Introdução: Fadiga é uma manifestação clínica importante na artrite reumatoide (AR). Atualmente, a avaliação de fadiga em AR é realizada através de questionários subjetivos, incluindo aspectos emocionais e sociais. No entanto, sabe-se que a fadiga pode estar acentuada no plano periférico e esta abordagem é pouco estudada nestes pacientes. Objetivo: Avaliar a relação entre a percepção de fadiga e fadiga muscular em pacientes com artrite reumatoide. Métodos: Trinta e oito pacientes do sexo feminino com AR foram incluídos. Os pacientes foram estratificados por DAS-28 e por três grupos etários (grupo I: 32-48 anos; grupo II: 49-54 anos de idade, e grupo III: 55-65 anos de idade). A fadiga muscular [avaliado por mudanças na magnitude (root mean square-RMS) e freqüência (média de freqüência-MDF) de ativação muscular durante os 60s do teste de força de quadríceps] e percepção de fadiga (FACIT-F) foram avaliadas. Além disso, dados demográficos [duração idade e doença, calculado pelo tempo decorrido a partir de diagnóstico], hemoglobina (g/ dL), DAS-28, HAQ, qualidade de vida (SF-36) e International Physical Activity Questionnaire (IPAQ, versão longa) foram medidos. A significância foi assumida quando p≤0.05. Resultados: Nenhuma associação foi observada quando os pacientes foram estratificados por DAS-28 e quando os pacientes foram estratificados por idade no grupo III. Moderada correlações estatisticamente significativas entre MDF e FACIT-F e FACIT-TOI (r = 0,6; p = 0,03 e r = 0,5; 0,04, respectivamente) foram encontrados no grupo I. No grupo II foram encontradas moderadas correlações estatisticamente significativas entre FACIT-TOTAL e RMS e MDF (r = 0,6; p = 0,01 e r = -0,5; p = 0,04, respectivamente). Conclusão: Moderada relação entre fadiga muscular e percepção de fadiga sugere que ambas as estratégias de avaliação podem ser complementares e têm um efeito benéfico sobre comorbidades AR. / Introduction: Fatigue is a major clinical manifestation in rheumatoid arthritis (RA). Actually, the assessment of fatigue in RA is realized through to subjective questionnaires, including emotional and socials aspects. However, known to that fatigue may be sharp in peripheral plane and this approach is little studied in these patients. Objective: To assess the relationship between perception of fatigue and muscle fatigue in patients with RA. Methods: Thirty eight female patients with RA were included. Patients were stratified by DAS-28 and by three age groups (group I: 32-48 years old; group II: 49-54 years old; group III: 55-65 years old). Muscle fatigue [assessed by changes in magnitude (i.e. root mean square-RMS) and frequency (i.e. median frequency-MDF) of muscle activation during a 60-s quadriceps strength test] and perception of fatigue (FACIT-F) were assessed. In addition, demographic data [age and disease duration, calculated by elapsed time from diagnostic], hemoglobin (Hb-g/dL), DAS-28, HAQ, quality of life (SF-36) and International Physical Activity Questionnaire (IPAQ, long version) were measured. Significance was assumed when p≤0.05. Results: No association was observed when patients were stratified by DAS-28 and when patients were stratified by age in group III. Moderate statistically significant correlations between MDF and FACIT-F e FACIT-TOI (r=0.6;p=0.03 and r=0.5;0.04, respectively) were found in group I. In group II moderate statistically significant correlations were found between FACIT-TOTAL and RMS and MDF (r=0.6;p=0.01 and r=-0.5;p=0.04, respectively). Conclusion: Moderate relationship between muscle fatigue and perception of fatigue suggests that both evaluation strategies can be complementary and have a beneficial effect on RA comorbidities.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-08-19T12:29:52Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese - Hildson Dornelas - Doutorado em Genética.pdf: 1858452 bytes, checksum: 4316ac97c9fa83b7550daecee991807e (MD5) / Made available in DSpace on 2016-08-19T12:29:52Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese - Hildson Dornelas - Doutorado em Genética.pdf: 1858452 bytes, checksum: 4316ac97c9fa83b7550daecee991807e (MD5) Previous issue date: 2016-03-19 / A artrite reumatoide (AR) é uma doença inflamatória, crônica e autoimune com manifestações articulares e sistêmicas, e atinge cerca de 1% da população mundial. Fatores genéticos, ambientais e