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ID PMID Title PublicationDate abstract
9407573 Psychosocial factors in fibromyalgia compared with rheumatoid arthritis: I. Psychiatric di 1997 Nov OBJECTIVE: Recent studies of the relationship between fibromyalgia and psychiatric disorders have yielded conflicting findings, and many of these inconsistencies seem to result from methodological differences. METHOD: We compared 36 patients with fibromyalgia and 33 patients with rheumatoid arthritis from a tertiary care clinic using physician-administered, structured psychiatric interviews and self-reported measures of illness appraisal, coping, and functional disability. RESULTS: Patients with fibromyalgia had significantly higher lifetime prevalence rates of mood and anxiety disorders, as well as higher mean numbers of medically unexplained physical symptoms across several organ systems. Ninety percent of the patients with fibromyalgia had a prior psychiatric diagnosis compared with less than half of the patients with rheumatoid arthritis. CONCLUSIONS: Despite the absence of organic pathology, the patients with fibromyalgia had equal or greater functional disability and were less well adapted to their illness. Although the pathophysiology of fibromyalgia remains unclear, co-morbid psychiatric disorders and functional disability remain an important focus of treatment in this population.
10666859 [Mannerfelt arthrodesis of the wrist joint in patients with chronic polyarthritis. A retro 1999 Nov AIM: Mannerfelt established his technique of wrist arthrodesis with stabilisation by an intraosseous rushpin as a secure method for patients with rheumatoid arthritis. This study was performed to evaluate the mid-term results in a consecutive group of patients. METHODS: Out of a group of 39 operations 24 wrist arthrodeses (61%) in 19 patients have been followed 12-96 months postoperatively (average 44 mths) by clinical testing and radiographic examination. All operations were performed in the original technique. All patients suffered from rheumatoid arthritis in an advanced stage (Larsen III-V). RESULTS: All but one patient were free of pain. Function and strength of the hand increased significantly in all patients. All patients had additional resection of the ulnar head that led to normal pro-supination of the forearm. 18 patients were very satisfied with the result of the procedure. All but one of the wrists showed complete fusion. In one case there was an intraoperative perforation of the pin through the radial cortex, in another case we saw a fissure of the shaft of the third metacarpal bone. One patient showed a dysesthesia in the third finger. CONCLUSION: The results in this group of patients confirmed the advantages of Mannerfelt's technique such as simple operative technique, high fusion rate and low incidence of complications.
9536824 Analysis of T cell receptor V alpha polymorphisms in rheumatoid arthritis. 1998 Jan OBJECTIVE: To test for association of T cell receptor (TCR) V alpha polymorphisms and rheumatoid arthritis (RA) in British and Swiss white populations. METHODS: TCRAV polymorphisms were analysed in RA patients and controls by single strand conformational polymorphism (SSCP) analysis. Associations were sought between defined genotypes and RA, and the effect of HLA-DR4 status analysed. Putative associations were then retested further in new groups of patients and controls. Overall, 360 RA patients and 197 controls were studied. RESULTS: No association between TCRAV5S1, V6S1, V8S1, V17S1 or V21S1 polymorphisms and RA were observed in the initial population screened. Stratification for DR4 status showed an increase of V5S1*01/*01 in DR4 positive versus DR4 negative patients (chi 2 = 7.19, p = 0.028 (2df), p = 0.14 after correction for multiple comparisons). This putative association was tested in three further patient groups, none of which showed significant increase of V5S1*01/*01 in DR4 positive patients, although an overall trend towards an increase in V5S1*01/*01 was observed. CONCLUSION: No evidence was found for a strong association of TCRAV genes and RA in a white population. However, these results suggest a weak association of V5S1*01/*01 with DR4 positive RA, although this requires confirmation using larger groups of patients and controls.
