A Doença Reumática Cardíaca (DRC) é uma séria complicação de orofaringite causada por determinados sorotipos de Streptococcus pyogenes não tratada adequadamente em indivíduos suscetíveis. É um grande problema de saúde pública, principalmente nos países não desenvolvidos e em desenvolvimento, como Brasil, Índia, países da África, regiões de população aborígine da Austrália, e Egito. É altamente debilitante e com alta taxa de mortalidade devido ao comprometimento cardíaco. As lesões miocárdicas iniciais regridem, mas as lesões valvares, principalmente a mitral e a aórtica, são irreversíveis e progressivas. Muitos estudos já caracterizaram a resposta imune celular (linfócitos T) e humoral nos indivíduos acometidos pela doença. Mimetismo molecular e espalhamento de epítopo são os principais mecanismos que se pensa estar envolvidos na patogênese da DRC. Avaliamos, nesta pesquisa, o perfil de expressão proteica em valvas mitrais de indivíduos acometidos por DRC. Para detectar alterações específicas desta doença, comparamos as expressões de proteínas nos grupos portadores de DRC com insuficiência (DRC-INS) e com estenose (DRC-EST) a um grupo de indivíduos com degeneração mixomatosa de valva mitral (DMX) e outro sem valvulopatias (CTL). Alterações especificamente observadas em tecido mitral na DRC-INS ou DRC-EST em fases avançadas da doença podem explicar o mecanismo de desenvolvimento desses dois tipos de lesão. Foram encontradas 25 \"spots\", correpondendo a 29 proteínas diferencialmente expressas nos grupos com valvulopatias, refletindo principalmente alterações na matriz extracelular. Encontramos importante clivagem diferencial da vimentina, cuja proteína íntegra possui 54 kDa, formando fragmentos com ~40 e ~45 kDa, aumentados na DRC, principalmente na DRC-INS. O colágeno do tipo VI, com aproximadamente 95 kDa, encontrou-se com expressão diminuída exclusivamente no grupo DRC-INS. A Vitronectina foi encontrou-se aumentada em na DMX e na DRC-EST, em relação ao grupo controle, principalmente na DRC-EST. Lumican, por sua vez, teve expressão diminuída na DMX e na DRC-EST, apesar de possuir um único \"spot\" com expressão aumentada na DRC. Utilizando métodos de análise de padrões de expressão protéica in silico foram identificados conjuntos de proteínas capazes de discriminar as amostras de valva mitral por etiologia da doença. O presente trabalho pode auxiliar na elucidação dos mecanismos de desenvolvimento da doença e de alterações estruturais do tecido mitral em resposta às lesões autoimunes, bem como no diagnósticoda DRC. / Rheumatic Heart Disease (RHD) is a serious complication of oropharingitis caused by some serotypes of Streptococcus pyogenes not properly treated in susceptible individuals. It is a public health concern, mainly for undeveloped and developing countries, such as Brazil, India, some countries in Africa, aboriginal regions in Australia, and Egypt. It is highly debilitating with a high mortality rate due to cardiac commitment. Initial myocardial lesions disappear, but valvar lesions, mainly mitral and aortic, are irreversible and progressive. Many studies have characterized cellular (T lymphocytes) and humoral responses in individuals affected by the disease. Molecular mimicry and epitope spreading are the main mechanisms thought to be involved in the pathogenesis of RHD. We evaluated, in this research, the profile of protein expression in mitral valves from individuals affected by RHD. To detect alterations specific of this disease, we compared protein expression in the group of RHD with regurgitation (RHD-RGT) and stenosis (RHD-STN) to a group of individuals with mitral valve myxomatous degeneration (MXD) and another group without valvulopathies (CTL). Alterations specifically observed in the mitral tissue of RHD-RGT and RHD-STN in advanced stages of the disease can explain the mechanism of development for these two kinds of lesions. Twenty-five spots, corresponding to 29 proteins were found to be differentially expressed in the valvulopathy groups, reflecting mainly alterations in extracellular matrix. We found important differential cleavage of vimentin, the whole protein having 54 kDa, in fragments with ~40 and ~45 kDa, increased in RHD, mainly in RHD-RGT. Collagen type-VI, with approximatelly 95 kDa, was found to have decreased expression exclusivelly in the RHD-RGT group. Increased expression of Vitronectin was detected in DMX and RHD-EST groups, compared to the CTL group, mainly in the RHD-STN. Lumican, in turn, had decreased expression in the MXD and RHD-STN groups. By using in silico methods for analysis of patterns of protein expression, we identified sets of proteins capable of discriminating mitral valve samples by disease etiology. The present study might help elucidating the mechanisms of disease development and structural alterations in the mitral tissue in response to the autoimmune lesions, as well as in the diagnosis of RHD.

