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ID PMID Title PublicationDate abstract
8210919 A comparison of the efficacy of etodolac SR (Lodine SR) and etodolac (Lodine) in patients 1993 The efficacy and safety of a sustained-release (SR) formulation of etodolac were compared with those of conventional etodolac in two separate, randomized, double-blind, multicenter, 6-week trials. This report presents an interim analysis of the data from these studies. One study included 174 patients with rheumatoid arthritis (RA): 58 received etodolac SR 400 mg once daily (q.d.), 59 received etodolac SR 600 mg q.d., and 57 received etodolac 200 mg twice daily (b.i.d.). The second study included 230 patients with osteoarthritis (OA): 80 patients received etodolac SR 400 mg q.d., 76 received etodolac SR 600 mg q.d., and 74 received etodolac 300 mg b.i.d. Efficacy was evaluated by physician's global and patient's global assessment (both studies), number of painful joints (RA study), number of swollen joints (RA study), pain intensity (OA study), and weight-bearing pain (OA study). The interim analyses of the data from the studies indicates that all three regimens produced significant improvements from baseline in all mean efficacy values at each assessment; there were no significant differences between the treatment groups. The incidence of study events, except for dyspepsia, was comparable among the treatment groups in each study; dyspepsia occurred at a significantly lower rate in patients treated with etodolac SR than in patients treated with the conventional formulation of etodolac. We conclude that etodolac SR is as effective and safe as conventional etodolac for the treatment of patients with RA or OA.
8724311 Diffuse interstitial pulmonary amyloidosis in rheumatoid arthritis. 1996 May We describe a woman with seronegative rheumatoid arthritis (RA) who presented with diffuse septal pulmonary amyloidosis mimicking interstitial rheumatoid lung disease. Her systemic amyloidosis was diagnosed by biopsy of the kidney, stomach mucosa, and salivary glands 28 years after the onset of RA. Diffuse interstitial pulmonary infiltrates had been noted since that diagnosis, but infiltrates had been considered due to rheumatoid lung. Results of pulmonary function tests, which revealed restrictive changes and decreased diffusion capacity, were also compatible with rheumatoid lung disease. Pulmonary amyloidosis was diagnosed at autopsy. Pulmonary amyloidosis should be considered a cause of pulmonary infiltrates in patients with longstanding RA.
9014584 Development of a functional scoring system for rheumatoid arthritis patients with cervical 1996 Dec OBJECTIVE: To be able to measure disability objectively in rheumatoid arthritis complicated by cervical myelopathy. METHODS: The responses to the Stanford health assessment questionnaire disability index were recorded from 250 consecutive patients (group 1) referred to our unit for spinal surgery. Using principal components analysis the questionnaire was reduced from 20 questions to 10 questions. In the second part of the study, the results of the questionnaire for those patients undergoing surgery from the original group of 250 patients were analysed with respect to outcome. RESULTS: The reduction in the number of questions results in no significant loss of information, reliability (internal consistency Cronbach's alpha = 0.968) or sensitivity. The new scale, the myelopathy disability index, measures only one dimension (Eigen value 6.97) and may be more finely tuned to the measurement of disability in these myelopathic patients. When administered to the 194 patients undergoing cervical spine (group 2) surgery the myelopathy disability index was an accurate predictor of neurological and functional outcome, as well as survival following surgery (P < 0.0001). CONCLUSIONS: The myelopathy disability index provides a much needed objective and reliable means of assessing disability in patients with rheumatoid involvement of the cervical spine and also in predicting outcome following surgical intervention. It also provides information for both the patient and surgeon alike, on what to realistically expect from surgery. Its adoption should facilitate comparisons between different forms of surgical intervention.
