Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
16331758 The relationship between social deprivation, disease outcome measures, and response to tre 2005 Dec OBJECTIVE: Patients with rheumatoid arthritis (RA) with lower socioeconomic status (SES) are known to have more severe disease, more comorbidity, and higher mortality. It is not known whether SES influences response to treatment in RA. We examined the relationship between area of residence (as a surrogate for SES) and baseline outcome measures and response to treatment, using data from the British Rheumatoid Outcome Study Group randomized controlled trial of aggressive versus symptomatic treatment of long-standing, stable RA. METHODS: A total of 466 patients from 5 centers were recruited to the trial. Baseline data included age, sex, smoking status, and comorbidity. Patients were assigned a Townsend score (a measure of social deprivation) according to their area of residence. Outcome measures including the Disease Activity Score (DAS28), Health Assessment Questionnaire, Medical Outcomes Study Short Form-36, and EuroQol (EQ5D) were recorded at the beginning and end of the 3 year trial. The baseline, 3 year values, and change data were examined by Townsend quintile adjusting for each treatment arm. RESULTS: Significant relationships between increasing social deprivation by area of residence and higher disease activity, higher pain, poorer physical function, poorer emotional aspects of mental health, and lower quality of life were found at baseline (adjusted for age, sex, disease duration, current smoking, treatment center, and treatment group). During the 3 year trial period, patients from the most deprived areas showed greater improvement, with statistically significant greater improvement on DAS28 (p = 0.041) and 28 tender joint count (p = 0.015). CONCLUSION: Area of residence is related to the severity of RA at recruitment and is a predictor of response in a clinical trial situation. The results suggest that measures of SES should be recorded for patients enrolled in clinical trials, longitudinal observational studies, and in the clinical setting.
16837491 Increased risk of tuberculosis in patients with rheumatoid arthritis in Japan. 2006 Dec OBJECTIVE: To determine the risk for tuberculosis infection in patients with rheumatoid arthritis before the anti-cytokine era in Japan. PATIENTS AND METHODS: A database of a single-institute-based large observational cohort study for rheumatoid arthritis at the Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan, was analysed. Information on the history of tuberculosis infection was collected by patient self-reporting during April and October 2003. The age-adjusted incidence rate and relative risk for tuberculosis infection were investigated. RESULTS: Among 5044 patients with rheumatoid arthritis, 483 (9.6%) patients claimed to have a history of tuberculosis infection before October 2002. The frequency of history of tuberculosis increased according to the age of the patient. Four cases of new-onset tuberculosis were identified among 5544 patients with rheumatoid arthritis during 1 year. The age-adjusted incidence of tuberculosis was 42.4/100,000 patients. The relative risk for tuberculosis was 3.21 (95% confidence interval (CI) 1.21 to 8.55), and that of men and women was 10.59 (95% CI 3.42 to 32.78) and 1.41 (95% CI 0.2 to 10), respectively. CONCLUSION: There was an increased risk of tuberculosis infection in Japanese patients with rheumatoid arthritis, especially in male patients before the introduction of anti-tumour necrosis factor treatment. These data should form the basis for the risk management of anti-cytokine treatment in Japan.
15975970 Standardisation of synovial tissue infiltrate analysis: how far have we come? How much fur 2006 Jan Changes in cellular infiltrate and expression of cytokines, chemokines, and cell adhesion molecules as a result of therapeutic interventions in rheumatoid arthritis can be demonstrated in the synovial membrane. However, before synovial tissue analysis can be used as an outcome measure in such studies, standardisation of the site and method of synovial tissue acquisition, methods of tissue processing, and appropriate methods of detection and measurement of cell lineage specific markers and relevant biological proteins is needed.
16369381 Serum antibodies to oral anaerobic bacteria in patients with rheumatoid arthritis. 2005 Jun 16 BACKGROUND: This study was conducted to determine the component that causes the disease in rheumatoid arthritis (RA), which shows great resemblance to periodontitis in a pathologic context. MATERIALS AND METHODS: Within this study, the pathogen-specific IgG levels formed against Porphyromonas gingivalis FDC 381, Prevotella melaninogenica ATCC 25845, Actinobacillus actinomycetemcomitans Y4, Bacteroides forsythus ATCC 43047, and Prevotella intermedia 25611 oral bacteria were researched from the blood serum samples of 30 RA patients and 20 healthy controls with the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The IgG levels of P gingivalis, P intermedia, P melaninogenica, and B forsythus were found to be significantly higher in RA patients when compared with those of the controls. Of the other bacteria antibodies, A actinomycetemcomitans was not found at greater levels in RA serum samples in comparison with the healthy samples. CONCLUSION: The antibodies formed against P gingivalis, P intermedia, P melaninogenica, and B forsythus could be important to the etiopathogenesis of RA.