9080302 A detailed lectin analysis of IgG glycosylation, demonstrating disease specific changes in 1997 Feb Serum IgG from rheumatoid arthritis patients contains a decreased number of oligosaccharide structures ending in galactose and thus there is an increase in N-acetylglucosamine as the terminal sugar, compared with healthy individuals. The relationship between these two sugars varies depending on the disease examined: IgG from patients with rheumatoid arthritis, juvenile onset chronic arthritis and Crohn's disease are at one extreme, and exhibit a reciprocal galactose:N-acetylglucosamine relationship, while Sjögren's syndrome and osteoarthritis IgG are at the other extreme, exhibiting a parallel increase in the expression of both galactose and N-acetylglucosamine. These results may occur as a consequence of more than one glycosylation site which is differentially glycosylated, but more likely by changes in the level of bisecting N-acetylglucosamine.
9487258 Elderly-onset rheumatoid arthritis and its association with HLA-DRB1 alleles in Japanese. 1998 Jan To assess the association between HLA-DRB1 and elderly-onset rheumatoid arthritis (RA) (EORA) in Japanese people, we analysed the HLA-DRB1 antigen frequencies of EORA patients. The age at onset distribution of 852 Japanese RA patients was analysed, and EORA was defined as an age at onset of 60 yr or older. Among the 852 RA patients, 120 (14.1%) were EORA patients. Their HLA-DRB1 antigen frequencies were assessed for significant deviation from those of the control (n = 652) and adult-onset RA (AORA; disease onset between 16 and 59 yr; n = 732) groups. The Japanese EORA patients were positively associated with DRB1*0101, *0405 and *1502, and the relative risks were 2.7, 1.9 and 2.2, respectively. The frequency of DRB1*1502 was also significantly higher among the EORA patients than in the AORA patients. The EORA patients showed different trends from the AORA patients in their frequency of HLA-DRB1 alleles, which suggests that EORA may be a different subset from AORA in light of its immunogenetic background.
10190600 Biaxial wrist replacement. Initial results in the rheumatoid patient. 1999 Feb We report a short term review of 26 patients after Biaxial total wrist replacement. The mean follow up was 33.6 months (range, 24-62). All except one patient with psoriatic arthropathy had either seropositive or negative rheumatoid arthritis. A significant improvement in the range of motion was obtained; however, only 14 of 26 achieved a "functional" range. Eighteen obtained an excellent or good result when graded using the Hospital for Special Surgery score. Two radial and three carpal components showed radiolucent lines. Follow-up, however, was too short to determine whether this indicates progressive loosening.
9317160 Constitutive intra-articular expression of human IL-1 beta following gene transfer to rabb 1997 Oct 1 To investigate the pathophysiologic effects of chronically elevated intra-articular levels of IL-1 beta, we used an ex vivo gene transfer method to deliver and express human IL-1 beta (hIL-1 beta) in the knee joints of rabbits. Expression of hIL-1 beta resulted in a severe, highly aggressive form of arthritis analogous to chronic rheumatoid arthritis in humans. Intra-articular manifestations included intense inflammation, leukocytosis, synovial hypertrophy and hyperplasia, and highly aggressive pannus formation with erosion of the articular cartilage and periarticular bone. Systemic effects were also observed, including diarrhea, fever, weight loss, and an increased erythrocyte sedimentation rate. In addition, the hIL-1 beta was found to induce elevated levels of both rabbit IL-1 beta and TNF-alpha in synovial fluid. Following the loss of hIL-1 beta transgene expression between 14 and 28 days post-transplantation, many of these changes began to normalize. These results suggest that chronically elevated intra-articular levels of IL-1 beta alone are sufficient to produce virtually all the pathologies found in rheumatoid arthritis, and furthermore, demonstrate that gene transfer can be used to investigate the roles of specific gene products in the pathogenesis of arthritis.
