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

ID PMID Title PublicationDate abstract
1279168 Chimeric CD7 monoclonal antibody therapy in rheumatoid arthritis. 1992 Sep Murine monoclonal antibody (Mab) therapy in patients with rheumatoid arthritis (RA) produces an antimouse immunoglobulin response by the recipient. We studied a chimeric (human/mouse) CD7 Mab, in a dose ranging tolerability study in 10 patients with RA. Modest improvements in disease activity occurred with frequent acute adverse effects of malaise, fever and nausea. After treatment, peripheral blood T lymphocyte numbers fell by 50% and CD7 expression fell by 97% for less than 7 days. Our study demonstrates chimeric Mab function in vivo and illustrates the influence of antibody isotype and patient characteristics on adverse effects.
7689748 Prevention of collagen-induced arthritis with an antibody to gp39, the ligand for CD40. 1993 Sep 3 The ligand for the CD40 antigen is a 39-kilodalton protein, gp39, expressed on the surface of activated CD4+ T cells and is essential for thymus-dependent humoral immunity. The role of gp39-CD40 interactions in autoimmune disease was investigated in vivo with the use of an antibody that blocks their interactions (anti-gp39). Arthritis induced in mice by immunization with type II collagen was inhibited by anti-gp39. Anti-gp39 blocked the development of joint inflammation, serum antibody titers to collagen, the infiltration of inflammatory cells into the subsynovial tissue, and the erosion of cartilage and bone. Thus, interference with gp39-CD40 interactions may have therapeutic potential in the treatment of autoimmune disease.
8282621 Effect of 8 wk of bicycle training on the immune system of patients with rheumatoid arthri 1993 Oct The effect of 8 wk of progressive bicycle training on the immune system was evaluated in a controlled study on 18 patients with rheumatoid arthritis and moderate disease activity. Maximal O2 uptake increased significantly, whereas heart rate at stage 2 and rate of perceived exertion decreased significantly, in the training group compared with the controls. Resting levels of a number of immune parameters were measured before and after 4 and 8 wk of training. Training did not induce changes in blood mononuclear cell subpopulations, proliferative response, or natural killer cell activity. Furthermore the plasma concentrations of interleukin-1 alpha, interleukin-1 beta, and interleukin-6 did not change in response to training. It is concluded that 8 wk of bicycle training does not influence the immune system of patients with rheumatoid arthritis.
8630106 Activation of the transcription factor nuclear factor-kappaB in human inflamed synovial ti 1996 Apr OBJECTIVE: The transcription factor nuclear factor kappaB (NF-kappaB) has been implicated in the inflammatory response and is known to be activated by a process involving reactive oxygen intermediates. The purpose of the present study was to demonstrate the presence and distribution of activated NF-kappaB in synovium samples from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and from autopsy subjects with no known history of arthritis. METHODS: Immunohistochemical staining was performed using both polyclonal and monoclonal "activity-specific" antibodies to the Rel-A (p65) subunit of NF-kappaB (anti-Rel-A nuclear location sequences). Histologic features of inflammation were also scored. RESULTS: Both antibodies demonstrated positive staining of synovial tissue, with a cellular distribution that was nuclear. The staining was associated with specific cell types within the tissue, in particular, type A synoviocytes and vascular endothelium. Notably, lymphoid aggregates were unstained. Using the monoclonal antibody, a further study was carried out to investigate the distribution of staining in tissues from patients with different disease activities and clinical diagnoses, as well as in normal control tissue obtained at autopsy. Patients with acute RA more commonly showed vessel staining (P = 0.05) and, conversely, showed less frequent staining of the synovial lining (P < 0.005) compared with OA patients. Synovial tissue from controls exhibited either no staining or only weak staining in the synovial lining. CONCLUSION: The activation of NF-kappaB in vascular endothelium and type A synovial lining cells is a feature of synovial tissue from both RA and OA patients. The distribution of this staining appears to be related to the clinical diagnosis.
