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ID PMID Title PublicationDate abstract
1455367 [The biochemical heterogeneity of rheumatoid arthritis]. 1992 The content of cyclic nucleotides (cAMP and cGMP) in plasma (or blood), synovial fluid and neutrophils was measured in 151 patients suffering from rheumatoid arthritis (RA) as was the content of prostaglandins (E2 and F2 alpha), ACTH, hydrocortisone, antioxidant system enzymes (superoxide dismutase and catalase). Part of the patients were examined over time. Relative stability of certain characteristics (the content of hydrocortisone, neuropeptides, superoxide dismutase, and so forth) was established throughout a long time, irrespective of the process activity or treatment provided. It is concluded that every RA patient has a "weak" biochemical component of his own, reflecting the activity or power of one or another regulatory system.
7655997 Association between degree of bone-erosion and synovial fluid-levels of tumor necrosis fac 1995 May OBJECTIVE: To determine whether concentrations of cytokines and matrix-degrading enzymes in synovial fluid of patients with rheumatoid arthritis or osteoarthritis are associated with the degree of bone-destruction in the same joint. METHODS: Determination of Interleukin-1 alpha, IL-1 beta, IL-1-receptor-antagonist, IL-6, IL-8, tumor necrosis factor alpha (by ELISA), collagenase-activity and caseinase-activity (by substrate-assays) in the SF (knee) of patients with RA (n42) or OA (n35). The degree of bone-destruction was assessed radiographically. RESULTS: SF cytokine- and enzyme-levels were higher in patients with RA than in those with OA. In the RA group, SF-levels of TNF alpha were positively correlated with the degree of bone destruction of the respective joint. No correlation was found between radiographically assessed joint changes and SF-concentrations of other cytokines, enzyme activities, serum CRP, or duration of disease. In the OA-group, none of the examined parameters was associated with the degree of joint destruction. CONCLUSIONS: Our data may support the assumption of TNF alpha playing an important role in joint destruction in RA. Possible alternative conclusions are discussed.
8484674 Depressed levels of dehydroepiandrosterone sulphate in postmenopausal women with rheumatoi 1993 Mar The sex hormones dehydroepiandrosterone sulphate (DHEAS), oestradiol, and sex hormone binding globulin (SHBG) were measured in 185 postmenopausal women (aged 45-65 years) with rheumatoid arthritis (RA) and related to assessments of bone mineral density at the spine and proximal femur. Compared with 518 postmenopausal control women (aged 45-65 years), DHEAS levels were below normal in the 120 patients with RA who had never taken corticosteroids and levels were further depressed in 39 patients currently using steroids. Twenty six patients who had completed steroid treatment also had lower DHEAS levels, suggesting a delayed recovery of adrenal androgen secretion. Oestradiol and SHBG levels were similar in all groups. There was no correlation between sex hormones and disease activity. Oestradiol correlated with bone mineral density at all sites. Although oestradiol correlated with DHEAS, there was no relation between DHEAS and bone mineral density. The cause of below normal levels of DHEAS in RA is unclear, whether a consequence of chronic illness, immune dysfunction, or a defect of adrenal androgen synthesis.
8976086 [Bronchiolitis obliterans preceding rheumatoid arthritis: effect of clarithromycin]. 1996 Nov A 62-year-old man was referred to our department because of exertional dyspnea and a 6-year history of coughing and sputum production. He had never smoked, and had had an operation for chronic paranasal sinusitis. Coarse crackles and rhonchi were audible over both lower lung fields. The cold hemagglutinin titers were high. pulmonary function tests showed airflow obstruction, and a sputum culture revealed Hemophilus influenzae A chest X-ray film and a CT scan showed diffuse micronodular shadows in the centrilobular regions, mild ectasis of bronchioles mainly in the lower lung fields, and mild hyperinflation. A specimen of lung tissue was obtained by thoracoscopic biopsy, and histologic examination showed bronchiolitis obliterans, with bronchiolar narrowing or obliteration due to submucosal fibrosis and inflammation. Rheumatoid arthritis was diagnosed 14 months after the operation. The patient was treated with clarithromycin for 3 years. Respiratory symptoms were relieved and pulmonary function gradually improved.
