Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclosporin A (Sandimmun) has gained wide acceptance by most transplant physicians as the immunosuppressant of choice for preventing rejection of solid organ grafts and graft-versus-host disease. The drug has a specific effect on T-lymphocytes in which it seems to prevent the transcription of genes for several lymphokines. The reduction in IL-2 prevents the clonal expansion of T-lymphocytes and their differentiation into effector T-cells. The reduction in IFN-tau interrupts the feedback mechanism between T-cells and macrophages and the aberrant expression of MHC class II molecules. Through these mechanisms Sandimmun exerts an immunosuppressive and anti-inflammatory effect. Considerable evidence has accumulated to suggest that rheumatoid arthritis (RA) is an auto-immune disease. Activated T-lymphocytes interrelate with macrophages, other inflammatory cells and effector cells in joint tissue, leading to symptoms of inflammation accompanied by joint destruction. Immunosuppressive treatment is already well established in this disease and several trials have already taken place using Sandimmun. A total of 224 patients with RA refractory to conventional disease-modifying drugs have participated in 11 published clinical studies. A review of these studies concludes that Sandimmun is efficacious in controlling inflammatory and functional symptoms, although this improvement is no generally accompanied by reductions in ESR and rheumatoid factor. The frequency of adverse events is comparable to that of other treatments but nephropathy remains the principal factor limiting the use of Sandimmun. Recent evidence suggests that with a strict dosage strategy and good monitoring this problem is controllable and reversible. Further studies are under way to confirm these claims.
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PMID:Sandimmun (cyclosporin A): mode of action and clinical results in rheumatoid arthritis. 307 82

The pituitary-testicular axis was investigated in 31 males with rheumatoid arthritis (age range 19-60 years, median 55 years) and 33 males with ankylosing spondylitis (age range 22-55 years, median 37 years) and compared with a control group of 95 normal male volunteers. Using analysis of covariance, patients with rheumatoid arthritis showed significantly lower serum testosterone (p less than 0.05) and derived free testosterone (p less than 0.01) concentrations and significantly higher serum LH and FSH concentrations (p less than 0.05) compared with controls. All patients had normal serum prolactin and cortisol concentrations. Serum testosterone correlated with ESR, haemoglobin concentrations and rheumatoid factor titres (r = -0.448, p less than 0.02; r = 0.440, p less than 0.02; r = -0.360, p less than 0.05 respectively) in the rheumatoid patients. Although there was a significant negative correlation between ESR and haemoglobin concentrations (p less than 0.005) in the patients with ankylosing spondylitis, neither variable correlated with serum testosterone concentrations. There was no association between testicular dysfunction and the presence of extra-articular features of rheumatoid arthritis. Ten patients (33 per cent) with rheumatoid arthritis and four (13 per cent) with ankylosing spondylitis admitted to periods of impotence while 15 (50 per cent) of the former and 12 (39 per cent) of the latter had periods of decreased libido. There was no evidence for increased rates of infertility in either group.
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PMID:Androgenic status and sexual function in males with rheumatoid arthritis and ankylosing spondylitis. 309 90

Mononuclear phagocyte system (MPS) Fc-receptor function in 20 patients with seropositive rheumatoid arthritis (RA) was investigated using radiolabelled autologous erythrocytes coated with an average of 5,800 molecules of anti-rhesus IgG (E. IgG). Although clearance times (T1/2) of E. IgG tended to be longer in RA patients than those in healthy controls (46 +/- 6 min vs 38 +/- 5 min, mean +/- s.e.m., P = 0.38), this did not reach statistical significance. Liver spleen uptake ratios (LS ratios) were increased in patients with RA (13/100 +/- 1/100 vs 7/100 +/- 1/100, P less than 0.05). There was no correlation of T1/2 or LS ratios with articular disease activity, vasculitis, ESR, IgM containing immune complex levels or Clq-binding immune complex levels. Although Clq-binding immune complex levels were significantly higher in patients with vasculitis than in those without (P less than 0.01), T1/2 and LS ratios did not differ in these two groups of patients. The T1/2 and LS ratios of E.IgG did not reveal a defect in MPS Fc-receptor function and did not correlate with one of the above-mentioned clinical and immunological parameters. We suggest that in order to establish a possible defect in Fc-receptor function correlating with disease activity and immune complex levels in RA patients, soluble immune complexes or immune complex-like material should be used as probes.
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PMID:Mononuclear phagocyte system Fc-receptor function in patients with seropositive rheumatoid arthritis. 311 62

