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ID PMID Title PublicationDate abstract
7987499 Determination of non-protein-bound iron in human synovial fluid by high-performance liquid 1994 Jun 17 Non-protein-bound iron in human synovial fluid was determined using high-performance liquid chromatography with electrochemical detection. The procedure was based on the separation of the iron-diethylenetriaminepentaacetic acid (DTPA) complex formed directly on a chromatographic column containing an anion-exchange resin followed by electrochemical detection. The method enabled more than 0.1 microM Fe(III) to be determined with an injection volume of 10 microliters. A mixture of synovial fluid, 20 microM DTPA and acetate buffer was incubated in the presence and absence of superoxide (O2-) generated by a xanthine-xanthine oxidase system and was ultrafiltered through a 30,000 molecular mass cut-off filter. No iron was detected in the ultrafiltrate at physiological pH. However, the presence of iron was observed in the ultrafiltrate at low pH, and O2- facilitated the release of iron into the synovial fluid. This result suggested that in an inflamed joint with generated O2- and decreased pH, iron may be released into the synovial fluid.
7682953 Human CD5-positive B cells in lymphoid malignancy and connective tissue diseases. 1993 Mar The current literature on human CD5-positive B cells (CD5 + B cells) has been analysed, with a special emphasis on non organ-specific auto-immune diseases. Malignant cells of most of the chronic lymphoid leukaemias of the B cell lineage express the CD5 molecule. Antibodies of the IgM class produced by leukaemic B cells are multispecific auto-antibodies. The CD5 + B cell subset may be expanded in non organ-specific autoimmune diseases, such as rheumatoid arthritis, primary Sjögren's syndrome, systemic lupus erythematosus. This holds true for various conditions, including organ-specific auto-immune diseases. Since auto-immune features are common in lymphoproliferative disorders, and the latter be a complication in non organ-specific auto-immune diseases, CD5 + B cells may represent an intermediary between these auto-immune diseases and B cell lymphoproliferations. Studies on the regulation of CD5 + B cell production and function are likely to shed light on the aetiology of, and pathogenetic mechanisms operating in the different disease states.
7638431 [The use of high resolution x-ray computed tomography in the diagnosis of hypersensitivity 1995 A hypersensitivity pneumonia is rare during gold therapy. The underlying mechanism is immunological in origin, of Gell and Coombs Type IV. As there are numerous possible pulmonary disorders during the course of inflammatory rheumatism treated with gold, the early detection is vital, in order to prevent progress to fibrosis. In parallel with broncho-alveolar lavage to look for a T8 lymphocytic alveolitis, which is very suggestive, high resolution computed tomography has a place in the early diagnosis, to characterise the lesions, to aid in an aetiological diagnosis, and also to assess progress on treatment. The authors present a case of pneumonitis induced by gold with visible interstitial lesions on computed tomography, accompanied by significant bronchial distortion and bronchiectasis suggestive of fixed lesions. These lesions partially regressed following steroid therapy; the diagnostic and prognostic role for high resolution computer tomography was discussed.
8493585 [A case report--pulmonary cryptococcosis associated with systemic lupus erythematosus and 1993 Feb A case of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) associated with pulmonary cryptococcosis which was successfully treated with fluconazole (FCZ) and flucytosine (5-FC) is described. A 63-year-old woman who had been treated with steroid for SLE and low dose methotrexate (MTX) for RA was admitted to Jichi Medical School Hospital because of abnormal shadow in the chest X-ray film. Physical examination revealed no abnormality. A chest CT film showed multiple nodular shadows localized in the right lower lobe. An ultrasonically guided trans-cutaneous lung biopsy performed on 10th hospital day established a diagnosis of pulmonary cryptococcosis. Following the treatment with FCZ and 5-FC for a month, her abnormal lung shadows improved and serum cryptococcal antigen level was decreased. A survey of the literature from 1955 to 1990 revealed 44 cases of SLE associated with cryptococcosis in Japan, in addition to our case, most of whom were on corticosteroid therapy. The majority of patients were young women, representing the usual population of patients with SLE. 34 of these patients had cryptococcal meningitis; 22, pulmonary cryptococcosis; 6, sepsis; 6 cutaneous cryptococcosis. Twenty patients died. Deep fungal infections should be considered whenever patients with SLE have fever of unknown origin, diffuse pulmonary infiltrates, or unexplained CNS symptoms.
