München, Techn. Univ., Diss., 2004.

Tierärztl. Hochsch., Diss., 2004--Hannover.

Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease that can lead to important functional impairment. Although improvements in treatment have been made, still there are a high proportion of patients in whom response to treatment is not complete. Fibromyalgia (FM) is a condition characterized by bodily pain that often coexists with RA. Cross-sectional studies have shown that patients with RA and FM symptoms, or fibromyalgic RA (FRA), have higher disease activity scores than patients with RA and no FRA. Concern has been raised regarding the validity of RA disease activity scores in patients with coexistent RA and FM. In this prospective study, we hypothesized that patients with FRA have an impaired response to treatment measured by traditionally used scores. The present analysis used a study sample obtained from the ESPOIR French cohort. This is a longitudinal prospective cohort of adults with early RA. Patients with RA were classified in two groups according to the presence of FRA. RA disease activity scores (DAS28, SDAI, CDAI and HAQ) were compared as a measure of response to treatment at 6, 12 and 18 months. Results showed that after adjusting for confounders, patients with FRA (120) had higher activity scores than patients with RA and no fibromyalgic characteristics (548). DAS28 and other disease activity scores started out higher in subjects with FRA and while they improved to a similar extent as in the isolated RA group, they remained consistently higher among FRA patients. Achievement of low disease activity and of remission according to established activity score cut-points was significantly less likely in subjects with FRA. In conclusion, patients with FRA and RA had a similar response to treatment according the decrease in indexes of disease activity but more frequently missed the target of remission or low disease activity. These findings may have implications in RA treatment in patients with FRA, as therapy is escalated not in relation to change in scores but to achieving remission.

Osteoarthritis (OA) is the most common degenerative joint disease, affecting primarily the hip, knee, and hand (Ip 2005). OA of the knee and hip is the 11th highest contributor to global disability (Cross et al. 2014). Hip OA is diagnosed using radiographs, computed tomography (CT), and/or magnetic resonance imaging (MRI). Hip OA affects the whole hip joint, causing pain and reduced range of motion (Altman et al. 1991). The cause of pain in OA is not well understood, but it may be attributed to abnormal growth of blood vessels and nerves in the subchondral bone of the femoral head (Kumar et al. 2013). Quantifying blood vessels and nerves and correlating their presence with diagnostic techniques such as MRI will establish a relationship between femoral head degeneration and pain levels and current diagnostic signs. The aims of this study were: (1) to develop a reproducible histological technique to identify blood vessels and nerves in bone sections; and (2) to apply this protocol to identify blood vessel and nerve characteristics within osteoarthritic femoral heads. Femoral heads were retrieved from 8 OA patients (age range: 40-76; 5 female and 3 male) undergoing total hip replacement surgery. Each sample was evaluated for the presence of subchondral bone cysts using micro-computed tomography (µCT), then regions containing cysts were isolated and dissected for histological processing. Different fixation times in paraformaldehyde (PFA) were tested in three samples to assess the effect of fixation time on binding of the primary antibody to the target. Samples were stained with hematoxylin and eosin to evaluate overall tissue morphology, safarin-O and fast green to visualize the integrity of articular cartilage, anti-CD31 to identify vascular endothelium, and anti-PGP 9.5 to identify peripheral nerve fibers. A protocol was successfully developed to identify CD31-positive blood vessels and PGP 9.5-positive nerves in osteoarthritic femoral heads. The immunohistochemistry protocols for staining with anti-CD31 and anti-PGP 9.5 were optimized for maximum intensity of target staining, minimal background staining, and minimal artefactual tissue folding. Fixation time in PFA was not found to have an effect on quality of staining with anti-CD31. Blood vessels were found in all eight of the samples collected, and peripheral nerves were found in five of the samples. Special attention was paid to regions with fibrous subchondral bone cysts, because these are the most likely type to undergo neurovascular invasion. Out of the five samples with fibrous subchondral bone cysts, blood vessels were identified in all five cyst regions, and peripheral nerves were identified in three cyst regions. Using the protocols developed in this study, blood vessels and nerves were found in osteoarthritic femoral heads. In future, a larger sample set will be used to correlate the nature of blood vessel density and nerves that are found in bone marrow lesions identified on MRI scans obtained before surgery and are associated with bone cysts. This is an important step towards identifying more effective treatments for OA that address the specific underlying causes and the development of non-treatable pain.

