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

ID PMID Title PublicationDate abstract
16570809 [Study on mechanism underlying the treatment of rheumatoid arthritis by Keshiling]. 2006 Jan OBJECTIVE: To explore the mechanism underlying the treatment of rheumatoid arthritis by Keshiling (KSL) in the rats model of FCA-induced arthritis. METHOD: The experimental arthritis was induced by FCA in the rats. The content of PGE2 in the inflammatory swelling toes was evaluated by ultraviolet spectrophotometric method. The ConA and LPS-induced lymphocytes proliferation and the production of interleukin-2 (IL-2) secreted by thymus were determined by MTT assay. RESULT: Results showed that the increases of lymphocyte proliferation and IL-2 production in AIA rats could be inhibited by KSL at the concentrations of 540 and 270 mg x kg(-1) in vivo and vitro. KSL at the same doses decreased the contents of PGE2 in inflammatory swelling toes, and the decreased A values were 25.6,16.1, 10.0 (A x 10(3)), respectively. After administration of KSL in vivo at 540 and 270 mg x kg(-1) the T lymphocyte proliferation were attenuated by 32.1% and 31.0%, and the production of IL-2 was inhibited by 17.5% and 14.0% respectively. While the inhibitory rates of T lymphocyte proliferation were reduced by 39.0% and 22.1% and the production of IL-2 was diminished by 27.3% and 18.2% respectively following the administration of KSL in vitro. CONCLUSION: KSL possesses the anti-inflammation function.
18519098 Rehabilitation in musculoskeletal diseases. 2008 Jun Occupational therapy and vocational rehabilitation are increasingly available for people with musculoskeletal diseases. Occupational therapy aims to improve or maintain function in work, leisure, self-care and domestic activities, social roles, and psychological status. A wide range of interventions is provided, including joint protection, assistive devices and splints. Vocational rehabilitation aims to improve ability to stay in or return to work. Comprehensive occupational therapy and some interventions (joint protection, assistive devices and splints), as well as vocational rehabilitation, are reviewed. There is moderate to good evidence for effectiveness of comprehensive occupational therapy in rheumatoid arthritis, and for joint protection and splints in rheumatoid arthritis and osteoarthritis. However, evidence for other aspects of occupational therapy is still scarce, and better-quality trials are needed. Vocational rehabilitation to prevent job losses in rheumatic diseases is effective, but once people are unemployed, return-to-work interventions are less successful. Evidence is moderate to good for work conditioning programmes using a cognitive behavioural approach in chronic low-back pain, and also for early return-to-work interventions in subacute low-back pain.
18466515 Genome-wide linkage and association analysis of rheumatoid arthritis in a Canadian populat 2007 Rheumatoid arthritis (RA) is an autoimmune disease with a moderately strong genetic component. Previous linkage and candidate gene studies have identified several regions that predispose to RA, including the HLA-DRB1 and PTPN22. We conducted genome-wide linkage analysis with 128 affected individuals from 60 families in a Canadian cohort that were genotyped using the Illumina linkage panel and genome-wide association analysis with 158 affected individuals from the same cohort that were genotyped using the Affymetrix 100 K platform. Multipoint nonparametric linkage scan revealed three linkage peaks with LOD scores greater than 1.5. We also identified 13 significantly associated SNPs at the genome-wide level of 0.05 after Bonferroni adjustment for multiple testing. Several of the significantly associated SNPs are located close to previously identified linkage regions, but not in the linkage peaks identified in the same cohort. We could not replicate association with HLA-DRB1 and PTPN22. Our results indicate that high coverage and sufficient sample size are crucial for the success of genome-wide association studies.
18349745 Quality of care in the rheumatic diseases: current status and future directions. 2008 Mar PURPOSE OF REVIEW: To review the recent literature examining quality of care for several prevalent rheumatic conditions, including rheumatoid arthritis, osteoarthritis, gout and osteoporosis, and to summarize quality measurement and improvement initiatives relevant to rheumatology in the USA. RECENT FINDINGS: In recent years, research has identified a significant gap between ideal and actual clinical practice in the USA. Consistent with trends seen in the US healthcare system as a whole, research suggests deficits in healthcare quality for populations with rheumatic conditions. We review the growing literature on quality of care for rheumatoid arthritis, osteoarthritis, gout and glucocorticoid-induced osteoporosis. SUMMARY: Existing evidence suggests suboptimal healthcare quality for four common rheumatic conditions, a finding that parallels trends in the healthcare system as a whole.
