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ID PMID Title PublicationDate abstract
7948616 Elevated cytokine levels in synovial fluid of rheumatoid arthritis correlates with the pre 1994 Synovial fluid aspirated from 34 patients with symptomatic rheumatoid arthritis (RA) was evaluated for the presence of human cytomegalovirus (CMV) genomic material using polymerase chain reaction (PCR), and for levels of interleukin 8 (IL-8) and IL-6 using enzyme-linked immunoadsorbence assay. IL-8 and IL-6 levels were significantly higher in CMV DNA-positive RA patients than CMV DNA-negative RA patients and at least 10-fold higher than in both corresponding control groups of patients with osteoarthritis (OA). These findings suggest an association between elevated IL-8 and IL-6 levels and the presence of the CMV genome in RA patients.
7631278 [Multiple joint replacement in chronic rheumatoid arthritis: results, indications]. 1995 Jul Rheumatoid arthritis, steadily progressive and affecting many joints, is a real challenge for the orthopaedic surgeon. Thorough assessment and long-term planning to maximize overall performance requires clear orthopaedic thinking based on wide experience. The final aim is to enable the patients to walk and be independent. Over the last 30 years, the surgery of the rheumatic diseases has become a well-established specialty within orthopaedic surgery. Open synovectomy still has a place. In badly damaged joints, however, only prosthetic joint replacement has a fair chance. Total hip replacement is now a common procedure. Yet many problems regarding long-term performance remain unclear. This is even more pertinent for total knee replacement. Operations on the upper limbs must enable the patient to become less dependent of other people's help. Artificial shoulder joints have become more popular, and elbow joint replacement has been a particularly important field at the Wilhelm Schulthess Clinic. Multiple joint replacement is often necessary and can improve the quality of life for these badly stricken patients.
7661913 Serial measurement of serum interleukin-2 receptor levels in patients with rheumatoid arth 1994 Dec To investigate the association of T cell activation with clinical exacerbations of RA, we measured serum levels of soluble interleukin-2 receptors (sIL2R), a marker of T cell activation, in serial samples obtained from 23 patients with RA. sIL2R measurements were performed on sera obtained from each patient every 2 weeks for up to 60 weeks, and levels were correlated with swollen joint counts, tender joint counts, physician global assessments, patient global assessments, pain scores, Health Assessment Questionnaire Disability Index scores, and Westergren erythrocyte sedimentation rates measured simultaneously. There were no significant correlations between changes in sIL2R levels and changes in any of the other measures, nor were lead-lag relationships detected, for the group as a whole. Examination of the time courses of individual patients revealed significant positive correlations between changes in sIL2R levels and changes in swollen joint counts in five patients; significant correlations with other measures were present in three or fewer patients. sIL2R levels also varied little over the 2-week time interval of greatest clinical change in each patient. These results suggest either that clinical exacerbations of RA are not associated with changes in T cell activation or that sIL2R levels do not accurately reflect such changes.
8239762 Role of the CS1 adhesion motif of fibronectin in T cell adhesion to synovial membrane and 1993 Sep OBJECTIVES: It has previously been shown that the very late antigen-4/vascular cell adhesion molecule-1 (VLA-4/VCAM-1) pathway functions as a receptor/ligand interaction system mediating the recruitment of activated lymphocytes to inflamed synovium of patients with rheumatoid arthritis. This study was performed to determine whether VLA-4 also affects lymphocyte adhesion to inflamed synovium through interaction with the alternatively spliced CS1 domain of fibronectin. METHODS: The effect of the synthetic peptide CS1 on lymphocyte binding to human synovial and peripheral lymph node high endothelial venules (HEVs) was measured in an in vitro frozen section assay. RESULTS: In the presence of the CS1 peptide or antibody to fibronectin, significant inhibition of binding was observed (54 and 51% respectively). Blocking with antibody to VCAM-1 yielded inhibition of binding to 46% of the control value. Maximum inhibition of binding was obtained with a combination of antibody to VCAM-1 and CS1 (65%) and with antibody to VLA-4 alpha (68%). Blocking the classical fibronectin receptor with antibody to VLA-5 alpha gave a slightly lower inhibition at 42%. In normal peripheral lymph nodes, the synthetic peptide CS1 and antibodies to fibronectin and VLA-5 also partially inhibited T cell binding to HEVs (45, 47, and 52% respectively). CONCLUSION: These results show that fibronectin mediates lymphocyte-HEV interactions not only through its classical VLA-5 receptor, but also through its CS1 adhesion motif in inflamed synovium and peripheral lymph nodes.
