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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
1385941 Pityriasis rosea and discoid eczema: dose related reactions to treatment with gold. 1992 Jul Sixteen cases of either a pityriasiform or discoid eczematous rash occurring in patients with rheumatoid arthritis receiving treatment with gold (sodium aurothiomalate and auranofin) were studied. The results suggest that this is a dose related, not allergic, reaction to gold. The development of this rash is not an absolute indication to stop treatment with gold. Control can often be effected with potent topical steroids or a reduction in the dose or frequency of treatment with gold.
8714797 Combination therapy with cyclosporin in rheumatoid arthritis. 1995 During the last few years, there have been rapid developments in the drug treatment of rheumatoid arthritis. This has led to research into the role of combination therapy. While past combinations of slow-acting antirheumatic drugs have resulted in either an excessive number of adverse events or a lack of increased efficacy over single agent therapy, newer combinations appear to be more promising. It has recently been demonstrated that the combination of cyclosporin and methotrexate is more effective than methotrexate alone, with no increase in adverse effects. Improved trial methodology and a better understanding of the mechanism of action of these newer agents are assisting in the development of new combinations.
7615597 Failure of the Ring polyethylene uncemented acetabular cup. 1995 Jul We report a high rate of failure of the Ring polyethylene cementless cup caused largely by granulomatous osteolysis. We have reviewed 126 prostheses inserted from 1986 to 1992 at from 11 to 90 months after surgery. There was radiological evidence of osteolytic granulomas adjacent to the external surface of the cup in 32%, appearing on average at three years from operation. In a subgroup of 59 prostheses followed for at least four years the incidence of such changes was 54%. A total of 27 cups (22%) have required revision, 21 for granulomatous loosening at an average follow-up of five years. In the retrieved prostheses there was obvious polyethylene abrasion and histological examination confirmed the presence of polyethylene wear debris. We found no significant correlation of osteolysis with cup size, although smaller cups were predominant among those having revision.
7679272 Increased levels of IgA antibodies to cytokeratin-18 and epidermal keratin in rheumatoid a 1993 Feb OBJECTIVE: To investigate whether levels of antibodies to cytokeratin-18 (CK-18) and epidermal keratin (EPK) were raised in patients with rheumatoid arthritis (RA). METHODS: We measured antibodies to CK-18 and EPK in patients with RA and in patients with osteoarthritis (OA), as well as in normal control subjects by means of an enzyme-linked immunosorbent assay. RESULTS: IgA antibodies to both CK-18 and EPK were significantly increased in patients with RA compared with the controls and with patients with OA (P < 0.0001). No difference was noted in the levels of IgG or IgM antibodies to CK-18 or EPK between controls and patients with OA or RA. CONCLUSION: Raised levels of IgA autoantibody to CK-18 and EPK may reflect damage to cytokeratin-containing cells (e.g., in synovial endothelium) and could be a useful disease marker in RA.
8027366 IgM ganglioside GM1 antibodies in patients with autoimmune disease or neuropathy, and cont 1994 Apr AIMS: To compare the titre of anti-ganglioside antibodies (AGA) to GM1 ganglioside in patients with central and peripheral neurological disease and pure motor and sensorimotor neuropathy, in patients with classic autoimmune diseases, and controls. METHODS: AGA to GM1 were measured using an enzyme linked immunosorbent assay (ELISA) technique, highly purified bovine GM1 ganglioside, and sequential dilution of control and test sera. Antibody titre was calculated using the optical density readings of three consecutive serum dilutions multiplied by the dilution factor. RESULTS: A considerable overlap was evident in the titre of AGA to GM1 in control and test sera. High antibody titres were most frequent in patients with multifocal motor neuropathy with conduction block (MMNCB). Low AGA titre were observed in several patient groups. Compared with the controls, the median titre of AGA to GM1 was significantly higher in patients with multiple sclerosis, rheumatoid arthritis, primary Sjögren's syndrome and systemic lupus erythematosus. In contrast, the median titre in patients with diabetic peripheral neuropathy, motor neurone disease, sensorimotor neuropathy and chronic inflammatory demyelinating polyneuropathy was no different from that in normal control subjects. CONCLUSIONS: Estimation of AGA to GM1 may be helpful in the diagnosis of MMNCB in patients with a pure motor neuropathy but in few other conditions. Low titre AGA to GM1 are evident in several autoimmune conditions. The pathogenetic importance of AGA to GM1 in patients with neuropathy is not clear.
