.001). Conclusions: The awareness of CFS was substantially lower in Brazil than the United Kingdom. The observed difference may influence patients` help-seeking behavior and both doctors` and patients` beliefs and attitudes in relation to fatigue-related syndromes. Attempts to promote the awareness of CFS should be considered in Brazil, but careful plans are required to ensure the delivery of sound evidence-based information. (c) 2008 Elsevier Inc. All rights reserved.

Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines

Because of the advent of a new influenza A H1N1. strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barre syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21.5 cases of Guillain-Barre syndrome and 5.75 cases of sudden death would be expected to occur within 6 weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86.3 cases of optic neuritis per 10 million population would be expected within 6 weeks of vaccination. 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination.

A Randomized Controlled Trial of Cognitive Behavioral Group Therapy for Bipolar Disorder

Background: This study evaluated the effectiveness of adjunctive cognitive behavioral group therapy (CBGT) to prevent recurrence of episodes in euthymic patients with bipolar disorder. Methods: A randomized controlled single-blind trial was conducted with 50 patients with bipolar disorder types I and II followed up for at least 12 months in an outpatient service and whose disease was in remission. An experimental CBGT manual was developed and added to treatment as usual (TAU), and results were compared with TAU alone. Results: Intention-to-treat analysis showed that there was no difference between groups in terms of time until any relapse (Wilcoxon = 0.667; p = 0.414). When considering type of relapse, there was still no difference in either depressive (Wilcoxon = 3.328; p = 0.068) or manic episodes (Wilcoxon = 1.498; p = 0.221). Although occurrence of episodes also did not differ between groups (chi(2) = 0.28; p = 0.59), median time to relapse was longer for patients treated with CBGT compared to TAU (Mann-Whitney = -2.554; p = 0.011). Conclusions:Time to recurrence and number of episodes were not different in the group of patients treated with CBGT. However, median time to relapse was shorter in the TAU group. Studies with larger samples may help to clarify whether our CBGT approach prevents new episodes of bipolar disorder. Our findings also indicated that CBGT is feasible in euthymic patients with bipolar disorder and should be investigated in future studies. To our knowledge, this is the first publication of a controlled trial of CBGT for euthymic patients with bipolar disorder. Copyright (C) 2011 S. Karger AG, Basel

Suicidality in Obsessive-Compulsive Disorder: Prevalence and Relation to Symptom Dimensions and Comorbid Conditions

Background: Suicidal thoughts and behaviors, also known as suicidality, are a fairly neglected area of study in patients with obsessive-compulsive disorder (OCD). Objective: To evaluate several aspects of suicidality in a large multicenter sample of OCD patients and to compare those with and without suicidal ideation, plans, and attempts according to demographic and clinical variables, including symptom dimensions and comorbid disorders. Method: This cross-sectional study included 582 outpatients with primary OCD (DSM-IV) recruited between August 2003 and March 2008 from 7 centers of the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders. The following assessment instruments were used: the Yale-Brown Obsessive Compulsive Scale, the Dimensional Yale-Brown Obsessive Compulsive Scale, the Beck Depression and Anxiety Inventories, the Structured Clinical Interview for DSM-IV Axis I Disorders, and 6 specific questions to investigate suicidality. After univariate analyses, logistic regression analyses were performed to adjust the associations between the dependent and explanatory variables for possible confounders. Results: Thirty-six percent of the patients reported lifetime suicidal thoughts, 20% had made suicidal plans, 11% had already attempted suicide, and 10% presented current suicidal thoughts. In the logistic regression, only lifetime major depressive disorder and posttraumatic stress disorder (PTSD) remained independently associated with all aspects of suicidal behaviors. The sexual/religious dimension and comorbid substance use disorders remained associated with suicidal thoughts and plans, while impulse-control disorders were associated with current suicidal thoughts and with suicide plans and attempts. Conclusions: The risk of suicidal behaviors must be carefully investigated in OCD patients, particularly those with symptoms of the sexual/religious dimension and comorbid major depressive disorder, PTSD, substance use disorders, and impulse-control disorders. J Clin Psychiatry 2011;72(1):17-26 (C) Copyright 2011 Physicians Postgraduate Press, Inc.

