A perimenopausa é a fase da vida reprodutiva feminina caracterizada diversas alterações, inclusive cognitivas devido ao hipoestrogenismo. Através de estudo duplo-cego randomizado com 16 mulheres na perimenopausa deprimidas que receberam estradiol e 16 que receberam placebo analisou-se as alterações cognitivas da atenção, memória e linguagem; o efeito da reposição hormonal com estradiol e a correlação entre os sintomas depressivos e menopausais com as alterações destas funções. Os resultados mostraram: melhora do controle inibitório, memória imediata e tardia (verbal e visual) e da capacidade de nomeação nos dois grupos; melhora dos sintomas depressivos e menopausais para o grupo que recebeu reposição hormonal: e não correlação entre a melhora destes sintomas e a melhora das funções cognitivas / Perimenopause is the female reproductive life period characterized by several changes including cognitive impairments related to hypoestrogenism. In a randomized double-blind study 16 depressive perimenopaused women took estradiol, while another group of 16 depressive perimenopaused women took placebo. Cognitive alterations associated to attention, memory and language, and estradiol hormone replacement therapy effects were evaluated. In addition, correlations among symptoms of depression and menopause, and cognitive alterations were also analyzed. The results had shown, in both groups, an improvement in inhibitory mental control, in immediate and delayed (verbal and visual) memory, and in naming capacity. In the group that received hormone replacement therapy our findings revealed a weakening of depression and menopause symptoms, which had shown no correlation with cognitive functions

Avaliamos as mudanças no padrão respiratório, movimento toracoabdominal e ventilação em portadores de DPOC e indivíduos sadios. Estudou-se 45 indivíduos entre 45 e 75 anos conforme o VEF1. Utilizou-se sistemas de pletismografia respiratória por indutância, análise metabólica de gases em posição semi-sentada ao repouso e radiografia de tórax para a mobilidade diafragmática. Os grupos DPOC apresentaram redução do TI, TTOT, aumento do VC/TI, f, VE, das relações VEM/VC, VE/VO2, VE/VCO2 e diminuição da SpO2. Redução da mobilidade do diafragma e aumento da VEM/VC associaram-se à ineficiência da ventilação e a alterações no modelo ventilatório utilizado, sem alterações no movimento toracoabdominal. / We assessed changes in breathing patterns, thoracoabdominal movement and ventilation in COPD sufferers and healthy individuals. Forty-five individuals between 45 and 75 were grouped by FEV1. Inductive plethysmographic equipment, respiratory metabolism measuring (with subject at rest in semi-recumbent position), and radiographic measurement of diaphragm mobility were used. The COPD groups presented reduction in TI and TTOT and increased VT/TI, f, VE, and VD/VT, VE/VO2, VE/VCO2 and decreased SpO2. Reduction in diaphragm mobility and increase of VEM/VC were associated with ventilatory inefficiency and alterations in the ventilatory model used. No alterations in thoracoabdominal movement

Methicillin-resistant Staphylococcus aureus (MRSA) is an antibiotic-resistant bacterium of epidemiologic importance in Canadian healthcare facilities. The contact between MRSA colonized or infected patients with other patients, healthcare workers (HCWs) and/or the healthcare environment can result in MRSA transmission and healthcare-associated MRSA (HA-MRSA) infections in hospitals. These HA-MRSA infections are linked with increased length of hospital stay, economic burden, morbidity and mortality. Although infection prevention and control programs initiated in 2009 in Canada and other developed countries (e.g., UK, France, Belgium, Denmark, etc.) have been relatively successful in reducing the rate of HA-MRSA infections, they continue to pose a threat to patients, especially to the more vulnerable in long term care and geriatric institutions. Historically, MRSA was a problem mainly in hospital settings but after mid-1990s new strains of MRSA have been identified among people without healthcare-related risks and have been classified as community-associated MRSA (CA-MRSA). Furthermore, the distinction between HA-MRSA and CA-MRSA strains is gradually waning due to both the introduction of HA-MRSA in communities, and the emergence of CA-MRSA strains in hospitals. The purpose of this thesis was to explore the feasibility of constructing healthcare networks to evaluate the role of healthcare providers (e.g., physicians) and places (e.g., patient rooms) in the transmission of MRSA in a large tertiary care facility. Method of investigation: a secondary data case-control study, using individual characteristics and network structure measures, conducted at The Ottawa Hospital (TOH) between April 1st, 2013 and March 31th, 2014. Results: It was feasible to build social networks in a large tertiary care facility based on electronic medical records data. The networks' size (represented by the number of vertices and lines) increased during the outbreak period (period 1) compared to the pre-outbreak period (period 0) for both groups and at all three TOH campuses. The calculated median degree centrality showed significant increase in value for both study groups during