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ID PMID Title PublicationDate abstract
8003635 Differential expression of the small inducible cytokines GRO alpha and GRO beta by synovia 1994 Jan Synovial pannus represents a hypertrophic and locally invasive connective tissue response to chronic inflammation that accounts in large part for the periarticular destruction of rheumatoid arthritis. Synovial fibroblasts cultured from rheumatoid synovia have been found to display an increased rate of proliferation and the constitutive expression of collagenases, growth factors, and inflammatory cytokines. The existence in rheumatoid synovium of both a pro-inflammatory state and growth dysregulation led us to investigate the expression by synovial fibroblasts of the closely homologous cytokines GRO alpha (gro/MGSA), GRO beta (MIP-2 alpha), and GRO gamma (MIP-2 beta). These cytokines are released by a variety of cell types and display overlapping growth regulatory and pro-inflammatory activities. In contrast to expectations, the majority of synovial fibroblast cell lines derived from osteoarthritic or non-inflammatory synovia showed a relative increase in the constitutive expression of GRO alpha and GRO beta when compared to synovial fibroblasts obtained from rheumatoid synovia. Considered together with evidence that GRO alpha is a growth regulator that modulates the expression of metalloproteinase activity, these findings provide evidence for a differential pathway of cytokine activation that may downregulate the proliferative and erosive response to chronic arthritis.
7714025 Progress in the immunogenetics of rheumatoid arthritis. 1995 Apr 15 Although much remains to be learned about environmental factors and putative pathogens, significant strides have been made on the genetic front. Genes appear to have a greater role in determining disease severity than disease risk. In particular, patients who are heterozygous for two HLA-DR4 subtypes are prone to severe erosive disease, making them candidates for early, aggressive therapy.
8767656 [Psoriatic osteoarthropathy and bone scintigraphy]. 1996 Jun Psoriasis is a generalized disease that affects bone as well as skin. Three patterns of bone involvement can be differentiated in psoriatic arthritis distal, central, and distal combined with central. Distal involvement is more specific for psoriatic arthritis, with radial and/or transverse involvement of the distal interphalangeal joints. The progression dynamic and the pattern of distribution are different from those pattern of rheumatoid arthritis: psoriatic arthritis originates in the periarticular bone and extends towards the synovia, whereas in rheumatoid arthritis it extends in the opposite direction. In psoriatic arthritis anterior chest wall syndrome, insertion tendinopathies, and localized or diffuse bone disease are often observed. Bone scintigraphy is more sensitive in the diagnosis of psoriatic bone involvement than clinical examination or conventional radiological imaging, allowing earlier diagnosis through the visualization and documentation of specific patterns and presence of disease in multiple sites. It also allows more discriminating selection of subsequent X-ray examinations to limit radiation exposure. Thus, bone scintigraphy is now the most important diagnostic tool in the assessment of psoriatic arthritis.
8441174 Plasminogen activators and plasminogen activator inhibitors in synovial fluid. Difference 1993 Jan The plasminogen activator (PA)/plasminogen activator inhibitor (PAI) system is believed to be involved in connective tissue remodelling in joint disease and both PA and PAI production has been shown in several cell types in the joint. We quantified immunoreactive PA and PAI in synovial fluid (SF) and correlated their levels to levels of cartilage derived proteoglycans, radiologically visible joint involvement and to signs of local inflammation. PAI-2 concentrations were increased, compared to normal plasma levels, in patients with rheumatoid arthritis (RA) and reactive arthritis, but not in patients with osteoarthritis (OA). Thirty percent of the patients with RA, but no patient with OA had increased concentrations of PAI-1. Increased concentrations of urokinase type PA (u-PA) were found in RA but not in OA. Tissue type PA (t-PA) concentrations were low in both disease groups. SF proteoglycan concentrations did not correlate with levels of PA or PAI. Concentrations of PAI-2 correlated significantly with SF leukocyte count and cytidine deaminase (CD) activity and u-PA concentrations correlated with CD activity. Both PAI-2 and u-PA were detected in supernatants from lysed polymorphonuclear cells. This suggests that in addition to release from synovial cells and chondrocytes these components may also be released from polymorphonuclear cells. Our results support a pathophysiological role for the fibrinolytic system in joint disease, possibly more pronounced in inflammatory disorders than in OA.