7912843 [Neurological complications caused by gold salts. Nosologic report apropos of a case]. 1993 Gold therapy is responsible for many neurological complications. We report a case presenting with the clinical and electrophysiological characteristics of neuromyotonia, polyradiculoneuritis and Morvan's fibrillary chorea. The various neurological complications of gold therapy and the possible relationships between these different syndromes are discussed.
7881628 Coculture of human articular chondrocytes with peripheral blood mononuclear cells as a mod 1994 Nov A model for the coculture of chondrocytes in gelified agarose with mononuclear cells was developed to serve as an in vitro equivalent for cytokine-mediated events at the cartilage-synovial pannus junction in destructive arthropathies. Chondrocytes cultured in agarose keep their phenotypic stability. They release cartilage-specific aggrecans into the surrounding artificial matrix. When activated with lipopolysaccharide for 1 h, mononuclear cells release Interleukin 1 beta and Tumor Necrosis Factor alpha, thereby stimulating the chondrocytes to produce Interleukin 6, to diminish incorporation of 35S into aggrecans, and to degrade these intercellular macromolecules. This coculture model is a useful tool for studying interactions between inflammatory cells and target cells. To demonstrate its usefulness, the effect of three anti-inflammatory drugs (piroxicam, sulphasalazine, and hydrocortisone) on cytokine release by mononuclear cells, and subsequently on chondrocyte aggrecan metabolism was studied. The drugs were unable to abrogate Interleukin 1 and Tumor Necrosis Factor alpha release by activated mononuclear cells. Therefore, these pharmacological agents did not protect the artificial target tissue against cytokine-mediated degradation.
8104358 [Gold salt-induced pneumonia and CD4 alveolitis]. 1993 In a 62-year old man who consulted for dyspnoea, clinical, radiological and functional examinations led to the diagnosis of immunoallergic lung disease caused by gold salt therapy. Regression of the symptoms when gold salt therapy was withdrawn supported this diagnosis. Contrary to previously published cases concerning treatment with gold salts, the study of bronchoalveolar lavage (BAL) fluid yielded a lymphocytic alveolitis with a very high CD4/CD8 ratio, as already reported with methotrexate, cyclothiazide and nitrofurantoin. This case can be added to the list of drugs that may induce CD4 alveolitis; it also reminds the existence of gold salt pneumonia and permits to discuss the value of a lymphocyte subpopulation study in the BAL fluid in patients with drug-induced immunoallergic lung diseases.
8185693 Aberrant production of gliostatin/platelet-derived endothelial cell growth factor in rheum 1994 May OBJECTIVE: To purify a protein inhibitor from rheumatoid arthritis (RA) synovial fluids which suppresses the apparent incorporation of 3H-thymidine into fibroblasts and synovial cells, and to define its biochemical features that have clinical relevance to the pathogenesis of RA. METHODS: Several standard chromatographic techniques were employed for the purification of the protein. Immunochemical methods with monoclonal antibody were used to quantify and visualize the protein in sera, synovial fluids, and tissues from RA patients. RESULTS: The chemical properties of purified inhibitor from RA synovial fluids confirmed its identity as gliostatin/platelet-derived endothelial cell growth factor (PD-ECGF), a potent angiogenic factor. The gliostatin/PD-ECGF level in synovial fluid and serum was higher in RA patients than in osteoarthritis controls. CONCLUSION: These findings strongly suggest that gliostatin/PD-ECGF might play an important role in the aberrant neovascularization of rheumatoid synovium.
