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ID PMID Title PublicationDate abstract
15487808 The MDR1 3435 polymorphism in patients with rheumatoid arthritis. 2004 Sep OBJECTIVE: Rheumatoid arthritis (RA) is a multifactorial disease, the pathogenesis of which involves immunological, genetic and environmental factors. P-glycoprotein (P-gp) encoded by the MDR1 gene, is an important transporter for many drugs, xenobiotics and cytokines and may be associated with many immunological processes and apoptosis. The activity of P-gp is genetically determined. Naturally occurring MDR1 polymorphisms have been described and correlated with potential clinical effects. Several mutations in the MDR1 gene have been recognized, but only some of them are associated with P-gp expression. The C3435T polymorphism was found to correlate with the activity of P-glycoprotein. The aim of the study was to evaluate the C3435T MDR1 polymorphism in patients with rheumatoid arthritis and to investigate a possible correlation with disease susceptibility, activity and severity. METHODS: The study was carried out in 92 patients with rheumatoid arthritis and 97 healthy subjects as a control group. The C3435T polymorphism was determined using the PCR-RFLP method. RESULTS: The distribution of C3435TT MDR1 genotypes in RA patients did not differ significantly from that in a control group and was as follows: 3435CC in 25 (26.9%) subjects, 3435CT in 50 (53.8%) and 3435TT in 17 (18.3%). The probability of remission of RA symptoms after therapy with methotrexate and glucocorticosteroids however, was 2.89-fold greater in patients with the 3435TT genotype compared to patients with the genotypes 3435CC and 3435CT. The risk of having an active form of rheumatoid arthritis resistant to therapy with disease-modifying antirheumatic drugs in patients with 3435CC and 3435CT genotypes was 2.89 times greater than in homozygous 3435TT subjects. CONCLUSION: We suggest that the C3435T MDR1 polymorphism is not an important genetic risk factor for RA susceptibility, but that this polymorphism may have an influence on the activity of the disease and its response to therapy with disease-modifying antirheumatic drugs.
12708777 Autoantibodies and glomerulonephritis in systemic lupus erythematosus. 2003 Autoantibody diversification to a variety of autoantigens is a hallmark for systemic autoimmunity. SLE represents a prototype. In this article the roots of the important questions probed by the Kunkel laboratory in SLE research are traced. Data from the recent animal work by the laboratory of Shu Man Fu are summarized to emphasize the importance of further exploration of autoantibody specificities in lupus with a special emphasis on nephritis and to suggest a broader perspective regarding lupus autoantibody reactivities in addition to those against nuclear components.
15468350 Fatigue assessments in rheumatoid arthritis: comparative performance of visual analog scal 2004 Oct OBJECTIVE: Fatigue has been recognized as an important domain in rheumatoid arthritis (RA) clinical trials and in patient care and outcome. However, lengthy fatigue questionnaires cannot be easily used in clinical care, and there are no data for the comparative performance of various short and long questionnaires. We compared a single-item visual analog scale (VAS) with 3 longer fatigue questionnaires, investigating 4 fatigues scales: the Multi-dimensional Assessment of Fatigue (MAF), the vitality scale from the Medical Outcomes Study Short Form 36 (SF-36), the Brief Fatigue Inventory (BFI), and the VAS. METHODS: Participants in a longitudinal outcome study of RA (N = 7760) completed the 4 questionnaires, and a subset of 5155 completed the same fatigue scales 6 months later. RESULTS: All questionnaires were highly correlated and were correlated at similar levels with clinical variables. The 3 longer questionnaires had slightly greater reliability in cross-sectional analyses, but the VAS was as good as or better than the longer questionnaires when sensitivity to change was considered. CONCLUSION: The single item VAS performs as well as or better than longer scales in respect to sensitivity to change, and is at least as well correlated with clinical variables as longer scales. The VAS fatigue scale is suitable for routine use in clinical care, an advantage that is lacking for the other scales. These results do not indicate advantages for longer fatigue scales compared with the VAS.
