Browse

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

ID PMID Title PublicationDate abstract
8185689 Minocycline in active rheumatoid arthritis. A double-blind, placebo-controlled trial. 1994 May OBJECTIVE: To determine the efficacy of minocycline in the treatment of rheumatoid arthritis (RA). METHODS: Minocycline (maximal oral daily dose 200 mg) or placebo was administered in a 26-week, randomized, double-blind study to 80 patients with active RA, who were treated or had previously been treated with at least one disease-modifying antirheumatic drug. RESULTS: There were 15 premature discontinuations: 6 (5 taking minocycline) because of adverse effects, 8 (all taking placebo) because of lack of efficacy, and 1 (taking placebo) because of intercurrent illness. There was a statistically significant improvement in the minocycline group over the placebo group. There was a pronounced improvement in laboratory parameters of disease activity; however, improvement in clinical parameters was less impressive. The observed adverse effects attributable to minocycline were mainly gastrointestinal symptoms and dizziness. CONCLUSION: The results of the present study suggest that minocycline is beneficial and relatively safe in RA patients.
8356412 Successful treatment of the anemia of rheumatoid arthritis with subcutaneously administere 1993 We performed a 24-week open clinical study in which 12 patients with rheumatoid arthritis (RA) and anemia (mean hemoglobin (Hb) value 102 g/l, range 90-109 g/l) were treated with recombinant human erythropoietin (rHuEPO). rHuEPO was given as a subcutaneous injection twice weekly with an initial dose of 300 U/kg/week. Nine of the 11 patients who completed the study responded with an increase in Hb value of 15 g/l or more within 3 to 17 weeks. Three months after treatment the Hb levels were significantly lower than the highest Hb levels (p < 0.0001). There was an inverse correlation between the response rate and the mean serum concentrations of C-reactive protein and serum amyloid A protein (p < 0.001 and p < 0.003, respectively). We conclude that rHuEPO can correct anemia in patients with RA, but the response seems to be adversely influenced by the inflammatory activity of the disease.
1356683 The effect of age and acetylator phenotype on the pharmacokinetics of sulfasalazine in pat 1992 Oct The pharmacokinetic disposition of sulfasalazine and its metabolites was studied in 8 young and 12 elderly patients with active rheumatoid arthritis. Equal numbers of slow and fast acetylators were included in each age group. Patients received enteric-coated sulfasalazine 2g daily for 21 days; specimens of serum and urine were collected for 96 h after administration on days 1 and 21. The elimination half-life of sulfasalazine was greater in the elderly patients. Many disposition parameters of sulfapyridine differed in slow and fast acetylators; of greatest significance were the increased values of steady-state serum concentration in the slow acetylators. There was no effect of age on any sulfapyridine disposition parameters. Values for the steady-state serum concentrations of N-acetyl-5-acetylsalicylic acid were greater in elderly than in young patients. The metabolism of sulfapyridine was markedly affected by acetylator phenotype and this was reflected in the composition of sulfapyridine-related material in the urine. Thus, age is a determinant of the steady-state concentrations of salicylate moieties but acetylator phenotype plays a greater role in determining the serum concentration of sulfapyridine, which has greater therapeutic implications in rheumatology.
8729127 Effects of modulation of inflammatory and immune parameters in patients with rheumatic and 1996 Mar To describe the rationale and status of n-3 and n-6 fatty acid dietary supplementation in patients with inflammatory disease. The most recent literature is reviewed with a focus on rheumatoid arthritis (RA) as most investigations have described the use of n-3 supplements in this disease entity. Investigations from Europe, the United States, and Australia have described consistent improvement in tender joint scores with many investigators also observing improvements in morning stiffness. A meta analysis has confirmed the predictable improvement in tender joints. Recent studies also suggest that some patients with RA are able to discontinue nonsteroidal antiinflammatory drugs (NSAIDs) while receiving n-3 fatty acids. A large number of peer reviewed publications from around the world have established the utility of dietary supplementation with n-3 fatty acids in reducing tender joint counts and morning stiffness in patients with RA. Some patients are also able to discontinue NSAIDs while on these supplements.