8687261 Gastrointestinal tract complications of nonsteroidal anti-inflammatory drug treatment in r 1996 Jul 22 BACKGROUND: Gastrointestinal tract (GI) complications associated with nonsteroidal anti-inflammatory drug (NSAID) use are the most common serious adverse drug reactions in the United States. Nonsteroidal anti-inflammatory drugs cause both minor GI side effects such as abdominal pain and vomiting and serious GI events such as ulcers and bleeding. This study evaluates the event rates for all NSAID-induced GI complications in patients with rheumatoid arthritis, describes the time course of these events, and evaluates the role of prophylactic therapy with antacids and H2 receptor antagonists. METHODS: We studied 1921 patients with rheumatoid arthritis from 8 ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System) centers. Patients were selected for the study if they were treated with NSAIDs and had at least 2.5 years of observation available. Information on GI complications attributed to NSAIDs was obtained from validated patient self-reports collected every 6 months and supplemented by review of hospital records for all hospitalizations. RESULTS: Approximately 15% of the 1921 patients reported an NSAID-induced GI side effect during the 2.5 year observation period. Forty-two patients had a serious GI complication requiring hospitalization; 34 of these 42 patients did not have a preceding GI side effect. Patients who were taking antacids and H2 receptor antagonists did not have a significantly lower risk for serious GI complications than did those not taking such medications. Asymptomatic patients taking these medications had a significantly higher risk for GI complications compared with those who did not take these medications (standardized odds ratio, 2.14;95% confidence interval, 1.06-4.32). CONCLUSIONS: A large majority of patients with serious GI complications do not have preceding mild side effects. Prophylactic treatment with antacids and H2 receptor antagonists is of questionable value and may increase the risk for subsequent serious GI complications.
8928570 [Practical significance of cytokine determination in joint fluid in patients with arthrose 1996 Jul OBJECTIVE: To determine whether the activity of cartilage-degrading enzymes in the synovial fluid (SF) of patients with rheumatoid arthritis and other joint diseases is correlated with the concentration of cytokines in the SF. METHODS: Cytokines and cartilage-degrading enzymes were determined in the SF of 97 patients with various disorders involving the knee joints (rheumatoid arthritis (RA) n 44; osteoarthritis (OA) n 35; meniscal trauma (Men) n 10; reactive arthritides (ReA) n 8). In these samples we measured the concentrations of interleukin-1 alpha and beta, IL-1-receptor antagonist (IL-1ra), IL-6, IL-8, tumor necrosis factor alpha (TNF alpha; all by ELISA), collagenase-activity and caseinase-activity (by substrate assays). RESULTS: With the exception of IL-1 alpha and IL-6, cytokine-concentrations were significantly higher in RA than in OA SF-samples (p < 0.05; ANOVA on ranks). IL-1ra, IL-6, and IL-1 beta were correlated best with the collagenase-activity in the SF (r = 0.63; 0.57; 0.55; Spearman's rank correlation), while IL-1 beta (r = 0.53) and IL-1ra (r = 0.52) were best correlated with the caseinase-activity in the samples. The SF-concentration of IL-1ra was well correlated with the levels of IL-6, IL-1 beta, II-8, and TNF alpha (r from 0.73 to 0.66; all p < 0.005), but not with IL1 alpha. The molar ratio of IL-1 to IL-1ra in the SF was neither correlated with the activity of collagenase nor caseinase. IL-1 beta and IL-1ra in the SF were positively correlated with the erythrocyte sedimentation rate (ESR). CONCLUSIONS: The determination of IL-1 beta and IL-1ra in the SF of patients with joint disorders as examined in this study seems to allow to a certain extent a prediction of the collagenase- and caseinase-activity contained in the diseased joint. We would favor.
8035382 Interleukin 1 beta enhances the response of rabbit synovial fibroblasts in vitro to dexame 1994 Apr OBJECTIVE: As a model system to understand the efficacy of patients with glucocorticoid (GC) treatment of joint inflammation of rheumatoid arthritis, we stimulated confluent rabbit synovial fibroblasts in culture with interleukin 1 beta (IL-1 beta) and studied the effects of dexamethasone (Dex). METHODS: Twenty-four h after IL stimulation Dex was added and the response of cells to Dex was estimated by [3H]thymidine uptake, cell count and lactate dehydrogenase release. Cellular and nuclear binding of [3H] Dex as well as the DNase sensitivity of isolated nuclei were estimated. RESULTS: Dex strongly inhibited the [3H]thymidine uptake by the stimulated cells in a dose dependent manner with Ki of lower than 10(-12) M, whereas it only slightly inhibited the unstimulated cells. With stimulation the sensitivity of cells increased 10-fold as estimated by lactate dehydrogenase release and 85-fold by counting the final cell density. We found also a 5-fold increase in the DNase I hypersensitive sites in the nuclei and a 2 to 3-fold increase in the cellular as well as the nuclear Dex binding sites following stimulation. CONCLUSION: In addition to the well documented inhibition of degradative enzyme production by the stimulated synovium, the efficacy of GC treatment of patients could be explained also on the basis of the sensitization of stimulated synovium to the GC mediated injury.