15675342 [Usefulness of anti-cyclic citrullinated peptide antibodies (anti-CCP) for the diagnosis o 2004 Dec Rheumatoid factor (RF) has been commonly used as a marker of rheumatoid arthritis (RA). RF can be detected in 60-80% of RA patients, but the specificity is low against other rheumatic diseases patients. We evaluated the diagnostic accuracy of anti-cyclic citrullinated peptide antibody (anti-CCP), a new diagnostic test for RA. Anti-CCP demonstrated higher sensitivity (81.0%) and specificity (92.4%). By the receiver operating characteristic (ROC) curve analysis, anti-CCP was superior to other markers (ie. RF, CARF, IgG-RF, and MMP-3). In early RA patients (RA patients who had had disease symptoms for < 2 years), sensitivity was 68.8%. Positivities of anti-CCP in RA patients became higher as the advance of stage defined by the Steinbrocker classification. We concluded that anti-CCP is a very valuable tool for the diagnosis of RA. Moreover, anti-CCP is a useful for finding RA of recent onset.
14969079 The safety of biologic agents in early rheumatoid arthritis. 2003 Sep Accompanying the excitement surrounding the prominent efficacy of biologic agents in rheumatoid arthritis (RA) has been concern regarding potential adverse effects. Data from clinical trials and pharmacovigilance has provided an assessment of their safety in patients with established RA. As biologic agents are utilized in patients with earlier disease, optimal determination of the risk/benefit will depend on continued careful monitoring, collection, reporting and analysis of safety information.
15049471 [Orthokin as new therapeutic option for orthopedic diseases]. 2004 Mar 1 The synthesis and introduction of interleukin-1 receptor antagonists established a promising strategy in the treatment of inflammatory diseases. This kind of therapy is claimed now to be available for osteoarthritis and other orthopedic disorders also. In the case of "orthokin", the interleukin-1 receptor antagonist is produced by stimulation of own blood-cells. It is not possible, to evaluate the practicability of this therapeutic approach because there are no published experimental data. We also found no results of clinical studies, which would allow an estimation of the effectiveness and the risks of this method. Therefore treatment with "orthokin" cannot be recommended at present.
12687514 Quality of life, social support, and knowledge of disease in women with rheumatoid arthrit 2003 Apr 15 OBJECTIVE: To examine the relationships between the quality of life (QOL) of women with rheumatoid arthritis (RA) and 1). their perceived levels of social support and 2). their primary caregivers' knowledge of RA and its treatment. METHODS: Women aged 40-60 years with established RA completed validated questionnaires on health status (Arthritis Impact Measurement Scales 2) and satisfaction with the levels of social support from their primary caregiver (Significant Others Scale A). In addition, both the caregivers and patients independently completed questionnaires that were designed to elicit knowledge of RA and its treatment. RESULTS: Fifty-eight patients and their primary caregivers completed the questionnaires. Analysis of the patients' health status demonstrated widespread biopsychosocial impairments. Arthritis pain, identified as the poorest health status dimension, was associated with the lowest levels of satisfaction, and received the highest priority for health status improvement. In contrast, the patients reported highest levels of satisfaction with social support from family and friends. Positive associations between social support variables and a number of QOL measures were observed. Both the caregivers and the patients displayed limited knowledge of RA and its treatment. Associations between the levels of knowledge and the patients' QOL measures were not observed. CONCLUSION: In this study of women with RA and their caregivers, a limited knowledge of disease did not appear to impact QOL measures. However, failure to detect an association between knowledge of disease and QOL may have been influenced by a combination of the relatively small study numbers and insufficient variation in caregivers' knowledge, such that a floor effect existed.
14579161 Expression of NKB1 on peripheral T cells in patients with rheumatoid arthritis. 2003 Oct NKB1 inhibits cytoxic activity of T lymphocytes mediated by superantigens, which is one of the contributing factors in the pathogenesis of rheumatoid arthritis (RA). In this study, we determined the expression of NKB1 on peripheral blood T cells in patients with RA. Our findings revealed that among patients with RA, NKB1(+) CD8(+ )T cells decreased significantly in comparison to controls (ratio: P < 0.05; absolute number: P < 0.005), and this decrease was not related to or influenced by HLA-Bw4 as a ligand of NKB1. This result may suggest that decreased expression of NKB1(+) CD8(+ )T cells contributes to the pathogenesis of RA mediated by the activation of CD8(+) T cells.
