Incidence and risk factors for agranulocytosis in Latin American countries - the Latin study

Purpose LATIN is a multinational case-control study designed to identify risk factors for agranulocytosis and to estimate the incidence rate of the disease in some Latin American countries. Methods Each study site in Brazil, Argentina and Mexico conducted an active search of agranulocytosis patients in hematology clinics and looked for possible associations with drug use. Results The overall incidence rate was 0.38 cases per 1 million inhabitant-years. Agranulocytosis patients more often took medications already associated with agranulocytosis than controls (p=0.01), mainly methimazole (OR 44.2, 95% CI 6.8 to infinity). The population attributable risk percentage (etiologic fraction) was 56%. The use of nutrient supplements was more frequent among patients than controls (p=0.03). Conclusions Agranulocytosis seems to be very rare in Latin America. The lower than expected number of cases identified during the study period precluded estimation of the risk associated to individual drugs, with the exception of methimazol. However, this is the longest series of agranulocytosis cases ever gathered in Latin America, and information on drug exposures was collected prospectively. The conclusion is that drug-induced agranulocytosis does not seem to be a major public health problem in the study regions.

AIDS in Latin America: assessing the current status of the epidemic and the ongoing response

Background This article provides a summary of the current status of the HIV/AIDS epidemic in Latin America, as well as an outline of the diverse responses to it. Methods A search of international databases (Pubmed and ISI-Web of Science), regional databases (Scielo and Lilacs), regional and national documents and UNAIDS reports. Data are presented according to subregion. Results In Mexico HIV remains concentrated among urban men who have sex with men (MSM), and has been growing among injecting drug users (IDU) and in rural areas in relation to migration. An increasing proportion of women among those affected is observed in all countries in Central America, the most affected region, as well as increasing the impact on other vulnerable groups, such as indigenous populations. The Andean Countries have urban epidemics concentrated among MSM. In Peru, non-traditional vulnerable populations were identified. In the Southern Cone heterosexual transmission became more relevant, probably in connection with IDU epidemics and is increasingly affecting lower income groups. Incidence rates have been declining since 2002 in Brazil, the first country to guarantee free, universal access to antiretrovirals, where one-third of drug-nave patients are still initiating treatment at an advanced stage. Generally, access to treatment has improved as a result of support from the Global Fund and other initiatives, but there are concerns regarding coverage, equity and sustainability. Conclusions HIV is still concentrated among MSM in Latin America. Non-traditional vulnerable groups such as migrants and lower income populations, usually considered part of the general population, deserve attention. Programmes confronting sexual exclusion are still needed. Access to treatment has improved over time, but inequalities persist.

Sensory phenomena in obsessive-compulsive disorder and tic disorders: A review of the literature

Introduction: A variety of subjective experiences have been reported to be associated with the symptom expression of obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). First described in TS patients, these subjective experiences have been defined in different ways. There is no consensus in the literature on how to best define subjective experiences. This lack of consensus may hinder the understanding of study results and prevents the possibility of including them in the search for etiological factors associated with OCD and TS. Methods: The objective of this article was to review the descriptions of subjective experiences in the English-language literature from 1980-2007. This meta-analytic review was carried out using the English-language literature from 1980-2007 available on MEDLINE, PsycINFO, and the Cochrane Library databases using the following search terms: premonitory urges, sensory tics, ""just-right"" perceptions, sensory phenomena, sensory experiences, incompleteness, ""not just-right"" phenomena, obsessive-compulsive disorder and TS, including OCD and/or TS, in all combination searches. We also searched for the references cited in each article previously found that referred to the aforementioned terms. Thirty-one articles were included in the study. Results: Subjective experiences, in particular, the sensory phenomena, were important phenotypic variables in the characterization of the tic-related OCD subtype and were more frequent in the early-onset OCD subtype. There is a paucity of studies using structured interviews to assess sensory phenomena, their epidemiology and the etiological mechanisms associated with sensory phenomena. Conclusion: The current review provides some evidence that sensory phenomena can be useful to identify more homogenous subgroups of OCD and TS patients and should be included as important phenotypic variables in future clinical, genetic, neuroimaging, and treatment-response studies.