7536415 Demonstration of granzyme A and perforin messenger RNA in the synovium of patients with rh 1995 Apr OBJECTIVE: To examine the gene expression of 2 highly specific markers of cytotoxic T lymphocyte (CTL) activation, the serine protease granzyme A and the pore-forming protein perforin, in synovial tissue of patients with rheumatoid arthritis (RA), and to compare the findings with those in osteoarthritis (OA) synovial tissue. METHODS: Snap-frozen synovial tissue specimens from 9 patients with RA and 5 patients with OA were examined. The number of CTL that expressed granzyme A or perforin messenger RNA was determined by in situ hybridization using nonradioactive riboprobes for granzyme A and perforin, and by a novel in situ reverse transcriptase technique. The signals were visualized by an immunogold-silver immunohistochemistry technique and compared with immunohistochemical labeling of T and B cells. Additional double-labeling was achieved using anti-type IV collagen, anti-macrophage (anti-CD68), anti-T lymphocyte (anti-CD45RO), anti-B lymphocyte (anti-CD20), and anti-natural killer cell (anti-CD56) antibodies in an alkaline phosphatase-anti-alkaline phosphatase assay. RESULTS: Granzyme A and perforin messenger RNA (mRNA) was observed in CTL in synovial specimens from all of the RA patients, whereas in specimens from OA patients only a few, single cells with a positive mRNA signal for these molecules could be detected. In the RA specimens, the number of lymphocytes showing a positive mRNA signal for granzyme A or perforin varied from 10% to 50%, reflecting the recent findings of other investigators studying synovial fluid. CONCLUSION: Our results demonstrate that gene expression of at least 2 CTL products, granzyme A and perforin, is up-regulated in the synovium of patients with RA compared with that in the synovium of patients with OA. These molecules presumably play an important role not only in lymphocyte-mediated cytotoxicity, but also in facilitating the migration of blood-borne mononuclear cells through the vascular basement membrane into the rheumatoid synovium.
8163972 Long-term outcome of Volz total wrist arthroplasties. 1994 Feb The authors determined the outcomes of 18 consecutive Volz total wrist arthroplasties that were followed for an average of 8.6 years. Nine of these wrists were followed for 10 or more years. Fourteen wrists were replaced for rheumatoid arthritis and four for post-traumatic degenerative joint disease. Forty-nine degrees of combined flexion and extension and 25 degrees of combined ulnar and radial deviation were maintained. The balance of wrist motion was dependent upon the design and location of the metacarpal prosthesis. A 24% loss in carpal height (subsidence) occurred during the study period. Four metacarpal components were loose (22%), three of which were placed in patients with degenerative joint disease. One radial component (6%) was loose. Fifteen of 18 wrists (83%) had little or no pain. The three wrists with moderate or severe pain were in patients with degenerative joint disease. There were five (28%) complications. One revision was performed and another was recommended. Overall, the long-term outcome of total wrist arthroplasty was favorable in patients with rheumatoid arthritis.
1538889 Nabumetone: a new NSAID for rheumatoid arthritis and osteoarthritis. 1992 Feb Fifteen nonsteroidal anti-inflammatory drugs (NSAIDs) are available in the United States today, yet no clear distinctions among their indications, risk-benefit profiles, or cost effectiveness have been proved. Nabumetone (Relafen), a new NSAID for the treatment of rheumatoid arthritis (RA) and osteoarthritis (OA), may differ from the others. Studies have shown that, when compared with currently available NSAIDs, nabumetone may be associated with a significantly lower incidence of gastroduodenal ulcer, and that nabumetone also appears to be safer for use in elderly patients and in those with renal or hepatic impairment.