imunológicos estão envolvidos na sua patogênese. Assim, investigamos a possível associação entre polimorfismos de base única (SNP): IL-6 (rs180079518), IL-12B (rs3212227) IL-17A (rs2275913), IL-17F (rs763780), IL-18 (rs549908), IL23R (rs10889677), TNF-α (rs1800629), IFN-γ (rs2430561), com características clínicas e susceptibilidade à AR. Para tal, realizamos um estudo de caso-controle com 90 pacientes e 189 controles saudáveis. A genotipagem foi realizada através da reação de polimerização em cadeia - polimorfismo de comprimento de fragmentos de restrição (PCR-RFLP). Nossos resultados mostraram que a média de início da doença foi de 45 anos com predominância feminina (9:1). A atividade da doença estava aumentada em 50% dos pacientes, enquanto 71% e 65% foram positivos para o fator reumatoide (FR) e para o anticorpo contra peptídeos citrulinados cíclicos (anti-CCP), respectivamente. Observamos associação entre o risco para AR com polimorfismos nos genes IL-18 (OR=3.77, p<0.0001) e IL-23R (OR=3.46, p<0.001). Além disso, foi observada também associação entre SNPs nos genes IL-17F com DAS28 (OR=5.44, p=0.031), IL-6 com FR (OR=4.47, p=0.0038) e anti-CCP (OR=3.91, p=0.0057). Nosso estudo mostrou associações entre polimorfismos em genes de importantes citocinas envolvidas na AR com a sua susceptibilidade e características clinicas desta doença na população do interior do Estado de São Paulo, Sudeste do Brasil. / Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with articular and systemic manifestations and affects about 1% of adults worldwide. Genetic, environmental and immunological factors are observed in the pathogenesis of this disease. Thus, our study investigated the possible association between single nucleotide polymorphisms (SNP): IL-6 (rs180079518), IL-12B (rs3212227) IL-17A (rs2275913), IL-17F (rs763780), IL-18 (rs549908), IL23R (rs10889677), TNF-α (rs1800629), IFN-γ (rs2430561), with the clinical features and RA susceptibility. For this, we conducted a case-control study with 90 patients and 189 healthy controls. Genotyping was performed by Polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). Our results showed that the onset of RA had a mean age of 45 years with predominance of women (9:1). About 50% of RA patients had high degree of disease activity, while 71% and 65% were rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) positive, respectively. It was observed associated between the risk of rheumatoid arthritis and the polymorphisms in genes IL-18 (OR=3.77 (IC=2.01-7.05), p<0.0001) and IL-23R (OR=3.46 (IC=1.96-6.09), p<0.001). Furthermore, was observed relationship of the SNPs in genes, IL-17F with DAS28 (OR=5.44 (IC=1.29-22.85) and IL-6 with RF (OR=4.47 (IC=1.69-11.79), p=0.0038) and ACPA (OR=3.91(IC=1.56-9.78), p=0.0057). Our study presents evidence of associations between polymorphisms in genes of important cytokines involved in RA with susceptibility to RA and their clinical characteristics in population in the state of São Paulo, Southeastern Brazil.

Methotrexate (MTX), as a pharmaceutical, is frequently used in tumor chemotherapy and is also a part of the established treatment of a number of autoimmune inflammatory disorders. Radiolabeled MTX has been studied as a tumor-diagnostic agent in a number of published studies. In the present study, the potential use of technetium-99m-labelled MTX (Tc-99m-MTX) as a radiotracer was investigated for the identification of inflammatory target sites. The labelling of MTX was carried out via a Tc-99m-gluconate precursor. Evaluation studies included in vitro stability, plasma protein binding assessment, partition-coefficient estimation, in vivo scintigraphic imaging and ex vivo animal experiments in an animal inflammation model. MTX was successfully labelled with Tc-99m, with a radiochemical purity of >95%. Stability was assessed in plasma, where it remained intact up to 85% at 4 h post-incubation, while protein binding of the radiotracer was observed to be similar to 50% at 4 h. These preclinical ex vivo and in vivo studies indicated that Tc-99m-MTX accumulates in inflamed tissue, as well as in the spinal cord, joints and bones; all areas with relatively high remodeling activity. The results are promising, and set the stage for further work on the development and application of Tc-99m-MTX as a radiotracer for inflammation associated with rheumatoid arthritis.

