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ID PMID Title PublicationDate abstract
9194210 Endothelial cells are the major source of sICAM-1 in rheumatoid synovial tissue. 1997 The objective of this research was to investigate the cellular source of soluble ICAM-1 (siCAM-1) from rheumatoid synovial tissue (RS) and its relation to sICAM-1 in synovial fluid (SF) and serum, and to study the expression of ICAM-1 in isolated cells of RS. sICAM-1 was determined by using the enzyme-linked immunosorbent assay (ELISA) and Western blot analysis in supernatants from RS cultured for short periods (n = 19), in SF (n = 7) and in serum (n = 19). ICAM-1 expression, vascularization and inflammatory infiltration (CD3, CD68, CD22) were characterized immunohistochemically in cytospin preparations (n = 18), cryosections (n = 18) and in conventionally stained paraffin sections (n = 19) of RS. The degree of RS vascularization was analysed morphometrically in immunohistochemically stained cryosections (factor VIII related antigen). We found 90-kD sICAM-1 in supernatants of cultured cells, in SF and in sera. sICAM-1 in cellular supernatant correlated significantly (P < 0.01) with SF sICAM-1. The amount of sICAM in cellular supernatants showed no correlation to the score of inflammatory infiltration, but correlated significantly (P < 0.001) with the vascularization index of RS. The percentage of ICAM-1-expressing cells correlated significantly (P < 0.001) with the percentage of CD68-positive macrophages, but not with CD3- and CD22-positive lymphocytes. Macrophages, multinucleated giant cells and endothelial cells exhibited a higher expression of ICAM-1 as compared to lymphocytes and fibroblasts. The differential expression of ICAM-1 on infiltrating leucocytes and resident cells of RS indicates a functional role of ICAM-1 in the local inflammatory process. SF sICAM-1 originated in RS, but serum sICAM-1 did not. Shedding of sICAM-1 by RS was independent of inflammatory infiltration, but depended on the degree of vascularization, indicating that endothelial cells are the major source of sICAM-1 in RS.
10943873 The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent 2000 Aug OBJECTIVE: To study the predictive value of anticyclic citrullinated peptide antibody (anti-CCP) in patients with recent-onset rheumatoid arthritis (RA). METHODS: Outcome in terms of physical disability (Health Assessment Questionnaire) and radiologic damage (modified Sharp method) over 3-year and 6-year periods was determined in an inception cohort of 273 RA patients who had had disease symptoms for <1 year at study entry. Anti-CCP titers were determined at baseline and considered positive as recently described. Their prognostic value was studied by means of multiple regression analysis, in which anti-CCP positivity, sex, age at study entry, IgM rheumatoid factor (IgM-RF) status, Disease Activity Score (DAS), HLA-DR4 status, and (in a separate group of patients) shared epitope status were used as independent variables, and radiologic damage and functional disability as dependent variables. RESULTS: Patients with anti-CCP had developed significantly more severe radiologic damage after 6 years of followup. In multiple regression analysis, radiologic damage after 6 years followup was significantly predicted by IgM-RF status, radiologic score at entry, and anti-CCP status. Functional disability was significantly predicted by sex, age at entry, IgM-RF status, and DAS. CONCLUSION: Our data show that in almost 70% of RA patients, anti-CCP antibody is present at the early stages of disease. Anti-CCP-positive patients developed significantly more severe radiologic damage than patients who were anti-CCP negative, although in multiple regression analysis the additional predictive value was rather moderate.
