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ID PMID Title PublicationDate abstract
7588084 Sulfasalazine. A review of its pharmacological properties and therapeutic efficacy in the 1995 Jul Sulfasalazine was first used for rheumatic polyarthritis in the 1940s and in the past 2 decades has become firmly established as a disease-modifying antirheumatic drug (DMARD). The drug is split by the action of bacterial azoreductases in the large intestine into sulfapyridine and mesalazine (mesalamine, 5-aminosalicylic acid), although whether the parent molecule or the sulfapyridine moiety, or both, is the active principle remains uncertain. Sulfasalazine is an effective treatment for rheumatoid arthritis (RA), producing improvements in disease parameters similar to those seen with penicillamine, hydroxychloroquine or oral or parenteral gold in comparative clinical trials. However, there are no direct comparisons of the drug with methotrexate. Most adverse events associated with sulfasalazine are minor and tend to occur within 3 months of starting therapy. A meta-analysis of studies investigating DMARD therapy, which included almost 5000 evaluable patients, concluded that sulfasalazine was close to methotrexate in terms of efficacy but was slightly less well tolerated. However, unlike sulfasalazine, many DMARDs may be unsuitable for women who are, or may become, pregnant because of their potential to cause teratogenic effects. Sulfasalazine may also offer a more rapid onset of action than other DMARDs and may slow down the radiological progression of RA. Combination therapy with other DMARDs, particularly methotrexate, appears more effective than single DMARD therapy. If the safety of these regimens is shown in large numbers of patients they are likely to become more widely used in the future. Sulfasalazine is a therapy of first choice in patients with RA and may be the DMARD of choice in women who are, or may become, pregnant.
8833056 Combination treatment of rheumatoid arthritis using azathioprine and methotrexate: a 48 we 1996 Mar To assess the relative efficacy of methotrexate (MTX), azathioprine (AZA), and their combination in the treatment of rheumatoid arthritis (RA), a double blind, prospective, multicenter, controlled trial was carried out. Two hundred nine patients with active RA were treated with escalating doses of MTX (5-15 mg/week), AZA (50-150 mg/day), or combination (5/50-7.5/100) with opportunity to increase dosage at 6 week intervals. Patients were evaluated for clinical and laboratory improvement and assessed for radiologic progression at 48 weeks. One hundred ten patients remained on the initial, randomly assigned therapy. Response was defined as 30% or greater improvement in at least 3 of 4 variables, and occurred in the following: 38% on the combination arm, 26% on AZA, and 45% on MTX (p = 0.06). A trend for decreased radiologic progression was seen in the MTX group. Adverse experiences and treatment termination occurred more frequently in the combination and AZA arms relative to the MTX group. The most frequent causes for treatment discontinuations were lack of effectiveness, gastrointestinal adverse effects and liver enzyme elevation. This study establishes that the combination of MTX and AZA in the dosages employed is not associated with more toxicity than treatment with single agents, but enhanced efficacy is not seen. A trend toward decreased radiographic progression was noted in the MTX treated patients.
8808186 Do changes in clinical improvement in rheumatoid arthritis patients treated with immunosup 1995 We sought to investigate whether clinical improvement after immunosuppressive treatment reflects changes in acute phase response (APR) in rheumatoid arthritis (RA). Fifty-eight patients (pts) were treated with methotrexate (MTX), nineteen with intravenous cyclophosphamide (CTX), and fifteen with cyclosporin A (CSA). C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), alpha-1 antichymotrypsin (ACT), and alpha-1 antitrypsin (AT) serum levels were measured by nephelometry or rocket immunoelectrophoresis. Clinical improvement was observed in 67% MTX pts, 53% CTX pts, and 47% CSA pts. Baseline serum levels of CRP, AGP, ACT, and AT were significantly higher as compared to healthy controls. After MTX and CTX therapy CRP level significantly decreased. The decrease in serum level of ACT and AT in CTX treated patients was also observed. All analyzed acute phase proteins remained substantially elevated after CSA therapy despite a clear reduction in disease activity. We established a correlation between changes in disease activity and all acute phase proteins (APP) in MTX and CTX pts. From our study we can conclude that clinical improvement after immunosuppressive treatment correlated with quantitative changes in all APR markers in MTX and CTX treated pts, and none in CSA pts. Although measurement of APP remains the best marker for monitoring RA pts, not always they properly reflect changes in disease activity.