8782124 Synovial fluid from patients with rheumatoid arthritis contains a unique inhibitor of inte 1996 Jun OBJECTIVE: To partially purify and characterize a specific inhibitor of interleukin 1 alpha (IL-1 alpha) activity from synovial fluids (SF) of patients with rheumatoid arthritis. METHODS: SF inhibitor of IL-1 alpha (SFI alpha) was partially purified by ammonium sulfate precipitation, gel filtration, anion exchange chromatography, and chromatofocusing. Specificity of inhibition of IL-1 alpha activity was tested in T lymphocyte proliferation assays. The mechanism of this inhibition was investigated by binding assays and mobility shift on gel filtration. RESULTS: The SFI alpha inhibited all in vitro activities of IL-1 alpha tested, but did not inhibit activities of IL-1 beta or IL-2. Inhibitor activity was not diminished by neutralizing antibodies against the IL-1 receptor antagonist, and was not removed by immunoadsorption with antibodies against IL-1 receptors. It was not depleted by monoclonal antibodies against human IgG subclasses, IgA, or IgM. The SFI alpha specifically inhibited binding of IL-1 alpha to cell surface receptors, and appeared to form a high molecular weight complex with IL-1 alpha. CONCLUSION: SFI alpha appeared to block biological activities of IL-1 alpha by specific binding to this cytokine, thereby preventing receptor occupancy. The SFI alpha did not appear to be related to previously described inhibitors of IL-1.
8712879 A 10 year follow up of parenteral gold therapy in patients with rheumatoid arthritis. 1996 Mar OBJECTIVES: To study the long term tolerance of parenteral gold and subsequent drug treatment in patients with rheumatoid arthritis, including prediction of outcome and 'survival' of sequential treatments. METHODS: A retrospective cohort study of 376 patients was made, including a detailed screening of 237 patients treated in 1989. Reasons for discontinuing treatment were analysed in life table analyses, which were used to compare patients receiving parenteral gold treatment in 1985 and 1989, and two groups of patients receiving disease modifying antirheumatic drugs after parenteral gold treatment. The causes of discontinuation were followed in sequential treatments. RESULTS: The estimated probability of discontinuation of parenteral gold treatment was 29% after six months and 42%, 55%, 74%, and 92% after 1, 2, 5, and 10 years, respectively. Mucocutaneous side effects were the main cause of discontinuation of parenteral gold treatment during the first three years, while the probability of discontinuation because of inefficacy dominated after four years. Side effects also constituted the main cause of discontinuation of treatments given after parenteral gold treatment during the first three years of follow up. No significant differences were found when comparing the termination rates between the first and the second and subsequent treatments after parenteral gold treatment. The main reasons for discontinuing one treatment could not predict the cause of discontinuation of the next treatment. CONCLUSION: Mucocutaneous side effects dominated initially, while inefficacy was the dominating cause of discontinuation of long term parenteral gold treatment. No serious side effects were registered. The cause of discontinuation of one treatment did not predict the cause of discontinuation of the following drug. Drug 'survival' was the same in both treatments after parenteral gold treatment.
8717103 Long-term tolerability of methotrexate at doses exceeding 15 mg per week in rheumatoid art 1996 The objective of this study was to examine longitudinally the tolerability of methotrexate (MTX) treatment at doses exceeding 15 mg/week in an open-label, prospective study. One hundred and eighty-five patients with rheumatoid arthritis were randomized to receive 15 mg or 25 mg MTX per week initially, and were followed over 30 months. Subsequent dose adjustments according to efficacy and tolerability resulted in levelling off of the mean dose at 18 mg/week, and the original treatment groups were combined for a longitudinal study comparing toxic events during months 1-12 and months 13-30. Withdrawals due to side-effects amounted to 17% during months 1-12 and 4% during months 13-30; dose reductions due to side-effects were 9% and 7%, respectively. The annual incidence of gastrointestinal side-effects increased from 26% to 39% (P = 0.05), that of liver enzyme elevation dropped from 43% to 10% (P < 0.001) and haemocytopenia remained stable at 5% and 7%. MTX pneumonitis was only observed during the first year, while airway complaints without evidence of parenchymal lung involvement increased to 10% beyond the first year. Fifty-six patients experienced 65 major infectious episodes over the 30-month period, with the respiratory tract being the most frequent site. This study showed that MTX treatment at doses exceeding 15 mg/week is tolerated over extended period of time. Major toxicity and withdrawals due to side-effects occurred predominantly during the first year of treatment and thus showed a decreasing trend over time, while minor toxic events continued throughout the study with a progressive rate of mucous membrane toxicity. MTX-treated RA appears to be a risk situation for major infection.