11315915 The stress protein BiP is overexpressed and is a major B and T cell target in rheumatoid a 2001 Apr OBJECTIVE: The ubiquitously expressed intracellular protein formerly designated p68 has been identified as autoantigen at both the antibody and the T cell level in rheumatoid arthritis (RA). METHODS: We used 2 independent approaches, Edman degradation and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry, to characterize p68, and we compared its features with those of the endoplasmic reticulum stress protein BiP. RESULTS: In synovial sections from RA patients, BiP was highly overexpressed as compared with control sections. Under in vitro stress conditions, BiP was found to translocate to the nucleus and the cell surface. BiP-specific autoantibodies were present in 63% of 400 RA patients, in 7% of 200 patients with other rheumatic diseases, and in none of the healthy subjects. Thus, BiP-specific autoantibodies represent a new diagnostic marker in RA. Furthermore, we found that BiP-specific T cell reactivity was altered in RA. In healthy individuals and patients with other rheumatic diseases, BiP-reactive T cells were undetectable. In RA, overt T cell reactivity to BiP was observed or could be induced by specifically blocking antigen presentation to potentially regulatory T cells. CONCLUSION: Since overexpression of BiP has been shown to decrease the sensitivity of cells to killing by cytotoxic T cells, BiP overexpression and BiP-specific autoimmunity may be involved in the pathogenesis of RA.
10555020 Intensified-dose (4 gm/m2) cyclophosphamide and granulocyte colony-stimulating factor admi 1999 Nov OBJECTIVE: To evaluate the feasibility, safety, and efficacy of intensified-dose cyclophosphamide (ID-CYC), followed by granulocyte colony-stimulating factor (G-CSF) administration for collection of peripheral blood hematopoietic stem cells (HSC), for patients with severe, refractory rheumatoid arthritis (RA). METHODS: Four patients with severe refractory RA were enrolled in this open study. They received a single infusion of CYC (4 gm/m2) at day 0 followed by G-CSF (5 microg/kg/day) from day 6 until the last day of leukapheresis (performed at the time of hematopoietic recovery) to harvest peripheral blood HSC. Patients were monitored for disease activity, adverse effects, and hematopoietic reconstitution following this procedure. RESULTS: For all patients, administration of ID-CYC induced an early, dramatic improvement of disease activity. Long-term followup indicates that partial disease relapse was observed for all patients. No adverse effect was directly attributable to the treatment procedure. For most patients, HSC collection was sufficient to provide a graft enriched in CD34+ cells by positive selection as well as an unselected rescue graft. CONCLUSION: Patients with severe, refractory RA can benefit from ID-CYC. This procedure, followed by G-CSF administration, appears safe and technically suitable. In addition, it allows immediate improvement of RA activity that can occasionally persist beyond 6 months.
17939240 Quantitative analysis of digitopalmar dermatoglyphics in women with rheumatoid arthritis. 1998 Quantitative analysis of digitopalmar ridge count was performed in 40 female patients with rheumatoid arthritis to assess the role of genetic factors. Twenty-two variables (ridge count on each of ten fingers, their sum on five and ten fingers, four traits on each palm, i.e. ridge count between a-b, b-c and c-d triradii, atd angles on two palms and their bilateral sum) were determined. The data obtained were compared with digitopalmar prints of 200 control group women. Statistically significant differences from the control group in terms of increased ridge count were found in nine variables, i.e. on the third, fourth and fifth finger bilaterally, and consequentially in the total ridge count on the fingers of the two hands and of both hands taken together. Dermatologyphics as one of the genetic methods could be used in the evaluation of the relative risk in family members with positive disease history.
11426007 Metacarpophalangeal joints in rheumatoid arthritis: laser Doppler imaging--initial experie 2001 Jul Laser Doppler imaging is a noninvasive method yielding a spatial perfusion map. With use of a near-infrared laser, elevated perfusion associated with the metacarpophalangeal joints was detectable in patients with active rheumatoid arthritis. Findings at laser Doppler imaging correlated with pain scores and synovitis detected at ultrasonography, whereas the power Doppler sign (red pixels inside the active green box) did not. Laser Doppler imaging has the potential to help assess soft-tissue inflammation.
