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ID PMID Title PublicationDate abstract
10325658 Cytokine production by synovial T cells in rheumatoid arthritis. 1999 Mar OBJECTIVE: To investigate the production of cytokines by T cells in patients with rheumatoid arthritis (RA), reactive arthritis (REA) and osteoarthritis (OA). METHODS: The lymphokines interleukin (IL)-2, IL-4, interferon gamma (IFN-gamma) and tumour necrosis factor beta (TNF-beta), as well as the monokines IL-1, IL-6 and TNF-alpha, were measured by immunoassays in sera and synovial fluid (SF) from patients with RA, REA and OA. In addition, cytokine expression was studied by immunohistochemistry in synovial membrane tissue sections from patients with RA and OA. RESULTS: Almost 60% of RA sera contained at least one of the cytokines investigated, though in low concentrations, whereas cytokines were generally not detectable in sera from REA and OA patients. In contrast, cytokines were found in virtually all SF; thus, the majority of SF from RA patients contained IFN-gamma (median level 17 pg/ml) in addition to the monokines IL-6 (4700 pg/ml) and TNF-alpha (157 pg/ml). IFN-gamma and IL-6 (but not TNF-alpha) were also frequently measured in SF from REA patients, whereas OA samples typically contained only IL-6. Immunohistochemical analysis of tissue sections from RA patients revealed lymphokine expression in 0.1-0.3% of T cells, particularly IL-2 and IFN-gamma, and to a lesser extent also IL-4. Interestingly, the expression of TNF-alpha and IL-6 by synovial T cells was also observed. The majority of cytokine-expressing T cells were CD4-positive T-helper cells typically found in perivascular areas, whereas cytokine-producing CD8-positive T cells were found distributed throughout the synovium. As expected, in specimens from OA patients, T cells were much less abundant and expression of cytokines could not be detected. CONCLUSION: These data clearly demonstrate production of cytokines by T cells in RA synovial tissue, indicating that activated T cells play a role in the pathophysiological events of RA.
9506578 Clonally expanded Valpha12+ (AV12S1),CD8+ T cells from a patient with rheumatoid arthritis 1998 Mar OBJECTIVE: Previously, we showed that 15-20% of patients with rheumatoid arthritis (RA) have oligoclonal expansions of peripheral blood CD8+ T cells expressing T cell receptors encoded by the V(alpha)12 (AV12S1) gene. To better understand the significance of these expansions, the present study was undertaken to determine their specificity. METHODS: We cloned and characterized V(alpha)12+,CD8+ T cells from the peripheral blood of 1 RA patient with a clonal expansion of these T cells. RESULTS: The T cell clones were autoreactive since they recognized autologous, but not allogeneic, antigen-presenting cells. Upon activation, these T cells secreted interleukin-4 and interleukin-10. The autoreactive T cell clones were class I major histocompatibility complex (MHC) restricted, by either HLA-B60 or HLA-Cw3. CONCLUSION: A large population of class I MHC-restricted CD8+ T cells in a patient with RA is clonally expanded and autoreactive. These cells define a novel immune aberration in RA and provide a tool for defining the autoantigens that activate expanded T cell populations in vivo.
10589351 Early developments in combination therapy. 1999 Nov The concept of combination therapy implies the concurrent use of two or more slow-acting antirheumatic drugs to treat rheumatoid arthritis. This review places such combination therapy into an historical context and evaluates studies carried out before 1990. There were no published studies before 1980 of combination therapy, and between 1980 and 1990 there were 11 published studies. Three were conventional randomised controlled trials, three were non-randomised studies of parallel group design, four were observational open studies, and one was a retrospective review. Altogether 486 patients were studied with the numbers of cases in each study varying between 12 and 101. The main combinations used were penicillamine + hydroxychloroquine or chloroquine, gold + hydroxychloroquine, and sulphasalzine + penicillamine. Six studies concluded that combination therapy helped patients, three suggested possible benefits, and two gave essentially negative findings. These two negative studies were randomised controlled trials. Most studies indicated an increase in adverse events with combination therapy. The average erythrocyte sedimentation rate on combination therapy fell by 21.4%. A majority of patients remained on the therapy for 6-12 months. The balance of evidence in 1990 suggested that combination therapy had a modest advantage. However, the trials were too small to detect its true value, and the combinations used were not ideal. In particular, combining gold or penicillamine with other drugs appeared to give too much toxicity. The future development of the field would depend on identifying more effective combinations of drugs and undertaking larger and better-designed trials.
