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ID PMID Title PublicationDate abstract
7816774 The present knowledge of the inflammatory process and the inflammatory mediators. 1994 Endothelial damage, synovial oedema, fibrin deposition, polymorphonuclear cell (PMN) invasion, and mild lining cell hyperplasia characterize acute inflammatory arthritis. Later on, perivascular tissue is infiltrated by mononuclear cells. The early events are mediated by interactions between PMNs and endothelial cells. Both parts in the adhesion event are activated with multiple stimuli resulting in complex interactions of varying intensity and duration. Adhesion molecules present on the surface of PMNs (L-selectin) or induced by inflammatory stimuli (beta 2-integrins) mediate PMN adhesion to activated endothelium, which has counter receptors (E-selectin for L-selectin and ICAM-1 and ICAM-2 for beta 2-integrins). At the initial phase L-selectin initiates the rolling of PMNs on endothelial cells. Further stimuli result in a more prolonged adhesion between PMNs and endothelium. At the side of endothelium, induction of P-selectin and PAF by histamine, thrombin and LTC4 contribute to the acute rolling of PMNs on endothelial surface. Tumor necrosis factor (TNF), interleukin-1 (IL-1) and lipopolysaccharide activate endothelial cells to synthesize interleukin-8 (IL-8), a potent chemotactic and proadhesive mediator for PMNs, and further adhesion molecule (E-selectin), a mediator of long-term adhesion between PMN and endothelium. After adhesion and migration to the focus of inflammation, PMNs induce inflammation by aggregating, releasing hydrolyzing enzymes, generating lipid peroxidation products such as prostaglandins and LTB4, and oxygen derived free radicals. In studies on the pathogenesis of seronegative spondyloarthropathies, we have shown persistently aberrant PMN function evidenced by enhanced chemotaxis and high production of toxic oxygen derived free radicals by PMN.(ABSTRACT TRUNCATED AT 250 WORDS)
8434872 The presence of antibodies against extractable nuclear antigens in serum: a comparison of 1993 Jan A commercial immunoblotting kit has recently been introduced to determine auto-antibodies against extractable nuclear antigens. We compared this new test with radial immunodiffusion for its usefulness in the routine laboratory procedures of a general hospital. Antigen preparation in immunoblotting includes a protein denaturation step prior to electrophoretic separation of the different proteins. In this way antigenic determinants that depend heavily on the protein superstructure are lost. In theory, auto-antibodies against these epitopes may be missed. In our series of 100 samples that had tested positively for antinuclear antibodies, radial immunodiffusion was able to detect one SSA positive sample that was negative by immunoblotting. However, 47 samples positive in immunoblotting, 37 positive for UBP, seven for anti-SSA, are for anti-Jo-1, one for anti-RNP and one for anti-Sm were missed by radial immunodiffusion. Most of these samples had low antinuclear antibody titres (1/80 or 1/160).
8124912 Interleukin-8 (IL-8) in synovial fluid of rheumatoid and nonrheumatoid joint effusions. 1993 Dec IL-8 was measured in knee joint synovial fluid of 60 patients with rheumatoid arthritis, 8 with gout, 6 with osteoarthritis and 4 with meniscus lesions. IL-8 could be demonstrated in most SF samples. The highest levels were observed in rheumatoid joint effusions, yet mean levels were not significantly different between the different subgroups (mean +/- SE; RA 1537 +/- 3049 pg/ml, gout 570 +/- 952 pg/ml, OA/ML 178 +/- 188 pg/ml). In RA patients, IL-8 levels could not be related to various serological, clinical or radiological parameters. However, a correlation was observed between SF levels of IL-8 with those of lactate, LDH, beta 2-microglobulin and glucose. These observations suggest that next to the laboratory parameters IL-8 will be a parameter of the activity of the local inflammatory process. The results also demonstrate that IL-8 is not a disease-specific marker of joint inflammation.