period 1 compared to period 0 for two of the TOH campuses (Civic and General). There was no significant difference between the median degree centrality calculated for each study group at the Heart Institute when compared for the two reference periods. The median degree centrality of the MRSA case group for period 0 showed no significant difference when compared to the same measure determined for the control group for all three TOH campuses. However, the median degree centrality calculated for period 1 was significantly increased for the control group compared to the MRSA case group for two TOH campuses (Civic and General) but showed no significant difference between the two groups from the Heart Institute. In addition, there was a correlation between the two network measures (degree centrality and eigenvector centrality) calculated to determine the most influential person or place in the MRSA case group networks. However, there was no correlation between the two network’s measures calculated for physicians included in MRSA case group networks. Conclusions: It is feasible to use social network analysis as an epidemiologic analysis tool to characterize the MRSA transmission in a hospital setting. The network's visible changes between the groups and reference periods were reflected by the network measures and supported also by known hospital patient movements after the outbreak onset. Furthermore, we were able to identify potential source cases and places just prior of the outbreak start. Unfortunately, we were not able to show the role of healthcare workers in MRSA transmission in a hospital setting due to limitations in data collection and network measure chosen (eigenvector centrality). Further research is required to confirm these study findings.

Les pneumonies chez l’enfant de moins de 5 ans restent à l’heure actuelle un enjeu majeur de santé publique. Afin d’étudier les agents étiologiques des pneumonies chez les enfants de moins de 5 ans dans les pays à revenu faible ou intermédiaire, une étude cas-témoins a été réalisée entre 2010 et 2014 dans cette population par le réseau Global Approach for Biological Research on Infectious Epidemics in Low Income Countries (GABRIEL). Notre travail s’est attaché à décrire la distribution des sérotypes de Streptococcus pneumoniae retrouvés dans la population de l’étude, d’évaluer la prévalence du virus infuenza et d’évaluer l’effet du virus sur la gravité de la pneumonie, et enfin d’étudier la fréquence des co-détections bactériennes et virales au niveau nasopharyngé ainsi que leur effet sur le risque de pneumonie. Les résultats montraient que la majorité des sérotypes pneumococciques retrouvés étaient inclus dans le vaccin pneumococcique conjugué 13-valent (PCV13) et suggèraient que les souches de S. pneumoniae retrouvées au niveau nasopharyngé et au niveau sanguin étaient identiques chez un même individu atteint de pneumonie. L’importance du virus influenza, et particulièrement d’influenza A H1N1 a été soulignée. Enfin, de nombreuses co-détections nasopharyngées de microorganismes étaient observées chez les cas mais aussi chez les témoins. Leur pathogénicité semblait différer selon les espèces et pourrait dépendre des interactions avec le microbiome du tractus respiratoire. Les résultats suggèraient que la mise en œuvre de campagnes de vaccination par PCV13 pourrait être efficace dans les pays étudiés. Néanmoins, de nouvelles études précisant le rôle des co-détections entre bactéries et virus dans la physiopathologie de la pneumonie sont nécessaires pour guider les décisions de santé publique de façon optimale / Pneumonia remains a public health issue in children under 5 years old. In order to study the etiological agents of pneumonia in this population, a case-control study was carried out between 2010 and 2014 by the Global Approach for Biological Research on Infectious Epidemics in Low Income Countries (GABRIEL) Network in 9 study sites located in 8 low or middle-income countries. The objectives of the present work were to describe the distribution of Streptococcus pneumoniae serotypes, to assess the burden of influenza virus and its effect on the severity of pneumonia, and to study bacterial/viral co-detection in nasopharyngeal samples and their effect on the risk of pneumonia. Results showed that most of S. pneumoniae serotypes detected were included in the pneumococcal 13-Valent conjugate vaccine (PCV13) and confirmed the assumption that the isolate carrying or causing disease in an individual were of the same serotype. The importance of the burden of influenza virus in pneumonia cases, and particularly A H1N1 influenza, was highlighted. Finally, numerous nasopharyngeal co-detections were found both in pneumonia cases and in control subjects. Pathogenicity of microorganisms differs between species and might depend of the interactions with the microbiome of the respiratory tract. Results suggested that the implementation of PCV13 vaccination policies might be effective in the study population. Nevertheless, further studies focused on the most important co-detections of micro-organisms are needed to improve the understanding of their role in the pathogenesis of pneumonia and to guide appropriate public health interventions

No description available.

