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ID PMID Title PublicationDate abstract
7542003 Antibody reactivity to mycobacterial 65 kDa heat shock protein: relevance to autoimmunity. 1995 Apr Reactivity to the mycobacterial 65 kDa heat shock protein (HSP 65) has been implicated in the pathogenesis of adjuvant arthritis in the rat, and may be involved in the pathogenesis of rheumatoid arthritis or other autoimmune diseases in humans. Accordingly this study sought quantitative or qualitative differences in the antibody reactivity to HSP 65 between normal controls, patients with the multisystem autoimmune diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and patients with the mycobacterial infections, tuberculosis (TB) and leprosy. Levels of antibodies to recombinant HSP 65 in serum were measured by ELISA in normal subjects and in patients with RA, SLE, TB or leprosy. Antibody reactivity was examined by Western blotting using polypeptide fragments of HSP 65 derived by recombinant DNA techniques, or by digestion with trypsin or cyanogen bromide (CNBr). Reactivity to a synthetic peptide, the adjuvant arthritis T-cell epitope of HSP 65 (180-188), was tested by ELISA. High levels of antibodies to full length recombinant HSP 65 from Mycobacterium bovis were present in all the groups tested. By Western blot analysis, most reactivity with intact HSP 65 was retained in a 32 kDa tryptic fragment, judged by sequencing and size estimations to represent amino acid residues 118- approximately 388. This sequence included a major T-cell epitope for adjuvant arthritis (180-188), but these nine amino acids were not essential for B-cell reactivity since most sera also reacted with residues 188-540 which lack the T-cell epitope. Moreover, the 180-188 synthetic peptide was unreactive by ELISA, and did not inhibit reactivity with the intact recombinant HSP 65. In conclusion, most individuals had antibodies to mycobacterial HSP 65, presumably resulting from previous bacterial infections. The magnitude of the response was unrelated to the occurrence of systemic autoimmune disease, and the pattern of antibody reactivity with recombinant and proteolytic fragments of HSP 65 suggests that the major B-cell epitope is conformational and consists of discontinuous regions of the molecule.
8871262 Cellular activation products in osteoarthritis synovial fluid. 1995 In order to address the issue of the role of mast cells (MC) and nitric oxide (NO) in rheumatic synovial-fluid diseases, synovial fluid (SF) collected from the knee of patients with osteoarthritis (OA), articular chondrocalcinosis (ACC) or rheumatoid arthritis (RA) was examined for the levels of mast cells (MC), histamine, tryptase, phospholipase A2 and nitrite. MC counts were found to be elevated in the SF of OA patients as compared with RA patients. Histamine content in SF parallelled the number of MC. Tryptase levels were elevated in OA in comparison to RA and ACC, but the difference was not statistically significant. Identical PLA2 levels were recorded among the 3 groups. Nitrite concentrations were also higher in SF from OA patients as compared to RA patients. These results suggest that mast cells (MC), in association with various inflammatory cells, may contribute to inflammation and cartilage breakdown in osteoarthritis (OA).
1404159 Pathogenetic role of Chlamydia, Yersinia and Borrelia in undifferentiated oligoarthritis. 1992 Aug We studied the cellular and humoral immune response to Chlamydia trachomatis, Yersinia enterocolitica and Borrelia burgdorferi in paired samples of peripheral blood and synovial fluid (SF) in undifferentiated oligoarthritis, reactive arthritis (ReA) and rheumatoid arthritis. Antigen specific lymphocyte proliferation was found in SF of 43% of patients with ReA and 34% of patients with undifferentiated oligoarthritis. C. trachomatis was the most frequent single agent. HLA-B27 was positive in 83% of patients with ReA and in 62% of patients with undifferentiated oligoarthritis with antigen specific lymphocyte proliferation. Antigen specific lymphocyte proliferation correlated poorly with the specific antibody response. Only chlamydial antigen was detected in SF cells using monoclonal antibodies. We conclude that some patients with undifferentiated oligoarthritis may have a forme fruste of ReA. This finding is important in view of recent evidence supporting the efficacy of antibiotic therapy in ReA.