11412819 Disease pattern recognition testing for rheumatoid arthritis using infrared spectra of hum 2001 Jun BACKGROUND: In view of the importance of the diagnosis of rheumatoid arthritis, a novel diagnostic method based on spectroscopic pattern recognition in combination with laboratory parameters such as the rheumatoid factor is described in the paper. Results of a diagnostic study of rheumatoid arthritis employing this method are presented. METHOD: The method uses classification of infrared (IR) spectra of serum samples by means of discriminant analysis. The spectroscopic pattern yielding the highest discriminatory power is found through a complex optimization procedure. In the study, IR spectra of 384 serum samples have been analyzed in this fashion with the objective of differentiating between rheumatoid arthritis and healthy subjects. In addition, the method integrates results from the classification with levels of the rheumatoid factor in the sample by optimized classifier weighting, in order to enhance classification accuracy, i.e. sensitivity and specificity. RESULTS: In independent validation, sensitivity and specificity of 84% and 88%, respectively, have been obtained purely on the basis of spectra classification employing a classifier designed specifically to provide robustness. Sensitivity and specificity are improved by 1% and 6%, respectively, upon inclusion of rheumatoid factor levels. Results for less robust methods are also presented and compared to the above numbers. CONCLUSION: The discrimination between RA and healthy by means of the pattern recognition approach presented here is feasible for IR spectra of serum samples. The method is sufficiently robust to be used in a clinical setting. A particular advantage of the method is its potential use in RA diagnosis at early stages of the disease.
9849754 Clinical trials on biologics in rheumatoid arthritis. 1998 Nov BACKGROUND: Cytokines and T cells play a major role in the pathogenesis of rheumatoid arthritis (RA). Biologic targeting is a novel therapeutic approach. Published trials in humans are discussed in this paper. METHODS: CD4-positive T cells, proinflammatory cytokines like TNF-alpha, IL-1, IL-6 and gamma-IFN were major targets for therapy. Biologics were constructed of monoclonal human and non-human antibodies, chimerics of both, antiinflammatory regulatory proteins like IL-1 receptor antagonist, IL-10, and fusion proteins consisting of receptors and immunoglobulins. RESULTS: More than 2000 humans with RA were exposed to biologics in the last decade. Both, toxic and safe, efficient and non-efficient drugs were tested. Phase II data could not confirm preliminary phase I data in several drugs tested. The pharmacokinetic profile of biologics is influenced by frequent induction of human anti drug antibodies. CONCLUSION: The major role of cytokines in RA has been confirmed. Due to the limited long-term experience immunomodulation does not replace conventional pharmacotherapy.
11094451 Cell-cell interactions in synovitis. Interactions between T lymphocytes and synovial cells 2000 Mechanisms whereby T lymphocytes contribute to synovial inflammation in rheumatoid arthritis are poorly understood. Here we review data that indicate an important role for cell contact between synovial T cells, adjacent macrophages and fibroblast-like synoviocytes (FLS). Thus, T cells activated by cytokines, endothelial transmigration, extracellular matrix or by auto-antigens can promote cytokine, particularly TNF alpha, metalloproteinase production by macrophages and FLS through cell-membrane interactions, mediated at least through beta-integrins and membrane cytokines. Since soluble factors thus induced may in turn contribute directly to T cell activation, positive feedback loops are likely to be created. These novel pathways represent exciting potential therapeutic targets.
11094421 Risk for rheumatic disease in relation to ethnicity and admixture. 2000 Risk of systemic lupus erythematosus (SLE) is high in west Africans compared with Europeans, and risk of rheumatoid arthritis (RA) is high in Native Americans compared with Europeans. These differences are not accounted for by differences in allele or haplotype frequencies in the human leucocyte antigen (HLA) region or any other loci known to influence risk of rheumatic disease. Where there has been admixture between two or more ethnic groups that differ in risk of disease, studies of the relationship of disease risk to proportionate admixture can help to distinguish between genetic and environmental explanations for ethnic differences in disease risk and to map the genes underlying these differences.