<p>Patients with rheumatoid arthritis (RA) are at increased risk of developing malignant lymphoma, although details about this association remain unclear. The aims of this thesis were to investigate risk factors for lymphoma in patients with RA and to characterize these lymphomas regarding subtype, presence of Epstein-Barr virus (EBV), clinical manifestations and prognosis. </p><p>The Swedish hospital discharge register and the cancer register were used to identify RA patients with lymphoma. Two case-control studies were performed, one smaller including RA patients with lymphoma hospitalised in Uppsala health care region 1964-1983 (n=41) and one larger study of hospitalised RA patients with lymphoma in Sweden 1964-1995 (n=378). RA patients from the same cohorts, but without lymphoma, were matched as controls. Medical records for cases and controls were scrutinized for exposure information. The lymphoma tissues were reclassified according to the WHO classification, and presence of EBV was analysed by EBER in situ hybridisation.</p><p>The most important risk factor for lymphoma development was high RA disease activity. No association was determined between treatment with traditional disease modifying drugs, non-steroidal anti-inflammatory drugs, aspirin, peroral and intra-articular corticosteroids and lymphoma risk. Diffuse large B-cell lymphoma (DLBCL) was more frequent in RA patients than in lymphoma patients in the general population and displayed stronger association with RA disease activity than other lymphoma subtypes. RA patients with DLBCL had increased extranodal involvement and more advanced lymphoma stage at presentation than DLBCL patients in general, and the prognosis was poor. </p><p>A further subdivision of DLBCL into germinal centre (GC) and non-GC subtypes by the expression patterns of CD10, bcl-6 and IRF-4 showed a predominance of the non-GC subtype. This suggested peripheral activated B-cells as the cells of origin in these lymphomas. </p><p>The presence of EBV was low in lymphomas in RA patients (12%). </p>

Background People with rheumatic or neurologic conditions are commonly referred for occupational therapy because of decreased ability to perform ADL tasks. Upon referral, occupational therapists use a client-centred, occupationfocused approach when evaluating a person's perceived and observed quality of ADL task performance to clarify the nature and extent of the person’s problems, plan interventions and determine effectiveness of interventions. Evaluation of the extent of problems and change following intervention require the use of linear measures of ADL. The aim of this doctoral thesis was to develop and validate linear measures of perceived and observed quality of ADL task performance for occupational therapy clinical praxis and research. Methods To develop linear measures of observed quality of ADL task performance based on Rasch measurement methods, clients with ABI (n=70) were evaluated using a 3-category rating scale and the ADL Taxonomy. Similarly, to develop linear measures of perceived quality of ADL task performance women with rheumatic diseases (n=118) reported their ability on a questionnaire and in an interview based on the ADL Taxonomy and a 4- category rating scale. To further validate the ADL ability measures of the Assessment of Motor and Process Skills (AMPS) data were collected in two samples. In a sample of women with chronic widespread pain (CWP) or fibromyalgia (FM) (n=50) the ADL ability measures were validated with regard to discrimination, stability and sensitivity to changes. Discrimination was examined by comparing AMPS data from women with CWP/FM to those of healthy women. Stability and sensitivity to change were examined based on repeated AMPS observations pre and post intervention. In addition, sensitivity to change was examined in a sample of clients with ABI (n=36) using a pre- and post-test design. Finally, the validity of the AMPS ADL ability measures in relation to perceived ADL ability was examined in women with rheumatic diseases (n=118) and women with CWP/FM (n=50). Results Based on the results of the four studies in this thesis, we were able to conclude that it was possible to obtain linear measures of observed quality of ADL task performance based on a revised version of the ADL Taxonomy (ADL-O). It was also possible to obtain linear measures of perceived quality of ADL task performance based on revised versions of the ADL Taxonomy using the formats of questionnaires (ADL-Q) and interviews (ADL-I). Moreover, it was possible to establish further evidence of validity of the ADL ability measures of the AMPS. Thus, the AMPS ADL ability measures could discriminate between women with CWP/FM and healthy women. The ADL ability measures of remained stable when no intervention was provided and the ADL motor ability measures were sensitive to change among women with CWP/FM. Moreover, the ADL ability measures were sensitive to change among clients with low ADL ability following ABI. Finally, only low to moderate correlations were found between measures of perceived and observed ADL ability. Conclusions Rasch analyses of revised versions of the ADL Taxonomy suggest that the majority of the ADL tasks and rating scales focused on quality of ADL task performance can be used to obtain linear measures of quality of ADL task performance based on methods of questionnaire, interview or observation. Furthermore, the studies provided evidence of validity of the ADL ability measures of the AMPS in relation to discrimination, stability and sensitivity to change and relation to perceived ADL ability. The results may, therefore, enhance the use of ADL instruments that provide linear measures of perceived and observed quality of ADL task performance in occupational therapy clinical praxis and research.