18689973 [A case of nail candidiasis with severe deformities treated with oral fluconazole]. 2008 We report a case of nail candidiasis with severe deformities. The patient was a 71-year-old woman who initially consulted our department on April 5, 2006. She had diabetes, chronic rheumatoid arthritis and multiple liver metastasis of unknown origin. She had taken prednisolone for treatment of chronic rheumatoid arthritis for a long period. The initial examination demonstrated deformation of 1/3 of the inner part of the nail plate in both the third and fourth fingers, with apparent hyperkeratosis under the deformed nail plates. KOH-prepared direct microscopy revealed the presence of numerous spores and pseudohyphae. Numerous fungal elements were detected by Grocott staining and PAS staining. Candida albicans was isolated and identified by cultivation on the ATG agar and PCR-RFLP. Fluconazole (100 mg/day) was administered from April 8, 2006. After 14 weeks of treatment her clinical findings had improved, however she died of multiple organ failure on July 25, 2006.
18466513 Evaluating gene x gene and gene x smoking interaction in rheumatoid arthritis using candid 2007 We examined the potential gene x gene interactions and gene x smoking interactions in rheumatoid arthritis (RA) using the candidate gene data sets provided by Genetic Analysis Workshop 15 Problem 2. The multifactor dimensionality reduction (MDR) method was used to test gene x gene interactions among candidate genes. The case-only sample was used to test gene x smoking interactions. The best predictive model was the single-locus model with single-nucleotide polymorphism (SNP) rs2476601 in gene PTPN22. However, no clear gene x gene interaction was identified. Substantial departure from multiplicativity was observed between smoking and SNPs in genes CTLA4, PADI4, MIF, and SNPs on chromosome 5 and one haplotype of PTPN22. The strongest evidence of association was identified between the PTPN22 gene and RA status, which was consistently detected in single SNP association, gene x gene interaction and gene x smoking interaction analyses.
18431370 Are modified-release corticosteroids good therapeutic options for patients with RA? 2008 Jun Glucocorticoids have good efficacy as anti-inflammatory agents but are associated with adverse effects. Buttgereit et al. have compared the efficacy of modified-release prednisone with that of standard, immediate-release prednisone for the treatment of rheumatoid arthritis. The modified-release tablets are designed to liberate the glucocorticoid approximately 4 h after ingestion, and can be taken at bedtime so that the prednisone release coincides with peaks in endogenous cortisol levels and symptoms of disease in the early hours of the morning. The authors of this study hypothesized that the modified release would improve the benefit-risk ratio of this glucocorticoid. The 12-week, multicenter, double-blind, randomized controlled trial included 251 patients who completed the study. In patients with active rheumatoid arthritis, prescription of the modified-release tablet for night-time ingestion resulted in a mean 29.2 min shorter duration of morning stiffness than in patients who received standard immediate-release prednisone tablets in the morning, and a total 44.0 min reduction in morning-stiffness duration at 12 weeks compared with baseline. The safety profiles of the modified-release and immediate-release forms of prednisone were similar.
18926919 Evolutionarily conserved antigens in autoimmune disease: implications for an infective aet 2009 Feb The immune system has evolved to eliminate or inactivate infectious organisms. An inappropriate response against self-components (autoantigens) can result in autoimmune disease. Here we examine the hypothesis that some evolutionarily conserved proteins, present in pathogenic and commensal organisms and their hosts, provide the stimulus that initiates autoimmune disease in susceptible individuals. We focus on seven autoantigens, of which at least four, glutamate decarboxylase, pyruvate dehydrogenase, histidyl-tRNA synthetase and alpha enolase, have orthologs in bacteria. Citrullinated alpha-enolase, a target for autoantibodies in 40% of patients with rheumatoid arthritis, is our main example. The major epitope is highly conserved, with over 90% identity to human in some bacteria. We propose that this reactivity of autoantibodies to shared sequences provides a model of autoimmunity in rheumatoid arthritis, which may well extend to other autoimmune disease in humans.
18831915 Chemokines and bone remodeling. 2008 Jul Bone remodeling is characterized by spatial and temporal coupling of bone resorption and formation and is necessary for skeletal growth and normal bone structure maintenance. Imbalance of this process is related to metabolic bone disorders such as osteoporosis or rheumatoid arthritis. For this reason, bone remodeling is under the control of several local and systemic factors, including molecules of the immune system. The importance of the interplay of both the skeletal and immune systems is reflected by the emerging interdisciplinary research field, called osteoimmunology, focused on common aspects of osteology and immunology. This review focuses on the role of inflammatory mediators, such as cytokines in bone remodeling and, in particular, a subfamily of chemotactic cytokines or chemokines which are involved not only in several aspects of physiological bone remodeling but also in pathological bone disorders, such as rheumatoid arthritis or osteoporosis. Understanding the role of inflammation and chemokines will provide new insights for the treatment of diseases affecting both skeletal and immune systems, by the development of new therapeutic strategies targeting common inflammatory mediators.