1398781 Profile of cytokines in synovial fluid specimens from patients with arthritis. Interleukin 1992 Jul The synovial fluid aspirated from patients with symptomatic arthritis was analyzed for the presence of tumor necrosis factor (TNF), interleukin 6 (IL-6) and interleukin 8 (IL-8). All three cytokines were found in both inflammatory and non-inflammatory arthritides: IL-8 levels ranged from less than 20 to 38,990 pg/ml, IL-6 from less than 10 to 72,300 pg/ml and TNF from less than 4 to 61 pg/ml. No inhibitors of cytokine activity were found. IL-8 and IL-6 were present in significantly higher levels in patients with inflammatory arthritis compared to patients with osteoarthritis, and there was significant correlation between the IL-6 and IL-8 levels. These findings document the presence of multiple cytokines in the synovial fluid specimens of patients with arthritis, and demonstrate that higher cytokine levels accompany inflammatory arthritis.
1550415 Comparison of two yttrium-90 regimens in inflammatory and osteoarthropathies. 1992 Feb Two yttrium-90 (90Y) radiosynovectomy procedures were compared. One procedure, performed at the Royal Perth Rehabilitation Hospital (RPRH) required a shorter immobilisation time than that performed at the Sir Charles Gardiner Hospital (SCGH). There were no significant differences in outcome between the two procedures for the groups with inflammatory and osteoarthropathy. Thirty two patients (45 joints) with inflammatory arthropathy were treated (25 with rheumatoid arthritis, three with psoriatic arthritis, two with ankylosing spondylitis, and two with unspecified inflammatory arthropathy) and 40 patients (58 joints) with osteoarthropathy. A separate assessment of local lymph node spread in patients treated by the RPRH showed a minor spread of 90Y in one of 37 joints assessed. A marked improvement in the patient evaluation scores in the inflammatory arthropathy group at three months persisted at 12 months. Good lasting responses were more common in patients with inflammatory arthropathy with a normal joint or early radiological disease. A marked improvement in the pain and evaluation scores occurred at three months in the group with osteoarthropathy but had disappeared by six months after treatment.
8228286 Human IgG preparations isolated by ion-exchange or protein G affinity chromatography diffe 1993 Nov 5 IgG from patients with rheumatoid arthritis (RA) is abnormally glycosylated in the Fc region, with sialic acid and galactose levels lower than normal. Protein G and DEAE purify populations which are differentially glycosylated. Significantly increased exposure of sialic acid was detected in normal IgG compared with that of RA IgG when ion exchange was used to prepare samples. However, when the same samples were prepared using protein G, no difference in the detection of sialic acid was seen between the two groups. When examining the heavy chain of IgG, more sialic acid, galactose and N-acetylglucosamine were detected in DEAE purified IgG compared with that prepared by protein G Detection of sialic acid and N-acetylglucosamine was also increased on light chains from IgG prepared by ion exchange chromatography. Since this occurs notably on rheumatoid light chains it would appear that this arrangement would contribute to the overall glycosylation changes in IgG. In the case of molecules lacking galactose the discrimination between the RA and normal IgG is significantly improved when ion exchange chromatography is used. Since differentiation between disease and normal groups relies on the purification technique used, we recommend that more than one method is employed before undertaking an analysis of glycosylation changes.