Introduction : Le cancer de l’ovaire est le cancer gynécologique le plus fatal dans le monde et est associé à un fardeau économique considérable pour les systèmes de santé publique, les patients et leurs familles. Actuellement, la prévention de ce cancer passe par l’identification des facteurs de risque, dont l’inflammation. Le double rôle de l’inflammation dans la carcinogenèse (transformation néoplasique et stimulation de la croissance pour l’inflammation chronique, mais également l’inhibition de la croissance pour inflammation aiguë) a déjà été observé au 19ième siècle, par Rudolf Virchow et par l’allemand Bruns, respectivement. Plusieurs preuves suggèrent aussi que le cancer de l’ovaire pourrait être lié à l’inflammation chronique de l’épithélium ovarien d’où l’hypothèse selon laquelle les analgésiques ayant une action anti-inflammatoire comme les anti-inflammatoires non stéroïdiens (AINS) et l’acétaminophène pourraient prévenir le cancer de l’ovaire. Contrairement à l’inflammation chronique, un autre facteur intéressant qui pourrait jouer un rôle sur le cancer de l’ovaire par le biais d’une inflammation aiguë est la mastite puerpérale qui est la forme la plus courante de mastite. Cependant, la littérature existante, examinant l’usage des analgésiques (aspirine, AINS non aspirine et acétaminophène) et le risque de cancer ovarien, est incohérente avec des différences populationnelles (cohortes de naissance différentes) et méthodologiques : variations des définitions de l’utilisation régulière, des variables d’ajustement, mais aussi dans la prise en compte d’une possible causalité inverse. De plus, aucune étude n’a tenté d’évaluer l’association dépendante du temps entre l’utilisation régulière de ces médicaments et le risque de cancer ovarien. Pour la mastite puerpérale pendant l’allaitement, deux articles avaient évalué son association avec le risque de cancer épithélial de l’ovaire (CEO), mais avec des limites méthodologiques : violation de la positivité avec l’inclusion des femmes qui n’ont jamais eu de grossesse et sur-ajustement avec la durée d’allaitement qui est dans le chemin causal. Objectif : Cette thèse visait à atteindre deux objectifs généraux qui sont de fournir de nouvelles preuves concernant les associations entre : 1) l’utilisation régulière d’analgésiques et le risque de CEO ; 2) la mastite puerpérale et le risque de CEO. Méthode : Nous avons utilisé les données d’une étude cas-témoin populationnelle visant à documenter les facteurs pour la prévention du cancer de l’ovaire au Québec (Étude PROVAQ). Cette étude a été menée dans la grande région de Montréal, Canada, de mars 2011 à septembre 2016 avec 498 cas et 908 témoins. Notre approche méthodologique a été effectuée en trois étapes. Premièrement, nous avons utilisé l’ensemble des données de PROVAQ pour l’évaluation des associations entre l’utilisation régulière de types de médicaments analgésiques, et aussi selon l’indication et le risque de CEO. Deuxièmement, à partir des données de PROVAQ, nous avons évalué l’association dépendante du temps entre l’utilisation régulière d’un type de médicaments et le risque de CEO à l'aide d'un indice cumulatif pondéré flexible d'exposition dans des modèles de régression logistique conditionnelle. Enfin, nous avons évalué l’association entre la mastite puerpérale et le risque de CEO chez les femmes allaitantes (174 cas et 431 témoins). La régression logistique a été utilisée pour estimer ces associations. Résultats : Nos résultats suggèrent que l'utilisation régulière d’aspirine et d'AINS non aspirine était inversement associée au CEO avec des rapports de cotes (RC) ajustés de 0,81 (IC à 95 % : 0,57–1,12) et 0,74 (IC à 95 % : 0,54–1,00), respectivement. Pour l'utilisation régulière d'AINS non aspirine, les RCs ajustés des COX-2 non sélective et sélective étaient de 0,73 (IC à 95 % : 0,50–1,00) et de 0,83 (IC à 95 % : 0,48–1,40), respectivement. Des associations similaires ont été observées selon le niveau de durée cumulative à vie ou de quantité cumulative à vie de prises d’aspirine et d’AINS non aspirine. Cependant, les associations entre les types de médicaments analgésiques et le CEO peuvent différer selon leurs indications. Aucune association n’a été trouvée entre le moment de l'utilisation régulière d’un type de médicaments analgésiques au cours des 40 années précédant la date index et le CEO. Aucune association significative n’a été aussi trouvée entre la mastite puerpérale pendant l'allaitement et le CEO (RC = 1,15 ; IC à 95 % : 0,71–1,84). Conclusions : Cette thèse fournit des preuves qui appuient l'hypothèse selon laquelle l'utilisation régulière d'aspirine et d'AINS non aspirine sont inversement associées au CEO. Nos résultats suggèrent également l'importance de considérer les indications d'utilisation lors de l'examen des relations