16097634 Imaging of lesions in a murine rheumatoid arthritis model with a humanized anti-interleuki 2005 Jun Rheumatoid arthritis (RA) has been attributed to the abnormal production of cytokine interleukin-6 (IL-6), which has a variety of physiological activities. In vivo IL-6-receptor imaging provides useful suggestions regarding the mechanism of anti-IL-6-receptor antibody action and indicates a basic therapeutic strategy for treating RA. Therefore, this study was designed to establish a method for radiolabeling anti-IL-6-receptor antibodies and to investigate the feasibility of using radiolabeled anti-IL-6-receptor antibodies in the scintigraphic imaging of lesions in an animal RA model. Anti-IL-6-receptor antibodies were conjugated with a bifunctional chelating agent, hydrazinonicotinamide (HYNIC), and radiolabeled with technetium-99m (99mTc) using the ligand exchange reaction of 99mTc-tricine complex. The binding affinity was estimated using the U266 cell line. Whole body scintigraphy, biodistribution and autoradiography were undertaken in mice containing synovial cells that had been transplanted from an RA patient. Our findings showed that the antibodies accumulated in the implanted tissue. When radiolabeled anti-IL-6-receptor antibodies are used in scintigraphic imaging, the distribution of the IL-6-receptors is associated with the inflammatory cell infiltration that is seen in the early stage of RA. Accordingly, imaging with humanized anti-IL-6-receptor antibodies appears to be useful for detecting early pathophysiological conditions and assessing the efficacy of antibody treatment as well as the prognosis of patients with RA.
16514820 [Systemic manifestations of rheumatoid arthritis, echostructural changes in brachiocephali 2005 AIM: To define echostructural and hemodynamic features of vascular lesions in rheumatoid arthritis (RA) with systemic manifestations. MATERIAL AND METHODS: Of 125 patients included in the study 70 had RA. They were compared to 40 patients with deforming osteoarthritis (DOA) and 15 patients with atherosclerosis of major cerebral arteries. Extra-articular systemic manifestations were diagnosed in 18 RA (25.7%) patients. Carotid, vertebral arteries and cerebral circulation were studied with ultrasonic duplex scanning on the unit "Vingmed system 5, Norway, 2002". RESULTS: The study group exhibited a significant reduction of linear perfusion velocity (LPV) with increased vascular resistance indexes in the carotids and vertebral arteries on the right and left. It was more evident in RA patients with systemic manifestations. Scanning carotids in RA with SM patients and RA patients without extra-articular manifestations showed differences suggesting that thickness of intima-media complex was larger when systemic manifestations were present. CONCLUSION: The revealed changes in circulation may indicate the systemic process.
17343253 Ultrasonography and magnetic resonance imaging of heel fat pad inflammatory-oedematous les 2006 Nov OBJECTIVE: To study heel fat pad (HFP) inflammatory-oedematous lesions in selected patients with rheumatoid arthritis (RA) using ultrasonography (US) and power Doppler US (PDUS), to describe and compare US features of these lesions with those obtained with magnetic resonance imaging (MRI), and to describe changes in the lesions after a short-term follow-up with conventional or anti-tumour necrosis factor-alpha (TNFalpha) therapy. METHODS: Twelve heels of eight RA outpatients with HFP inflammatory-oedematous lesions were studied by US, PDUS, and unenhanced MRI. All the patients were followed up and US was performed after 3 months. Five patients started on anti-TNFalpha therapy. RESULTS: HFP lesions appeared at US as a heterogeneous and hypoechoic subcalcaneal mass, with loss of normal lobular structure and increased thickness of HFP, because of focal rupture of fibrous septae with oedema and fluid. PDUS showed peripheral vascularization of HFP lesions in 9/12 heels. In 3/12 heels some vascular signals was also detectable inside the lesion, always along the residual echoic septa. No detectable flow was observed within the central fluid-filled spaces. MRI of the HFP lesions showed areas of mean intensity in T1-weighted sequences and high intensity in T2-weighted sequences, with poorly or well-defined margins. After 3 months, PDUS showed reduction in HFP lesion vascularity (associated with reduction in pain) in 10/12 heels, while poor regression of grey-scale US abnormalities was observed. CONCLUSIONS: Both US and MRI are capable of demonstrating structural abnormalities in the HFP. PDUS is useful to assess and monitor inflammatory vascularization of the HFP lesions.