8882380 Meloxicam. 1996 Mar Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) developed for the treatment of rheumatoid arthritis and osteoarthritis. It has greater in vitro and in vivo inhibitory action against the inducible isoform of cyclo-oxygenase (COX-2), which is implicated in the inflammatory response, than against the constitutive form of this enzyme (COX-1), inhibition of which is associated with gastric, renal and other adverse effects. It has anti-inflammatory effects similar to or better than those of other NSAIDs in animal models, and a greater therapeutic ratio (ulcerogenic potential:efficacy in adjuvant arthritis). In healthy volunteers meloxicam 7.5 or 15 mg caused less gastrointestinal mucosal damage on endoscopy than piroxicam 20 mg, with a significant difference between meloxicam 7.5 mg and piroxicam. In comparative clinical trials, meloxicam was at least as effective as piroxicam and naproxen in patients with rheumatoid arthritis, and diclofenac and piroxicam in patients with osteoarthritis. Meloxicam was at least as well tolerated as piroxicam, diclofenac or naproxen overall but had improved gastrointestinal tolerability compared with these agents.
8187453 Effects of tenoxicam on neutrophil chemotaxis in rheumatoid arthritis and healthy controls 1994 Mar Using a modified Boyden chambers method, polymorphonuclear leucocyte (pmnl) random migration and chemotactic responsiveness were compared in 20 rheumatoid arthritis patients with that of 10 healthy controls receiving tenoxicam. Random migration and chemotaxis of neutrophils were examined before drug administration, following 2 hours and 7 days of drug administration and one week after the end of the 7-day-administration of this compound. There was no statistically significant difference between the chemotactic migration of neutrophils in healthy volunteers and patients with RA. The mean chemotactic value in patients with RA and healthy controls was significantly low at 2 hours after drug administration when compared with that before drug administration (p < 0.01). The comparison of the decreases in mean chemotactic values in patients with RA and healthy controls showed no statistical difference. At the end of 7-day-administration, neutrophil chemotaxis was significantly decreased in patients with RA (p < 0.01); however, in healthy controls it was decreased as well, but statistical difference could not be obtained. One week after drug withdrawal, neutrophil chemotaxis turned to baseline values in both groups. We suggest that tenoxicam is a potent inhibitor of neutrophil chemotaxis.
8070215 Risk factors affecting radiological failure of the socket in primary Charnley low friction 1994 Sep To identify the factors affecting Hodgkinson Type 3 or 4 radiological demarcation (presence of complete demarcation or migration, respectively) of the Charnley socket, 328 sockets with 10- to 20-year followup were studied. Fifty-five sockets (16.8%) developed Type 3 or 4 demarcation. In the osteoarthrosis group (237 sockets), removal of eburnated bone at the acetabular roof, the presence of large acetabular angles before and after surgery, and high placement of the socket were related to development of Type 3 or 4 demarcation. In the rheumatoid group (32 sockets), young patient age predisposed the socket to Type 3 or 4 demarcation. Rapid polyethylene wear, correlated with young age, male gender, and thin cement mantle in Zones I and II, was another important factor related to Type 3 or 4 demarcation in both groups and in the entire series. These risk factors should be taken into account when assessing the indications for arthroplasty, when performing arthroplasty, and when educating the patient.
8207227 High expression of V gamma 8 is a shared feature of human gamma delta T cells in the epith 1994 Jun 15 We have analyzed the V-gene usage in gamma delta T cells of the human gut and joint by using a new mAb (B18) specific for V gamma 8 of human TCR-gamma delta+ T cells. The B18+ population constituted a minor subset of the gamma delta T cells in peripheral blood (PB) of healthy persons (6 +/- 5%) and only 1 of 35 gamma delta T cell clones analyzed was positive. In contrast, the B18+ subset was a dominant gamma delta T cell population among intraepithelial lymphocytes (IEL) derived from the human intestine (74 +/- 29, p < 0.002), and two of three IEL clones from patients with coeliac disease were B18+. Interestingly, a higher proportion of B18+ gamma delta T cells was found in the synovial fluid of patients with rheumatoid arthritis (RA) (21 +/- 18%, 0.02 < p < 0.05) compared with normal PB. Furthermore, the B18+ subset was more frequent among IL-2-expanded gamma delta T cells (42 +/- 20%) derived from synovial tissue than among IL-2-expanded cells derived from synovial fluid (p < 0.002) and PB from RA patients (p < 0.02) as well as normal PB (p < 0.002). The V-gene usage of 13 gamma delta T cell clones from the synovial fluid of arthritic patients was analyzed. All B18+ clones (n = 7) expressed mRNA for V gamma 8 together with mRNA for V delta 1 (n = 5) or mRNA for V delta 3 (n = 2). None of the B18- clones expressed V gamma 8 (n = 6). We conclude that the gamma delta T cell that expresses V gamma 8, together with mainly V delta 1, is a major gamma delta T cell subset among the IEL of the gut and a highly frequent subset in the synovial tissue of patients with RA. This subset may correspond to the mouse V gamma 7+ IEL, which has a high degree of amino acid sequence homology with the human V gamma 8 protein.
