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ID PMID Title PublicationDate abstract
8095785 Use of a chimeric monoclonal anti-CD4 antibody in patients with refractory rheumatoid arth 1993 Mar OBJECTIVES: To evaluate the safety, immunogenicity, and biologic effects of chimeric monoclonal anti-CD4 (cM-T412) in patients with refractory rheumatoid arthritis (RA), and to obtain preliminary data on the clinical response to this treatment. METHODS: Twenty-five patients with active refractory RA were treated with incremental doses (10 to 700 mg) of cM-T412 in an open-label, escalating-dose phase I trial. RESULTS: Infusion with cM-T412 was followed by an immediate, rapid decline in CD4+ T cells. The level of circulating CD4+ T cells remained depressed in most patients even at 6 months posttreatment. Following antibody infusion, proliferative responses of peripheral blood lymphocytes to mitogens and antigens were determined; mitogen and antigen responses were decreased compared with pretreatment responses. Mitogen responses tended to return to baseline values more rapidly than did responses to antigen. Adverse events included fever (19 patients), which was associated with myalgias, malaise, and asymptomatic hypotension; these symptoms were self-limited and appeared to correlate with transient elevations in interleukin-6. No significant human antibody response to the cM-T412 variable region was detected; only 2 patients developed transiently low levels of antibodies reactive with cM-T412. Significant clinical improvement, defined as > or = 50% decrease in tender joint counts compared with baseline, was noted in 43% of patients at 5 weeks and 33% at 6 months following cM-T412 infusion. CONCLUSIONS: Treatment of refractory RA with cM-T412 appears to be safe and is associated with sustained decreases in circulating CD4+ T cell counts and depressed in vitro T cell responses. No significant human antichimeric antibody response was detected. Nonblinded assessment of clinical end points suggests that treatment with cM-T412 may have beneficial effects in these patients with refractory RA. A double-blind clinical trial is warranted to determine its clinical efficacy in treating RA.
8402005 Malignant 'angioendotheliomatosis'--(intravascular lymphomatosis) an unusual cutaneous lym 1993 Oct A case of cutaneous malignant 'angioendotheliomatosis' (intravascular lymphoma) is described in a patient with RA and Sjögren's syndrome. The association of RA with this rare form of lymphoma has not been reported in the literature.
8806945 A possible association of HLA-DR beta 1*04 subtypes and rheumatoid arthritis of peptide bi 1996 HLA-DR beta 1*04 subtypes associated with rheumatoid arthritis (RA) were studied by polymerase chain reaction with sequence specific primers and the 86th amino acid of the DR beta 1 chain was analysed in RA patients vs healthy controls. The frequency of HLA-DR beta 1*0401 and 0404/0407 alleles was significantly increased in RA patients vs the controls, HLA-DR beta 1*0401 and 0404 being the dominant variants in RA. In most RA patients hydrophilic glycine proved to be the 86th amino acid of the peptide binding region thus it could have an effect on the development of RA.
8884998 Pleural fluid beta-2-microglobulin and angiotensin-converting enzyme concentrations in rhe 1996 Concentrations of beta 2-microglobulin (B2M) and angiotensin-converting enzyme (ACE) were measured in pleural fluid (Pf) and serum (S) of 364 patients with pleural effusions. Eleven patients had rheumatoid arthritis (RA), 36 verified tuberculosis (TB), 15 suspected TB, 120 cancer, 21 empyema, 34 pneumonia, 33 various defined diseases, 67 effusions of unknown aetiology and 27 congestive heart failure. The median concentrations of Pf-B2M and Pf-ACE were significantly higher in patients with RA than in patients with any other disease (p < 0.005). Tuberculous effusions contained higher Pf-ACE concentrations than any other type of non-rheumatoid effusion (p < 0.05). With sensitivities of 91%, the specificity of Pf-B2M and Pf-ACE for the diagnosis of RA was 86% and 55%, respectively. Local cellular immune events probably account for the abundance of B2M and ACE in rheumatoid and tuberculous pleural effusions. Pf-B2M and Pf-ACE determinations may aid in the differentiation of rheumatoid and tuberculous pleurisy from other types of pleural disease.