8628978 Clinical implications of selective cyclooxygenase-2 inhibition. 1996 Inducible cyclooxygenase-2 (COX-2), but not constitutive COX-1, can be upregulated in rheumatoid synovial tissue by interleukin-1 beta and phorbol esters and is inhibited by dexamethasone. This supports the role of COX-2 in acute inflammation in arthritis. Selective inhibition of COX-2 by non-steroidal anti-inflammatory drugs (NSAIDs) has been proposed as an approach to reduce their associated side effects while maintaining efficacy. The improved safety profile of selective COX-2 inhibitors will allow more widespread and sustained use than is currently possible with standard NSAIDs. In rheumatoid arthritis they may be used as effective symptomatic relief, in combination with disease modifying therapy at an early stage of disease. In osteoarthritis, and, more particularly, soft tissue rheumatism, pain contributes to the development of chronic disease, therefore the main benefit of selective COX-2 inhibition will be to provide safe, effective pain relief to maintain mobility and reduce disability.
8934319 Conversion of failed modern unicompartmental arthroplasty to total knee arthroplasty. 1996 Oct Between January 1983 and January 1991, 29 patients (31 knees) with a failed Robert Brigham metal-backed knee arthroplasty (Johnson & Johnson, Raynham, MA) underwent revision to a total knee arthroplasty (TKA). Twenty-five patients had osteoarthritis, three avascular necrosis, and one rheumatoid arthritis. The average patient age was 72.3 years (range, 49-88 years), and the average weight was 179 lb. (range, 112-242 lb.). The interval between the primary and secondary index procedures averaged 62 months (range, 7-106 months), and mean postrevision follow-up period was 45 months (range, 24-104 months). The primary mechanism of failure of the UKA was tibial polyethylene wear in 21 knees and opposite compartment progression of arthritis in 10 knees. Sixteen knees had particulate synovitis with dense metallic staining of the synovium. At revision, the posterior cruciate ligament was spared in 30 knees and substituted in 1 knee. Restoration of bony deficiency at revision required cancellous bone-graft for contained defects in seven knees, tibial wedges in four knees, and femoral wedges in two knees. No defects received structural allografts. The data suggest that failed, modern unicompartmental knee arthroplasty can successfully be converted to TKA. In most cases, the posterior cruciate ligament can be spared and bone defects corrected with simple wedges or cancellous grafts. Moreover, the results of revision of failed unicompartmental knee arthroplasty are superior to those of failed TKA and failed high tibial osteotomy and comparable to the authors' results of primary TKA with similar-length follow-up periods. Although these results are encouraging, longer-term follow-up evaluation is required to determine survivorship of these revision arthroplasties.
7683586 Expression of CD5 and CD72 on T and B cell subsets in rheumatoid arthritis and Sjögren's 1993 May A minority of B cells express the CD5 marker, which is found on virtually all T cells, and CD72 has been defined as the CD5 ligand on the B cell membrane. The mean fluorescence intensity (MFI) of the CD5 molecules was shown to be higher on CD4+CD29+ than CD4+CD45RA+ in peripheral blood (PB) and synovial fluid (SF) of rheumatoid arthritis (RA) patients (P < 0.0001 and < 0.001), and PB of Sjögren's syndrome (SS) patients and normal controls (P < 0.02 and < 0.03). This MFI declined once the CD4 expressed HLA-DR in PB of SS patients (P < 0.004) and normal controls (P < 0.02) or CD25 in PB of RA (P < 0.004) and SS patients (P < 0.0004). There was a correlation between the CD5 MFI on CD4+CD45RA+ and CD4+CD29+ in RA (P < 0.001) as well as SS (P < 0.0007) PB. The CD72 MFI was impressively higher on CD5+ than CD5- B cells in PB and SF of RA patients (P < 0.0001 and P < 0.005) and PB of SS patients (P < 0.005) and normal controls (P < 0.005). Our data suggest that, in association with CD4CD29, CD5 is involved in CD5+B/CD5+ B cell interactions in non-organ-specific autoimmune diseases.