11507132 Posterior cruciate ligament-retaining total knee arthroplasty in patients with rheumatoid 2001 Aug BACKGROUND: Although initial reports on posterior cruciate ligament-retaining total knee arthroplasty in patients with rheumatoid arthritis have been encouraging, a high rate of late instability necessitating revision has been reported recently. The purpose of the present prospective study was to analyze the results of posterior cruciate ligament-retaining total knee arthroplasty in patients with rheumatoid arthritis. METHODS: Seventy-two posterior cruciate ligament-retaining total knee arthroplasties in fifty-one patients with rheumatoid arthritis were studied prospectively. All procedures were performed with the Miller-Galante I prosthesis. Eighteen patients (twenty-four knees) died before the eight-year follow-up and one patient (two knees) was lost to follow-up, leaving forty-six knees (thirty-two patients) for review. These forty-six knees were evaluated clinically (with particular attention to posterior instability) and radiographically at annual intervals for a mean of 10.5 years (range, eight to fourteen years). RESULTS: Forty-four (95%) of forty-six knees had a good or excellent result at a mean of 10.5 years. However, nine (13%) of the original seventy-two knees had revision of the implant, with six of the revisions performed because of failure of a metal-backed patellar component. The rate of survival at ten years was 93% 4% with femoral or tibial revision for any reason as the end point and 81% 5% with any reoperation as the end point. There was no aseptic loosening in any knee. Posterior instability was identified clinically and/or radiographically in two (2.8%) of the original seventy-two knees; both unstable knees were in the same patient. CONCLUSION: Posterior cruciate ligament-retaining total knee arthroplasty yielded satisfactory clinical and radiographic results in patients with rheumatoid arthritis at intermediate-term follow-up (mean, 10.5 years). Therefore, we believe that it remains an excellent treatment option for these patients.
9002004 The acute phase and function in early rheumatoid arthritis. C-reactive protein levels corr 1997 Jan OBJECTIVE: To discover whether normalization of C-reactive protein (CRP) in patients with rheumatoid arthritis (RA) results in stabilization of their functional state, and whether a measure of disease activity can be used as a predictor of functional outcome. To examine the relationship between change of CRP and Health Assessment Questionnaire (HAQ) over a 24 mo period to define the sensitivity of HAQ to change. METHODS: A prospective study of 109 consecutive patients who fulfilled the American College of Rheumatology criteria for RA and had elevated CRP before steroid or 2nd line therapy. A full clinical assessment including HAQ was performed at presentation and at 3, 6, 12, and 24 mo. On the basis of the change in CRP at 6 mo, patients were divided into 3 groups: (1) CRP suppression to normal, (2) 50% reduction in CRP, and (3) less than 50% CRP change. RESULTS: The 3 groups were clinically and immunologically similar at onset. At 6 mo the median HAQ fell to 5 (lower to upper quartiles 7.5 to 19) in Group 1 (CRP normalized, n = 34), 6 (3.75 to 10) in Group 2 (CRP reduced by 50%, n = 30), and 12 (6 to 18) in Group 3 (less than 50% CRP change, n = 44), p < 0.005 for Groups 1 and 2 versus Group 3. At 12 and 24 mo HAQ remained significantly lower in Groups 1 and 2 compared with Group 3. In Group 1, patients either maintained a normal CRP (n = 28) or their CRP became elevated (n = 6). Only in those patients in whom a re-elevation of the CRP occurred was deterioration in HAQ subsequently seen. CONCLUSION: Suppression of elevated CRP in patients with active RA is associated with improvement in functional score, whereas persistent elevation of CRP is associated with functional deterioration. Once abnormal CRP is suppressed, no functional deterioration is likely to occur without re-elevation in CRP. Therefore, elevated CRP provides a convenient short term correlation with functional outcome and can be used as a guide for therapy. A HAQ score is a sensitive indicator of change in early disease.