Adenosine deaminase and tuberculous meningitis-A systematic review with meta-analysis

Tuberculous meningitis (TBM) is a severe infection of the central nervous system, particularly in developing countries. Prompt diagnosis and treatment are necessary to decrease the high rates of disability and death associated with TBM. The diagnosis is often time and labour intensive; thus, a simple, accurate and rapid diagnostic test is needed. The adenosine deaminase (ADA) activity test is a rapid test that has been used for the diagnosis of the pleural, peritoneal and pericardial forms of tuberculosis. However, the usefulness of ADA in TBM is uncertain. The aim of this study was to evaluate ADA as a diagnostic test for TBM in a systematic review. A systematic search was performed of the medical literature (MEDLINE, LILACS, Web of Science and EMBASE). The ADA values from TBM cases and controls (diagnosed with other types of meningitis) were necessary to calculate the sensitivity and specificity. Out of a total of 522 studies, 13 were included in the meta-analysis (380 patients with TBM). The sensitivity, specificity and diagnostic odds ratios (DOR) were calculated based on arbitrary ADA cut-off values from 1 to 10 U/l. ADA values from 1 to 4 U/l (sensitivity > 93% and specificity < 80%) helped to exclude TBM; values between 4 and 8 U/l were insufficient to confirm or exclude the diagnosis of TBM (p = 0.07), and values > 8 U/l (sensitivity < 59% and specificity > 96%) improved the diagnosis of TBM (p < 0.001). None of the cut-off values could be used to discriminate between TBM and bacterial meningitis. In conclusion, ADA cannot distinguish between bacterial meningitis and TBM, but using ranges of ADA values could be important to improve TBM diagnosis, particularly after bacterial meningitis has been ruled out. The different methods used to measure ADA and the heterogeneity of data do not allow standardization of this test as a routine.

Brain Structural Variability due to Aging and Gender in Cognitively Healthy Elders: Results from the Sao Paulo Ageing and Health Study

BACKGROUND AND PURPOSE: Several morphometric MR imaging studies have investigated age- and sex-related cerebral volume changes in healthy human brains, most often by using samples spanning several decades of life and linear correlation methods. This study aimed to map the normal pattern of regional age-related volumetric reductions specifically in the elderly population. MATERIALS AND METHODS: One hundred thirty-two eligible individuals (67-75 years of age) were selected from a community-based sample recruited for the Sao Paulo Ageing and Health (SPAH) study, and a cross-sectional MR imaging investigation was performed concurrently with the second SPAH wave. We used voxel-based morphometry (VBM) to conduct a voxelwise search for significant linear correlations between gray matter (GM) volumes and age. In addition, region-of-interest masks were used to investigate whether the relationship between regional GM (rGM) volumes and age would be best predicted by a nonlinear model. RESULTS: VBM and region-of-interest analyses revealed selective foci of accelerated rGM loss exclusively in men, involving the temporal neocortex, prefrontal cortex, and medial temporal region. The only structure in which GM volumetric changes were best predicted by a nonlinear model was the left parahippocampal gyrus. CONCLUSIONS: The variable patterns of age-related GM loss across separate neocortical and temporolimbic regions highlight the complexity of degenerative processes that affect the healthy human brain across the life span. The detection of age-related Ill GM decrease in men supports the view that atrophy in such regions should be seen as compatible with normal aging.

Quantitative myocardial contrast echocardiography during pharmacological stress for diagnosis of coronary artery disease: a systematic review and meta-analysis of diagnostic accuracy studies

Aims We conducted a meta-analysis to evaluate the accuracy of quantitative stress myocardial contrast echocardiography (MCE) in coronary artery disease (CAD). Methods and results Database search was performed through January 2008. We included studies evaluating accuracy of quantitative stress MCE for detection of CAD compared with coronary angiography or single-photon emission computed tomography (SPECT) and measuring reserve parameters of A, beta, and A beta. Data from studies were verified and supplemented by the authors of each study. Using random effects meta-analysis, we estimated weighted mean difference (WMD), likelihood ratios (LRs), diagnostic odds ratios (DORs), and summary area under curve (AUC), all with 95% confidence interval (0). Of 1443 studies, 13 including 627 patients (age range, 38-75 years) and comparing MCE with angiography (n = 10), SPECT (n = 1), or both (n = 2) were eligible. WMD (95% CI) were significantly less in CAD group than no-CAD group: 0.12 (0.06-0.18) (P < 0.001), 1.38 (1.28-1.52) (P < 0.001), and 1.47 (1.18-1.76) (P < 0.001) for A, beta, and A beta reserves, respectively. Pooled LRs for positive test were 1.33 (1.13-1.57), 3.76 (2.43-5.80), and 3.64 (2.87-4.78) and LRs for negative test were 0.68 (0.55-0.83), 0.30 (0.24-0.38), and 0.27 (0.22-0.34) for A, beta, and A beta reserves, respectively. Pooled DORs were 2.09 (1.42-3.07), 15.11 (7.90-28.91), and 14.73 (9.61-22.57) and AUCs were 0.637 (0.594-0.677), 0.851 (0.828-0.872), and 0.859 (0.842-0.750) for A, beta, and A beta reserves, respectively. Conclusion Evidence supports the use of quantitative MCE as a non-invasive test for detection of CAD. Standardizing MCE quantification analysis and adherence to reporting standards for diagnostic tests could enhance the quality of evidence in this field.