8882030 Quantitative measurement of erosion growth and joint space loss in rheumatoid arthritis ha 1996 Feb OBJECTIVE: To evaluate the performance of simple, inexpensive quantitative techniques for measuring erosion growth and joint space loss in serial hand radiographs of patients with rheumatoid arthritis (RA). METHODS: Erosions were measured using a plastic overlay template of sample erosion sizes. Joint spaces were measured with a hand held measuring micrometer. In the first phase of testing, a spectrum of individual erosions and joint spaces was measured to determine intra and interobserver correlations and variability. In the 2nd phase, the tools were used to measure serial changes in RA hand radiographs. Observer correlations and the ability to discriminate serial changes were determined and compared to the scoring method of Sharp. RESULTS: Measurements of individual erosion areas and joint spaces were highly reproducible. Intra and interobserver correlations were significant (p < 0.05) for serial erosion growth and joint space loss measurements, as well as changes in Sharp scores. Quantitative measurements correlated highly with the corresponding Sharp score changes. Of all measurements or scores recorded, quantitative joint space loss measurements were statistically superior in discriminating serial change in RA hand radiographs. Quantitatively measured joint space loss correlated well with both erosion growth measurements and serial change in total Sharp scores. CONCLUSION: Quantitative measurement of erosion growth and joint space loss is possible with simple inexpensive techniques. Further study is needed to confirm our data, which suggest that quantitative measurement of joint space narrowing may be the most useful discriminator of serial changes in RA hand radiographs.
7945500 Type VI collagen-specific messenger RNA is expressed constitutively by cultured human syno 1994 Sep OBJECTIVE: Type VI collagen is a prominent constituent of the synovial extracellular matrix. The cellular source of this matrix protein and the identity of local factor sin synovium that may regulate its expression have not been delineated, however. We examined the capacity of human fibroblast-like synovial cells to synthesize type VI collagen as well as the effect of interleukin-1 (IL-1) on this expression. METHODS: RNA was extracted from cultured human synovial cells derived from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Northern blots were analyzed using sequence-specific probes, and steady-state messenger RNA (mRNA) levels of the 3 alpha (VI) procollagen chains were measured. The effect of IL-1 treatment on these levels was determined. RESULTS: Abundant expression of 3 characteristic mRNA transcripts, corresponding to the alpha 1 (4.2-kb), alpha 2 (3.5-kb), and alpha 3 (8.5-kb) chains of type VI procollagen, was observed in untreated cells derived from RA and OA patients. IL-1 treatment consistently suppressed steady-state mRNA levels for all 3 alpha (VI) procollagen chains in a time- and dose-dependent manner. Tumor necrosis factor alpha induced a response similar to that of IL-1, while IL-2 was ineffective in this regard. Indomethacin partially restored alpha (VI) mRNA expression in IL-1--treated cells. CONCLUSION: These studies provide novel data demonstrating abundant steady-state levels of mRNA transcripts coding for all 3 type VI procollagen polypeptides in human synovial fibroblast-like cells, as well as coordinated down-regulation of these transcripts by IL-1. Local production of IL-1 may thus constitute an important means in vivo of regulating the production of type VI collagen.
8997915 Risk factors for depression in rheumatoid arthritis. 1996 Aug OBJECTIVE: To identify risk factors for the development of depression in persons with rheumatoid arthritis (RA). METHODS: Subjects were divided into depressed versus nondepressed groups on the basis of the Center for Epidemiologic Studies-Depression Scale; a range of psychological, pain-related, disease-related, and demographic variables were analyzed to predict depression. Both cross-sectional and longitudinal predictive models were examined. RESULTS: A series of analyses, including multiple logistic regression, found that the optimal predictors of depression in RA were average daily stressors, confidence in one's ability to cope, and degree of physical disability. The model was successfully cross-validated on separate data sets (i.e., same subjects at different time points). CONCLUSION: All of the identified risk factors for depression in RA are preventable to some extent and, therefore, should be addressed in comprehensive, rheumatology team care.