10371279 Familial aggregation of rheumatoid arthritis in The Netherlands: a cross-sectional hospita 1999 May OBJECTIVES: To study the familial aggregation of rheumatoid arthritis (RA) in The Netherlands and to analyse the effect of proband characteristics on the concordance rates for RA. Secondary aims were to compare the characteristics of patients in an early RA inception cohort with those of regular patients and to select Dutch families for the genome-wide scan carried out by the European Consortium on RA families (ECRAF). METHODS: A cross-sectional, hospital-based survey aimed to identify affected sibpair (ASP) families among our whole RA population. Familial RA, or an ASP family, was defined by the presence of at least two siblings fulfilling the 1987 ACR criteria for RA. RESULTS: The estimated prevalence for familial RA was 9.8% and similar to that found in previous hospital series. The true-positive reporting rate for RA in sibs was 60%. Sibship size in ASP families (mean +/- S.D. = 7.8+/-3.3) was significantly larger than in the Dutch population. Probands with familial RA were more often rheumatoid factor positive and had a longer follow-up. Male gender and history of joint replacements were associated with higher concordance rates for RA. However, regression analysis showed that, correcting for sibship size, the concordance rate for RA was largely not explained by proband characteristics. Compared to regular RA patients, our inception cohort encompassed more male and/or rheumatoid factor-negative patients, but had similar performance in the study and rate of familial aggregation. CONCLUSIONS: The familial aggregation of RA in The Netherlands is not increased and occurs preferentially in large sibships. Among proband characteristics, sibship size is most clearly related to the recurrence of RA in particular families. Patients' recognition of RA manifestations in relatives is not optimal.
9291856 Auranofin is safe and superior to placebo in elderly-onset rheumatoid arthritis. 1997 Aug The efficacy, toxicity and possible steroid-sparing properties of auranofin in the treatment of elderly-onset rheumatoid arthritis (EORA) were studied in a 2 yr prospective double-blind placebo-controlled clinical trial. Sixty-five patients with onset of arthritis after the age of 60 yr were randomized to either auranofin 3 mg b.i.d. [n = 31, age 70 (61-84) yr, median (range)] or placebo tablets [n = 34, age 72 (60-81) yr]. Oral prednisolone, starting dose 7.5 or 20 mg daily, was used as a rescue drug in patients with intolerable joint pain and stiffness and with C-reactive protein (CRP) > or = 20 mg/l, and was tapered down according to protocol guidelines. Patients receiving auranofin continued therapy for a longer period of time (55% completers) than those on placebo medication (18% completers). The auranofin group consumed significantly less prednisolone, 2.64 (0-11.85) mg/day [median (range)], compared to 5.0 (0-18.33) mg/day in the placebo group (P = 0.006). No group differences at 2 yr follow-up were found for changes in joint pain (P = 0.49), number of swollen joints (P = 0.61), Health Assessment Questionnaire score (P = 0.18) and radiographic damage score (Larsen-Dale index) of the hands (P = 0.84). Within-group changes in radiographic scores were also insignificant. The drop-out rate due to adverse events was surprisingly higher in the placebo group (41%) than in the auranofin group (10%) and, as expected, higher due to lack of effect (29 and 16%). The results indicate that auranofin is safe, superior to placebo and has steroid-sparing capacity in the treatment of EORA. The favourable radiographic outcome in both groups needs confirmation in future studies.
11469522 Slowing of disease progression in rheumatoid arthritis patients during long-term treatment 2001 Radiographic disease progression with leflunomide and sulfasalazine treatment was assessed in rheumatoid arthritis patients in a double-blind trial that was placebo controlled for the first 6 months. Completers at 6 months opted to continue on 12- and 24-month double-blind extensions; patients in the placebo group were switched to sulfasalazine. Changes in Larsen scores were assessed in evaluable patient cohorts at 6 (n=228), 12 (n=136), and 24 (n=65) months. Changes in Larsen scores and erosive joint counts with leflunomide and sulfasalazine at 6 months showed significantly less radiographic progression than placebo. Sustained retardation of radiographic progression was seen in the 24-month intent-to-treat cohorts (delta Larsen scores: leflunomide -0.07, sulfasalazine -0.03). Changes in erosive joint counts within the 24-month leflunomide cohort suggest halting of disease progression for patients who continued in the study for 2 years (leflunomide -0.92, sulfasalazine 0.80). Leflunomide was well tolerated with no unexpected adverse events during the 2-year period. This study demonstrates that slowing of disease progression with leflunomide, observed as early as 6 months, is maintained long term in patients who complete 2 years of treatment.