7473468 Trends in hospitalizations for gastrointestinal bleeding among patients with rheumatoid ar 1995 Aug OBJECTIVE: Estimates of the incidence of significant gastrointestinal (GI) bleeding among patients with rheumatoid arthritis (RA) vary and population based estimates of this event have been unavailable. We examine the incidence of this event in a well defined cohort of patients with RA. METHODS: The study cohort consisted of patients with RA incident in Rochester, MN, between 1950 and 1974 and reported by Linos, et al (Am J Epidemiol 1980;111:87-98). These patients were followed for up to 40.5 yrs, and retrospective analysis of hospitalization for GI bleeding was performed. RESULTS: A total of 58 patients with RA were hospitalized for GI bleeding, including 46 patients who had a first episode of bleeding after the diagnosis of RA was made, for a first episode incidence rate of 0.52% per person-year of followup. These 46 patients experienced 72 hospitalizations for GI bleeding. Patients diagnosed with RA after 1963 and patients older than 53 yrs of age at the time of diagnosis of RA had a higher incidence of hospitalization for GI bleeding. Overall survival among all patients with RA was slightly less than expected in the general population, while survival in patients hospitalized for GI bleeding was significantly lower than that of nonhospitalized patients. In a nested case-control study, nonsteroidal antiinflammatory drug use was found to be a significant risk factor for hospitalization for GI bleeding (odds ratio 3.25:1 compared with nonusers). CONCLUSION: Estimates of the overall incidence of hospitalization for GI bleeding in this population based cohort of patients with RA may be somewhat lower than some reported for referral populations, but an upward trend in recent years is noted.
8697642 Analysis of V kappa genes in rheumatoid arthritis (RA) synovial B lymphocytes provides evi 1996 Jul To define mechanisms of sustained activation of synovial B lymphocytes in RA, we studied hybridomas established from the local synovial B cell repertoire of two RA patients for V kappa gene expression and for antigen-binding specificity. The analyses revealed that members of the main V kappa families (I, II and III) were utilized at frequencies consistent with random V kappa gene family use. Furthermore, although the hybridomas expressed genes frequently seen in response to other self- and exogenous antigens, only one V kappa I- and two of three V kappa III-expressing hybridomas exhibited reactivity with self-antigens. Nucleotide sequence analysis revealed that all hybridomas, with the exception of rheumatoid factor (RF)-producing hybridomas, expressed V kappa genes highly related to known germ-line genes (99.3-100% homology) and that diversity was generated by deletions and random nucleotide insertions at the V kappa-J kappa junction. Examination of the few nucleotide changes seen with the V kappa genes revealed a predominance of silent to replacement changes. Moreover, most of these changes can be attributable either to allotypic variations or to limited random nucleotide replacements independent of antigen selection. In contrast, one IgG-RF (B4D8) exhibited predominantly replacement nucleotide changes in the complementarity-determining regions, suggestive of antigen-driven selection. The random expression of immunoglobulin variable region genes with no, or little, evidence of mutation in the synovial B lymphocyte repertoire, including natural polyreactive antibodies, alongside mutated IgG-RF, suggest that both polyclonal activation and antigen-driven responses occur in RA synovia.
8520659 Cylindrical cemented ankle arthroplasty: a prospective series with long-term follow-up. 1995 Aug From 1981 to 1985 28 ankle arthroplasties were performed using a congruent and cylindrical ankle design. The talus component was an anatomically shaped cap to cover the talus dome and the facets. The tibial component was congruent toward the talus and had two parallel bars on the back for fixation into the distal tibia. The diagnosis was osteoarthritis in 15 cases and rheumatoid arthritis in 11 cases (two bilateral cases). There were seven failures, giving a cumulative estimated survival rate of 70% for the prosthesis at 12 years.