7966084 Intravenous cyclophosphamide pulses in the treatment of pyoderma gangrenosum associated wi 1994 Jul Pyoderma gangrenosum is a chronic ulceronecrotic inflammatory cutaneous disorder that can be associated with diseases such as rheumatoid arthritis (RA). No definitive treatment exists for this condition; steroids have been the mainstay of therapy, and the addition of immunosuppressives has been advocated. We describe 2 patients with pyoderma gangrenosum occurring in the setting of RA who, in addition to steroids, received pulse intravenous cyclophosphamide and had a remarkably good and lasting response. This is the first report of such a therapeutic approach. The pertinent literature is discussed. We conclude that pulse cyclophosphamide is another possible therapy for pyoderma gangrenosum.
8895163 Successful treatment with cyclosporin A of pure red cell aplasia associated with rheumatoi 1996 Oct We describe the first report of a patient with rheumatoid arthritis (RA) who developed refractory pure red cell aplasia that was successfully treated with cyclosporin A (CyA). Since no inhibitory activity against bone marrow was observed in the whole serum, it is possible that the clinical efficacy of CyA on both RA and aplasia was explained by its effects on T cells that might be involved in the development of these diseases.
1529288 Sonographic evaluation of femoral condylar cartilage in osteoarthritis and rheumatoid arth 1992 Employing a real-time sonographic scanner with a 5 MHz linear probe, the articular cartilage of the knee was studied in four groups of subjects: normal subjects aged 18-36 years and 50-63 years, patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA). Cartilage thickness was diminished both in RA and in OA knees compared to the two groups of normal joints, even if in RA the reduction was less. The cartilage surface appeared irregular more frequently in OA than in RA. Our survey suggests that the sonographic technique is a useful, non-invasive diagnostic method to study the articular cartilage of the knee.
7698317 Detection and investigation of the molecular nature of low-molecular-mass copper ions in i 1995 Mar 20 Low-molecular-mass copper(II) species have been detected and quantified in ultrafiltrates (n = 7) of rheumatoid synovial fluid (SF) by a highly-sensitive HPLC-based assay system with the ability to determine Cu(II) concentrations of < 10(-7) mol.dm-3. High field 1H NMR spectroscopy demonstrated that addition of Cu(II)(aq.) to isolated samples of RA SF ultrafiltrates resulted in complexation by histidine > alanine > formate > threonine > lactate > tyrosine > phenylalanine, their effectiveness in this context being in the given order. CD spectra of Cu(II)-treated samples of intact SF exhibited absorption bands typical of copper(II)-albumin complexes, in addition to a band attributable to a low-molecular-mass histidinate complex (lambda min 610 nm). Since both albumin and histidine are potent radical scavengers, these results indicate that any .OH radical generated from bound copper ions will be 'site-specifically' scavenged. Hence, low-molecular-mass copper complexes with the ability to promote the generation of .OH radical which can then escape from the metal ion co-ordination sphere (and in turn, cause damage to critical biomolecules) appear to be absent from inflammatory SF.
1729275 Gold-specific T cells in rheumatoid arthritis patients treated with gold. 1992 Jan Gold-specific T lymphocyte clones were isolated from a patient with rheumatoid arthritis who developed delayed type hypersensitivity reactions to gold. All of the isolated T cell clones required histocompatible antigen presenting cells as well as gold for induction of proliferation. Using a panel of HLA-homozygous Epstein Barr virus-transformed B (EBV-B) cells and anti-HLA antibodies, the clones were shown to recognize gold in the context of DR1 molecules. Gold recognition did not require active antigen processing since specific proliferation was not affected by glutaraldehyde fixation of the DR1 homozygous antigen presenting cells. Furthermore, we could show that gold salts inhibited peptide-induced responses of a peptide-specific T cell clone. In addition to providing evidence for gold-specific T cells in gold-treated RA patients exhibiting delayed type hypersensitivity responses, these data suggest that gold can alter MHC-peptide complexes. The latter observation may in part explain the mechanism/s responsible for both the therapeutic and the toxic effects of gold.