7761078 [Low-dose methotrexate therapy of rheumatoid arthritis in the elderly]. 1995 May 28 Two years results of methotrexate treatment (13 patients, 7.5-10 mg weekly dose) in elderly onset rheumatoid arthritis are reported in comparison to other therapies (10 patients, im. gold 50 mg weekly or per os steroid max. 10 mg daily). Clinical activity of rheumatoid arthritis was measured with standard rheumatological parameters whereas progression of the disease was defined by means of a radiological method. Methotrexate caused better clinical improvement and retarded progression to a greater extent than the other therapies. Methotrexate achieved its maximum effect during the first 6 months of therapy. Methotrexate was well tolerable. Long term applicability of low dose methotrexate treatment in elderly age is emphasized.
8003054 The sensitivity and specificity of computerized databases for the diagnosis of rheumatoid 1994 Jun OBJECTIVE: To examine the accuracy of a computerized medical database for the diagnosis of rheumatoid arthritis (RA). METHODS: The complete medical records of all prevalent cases of RA (according to the 1987 American College of Rheumatology diagnostic criteria) on January 1, 1987 were reviewed to determine the sensitivity, specificity, and predictive value of database diagnoses compared with those obtained by medical record review. Agreement between database and medical record diagnoses was calculated using the kappa statistic. RESULTS: Computerized database diagnoses of RA had a sensitivity of 89%, a specificity of 74%, a positive predictive value of 57%, and a negative predictive value of 94% compared with diagnoses based on clinical information abstracted from the complete medical record. Agreement between database and medical record diagnoses was poor (kappa = 0.54). CONCLUSION: The sole reliance on such databases for the diagnoses of RA can result in substantial misdiagnosis.
8912630 Fas-mediated stimulation induces IL-8 secretion by rheumatoid arthritis synoviocytes indep 1996 Nov 1 In this study, we investigated the IL-1 beta converting enzyme (ICE) family cysteine proteases responsible for the Fas-mediated apoptosis of rheumatoid arthritis (RA) synoviocytes and their involvement in proinflammatory cytokine production. CPP32 inhibitor, but not ICE inhibitor, was capable of inhibiting the Fas-mediated apoptosis of RA synovial cells. CPP32, but not ICE, was activated in response to anti-Fas stimulation. IL-8, but not IL-1 beta, was secreted from the anti-Fas-stimulated RA synoviocytes even in the presence of CPP32 inhibitor. These results demonstrated that CPP32, but not ICE, is the predominant cysteine protease that mediates the Fas-mediated apoptosis of RA synovial cells. We also demonstrated that anti-Fas stimulation of RA synoviocytes leads to IL-8 secretion independently of the CPP32-mediated apoptosis, which would accelerate inflammation.
7570210 [Detection of myocardial lesions by dipyridamole thallium-201 scintigraphy in patients wit 1995 Jun Dipyridamole Thallium-201 (T1) scintigraphic studies to evaluate microcirculation of the heart were performed in 54 patients with rheumatoid arthritis (RA) who had neither cardiac complaints nor myocardial damages on ECG. Twenty seven of 54 RA patients showed some perfusion defects in this study. The values of ESR, CRP and rheumatoid factors of IgM and IgG classes were significantly higher in these patients with perfusion defect comparing with those in the rest of RA patients with normal perfusion. The scintigraphic perfusion defects improved relating with the reduction of inflammatory activities of RA. The histological specimens of heart in 12 RA autopsy cases were reviewed to study the etiology of these perfusion defects. In 7 of 12 cases, microvasculitis and microthrombosis were observed without any macroscopic findings compatible with myocardial infarction. Our results suggest that RA patients have frequently microcirculatory disturbances in the heart due to microvasculitis without any clinical symptoms of ECG changes.