7492225 Differential distribution of annexins-I, -II, -IV, and -VI in synovium. 1995 Oct OBJECTIVES: To examine the distribution of four annexins in non-inflamed rheumatoid arthritic and osteoarthritic synovial tissue. METHODS: Frozen sections were stained with monoclonal antibodies (MAb) specific for annexins-I, -II, -IV, and -VI, and for cell lineage related markers including CD68 and CD14 (macrophages), prolyl hydroxylase (fibroblasts), and CD3 (T cells). RESULTS: Each of the annexins was present in synovial tissues in significant amounts in the three groups studied. Annexin-I was predominantly found within the synovial lining layer and double labelling showed it to be present predominantly in cells of the macrophage lineage. In rheumatoid specimens there was increased staining within the lining layer, perivascularly and on macrophages within the tissue stroma. Annexin-II was present in a distribution similar to that of annexin-I, but with more prominent perivascular staining. Annexins-IV and -VI were seen chiefly in association with areas of lymphocyte infiltration in rheumatoid tissue, whereas annexins-I and -II were absent from these areas. Endothelial cells stained weakly positive for annexins-I and -II, and more strongly for -IV and -VI. CONCLUSIONS: This study demonstrates that annexins (particularly annexin-I, a putative mediator of the anti-inflammatory activities of glucocorticoids) are abundant in rheumatoid and non-rheumatoid synovial tissue, annexins-IV and -VI having a distribution distinct from that of -I and -II.
8212918 [Potential influence of nutrition with supplements on healthy and arthritic joints. II. Nu 1993 Jul A short period of fasting leads, in the mouse, to usually reversible damage to chondrocytes and in patients with rheumatoid arthritis often to a temporary improvement. Slight hypo-alimentation and a low-caloric diet reduce the spontaneous development of osteo-arthritis in the mouse, whereas a high-caloric diet promotes the disease. In man, mice, and, in particular, fattened animals, obesity is often associated with forms of osteo-arthritis. In such cases, it may be assumed that metabolic damage to cartilage is involved as well as damage due to weight-bearing forces. Elderly people, i.e., persons with a predisposition to osteo-arthritis, often suffer from a generalized vitamin deficiency. Vitamins E, B2, and C have been shown to exert an inhibitory effect on osteo-arthritis in animals, and it has been found that supplementation therapy, particularly with vitamin E and the combination of vitamins B1, B6, and B12, can exert a beneficial effect on the symptomatology of human degenerative joint disease. Mineral deficits in calcium, zinc and selenium (Kashin-Beck disease; endemic osteo-arthritis deformans) can provoke skeletal damage in humans and animals. On the other hand, calcium, iron, and copper have been reported to give rise to storage diseases, in some cases with involvement of articular cartilage. There have been indications that chondrotoxic damage may result from food contaminants. So far very little is known about the influence of phytopharmacodynamic substances (other than derivatives of rutin and rhein) on osteo-arthritis. The large gaps in our knowledge of the chondrotropic properties of the constituents of food and common stimulants underline the need for further investigations.
8913658 Low incidence of colorectal cancer in patients with rheumatoid arthritis. 1996 Sep OBJECTIVE: Aspirin (ASA) and also nonsteroidal anti-inflammatory drug (NSAID) use has been associated with a low incidence of colorectal cancer. The incidence of colorectal cancer in a cohort of patients with rheumatoid arthritis (RA) is reported here. METHODS: Cancer incidence was studied in a cohort of 9469 persons hospitalized for RA during 1970-1991 in Finland. The follow-up time was about 65,400 person-years. RESULTS: The incidence of colon cancer was significantly lower than in the general population [standardized incidence ratio (SIR) 0.57; 95% confidence interval (CI) 0.33-0.93], and the combined SIR for colorectal cancer was 0.62 (95% CI 0.42-0.88), while the combined incidence of all malignancies (SIR 1.16; 95% CI 1.07-1.26) was higher in RA patients than in the general population. CONCLUSION: Chronic use of NSAIDs or ASA, including antiinflammatory doses, is probably the main explanation for the low incidence of colorectal cancer in RA patients.
