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ID PMID Title PublicationDate abstract
11557647 Predictors of radiographic joint damage in patients with early rheumatoid arthritis. 2001 Oct OBJECTIVE: To determine factors at diagnosis, associated with radiographic damage at diagnosis and after one year, in patients with early rheumatoid arthritis (RA). METHODS: New patients with early RA were followed up for one year. Possible prognostic factors were duration of complaints, morning stiffness, disease activity score (DAS28), functional status (Health Assessment Questionnaire (HAQ) score), rheumatoid factor (IgM RF), and C reactive protein (CRP). Outcome was defined as radiographic damage of the hands and feet (Sharp/van der Heijde score). For the statistical analysis, one way analysis of variance and a forward stepwise logistic regression model was used. RESULTS: 130 patients with RA (68% female; median age 64 years, range 21-86) were included. Despite the fact that the median duration of complaints was short (15 weeks, range 2-106) the radiographic damage at diagnosis was significantly correlated with the duration of complaints (p<0.05). Patients with a duration of complaints of >34 weeks had significantly more radiographic joint damage at diagnosis than patients with a shorter duration of complaints. Radiographic progression at one year was correlated with high radiographic joint damage, high CRP level, and a positive IgM RF at entry. CONCLUSIONS: In early RA, the number of radiographic lesions was correlated with a longer duration of complaints at the first visit. Progression of these lesions was predicted by a high baseline joint damage, high CRP level, and a positive IgM RF. Further reduction of the delay in referral and early treatment may further decrease joint damage in patients with recent onset polyarthritis.
11469525 Extraction and validation of a lower limb HAQ by comparison with objective measurement of 2001 OBJECTIVES: Both the Health Assessment Questionnaire (HAQ) and the measurement of spontaneous ambulatory activity are measures that can be used to evaluate disability in RA. METHODS: A cross sectional survey was conducted of 105 RA patients where the HAQ was compared with ambulatory activity from the Numact monitor. Rank correlation was used to evaluate the relationships between activity and the complete and individual sections of the HAQ. RESULTS: Correlation of activity with total HAQ produced significant results (r= -0.29 to -0.48). Correlation with individual sections showed the strongest association with "Hygiene", followed by "Activities", and "Walking". A lower limb HAQ was devised using these and the dressing and rising items. CONCLUSIONS: HAQ and recorded activity measure different but related aspects of disability. Activity should be used if the ability to quantify the result outweighs the extra effort involved in the study.
11578017 Antifilaggrin antibodies in early rheumatoid arthritis may predict radiological progressio 2001 OBJECTIVE: To elucidate the possibility that autoantibodies to filaggrin, detected in patients with early RA (having a disease duration of not more than one year), may predict joint destruction assessed after five years of observation. METHODS: This is a 5 yr extension of a previous study (1) of 112 consecutive patients with early RA. Serum antifilaggrin autoantibodies were detected by immunoblotting (AFA) and by indirect immunofluorescence ("AKA"). DAS28, pain on a VAS. HAQ, and CRP were measured. Plain X-ray films were taken from hands and forefeet and a Larsen score was calculated. RESULTS: Ninety-two of the original 112 patients had baseline X-rays available and constituted the study material. At 5 year follow-up, 67 of these 92 have been assessed and for 63 of these X-rays were available. For the whole patient material, significant radiological progression, measured by Larsen scores, occurred while disease activity and function (pain VAS, DAS28, CRP, and HAQ) improved significantly over five years. The groups of patients having AFA or "AKA" at baseline had significantly (p=0.006 and p<0.001, respectively) higher Larsen scores five years later than the groups without these antibodies. No clear relation of these antibodies to disease activity or function was demonstrated, except that the group of patients with "AKA" had significantly higher median CRP (p=0,003) after five years. CONCLUSIONS: The present study shows that antifilaggrin autoantibodies may predict radiological progression. The prognostic value of these antibodies will be further evaluated in relation to other potential markers in a larger patient material.
