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Made available in DSpace on 2014-06-11T19:27:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-06-21Bitstream added on 2014-06-13T19:14:39Z : No. of bitstreams: 1 pereira_dfa_me_sjc.pdf: 933077 bytes, checksum: 1cf55e305807271fd95bf2e3e95495ba (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A espondilite anquilosante (EA) é uma doença inflamatória crônica de etiologia desconhecida, caracterizada pelo acometimento predominante do esqueleto axial. A terapia convencional inclui o uso de antiinflamatórios não hormonais e drogas anti-reumáticas modificadoras da evolução da doença (DMARDs). O uso de agentes imunobiológicos, como o anti-TNF, tem sido considerada uma excelente opção terapêutica em casos mais graves e refratários, porém estudos prévios demonstraram maior risco de infecções após o tratamento. Reservatórios bucais de microrganismos oportunistas podem causar infecções sistêmicas, uma vez que a cavidade bucal representa uma porta de entrada para patógenos, especialmente em pacientes imunocomprometidos. O objetivo do presente estudo foi avaliar a presença e a sensibilidade aos antimicrobianos de Candida spp., Staphylococcus spp., Enterobacteriaceae e Pseudomonas spp. na cavidade bucal de pacientes com EA em uso de anti-TNF comparando-os com indivíduos controle. Foram incluídos no estudo: grupo anti-TNF (35 indivíduos, diagnosticados portadores de EA com idade entre 17 a 63 anos e sob terapia anti-TNF); grupo Convencional (35 pacientes portadores de EA, com idade entre 21 e 74 anos sob tratamento convencional não imunobiológico; e respectivos grupos controle composto por indivíduos saudáveis pareados na idade, gênero e condições bucais aos grupos com EA. Foram realizados exame clínico, anamnese, bem como coleta de enxágüe bucal de cada indivíduo a qual foi semeada em meios de cultura específicos para cada microrganismo e posterior obtenção do número de unidades formadoras de colônia por militros (UFC/mL). Os isolados foram identificados pelo Sistema API, bem como fora realizados testes de sensibilidade aos antifúngicos dos isolados de leveduras, e, antibióticos dos isolados bacterianos... / The Ankylosing Spondylitis (AS) is a chronic inflammatory disease of unknown etiology, particularly characterized by a compromise of the axial skeleton. The conventional therapy includes the use of non-hormonal anti-inflammatory and Disease-modifying antirheumatic drugs (DMARDs). The use of immunobiological agents, such as anti-TNF, has been considered an excellent therapeutical option in more serious and refractory cases. However, previous studies demonstrated an increased risk of infections after the treatment is completed. Oral reservoirs of opportunist microorganisms can cause systemic infections, once that the oral cavity represents a door of entrance for pathogens, especially in immunocompromised patients. The aim of the present study was to evaluate the presence and antimicrobial susceptibility of Candida spp., Staphylococcus spp., Enterobacteriaceae and Pseudomonas spp. in the oral cavity of patients with AS treated with anti-TNF in comparison to healthy individuals. The following groups were included in the study: anti-TNF group (35 AS patients, aged between 17 and 63 years and under anti-TNF therapy); Conventional group (35 AS patients aged between 21 and 74 years under non-immunobiological conventional treatment); and respective Control groups (composed by healthy individuals paired in age, gender and oral conditions with AS groups). After clinical examination and anamnesis, oral rinses of each individual was collected. The rinses were plated in specific culture media for each microorganism. The number of colony-forming units per milliters (CFU/mL) was obtained. Isolates were identified by API system. Next, sensitivity tests to antifungicals agents were done for yeasts isolates and antibiotics for bacterial isolates. For Staphylococcus spp., the CFU counts for the anti-TNF group and Conventional group was statistically higher than the respective control groups... (Complete abstract click electronic access below)