7788332 HLA-DPB1*0201 is associated with particular clinical features of rheumatoid arthritis. 1995 Mar AIMS: to determine the effect of HLA-DPB1 status on rheumatoid arthritis (RA) susceptibility and disease expression. METHODS: HLA-DPB1 alleles were identified in 158 RA patients and 106 controls using PCR-sequence specific oligonucleotide probing. HLA-DPB1 allele frequencies were compared between patient and control groups and the strength of associations assessed using odds ratios and with 95% confidence intervals (CI). Associations observed in the total RA group were confirmed using a relative predispositional effect (RPE) analysis. RESULTS: an association between DPB1*0201 and RA was observed (OR 1.8, 95% CI 1.0-3.4). By contrast, negative associations were found with DPB1*0301 (OR 0.5, 95% CI 0.3-1.0) and DPB1*1101 (OR 0.06, 95% CI 0.001-0.5). These associations were confirmed using RPE analysis. On further analysis the increase in DPB1*0201 and decrease in DPB1*0301 frequencies in RA was found to be independent of DR4 status. The association of DPB1*0201 with RA appears to be most pronounced in male patients (OR 3.3, 95% CI 1.3-8.3), seronegative patients (OR 2.6, 95% CI 0.9-7.3) those with non-erosive disease (OR 2.6, 95% CI 0.9-7.3) or in patients with high titre antinuclear antibodies (OR 2.4, 95% CI 0.8-7.1). CONCLUSIONS: HLA-DPB1 alleles may be associated with the pattern of disease expression in certain RA patients and in some cases confer protection against disease.
7597377 Does the serum level of IgA-alpha-1-antitrypsin complex correlate with radiological progre 1995 We followed the levels of serum IgA-alpha-1-antitrypsin (IgA-AT) complex in 37 patients with early rheumatoid arthritis (RA) during the first 3 years of the disease. The changes in IgA-AT were correlated with a radiological damage score (DS) of the hands assessed according to Larsen. At the onset of the disease, the IgA-AT serum concentration was significantly higher as compared to the control group (0.72 +/- 0.22 U vs 0.29 +/- 0.14 U, P < 0.01). The level significantly decreased during the 3-year observation period. The DS was significantly higher after 3 years. However, this difference was due to changes in only 11 patients; in 26 patients the DS was almost unchanged. In the group of 11 patients with radiological progression, the level of IgA-AT either remained high or increased significantly (0.95 +/- 0.18 U at the onset, 0.97 +/- 0.25 U after 3 years), whereas we observed a decrease in IgA-AT in 26 patients without radiological progression (0.63 +/- 0.16 U at the onset of the disease, 0.45 +/- 0.10 U after 3 years, P < 0.01). Moreover, a relationship between changes in IgA-AT serum level and radiological progression was shown (r = 0.60, P < 0.01). Our studies suggested that the relationship between IgA-AT level and radiological progression of the disease should be considered. We cannot exclude the possibility that the constant high level of IgA-AT may cause worsening in bone erosions.
1534001 Increase in neutrophil Fc gamma receptor I expression following interferon gamma treatment 1992 Apr The therapeutic potential of interferon gamma (IFN gamma) in a number of disease states is still being explored, but progress is hampered by the lack of a suitable measure of in vivo biological activity. To assess the in vivo biological effects of recombinant human IFN gamma (rhIFN gamma), 14 patients were studied in a randomised, prospective, double blind, placebo controlled trial of this cytokine for the treatment of rheumatoid arthritis. The levels of Fc gamma receptors on peripheral blood neutrophils were measured at baseline and after 21 days of once daily, subcutaneous injections of rhIFN gamma or placebo. An induction of neutrophil Fc gamma receptor type I (Fc gamma RI) was seen in the group of patients receiving recombinant human rhIFN gamma but not in those receiving placebo. No change in the expression of Fc gamma RII or Fc gamma RIII was detected. The amount of induction of Fc gamma RI detected on the neutrophils of patients receiving rhIFN gamma did not correlate with clinical measures of response at either 21 days or at the end of the study (24 weeks). No significant clinical responses were observed in the rhIFN gamma group at these times. These data confirm that the reported in vitro effect of IFN gamma on human neutrophil Fc receptor expression can be reproduced in vivo.