8457640 Cellular fibronectin in plasma: its implications in fibrinogen-associated cryoprecipitatio 1993 Feb Elimination of cryoprecipitable plasma components (cryogels) by cryofiltration from the circulating blood of patients with drug-resistant rheumatoid arthritis (RA) alleviates clinical symptoms including morning stiffness and arthralgia. The cryogels thus isolated from the blood were found to consist mainly of fibrinogen (Fbg) and fibronectin (FN). Analysis by immunoblotting with an anti-cellular FN monoclonal antibody revealed that cellular FN (cFN) co-existed with plasma FN (pFN) in the cryogels derived from the patients. Using an ELISA, we assessed cFN together with the total FN (pFN+cFN) in plasmas and cryogels derived from the patients. The cFN/total FN ratio was distinctly higher in the cryogels than in the plasmas, suggesting that cFN was more readily precipitated than pFN in association with Fbg under cold conditions.
8425922 Cytokine-induced expression of mRNAs for chemotactic factors in human synovial cells and f 1993 Feb In response to interleukin 1 or tumor necrosis factor, human synovial cells and fibroblasts expressed several genes encoding known chemotactic factors or related proteins. Transcripts for interleukin 8 (IL-8), gro/MGSA, pAT 464, IP-10, pAT 744 and Monocyte Chemotactic and Activating Factor (MCAF) accumulated rapidly in IL-1 and TNF-treated cells. The inhibition of protein synthesis led to the superinduction of IL-8 and gro/MGSA mRNAs in IL-1, but not in TNF-treated cells. Thus, IL-1 and TNF are likely to regulate the expression of these mRNAs by different mechanisms. Important cell-specific differences in mRNA accumulation characterized the expression of chemotactic factor genes. Moreover, only a subset of the same genes was activated in quiescent cells stimulated by serum. Therefore, genes encoding closely related proteins each had a distinct pattern of expression. continuous stimulation of fibroblasts and synovial cells with IL-1 resulted in high and prolonged expression of IL-8 and gro/MGSA mRNAs. These results extend the list of chemotactic factor genes expressed by mesenchymal cells in vitro and suggest a pivotal role for these cells in processes such as chronic inflammation.
8023589 Immunological studies in patients with rheumatoid arthritis treated with methotrexate or c 1994 Mar One-hundred-and-two-patients (pts) with rheumatoid arthritis (RA) were observed for 12 months. Forty-eight pts were treated with a weekly low-dose of methotrexate (MTX), 23 pts with cyclophosphamide (CTX) (eight pts with one single intravenous dose, and 15 pts orally with a single daily dose), and 31 pts with nonsteroidal antiinflammatory drugs (NSAID) only. In all individuals acute phase response, i.e., C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP) serum levels, and AGP microheterogeneity using affinoimmunoelectrophoresis with concanavalin A were evaluated. The phenotype of lymphocytes isolated from peripheral blood was characterized using immunofluorescence technique. Following treatment the increased level of CRP significantly decreased whereas AGP serum level remained unchanged. Among the patients, microheterogeneity of AGP expressed as reactivity coefficient (RC) was lower before treatment when compared with 17 controls (0.95 +/- 0.23 vs. 1.35 +/- 0.15, p < 0.01). After 12 months of MTX therapy AGP-RC rose significantly (1.19 +/- 0.13, p < 0.01). No changes were observed in AGP-RC levels in CTX and NSAID treated individuals. No significant differences were observed in the percentage of CD3+, CD4+, and CD8+ cells in all the patient groups, except in CTX intravenously treated patients. In this group of patients a decrease of CD4+ cells was noticed (60.1 +/- 11.5% and 43.8 +/- 12.5% before and after treatment respectively -p < 0.01). The percentage of CD19 positive cells decreased significantly during 12 months of treatment with MTX and CTX. The percentage of activated T cells (CD25+ cells and HLA-DR+ cells) remained unchanged in MTX treated patients and was reduced in both CTX groups.(ABSTRACT TRUNCATED AT 250 WORDS)
7796661 [Rheumatic diseases in China]. 1995 Feb To determine the prevalence of rheumatic diseases in Chinese of Han nationality in the north and the south of China, samples of 4,192 adults in Beijing (north) and 5,057 in Shantou (south) area were studied. The same questionnaire was administered to each subject surveyed. Physical examinations were done in all who gave positive answers. For those who gave positive response to certain set of questions, blood antinuclear antibody and rheumatoid factor tests and radiographs of hand and/or sacroiliac joint were done. The prevalence of definite rheumatoid arthritis (RA) was 0.34% in the north (95% confidence interval 0.20-0.51) and 0.32% (0.95% CI 0.16-0.47) in the south and ankylosing spondilitis was noted in 0.26% of both samples (95% confidence interval in the north 0.11-0.42 and in the south 0.14-0.40). Only 3 cases of systemic lupus erythematosus in the north and one in the south were identified. General rheumatic pain was reported more frequently in the north. Lumbar problems were recorded on examinations 5 times more commonly in the north than in the south (men 25.0% vs 5.3%, women 38.0% vs 6.5%) and knee problems 10 times (men 24.0% vs 1.8%, women 36.0% vs 3.4%) more commonly in the north; the difference was greatest in the age of 55-64. A further study in the south is planned to assess the contribution of inter-observer error and/or difference in cultural response to the north/south difference observed in the prevalence of general rheumatic symptoms and back pain. A search for environmental risk factors such as climate, diet, degeneration or overuse would then be indicated to explain these differences.