Patients with rheumatoid arthritis (RA) are at increased risk of developing malignant lymphoma, although details about this association remain unclear. The aims of this thesis were to investigate risk factors for lymphoma in patients with RA and to characterize these lymphomas regarding subtype, presence of Epstein-Barr virus (EBV), clinical manifestations and prognosis. The Swedish hospital discharge register and the cancer register were used to identify RA patients with lymphoma. Two case-control studies were performed, one smaller including RA patients with lymphoma hospitalised in Uppsala health care region 1964-1983 (n=41) and one larger study of hospitalised RA patients with lymphoma in Sweden 1964-1995 (n=378). RA patients from the same cohorts, but without lymphoma, were matched as controls. Medical records for cases and controls were scrutinized for exposure information. The lymphoma tissues were reclassified according to the WHO classification, and presence of EBV was analysed by EBER in situ hybridisation. The most important risk factor for lymphoma development was high RA disease activity. No association was determined between treatment with traditional disease modifying drugs, non-steroidal anti-inflammatory drugs, aspirin, peroral and intra-articular corticosteroids and lymphoma risk. Diffuse large B-cell lymphoma (DLBCL) was more frequent in RA patients than in lymphoma patients in the general population and displayed stronger association with RA disease activity than other lymphoma subtypes. RA patients with DLBCL had increased extranodal involvement and more advanced lymphoma stage at presentation than DLBCL patients in general, and the prognosis was poor. A further subdivision of DLBCL into germinal centre (GC) and non-GC subtypes by the expression patterns of CD10, bcl-6 and IRF-4 showed a predominance of the non-GC subtype. This suggested peripheral activated B-cells as the cells of origin in these lymphomas. The presence of EBV was low in lymphomas in RA patients (12%).

Diss. (sammanfattning) Umeå : Umeå universitet, 2010.

Made available in DSpace on 2015-07-22T20:49:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-07-27 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Introdução: Pacientes com Hepatite C frequentemente tendem a produzir autoanticorpos. No teste fator antinúcleo em células HEp-2 (ANA-HEp-20), esses autoanticorpos geram diversos padrões de imunofluorescência, sendo o nuclear pontilhado fino o mais frequente deles. Recentemente, tem sido descrito um novo padrão de ANA-HEp-2 em pacientes com HCV, denominado padrão Rods e Rings (R&R), caracterizado por anéis e bastões. Objetivos: Avaliar as características clínicas, virológicas e padrão de resposta terapêutica dos pacientes que apresentam autoanticorpos que geram o padrão R&R, bem como proceder a uma avaliação preliminar dos aspectos celulares e moleculares desse novo sistema de autoantígenos. Métodos: Amostras de soro coletadas de 1998 até 2008 de 597 pacientes foram submetidas ao teste de ANA-HEp-2 em lâminas Euroimmun ou INOVA e classificados como R&R positivos quando apresentaram fluorescência sob forma de bastões de 3 a 10μm de comprimento e anéis de 2 a 5μm de diâmetro no citoplasma das células HEp-2. Entre os pacientes testados, 342 tinham HCV e 200 tinham outras doenças hepáticas crônicas ou autoimunes reumáticas, além de 55 pacientes co-infectados com HCV+HIV. As informações clínicas, virológicas e terapêuticas foram coletadas de bancos de dados atrelados às amostras de soro dos pacientes. Células HEp-2, 3T3 e MH22A foram cultivadas normalmente e/ou submetidas à tratamentos in vitro (tripsina e ribavirina) e com dois métodos alternativos de fixação, para estudo das estruturas do R&R por imunofluorescência indireta simples ou com técnicas de dupla-marcação com amostras R&R-positivas e anticorpos antitubulina-alfa e anti-CTP-sintase. Resultados: Dos 342 pacientes com HCV, 51 (15%) apresentaram o padrão R&R, enquanto que dos 200 pacientes com outras doenças hepáticas ou autoimunes, apenas um apresentou o padrão R&R (p<0.0001). Dos pacientes com HCV, 174 eram tratados e 168 não tratados. Dos 174 tratados, 49 (28%) apresentaram o padrão R&R contra apenas dois (1%) dos não tratados (p<0.0001). De 134 tratados e com informação adequada sobre a medicação utilizada, 108 tomavam interferon-α e ribavirina e 23 tomavam apenas interferon-α. Quarenta e um (38%) dos 103 que tomavam interferon-α e ribavirina apresentaram o padrão R&R contra nenhum (0%) dos 23 que tomavam apenas interferon-α (p= 0.0001). Quanto aos outros padrões de ANA-HEp-2, dos 23 pacientes que tomavam apenas interferon-α, 12 (52%) foram positivos enquanto apenas 27 (25%) dos que tomavam interferon-α e ribavirina foram positivos (p= 0.010). 