Browse

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

ID PMID Title PublicationDate abstract
11308066 Involvement and satisfaction: a Norwegian study of health care among 1,024 patients with r 2001 Feb OBJECTIVE: To investigate involvement in and satisfaction with health care among patients with rheumatoid arthritis (RA) and persons with chronic noninflammatory musculoskeletal pain, to identify target areas for improvement. METHODS: Data were collected from postal surveys carried out in 1994 in Oslo, Norway, with 1,542 patients with RA and 10,000 randomly selected adults. Patients with RA and persons with noninflammatory musculoskeletal pain were asked 3 questions about their involvement with treatment and 1 question about their satisfaction with health care. Levels of involvement and of satisfaction were related to demographic measures, health status measures, use of health services, and, for patients with RA, self-efficacy. RESULTS: Of the respondents with RA (n = 1,024), 40% scored low on at least 1 question on involvement and 11% reported global dissatisfaction. Being young, well educated, physically disabled, in good mental health, and self-efficient and having visited a rheumatologist in the last 12 months were associated with a high level of involvement; being female and having a low pain level, good mental health, and high self-efficacy were associated with satisfaction with health care. Of persons with noninflammatory musculoskeletal pain of more than 5 years duration (n = 1,509), 57% scored low on at least 1 question on involvement and 27% reported global dissatisfaction. Being well educated, having visited a general practitioner in the last 12 months, and having ever visited a rheumatologist were associated with a high level of involvement. Being older and having a low pain level and good mental health were associated with satisfaction. A low score on involvement was a strong independent predictor of global dissatisfaction in both groups. CONCLUSION: High education level and health service provided by rheumatologists were consistently associated with a high level of involvement. Good mental health and high involvement were associated with satisfaction with the care received. Efforts to achieve a higher level of patient involvement should especially be directed toward patients with low education, emotional distress, and a chronic physical disorder.
11094921 Characteristics of rheumatoid arthritis patients: who participates in long-term research a 2000 Feb OBJECTIVE: A 10-year study of rheumatoid arthritis (RA) patients was conducted to identify characteristics associated with continued participation in a long-term research project. METHODS: Nine hundred eighty-eight RA patients were recruited from 56 private rheumatology practices. Over the course of the study, 45 patients died and were eliminated from the analysis. Patients were interviewed by phone each year for 10 years, and their physicians provided clinical data. Variables measured included demographic characteristics, perceived health status, employment status, family responsibilities, social support, and clinical health status. RESULTS: Forty-six percent of patients remained in the study after 10 years. Survival analysis using Cox regression techniques assessed baseline factors that significantly predicted characteristics of patients who remained in the study. The multivariate analysis found that more educated patients, female patients, those with moderate to high levels of social support, patients having fewer joint groups with flares, and employed patients were more likely to remain in the study. Disease characteristics of stage of disease, level of pain, self-reported level of physical disability, and duration of RA were not significantly associated with continued study participation. CONCLUSION: The results suggest that psychosocial and socioeconomic factors are more important determinants of continued participation in long-term research studies than are most clinical disease characteristics. Among clinical variables, only the active disease characteristic of joint flares predicted continued study participation. Overall disease characteristics such as disease stage or duration did not predict subject attrition.
9313345 IL-1 modifies system A transport activity in human rheumatoid synovial cells. 1997 Jul Given the importance of interleukin-1 in both rheumatic diseases and the modulation of cell metabolic activities, we studied the action of this cytokine on the neutral amino acid transport A system on rheumatoid synovial cells. In these cells IL-1 (1 ng/ml) induced amino transport stimulation from 5 min to 5 h. This effect was obtained only after a starvation period. No concentration-related effect was found for IL-1-stimulated MeAIB uptake, and the IL-1-mediated MeAIB uptake stimulation is independent of protein synthesis. Neosynthesis or post-translational maturation of protein transport is a prerequisite for obtaining this effect. In conclusion, rheumatoid synovial cells exhibit a higher sensitivity for IL-1 than osteoarthritic ones, probably related to their intense metabolic activity.