11469486 Evaluation and documentation of rheumatoid arthritis disease status in the clinic: which v 2001 Jul To determine in clinical practice which rheumatoid arthritis (RA) clinical status variables are most associated with a change in disease modifying antirheumatic drug (DMARD) therapy, we studied 26,240 observations from 1905 RA patients occurring over 25 years. Variables included tender joint count, erythrocyte sedimentation rate (ESR), grip strength, visual analog scale for pain, global severity, fatigue and sleep, Health Assessment Question functional disability scale (HAQ), anxiety, depression and morning stiffness. Only the tender joint count required a physician. Observations at which a change in DMARD therapy occurred were compared to those where a change did not occur using generalized estimating equations (GEE) and classification and regression tree analysis (CART). Tender joint count, pain, global severity, and ESR were the 4 variables most strongly predictive of DMARD change. CART modeling indicated a special role for fatigue and sleep disturbance in some patients. These data add support in clinical practice for the ACR core set and the DAS set of variables. In addition, they validate the use of these variables in a practice setting. We suggest a minimum set of evaluations comprising: joint count, ESR or CRP, measures of pain and/or severity, a fatigue scale (fatigue being a surrogate for sleep disturbance), and a measure of function such as the HAQ or modified HAQ. Because only joint count requires physician participation, these evaluations are practical for the clinic, and allow quantitative measurement of RA status. With the use of quantile charts, the comparative status of RA and the change in RA status can be determined easily.
9769721 [Circadian rhythm in hand grip strength in patients with rheumatoid arthritis]. 1997 In 34 inpatients, 22 with diagnosis of rheumatoid arthritis according to revised ACR criteria and 12 with diagnosis of other diseases without affection of the hands served like control group we measured grip strength in 4 time period during the day (7, 11, 15, 19 hours) with the Martin's vigorimeter. Mean grip strength value was statistically lower in patients with rheumatoid arthritis in all four time periods (P < 0.005). There is general trend of the rising grip strength since morning to evening without statistically relevance. Grip strength firmly linear negatively correlated with the grade of morning stiffness.
10949812 [Eye complications in 458 children with rheumatoid arthritis]. 2000 Jul BACKGROUND: Besides arthritis or other systemic manifestations, endogenous inflammation (most commonly uveitis) can be a symptom of rheumatoid arthritis in children. The uveitis of children shows certain differences compared to that in adults. This study will show these differences and their incidences. PATIENTS AND METHODS: Retrospective analysis of the histories of 458 children that were admitted to the pediatric clinic due to rheumatism related diseases. An analysis of the general and pediatric data, laboratory results and therapy were combined with the ophthalmologic data. RESULTS: 45 (9.8%) of the 458 patients suffered from uveitis at least once during the studied time period between 1992 and 1996. Most common complications of the therapy were clouding of the lens up to full cataract (in both eyes in eight out of nine patients). Seven patients underwent cataract operation. Further complications are synechiae, band shaped keratopathy, secondary glaucoma and retinal diseases. CONCLUSION: Since the pediatric uveitis usually does not take an acute course and since children rarely can articulate themselves precisely, a regular ophthalmologic examination of pediatric rheumatology patients is necessary, as well as every uveitis in children should warrant pediatric-rheumatologic diagnostics. The impact of uveitis is much more severe for children when compared to adults, since it not only endangers the vision but the whole development of the child.
10529122 Analysis of serial synovial biopsies in patients with rheumatoid arthritis: description of 1999 Oct OBJECTIVE: Analysis of serial synovial biopsy specimens is increasingly used as an outcome measure for the evaluation of therapeutic interventions. However, observations in placebo treated groups are scarce. We describe the immunohistologic features of the synovium in placebo treated patients with RA and in those who received interleukin 10 (IL-10). METHODS: Ten patients with active RA received dosages of either placebo (n = 7) or 5 microg/kg (n = 1) or 10 microg/kg (n = 2) of recombinant human IL-10 (rhIL-10; SCH 52000, Schering-Plough, Kenilworth, NJ, USA) daily for 28 consecutive days. Synovial biopsy specimens from the knee joint were obtained by needle arthroscopy before and 4 weeks after initiation of treatment. Immunohistochemistry was performed using monoclonal antibodies specific for the following surface markers and cytokines: CD3, CD4, CD8, CD38, CD68, CD55, IL-1beta, IL-6, and tumor necrosis factor-alpha. RESULTS: No patient exhibited clinical improvement after treatment with placebo or any rhIL-10 dosage. Microscopic analysis of synovial tissue revealed no significant change in the scores for infiltration by inflammatory cells or in the scores for the expression of cytokines after treatment. CONCLUSION: Studies of serial synovial biopsies from patients treated with placebo or IL-10 revealed no changes in immunohistologic scores. This suggests that the biopsy procedure itself has no effect on the features of the synovium.