Resumo: A espondilite anquilosante (EA) é uma doença inflamatória crônica de etiologia desconhecida, caracterizada pelo acometimento predominante do esqueleto axial. A terapia convencional inclui o uso de antiinflamatórios não hormonais e drogas anti-reumáticas modificadoras da evolução da doença (DMARDs). O uso de agentes imunobiológicos, como o anti-TNF, tem sido considerada uma excelente opção terapêutica em casos mais graves e refratários, porém estudos prévios demonstraram maior risco de infecções após o tratamento. Reservatórios bucais de microrganismos oportunistas podem causar infecções sistêmicas, uma vez que a cavidade bucal representa uma porta de entrada para patógenos, especialmente em pacientes imunocomprometidos. O objetivo do presente estudo foi avaliar a presença e a sensibilidade aos antimicrobianos de Candida spp., Staphylococcus spp., Enterobacteriaceae e Pseudomonas spp. na cavidade bucal de pacientes com EA em uso de anti-TNF comparando-os com indivíduos controle. Foram incluídos no estudo: grupo anti-TNF (35 indivíduos, diagnosticados portadores de EA com idade entre 17 a 63 anos e sob terapia anti-TNF); grupo Convencional (35 pacientes portadores de EA, com idade entre 21 e 74 anos sob tratamento convencional não imunobiológico; e respectivos grupos controle composto por indivíduos saudáveis pareados na idade, gênero e condições bucais aos grupos com EA. Foram realizados exame clínico, anamnese, bem como coleta de enxágüe bucal de cada indivíduo a qual foi semeada em meios de cultura específicos para cada microrganismo e posterior obtenção do número de unidades formadoras de colônia por militros (UFC/mL). Os isolados foram identificados pelo Sistema API, bem como fora realizados testes de sensibilidade aos antifúngicos dos isolados de leveduras, e, antibióticos dos isolados bacterianos... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The Ankylosing Spondylitis (AS) is a chronic inflammatory disease of unknown etiology, particularly characterized by a compromise of the axial skeleton. The conventional therapy includes the use of non-hormonal anti-inflammatory and Disease-modifying antirheumatic drugs (DMARDs). The use of immunobiological agents, such as anti-TNF, has been considered an excellent therapeutical option in more serious and refractory cases. However, previous studies demonstrated an increased risk of infections after the treatment is completed. Oral reservoirs of opportunist microorganisms can cause systemic infections, once that the oral cavity represents a door of entrance for pathogens, especially in immunocompromised patients. The aim of the present study was to evaluate the presence and antimicrobial susceptibility of Candida spp., Staphylococcus spp., Enterobacteriaceae and Pseudomonas spp. in the oral cavity of patients with AS treated with anti-TNF in comparison to healthy individuals. The following groups were included in the study: anti-TNF group (35 AS patients, aged between 17 and 63 years and under anti-TNF therapy); Conventional group (35 AS patients aged between 21 and 74 years under non-immunobiological conventional treatment); and respective Control groups (composed by healthy individuals paired in age, gender and oral conditions with AS groups). After clinical examination and anamnesis, oral rinses of each individual was collected. The rinses were plated in specific culture media for each microorganism. The number of colony-forming units per milliters (CFU/mL) was obtained. Isolates were identified by API system. Next, sensitivity tests to antifungicals agents were done for yeasts isolates and antibiotics for bacterial isolates. For Staphylococcus spp., the CFU counts for the anti-TNF group and Conventional group was statistically higher than the respective control groups... (Complete abstract click electronic access below) / Orientador: Cristiane Yumi Koga Ito / Coorientador: Marcelo de Medeiros Pinheiro / Banca: Fernanda Lourenção Brighenti / Banca: Emilia Inoue Sato / Mestre

Ankylosing spondylitis (AS) is a chronic, inflammatory rheumatic disease that has a highly variable disease course. Three biologic agents, adalimumab, etanercept, and infliximab, have been developed for the treatment of AS. We conducted three studies: 1) an exploratory analysis of a year-long longitudinal dataset to gain insight into the variability of disease activity, physical function, and well-being and to explore the relationship between these outcome measures; 2) a systematic review of the available evidence for the efficacy of biologic treatment; 3) a systematic review of potential adverse effects of this treatment. We found that repeated measures of disease activity, function and well-being fluctuate considerably between patients, with complex patterns occurring over time within patients. There was mostly high quality evidence that these biologics are efficacious against placebo. We did not find evidence of an increase in serious adverse events or serious infections from short-term randomized controlled trials.

