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

ID PMID Title PublicationDate abstract
10479237 Rheumatoid arthritis treated with vegetarian diets. 1999 Sep The notion that dietary factors may influence rheumatoid arthritis (RA) has been a part of the folklore of the disease, but scientific support for this has been sparse. In a controlled, single-blind trial we tested the effect of fasting for 7-10 d, then consuming an individually adjusted, gluten-free, vegan diet for 3.5 mo, and then consuming an individually adjusted lactovegetarian diet for 9 mo on patients with RA. For all clinical variables and most laboratory variables measured, the 27 patients in the fasting and vegetarian diet groups improved significantly compared with the 26 patients in the control group who followed their usual omnivorous diet throughout the study period. One year after the patients completed the trial, they were reexamined. Compared with baseline, the improvements measured were significantly greater in the vegetarians who previously benefited from the diet (diet responders) than in diet nonresponders and omnivores. The beneficial effect could not be explained by patients' psychologic characteristics, antibody activity against food antigens, or changes in concentrations of prostaglandin and leukotriene precursors. However, the fecal flora differed significantly between samples collected at time points at which there was substantial clinical improvement and time points at which there were no or only minor improvements. In summary, the results show that some patients with RA can benefit from a fasting period followed by a vegetarian diet. Thus, dietary treatment may be a valuable adjunct to the ordinary therapeutic armamentarium for RA.
11401174 Component size asymmetry in bilateral total knee arthroplasty. 2001 Spring A review of 268 consecutive patients undergoing bilateral total knee arthroplasty (TKA) was performed to determine whether component size asymmetry exists in patients undergoing bilateral TKAs. Component sizes were selected based on preoperative radiographic templating and intraoperative sizing measurements irrespective of the component sizes chosen for the other knee. All radiographs were evaluated according to described criteria. Component sizes used for the femur, tibia, and patella were compared between the right and left knees. Of the 268 bilateral TKAs, 18 (6.7%) femoral components varied in size between right and left knees. There were no statistical differences for patellar or tibial component size asymmetry or knee function pre- or postoperatively. Patients with asymmetrically sized femoral components had no statistical difference between left and right knees with respect to knee score, pain, function, range of motion, incidence of lateral release, or complications.
10812469 [Increased occurrence of autoimmune thyroiditis in patients with chronic rheumatoid arthri 2000 The frequent occurrence of both rheumatoid arthritis and autoimmune thyroiditis was already investigated with in part many conflicting results. We investigated a number of 792 patients (383 of them suffering from rheumatoid arthritis and 409 with osteoarthritis). In all patients antithyroid peroxidase and antithyroglobulin antibodies were determined. Patients with rheumatoid arthritis showed a significantly higher occurrence of circulating thyroid antibodies than those with osteoarthritis (9.1% versus 3.7%, p = 0.0016). We conclude that there exists a cumulate coincidence of both diseases. Patients suffering from rheumatoid arthritis should undergo a thyroid examination especially for the presence of autoimmune thyroiditis.
10357220 Frequency of clonally expanded T cells evaluated by PCR from a single cell. 1999 Apr 22 In analyses of antigen-specific immune responses, it is essential to estimate the frequency of individual T cell clonotypes. This frequency has been estimated, however, only indirectly by the frequency of T cell receptor (TCR) mRNA. We have developed a method to determine T cell frequency directly by cell count using reverse transcription polymerase chain reaction (RT-PCR) amplification of TCR beta genes from single cell-derived cDNA (single cell PCR). In a study of clinical samples, the frequency of clonally expanded T cells estimated by TCR frequency analysis was found to be higher than that by single cell PCR. Single cell PCR can estimate T cell frequency accurately, as it is not affected by skewed PCR amplification or different TCR mRNA expressions in individual T cells.
