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ID PMID Title PublicationDate abstract
9666412 The burden of rheumatoid arthritis: facts and figures. 1998 Jul In the most recent comprehensive economic study in the United States, the cost of arthritis, including rheumatoid arthritis (RA) and osteoarthritis (OA), was $64.8 billion US in 1992. Of the total costs of these diseases, about half were due to expenditures for medical care (direct costs) and about half were due to lost wages (indirect costs). Studies of the cost of RA undercount the true costs of this illness. Overall, costing methods create a bias against illnesses that occur disproportionately among women. The bias arises because the women with these conditions have historically had much lower labor force participation rates than men, and because women earn lower wages than men for similar work. In addition, there are many effects of RA that cannot be easily priced in the marketplace, although they are vital to the person and family affected by this disease. New approaches to therapy, which include earlier and more aggressive intervention, new drugs, and combinations of drugs, appear necessary to provide adequate control of inflammation, so that the longterm damage of RA might be prevented and the considerable costs reduced. The incremental costs, side effects, and benefits of therapies, compared to the average costs of disease, become much more relevant in policy discussions and clinical decision making. The possible adverse effects and costs of treatment must be balanced against the adverse effects and underestimated costs of RA.
10390967 [Chronic eosinophilic pneumonia associated with rheumatoid arthritis]. 1999 Apr We encountered a 45-year-old woman with chronic eosinophilic pneumonia associated with rheumatoid arthritis. In May 1997, she was given a diagnosis of rheumatoid arthritis and prescribed non-steroidal anti-inflammatory drugs. After a month, she visited our hospital because of fever and cough. A chest roentgenogram and computed tomographic scan on first admission revealed peripheral infiltrative shadows in the upper fields of both lungs. Approximately 30% of peripheral blood cells were eosinophils. Furthermore eosinophils were elevated in bronchoalveolar lavage fluid and transbronchial lung biopsy specimens. A conclusive diagnosis of chronic eosinophilic pneumonia was made on these grounds. The patient responded well to steroid treatment, but was readmitted a week later because of worsening joint pain and skin eruptions in the lower extremities of both legs. A skin biopsy showed perivascular and interstitial eosinophil infiltration. The combination of steroids, a disease modifying anti-rheumatic drug, and a non-steroidal anti-inflammatory drug proved to be effective.
11592367 Raised serum vascular endothelial growth factor levels are associated with destructive cha 2001 Sep OBJECTIVE: To determine whether elevated levels of the angiogenic cytokine vascular endothelial growth factor (VEGF), detected on presentation to an early arthritis clinic, are associated with the development of chronic and erosive arthritis. METHODS: Concentrations of VEGF and its soluble receptor, soluble fms-like tyrosine kinase 1 (sFlt-1), were measured by enzyme-linked immunosorbent assay in serum samples from patients with early (<2 years from onset) arthritic symptoms in the peripheral joints, namely early rheumatoid arthritis (RA), self-limiting arthritis (viral, reactive, and idiopathic inflammatory arthritis), or psoriatic arthritis. In addition, measurements were made in random samples from patients with longstanding (>3 years from symptom onset) RA treated with disease-modifying antirheumatic drugs, from patients with osteoarthritis (OA), and from patients with polyarthralgia without arthritis, as well as from nonarthritic controls. RESULTS: Serum VEGF levels at presentation were elevated in patients with inflammatory arthritis (RA, psoriatic, and self-limiting arthritis) as well as in patients with OA, in comparison with nonarthritic controls. Moreover, serum VEGF concentrations were significantly higher in patients with early RA than in patients with self-limiting arthritis. Serum VEGF levels at presentation in patients with early RA correlated significantly with the development of radiographic damage after 1 year. Improvement in the clinical symptoms of RA was associated with a reduction in serum VEGF levels. Serum sFlt-1 levels were raised in patients with early and longstanding RA and in those with self-limiting arthritis, and correlated positively with the serum VEGF concentrations in patients with inflammatory arthritis. CONCLUSION: These findings implicate the proangiogenic cytokine VEGF in the persistence of inflammatory arthritis, and support the hypothesis that expansion of the synovial vasculature is important for the development of joint destruction in RA.
