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

ID PMID Title PublicationDate abstract
10643141 Estimation & significance of serum & synovial fluid malondialdehyde levels in rheumatoid a 1999 May Serum and synovial fluid (SF) levels of malondialdehyde (MDA), a marker of free radical induced lipid peroxidation, were estimated in patients of rheumatoid arthritis (RA) and compared with healthy controls and patients of osteoarthritis (OA). While serum MDA levels were similar in healthy controls (0.24 +/- 0.10 nmol/ml) and OA (0.28 +/- 0.11 nmol/ml), the serum levels in RA (0.47 +/- 0.19 nmol/ml) were significantly higher as compared to both healthy controls and OA patients; and correlated with synovial fluid (SF) MDA levels. No difference was observed in SF-MDA levels in RA (0.17 +/- 0.07 nmol/ml) and OA (0.16 +/- 0.09). MDA levels did not correlate with markers of disease activity in RA like joint counts, duration of morning stiffness, erythrocyte sedimentation rate etc. Increased serum MDA levels in RA suggest the role of free radicals in the pathogenesis of this inflammatory arthropathy and support the need for further studies assessing the therapeutic role of free radical scavengers in RA.
10036560 Determinants of compliance with medication in patients with rheumatoid arthritis: the impo 1999 Jan In this study we examine which factors are related to compliance with medication in patients suffering from rheumatoid arthritis (RA). PATIENTS: persons suffering recently developed, active RA, who cooperated in a randomized study on the effect of patient education. We analyzed the relation between adherence to Sulphasalazine therapy and personal factors, environmental influences, demographic factors, disease-related factors, and barriers to compliance. Moreover, a logistical regression analysis was performed on these factors, considering > or = 80% a high compliance, both with compliance as dependent factor. Only self-efficacy correlated with compliance (r = 0.58; P < 0.001). The logistical regression analysis identified self-efficacy as the only factor determining > or = 80% adherence (P = 0.01). Self-efficacy regarding the use of prescribed medication is related to compliance with this treatment. Further study is needed to determine the test characteristics of self-efficacy as a predictor for compliance with medication.
11692697 [Comparative study of the effects of thymalin and vitamin E on certain indices for local p 2001 Jul In experimental rheumatoid arthritis, certain indices for local defence of the lung were studied together with effects on these of preparations of vitamin E and thymalin. Noted in experimental rheumatoid arthritis are manifest changes in quantitative indices for cellular population of the bronchoalveolar space and disturbances in humoral mechanisms of defence of the lungs. The drugs employed for the treatment of the affliction have a positive effect on quantitative indices for the cell population of the lung local defence factors. But no significant effects could be demonstrated of thymalin on humoral factors of defence of the lungs. Unlike thymalin, tocopheroli acetas is noted to augment the secretion of lysozyme, to decrease the activity of phospholipase A2, to improve the surface-active properties of the lung surfactant. It is suggested that its antioxidant, membrane-stabilizing action may be responsible for the positive effect on indices for local defence of the lung.
10890256 Leflunomide, a novel immunomodulator for the treatment of active rheumatoid arthritis. 1999 Nov Rheumatoid arthritis (RA) is a chronic disease affecting 0.8% of the population. Nonsteroidal anti-inflammatory drugs reduce the pain and inflammation of RA and improve mobility but do not slow the progression of joint damage. Disease-modifying antirheumatic drugs (DMARDs), which limit potentially irreversible joint damage, may influence the course of disease progression. This review describes the recently approved DMARD leflunomide, an isoxazole-based immunomodulator. Unlike other DMARDs, leflunomide arrests the growth of activated lymphocytes by inhibiting the enzyme dihydroorotate dehydrogenase, a critical link in the production of uridine monophosphate. Leflunomide is rapidly metabolized to the active major metabolite A77 1726, which is responsible for the drug's pharmacologic activity. Leflunomide has exerted inhibitory activity in animal models of RA. Its clinical efficacy has been demonstrated in a number of controlled trials. In two multinational 52-week studies and two 24-week studies, all leflunomide-treated patients received an initial loading dose of 100 mg for 3 days, followed by 20 mg/d. The effects on the signs and symptoms of RA were evaluated using the American College of Rheumatology (ACR) 20 responder index, tender and swollen joint counts and scores, patients' and physician's global assessments, and pain intensity index. Erosions and joint-space narrowing were assessed by radiography. Compared with placebo, leflunomide significantly improved the signs and symptoms of RA (41%-64% improvement) by ACR 20 responder criteria (P < 0.001). Leflunomide, methotrexate, and sulfasalazine were equally effective in terms of symptom outcomes. In terms of retarding the progression of disease, leflunomide was significantly superior to placebo, with no consistent difference from methotrexate or sulfasalazine. In a trial using a combination of leflunomide and methotrexate therapy, 53% of patients were responders by ACR 20 criteria. Adverse effects in RA patients receiving leflunomide included diarrhea, elevated liver enzymes, alopecia, and rash. Additional adverse events occurring with a frequency >5% included allergic reaction, asthenia, abdominal pain, back pain, and hypertension, among others. Thus leflunomide may be used in selected RA patients (ie, those starting RA therapy for the first time or failing earlier DMARD therapy). However, the product labeling requires monthly monitoring of liver enzymes until stable concentrations are reached. Other labeled warnings include a risk of immunosuppression and an increased risk of fetal death or teratogenic effects in pregnant women. Methotrexate, which is also hepatotoxic, is usually the initial DMARD recommended for use in patients with aggressive RA.
