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ID PMID Title PublicationDate abstract
1328631 Effects of a single dose of methotrexate on 5- and 12-lipoxygenase products in patients wi 1992 Jun The inhibition of 5-lipoxygenase could be involved in the mechanism of action of methotrexate (MTX). We studied 8 patients with active rheumatoid arthritis (RA) immediately before and the day after the first dose of MTX (10 mg intramuscularly). Leukotriene B4 (LTB4) formation by polymorphonuclear leukocytes was significantly decreased (32%, p less than 0.01). This essentially involved released LTB4. A slight decrease was also obtained in omega-oxidation products. Similar results were obtained for plasma LTB4 (30%, p less than 0.02). A non-significant decrease in 5-HETE was noted. Conversely, 12-HETE was not modified. Our results suggest MTX has an effect on the 5-lipoxygenase pathway, particularly at the LTA4 epoxide hydrolase step, since 5-HETE and 6-trans-LTB4 isomers are not involved.
7805751 Interleukin-4 but not interleukin-10 inhibits the production of leukemia inhibitory factor 1994 Dec The expression of the proinflammatory cytokine leukemia inhibitory factor (LIF) has been reported in the cartilage and synovium of rheumatoid arthritis (RA) patients. Here, we show that high levels of LIF were constitutively produced by cultures of synovium pieces. Low levels of LIF were produced spontaneously by isolated synoviocytes, but interleukin (IL)-1 beta caused a fourfold enhancement of this secretion. The anti-inflammatory cytokine IL-4 reduced the production of LIF by synovium pieces by 75%, as observed earlier with IL-6, IL-1 beta and tumor necrosis factor (TNF)-alpha. IL-4 had a direct effect since it inhibited LIF production by unstimulated and IL-1 beta- or TNF-alpha-stimulated synoviocytes. Conversely, IL-4 enhanced the production of IL-6, which shares with LIF biological activities and receptor components. The inhibitory effect of IL-4 was dose dependent and was reversed using a blocking anti-IL-4 receptor antibody. Similar inhibitory action of IL-4 on LIF production was observed on synovium pieces from patients with osteoarthritis and on normal synoviocytes. IL-10, another anti-inflammatory cytokine acting on monocytes, had no effect on LIF production by either synovium pieces or isolated synoviocytes. Thus, the production of LIF by synovium tissue was inhibited by IL-4 through both a direct effect on synoviocytes and an indirect effect by inhibition of the production of LIF-inducing cytokines.
8779790 [Prospective clinical study of the combination therapy of auranofin and methotrexate for r 1996 Jun In a study to evaluate the usefulness of DMARDs combination therapy for RA, AF and MTX were concurrently given to RA patients who had responded poorly to over three months of monotherapy of either AF or MTX. The study was composed of two stages. In the first stage, patients were concurrently given AF and MTX for six months in order to evaluate the efficacy of combination therapy. In the second stage, patients who had responded to the earlier combination therapy were again put on monotherapy of the additive DMARD. Safety evaluation was conducted with 126 patients, and both efficacy and utility were evaluated in 100 patients. Lansbury index for RA significantly improved in both groups of patients starting with the AF and followed by the MTX combination (Group I) and those who started with MTX alone followed by the AF combination (Group II). The ratio of patients who achieved slight improvement or better in the overall improvement rating was significantly higher in Group I at 74.6%, vs. 51.1% in Group II patients. Ten patients (16.9%) and 2 patients (4.9%) were switched to their additive DMARD monotherapy of MTX and AF respectively, having responded to the combination therapy in stage I with slight improvement or a better rating. Adverse events were observed in 44 patients (34.9%), but the combination therapy neither increased the incidence of adverse events nor caused new adverse events. Combination therapy of AF and MTX appeared to be useful both in terms of efficacy and safety for patients who have experienced the dwindling effect of monotherapy.