10902748 Relationship between time-integrated C-reactive protein levels and radiologic progression 2000 Jul OBJECTIVE: An elevated acute-phase response is associated with increased radiologic damage in rheumatoid arthritis (RA), but development of damage in previously normal joints ("new joint involvement") has not previously been investigated. This study was undertaken to investigate the hypothesis that when there is suppression of disease activity as judged by the C-reactive protein level, new joint involvement is reduced to a greater extent than is progression in already damaged joints ("damaged joint progression"). METHODS: Three hundred fifty-nine patients with active RA were studied as part of a 5-year randomized, prospective, open-label study of disease-modifying antirheumatic drug therapy. Time-averaged CRP was calculated from samples obtained every 6 months, and patients were divided into groups with CRP values of <6, 6-<12, 12-<25, and > or =25 mg/liter. Radiographs of the hands and feet were scored by the Larsen method; a damaged joint was defined as one with a score of > or =2. RESULTS: The rank correlation between time-integrated CRP and increase in Larsen score was 0.50; the correlation increased to 0.59 for patients entering the study with disease duration of < or =2 years. The percentage of new joint involvement over 5 years varied markedly with time-integrated CRP, from 7.3% in the CRP <6 mg/liter group to 39.1% in the CRP > or =25 mg/liter group (5.4-fold increase). The percentage of damaged joint progression increased from 26.1% in the CRP <6 mg/liter group to 41.6% in the CRP > or =25 mg/liter group (1.6-fold increase). CONCLUSION: The results of this study provide further confirmation that high CRP levels over time are associated with greater radiologic progression. Although radiologic progression still occurred in both previously normal and damaged joints despite the presence of normal CRP levels, this consisted of proportionately less new joint involvement compared with damaged joint progression. These findings support the idea that disease-suppressive therapy should be instituted at an early stage in patients with RA, before erosive damage has occurred.
11407685 A novel single-nucleotide polymorphism at the 5'-flanking region of SAA1 associated with r 2001 Jun OBJECTIVE: To address whether the gamma haplotype at exon 3 of the SAA1 gene is directly associated with type AA amyloidosis or is merely in linkage with an unknown polymorphism that is primarily associated with disease risk, we examined the SAA1 gene for new polymorphisms. METHODS: We analyzed DNA samples from 44 rheumatoid arthritis (RA) patients with AA amyloidosis (amyloid group), 55 RA patients without AA amyloidosis (RA group), and 58 non-RA healthy subjects (non-RA group). We also examined DNA samples from 50 Caucasians to compare linkage disequilibrium relationships involving SAA1 region polymorphisms between Japanese and Caucasoid populations. RESULTS: We observed 3 novel single-nucleotide polymorphisms (SNPs) in the 5'-flanking region of SAA1: -61C/G, -13T/C, and -2G/A. Comparison of allele frequencies and ratios of individuals with particular alleles between the study groups revealed statistically significant differences between the amyloid and RA groups and between the amyloid and non-RA groups. Statistical analysis revealed that the -13T/C SNP was strongly associated with AA amyloidosis. In addition, we found tight linkage between the -13T allele and the alpha haplotype, rather than the beta haplotype, at exon 3 in the Caucasoid population, while -13T was closely linked to the gamma and beta haplotypes, rather than the alpha haplotype, in the Japanese population. Since the linkage disequilibrium relationship was reversed between the Japanese and Caucasoid populations, different exon 3 haplotypes of SAA1 are found to be associated with the risk of AA amyloidosis in different ethnic groups. CONCLUSION: Our data suggest that the SAA1 -13T allele, rather than SAA1 exon 3 haplotypes, is primarily associated with AA amyloidosis risk.