11547372 Patient satisfaction after total knee arthroplasty: a comparison between subjective and ob 2001 Sep We used a visual analog scale (VAS) to assess the satisfaction after total knee arthroplasty (TKA) in a group of 108 patients (126 TKAs) with short-term to medium-term follow-up. We also used the Knee Society scoring system, Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), pain VAS, and survival analysis. A comparison between the subjective and objective outcome systems revealed only poor correlations. This comparison suggests that the concerns and priorities of patients and surgeons differ. The outcome assessed with the satisfaction VAS revealed a significantly better subjective outcome in rheumatoid arthritis patients compared with osteoarthritis patients, whereas Knee Society scores were not different. The satisfaction VAS provides additional information about subjective outcome after TKA.
9002007 Prediction of articular destruction in rheumatoid arthritis: disease activity markers revi 1997 Jan OBJECTIVE: To assess the predictive value for joint damage progression of commonly used disease activity or process measures in rheumatoid arthritis (RA). METHODS: Seventy-two patients fulfilling the American Rheumatism Association criteria for RA were assessed twice yearly for 2 years. Primary outcome variables were progression of articular destruction, evaluated by Sharp's method, for 6, 12, 18, and 24 month periods. RESULTS: Regression analysis, using random effects linear models, showed that only C-reactive protein, alpha 1-acid glycoprotein, iron, and erythrocyte sedimentation rate were significantly, but not independently, associated with 6 month radiographic progression. Traditional clinical measures were not predictive. No assessed marker was able to predict longer term outcome (12 or 18 month joint damage progression). Recent onset disease and older age were also associated with more severe radiographic progression. CONCLUSION: The lack of association between clinical measures and laboratory markers as predictors of the progression of articular destruction is further evidence of the need to reconsider processes and outcomes in RA. This study also suggests that clinical measures and laboratory markers probably do not reflect the same underlying process, arguing against gathering these measures under the same heading of "disease activity measures".
9558161 Mannan binding lectin in rheumatoid arthritis. A longitudinal study. 1998 Apr OBJECTIVE: Low serum levels of mannan binding lectin (MBL) are associated with increased risk of recurrent infections. We determined whether there was an association between serum MBL levels and the course and prognosis of rheumatoid arthritis (RA). METHODS: MBL was analyzed in sera from 99 patients with RA who were included in a longterm prospective study. RESULTS: Compared with controls, a high fraction of patients lacked detectable MBL in serum (11 vs 3%; p = 0.025). Comparing patients with MBL serum levels above and below the median revealed that those with levels below the median were younger at onset of RA (p = 0.043) and had higher erythrocyte sedimentation rate (p = 0.006), joint swelling score (p = 0.019), limitation of joint motion score (p = 0.027), and annual increase in radiographic destruction score (p = 0.053). CONCLUSION: MBL insufficiency may be a contributing pathogenetic factor in RA.
10627713 Bone abnormalities in the surgical treatment of patients with rheumatoid arthritis. 1999 Sep Profound abnormalities of bone are an important component of the morbidity of rheumatoid arthritis and partly determine the orthopaedic treatment of patients. The principal bone abnormality, which is osteoporosis associated with rapid remodeling, degrades the mechanical properties of the skeleton in juxtaarticular bone, in the diaphyses of long bones, in the pelvis, and in the base of skull. Abnormalities of bone affect clinical decision making in the surgical treatment of patients with rheumatoid arthritis and must be considered for the optimal treatment of these patients. Increased fracture risk and compromised bony fixation complicate fracture treatment. Techniques of surgery must be modified to protect bone from intraoperative fracture. Methods of fixation of implants and other devices must be appropriate to the biomechanics of the bone. Bone healing usually is rapid if not compromised by mechanical instability. Specific patterns of bone deformation and failure can be identified in the evolution of rheumatoid arthritis. Bone graft used in reconstruction of the protruded acetabulum is incorporated rapidly. Bone resorption with joint instability is a common feature of rheumatoid arthritis; however, the opposite pattern of bony ankylosis with stiffness is observed in a smaller percentage of patients. Recognition of the tissue type is necessary for the individualization of surgical procedures to achieve optimal joint stability and mobility. Based on growing understanding of the pathophysiology of bone in patients with rheumatoid arthritis, new pharmacologic therapies may become available for the prevention and treatment of bone abnormalities in patients with rheumatoid arthritis.