8136468 The role of adhesion molecules in the pathogenesis of rheumatoid arthritis. 1993 Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by infiltration of mononuclear cells, mainly T lymphocytes, into the synovial membrane (SM). The interaction of peripheral blood T cells with the different components of the rheumatoid synovium is mediated by cell surface proteins such as selectins, integrins, members of the immunoglobulin superfamily and homing receptors. T lymphocytes infiltrating the rheumatoid SM show an activated phenotype and display an increased avidity of their adhesion receptors that results in an enhanced interaction of these cells with both extracellular matrix proteins (ECM) and cellular ligands (VCAM-1, ICAMs). The interaction of T cell integrins with their ligands, besides an additional antigenic stimulus, could trigger a mitogenic response on these cells, a phenomenon that can contribute to increased cellularity observed into the rheumatoid SM. Moreover, cell attachment to ECM through integrins induces the secretion of several proteases that can contribute to the tissue damage observed in RA. The increased knowledge about the role of adhesion receptors in the pathogenesis of RA and other inflammatory diseases will allow the introduction of a new therapeutic approach by: the use of specific blocking reagents designed to interfere with the function of adhesion molecules.
8189099 [Fibronectin in the synovium and synovial fluid in rheumatoid arthritis and in osteoarthri 1994 Apr Fibronectin (FN) in the rheumatoid, and osteoarthritic, synovium was examined by light microscopy using immunostaining by fluorescein-labeled anti-fibronectin, or by peroxidase-labeled anti-fibronectin. Immunofluorescent FN was found more in the rheumatoid synovium than in the osteoarthritic synovium. The mean fluorescence intensity in a given area of the synovium including the synovial surface in rheumatoid arthritis was significantly higher than in osteoarthritis. As there was a significant correlation between the fluorescence intensity in the synovium and the number of synovial lining cells immunostained with peroxidase-labeled anti-fibronectin, the fluorescence intensity appeared to depend on the number of synovial lining cells containing FN. FN in the rheumatoid synovium and synovial fluid cells was examined by electron microscopy after immunoperoxidase staining. Immunoelectron microscopy of the rheumatoid synovium demonstrated FN on the surface of both type-A and type-B cells, the collagen fibers, and within the mitochondria, in the endoplasmic reticulum of type-B cells, and in the intercellular contact zone. These findings suggested that FN was mainly produced in the type-B cells, and played a role in maintaining the synovial structure. Immunoelectron microscopy of the rheumatoid synovial fluid cells confirmed the presence of FN on their surfaces. This suggested that FN opsonized by adhering debris to FN on the cell surfaces in the synovial fluid. The concentration of FN in the rheumatoid, and osteoarthritic, synovial fluids was measured by single radial immunodiffusion. The FN concentration in the rheumatoid synovial fluids was significantly higher than in the osteoarthritic synovial fluids. However, it was not significantly correlated with the indices of inflammatory activity such as with the C-reactive protein, the erythrocyte sedimentation rate, or catalase activity measured by a gasometry, or with the number of polymorphonucleated cells.
1559653 [A case of primary biliary cirrhosis with negative anti-mitochondrial antibody anteceded b 1992 Mar We report a case of primary biliary cirrhosis with negative anti-mitochondrial antibody which were anteceded by rheumatoid arthritis. The patient was a 46-year-old female who was admitted due to low grade fever and elevated serum alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (gamma-GTP) levels. She had been diagnosed as having erythema nodosum and rheumatoid arthritis 6 years before. Her family history disclosed that her mother had rheumatoid arthritis and her sister systemic lupus erythematosus. On admission, she had moderately elevated erythrocyte sedimentation rate, and elevated serum ALP, gamma-GTP and IgM levels. Anti-mitochondrial antibody and anti-pyruvate dehydrogenase complex antibody were negative but anti-nuclear antibody was positive. However, the histology of liver showed chronic non-suppurative destructive cholangitis. AMA was always negative and serum ALP and bilirubin levels remained constant during the following two years. The pathogenesis of primary biliary cirrhosis with negative anti-mitochondrial antibody is discussed.
