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ID PMID Title PublicationDate abstract
8552993 Tenidap, but not nonsteroidal anti-inflammatory drugs, inhibits T-cell proliferation and c 1995 Dec T-lymphocytes are involved in the inflammatory response that occurs in affected joints of patients with rheumatoid arthritis (RA). Some second-line disease modifying anti-rheumatic drugs used in the treatment of patients with RA are known to block T-cell activation. The present study assessed whether tenidap, an investigational anti-rheumatic drug, affects in vitro T-cell responses such as proliferation and cytokine production. It was found that tenidap, in contrast to several nonsteroidal anti-inflammatory drugs, inhibits anti-CD3 or IL-2 driven proliferative responses of cloned human T-cells. Furthermore, tenidap was found to inhibit IFN-gamma production as well as the induction of mRNA encoding IFN-gamma or TNF-alpha. The results indicate that tenidap may exert at least part of its anti-inflammatory activity via inhibition of T-cell function and cytokine production.
1531390 Characterization of T-cell receptor alpha beta repertoire in synovial tissue from differen 1992 Feb With the aim of investigating the distribution of T cells expressing different T-cell receptors (TCR) in the inflamed synovial tissue of rheumatoid arthritis patients, we have used the polymerase chain reaction to amplify TCR V alpha and V beta transcripts from synovial biopsies obtained by arthroscopy from patients with arthritis of variable duration. From each of nine patients a single biopsy was taken. Southern hybridization analysis of amplified products revealed extensive heterogeneity of TCR V beta in most patients. On the other hand, restriction in V alpha gene expression was seen in several patients. A highly restricted V alpha repertoire was observed in all cases with arthritis of short duration. In addition, two of three samples of short duration yielded a more limited number of V beta transcripts than the others. No conformity was, however, seen in usage of individual V alpha and V beta transcripts among the investigated patients. The present data thus demonstrate variability in synovial TCR expression between rheumatoid arthritis patients, but they also indicate a development towards greater diversity with increasing disease duration, implicating the necessity for careful choice of cases, preferentially selecting for early stages of disease, when further analysing rheumatoid synovial T cells for TCR usage as well as for antigen specificity.
8914679 Positivity for antinuclear antibody in patients with advanced rheumatoid arthritis. 1996 Oct Some patients with rheumatoid arthritis (RA) as well as those with other collagen diseases are positive for antinuclear antibody (ANA). We investigated the frequency of positivity for ANA in 104 patients with RA and evaluated the clinical features and laboratory data in the ANA-positive and -negative groups. The presence of ANA in sera was studied by indirect immunofluorescence using HEp-2 cells as the antigen substrate. Sera with a positive fluorescence at a dilution of 1:20 were considered to be positive for ANA. Of the 104 patients, 39 (37.5%) were positive for ANA. The staining pattern in the positive cases varied, but most were speckled (64.1%) and homogeneous (48.7%). A small number showed a nucleolar (20.5%) or a centromere (10.3%) pattern. None showed a shaggy pattern. The ANA titer was lower in RA patients compared with those with other collagen-related diseases such as systemic lupus erythematosus or progressive systematic sclerosis. None of the patients positive for ANA with either a nucleolar or centromere staining pattern had progressive systemic sclerosis or the CREST syndrome. One patient each had Raynaud's phenomenon and pulmonary fibrosis. There was no correlation between ANA positivity and indicators of joint inflammation. The prevalence of ANA positivity in patients with advanced or prolonged disease was higher than those with early stages or short durations. There was no correlation with drug therapy.
8455914 Detection and quantitative analysis of joint activity inflammation with 99Tcm-polyclonal h 1993 Mar 99Tcm-polyclonal human immunoglobulin G (HIG) scintigraphy was used to detect active joint inflammation and to obtain ratios of joint uptake in noninvolved and inflammatory joints. Imaging was performed at 4 and 24 h in 16 patients with rheumatoid arthritis (RA) and 16 with degenerative joint disease (control group). All joints (total of 1344) were scored for pain, swelling and visual analysis of uptake in both scans. Joint to background (J:B) ratios were also calculated. Clinical and visual scores correlated in both scans (r = 0.7, P < 0.01). In RA patients, 246 joints were clinically involved. Visual analysis of scans detected 213 (87%) of them at 4 h and 196 (80%) at 24 h. Joints with no pain or swelling showed significantly higher J:B ratios than the control group and lower ratios than joints clinically involved. In the control group, statistically significant differences in J:B ratios between the various joints were found, so it was necessary to establish a normal range for every joint. J:B ratios were significantly higher at 4 h than at 24 h in both groups of patients. 99Tcm-HIG scintigraphy allows detection and measurement of joint inflammation. Scans performed at 4 h are preferable to scans at 24 h. Quantitative analysis can measure more objectively the degree of activity and could be useful in the management of these patients.