9% dos pacientes co-infectados com HCV+HIV apresentaram o padrão R&R. Não encontramos relação entre a presença do padrão R&R e o genótipo do vírus, a carga viral e os dados demográficos dos pacientes com HCV. A porcentagem de respondedores ao tratamento foi ligeiramente menor nos pacientes que apresentaram o R&R, porem sem atingir nível de significância estatística (p=0,150). Lâminas ANA-HEp-2 de algumas marcas comerciais que não Euroimmun e INOVA e aquelas elaboradas no próprio laboratório não apresentaram as estruturas do R&R. Quando tratadas in vitro com ribavirina ou tripsina, as células HEp-2 ou 3T3 e MH22A de camundongo cultivadas expressaram vários anéis e bastões reconhecidos pelas amostras de soro R&R-positivas. Não observamos colocalização das estruturas R&R com microtúbulos e observamos fraca colocalização dos anéis e bastões com CTP-sintase. Conclusões: Autoanticorpos associados ao padrão R&R ocorreram em íntima associação ao uso de interferon-α e ribavirina em pacientes com hepatite HCV, independentemente de serem portadores do HIV. Não houve associação às características demográficas dos pacientes, ao perfil de resposta terapêutica, ao genótipo do HCV ou à carga viral. As estruturas em anéis e bastões associadas ao padrão R&R não ocorrem nas condições normais avaliadas, podendo ser induzidas in vitro pela exposição à ribavirina ou à tripsina. Há algum grau de conservação filogenética dos autoantígenos associados ao padrão R&R. Evidências preliminares indicam a presença da enzima CTP-sintase nas estruturas em anéis e bastões reconhecidas pelos autoanticorpos humanos. / Introduction: Patients with Hepatitis C frequently produce autoantibodies. In the antinuclear antibody assay on HEp-2 cells (ANA-HEp-2) these autoantibodies generate several immunofluorescence patterns, and the nuclear fine speckled pattern is the most common. A novel ANA-HEp-2 pattern has been recently reported, characterized by the presence of rods and rings in the cytoplasm. Objectives: To study the clinical and virological features, as well as the profile of therapeutic response of patients presenting autoantibodies generating the rods and rings (R&R) ANA-HEp-2 pattern and to perform a preliminary analysis of the cellular and molecular aspects of this novel autoantigen system. Methods: Serum samples obtained from 1988 to 2008 from 597 patients were processed in the ANA-HEp-2 assay on Euroimmun or INOVA slides and classified as R&R-positive when presenting immunofluorescence as 3-10μm long rods and 2-5μm diameter rings in the cytoplasm of HEp-2 cells. Among the tested patients, 342 had HCV, 200 had other chronic liver diseases or rheumatic autoimmune diseases, and 55 had HCV and HIV. Clinical, virological, and treatment information was obtained from the clinical data bank. Human HEp-2, and murine 3T3, and MH22A cell lines were cultured as usual and under special stimuli (exposure to trypsin or ribavirin), and prepared with alternative fixation protocols for processing in single or double indirect immunofluorescence with human anti-R&R serum and antibodies to tubulin and to CTP-synthase. Results: Among the 342 HCV patients, 51 (15%) presented the R&R pattern as opposed to only one among the 200 patients with other liver diseases and autoimmune rheumatic diseases (p<0.001). Among the HCV patients, 174 had been treated and 168 had received no treatment. Among the 174 treated patients, 49 (28%) presented the R&R pattern as opposed to only two (1%) of the 168 non-treated HCV patients (p<0.001). Among 134 HCV treated patients with detailed information on the treatment protocol, 108 used interferon-α and ribavirin and 23 used only interferon-α. Forty-one (38%) of the R&R pattern as opposed to none of the 23 patients receiving only interferon-α (p=0.0001). In contrast, 12 (52%) of the 23 patients receiving only interferon-α presented other non-R&R ANA-HEp-2 patterns as opposed to only 27 (25%) of the 108 patients under interferon-α and ribavirin (p=0.01). 