8710805 Short communication: selective placental transport of maternal IgG to the fetus. 1995 Dec During pregnancy there is a dramatic reduction in the serum levels of agalactosyl IgG (G0IgG) in both normal women and those with rheumatoid arthritis. In order to determine if a similar reduction in G0IgG were apparent in fetal serum, a comparison of the galactose content of IgG from nine paired samples of umbilical vein or fetal blood and peripheral maternal serum, at gestational ages ranging from 16-41 weeks was performed. The full-term maternal IgG samples were highly galactosylated, so confirming previous observations of reduced G0IgG levels during pregnancy. In addition every paired sample of fetal IgG had a higher level of galactosylation than the corresponding maternal IgG. Therefore, during pregnancy there is both a reduced biosynthesis of the G0IgG glycoform by the mother, and a restriction of its transport across the placenta. The ratio of estimated G0IgG in fetal and maternal serum was found to be related to changes in IgG transport, and in particular the active transport of IgG1 across the placenta during gestation. Our data suggest that the placental IgG transport mechanism is either carbohydrate independent by discriminating for IgG1, or is carbohydrate dependent selecting for highly galactosylated IgG glycoforms. This study emphasizes the need for further investigations on the biological function of G0IgG in normal physiological states, in addition to disease states, such as juvenile and adult rheumatoid arthritis, where elevated G0IgG levels correlate with disease activity.
8630639 An open study to assess the safety and tolerability of meloxicam 15 mg in subjects with rh 1996 Apr Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) which has shown potent anti-inflammatory properties but good gastrointestinal (GI) renal tolerability. The safety and tolerability profile of orally administered meloxicam 15 mg given once daily over a 28 day treatment period in renally impaired patients with rheumatic disease is presented here. A total of 25 patients (aged 43-78 yr, mean age 70 yr) with rheumatic disease and mild renal impairment were enrolled in this multicentre, open-label study, with 22 patients completing the 28 day treatment period. The median estimated creatinine clearance and N-acetyl-beta-glucosaminidase/creatinine ratios (a marker of renal tubular damage) recorded at day 14, day 28 or 4-7 days after meloxicam treatment was terminated, were not statistically significantly different from baseline values. There was no evidence of accumulation of meloxicam. Overall, meloxicam was well tolerated. The most common adverse events were GI complaints of abdominal pain and dyspepsia. No adverse events related to the urinary system, or increases in serum urea or potassium were recorded. The results suggest that meloxicam, 15 mg once daily, does not further compromise renal function or result in accumulation of meloxicam over this treatment period in patients with pre-existing mild renal impairment.
8000397 [Leukocyte expression of the LFA-1 adhesion molecule in spondylarthropathies]. 1994 Jan The expression of adhesion molecule Leukocyte Function Antigen-1 (LFA-1) on peripheral blood leukocytes was evaluated (using a monoclonal antibody anti CD11a/LFA-1) in 52 spondylarthropathies (SA) (35 HLA B27 positive), 12 healthy patients, 24 active rheumatoid arthritis (RA) and 12 systemic lupus (SLE) patients. LFA-1 expression on lymphocytes was similar in the different groups of patients, but LFA-1 expression on granulocytes was higher in SA than in controls (p < 0.05) or in RA or SLE. Fluorescence intensity of anti LFA-1 staining on SA granulocytes correlated with serum IgA levels. There was no difference between HLA B27 positive/negative, biologically inflammatory (CRP > 21 mg/l)/non inflammatory SA patients. This study seems to confirm the granulocyte and IgA involvement in immunopathogenesis of spondylarthropathies.
8077975 Cementless or hybrid total elbow arthroplasty with titanium-alloy implants. A study of int 1994 Jun Twenty-six patients (32 elbows) with rheumatoid arthritis had a total elbow arthroplasty with insertion of a cementless prosthesis. The humeral component was made of titanium alloy and it was fixed without cement in all elbows. The patients were followed for an average of 3 years 1 month (range, 2 years 2 months to 4 years 4 months). A good result was seen in 25 elbows, a fair result in 2, and a poor result in 5. The reason for the poor results was a breakage of the humeral component at the junctional portion of its stem. In all five of these elbows a marked resorption of bone mass within the condylar portion of the humeral component was observed on the lateral radiograph. The five elbows with a poor result had a revision operation, and in each of these black staining of the soft tissues within the joint was seen. This tissue metallosis due to wear debris of the titanium alloy was responsible for the osteolysis within the condylar portion. It became clear from this study that even in a non-weight-bearing joint, such as the elbow, titanium alloy may wear and result in tissue metallosis when used as a bearing surface of the implant. However, it was also found that in the majority of the elbows an establishment of the biologic fixation of the porous-coated stem could be achieved by use of this alloy.