8209208 [D-penicillamine-induced myasthenia gravis]. 1994 May 21 D-penicillamine has been used in the treatment of rheumatoid arthritis for years. As a rare complication of this treatment the occurrence of myasthenia gravis has been described, the clinical features of this complication being indistinguishable from that of idiopathic myasthenia gravis. Both D-penicillamine induced and idiopathic myasthenia gravis show elevated titers of acetylcholine receptor antibodies and respond to acetylcholinesterase inhibitor treatment. We report on a patient with rheumatoid arthritis who, under treatment with D-penicillamine, developed severe myasthenia gravis which required temporary acetylcholinesterase inhibitor therapy. 8 months after D-penicillamine was discontinued the acetylcholine receptor antibodies had disappeared and the acetylcholinesterase inhibitors could be withdrawn. Clinical findings and possible pathogenetic aspects of D-penicillamine induced myasthenia gravis are discussed.
1466799 Cytokines in autoimmunity. 1992 Dec It is now generally accepted that many cytokines are involved in the pathogenesis of autoimmune disease, either directly by causing tissue destruction or indirectly through the activation of autoreactive and inflammatory cells. Thus, cytokines, such as tumor necrosis factor-alpha, are implicated in the pathogenesis of rheumatoid arthritis based on in vitro studies on synovial tissue from patients with rheumatoid arthritis, which suggest that the effects of tumor necrosis factor-alpha are amplified by its potential to induce other pro-inflammatory cytokines, such as interleukin-1 and granulocyte-macrophage colony-stimulating factor. Transgenic mouse technology has shown that mice expressing the human tumor necrosis factor-alpha gene develop a polyarthritis. Interleukin-2 has also been identified by transgenic technology as a cytokine involved in the pathogenesis of insulin-dependent diabetes mellitus through the activation and stimulation of growth of autoreactive T cells.
7569733 Lipoprotein(a) in relation to acute phase reaction in patients with rheumatoid arthritis a 1995 Jul The effect of altered inflammatory activity, as reflected by acute phase protein levels, on the concentration of lipoprotein(a) was analysed in 51 patients with rheumatoid arthritis (RA), and in 25 patients with polymyalgia rheumatica (PMR). Despite significantly decreased acute phase proteins in RA, the Lp(a) concentration increased significantly between the two observations in the group as a whole. In one subgroup with initially high Lp(a) levels, large intraindividual variations between the samplings and a high correlation to the ESR changes were found. Another subgroup with initially low levels showed small variations of Lp(a) without correlation to any acute phase reactant. In the PMR group, Lp(a) decreased in line with diminishing acute phase reactivity.