Diphosphonates reduce the rate of bone turnover. They have additional pharmacological properties improving adjuvant arthritis in rats and lowering ESR in this condition. We have evaluated etidronate disodium, a diphosphonate commonly prescribed in the United Kingdom for Paget's disease in patients with rheumatoid arthritis. Apart from an early improvement in articular index, perhaps reflecting anti-inflammatory activity, no significant change occurred in clinical variables or in laboratory indices of 'secondline' action at a dose of 5 mg/kg/day.
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PMID:A clinical and biochemical assessment of etidronate disodium in patients with active rheumatoid arthritis. 313 66

The pituitary-gonadal axis was assessed in 10 male patients during hospital admissions lasting 3-6 weeks (median 3 weeks) for flares for rheumatoid arthritis. Despite significant improvements in the Ritchie indices from median 16 (range 9-23) to 8.5 (range 5-20) (p less than 0.01) and ESR from median 67 mm/h (range 46-115 mm/h) to 58 mm/h (range 15-116 mm/h) (p less than 0.05) there were no significant changes in serum testosterone, LH, FSH, prolactin (PRL), cortisol or androstenedione during the admission periods. At follow-up (median 14 months, range 5-18 months after admission) there were further improvements in articular indices (median 7, range 3-13; p = NS) and ESR (median 20 mm/h, range 4-62 mm/h; p less than 0.05) and rheumatoid factor titres had fallen from median 1/1025 (range 1/126 to 1/1024) to median 1/512 (range 1/64 - 1/512). One patient showed biochemical features of progressive testicular failure. In the remaining patients, serum and derived free testosterone levels were significantly increased (p less than 0.01 respectively) and serum LH reduced (p less than 0.01). There were no changes, at this time, in prolactin, cortisol or androstenedione. Rheumatoid flares appear to be associated with prolonged suppression of testicular function.
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PMID:Prolonged hypogonadism in male patients with rheumatoid arthritis during flares in disease activity. 314 8

Progressive joint damage characterises rheumatoid arthritis despite treatment with slow-acting drugs such as penicillamine. We examined a cohort of 145 RA patients, treated with 250 or 500 mg penicillamine daily for 18 months to study progressive joint damage measured using Larsen's standard radiographs. Overall damage increased significantly over 18 months at both doses of penicillamine. Radiological changes between 6-18 months were studied in detail in 55 cases. They were divided into rapidly progressive (increases in Larsen score of more than 5) or slowly progressive (increases in Larsen score of 5 or less). Overall clinical response, visual analogue pain score, ESR, haemoglobin and platelet count were significantly lower in the slowly progressive patients; articular index and duration of morning stiffness were slightly lower; latex titre, RAHA titre, joint size and white cell count showed no differences between groups. There is an indirect relationship between progressive joint damage and some clinical and laboratory measures. The reasons underlying our failure to control progression in some cases need further definition.
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PMID:Progressive joint damage during penicillamine therapy for rheumatoid arthritis. 317 51

