Atmospheric pollution: influence on hospital admissions in paediatric rheumatic diseases

Objective: To investigate the lag structure effects from exposure to atmospheric pollution in acute outbursts in hospital admissions of paediatric rheumatic diseases (PRDs). Methods: Morbidity data were obtained from the Brazilian Hospital Information System in seven consecutive years, including admissions due to seven PRDs (juvenile idiopathic arthritis, systemic lupus erythematosus, dermatomyositis, Henoch-Schonlein purpura, polyarteritis nodosa, systemic sclerosis and ankylosing spondylitis). Cases with secondary diagnosis of respiratory diseases were excluded. Daily concentrations of inhaled particulate matter (PM10), sulphur dioxide (SO2) nitrogen dioxide (NO2), ozone (O-3) and carbon monoxide (CO) were evaluated. Generalized linear Poisson regression models controlling for short-term trend, seasonality, holidays, temperature and humidity were used. Lag structures and magnitude of air pollutants' effects were adopted to estimate restricted polynomial distributed lag models. Results: The total number of admissions due to acute outbursts PRD was 1,821. The SO2 interquartile range (7.79 mu g/m(3)) was associated with an increase of 1.98% (confidence interval 0.25-3.69) in the number of hospital admissions due to outcome studied after 14 days of exposure. This effect was maintained until day 17. Of note, the other pollutants, with the exception of O-3, showed an increase in the number of hospital admissions from the second week. Conclusion: This study is the first to demonstrate a delayed association between SO2 and PRD outburst, suggesting that oxidative stress reaction could trigger the inflammation of these diseases. Lupus (2012) 21, 526-533.

Prior history of sexually transmitted diseases in women living with AIDS in Sao Paulo, Brazil

Objectives: To describe the epidemiological profile, risk behaviors, and the prior history of sexually transmitted diseases (STDs) in women living with acquired immunodeficiency syndrome (AIDS). Methods: Cross-sectional study, performed at the Centro de Referencia e Treinamento em DST/AIDS of Sao Paulo. The social, demographic, behavioral, and clinical data such as age, schooling, marital status, age at first sexual intercourse, number of sexual partners, parity, use of drugs, time of HIV diagnosis, CD4 count, and viral load determination were abstracted from the medical records of women living with AIDS who had gynecological consultation scheduled in the period from June 2008 to May 2009. Results: Out of 710 women who were scheduled to a gynecological consultation during the period of the study, 598 were included. Previous STD was documented for 364 (60.9%; 95% CI: 56.9%-64.8%) women. The associated factors with previous STDs and their respective risks were: human development index (HDI) <0.50 (ORaj = 5.5; 95% CI: 2.8-11.0); non-white race (ORaj = 5.2; 95% CI: 2.5-11.0); first sexual intercourse at or before 15 years of age (ORaj = 4.4; 95% CI: 2.3-8.3); HIV infection follow-up time of nine years or more (ORaj = 4.2; 95% CI: 2.3-7.8)]; number of sexual partners during the entire life between three and five partners (ORaj = 2.2; 95% CI: 1.1-4.6), and six or more sexual partners (ORaj = 3.9; 95% CI: 1.9-8.0%); being a sex worker (ORaj = 1.9; 95% CI: 1.1-3.1). Conclusions: A high prevalence of a prior history of STDs in the studied population was found. It is essential to find better ways to access HIV infection prevention, so that effective interventions can be more widely implemented. (C) 2012 Elsevier Editora Ltda. All rights reserved.

JC virus-associated central nervous system diseases in HIV-infected patients in Brazil: clinical presentations, associated factors with mortality and outcome

Introduction: Several presentations of neurologic complications caused by JC virus (JCV) in human immunodeficiency virus (HIV)-infected patients have been described and need to be distinguished from the "classic" form of progressive multifocal leukoencephalopathy (PML). The objectives of this study were: 1) to describe the spectrum and frequency of presentations of JCV-associated central nervous system (CNS) diseases; 2) identify factors associated with in-hospital mortality of patients with JCV-associated CNS disease; and 3) to estimate the overall mortality of this population. Material and methods: This was a retrospective study of HIV-infected patients admitted consecutively for JCV-associated CNS diseases in a referral teaching center in Sao Paulo, Brazil, from 2002 to 2007. All patients with laboratory confirmed JCV-associated CNS diseases were included using the following criteria: compatible clinical and radiological features associated with the presence of JCV DNA in the cerebrospinal fluid. JCV-associated CNS diseases were classified as follows: 1) classic PML; 2) inflammatory PML; and 3) JC virus granule cell neuronopathy (GCN). Results: We included 47 cases. JCV-associated CNS diseases were classified as follows: 1) classic PML: 42 (89%); 2) inflammatory PML: three (6%); and 3) JC virus GCN: four (9%). Nosocomial pneumonia (p = 0.003), previous diagnosis of HIV infection (p = 0.03), and imaging showing cerebellar and/or brainstem involvement (p = 0.02) were associated with in-hospital mortality. Overall mortality during hospitalization was 34%. Conclusions: Novel presentations of JCV-associated CNS diseases were observed in our setting; nosocomial pneumonia, previous diagnosis of HIV infection, and cerebellar and/or brainstem involvement were associated with in-hospital mortality; and overall mortality was high. (C) 2012 Elsevier Editora Ltda. All rights reserved.