7738179 Correlation between disease phenotype and genetic heterogeneity in rheumatoid arthritis. 1995 May RA is a heterogeneous group of disorders characterized by variations in clinical manifestations, disease course, and probably response to therapeutic interventions. We have addressed the question whether genetically and potentially etiologically more homogeneous subgroups of RA patients can be defined based upon the expression of the RA-linked sequence motif in the third hypervariable region of the HLA-DRB1 gene. Genetic comparison of patients classified upon clinical manifestation and disease course demonstrated that patients with mild disease were genetically distinct from those progressing to severe and destructive disease. Specifically, rheumatoid factor (RF) negative patients preferentially expressed RA-linked HLA-DRB1 alleles with an arginine substitution in position 71, whereas the alleles with a lysine substitution in position 71 accumulated in RF+ patients. RF- patients were further subdivided based on clinical markers (time of onset of erosive disease and requirement for aggressive therapy). Clinical heterogeneity correlated with genetic heterogeneity. Patients with early erosive disease and patients requiring aggressive therapy frequently typed HLA-DRB1*04+. Patients with late erosive/nonerosive disease or a benign disease course manageable with nonaggressive treatment preferentially expressed HLA-DRB1*01 or lacked an RA-linked haplotype. These data indicate that the heterogeneity of RA reflects genetic differences. Sequence variations within the disease-linked sequence motif, as well as polymorphisms surrounding the candidate genetic element, affect pattern, course, and treatment response of RA. Amino acid position 71 in the HLA-DRB1 gene has a unique role, the understanding of which may provide important clues to disease etiology.
1730923 Assessment of in vivo frequency of mutated T cells in patients with systemic lupus erythem 1992 Jan 1 The frequency of mutant T cells (FMC) in blood lymphocytes from patients with systemic lupus erythematosus (SLE) was measured by growing cells in the presence and in the absence of 6-thioguanine. Patients with SLE had a spectrum of FMC ranging from normal to about 100 times normal. This high FMC among cells from SLE patients appears to reflect excessive in vivo activation and proliferation during the course of the disease. This represents the first demonstration of such a T cell abnormality in SLE; it supports the hypothesis that SLE T cells demonstrate increased in vivo division and/or survival.
1471431 [Developing occupational integration of patients with chronic polyarthritis during product 1992 Rheumatoid arthritis is a common disorder that depends on the activity of the disease, the severeness of the functional losses, and the degree of suffering from pain. In a study of 817 RA patients it could be shown that the occupational status depends as much on the severing of the disease as on the job status, educational status, and income.
8978952 Lipoproteins, anticardiolipin antibodies and thrombotic events in rheumatoid arthritis. 1996 Nov OBJECTIVE: To investigate lipoprotein levels in rheumatoid arthritis (RA) patients with and without anticardiolipin antibody (aCL) positivity and to evaluate whether an abnormal lipid profile might be associated with an altered risk of vascular disorders. METHODS: 137 female patients were evaluated for their aCL levels (isotypes IgG and IgM); concentrations of plasma lipids, lipoproteins, and apolipoproteins; and for the occurrence of thrombotic events. The patients were grouped according to their aCL positivity. RESULTS: Higher rates of venous and/or arterial thrombosis were diagnosed in all the RA patients compared to the controls (p = 0.01). Lower levels of the high density lipoprotein cholesterol, apolipoprotein AI, were found in these patients (p = 0.001). Higher levels of lipoprotein (a) were observed in RA patients when compared to controls in both aCL positive and negative RA patients (P = 0.001 and p = 0.01, respectively). CONCLUSION: The presence of aCL and an altered lipid profile may represent an important risk factor for thrombotic events in patients affected by RA.
8913656 Shift in the incidence of rheumatoid arthritis toward elderly patients in Finland during 1 1996 Sep OBJECTIVE: To obtain information on changes in the age distribution of new cases of rheumatoid arthritis (RA) in Finland. METHODS: The present study covered those subjects entitled under the nationwide sickness insurance scheme to receive specially reimbursed medication for RA in 5/21 central hospital districts in Finland (population base about one million adults) in 1975, 1980, 1985, and 1990. RESULTS: During the four study years 1321 incident cases occurred, which satisfied the American Rheumatism Association 1987 classification criteria for RA. The mean age at diagnosis increased by 7.6 years from 1975 (50.2 years) to 1990 (57.8 years). No appreciable differences occurred between men and women. The incidence rates declined in the younger age groups. CONCLUSION: The epidemiology of RA is in a dynamic state. The trends may reflect marked changes in the host-environment relationship.