8453505 Differential effects of glucocorticoids on cortical appendicular and cortical vertebral bo 1993 Jan The susceptibility to glucocorticoid-induced bone loss may vary in different parts of the skeleton. We studied 62 patients with rheumatoid arthritis, 26 of whom were on low-dose glucocorticoid treatment. Bone mineral content (BMC) in the forearm was measured by single photon absorptiometry at a cortical, diaphyseal, and at a mixed cortical and trabecular, metaphyseal site. Lumbar BMC was measured by dual energy computed tomography in a trabecular and a cortical region of interest. The presence of vertebral deformities was evaluated on lateral spine radiographs. After correction for possibly confounding variables, prednisone therapy significantly influenced BMC at both the trabecular (-22.0%, 95% confidence interval -36.0% to -8.1%) and cortical (-24.8%, 95% confidence interval -39.3% to -10.3%) lumbar site. A significant effect was also seen at the metaphyseal (-15.7%, 95% confidence interval -27.1% to -4.2%), but not the diaphyseal (-3.9%, 95% confidence interval -14.1% to 6.4%) site in the forearm. Correlations between peripheral and vertebral BMC were moderate at best. The diaphyseal to metaphyseal BMC ratio did not identify patients with vertebral osteoporosis. It is concluded that the anterior cortical rim of the vertebral body is more susceptible to the effects of glucocorticoids than the cortical bone in the forearm, and that measurements of trabecular and anterior cortical vertebral BMC are essential in the management of patients with possible glucocorticoid-associated osteoporosis.
8103722 Proinflammatory cytokines enhance human synoviocyte expression of functional intercellular 1993 Sep We determined the ability of proinflammatory cytokines to enhance ICAM-1 (CD54) expression on, and PBMC adhesion to, human synoviocytes. Surface molecules were characterized by cell ELISA and by flow cytometry. Adhesion of PBMC to synoviocyte monolayers was measured by direct counting or by colorimetric staining. Most cytokines upregulated ICAM-1 expression (IL-1 beta > TNF alpha > IFN-gamma >> PDGF-bb, IL-6), but not GM-CSF or TGF beta. A similar concentration-dependent increase was observed for synoviocytes derived from patients with rheumatoid or osteoarthritis. Kinetic studies of ICAM-1 expression differed among several cytokines: an early rise with IL-1 beta or TNF alpha stimulation, a gradual increase with IFN-gamma, a transient increase with PDGF-bb, and a plateau with IL-6. Adhesion of PBMC to synoviocytes was increased by IL-1 beta or TNF alpha and reduced by MAb to CD54 or CD18. Increased synoviocyte adhesiveness may promote interactions with infiltrating inflammatory cells.
7818564 Azathioprine-related bone marrow toxicity and low activities of purine enzymes in patients 1995 Jan OBJECTIVE: Azathioprine (AZA) metabolism largely parallels the endogenous purine pathways. To date, thiopurine methyltransferase (TPMT) deficiency has been reported as a cause of AZA-related bone marrow toxicity in 1 patient with rheumatoid arthritis (RA). We therefore studied purine enzyme activities in 3 patients with RA who experienced AZA-related bone marrow toxicity. METHODS: Lymphocyte activity of purine nucleoside phosphorylase and 5'-nucleotidase (5NT) and erythrocyte activity of TPMT, key enzymes in thiopurine catabolism, were measured in 3 RA patients who had experienced AZA-related bone marrow toxicity and in 16 RA patients without signs of toxicity despite at least 6 months of treatment with AZA. RESULTS: Two patients with AZA-related bone marrow toxicity were found to have a TPMT deficiency, 1 partial and 1 total. In the third patient, 5NT activity was found to be well below the lowest level observed in the control subjects. CONCLUSION: All 3 patients with severe AZA-related bone marrow toxicity had abnormal purine enzyme activities. Deficiency of purine enzymes, including TPMT and 5NT, may be a cause of AZA-related bone marrow toxicity in patients with RA.