7979585 Absence of Mycobacterium tuberculosis DNA in synovial fluid from patients with rheumatoid 1994 Oct OBJECTIVES: To determine whether Mycobacterium tuberculosis DNA can be detected in synovial fluid of patients with rheumatoid arthritis (RA). METHODS: The polymerase chain reaction was applied to cellular components of synovial fluid. RESULTS: No evidence of M tuberculosis DNA was found in synovial fluid from 31 patients with RA and 13 control patients. CONCLUSION: The findings do not support a role for persistent M tuberculosis infection in the pathogenesis of RA.
8266027 Use of anti-thymocyte globulin in the management of refractory systemic autoimmune disease 1993 The purpose of our pilot study was to evaluate the short-and long-term efficacy of T-lymphocyte depletion in the management of patients with refractory, systemic autoimmune diseases. Nine patients with severe, therapy-resistant autoimmune diseases were subjected to T-cell depletion procedure using polyclonal anti-T-cell antibodies combined with peroral administration of azathioprine and/or cyclosporine. The proband group consisted of 4 patients with systemic lupus erythematosus, 3 with progressive systemic sclerosis, and 2 with rheumatoid arthritis. Administration of polyclonal anti-T-cell antibodies was performed at a single occasion via a central venous catheter during 9-10 days. Immunological analyses of T-cell phenotypes and function and assessment of organ function (kidneys, lungs, bone-marrow) has been performed prospectively in all the patients studied. This treatment resulted in prompt and long-lasting (mean follow-up time: 25.6 months) improvement of autoimmune hemolytic anemia, glomerulonephritis, lung fibrosis, skin and joint involvements in the majority of cases. Adverse effects of this treatment included two episodes of infection (E. coli and Cytomegalovirus) and three cases of serum sickness, and were all easily managed. We suggest that this treatment modality adopted from transplant rejection therapy could be employed in cases of severe autoimmune diseases unresponsive to regular immunosuppressive treatment.
1645047 Original versus generic piroxicams, their cost-effective evaluation in rheumatoid arthriti 1992 Feb This was a 12 week double-blind cross over study of 14 patients with rheumatoid arthritis on the cost-effectiveness of different priced piroxicams. All three drugs affected a significant improvement over baseline measurements in most of the clinical parameters assessed with statistical comparable efficacy. Pharmacokinetic analysis also showed similar properties except for the time to reach maximum concentration which was in favor of drug A. This property may be advantageous in treating acute conditions such as gouty attacks. However, in chronic disease like rheumatoid arthritis, there was no significant difference in pharmacologic and clinical efficacy among the three different piroxicams marketed in Thailand.
8975275 [The pathogenesis of joint destruction in chronic polyarthritis]. 1996 Aug Joint destruction, a hallmark of rheumatoid arthritis, is described with respect to different mechanisms: destruction by inflammatory cells of the synovial fluid, pannus tissue and even ischemic bone necroses. Destruction via the synovial fluid is due to polymorphonuclear neutrophils (PMN) that can invade the pannus-free cartilage surface. In the absence of anti-proteases as a result of direct contact between the PMN and cartilage, enzymatic degradation can occur. Pannus tissue usually develops from the synovial insertion. Increased cellular proliferation in this area leads to a superficial pannus tissue that covers the cartilage (Fig. 4b); granulation tissue from the synovial insertion can destroy cortical bone and invade the subchondral tissue. The problem of isolated subchondral inflammatory foci is briefly discussed. The effector cells of cartilage destruction are identified as macrophages, PMN, and mast cells -cells that produce or activate destructive enzymes. Bone destruction is due to osteoclasts and even macrophages. Acute destruction via the granulation tissue may be followed by defect healing-scar tissue or chondroid metaplastic tissue can be present in the final stages of the disease. Ischemic bone necrosis leading to pseudocysts may also contribute to joint destruction.