Cardiopulmonary Manifestations of Hepatosplenic Schistosomiasis

Background -Schistosomiasis is a highly prevalent disease with >200 million infected people. Pulmonary hypertension is one of the pulmonary manifestations in this disease, particularly in its hepatosplenic presentation. The aim of this study was to determine the prevalence of pulmonary hypertension in schistosomiasis patients with the hepatosplenic form of the disease. Methods and Results -All patients with hepatosplenic schistosomiasis followed up at the gastroenterology department of our university hospital underwent echocardiographic evaluation to search for pulmonary hypertension. Patients presenting with systolic pulmonary artery pressure >40 mm Hg were further evaluated through right heart catheterization. Our study showed an 18.5% prevalence of patients with elevated systolic pulmonary artery pressure at echocardiography. Invasive hemodynamics confirmed the presence of pulmonary hypertension in 7.7% (95% confidence interval, 3.3 to 16.7) of patients, with a prevalence of precapillary (arterial) pulmonary hypertension of 4.6% (95% confidence interval, 1.5 to 12.7). Conclusions -Our study reinforces the role of echocardiography as a screening tool in the investigation of pulmonary hypertension, together with the need for invasive monitoring for a proper diagnosis. We conclude that hepatosplenic schistosomiasis may account for one of the most prevalent forms of pulmonary hypertension worldwide, justifying the development of further studies to evaluate the effect of specific pulmonary hypertension treatment in this particular form of the disease. (Circulation. 2009; 119: 1518-1523.)

Epidemiology of urogenital tuberculosis worldwide

Objectives: To characterize the epidemiology of urogenital tuberculosis worldwide and to compare the features of patients from developing countries to those from developed countries. Methods: A comprehensive search of articles published up to April 2008 using a combination of the terms `tuberculosis`, `genitourinary`, `renal` and `urogenital` was performed. Results: Urogenital tuberculosis affects more men than women (2:1), with a mean age of 40.7 years (range 5-90). In 26.9% of cases there is a non-functioning unilateral kidney and in 7.4%, renal failure. Patients from developing countries are more likely to have a delayed diagnosis with a higher frequency of renal failure, unilateral non-functioning kidney, ablative surgery and contracted bladder. Conclusions: Urogenital tuberculosis is a worldwide disease with more destructive behavior in developing countries where urgent strategies for early detection are particularly warranted.

Reliability assessment of Cobb angle measurements using manual and digital methods

BACKGROUND CONTEXT: The vertebral spine angle in the frontal plane is an important parameter in the assessment of scoliosis and may be obtained from panoramic X-ray images. Technological advances have allowed for an increased use of digital X-ray images in clinical practice. PURPOSE: In this context, the objective of this study is to assess the reliability of computer-assisted Cobb angle measurements taken from digital X-ray images. STUDY DESIGN/SETTING: Clinical investigation quantifying scoliotic deformity with Cobb method to evaluate the intra- and interobserver variability using manual and digital techniques. PATIENT SAMPLE: Forty-nine patients diagnosed with idiopathic scoliosis were chosen based on convenience, without predilection for gender, age, type, location, or magnitude of the curvature. OUTCOME MEASURES: Images were examined to evaluate Cobb angle variability, end plate selection, as well as intra- and interobserver errors. METHODS: Specific software was developed to digitally reproduce the Cobb method and calculate semiautomatically the degree of scoliotic deformity. During the study, three observers estimated the Cobb angle using both the digital and the traditional manual methods. RESULTS: The results showed that Cobb angle measurements may be reproduced in the computer as reliably as with the traditional manual method, in similar conditions to those found in clinical practice. CONCLUSIONS: The computer-assisted method (digital method) is clinically advantageous and appropriate to assess the scoliotic curvature in the frontal plane using Cobb method. (C) 2010 Elsevier Inc. All rights reserved.