11361205 Measurements of rheumatoid arthritis disease activity and damage using magnetic resonance 2001 May Magnetic resonance imaging (MRI) is a tool with unprecedented capabilities. Rheumatoid arthritis (RA) abnormalities that can be measured with MRI include erosions, articular cartilage thickness, synovial membrane volume, and pannus. However, as access to MRI increases, there is a risk that its use will not be evaluated using rigorous scientific measurement principles. We reviewed published MRI measurement methods for RA and investigated whether the methods were systematically evaluated for reliability, validity, and responsiveness to change--components of the OMERACT filter. Medline and Embase databases were searched from 1966 to 1999. Titles and abstracts were scanned to identify publications on MRI methods used to assess either disease activity or damage in RA. A data extraction template was developed and 68 peer reviewed publications from 40 research groups were appraised; 40 addressed RA disease activity, 4 RA damage, and 24 both activity and damage. Joints most frequently assessed were knee (32 publications) and wrist (31 publications). Ninety-one percent of publications evaluated either reliability or validity or responsiveness to change. Thirteen percent evaluated all 3 and only 9% evaluated none of these measurement properties. Validity was evaluated in 85%, responsiveness to change in 37%, and reliability in 35% of publications. Only 12% of publications evaluated both intra and inter-reliability. Few publications of MRI measures of disease activity or damage in RA met the OMERACT filter for all measurement properties. It would be regrettable if MRI measures are developed ad hoc, with little regard to considerations of scaling, reliability, validity, and responsiveness to change, because this will severely limit their ability to confidently assess treatment efficacy and prognostic indicators.
10743580 [Interstitial granulomatous dermatitis with arthritis]. 2000 Feb Interstitial granulomatous dermatitis with arthritis is a rare dermatologic disorder seen in patients suffering from diseases in which circulating immune complexes occur. The typical cutaneous signs are linear cords usually located on the lateral aspect of the trunk. The characteristic, although not specific, histology reveals a dense diffuse infiltrate composed mostly of histiocytes, accompanied by neutrophils and eosinophils, and degenerated collagen surrounded by palisades of histiocytes. We discuss this disorder and its differential diagnosis.
10755432 Treatment of the mobile, painful arthritic elbow by distraction interposition arthroplasty 2000 Mar Between 1986 and 1994, 13 patients with mobile painful arthritic elbows were treated by distraction interposition arthroplasty using fascia lata. The mean period of follow-up was 63 months. An elbow distractor/fixator was applied for three to four weeks to separate the articular surfaces and to protect the fascial graft. Nine of the 13 patients (69%) had satisfactory relief from pain; eight (62%) had an excellent or good result by the objective criteria of the Mayo Elbow Performance score. Four have required revision to total elbow arthroplasty at a mean of 30 months with good results to date. Instability of the elbow, both before and after surgery, was found to be associated with unsatisfactory results. The rate of success when the procedure was performed for inflammatory arthritis was similar to that for post-traumatic arthritis, about 67%. Eight complications occurred in six patients, all in the group with post-traumatic arthritis. Two of these required further surgical procedures such as transposition of the ulnar nerve or repair of hernia of the fascia lata. Although less reliable than prosthetic replacement, distraction interposition arthroplasty is a useful option in the treatment of young, high-demand patients with arthritis of the elbow. It is rarely indicated in the presence of generalised inflammatory arthritis, but may be of value in those patients in whom the disease is limited primarily to the elbow.