9214430 Inhibition of rheumatoid synovial fibroblast proliferation by antisense oligonucleotides t 1997 Jul OBJECTIVE: To evaluate the feasibility of antisense oligonucleotides as therapeutic agents to inhibit synovial cell growth in rheumatoid arthritis (RA). METHODS: Fibroblast-like cells established from RA synovium were stimulated with interleukin-1beta (IL-1beta) and treated with antisense or sense oligonucleotides targeting proliferating cell nuclear antigen (PCNA) messenger RNA (mRNA). Proliferation of these cells was determined by 3H-thymidine incorporation. Effects of antisense oligonucleotides on the expression of mRNA and protein were evaluated by reverse transcriptase-polymerase chain reaction and immunohistochemical staining, respectively. RESULTS: Antisense oligonucleotides targeting PCNA inhibited IL-1-stimulated fibroblast proliferation, whereas sense oligonucleotides had no effect. Both mRNA and protein levels of PCNA were suppressed in the cells treated with antisense oligonucleotides, indicating that the antiproliferative effect was occurring through an antisense mechanism. CONCLUSION: These results suggest that antisense strategies designed to suppress PCNA expression have potential use as therapeutic agents for RA.
11155790 Replacement therapy with DHEA plus corticosteroids in patients with chronic inflammatory d 2000 A dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis was found in animal models of chronic inflammatory diseases, and the defect was located in more central portions of the HPA axis. This defect of neuroendocrine regulatory mechanisms contributes to the onset of the model disease. Since these first observations in animal models were made, evidence has accumulated that the possible defect in the HPA axis in humans is more distal to the hypothalamus or pituitary gland: In chronic inflammatory diseases, such as rheumatoid arthritis, an alteration of the HPA stress response results in inappropriately low cortisol secretion in relation to adrenocorticotropic hormone (ACTH) secretion. Furthermore, it has recently been shown that the serum levels of another adrenal hormone, dehydroepiandrosterone (DHEA), were significantly lower after ACTH stimulation in patients with rheumatoid arthritis without prior corticosteroids than in healthy controls. These studies clearly indicate that chronic inflammation alters, particularly, the adrenal response. However, at this point, the reason for the specific alteration of adrenal function in relation to pituitary function remains to be determined. Since one of the down-regulated adrenal hormones, DHEA, is an inhibitor of cytokines due to an inhibition of nuclear factor-kappa B (NF-kappa B) activation, low levels of this hormone may be deleterious in chronic inflammatory diseases. We have recently demonstrated that DHEA is a potent inhibitor of IL-6, which confirmed an earlier study in mice. Since IL-6 is an important factor for B lymphocyte differentiation, the missing down-regulation of this cytokine, and others such as TNF, may be a significant risk factor in rheumatic diseases. Since in these patients, administration of prednisolone or the chronic inflammatory process itself alters adrenal function, endogenous adrenal hormones in relation to proinflammatory cytokines change. Furthermore, these mechanisms may also lead to shifts in steroidogenesis which have been demonstrated in chronic inflammatory diseases. It was repeatedly demonstrated that the serum level of the sulphated form of DHEA (DHEAS) was significantly lower in patients with chronic inflammatory diseases. Since DHEAS is the pool for peripheral sex steroids, such as testosterone and 17 beta-estradiol, lack of this hormone leads to a significant sex hormone deficiency in the periphery. This overview will demonstrate mechanisms why DHEAS is reduced in chronic inflammatory diseases. The importance of DHEAS deficiency will be demonstrated with respect to osteoporosis. As a consequence, we suggest a combined therapy with corticosteroids plus DHEA in chronic inflammatory diseases.
11713759 Interleukin-1 receptor antagonist gene therapy for arthritis. 1999 Aug Rheumtatoid arthritis (RA) is a crippling, autoimmune disease, and is characterized by inflammation and destruction of joint tissue. Interleukin-1 (IL-1) has been identified as a key pro-inflammatory cytokine responsible for inflammation. One of the mechanisms of regulation of activity of IL-1 is IL-1 receptor antagonist (IL-1ra)-mediated: IL-1RA competes with IL-1 for binding to the IL-1 receptor. Significant progress has been made in the potential application of IL-1ra gene therapyfor the treatment of arthritis. Various vectors have been tested for the delivery of the IL-1ra gene to the intra-articular region. Recent studies in humans have provided encouraging prospects for IL-1ra-mediated arthritis gene therapy.