1455376 [The preliminary results of using tramal in rheumatoid arthritis patients]. 1992 Patients suffering from active rheumatoid arthritis (RA) were examined for the analgesic effect of tramal. All the patients were administered basic therapy and nonsteroidal anti-inflammatory drugs. Tramal produced a beneficial effect in 79% of the patients. The stable analgesic effect ensued on days 3-5 since the onset of continuous treatment. Provided the drug was administered for a short period of time (not more than 14 days), addiction to tramal was not recorded. Only 11% of the patients demonstrated tramal-induced side effects (drowsiness, dizziness, skin itch), seen in cases where the daily dose exceeded 300 mg.
7917079 A risk-benefit assessment of slow-acting antirheumatic drugs in rheumatoid arthritis. 1994 Jul There is no ideal slow-acting antirheumatic drug. Therapy of rheumatoid arthritis (RA) is currently being modified, with strong recommendations to abandon the traditional pyramidal approach. The call is for a more aggressive, earlier approach to suppress inflammation. Combination therapy rather than the use of a single agent is advocated by some. Improved methods for assessing disease activity as well as measurement of outcome have been developed. Markers of poor prognosis have helped to define patients for earlier treatment. Comparison of toxicity among such a diverse group of drugs is probably best achieved with a toxicity index measuring the number of episodes expressed in terms of patient-years of exposure. Toxicity remains the commonest reason for discontinuing an agent, while remission beyond 36 months on therapy is uncommon, except with methotrexate. The profile of toxicity is clearly defined for individual agents, but combination therapy may reveal an entirely different set of toxic manifestations. There is an urgent need to develop a set of risk factors to predict toxicity in an individual patient. Juvenile chronic arthritis behaves differently from adult RA. Drug toxicity profiles are similar, but less common. Outcome is more difficult to measure, with the major impact of disease and therapy being on growth retardation.
8934329 Multiple prosthetic infections after total joint arthroplasty. Risk factor analysis. 1996 Oct The relative risk of age, sex, underlying diagnosis, corticosteroid usage, diabetes mellitus, and major nonprosthetic infection for the development of multiple prosthetic infections was assessed retrospectively. Deep infection occurred in 174 replacement arthroplasties in 145 patients between 1981 and 1993. Patients with rheumatoid arthritis had a significantly larger number of implants per patient (P < .001). Twenty-seven of 145 patients developed a second prosthetic infection, for an overall incidence of 19%. Of these 27, the underlying diagnoses were rheumatoid arthritis in 19, osteoarthritis in 6, neuropathic arthritis in 1, and systemic lupus erythematosus in 1. Rheumatoid arthritis and the occurrence of a major nonprosthetic infection (sepsis) were found to be highly associated with the development of a second prosthetic infection (P < .001 and P = .0001, respectively). In those rheumatoid patients with multiple infections, there was a significantly larger proportion with American Rheumatism Association class III and IV function than those with a single prosthetic infection (P = .0002). In 14 of the 27 cases of more than one prosthetic infection, the infected implants presented clinically within the same month. Ten of these 14 had an associated nonprosthetic infection. It is therefore not possible to accurately calculate the risk that one infected arthroplasty poses to other implants.
8474058 Methotrexate inhibits proliferation but not interleukin 1 stimulated secretory activities 1993 Feb The effect of methotrexate (MTX) on proliferation and on interleukin 1 stimulated secretory activities of human synovial fibroblasts in culture was investigated. MTX caused a dose dependent inhibition of growth over the concentration range 0.07-2.2 microM with a half-maximal effect at 0.37 microM. INhibition was competitively relieved by coaddition of leucovorin. Cell growth was fully restored after MTX pretreatment of 24 h but not after 48 h, even on subsequent leucovorin addition. Cell viability was unaffected by MTX treatment. MTX had no effect on interleukin 1 stimulated production of prostaglandin E, hyaluronic acid and collagenase. Our results raise the possibility that one of the mechanisms contributing to the therapeutic effects of MTX in patients with rheumatoid arthritis may involve modulation of synovial fibroblast growth.