9517759 Methotrexate and cyclooxygenase metabolism in cultured human rheumatoid synoviocytes. 1998 Mar OBJECTIVE: Our objective was to characterize the effect of methotrexate (MTX) on prostaglandin E2 (PGE2) synthesis in cultured human rheumatoid synovial cells. Prostaglandins (PG) are important mediators of inflammation and joint destruction in rheumatoid arthritis (RA). Two isoforms of cyclooxygenase (COX), the key enzyme in PG synthesis, have been characterized: a constitutively expressed form, COX-1, and an inducible form, COX-2. The mechanisms of action of low dose MTX in RA treatment are still poorly understood. As the clinical effects are often first noticed within a month of starting MTX therapy, an antiinflammatory action has been proposed. METHODS: Adherent synovial cells were obtained by collagenase digestion of rheumatoid synovium, isolated from patients with RA undergoing synovectomy. Between passages 3 and 6, cultured synovial cells were incubated with or without MTX for 54 h, at various concentrations. Interleukin (IL)-1beta (1 ng/ml) was added or not for the last 6 h of incubation. Supernatants were harvested and assayed for PGE2 by enzyme immunoassay (EIA). Exogenous [1-14C]arachidonic acid metabolism of synoviocytes was analyzed by reverse phase high performance liquid chromatography (RP-HPLC). COX-1 and COX-2 mRNA expression was determined by total RNA extraction and reverse transcription polymerase chain reaction. RESULTS: Cellular viability was not affected by MTX. EIA showed that MTX decreased IL-1beta induced PGE2 production by synoviocytes in a dose dependent manner. RP-HPLC analysis confirmed the inhibition of PGE2 and (12S)-12-hydroxy-5,8,10-heptadecatrienoic acid production. COX-1 and IL-1beta induced COX-2 mRNA expression were not inhibited by MTX. CONCLUSION: MTX has an inhibitory effect on IL-1beta stimulated production of PGE2 by cultured human rheumatoid synoviocytes, without affecting either COX mRNA expression. Among various biochemical and immunologic events, MTX could have an antiinflammatory action by decreasing PGE2 release.
10902747 A comparison of three radiologic scoring systems for the long-term assessment of rheumatoi 2000 Jul OBJECTIVE: To compare the sensitivity and efficiency of 3 different radiologic scoring systems in measuring radiologic progression of rheumatoid arthritis (RA) over a 12-year period. METHODS: Radiographs of the hands and feet of 112 RA patients were assessed at 0, 3, 6, and 12 years of disease duration using the Sharp score as modified by van der Heijde (SHS), the Sharp score with increased maximum scores (Sharp Max), and the Kellgren score. The sensitivity to change was tested using the standardized response mean (SRM); the efficiency was determined by calculating the number of patients needed to detect 50% difference in progression between 2 patient groups. RESULTS: Radiologic abnormalities were steadily progressive irrespective of the scoring method used. In early disease, the SRM was significantly larger for the SHS and Kellgren scores compared with the Sharp Max score. In late disease, the Kellgren score was slightly more sensitive to change compared with the SHS and Sharp Max scores; the difference, however, did not reach significance. In erosive disease, the SRM was significantly larger for the Kellgren compared with the SHS and Sharp Max scores. The numbers of patients needed to detect a 50% difference during the 0-3-year followup period were 129, 138, and 124 for the SHS, the Sharp Max, and the Kellgren, respectively. The numbers of patients needed to detect a 50% difference during the 6-12-year followup period were 117, 121, and 104, respectively. The numbers of patients needed to detect a 50% difference during the 6-12-year followup in patients with erosive disease were 74, 78, and 68, respectively, for the 3 scores. The Kellgren required 33 minutes to score 10 sets of radiographs of the hands and feet; the SHS score took 55 minutes. CONCLUSION: The Kellgren scoring system is the most efficient method for monitoring the radiologic progression of RA. The Kellgren and the SHS are equally sensitive to change early in the disease, whereas the Kellgren score becomes more sensitive to change late in the disease in patients with erosions.
9145299 Pathological evaluation of effect of anti-rheumatic drugs on type II collagen-induced arth 1997 Apr The effects of anti-rheumatic drugs (dexamethasone 0.1 mg/kg and naproxen 5 mg/kg) were evaluated immunologically and histopathologically on type II collagen-induced arthritis in Lewis rats. Increased paw volume in the hind limbs was significantly suppressed in the groups treated with dexamethasone or naproxen, but noticeable retardation of body weight gain was observed in the group treated with dexamethasone. Serum anti-type II collagen IgG was significantly suppressed in the group treated with dexamethasone but not naproxen. Histopathological evaluation by our grading system, classification of the stages in arthritic lesion development, revealed suppression of the inflammatory changes in the tarsal joints of the animals treated with dexamethasone or naproxen. From our results, histopathological evaluation is considered to be more suitable for assessment of the efficacy of anti-rheumatic drugs on type II collagen-induced arthritis, an animal model for human rheumatoid arthritis.