15170915 Radiographic hand joint space width assessed by computer is a sensitive measure of change 2004 Jun OBJECTIVE: To compare changes in the computerized measurement of radiographic hand joint space width (JSW) to changes in modified Sharp scores in a retrospective 2-year study of early rheumatoid arthritis (RA). METHODS: First and last standard clinical hand radiographs of 245 patients with RA were analyzed blind using purpose-written computer software to measure changes in JSW for proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints in the 3 middle fingers of each hand. Before measurement, the radiographs were scored independently by 2 radiologists using a modification of Sharp scoring. RESULTS: The paired changes in JSW (-0.051 +/- 0.005 mm) and Sharp score (+3.81 +/- 0.50) were both significant over the study duration. In measured joints showing an increase in joint space narrowing (JSN) score, 92% had a corresponding reduction in JSW. In patients with an increase in total score, including JSN and erosion scores in fingers and wrists, 84% had a corresponding reduction in mean (PIP + MCP) JSW. Patients with no change in Sharp score (47%) still experienced a significant reduction in measured JSW (-0.027 +/- 0.006 mm). HLA-DR genetic markers of severe disease progression were associated with significantly greater reductions in JSW but not increases in Sharp score. ( VALUES: mean +/- standard error of mean). CONCLUSION: Measured JSW averaged over 6 PIP and 6 MCP joints was a valid and more sensitive measure of change than total Sharp score in this study of early RA.
14719188 Low expression levels of soluble CD1d gene in patients with rheumatoid arthritis. 2003 Dec OBJECTIVE: To examine whether the expression of intact CD1d, a critical molecule for the presentation of glycolipid antigens to natural killer T (NKT) cells, and its variants differs between patients with autoimmune diseases including rheumatoid arthritis (RA) and healthy subjects. Recently, we identified 8 different CD1d variants, generated by alternative splicing. V1 lacking exon 4 (CD1d without beta2 microglobulin, beta2m) and V2 lacking exons 4 and 5 (soluble CD1d) may be functional molecules, because the antigen binding sites (exons 2 and 3) are intact. METHODS: Peripheral blood mononuclear cells (PBMC) from 44 patients with autoimmune disease (RA 19, systemic lupus erythematosus, SLE 10, Sjögren's syndrome, SS 15) and 15 healthy controls were separated and complementary (c)DNA was prepared. The expression of intact CD1d on PBMC was detected by flow cytometry. Alternatively spliced CD1d variants were quantified by TaqMan PCR using polymerase chain reaction with confronting 2-pair primers (PCR-CTPP) based amplification. RESULTS: The mean (+/- SEM) transmembrane and beta2m binding site deleted CD1d mRNA level in 19 patients with RA (2.0 +/- 0.33) was significantly lower than in 15 controls (6.9 +/- 2.08; p < 0.05), whereas there were no differences in beta2m deleted variants and intact CD1d mRNA. CONCLUSION: Our findings suggest that low expression of soluble CD1d variants might play a role in the formation of symptoms or pathogenesis of RA.
15206742 Kynurenine and neopterin levels in patients with rheumatoid arthritis and osteoporosis dur 2003 The kynurenine pathway from tryptophan generates compounds which can act on glutamate receptors in peripheral tissues or modulate free radical activity. We have measured the concentrations of several of these compounds in the plasma of patients with rheumatoid arthritis (RA) and osteoporosis (OP) before treatment with drugs and then at monthly intervals for 6 months during treatment. Kynurenine analysis was performed by HPLC. Compared with healthy controls, RA patients showed significantly decreased baseline levels of tryptophan, 3-hydroxykynurenine and 3-hydroxyanthranilic acid and increased levels of kynurenine and xanthurenic acid, while kynurenic acid concentrations were normal. Different results were recorded from patients with OP with only a significant reduction in tryptophan and 3-hydroxyanthranilic acid when compared with healthy controls. During 6 months of treating the RA patients with prednisolone or methotrexate, and the OP patients with raloxifene or etidronate and calcium there were significant therapeutic responses and a significant trend towards a reduction in levels of neopterin in RA patients receiving methotrexate but no changes in the profiles of tryptophan metabolites. The results are consistent with the induction of indoleamine-2,3-dioxygenase (IDO) in both RA and OP but with far greater activation of the pathway in the much more inflammatory condition, i.e. RA. It is concluded that there are changes in the kynurenine pathway, which may modify the activation of tissue glutamate receptors, in RA and OP, but that these are not affected by the drug treatments studied.