Septic arthritis has the potential to be a highly destructive joint disease. Although numerous bacterial species are capable of inducing septic arthritis, Staphylococcus aureus is most commonly implicated, accounting for up to 65% of cases. Whilst this organism is known to produce a diverse array of potential virulence factors, studies investigating a variety of S. aureus-related infections have implicated alpha(Hla)-, beta(Hlb)- and gamma(Hlg)-haemolysins as key damaging toxins, with the ‘pore-forming’ Hla considered to be the most potent. The work presented in this study focused on gaining further insight into the interaction between S. aureus toxins and in situ chondrocytes during an episode of septic arthritis. An in vitro bovine osteochondral explant model of S. aureus-induced septic arthritis was developed in this study. Utilising fluorescence-mode confocal laser scanning microscopy (CLSM), the model, which avoided the complexities of a host immune response, permitted an assessment of the following: (1) the spatial and temporal quantification of in situ chondrocyte viability following exposure to both a laboratory ‘wild-type’ (S. aureus 8325-4) and clinical strains of S. aureus; (2) the influence of Hla, Hlb and Hlg on in situ chondrocyte viability through the use of specific ‘haemolysin-knockout’ mutant strains; (3) the influence of altered culture medium osmolarity and extracellular Ca2+ on Hla-induced in situ chondrocyte death; and (4) dynamic changes in intracellular Ca2+ within in situ chondrocytes following Hla exposure. S. aureus 8325-4 and S. aureus clinical strains rapidly reduced in situ chondrocyte viability ( > 45% chondrocyte death at 40hrs). The increased acidity, observed during bacterial culture, had a minimal effect on chondrocyte viability. Chondrocyte death commenced within the superficial zone (SZ) of cartilage and rapidly progressed to the deep zone (DZ). Simultaneous exposure of SZ and DZ chondrocytes to S. aureus 8325-4 toxins (achieved with the use of subchondral bone-free explants) demonstrated that SZ chondrocytes were more susceptible to the toxins than DZ chondrocytes. When explants were cultured in the presence of a selection of isogenic S. aureus mutants, with varying Hla, Hlb and Hlg production capabilities (all originating from S. aureus 8325-4), Hla-producing mutants induced significant in situ chondrocyte death compared to toxin deficient controls (Hla-Hlb-Hlg-). In contrast, mutants producing Hlb and Hlg in the absence of Hla were unable to induce significant chondrocyte death. Hla alone was therefore identified as the key damaging toxin to in situ chondrocyte viability. Raised culture medium osmolarity had no influence on Hla-induced in situ chondrocyte death. In the absence of Hla, a high extracellular Ca2+ concentration (20mM) had no influence on chondrocyte viability during the experimental period. Hla-induced chondrocyte death increased in the presence of raised extracellular Ca2+ concentrations thereby confirming a role of Ca2+ in the chondrocyte death pathway. There was no significant difference between S. aureus growth in high and low Ca2+ culture media. Finally, when live osteochondral explants stained with the Ca2+-sensitive fluorophore Fluo-4 were cultured with an Hla-containing S. aureus supernatant (S. aureus 8325-4 (Hla+Hlb+Hlg+)) there was a significant rise in intracellular Ca2+ in comparison to those explants exposed to a non-Hla-containing supernatant (S. aureus DU5938 (Hla- Hlb-Hlg-)). The Hla-induced Ca2+ transients were always followed by chondrocyte death. Thus, it is likely that Hla-induced chondrocyte death was associated with a rise in intracellular Ca2+. These findings are of translational relevance. Firstly, toxins released by S. aureus have a rapid and fatal action on in situ chondrocytes, thereby advocating the prompt and thorough removal of bacteria and their toxins during the treatment of septic arthritis. Secondly, the identification of Hla alone as the key damaging toxin to in situ chondrocyte viability, with its destructive action being associated with a rise in intracellular Ca2+, may enable the development of future targeted therapeutic strategies in order to reduce the extent of cartilage destruction during and after an episode of septic arthritis.