Advancing the management of primary immunodeficiency diseases in Latin America: Latin American Society for Immunodeficiencies (LASID) Initiatives

Primary immunodeficiency diseases (PIDD) are associated with significant morbidity and mortality and result in a significant public health burden. This is in part due to the lack of appropriate diagnosis and treatment of these patients. It is critical that governments become aware of this problem and provide necessary resources to reduce this impact on health care systems. Leading physicians in their respective countries must be supported by their own governments in order to implement tools and provide education and thus improve the diagnosis and treatment of PIDD. The Latin American Society of Primary Immunodeficiencies (LASID) has initiated a large number of activities aimed at achieving these goals, including the establishment of a PIDD registry, development of educational programmes and guidelines, and the introduction of a PIDD fellowship programme. These initiatives are positively impacting the identification and appropriate treatment of patients with PIDD in Latin America. Nevertheless, much remains to be done to ensure that every person with PIDD receives proper therapy. (C) 2011 SEICAP. Published by Elsevier Espana, S.L. All rights reserved.

The therapeutic journey of families of children with respiratory diseases in the public health service

This study's purpose was to identify the therapeutic journey of families seeking health care for their children with respiratory diseases. This qualitative study had the participation of parents of children younger than five years old who were hospitalized with respiratory diseases. Path mapping was used as an instrument to collect data, which was analyzed through thematic analysis. The finding indicate that families sought the health services as soon as they perceived symptoms and had access to medical care, however such care was not decisive in resolving their health issues. Even though the families returned to the service at least another three times, the children had to be hospitalized. The attributes of primary health care were not observed in the public health services, while therapeutic encounters had no practical success.

Advanced QSAR Studies on PPAR delta Ligands Related to Metabolic Diseases

PPAR delta is a nuclear receptor that, when activated, regulates the metabolism of carbohydrates and lipids and is related to metabolic syndrome and type 2 diabetes. To understand the main interactions between ligands and PPAR delta, we have constructed 2D and 3D QSAR models and compared them with HOMO, LUMO and electrostatic potential maps of the compounds studied, as well as docking results. All QSAR models showed good statistical parameters and prediction outcomes. The QSAR models were used to predict the biological activity of an external test set, and the predicted values are in good agreement with the experimental results. Furthermore, we employed all maps to evaluate the possible interactions between the ligands and PPAR delta. These predictive QSAR models, along with the HOMO, LUMO and MEP maps, can provide insights into the structural and chemical properties that are needed in the design of new PPAR delta ligands that have improved biological activity and can be employed to treat metabolic diseases.

Anti-aquaporin-4 antibodies in the context of assorted immune-mediated diseases

Background and purposes: Anti-aquaporin 4 antibodies are specific markers for Devics disease. This study aimed to test if this high specificity holds in the context of a large spectrum of systemic autoimmune and non-autoimmune diseases. Methods: Anti-aquaporin-4 antibodies (NMO-IgG) were determined by indirect immunofluorescence (IIF) on mouse cerebellum in 673 samples, as follows: group I (clinically defined Devic's disease, n = 47); group II [ inflammatory/demyelinating central nervous system (CNS) diseases, n = 41]; group III (systemic and organ-specific autoimmune diseases, n = 250); group IV (chronic or acute viral diseases, n = 35); and group V (randomly selected samples from a general clinical laboratory, n = 300). Results: MNO-IgG was present in 40/47 patients with classic Devic's disease (85.1% sensitivity) and in 13/22 (59.1%) patients with disorders related to Devic's disease. The latter 13 positive samples had diagnosis of longitudinally extensive transverse myelitis (n = 10) and isolated idiopathic optic neuritis (n = 3). One patient with multiple sclerosis and none of the remaining 602 samples with autoimmune and miscellaneous diseases presented NMO-IgG (99.8% specificity). The autoimmune disease subset included five systemic lupus erythematosus individuals with isolated or combined optic neuritis and myelitis and four primary Sjogren's syndrome (SS) patients with cranial/peripheral neuropathy. Conclusions: The available data clearly point to the high specificity of anti-aquaporin-4 antibodies for Devic's disease and related syndromes also in the context of miscellaneous non-neurologic autoimmune and non-autoimmune disorders.