17117588 Estrogen receptor ligands in the control of pathogenic inflammation. 2006 Nov Inflammation is recognized as a key component in a number of diseases, including rheumatoid arthritis, inflammatory bowel disease and atherosclerosis. Although well known for their classic effects on the reproductive tract and action by means of estrogen response elements in gene promoters, estrogens are also known to possess anti-inflammatory activity. This was originally highlighted with the observation that pregnancy ameliorates symptoms of rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. Furthermore, the antagonistic cross talk between nuclear factor kappaB and estrogen receptor signaling pathways has been well documented. Recently, novel estrogen receptor ligands, pathway-selective ligands and estrogen receptor beta-selective ligands have been identified which demonstrate potent anti-inflammatory activity; these ligands are being analyzed for their therapeutic potential in pathogenic inflammation.
16816838 B cells move to centre stage: novel opportunities for autoimmune disease treatment. 2006 Jul The B-cell arm of the immune system has long been appreciated for its crucial role in pathogen resistance, but in the study of many autoimmune diseases, T cells have dominated the limelight for decades. However, the development of the B-cell-depleting antibody rituximab as a lymphoma therapy has provided a tool to probe the contribution made by B cells in several immune disorders. Recently, the success of B-cell depletion with rituximab in the treatment of rheumatoid arthritis has stimulated investigation of its effects in several other immune disorders, and considerable interest in the potential of drugs that can modulate B-cell function for the treatment of such diseases in general. This article discusses the role of B cells in a range of autoimmune disorders, including rheumatoid arthritis and systemic lupus erythematosus, and analyses approaches to therapeutic B-cell manipulation.
19030963 Multiple rice body formation accompanying the chronic nonspecific tenosynovitis of flexor 2008 Nov Rice body formation is generally a rare disorder related to rheumatoid arthritis. It can also be observed in cases of systemic lupus erythematosus, seronegative arthritis, infectious arthritis (tuberculosis, atypical mycobacterial infection), nonspecific arthritis, and osteoarthritis. It is generally located within joints or bursae. Multiple rice bodies of tendon sheaths are rarely encountered. Rice body formation may also be encountered without underlying systemic disorders. We present a case of multiple rice body formation that accompanied chronic nonspecific tenosynovitis of the flexor tendons of the wrist.
16868981 RANTES and monocyte chemoattractant protein 1 as sensitive markers of disease activity in 2006 Aug OBJECTIVE: To longitudinally investigate serum and synovial fluid (SF) levels of RANTES and monocyte chemoattractant protein 1 (MCP-1) as well as in vitro migration of mononuclear cells toward SF in patients with juvenile rheumatoid arthritis (JRA). METHODS: Serum and SF levels of RANTES and MCP-1 were determined by enzyme-linked immunosorbent assay. Chemotaxis was performed using the modified Boyden chamber method. RESULTS: Serum RANTES levels were significantly increased in all onset types of JRA, with the highest levels present in systemic-onset JRA. Serum MCP-1 levels were significantly elevated in patients with systemic-onset JRA and were associated with current systemic features. Although serum levels of RANTES and MCP-1 decreased significantly after treatment, RANTES and MCP-1 levels during disease remission were still significantly higher in JRA patients than in controls. A relationship was found between serum RANTES levels during remission and the duration of clinical remission, with low levels being associated with prolonged clinical remission and high levels with shorter clinical remission. Serum RANTES levels correlated with C-reactive protein concentrations, hemoglobin values, white blood cell (WBC) counts, and platelet counts, whereas serum MCP-1 levels correlated with WBC counts and serum ferritin levels. Levels of RANTES and MCP-1 in SF were elevated as compared with levels in serum. SF chemotactic activity for mononuclear leukocytes was significantly inhibited by either anti-RANTES or anti-MCP-1 antibody. CONCLUSION: RANTES is a key molecule in the pathogenesis of all onset groups of JRA, whereas MCP-1 is particularly important in systemic-onset JRA. Serum levels of these CC chemokines represent more highly sensitive markers of disease activity than conventional markers of inflammation.