8535639 How and when should combination therapy be used? The role of an anchor drug. 1995 Nov Most patients with rheumatoid arthritis do not achieve a complete response to monotherapy; some achieve a sub-optimal response and others become resistant to therapy and escape from control after an initial good response. It is essential to recognize those with an incomplete response early and to introduce combination therapy promptly so as to induce remission and minimize joint damage and disability. The main concern about combination therapy has been the risk of additive or synergistic toxicity. The aim is therefore to choose drugs that are the least toxic and that also have a rapid and sustained action. Sulphasalazine (SASP) possesses these properties; it has a mild toxicity profile and good long-term tolerability. Most adverse events occur during the first few months of therapy and accumulative toxicity on stable maintenance doses is rare. It also has a rapid onset of action and sustained efficacy. On these grounds we recommend that SASP is used in combination therapy as the 'anchor drug' to which other drug(s) can be added sequentially. This sequential regimen allows those patients who respond to monotherapy to be identified, and gives flexibility of dose control so that the drugs can be tailored to the individual patient. Combination therapy may have real advantages in inducing remission and preventing resistance to therapy. it also has the potential for long-term disease modification.
1395221 Synovial extracellular matrix II. Specific incorporation of immunoglobulin into the cell-f 1992 Jul To determine whether immune complex-like material is incorporated into the extracellular matrix (ECM) of proliferated RA synovium, cell-free matrices were isolated from pannus removed at joint replacement surgery, and were subjected to differential extraction. When the IgG and albumin concentrations in the ECM extracts were compared to those in simultaneously obtained synovial fluids, the IgG was found to be enriched 8.8-fold. Approximately 95% of the IgG was extractable with 6M Guanidine-HCl and 8 M Urea-B-ME. Further extraction with collagenase and low-pH buffers did not result in any additional recovery of IgG. Matrix-associated IgG demonstrated a restricted mobility on IEF with a pI of 4.8. The extracellular matrix of RA pannus is enriched in an acidic IgG species. Incorporation of IgG appears to be secondary to non-covalent interactions and may represent an additional reservoir of immune complex material in the rheumatoid joint.
1360191 Helicobacter pylori and peptic ulcers in rheumatoid arthritis patients receiving gold, sul 1992 Dec The conflicting reports on gold and Helicobacter pylori could be related to the use of serological tests of unproven value in NSAID patients, and to the lack of the appropriate control groups. More important is the fact that the endoscopic consequences of the possible effect of gold on H. pylori have not been investigated. We therefore decided to assess the prevalence of H. pylori and peptic ulcers in rheumatoid patients being treated with gold sodium thiomalate (GST) plus NSAID, sulfasalazine plus NSAID, or NSAID only. Eighty-five patients receiving treatment for at least 6 months were endoscoped, and H. pylori was studied in gastric antral biopsies by both culture and histology. Endoscopic abnormalities were classified into ulcers (measuring 5 mm in diameter or more) and erosions (smaller lesions). H. pylori (and ulcers) were found in 17 (12 ulcers) of 31 patients on NSAID only and 21 (9 ulcers) of 27 patients on sulfasalazine plus NSAID, compared with nine (3 ulcers) of 27 patients receiving GST plus NSAID, p < 0.05, analysis of variance. Patients treated with GST and NSAID had the lowest prevalence of detectable H. pylori. This could explain the apparent reduction in the prevalence of peptic ulcers in this group and, if confirmed in larger randomized studies, might have therapeutic implications.
8199147 Lateral open bite resulting from acute temporomandibular joint effusion. 1994 Apr Two cases of acute open bite, one arising from trauma to the mandible without actual fracture, and one from an acute episode of rheumatoid arthritis, are presented. The resultant malocclusions were due to a sudden increase of volume in the temporomandibular joint space with subsequent displacement of the mandibular condyle, following acute effusion.