7685686 Review of the safety of diclofenac/misoprostol. 1993 The safety of a fixed combination of diclofenac 50mg/misoprostol 200 micrograms has been evaluated in clinical trials involving almost 2000 patients. Short term trials have been conducted in patients with osteoarthritis (n = 1032) and rheumatoid arthritis (n = 685) over 1 or 3 months. Patients randomly received either diclofenac alone or diclofenac/misoprostol. In both groups, the most frequently reported adverse events were gastrointestinal in nature, with abdominal pain reported most frequently (in 22.6% of patients receiving diclofenac/misoprostol and 19.8% of patients receiving diclofenac), followed by diarrhoea (19.5 vs 11.3%), nausea (11.0 vs 6.5%) and dyspepsia (10.6 vs 7.8%). The most frequent nongastrointestinal adverse event was headache, which occurred in 7.9% of diclofenac/misoprostol recipients and 9.3% of diclofenac recipients. Although diclofenac/misoprostol was associated with a slightly higher prevalence of adverse events than diclofenac in these studies, the majority were of mild or moderate severity, and the treatment groups were similar as regards the number of patient withdrawals resulting from adverse events. An interim analysis of the results of an ongoing trial of longer term administration of diclofenac/misoprostol (for up to 24 months) has been conducted. In this uncontrolled study, patients with rheumatoid arthritis, osteoarthritis or ankylosing spondylitis received diclofenac/misoprostol for up to 24 months; to date 1003 patients have been enrolled and treatment has been continued for 6, 12, 18 and 24 months in 640, 327, 108 and 13 patients, respectively. As in the short term trials, the adverse events reported most commonly in this study have been predominantly gastrointestinal.(ABSTRACT TRUNCATED AT 250 WORDS)
7842536 Cutaneous infection with rapidly growing mycobacteria in patients with systemic rheumatic 1994 Sep We report two patients with systemic rheumatic disease being treated with steroids whose cases were complicated by subcutaneous nodules. In both, clinical and histological features suggested cutaneous infection and M. chelonae was isolated from skin specimens. Antibiotic therapy in both and surgery in one led to healing after a prolonged course. A review of the literature and our experience with these two patients suggest that rheumatic patients on steroid therapy are at risk of infection with these unusual pathogens. Knowledge of the risk factors and the distinctive picture of cutaneous mycobacteriosis should improve its diagnosis and therapy.
8448620 Systemic lupus erythematosus-like syndrome with focal proliferative glomerulonephritis dur 1993 Mar We report a patient with RA who developed serological evidence for lupus disease in the presence of a crescentic immune complex glomerulonephritis (GN). This occurred after 4 years therapy with penicillamine and resolved on withdrawal of this drug and following treatment with cyclophosphamide.