Family context and duration of untreated psychosis (DUP): Results from the Sao Paulo Study

Background: Duration of untreated psychosis (DUP) depends on several factors, including socio-demographic, socioeconomic, clinical and contextual circumstances, such as availability of mental health services. Living arrangements may also play a role, especially in low- and middle-income countries, where most people who develop psychosis live with their relatives. Methods: Population-based study of first-episode psychosis in Sao Paulo, Brazil. Participants were aged 18-64 years, lived in a defined geographic area of the city and had a first contact in life with mental health services due to a psychotic episode. Duration of untreated psychosis was defined as the period between onset of first psychotic symptom and first contact with health service due to psychosis. The median DUP was used to classify participants into short and long DUP. Psychopathology, social adjustment and psychiatric diagnoses were made with standardized assessments. Type of service sought and living arrangements were examined. Results: Two hundred participants were included (52% women, 61% non-affective psychoses). The median DUP was 4.1 weeks (inter-quartile range: 1.9-11.4), and was shorter for affective psychoses. Most participants had their first contact with psychiatric emergency services. Those who did not live with a relative (children older than 18 years, parents, partner) were more likely to present long DUP (OR: 2.63; 95%Cl: 0.98-7.04); p = 0.05). Conclusion: The DUP in Sao Paulo was shorter than expected. Living arrangements may play an important role in shortening the DUP in urban centres of low- and middle income countries that have a network of mental health services. (C) 2009 Elsevier B.V. All rights reserved.

Profiles of functional deficits in mild cognitive impairment and dementia: benefits from objective measurement

The magnitude Of functional impairment that may indicate the threshold between MCI and incipient Alzheimer`s disease (AD) has not been clearly defined. The objective was to examine the pattern of functional impairment in the continuum MCI-AD. Eighty-nine older adults (32 cognitively unimpaired, 31 MCI, and 26 AD patients) were examined with the Brazilian version of the Direct Assessment of Functional Status (DAFS-BR) at a University-based memory clinic. MCI patients were sub-divided according to the progression to AD upon follow-up, and had baseline cognitive, functional and biological variables analyzed. MCI patients displayed mild deficits in functional abilities, with intermediate scores as compared to controls and AD. The DAFS-BR items that differentiated MCI from controls involved the ability to deal with finances and shopping skills. At baseline, scores obtained by MCI patients who converted to AD were not significantly different from scores of nonconverters. The magnitude of functional deficits was associated with AD-like pathological findings in the CSF. In conclusion, MCI patients present with early functional changes in complex, instrumental abilities that require the integrity of memory and executive functions. The objective measurement of the functional state may help identify older adults with increased risk of developing dementia in the MCI-AD continuum. (JINS, 2010, 16, 297-305.)

Case Series: Sensory Intolerance as a Primary Symptom of Pediatric OCD

Introduction. Marked intolerance or intrusive re-experiencing of ordinary sensory stimuli that in turn drive functionally impairing compulsive behaviors are occasionally seen in voting children with OCD. Methods. We describe a number of children with DSM-IV OCD ascertained from of family genetic study of pediatric OCD, whose intolerance: of ordinary sensory stimuli created significant subjective distress and time-consuming ritualistic behavior that was clinically impairing. Results. In each case these sensory symptoms were the primary presenting symptoms and were experienced in the absence of intrusive thoughts, images, or ideas associated with ""conventional"" OCD symptoms. Conclusions. These symptoms suggest abnormalities in sensory processing and integration in at least a subset of OCD patients. Recognition of these sensory symptoms and sensory-driven behaviors as part of the broad phenotypic Variation in children with OCD could help clinicians more easily identify OCD patients and,facilitate treatment.