15868614 Validation of the Functional Assessment of Chronic Illness Therapy Fatigue Scale relative 2005 May OBJECTIVE: This study validated a brief measure of fatigue in rheumatoid arthritis (RA), the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale. METHODS: The FACIT Fatigue was tested along with measures previously validated in RA: the Multidimensional Assessment of Fatigue (MAF) and Medical Outcomes Study Short-Form 36 (SF-36) Vitality. The sample included 636 patients with RA enrolled in a 24 week double blind, randomized clinical trial (RCT) of adalimumab versus placebo. RESULTS: The FACIT Fatigue showed good internal consistency (alpha = 0.86 to 0.87), strong association with SF-36 Vitality (r = 0.73 to 0.84) and MAF (r = -0.84 to -0.88), and the ability to differentiate patients according to clinical change using the American College of Rheumatology (ACR) response criteria (ACR 20/50/70). Psychometric performance of the FACIT Fatigue scale was comparable to that of the other 2 fatigue measures. A minimally important difference in FACIT Fatigue change score of 3-4 points was confirmed in a separate sample of 271 patients with RA enrolled in a second double blind RCT of adalimumab versus placebo. CONCLUSION: The FACIT Fatigue is a brief, valid measure for monitoring this important symptom and its effects on patients with RA.
15807842 New therapies for rheumatoid arthritis. 2005 May Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease, which continues to cause significant morbidity in affected persons. In the past few years, a number of new exciting therapeutic options have become available. These reflect the application of knowledge obtained from advancements in understanding of disease pathogenesis and underlying molecular mechanisms. A number of these therapies are outlined in the following review, including the various biological modifiers, in particular, anti-tumour necrosis factor-alpha agents and interleukin-1 (IL-1) receptor antagonists, which have been developed in recognition of the role of pro-inflammatory cytokines in RA. Also notable, is the current interest centring on the development and trials with B cell depletion therapies, specifically rituximab, in patients with RA. This demonstrates acknowledgment for a more significant role for B cells in the aetiology of RA, in contrast to the long held view that RA was a predominantly T cell mediated disease. To evaluate this therapeutic option for RA, salient features from recent rituximab trials have been collated. Finally, a selection of other therapeutic alternatives, including anti-IL-6 receptor monoclonal antibody and tacrolimus, and newer anti-rheumatic therapies presently in development are summarized.
15743776 Plasminogen activation/plasmin in rheumatoid arthritis: matrix degradation and more. 2005 Mar Rheumatoid arthritis (RA) is one of the most common and most debilitating joint diseases, producing high personal, social, and economic costs.(1,2) Patients with RA suffer pain and functional losses, often followed by disability and premature death. Although the etiology of RA is unknown, substantial efforts have been directed toward studying the transition of the joint from normal to diseased. The maintenance of normal joint architecture and function requires equilibrium between the synthesis and degradation of the specialized extracellular matrices that make up bone, cartilage, and tendons. In RA, the balance of tissue remodeling is disturbed,(3) and excessive proteolytic degradation of the joint matrices leads to joint destruction.(4,5) The early phase of RA is characterized by the infiltration of immune and inflammatory cells into the synovium and by hyperplasia of the fibroblasts in the synovial lining. This leads to pannus formation, cartilage breakdown, and eventual bone destruction.(1,2) Through the use of an experimental mouse model of RA, Li and colleagues(6) have implicated plasmin as an essential component of the early phase of RA, as reported in this issue of The American Journal of Pathology.
15338447 Relationship between high-resolution computed tomography findings and the Stoke index in p 2005 Feb The aim of this study was to evaluate the relationship between high-resolution computed tomography (HRCT) findings and the Stoke index (SI) in patients with rheumatoid arthritis (RA). Forty RA patients (31 women, 9 men) were evaluated. All patients fulfilled the criteria proposed by the American College of Rheumatology. Clinical evaluation, haematological data, chest radiography, pulmonary function tests (PFTs) and HRCT were obtained in all patients. The SI was used to assess disease activity. In 17 (42.5%) patients, there were no signs of pulmonary involvement on HRCT; 23 (57.5%) of 40 patients had abnormal HRCT findings. Of 23 patients with HRCT abnormalities, six (two male, four female) had respiratory symptoms, four (one male, three female) had abnormalities on chest radiography and five (all female) had abnormalities on PFTs. There was no relationship between pulmonary changes observed on HRCT, clinical and laboratory disease activity parameters, chest X-ray and PFTs. There was no difference in the mean SI between patients included in the HRCT (+) and those included in the HRCT (-) groups. No significant correlations between the HRCT and the SI were seen. The main findings of this study are that HRCT can give useful information on RA-associated lung changes and that there was no relationship between the SI and the HRCT findings of patients with RA.