9922986 Expression of CD44 variant isoforms in leukocytes of the joint fluid of rheumatoid arthrit 1998 Oct Several CD44 variant isoforms have been reported in the synovium of patients with rheumatoid arthritis (RA), but the physiological and pathological roles of these isoforms have not been identified. In this study, we investigated the expression of CD44 variant isoform mRNA using the reverse transcription-polymerase chain reaction (RT-PCR) and TaqMan PCR methods in leukocytes of blood and joint fluid obtained from the knee joints of 20 RA patients. We also examined the effects of steroids (prednisolone and/or dexamethasone palmitate) and some disease-modifying antirheumatic drugs (DMARDs) on the expressions of CD44 variants. The expressions of CD44H mRNA and CD44V10 mRNA of leukocytes were significantly higher in both the blood and joint fluid samples of the RA patients compared with the samples of healthy volunteers. The level of CD44V10 mRNA in the leukocytes of the joint fluid was higher than that in the blood of the RA patients. These results suggest that the increase of CD44V10 mRNA expression in the leukocytes of RA patients can induce a focusing of leukocytes on synovial tissue and an infiltration of leukocytes into the joint fluid. In the steroid-treated RA patients, the expression of CD44H mRNA in the leukocytes was significantly decreased in the joint fluid samples, whereas the expression of CD44V10 mRNA of leukocytes was a higher level. None of the DMARDs used here showed any influence on the expressions of CD44 variants. These results suggest that steroid treatment affects CD44H mRNA expression, whereas steroids and DMARDs have no influence on CD44V10 mRNA expression. Therefore, only the suppression of CD44H mRNA expression will not be enough to control RA. It is possible that the expression of CD44V10 is associated with a pathway of RA immunological processes.
11035134 IL-4 VNTR gene polymorphism in chronic polyarthritis. The rare allele is associated with p 2000 Oct OBJECTIVE: To evaluate the occurrence of variants of the interleukin 4 (IL-4) and IL-4 receptor (IL-4R) genes in patients with rheumatoid arthritis (RA) and their possible contribution to joint destruction. METHODS: Allelic frequencies for polymorphisms in the IL-4 [variable number of tandem repeat (VNTR) polymorphism in intron 3] and IL-4 receptor alpha chain (transition at nucleotide 1902) genes were assessed in 335 RA patients and 104 controls. Clinical indices of disease activity, disability and joint destruction and plasma levels of IL-1beta, IL-1Ra and sCD23 were assessed to evaluate a possible functional effect. RESULTS: Carriage of the rare IL-4(2) allele was higher in patients with non-destructive RA (40%) than in those with destructive RA (22.3%; odds ratio = 1.9, 95% confidence interval 1. 1-3.5, P = 0.0006) and in controls (26%, P = 0.002). Patients positive for this rare allele had significantly less joint destruction, assessed by the Larsen wrist index (P = 0.004) and a lower erythrocyte sedimentation rate (P = 0.04). A significantly higher carriage rate of IL-4(2) was seen in HLA-DR4/DR1(-) patients with non-destructive RA than in those with destructive RA. The IL-4 receptor polymorphism was not over-represented. Plasma levels of IL-1beta, IL-1Ra and sCD23, known to be modified by IL-4, were not different in individuals having different alleles. CONCLUSION: This IL-4 VNTR gene polymorphism may be a protective factor for severe joint destruction in RA that could be used as a prognostic marker early in the course of the disease.
9090247 Joint pain and weather. A critical review of the literature. 1997 Mar Many people believe that weather conditions can influence joint pain, but science offers no proof. If the phenomenon were real, cause-and-effect mechanisms might provide clues that would aid joint pain treatment. Literature on the subject is sparse, conflicting, and vulnerable to bias, and further physiologic investigations are not likely to produce useful information. However, for patients who believe that weather can influence their pain, the causes may be unknown, but the effect is real.
10774461 Anti-cytokine therapy for rheumatoid arthritis. 2000 Tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) are important in mediating inflammation in rheumatoid arthritis (RA). Randomized phase II and III clinical trials of anti-TNF reagents (infliximab and etanercept) have demonstrated an acceptable safety profile and marked clinical efficacy in cases of RA that have not responded adequately to conventional therapy. Combination therapy with methotrexate (MTX) appears to be particularly effective in patients whose disease activity persists despite prior disease-modifying antirheumatic drugs (DMARDs) and ongoing MTX monotherapy. DMARD-recalcitrant disease may become the main indication for the use of anti-TNF drugs in patients with RA. Trials of IL-1 receptor antagonist show a relatively modest anti-inflammatory effect and a possible retardation of joint damage. Whether anti-TNF therapy protects joints from structural damage is under investigation. One anti-TNF reagent has already been approved in the United States for the treatment of RA, and other cytokine antagonists or agonists are under development.