9627011 Cellular immunity to the G1 domain of cartilage proteoglycan aggrecan is enhanced in patie 1998 Jun OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) express cellular immunity to the purified G1 globular domain of cartilage proteoglycan (PG) aggrecan and whether it is influenced by the removal of keratan sulfate (KS) chains from the molecule. METHODS: The G1 globular domain of PG was purified from mature bovine articular cartilage, digested with keratanase, and used in proliferation assays with peripheral blood lymphocytes (PBL) isolated from 43 patients with RA, 11 patients with nonarticular rheumatism (NAR), including soft tissue rheumatism and mechanical back pain, and 13 healthy age- and sex-matched control subjects. RESULTS: Removal of KS chains from the G1 globular domain resulted in significantly increased prevalence and values of cellular immune responses to G1 in RA patients compared with the control and NAR groups. In the majority of RA patients, KS chains on G1 significantly inhibited its immune recognition by PBL. There was no significant effect of KS removal on the immunity to G1 in patients with NAR and in the healthy control group. CONCLUSION: These results reveal that immune reactivity to the G1 globular domain of the cartilage PG aggrecan is enhanced in patients with RA but only when KS chains are removed. Thus, KS chains inhibit immune responses to this domain of aggrecan. Since immunity to the G1 globular domain of aggrecan induces an erosive polyarthritis in BALB/c mice after removal of KS chains, immunity to the G1 globular domain, cleaved by proteases to remove KS chains, may play a role in the pathogenesis of RA.
10464565 The urokinase-type plasminogen activator system and inflammatory joint diseases. 1999 Jul Much evidence indicates that the urokinase plasminogen activator (u-PA), the urokinase receptor (u-PAR) and the serpin inhibitors are critical in cell invasion processes. The balance between u-PAR-bound u-PA and inhibitors modulate a pericellular proteolytic activity able to give "stop and go" signals to invading cells. The plasminogen activation system operates both directly and in concert with the matrix-metalloproteinase system. Direct interactions of u-PAR with vitronectin and integrins further regulate cell invasion. Another line of evidence suggests that u-PA-u-PAR interaction elicits chemotaxis, chemoinvasion and cell multiplication, events that do not require plasmin generation and therefore are referred to as "plasminogen-independent". Following the description of the main molecular and functional characteristics of the cell-surface-associated plasminogen activation system, we discuss here the observations indicating a role of this system in many aspects of the rheumatic diseases, ranging from the infiltration of inflammatory cells into the affected joint, infiltration of synovial cells into the underlying cartilage, and remodeling of the cartilage itself. Evidence of the intraarticular cytokine- and growth factor-dependent regulation of the components of the plasminogen activation system are presented in terms of the paracrine and autocrine regulation of receptor-associated fibrinolysis. The roles of plasminogen-dependent and plasminogen-independent u-PAR-associated events in various phases of joint inflammation are also discussed. A knowledge of these processes is required for the therapeutic utilization of antagonists of the u-PA/u-PAR system able to control the activity of proliferating and invading cells in inflammatory joint diseases.
9175932 Increase in age at onset of rheumatoid arthritis in Japan over a 30 year period. 1997 May OBJECTIVES: To determine changes in demographic variables and severity of rheumatoid arthritis (RA) that may have occurred during the 30 year period from 1960 to 1990 in Japan. METHODS: Using records of patients diagnosed with RA from two hospitals, demographic and clinical features at initial visit were compared between two groups, one from 1960 to 1965 (group I) and the other from 1985 to 1990 (group II). RESULTS: Mean age at the time of onset of the disease increased significantly from 37.5 years in group I to 46.9 in group II. The peak age at onset of RA shifted from the third to the fifth decade between group I and group II. There was no obvious change in morbidity as determined by seropositivity, rheumatoid nodules, and assessments of hip involvement. CONCLUSION: The age at onset of RA was delayed during a recent 30 year period in Japan. This increase in age at onset might result from environmental changes that occurred in Japan or may reflect a birth cohort phenomenon. Improvement of severity of disease was not found in this study.