11508426 Corticotropin-releasing hormone signaling in synovial tissue from patients with early infl 2001 Aug OBJECTIVE: Elevated levels of corticotropin-releasing hormone (CRH) are produced locally in inflamed human synovial tissue, and previous observations indicate a role for CRH in the pathogenesis of inflammatory joint disease. To further elucidate the biologic role of CRH at peripheral sites, we examined the expression of known CRH receptor subtypes in inflamed human synovium and compared the expression patterns in normal synovium. METHODS: Immunohistochemical analysis was used to confirm enhanced expression of specific CRH receptor subtypes in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) synovium. Immunofluorescence double-labeling was used to further characterize CRH receptor-expressing cells. Reverse transcriptase-polymerase chain reaction analysis was performed to examine CRH receptor subtype messenger RNA (mRNA) expression in RA, PsA, and normal synovial tissue. In addition, CRH receptor expression was examined in isolated synovial endothelial cells and synoviocytes. RESULTS: Selective up-regulation of CRH receptors in inflamed synovial tissue indicated that CRH functions locally, in an autocrine/paracrine receptor-mediated manner. Immunoreactive CRH receptor type 1 (CRH-R1) was expressed abundantly on vascular endothelial cells and discrete perivascular cell populations, identified as mast cells. In all samples of inflamed synovium studied, CRH-R1alpha mRNA was detected; however, we were unable to identify CRH-R1beta or any CRH-R2 isoforms in samples from the same cohort of, patients. CRH receptor subtype expression in separated synovial cell populations revealed a pattern of staining similar to that seen in vivo. In contrast, neither CRH receptor subtype was expressed in normal synovial tissue. CONCLUSION: Our findings suggest that CRH signaling, via CRH-R1alpha, may play a role in both the vascular changes and the pathologic mechanisms associated with joint inflammation in human arthritis.
9310102 Early diagnosis of rheumatoid cervical myelopathy. 1997 The purpose of this study was to detect early signs of cervical myelopathy on the basis of clinical finding, radiographs, somatosensory evoked potentials (SSEPs) for n. medianus in 56 patients and transcranial dopler (TCD) for vertebral arteries in 35 patients. Radiological findings, SSEPs, and TCD were registered in neutral and functional scanning positions. Forward AA dislocation was verified in 25 patients with mean value 4.7 mm. The total of 12 (3 in neutral and 9 in functional positions) out of 56 patients had pathological findings of SSEPs for n. medianus. Out of 35 patients 13 (8 in standard imaging position and 5 in rotations) had abnormal values of mean blood flow velocities (MBFV). Movements can provoke neural conduction disturbances through spinal cord and interrupt vertebral arteries blood flow. The early detection of the cervical myelopathy is possible when changing the head position during SSEPs and TCD recordings. On the basis of clinical, x-ray, SSEPs and TCD analyses we suggest that patients with risk of developing myelopathy should be separated.
9584370 Arthritis and arthrodesis of the hindfoot. 1998 Apr Arthritic involvement of the subtalar, talonavicular, and calcaneocuboid joints is a common cause of pain in the mature hindfoot. Inflammatory, degenerative, and crystalline forms of arthritis may lead to deformity and instability of joints. When medical and nonoperative management fails, painful joints are stabilized best by selective arthrodeses. Whereas, in the past, the triple arthrodesis was used extensively for many types of hindfoot deformities, single joint fusions now are used more commonly. More limited arthrodesis still may allow preservation of some hindfoot motion, thereby resulting in greater function. Various hindfoot arthritides and their biomechanical sequelae, resultant deformities, and treatment options are discussed. Arthrodesis continues to be the best treatment option for patients who have extensive hindfoot arthrosis, regardless of the underlying process.