8607888 Increased bone mass with pamidronate treatment in rheumatoid arthritis. Results of a three 1996 Mar OBJECTIVES: Osteoporosis is a frequent complication of rheumatoid arthritis (RA). We therefore investigated the effect of oral pamidronate therapy as a specific bone-sparing agent in RA. METHODS: The study design was a 3-year randomized, double-blind trial of 300 mg oral pamidronate/day compared with placebo in 105 RA patients. Bone mineral density (BMD) measured at 12-month intervals was the primary efficacy parameter. RESULTS: In 3 years, lumbar spine and forearm BMD increased significantly in the pamidronate-treated group (by 8.4 +/- 6.9% [mean =/- SEMI] [P < 0.00011 and 5.2 =/- 6.5% [P < 0.005], respectively), compared with nonsignificant changes in the placebo-treated patients (increase of 0.6 =/- 5.2% and decrease of 1.2 =/- 5.8%, respectively). Femoral neck BMD increased in the pamidronate-treated group (by 2.6 =/- 8.6%) and decreased significantly in the placebo-treated group (by 4.0=/- 1.3% [P < 0.005]). The changes in BMD with time at all 3 measurement sites were significantly different between the treatment groups (P < 0.0001). Changes in radiographic signs of joint damage and in disease activity were similar in the 2 groups. CONCLUSION: The present study provides the first evidence that long-term treatment with an orally administered bisphosphonate overcomes bone loss and increases bone mass when compared with placebo. This finding may have significance with regard to the treatment of patients with RA.
9208605 [The effects of a single active ingredient (T4) of Tripterygium Wilfordii Hook on the prod 1996 Apr Encouraged by good therapeutic results of the semipurified preparations of Tripterygium Wilfordii Hook (TWH) (code name T4) a single-active ingredient of TWH with the code name of T4 was obtained. The in vitro effects of T4 on the bioactivity of TNF produced by PBMC of normal subjects (n = 10) and RA patients (n = 6) or the RA digested synovium single cells (DSSC) were studied. The results showed that under pretreatment of PBMC of healthy persons with T4 (35 ng/ml) for two hours, TNF were reduced to 36.13 +/- 1.75% in comparison with the control of 63.33 +/- 2.51% (P < 0.001), with an inhibition rate of 40.31%. Similarly, the inhibition rate for the PBMC of RA patients (P < 0.001), was 25.54%. The fact that coculture of PBMC and T4 for 6 hours instead of treatment with T4 for 2 hours caused an inhibition rate of 40.51% (P < 0.01), might indicate that time of interaction was also a factor of importance. T4 also reduced TNF secretion by RA-DSSC from 72.1 +/- 6.1% to 51.6 +/- 2.0% with an inhibition rate of 28.4%. The aformentioned indicates that T4 appears to possess suppressive actions on production of TNF by PBMC and DSSC of RA patients. Therefore, it is possible that T4 may be used clinically for RA patients.
7566289 Non-coeliac sprue possibly related to methotrexate in a rheumatoid arthritis patient. 1995 Sep We describe a case of non-coeliac sprue in a low-dose methotrexate treated patient suffering from rheumatoid arthritis. This is the first case report of this possibly reversible complication of methotrexate therapy. The diagnosis was confirmed by a duodenal mucosal biopsy revealing the characteristic intestinal histopathology of coeliac sprue. After discontinuation of the drug a repeat biopsy was almost normal, and completely normal after reintroduction of a normal diet. One could speculate about the methotrexate related mechanism of the villous atrophy: it might be either a direct toxic effect or a secondary effect of the immunosuppression.
7699679 Examination of pharmacokinetic variables in a cohort of patients with rheumatoid arthritis 1995 Jan OBJECTIVE: To compare pharmacokinetic variables of a 7.5 mg dose of MTX in a cohort of patients with rheumatoid arthritis (RA) beginning therapy with the drug with a cohort of patients receiving the drug for a mean period of 81 months. METHODS: Standard pharmacokinetic measures were performed in 35 patients beginning MTX therapy and 15 patients who had received the drug for a mean of 81 months. RESULTS: No significant differences in area under the serum concentration versus time curve (AUC), maximal methotrexate concentration following dosing (Cmax), time to Cmax (Tmax), bioavailability (F), urinary MTX, renal clearance of MTX or creatinine clearance were observed between the 2 cohorts. CONCLUSION: We were unable to demonstrate significant differences in pharmacokinetic variables in these cohorts with a 7.5 mg standard dose of MTX. It is possible that a difference may exist when a standard higher dose of MTX is compared in these types of patients.