8525387 Hormonal and pregnancy relationships to rheumatoid arthritis: convergent effects with immu 1995 Aug OBJECTIVE: To review sex hormones and rheumatoid arthritis (RA) and the interrelationships between hormonal, immunological, and vascular systems. DATA SOURCES: Publications detailing serum sex hormone levels and their HLA interactions, steroidogenesis, pregnancy, and therapeutic uses of sex hormones in RA. STUDY SELECTION: Controlled studies of sex hormone levels in RA patients not previously treated with glucocorticoids. DATA EXTRACTION: Mean (+/- SD) serum levels of dehydroepiandrosterone sulfate (DHEAS), testosterone (T), and estradiol (E2). DATA SYNTHESIS: Mean (+/- SD) levels were collated into tables for women with pre-versus postmenopausal onsets of disease and men. Data were also ordered across all study groups by increasing mean levels of the control subjects. Pooled data were summarized statistically, and major sources of variation between the studies were identified. CONCLUSIONS: Serum DHEAS, an adrenal androgen, was impressively decreased among women with premenopausal onset of RA. One study showed such deficiency years before disease onset. Serum T was somewhat decreased in the premenopausal onset group, but could be explained by decreased peripheral conversion of the lower levels of adrenal androgens. Women with postmenopausal onset of RA had modestly decreased serum DHEAS levels overall, but no difference in serum T, compared with controls. Male RA cases had consistently decreased serum levels of T, but not of DHEAS. Serum E2 was comparable in all RA versus control groups. The complex biology of pregnancy was interpreted as an example of vital interactions between hormonal, immunological, and vascular systems, as they may relate to the physiopathology of RA. The major age, sex, and hereditable determinants of RA were compared within a composite table of estimated relative risks. Elucidation of the interacting risk factors offers promising avenues of research in this complex disease.
7540690 Peripheral blood and synovial fluid monocyte expression of interleukin 1 alpha and 1 beta 1995 Apr OBJECTIVE: To investigate the mononuclear cell (MNC) types from peripheral blood (PB) and synovial fluid (SF) of patients with rheumatoid arthritis (RA) expressing interleukin-1 beta and -1 alpha (IL-1 beta, IL-1 alpha). METHODS: PB and SF MNC from 16 patients with classical or definite RA and controls were analyzed by flow cytometry for IL-1 beta and IL-1 alpha staining. RESULTS: MNC from normal individuals do not stain for either IL-1 beta or IL-1 alpha. By contrast, PB and SF CD14+ monocytes from patients with active RA show significant staining for surface and intracellular IL-1 beta and IL-1 alpha. Furthermore, the erythrocyte sedimentation rate (ESR) correlates with the surface expression of IL-1 alpha (r = 0.52, p < 0.05) while the number of active joints (i.e., tender and/or swollen) correlate with the intracellular expression of IL-1 beta (r = 0.58, p < 0.03) in CD14+ monocytes. CONCLUSION: The analysis of IL-1 beta and IL-1 alpha expression on CD14+ monocytes from peripheral blood by flow cytometry could be a potential immunological marker of disease activity in RA and its variation could be used to monitor the effects of therapy.