11229470 Detection of autoantibodies to killer immunoglobulin-like receptors using recombinant fusi 2001 Feb OBJECTIVE: To investigate the existence of autoantibodies to killer immunoglobulin-like receptors (KIRs), especially p58.1 (KIR2DL1) and p58.2 (KIR2DL3), in patients with systemic autoimmune diseases. METHODS: Sera from 30 patients with systemic lupus erythematosus (SLE), 30 patients with rheumatoid arthritis (RA), 22 patients with Behçet's disease, and 20 healthy control subjects were tested for anti-p58.1 and anti-p58.2 antibodies by Western blot analysis using recombinant p58.1 and p58.2 proteins. Furthermore, clinical features and laboratory data were compared between the anti-p58.1/58.2 antibody-positive and -negative patients. RESULTS: Anti-p58.1 antibodies were detected in 7 (23.3%) of the 30 patients with SLE, 9 (30%) of the 30 patients with RA, and 6 (27.3%) of the 22 patients with Behçet's disease. Anti-p58.2 antibodies were detected in the same 22 patients who were positive for the anti-p58.1 antibodies. None of the serum samples from the healthy donors were positive for antibodies to the recombinant p58.1 or p58.2 molecules. Compared with the anti-p58.1/ 58.2 antibody-negative patients, the anti-p58.1/58.2 antibody-positive patients had significantly elevated levels of serum IgG in all 3 diseases tested, an accelerated erythrocyte sedimentation rate in RA and SLE, and decreased white blood cell counts in RA. CONCLUSION: This report is the first to describe the presence of autoantibodies to KIR2DL (p58.1 and p58.2) in the sera of patients with systemic autoimmune diseases. Considering the correlation with several clinical features, these autoantibodies may be involved in the pathologic process of the autoimmune diseases.
11762945 PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced a 2001 Dec OBJECTIVE: To verify whether the prototypical long pentraxin PTX3 represents an indicator of the activity of small-vessel vasculitis. METHODS: Concentrations of PTX3, a pentraxin induced in endothelium by cytokines, were measured by enzyme-linked immunosorbent assay in the sera of 43 patients with Churg-Strauss syndrome, Wegener's granulomatosis, and microscopic polyangiitis. PTX3 was also measured in the sera of 28 patients with systemic lupus erythematosus (SLE), 22 with rheumatoid arthritis, and 16 with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias). Serum concentrations of C-reactive protein (CRP) were measured by immunoturbidimetry. The cells involved in PTX3 production in vivo were identified in skin biopsy samples. RESULTS: Patients with active vasculitis had significantly higher concentrations of PTX3 than did those with quiescent disease (P < 0.001). PTX3 levels in the latter group were similar to those in healthy controls. PTX3 levels were higher in patients with untreated vasculitis and lower in patients who underwent immunosuppressive treatments (P < 0.005). In contrast, patients with active SLE had negligible levels of the pentraxin. PTX3 levels did not correlate with CRP levels in vasculitis patients. Endothelial cells produced PTX3 in active skin lesions. CONCLUSION: PTX3 represents a novel acute-phase reactant produced at sites of active vasculitis.
9437598 Total shoulder arthroplasty with the Neer prosthesis: long-term results. 1997 Nov We determined the outcome of 113 total shoulder replacement arthroplasties performed with a Neer prosthesis between 1975 and 1981. The operations were performed for the treatment of osteoarthritis, rheumatoid arthritis, and old fractures or dislocations with traumatic arthritis. The probability of implant survival was 93% after 10 years and 87% after 15 years. Complications requiring reoperation developed in 14 shoulders. Seventy-nine patients with 89 replacements were available for follow-up a minimum of 5 years after the operation (mean 12.2 years, range 5 to 17 years). Relief from moderate or severe pain was achieved in 83% of shoulders. Active abduction improved by an average of 40 degrees to an average of 117 degrees. The amount of elevation that was regained was related to the amount of rotator cuff disease. Seventy-five glenoid components developed bone-cement radiolucencies, and 39 (44%) glenoid components had radiographic evidence of definite loosening. Glenoid loosening was associated with pain. A shift in position of the humeral component occurred in 49% of the press-fit stems and in none of the cemented stems. Humeral component loosening was not associated with pain.