entre les types de médicaments analgésiques et le CEO. Elle n’a pas trouvé d'association entre le moment de l'utilisation régulière d’analgésiques et le CEO mais aussi entre la mastite puerpérale pendant l’allaitement et le CEO. Cependant, notre étude a manqué de puissance. / Introduction: Ovarian cancer is the most fatal gynecological cancer in the world and is associated with a considerable economic burden for public health systems, patients and their families. Currently, the prevention of this cancer requires the identification of risk factors including inflammation. The dual role of inflammation in carcinogenesis (neoplastic transformation and stimulation of cancer growth for chronic inflammation, but also inhibition of cancer growth for acute inflammation) has already been observed in the 19th century, by Rudolf Virchow and by the German Bruns, respectively. Several pieces of evidence also suggest that ovarian cancer could be linked to chronic inflammation of the ovarian epithelium, hence the hypothesis that analgesics with an anti-inflammatory action such as nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen could prevent ovarian cancer. Unlike chronic inflammation, another interesting factor that could play a role in ovarian cancer through acute inflammation is puerperal mastitis which is the most common form of mastitis. However, the existing literature examining the use of analgesics (aspirin, non-aspirin NSAIDs and acetaminophen) and the risk of ovarian cancer is inconsistent with population (different birth cohorts) and methodological differences: variations in definitions of regular use, adjustment variables but also in taking into account a possible reverse causality. In addition, no studies have attempted to assess the time-dependent association between regular use of these drugs and the risk of ovarian cancer. For puerperal mastitis during breastfeeding, two articles had assessed its association with the risk of epithelial ovarian cancer (EOC) but with methodological limitations: violation of positivity with the inclusion of women who never had of pregnancy and over-adjustment with the duration of breastfeeding which is in the causal path. Objective: This thesis aimed to achieve two general objectives which are to provide new evidence regarding the associations between: 1) the regular use of analgesics and the risk of EOC; 2) puerperal mastitis and the risk of EOC. Method: We used data from a population-based case-control study aimed at documenting factors for the prevention of ovarian cancer in Quebec (PROVAQ study). This study was conducted in the greater Montreal area, Canada, from March 2011 to September 2016 with 498 cases and 908 controls. Our methodological approach was carried out in three stages. First, we used the PROVAQ dataset to assess associations between regular use of analgesic drugs types, and also by indication and EOC risk. Second, from PROVAQ data, we evaluated the time-dependent association between regular use of a type of medication and the risk of EOC using a flexible weighted cumulative index of exposure in conditional logistic regression models. Finally, we evaluated the association between puerperal mastitis and the risk of EOC in lactating women (174 cases and 431 controls). Unconditional logistic regression was used to estimate associations between regular use of analgesic drugs types, puerperal mastitis during breastfeeding and EOC risk. Results: Our results suggest that regular use of aspirin and non-aspirin NSAIDs were inversely associated with EOC with adjusted ORs of 0.81 (95% CI: 0.57–1.12) and 0.74 (95% CI: 0.54–1.00), respectively. For regular non-aspirin NSAID use, the adjusted ORs for non-selective and selective COX-2 were 0.73 (95% CI: 0.50–1.00) and 0.83 (95% CI: 0.48–1.40), respectively. Similar associations were observed according to the level of lifetime cumulative duration or lifetime cumulative quantity of aspirin and non-aspirin NSAID. However, the associations between analgesic drug types and EOC may differ according to their indications. No association was found between the time of regular use of any type of analgesic medication in the 40 years prior to the index date and EOC. No significant association was also found between puerperal mastitis during breastfeeding and EOC (OR = 1.15; 95% CI: 0.71–1.84). Conclusions: This thesis provides evidence that supports the hypothesis that regular use of aspirin and non-aspirin NSAIDs are inversely associated with EOC. Our results also suggest the importance of considering indications for use when examining relationships between analgesic drug types and EOC. We found no association between the timing of regular analgesic use and EOC but also between puerperal mastitis during breastfeeding and EOC. However, our study was underpowered.