10668522 Disease modification in rheumatoid arthritis with leflunomide. 1999 Rheumatoid arthritis (RA) is characterized by chronic inflammation and irreversible destruction of articular cartilage and bone. Disease progression as assessed by radiographic imaging of structural joint damage is a key outcome measure in RA. Joint damage is especially rapid during early phases of RA, thus the current trend of early aggressive therapy with disease-modifying antirheumatic drugs (DMARDs). Radiographic analysis of disease progression with the novel DMARD leflunomide was compared to methotrexate and sulfasalazine in two large, placebo-controlled, randomized Phase III studies (N = 580). The results as indicated by changes in x-ray scores indicate that leflunomide and both active comparators slow disease progression significantly better than placebo (P < or = 0.01). Slowing of disease progression with leflunomide was similar to sulfasalazine at 6 months but better than methotrexate (P < or = 0.049) at 12 months. These data verify the ability of leflunomide to slow disease progression and confirm its disease-modifying potential.
9296242 Ibuprofen-induced aseptic meningitis in rheumatoid arthritis. 1997 Sep OBJECTIVE: To report a case of aseptic meningitis related to ibuprofen ingestion. CASE SUMMARY: We discuss the case of a 56-year-old white man with a history of rheumatoid arthritis and hypertension who became confused, nauseated, and began to vomit within 2 hours of the ingestion of ibuprofen. A diagnosis of ibuprofen-induced aseptic meningitis was made based on the patient's physical and laboratory findings, the quick onset and resolution of symptoms, and his medical history. DISCUSSION: Ibuprofen-induced aseptic meningitis has been most frequently reported in patients with systemic lupus erythematosus. However, there have been reports of this reaction in patients with other underlying disease states. Various nonsteroidal antiinflammatory drugs have been reported to cause this reaction, but ibuprofen is the most common offending agent. A drug-related cause should be considered in any patient who presents with typical meningitis symptoms, such as fever, headache, and stiff neck, that occur within hours of ingesting a drug. CONCLUSIONS: Although persons with systemic lupus erythematosus appear to have an increased risk for this type of reaction, the development of signs and symptoms in other patients warrants the consideration of nonsteroidal antiinflammatory drugs as the cause of aseptic meningitis.
9310106 HLA-B27 in French patients with rheumatoid arthritis. 1997 Aims were to determine the prevalence of the HLA-B27 phenotype in a group of patients with RA, and to evaluate the clinical, radiological and, serological characteristics of RA in relation to this phenotype. All relevant information was obtained retrospectively from the standardized clinical records of 311 RA in-patients first admitted to the Rheumatology Unit of the Brest University Medical School. In the control population of Britanny, the frequency of HLA-B27 has been shown to be 12%, while HLA-B27 was present in 30 (9.6%) of the 311 RA patients. There was no significant association between demographic, clinical, biological, or radiological characteristics of the patients on the one hand, and the presence of the HLA-B27 allele on the other. The subgroup of RA patients with HLA-B27 had however a slightly higher IgA level than that without HLA-B27. Ankylosing spondylitis were found to coexist in three patients who all were HLA-B27 positive. We conclude (1) that the prevalence of HLA-B27 is not higher in French RA patients than in the normal controls, and (2) that HLA-B27 typing is not useful in RA. HLA-B27 does not confirm nor does it reject the diagnosis of associated ankylosing spondylitis.
10365848 Synovitis in rheumatoid arthritis: scoring of characteristic histopathological features. 1999 Apr Synovial tissue specimens obtained from the knee joints of 40 patients with rheumatoid arthritis (RA) and from 22 patients with osteoarthritis (OA) were examined histologically. The histopathological features of RA synovitis and OA synovitis were then compared. Seven criteria items of histopathological features characteristic to RA synovitis were given a score of 1-3 points each in order to evaluate the histological severity of the seven items. Their total scores were then calculated. A comparison of the total RA synovitis score and the total OA synovitis score revealed that RA synovitis showed more than 11 points (maximum 20 points), while OA synovitis showed less than 10 points in all but two cases. Furthermore, the total scores of RA synovitis were then determined in the same manner for other joints, where it was confirmed that five other joints had scores of more than 11 points as well; that is, the intercarpal, wrist, elbow, ankle and hip joints in 52 patients with RA. From these results, it was concluded that in the histological examination of biopsied synovial tissue of RA, if the total score for synovitis is more than 11 points (maximum 20 points), an histological diagnosis of RA synovitis can be confirmed.