8126040 The use of porous prostheses in delayed reconstruction of total hip replacements that have 1994 Mar Between March 1984 and March 1989, thirty-four patients who had an infection at the site of a cemented total hip prosthesis were managed with resection arthroplasty and delayed implantation of a porous total hip prosthesis without cement. The interval from the time of the resection arthroplasty to the implantation of another prosthesis averaged eight months (range, three to nineteen months). At an average of forty-seven months (range, twenty-four to seventy-two months) after the reimplantation, six patients (18 per cent) had recurrence of the infection. Patients who had rheumatoid arthritis were at significantly higher risk for the development of a recurrent infection (p < 0.01). Of the twenty-eight patients who did not have a recurrent infection, six had definite radiographic evidence of loosening of the femoral component at the latest follow-up evaluation. For twenty-five of the twenty-eight patients, sufficient data were available for calculation of the Mayo Clinic hip score; only fourteen (56 per cent) of these patients had a satisfactory functional outcome. The high (68 per cent) rate of complications and the long-term durability of the prosthesis in these patients remain a concern. The fact that 18 per cent of the patients had a recurrent infection suggests that avoidance of the use of bone cement does not improve the rate of resolution of infection after a delayed revision operation in patients who have an infection following a total hip arthroplasty.
1740665 Genetic analysis of self-associating immunoglobulin G rheumatoid factors from two rheumato 1992 Mar 1 Although much has been learned about the molecular basis of immunoglobulin M (IgM) rheumatoid factors (RFs) in healthy individuals and in patients with mixed cryoglobulinemia and rheumatoid arthritis, little is known about the genetic origins of the potentially pathogenic IgG RFs in the inflamed rheumatoid synovia of patients. Recently, we generated from unmanipulated synovium B cells several hybridomas that secreted self-associating IgG RFs. To delineate the genetic origins of such potentially pathogenic RFs, we adapted the anchored polymerase chain reaction to rapidly clone and characterize the expressed Ig V genes for the L1 and the D1 IgG RFs. Then, we identified the germline counterparts of the expressed L1 IgG RF V genes. The results showed that the L1 heavy chain was encoded by a Vh gene that is expressed preferentially during early ontogenic development, and that is probably located within 240 kb upstream of the Jh locus. The overlap between this RF Vh gene and the restricted fetal antibody repertoire is reminiscent of the natural antibody-associated Vh genes, and suggests that at least part of the "potential pathogenic" IgG RFs in rheumatoid synovium may derive from the "physiological" natural antibody repertoire in a normal immune system. Indeed, the corresponding germline Vh gene for L1 encodes the heavy chain of an IgM RF found in a 19-wk-old fetal spleen. Furthermore, the comparisons of the expressed RF V genes and their germline counterparts reveal that the L1 heavy and light chain variable regions had, respectively, 16 and 7 somatic mutations, which resulted in eight and four amino acid changes. Strikingly, all eight mutations in the complementarity determining regions of the V gene-encoded regions were replacement changes, while only 6 of 11 mutations in the framework regions caused amino acid changes. Combined with L1's high binding affinity toward the Fc fragment, these results suggest strongly that the L1 IgG RF must have been driven by the Fc antigen.