7660685 Oral tolerance in the control of experimental models of autoimmune disease. 1995 May Autoimmune inflammatory diseases, including many human arthritides, cause significant morbidity and mortality. The control of their immunological aspects is central to management of the diseases and usually involves drugs that are, in the immunological sense, non-specific in their effects. The efficacy of such drugs may be limited, and they may have side-effects so serious that if immunologically specific means were available to control these diseases, there would be significant benefits. Immunological specificity is carried only by antibodies, T cell receptors, MHC molecules and, of course, antigen. Based upon the experimental outcome of inducing systemic specific immunological unresponsiveness-the so-called oral tolerance effect-by feeding antigens, several groups have investigated the effects on experimental autoimmune diseases of delivering autoantigens across gastric and respiratory mucosal surfaces. Three forms of arthritis, those induced by type II collagen, adjuvant and oil, respectively, have been examined in this way, and the results from these studies show that disease can be specifically prevented or ameliorated. In parallel, examination of experimental encephalitis and uveitis, as examples of neurological diseases, and diabetes in the NOD mouse, have produced the same results. This review discusses the results of these experimental studies and draws out their common features. The uniform finding is that T cells are made hyporesponsive, and that the most likely mechanism is one of active suppression mediated through the selective activation of T cells, of either CD4+ or CD8+ phenotype, that make cytokines which in turn can suppress pathological T cells responsible for the disease lesions. There are many unanswered questions concerning optimal dosage regimes, routes and vehicles for antigen delivery and antigen pharmacokinetics that need to be answered if the promising results of early human trials are to be exploited with benefit. At the fundamental level, the full identity of the cell type, or types, responsible for the tolerance, most likely to be active peripheral suppression, is still elusive. Given the complexity of disease processes in the different situations that have been examined, it is likely that no one mechanism applies in all, and that therefore different therapeutic approaches will need to be tailored accordingly.
8543073 Prevention of immune-mediated corneal graft destruction with the anti-lymphocyte monoclona 1995 We report a patient with peripheral rheumatoid corneal melting who developed a corneal perforation in one eye requiring tectonic keratoplasty. Nine consecutive corneal grafts were rapidly destroyed despite systemic immunosuppression with corticosteroid, cyclophosphamide, azathioprine and cyclosporin A. A rejection episode was observed in one graft before it melted and allograft rejection may have contributed to the destruction of other grafts. Corneal graft survival was ultimately achieved by systemic immunosuppression with the anti-lymphocyte monoclonal antibody, CAMPATH-1H. A single episode of rejection developed in the early post-operative period which was easily reversed by topical corticosteroid. Corneal melting has not recurred and the graft has now remained intact and clear for 24 months. Anti-lymphocyte monoclonal antibodies may therefore provide effective immunosuppression in the treatment of refractory ocular disorders.
8392222 Heterogeneity of the TCR repertoire in synovial fluid T lymphocytes responding to BCG in a 1993 Jul T lymphocytes have been implicated in the pathogenesis of rheumatoid arthritis. Interestingly, many of the activated T cells isolated from the synovial fluid of individuals with rheumatoid arthritis react with antigens from Mycobacterium tuberculosis or BCG. This response is seen to a much lesser extent in the peripheral blood of these patients. To investigate the nature of the T-cell response to BCG in RA, we isolated T cells from the synovial fluid of a patient with early-stage rheumatoid arthritis, stimulated them with BCG and cloned by limiting dilution. Staining with monoclonal antibodies specific for different V beta gene families revealed a statistically significant greater proportion of synovial-derived T-cell clones expressing the V beta 8 gene family product compared with peripheral blood clones. While the antigen specificity of some of the clones could not be determined, several of the clones displayed distinct antigen reactivities. Sequencing the TCR beta chain genes of these T cells suggested that although the V beta 8 gene products appeared to be over-represented in these BCG-specific clones, each clone utilized distinct J beta gene segments and used N segment addition to different extents. In addition, no common motifs were identified in the beta chain CDR3s of the clones sequenced. Analysis of bulk cultured BCG-specific SF T cells and unstimulated peripheral blood T cells for V beta 8 gene expression also revealed a large amount of diversity within the CDR3 region. Thus, the T-lymphocyte response to BCG in this patient with early rheumatoid arthritis appears to be quite heterogeneous.
8372720 Comparison of clinical effects of bucillamine between additive combination and single admi 1993 In a multicentre double blind study, it was demonstrated that bucillamine (Bu) 100 mg was more effective than placebo in patients with rheumatoid arthritis who are partially remitted by gold injections for more than six months. Global effectiveness and usefulness rates of 100 mg Bu in the combination therapy were almost the same as those of 3200 mg Bu in single administration. Side effects were also similar in the two regimens.