1530567 Activation of neutrophil reactive-oxidant production by synovial fluid from patients with 1992 Sep 1 Cell-free synovial fluid from patients with rheumatoid arthritis stimulated the NADPH oxidase activity in human neutrophils, which reached a peak 15-20 min after addition. Insoluble immunoglobulin aggregates isolated from these fluids activated a similar pattern of oxidase activity. However, when synovial fluid was added to neutrophil suspensions which had been previously exposed to granulocyte-macrophage colony-stimulating factor, the stimulated oxidase activity was biphasic, in that an additional transient activity was observed which reached a peak within 5 min of addition. The additional neutrophil-stimulating activity could not be sedimented by centrifugation at 330,000 g-min, and only activated oxidase activity in neutrophils which had previously been primed. The neutrophil-stimulating activity in this soluble fraction was removed by Protein A affinity chromatography, and activity was recovered in eluates from this column. Thus activity in this soluble fraction from synovial fluid is attributed to the presence of soluble immunoglobulin aggregates. Whereas oxidase activity stimulated by the isoluble immunoglobulin aggregates was inhibited by staurosporine (and hence largely dependent on the activity of protein kinase C), the activity stimulated by the soluble immunoglobulin aggregates was staurosporine-insensitive. The soluble immunoglobulin aggregates were present at significantly higher levels in synovial fluids from patients with rheumatoid arthritis compared with those from other joint arthropathies. Thus rheumatoid synovial fluids possess heterogeneous immunoglobulin aggregates which activate neutrophils via distinct molecular pathways. As neutrophils within rheumatoid joints are primed, the soluble immunoglobulin aggregates are likely to be of importance in disease pathology.
8329189 Circulating tumor necrosis factor alpha in rheumatoid arthritis. 1993 Jan Tumor Necrosis Factor alpha is an important mediator of immunity and inflammation, and because of its biologic activities (activation of neutrophils, release of arachidonic acid metabolites from synovial cells, induction of cartilage resorption and inhibition of proteoglycan release in cartilage) is one of the potential mediators of the chronic inflammation in rheumatoid arthritis. A commercially available ELISA was used to evaluate serum levels of Tumor Necrosis Factor alpha (TNF alpha) in patients with rheumatic diseases. We tested sera from patients with rheumatoid arthritis, seronegative arthritis, osteoarthritis, post-traumatic arthritis, systemic lupus erythematosus, progressive systemic sclerosis and normal healthy subjects as controls. Furthermore, we statistically analysed data to investigate whether a correlation exists between serum levels of TNF alpha and some humoral indexes of disease activity. The results show strikingly higher TNF alpha levels in Rheumatoid Arthritis patients when compared both to normal controls and arthritis or connective tissue disease controls. TNF alpha was also found to correlate positively with levels of the rheumatoid factor as measured either by means of the latex agglutination test (LAT) or by nephelometry. These results support the suggestion that TNF alpha plays a central role in the pathogenesis of rheumatoid arthritis.
7546814 [Myokimia induced by gold salts]. 1995 Jun We report a 44 year old male suffering from rheumatoid arthritis that developed myokymias when treated with gold salts. Myokymia is a clinical phenomenon characterized by involuntary repetitive contractions of muscle fibres, which give an undulating appearance to the overlying skin, last a few seconds, and with a typical electromyographic activity described as myokymic discharges. The difference between the single twitch of the fasciculation and the tetanic contraction of myokymia may be evident only on electromyography in difficult cases. Neurological complications associated with gold are infrequent, and they include myokymia, peripheral neuropathy, Guillain-Barré syndrome, cranial nerves paralysis and encephalopathy.
1609082 Small bowel stricture caused by rheumatoid vasculitis. 1992 Jul Small bowel involvement in rheumatoid arthritis is rare and is caused by vasculitis, which results in ulceration, perforation, and necrosis of the small bowel. The authors present a case of rheumatoid vasculitis associated with a small bowel stricture. The patient had a 3-week history of daily postprandial bloating, abdominal cramping, and vomiting. Barium study demonstrated partial small bowel obstruction. Pathologic examination of a resected segment of the small bowel proved that the stricture was caused by rheumatoid vasculitis. To the authors' knowledge, this is the first reported case of such an association in the radiology literature.