1489098 Characterization of immune complex components by dot blot analysis. 1992 Nov 15 A method is described for the characterization of immune complex components by dot blot analysis. After isolation by chromatographic techniques and precipitation with polyethylene glycol, immune complexes were dissociated in 0.1 M phosphate (pH 2) and bound to a nitrocellulose membrane in a dot blot unit. Biotinylated probes were then used to identify the following immune complex components: specific antigens, biologically active antibodies, antibody isotypes, antibody subclasses, antibody idiotypes, and rheumatoid factors. This nonradioactive procedure takes less than 2 h to perform and has been used to analyze immune complexes isolated from sera (rabbit and human) and synovial fluid (human).
8275581 Use of the Stoke Index to differentiate between disease-modifying agents and non-steroidal 1993 Sep The Stoke Index is a validated composite algorithm that has been designed to give a global measure of disease activity in rheumatoid arthritis (RA). The use of this single measure of disease activity in RA simplifies the critical evaluation of drug therapy. 368 patients with RA of varying duration and severity, entered into comparative drug trials between 1980 and 1987, had the algorithm calculated four weeks prior to therapy, at the start of treatment, and bi-monthly to six months. The index score was significantly improved by drugs with known slow acting anti-rheumatic drug (SAARD) activity and improvement could be seen as early as two months after the beginning of treatment. Non-steroidal anti-inflammatory drugs (NSAIDs) did not improve the score. The index differentiates between treatments in patients with minor or major disease activity. We conclude that this composite index of disease activity provides a sensitive, meaningful measure for the evaluation of therapy in RA.
7794824 Differential sensitivity to transforming growth factor (TGF)-beta of CBA and of CBA/N B ce 1995 Mar Synovial fluid from patients with rheumatoid arthritis (RA-SF) contains in vivo produced cytokines and inflammatory mediators, including a factor that induces IgG2b production of lipopolysaccharide (LPS) preactivated murine B lymphocytes. In order to determine the mechanism by which RA-SF acts on LPS activated mouse B cells, CBA/N mice were used as an experimental model. The X-linked immunodeficiency of these mice is caused by a point mutation in the Bruton's tyrosine kinase (btk) gene. We have earlier shown that RA-SF can reconstitute the CBA/N B cell deficiency in vitro and in vivo, with regard to IgG2b production after LPS stimulation. Since transforming growth factor (TGF)-beta has been suggested to be a switch factor for IgG2b, we aimed at investigating the role of TGF-beta in our experimental system. We found that TGF-beta could not mimic the effect of RA-SF on CBA spleen cells. A small increase of IgG2b secretion was observed with spleen cells from normal CBA mice, whereas Ig secretion of all isotypes was suppressed in CBA/N spleen cells treated with TGF-beta at any concentration. Neutralizing antibodies against TGF-beta suppressed the response of CBA B cells, whereas the response by CBA/N B cells was enhanced by the same antibody preparation. Here we also show that the abnormal B cell responsiveness to TGF-beta, typical of CBA/N, co-segregates with the btk mutation in male (CBA x CBA/N)F2 spleen cells. This was determined by allele specific PCR recognizing the identified base substitutions of the btk gene, typical of the two strains. We propose that RA-SF contains a factor, separate from TGF-beta, that is involved in the differentiation of IgG2b expressing cells.
