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Chronic inflammation follows defined phases of induction, inflammation, and resolution. The resolution phase requires cycloxygenase-2 (COX-2) activity. This study aims to address what other molecules are required for a functional resolution phase. We demonstrated that in murine collagen-induced arthritis the transcription factor, PPARgamma plays a role in the resolution phase. Inhibition of COX-2 activity results in fewer PPARgamma positive cells in the arthritic synovium. Treatment with a PPARgamma antagonist, SR202, alone, also disrupts the process of resolution. PPARgamma antagonist treatment results in a decrease in eNOS phosphorylation within the arthritic synovium. These observations indicate that PPARgamma may function to regulate eNOS activity. The source of pro-resolving nitric oxide is eNOS but not, iNOS. The effect of COX-2 inhibition on the resolution phase is ameliorated by injection of a PGE2 analog. Restoration of PGE2 levels results in an increase in PPARgamma positive cells in the arthritic synovium which correlates with this restoration of resolution. Thus, this study provides in vivo evidence for the pro-resolving role of PPARgamma and its relationship with PGE2 and eNOS. / Microbiology and Immunology

We examined the nutrient intake of women with rheumatoid arthritis (RA) before and after initiation of treatment with arthritis medication. Results of past (before taking arthritis medication) and present diets of RA subjects were compared to the past and present diets of the non-RA group. Subjects with RA were 19 women with a mean age of 65 ± 9 years who were diagnosed with RA and were receiving arthritis medication on a regular basis. The non-RA subjects were 19 women with a mean age of 57 ± 3 years who were apparently healthy and were not taking any prescription medication. Both groups were interviewed to determine past and present dietary nutrient intake by using the Health Habits and History food frequency questionnaire (FFQ) developed by the National Cancer Institute. Nutrient intake determined from 3-day dietary records and present diet FFQs were comparable. Total energy and fat in the past diets of the RA group were significantly higher (p<0.05) than the past diets of the non-RA group. Within each group there were significant reductions (p<0.05) between the past and present mean dietary intakes of total energy, fat and protein. There were no significant differences between the past and present micronutrient intakes between or within the two groups. However, the micronutrient content of the present diets of the RA group was lower in calcium, iron, thiamin and riboflavin than the non-RA group as measured by the number of subjects who had <67% of the RDA. There was a significant (p<0.05) decrease in the mean daily consumption of the meat, poultry, fish, eggs and bean group in both non-RA and RA groups. There was also a significant (p<0.05) decrease in the mean daily consumption of the fat, oil and sweets group among the RA subjects. RA subjects were taking an average of 3±1 arthritis medications. There were no significant correlations between the number of medications taken by the RA group and their dietary nutrient intake. However, the significant (p<0.05) decline in total energy intake by the RA group could possibly be due to medication side effects. Since present total energy intake was lower in both groups, these results could reflect the general decline in energy intake with advancing age. There were significant (p<0.05) differences between the past and present self-reported weights of the non-RA and RA groups showing a general reduction in weight over time in both groups. Mean body mass indexes (BMI) for RA subjects was higher than the non-RA subjects', possibly reflecting the lower activity level of the RA group. / Graduation date: 1996

The goal of this study was to explore the relationship between psychosocial and demographic characteristics associated with success among individuals with rheumatoid arthritis. Unlike previous research which has predominantly focused on the limiting effects of rheumatoid arthritis, the present study sought to identify factors that were related to success. One hundred and ninety-eight individuals who met the criteria for this study, returned completed questionnaires. Success for people with rheumatoid arthritis was measured on the scales of self-esteem, social activity, and physical activity. Participants were categorized as either "high" or "low" on the success scales in order to see what demographic and psychosocial variables were related levels of self-esteem, social activity, and physical activity. Data analysis included reliability of the success scales, and analysis of variance to determine the relationship among the three scales and selected demographic characteristics. Discriminant analysis was used to explore what demographic and psychosocial factors were related to high (as opposed to low) self-esteem, social activity, and physical activity among 24 participants. The success scales were found to be reliable. There was no significant relationship among the success scales and sex, occupational level, and ethnicity. Results of the discriminant function identified that generally, individuals with high (as opposed to low) self-esteem were very motivated and had a positive outlook on life. People with high (as opposed to low) social activity had fewer physical limitations and a better view of themselves. High (as opposed to low) physical activity was found among people who generally were highly motivated and believed they had some control over their rheumatoid arthritis.