11276037 Displaying clinical data relationships using scaled rectangle diagrams. 2001 Apr 15 A method is presented to draw rectangles to represent categorical data relationships. The idea is an adaptation of a scaled Venn diagram. Rectangles are drawn with area proportional to the frequency of categories and the rectangles are positioned to overlap each other so that the areas of overlap are in proportion to the joint frequencies of the characteristics. The diagrams are especially useful to illustrate symptom co-occurrence.
11518137 Rapid improvement of osteomalacia by treatment in a case with Sjögren's syndrome, rheumat 2001 Aug We present here a case of Sjögren's syndrome (SjS) with osteomalacia based on renal tubular acidosis type 1 (RTA-1). A 53-year-old woman, diagnosed as having rheumatoid arthritis (RA) at the age of 33, was admitted to our hospital because of sicca complex, fatigability and worsening general aching. The activity of RA had been low, but it was complicated by SjS, RTA-1 and remarkable osteomalacia. Acidosis was corrected by alkali supplement therapy. By treatment with a regimen consisting of alfacalcidol, calcium L-aspartate, elcatonin and ipriflavone, her bone mineral density (BMD) was remarkably improved within months and the generalized aching gradually diminished.
9164467 TNF blockade in rheumatoid arthritis: implications for therapy and pathogenesis. 1997 Apr The role of the immune response in rheumatoid arthritis (RA) is a subject of debate, although it is widely believed to be a T-cell-driven disease. Progress is being hindered by lack of convincing evidence of a defined specific antigen initiating or perpetuating the response. Clinical trials using monoclonal antibodies directed against T-cell surface molecules such as CD4. CD5, and CD7 have thus far not provided evidence of efficacy. The negative data may reflect inadequate dosing or could suggest that indiscriminate depletion of T cells is insufficient by itself as a therapeutic strategy. Blocking proinflammatory cytokines (e.g. TNF alpha, IL-1) or augmenting anti-inflammatory cytokines (e.g. IL-10) offers an alternative approach to therapy. Clinical trials using monoclonal anti-TNF alpha have been particularly successful in controlling inflammation and markedly reducing acute phase proteins and cellular ingress. However, because disease invariably relapses, repeated therapy is necessary. Preliminary experience suggests that this is possible. Anti-TNF therapy for RA has defined a molecular target and new approach for treating immuno-inflammatory disorders.
9706423 Levels of circulating cellular fibronectin are increased in patients with rheumatoid vascu 1998 Jul OBJECTIVE: To investigate whether serum levels of circulating cellular fibronectin (cFN) are increased in patients with rheumatoid arthritis (RA) complicated by vasculitis. METHODS: Levels of serum cFN were determined by an enzyme-linked immunosorbent assay (ELISA) in 26 RA patients with histologically proven vasculitis of recent onset (RV) and were compared to the levels in 47 RA patients with extraarticular manifestations of recent onset but no histological evidence of vasculitis (RA+), 43 patients with uncomplicated RA (RA-), 16 patients with systemic lupus erythematosus and active disease (SLE), 30 patients with active Crohn's disease (CD), 21 young healthy controls (yHC) and 17 elderly healthy controls (eHC). Plasma levels of cFN and von Willebrand factor antigen were also determined in the RA patients. RESULTS: In RV patients, the median cFN level was significantly (P = 0.01) higher compared to that of RA+ patients, and was also significantly (P < 0.0000) higher compared to the cFN level in the RA-, SLE, CD, yHC and eHC groups. When compared to eHC, the cFN level was significantly higher in RA+ (P = 0.008); it was also higher in RA-, although not significantly (P = 0.42). 77% of the RV patients, 55% of the RA+ patients, and 37% of the RA-patients had a cFN level > 2 SD above the mean level for eHC. At an optimal cut-off titre the sensitivity of the cFN ELISA in discriminating RV patients from RA+ patients was 90%, the specificity was 46% and the accuracy was 68%. Plasma levels of cFN correlated significantly (r = 0.62; P < 0.001) with the von Willebrand factor antigen levels. CONCLUSIONS: Increased levels of serum cFN are present in patients with RA, and are frequently found in RA patients with extraarticular manifestations, particularly in those with vasculitis.