9461147 Glycosaminoglycan components in temporomandibular joint synovial fluid as markers of joint 1998 Feb PURPOSE: This study investigated the correlation between temporomandibular joint (TMJ) disease and the composition of glycosaminoglycans (GAGs) components in the synovial fluid (SF). MATERIALS AND METHODS: Synovial fluid (SF) was obtained from 30 TMJs of 28 female patients diagnosed as having a displaced disc with reduction (WR) (seven joints), a displaced disc without reduction (WOR) (13 joints), osteoarthritis (OA) (five joints), or rheumatoid arthritis (RA) (five joints) by MR imaging and clinical examination. After the SF was directly aspirated, It was digested with chondroitinase ABC and hyaluronidase, and the concentration of unsaturated disaccharide isomers of chondroitin 6-sulfate (delta di-6S), chondroitin 4-sulfate (delta di-4S) and hyaluronic acid (delta di-HA) were measured by high-performance liquid chromatography (HPLC) combined with fluorometry. The ratio of delta di-6S or delta di-4S to delta di-HA, and delta di-6S to delta di-4S, were calculated. RESULTS: There were no significant differences in concentrations of delta di-6S, delta di-4S, or delta di-HA among the groups. The ratio of delta di-6S to delta di-4S was 2.7 +/- 1.4 in OA, 2.6 +/- 0.9 in joints with WOR, 2.9 +/- 1.2 in joints with WR, and 1.3 +/- 0.4 in RA synovial fluid. Differences in the delta di-6S: delta di-4S ratio between RA and the other conditions were statistically significant (P < .05). CONCLUSION: These results suggest that the delta di-6S:delta di-4S ratio in the synovial fluid of the TMJ reflects the proteoglycan metabolism of the joint tissues, particularly of the articular cartilage and synovial tissue. This ratio could be used to diagnose joint diseases and to predict articular cartilage destruction or synovial proliferation caused by these diseases.
10450503 Walking through the forest of transgenic models of human disease. 1999 Jun In the investigation of human disease, molecular biology has provided immunologists with several enormously powerful tools. Transgenic and knockout mice provide animal models to investigate mechanisms, as well as aid in the design of therapies for these diseases. These mice have been useful in several different ways. First, as direct models of disease they provide direct tools for the study of the disease. Second, expression of individual molecules can be altered in the context of established disease models. We describe here some of the models in use as well as the limitations and promise of this research.
9328127 Autoantibody reactive with the human general transcription factor TFIIF in sera from patie 1997 Sep Transcription factor (TF) IIF, a heteromeric protein composed of two subunits, RAP30 and RAP74, is required for both specific initiation and elongation of mRNA synthesis by RNA polymerase II. We have identified high titre of specific autoantibodies against the RAP74 subunit of TFIIF in sera from patients with systemic lupus erythematosus (SLE) as well as those with rheumatoid arthritis (RA), periarteritis nodosa (PN), Sjögren's syndrome (SS), dermatomyositis (DM), and mixed connective tissue disease (MCTD) by Western blot or immunoprecipitation. The epitopes recognized by autoantibodies were shown to be preferentially clustered at the central charged region. Anti-RAP74 autoantibody was shown to suppress the activity of TFIIF-stimulated elongation of mRNA synthesis by RNA polymerase II. It is concluded that some patients with autoimmune disorders develop specific autoantibodies against the RAP74 subunit of TFIIF.
11094434 Physiologic role of interleukin-1 receptor antagonist. 2000 Recent studies have described the spontaneous development of arthritis or vasculitis in IL-1 receptor antagonist (IL-1Ra) knockout mice bred on specific and different genetic backgrounds. The levels of both secreted and intracellular isoforms of IL-1Ra produced in the rheumatoid joint or in the arterial wall may not be adequate to effectively inhibit the excess amounts of locally produced IL-1. Thus, an imbalance between IL-1 and IL-1Ra may predispose to local inflammatory disease in particular tissues in the presence of other as yet unknown genetically influenced factors.