8046314 A comparison of severe gastric damage as a result of pirprofen and naproxen treatment in r 1994 Aug OBJECTIVE: The aim of this controlled endoscopic study was to compare the therapeutic efficacy and the gastric tolerance of two nonsteroidal anti-inflammatory drugs, pirprofen versus naproxen. DESIGN: A randomized endoscopic double-blind double-dummy study. SETTING: The gastrointestinal unit of a teaching hospital. SUBJECTS: Forty patients suffering from rheumatoid arthritis were enrolled. After an initial upper gastrointestinal endoscopy to rule out the presence of gastric mucosal lesions, the patients were randomly allocated in a double-blind, double-dummy manner, to receive either pirprofen (400 mg t.i.d.) or naproxen (500 mg b.i.d.) for 4 weeks; endoscopic control followed this treatment period, or was anticipated in the event of painful dyspepsia. INTERVENTIONS: Endoscopy at the beginning of the study and at 4 weeks, or anticipated in the event of painful dyspepsia. MAIN OUTCOME MEASURES: Primary outcome measure of the study was the possibility that pirprofen was less toxic to the gastric mucosa than naproxen, and at least as effective. RESULTS: Both drugs proved effective in relieving clinical symptoms, without a statistically significant difference. Gastric mucosa lesions were observed in 90% of pirprofen-treated patients and in 60% of those on naproxen (P = 0.03). The most severe lesions (grades 3 and 4) were found in 65% of subjects treated with pirprofen, as opposed to 15% of those treated with naproxen (P = 0.001). CONCLUSIONS: This study shows that pirprofen is at least as active as naproxen in relieving rheumatic symptoms, but its administration results in a significantly severe degree of gastric damage.
7917014 V alpha gene usage in rheumatoid compared with osteoarthritic synovial tissue T cells. 1994 Sep While many investigators have examined V gene usage by the clonotypic T-cell receptor (TCR) in rheumatoid arthritis (RA) joints, few have reported on arthritic controls. We compared TCR alpha-chain V gene usage in knee synovial tissue specimens from 9 RA and 5 osteoarthritis (OA) patients. There was no significant difference in the number of V gene families used in RA compared with OA synovium. However, there was an increased prevalence of V alpha 28, V alpha 10, V alpha 17, and V alpha 18 and under representation of V alpha 15 in RA compared with OA synovium. Of these, V alpha 28 was also recently described by us as being present in RA synovial tissue early in the course of disease. V alpha 28 associated J region usage, and N-regional diversity was surveyed in T-cell receptors from additional rheumatoid synovial tissue T-cell populations and normal peripheral blood. Oligoclonality was observed in 6/10 rheumatoid specimens either by direct sequencing or where three or more molecular clones were sequenced, compared with 0/5 normal PBMCs. The oligoclonal populations included 2/3 cell lines stimulated with interleukin-2 (IL-2) alone. Several novel J regions were observed, with some recurrent residues observed at N-region positions. These data indicate an increased prevalence of certain TCR V region families in RA versus OA synovium, and suggest an antigen-driven expansion of V alpha 28-expressing T cells in RA synovium.
1627786 Tumor necrosis factor and interferon gamma: relevance for immune regulation and genetic pr 1992 Jun The role of TNF-alpha and IFN-gamma in various models of autoimmune disease were analyzed. These include murine models of lupus, type 1 diabetes in NOD mice and the adjuvant arthritis model in rats. Rather than being involved mainly in the effector arm of the inflammatory process of autoimmune organ destruction, our data suggest a primary involvement of these cytokines in some of the basic mechanisms of the autoimmune process. Evidence has been presented that emphasizes the possibility of the involvement of TNF-alpha in the genetic predisposition to SLE. Based on the data presented, one should be cautious in extrapolating the effects of these cytokines in various in vitro systems to the in vivo situation.
7667645 Infections during low-dose methotrexate treatment in rheumatoid arthritis. 1995 Jun We studied the infection rate in patients with rheumatoid arthritis (RA) treated with low-dose methotrexate (MTX) in a 6-year open prospective study and in a 12-month randomized double blind trial comparing MTX with azathioprine (AZA) that was followed by a 3-year open prospective study. The literature on infections during low dose MTX in RA was reviewed. We also did a search for therapy-related opportunistic infections in RA and in MTX-treated psoriasis and psoriatic arthropathy patients. In our studies the infection rate during MTX treatment was higher in severe RA than in moderate RA. In severe RA there were often 2 infections simultaneously. The majority of the infections occurred in the first 1.5 years of treatment. There was no difference in the infection rate of MTX and AZA in the comparative trial. In the literature the infection rate was highest in short-term double-blind studies. Opportunistic infections are increasingly reported in RA treated with MTX and rarely with AZA, cyclosporine A, and cyclophosphamide or in MTX treated psoriasis and psoriatic arthropathy. In RA it appears that the initial period of treatment with MTX is the most vulnerable phase for infections, with the exception of opportunistic infections, which are not limited to a certain treatment period. Probably there are more MTX-associated infections in severe RA than in moderate RA.