10534544 Changes in plasma free fatty acid concentrations in rheumatoid arthritis patients during f 1999 Oct OBJECTIVE: To measure whether changes in the concentrations of circulating free fatty acids (FFAs) after a 7 day fast in rheumatoid arthritis (RA) patients would inhibit in vitro T-lymphocyte proliferation. METHODS: The concentration and composition of plasma FFAs were measured in nine RA patients at the conclusion of a 7 day fast. A FFA mixture was made up based on these findings (20% linoleic, 43% oleic, 10% stearic, 27% palmitic acid). Mitogen-induced lymphocyte proliferative responses were measured after co-culture of peripheral blood mononuclear cells (PBMC) from healthy individuals in the presence of increasing concentrations of this FFA mixture (from 0 to 2000 microM) and in the presence of FFA mixtures where the relative proportions of fatty acids varied. RESULTS: Both the concentration of the FFA mixture and the ratio between the unsaturated and saturated fatty acids significantly influenced in vitro lymphocyte proliferation (P<0.0001). Unexpectedly, the highest concentrations of the FFA mixture increased lymphocyte proliferation. At equimolar concentrations (600 microM), manipulating the amounts of oleic and linoleic fatty acids relative to stearic and palmitic fatty acids had a potent inhibitory effect upon lymphocyte proliferation. CONCLUSION: Fasting-associated increases in total plasma FFA concentrations do not inhibit, but rather enhance, in vitro lymphocyte proliferation. An inhibitory effect could only be achieved by manipulating the balance between the unsaturated and saturated fatty acids.
11205827 Crystal deposition in normal and diseased articular cartilage: an extended report. 1999 Sep Particles observed on the surfaces of human articular cartilage following trauma and from chondromalacic, osteoarthritic and rheumatoid joints using the scanning electron microscope were analysed by x-ray diffraction technique. The particles contained calcium and phosphorus and they were identified only in structurally abnormal cartilage. These findings suggest that local abnormality of articular cartilage probably underlies crystal-deposition.
9128419 [Toxicity of low-dose methotrexate in rheumatoid arthritis--clinical characteristics in pa 1997 Feb Pancytopenia and interstitial pneumonitis are one of the most serious and unpredictable adverse effects of low dose, pulse methotrexate (MTX) in treating rheumatoid arthritis (RA). It is important to investigate the historical, clinical or immunologic features associated with the development of such toxicity, in order to use MTX more appropriately. Two hundred eighty four patients (female 230 male 54) with rheumatoid arthritis had been treated with pulse weekly oral MTX with a mean follow-up of 33.2 months. Adverse effects which required the discontinuation of MTX occurred in 47 patients (16.5%). Gastrointestinal toxicity occurred most frequently (14 patients) and liver dysfunction occurred in 9 patients. Four patients (1.4%) developed pancytopenia, and six patients (2.1%) developed interstitial pneumonitis. All patients who developed pancytopenia were old female with long history of active, deforming rheumatoid arthritis, The cumulative dose of MTX ranged from 15 mg to 760 mg at the time pancytopenia developed. Impaired renal function, hypoalbuminemia, and multiple medication were observed, and antinuclear antibodies were positive in most patients. It should be noted that severe stomatitis preceded or accompanied with pancytopenia in all patients. Blood counts returned to the normal level in 7 to 14 days. All patients who developed interstitial pneumonitis were old female. The cumulative dose ranged from 65 mg to 580 mg. Pre-existance of lung diseases, history of adverse effects of other DMARDs, the presence of Raynaud's phenomenon, and antinuclear antibodies appeared to be risk factors for interstitial pneumonitis. All patients recovered with high dose of corticosteroid and mechanical ventilation. Such clinical characteristics that are associated with MTX-induced pancytopenia or interstitial pneumonitis should be reminded in the treatment of rheumatoid arthritis with MTX.