8624620 Differential expression of the costimulatory molecules B7.1 (CD80) and B7.2 (CD86) in rheu 1996 Jan CD4+ T-lymphocytes require two signals to become activated--antigen receptor (TcR) occupancy and an antigen-presenting cell (APC)-derived costimulus. The latter may be provided by B7.1 (CD80) or B7.2 (CD86) on APC interacting with CD28 on T-cells. We have studied the expression of these costimulatory molecules in rheumatoid and osteoarthritic synovial membrane. Very few B7.1-positive cells were seen in synovial tissue from either established or early rheumatoid disease, or in rheumatoid arthritis (RA) or osteoarthritis (OA) synovia at arthroplasty. In contrast, B7.2 was readily detected in rheumatoid synovia, predominantly in the lining layer, in a pattern of expression that corresponded to the presence of CD68-positive macrophages. Only occasional B7.2-positive cells were seen in OA synovia. The presence of B7.2 but the relative lack of expression of B7.1 may be partly responsible for the observations of 'frustrated' T-cell activation or T-cell hyporesponsiveness in the rheumatoid synovium.
8182622 Seronegative rheumatoid arthritis and HLA-DR4. 1994 Feb OBJECTIVE: To investigate the prevalence of HLA-D region antigens in patients with seronegative rheumatoid arthritis (RA). METHODS: The distribution of HLA-D region antigens was studied in 33 patients with seronegative RA. All patients were followed for at least 3 years, during which tests for IgM rheumatoid factor were negative on at least 3 occasions. HLA-D region antigens were defined by serological and molecular techniques (oligonucleotide typing). RESULTS: Our data demonstrate that DR4 was significantly (p < 0.021) increased in patients (45.5%) compared to normal controls (22.9%). Although the prevalence of DR1 was essentially the same in patients (15.2%) as in healthy controls (14.3%), the frequency of DR1 and/or DR4 was significantly (p < 0.018) increased in patients (60.6%) compared to healthy subjects (35.7%). The prevalence of remaining DR antigens and of DQ and DP specificities in patients with seronegative RA was not different from that in healthy controls. CONCLUSION: Our results together with those published by other investigators suggest that both seropositive and seronegative RA are associated with DR4 and may therefore share the same immunogenetic bases.
7728397 T-cell clonality in synovial fluid from rheumatoid joints before and after culture in inte 1995 Mar T-cell receptor (TCR) gamma gene rearrangements which have been amplified in polymerase chain reactions (PCRs) and analysed by high resolution polyacrylamide gel electrophoresis have been used to investigate the clonal diversity of T-cells in joint effusions from 16 patients with rheumatoid arthritis, one with systemic lupus erythematosus and one with psoriatic arthropathy. Polyclonality was found in every case but an oligoclonal subset of dominant rearrangements was also demonstrated in all but the patient with psoriasis. Marked changes in the relative preponderance of the various clonotypes were observed in 29 of 48 paired tests from 12 cases before and after culture in media containing interleukin-2 (IL-2) showing that SF mononuclear cells cultured in vitro with IL-2 are not representative of those present in vivo.
8129458 Respiratory abnormalities due to craniovertebral junction compression in rheumatoid diseas 1994 Feb OBJECTIVE: To assess the extent and severity of respiratory insufficiency associated with severe rheumatoid atlantoaxial dislocation and its relation to compression of the neuraxis. METHODS: Twelve patients with severe atlantoaxial dislocation due to rheumatoid disease were studied. Detailed clinical, CT myelography and respiratory assessment including nocturnal oximetry, were performed on all patients. RESULTS: All patients were severely disabled by their underlying disease but none had symptoms of hypoventilation. All the patients with C1 compression had myelopathic features. Those with medullary deformation (moulding and/or stretch) had abnormal noctural oximetry whilst no significant desaturations were seen in the remaining patients. Post-operative studies showed resolution of noctural desaturations. CONCLUSION: This study suggests that clinically unsuspected respiratory insufficiency may be common in patients with severe medullary compression associated with rheumatoid atlantoaxial dislocation. It emphasises the importance of careful respiratory monitoring including nocturnal oxygen saturation in patients with major atlantoxial dislocation due to rheumatoid disease.