16544925 [Armentarium and strategies for the treatment of rheumatoid arthritis]. 2005 Dec 15 Rheumatoid arthritis is characterized by chronic synovitis resulting in bone and joint destruction in various delays, and ultimately leading to handicap. Remission can be induced at the beginning of the disease. It is well established that slow-acting remitting drugs can efficiently halt radiological progression and improve functional outcome. Besides symptomatic agents (NSAID, steroids, joint injections and synoviorthesis), several long-acting treatment strategies have been proposed based upon methotrexate, alone or in combination with sulfasalazine, hydroxychloroquine, and also anti-TNF agents. Several strategies have been compared according to the disease profile, and suggested that both combination and mainly tight control of the disease clearly improve the clinical, radiological and functional outcomes. The indication of anti-TNF agents is still discussed case by case with respect to treatment failure and risk-benefit ratio at mid and long term. General practitioners should contribute to an early management and regular follow-up by rheumatologists and to general managements of comorbidities.
17159837 [Periodontal tissues state in patients with systemic osteoporosis]. 2006 The results of the study of periodontal tissues in patients with systemic osteoporosis in rheumatoid arthritis are presented. The reduction of bone density in the region of interalveolar septa, insignificant bone tissue loss of the horizontal type and pathological teeth mobility were reported.
17036499 [Clinical image of oral mucous membrane in rheumatoid arthritis patients]. 2006 The aim of the study was to evaluate the character and frequency of pathological changes in the oral cavity mucous membrane and xerostomy in patients with prolonged hospital and ambulatory treatment due to rheumatoid arthritis (RA). EXAMINATION MATERIAL: The study was conducted in 120 patients with RA, average age 54, and in the control group of 40 generally healthy examinees, average age 53. RESULTS: In patients with RA pathological changes in the oral cavity appeared much more frequently: erosions, fissures, perleche, candidiasis oris, lichen Wilsoni, leukoplakia and persistent xerostomy. RA patients more often used partial prosthesis and more frequently were edentulous. CONCLUSIONS: The treatment of oral cavity diseases and prophylaxis should be provided together with the RA treatment, with special emphasis put on the elimination of xerostomy. Good cooperation of rheumatologists and periodontologists is recommended RA diagnosis.
16305765 [Early referral and treatment of patients with acute arthritis. Experiences from two early 2005 Nov 21 INTRODUCTION: Our aim was to describe the referral pattern among patients admitted to early arthritis clinics (EAC) in the counties of Funen and South Jutland, Denmark. MATERIALS AND METHODS: In order to accelerate the diagnostic workup of patients with suspected rheumatoid arthritis (RA), general practitioners, rheumatology specialists and neighbouring hospital departments were invited to refer to the EAC patients who had synovitis in at least one joint lasting more than 6 weeks but less than 12 months. RESULTS: 226 patients were admitted. The median total lag time from onset of joint complaints to visiting the EAC was 89 days (IQ 57-154). The average lag time between receipt of the referral to the first visit to the EAC was 18 days (IQ 5-31). 91 (40%) of the patients had synovitis upon clinical examination. 51 (23%) of these fulfilled the ACR 1987 classification criteria for RA, and 40 (17%) had synovitis of other aetiologies than RA. Compared with non-RA patients, the RA subset was characterised by older age, female preponderance, higher joint counts and disability and a more pronounced acute phase response. Despite the short duration of the disease, 17% of the RA patients had X-ray erosions. DISCUSSION: In spite of the rigid criteria for referral to the EAC, synovitis was demonstrated by clinical examination in only 40% of the patients. Half of these were classified as RA. The total median lag time of three months from the onset of joint symptoms to the first visit to the EAC accords with current recommendations. Standardised criteria for referral to EACs should be prepared and combined with educational efforts to improve joint assessment skills.