11508424 Synovial tissue protease gene expression and joint erosions in early rheumatoid arthritis. 2001 Aug OBJECTIVE: To relate the expression of proteases in the lining and sublining layers of the synovial membrane to the rate of joint damage during 1 year in patients with early inflammatory arthritis. METHODS: Samples of synovial membrane were obtained by closed-needle biopsy or needle arthroscopy from inflamed knees of 20 patients with early inflammatory polyarthritis (mean disease duration 9.6 months, range 2 weeks to 18 months). Expression of matrix metalloproteinase 1 (MMP-1), cathepsin B (CB), and cathepsin L (CL) was examined using in situ hybridization. Immunohistochemistry was used to identify infiltrating mononuclear cell populations. Radiographs of the hands and feet, performed at presentation and after 1 year, were evaluated for the development of new erosions. RESULTS: Twelve patients had rheumatoid arthritis (RA), 6 had psoriatic arthritis (PsA), 1 had gout, and 1 had an undifferentiated arthritis. Six patients had erosions at presentation. Eleven patients (10 with RA, 1 with PsA) demonstrated at least 1 new erosion after 1 year of followup. MMP-1, CB, and CL messenger RNA (mRNA) were expressed in the synovial membrane of all patients and were present throughout the lining layer, as well as in perivascular cellular infiltrates and endothelial cells in the sublining layer. In the lining layer, the mean percentages of protease mRNA-positive cells per high-power field were higher in those patients who developed new joint erosions than in those without evidence of joint damage. A similar pattern was observed in the sublining layer, where mean numbers of protease mRNA-positive cells were also greater in patients with new joint erosions. There were significant differences between the two groups in MMP-1 mRNA expression in both the lining and sublining layers (P = 0.0007 and P = 0.0027, respectively), as well as in sublining layer CL mRNA expression (P = 0.017), but not in CB mRNA expression. Numbers of lining layer CD68+ cells correlated positively with lining layer MMP-1 mRNA expression (P = 0.043) and with the development of new joint erosions (P = 0.002). CONCLUSION: The detection of MMP-1, CB, and CL in the synovium soon after the onset of symptoms highlights the potential for early joint destruction in patients with RA. High levels of MMP-1 mRNA expression in the lining layer distinguished patients with more rapidly progressive erosive disease. This is the first study to demonstrate features of early synovial pathophysiology that may identify patients at increased risk of developing new joint erosions.
10825240 Gap junctions in human synovial cells and tissue. 2000 Jul Our objective was to establish the existence of intercellular communication through gap junctions in synovial lining cells and in primary and passaged cultures of human synovial cells. Communication between cells was assessed using the nystatin perforated-patch method, fluorescent dye transfer, immunochemistry, transmission electron microscopy, and immunoblotting. Functional gap junctions were observed in primary and passaged cultures and were based on measurements of the transient current response to a step voltage. The average resistance between cells in small aggregates was 300 +/- 150 MOmega. Gap junctions were also observed between synovial lining cells in tissue explants; the size of the cell network in synovial tissue was estimated to be greater than 40 cells. Intercellular communication between cultured cells and between synovial lining cells was confirmed by dye injection. Punctate fluorescent regions were seen along intercellular contacts between cultured cells and in synovial membranes in cells and tissue immunostained for connexin43. The presence of the protein was verified in immunoblots. Regular 2-nm intermembrane gap separations characteristic of gap junctions were seen in transmission electron micrographs of synovial biopsies. The results showed that formation of gap-junction channels capable of mediating ionic and molecular communication was a regular feature of synovial cells, both in tissue and in cultured cells. The gap junctions contained connexin43 protein and perhaps other proteins. The physiological purpose of gap junctions in synovial cells is unknown, but it is reasonable to anticipate that intercellular communication serves some presently unrecognized function.