15323397 Magnetic resonance imaging of the rotator cuff in destroyed rheumatoid shoulder: compariso 2004 Jul PURPOSE: To evaluate the predictive value of preoperative magnetic resonance imaging (MRI) with respect to rotator cuff ruptures. MATERIAL AND METHODS: Thirty-one patients with rheumatic disease underwent preoperative MRI before shoulder arthroplasty. The scans were reviewed independently by two experienced radiologists. Three surgeons performed all the replacements (hemiarthroplasties), and the condition of the rotator cuff was assessed. Complete and massive tears of the rotator cuff were recorded and compared at surgery and on MRI. RESULTS: With MRI, 21 shoulders (68%) were classified as having complete or massive tears of the rotator cuff and at surgery 14 shoulders (45%). Cohen's kappa coefficient was 0.44 (95% CI: 0.16 to 0.72) and accuracy 0.71 (95% CI: 0.52 to 0.86). CONCLUSION: In severely destroyed rheumatoid shoulder, the findings of soft tissues were incoherent both with MRI and at surgery. The integrity of tendons could not readily be elucidated with MRI because of an inflammatory process and scarred tissues; in surgery, too, changes were frequently difficult to categorize. Preoperative MRI of severely destroyed rheumatoid shoulder before arthroplasty turned out to be of only minor importance.
12931310 Experience using the latest OrthoPilot TKA software: a comparative study. 2003 The OrthoPilot (Aesculap, Tuttlingen, Germany) Knee Navigation System represents a computed tomography (CT)-free system. In older software versions, a rigid-body at the iliac crest was necessary to calculate the centre of the hip. The latest software versions, 3.0 and 4.0, use a new mathematical algorithm to reconstruct the mechanical axis. Using the OrthoPilot system, an intraoperative cinematic study can be done that results in calculation of the mechanical axis and navigation of resection cuts. According to flexion- and extension-gap balancing, the anterior/posterior (a.p.) position and rotation of the femoral component also are navigated. Thirty navigated SEARCH (Aesculap, Tuttlingen, Germany) total knee arthroplasties (TKA) using the software version 3.0 of an uninterrupted series were evaluated, versus 30 navigated knees using older software and a manual group. Results concerning alignment were determined to be superior to the older navigation and manual groups. The number of cases with a good mechanical axis, 0; low; or 2 of deviation from optimum, was reached in 17 of the manual, 19 of the older-version, and 27 of the newer-version navigation cases. More features were solved in a convincing manner. The numbers of ouliers were diminished. Navigation in TKA using the OrthoPilot has become more safe and effective.
12692987 [Development of disease burden score concerning bone and joint diseases: comparison betwee 2003 Feb OBJECTIVES: To develop disease burden score concerning bone and joint diseases by evaluating the burdens of rheumatoid arthritis (RA) and osteoarthritis (OA) based on two quantitative measures of quality of life (QOL). METHODS: In a questionnaire, the qualified doctors of Japan Rheumatism Foundation were asked to evaluate patients' QOL, including 6 items of physical functions, 7 items of daily living activities and 3 items of social activities, for three severity levels defined by treatment status. The burdens of RA and OA were determined based on two quantitative measures of QOL, that is, 'principal component score' and '0-0.5-1 score'. RESULTS: In the two-way ANOVA of severity level and doctor's specialism, two quantitative measures of QOL showed significant differences by severity level, having approximately the same F-statistics each other. The burden of RA was 1.4-times (for 'principal component score') and 1.6-times (for '0-0.5-1 score') as great as that of OA. The differences in burden between RA and OA were observed especially in daily living activities and social activities. CONCLUSIONS: Our methodology may be applicable to examining differences in burden between bone and joint diseases.