9459406 Bone marrow infection caused by Actinobacillus ureae in a rheumatoid arthritis patient. 1997 Nov A patient with rheumatoid arthritis is described who presented with low-grade fever for 3 months, in whom Actinobacillus ureae was cultured from bone marrow aspirate. Fever responded favourably to penicillin therapy. It is the first reported isolation of A. ureae from bone marrow.
10082435 HLA-DRB1*01 and DRB1*04 alleles in Sardinian rheumatoid arthritis patients. 1999 Jan In Sardinia, like in other Caucasoid populations, rheumatoid arthritis (RA) is significantly associated with HLA-DR4 and DR1 antigens. To discover which DR4 and DR1 alleles were associated with the disease we selected 22 Sardinian patients affected by RA. Fifty DR4+ and 28 DR1+ healthy individuals coming from the same geographical area were used as controls. In the Sardinian patients only two DRB1*04 alleles were observed: DRB1*0405 in 11 and DRB1*0403 in three patients. The DRB1*0102 allele was observed in two patients and DRB1*0101 in six patients. Hereditary predisposition to RA in Sardinia therefore seems to be almost exclusively associated with the DRB1*0405 and DRB1*0101 alleles which share the 67LLEQRRAA74-85VG86 epitope in the peptide binding groove.
9448991 Vasculitis associated with primary rheumatologic diseases. 1998 Jan Vasculitis is an uncommon but important manifestation of autoimmune rheumatic diseases. Although the blood vessels of any organ can be involved, cutaneous involvement of arterioles and venules is the most common. Autoimmune rheumatic diseases may present as systemic vasculitis, and systemic vasculitis may simulate autoimmune rheumatic diseases. A crucial event in the initiation, localization, and propagation of vascular injury involves activation of the vascular endothelium by a variety of stimuli, including cytokines, complement split products, and cognate interactions between endothelial and T cells. Endothelial cell permissiveness to the deposition of circulating immune complexes or in situ formation of immune complexes in the vessel wall is also important. Vascular injury may be mediated by local or systemic activation of the complement system as well as autoantibody or T-cell-dependent mechanisms. This review focuses on the clinical features and pathogenic mechanisms involved in vasculitis complicating autoimmune rheumatic diseases.
9631614 Investigation of xerostomia in patients with rheumatoid arthritis. 1998 Jun The authors investigated the prevalence of xerostomia in a group of 604 subjects participating in a rheumatoid arthritis, or RA, study to explore the relationship of reduced salivary flow symptoms and demographic, clinical and medical characteristics. Forty-three percent of these subjects exhibited one or more severe xerostomia symptoms. Separate analyses revealed that the subjects who had the most physical disease symptoms were at greater risk of having reduced salivary flow. The study's results suggest that patients with RA should be screened for xerostomia symptoms so appropriate clinical interventions can be initiated.
11147752 Unsuccessful treatment with fludarabine in four cases of refractory rheumatoid arthritis. 2000 The aim of this study was to evaluate the efficacy of fludarabine treatment in patients suffering from refractory rheumatoid arthritis. Four patients affected by refractory seropositive rheumatoid arthritis underwent treatment with fludarabine for 6 months. The drug was administered intravenously at a dose of 25 mg the first month in a single infusion, and then monthly for 5 months at a dose of 25 mg for 3 consecutive days. All four patients obtained no clinical benefit from the treatment; moreover, inflammation indices worsened and the prednisone dosage was increased during the trial, in spite of a significant fall in CD4+ T cells. In our experience low-dose fludarabine is not useful in the treatment of refractory rheumatoid arthritis.