8456646 Are antibodies reactive with chondrocyte proteins enriched in synovial fluids of patients 1993 In this study we examined the reactivity of synovial fluid (SF) antibodies (Abs) from patients with rheumatoid arthritis (RA) against chondrocyte proteins. The levels of IgG, IgM and IgA in the synovial fluids varied from patient to patient, but were similar to the levels found in each individual's serum. Although the Abs in SF and serum of RA patients reacted with several molecular weight classes of chondrocyte proteins, this reactivity was very low. Synovial fluid and serum Abs from the same patients reacted with similar chondrocyte proteins and to a similar extent, suggesting that the level of Abs reactive with chondrocyte proteins is not enriched in the SF. These data demonstrate that SF from RA patients contain high levels of Abs, however, there is very little reactivity with chondrocyte proteins beyond that observed in serum of normal and RA patients.
8296639 Anti-granulocyte perinuclear antibodies but not anti-neutrophil cytoplasmic antibodies (AN 1993 We studied 45 patients with rheumatoid arthritis for the presence of ANCA. These antibodies were determined by indirect immunofluorescence (IIF) and by enzyme-linked immunosorbent assays (ELISAs) using as a substrate purified myeloperoxidase and purified extract of azurophilic granules. By IIF, we found a characteristic perinuclear immunostaining pattern in 21 cases (47%). However, no patient had a positive result by the two ELISAs performed. Patients with a positive IIF result had significantly higher levels of anti-nuclear and anti-ds DNA antibodies than those with a negative IIF result. Therefore, these antibodies must correspond to the previously reported as granulocyte specific antinuclear antibodies (GS-ANA).
1628171 Rheumatologists and their patients who seek alternative care: an agreement to disagree. 1992 Jul Alternative treatment, such as homoeopathy, acupuncture and spiritual healing, are popular among patients with rheumatic diseases. Rheumatologists are therefore likely to be confronted with patients who make use of less orthodox health care. Patients' and rheumatologists' views on the subject and on the rheumatologists' role, however, have not yet been assessed. A questionnaire on alternative medicine was sent to all 101 practising Dutch rheumatologists (response rate: 70%). After the results had been analysed 17 rheumatologists, seven rejecting alternative medicine and ten accepting it, handed out a questionnaire to a sample of their patients: 1466 patient questionnaires were distributed (response rate: 80%). Of the respondents 43% had visited an alternative practitioner at least once for their rheumatism and 26% in the year before the survey was held. Hand healers, homoeopaths and acupuncturists were most often visited. Rheumatologists, on their part, were not too enthusiastic about these visits. Only patients' visits to spa treatment centres were welcomed by a majority of them; visits of their patients to manipulative therapists, acupuncturists and homoeopaths were judged positively by a large minority, whereas other therapies were strongly disapproved. Nevertheless, most patients informed their rheumatologist about their visiting an alternative practitioner. A surprisingly low percentage of these patients noticed that the rheumatologist did not sympathize with it. Although many patients paid a visit to an alternative practitioner because regular care did not really help them, their satisfaction with the alternative treatment turned out to be less than their satisfaction with the rheumatologists' help.(ABSTRACT TRUNCATED AT 250 WORDS)
8891978 Carpometacarpal arthritis of the thumb. 1996 Sep Forty-five flexor carpi radialis (FCR) tendon interposition arthroplasties of the trapezium for the treatment of carpometacarpal osteoarthritis were reviewed. The average follow-up period was 103 months (range, 22-213 months). Pain was reduced in 42 (93%) of the cases. Mobility was equal to that of the unoperated side. Key pinch and grip strengths compared to the unoperated thumb measured 86% and 90%, respectively. The mean distance between the scaphoid and the base of the first metacarpal bone was 7 mm (range, 2-12 mm). Function was improved in 39 (87%) of the cases, and in 42 (93%) of the cases the overall results were satisfactory. The results of this study show that FCR tendon interposition arthroplasty gives satisfactory long-term results.