1409189 Treatment of Raynaud's phenomenon with triiodothyronine corrects co-existent autonomic dys 1992 Apr Cardiovascular autonomic function was assessed in 9 subjects with Raynaud's phenomenon. The underlying diseases were systemic lupus erythematosus (n = 5), systemic sclerosis (n = 3) and rheumatoid arthritis (n = 1). Five standard non-invasive tests, 3 of heart rate and 2 of blood pressure, were employed. Compared with age and sex matched controls (n = 25), the number of values abnormal was 24 of 45 (53%) overall and between one and 4 (median, 2) individually. Significant differences were present for 3 tests, two of heart rate and one of blood pressure. The subjects were given triiodothyronine, 60 to 80 micrograms per day, for vasospastic attacks. Autonomic function was reassessed between weeks 4 and 9 (9 subjects) and between weeks 12 and 18 (8 subjects) after introduction of triiodothyronine. Test results showed a considerable improvement. At the second reassessment, the number of values abnormal was now 5 of 40 (12.5%) overall and nil (n = 4) or one (n = 4) individually. Significant differences remained for one heart rate test only. Adverse side effects to triiodothyronine occurred in a single subject and were readily controlled. Evidence of somatic neuropathy was present electrophysiologically in all 9 subjects and clinically in 8. Triiodothyronine may have corrected autonomic dysfunction by increasing blood flow to ischaemic peripheral nerves or by acting on the autonomic system more directly. Further study of triiodothyronine in autonomic insufficiency appears merited.
7685772 Monocyte-endothelial adhesion in chronic rheumatoid arthritis. In situ detection of select 1993 Jun Blood monocytes are the principal reservoir for tissue macrophages in rheumatoid synovitis. Receptor-mediated adhesive interactions between circulating cells and the synovial venules initiate recruitment. These interactions have been studied primarily in cultured endothelial cells. Thus the functional activities of specific adhesion receptors, such as the endothelial selectins and the leukocytic integrins, have not been evaluated directly in diseased tissues. We therefore examined monocyte-microvascular interactions in rheumatoid synovitis by modifying the Stamper-Woodruff frozen section binding assay initially developed to study lymphocyte homing. Specific binding of monocytes to venules lined by low or high endothelium occurred at concentrations as low as 5 x 10(5) cells/ml. mAbs specific for P-selectin (CD62, GMP-140/PADGEM) blocked adhesion by > 90% in all synovitis specimens examined. In contrast, P-selectin-mediated adhesion to the microvasculature was either lower or absent in frozen sections of normal foreskin and placenta. mAbs specific for E-selectin (ELAM-1) blocked 20-50% of monocyte attachment in several RA synovial specimens but had no effect in others. mAbs specific for LFA-1, Mo1/Mac 1, the integrin beta 2-chain, and L-selectin individually inhibited 30-40% of adhesion. An mAb specific for the integrin beta 1-chain inhibited the attachment of elutriated monocytes up to 20%. We conclude that P-selectin associated with the synovial microvasculature initiates shear-resistant adhesion of monocytes in the Stamper-Woodruff assay and stabilizes bonds formed by other selectins and the integrins. Thus the frozen section binding assay permits direct evaluation of leukocyte-microvascular adhesive interactions in inflamed tissues and suggests a prominent role for P-selectin in monocyte recruitment in vivo.
8883432 The relevance of chondroitin and keratan sulphate markers in normal and arthritic synovial 1996 Oct This study investigated the synovial fluid concentrations of glycosaminoglycan (GAG), keratan sulphate (KS) epitope 5D4 and chondroitin sulphate (CS) sulphation patterns in healthy volunteers and patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Synovial fluids were collected from knee joints of healthy volunteers (n = 24), and patients with OA (n = 28) and RA (n = 29). Concentrations of GAG and the keratan sulphate epitope 5D4 were measured in 15 of the healthy volunteers, and all of the OA and RA synovial fluids. Total GAG was measured using a dye-binding method and 5D4 by an ELISA. The unsaturated CS disaccharides delta C4 and delta C6 were measured by capillary electrophoresis in all synovial fluids. The concentrations of GAG, 5D4 and delta C6 in the normal synovial fluid were higher but that of delta C4 lower than those of the disease groups. The delta C6:delta C4 ratios correlated with age (r = -0.437, P < 0.001) and the mean value was lower in females than males (2.92 compared with 5.22, P < 0.001). After allowing for age and sex, the delta C6:delta C4 ratio in the control group was significantly elevated (P < 0.001) compared to both OA and RA. The ratio was also related to proteoglycan markers (r = 0.383 for 5D4 and r = 0.357 for GAG). The finding that 5D4 and delta C6:delta C4 ratios are higher in synovial fluid from healthy volunteers compared to OA and RA suggests that they may be markers of the susceptibility of articular cartilage to early damage in arthritis.