8371206 A reevaluation of the symptom of morning stiffness. 1993 Jul OBJECTIVE: To study, both qualitatively and quantitatively, morning stiffness in consecutive patients attending a rheumatology clinic. METHODS: A detailed interview from 93 patients with rheumatoid arthritis (RA) and 46 patients with noninflammatory joint disease. RESULTS: Occurrence, duration and severity of morning stiffness were similar in both groups, as was its detailed qualitative description. Patients with RA with active disease had higher severity scores of morning stiffness than those with inactive disease. CONCLUSION: Morning stiffness is a poor discriminator between RA and noninflammatory joint disease. Its assessment by a severity score is better than one based on duration.
8857074 A limited sampling method to estimate methotrexate pharmacokinetics in patients with rheum 1996 This paper describes a methodology to calculate methotrexate (MTX) pharmacokinetic parameters after intramuscular administration using two samples and the population parameters. Total and free MTX were measured over a 36-h period in 56 rheumatoid arthritis patients; 14 patients were studied after a two-dose scheme at 15-day intervals. The Hill equation was used to relate the free MTX to the total MTX changes in plasma concentrations, and a two-compartment open model was used to fit the total MTX plasma concentrations. A non-linear mixed effect procedure was used to estimate the population parameters and to explore the interindividual variability in relation to the following covariables: age, weight, height, haemoglobin, erythrocyte sedimentation rate, platelet count, creatinine clearance, rheumatoid factor, C-reactive protein, swelling joint count, and Ritchie's articular index. Population parameters were evaluated for 40 patients using a three-step approach. The population average parameters and the interindividual variabilities expressed as coefficients of variation (CV%) were: CL, 6.94 l center dot h-1 (20.5%); V, 34.8 l (32.2%); k12, 0.0838 h-1 (47.7%); k21, 0.0769 h-1 (61.6%); ka, 4.31 h-1 (58%); Emax, 1.12 mu mol center dot l-1 (19.7%); gamma, 0.932 (12.3%); and EC50, 2.14 mu mol center dot l-1 (27.3%). Thirty additional data sets (16 new patients and 14 patients of the previous population but treated on a separate occasion) were used to evaluate the predictive performance of the population parameters. Twelve blood samples were collected from each individual in order to calculate individual parameters using standard fitting procedures. These values were compared to the ones estimated using a Bayesian approach with population parameters as a priori information together with two samples, selected from the individual observations. The results show that the bias was not statistically different from zero and the precision of these parameters was excellent.
8275585 Down-regulation by eel calcitonin of interleukin-1 release and production by peripheral bl 1993 Sep To clarify the reason for the therapeutic efficacy of Elcatonin (eCT), an eel calcitonin derivative, in rheumatoid arthritis (RA), we studied the effect of eCT on the extracellular (EC) release and intracellular (IC) production of interleukin-1 (IL-1) by peripheral blood monocytes from patients with RA. In vitro treatment of RA monocytes with eCT reduced predominantly the EC release of both IL-1 alpha and IL-1 beta. Moreover, EC release and IC production of IL-1 alpha and IL-1 beta by monocytes from RA patients who received non-steroidal anti-inflammatory drugs (NSAIDs) plus eCT (CT group) were significantly lower than in those who received NSAIDs only (NSAID group). The anti-rheumatic effect of eCT may be mediated via the inhibition of EC release and the IC production of IL-1 from RA patients.
7634701 The use of grommets for flexible hinge toe implants. A case report. 1995 Jul The postmortem examination of bilateral first metatarsophalangeal flexible hinge toe implants in a 66-year-old woman with rheumatoid arthritis is reported. The prosthesis had been inserted with grommets in 1 joint and without grommets in the other 2.5 years before her death. The implants were removed, and the bone/implant interfaces were examined microscopically by hematoxylin eosin stains and an electron probe microanalyzer. Surfaces of the implants were examined by scanning electron microscopy. Silicone particles within the fibrous tissue at the bone/implant interface, and a tear and significant scuffing of the implant surface, were detected in the joint without grommets. Such changes were not detected in the joint with grommets. These findings suggest that grommets may improve implant durability and preventing silicone synovitis.