9376976 Perioperative use of methotrexate--a survey of clinical practice in the UK. 1997 Sep We have surveyed the use of methotrexate in the perioperative period in patients with rheumatoid arthritis (RA) undergoing surgery. A total of 200 consultant rheumatologists and 200 consultant orthopaedic surgeons in the UK were sent a postal questionnaire. Thirty-five per cent of rheumatologists and 46% of orthopaedic surgeons were concerned that the drug may increase the risk of post-operative complications, although significantly less 'always' stopped the drug around the time of surgery. There was great variation in the timing of stopping the drug with most stopping treatment within 2 weeks before surgery and restarting within 2 weeks after surgery. The majority of clinicians surveyed (70%) felt that national guidelines for the perioperative use of methotrexate would be helpful.
11352235 Leflunomide-associated weight loss in rheumatoid arthritis. 2001 May OBJECTIVE: To determine the frequency of weight loss in patients treated with leflunomide for rheumatoid arthritis at an arthritis referral center. METHODS: We queried 35 rheumatologists at the Robert Breck Brigham Arthritis Center to determine if weight loss had occurred as an adverse event in patients treated with leflunomide between November 1998 and January 2000. Five such patients were identified and their clinical course was reviewed. RESULTS: Five of 70 patients who had begun leflunomide therapy had significant weight loss that could not be linked to other identifiable etiologies. The amount of weight loss was substantial in this group of patients, ranging from 19 pounds to 53 pounds. All patients had normal levels of thyroid-stimulating hormone and no other gastrointestinal complaints; evaluation revealed no other cause for the weight loss. Despite the significant weight loss, 4 of the 5 patients continued to take the drug due to its efficacy. CONCLUSION: Significant weight loss is a potential adverse event in patients with rheumatoid arthritis treated with leflunomide. Awareness of this may obviate the need for extensive medical evaluations.
10846698 [Study of bone mineral density in postmenopausal women with rheumatoid arthritis treated w 2000 Apr 1 BACKGROUND: To study bone mineral density (BMD) in a group of postmenopausal women with rheumatoid arthritis (RA) treated with low doses of corticosteroids. PATIENTS AND METHODS: One hundred and eleven patients were included. Mean age (SD) was 63.8 (8.8) years, mean duration of postmenopausal period was 16.4 (10.1) years and the mean disease duration was 12.5 (8.2) years. RESULTS: A significant reduction of lumbar BMD (p < 0.05) and femoral BMD (p < 0.0001) was observed. The prevalence of osteoporosis was of 47%. CONCLUSIONS: The study supports, in the Spanish population, that postmenopausal women with RA treated with low doses of corticosteroids, have low BMD. We consider that the prevalence of osteoporosis in these patients is high.
10204847 Genetic analysis of the 3' untranslated region of the tumour necrosis factor shows a highl 1999 Mar Tumour necrosis factor (TNF) is a key proinflammatory mediator in rheumatoid arthritis (RA). The TNF locus, situated in the class III region of the MHC, is flanked by five microsatellite markers. It has previously been shown that this region influences susceptibility to RA; two TNF microsatellite haplotypes were found to be associated with RA. Evidence from murine studies has indicated that variation in the TNF 3' untranslated region (UTR) could be associated with altered regulation of TNF biosynthesis. In order to identify possible RA associated polymorphisms, more than 800 bp of the TNF 3' UTR was genetically analysed in RA affected and unaffected subjects possessing specific RA and non-RA associated TNF microsatellite haplotypes. The TNF 3' UTR region was analysed using two mutation detection methods, PCR-SSCP and NIRCA analysis and DNA sequencing. No genetic differences were observed in the human TNF 3' UTR between subjects, that is, irrespective of RA status or TNF haplotype, and also compared with previously published TNF sequences from human sources. Therefore it can be concluded that the TNF 3' UTR in this population was highly conserved and did not influence susceptibility to RA.