7598299 Most African-American patients with rheumatoid arthritis do not have the rheumatoid antige 1995 Aug 1 OBJECTIVE: To evaluate the relation between the presence of the "rheumatoid epitope," defined by a sequence motif in the HLA-DRB1 alleles, and disease severity in African-American patients with rheumatoid arthritis. DESIGN: Cross-sectional study. SETTING: Rheumatology outpatient clinics at two university medical centers. PATIENTS: 86 African-American patients with rheumatoid arthritis (66 seropositive and 20 seronegative for the rheumatoid factor) attending the clinics and 88 healthy African-American persons. MEASUREMENTS: HLA-DRB1 alleles were determined by restriction fragment length polymorphism and by allele-specific oligonucleotide typing of polymerase chain reaction-amplified HLA-DRB1 second exons. RESULTS: With the exception of an increased frequency of HLA-DRB1*04 alleles in seropositive patients with rheumatoid arthritis (27.3%) compared with controls (13.1%) (P = 0.02), the frequencies of HLA-DRB1 alleles were similar in patients and controls. Most seropositive (48 of 66) and seronegative (15 of 20) patients were HLA-DR4 negative, but some (7 of 48 seropositive patients and 3 of 15 seronegative persons) inherited the rheumatoid epitope on a non-DR4 allele. Disease features, including severity, were similar for patients without the epitope and for those with either a single or a double dose of an epitope-positive allele. Positivity for rheumatoid factor, but not for the rheumatoid epitope, was weakly associated with severity in these patients. CONCLUSION: Most African-American patients with rheumatoid arthritis did not express the rheumatoid epitope. The predisposition to and severity of rheumatoid arthritis in African-Americans appears to be independent of the presence and dose of the shared rheumatoid epitope.
1282716 [Monoclonal antibodies in the treatment of rheumatoid arthritis]. 1992 Oct 31 Monoclonal antibodies (MoAb's) make it possible to treat rheumatoid arthritis with selective immunotherapy. These antibodies may be directed against various targets, such as lymphocyte activation antigens, cytokines or subpopulations of lymphocytes (notably TCD4 +), involved in the pathogenesis of the disease. Recent open studies have demonstrated the feasibility and safety of this therapeutic method, but the number of patients who entered the trials is still low, and the clinical, biological and immunological results vary considerably in importance and duration, without remission. No response predictive factor could be elicited from these studies. The murine origin of these MoAb's exposes to the frequent risk of immunization which may interfere with the effectiveness and safety of a second treatment. Some possibilities can already be envisaged, including potentiation of the MoAb by coupling with a cytotoxic agent (anti-CD5 + ricin) and "humanization" of murine MoAb's (chimeric anti-CD4) reducing the risk of immunization. Further (controlled) trials therefore are indispensable to evaluate the true rank occupied by this therapeutic method in rheumatoid arthritis.
8824718 Detection of human-specific anti-la(SSB) antibodies in patients with rheumatoid arthritis. 1995 Dec Sera from anti-Ro(SSA) positive and negative patients with rheumatoid arthritis (RA) were compared with those from patients with primary Sjogren's syndrome (pSS) and systemic lupus erythematosus (SLE) with regard to anti-La(SSB) antibodies. Several assays for anti-La(SSB) (RNA precipitation, counterimmunoelectrophoresis, and immunoblotting) demonstrated the presence of such antibodies in selected anti-Ro(SSA) positive (10/19 in RA and 18/37 in pSS and SLE) but not in anti-Ro(SSA) negative sera. In agreement with previous reports, anti-La(SSB) antibodies from pSS and SLE patients uniformly reacted with various cellular extracts used as sources of La(SSB) antigen, including extracts from human cultured cells (HeLa), calf thymus and rabbit thymus. In contrast, while all 10 anti-La(SSB) sera from RA patients reacted with the human HeLa cell extracts, only three of them also reacted with calf and rabbit thymus extracts. These results were further supported by the analysis of a cohort of 70 consecutively selected sera (displaying monospecific anti-Ro(SSA) reactivity against calf thymus extract) from patients with various rheumatic disorders, where human-specific anti-La(SSB) were detected in two out of the five of RA patients studied.