1295222 [The therapeutic action of the low-water bulk of therapeutic sea mud]. 1992 Sep Clinical and laboratory investigations were carried out in 404 patients with rheumatoid arthritis and 205 with osteoarthrosis deformans, treated either with low-water curative sea mud mass, native sea mud or with combined mud and radon-bath treatment. It was found that reducing the water content of Haapsalu sea mud did not essentially influence the therapeutic effect, in consequence of which the low water curative sea mud mass may be successfully used in the treatment and rehabilitation of various patients.
7720354 [Intra-articular treatment with somatostatin 14 in rheumatoid arthritis]. 1994 Dec 19 patients with RA underwent six intraarticular injections of 750 micrograms of Somatostatin 14 in one knee at 15-day intervals. In all patients some clinical parameters were evaluated: articular function, pain on pressure, spontaneous pain, pain on movement, duration of morning stiffness. Also some laboratory parameters were examined: complete blood cell count, ESR and CRP. An overall and significant improvement of the symptomatology of the treated knee was seen in all patients especially after the 3rd infiltration and still more after the 5th. At follow up 3 months after the end of treatment 12 patients were controlled, 11 of these showed a persistence of the improvement. No side-effects were seen.
8978957 D-penicillamine in early rheumatoid arthritis: experience from a 2-year double blind place 1996 Nov OBJECTIVE: To evaluate the usefulness of early treatment with D-Penicillamine (DPA) in rheumatoid arthritis. METHODS: The patients were recruited from a Swedish early RA cohort comprising 180 patients. All patients experiencing active and/or erosive disease 2 years from onset were asked to participate in a 2-year placebo-controlled DPA trial. Previous treatment with slow-acting anti-rheumatic drugs (SAARDs) or oral corticosteroids was not allowed. The main outcome variable was radiographic progression in the hands and feet evaluated according to Larsen. Clinical assessment including the Ritchie index, active joint count, and the HAQ-disability index was performed every 6th month. Patients were included in the analyses of efficacy until the endpoint of therapy. RESULTS: 111/180 patients were eligible for treatment, and 74 agreed to participate in the trial. 21/33 patients on DPA and 22/41 on placebo completed the study. More patients taking placebo stopped due to lack of response (p < 0.01). 27% of the patients on DPA were withdrawn due to side effects. Radiographic deterioration increased but most clinical variables improved in both trial arms. A large inter-individual variation was observed. The only significant difference in trend over 2 years between DPA and placebo was found for joint tenderness. However, the median trends for most clinical variables showed a more positive effect for DPA. The 37 patients who refused to participate in the trial in general fared somewhat worse than patients taking DPA and somewhat better than patients taking placebo. The remission rate was about the same in all 3 groups (12-13.5%). CONCLUSIONS: About two-thirds of all early definite RA patients were eligible for treatment using current criteria. Psychological readiness for early therapy was fairly modest with a high refusal rate. The difference in efficacy between DPA and placebo was small, but was in favour of DPA for most clinical variables. However, only joint tenderness showed a significantly better trend. No significant slowing of radiographic progression by DPA was found.