9% of the patients with HCV and HIV presented the R&R pattern. There was no association between the occurrence of the R&R pattern and HCV genotype, viral load, and demographic features. The frequency of sustained virologic response was slightly lower in the R&R-positive patients but the difference did not reach statistical significance (p=0.15). ANA-HEp-2 slides from brands other than Euroimmun and INOVA, as well as in-house produced slides did not express the R&R structures. When treated in vitro with ribavirin or trypsin, HEp-2 cells and murine 3T3, and MH22A cell lines expressed prominent R&R structures recognized by human HCV serum samples. There was partial weak colocalization of CTP-synthase in the R&R structures but no colocalizadion of microtubule. Conclusions: autoantibodies associated with the R&R pattern were strongly associated with the use of interferon-α and ribavirin in patients with HCV, independently of co-infection with HIV. There was no association with demographic characteristics, the profile of therapeutic response, HCV genotype, and viral load. The rods and rings structures associated with the R&R pattern did not occur under normal conditions, but could be induced in vitro by exposure to ribavirin or trypsin. There is some degree of phylogenetic conservation of the autoantigens associated to the R&R pattern. Preliminary evidence indicates the presence of CTP-synthase in the cytoplasmic rods and rings structures recognized by human autoantibodies from HCV patients. / FAPESP: 2009/03796-5 / FAPESP: 2010/50710-6 / TEDE / BV UNIFESP: Teses e dissertações

A Doença Reumática Cardíaca (DRC) é uma séria complicação de orofaringite causada por determinados sorotipos de Streptococcus pyogenes não tratada adequadamente em indivíduos suscetíveis. É um grande problema de saúde pública, principalmente nos países não desenvolvidos e em desenvolvimento, como Brasil, Índia, países da África, regiões de população aborígine da Austrália, e Egito. É altamente debilitante e com alta taxa de mortalidade devido ao comprometimento cardíaco. As lesões miocárdicas iniciais regridem, mas as lesões valvares, principalmente a mitral e a aórtica, são irreversíveis e progressivas. Muitos estudos já caracterizaram a resposta imune celular (linfócitos T) e humoral nos indivíduos acometidos pela doença. Mimetismo molecular e espalhamento de epítopo são os principais mecanismos que se pensa estar envolvidos na patogênese da DRC. Avaliamos, nesta pesquisa, o perfil de expressão proteica em valvas mitrais de indivíduos acometidos por DRC. Para detectar alterações específicas desta doença, comparamos as expressões de proteínas nos grupos portadores de DRC com insuficiência (DRC-INS) e com estenose (DRC-EST) a um grupo de indivíduos com degeneração mixomatosa de valva mitral (DMX) e outro sem valvulopatias (CTL). Alterações especificamente observadas em tecido mitral na DRC-INS ou DRC-EST em fases avançadas da doença podem explicar o mecanismo de desenvolvimento desses dois tipos de lesão. Foram encontradas 25 \"spots\", correpondendo a 29 proteínas diferencialmente expressas nos grupos com valvulopatias, refletindo principalmente alterações na matriz extracelular. Encontramos importante clivagem diferencial da vimentina, cuja proteína íntegra possui 54 kDa, formando fragmentos com ~40 e ~45 kDa, aumentados na DRC, principalmente na DRC-INS. O colágeno do tipo VI, com aproximadamente 95 kDa, encontrou-se com expressão diminuída exclusivamente no grupo DRC-INS. A Vitronectina foi encontrou-se aumentada em na DMX e na DRC-EST, em relação ao grupo controle, principalmente na DRC-EST. Lumican, por sua vez, teve expressão diminuída na DMX e na DRC-EST, apesar de possuir um único \"spot\" com expressão aumentada na DRC. Utilizando métodos de análise de padrões de expressão protéica in silico foram identificados conjuntos de proteínas capazes de discriminar as amostras de valva mitral por etiologia da doença. O presente trabalho pode auxiliar na elucidação dos mecanismos de desenvolvimento da doença e de alterações estruturais do tecido mitral em resposta às lesões autoimunes, bem como no diagnósticoda DRC. / Rheumatic Heart Disease (RHD) is a serious complication of oropharingitis caused by some serotypes of Streptococcus pyogenes not properly treated in susceptible individuals. It is a public health concern, mainly for undeveloped and developing countries, such as Brazil, India, some countries in Africa, aboriginal regions in Australia, and Egypt. It is highly debilitating with a high mortality rate