8670580 Are we making the most of the Stanford Health Assessment Questionnaire? 1996 Jun For many years, the Stanford Health Assessment Questionnaire (HAQ) has provided an effective measure of disability. Recently, some debate has emerged about whether or not the HAQ is an "ordinal' or "interval' scale. The opportunity to test its level of measurement arose when the scale was applied in a community survey which undertook a two-stage random sample using postal questionnaires to ascertain the health care needs of those with arthritis. The HAQ data are fitted to the Rasch model which tests for the presence of certain desirable characteristics of measurement, e.g. unidimensionality. The fit of the data to the model for those self-reporting rheumatoid arthritis (RA) was adequate. The transformed HAQ score, derived from the Rasch analysis, is compared with the ordinary HAQ (raw) score. This shows that, for those with RA, incremental units of the raw score at the margins of the scale reflect an increasing level of (dis)ability compared to similar units in the centre of the scale. Thus, the traditional HAQ score (range 0-3) is an ordinal score. The findings also indicate that scoring all 20 items may lead to greater sensitivity. Questions are also raised about the construct validity for those with other types of arthritis. For osteoarthrosis, the grip item does not appear to belong to the same underlying construct as the other items.
8587068 What explains the variation among rheumatologists in their use of prednisone and second li 1995 May OBJECTIVE: To determine the extent to which characteristics of rheumatologists and their practices explain the variation in their use of prednisone and 2nd line agents for the treatment of rheumatoid arthritis (RA). METHODS: We used multiple logistic regression to examine the relationship between the use of prednisone, hydroxychloroquine, intramuscular gold, and methotrexate, and the following categories of rheumatologist characteristics: professional experience, primary payment method, practice setting, location of rheumatology training, and demographic characteristics. Our explanatory variables also included 12 patient characteristics and a random effect term. RESULTS: Much of the variation among rheumatologists in the use of these agents is explained by the rheumatologist characteristics. Depending on the agent, professional experience explained 15 to 54%, payment method 3 to 27%, practice setting 6 to 39%, training location 12 to 53%, and demographic characteristics 3 to 23% of the rheumatologist associated variation in use of each agent. CONCLUSION: There are identifiable characteristics of rheumatologists and their practices that strongly influence their treatment decisions for RA. These findings have important policy implications.
7881839 Small joint synovitis in rheumatoid arthritis: should it be assessed separately? 1995 Jan In the assessment of disease activity in rheumatoid arthritis (RA) small joint synovitis is traditionally included only as a component of active, tender or swollen joint counts. By contrast, in the assessment of disease damage in RA, the X-ray score of hands and feet represents one of the most common parameters used and is regarded as a major indicator of outcome. Data presented in this study lead us to hypothesize that the small joints require separate assessment in any study of disease activity or outcome in RA: (i) there is clear evidence that small joint synovitis often occurs in the absence of an abnormal acute phase response (ESR or C-reactive protein) and (ii) measured synovitis is an individual (PIP) joint has been shown to be reliable and to be related to subsequent X-ray changes in the same joint. Our findings show that, in a study of a treatment of RA, it is quite possible for disease activity measures to appear controlled while inflammation continues in the small joints causing radiological damage. This radiological damage is reflected as an adverse outcome. Hence the paradox of improving disease activity but not outcome. We argue that small joint inflammation and damage should be recognized as one aspect of the RA disease process offering unique information and as such should be assessed independently.
8676122 Survivorship analysis of cemented total condylar knee arthroplasty. A long-term follow-up 1996 Jan Survivorship analysis was used in the evaluation of 348 consecutive primary total condylar knee arthroplasties (total knee arthroplasties) performed on 253 patients in a 27-month period, with a maximum follow-up period of 12 years. The diagnosis was osteoarthrosis in 184 cases and rheumatoid arthritis in 164 cases. Ten patients (10 total knee arthroplasties) were lost to follow-up evaluation. The endpoint was defined as prosthesis not in situ. The variables considered were age, sex, body mass index, and diagnosis. The overall cumulative survival rate was 92%. The survival rate of the osteoarthrosis group was significantly higher (97%) than that of the rheumatoid arthritis group (87%). None of the other variables affected survival rate significantly.