12563674 Modified Larsen scoring of digitized radiographs in rheumatoid arthritis. 2003 Feb OBJECTIVE: To facilitate storage, retrieval, and analysis of radiographic images we assessed the validity of a film digitizer and computer based system. METHODS: A total of 101 sets of radiographs of hands and feet from patients with early rheumatoid arthritis were digitized according to standards defined by the American College of Radiology. Two blinded observers applied the modified Larsen score to the digitized images and the original radiographs. RESULTS: There was good concordance between the scoring of digitized images and radiographic films; intraclass correlation coefficient was 0.89. Regression analysis of a Bland-Altman plot revealed that there was no significant systematic bias. It was noted that scoring the digital images took more than twice as long as scoring the radiographic films. CONCLUSION: Our results indicate that modified Larsen scoring of adequately digitized films on standard computer displays is valid and shows good agreement with conventional techniques. Scoring digitized images appears to require more time, but this may be outweighed by the considerable advantages of computer storage and retrieval of radiographic images.
14743200 Impaired bone marrow hematopoietic progenitor cell function in rheumatoid arthritis patien 2004 Apr We have evaluated bone marrow morphology, percentage of bone marrow CD34(+) cells, proliferative activity of bone marrow precursors, clonogenic assay (BFU-E and CFU-GM) in short-term bone marrow cultures, and bone marrow cell apoptosis, together with serum TNF-alpha and IL-6, in 16 chronic, refractory RA patients, as well as in five healthy controls. Of 16 RA patients (68.7%), 11 showed a reduced bone marrow cellularity, while it was normal in all the controls. In RA patients, the median percentage of CD34(+) bone marrow cells, the median percentage of proliferating bone marrow myeloid precursors, and the median number of both BFU-E and CFU-GM colonies were significantly lower than observed in the controls. As far as TNF-alpha and IL-6 titers is concerned, the latter did not significantly differ from controls' values, while TNF-alpha titers were significantly lower in healthy controls. Finally, the median apoptotic index of early bone marrow myeloid cells of RA patients was significantly higher compared with controls. These observations may identify the biological risk factors for impaired mobilization and/or engraftment when RA patients are candidates for autologous hematopoietic stem cell grafting.
15940561 Serum cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis and knee osteoart 2005 Jun The cartilage oligometrix matrix protein (COMP) is a noncollagenous protein, a glycoprotein, the function of which is to bind to type II collagen fibres and stabilise the collagen fibre network in the articular cartilage. In the serum of the normal population the COMP level is 5 mug/ml. An increased level of COMP in the synovial fluid was described in the early stage of rheumatoid arthritis (RA), whereas in advanced stages of RA, the level of COMP decreased. In this study we assessed the serum COMP level in patients with RA and knee osteoarthritis (OA) and found a correlation between the serum COMP level and other markers as well as bone mass density (BMD) changes, activity of disease, disease duration and the age of the patients. The blood was collected from 30 RA patients and 30 OA patients who constituted the control group. The serum COMP level was determined using an inhibition enzyme-linked immunosorbent assay (ELISA). The average value of the serum COMP level in RA patients was 10.4+/-3.6 U/l. There was a correlation between the serum COMP level and the age of RA patients (p<0.005) and disease activity score (DAS) value (p<0.01). According to correlation coefficients, the serum COMP level was independent of stage of disease, number of painful and swollen joints, duration of morning stiffness, disease duration and titre of the Waaler-Rose test. The influence of rheumatoid nodule presence on the serum COMP level was shown (p<0.05). In RA patients with erythrocyte sedimentation rate (ESR) values below 20 mm/h compared with patients with ESR values over 60 mm/h, the serum COMP level was observed to be significantly lower (p<0.05). The average value of COMP in OA patients was 10.4+/-2.7 U/l. No correlation was found between the serum COMP level and patients' age and disease duration. There was a correlation between the serum COMP level and Western Ontario and McMaster Universities (WOMAC) index pain scale for the lower limbs (p<0.005) and T-score value of densitometry examinations (p<0.036) in OA patients. No statistical differences were found between the average serum COMP level in RA and OA patients.