11845344 Reliability of the transepicondylar line as a parameter of femoral axial alignment. 2001 The purpose of this research was to determine the significance of the transepicondylar line as a parameter of femoral axial alignment. Standing full-length X-ray films of 124 knees of 91 patients (63 women, 28 men) with osteoarthritis, rheumatoid arthritis, or osteonecrosis were used in this study, in which the lateral angles formed by the femoral anatomical axis intersecting with the transepicondylar line (angle a'), horizontal line (angle b'), and femoral condylar line (angle r') were measured. The mean value of angle b' in knees with neutral alignment was significantly smaller than that in knees with varus alignment, and significantly larger than that in knees with valgus alignment; no significant difference was found in angle a'. Also, there was no significant difference in angle a' among the patients with osteoarthritis, rheumatoid arthritis, and osteonecrosis. These findings suggest that the transepicondylar line, which is a stable reference of femoral rotation, is also a very reliable parameter of axial alignment of the femur. In the future design of extramedullary guiding for total knee arthroplasty, the transepicondylar line may play an important role as a parameter for proper and accurate implant setting.
10622199 Correlation between objective and subjective measures of hand function in patients with rh 1999 Oct The association between the Sollerman test of hand grip and the Sequential Occupational Dexterity Assessment (SODA) and their relationship to impairment and subjective disability measures were examined. Twenty-five patients with rheumatoid arthritis affecting their hands participated in a clinical and subjective evaluation. Clinical evaluation included the use of the two hand function instruments and measurement of finger range of motion. Subjective evaluation was done by means of a patient questionnaire comprising 20 questions from the Health Assessment Questionnaire and by visual analog scales for rating pain severity and hand function. Results confirmed a strong association between the Sollerman test of hand grip and the SODA. Both instruments were found to correlate significantly with subjectively assessed hand function. Associations between the results of the two hand function tests and subjective pain and disability assessments in global daily tasks were weak. The SODA instrument more consistently correlated to the limitations in finger motion than did the Sollerman test of hand grip. This study demonstrates that the SODA and the Sollerman test of hand grip produce similar information under controlled conditions in this patient group despite their differences in conceptual development and measurement properties. A generalized measure such as the Health Assessment Questionnaire or the pain visual analog scale alone is insufficient to represent what patients can do with their hands in daily life.
10589370 Combination biologic therapy. 1999 Nov Biologic therapies refer to genetically engineered treatments such as monoclonal antibodies and receptor-immunoglobulin fusion proteins. Following many disappointments, the introduction of anti-tumor necrosis factor (anti-TNF alpha) therapies into the clinic has clearly demonstrated the exciting potential of biologic agents. Many of these have been designed to modulate a specific aspect of the underlying autoimmune process, thus avoiding generalized immunosuppression. They include products which interfere with the trimolecular complex of major histocompatibility complex II-Antigen-T cell receptor interaction; others designed to block the secondary signals for T cell activation and T cell interaction with antigen-presenting cells; and cytokine agonists as well as antagonists. Whilst reducing the degree of global immunosuppression associated with therapy, this targeted specificity may reduce the likelihood that a single therapeutic agent will provide long-term disease control. On the other hand, animal models have demonstrated synergy of combination biologic therapy, particularly for the re-induction of self-tolerance. As our knowledge of immune physiology and, particularly, immune regulation improves, it can be expected that many combination biologic therapies will be tested in the clinic. Pilot studies of combined anti-CD4 and TNF alpha blockade are underway; combination use of TNF alpha and interleukin-1 beta inhibitors are expected. This article reviews the potential for combination biologic therapy, including likely adverse effects, for the treatment of rheumatoid arthritis and other autoimmune diseases.
11338857 [Comparative evaluation of tissue microcirculation in patients with aseptic necrosis of th 2001 AIM: Comparative investigation of tissue microcirculation above hip joints affected with verified aceptic necrosis of the heads of the femur (ANHF) in patients with rheumatoid arthritis (RA) and SLE. MATERIAL AND METHODS: The microcirculation was compared in 44 RA and 22 SLE patients. Capillary blood flow above the necrotic heads of the femur was studied by 133-Xe clearance from the intratissue depot. Laser doppleroflowmetry examined basal blood flow and factors of its regulation. RESULTS: Effective skin blood flow decreased both in RA and SLE patients at ANHF stage I, remained low at stage II, went up a little at stage III. At stage IV the flow continued to rise in RA patients but fell sharply in SLE. Laser dopplerflowmetry with functional tests reflects ANHF evolution both in RA and SLE. CONCLUSION: Changes in capillary blood flow in SLE above the necrotic heads of the femur are more severe and account for more extensive destruction in the heads of the femur than in patients with RA.