Aim: To study patient-related functional outcome measures, implant survival and radiographic loosening after total wrist arthroplasty (TWA) using four different implants. To evaluate a new TWA design biomechanically and clinically. Methods: The studies included two cohort studies with prospectively collected data (n=206 and n=219), an anatomic and kinematic analysis in a cadaveric model and a pilot study (n=20). Results: The Maestro TWA had a significantly greater improvement of radial/ulnar deviation than the Biax and Remotion TWAs. Summarized patientrelated functional outcome was significantly better for the Maestro than for the Remotion TWA. Cumulative implant survival after 8 years was 94% for Remotion, and 95% for Maestro implants. Radiographic loosening five years postoperatively was present in 26% of the Biax wrists, 18% of those with Remotion, and 2% of those with Maestro. Following TWA with the new implant design in a cadaveric model, there were no statistically significant changes compared to a native wrist regarding flexion, extension, radial deviation, the extension/radial deviation component of the dart-thrower’s motion, or the circumduction range of motion. Clinically, there was significant improvement of COPM, PRWE and VAS pain scores. Wrist extension and ulnar deviation improved, while grip strength remained largely unchanged. Conclusions: TWA is a surgical procedure which may offer a high level of patient satisfaction. Implant design may affect patient-related functional outcome after TWA. Implant survival as well as the frequency of radiographic loosening differed considerably between the four types of implants and might be a result of different implant design. Kinematic analysis of the new TWA design suggests that a stable and functional wrist is achievable with this design. Surgical placement of the new total wrist implant was reproducible and the implant yielded good patient-related outcome measures in the short term. Since TWA is an evolving procedure, further studies are warranted in order to refine indications and the place for TWA in modern hand surgery.

Abstract Swanson silastic arthroplasty, introduced by Alfred Swanson in the late sixties, has long been the treatment of choice for metacarpophalangeal (MCP) arthroplasty in cases of rheumatoid arthritis. Silastic implant arthroplasty has a significant role in the reconstruction of eroded MCP joints, but the method does not recreate a normal MCP joint. The Sutter implant has been designed to improve the function of the MCP joint, and especially to reduce the extension deficit. There are numerous studies concerning the Swanson implant, but limited number of previous articles on the use of the Sutter implant. The aim of this thesis was to determine the outcome of MCP arthroplasty with the Sutter implant in patients with inflammatory joint disease. This thesis is based on two studies concerning Sutter implant arthroplasty in patients with advanced rheumatoid arthritis. One of these was a prospective study performed at Oulu University Hospital in which patients were randomised into Swanson and Sutter implant groups representing 49 hands and 174 implants, with a mean follow up time of 4.8 years, and the other was a prospective study performed at the Rheumatism Foundation Hospital in Heinola in which Sutter implant arthroplasty was carried out on 117 hands employing 350 implants, with a mean follow-up time of 5.3 years. The main results were that arthroplasty yields similar results with both of these implants with respect to clinical parameters such as range of motion, ulnar deviation, grip strength and pain. Furthermore, the revision rate in our Sutter follow-up study was high, and survival, with revision surgery as the end point, was poor. We created a new radiographic grading system for bone resorption, i.e. osteolysis, in MCP arthroplasty and found this to be more severe after Sutter than Swanson implant arthroplasty, for some unknown reason. Moreover, we found that osteolysis was symptom-free but related to implant fractures. As a conclusion silicone implant arthroplasty should be used only with rheumatoid patients with advanced destruction. High implant fracture rates and high amounts of osteolytic changes in radiographs are not favourable for the use of the Sutter implant. If continuous development of new prostheses achieves implant with as good clinical outcome and reasonable costs as Swanson implant, the use of the silicone implants will be questionable.