8774168 Urinary glucaric acid excretion in rheumatoid arthritis: influence of disease activity and 1996 Jul OBJECTIVE: To examine if a correlation exists between cytochrome P-450 enzyme induction and disease activity in patients with rheumatoid arthritis (RA), measuring urinary excretion of D-glucaric acid (GA) as an index of phase II drug metabolism. METHODS: Patients with RA were treated with sulphasalazine, sodium aurothiomalate, or D-penicillamine in standard dose regimens, for 24 weeks. Patients with ankylosing spondylitis (AS) or non-inflammatory arthritis (NIA) acted as controls. The urinary GA:creatinine ratio was measured at 0, 12, and 24 weeks of treatment. RESULTS: Patients with RA had a slightly greater urinary GA:creatinine ratio than patients with AS or NIA at baseline; this increased during treatment with disease modifying antirheumatic drugs (DMARDs). Sulphasalazine treatment had a greater effect on GA excretion than sodium aurothiomalate or D-penicillamine; this difference was statistically significant between weeks 0 and 12 (p = 0.01). Gamma glutamyltranspeptidase concentration showed a weak correlation with GA excretion between weeks 0 and 12 (p = 0.03), but all other measurements of changes in disease activity (plasma viscosity, C reactive protein, platelets, and articular index) were found not to correlate with GA excretion between weeks 0-12 or 0-24. CONCLUSION: The increased excretion of GA in patients with RA receiving DMARD treatment is probably the result of an indirect effect on hepatic metabolism bearing no relationship to disease activity.
7543497 Collagen-induced arthritis in the BB rat. Prevention of disease by treatment with CTLA-4-I 1995 Aug Antigen-specific T cell activation requires two independent signalling events, one mediated through T cell receptor engagement by the antigen-presenting cell-expressed peptide/class II major histocompatibility complex, and the second through the cognate interactions of costimulatory molecules expressed on the T cell and antigen-presenting cell. There is evidence from in vitro and in vivo experimental systems suggesting that the CD28/B7 costimulatory pathway is crucial for induction of maximal T cell proliferation and T helper-B cell collaboration for IgG production. This pathway can be blocked by CTLA-4-Ig, a soluble form of CTLA-4 which binds with high avidity to the CD28 ligands, B7-1 and B7-2. Here, we show that CTLA-4-Ig treatment prevents clinical and histological manifestations of disease in a collagen-induced arthritis model of rheumatoid arthritis in the diabetes resistant BB/Wor rat, when therapy is initiated before immunization with bovine type II collagen (BIIC). Anti-BIIC antibody titers are reduced in CTLA-4-Ig-treated rats compared to diseased control animals. Histologically, joints from CTLA-4-Ig-treated animals show no histological abnormalities, in contrast to control antibody-treated animals, which show complete erosion of the articular cartilage and bone. Despite the efficacy of CTLA-4-Ig in preventing clinical and histological signs of arthritis and reducing antibody responses to BIIC, delayed type hypersensitivity responses to collagen 18 d or more after CTLA-4-Ig treatment ends are similar in CTLA-4-Ig-treated and untreated rats, suggesting that the prolonged disease suppression observed does not result from induction of T cell anergy.
8876948 Diagnostic radiography in rheumatoid arthritis: benefits and limitations. 1996 Aug In the light of more modern techniques such as sonography and magnetic resonance imaging, the reader may well ask if plain radiography has still a role in the diagnostic work-up of rheumatoid arthritis. However, in daily routine, the value of diagnostic radiography in support of the clinical and laboratory diagnosis of rheumatoid arthritis is unrivaled. It allows differentiation from other joint diseases, such as osteoarthritis or crystal arthropathies, when the ARA criteria are not conclusive for the diagnosis of rheumatoid arthritis. Further, plain radiography is part of the basic documentation of the disease in measuring disease progression. Therapeutic decisions, such as systemic versus local therapy, and selection of drugs, as well as the form of local therapy, are heavily dependent on radiographs. However, the limitations of radiography in evaluating disease progression have to be recognized. Ultrasonography, as a 'bedside method', and MRI are indispensable adjuncts to radiography, because they are superior in detecting synovitis, early forms of cartilage damage as well as bone reaction such as erosions and cysts. A superior assessment of the degree of synovial changes is also possible with MRI.