due to cardiac commitment. Initial myocardial lesions disappear, but valvar lesions, mainly mitral and aortic, are irreversible and progressive. Many studies have characterized cellular (T lymphocytes) and humoral responses in individuals affected by the disease. Molecular mimicry and epitope spreading are the main mechanisms thought to be involved in the pathogenesis of RHD. We evaluated, in this research, the profile of protein expression in mitral valves from individuals affected by RHD. To detect alterations specific of this disease, we compared protein expression in the group of RHD with regurgitation (RHD-RGT) and stenosis (RHD-STN) to a group of individuals with mitral valve myxomatous degeneration (MXD) and another group without valvulopathies (CTL). Alterations specifically observed in the mitral tissue of RHD-RGT and RHD-STN in advanced stages of the disease can explain the mechanism of development for these two kinds of lesions. Twenty-five spots, corresponding to 29 proteins were found to be differentially expressed in the valvulopathy groups, reflecting mainly alterations in extracellular matrix. We found important differential cleavage of vimentin, the whole protein having 54 kDa, in fragments with ~40 and ~45 kDa, increased in RHD, mainly in RHD-RGT. Collagen type-VI, with approximatelly 95 kDa, was found to have decreased expression exclusivelly in the RHD-RGT group. Increased expression of Vitronectin was detected in DMX and RHD-EST groups, compared to the CTL group, mainly in the RHD-STN. Lumican, in turn, had decreased expression in the MXD and RHD-STN groups. By using in silico methods for analysis of patterns of protein expression, we identified sets of proteins capable of discriminating mitral valve samples by disease etiology. The present study might help elucidating the mechanisms of disease development and structural alterations in the mitral tissue in response to the autoimmune lesions, as well as in the diagnosis of RHD.

\\OBJETIVOS: Avaliar a imunogenicidade e a segurança a curto prazo da vacina H1N1 pandêmica em pacientes com artrite reumatóide (AR) e espondiloartrites [ESa - artrite psoriática (AP) e espondilite anquilosante (EA)] recebendo classes distintas de terapia anti-TNF, assim como comparação com pacientes que receberam drogas modificadoras de doenças reumáticas (DMARDs) e controles saudáveis. MÉTODOS: Cento e vinte pacientes (AR, n=41; EA, n=57 e artrite psoriática - AP, n=22) em uso de agentes anti-TNF (monoclonal, n=94 e receptor solúvel, n=26) foram comparados com 116 pacientes com artrite inflamatórias em uso de DMARDs e 117 controles saudáveis. Soroproteção (SP), soroconversão (SC), médias geométricas dos títulos (MGTs), fator de aumento (FI) das MGT e eventos adversos foram avaliados 21 dias após a vacinação. RESULTADOS: Após a imunização, as taxas de SC (58,2% vs 74,3%, p=0,017) foram significativamente menores nos pacientes com espondiloartrites que receberam a terapia anti-TNF, enquanto nenhuma diferença foi observada em pacientes com AR que recebem esta terapia, em comparação com controles saudáveis (p=0,067). Pacientes com espondiloartrites que receberam anticorpos monoclonais (infliximabe/adalimumabe) tiveram uma taxa de SC significativamente menor em comparação com controles saudáveis (51,6% vs. 74,3%, p=0,002) ou para aqueles em uso de DMARDs (51,6% vs. 74,7%, p=0,005), por sua vez não houve diferença para pacientes em uso de etanercepte (86,7% vs. 74,3%, p=0,091). Uma análise dos pacientes com espondiloartrites que apresentaram SC e os que não apresentaram SC revelou que o primeiro grupo teve maior média de idade (p=0,003), maior frequência de anti-TNF (p=0,031) e anticorpos monoclonais (p=0,001), e uma menor frequência de metotrexate (p=0,028). Na regressão logística multivariada, apenas a idade avançada (p=0,015) e tratamento anticorpos monoclonais (p=0,023) permaneceram fatores importantes para a não SC em pacientes com espondiloartrites. CONCLUSÕES: Este estudo mostrou um padrão distinto da resposta imune à vacina contra a gripe pandêmica em pacientes com artrite inflamatória que receberam agentes anti-TNF, com uma imunogenicidade reduzida apenas em pacientes com espondiloartrites usando anticorpos monoclonais / OBJECTIVES: To evaluate the immunogenicity of the anti-influenza A H1N1/2009 vaccine in rheumatoid arthritis (RA) and spondyloarthritis patients receiving distinct classes of anti-TNF agents compared with