Abstract Collagen IX belongs to the superfamily of collagenous proteins and is present on the surface of the heterotypic collagen fibrils that are predominantly composed of collagen II, and also collagen XI. The major sites of expression of collagen IX include the articular cartilage, intervertebral disc, inner ear and the vitreous body of the eye. Previous reports have indicated that mutations in the genes encoding the three polypeptide chains of collagen IX may lead to intervertebral disc disease and multiple epiphyseal dysplasia, a chondrodysplasia characterized by early onset osteoarthritis. These observations and results from genetically modified mouse lines suggest that collagen IX is crucial in the maintenance of the long-term integrity of tissues. However, the structure-function relationship as well as detailed information concerning the functional roles of this protein has remained unclear. Recombinant human collagen IX was obtained using an insect cell expression system. Besides full-length molecules, five truncated variants of collagen IX were produced to examine chain association and trimerization. Contrary to previous observations, it was shown that the COL1 and NC1 domains are not essential for trimerization. Instead, they seem to play an important role in the specificity of chain selection. The results also suggest that the N-terminal domains, NC3 or COL3, are required for complete folding and stabilization of collagen IX molecules, implicating cooperativity between different domains in the folding process. Collagen IX was found to mediate cell adhesion and bind efficiently to collagen receptor integrins α1β1, α2β1, α10β1 and α11β1. The binding was found to represent a novel type of mechanism, and the binding site of the integrin I domain was located at the N-terminal end of the COL3 domain in collagen IX. The obtained results suggest that the FACITs may play an important role as mediators of cell adhesion to collagen fibrils. Antibodies binding to human recombinant collagen IX were measured among 53 patients with seropositive rheumatoid arthritis (RA). These autoantibodies were significantly elevated among the RA patients when compared to the controls, suggesting that autoantibodies to collagen IX show diagnostic potential in early RA. However, no association was found between the antibody levels and outcome.

No description available.

La polyarthrite rhumatoïde (PR) est une maladie inflammatoire chronique caractérisée par des atteintes articulaires. Les synoviocytes, cellules qui tapissent la membrane synoviale, deviennent réfractaires à l‘apoptose et, en produisant la cytokine inflammatoire Interleukin 6 (IL-6), participent à la chronicité de l‘inflammation qui est à l‘origine de la perte osseuse dans la PR.Le zinc (Zn) et le cadmium (Cd) partagent leurs propriétés physico-chimiques et leurs mécanismes de transport cellulaire. Le Zn régule des fonctions du système immunitaire, contrairement au Cd avec des propriétés sur le système immunitaire peu décrites dans la littérature.Notre travail vise à identifier les mécanismes impliqués dans la modification de l‘homéostasie des métaux dans les synoviocytes par l‘inflammation et les conséquences de cette altération.L‘inflammation induit l‘accumulation des métaux dans les synoviocytes en augmentant l‘expression de l‘importeur ZIP-8. En revanche, l‘expression de l‘exporteur ZnT1 et des metallothionéines (MTs, régulateurs de l‘homéostasie des métaux) est dépendante de la présence des métaux. L‘affinité Cd-MTs permet une accumulation irréversible du Cd dans les cellules qui réduit leur prolifération et la production d‘IL-6.Les effets antiprolifératif et anti-inflammatoire du Cd ont été testés dans le modèle d‘arthrite chez le rat où une seule injection intra-articulaire de Cd à faible dose prévient la perte osseuse et réduit les scores cliniques d‘arthrite. Cela pourrait représenter une nouvelle approche thérapeutique pour le traitement de la PR et d'autres pathologies caractérisées par une hyperplasie et une inflammation localisées / Rheumatoid arthritis (RA) is a chronic inflammatory disease. Synoviocytes, cells forming the inner layer the synovium, become refractory to apoptosis and participate in the chronicity of inflammation through the production of IL-6. The perpetuation of inflammation causes an important induction of bone loss in joints.Zinc (Zn) and Cadmium (Cd) share many physico-chemical properties and cell transport mechanism. Zn is known as a regulator of the normal function of the immune system, while Cd properties on the immune system are not well defined.Our aim was to provide information on the metal homeostasis mechanisms in synoviocytes during chronic inflammation and on the consequences of metal homeostasis changes. After studying the differential effect of Zn and Cd at the cellular level, we could provide an innovative tool to control synoviocyte contribution to rheumatoid arthritis, which was tested on an in vivo model of arthritis.Results show that IL-17/TNF-a combination drives the accumulation of metals inside synoviocytes through the enhancing of ZIP-8 importer expression and regardless of the concentration of metals in the culture medium. In contrast, the expression of the metal exporter ZnT1 and of the homeostasis regulators metallothioneins (MTs) was primarily dependent on metal levels.Addition of Zn stimulated the inflammatory response, while addition of Cd can reduce both viability and inflammation.The anti-proliferative and anti-inflammatory properties of Cd were used in the rat model of arthritis as intra-articular treatment to reduce local inflammation and joint destruction and it may represent a new local therapeutic approach for RA treatment