10328579 Signaling and effector pathways. 1999 May There is increasing evidence that distinct signaling and effector pathways in the rheumatoid synovium result in a cascade of pathophysiologic events. These interactions, which finally lead to progressive joint destruction, are different from all other joint diseases in numerous aspects. As outlined in this review, molecular biology techniques allow detection of key pathways ranging from external stimuli to subcellular gene regulation mechanisms operative in various cells within the rheumatoid synovium. To alter these pathways, inhibitory factors need to be applied to these "hot zones" for an extended period, which can be achieved either by repeated drug administration or by local synthesis using genetically altered synovial cells. Both adenovirus and retroviral constructs, as well as ex vivo and in vivo strategies, can be used for gene transfer into these cells, and routine delivery of "protective" genes into the affected joints might be achieved within the next decade.
9588286 A case of sulindac-induced enteropathy resulting in jejunal perforation. 1998 Jan Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for rheumatic conditions. Their effects on the upper gastrointestinal tract are well recognised. Clinically important damage to the small intestines is less common and often unrecognised. We report a case of sulindac-induced jejunal perforation in a rheumatoid arthritis (RA) patient with previous gastrectomy for gastric carcinoma. The prevalence, diagnosis, pathogenesis and treatment options of NSAID-induced enteropathy will be discussed.
10325659 Quantitation of interferon gamma- and interleukin-4-producing T cells in synovial fluid an 1999 Mar OBJECTIVE: The balance between T cells able to produce interferon gamma (IFN-gamma) (type 1) and interleukin-4 (IL-4) (type 2) is considered to be important in the development of autoimmunity. In this study, we quantitated the percentage of both cell types in synovial fluid (SF) and peripheral blood (PB) of rheumatoid arthritis (RA) patients, non-rheumatoid arthritis patients and healthy controls. METHODS: After short-term stimulation of synovial mononuclear cells with phorbol ester and ionomycin, cytokine-producing cells were quantitated using an intracellular staining technique and flow cytometric analysis. RESULTS: Although no significant differences in CD8 + cells were found, significantly higher percentages of IFN-gamma-producing CD4 + (Th 1) and IL-4-producing CD4 + (Th2) cells were found in the peripheral blood of RA patients in comparison with healthy controls. However, the Th1/Th2 ratio was not different between the two groups. Comparative studies between PB and SF showed that in both RA and non-RA patients, percentages of Th1 cells were higher in SF than in PB, while Th2 cells were preferentially found in the PB, resulting in a higher Th1/Th2 ratio in the SF. The Th1/Th2 ratio in the SF correlated with disease activity as estimated by the erythrocyte sedimentation rate. CONCLUSION: These results are in agreement with the hypothesis that Th1 cells preferentially home to inflamed joints in both RA and non-RA patients, but show that this does not result in an altered Th1/Th2 ratio in the PB of RA patients.
9566668 Steroid pulse therapy for rheumatoid arthritis: effect on lymphocyte subsets and mononucle 1998 Mar Eighteen patients with clinically active rheumatoid arthritis, satisfying the ARA criteria, were admitted to hospital for i.v. methylprednisolone pulse therapy. Studies of circulating lymphocyte subsets 1 h before and 24 h after pulsing were carried out together with studies on their adhesion to endothelium-containing lamina propria of porcine gut at various time points. Additionally, circulating VCAM-1 was estimated pre- and post-pulse by ELISA. We observed a marked fall (59%) in mononuclear cell adhesion 24 h post-pulse therapy (P < 0.001). Accompanying this was a significant, though slight, fall in circulating mononuclear cells (P < 0.01), mainly involving T cells. However, the degree of reduction in cell adhesion did not appear to reflect change in any particular circulating subset, but was more likely due to changes in adhesion molecule expression of several subsets. No significant change in circulating VCAM-1 was observed. It would appear, therefore, that the early beneficial effect of steroid pulsing in rheumatoid arthritis coincides with a demonstrable reduction in cell adhesion to gut. This may have implications for the pathogenesis of this disease.
10695684 Cytokine blockade as a new strategy to treat rheumatoid arthritis: inhibition of tumor nec 2000 Feb 28 Rheumatoid arthritis (RA) is a common, frequently severe, chronic inflammatory disease. Although the cause of RA remains unknown, recent advances in understanding its pathogenesis have been substantial. Despite the use of a variety of medications, particularly methotrexate, treatment of RA is not fully effective in most patients. Until recently, insights into inflammatory mechanisms in RA had not been successfully translated into novel classes of therapeutic agents. This gap now will likely be bridged in the form of a new strategy for treating RA-cytokine blockade. Although a variety of cytokines are important in the pathogenesis of RA, tumor necrosis factor (TNF) seems to play a pivotal role. Neutralizing TNF in patients with RA, by means of soluble TNF receptors or anti-TNF monoclonal antibodies, has proven to be a powerful means of controlling disease activity. Studies are in progress to obtain additional information regarding long-term safety of TNF blockade and its effects on disease progression.