Thesis (M.S.W.)--University of Hong Kong, 1991.

The Human Leukocyte Antigen (HLA)-B27 is a Major Histocompability Complex (MHC) class I antigen that is strongly associated with development of a group of closely related arthritic diseases, collectively known as the spondyloarthropathies (SpA). However, the mechanism by which HLA-B27 confers this susceptibility is unclear. Studies have shown that HLA-B27 heavy chains can form classical heterotrimers associated with peptide and β2-microglobulin (B27HT), and also non-classical heavy chain homodimers (B27₂). B27₂ assemble intracellularly during maturation and are also expressed at the cell surface following endosomal recycling of B27HT. A pathogenic role for B27₂ has been proposed in two of the current theories of pathogenesis: the B27 homodimer theory and the B27 misfolding and UPR theory. Yet, determinations of the extent, distribution, and triggers of B27₂ expression, as well as the functional consequences of its receptor interactions in AS pathogenesis, have been hampered by the lack of a specific detection reagent. Therefore, to investigate the role of B27₂ in AS, we generated a novel antibody to B27₂ – HD6 – using phage display technology, which binds to in vitro refolded B27₂ but not B27HT complexes by ELISA. This thesis provides evidence that HD6-reactive molecules, which include B27₂, are expressed at the cell surface in both cell lines and in the context of a disease setting. Recognition is B27-specific and strongly correlated with the magnitude of B27 expression, which could account for the lack of staining in some cell subsets. Moreover, staining was comparable in cell lines expressing the disease-associated B*27:05 and the less disease-associated subtype B*27:09. In addition, I have shown cells expressing physiologic levels of B27, including EBV-transformed BCLs and AS patient PBMCs, are capable of expressing the HD6 epitope upon low pH treatment. Interestingly, these ‘acid-inducible HD6’ molecules were absent from cells lacking a functional PLC. Finally, I have shown that HD6-reactive molecules can derive from pre-existing folding B27 molecules at the cell surface, which may be inhibited by the addition of exogenous B27-binding peptides. These findings are consistent with a mechanism of pathogenesis involving the surface expression and recognition of B27₂ and/or other aberrantly folded forms of B27, as proposed in the homodimer theory. HD6 will be a powerful tool to address the potential pathogenic role of B27₂ in SpA and may additionally have therapeutic potential.

SAMMANFATTNING Hydroterapi har under en längre tid använts som behandlingsform, men det är brist på forskning inom området. Syftet med denna studie var att undersöka upplevelsen av hydroterapi hos personer med reumatisk sjukdom. En kvalitativ ansats anlades och enskilda semistrukturerade intervjuer användes. Deltagarna rekryterades genom bekvämlighetsurval via en kontakt på en reumatologklinik. Sex personer inkluderades: fem hade reumatoid artrit och en hade pelvospondylit. Resultatet tolkades med hjälp av en kvalitativ innehållsanalys, som visade på att deltagarna i denna studie var positivt inställda till hydroterapi. Deltagarna upplevde att hydroterapin ledde till minskad smärta, ökad rörlighet samt ett ökat välmående. Utöver de upplevda positiva effekterna återfanns även upplevda negativa effekter i form av träningsvärk och en ökad stelhet under sommaruppehållen. Det sociala samspel som uppstod i samband med hydroterapin upplevdes av de flesta deltagare ha haft positiv betydelse. Deltagarnas upplevelser kunde i diskussionen kopplas till operant och respondent inlärningsteori, där tänkbara konsekvenser och stimulin identifierades. Slutsatsen som drogs var att deltagarna upplevde hydroterapin som ett sätt att få tillbaka sin friska kropp genom att symtomen minskade. Då deltagarna upplevde att uppehåll orsakade försämring behövs hydroterapi som kontinuerlig behandlingsform för dem. Vidare forskning inom området bör fokuseras på enskilda patientgrupper samt inkludera ett större antal deltagare per patientgrupp. Nyckelord: hydroterapi, intervju, kvalitativ, pelvospondylit, reumatoid artrit.

Abstract can be viewed in PDF document. / Thesis (Ph.D)-University of KwaZulu-Natal, Durban, 2008.

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