17328076 Musculoskeletal abnormalities of the tibia in juvenile rheumatoid arthritis. 2007 Mar OBJECTIVE: To characterize local bone geometry, density, and strength, using peripheral quantitative computed tomography (pQCT), compared with general bone characteristics as measured using dual x-ray absorptiometry (DXA), and to assess their relationship to disease-related factors in children with juvenile rheumatoid arthritis (JRA). METHODS: Forty-eight children ages 4-18 years with JRA (17 pauciarticular, 23 polyarticular, 8 systemic) were compared with age-matched healthy controls (n = 266). Measurements included cortical and trabecular bone geometry, density, and strength at the distal and midshaft tibia determined by pQCT, and whole-body, lumbar spine, and femoral neck measurements by DXA. RESULTS: Methotrexate (MTX) was prescribed to 23 of 48 patients (47.9%) and glucocorticoids and MTX were prescribed to 15 of 48 patients (31.3%), with the greatest use in children with systemic JRA. All JRA patients had decreased tibia trabecular bone density, cortical bone size and strength, and muscle mass. Children with systemic JRA had lower femoral neck densities. Systemic JRA was associated with a shorter, less mineralized skeleton, while a narrower, less mineralized skeleton was observed in polyarticular JRA. The tibia diaphysis was narrower with decreased muscle mass, but normal, size-adjusted bone mineral in all subtypes indicated a localized effect of JRA on bone. Patients exposed to glucocorticoids and MTX or to glucocorticoids or MTX alone had greatly reduced trabecular density, cortical bone geometry properties, and bone mineral content, muscle mass, and bone strength. CONCLUSION: Children with JRA have decreased skeletal size, muscle mass, trabecular bone density, cortical bone geometry, and strength. Not surprisingly, these bone abnormalities are more pronounced in children with greater disease severity.
16739206 Differences in disease outcomes between medicaid and privately insured children: possible 2006 Jun 15 OBJECTIVE: To determine the relationship between health insurance status and disease outcome in children with juvenile rheumatoid arthritis (JRA). METHODS: JRA patients followed at a tertiary pediatric rheumatology center were assessed for the number of active joints and number of joints with limited range of motion. Disease activity, patient well-being, and pain were measured. Disability was assessed by the Childhood Health Assessment Questionnaire, health-related quality of life by the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale, and the PedsQL Rheumatology Module. Health care resource utilization was estimated based on the number of billing events for health services coded in administrative databases; these databases also provided information on patient health insurance status. Children insured by Medicaid or similar state programs for low-income families were considered to have Medicaid status. Disease outcomes of children with Medicaid status was compared with that of children with private health insurance. RESULTS: Forty (14%) of the 295 children with JRA had Medicaid status. Patients with Medicaid status were more often of nonwhite race (P < or = 0.04) and more frequently had a polyarticular or systemic disease course (P = 0.04) compared with other patients (n = 255). After correction for differences in disease duration, race, JRA onset, and JRA course between groups, children with Medicaid status continued to have significantly higher disability (P < 0.0003), and lower mean PedsQL Generic Core Scale scores (P < 0.05), while health resource utilization appeared similar between groups. CONCLUSION: Despite apparently similar health resource utilization and joint involvement, Medicaid status is associated with significantly lower health-related quality of life and higher disability in JRA.
18038609 [Pain versus activity and fatigue in adolescents hospitalized because of cancer and rheuma 2006 INTRODUCTION: Chronic disease in adolescence is followed by many negative effects of somatic and psychosocial nature. These effects can be observed especially in oncological and rheumatologic diseases. This is due not only to the character of the disease, its chronic course, but also aggressive treatment. The objective of this work was to evaluate relationship between pain experience and sleep, fatigue and physical, social and intellectual functioning of teenage patients. MATERIAL AND METHODS: 124 adolescents, 14 to 20 years old, hospitalized because of cancer and juvenile rheumatoid arthritis participated in the study. Level of experienced pain was measured with VAS--Visual Analog Scale and NRS--Numeric Rating Scale. Quality of sleep was assessed with Polish version of Melzacks Questionnaire. Fatigue and activity were assessed with a questionnaire of our own construction. RESULTS: Pain was a significant symptom accompanying rheumatologic and oncological disease, although the sources of pain experience were different. Significant percentage of participants suffered from sleep disruption and activity impairment. An important relationship between increase of pain intensity and sleep disruption in oncological patients was found. Significant relationships between pain intensity vs. fatigue and also pain intensity vs. functioning were identified. CONCLUSIONS: Pain, fatigue and sleep disruption account for important factors in rheumatologic and oncological diseases. They also cause decrease in physical, social and mental functioning of teenage patients. Results show that there is a significant relationship between outcomes of disease, its treatment and impact on functioning and developmental course of adolescents. Care delivered to those patients must be integrated and involve multidisciplinary factors.