9082769 Clinical analyses of focus tonsil and related diseases in Japan. 1996 Clinical analyses were performed in groups of patients with several diseases that are regarded as diseases of focus tonsils. These patients underwent tonsillectomy from 1981 to 1993 in our department. They included 289 cases of pustulosis palmaris et plantaris (PPP), 35 cases of psoriasis vulgaris (PV), 100 cases of sternocostoclavicular hyperosteosis (SCCH), and 18 cases of rheumatoid arthritis (RA). Tonsillectomy was found to significantly alleviate clinical symptoms of the above diseases as follows: 88.1% of the PPP cases, 48.6% of the PV cases, 80.9% of the SCCH cases, and 66.7% of the RA cases. Age distribution of the patients, relation between the effect of tonsillectomy and age, sex and other factors were also analyzed.
7880115 Causes and investigation of increasing dyspnoea in rheumatoid arthritis. 1995 Jan Fibrosing alveolitis and bronchiolitis obliterans are two of the many pulmonary manifestations of the connective tissue disorders. When shortness of breath is the main complaint, it is often difficult to diagnose the individual causative lesion from the clinical examination, lung function tests, and chest radiographic findings. In such cases high resolution computed tomography, with its increased sensitivity and specificity for analysis of the pulmonary parenchyma, provides an excellent diagnostic tool for determining the presence and type of pulmonary abnormality.
7496133 Evaluation of beta 1,4-galactosyltransferase in rheumatoid arthritis and its role in the g 1995 Jun Evidence indicating an important link between glycosylation changes and autoimmune rheumatic disease is presented. Attention is especially focused on the interrelationship between reduced galactosylation of the oligosaccharides of IgG, auto-sensitization which is thought to be of central importance in the pathogenesis of rheumatoid arthritis (RA), and the enzyme beta 1,4-galactosyltransferase (GTase) that catalyses the addition of galactose to the oligosaccharide chains on this molecule. Data are presented to indicate that GTase undergoes a variety of normal and disease associated changes. These variations are believed to contribute to the pathological processes in rheumatoid disease, and a hypothesis is suggested, whereby disease is associated with the dysregulation of an integrated glycosylation network, comprising IgG galactosylation, lymphocytic GTase and anti-GTase antibodies, that is a component of the normal immune system.
8620301 Serum cholesterol and risk of rheumatoid arthritis in a cohort of 52 800 men and women. 1996 Mar Recent epidemiological studies have suggested that joint risk factors occur for rheumatoid arthritis (RA) and coronary heart disease. We studied serum cholesterol concentration for its association with the incidence or RA in 28 362 men and 24 444 women free from arthritis at baseline. During a mean follow-up of 21 yr, 161 men and 351 women developed RA. Of these incident cases, 119 men and 229 women were rheumatoid factor (RF) positive. The serum cholesterol concentration was directly proportional to the risk of RF-positive RA among women and RF-negative RA among men; the age-adjusted relative risks (95% confidence intervals) per S.D. (1.4 mM/l) of the cholesterol distribution were 1.20 (1.05-1.38) and 1.56 (1.15-2.10), respectively. No association was observed, however, for RF-negative RA among women or RF-positive RA among men. The results suggest that a still unknown factor closely associated with serum cholesterol may be involved in the aetiology of RA, but complex interactions with sex and RF status seem to occur.
7552068 T cell receptor usage in rheumatoid arthritis. 1995 Apr The structure of alpha beta T cell receptors (TCR) is restricted in a number of rodent and human antigen responses. In several rodent EAE models of multiple sclerosis a limited range of T cell receptors are expressed by T cells which respond to the inciting antigen and are capable of transferring the disease to naive animals. These observations have raised the question of whether in rheumatoid arthritis (RA), a particular T cell receptor structural signature can be identified among T cells derived from the synovium compared to autologous peripheral blood. The parameters which are usually measured are TCR variable region usage, oligoclonality and/or limited junctional region usage. A large number of studies have been carried out and results are variable with some authors claiming evidence for the effect of uncharacterised superantigens expanding or deleting T cells with particular V beta regions while others have suggested that observations of restricted V region usage and limited junctional regions imply that clones of cells have been expanded by antigen. So far none of these studies have led to the identification of an antigen or superantigen which plays a role in RA pathogenesis.