9164974 Accelerated collagen-induced arthritis in IFN-gamma receptor-deficient mice. 1997 Jun 1 Collagen-induced arthritis (CIA) is a model for rheumatoid arthritis. Here, we describe experiments showing that IFN-gamma receptor knockout (IFN-gammaR alpha KO) mice of the DBA/1 strain develop CIA more readily than their wild-type counterparts. Symptoms of disease started 10 days earlier and the cumulative incidence of arthritis was significantly higher in the mutant mice than in wild-type mice. Similarly, accelerated onset of the disease was also found in wild-type DBA/1 mice treated with neutralizing mAbs against IFN-gamma. Histologic examination of the joints revealed a massive infiltration of the synovium with mononuclear cells and neutrophils, hyperplasia, and severe pannus formation in IFN-gammaR alpha KO mice when such inflammatory lesions were not yet detectable in wild-type mice. Serum levels of anti-collagen type II Abs, including total IgG and IgM, as well as IgG1, IgG2a, and IgG2b isotypes were found to be lower in the mutant mice. IL-2 and IL-4 remained undetectable in sera of both groups of mice, but did appear in the circulation after anti-CD3 Ab challenge. Significantly higher IL-2 and lower IL-4 serum levels were found in anti-CD3-challenged IFN-gammaR alpha KO mice than in wild-type counterparts, both at an early and at a later stage of the disease. These observations indicate that endogenous IFN-gamma counteracts development of collagen-induced arthritis and suggest that IFN-gamma does so by up-regulating IL-4 production and/or down-regulating IL-2 production. The data are in line with the concept of a pathogenic role of Th1-type cellular immunity in CIA in spite of a decreased Ab response to collagen type II.
11783301 [Clinical and experimental study on effect of Shuguan granule on mid-late rheumatoid arthr 1999 Feb OBJECTIVE: To explore the therapeutic mechanism of Shuguan Granule (SGG) in treating mid-late rheumatoid arthritis. METHODS: Based on the principle of reinforcing Kidney to treat arthritis, removing phlegm to remove stasis, two SGG, Shuguan Wenjing granule (SW) and Shuguan Qingluo granule (SQ) were prepared and used to treat mid-late 44 and 43 patients of rheumatoid arthritis respectively. The clinical result was compared with that of Wangbi Granule. Animal experiments on the effect of the two SGG were conducted. RESULTS: The total effective rate of the SW, SQ and control group was 88.64%, 93.02% and 73.17% respectively. Results of experimental studies in rats with adjuvant-induced arthritis showed that the two SGG obviously raise the level of serum SOD, and lowered the levels of serum interleukin-1, plasma prostaglandin E2 and thromboxane B2, as compared with the model group, the difference was significant (P < 0.05, P < 0.01). CONCLUSION: The two SGG have a comprehensive function of anti-inflammatory, analgesia, antioxidation, antihypercoagulation and immunoregulation.
10229417 Unusual onset of rheumatoid arthritis with diffuse pulmonary nodulosis: a diagnostic probl 1999 Apr We describe a case of a 50-year-old woman presenting articular manifestations of rheumatoid arthritis associated with severe interstitial lung involvement related to multiple pulmonary nodules. Diagnosis of diffuse pulmonary rheumatoid nodulitis was made only after video assisted thoracoscopic lung biopsies.
10087644 The psychosocial effects of rheumatoid arthritis on the patient and the well partner. 1999 Mar Rheumatoid arthritis (RA) is a chronic disorder that can have a severe impact on patient's lives. This present study investigated four questions regarding the psychosocial effects on patients and their well partners. First we found that depression for both patients and partners were slightly elevated and 35.7% of patients and 23.3% of well partners had scores above the cut-off for possible clinical depression on the Center for Epidemiological Studies Depression Scale. Second, there was no significant difference between the patients' level of distress and that of the partners. Third, there were moderate positive correlations between patients' and partners' scores on measure of psychological functioning. Fourth, there were no differences in either the patients' or partners' well-being based on the gender of the patient. Finally, an exploratory analysis was conducted to examine the factors which influence the patients' and partners' depression and their view of the relationship.