1561484 [The validity and reliability of the Italian version of the Arthritis Impact Measurement S 1992 Jan The validity and the reliability of the Italian version of AIMS (Arthritis Impact Measurement Scales) was tested in Rheumatoid Arthritis (RA). The factorial analysis performed on tests obtained from 274 patients showed a strict similarity with the original version. The five extracted factors (upper-limb function, lower-limb function, psycho-affective dimension, social dimension and pain) explain 80% of the common variance. The internal consistency (Cronbach's alfa coefficient = 0.78) and the test-retest performance (r = 0.86) support the reliability of the Italian AIMS. The analysis of the correlations with clinical parameters (the Ritchie's and Thompson's articular indexes, the systemic Lansbury's index, the joint count, the grip strength and morning stiffness), with pain measures (VAS, MPQ, PPI) and psychometric measures (ZDI, ZAI) assessed in 143 out of 274 patients, demonstrates the concurrent validity. The results show that the Italian version of AIMS is a practical value in the management of RA patients. The construct certainly allows its application even in other common chronic diseases.
1289143 Corneal autoimmunity in patients with peripheral ulcerative keratitis (PUK) in association 1992 Serum antibodies to the cornea were investigated in patients with peripheral ulcerative keratitis (PUK) in isolation or in association with a systemic disease (rheumatoid arthritis or Wegener's granulomatosis). Indirect immunofluorescence on bovine corneal sections demonstrated that antibodies bound to epithelial antigens in two distinct patterns: a lattice-like pattern, probably staining intercellular membrane antigens, and a diffuse pattern covering the entire surface of the epithelium. Both patterns were associated with PUK rather than systemic disease whilst the presence of the lattice pattern was more associated with the onset of the PUK. Immunoblotting of sera to corneal epithelial protein extracts demonstrated that a number of corneal antigens were targeted by antibodies. Two antigens, 54 kDa and 70 kDa, were of particular interest. Antibodies to the 54 kDa antigen, the major corneal-specific antigen, were also detected by enzyme-linked immunosorbent assay (ELISA). Longitudinal studies showed that these antibodies often first occurred after an episode of PUK. Antibodies to the 70 kDa antigen were related to the Wegener's granulomatosis rather than the PUK.
8690077 The C1q binding activity of IgG is modified in vitro by reactive oxygen species: implicati 1996 Jun 17 IgG can be denatured in vitro by reactive oxygen species (ROS). Native IgG activates the complement cascade through C1q. Using a modified ELISA, C1q binding activity of rheumatoid IgG has been compared to IgG denatured by neutrophil-derived ROS. The C1q binding activity of rheumatoid synovial fluid IgG is greater than the corresponding serum IgG (P < 0.01). Denaturation of IgG by activated polymorphs or the Fenton reaction decreased its C1q binding activity (P < 0.01). In vitro exposure of IgG to OH. and ROO. increased its interaction with C1q (P < 0.01). Hypochlorous acid had no effect. ROS-induced alteration to IgG-C1q binding activity may promote the inflammatory response in rheumatoid arthritis.