1593574 A comparison of tenoxicam and piroxicam in the treatment of rheumatoid arthritis. 1992 Apr Tenoxicam 20 mg OD was compared with piroxicam 20 mg OD for patients with rheumatoid arthritis (RA). One hundred and two patients from 5 centers were enrolled: 51 in the tenoxicam group and 51 in the piroxicam group. Evaluation of the primary efficacy variables demonstrated no difference in efficacy between treatment groups. The overall incidence of adverse clinical/laboratory experiences was similar between treatment groups. Six patients discontinued the study because of gastrointestinal intolerance, 3 from each treatment group. Our study demonstrates that tenoxicam 20 mg OD and piroxicam 20 mg OD have similar efficacy and safety in patients with active RA.
1290729 A comparison of ketoprofen SR and sulindac in the elderly with rheumatoid arthritis. 1992 Winter The elderly (age > 65 years) are more vulnerable to side-effects induced by non-steroidal anti-inflammatory drugs (NSAIDs). We therefore performed a double-blind comparative study of ketoprofen SR and sulindac in patients with active rheumatoid arthritis, 65 years of age or older. Sulindac was chosen because of its possible renal sparing effects, and ketoprofen SR because of its short half life and sustained release delivery system. Eighty patients were entered. More patients withdrew from the study due to side-effects in the sulindac group; both treatment groups had a high incidence of side-effects during this study and during previous exposure to other NSAIDs, demonstrating that the elderly are susceptible to side-effects from NSAIDs.
8863974 Musculofascial flaps based on the dorsalis pedis vascular pedicle for coverage of the foot 1996 Aug Soft-tissue reconstruction of the foot and ankle has long presented challenging problems for the plastic surgeon. Limitations of available local tissue, the need for specialized tissue, and donor site morbidity restrict the options available to the reconstructive surgeon. In an effort to solve these difficult problems, we have begun to use musculofascial flaps based on the branches of the dorsalis pedis artery. We present our early experience of 5 patients treated with an extensor digitorum brevis muscle flap with fascial extensions often containing the contents of the first web space. Our patients ranged from 6 to 60 years in age and included 4 males and 1 female. The etiologies of the wounds were secondary to trauma (N = 2), complications of surgery for rheumatoid arthritis (N = 2), and were secondary to a defect following resection of an arteriovenous malformation (N = 1). The flaps had antegrade blood flow in 3 patients and reverse flow in 2 patients. The flaps were covered with a split-thickness skin graft and the donor site was closed primarily. The donor sites healed without the need for further surgery. One patient required additional procedures. This flap proved to be both versatile and effective for closure of difficult wounds of the foot and ankle.
7562751 Comparison of phenytoin with auranofin and chloroquine in rheumatoid arthritis--a double b 1995 Jul OBJECTIVE: To evaluate efficacy of phenytoin in modifying the course of rheumatoid arthritis (RA) by comparing it to gold (auranofin) and chloroquine. METHODS: A double blind, randomized study of 6 months' duration was conducted at the Nizam Institute of Medical Sciences, Hyderabad, India. One hundred and thirty-two patients with active RA (defined by the 1987 ARA criteria) were entered into the study and randomized into 3 groups: phenytoin, chloroquine, or auranofin. RESULTS: Full data were evaluable in 100 patients who satisfactorily completed the protocol (phenytoin, 35; auranofin, 30; and chloroquine, 35). Twenty-four patients were noncompliant and did not take medication or return for evaluation; 8 patients had the drug withdrawn because of side effects before study completion. For each of the 3 drugs all clinical and laboratory variables improved when pre and posttreatment values (p < 0.05 to 0.001) were compared. There was a greater reduction in posttreatment mean morning stiffness in the chloroquine group than in the phenytoin and auranofin groups (p < 0.05). Posttreatment grip strength was also greatest in the chloroquine group. On the other hand, there were statistically significant decreases in IgM levels in both the phenytoin and auranofin groups (p < 0.001), but not with chloroquine. Among the 53 patients with a disease history of 3-6 months, global outcome was best with phenytoin (16/17), compared to chloroquine (12/18) and auranofin (12/18) (p < 0.03). However, there was no such difference in the 47 patients in all 3 groups with a disease history longer than 6 months. Eight patients had side effects (phenytoin, auranofin, 2; chloroquine, 1) requiring withdrawal of the drug. However, the incidence of side effects was not significantly different for the 3 drugs. CONCLUSION: Our data indicate that phenytoin is comparable to auranofin and chloroquine in its efficacy in RA and may be considered an alternative disease modifying agent for RA.