7664026 Circulating interleukin 10 and interleukin-6 serum levels in rheumatoid arthritis patients 1995 Jan In order to evaluate the relationship between serum concentrations of interleukin-10 (IL-10), IL-6, and acute phase proteins in rheumatoid arthritis (RA) patients treated with methotrexate (MTX) or intramuscular gold (IMG) we determined IL-10, IL-6, C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP) and alpha-1-antichymotrypsin (ACT) in the sera of 35 RA patients. IL-10 and IL-6 levels were evaluated using an enzyme-linked immunoassay (ELISA). AGP and ACT level were measured using rocket immunoelectrophoresis. IL-10 serum level was not increased in RA patients as compared to controls (58.7 +/- 18.1 pg/ml vs. 57.2 +/- 11.9 pg/ml). IL-6 level was significantly elevated (91.6 +/- 46.9 pg/ml vs. 45 +/- 19 pg/ml, p < 0.05). CRP was significantly increased as compared to healthy controls (35 +/- 19 mg/l vs. 3 +/- 2 mg/l, p < 0.05). Patients treated with MTX or IMG presented an increased level of IL-10 and decreased amounts of IL-6, as compared to those treated with NSAID only. However, only changes between patients treated with IMG and NSAID were found to be statistically significant. A good negative correlation between IL-10 and IL-6 serum level was found (r = -0.75, p < 0.05). A positive significant correlation between IL-6 serum level and CRP (r = 0.62, p < 0.05), AGP (r = 0.78, p < 0.05) and ACT (r = 0.45, p < 0.05) was established.(ABSTRACT TRUNCATED AT 250 WORDS)
8630820 [The combined use of diprospan and laser irradiation of the joints in rheumatoid arthritis 1995 May An evaluation was done of effectiveness of diprospane (prolonged action glucocorticosteroid) in rheumatoid arthritis. There have been studied parameters characterizing the articular syndrome, laboratory values during the course of complex therapy that incorporated intraarthrous administration of diprospane and a course of laser irradiation of the joints against a background of intake of non-steroid antiinflammatory preparations and basis therapy with methotrexate. Topical therapy incorporated into the complex of therapeutic measures applied in patients with rheumatoid arthritis was found to be associated with most stable and pronounced effect, especially in the arthrous form of the malady. Combined use of intraarthrous administration of diprospane and a course of laser therapy permits achieving a favourable effect after a single administration of this drug preparation.
1593585 Acute polyarthritis associated with birefringent lipid microspherules occurring in a patie 1992 Apr We describe a 52-year-old patient with longstanding rheumatoid arthritis (RA) who developed an acute polyarthritis of her hands and wrists. Synovial fluid analysis revealed the presence of intra and extracellular lipid microspherules with the typical appearance of Maltese crosses under polarized light microscopy. No other specific cause could be identified. This is the first description of an acute polyarthritis associated with lipid microspherules in RA.
8832981 Effects on fibrogenesis markers of rheumatoid arthritis therapy with methotrexate. 1996 Mar OBJECTIVE: To evaluate the level of 2 serum markers of hepatic fibrogenesis, aminoterminal peptide of type III procollagen (NPIIIP) and laminin P1 fragment (Lam), in patients with rheumatoid arthritis at baseline and after one year of low dose methotrexate (MTX) therapy. METHODS: Serum levels of NPIIIP and Lam were measured in 20 patients, 17 women and 3 men, mean age 48.83 +/- 9.25 yrs. before and after MTX treatment and compared to levels from 20 sex and age matched, healthy controls. RESULTS: The baseline values of NPIIIP was higher in patients than in controls; it normalized after MTX treatment. The Lam level did not differ between patients and controls; moreover, it did not change after treatment. CONCLUSION: Low dose MTX therapy does not increase serum indicator levels of hepatic fibrogenesis.
8274847 Tru-cut needle biopsy of subcutaneous fat in the diagnosis of secondary amyloidosis in rhe 1993 Summer In order to investigate the presence of secondary amyloidosis in patients with rheumatoid arthritis (RA), we performed an abdominal subcutaneous fat biopsy with a tru-cut needle in 50 patients. The tissue was stained with Congo red and was observed with polarized light microscopy. We found amyloid deposits in 78% of our patients. We randomly selected ten patients with a positive biopsy and a second procedure was performed. Tissues were studied with electron microscopy. We found unbranched fibrils characteristic of amyloid in all of them. We found a direct correlation with rheumatoid factor titers: the more intense the amyloid deposit, the higher the rheumatoid factor titers (p < 0.001). We did not find any correlation between amyloid deposits and clinical manifestations of disease. Amyloid deposits in RA are more frequent than previously thought, and their clinical importance remains to be determined.