10371277 Serum MMP-3 in rheumatoid arthritis: correlation with systemic inflammation but not with e 1999 May OBJECTIVE: Metalloproteinases (MMP) play an important role in the remodelling of the extracellular matrix. However, evidence that they are responsible for tissue damage in pathological situations remains circumstantial. Stromelysin (MMP-3) production is increased in rheumatoid arthritis (RA), and has been proposed as a marker of joint damage. The relevance of serum levels of MMP-3 to erosions in RA was studied. METHODS: Fifty-three patients with active RA of > 5 yr duration and with available X-rays were stratified according to disease duration. Hand X-rays were scored for erosions. Patients were then classified into upper and lower quartiles. Serum MMP-3 levels were compared between these two groups. RESULTS: No significant differences in serum MMP-3 were seen between high and low eroders. A statistically significant correlation was observed between sMMP-3 and erthyrocyte sedimentation rate and C-reactive protein. CONCLUSIONS: Serum MMP-3 is not an independent marker of joint damage, but is correlated with systemic inflammation. Its precise role in joint damage in RA remains to be elucidated.
9156592 [A proposal for the MR staging of early rheumatoid arthritis in the metacarpophalangeal an 1997 Mar PURPOSE: MRI can demonstrate pathology of joint disease in the early course of rheumatoid arthritis prior to destructions seen on conventional radiographs. In a prospective study, we tried to develop a systematical classification of joint pathology demonstrated by MRI, which would be essential for scoring the course of the disease. PATIENTS AND METHOD: Metacarpophalangeal and interphalangeal joints of 48 patients suffering from early rheumatoid arthritis (mean disease duration: 6.4 months) were evaluated by MRI using a high-resolution transmitter-receiver coil. Examinations included 2 mm sliced T2-, T1- and gadolinium enhanced T1-SE sequences in coronal and axial orientation. In consideration of pathological findings on MRI and histopathogenetical pathways of destruction in rheumatoid arthritis a MR-score (0-5) was established. RESULTS: This allowed to score each joint examined: score 0 (normal) in 47.8%/49.5%, score 1 in 35.5%/50.5%, score 2 in 4.2%/0%, score 3 in 10.8%/0%, score 4 in 1.5%/0% of the metacarpophalangeal/interphalangeal joints, respectively. CONCLUSIONS: Using the MR-score a relative individual destruction number can be calculated, which may be used to follow up patients in the early course of rheumatoid arthritis (e.g. drug therapy studies). The presented MR scoring system has to be evaluated further in longitudinal studies and must be correlated to radiographical and clinical findings.
9043932 Generation of reactive oxygen species is required for bucillamine, a novel anti-rheumatic 1997 Jan Rheumatoid arthritis (RA) is considered to be a proliferative disorder of synovial tissue, which is composed of macrophage-like, fibroblast-like and dendritic cells. Bucillamine (BUC) is a novel disease-modifying anti-rheumatic drug, which is a structural analogue of cysteine. Some of the pharmacological actions of BUC have been shown to depend on the generation of reactive oxygen species (ROS) in the presence of copper. In this study, we examined whether BUC in concert with copper can induce apoptosis via generation of ROS. THP.1, a human monocytic cell line, was used as surrogate for synovial cells. We observed that BUC plus copper can induce THP.1 to undergo apoptosis, as evidenced by the presence of DNA degradation, which is preceded by ROS generation and increase in membrane permeability. Moreover, catalase rescued THP.1 from BUC-mediated cell death, indicating that generation of ROS is essential for the induction of apoptosis Red blood cells (RBC), probably acting as a scavenger of ROS, also rescued THP.1 from cell death mediated by BUC plus copper. Collectively, we suggest that ROS derived from BUC in the presence of copper may suppress the outgrowth of rheumatoid arthritis synovial cells in vivo through the induction of apoptosis.