7531471 [A new titanium-carbon finger joint implant. Apropos of 15 initial cases]. 1994 Arthroplasty of the MP and PIP joint remains a therapeutic challenge for the hand surgeon. The poor results of the currently available implants are due to their mechanical conception (non strained) or their material (silicone causing instability, ruptures and silicone synovitis). The authors present the preliminary results of a new digital articular implant (IAD). It is a strained implant with a rigid hinge allowing 105 degrees of range of movement (0 degree to 105 degrees). Three sizes are available and very soon four. The intramedullary stems are in titanium alloy (TA6V) and the gliding surfaces in pyrolytic carbon. This association allows solidity, endurance, excellent gliding and no wear debris. 15 implants were evaluated (13 PIP and 2 MP joints) with a follow-up from 4 to 1 year. A painless range of motion were restored in 11 cases and 4 articulations were only lightly painful during motion requiring strength and at the end of the movement. The gain of the range of movement was 50 degrees always in a useful sector. The grasp was 60% better in post than in pre operative conditions. No infection was found. It is only the beginning of this implant but the indications seem to be good for all the articular destructions of the digital joints what ever was the aetiology (traumatic, infection or rheumatoid arthritis).
1539125 [Interleukin-6 (IL-6), soluble interleukin-2-receptor (sIL-2R) and microheterogeneity of a 1992 Feb 15 Cytokines and the different glycosylation profiles of some acute phase proteins appear to be of great value in investigating the activity of inflammatory rheumatic diseases. Using an ELISA to measure the serum concentration of sIL-2R and IL-6 and an affinity electrophoresis with Concanavalin A as a lectin to determine the microheterogenity of the alpha-1-acid-glycoprotein (AGP), we tested the sera of 63 patients with various rheumatic and infectious diseases and 17 healthy persons and compared the results with the usual markers of inflammation, e.g. erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and with the clinical activity of the disease. ESR, CRP and sIL-2R were significantly elevated (p less than 0.001) in seropositive rheumatoid arthritis (RA) and in acute bacterial infection. ESR and CRP showed a better correlation with the clinical activity of RA than sIL-2R. Marked elevation of IL-6 was found only in 30% of RA patients in the early stage of the acute phase reaction (APR). The AGP reactivity coefficient (AGP-RC) was significantly decreased in RA (p less than 0.01) but increased in bacterial infections (p less than 0.001). Our results show that there is no advantage in measuring sIL-2R in the routine diagnosis of rheumatic diseases. Raised IL-6 levels seem to indicate an early stage of APR. If ESR and CRP are elevated, the AGP-RC helps to differentiate between infection and chronic inflammatory rheumatic diseases.