Yes / To determine whether jugular venous reflux (JVR) is associated with cerebral white matter changes (WMCs) in individuals with Alzheimer's disease (AD), we studied 12 AD patients 24 mild cognitive impairment (MCI) patients, and 17 elderly age- and gender-matched controls. Duplex ultrasonography and 1.5T MRI scanning was applied to quantify cerebral WMCs [T2 white matter (WM) lesion and dirty-appearing-white-matter (DAWM)]. Subjects with severe JVR had more frequently hypertension (p = 0.044), more severe WMC, including increased total (p = 0.047) and periventricular DAWM volumes (p = 0.008), and a trend for increased cerebrospinal fluid volumes (p = 0.067) compared with the other groups. A significantly decreased (65.8%) periventricular DAWM volume (p = 0.01) in the JVR-positive AD individuals compared with their JVR-negative counterparts was detected. There was a trend for increased periventricular and subcortical T2 WMC lesion volumes in the JVR-positive AD individuals compared with their JVR-negative counterparts (p = 0.073). This phenomenon was not observed in either the control or MCI groups. In multiple regression analysis, the increased periventricular WMC lesion volume and decreased DAWM volume resulted in 85.7% sensitivity and 80% specificity for distinguishing between JVR-positive and JVR-negative AD patients. These JVR-WMC association patterns were not seen in the control and MCI groups. Therefore, this pilot study suggests that there may be an association between JVR and WMCs in AD patients, implying that cerebral venous outflow impairment might play a role in the dynamics of WMCs formation in AD patients, particularly in the periventricular regions. Further longitudinal studies are needed to confirm and validate our findings.

Os alelos HLA-DPB1*04 e HLA-DRB1*15 estão fortemente associados à Granulomatose com poliangeíte (GPA). Neste estudo, analisamos se os pacientes brasileiros com diagnóstico de GPA apresentam uma base genética na região HLA. Conduzimos um estudo caso-controle, em que analisamos os alelos da região HLA classe I e II em 55 pacientes com diagnóstico de GPA, atendidos no ambulatório de Vasculites Pulmonares do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, e comparamos com os resultados de 110 controles saudáveis. Comparamos também quatro diferentes apresentações clínicas da GPA e a positividade do anticorpo anticitoplasma de neutrófilos (ANCA) com os alelos da região HLA classe I e II. Foi também construída uma árvore de decisões, usando o algoritmo de CART, para a verificação da associação entre os alelos HLA e GPA. Como resultados, observamos que a GPA esteve fortemente associada à presença dos alelos DPB1*04 e DRB1*15 (p = 0,007, odds ratio [OR]: 2,9, 95% intervalo de confiança [IC]: 1,09-3,8; p = 0,006, OR: 2,87, 95% IC: 1,44-4,75, respectivamente) e não à presença do alelo DRB1*04. O alelo DRB1*13 esteve associado com proteção contra GPA (p = 0,042, OR: 0,42, 95% CI: 0,21-0,99). O alelo DPB1*04 esteve significativamente associado a GPA e ANCA-C positivo (OR: 5,47) e à presença de insuficiência renal aguda (p = 0,01037). Concluímos que houve uma interdependência significativa entre os alelos DPB1*0401, DPB1*0402, DRB1*13, C*2 e GPA. Na população estudada, quando o alelo DPB1*04 esteve presente em homozigose, o risco de GPA foi de 81%. Quando o alelo DPB1*0401 esteve ausente ou em heterozigose com o DPB1*0402, como o outro alelo, ou DPB1*0402 esteve em homozigose, o risco da GPA foi de 52,9%. No caso de ausência dos alelos DPB1*0401, DPB1*0402 e DRB1*13, a presença do alelo C*2 aumentou o risco da GPA para 62,5%. Finalmente, na ausência do alelo DPB1*0401 e DPB1*0402 e na presença do alelo DRB1*13, o risco de GPA diminuiu para 0% / The alleles HLA-DPB1*04 and HLA-DRB1*15 are strongly associated with granulomatosis