16873089 Immunomodulatory effects of lingzhi and san-miao-san supplementation on patients with rheu 2006 Rheumatoid arthritis (RA) is an autoimmune joint disease. We evaluated a standard preparation of Lingzhi (Ganoderma lucidum) and San-Miao-San (Rhizoma atractylodis, Cortex phellodendri, Radix achyranthes bidentatae) capsules (TCM group) for its supplementary treatment efficacy for RA. There was no significant difference in the absolute count, percentage, and ratios of CD4(+)/CD8(+)/natural killer/B lymphocytes between the TCM and placebo groups after taking the capsules (all p > 0.05). There was no significant change in concentrations of plasma cytokines of interferon-gamma-induced protein-10 (IP-10), monocyte chemoattractant protein-1, monokine induced by IFN-gamma, regulated upon activation normal T-cell expressed and secreted, interleukin (IL)-8, and IL-18 after taking the capsules for 8 and 24 weeks (all p > 0.05). The percentage change in ex vivo-induced level of inflammatory cytokine IL-18 was significantly lower in the TCM group than in the placebo group after taking the capsules for 24 weeks (p < 0.05). Therefore, Lingzhi and San-Miao-San capsules might exert a beneficial immunomodulatory effect in patients with rheumatoid arthritis.
17134042 Atlantoaxial instability secondary to rheumatoid arthritis. 2006 Nov Multiple elements contribute to the stability of the anterior C1-C2 articulation, making this region subject to pathologies including trauma, inflammation, infection, and congenital deformities. C1-C2 instability places a patient at risk for significant neurologic compromise. Radiologic imaging plays a fundamental role in diagnosing atlantoaxial instability, indicating etiology, showing details of associated abnormalities, and providing information for planning treatment.
16751154 Anakinra (interleukin-1 receptor antagonist) has positive effects on function and quality 2006 Mar Rheumatoid arthritis (RA) has severe and lasting effects on quality of life. This review (1) describes the disease progression, disability, and joint destruction that seriously alter a patient's quality of life, and (2) explains how the interleukin-1 receptor antagonist (IL-1Ra), anakinra, retards the progress of disease, thereby improving outcomes. Relevant articles were reviewed with a focus on RA, anakinra, and functional and quality-of-life outcomes. In randomized, controlled trials, the IL-1Ra anakinra provided meaningful benefits for patients with active RA, such as decreased signs and symptoms of disease, slower radiographic disease progression, reduced disability, and improved health-related quality of life. The biologic agent, anakinra, provides to patients with RA a valuable treatment option that has a positive impact on both function and quality of life.
16321818 B cell reductive therapy in the treatment of autoimmune diseases: a focus on monoclonal an 2005 Dec The therapeutic approach to patients with autoimmune disorders is in the midst of a dramatic change. Monoclonal antibody technology has allowed us to dissect and now manipulate the human immune system with greater precision. It is now widely recognized that B lymphocytes play a role in the pathogenesis of many autoimmune diseases, though the extent and contribution is a matter of debate and active investigation. There is emerging data to suggest that both antibody-dependent and independent mechanisms contribute to disease pathogenesis. However, given the heterogeneous nature of autoimmune diseases, and the varied responses to B lymphocyte reduction, the role of B lymphocytes is likely disease-specific. The two clinical trials discussed in this review demonstrate remarkable consistency in the ability of B cell reduction to ameliorate the clinical manifestations of rheumatoid arthritis with minimal toxicity. B lymphocyte targeted approaches to autoimmune disease in general, and RA specifically, will not only provide an effective and potentially less toxic alternative treatment option, but also allow for a better understanding of the pathogenesis of these complex and morbid diseases.
16164395 Protective effects of angiotensin II interruption: evidence for antiinflammatory actions. 2005 Sep Angiotensin II, the major effector molecule produced from the renin-angiotensin-aldosterone axis, is a vasoconstrictor contributing to hypertension. Evidence indicates, however, that angiotensin II also is a potent proinflammatory mediator with growth and remodeling effects. In vitro and in vivo studies have shown that angiotensin II blockade significantly reduces concentrations of proinflammatory mediators and oxidative stress products in numerous inflammatory models. Interruption of angiotensin II activity with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers has been beneficial for patients with inflammatory diseases. Much of this benefit occurs independent of the antihypertensive effect of angiotensin II interruption, suggesting a distinctive protective mechanism. Angiotensin II receptor blockers may represent a novel class of antiinflammatory drugs with indications far beyond cardiovascular diseases.