8288080 [Decrease of fecal beta-galactosidase activity in Crohn disease]. 1993 An increased degradation of colonic mucus by bacterial enzymes might participate in the development of mucosal lesions in inflammatory bowel disease. The biodisponibility of drugs used in the treatment of such disease relies upon the metabolic activity of colonic bacterial flora. This activity can be indirectly assessed by measuring fecal enzymatic activities. The aim of this study was to compare fecal beta-galactosidase (beta-gal) activity in controls, in patients suffering from extradigestive inflammatory disease and in patients with Crohn's disease (CD). Three groups were studied including 11 healthy volunteers (6 F, 5 M) mean age 29 years (21-37), 20 patients with rheumatoid arthritis (RA) (17 F, 3 M), mean age 61.5 years, and 34 patients with non operated CD (21 F, 13 M) mean age: 27 years (13-50). The Crohn disease activity index (CDAI) was > 150 in 24 and < 150 in 10. beta-gal activity was measured in fecal extracts by its ability to hydrolyze paranitrophenyl beta-D-galactopyranoside and expressed as units of enzymatic activity/gram of fecal proteins. beta-gal activity was significantly decreased in patients with CD (16 +/- 4.5 U/g) (m +/- sem) as compared with patients with RA (353 +/- 64 U/g) (P < 0.0001) and to controls (263 +/- 40 U/g) (P = 0.002). beta-gal activity was not significantly different in controls and in patients with RA. Patients with active CD had a significantly lower beta-gal activity than patients with quiescent CD (9.5 +/- 3.7 U/g vs 31.4 +/- 11.5 U/g) (P = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)
8187432 Elderly onset of adult Still's disease: report of a case. 1994 Mar Adult Still's disease is a variant of juvenile rheumatoid arthritis occurring most frequently in women 16-35 years of age, but rarely in elderly people. We describe a 75-year-old woman who was considered as having adult Still's disease.
8349314 Increased expression of C1q receptors on neutrophils from inflammatory joint fluids. 1993 May C1q receptor (C1qR) expression was determined by immunofluorescence flow cytometry on neutrophils from paired peripheral blood and synovial fluid samples from 21 patients with rheumatoid arthritis (RA) and 13 patients with other articular diseases (OAD). In both patient groups the levels of C1qR on circulating neutrophils were similar to that observed for normal control subjects, whereas on synovial fluid neutrophils significantly higher levels of receptor expression were observed. The mean percentage increases observed were: RA patients 47%, OAD patients 72%. C1q-bearing immune complexes were most prevalent in patients with RA, with the highest concentrations being found in synovial fluid samples. No correlation between immune complex levels and neutrophil C1qR expression was noted. Upregulation of C1qR expression is a feature of activated neutrophils from inflammatory joint fluids.
8848408 [Investigations concerning the effect of nabumetone on gastric mucosa]. 1996 May The investigations were carried out in 9 patients (6 women and 3 men) with rheumatoid arthritis or degenerative joint disease. All subjects were given 1000 mg nabumetone (NA) in a single daily dose at the evening, during 21 days. Before and after the therapeutic course, endoscopic examination of the upper digestive tract was carried out. On day at the begin and on the 22nd day of the NA treatment, the gastric transmucosal electric potential difference (PD) was determined, in (a) standard condition, (b) after intragastric application of 1000 mg NA, and (c) after a similar application of 1000 mg of acetylsalicylic acid (AAS). On the contrary to the effect caused by AAS (p < 0.001), NA did not result any significant change of the PD (p > 0.05), neither after a single nor after 21 day-long application (the lowest PD value before the NA therapeutic course was after a single NA dose -45.8 +/- 2.7 mV and after a single dose of AAS -40.4 +/- 2.45 mV; after the end of the NA therapy course the values were: after additional NA dose -46.7 +/- 3.5 mV and after AAS -40.5 +/- 2.7 mV) Endoscopically, any changes of the upper digestive tract mucosa which could be related to the NA therapeutic course were not detected.
7923998 Serologic testing for reactive arthritis. 1994 Jun The objective of the study was to determine the sensitivity and specificity of quantitative serum antibody response to Salmonella enteritidis lipopolysaccharide (LPS) as a diagnostic test for post-Salmonella reactive arthritis (ReA). In a single food-source outbreak of Salmonella enteritidis, serum was collected from dysenteric individuals with and without ReA at 6, 12, and 24 months post infection. Serum was also collected from control patients with no prior exposure to Salmonella infection. Quantitative measurements of isotypic antibodies to Salmonella enteritidis LPS were performed by an ELISA. Sensitivity and specificity of quantitative isotypic antibody levels over time were plotted on receiver operator characteristic (ROC) curves. Serum IgG and IgA anti-LPS were found to be present in higher levels in the ReA patients than in controls. Using the optimal cutoff of 0.10 selected from an ROC curve, IgG anti-LPS is 88% sensitive and 94% specific, and IgA anti-LPS is 75% sensitive and 100% specific. We conclude that IgA anti-LPS is both sensitive and specific in distinguishing prior exposure to Salmonella LPS in ReA patients compared to unexposed controls.