7540526 Treatment of vasculitic leg ulcers in connective tissue disease with iloprost. 1995 Mar Leg ulcers are a recognised manifestation of cutaneous vasculitis in connective tissue diseases (CTDs) including rheumatoid arthritis (RA). Iloprost a stable prostacyclin analogue has been successfully used to treat Raynaud's phenomenon and digital ulcers associated with CTD's. Our aim was to assess iloprost in the treatment of vasculitic leg ulcers in CTD. In this paper we describe eight cases of vasculitic leg ulceration in association with RA and CTD, treated with intravenous iloprost. The iloprost was administered for 6-8 hours daily and continued for 21-28 days. Immunosuppressive therapy was required in three patients with severe necrotising vasculitis (RAnv). Complete ulcer healing was achieved in four patients within 6 weeks of commencing therapy while rapid improvement occurred in the other four patients. This suggests that iloprost may be useful as an adjunct to therapy for vasculitic leg ulcers. A double-blind placebo controlled study of iloprost therapy for RA leg ulcers is under way.
7586733 Expression of adhesion molecules in early rheumatoid synovial tissue. 1995 Dec The objective of this paper is to define the expression of adhesion molecules in synovial tissue (ST) from patients with rheumatoid arthritis (RA) with respect to disease duration. Antibodies against adhesion molecules were used for immunohistochemistry to examine ST sections from 11 patients with early RA ( < 1 year), 14 patients with long-standing RA ( > 5 years), and 15 patients with osteoarthritis (OA). Increased cellular infiltration and increased expression of E-selectin, ICAM-1, VCAM-1, PECAM-1, VLA-4, and Mac-1 were found in ST from patients with RA compared to ST from patients with OA. The immunohistological findings were similar for the different stages of RA. The upregulation of adhesion molecules in ST of patients with RA of < 1 year's duration suggests the activation of chronic inflammatory processes in these patients. Therefore, the mechanisms by which therapies directed toward these adhesion molecules exert their effects are likely to be similar for patients with so-called early RA and patients with long-standing RA.
7577218 Femoral head bone grafting for reconstruction of the acetabular wall in dysplastic hip rep 1995 From 1980 through 1991 we screwed a preshaped cortico-cancellous bone graft onto the ileum wall to compensate acetabular deficiency in 94 consecutive total hip replacements. We report the results of 87 hips (79 patients) with an average follow-up of 30 months (12-75 months) postoperatively. Pain in dysplasia-coxarthrosis and congenital dislocation of the hip, destructive coxitis in rheumatoid arthritis and cup loosening was the main indication for surgery. According to the Merle d'Aubigné score the postoperative clinical evaluation demonstrated 77% very good and 18% good results. Due to component loosening the results had to be classified as unsatisfactory in 4 hips (2 cups and 2 stems). At the time of evaluation 90% of the arthroplasties was osseously consolidated as evidenced by trabecular bridging and structural integrity with host bone. Resorptions of the graft were noted in 32 hips. One cup was removed because of complete resorption and consecutive loosening, a further one was considered clinically and radiologically loose because of partial graft resorption. Two further complete resorptions and 28 partial lateral resorptions had no influence on the secondary stability of the implant. We are aware that these are short-term results. Nevertheless, we recommend the described method as a valuable addition to arthroplasties for acetabular rim defects both in osteoarthritis and in revision surgery.
7732489 [Immunoglobulin and LST in RA patients treated with bucillamine]. 1995 Feb In 79 RA patients treated with Bucillamine (Bu) we monitored IgG, A, M and total protein concentration x gamma-globulin% (Ig) before and after Bu. All of these four were lowered after Bu in both groups with and without adverse reaction. In the group with adverse reactions the serum level of IgG, A and Ig was significantly lower after Bu treatment than in the group without adverse reactions. The decreases of IgG and IgA were statistically significantly greater in the group with adverse reactions than those in the group without adverse reaction. The serum level of IgM after Bu in the effective group was significantly lower than that in the non-effective group. We also examined lymphocyte stimulation test (LST) in 44 RA patients treated with Bu. In the effective group Bu inhibited lymphocyte proliferative response to PPD more significantly than in the non-effective group. Bu also inhibited lymphocyte proliferative response after stimulation with PPD in the non-effective group doseresponsively. We concluded that the considerable decreases of IgG and IgA might correlate with the adverse reactions of Bu. The decrease of IgM and inhibition of LST with Bu might correlate with the efficacy of Bu.