Increased rates of white matter hyperintensities in late-onset bipolar disorder

Objectives: Magnetic resonance imaging (MRI) studies have reported an increased frequency of white matter hyperintensities (WMH) in association with late-onset (LO) depression, and this has supported the notion that vascular-related mechanisms may be implicated in the pathophysiology of LO mood disorders. Recent clinical studies have also suggested a link between LO bipolar disorder (LO-BD) and cerebrovascular risk factors, but this has been little investigated with neuroimaging techniques. In order to ascertain whether there could be a specific association between WMH and LO-BD, we directly compared WMH rates between LO-BD subjects (illness onset 60 years), early-onset BD subjects (EO-BD, illness onset < 60 years), and elderly healthy volunteers. Methods: T2-weighted MRI data were acquired in LO-BD subjects (n = 10, age = 73.60 +/- 4.09), EO-BD patients (n = 49, age = 67.78 +/- 4.44), and healthy subjects (n = 24, age = 69.00 +/- 7.22). WMH rates were assessed using the Scheltens scale. Results: There was a greater prevalence of WMH in LO-BD patients relative to the two other groups in the deep parietal region (p = 0.018) and basal ganglia (p < 0.045). When between-group comparisons of mean WMH scores were conducted taking account of age differences (ANCOVA), there were more severe scores in LO-BD patients relative to the two other groups in deep frontal and parietal regions, as well as in the putamen (p < 0.05). Conclusions: Our results provide empirical support to the proposed link between vascular risk factors and LO-BD. If extended in future studies with larger samples, these. findings may help to clarify the pathophysiological distinctions between bipolar disorder emerging at early and late stages of life.

Individual risk prediction of nodal and distant metastasis for patients with typical bronchial carcinoid tumors

Objective: Bronchial typical carcinoid tumors are tow-grade malignancies. However, metastases are diagnosed in some patients. Predicting the individual risk of these metastases to determine patients eligible for a radical lymphadenectomy and patients to be followed-up because of distant metastasis risk is relevant. Our objective was to screen for predictive criteria of bronchial typical carcinoid tumor aggressiveness based on a logistic regression model using clinical, pathological and biomolecular data. Methods: A multicenter retrospective cohort study, including 330 consecutive patients operated on for bronchial typical carcinoid tumors and followed-up during a period more than 10 years in two university hospitals was performed. Selected data to predict the individual risk for both nodal and distant metastasis were: age, gender, TNM staging, tumor diameter and location (central/peripheral), tumor immunostaining index of p53 and Ki67, Bcl2 and the extracellular density of neoformed microvessels and of collagen/elastic extracellular fibers. Results: Nodal and distant metastasis incidence was 11% and 5%, respectively. Univariate analysis identified all the studied biomarkers as related to nodal metastasis. Multivariate analysis identified a predictive variable for nodal metastasis: neo angiogenesis, quantified by the neoformed pathological microvessels density. Distant metastasis was related to mate gender. Discussion: Predictive models based on clinical and biomolecular data could be used to predict individual risk for metastasis. Patients under a high individual risk for lymph node metastasis should be considered as candidates to mediastinal lymphadenectomy. Those under a high risk of distant metastasis should be followed-up as having an aggressive disease. Conclusion: Individual risk prediction of bronchial typical carcinoid tumor metastasis for patients operated on can be calculated in function of biomolecular data. Prediction models can detect high-risk patients and help surgeons to identify patients requiring radical lymphadenectomy and help oncologists to identify those as having an aggressive disease requiring prolonged follow-up. (C) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Mucosal and systemic anti-GAG immunity induced by neonatal immunization with HIV LAMP/gag DNA vaccine in mice