No description available.

Made available in DSpace on 2014-06-11T19:28:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2004-02-19Bitstream added on 2014-06-13T19:57:16Z : No. of bitstreams: 1 ishi_ep_me_arafo.pdf: 346197 bytes, checksum: 6795ce77ad2dd590c6c320a2852cea60 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Tendo em vista que existem controvérsias na literatura quanto à existência de associação entre a doença periodontal e a artrite reumatóide e que as metodologias empregadas são tão diversas quanto os seus resultados e conclusões, este estudo transversal teve por objetivo avaliar a condição periodontal em portadores de artrite reumatóide e verificar se existe associação entre essas duas condições. Para isso, foram aplicados questionários de saúde geral e bucal, e foi realizado o exame periodontal em 49 portadores de artrite reumatóide e em 22 indivíduos não portadores de artrite reumatóide ou qualquer outra doença auto-imune. Fumantes e portadores de diabetes mellitus foram excluídos deste estudo. Os resultados indicaram que portadores de artrite reumatóide possuem menor número de dentes na cavidade bucal, apresentam maior extensão de placa bacteriana e maior proporção de sítios com perda de inserção periodontal avançada do que os indivíduos não portadores de artrite reumatóide Apesar da maior extensão de placa bacteriana dentre portadores de artrite reumatóide, a porcentagem de sítios que apresentaram sangramento marginal foi semelhante nos dois grupos, provavelmente devido ao uso de drogas antiinflamatórias e drogas de base, imunoreguladoras. Além disso, portadores de artrite reumatóide que utilizavam a associação de drogas de base apresentaram menor perda de inserção periodontal do que aqueles que não utilizavam a associação dessas drogas. Os resultados do estudo sugerem que existe associação entre periodontite e artrite reumatóide e que novos estudos serão necessários para identificar os fatores presentes nos portadores de artrite reumatóide que predispõem esses indivíduos a uma maior perda de inserção periodontal. / There are controversies in the literature concerning the association between periodontal disease and rheumatoid arthritis. There are no consistent methodologies and results. The aim of this cross-sectional study was to assess periodontal condition in rheumatoid arthritis patients and verify if there is an association between these two conditions. We have produced general and dental health questionnaires and periodontal examination was achieved in 49 rheumatoid arthritis patients and 22 healthy individuals. Smokers and diabetes mellitus patients were excluded of the sample. Our results indicated that rheumatoid arthritis patients had lesser remaining teeth, higher extension of dental plaque and higher proportion of sites presenting advanced attachment loss than controls. Although rheumatoid arthritis patients had higher extension of dental plaque than the control group, gingival bleeding was similar between them, maybe because of the fact that rheumatoid arthritis patients take anti-inflammatory and disease-modifying antirheumatic drugs (DMARDs) for their treatment. Rheumatoid arthritis patients who were taking an association of two or more disease-modifying antirheumatic drugs had lesser attachment loss than patients that were taking only one of these drugs. Our results suggest that there is an association between periodontitis and rheumatoid arthritis and that more studies are required to identify specific risk factors for attachment loss in rheumatoid arthritis patients.