7554557 Impaired binding capacity of asialyl and agalactosyl IgG to Fc gamma receptors. 1995 May OBJECTIVE: Autoimmunity in rheumatoid arthritis has been associated with deficient glycosylation of serum and synovial IgG which could potentially be mediated through the binding of the Fc portion of the molecule to its cognate receptor. METHODS: Normal IgG1 and IgG3 were affinity-purified, and sialic acid and galactose were clipped off using neuraminidase and beta-galactosidase, respectively. The binding of these sugar-depleted IgG to the Fc gamma receptors (Fc gamma R)IIIb on polymorphonuclear leukocytes (PMN) was assessed by flow cytometry. RESULTS: The binding of both asialyl and agactosyl IgG1 and IgG3 to PMN was significantly lower than that of the native IgG1 and IgG3. CONCLUSION: These data indicate that agalactosyl and, to a lesser degree, asialyl IgG, do not bind as efficiently as native IgG to Fc gamma R. Such a reduction in the perspective of the heterogeneity of the PMN Fc gamma RIIIb.
8026822 Lymphoid neoplasms in patients with rheumatoid arthritis and dermatomyositis: frequency of 1994 Jul We recently reported two cases of reversible Epstein-Barr virus (EBV)-associated lymphomas in patients undergoing methotrexate therapy for rheumatic disease. The current study was undertaken to investigate how frequently lymphoid neoplasms in patients with rheumatic disease show features of lymphoproliferations occurring in immunocompromised patients. Eighteen patients (including the two previously reported patients) with rheumatoid arthritis or dermatomyositis who developed lymphoproliferative lesions and on whom detailed clinical information was available were studied. As a group these patients developed a spectrum of lymphoproliferative lesions; however, a subset of patients developed neoplasms with features associated with immunosuppression. The neoplasms occurred in extranodal sites in 10 (56%) patients, showed a diffuse large-cell histology in nine (50%) patients, and contained EBV (EBER1) transcripts and EBV latent membrane protein in six (33%) patients. In three (17%) patients the neoplasms showed the entire constellation of features typical of immunosuppression-associated lymphoproliferations, including extranodal location, large-cell or polymorphous histology, geographic areas of necrosis, and the presence of EBV. These three patients were receiving both steroids and methotrexate at the time they developed their neoplasms. The findings of this study support the hypothesis that a subset of lymphoid neoplasms in rheumatic patients occurs in an immunocompromised setting and suggest that therapeutic immunosuppression may contribute, at least in part, to the development of these lymphoid neoplasms.
8413047 [Epidemiology of antirheumatic drug-induced ulcer in comparison with peptic gastroduodenal 1993 Aug 15 Within the framework of a five-year analysis of a hospital population (n = 503), the epidemiological and diagnostic data of patients with non-steroidal anti-inflammatory drugs-associated ulcers of the stomach and duodenum (AIU) were evaluated and compared with those of patients with peptic ulcers (PUC) in the stomach and duodenum with no history of NSAIDs use. With respect to age and sex, patients with AIU were significantly older, in particular in the case of gastric ulcer, and revealed a predominance of female sex as compared with those with PU. Episodes of ulcer disease showed no seasonal dependence, either in the AIU or in the PU group. The use of tobacco and alcohol was comparable in both groups. Nor was any difference found between city and rural populations in either group. Laboratory data revealed a higher rate of pathological deviations in the AIU as compared with the PU group, which, however, was unequivocally due to the larger percentage of elderly patients in the former. With respect to blood group distribution, no differences were observed between the groups. An analysis of ulcer site showed a small preponderance of gastric ulcer (59%) over duodenal ulcer (41%) in the AIU group, while the distribution in the case of the PU group was virtually identical (gastric ulcer 51%, duodenal ulcer 49%), with only small differences in site within the stomach and duodenal bulb resp. Analysis of the risk indicators for ulcer bleeding (AIU 66%, PU 50%) revealed the following pattern: in the case of AIU, patients aged over 65, and in the case of AIU and PU, overweight males, bled significantly more often than, respectively, younger patients and female or normal-weight patients.(ABSTRACT TRUNCATED AT 250 WORDS)
7806118 [Clinical relevance of the antiphospholipid syndrome. Antiphospholipid antibodies in a mix 1994 Oct 30 The antiphospholipid syndrome may occur either in association with systemic lupus erythematosus (SLE) or as a primary condition. Diagnostic criteria include the detection of antiphospholipid antibodies using cardiolipin antigen (anticardiolipin antibodies, ACA) or lupus anticoagulant, and at least two clinical manifestations, primarily venous or arterial thrombosis, thrombocytopenia or repeated miscarriage. Among 200 patients with various rheumatic diseases, a pathological ACA test in excess of 44 U/ml was detected with ELISA in 81 cases (41%), and of these 30% had values exceeding 100 U/ml. Both overall positive reactions and the particularly high titers were clearly more common among patients with rheumatoid arthritis (RA) and collagen disease, namely 51% and 33%, respectively, than in patients with sero-negative spondylarthritis and non-inflammatory diseases of the locomotory system (22% pathological, 13% highly pathological, titers. Correlations were also found with miscarriage in women, positive rheumatoid and antinuclear factors, and the number of diagnostic criteria of RA or SLE presenting. A questionnaire survey - evaluating 84 subjects, half with positive and half with negative, ACA reactions - confirmed the correlation between miscarriage and the detection of ACA.