11497222 A sandwich ELISA for detection of soluble GPI-80, a glycosylphosphatidyl-inositol (GPI)-an 2001 GPI-80, mainly distributed on human neutrophils and monocytes, is a novel glycosylphosphatidylinositol (GPI)-anchored protein regulating neutrophil adherence and migration. We prepared a polyclonal antibody specific to GPI-80 by immunizing rabbits with the purified GPI-80 and established a sandwich ELISA for detecting soluble GPI-80. We found that soluble GPI-80 was released from fMLP activated neutrophils and was present at high concentrations in synovial fluids but not sera of rheumatoid arthritis patients, suggesting that GPI-80 may play a role in inflammatory diseases. The detection of soluble GPI-80 may help us to understand its physiological and pathological functions.
9411412 [Echocardiographic evaluation of cardiac structures in patients with rheumatoid arthritis] 1997 Apr Since heart lesions were found at autopsy in 55-60% of rheumatoid arthritis patients, we decided to assess echocardiographically their clinical significance. The study comprised 100 consecutive patients with rheumatoid arthritis (77 females and 23 males) of the mean age 55.7 +/- 12.5 yrs (range 18-83 yrs) and the disease duration of 8.3 +/- 8.0 yrs (range 1-35 yrs). The control group consisted of 100 consecutive age and sex matched patients admitted to university hospital. All the patients underwent echocardiographic examinations in apical and parasternal projections. The activity of the rheumatoid process, the severity of articular lesions, the presence of extraarticular sings as well as HLA DR and DQ antigens were determined clinically and with laboratory tests. Twenty six patients with rheumatoid arthritis had pericardial effusion, 10 revealed the sings of chronic pericarditis, in the control group 4 and 0 respectively (p = 0.001 and p = 0.025). No difference was shown in the wall contractions disturbances, size of the cardiac cavity, or thicknesses of the interventricular septum or posterior wall. In 3 rheumatoid arthritis patients, a valvular heart disease was diagnosed, this number was not significantly different from that in the control group (2 patients). There was no correlation between the lesions observed in the heart and the rheumatoid process activity estimated with clinical and laboratory indices.
11361186 Comparison of radiological severity in psoriatic arthritis and rheumatoid arthritis. 2001 May OBJECTIVE: To compare the radiological severity of patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA). METHODS: Patients were identified from the University of Toronto PsA and RA databases. Using the earliest available radiographs, each RA patient was matched to a single PsA patient on the basis of sex, age, and disease duration. Two rheumatologists blinded to the patient's diagnosis scored the radiographs using the modified Steinbrocker method. RESULTS: PsA and RA groups were similar with respect to demographics as well as the use of disease modifying antirheumatic medications. No significant difference in Steinbrocker score for the hands and feet or the hands only was noted. Patients with RA had a higher radiological score in the feet. The 2 groups were similar in the number of joints with significant radiological damage (Steinbrocker 3 and 4). CONCLUSION; Overall the radiological severity in the hands and feet of patients with PsA was comparable to that of patients with RA.
11508582 Methotrexate inhibits rheumatoid synovitis by inducing apoptosis. 2001 Aug OBJECTIVE: To clarify the pharmacological action of methotrexate (MTX) on the synovium of patients with rheumatoid arthritis (RA) using severe combined immunodeficient (SCID) mice in which human RA synovial tissue had been grafted (SCID-HuRAg). METHODS: One month after engraftment of human RA tissue into SCID mice, MTX (0.3 mg/kg) was administered orally, then the appearance of apoptosis in the grafted tissue was examined by TdT mediated dUTP nick end labeling (TUNEL) staining and electron microscopy at various time points after MTX administration. In cultured synovial cells, synovial apoptotic changes after MTX treatment were studied by agarose gel electrophoresis and flow cytometric analysis. To compare the histological changes induced by MTX with those induced by other disease modifying antirheumatic drugs (DMARD) and a nonsteroidal antiinflammatory drug, histological examination of the grafted synovial tissues from SCID-HuRAg mice was conducted after 4 weeks of oral administration of MTX (0.3 mg/kg/week), salazosulfapyridine (30 mg/kg/day), auranofin (0.2 mg/kg/day), bucillamine (10 mg/kg/day), or indomethacin (2 mg/kg/day). RESULTS: A significant decrease in the number of inflammatory cells was observed in the grafted synovial tissue of MTX treated SCID-HuRAg. A similar antiinflammatory effect was not observed with the other DMARD. Induction of apoptosis was noted with MTX treatment but not with the others. The pro-apoptotic effect of MTX was also observed in synovial cell cultures. CONCLUSION: MTX induces apoptosis in RA synovium that, in turn, may contribute to its antiinflammatory effect on RA synovitis.