11669155 Magnetic resonance imaging of the wrist and finger joints in patients with inflammatory jo 2001 Oct OBJECTIVE: To study magnetic resonance imaging (MRI) features in the wrist and metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints in 4 patient groups: early rheumatoid arthritis (RA) (< 3 yrs); established RA (> 3 yrs); other arthritis; arthralgia. METHODS: MRI was obtained before and after contrast (gadodiamide) injection of the wrist and finger joints in 103 patients and 7 controls. The study included: (1) 28 patients with disease duration < 3 yrs who fulfilled the American College of Rheumatology (ACR) criteria for RA; (2) 25 patients with RA disease duration > 3 yrs who fulfilled the ACR criteria. (3) 25 patients with reactive arthritis, psoriatic arthritis, or mixed connective tissue disease; and (4) 25 patients with arthralgia. The following MRI variables were assessed: number of joints with enhancement after contrast injection, number of joints with joint fluid, and number of bones with edema in the wrist and fingers. The volume of the enhancing synovial membrane after contrast injection in the MCP, PIP, and DIP joints was manually outlined. MR images were scored independently under blinded conditions. RESULTS: Bone marrow edema was found in 68% of the patients with established RA, and the number of bones with edema was significantly higher in patients with established RA compared to patients with early RA, other arthritis, and arthralgia (Mann-Whitney p < 0.04). Bone edema was not found in patients with arthralgia. There was marked overlap within and between the patient groups. No differences in MRI features were found between patients with early RA and patients with other arthritis. The volumes of the synovial membrane in the MCP, PIP, and DIP joints were significantly higher in patients with arthritis compared to patients with arthralgia. CONCLUSION: Although there was marked overlap between the arthritis patient groups, MRI determined bone marrow edema and synovial membrane volumes provided additional information about disease activity and may be used as a marker of it. Bone marrow edema appeared with the highest percentage in patients with long duration of RA (> 3 yrs) and is probably secondary to changes in inflammatory activity.
9841695 Recurrent embolism caused by floating thrombus in the thoracic aorta. 1998 Nov A case of embolic recurrent episodes resulting in acute lower-limb ischemia from an unusual source is reported. This occurred in a patient on steroids for rheumatoid arthritis. Femoropopliteal thromboembolectomy successfully restored arterial flow. Diagnostic evaluation for identifying the source of embolism revealed a large, pedunculated and mobile thrombus arising from a nonaneurysmatic and nonatherosclerotic descending thoracic aorta. The thrombus was identified by transesophageal echocardiography and was successfully removed by aortic thromboendarterectomy. We emphasize the importance of transesophageal echocardiography as a reliable method for the diagnosis of thoracic aorta diseases and for identification of aortic thrombi. An aggressive surgical approach is recommended in the low-risk patient to prevent further embolic episodes.
10769425 [Concept for nationwide cooperation in planning and implementing multicenter studies]. 2000 Feb In Germany, good clinical multicenter studies that are not supported by pharmaceutical companies are rarely performed. Good supranational industry-sponsored studies are usually aimed at the registration of new (expensive) drugs. The preconditions for co-operation in conducting industry-independent studies which are of interest for the scientific community have been improved substantially in Germany by instituting the working group of co-operating arthritis centers, the so-called core documentation where 32,000 patients with rheumatic conditions were documented in 1997 and the institution of a sophisticated information system ("RheumaNet"). The executive board of the German Rheumatology Association has set up an "ad hoc commission" that agreed to institute a "Committee for the Coordination of Clinical Studies in Rheumatic Diseases". In this committee rheumatologists subspecialized from medicine, orthopedic, pediatrics working in universities, hospitals and private practice as well as specialists in statistics and epidemiology shall be represented. In principle this committee is independent of the co-operating arthritis centers and the RheumaNet. All members of the German Rheumatology Association are invited to cooperate with this committee by contributing to the clinically important questions and participating in clinical studies. The committee has to define key questions in rheumatology and shall plan and organize multicenter studies to answer these questions. In addition, study protocols of pharmaceutical companies may be examined as to their importance, quality, and feasibility.
9481903 [Differences in morbidity between the Eastern central city district and the suburban Weste 1998 Jan 10 Oslo, the capital of Norway, has a population of 500,000. Living conditions vary considerably within the city, and the mortality rate in the most deprived area is almost three times as high as in the most affluent one. We wanted to explore how morbidity varies within Oslo. We used four town-wide disease registers to study the prevalence of the four diseases in the most deprived and the most affluent part of the city. We found that tuberculosis occurs more frequently in the poor area, while type 1 diabetes mellitus in children occurs more frequently in the most affluent area. For multiple sclerosis and rheumatoid arthritis we could not find any differences between the areas.