9805193 The electroneurophysiological evaluation of rheumatoid arthritis patients. 1998 In Rheumatoid Arthritis (RA), one clinical hallmark of the vasculitis is the appearance of neurological findings. However, it is often difficult to diagnose these slight or early neuropathies and the study of the peripheral neuromuscular system is often made difficult by symptoms resulting from pain in the joints, and limitations of movement. It is nevertheless often possible, by means of electroneuromyography to show objectively the existence and distribution of even subclinical neuropathies. In order to evaluate the neurophysiological functions of RA patients by means of the peripheral nerve conduction and somatosensory evoked potential studies, 33 RA patients and 20 healthy controls were included in this study. Two (6%) patients were found to have carpal tunnel syndrome, while 6 (18%) patients had mononeuritis multiplex. Delayed N12, N13, N1 and P1 latencies were detected in 6 (18%) of 33 RA patients suggesting central nervous system involvement with intact peripheral nervous system. Our results confirm earlier observations that symptoms of neuropathy are fairly common in cases of RA without there being any clear correlation with any clinical variable. Therefore, the inclusion of an electroneurophysiologic examination of the RA patients is recommended in routine diagnostic procedure.
10555889 Myopathy and neuropathy in rheumatoid arthritis. A quantitative controlled electromyograph 1999 Nov OBJECTIVE: To test the hypothesis that patients with rheumatoid arthritis (RA) have clinical or subclinical evidence of peripheral neuropathy or myopathy. METHODS: We studied 40 seropositive women with RA, mean age 46.6 years (SD 6.4), and 56 healthy controls, mean age 43.0 years (SD 9.1). Patients had a mean disease duration of 13.0 years (SD 7.8). We performed electromyographic examination of 4 muscles [extensor digitorum communis (EDC), biceps brachii (BB), vastus lateralis (VL), and tibialis anterior (TA)] on the right side in both groups. Quantitative data included percentage of polyphasic potentials, motor unit potential amplitude, area, duration, turns, and number of polyphasic potentials. RESULTS: There were statistically significantly higher proportions of polyphasic potentials in 3 muscles in patients compared with controls. Mean number of phases in EDC was 4.6 (SD 0.4) in the patients and 4.1 (0.5) in controls (p = 0.0001). The values for the VL were 4.1 (SD 0.4) in patients compared with 3.6 (0.4) in controls (p = 0.0001), and in the TA 4.5 (SD 0.5) versus 4.0 (0.4) (p = 0.0001). We also found significantly increased duration of motor unit potentials in the VL and TA of patients. The amplitudes of motor unit action potentials were not significantly different in the 2 groups. CONCLUSION: The study reveals an increased prevalence of neurogenic but not myogenic changes in patients with RA compared with controls.
9710892 T-cell receptor peptide vaccination in the treatment of rheumatoid arthritis. 1998 Aug In several human T-cell-mediated autoimmune diseases and animal models of such illnesses, T-cell receptors (TCR) specific for antigens that initiate or perpetuate the disease share a limited number of variable region determinants. Vaccinations with peptides derived from over-represented TCRs are effective treatment for some of these disorders. RA is a chronic inflammatory disease in which there is prominent T-cell infiltration in the synovial lining layer. TCR V beta 3, V beta 14, and V beta 17 have been found to be over-represented among IL-2 receptor-positive T-cells from patients with RA. A phase II clinical trial in RA, using a combination of three peptides derived from V beta 3, V beta 14, and V beta 17, has yielded promising results. Larger clinical efficacy and safety studies must be performed to determine if TCR peptide vaccination will become a viable treatment alternative for patients with RA.
9225877 Ultrasound guided synovial biopsy of the wrist. 1997 Seven patients (4 female and 3 male, mean age 46) with arthritis of the wrist (n = 7) without known etiology were evaluated. High-definition ultrasound equipment was used for localization of synovial hypertrophy, suitable for ultrasound guided biopsy without risk. A 18-gauge diameter Tru-cut biopsy needle was used in an automated gun. Two passes were performed with continuous guidance of the needle-tip. In all patients representative synovial tissue was obtained in adequate amount. No complications were encountered. Ultrasound guided biopsy is proposed as an effective technique which can be performed with low patient discomfort on an outpatient basis.