Vaccines capable of inducing mucosal immunity in early postnatal life until adulthood, protecting early sexual initiation, should be considered as strategies to vaccination against HIV. The HIV-1 GAG protein as a chimera with the lysosome-associated membrane protein (LAMP/gag), encoded by a DNA vaccine, is targeted to the endosomal/lysosomal compartment that contains class II MHC molecules and has been shown to be immunogenic in adult mice. Assuming that one such strategy could help to overcome the immunological immaturity in the early postnatal period, we have evaluated the systemic and mucosal immunogenicity of LAMP/gag immunization in neonatal mice. Intranasal immunization with LAMP/gag vaccine induced higher levels of sIgA and IgG anti-GAG antibodies in intestinal washes than did the gag vaccine. The combination of ID injections and the IN protocol with the chimeric vaccine promoted the increase of Ab levels in sera. Both vaccines induced splenic IFN-gamma- secreting cells against GAG peptide pools, as well as in vivo cytotoxic T lymphocyte (CTL) function, and increased the percentage of CD8+ T cells to the immunodominant class I peptide in gut and spleen. However, only the chimeric vaccine was able to enhance Th1/Th2 cytokine secretion in response to class II GAG peptide and to enhance IL-4-secreting cells against GAG peptides and p24 protein stimuli. Long-lasting humoral and cellular responses were detected until adult age, following neonatal immunization with the chimeric vaccine. The LAMP/gag vaccination was able to induce potent GAG-specific T and B cell immune responses in early life which are essential to elicit sustained and long-lasting mucosal and systemic humoral response. (C) 2010 Elsevier GmbH. All rights reserved.

Anemia During Pregnancy after Silastic Ring Roux-en-Y Gastric Bypass: Influence of Time to Conception

Bariatric surgery before pregnancy may help prevent obesity-related gestational complications. However, maternal malnutrition is not without potential risks during pregnancy. The objective was to evaluate the influence of time to conception after silastic ring Roux-en-Y gastric bypass (SRYGB) on maternal anemia. Patients who underwent SRYGB for morbid obesity and who subsequently became pregnant were followed up at the prenatal. Thirty pregnancies occurred between July 2001 and September 2009. The patients were analyzed according to time to conception after bariatric surgery: 17 patients with time to conception < 4 years (48 months) and 13 patients with a parts per thousand yen4 years. First trimester hemoglobin levels were significantly lower in patients with time to conception a parts per thousand yen4 years (48 months) (median 9.6 g/dL, range 5.8-13.2 g/dL) than in patients with time to conception < 4 years (median 11.1 g/dL, range 9.8-13.6 g/dL; p = 0.047). The need for intravenous iron therapy or packed red cell transfusion was significantly more frequent among women who became pregnant a parts per thousand yen4 years after SRYGB compared to < 4 years (30.8% vs. 0%, p = 0.026). Pregnancy after 4 years of SRYGB is associated with maternal anemia and the need for more strict iron supplementation.

Right Orbitofrontal Corticolimbic and Left Corticocortical White Matter Connectivity Differentiate Bipolar and Unipolar Depression

Objectives: The absence of pathophysiologically relevant diagnostic markers of bipolar disorder (BD) leads to its frequent misdiagnosis as unipolar depression (UD). We aimed to determine whether whole brain white matter connectivity differentiated BD from UD depression. Methods: We employed a three-way analysis of covariance, covarying for age, to examine whole brain fractional anisotropy (FA), and corresponding longitudinal and radial diffusivity, in currently depressed adults: 15 with BD-type I (mean age 36.3 years, SD 12.0 years), 16 with recurrent UD (mean age 32.3 years, SD 10.0 years), and 24 healthy control adults (HC) (mean age 29.5 years, SD 9.43 years). Depressed groups did not differ in depression severity, age of illness onset, and illness duration. Results: There was a main effect of group in left superior and inferior longitudinal fasciculi (SLF and ILF) (all F >= 9.8; p <= .05, corrected). Whole brain post hoc analyses (all t >= 4.2; p <= .05, corrected) revealed decreased FA in left SLF in BD, versus UD adults in inferior temporal cortex and, versus HC, in primary sensory cortex (associated with increased radial and decreased longitudinal diffusivity, respectively); and decreased FA in left ILF in UD adults versus HC. A main effect of group in right uncinate fasciculus (in orbitofrontal cortex) just failed to meet significance in all participants but was present in women. Post hoc analyses revealed decreased right uncinate fasciculus FA in all and in women, BD versus HC. Conclusions: White matter FA in left occipitotemporal and primary sensory regions supporting visuospatial and sensory processing differentiates BD from UD depression. Abnormally reduced FA in right fronto-temporal regions supporting mood regulation, might underlie. predisposition to depression in BD. These measures might help differentiate pathophysiologic processes of BD versus UD depression.

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.