Made available in DSpace on 2014-06-11T19:29:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-09-02Bitstream added on 2014-06-13T19:38:45Z : No. of bitstreams: 1 carvalho_sm_me_botfm.pdf: 851185 bytes, checksum: eea10cd209e9c4f24efd8d9bd0d1f8fb (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A febre reumática (FR) é uma doença pós-infecciosa, causada pelo Streptococus β hemolítico do Grupo A de Lancefield, de mecanismo auto-imune. As suas manifestações clínicas principais são denominadas sinais maiores, incluindo a artrite, cardite, coréia, nódulos subcutâneos e eritema marginado. Entre as manifestações denominadas sinais menores estão o aumento do intervalo P-R no eletrocardiograma, febre, provas de fase aguda positivas, como a VHS e a proteína C reativa. A comprovação de infecção recente pelo estreptococo é considerada um critério essencial. A FR é ainda prevalente nos países em desenvolvimento e emergentes, tendo como complicações crônica o dano valvular causado pela cardite. A sua prevenção é realizada com a erradicação do estreptococo na orofaringe, por meio da profilaxia primária com penicilina benzatina e a profilaxia secundária com a manutenção da penicilina benzatina em intervalos de 21 dias, de acordo com a recomendação da OMS. Como a FR pode apresentar seqüelas, impacto social e na qualidade de vida, justifica-se a avaliação do desfecho clínico e as suas manifestações em longo prazo. Examinar a epidemiologia, as características clínicas e o desfecho da FR em uma série de casos, nos últimos 20 anos em uma unidade acadêmica dedicada à reumatologia pediátrica (HC-FMB-UNESP). 178 casos foram identificados no período de 1986 a 2007 e destes, 134 foram revisados de acordo com um protocolo listando as manifestações clínicas e laboratoriais, o uso de medicação, o período de acompanhamento e os episódios de recorrência durante o seguimento para vigilância da profilaxia secundária. Os dados demográficos, assim como as manifestações clínicas, laboratoriais e de desfecho são apresentados por meio de freqüência para os dados categóricos e pela estatística descritiva para variáveis contínuas. A probabilidade... / Rheumatic Fever (RF) is a post-infectious disease caused by group A Streptococcus, with autoimmune mechanism. The main clinical features are named major signs as arthritis, carditis, chorea, subcutaneous nodules and erythema marginatum. Among other features, there are the minor signs as increased P-R interval on electrocardiogram (ECG), fever and acute phase reaction measured by erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). Evidence of previous streptococcal infection is considered a core criteria. RF is highly prevalent in developing countries, where the main complication is damaged heart valves due to carditis. Prophylaxis is called primary when long-acting benzyl penicilin is administered for the first time after diagnosis and it is called secondary prophylaxis for maintenance treatment with long-acting benzyl penicilin every 3 weeks, according to the WHO guidelines. As RF may result in heart damage with both quality of life and social impact, it is valuable to assess its long term outcome. To examine epidemiology , clinical features and outcome of RF in a paediatric case series, seen in an academic unit dedicated to paediatric rheumatology (HC-FMB-UNESP) during the last 20 years. 178 cases were identified from 1986 to 2007, of those 134 were fully revised according to a standardized protocol checking for clinical and laboratorial features, treatment, follow up and acute RF relapse during follow up for prophylaxis surveillance. Demographics, clinical and laboratorial features as well as outcome data are reported by frequency for categorical variables. Continuous variables are presented by descriptive statistics. The probability of carditis, valve damage and RF relapses were examined by survival analysis with actuarial survival plots. Of 134 revised cases, age at onset was from 4 to 13.8 years, follow up duration was from 1.1 to 16.9 years mean 6.8 SD (3.6) and median... (Complete abstract click electronic access below)