7641474 The effect of heterotopic bone formation on prosthetic loosening after total hip replaceme 1995 Apr Seven hundred thirty-two total hip replacements performed from 1970 to 1980 were evaluated for the degree of heterotopic bone formation postoperatively and its effect on long-term mechanical loosening. There were 231 Charnley total hip replacements, of which 152 had no heterotopic bone formation, 58 had Grade 1 formation, and 21 had Grade 2 or 3 formation. Among the 123 Mueller total hip replacements, 98 had no heterotopic bone formation, 19 had Grade 1 formation, and 6 had Grade 2 or 3 formation. For the 378 T-28 total hip replacements, there were 305 with no heterotopic bone formation, 59 with Grade 1 formation, and 14 with Grade 2 or 3 formation. Survival analyses using the definition of failure as loosening, fracture, or revision of the acetabulum or femoral components were constructed. There was no correlation between mechanical loosening, fracture, or revision of the total hip replacement and any degree of heterotopic bone formation.
7550952 Tibiocalcaneal arthrodesis. 1995 Jul A review of eight patients who underwent nine tibiocalcaneal arthrodeses was performed. The surgical indications were failed previous surgery, posttraumatic talar avascular necrosis, and rheumatoid arthritis. The average age at the time of operation was 54 years. The average time of follow-up was 40 months after the operation. Fusion was achieved in all nine feet, with an average time of fusion of 5 months. Results were excellent in three feet, good in four feet, fair in one foot, and poor in one foot. The average leg length discrepancy was 2 cm. The average position of fusion was 6 degrees of valgus and 2 degrees of plantarflexion. All patients stated that they had improvement of pain and function. Seven of the eight patients stated that they would have the procedure done again. Complications were local infection in two patients, malunion in two patients, wound slough in one patient, and a prominent fibula in one patient. Tibiocalcaneal arthrodesis should be reserved as a salvage procedure because it is technically difficult and has a significant risk of complications.
1349769 T cells cloned from human rheumatoid synovial membrane functionally represent the Th1 subs 1992 May The presence of activated T cells in the synovial membrane of patients with rheumatoid arthritis (RA) suggests a role for these cells in the pathogenesis of the disease. Recent evidence indicates that human T cells may fall into functional categories dependent on their cytokine profile and cytotoxic capacity. The human Th1 subset is cytolytic and produces high levels of IFN-gamma whereas the Th2 type of T cell produces IL-4. In order to investigate whether Th1 or Th2 type cells are present in the inflammatory synovial membrane in RA, a panel of synovial membrane derived T-cell clones (n = 19) was generated and studied functionally. Anti-CD3-induced cytotoxicity assays were performed to demonstrate the cytotoxic potential of clones. Except for two, all clones were cytolytic in this test. Clone cells were activated to initiate cytokine production and assessment of the cytokine levels showed that all clones produced large amounts of IFN-gamma (18 out of 19 clones: over 50,000 pg/ml) whereas IL-4 was absent or present in minimal amounts (17 out of 19 clones: less than 1000 pg/ml). The production of IL-1, IL-2 and IL-6 was variable. The functional characteristics of the clones studied indicate that they may resemble the Th1 subtype of T cells. Our data suggest a relation between Th1-type functions the chronic inflammation characteristic of RA.
7849971 A metallic hemiarthroplasty resurfacing prosthesis for the hallux metatarsophalangeal join 1994 Nov Two-hundred seventy-nine arthritic hallux metatarsophalangeal joints treated surgically with a metallic resurfacing hemiarthroplasty over a 40-year period were reviewed. The implant, which is made available in three evenly graded sizes, is designed to replace only the articular surface of the proximal phalanx, with minimal resection of bone stock. The pathologic indications for surgery included classical hallux rigidus, rheumatoid arthritis, and degenerative changes associated with hallux valgus and bunion deformity. Follow-up at 8 months to 33 years after surgery revealed good or excellent clinical results in 95%. The time to follow-up was in excess of 5 years in 101 (36%) of the procedures, beyond 10 years in 62 (22%), and longer than 20 years in 23 (8%). Unlike other available surgical options for this debilitating condition, biomechanics of the hallux metatarsophalangeal joint remained unaffected and problems associated with prosthetic wear or mechanical failure were not encountered.