with polyangiitis (GPA). In this study, we examined whether Brazilian patients with GPA had an HLA region genetic background. We conducted a case-control study, in which we analysed alleles of HLA region class I and II from 55 patients with GPA (at the Pulmonary Vasculitis Clinic of the University of São Paulo) and compared the results with those from 110 healthy controls. Comparisons were also performed for 4 different clinical presentations of GPA and anti-neutrophil cytoplasmic antibody (ANCA) positivity and the HLA class I and II region alleles. A tree model decision analysis was conducted using CART algorithm. Our results showed that GPA was strongly associated with alleles DPB1*04 and DRB1*15 (p = 0.007, odds ratio [OR]: 2.9, 95% confidence interval [CI]: 1.09-3.8; p = 0.006, OR: 2.87, 95% CI: 1.44-4.75, respectively) and not with the allele DRB1*04. DRB1*13 allele was associated with protection against GPA (p = 0.042, OR: 0.42, 95% CI: 0.21-0.99). DPB1*04 was significantly associated with GPA plus positive C-ANCA (OR: 5.47) and acute renal failure (p = 0.01037). We concluded that there was a significant interdependence among alleles and GPA. In our population, when allele DPB1*04 was presented in homozygous, the risk of GPA was 81%. When DPB1*0401 allele was absent or heterozygous with DPB1*0402 as the other allele, or DPB1*0402 was homozygous, the risk of disease was 52.9%. If DPB1*0401, DPB1*0402, and DRB1*13 were absent, the presence of C*2 increased the risk of GPA to 62.5%. Finally, in the absence of DPB1*0401 and DPB1*0402 and the presence of DRB1*13, the risk of GPA decreased to 0%

Os alelos HLA-DPB1*04 e HLA-DRB1*15 estão fortemente associados à Granulomatose com poliangeíte (GPA). Neste estudo, analisamos se os pacientes brasileiros com diagnóstico de GPA apresentam uma base genética na região HLA. Conduzimos um estudo caso-controle, em que analisamos os alelos da região HLA classe I e II em 55 pacientes com diagnóstico de GPA, atendidos no ambulatório de Vasculites Pulmonares do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, e comparamos com os resultados de 110 controles saudáveis. Comparamos também quatro diferentes apresentações clínicas da GPA e a positividade do anticorpo anticitoplasma de neutrófilos (ANCA) com os alelos da região HLA classe I e II. Foi também construída uma árvore de decisões, usando o algoritmo de CART, para a verificação da associação entre os alelos HLA e GPA. Como resultados, observamos que a GPA esteve fortemente associada à presença dos alelos DPB1*04 e DRB1*15 (p = 0,007, odds ratio [OR]: 2,9, 95% intervalo de confiança [IC]: 1,09-3,8; p = 0,006, OR: 2,87, 95% IC: 1,44-4,75, respectivamente) e não à presença do alelo DRB1*04. O alelo DRB1*13 esteve associado com proteção contra GPA (p = 0,042, OR: 0,42, 95% CI: 0,21-0,99). O alelo DPB1*04 esteve significativamente associado a GPA e ANCA-C positivo (OR: 5,47) e à presença de insuficiência renal aguda (p = 0,01037). Concluímos que houve uma interdependência significativa entre os alelos DPB1*0401, DPB1*0402, DRB1*13, C*2 e GPA. Na população estudada, quando o alelo DPB1*04 esteve presente em homozigose, o risco de GPA foi de 81%. Quando o alelo DPB1*0401 esteve ausente ou em heterozigose com o DPB1*0402, como o outro alelo, ou DPB1*0402 esteve em homozigose, o risco da GPA foi de 52,9%. No caso de ausência dos alelos DPB1*0401, DPB1*0402 e DRB1*13, a presença do alelo C*2 aumentou o risco da GPA para 62,5%. Finalmente, na ausência do alelo DPB1*0401 e DPB1*0402 e na presença do alelo DRB1*13, o risco de GPA diminuiu para 0% / The alleles HLA-DPB1*04 and HLA-DRB1*15 are strongly associated with granulomatosis with polyangiitis (GPA). In this study, we examined whether Brazilian patients with GPA had an HLA region genetic background. We conducted a