abstract: Purpose: To examine: (1) whether Non-Hispanic Blacks (NHB) and Non-Hispanic Whites (NHW) with diagnosed arthritis differed in self-reported physical activity (PA) levels, (2) if NHB and NHW with arthritis differed on potential correlates of PA based on the Social Ecological Model (Mcleroy et al., 1988), and (3) if PA participation varied by race/ethnicity after controlling for age, gender, education, and BMI. Methods: This study was a secondary data analysis of data collected from 2006-2008 in Chicago, IL as part of the Midwest Roybal Center for Health Promotion. Bivariate analyses were used to assess potential differences between race in meeting either ACR or ACSM PA guidelines. Comparisons by race between potential socio-demographic correlates and meeting physical activity guidelines were assessed using Chi-squares. Potential differences by race in psychosocial, arthritis, and health-related and environmental correlates were assessed using T-tests. Finally, logistic regression analyses were used to examine if race was still associated with PA after controlling for socio-demographic characteristics. Results: A greater proportion of NHW (68.1% and 35.3%) than NHB (46.5% and 20.9%) met both the arthritis-specific and the American College of Sports Medicine (ACSM) recommendations for physical activity, respectively. NHB had significantly lower self-efficacy for exercise and reported greater impairments in physical function compared to NHW. Likewise, NHB reported more crime and less aesthetics within their neighborhood. NHW were 2.56 times more likely to meet arthritis-specific PA guidelines than NHB after controlling for age, gender, education, marital status, and BMI. In contrast, after controlling for sociodemographic characteristics, age and gender were the only significant predictors of meeting ACSM PA guidelines. Discussion: There were significant differences between NHB and NHW individuals with arthritis in meeting PA guidelines. After controlling for age, gender, education, and BMI non-Hispanic White individuals were still significantly more likely to meet PA guidelines. Interventions aimed at promoting higher levels of physical activity among individuals with arthritis need to consider neighborhood aesthetics and crime when designing programs. More arthritis-specific programs are needed in close proximity to neighborhoods in an effort to promote physical activity. / Dissertation/Thesis / M.S. Exercise and Wellness 2013

A artrite reumatoide (AR) Ã uma condiÃÃo autoimune caracterizada por uma inflamaÃÃo das articulaÃÃes. As medicaÃÃes mais utilizadas no tratamento da AR sÃo drogas antireumÃticas modificadoras da doenÃa (DMARD), como o metotrexato (MTX) e agentes biolÃgicos, dentre estes os inibidores do fator de necrose tumoral alfa (anti-TNF-α). Trabalhos recentes relacionam estes fÃrmacos a um maior acometimento de infecÃÃes. O objetivo do estudo foi avaliar a ocorrÃncia de inflamaÃÃo, dor, cicatrizaÃÃo e presenÃa de infecÃÃes apÃs exodontias em pacientes com AR sob tratamento com anti-TNF-α e MTX que fizeram uso prÃ-operatÃrio ou pÃs-operatÃrio de amoxicilina. Os pacientes com AR foram distribuÃdos, de forma randÃmica, em dois grupos: grupo A (profilaxia antibiÃtica â utilizaram 4 cÃpsulas de 500mg de amoxicilina uma hora antes do procedimento) e grupo B (cobertura antibiÃtica- fizeram uso de uma cÃpsula de 500mg de amoxicilina de 8 em 8 horas por 5 dias). AlÃm desses, para fins de controle, um terceiro grupo foi formado por pacientes sem AR e sem prescriÃÃo de antibiÃticos. ApÃs avaliaÃÃo de exames hematolÃgicos e radiogrÃficos, foram realizadas 30 exodontias (13 pacientes com AR e 12 do grupo controle) por um mesmo operador nos 3 grupos. Esse operador, assim como os pacientes dos grupos A e B, desconhecia qual esquema de medicaÃÃo empregada. AvaliaÃÃes periÃdicas (24 horas, 72 horas, 7 dias, 14 dias e 30 dias apÃs o procedimento) foram feitas para identificar sinais clÃnicos e radiogrÃficos de infecÃÃo e de inflamaÃÃo. A avaliaÃÃo da cicatrizaÃÃo da ferida cirÃrgica foi feita atravÃs de mediÃÃes com um paquÃmetro nos intervalos de 24 horas, 72 horas, 7 dias e 14 dias. Para verificaÃÃo da sintomatologia dolorosa, utilizou-se uma escala visual analÃgica (VAS) que foi entregue aos