8833062 Clinical pharmacology of combination DMARD therapy in rheumatoid arthritis. 1996 Mar Knowledge about disease modifying antirheumatic drug (DMARD) mechanism(s) of action, kinetics and toxicities can be used to help develop rational DMARD combinations. While limited by the present lack of knowledge in these areas, the present DMARD characteristics will be used to develop rational DMARD combinations. Combinations of methotrexate (MTX) plus azathioprine, and MTX plus gold might be expected to be poor DMARD combinations, a prediction borne out by experimental studies. MTX plus cyclosporine, on the other hand, should be an effective combination, again demonstrated by a recently published clinical study. Also, hydroxychloroquine plus MTX should be a good combination, and an observational study seems to support this. However, not all predictions are accurate (probably due to inadequate data about mechanisms, kinetics, and toxicities). For example, hydroxychloroquine plus D-penicillamine had a negative interaction when tested, a result not predicted by the suggested approach. In addition, predictions are inevitably oversimplified so that what appears to be a negative interaction between MTX and sulfasalazine is not actually one when the details of the potential negative interaction between these 2 drugs are examined. Ultimately, use of a construct such as the one suggested should improve the chances of success and decrease the costs of testing DMARD drug concentrations.
1411083 Spontaneous expression of immediately-early response genes c-fos and egr-1 in collagenase- 1992 In view of the important role of interstitial collagenase in the pathogenesis of rheumatoid arthritis (RA), we studied the expression of fibroblast-type collagenase in rheumatoid synovium and searched for its potential transcription factors, namely the oncoprotein c-fos and the early-growth-response gene-1 (egr-1), an inducible zinc-finger encoding gene. Elevated levels of RNA sequences complimentary to c-fos and egr-1 cDNA probes could be detected in cytoplasmic extracts of collagenase-expressing synovial fibroblast-like cells when compared to equivalent RNA amounts isolated from control fibroblasts. Utilizing immunocytochemistry, immunoreactivity for c-fos oncoprotein was found in 13 of 19 joint specimens obtained from patients with active RA. These oncoprotein data were positively correlated to the collagenase expression in the same specimens. Moreover, immunohistochemical analysis confirmed the localization of both oncoprotein c-fos and fibroblast-type collagenase within synovial fibroblast-like cells attached to bone erosions.
9103057 [Quantification of macrophages and granulocytes at the joint cartilage-pannus junction in 1996 Nov Rheumatoid-Arthritis (RA) is a systemic disease with chronic joint inflammation caused by complex immune mechanisms. Aim of our study was the analysis of the distributions of macrophages and neutrophils at the cartilage-pannus junction in order to assess the possible functional relationship of both cell types in cartilage damage. We used 39 samples of synovectomies from patients suffering from RA. The samples were stained by histological (Hematoxilin-Eosin, HE), enzymehistological (Naphtol-ASD) and immunohistochemical (Peroxidase-antiperoxidase, alkaline phosphatase-antialkaline phosphatase) techniques and examined by light microscopy. Lysozyme alpha-1-antitrypsin and alpha-1-antichymotrypsin were stained with peroxidase-antiperoxidase-technique, the monoclonal antibody for macrophages CD 68 were used in alkaline phosphatase-antialkaline phosphatase technique. We found a clear domination of macrophages at the cartilage-pannus junction compared to the number of neutrophils. Over 90% of the analyzed cells were identified as macrophages, which were presumably activated macrophages. The macrophages accumulated directly underneath the erosion front and infiltrated the cartilage. The cartilage showed erosions with clear infiltrations by macrophages. We conclude that this distribution is a clear sign of active cartilage destruction by macrophages and emphasize their role in perpetuation of the rheumatoid inflammation.
8575145 Cytidine deaminase may be a useful marker in differentiating elderly onset rheumatoid arth 1995 Sep OBJECTIVE: PMR/GCA is a relatively common inflammatory disease in the elderly population. Clinical differentiation from a polymyalgic onset of RA in the elderly can be difficult. We have examined in a preliminary study the hypothesis that serum cytidine deaminase (CD) may be valuable in the differential diagnosis of these disorders. METHODS: CD was assayed by a spectrophotometric method in 20 patients with active PMR/GCA, both before and after treatment with prednisolone, and was compared with serum CD levels in 20 patients with active RA. RESULTS: CD levels were within the normal range (< 10 units/ml) in 36 of the 40 samples from patients with PMR/GCA: The mean CD in pre-treatment samples was 8.64 units/ml (SD 7.09), and after treatment 7.20 units/ml (SD 3.53). The mean serum CD in the RA patients was 21.33 units/ml (SD 8.94), significantly higher than in PMR/GCA (p < 0.0001). CONCLUSION: Serum CD levels were significantly different when proven PMR was compared with established, long-standing RA. Therefore, serum CD could be a useful diagnostic marker for differentiating PMR/GCA from active RA in older patients.