9473383 Effects of thrombospondin-1 on disease course and angiogenesis in rat adjuvant-induced art 1998 Feb Leukocyte extravasation into the synovium is important in rheumatoid arthritis (RA). Thrombospondin (TSP)-1 mediates cell adhesion and migration and inhibits angiogenesis, and it has been implicated in RA. However, little information is available on the role of TSP-1 in arthritis-associated inflammation and neovascularization. Therefore, we analyzed the effects of TSP-1 in adjuvant-induced arthritis (AIA), a rat model for RA. Hydron pellets containing TSP-1 were implanted in one ankle of AIA rats post-adjuvant injection, while the contralateral ankle received sham implants. Body weight loss and joint swelling were determined in comparison to nonimplanted AIA controls. In addition, synovial vessel counts were obtained in TSP-1-versus sham-implanted ankles of the same rat. The implantation of TSP-1 pellets into one ankle resulted in an enhancement of swelling in both ankles. Furthermore, TSP-1 exhibited a biphasic modulatory effect on synovial vessel counts (P < 0.05). In conclusion, TSP-1 implanted into one ankle of AIA rats may augment the severity of the disease. One possible explanation, among others, for the modulating effect of TSP-1 on inflammation may be its effect on arthritis-related angiogenesis.
10685829 Alternative methods for analysis of radiographic damage in a randomized, double blind, par 2000 Feb Radiographic data of a 48-week double-blind, randomized, parallel trial comparing hydroxychloroquine (HCQ) and sulfasalazine (SASP) and its open label extension to 3 years of follow-up are analyzed in various ways. The focus of the paper is the methodological issues involved in analyses of radiographic data in a trial. Both the traditional method of increase in erosions and total score calculated on a group level, as well as individual progression on a patient level are presented. Regardless of which method is used, there is a statistically significant reduction in radiographic progression in the SASP group compared to the HCQ group.
11315914 High-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients 2001 Apr OBJECTIVE: To assess the feasibility, safety, and efficacy of high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT) in patients with severe, refractory rheumatoid arthritis (RA). METHODS: Fourteen patients (3 male, 11 female, mean age 43 years, mean disease duration 10 years) with active, destructive, refractory RA entered the study. Autologous hematopoietic stem cells were collected by leukapheresis after mobilization with a single infusion of cyclophosphamide (CYC; 4 gm/m2) and subcutaneous injections of filgrastim (granulocyte colony-stimulating factor). Immunomagnetic selection of CD34+ cells from the leukapheresis products was performed to deplete potentially autoreactive lymphocytes. The conditioning regimen consisted of intravenous administration of high doses of CYC (cumulative dose 200 mg/kg), with subsequent reinfusion of the graft. Patients were monitored for disease activity, disability, adverse effects, and hematopoietic and immunologic reconstitution. RESULTS: All 14 patients completed the mobilization and leukapheresis procedures successfully, and 12 proceeded to receive conditioning and transplantation. Engraftment occurred in all of these patients, with rapid hematologic recovery. No major unexpected toxicity was observed. Marked improvement of disease activity was recorded in 8 of 12 patients at >50% of the visits, with a followup ranging from 7 months to 21 months. The clinical responders included 2 patients who had previously failed treatment with tumor necrosis factor (TNF) blocking agents. CONCLUSION: High-dose chemotherapy followed by autologous HSCT is feasible and safe, and can result in long-term improvement of disease activity in patients whose condition previously did not respond to conventional antirheumatic drugs or TNF blocking agents. The persistence of active disease in some patients may reflect the heterogeneity of the underlying disease process.
9058647 Cardiovascular morbidity and mortality in patients with seropositive rheumatoid arthritis 1997 Mar OBJECTIVE: To investigate the overall and the cardiovascular mortality in rheumatoid arthritis (RA) in Northern Sweden. To analyze the effect of traditional risk factors and factors associated with rheumatoid disease and its treatment on the progression of cardiovascular disease (CVD) and on mortality by all causes. METHODS: A cohort of 606 patients with seropositive RA were followed from 1979 to the end of 1994 or to the death of the patient. Standardized mortality ratio and survival curves were estimated with the population of Vasterbotten as reference. Sex, age at disease onset, treatment with corticosteroids, use of disease modifying antirheumatic drugs (DMARD) and hormone replacement therapy (HRT), hypertension, diabetes mellitus, HLA types, and cause of death were recorded from disease onset. Cox's proportional hazards regression was used to identify important predictors for death and cardiovascular event during followup. RESULTS: The standardized mortality ratio in both sexes was significantly higher (1.57) for all underlying causes together, for CVD (1.46) and for ischemic heart disease (IHD) (1.54) compared to the reference population. The death rate increased over time. In multiple Cox regression analyses, male sex, higher age at disease onset, and former cardiovascular event increased the death rate. Male sex, high age at disease onset, and hypertension increased the risk of cardiovascular event. Diabetes mellitus, treatment with corticosteroids, DMARD, or HRT did not influence the risks of death or first cardiovascular event. CONCLUSION: The overall mortality and death due to CVD and IHD were in both sexes increased in seropositive RA. Male sex and high age at disease onset predicted death and cardiovascular event. Except for hypertension, which increased the risk for cardiovascular event, neither of these traditional cardiovascular risk factors nor corticosteroid treatment influenced mortality by all causes or by cardiovascular event.