case-control study, in which we analysed alleles of HLA region class I and II from 55 patients with GPA (at the Pulmonary Vasculitis Clinic of the University of São Paulo) and compared the results with those from 110 healthy controls. Comparisons were also performed for 4 different clinical presentations of GPA and anti-neutrophil cytoplasmic antibody (ANCA) positivity and the HLA class I and II region alleles. A tree model decision analysis was conducted using CART algorithm. Our results showed that GPA was strongly associated with alleles DPB1*04 and DRB1*15 (p = 0.007, odds ratio [OR]: 2.9, 95% confidence interval [CI]: 1.09-3.8; p = 0.006, OR: 2.87, 95% CI: 1.44-4.75, respectively) and not with the allele DRB1*04. DRB1*13 allele was associated with protection against GPA (p = 0.042, OR: 0.42, 95% CI: 0.21-0.99). DPB1*04 was significantly associated with GPA plus positive C-ANCA (OR: 5.47) and acute renal failure (p = 0.01037). We concluded that there was a significant interdependence among alleles and GPA. In our population, when allele DPB1*04 was presented in homozygous, the risk of GPA was 81%. When DPB1*0401 allele was absent or heterozygous with DPB1*0402 as the other allele, or DPB1*0402 was homozygous, the risk of disease was 52.9%. If DPB1*0401, DPB1*0402, and DRB1*13 were absent, the presence of C*2 increased the risk of GPA to 62.5%. Finally, in the absence of DPB1*0401 and DPB1*0402 and the presence of DRB1*13, the risk of GPA decreased to 0%

BACKGROUND: Many women of reproductive age are employed in industries involving exposure to organic solvents. Animal toxicological studies and human case reports demonstrate that exposure to organic solvents can cause neuropsychological deficits in exposed offspring; however, there is limited data from prospective controlled human studies. OBJECTIVE: To compare neuropsychological functioning between children whose mothers were occupationally exposed to organic solvents during pregnancy with a non-exposed matched comparison group. METHODS: Participants were 48 women who had previously contacted the Motherisk Program in Toronto, Canada during pregnancy regarding occupational exposure to organic solvents and a matched comparison group of women with no known exposure to teratogens during pregnancy. Children (18 months to 8 years 11 months at time of study) were compared in areas of cognitive, language, motor, and behavioral functioning. RESULTS: Children whose mothers were exposed to organic solvents during pregnancy displayed a lower level of functioning when compared with their matched peers in areas of cognitive, language, motor, and behavioral domains. Although the scores on measures of behavioral functioning were not in the clinical range, the mothers of exposed children reported more challenging behavioral problems. In order to determine whether exposure predicted neuropsychological outcomes above and beyond maternal intellectual functioning, hierarchical regressions were run with maternal IQ and maternal education at Step 1and exposure status added at Step 2. In utero exposure to organic solvents predicted lower sores on global measures of Verbal IQ, receptive and expressive language scales above and beyond maternal intellectual functioning. Factors associated with higher levels of exposure (detecting odor, longer duration and total number of toxicity symptoms) was associated with poorer outcome on behavioral and motor functioning tests. CONCLUSION: Despite the fact that the exposed mothers experienced minimal symptoms of toxicity, detrimental effects were still evident in their offspring. Current safety standards for exposure were designed for adults and need to be reevaluated. Further studies addressing exposure to specific organic solvents, dose, and gestational timing of exposure are warranted.