11327015 [Effects of tripchlorolide (T4) of Tripterygium Wilfordii Hook on the production of immuno 1997 Tripchlorolide(T4) is an active ingredient recently isolated from Tripterygium Wilfordii Hook. The in vitro effects of T4 on the peripheral blood mononuclear cells(PBMC) of healthy persons(n = 10), the digested single synovium cells(DSSC) (n = 3) and PBMC(n = 6) from RA patients on production of immunoglobulins (Ig) were studied using Elisa method. The results showed that T4 at concentrations from 5 ng.ml-1 to 35 ng.ml-1 significantly reduced the production of Ig by PWM-stimulated PBMC of healthy persons in a dose dependent manner. At concentration of 25 ng.ml-1, T4 also reduced the Ig secretion of RA-PBMC and DSSC. It is hoped that T4 would be an encouraging new drug of herbal nature for the treatment of RA.
10719816 Expression of cyclooxygenase-1 and -2 in rheumatoid arthritis synovium. 2000 Feb The aim of this study was to investigate the expression and localization of cyclooxygenase-1 and -2 (COX-1 and COX-2) in synovial tissues from patients with rheumatoid arthritis (RA). Synovial tissues from 9 patients with RA and 5 patients with osteoarthritis (OA) were examined for COX-1 and COX-2 expressions by immunohistochemical staining using 2 polydonal COX-1 and COX-2 antibodies. In RA synovia, synovial lining cells showed intense immunostaining for COX-1, whereas slight to moderate staining was observed in inflammatory cells, stromal fibroblast-like cells and vascular endothelial cells. There was no significant difference in COX-1 expression between RA and OA synovia. The localization of COX-2 expression dearly differed from that of COX-1 expression, being most intense in inflammatory cells. However, there was no difference in COX-1 and COX-2 expressions between RA and OA synovial tissues. Our observations support that inflammatory mechanisms modulated by COX-1 and COX-2 in chronic RA synovium might be similar to those in chronic OA synovium.
10511060 A population pharmacokinetic-pharmacodynamic analysis of single doses of clenoliximab in p 1999 Sep Clenoliximab (IDEC-151) is a macaque-human chimeric monoclonal antibody (immunoglobulin G4) specific for the CD4 molecule on the surface of T lymphocytes. It is being studied in patients with rheumatoid arthritis in which T cell activation orchestrates inflammation and tissue damage. In this initial study in humans, the pharmacokinetics and pharmacodynamics of clenoliximab were investigated after single intravenous infusion. Blood was collected up to 12 weeks after dose administration to measure clenoliximab concentration, CD4+ T-cell count, CD4 antigen coating, and CD4 cell surface density. Clenoliximab displayed nonlinear pharmacokinetic behavior and caused an 80% reduction in CD4 density for up to 3 weeks, without depleting T cells. A pharmacokinetic-pharmacodynamic model was developed that described the relationship between antibody concentration, antigen coating, and the observed decreases in CD4 cell surface density. This was used to anticipate the effects of clenoliximab in untested regimens and optimize the design of future clinical trials.
10441831 [The femoropatellar endoprosthesis--still of value today?]. 1999 May PURPOSE: Aim of this study was the examination of clinical middle- and long-term results of total femoropatellar endoprostheses type Lubinus (Link, Germany). METHOD: From 1983 to 1996 12 patients (15 joints) underwent total femoropatellar joint replacement (type Lubinus, Link, Hamburg). All of them have been controlled 7.2 +/- 2.6 years (2 to 12 years) after surgery. The indication was primary osteoarthritis in 6, chondrocalcinosis in 2 and rheumatoid arthritis in 7 cases. In addition to the femoropatellar implants femorotibial endoprostheses have been used in 10 knees: 2 unicondylar medial, 1 unicondylar lateral and 7 bicondylar unicompartimental ones. RESULTS: According to a modified Hungerford knee rating scale 8 knees resulted excellent, 2 fair and 4 poor. One knee was excluded after revision surgery due to a loosened tibial component of a medial unicompartimental knee arthroplasty. The 4 poor outcomes resulted from femoropatellar replacements in chondrocalcinosis (2 cases), rheumatoid arthritis and osteoarthritis, (one case each), affecting the femorotibial joint as well. CONCLUSIONS: In those cases of simultaneous femorotibial joint affection--even if this is merely slight and beginning and if the femoropatellar complaints are actually clearly dominating--the sole femoropatellar surface replacement seems to be contraindicated according to our experiences. Providing correct and strict indications this endoprosthesis can be recommended for sole femoropatellar osteoarthritis especially since loosening of endoprosthetic components was not been found in this study.