8480035 [Magnetic resonance in the diagnosis of lesions of the carpal triangular fibrocartilage. T 1993 Jan In order to evaluate the diagnostic capabilities of MR Imaging in defining triangular fibrocartilage (TFC) lesions, 49 selected patients--21 with rheumatoid arthritis, 13 with traumatic injury and 15 with wrist fracture--presenting chronic wrist pain were examined with MR Imaging. The wrists of 12 healthy subjects were also studied as a control group. MR examinations were performed by means of a superconductive 1.0 T unit (Magnetom-Siemens); SE and GE T1- and T2-weighted pulse sequences were employed to acquire images of the wrists on the coronal, axial and, if necessary, sagittal planes. The results showed peripheral TFC tears in 10 cases, central TFC lesions in 12 cases and TFC lesions with collateral insertion involvement in 9 cases. In 4 patients focal thickening of TFC without disruption was observed. The correct diagnosis was made in all the 19 surgically verified cases. Our experience confirms the clinical value of MR Imaging in the evaluation of TFC lesions in patients with chronic ulnar pain syndrome.
1349846 Fatal neutropenic enterocolitis associated with sulphasalazine therapy for rheumatoid arth 1992 May Neutropenia is a recognized complication of sulphasalazine therapy in patients with rheumatoid arthritis. It is usually mild, transient and rarely associated with serious sequelae. We describe a patient with rheumatoid arthritis who developed fatal neutropenic enterocolitis complicated by tracheo-oesophageal fistula following treatment with sulphasalazine.
8448633 Approaches to the management of rheumatoid arthritis: rationale for early combination ther 1993 Mar In evaluating current therapy of RA, it is becoming recognized that sequential single drug treatment, as exemplified by the traditional therapeutic pyramid, is often too little and too late in patients with aggressive 'at risk' synovitis. Evidence exists that prevention of joint damage correlates best with control of clinical and laboratory measures of inflammation, regardless of the medication used. Until a major breakthrough occurs in this disease, it is recommended that patients with 'at risk' RA be treated aggressively to achieve early control of inflammation, and then 'bridge down' to a simplified maintenance programme. While currently available fast and slow acting drugs might be used in combination today for early induction therapy, newer drugs, cancer chemotherapeutic preparations, biologic agents, or novel therapies may prove more effective and superior tomorrow. Control trials will be necessary to establish the most effective and least toxic induction and maintenance programmes.
8188457 Effect of cyclosporin on the activity of cytidine deaminase and adenosine deaminase in the 1993 Cytidine deaminase (CDA) and adenosine deaminase (ADA) were investigated in the serum and polymorphonuclear leukocytes (PMNLs) of healthy controls and ten patients with rheumatoid arthritis before and during cyclosporin therapy. CDA was significantly raised in the serum and decreased in the cells of patients. A dramatic increase (10-fold or more) in CDA activity was observed in the cells of some patients after only one month of cyclosporin therapy. Serum CDA significantly increased after three months' therapy. While the increase in serum CDA level during therapy was transient, the enzyme level in cells remained permanently raised, as shown in two patients evaluated for sixteen months. ADA in the serum of RA patients was somewhat higher as compared with healthy controls and remained almost unchanged during cyclosporin therapy. ADA activity in the cells also increased, but compared with the increase in CDA activity this increase was lower. Cyclosporin increased both CDA and ADA activities in PMNLs of RA patients. The dramatic increase in CDA observed in PMNLs of patients could be the cause of the transient increase in CDA in the serum. Further investigations will show to what extent this property of cyclosporin can reflect the immunoregulatory effect of this drug.