16763455 Synovial biomarkers in the spondylarthropathies. 2006 Jul PURPOSE OF THE REVIEW: To explore the concept of a biomarker, or surrogate endpoint, to enhance early diagnosis or predict the response to therapeutic intervention in patients with spondylarthropathy. RECENT FINDINGS: Immunopathologic studies have suggested that the features of spondylarthropathy are distinctive, supporting a prominent role for innate immune cells, and can be consistently differentiated from rheumatoid arthritis. Successful treatment of spondylarthropathy synovitis resulted in rapid and sustained decrease in infiltration by macrophage populations and neutrophils, and decreased expression of many proinflammatory mediators. Consistent with studies in rheumatoid arthritis, significant correlations between the effects of both methotrexate and infliximab on disease activity and sublining macrophage populations were reported. These observations highlight the possibility that macrophage populations may be a synovial tissue biomarker of therapeutic intervention in spondylarthropathy. Preliminary studies have evaluated advanced genomic and proteomic methodologies in spondylarthropathy. SUMMARY: Defining the immunopathology of spondylarthropathy has been associated with identifying potential biomarkers of the clinical response to therapeutic intervention. A surrogate marker of arthritis activity in spondylarthropathy could profoundly enhance screening for efficacy and optimization of dose ranges in early-phase randomized clinical trials.
16777575 Psoriatic arthritis: one or more diseases? 2006 Jun Psoriatic arthritis (PsA) is a common, debilitating auto-immune disease with diverse clinical features. In this paper, published evidence is examined, which addresses the issues that (a) PsA exists; and (b) PsA can or cannot be viewed as a distinct rheumatic disease from other spondyloarthritides. Evidence derived from epidemiological, clinical, genetic and immunohistological studies is included. Summarizing the evidence, it is clear that PsA does indeed exist, with the prevalence of rheumatic disease in patients with psoriasis (Ps) higher than would be expected. Certain clinical features also occur more commonly in PsA, although none can differentiate consistently from other arthropathies. Both genetic and immunohistological studies suggest that PsA, both oligo- and polyarticular disease, can be clearly separated from rheumatoid arthritis and that it belongs to the family of spondyloarthritides. The presence of Ps may confer a more severe clinical phenotype with poor radiological outcome. It may be that, with time, a specific genetic marker or diagnostic feature will emerge; additional, more detailed pathogenic studies are required. In the meanwhile, particularly with new treatments being evaluated, it is important to continue to develop specific classification or diagnostic criteria and to define both clinical and laboratory-based outcome measures.
17710040 Rheumatoid lung disease as seen on PET/CT scan. 2007 Sep We present the case of a 63-year-old woman chronic smoker with a history of severe rheumatoid arthritis, who presented with dyspnea and cough. Her chest x-ray film and CT scan (as part of a PET/CT scan) showed multiple lung nodules and a left pleural effusion. A PET scan (as part of a PET/CT scan) revealed no uptake in the larger lung nodules and intense left pleural uptake. The findings favored rheumatoid lung disease with rheumatoid pleural involvement, but malignant involvement was not excluded. A CT-guided lung and pleural biopsy confirmed the diagnosis of rheumatoid lung disease. On the basis of these findings, the patient was put on immunomodulators and responded to treatment.
17004912 Mulberry extract supplements ameliorate the inflammation-related hematological parameters 2006 Fall Mulberry fruit (Morus Lhou Koidz.), a rich source of the major anthocyanin, cyanidin 3-glucoside (C3G), has traditionally been used for the treatment of inflammatory conditions including rheumatic arthritis. In this study, we evaluated the efficacy of orally administrated methanolic mulberry fruit extract (ME) in carrageenan-induced arthritic rats, based on previously observed in vitro antioxidant and anti-inflammatory activities. A significant attenuation of hind paw inflammation characterized by fluid accumulation, uric acid production, and rheumatoid factors induced by carrageenan was observed following the intake of both ME (50 mg/kg of body weight) and C3G (10 mg/kg of body weight). Moreover, alterations in hematological parameters such as serum triglyceride, high-density lipoprotein-cholesterol, and atherogenic index following carrageenan administration were partially reversed by the administration of ME. It is concluded that dietary mulberry fruit extracts elicited protection against carrageenan-induced inflammation.