8187428 A high dose (up to 200 mg) tolerance and efficacy study of intra-articular rimexolone (Org 1994 Mar Twenty patients with classical or definite rheumatoid arthritis received one intra-articular injection of 40, 80, 120, 160 or 200 mg rimexolone (Org 6216) into one knee joint. Rimexolone was well tolerated and the incidence of side-effects was low. A beneficial effect was sustained over the study period of 94 days and a long-lasting effect was observed in 84% of the patients after one year and in 79% after 2 years. Safety parameters remained unaffected. Individual changes in adrenal response to ACTH and morning cortisol levels did not correlate with the dose or with serum levels of rimexolone. Rimexolone showed linear kinetics. The mean residence time in the intra-articular depot was 44 days (SD +/- 53) with a median of 26 days. Ninety percent was absorbed after 4 months. Outside the intra-articular depot the mean residence time was less than 0.1 days.
8369898 A case of steroid-responsive organizing pneumonia in a patient with rheumatoid arthritis s 1993 Sep A 59-year-old Japanese man with RA was referred to us with arthralgia and pulmonary infiltration. Chest roentgenogram showed migratory infiltration and pleural effusion, the glucose levels of the pleural fluid were not reduced. Transbronchial lung biopsy showed granulation tissue plugging the alveolar ducts, indicating organizing pneumonia and interstitial inflammation. These pathological findings were identical with those for cryptogenic organizing pneumonitis (COP). There was a good clinical and roentgenographic response and the pleural effusion responded well to corticosteroids. The characteristic migratory infiltration in rheumatoid lung disease responds well to corticosteroids.
7858575 [The risk/benefit ratio of low-dose cyclosporin in the treatment of severe rheumatoid arth 1994 Dec Although the efficacy of cyclosporine therapy in rheumatoid arthritis has been established, there have been no long term studies of the risk/benefit ratio of cyclosporine A in severe rheumatoid arthritis. A prospective, open-label one-year study included 106 patients (83 women and 23 men; mean age 53 years; mean disease duration, 11 years) with rheumatoid arthritis. Mean number of previous second-line treatments was four and 69% of patients had failed methotrexate therapy. The initial dosage of cyclosporine was 3 mg/kg/d and was increased if needed up to 5 mg/kg/d. The dosage was reduced in the event of serum creatinine elevation (by more than 30% versus baseline) or diastolic blood pressure elevation (above 95 mmHg). The statistical analysis was performed on an intention-to-treat basis. In the 45 patients who completed the one-year study period, the mean dosage was 3.6 +/- 1 mg after six months and 3.3 +/- 1 mg/kg/d after one year. Significant improvements were seen in all the clinical efficacy parameters. The mean reduction in corticosteroid dosage was 0.5 mg/d. The study drug was discontinued prematurely in 61 patients (36 because of adverse events and 21 because of inefficacy). Twelve of the 56 patients with serum creatinine level elevation on at least one occasion and seven of the 35 patients with diastolic blood pressure elevation were taken off the study drug.
8768145 [Comparison of rheumatoid test procedures--value and critical interpretation of sensitivit 1996 May In this prospective study, sera of 440 patients with rheumatic and degenerative joint diseases were tested for the presence of rheumatoid factor (RF). The Latex agglutination test (LFT), Waaler-Rose hemagglutination, laser nephelometry and IgM-Enzyme immunoassay (IgM-EIA) were used for detecting IgM-rheumatoid factors. In addition, rheumatoid factor of IgA isotype was measured by an IgA-Enzyme immunoassay. Sensitivity, specificity, pre-test- and post-test-probability were evaluated based on the data obtained to compare the test systems used. Under prospective patient selection, none of the test systems used reached a sensitivity of 100% concerning its cut off level. Despite this limitation, latex agglutination and IgM-EIA reached the highest sensitivity. Waaler-Rose test (90,8%) showed the best result for specificity. The IgA-EIA held the third position in sensitivity, specificity and efficiency. By comparing sensitivity with specificity, no test system can be recognized as the absolutely best one, since the receiver operating characteristic curves (ROC) overlapped. Practically rheumatoid factor measurement should initially use a highly sensitive assay, such as LFT and IgM-EIA to screen for RF. In the case of a positive result a more specific assay should be used, for example laser nephelometry, to confirm the result.