patients receiving DMARDs and healthy controls. METHODS: One hundred and twenty patients (RA, n=41; ankylosing spondylitis - AS, n=57 and psoriatic arthritis - PsA, n=22) under anti-TNF agents (monoclonal, n=94 and soluble receptor, n=26) were compared to 116 inflammatory arthritis patients under DMARDs and 117 healthy controls. Seroprotection (SP), seroconversion (SC), geometric mean titre (GMT), factor increase (FI) in GMT and adverse events were evaluated 21 days after vaccination. RESULTS: After immunisation, SC rates (58.2% vs. 74.3%, p=0.017) were significantly lower in spondyloarthritis patients receiving anti-TNF therapy, whereas no difference was observed in RA patients receiving this therapy compared to healthy controls (p=0.067). Spondyloarthritis patients receiving monoclonal antibodies (infliximab/adalimumab) had a significantly lower seroconversion rate compared to healthy controls (51.6% vs. 74.3%, p=0.002) or to those under DMARDs (51.6% vs. 74.7%, p=0.005), whereas no difference was observed for patients under etanercept (86.7% vs. 74.3%, p=0.091). Further analysis of non-seroconverting and seronconverting spondyloarthritis patients revealed that the former group had a higher mean age (p=0.003), a higher frequency of anti-TNF (p=0.031) and monoclonal antibodies (p=0.001), and a lower frequency of methotrexate (p=0.028). In multivariate logistic regression, only older age (p=0.015) and monoclonal antibodies treatment (p=0.023) remained significant factors for nonseroconversion in spondyloarthritis patients. CONCLUSIONS: This study revealed a distinct disease pattern of immune response to the pandemic influenza vaccine in inflammatory arthritis patients receiving anti-TNF agents, illustrated by a reduced immunogenicity solely in spondyloarthritis patients using monoclonal antibodies

Introdução e Objetivo: No Brasil, procedimentos valvares representam no mínimo 30% das cirurgias cardíacas realizadas no país. Em nosso meio ainda predominam as lesões valvares decorrentes da febre reumática e doenças degenerativas. Nos pacientes reumáticos, a valva mitral é a mais acometida, predominando a estenose devido à fusão comissural e lesões no plano subvalvar; porém espessamento e retração de cúspides também são comuns, determinando dupla lesão ou insuficiência desta valva. Em processos degenerativos, as cordas tendíneas podem se apresentar alongadas. Na tentativa de utilização futura do laser como método auxiliar na correção cirúrgica dessas valvopatias, iniciamos estudo experimental com o objetivo de comparar histologicamente o tecido valvar mitral de suínos (cordas tendíneas e cúspides) submetido com e sem o laser de alta potência (LAP). Métodos: Foram estudadas cordas tendíneas e cúspides mitrais de suínos jovens e saudáveis, divididos em 6 grupos: G1-Aplicação do laser em cordas tendíneas com o tempo de 15 s; G2- Aplicação do laser em cordas tendíneas com o tempo de 20 s; G3- Aplicação do laser em cordas tendíneas com o tempo de 30 s; G4- Grupo controle relacionado a G1, G2 e G3; G5- Grupo cúspide submetido a corte com lâmina de bisturi; G6- Grupo cúspide submetido a corte com laser. As cordas tendíneas dos grupos G1, G2 e G3 receberam tratamento com laser de diodo (=980 nm, P=3,0 W) e o grupo G6 com laser de diodo em outros parâmetros (=980 nm, P=9,0 W, T=12s). Termografia e tomografia por coerência óptica foram utilizadas durante o experimento. Parte da amostra foi preservada em formaldeído e glutaraldeído para análise microscópica e a outra parte foi preservada em solução fisiológica 0,9% para análise mecânica. Resultados: Houve um decréscimo significante no comprimento das cordas tendíneas após aplicação do laser quando comparado ao comprimento inicial (p=0,005 em G1 e G2 e p=0,004 em G3). À microscopia óptica, G1, G2 e G3 apresentaram áreas hialinas ocupando quase a totalidade da espessura da corda, quando coradas pela Hematoxilina-Eosina (HE), áreas vermelho-escura na região central da corda quando coradas pelo Tricrômico de Masson e áreas com birrefringência diminuída quando coradas pelo Picrosírius vermelho. Na avaliação mecânica, os grupos lasers apresentaram diminuição da rigidez do material, assim como na força máxima durante a ruptura, entretanto o deslocamento foi maior em relação ao grupo controle (p=0,005). No G5, evidenciamos ausência de qualquer alteração histológica. No G6 foram identificadas áreas de menor birrefringência do colágeno quando