11168011 Reduced systemic IgG levels against peptidoglycan in rheumatoid arthritis (RA) patients. 2001 Jan The gut flora is believed to play a role in the pathogenesis of RA. Peptidoglycan, a major cell wall component of Gram-positive bacteria, is a candidate antigen because of its capability to trigger production of proinflammatory cytokines, to induce arthritis in rodents, and because of its presence in antigen-presenting cells in RA joints. We investigated whether the systemic and local antibody levels against a peptidoglycan-polysaccharide (PG-PS) are related to the presence and disease activity of RA. Significantly lower levels of systemic IgG directed against PG-PS were found in healthy females compared with healthy males, and systemic IgA levels specific for PG-PS were negatively correlated with age. Levels of systemic IgG directed against PG-PS were significantly reduced in RA patients compared with sex- and age-matched healthy controls. Local (synovial fluid) levels of IgG did not correlate with disease activity whereas synovial fluid levels of IgA correlated positively with disease activity. These data suggest that IgG in healthy people mediates protection against spreading of PG to non-mucosal sites.
11123053 Non-HIV retroviral associations with rheumatic disease. 2000 Apr While the human T-cell lymphotropic virus type I (HTLV-I) is the recognized cause of adult T cell leukemia, it is also associated with non-neoplastic, ostensibly autoimmune conditions, such as tropical spastic paraparesis. Moreover,among carriers of HTLV-I, the virus is strongly implicated in the development of a type of arthritis, which resembles rheumatoid arthritis (RA). Mice transgenic for HTLV-I tax develop RA-like pathology and Sjögren's syndrome. Patients with RA and SS in HTLV-I nonendemic regions, such as the United States, are usually serologically negative for antibodies to the structural proteins of HTLV. However, they appear to harbor HTLV-I tax in their peripheral blood mononuclear cells three times as often as individuals who present as healthy blood donors. Because HTLV-I tax transactivates numerous inflammatory cytokines and is not normally found in the human genome, treatment with tax antisense oligonucleotides may provide a new therapeutic approach for selected RA patients proven to be HTLV-I "tax only" positive.
11527029 Outcome of ankle arthrodesis performed by dowel technique in patients with rheumatic disea 2001 Aug Between the years 1988 and 1994, 19 ankle arthrodeses were performed on 18 patients (nine men) using the dowel technique. Patients were followed until a fusion had occurred, a non-union was successfully rearthrodesed, or a pseudoarthrosis was stabilized with orthosis treatment. Patients' radiographs and documents were analyzed both preoperatively and during the healing period. Subtalar fusion had been performed previously in eight ankles and rheumatoid destruction of subtalar complex was observed in seven other hindfeet. The original dowel method was used in 13 ankles and a modified procedure was performed in six. Local bone grafts were utilized. Solid fusion was achieved in 13 ankles (68%), but with delayed union in two cases. Non-union was present in six ankles, and two re-arthrodeses were performed with successful fusion in the other. Orthosis treatment was necessary in three of five ankles with permanent non-union. One chronic infection leading to non-union was detected. Only two of the six ankles (33%) with the modified technique using additional exposures healed without complications. In the dowel technique, the preoperative position of the ankle and location of the guiding Kirschner wire are of crucial importance and the original technique with a large cutter should be used. In patients with rheumatic disease, this fusion method did not yield acceptable results.
9288869 Granulocytapheresis in the treatment of patients with rheumatoid arthritis. 1997 Sep The G-1 column is an extracorporeal type granulocytapheresis device packed with 220 g cellulose acetate beads to which granulocytes and monocytes specifically adhere. A total of 59 rheumatoid arthritis patients with elevated granulocyte counts from 4 hospitals in Japan received 2 apheresis sessions of 1 h duration/week for a total of 8 times over a period of 4 weeks. About 55% of the leukocytes which entered the G-1 column were adsorbed onto the beads: 95% were granulocytes, 3.5% monocytes, and 0.4% lymphocytes. Clinical and efficacy assessments showed improvements in swollen joints (p < 0.01), tender joints (p < 0.001), the active joint score (p < 0.001), duration of morning stiffness (p < 0.01), and grip strength (p < 0.001). In good responders, the improvements were observed for up to 12 weeks following the last apheresis. Exacerbation was noted in 2 patients. It is suggested that the efficacy of the G-1 column is attributable to the removal or suppression of hyperactive leukocytes and inflammatory cytokines, inducing a kind of immunomodulation.