8496681 Clonal V alpha 12.1+ T cell expansions in the peripheral blood of rheumatoid arthritis pat 1993 Jun 1 Rheumatoid arthritis (RA) represents a heterogenous disease characterized by chronic polyarthritis. Most patients with adult RA inherit HLA-DR4 or -DR1 major histocompatibility complex (MHC) genes. While the molecular basis for this genetic predisposition is unknown, the major function of these MHC-encoded molecules is to present peptides to T lymphocytes. It is hypothesized that an endogenous or environmental antigen initiates a MHC-restricted immune response mediated by T lymphocytes, which is followed by a chronic inflammatory reaction involving many cell types. In chronic RA, previous or ongoing antigenic activation might result in detectable skewing of the peripheral alpha/beta T cell receptor (TCR) repertoire. Here we demonstrate a marked expansion of V alpha 12.1-bearing CD8+ T cells in the peripheral blood (mean, 22%; range, 10-43%) of > 15% of RA patients. A major proportion of these patients shared HLA-DQ2 in addition to the expected high frequency DR1 and DR4 alleles. Detailed molecular analysis in three of the RA patients with elevated V alpha 12.1+ T cells identified repeated TCR alpha chain sequences consistent with clonal V alpha 12.1+,CD8+ T cell expansion. In addition to shared TCR V alpha 12.1 germline gene usage among unrelated subjects, a conserved J alpha motif was also detected. Together, these results suggest an antigen-driven mechanism of T cell expansion in these patients and may offer a new approach in examining specific antigen that stimulate T cells in RA.
8091041 Analysis of repeated categorical data using generalized estimating equations. 1994 Jun 15 Moment methods for analysing repeated binary responses have been proposed by Liang and Zeger, and extended by Prentice and Zhao and Prentice. In these estimating equations, models are proposed for the correlation between the repeated binary responses. We extend Liang and Zeger's method to models for the correlation between repeated nominal or ordinal categorical responses; in particular, when the repeated responses are binary, our methods reduce to Liang and Zeger's method. Our method is illustrated with two datasets. One dataset contains repeated observations of self-assessment of arthritis, an ordered variable with three categories, collected during a randomized comparative study of alternative treatments of patients with rheumatoid arthritis. The second dataset is a longitudinal study of the health effects of air pollution, in which the repeated ordered multinomial response is the wheezing status (no wheeze, wheeze with cold, wheeze apart from cold) of a child at ages 9, 10, 11 and 12 years.
8065718 Histopathologic changes of the temporomandibular joint disk in patients with chronic arthr 1994 Jun Histopathologic examination was performed of the disk and the posterior attachment extirpated from 17 temporomandibular joints from 15 patients with chronic arthritic disease. Seven patients had rheumatoid arthritis (including two with juvenile type), five had ankylosing spondylitis, and three had psoriatic arthropathy, which affected more joints than the temporomandibular joint. Specimens removed from 16 temporomandibular joints from 15 patients with internal derangement were used for histopathologic comparison. In both groups of patients, inflammatory changes were observed, but no specific histopathologic signs could distinguish the groups. Patients with chronic arthritic disease seemed to have more pronounced changes of vascular proliferation, perivascular cellular infiltrate, inflammatory cells, and fibrosis throughout the soft tissues. Destruction of the disk was another finding evident in patients with chronic arthritic temporomandibular joint disease; there was no visible disk structure in 8 of these 17 joints, compared with 1 of the 16 joints in the internal derangement group.
7569402 Collagen vascular diseases. 1995 Jun Systemic lupus erythematosus, polymyositis/dermatomyositis, connective tissue disease, and polyarteritis nodosa are the collagen vascular diseases (CVDs) most likely to mimic pneumonia. All can be associated with an acute illness characterized by fever, cough, dyspnea, pleural symptoms, and an abnormal chest roentgenogram. Recognition of the CVD-associated pulmonary process requires sophisticated serological testing and chemical pleural fluid analysis coupled with the exclusion of pulmonary infection and pulmonary embolization. This review emphasizes the clinical characteristics of these CVDs, the diagnostic tests most helpful in recognizing them, and the differential diagnosis of pleuroparenchymal disorders that occur in these patients.