8778950 The efficacy and tolerability of aceclofenac compared to indomethacin in patients with rhe 1996 The efficacy and tolerability of aceclofenac (100 mg bid; n = 109), a new non-steroidal anti-inflammatory agent, was compared to that of indomethacin (50 mg bid; n = 110) in a multi-centre, 12-week, randomized, double-blind clinical trial in patients with rheumatoid arthritis. The efficacy of aceclofenac, on the basis of several clinical features characteristic for rheumatoid arthritis, was comparable to that of indomethacin. Patients in both treatment groups showed a notable and significant improvement during the study. Under aceclofenac treatment, the number of painful and swollen joints decreased by a median of six and nine, respectively, morning stiffness was shortened by 1 h, and the grip strength of both hands increased by a median of 8 mmHg. Pain at rest was relieved in 65.3% of aceclofenac-treated patients and in 67.1% of those treated with indomethacin (n.s.). With regard to safety, aceclofenac tended to be better tolerated than indomethacin. Among the 109 aceclofenac-treated patients, 26 incidents of adverse effects due to the drug were noted in 20 patients (18.4%). Sixty-four incidents of adverse events were documented in 32 (29.1%) of the 110 patients treated with indomethacin. The most common adverse events reported during treatment with aceclofenac were heartburn (four patients) and vertigo (three patients).
8507218 Stimulation of the secretion of latent cysteine proteinase activity by tumor necrosis fact 1993 Jun OBJECTIVE: Cultured synovial fibroblast-like cells from 3 patients with rheumatoid arthritis (RA) and 3 patients with osteoarthritis (OA) were evaluated for their potential to secrete cysteine proteinases spontaneously and after stimulation by tumor necrosis factor alpha (TNF alpha) or interleukin-1 (IL-1). METHODS: Culture media and cell lysates were analyzed before and after high performance liquid chromatography (HPLC) using the enzymatic substrate, Z-Phe-Arg-AMC, and by immunoblotting with anti-cathepsin B antiserum. Immunolocalization of cathepsin B was studied on cell monolayers. RESULTS: Latent cysteine proteinase activity was found to be secreted spontaneously by cultured synovial fibroblast-like cells. This activity was increased after treatment with either TNF alpha or IL-1. Stimulated protease activity was eluted by HPLC at a peak coincident with that of purified cathepsin B. By immunoblot, cell supernatants contained a 43-kd form of cathepsin B, while cell lysates contained a 30-kd form, consistent, respectively, with cathepsin B before and after cleavage of its propeptide. An intracellular increase in cathepsin B after treatment with TNF alpha was also seen with immunohistochemical studies. CONCLUSION: TNF alpha (in the 6 cases studied) and IL-1 (in 4 cases) stimulated the secretion of a latent cysteine proteinase activity from synovial fibroblast-like cells, which appears to represent primarily cathepsin B.
1550409 IgA antibody response to klebsiella in ankylosing spondylitis measured by immunoblotting. 1992 Feb IgA antibodies to Klebsiella pneumoniae var oxytoca and Proteus mirabilis were measured in 66 patients with ankylosing spondylitis (AS) and 31 with rheumatoid arthritis (RA) and in 51 healthy control subjects, using an immunoblotting technique. The number of antigenic bands to klebsiella on nitrocellulose membrane was higher in 28 patients with active AS than in 38 patients with inactive AS, 31 patients with RA, and 51 healthy control subjects; comparatively smaller increases were found against proteus. In two patients with AS the synovial fluid and the corresponding serum sample showed an identical antibody pattern. Increases in IgA antibodies to klebsiella in patients with AS confirm previous studies using other techniques.