7620863 Evaluation of the anatomic patellar prosthesis in uncemented porous-coated total knee arth 1995 May We studied 41 patients (56 knees; mean patient age, 55.3 years) who were followed up for a minimum of 7 years (range, 84 to 90 months) after primary resurfacing arthroplasty of the patella with an anatomic patellar prosthesis during uncemented porous-coated anatomic total knee arthroplasty. The operative diagnosis was osteoarthritis in 33 knees; rheumatoid arthritis in 16; tuberculous arthritis in 4; posttraumatic arthritis in 2; and ankylosis in 1. The average preoperative Hospital for Special Surgery knee score was 33 points (range, 10 to 69 points), which improved to 81 points (range, 54 to 100 points) at the final follow-up examination. There was a high rate of component loosening (23 knees or 41%). A total of 27 of 33 solidly fixed patellar prostheses (82%) had osteolysis in the patella. Forty-two knees (75%) had wear of the tibial polyethylene liners; a mean of 2.5 mm in the medial compartment and 1.7 mm in the lateral compartment. Our experience does not support the continued use of this prosthesis.
7486797 Bone alkaline phosphatase in rheumatic diseases. 1995 Jul A double monoclonal immunoradiometric assay specific for bone alkaline phosphatase (BAP) was used to determine whether the raised total alkaline phosphatase (TAP) often found in patients with active rheumatoid arthritis (RA) and ankylosing spondylitis (AS) is derived from bone or liver. Fifty-eight patients with RA were compared to 14 with AS and 14 with non-inflammatory rheumatic diseases (NI). None had clinical liver disease and only one had a slightly elevated aspartate transaminase activity. Elevated BAP concentrations were found in seven patients (5 RA, 1 AS, 1 NI), only two of whom also had abnormal TAP. Abnormal TAP activities were found in only three patients (all RA). BAP did not correlate with disease activity in RA or AS. In contrast, TAP correlated with disease activity (assessed by plasma viscosity) in RA (P < 0.002) and gamma-glutamyl transferase (GGT) also correlated with plasma viscosity in RA (P < 0.01). Both TAP and BAP were significantly correlated with GGT in RA (P < 0.001 and P < 0.02, respectively). These findings are discussed, together with possible reasons for the conflicting nature of some of the observations.
8472447 Total elbow arthroplasty. An 18-year experience. 1993 May In 34 primary and 18 revision total elbow arthroplasties (TEAs), rheumatoid arthritis (RA) was the most common indication, with traumatic arthritis next most common. The indications were primarily pain and decreased range of motion. Follow-up time averaged 7.6 years for index arthroplasties. Complication rates of primary arthroplasties were high, with 40% neural problems, 9.3% aseptic loosening, and 13.3% early postoperative infection. Overall function was satisfactory in 68% of patients with RA. In agreement, the rates of revision were high. Overall satisfaction was good, and function was fair in patients with TEA.
7634015 Knee arthrodesis using a short locked intramedullary nail. A new technique. 1995 Spring This article reports on the use of a new intramedullary nail designed specifically for fixation of knee fusions. The nail is a short locked stainless steel nail that is inserted through a single anterior knee incision and uses an outrigger targeting rod to guide the insertion of the locking screws. The successful use of this technique is illustrated in two cases. The advantages of this nail compared with previously reported techniques of fixation for knee fusions are that the short locked nail avoids the second incision required for the insertion of long knee fusion nails, the bulkiness of the double plating technique in the relatively subcutaneous anterior knee area, and the difficulties inherent with the prolonged use of pins for external fixation.
7585040 Glycosylation changes of IgG associated with rheumatoid arthritis can activate complement 1995 Mar The glycosylation of the circulating immunoglobulin-gamma (IgG) antibody molecules changes in rheumatoid arthritis. The extent of the changes correlates with the disease severity and reverses in remission. We demonstrate here that the alteration in glycosylation associated with rheumatoid arthritis can create a new mode for the interaction of IgG with complement through binding to the collagenous lectin mannose-binding protein (MBP). Rheumatoid arthritis is associated with a marked increases in IgG glycoforms that lack galactose (referred to as G0 glycoforms) in the Fc region of the molecule and that terminate in N-acetyl glucosamine (GlcNAc). We show, using nuclear magnetic resonance (NMR) and X-ray data, that these terminal GlcNAc residues become accessible for MBP binding. We further demonstrate that multiple presentation of IgG-G0 glycoforms to MBP results in activation of the complement. This suggests that a contribution to the chronic inflammation of the synovial membrane could arise from the localization of the IgG-G0 glycoforms in the affected joint and from resulting activation of complement.