7940328 [The chronobiological aspects of lysosomal enzyme activity in the synovial fluid and of re 1994 A study of activity of 4 lysosomal enzymes (LE) (deoxyribonuclease, acid phosphatase, acid cathepcines and beta-galactosidase) in synovial fluid (SF) depending on month of obtaining of the sample was conducted in 112 patients with rheumatoid arthritis (RA). A statistically significant chronobiological difference in this parameter was shown for all investigated enzymes with its increasing in spring and autumn and decreasing in summer and winter. The mean duration of the disease was 9.05 +/- 0.51 years. The dependence of duration of the effect after single intraarticular injection of glucocorticosteroids (methylprednisolone acetate, triamcinolone acetonide, the composition of the latest with cyclophosphamide and dymethylsulfoxide) upon the month of the puncture was investigated in 194 patients with RA. A statistically significant fluctuation (r < 0.05) of remission duration after single injection was shown only for triamcinolone acetonide +/- cyclophosphamide, but the analysis of graphic distribution gives an opportunity to imagine such a chronobiological law for other lysosomal enzymes. The identical distribution of extremes of LE activity and duration of effect after single intraarticular injection of glucocorticosteroids suggests the chronobiological link of these two parameters.
7617051 [Family physician consultation by patients with rheumatoid arthritis or gonarthrosis/coxar 1995 Jul 1 OBJECTIVE: To determine how often patients with rheumatic joint disease consult their general practitioner (GP), and if there are disease and patient characteristics that influence GP consultation of gonarthrosis/coxarthrosis patients. DESIGN: Prospective record investigation. SETTING: Seven GP centres in the southeast of the Netherlands. METHOD: All patient contacts were registered prospectively in the seven GP centres: 46 concerned patients with rheumatoid arthritis (RA), 122 patients with gonarthrosis/ coxarthrosis. Patient and disease characteristics were collected on intake sheets. RESULTS: Three-quarters of the RA patients were periodically seen (mostly by a specialist), and 47% of the gonarthrosis/coxarthrosis patients (as often by their GP as by a specialist). Of the RA patients and of the gonarthrosis/coxarthrosis patients 74% and 89% respectively consulted their GPs in one year (the average numbers of contacts were 4.7 and 5.0); 50% and 57% did so because of the chronic joint disease (with 2.2 and 1.6 contacts respectively). No disease characteristics and only a few patient characteristics (arthroplasty, chronic use of medication) of patients with gonarthrosis/coxarthrosis influenced GP consultation. CONCLUSION: Patients with rheumatic joint disease often consult their GP, but not always because of this illness. If they consult their GP, they usually do so more than once a year.