7939728 Histological appearance of the synovium in early rheumatoid arthritis. 1994 Jun This report reviews and discusses studies on the synovial fluid and biopsy specimens of synovial membrane obtained during the first 6 weeks of synovitis that evolved into rheumatoid arthritis (RA). Five previously unreported cases are described. Early changes in the microvasculature and synovial lining seem to antedate the classical chronic inflammation of established RA. Further characterization in the joint tissues in very early RA offers opportunities for identification of exogenous triggers and may allow more appropriate targeting of early therapy to potentially reversible aspects of pathogenesis.
1563102 Modulation of human T cell functions by surface sulphydryl groups: differential effects on 1992 Apr An impermeable thiol blocker has been used to investigate the role of sulphydryl (SH) groups in the production of and responsiveness to IL-2 by normal human T lymphocytes. Surface SH blockade of mononuclear cells prior to incubation with mitogen (phytohaemagglutinin, concanavalin A, CD3 MoAb) had no effect on production of IL-2 but markedly impaired cellular responsiveness to exogenous IL-2. Studies using MoAbs indicated that this effect was accompanied by decreased expression of both the CD25 and p75 subunits of the IL-2 receptor. Blocking surface SH groups did not affect binding of IL-2 to p75 on unstimulated mononuclear cells, but inhibited binding to high-affinity receptors on a T lymphoma cell line. The data are consistent with the hypothesis that sulphydryl groups on the IL-2 receptor are required for its function and may be involved in the interaction of the CD25 and p75 subunits leading to generation of the high-affinity binding site. The surface thiol identified on the IL-2 receptor may be a candidate for oxidation on cells from patients with chronic inflammatory diseases such as rheumatoid arthritis and thus contribute to the aberrant function of T cells in these patients.
8965405 [Follicular bronchiolitis associated with rheumatoid arthritis]. 1996 Aug A 52-year-old man with an 8-year history of rheumatoid arthritis was admitted to the hospital because of coughing and purulent sputum. A chest X-ray film obtained on admission showed small nodular shadows without overinflation in both lower lung fields, and a high-resolution CT scan showed many micronodular shadows in the centrilobular regions. Follicular bronchiolitis was diagnosed from the results of an open-lung biopsy, and prednisolone therapy was started at a dosage of 40 mg/day. Sinusitis developed 4 years later. Five years after the start of steroid therapy, dilation of bronchi and thickening of bronchial walls appeared on a CT scan, which also showed areas of low attenuation that were presumed to be bronchiolitis obliterans. These findings suggest that the pattern of airway disease can vary during the course of rheumatoid arthritis.
1540032 Presence of paf-acether in rheumatic diseases. 1992 Jan Paf-acether (paf) is a naturally occurring phospholipid involved in inflammatory processes. The presence of paf, its precursor lyso paf, and lipo-paf has been determined in blood and synovial fluid from 13 patients with rheumatoid arthritis (RA), 11 with spondylarthropathies, eight with other inflammatory rheumatisms, 13 with chondrocalcinosis, 15 with osteoarthritis, and also in blood from nine healthy subjects. Paf and lipo-paf were measured by rabbit platelet aggregation after isolation by high performance liquid chromatography, whereas lyso paf was first chemically acetylated to give paf. Lipo-paf in blood was higher in patients than in controls; lipo-paf concentrations in blood and in synovial fluid were significantly higher in rheumatoid arthritis than in osteoarthritis and chondrocalcinosis. By contrast, paf and lyso paf reached their lower values in rheumatoid arthritis. The amounts of lipid mediators were not correlated with biological parameters of inflammation. Lipo-paf, which is considered as a storage form of paf, may be the important form of paf in active inflammatory rheumatism.
1362531 The three week sulphasalazine syndrome. 1992 Dec We report a 53-year-old man with sero-negative rheumatoid arthritis who developed a fever, rash and hepatitis 3 weeks after starting sulphasalazine therapy. This was associated with a T cell lymphocytosis, eosinophilia and evidence of classical complement pathway activation. He responded to high dose corticosteroids. This is a rare but characteristic reaction which is likely to be encountered by rheumatologists more frequently with the increasing use of sulphasalazine. It should be recognized promptly as it may be fatal and can be confused with other systemic diseases.