The validity and reliability under Swedish conditions of a translated and slightly modified version of the Stanford Health Assessment Questionnaire (HAQ), referred to here as the ADL questionnaire, was studied. Sixty-four patients with definite/classical rheumatoid arthritis (RA) participated in the major part of the investigation. In addition, inter-observer reliability was studied in the testing of 15 other patients with RA. The questionnaire was filled in by the patients twice (ADL Tests 1 and 2) with a one-week interval between. A physiotherapist or occupational therapist also assessed each of the patients on a sample of ADL functions (ADL Test 3). Joint mobility, grip-strength, pain, Ritchie index and ESR were likewise checked. Results indicated inter-observer reliability to be high for the ADL (r(S) = 0.98), for joint mobility (r(S) = 0.86), and for the Ritchie index (r(S) = 0.83). The test-retest reliability for the ADL questionnaire which the patients filled in (Tests 1 and 2) was high r(S) = 0.91. Results of the ADL questionnaires the patients completed were found to correlate fairly closely with the observations of the therapists, r(S) = 0.71. The validity of the scoring system was found to be sufficient, using Ward's cluster analysis for comparing the original HAQ scores with scores on all the questions included in the questionnaire. Thus, the translated and somewhat modified version of the ADL questionnaire studied here appears to possess a high degree of reliability and validity in assessing patients with RA.
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PMID:Assessing disability in patients with rheumatoid arthritis. Use of a Swedish version of the Stanford Health Assessment Questionnaire. 318 57

The magnitude of thrombocytosis and the possible confounding effect of platelet clumping, an in vitro artifact resulting in spuriously low platelet counts, in active rheumatoid arthritis (RA) was evaluated by a prospective survey of 57 consecutive patients, 60% of whom had thrombocytosis. Five cases (9%) of platelet clumping, assessed by H6000 pictures, were found. A low-grade platelet loss in many of the samples anticoagulated by EDTA was suggested by comparison with platelet counts obtained in parallel blood samples anticoagulated by citrate. Thus, the possibility of spuriously low platelet counts due to laboratory artifacts must always be taken into consideration in RA patients. The relation between thrombocytosis and other estimates of disease activity was also studied. The platelet count in citrated blood in active RA was significantly correlated with ESR, acute phase plasma proteins, and neutrophil, basophil and monocyte counts. In a multivariate regression model, however, only the correlation with haptoglobin (p = 0.06) approached significance.
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PMID:Thrombocytosis in active rheumatoid arthritis. Relation to other parameters of inflammatory activity and confounding effect of automated cell counting. 322 78

Immunoglobulins are often high in active rheumatoid arthritis and fall when treatment with a slow-acting anti-rheumatic drug is instituted. We assessed the value of monitoring immunoglobulins during penicillamine therapy; 145 patients were followed for up to 5 years, IgA, IgM and IgG levels were compared to 12 other clinical and laboratory variables on 903 occasions. Mean levels of IgA and IgG fell by 10-30%. These changes were less than with ESR or clinical measures such as articular index and duration of morning stiffness. Immunoglobulin levels showed weak correlations with other variables. Only a small number of patients had hypogammaglobulinemia. Initially, 5 cases had low IgA with subsequent falls in 3 more. Initially, 2 cases had low IgG with subsequent falls in 5 more. No patients had low IgM levels. These changes seemed clinically irrelevant. Radiological progression was related to IgA levels. Patients with persistently high rates of radiological progression had persistently higher serum IgA. We conclude that IgM gives the most "acute phase" pattern of response. IgA gives more theoretically interesting information, especially concerning radiological progression. There is only a limited amount of clinically valuable information gained from measuring immunoglobulins.
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PMID:The clinical value of measuring immunoglobulins when assessing penicillamine therapy in rheumatoid arthritis. 322 80

Using ELISA antibodies, titres to collagen type I, II and III in sera of patients with juvenile chronic arthritis (JCA) were assayed. Results were compared with titres of patients with rheumatoid arthritis (RA). Increased antibodies titres to all three collagen types were found in comparison with healthy individuals of the same age. Average titres in patients with RA were higher than those of the JCA group. When antibodies titres were correlated with erythrocyte sedimentation rate in 1 hour (ESR/1h) statistical significance was found only in RA group for collagen type II.
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PMID:Anticollagen antibodies in patients with juvenile chronic arthritis. 322 82


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