9433876 Susceptibility of stromelysin 1-deficient mice to collagen-induced arthritis and cartilage 1998 Jan OBJECTIVE: It has long been proposed that stromelysin is one of the major degradative matrix metalloproteinases responsible for the loss of cartilage in rheumatoid arthritis (RA) and osteoarthritis (OA). This hypothesis was tested by examining the arthritic paws of stromelysin 1 (SLN1)-deficient mice for loss of cartilage and for generation of neoepitopes that would be indicative of aggrecan cleavage. METHODS: The SLN1 gene was inactivated in murine embryonic stem cells, and knockout mice deficient in SLN1 activity were bred onto the B10.RIII background. The incidence and severity of collagen-induced arthritis (CIA) were compared in wild-type and knockout mice. Paws from mice with CIA were examined for loss of cartilage and for proteoglycan staining, as well as for the generation of the neoepitope FVDIPEN341. RESULTS: SLN1-deficient mice developed CIA, as did the wild-type N2 mice. Histologic analyses demonstrated no significant differences among the B10.RIII, wild-type, and knockout mice in loss of articular cartilage and proteoglycan staining. No decrease in the FVDIPEN341 epitope was observed in the SLN1-deficient mice. CONCLUSION: Disruption of the SLN1 gene neither prevents nor reduces the cartilage destruction associated with CIA. Moreover, SLN1 depletion does not prevent the cleavage of the aggrecan Asn341-Phe342 bond.
10857797 Antineutrophil cytoplasmic antibodies in patients with early rheumatoid arthritis: an earl 2000 Jun OBJECTIVE: To evaluate the clinical associations of antineutrophil cytoplasmic antibodies (ANCA) in patients with early rheumatoid arthritis (RA), as well as the possible predictive role of ANCA. We also assessed the overlap of ANCA with other specific serologic markers of RA. METHODS: Eighty-two RA patients with symptoms for < or = 12 months were studied for the presence of ANCA by immunofluorescence and specific enzyme immunoassays. ANCA were determined and clinical, radiographic, and laboratory data were collected at study entry and later at 12, 36, 60, and 84 months. RESULTS: In 2 patients, the first serum samples (obtained at study entry) were no longer available for the determination of ANCA. Perinuclear ANCA (pANCA) were found in 40 patients (50%), and atypical cytoplasmic ANCA were found in 3 patients (4%) at study entry. Perinuclear ANCA-positive patients were significantly more frequently positive for rheumatoid factor (78%) than were ANCA-negative patients (54%) (P = 0.0297). Fifty-five percent of pANCA-positive patients and 22% of ANCA-negative patients were positive for antiperinuclear factor (P = 0.0044). Similarly, pANCA-positive patients had antikeratin antibodies more frequently than did ANCA-negative patients (35% versus 20%). During a 7-year followup, the progress of radiographic joint destruction, assessed with Larsen scores, was significantly more rapid in patients who were pANCA positive at study entry than in those who were ANCA negative (P = 0.0015). Also, the mean titer of pANCA at study entry was significantly higher in those patients who subsequently had advanced radiographic joint destruction at 60 and 84 months. The association of pANCA with rapid radiographic destruction in patients with early RA was further corroborated by a logistic regression analysis that selected pANCA positivity as an independent and statistically significant predictor of rapid radiographic joint destruction. CONCLUSION: In patients with early RA, pANCA are associated with specific serologic markers of RA and predict rapid radiographic joint destruction.
9619476 Examining the impact of illness representations on psychological adjustment to chronic ill 1998 May Illness representations were assessed in 63 adults with rheumatoid arthritis (RA) and 66 with multiple sclerosis (MS). The relationship of illness representations to concurrent and later mood was explored. MS patients' beliefs in symptom variability were associated with higher depressed mood 4 months later, over and above initial levels of depression. RA patients who saw RA as curable or who saw themselves as responsible for the illness reported significant increases in depression over time. Belief in the serious consequences of RA interacted with later illness severity to predict change in depression. When belief in the serious consequences of RA was high, less severe illness status was associated with less depression and more severe illness status was associated with more depression. When RA was initially viewed as only moderately serious, less severe illness was associated with somewhat higher levels of depression.