7654629 Rheumatic disorders in patients with silicone implants: a critical review. 1995 More than 1000 patients with rheumatic disorders and silicone implants have been reported. In this review, the clinical features of patients with scleroderma, inflammatory myositis, systemic lupus erythematosus and silicone implants are discussed. The clinical features of the most common rheumatic disorder associated with silicone implants, the "Silicone Implant Associated Syndrome", are introduced. In addition, other local regional, and neurologic disorders associated with silicone implants are discussed. This comprehensive clinical review provides the clinician with information regarding the common symptoms, signs and laboratory features of rheumatic disorders of patients with silicone implants.
8323399 Expression of CD69 antigen on synovial fluid T cells in patients with rheumatoid arthritis 1993 Jun OBJECTIVES: The expression of the CD69 antigen on synovial fluid and peripheral blood lymphocytes was studied in 12 patients with rheumatoid arthritis (RA), five subjects with other forms of chronic synovitis, and on the peripheral blood lymphocytes of 15 patients with systemic lupus erythematosus (SLE) and immune vasculitis. METHODS: The CD69 antigen and other activation markers (HLA-DR, interleukin 2 receptor (IL-2R), transferrin receptor) were measured by cytometric analysis. In patients with RA soluble IL-2R was determined by enzyme linked immunosorbent assay (ELISA). RESULTS: The percentage of T cells bearing CD69 was significantly increased in synovial fluid from patients with RA (30.3 (13)%) and other chronic synovitis (18 (9)%). The expression of CD69 on peripheral blood lymphocytes of patients with RA, other chronic synovitis, and SLE and immune vasculitis was within the normal range 2.1 (1.2)%. According to previously published work, a high proportion of synovial fluid T cells are HLA-DR positive (64.2 (12.4)% in synovial fluid from patients with RA and 61 (1.2)% in synovial fluid from patients with other chronic synovitis). Transferrin receptor expression on synovial fluid was up-regulated compared with that on peripheral blood. The increase of IL-2R expression on synovial fluid lymphocytes v peripheral blood was not significant; the quantitative determination of soluble IL-2R levels gave a mean value of 921 (351) U/ml in synovial fluid of patients with RA, 672 (229) U/ml in the serum of the same patients, and 273 (100) U/ml in serum from normal subjects. CONCLUSIONS: Synovial fluid lymphocytes are in a different functional state than peripheral blood lymphocytes. CD69 antigen is an interesting cellular marker which should be studied in patients with chronic synovitis. The unusual expression of the activation antigens and the sequence of their appearance require further study.
8079829 Interrelationships between interleukin (IL)-1, IL-6 and IL-8 in synovial fluid of various 1994 Mar High levels of many cytokines, including interleukin (IL)-1, IL-6 and IL-8, were found in various arthropathies suggesting that they play a role in the pathogenesis of disease, although their relationship with the type and activity of disease is still not clear. The synovial fluid (SF) of 24 patients with rheumatoid arthritis (RA), 19 with psoriatic arthritis (PA) and 33 with osteoarthritis (OA) was analyzed for IL-1 beta, IL-6 and IL-8. The highest concentration of the three cytokines was found in the SF of RA. IL-beta detectable levels (> or = 20 pg/ml) were observed in 8/24 (33.3%) patients with RA, in one patient with PA but in no patient with OA. IL-6 (mean +/- SD) (1610.37 +/- 1781.65 pg/ml) was higher in RA than in PA (672.47 +/- 867.40 pg/ml, p = 0.043) and OA (89.45 +/- 120.52 pg/ml, p = 0.0001). IL-8 (1042.72 +/- 698.64 pg/ml) was higher in RA than in PA (660.36 +/- 625.11 pg/ml, p = 0.03) and OA (89.9 +/- 45.88 pg/ml, p = 0.0001). A correlation between IL-1 beta, IL-6 and IL-8 was found in RA. In all patients a correlation between IL-6 and IL-8 levels was found; moreover, these two cytokines were associated with SF indices of inflammation, such as white blood cells (WBC) count and total protein (TP) concentration. Our findings suggest that these interrelationships play a role in the evolution of more severe erosive arthropathy such as RA.