Vesicles as carriers of virulence factors in parasitic protozoan diseases

Different types of shed vesicles as, for example, exosomes, plasma-membrane-derived vesicles or microparticles, are the focus of intense research in view of their potential role in cell cell communication and under the perspective that they might be good tools for immunotherapy, vaccination or diagnostic purposes. This review discusses ways employed by pathogenic trypanosomatids to interact with the host by shedding vesicles that contain molecules important for the establishment of infection, as opposed to previous beliefs considering them as a waste of cellular metabolism. Trypanosomatids are compared with Apicomplexa, which circulate parasite antigens bound to vesicles shed by host cells. The knowledge of the origin and chemical composition of these different vesicles might lead to the understanding of the mechanisms that determine their biological function. (C) 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Respiratory diseases and associated factors: population-based study in Sao Paulo, Brazil, 2008-2009

OBJECTIVE: To assess the prevalence of acute bronchitis, rhinitis, and sinusitis among children and adolescents and identify associated factors. METHODS: This is a population-based, cross-sectional study. A household survey was conducted with 1,185 children and adolescents from the city of Sao Paulo (Southeastern Brazil), from 2008 to 2009. The participants were selected by means of probability sampling, stratified by sex and age, and by two-stage cluster sampling. For the adjusted analysis, multiple Poisson regression was used. RESULTS: Of the respondents, 7.3% reported acute bronchitis, 22.6% rhinitis and 15.3% sinusitis. After the adjusted analysis, the following characteristics were associated with self;reported acute bronchitis: age 0 to 4 years (PR=17.86; 95%Cl: 3.65;90.91), 5 to 9 years (PR=37.04; 95%CI: 8.13;166.67), 10 to 14 years (PR.=20,83; 95%Cl: 4.93;90.91), allergy (PR=3.12; 95%Cl: 1.70;5.73), black and mixed-ethnicity (black and white) skin color (PR=2.29; 95%Cl: 1.21;4.35), and living in a household with 1 to 3 rooms (PR=1.85; 95%Cl: 1.17;2.94). As to self-reported rhinitis, the following characteristics were associated: age 10 to 14 years (PR=2.77; 95%Cl: 1.60;4.78), 15 to 19 years (P.R=2.58; 95%Cl: 1.52;4.39), allergy (PR=4.32; 95%Cl: 2.79;6.70), asthma (PR=2.30; 95%CI: 1.30;4.10) and living in flats (PR=1.70; 95%Cl: 1.06;2.73). Concerning self-reported sinusitis, the following characteristics were associated: age 5 to 9 years (PR=2.44; 95%Cl: 1.09;5.43), 10 to 14 years (PR=2.99; 95%CI: 1.36;6.58), 15 to 19 years (PR=3.62; 95%Cl: 1.68;7.81), allergy (PR=2.23 (95%CI: 1.41;3.52) and obesity (PR=4.42; 95%Cl: 1.56;12.50). CONCLUSIONS: Respiratory diseases were more prevalent in population groups with defined characteristics, such as age group, self-reported diseases, type of household and obesity.

Retinal nerve fiber evaluation in neuro-ophthalmic diseases of the anterior visual pathway

Retinal nerve fiber evaluation is important in the diagnosis and management of several diseases of the anterior visual pathway. In this report we review the clinical findings and the current techonologies avalilable to analyse the retinal nerve fiber layer. We furthermore review the main findings in several disease of the anterior visual pathways including inflammatory, ischemic, toxics, hereditary, compressive and traumatic optic neuropathies as well as lesion of the optic chiasm, optic tract and lateral geniculate body.

Transplantation for Autoimmune Diseases in North and South America: A Report of the Center for International Blood and Marrow Transplant Research

Hematopoietic cell transplantation (HCT) is an emerging therapy for patients with severe autoimmune diseases (AID). We report data on 368 patients with AID who underwent HCT in 64 North and South American transplantation centers reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2009. Most of the HCTs involved autologous grafts (n = 339); allogeneic HCT (n = 29) was done mostly in children. The most common indications for HCT were multiple sclerosis, systemic sclerosis, and systemic lupus erythematosus. The median age at transplantation was 38 years for autologous HCT and 25 years for allogeneic HCT. The corresponding times from diagnosis to HCT were 35 months and 24 months. Three-year overall survival after autologous HCT was 86% (95% confidence interval [CI], 81%-91%). Median follow-up of survivors was 31 months (range, 1-144 months). The most common causes of death were AID progression, infections, and organ failure. On multivariate analysis, the risk of death was higher in patients at centers that performed fewer than 5 autologous HCTs (relative risk, 3.5; 95% CI, 1.1-11.1; P = .03) and those that performed 5 to 15 autologous HCTs for AID during the study period (relative risk, 4.2; 95% CI, 1.5-11.7; P = .006) compared with patients at centers that performed more than 15 autologous HCTs for AID during the study period. AID is an emerging indication for HCT in the region. Collaboration of hematologists and other disease specialists with an outcomes database is important to promote optimal patient selection, analysis of the impact of prognostic variables and long-term outcomes, and development of clinical trials. Biol Blood Marrow Transplant 18: 1471-1478 (2012) (C) 2012 Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation

Advances in primary immunodeficiency diseases in Latin America: epidemiology, research, and perspectives

Primary immunodeficiencies (PIDs) are genetic disorders of the immune system comprising many different phenotypes. Although previously considered rare, recent advances in their clinical, epidemiological, and molecular definitions are revealing how much we still need to learn about them. For example, geographical and ethnic variations as well as the impact of certain practices influence their frequency and presentation, making it necessary to consider their study in terms of regions. The Latin American Society for Immunodeficiencies was established as an organization dedicated to provide scientific support for basic and clinical research and to develop tools and educational resources to promote awareness in the medical community. Initiatives such as these are positively influencing the way PIDs are tackled in these countries, as shown by recent reports and publications. This paper provides a historical compilation and a current view of the many issues faced by scientists studying these diseases in these countries, highlighting the diverse scientific contributions and offering a promising perspective for the further developments in this field in Latin America.

Oxidized low-density lipoproteins and their antibodies: Relationships with the reverse cholesterol transport and carotid atherosclerosis in adults without cardiovascular diseases

Background: Metabolic predictors and the atherogenicity of oxidized LDL (oxLDL) and the specific antibodies against oxLDL (oxLDL Ab) are unclear and controversial. Methods: In 107 adults without atherosclerotic manifestations, we measured oxLDL and oxLDL Ab, and also the activities of CETP. PLTP, lipases and the carotid intima-media thickness (cIMT). Comparisons were performed for the studied parameters between the lowest and the highest tertile of oxLDL and oxLDL Ab, and the relationships between studied variables were evaluated. Results: Subjects with higher oxLDL Ab present reduced hepatic lipase activity and borderline increased cIMT. In the highest oxLDL tertile, besides the higher levels of total cholesterol, LDL-C and apoB100, we found reduced CETP activity and higher cIMT. A significant correlation between oxLDL Ab and cIMT, independent of oxLDL, and a borderline correlation between oxLDL and cIMT independent of oxLDL Ab were found. In the multivariate analysis, apoAl was a significant predictor of oxLDL Ab, in contrast to regulation of oxLDL by apoB100, PLTP and inverse of CETP. Conclusions: In adults without atherosclerotic disease, the metabolic regulation and carotid atherosclerosis of oxLDLAb and oxLDL groups, characterized a dual trait in oxLDL Ab, as a contributor to carotid atherosclerosis, much less so than oxidized LDL, and with a modest atheroprotective role. (C) 2012 Elsevier B.V. All rights reserved.

Bioethical Aspects Across Medicine: The Care of Cardiovascular Diseases in Brazil

Bioethics applied to medicine extrapolates the traditional medical concepts of non-maleficence (primum non nocere) and beneficence (bonum facere) and regards to justice, autonomy, equity, protection, compassion and humanization, not considering people just like patients, but understanding the complex existence of each single person. Worldwide, the morbidity and mortality indices regarding to diseases of heart and blood vessels became progressively grater. For countries in development, like Brazil, these numbers are even more expressive and this increase trend seems to be caused by wider exposition of population to some risk factors. This article broaches an intersection between bioethics and medicine, focusing the reality of cardiovascular diseases in Brazil and the necessity of doctors to base their behavior in bioethical paradigms.

Structure- and ligand-based drug design approaches for neglected tropical diseases

Drug discovery has moved toward more rational strategies based on our increasing understanding of the fundamental principles of protein-ligand interactions. Structure( SBDD) and ligand-based drug design (LBDD) approaches bring together the most powerful concepts in modern chemistry and biology, linking medicinal chemistry with structural biology. The definition and assessment of both chemical and biological space have revitalized the importance of exploring the intrinsic complementary nature of experimental and computational methods in drug design. Major challenges in this field include the identification of promising hits and the development of high-quality leads for further development into clinical candidates. It becomes particularly important in the case of neglected tropical diseases (NTDs) that affect disproportionately poor people living in rural and remote regions worldwide, and for which there is an insufficient number of new chemical entities being evaluated owing to the lack of innovation and R&D investment by the pharmaceutical industry. This perspective paper outlines the utility and applications of SBDD and LBDD approaches for the identification and design of new small-molecule agents for NTDs.