Disease progression in rheumatoid arthritis (RA) is assessed by standard clinical, radiological and functional measures. Clinical disease activity in RA is graded as no disease (remission), low, moderate and high disease, based on validated criteria. Radiological progression in RA is monitored by serial x-rays of hands and feet, and by quantification of structural damage, using various scoring methods. This proves to be a valuable outcome measure in RA studies. RA patients with active disease usually develop progressive radiological damage. However, it has been shown that clinical disease activity may not correlate with radiological damage, particularly in early RA. Therefore, this thesis was mainly aimed to test the hypothesis that, „radiological damage can progress despite clinical disease inactivity or remission‟ and to investigate possible underlying mechanisms including disease heterogeneity, treatment effect and scoring methodology. Disease progression, outcomes and prognostic factors were analysed in an inception cohort of early RA (Early Rheumatoid Arthritis Study/ERAS) for this thesis. In this study of early RA patients, sustained remission was less frequent than remission at individual time points and baseline variables such as gender, duration of symptoms, disease activity (DAS) and health assessment questionnaire (HAQ) scores have shown predictive value for sustained remission. Structural damage on x-rays progressed despite clinical disease inactivity or remission in a subgroup of patients and disease heterogeneity was the most likely explanation for the disconnect between clinical disease activity and radiological damage in the ERAS cohort. This study has also found that scoring methods as well as reading order of x-ray films could influence radiographic progression in early RA, particularly at individual level. Male sex, rheumatoid factor (RF) and radiographic damage at baseline showed prognostic value in predicting radiographic progression despite remission. Study patients with persistent clinical disease inactivity have shown better radiological, surgical, functional, and other outcomes compared to relapsing-remitting or persistent disease activity. There was no significant difference in functional and other outcomes between patients in remission with x-ray progression and those in remission without xray progression. Therefore, x-rays of hands and feet at regular intervals are valuable in determining true disease progression in early RA, even during clinical disease inactivity. Scoring methodology in itself could have an influence on the type of radiographic progression in RA studies. Sustained disease inactivity in RA is more favourable than relapsingremitting disease.

Li, Martin. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 187-208). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Introdução: A estratégia de tratamento baseado em metas tem sido extensamente estudada em pacientes com AR inicial. No entanto, estudos sobre os benefícios de longo prazo do controle de atividade de doença em pacientes com AR estabelecida ainda são escassos. Objetivo: Avaliar a efetividade de longo prazo da estratégia de tratamento baseado em metas em pacientes com artrite reumatoide estabelecida na prática diária. Métodos: Pacientes com AR, previamente tratados de forma convencional, iniciaram estratégia de tratamento baseado em metas, sendo incluídos de março de 2005 a fevereiro de 2007 e acompanhados até dezembro de 2014. Os pacientes eram avaliados a cada 3 meses até remissão ou baixa atividade de doença serem alcançadas, e após a cada 6 meses. O tratamento seguiu um escalonamento de acordo com as recomendações vigentes. A atividade de doença foi mensurada através do DAS28 e do CDAI e a capacidade funcional, através do HAQ-DI. As informações foram extraídas pela revisão de formulários e de tabelas padronizadas. Variações na atividade de doença e na capacidade funcional foram comparadas pelo teste de Wilcoxon e Equações de Estimativas Generalizadas (GEE) A mortalidade foi avaliada através da curva de Kaplan-Meier. Resultados: Duzentos e vinte e nove pacientes foram incluídos, com duração média de doença 10,6±7,4 anos. Dentre os pacientes em moderada e alta atividade de doença no início da coorte, houve significativa redução do DAS28 (4,6±0,1 vs. 3,1±0,1; p<0,001) e do CDAI (21,2±1,0 vs. 7,9±0,7; p<0,001). Também houve redução do HAQ-DI (1,3±0,05 vs 1,0±0,1; p<0,001). A proporção de pacientes em remissão ou em baixa atividade de doença aumentou de 20% para 62% pelo DAS28. Com a estratégia de tratamento baseado em metas, houve um aumento na proporção de pacientes em uso de biológico para 30%. A taxa de mortalidade foi de 24,2 por 1000 pacientes-ano, discretamente superior à descrita na literatura. Conclusão: A estratégia de tratamento baseado em metas com objetivo de remissão e de baixa atividade de doença é efetivo em pacientes com AR estabelecida. / Introduction: Treating RA to a target has become a landmark strategy to be pursued in every patient. Nonetheless, few studies have addressed the true long-term impact of a T2T strategy in a real-world setting with established RA patients. Objective. To examine the long-term effectiveness of a treat-to-target (T2T) strategy in patients with established rheumatoid arthritis (RA) in daily practice. Methods. Patients with RA who were previously given the standard of care were started on a T2T strategy between March 2005 and February 2007 and followed through December 2014. Participants were seen every 3 months until remission/low disease activity was achieved and every 6 months thereafter. Treatment escalation followed a step-up strategy, according to national recommendations. Disease activity was measured by the DAS28 score and Clinical Disease Activity Index (CDAI), and physical function by the Health Assessment Questionnaire (HAQ). Data were extracted with standardized forms and a chart review. Changes in disease activity and physical function were compared using Wilcoxon’s test and generalized estimating equations. Mortality was analyzed using a Kaplan–Meier survival curve. Results. Two hundred and twenty-nine patients were included, with a mean (S.D.) disease duration of 10.6 (7.4) years. Significant reductions were observed in DAS28 (4.6±0.1 vs. 3.1±0.1; p<0.001), CDAI (21.2±1.0 vs. 7.9±0.7; p<0.001), and HAQ (1.3±0.05 vs 1.0±0.1; p<0.001) scores. The proportion of participants in remission/with low disease activity according to DAS28 increased from 20% to 62%. During implementation of the T2T strategy, a gradual increase in the proportion of participants using biologics was observed, to nearly 30%. The mortality rate was 24.2 per 1000 patient-years, slightly higher than that reported in other cohorts. Conclusion. A treat-to-target strategy aiming for remission or low disease activity is effective in patients with established RA.

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Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.