11422910 Acanthamoeba polyphaga in rheumatoid arthritis: possibility for a chronic infection. 2001 Jun Acanthamoeba polyphaga (AP) is ubiquitous in nature and frequently infects humans. AP has some features, such as persistence, which makes it an attractive candidate in studies of a possible infectious aetiology in rheumatoid arthritis (RA). In this study the occurrence of AP-specific antibodies was compared between RA patients and matched controls.
11593157 [Beginning rheumatoid arthritis revealed during bronchiectasis surinfections. Value of cyc 2001 Sep Incidence of symptomatic bronchiectasis (BR) occurs in around 2% in patients with late rheumatoid arthritis (RA). Its seems that the association BR-RA could be a worsening factor for outcome of RA patients. A 58-year-old woman without dry syndrome, suffering from bronchial purulence over one year was admitted to the Department of Pneumology for hemoptysis and arthritis (knees, ankles, and wrists). Three prior episodes of inflammatory articular pain had occurred after transient bronchial purulence or pneumonitis. CT-scan showed bilateral bronchiectasis. Diagnosis of early RA was proved after the third episode of bronchial purulence related to a strain of Haemophilus influenzae. A strain of Coxiella burnetii was probably responsible for one of the three bronchial surinfections. Latex and Waaler Rose tests were transiently positive during the first episode, and became positive after the third one. At that time, RA was relevant in view of ARA criteria. Cyclic prophylactic antibiotic regimens could be proposed to patients suffering from RA-BR association, in contrast to the cases of patients with isolated BR. This approach could prevent destabilization of RA and reinforce of anti-rheumatic therapy. Activation and release of cytokines (NFk-B, TNF-alpha), and/or bacterial epitopes seems to be directly responsible for the articular destabilization.
11845347 A radiographic analysis of anterior-posterior translation in total knee arthroplasty. 2001 We performed radiological analyses to examine the relationship between the knee flexion angle and the anteroposterior translation movement relative to the prosthetic components (NexGen type) after total knee arthroplasty (TKA). Cruciate-retaining (CR) type TKA was performed in 12 knees with osteoarthritis (OA) and 9 knees with rheumatoid arthritis (RA) in which no posterior cruciate ligament (PCL) tear was present. Posterior-stabilized (PS) type TKA was performed in 7 OA knees and 7 RA knees in which the PCL was defective or resected. The measurements were performed according to the methods of Watanabe. The contact point ratio (percentage) was calculated by dividing the distance to the contact point (CP; the closest point of contact between the femoral and tibial components) by the antero-posterior length of the tibial component. After TKA, the CP at full extension was positioned more posteriorly than in the normal knee both under weight-bearing and non-weight-bearing conditions. Except for the RA knees in the PS group, the CP translated anteriorly in the early phase of flexion and then posteriorly. Under weight-bearing conditions, the posterior translation occurred earlier and was smaller in magnitude. For RA knees in the PS group, the CP moved gently posteriorly right from the beginning.