11102775 Human autoimmunity genes in mice. 2000 Dec In the post-genomic era, the expression and investigation of human (auto)immunity genes seems more relevant than ever. The generation of humanized animal models of human diseases will be useful to study the interplay between genetic and non-genetic factors in disease development and may form a basis for the development of new drugs that act more specifically than the ones currently in use. Transgenic mice have been generated that express various human proteins--candidate autoantigens, disease-associated MHC class II molecules, TCRs and/or CD4--in order to study diseases such as rheumatoid arthritis, multiple sclerosis and diabetes.
9002009 Indirect and nonmedical costs among people with rheumatoid arthritis and osteoarthritis co 1997 Jan OBJECTIVE: Compared to rheumatoid arthritis (RA), osteoarthritis (OA) is considered much more benign and much less costly. We sought to describe the economic effects of RA and OA, in terms of the indirect and nonmedical expenditures, compared to nonarthritic controls. METHODS: Using our unique population based data resources, we developed a model for estimating and comparing disease specific costs among 2 randomly selected, community based samples of 200 patients each with RA and OA and a control group of 200 individuals from the same community who do not have arthritis. Data were collected using a pretested postal survey. Age and sex adjusted comparisons were conducted across the 3 groups, and predictors of cost and utilization were identified using logistic regression modeling. RESULTS: There were 123, 116, and 94 respondents among the RA, OA, and nonarthritis groups, respectively. The average age and the female-to-male ratios were higher in the OA and RA groups compared to the nonarthritis group. Patients with RA and OA required 3 times more days of care for their conditions compared to nonarthritics (p < 0.0001) and incurred significantly more expenditures for home or child care (p = 0.01) and other services (p = 0.001) (i.e., medical equipment, assistive devices, or home remodeling) compared to nonarthritics. In addition, patients with RA were significantly more likely to have lost their job or to have retired early due to their illness (p = 0.001); were the most likely to have reduced their work hours or stopped working entirely due to their illness (p = 0.003); and were 3 times more likely to have had a reduction in household family income than either individuals with OA or those without arthritis (p = 0.0001). Fifteen percent of respondents with RA were unable to get a job because of their illness, while 3% of respondents with OA and only 1% of nonarthritic respondents reported this experience (p = 0.001). Logistic regression analysis revealed that functional status and pain score, as well as the presence of either RA or OA, were significant predictors of cost and health services utilization. CONCLUSION: Disease specific indirect and nonmedical costs for OA are substantial and approach those for RA. This has important societal implications, given the high prevalence of OA.
10093808 Simultaneous bilateral total knee arthroplasty in a single procedure. 1998 Eighty-eight consecutive patients undergoing total knee arthroplasty (TKA) were reviewed retrospectively and divided into two groups. Group I (64 patients) had both knees replaced simultaneously by one team in a single procedure while Group II (24 patients) had 2 operations staged about 7 days apart. The blood loss, operative time, knee functional score, period of hospitalisation and complications were documented in order to compare the 2 groups. Performing simultaneous bilateral TKA (Group I) did not increase the incidence of operative or post-operative complications. Equally, the functional score and mean intra- and post-operative blood loss were not influenced. The operative time and duration of hospitalisation were significantly shorter in Group I than in Group II. On the basis of the results of this study, it appears that simultaneous bilateral TKA is beneficial.
9311282 [A case of rheumatoid arthritis (RA) with drug-induced acute pancreatitis due to mizoribin 1997 Aug A rare case of mizoribine-induced acute pancreatitis is presented. A 39-year-old female with RA was admitted to our hospital because of upper abdominal pain, fever and the elevation of serum amylase concentration. Acute pancreatitis was diagnosed. Mizoribine (MZB) had been administered for 12 days for the treatment of RA before the onset of pancreatitis. Withdrawal of MZB soon resulted in the improvement of the disease. She was asymptomatic for the next few weeks. The pancreatitis recurred 36 hours after she took MZB again on her own judgement for arthralgia. This clinical course strongly suggested that her pancreatitis was due to MZB. Acute pancreatitis due to MZB has never, to our knowledge, been reported. MZB is commonly used for the treatment of RA. Therefore the clinician should take care for the complication of acute pancreatitis even though it is rare.