8372202 Cervical spine evaluation: efficacy of open-mouth odontoid view for nontraumatic radiograp 1993 Oct PURPOSE: The open-mouth odontoid view has been a standard component of radiographic cervical spine series regardless of setting or indication. This study examines the prevalence of disease in C-1 to C-2 in an outpatient setting for nontraumatic neck evaluations. MATERIALS AND METHODS: Reports of 1,033 nontraumatic cervical spine series on file at two large medical centers and at a large multispecialty clinic were reviewed retrospectively for patient characteristics, indications, and radiologic evaluations. RESULTS: The odontoid view in 10 patients demonstrated radiographic abnormalities in C-1 to C-2. Four of these patients had rheumatoid arthritis, two had metastatic carcinoma, one had Down syndrome, and the remaining three had no predisposing conditions for disease in C-1 to C-2. CONCLUSIONS: Odontoid view radiography is warranted in patients with conditions with increased risk for disease in C-1 to C-2, but for the vast majority of outpatients it is not worth the technical difficulty, radiation exposure, or expense.
8990934 [Clinical evaluation of immuno-serological laboratory data]. 1996 Dec Clinical evaluations of various laboratory data from immuno-serological tests such as rheumatoid factor, anti-nuclear antibody, and other auto antibodies were reviewed. Rheumatoid factors (RF) were discussed in relation to positivity in various diseases, immunoglobulin class of RF, and correlation between titers of RF and circulating immune complex (IC). As a result, higher frequency and higher titers of IgA-RF were found in Sjögren syndrome patients. Titers of RF did not show disease activity of RA, but those of ESR and CRP did. Anti-nuclear antibodies (ANA) were discussed in relation to positivity in healthy subjects, specific antibodies and corresponding specific disease, correlation among titers of anti-dsDNA antibody, CH50 and circulating immune complex. As a result, an ANA frequency of 40% was found in healthy young women. Values of CH50 were much better than ANA titers for evaluating clinical activity in SLE patients. Findings of anti-cardiolipin antibody in thrombosis patients with connective tissue vascular disease (CVD), anti-centromere antibody in various CVD patients as well as CREST patients and primary biliary cirrhosis patients and anti-neutrophil cytoplasmic antibodies in various vascular diseases along with inflammatory bowel disease patients were presented. Finally, useful laboratory data at different clinical steps such as diagnosis, evaluation of disease activity and estimation of prognosis were demonstrated in CVD.
8507221 Low-dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthr 1993 Jun OBJECTIVE: To determine whether the side effects of methotrexate can be decreased by the concurrent use of leucovorin, without affecting the efficacy of the methotrexate. METHODS: We conducted a multicenter randomized, double-blind, placebo-controlled trial of leucovorin administration, 2.5-5.0 mg orally, to be given 24 hours after the single, weekly, oral dose of methotrexate. Every 3 weeks for 52 weeks, patients were evaluated for rheumatic disease activity and side effects. Dosage adjustments for both methotrexate and leucovorin were made as needed, according to a defined protocol. The primary outcome evaluated was the frequency of study withdrawals because of side effects and/or inefficacy. Secondary outcomes evaluated included the frequency of side effects and the relative efficacy of methotrexate in the leucovorin and placebo treatment groups. RESULTS: Ninety-two evaluable patients were analyzed (44 took leucovorin and 48 placebo). Twenty-two patients withdrew early because of side effects unresponsive to our protocol, and 1 because of inefficacy; 17 had been taking placebo and 6 had been taking leucovorin (35% versus 14%, P < 0.02). The number of visits during which side effects were reported was reduced by almost 50% in the leucovorin treatment group (P < 0.001). There were significant reductions in the frequencies of all common side effects. At 52 weeks, disease activity was similar in both patient groups. CONCLUSION: The methotrexate-leucovorin protocol used significantly reduces common side effects of methotrexate therapy without significantly altering efficacy.