1440085 [A case of rheumatoid arthritis complicated with pseudotumor around odontoid process succe 1992 Oct A 69-year-old-female with a history of rheumatoid arthritis since 1975 had suffered from dysesthesia of extremities since October 1989. Radiating pain and weakness occurred when she tried to stand up on Dec. 25 in 1989. She was admitted to our hospital in October 1990. Physical examination showed emaciation, hypesthesia of extremities, hypesthesia over the right chest and back, impaired vibration and position sense, and hyperreflexia. Laboratory findings revealed that the erythrocyte sedimentation rate was elevated to 46mm/hr, rheumatoid factor (RF) to 83.1IU/ml and CRP to 3.7mg/dl. Her blood sugar was high and she was diagnosed as having diabetes mellitus. Cervical X ray film showed atlanto-axial subluxation. A pseudotumor around the odontoid process bulging into the spinal canal and compression of the upper cervical cord was observed by MRI. In spite of administration of bucillamine (100mg/day), the size of pseudotumor did not change. Methotrexate (MTX) at a dose of 5mg/week was started in February 1991 and the pseudotumor decreased in size with a concurrent reduction of ESR, RF and CRP. However, the high intensity lesion by T2 weighed image did not change and dysesthesia persisted. The pseudotumor was thought to be due to pannus and it was revealed that MTX was effective for reduction. The persistent dysesthesia was probably due to the degeneration of the upper cervical cord, although diabetic neuropathy may also have played a role.
1466596 Comparison of two approaches to measuring change in health status in rheumatoid arthritis: 1992 Nov As an alternative to the calculation of change scores for health status questionnaires used in clinical trials or longitudinal studies, transitional questions have been developed for patients to assess changes directly themselves. Here the original Health Assessment Questionnaire (HAQ) is compared with a modified version of the HAQ (MHAQ) which contains transition questions used at follow up. These, together with a set of standard rheumatological tests, were all completed by 100 patients with rheumatoid arthritis on two occasions, three months apart. Change scores were calculated for the HAQ and for the clinical measures and compared with the MHAQ. The results were strikingly in favour of encouraging patients to assess their own degree of change through the use of transition questions in the MHAQ.
7699615 No evidence of adenoviral hexon regions in rheumatoid synovial cells and tissue. 1994 Dec OBJECTIVE: To investigate whether adenoviral DNA is present in synovial specimens from patients with rheumatoid arthritis (RA). METHODS: Synovial fluid (SF) cells from 53 patients with early RA (duration less than 1 year) and synovial tissue samples of 20 patients with advanced RA were studied by using polymerase chain reaction for the presence of adenoviral DNA. The controls were 21 patients with other arthropathies. RESULTS: No adenoviral DNA was found in the SF leukocytes or synovial tissue of any of the patients with arthritis. CONCLUSION: These findings do not indicate that adenoviruses play a role in the etiology of RA. However, they do not exclude adenoviruses as an occasional cause of persistent or recurrent inflammatory arthritis.
7812288 [Side-effects during treatment of rheumatoid arthritis with methotrexate]. 1994 May Methotrexate is the drug with the highest long-term continuation rate in rheumatoid arthritis patients. However, toxicity is the main reason for methotrexate withdrawal. Most adverse effects are mild abnormalities, such as digestive symptoms, stomatitis, elevations in transaminase levels, and moderate decreases in peripheral blood cell counts. Potentially life-threatening effects include hypersensitivity pneumonitis and pancytopenia. Cirrhosis is less common than in patients with psoriasis. Opportunistic infections and Epstein-Barr virus-related lymphomas have been reported. Neurological disorders, cutaneous reactions and renal lesions have been ascribed to low-dose methotrexate. Prior renal dysfunction and concomitant administration of a number of drugs, including cotrimoxazole, have been shown to increase methotrexate toxicity. However, susceptibility to the toxic effects of methotrexate varies widely across individuals. The effectiveness of folate supplementation in preventing methotrexate toxicity remains controversial.