10614887 Measurement of bone mineral density by dual-energy X-ray absorptiometry around an uncement 1999 Dec Dual-energy x-ray absorptiometry allows the measurement of bone mineral density (BMD) around an uncemented hip prosthesis, but has not so far been widely used to measure BMD around a knee prosthesis. We studied 16 patients undergoing total knee replacement using a Miller-Galante uncemented prosthesis for either osteoarthritis or rheumatoid arthritis of the knee. The precision of the measurement was improved by using a leg brace. The pattern of bone loss differed in the lateral projection by region (P = .001). There was significant loss of bone from the distal femur but not from the patella or proximal tibia over the 6-month period after insertion of a knee prosthesis.
9266132 Statistical considerations concerning clinical studies designed to assess DC-ARTs. 1997 May The aim of this paper is to contribute to the current ongoing debate regarding how to optimise clinical research on rheumatoid arthritis. Bearing in mind the main difficulties represented by the particular characteristics of the disease and its treatment, as well as the limitations of some of the trials that have been carried out over the last thirty years, we discuss how some of the general statistical considerations regarding all clinical trials should be applied to those specifically designed to assess disease-controlling antirheumatic therapies.
11225133 Neuropathy in rheumatoid arthritis. 2001 Feb BACKGROUND: Paucity of Indian literature on rheumatoid neuropathy creates a lacuna in the critical evaluation and discussion of the subject. We did this study to find out the incidence and pattern of neuropathy and to correlate it with disease parameters and other extra-articular involvement. MATERIAL AND METHODS: We studied 31 patients of rheumatoid arthritis (RA) classified by ACR criteria. Electromyography and nerve conduction studies (EMG/NCV) were done in all the patients apart from routine laboratory and radiological investigations. Electrocardiograph (ECG), pulmonary function tests (PFT) and ophthalmological examination were also carried out to ascertain extra-articular involvement. RESULTS: Ten out of 31 RA patients had neuropathy of which five each were overt and subclinical respectively. Only one patient had entrapment neuropathy. Four of the ten patients had pure motor neuropathy whereas the other six were sensori-motor neuropathies. Four patients had mononeuritis multiplex and five had symmetrical peripheral neuropathy. Nine of the ten neuropathic patients had RA for more than 2 years. Seven patients had other extra-articular features along with neuropathy. CONCLUSIONS: One-third of patients with RA have evidence of neuropathy. Disease parameters such as activity, rheumatoid factor and functional and radiological grade do not correlate with neuropathy. Non-entrapment sensori-motor type of neuropathy is the most common type.
9734684 Methotrexate treatment in Felty's syndrome. 1998 Aug Felty's syndrome is a rare disorder characterized as a systemic manifestation of severe rheumatoid arthritis associated with granulocytopenia and splenomegaly. We report a retrospective analysis of a series of seven patients treated successfully with low-dose methotrexate. leading to sustained clinical improvement (number of swollen joints) and normalization of the granulocyte count for an observation period of 1 yr. Our cohort is the largest ever published with methotrexate treatment of this rare condition. Our results confirm earlier single case reports suggesting methotrexate to be the first-choice treatment nowadays in Felty's syndrome.
9686690 Systemic diseases involving the orbit. 1998 Jun A variety of systemic pathological processes may involve the eye and the surrounding orbital adnexae. CT and MRI of the orbit have become useful clinical adjuvants, not only in establishment of the diagnosis, but also in suggesting the appropriate clinical treatment, sometimes preventing needless biopsy. Grave's disease, Wegener's granulomatosis, and sarcoidosis may all present initially with orbital disease before the onset of systemic manifestations. Idiopathic inflammatory disease of the orbit and lymphoproliferative disease of the orbit continue to remain radiological and clinical challenges. The article discusses the CT and MRI appearance of many of the common systemic diseases in adults with attention to features useful in clinical practice as well as in differential diagnosis.