7888035 Antibodies to collagen: comparative epitope mapping in women with silicone breast implants 1994 Dec Women with silicone breast implants have a significantly increased frequency of antibodies to collagen types I and II. To characterize the specificity of these antibodies, 70 women without a specific autoimmune disease, according to the criteria of the American College of Rheumatology, but who had silicone breast implants were studied for the presence of serum antibodies to native and denatured human types I and II collagen by ELISA. Positive sera were further studied by immunoblotting using peptides derived by cyanogen bromide digestion of the collagens. Samples of 82 women with systemic lupus erythematosus (SLE), 94 women with rheumatoid arthritis (RA), and 133 healthy controls were studied concurrently. There was a high frequency of autoantibodies to collagen in each of the study groups when compared to the healthy controls. However, and of particular interest, the epitope specificity of the autoantibodies differed markedly. Sera from women with silicone implants reacted strongly in an individual-specific manner with multiple peptides of type I collagen, whereas sera from women with SLE and RA reacted only weekly with a restricted range of peptides of type I collagen. Sera from women with RA reacted strongly with multiple peptides of type II, whereas sera from women with silicone implants or SLE reacted only weakly. The reactivity of women with silicone implants suggests that silicone or its biodegradation products can act as adjuvants in situ to enhance the immunogenicity of type I collagen, or protein-silicone conjugates.
7711875 Identification of the thyroid Na+/I- cotransporter as a potential autoantigen in thyroid a 1995 Apr The thyroid gland is the target of several autoimmune diseases. Specific thyroid proteins have been identified as autoantigens associated with these diseases (e.g. thyroperoxidase, thyroglobulin and the thyrotrophin (TSH) receptor). In this paper, we report that the serum of a patient suffering from Hashimoto's thyroiditis, autoimmune gastritis and rheumatoid arthritis was able to inhibit the chronic TSH-induced I- uptake of dog thyrocytes in culture, even at a 1:1000-fold dilution, without affecting their 86Rb+ uptake. This blocking activity is rare as 147 sera (from patients positive for antibodies to the thyroid microsomes and the gastric parietal cell antigen, patients with Sjögren's syndrome, patients with a high titre of microsomal antibodies and low or negative for antibodies to thyroperoxidase, and patients with a high titre of microsomal antibodies and frank hypothyroidism) were negative when tested for their ability to inhibit I- uptake. Subsequently we tested 20 murine monoclonal antibodies previously obtained by immunizing mice with a crude human thyroid membrane preparation, which were all negative when tested against thyroglobulin and thyroperoxidase. One of the monoclonal antibodies displayed a 50% inhibition of the chronic TSH-induced 125I- uptake of dog thyrocytes without affecting the 86Rb+ uptake of the cells. Immunoglobulins purified from the ascite fluid by affinity chromatography on a protein A cellulose column had the same characteristics. Taken together, the data suggest that thyroidal 125I- uptake can be inhibited by antibodies, that autoantibodies in the patient's serum are most probably responsible for the observed inhibition and therefore that the Na+/I- cotransporter is probably an autoantigen.
7918840 The detection, quantification and partial characterisation of cathepsin B-like activity in 1994 Jun In this study, the levels of the cysteine proteinase--cathepsin B were measured in diseased synovial fluids using a steady state fluorometric assay. Cathepsin B-like activity was shown to be present in all the samples analysed, with the rheumatoid arthritic synovial fluids possessing significantly higher concentrations (mean value ca. 416 mg/l) than the osteoarthritic fluids (mean value ca. 142.4 mg/l). In addition, upon treatment with pepsin, all of the rheumatoid arthritis samples were shown to possess additional cathepsin B-like activity, suggesting the presence of a reservoir of latent precursor molecules. By utilising a recently developed biotinylated affinity label for cathepsin B-like proteinases and sheep anti-(human cathepsin B) antibodies, used in combination with SDS-PAGE and Western blotting, the rheumatoid arthritic synovial cathepsin B was shown to exist in two forms with apparent molecular masses of M(r) 29,000 and 42,000. We propose that the former is a functionally active proteinase, whereas the latter is a pepsin activatable proform which, when cleaved by this aspartyl proteinase, is converted into a catalytically competent species of M(r) 20,000.