Evaluation of rhBMP-2 and Natural Latex as Potential Osteogenic Proteins in Critical Size Defects by Histomorphometric Methods

This in vivo study evaluated the osteogenic potential of two proteins, recombinant human bone morphogenetic protein-2 (rhBMP-2) and a protein extracted from natural latex (Hevea brasiliensis, P-1), and compared their effects on bone defects when combined with a carrier or a collagen gelatin. Eighty-four (84) Wistar rats were divided into two groups, with and without the use of collagen gelatin, and each of these were divided into six treatment groups of seven animals each. The treatment groups were: (1) 5 mu g of pure rhBMP-2; (2) 5 mu g of rhBMP-2/monoolein gel; (3) pure monoolein gel; (4) 5 mu g of pure P-1; (5) 5 mu g of P-1/monoolein gel; (6) critical bone defect control. The animals were anesthetized and a 6 mm diameter critical bone defect was made in the left posterior region of the parietal bone. Animals were submitted to intracardiac perfusion after 4 weeks and the calvaria tissue was removed for histomorphometric analysis. In this experimental study, it was concluded that rhBMP-2 allowed greater new bone formation than P-1 protein and this process was more effective when the bone defect was covered with collagen gelatin (P < 0.05). Anat Rec, 293:794-801, 2010. (C) 2010 Wiley-Liss, Inc.

Evaluation of Adult Chronic Chagas` Heart Disease Diagnosis by Molecular and Serological Methods

Chagas` disease caused by Trypanosoma cruzi is endemic in Latin America. T. cruzi presents heterogeneous populations and comprises two main genetic lineages, named T. cruzi I and T. cruzi II. Diagnosis in the chronic phase is based on conventional serological tests, including indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA), and diagnosis in the acute phase based on parasitological methods, including hemoculture. The objective of this study was to evaluate the diagnostic procedures of Chagas` disease in adult patients in the chronic phase by using a PCR assay and conventional serological tests, including TESA-blot as the gold standard. Samples were obtained from 240 clinical chronic chagasic patients. The sensitivities, compared to that of TESA-blot, were 70% for PCR using the kinetoplast region, 75% for PCR using the nuclear repetitive region, 99% for IIF, and 95% for ELISA. According to the serological tests results, we recommend that researchers assess the reliability and sensitivity of the commercial kit Chagatest ELISA recombinant, version 3.0 (Chagatest Rec v3.0; Wiener Lab, Rosario, Argentina), due to the lack of sensitivity. Based on our analysis, we concluded that PCR cannot be validated as a conventional diagnostic technique for Chagas` disease. These data have been corroborated by low levels of concordance with serology test results. It is recommended that PCR be used only for alternative diagnostic support. Using the nuclear repetitive region of T. cruzi, PCR could also be applicable for monitoring patients receiving etiologic treatment.

Evaluation of computational methods for the reconstruction of HLA haplotypes

Human leukocyte antigen (HLA) haplotypes are frequently evaluated for population history inferences and association studies. However, the available typing techniques for the main HLA loci usually do not allow the determination of the allele phase and the constitution of a haplotype, which may be obtained by a very time-consuming and expensive family-based segregation study. Without the family-based study, computational inference by probabilistic models is necessary to obtain haplotypes. Several authors have used the expectation-maximization (EM) algorithm to determine HLA haplotypes, but high levels of erroneous inferences are expected because of the genetic distance among the main HLA loci and the presence of several recombination hotspots. In order to evaluate the efficiency of computational inference methods, 763 unrelated individuals stratified into three different datasets had their haplotypes manually defined in a family-based study of HLA-A, -B, -DRB1 and -DQB1 segregation, and these haplotypes were compared with the data obtained by the following three methods: the Expectation-Maximization (EM) and Excoffier-Laval-Balding (ELB) algorithms using the arlequin 3.11 software, and the PHASE method. When comparing the methods, we observed that all algorithms showed a poor performance for haplotype reconstruction with distant loci, estimating incorrect haplotypes for 38%-57% of the samples considering all algorithms and datasets. We suggest that computational haplotype inferences involving low-resolution HLA-A, HLA-B, HLA-DRB1 and HLA-DQB1 haplotypes should be considered with caution.