Inflammatory arthritis (IA) types such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) and psoriatic arthritis (PsA) have been shown to exhibit common clinical features. As complex diseases they have a known genetic component, some of which is known to be shared. The aim of this study was to assess the genetic overlap between 3 types of IA (RA, JIA and PsA) using genotype data generated on the Immunochip array and to select a biologically promising overlapping region for further genetic and functional investigation. Overlap analysis was performed using association data generated for a large cohort of inflammatory arthritis cases and shared controls (11,475 RA; 2816 JIA; 929 PsA respectively). 50 genetic regions were identified as being associated with more than 1 type of IA (p < 1x10-3), with several interesting similarities and differences observed between the diseases. As several of the overlapping regions detected represented novel disease associations, they required replication in an independent sample cohort. 12 variants were selected for replication in an independent RA cohort of 3879 cases and 2561 controls. Of these, 2 variants in the CTLA4 and MTMR3 regions were successfully replicated in RA at p<0.05. Bioinformatics analysis was performed for the 50 overlapping regions, with one particularly promising region, RUNX1, selected for further investigation. In this region, the same variant (rs9979383) is associated across the 3 diseases, with similar odds ratios (OR 0.8-0.9) observed in each disease. As this region represented both a novel IA association and had not been densely genotyped on the Immunochip array, fine mapping was performed by genotyping 51 SNPS in 3491 cases and 2359 controls. This resulted in replication of the association at rs9979383 (p=0.02) with no additional significant genetic effects detected, therefore this variant was selected for further functional analysis. As rs9979383 lies ~280kb upstream of the RUNX1 gene, a cis-eQTL analysis was performed to identify if the variant acts by regulation of RUNX1 gene expression. This was performed in whole blood, CD4+ and CD8+ lymphocytes from 75 (and a subset of 23) healthy volunteers respectively. No significant eQTLs were detected between rs9979383 and RUNX1 in whole blood (p =0.9) or RUNX1/LOC100506403 CD4+ and CD8+ lymphocytes (p=0.1). This study has provided insight into the genetic similarities and differences between different types of inflammatory arthritis, which can be applied to further investigations into disease susceptibility. Although no significant cis-eQTL was detected in any of these tissues with either RUNX1 or the nearby lnc-RNA LOC100506403, in cells from healthy volunteers under unstimulated conditions, these findings will direct future functional investigations into the role of this overlapping region in the susceptibility of IA.

Introduction: Rheumatoid arthritis (RA) is a chronic disease and one of the more common auto-immune diseases. Patients with RA rely almost solely on pharmaceutical intervention to manage the disease. Autonomic impairment has been proven in previous studies on patients with RA. The positive effect of exercise on autonomic impairment has also previously been demonstrated, but not in the RA population. The purpose of this study was firstly to confirm autonomic impairment in a South African based female population with RA and secondly to evaluate the effect of exercise on the autonomic cardiac function (as measured by short-term heart rate variability), disease activity and functional capacity. Methods: The study was conducted at the University of Pretoria during 2009 and 2010. In the first phase of the study female RA patients were recruited from all rheumatology practices in Pretoria and healthy controls were recruited from family and friends of the research team and of the RA group. Cardiac autonomic function was compared between the two groups by means of short-term heart rate variability. Three techniques were used: time domain, frequency domain and Poincare plot analysis. In the second phase of the study, females with confirmed RA were randomly assigned to an exercise group and a control group. The exercise group was requested to train under supervision two to three times per week for a period of twelve weeks, while the control group continued with their sedentary lifestyle. At study completion the two groups were compared for the effect of exercise intervention on the following three aspects: <ul><li> Autonomic function (as measured by heart rate variability) </li><li> Disease activity (as measured by Disease Activity Score, Visual Analogue Scale and Health Activity Questionnaire) </li><li> Functional capacity (as measured by strength, flexibility and aerobic capacity) </li></ul> Results: In the first phase of the study comparing females with RA (n=45) to healthy females (n=39), the basal heart rate was significantly higher in the RA group. In the supine position significant differences existed between the RA group and the control group (p ≤ 0.01). Indicators of parasympathetic activity showed significantly lower variation in the RA group [RMSSD=14.70, pNN50=0.50, SD1=10.50, HF(ms2)=31] compared to the control group [RMSSD=29.40, pNN50=7.8, SD1=20.9, HF(ms2)=141.00]. Indicators of sympathetic variation were also significantly lower in the RA Group [SD2=36.70, LF(ms2)=65) compared to the Control group (SD2=49.50, LF(ms2)=175]. In the standing position 8 variables indicated autonomic impairment by significant differences (p≤0.01) between the 2 groups. The response of the RA Group to an orthostatic stressor showed less vagal withdrawal, [p-values for RMSSD=0.038, pNN50=0.022, SD1=0.043 and HF(ms2)=0.008 respectively]; and lower sympathetic response [p-values for SD2=0.001 and LF(ms2)<0.001] when compared to the Control group. In the second phase of the study, comparing an RA exercise group to a RA sedentary group, three aspects were evaluated: 1. Heart rate variability At baseline the control group (n=18) had significantly higher variability compared to the exercise group (n=19) for most heart rate variability (HRV) indicators. At study completion the variables showing significant changes (p=0.01 to 0.05) favoured the exercise group in all instances. Wilcoxon signed rank tests were performed to assess changes within groups from start to end. The exercise group showed significant improvement for most of the standing variables, including measurements of combined autonomic influence e.g. SDRR (p=0.002) and variables indicating only vagal influence e.g. pNN50 (p=0.014). The control group mostly deteriorated with emphasis on variables measuring vagal influence [RMSSD, pNN50, SD1 and HF(ms2)]. 2. Disease activity At baseline the two groups were comparable. At the end of the intervention, the exercise group had significant improvement for the tender joint count (p=0.015), swollen joint count (p=<0.001), physician global assessment (p=0.003) and DAS score (p=0.003) compared to the control group. To assess changes that happened within each group from start to end, Wilcoxon signed rank tests were performed. The exercise group improved significantly with regards to tender joint count (p=0.002), swollen joint count (p=0.001), physician global assessment (p=0.001), DAS score (0.001) and the visual analogue scale (p=0.032). The sedentary group improved significantly only in the health assessment questionnaire (p=0.032). 3. Functional capacity Comparing the groups at baseline the exercise group had better knee- and hip flexion on the left hand side but it took them longer to complete the arm curl test. At study completion the exercise group was mostly favoured with regards to flexibility (significant p-values ranging between 0.001 – 0.049), strength (handgrip right p<0.001, leg strength p=0.035, arm curl test p=0.010, sit to stand test p=0.025) and aerobic fitness (1 mile walk test p<0.001 and VO2 max p=0.007). Changes within each group were assessed by Wilcoxon signed rank tests. The exercise groups showed significant changes for many parameters in the three categories, i.e. flexibility (8 of 18), strength (5 of 5), and aerobic fitness (4 of 8). The control group mostly deteriorated in flexibility, while their strength also improved, but not to the same extent as for the exercise group. Their aerobic fitness did not change. Discussion: In the first phase of this study, using standardised methods to measure short-term HRV, females with RA showed less variability compared to a healthy age- and sex matched control group. An inability of the autonomic nervous system to efficiently compensate to internal and external environmental changes may predispose RA patients to arrhythmias thereby increasing cardiovascular mortality. All 3 methods used showed the same outcome, implying decreased HRV and thus an increased risk for arrhythmias in RA patients. Evaluating the autonomic nervous system might be critical in planning management of RA. In the second phase study results indicated that twelve weeks of exercise intervention, had a positive effect on cardiac autonomic function as measured by short-term HRV, in females with RA. Several of the standing variables indicated improved vagal influence on the heart rate. Exercise can thus potentially be used as an instrument to improve cardiac health in a patient group known for increased cardiac morbidity. The exercise programme was also effective in decreasing perception of pain as well as disease activity in female RA patients. Given our findings it seems warranted to include physical exercise as part of the treatment prescription of patients with class I and II RA. Lastly this research has shown that regular, controlled exercise for RA patients with controlled disease can decrease joint stiffness and improve joint mobility, strength and aerobic capacity without exacerbating pain or disease activity. Also, if one observes the decline in the sedentary group for many parameters, it is important to note that this happened over a relative short time period and that even a small change may have a detrimental impact on the RA patient. The current report supports previous literature on autonomic impairment in patients suffering from RA as well as the meaningful positive effect of exercise on disease activity and functional capacity. It is the only study on the effect of an exercise intervention on the cardiac autonomic function of RA patients. Future research in this field should aim for larger study samples, longer intervention periods and perhaps add analysis of blood pressure variability to support results obtained by HRV analysis. / Thesis (MD)--University of Pretoria, 2012. / Internal Medicine / unrestricted