8408923 Vitiligo, rheumatoid arthritis and pernicious anemia. 1993 Jul A patient with a 46-year history of vitiligo who also presented rheumatoid arthritis and pernicious anemia is described. Meticulous physical examination excluded further systemic or cutaneous involvement. The immunological workup revealed a low CD4 cell percentage with T cells mostly composed of CD8 cells, a discrepancy between the high percentage of cumulative CD4 + CD8 cells and the measured CD3 proportions, very low NK cytotoxicity toward K562 cells, and almost negligible responses to PHA, Con A and PWM mitogens. The results point to severe T and NK cell functional defects. The pathogenetic significance of these data is discussed.
7756719 Minocycline for rheumatoid arthritis. 1995 Feb Minocycline may prove to be a valuable agent in adjunctive treatment of RA. The use of minocycline is attractive because of its relatively benign adverse effect profile in common dosages, although vestibular toxicity has occurred frequently when doses of 400 mg/d have been used. Adverse effects that do occur usually subside after discontinuation of the drug. Currently, the studies available offer no definitive conclusion concerning the use of tetracyclines for this purpose. These trials do show promise, however, and suggest that larger, controlled, double-blind studies with prolonged use of minocycline in patients are needed for confirmation of its efficacy in RA.
8350316 Axillary lymphadenopathy due to Swanson implants. 1993 Jun We describe a case of unilateral axillary lymphadenopathy in an elderly woman with a long history of rheumatoid arthritis, 7 years status post placement of Swanson silastic elastomer implants in her right hand with good surgical outcome and with no outward reason for adenopathy. Though there was concern for malignancy, pathologic evaluation of the lymph node revealed foreign body giant cells reacting to silastic from her hand implants and no evidence of malignancy. This is only the 10th such case reported, despite the number of implants placed.
8216423 Synergistic effect of interleukin-1 beta and tumor necrosis factor alpha on interleukin-8 1993 Sep OBJECTIVE: To investigate both the involvement of chemokines in general and the relative importance of specific chemokines in rheumatoid arthritis (RA), we characterized the effect of the monokines tumor necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) on the synthesis of neutrophil-activating factors by synovial fibroblasts isolated from the joints of patients with RA. METHODS: Neutrophil-stimulating activity was assessed by determining intracellular calcium mobilization. IL-8 synthesis and secretion was assessed by specific enzyme-linked immunosorbent assay, and IL-8 messenger RNA (mRNA) levels were determined by Northern blot. RESULTS: Treatment of synovial fibroblasts with IL-1 beta and TNF alpha resulted in the production of an activity which induced intracellular calcium mobilization in peripheral blood neutrophils. The 2 monokines combined had a synergistic effect on the release of the neutrophil-stimulating activity. The effect of the 2 monokines required gene transcription and translation, and closely mimicked the pattern of IL-8 secretion induced in these cells by the monokines. We confirmed that the majority of the neutrophil-stimulating activity was IL-8 by 3 different approaches: cross-desensitization experiments with IL-8, melanoma growth-stimulatory activity, and neutrophil-activating peptide 2, stimulation of calcium mobilization in cells transfected with the IL-8 receptor complementary DNA, and inhibition of the activity following pretreatment of the supernatants with an anti-IL-8 antibody. TNF alpha and IL-1 beta induced a time- and dose-dependent release of immunoreactive IL-8. A synergistic effect of TNF alpha and IL-1 beta was also observed for both IL-8 production and accumulation of IL-8 mRNA. CONCLUSION: These results indicate that the monokines TNF alpha and IL-1 beta synergistically activate IL-8 expression and protein secretion by synovial fibroblasts, and that under these conditions, IL-8 appears to be the major neutrophil-activating factor released.
9601762 [Comparison of the major cardio-rheumatologic diseases at the Pediatric Clinic before and 1996 This article presented the analysis of structure of morbidity of cardiorheumatological diseases at Pediatric's Clinic Sarajevo, before and during the war. The results showed that number of acquired heart diseases has not decreased, with permanent presence of streptococci.