7544938 Oral desensitization in the treatment of human immune diseases. 1995 May Oral desensitization or oral tolerance is induced by giving antigenic peptides by the mucosal route. In man only the oral route has been used up to now. Experiments in animal models of human autoimmune diseases, have shown that it is not necessary to use the primary antigen responsible for disease induction. Antigens implicated in secondary immune phenomenon can act similarly by means of the so-called "bystander suppression". Thus for diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA) candidate antigens for desensitization are available. Many patients with MS have immunity to myelin basic protein (MBP). A recent controlled trial giving MBP to patients with MS is discussed (Weiner et al., Science 259, p. 1321, 1993). No clear-cut effect was obtained. Collagen II is used to induce experimental arthritis in rats; signs of immunity against it can be found in patients with RA. Collagen-induced arthritis has been successfully modified in animals by feeding of collagen II. In man one open uncontrolled trial and one other placebo controlled blind trial have been reported, and these are discussed (Trentham et al., Science 261, 1727, 1993). These trials suggest that oral desensitization might be useful and devoid of side effects. Subreum is a peptic E. coli extract containing heat shock protein 60. Its efficacy as a disease-controlling agent in RA has been documented (Clin. Exp. Rheum. 11, p. 121, 1993). It is given orally. Data suggesting that Subreum acts by oral desensitization are discussed. Considering the low incidence of side effects observed with oral desensitization, this therapeutic approach should also be tested in other forms of arthritis and other inflammatory diseases.
7680648 Expression of the cytokine RANTES in human rheumatoid synovial fibroblasts. Differential r 1993 Mar 15 A chronic inflammatory disease may be characterized by an accumulation of activated leukocytes at the site of inflammation. Since the chemokine RANTES may play an active role in recruiting leukocytes into inflammatory sites, we investigated the ability of cultured human synovial fibroblasts isolated from patients suffering from rheumatoid arthritis to produce this chemokine and compared its regulation to that of the closely related chemokine gene, interleukin-8 (IL-8). In unstimulated synovial fibroblasts, the expression of mRNA for both chemokines was undetectable, but was increased in both a time- and dose-dependent manner upon stimulation with the monokines tumor necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1 beta). Preincubation of the cells with cycloheximide "superinduced" the level of IL-8 mRNA stimulated by TNF alpha and IL-1 beta and RANTES mRNA stimulated by IL-1 beta, but decreased the expression of RANTES mRNA in response to TNF alpha. In addition, differential regulation of these genes was noted when synovial fibroblasts were stimulated with a combination of cytokines. IL-4 down-regulated and IFN gamma enhanced the TNF alpha- and IL-1 beta-induced increase in RANTES mRNA, whereas the induction of IL-8 mRNA by TNF alpha or IL-1 beta was inhibited by IFN gamma and augmented by IL-4. Moreover, a combination of TNF alpha and IL-1 beta synergistically induced IL-8 mRNA expression, whereas under the same conditions, the level of expression of RANTES mRNA was less than that induced by TNF alpha alone. These observations were also reflected at the level of chemokine secretion. These studies demonstrate that by expressing the chemokines RANTES and IL-8, synovial fibroblasts may participate in the ongoing inflammatory process in rheumatoid arthritis. In addition, the observation that these chemokine genes are differentially regulated, depending upon the presence of different cytokines, indicates that the type of cellular infiltrate and the progress of the inflammatory disease is likely to depend on the relative levels of stimulatory and inhibitory cytokines.
7835022 Combination therapy for rheumatoid arthritis and drug-induced systemic lupus erythematosus 1994 Sep Development of drug-induced systemic lupus erythematosus (SLE) is an uncommon complication of the use of D-penicillamine and sulphasalazine. We report two cases of patients with rheumatoid arthritis (RA) who developed symptoms and signs of SLE and suggest that increasing use of these two agents as combination therapy in RA may cause an additive risk to the occurrence of this complication.
7536953 Measurement of colony-stimulating factors in synovial fluid: potential clinical value. 1995 In this study, 100 synovial fluid (SF) samples from patients with a variety of arthritides were assayed for levels of colony-stimulating factors (CSFs) using a human bone-marrow bioassay and enzyme immunoassays for granulocyte (G-) and granulocyte-macrophage (GM-) CSFs. GM-CSF was found more frequently in samples from rheumatoid arthritis (RA) subjects (49%) than in non-RA samples (29%). Absence of GM- but not G- or bioassay CSFs characterised samples from subjects with psoriatic arthritis and ankylosing spondylitis (n = 14). There was strong evidence of an antagonistic relationship between levels of G- and GM-CSFs in samples from RA patients, an effect independent of drug treatment. However, treatment with non-steroidal anti-inflammatory agents (NSAIDs) may affect reported CSF concentrations: G-CSF levels were significantly lower in samples from subjects not taking NSAIDs. These results suggest that SF-CSF estimations using commercially available assays could provide useful diagnostic clues for clinicians, but careful interpretation is warranted particularly in patients on long-term NSAID treatment.