8121259 Felty's syndrome: a case presentation. 1993 Nov A 64-year-old male patient with Felty's syndrome was treated with antibiotics, Plaquenil (hydroxychloroquine sulfate), and gold salts. In the fourth week of hospitalization, the patient died. Autopsy showed extensive bronchopneumonia, fibrous pleuritis, congestive splenomegaly, mild atherosclerosis, reactive lymphoid hyperplasia, congested passive liver, severe rheumatoid arthritis, and hypercellular bone marrow.
7522456 Antibodies to the collagen-like region of C1q and type II collagen are independent non-cro 1994 Jun The collagen-like region (CLR) of the first component of complement, C1q, and type II collagen are structurally similar, raising the possibility of epitopes in common, and of the existence of autoantibodies that are cross-reactive. Accordingly, antibodies to the CLR of C1q and to type II collagen were measured in patients' sera with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) by an ELISA. IgG antibodies to the CLR of C1q were present in 17% of patients with SLE but none with RA, and IgA antibodies were present in 10% and 8% of patients with SLE and RA, respectively. IgG antibodies to type II collagen were present in 15% and 25% of patients with SLE and RA, respectively, and IgA antibodies in 15% and 28% of patients with SLE and RA, respectively. There was no correlation in either disease between the serum levels of antibodies to the CLR of C1q and antibodies to type II collagen. For sera with antibodies to both antigens, neither competitive inhibition by ELISA nor preabsorption with the alternative antigen affected the level of reactivity to the other antigen. Thus antibodies to the CLR of C1q and antibodies to type II collagen are independent and non-cross-reactive populations, and presumably occur by different types of immunogenic stimulation.
7880119 Interleukin-6 in relation to other proinflammatory cytokines, chemotactic activity and neu 1995 Jan OBJECTIVE: To evaluate the relation between synovial fluid (SF) concentrations of interleukin-6 (IL-6) and other mediators of inflammation which are responsible for joint degradation in rheumatoid arthritis (RA). METHODS: We measured IL-6, IL-1 beta, tumour necrosis factor alpha (TNF alpha), granulocyte macrophage colony stimulating factor, IL-8, and polymorphonuclear leucocyte (PMNL) chemotaxis and degranulation in SF from patients with RA (n = 30) in the early phase of the disease. RESULTS: In a cross-sectional study IL-6 concentrations correlated with those of IL-1 beta, IL-8 and with PMNL activation as reflected by lactoferrin concentrations. In a longitudinal study, changes in IL-6 concentrations correlated with changes in TNF alpha, IL-8 and lactoferrin concentrations. CONCLUSION: IL-6 in SF appears to reflect the local proinflammatory, potentially erosive activity in RA. This supports the use of acute phase proteins, which are mainly induced by IL-6, as variables to monitor the course of RA.
1478694 Antibodies to 65 kDa and 70 kDa heat shock proteins in rheumatoid arthritis and systemic l 1992 Oct To test the potential role of autoimmunity to the highly conserved heat shock proteins (HSP) in immune arthritides, the sera from 99 patients with rheumatoid arthritis (RA), 48 patients with systemic lupus erythematosus (SLE) and 65 normal controls were examined by ELISA for IgG and IgM antibodies to the 65 kDa and 70 kDa heat shock proteins from Mycobacterium bovis (Bacille Calmette-Guerin; BCG). In RA sera there are significant numbers of individuals with increased IgM anti-65 kDa and anti-BCG reactivity as well as IgG anti-70 kDa when compared with controls. In SLE both IgM and IgG anti-BCG, together with IgM anti-65 kDa, differed significantly from controls. The results were compared with previous reports in similar groups of patients, and it is clear that no consistent pattern of reactivity emerges. While further work may be justified looking carefully at the disease duration and other subsets of both RA and SLE, it is difficult at this stage to conclude that antibodies to autologous HSP that cross-react with mycobacterial HSP play a major role in disease pathogenesis.