corado pelo Picrosírius vermelho, áreas estas que apresentavam aspecto basofilico hialino no HE e coloração vermelho-escura ao Tricrômico de Masson. Conclusão: As cordas tendíneas de valvas mitrais de suínos submetidas ao laser de alta potência apresentaram redução do seu comprimento final, diminuição na birrefringência e alteração na distribuição dos feixes de colágeno. Além disso, apresentaram queda da rigidez, maior fragilidade de rotura e maior deslocamento ao teste de tração mecânica quando comparada ao grupo controle. Com relação às cúspides, os danos térmicos encontrados no grupo corte com laser de alta potência foram maiores do que em relação ao bisturi de lâmina, quando evidenciados pela microscopia óptica / Introduction and Objective: In Brazil, valvar procedures represent at least 30% of cardiac surgeries performed in the country. It still predominate valvar lesions resulting from rheumatic fever and degenerative diseases. In rheumatic patients, the mitral valve is the most affected, predominantly stenosis due to commissural fusion and lesions in the subvalvar plane, however, thickening and retraction of the leaflets are also common, causing double lesion or mitral insufficiency. In degenerative process, the chordae tendineae may present elongated. In an attempt to further use of the laser as an auxiliary method in the surgical correction of valvar heart disease, we started experimental study with the purpose of comparing the histological swine tissue mitral valve (chordae tendineae and cusps) with and without high-power laser (HPL) application. Methods: Normal porcine mitral valve chordae and cups were studied and divided randomly into the following 6 groups: G1- Laser in the chordae tendineae with time of 15s; G2- Laser in the chordae tendineae with time of 20s; G3- Laser in the chordae tendineae with time of 30s; G4- Control Group; G5- Cusp group cut with a scalpel blade; G6- Cusp group cut with laser. Chordae tendineae from G1, G2 e G3 received diode laser (=980 nm, P=3,0 W) and G6 diode laser with other parameters (=980 nm, P=9,0 W, T=12s). Termography and optical coherence tomography were included during the procedure. Part of the sample was preserved in formaldehyde and glutaraldehyde for microscopic analysis and another part was stored in 0.9% saline for mechanical analysis. Results: There was a significant decrease in chordae length after laser application when compared to the initial length (p=0,005 to G1 and G2; p=0,004 to G3). In laser groups, histological analysis revealed a typical hyaline areas occupying almost the entire thickness of the chordae, when stained with Hematoxylin-Eosin (HE); dark red central areas when stained with Masson Trichrome and a birefringence decrease when stained with Picrocirius red. In mechanical analysis, we found lower stiffness, maximum rupture force decrease and larger displacement compared with the Control Group (p=0,005). In G5, was evidenced absence of any histological abnormality and a homogeneous blue appearance, typical of the cusp. However in G6, a basophilic hyaline aspect was found focally when stained with HE, dark red areas when stained with Masson Trichrome and a birefringence decrease when stained with Picrocirius Red. Conclusion: Chordae tendineae of normal porcine submitted to a high-power laser presented with reduced length, birefringence decrease and the collagen bundles organized into different orientations. Besides, presented lower stiffness, maximum rupture force decrease and larger displacement compared with the control group. Regarding cups, thermal changes were bigger in the cusp group cut with laser compared cusp group cut with scalpel blade, observed by optical microscopy

Rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis belong among serious disorders, that effect joints and connective tissue. The patients suffer from pain and stiffness. Disease modifying drugs are an important part in the management of rheumatical disorders. When disease modifying drugs are failing, than biologic treatment is applied. For biologic treatment are registred etanercept (Enbrel), adalimumab (Humira), rituximab (MabThera), abatacept (Orencia) and infliximab (Remicade). In the Czech Republic was established the National registry of rheumatic disorders. There is a need of long term observations of patients, who have biologic treatment, to evaluate safety and socioeconomic data of the biologic treatment.