pacientes apÃs a exodontia. Todos os pacientes fizeram 3 radiografias periapicais (antes da exodontia, com 24 horas e apÃs 30 dias) que foram digitalizadas e analisadas pelo software ImageJÂ com intuito de verificar o perÃodo cicatricial radiogrÃfico por meio da modificaÃÃo da Ãrea radiolÃcida alveolar. A maioria dos pacientes participantes foi mulheres, tanto no grupo controle (58,3%) quanto nos grupos A e B (83,3% e 100% respectivamente). Os nÃveis de plaquetas dos pacientes dos grupos A e B foram superiores aos do grupo controle (p=0,008). No que se refere aos sinais inflamatÃrios e de infecÃÃo, nÃo houve diferenÃa significativa entre os trÃs grupos, assim como nos Ãndices de dor e na cicatrizaÃÃo Ãssea avaliada radiograficamente, diferentemente dos Ãndices de cicatrizaÃÃo tecidual, onde os grupos A e B apresentaram menores Ãreas das feridas cirÃrgicas e melhor contraÃÃo das feridas que o grupo controle (p=0,005). Os pacientes dos grupos A e B apresentaram reparo Ãsseo, Ãndice de inflamaÃÃo e de infecÃÃo semelhantes ao grupo controle, entretanto, os parÃmetros de cicatrizaÃÃo tecidual nos grupos A e B foram superiores quando comparados ao grupo controle. Com isso, sugere-se que o uso da amoxicilina de forma profilÃtica seja o mais adequado e racional, uma vez que nÃo houve diferenÃa entre os esquemas antibiÃticos empregados. / Rheumatoid arthritis (RA) is an autoimmune condition characterized by an inflammation of the joints. The medications most commonly used in the treatment of RA are disease modifying antirheumatic drugs (DMARDs) such as methotrexate (MTX) and biological agents such as tumor necrosis factor alpha inhibitors (anti-TNF-α). These drugs are immunosuppressive and they are related to a higher incidence of infections. The aim of this study was to evaluate the occurrence of inflammation, pain, scarring, and the presence of infections after tooth extraction in patients with RA treated with anti-TNF-α and MTX that used pre or postoperative amoxicillin. The RA patients were divided randomly into two groups: Group A (antibiotic prophylaxis â a single dose of amoxicillin 2g orally, 1h prior to the procedure) and group B (postoperatively antibiotic - 500mg of amoxicillin 8/8h for 5 days). In addition, a third group was created for control purposes that consisted of patients without RA and with no prescription of antibiotics. After evaluation of hematologic and radiographic parameters were performed 30 extractions (13 patients with RA and 12 in control group) by a single operator. The distribution of medications was made randomly and double-blind. Periodic evaluation (1,3,7,14 and 30 days after the procedure) were taken in order to identify clinical and radiographic signs of infection, inflammation. The evaluation of wound healing was done through measurement with a caliper at intervals of 24 hours, 72 hours, 7 days, and 14 days. A visual analogue scale (VAS) was used for verification of painful symptoms which was delivered to the patients after the extractions. All patients had 3 periapical radiographs (before extraction, with 24 hours and after 30 days) that were digitized and analyzed by ImageJÂ software to verify radiographic healing period by modifying the alveolar radiolucent area. Most participants were women in control group (58.3%) and in groups A and B (83.3% and 100% respectively). Platelet levels of patients in groups A and B were higher than the control group (p = 0.008). In regard to inflammatory and infection signs, there was no significant difference between the three groups, as well as in pain levels and bone regeneration assessed radiographically, unlike tissue healing rates, where the groups A and B showed smaller areas of surgical wounds and the wounds contraction better than the control group (p = 0.005). Patients in groups A and B showed bone healing, inflammation and infection rate similar to the control group, however, the tissue healing parameters in groups A and B were higher when compared to the control group. In conclusion, it might be wise to suggest the use of amoxicillin prophylaxis considering rational antimicrobial use, since there was no difference between antibiotic regimens employed.