7972746 Lung changes in rheumatoid arthritis: CT findings. 1994 Nov PURPOSE: To evaluate lung changes in rheumatoid arthritis (RA). MATERIALS AND METHODS: The authors reviewed the computed tomographic (CT) scans from 84 patients with RA with a mean articular disease duration (+/- standard deviation) of 12 years +/- 8 (range, 0.3-45 years). Fifteen patients underwent sequential CT evaluation during 5-65-month follow-up (mean, 18 months). RESULTS: Thirty-eight patients (49%) had abnormal CT scans showing the following abnormalities: (a) bronchiectasis and/or bronchiolectasis (n = 23, 30%), (b) pulmonary nodules (n = 17, 22%), (c) subpleural micronodules and/or pseudoplaques (n = 13, 17%), (d) nonseptal linear attenuation (n = 14, 18%), (e) areas of ground-glass attenuation (n = 11, 14%), and (f) honeycombing (n = 8, 10%). Abnormal CT examinations were recorded in 11 of 38 asymptomatic patients (29%) and 27 of 39 symptomatic patients (69%). The following CT abnormalities were found with a significantly higher frequency among patients with respiratory symptoms: (a) bronchiectasis and/or bronchiolectasis, (b) rounded areas of attenuation, (c) areas of ground-glass attenuation, and (d) honeycombing. CONCLUSION: CT may be a useful noninvasive tool for recognition of RA-associated lung disease with special emphasis on bronchial and bronchiolar changes.
8055195 Expression of complement regulatory molecules and other surface markers on neutrophils fro 1994 Aug In an effort to elucidate the activation status of neutrophils (PMN) in inflammatory joint disease the expression of relevant cell surface proteins was examined using immunofluorescence and flow cytometry. Paired samples of SF and peripheral blood were obtained from 18 patients with RA and PMN purified using methods designed to minimize activation in vitro. We then used flow cytometry to measure expression of the four membrane complement regulatory molecules, decay accelerating factor (DAF; CD55), complement receptor 1 (CR1; CD35), membrane cofactor protein (MCP; CD46) and CD59; two adhesion molecules of the integrin family LFA1 (alpha chain, CD11a), complement receptor 3 (CR3; alpha chain, CD11b), and their common beta chain (CD18); the major receptor for immune complexes Fc gamma RIII (CD16), and the leucocyte common antigen tyrosine phosphatase (L-CA; CD45). Expression of these molecules was also measured on peripheral blood PMN from 18 age- and sex-matched normal controls. In RA, SF PMN expressed significantly higher levels of the complement regulators CD55 and CD35, the adhesion molecule CR3 (CD11b/CD18) and of CD45 but significantly lower levels of CD46 and CD11a in comparison with blood PMN from the same patient. Expression of CD59 and CD16 did not differ between the two groups. These changes may increase adhesiveness and complement resistance of PMN in SF compared with blood. PMN from RA expressed significantly less of all the complement C3 convertase regulators (CD55, CD46, CD35), all the adhesion molecules (CD11a, CD11b, CD18) and the phosphatase CD45 than did blood PMN from age and sex-matched control individuals.
7743739 Quality of life assessment: a comparison of four questionnaires: for measuring improvement 1995 Jan Three experimental questionnaires were compared with the Influence of Rheumatic Diseases on Health and Lifestyle (IRGL) questionnaire, a Dutch version of the Arthritis Impact Measurement Scales. Sixty-two patients with osteoarthritis (OA) and 35 patients with rheumatoid arthritis (RA), all of whom underwent hip arthroplasty, completed the study. Results showed that visual analogue scales for pain, stiffness, fatigue, and anxiety were strongly correlated with a number of the IRGL scales. Patient preference scales were sensitive to change and provided additional information on aspects of the patients' quality of life (QOL) that were felt to be important by the patients themselves. The questionnaire on performance in various roles in life was insensitive to change. In existing questionnaires, there is an attempt to represent the concept of QOL in terms of its most important aspects. Such realizations of the concept of QOL are not entirely suitable for application in clinical trials. The IRGL is overly complex, and its sometimes comprehensive scales do not deal with the possible effects of treatment. Neither of these properties is conducive to sensitivity to change. Visual analogue scales reduce the complexity. A simpler representation of QOL that can evaluate aspects relevant to treatment is recommended.