Comparative analysis of two immunohistochemical methods for antigen retrieval in the optical lobe of the honeybee Apis mellifera: Myosin-v assay

The present study compared two heating methods currently used for antigen retrieval (AR) immunostaining: the microwave oven and the steam cooker. Myosin-V, a molecular motor involved in vesicle transport, was used as a neuronal marker in honeybee Apis mellifera brains fixed in formalin. Overall, the steam cooker showed the most satisfactory AR results. At 100 degrees C, tissue morphology was maintained and revealed epitope recovery, while evaporation of the AR solution was markedly reduced; this is important for stabilizing the sodium citrate molarity of the AR buffer and reducing background effects. Standardization of heat-mediated AR of formalin-fixed and paraffin-embedded tissue sections results in more reliable immunostaining of the honeybee brain.

Methods for exploring the morpho-functional relations of the aortic depressor nerve in experimental diabetes

The present study investigated morpho-functional relations of the aortic depressor nerve (ADN) 5, 15 and 120 days after the onset of streptozotocin-induced diabetes in rats. Time control animals received vehicle. Under pentobarbital anesthesia, ADN activity was recorded simultaneously with arterial pressure. After the recordings, nerves were prepared for light microscopy study and morphometry. ADN function was accessed by means of pressure-nerve activity curve (fitted by sigmoidal regression) and cross-spectral analysis between mean arterial pressure (MAP) and ADN activity. The relation between morphological (myelinated fibers number and density, total myelin area, total fiber area and percentage of occupancy) and functional (gain, signal/noise relation, frequency) parameters were accessed by linear regression analysis and correlation coefficient calculations. Functional parameters obtained by means of the sigmoidal regression curve as well as by cross-spectral analysis were similar in diabetic and control rats. Morphometric parameters of the ADN were similar between groups 5 days after the onset of diabetes. Average myelin area and myelinated fiber area were significantly smaller on diabetic rats 15 and 120 days after the onset of diabetes, being the myelinated fiber and respective axons area and diameter also smaller on 120 days group. Nevertheless, G ratio (ratio between axon and fiber diameter) was nearly 0.6 and not different between groups or experimental times. No significant relationship between morphological and functional parameters was detected in all experimental groups. The present study suggests that ADN diabetic neuropathy was time-dependent, with damage to myelinated fibers to be the primary event, not evidenced by physiological methods. (C) 2010 Elsevier B.V. All rights reserved.

Genital Manifestation of Graft-vs.-Host Disease: A Series of Case Reports

Introduction. After hematopoietic stem cell transplantation (HSCT), many patients present genital graft-vs.-host disease (GVHD) that can culminate with sexual problems, which are poorly dimensioned. Aim. We hope to draw attention to the need to perform genital biopsy to diagnose genital GVHD, and thus to call attention to the need to incorporate careful attention to sexual health in the treatment of these patients. Methods. Five allogeneic stem cell transplant recipients complaining of coital pain after HSCT were clinically diagnosed for genital GVHD. Genital biopsies were given for histological analysis, and microphotographs of the corresponding marked field in the slide were taken. Specimens were evaluated by the site pathologist and then sent to a reference pathologist, each blinded to the histological findings. A literature search was performed in PubMed/MEDLINE (1966-2009) for cross-sectional and cohort studies or trials related to genital GVHD. Expert opinions peer reviews and case reports were also considered. Main Outcome Measures. HSCT, genital GVHD, genital biopsy. Results. The biopsy showed evidence of dilated apoptotic cells in the basal layer and detachment of the epithelial lining of the mucosa, hyalinization and thickening of collagen fibers, capillary ectasia, and mononuclear inflammatory infiltrate of the submucosa. Three patients presented vulval lesion such as leucoplasia and ulcer on the large lip. Histological analyses showed evidence of epithelial hyperplasia and influx of inflammatory cells to the epithelial surface, intercellular edema and spongiosis, apoptotic bodies on the basal layer of the epithelium, spongiosis, and nuclear vacuolization. A common treatment based on corticotherapy resulted in complete remission of coetaneous or mucous genital lesions in all five patients. Conclusion. Genital biopsy is important to differentially diagnose GVHD and secondary symptoms due to hypoestrogenism. Prevention is the most important step in controlling the evolution GVHD in the vagina to prevent vaginal obstruction and sexual dysfunction. da Silva Lara LA, de Andrade JM, Mauad LMQ, Ferrarese SR, Marana HRC, Tiezzi DG, and de Sa Rosa e Silva ACJ. Genital manifestation of graft-vs.-host disease: A series of case reports. J Sex Med 2010;7:3216-3225.