12604153 Advances in rheumatology: coxibs and beyond. 2003 Feb Arthritis is a growing health concern in the US with approximately 70 million Americans currently affected. This figure will inevitably rise as the population ages. The pain and decreased mobility associated with arthritis have a significant impact on quality of life and because patients with arthritis are less active than the general population, they are at risk of additional conditions such as obesity, heart disease, diabetes, and hypertension. There are currently no disease modifying osteoarthritis (OA) drugs available; therefore anti-inflammatory, and/or analgesic medications such as acetaminophen and NSAIDs and simple analgesics form the mainstay of treatment. Coxibs may be preferred to traditional NSAIDs because of their improved gastrointestinal (GI ) safety and tolerability profile. The use of topical agents may also be beneficial in some patients. In rheumatoid arthritis (RA) where disease modifying drugs (DMARDs) are available, anti-inflammatory agents such as NSAIDs and coxibs are used as adjuncts to disease modifying therapy. However, patients with RA are at increased risk of NSAID-related GI injury, particularly if they are also on corticosteroid medication. Pharmacological treatment of both RA and OA should be combined with appropriate nonpharmacological modalities such as patient education, exercise programs, and joint motion and strengthening exercises. Such activities may delay joint degradation and help maintain physical function.
15474389 Evaluation of metacarpophalangeal joint synovitis in rheumatoid arthritis by power Doppler 2004 Sep OBJECTIVE: To evaluate intra-articular vascularization and flow patterns of the metacarpophalangeal (MCP) joints in rheumatoid arthritis (RA) patients by using power Doppler technique. The relationship between the flow patterns and the regional bone mineral density (BMD) measurements of MCP joints using dual-energy X-ray absorptiometry (DXA) was also assessed. METHODS: Fifteen patients (mean age 48.5 +/- 13.8) with a disease duration of 6.8 +/- 4.9 years were included into the study. Thirty MCP joints of three healthy subjects were also assessed as controls. Clinical activity of MCP joint inflammation was classified according to a modified index for synovitis activity based on joint swelling, warmness and pain. Ultrasonography was performed using LOGIQ 7 unit by means of a 6-13 MHz linear array transducer. Gray-scale US and power Doppler sonography (PDS) examination was performed. Using spectral Doppler the quality of flow was determined and the indices of pulsatility (PI) and resistance (RI) were measured in longitudinal plane. The erosive scores of the MCP joints were determined on the plain hand radiographs using Sharp/van der Heijde method. Hand BMD, MCP BMD and the ratio of MCP BMD to whole hand BMD (rBMD) were measured using a Lunar DPX densitometer. RESULTS: Total 150 MCP joints of 15 patients and 30 MCP joints of three healthy controls were examined in both hands. Flow was determined in 31 joints (10 moderately active, 21 active) in eight patients whereas seven patients had no quantifiable flow in MCP joints. MCP joints of healthy controls had no quantifiable flow. Mean PI of these joints were 2.17 +/- 2.37 in moderately active and 2.12 +/- 1.93 in active MCP joints. RI was 0.76 +/- 0.12 in moderately active and 0.75 +/- 0.15 in active MCP joints. There was no significant difference in RI and PI of these active and moderately active MCP joints. There was a significant correlation between erosive scores and PI, RI of total MCP joints (r = 0.40 and r = 0.41, P < 0.05). PI and RI also negatively correlated with rBMD (r = -0.46, P < 0.01 and r = -0.36, P < 0.05, respectively). PIc was 4.07 +/- 3.26 and RIc was 0.88 +/- 0.16 in the neighboring soft tissues which were significantly higher than PI and RI of MCP joints (P < 0.001). CONCLUSION: Power Doppler ultrasonography (PDUS) is a useful method demonstrating synovial vascularization and flow patterns and offers new alternatives for monitoring disease activity and measurement of therapeutic response. Flow patterns had intimate correlation with intra-articular bone and cartilage destruction.
15061567 Phagocytes: mechanisms of inflammation and tissue destruction. 2004 Feb Macrophages and neutrophils are the professional phagocytes of the innate immune system. Once in the inflammatory joint or the vasculitic lesion, macrophages and neutrophils contribute to the pathology observed. This article examines the mechanisms by which phagocytes contribute to the pathogenesis of these diseases.