9262055 Genomic cloning and sequence analysis of Taiwan-3 human polyomavirus JC virus. 1997 Jul Four different-strains of human polyomavirus JC virus (JCV), CY, Taiwan-1, Taiwan-2, and Taiwan-3, have been found in pregnant women and autoimmune disease patients in Taiwan. In this study, we report the cloning and sequencing of the Taiwan-3 JCV, virus isolated from the urine of an immunosuppressed patient with rheumatoid arthritis. The viral genome was amplified by polymerase chain reaction and then cloned into a prokaryotic replicative plasmid, pGEM-7Zf(-). The genomic DNA was sequenced and found to comprise 5,111 base pairs. The enhancer-promoter region of the viral genome lacks a copy of pentanucleotide-A (GGGAA) and pentanucleotide-B (AAAGC) compared to the CY archetypal JCV. There are 108 nucleotides altered in the total genome, excluding the variable part of the enhancer-promoter region, between Mad-1 (the prototype JC virus) and Taiwan-3. The enhancer-promoter region has approximately 25% of the altered nucleotides, resulting in amino acid changes in the open reading frames for I.T. capsid proteins (VP1, VP2, and VP3), and the agno protein. The cloned Taiwan-3, genome will provide an source for physiologic and pathologic investigation of the JCV virus in the future.
9027971 Polymorphism at the TNF loci in rheumatoid arthritis. 1997 Jan The purpose of this work was to analyze the possible influence of TNF loci polymorphism on the susceptibility and/or the disease profile of rheumatoid arthritis (RA). Tumor necrosis factor (alpha and beta) genotypes were determined in 60 patients with RA and 102 healthy subjects by a method based on PCR-RFLP with amplification-created restriction sites. The results obtained in the present study showed that there is not a significant association of either TNF alpha promoter variation (at positions -308 and -238) or TNF beta polymorphism with susceptibility to RA. However, a significant difference in the mean age at disease onset was found between -238 TNF alpha genotypes. In addition, a difference in the presence of nodular disease was observed between -308 TNF alpha genotype. The results of this study suggests that the TNF alpha gene may play a role in the disease profile of rheumatoid arthritis.
9844761 Prevalence of antibodies to neurofilament polypeptides in patients with rheumatoid arthrit 1998 Nov OBJECTIVE: Neurofilaments are essential components of the axon cytoskeleton. Neurofilament defects are suspected in several neurodegenerative conditions, and antibodies to neurofilaments have been found in autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Our main objectives were: (i) to determine the prevalence of anti-neurofilaments antibodies in patients with rheumatoid arthritis (RA) complicated by peripheral neuropathy; and (ii) to relate the clinical features of RA and peripheral neuropathy to anti-neurofilament antibodies. METHODS: In this study we used an ELISA technique to measure IgG antibody levels against three neurofilament polypeptides (NF-L, 70 kD; NF-M, 150 kD; and NF-H, 200 kD) in RA patients with peripheral neuropathy, and compared them with the antibody levels in uncomplicated RA controls and healthy volunteers. RESULTS: Abnormal antibody levels to one or more of the neurofilament polypeptides were found in 9 (32%) of the peripheral neuropathy patients, but only in 3 (9%) of the RA and healthy controls. There were significant correlations between the levels of antibodies against the different neurofilaments; the cross-reactivity of some sera with different neurofilament proteins was also observed. There was no significant correlation between the levels of anti-neurofilament antibodies and measures of RA disease activity. CONCLUSIONS: We conclude that a significant proportion of our RA patients with neuropathy had abnormal antibody levels to one or more neurofilaments and that the measurement of these antibodies may provide a useful diagnostic test.
10052597 Detection of disease-specific augmentation of abnormal immunoglobulin G in sera of patient 1998 Sep Galactose-free immunoglobulin G (IgG), which is known to be higher in the sera of patients with rheumatoid arthritis, was prepared from IgG of healthy volunteers using enzymes. Its reactivity to lectins was analyzed. The galactose-free IgG showed no reactivity to Ricinus communis agglutinin 120 but displayed greater reactivity to concanavalin A and Lens culinaris lectin than did intact human IgG. Then, IgG in serum samples was bound to protein A immobilized on a nitrocellulose membrane, and its reactivity to biotinylated concanavalin A was measured with streptavidin-conjugated horseradish peroxidase. When the reactivity to concanavalin A of IgG in sera from healthy individuals and patients with rheumatoid arthritis (RA), osteoarthritis, systemic lupus erythematosus, or hepatic disease was compared, higher levels were shown in patients with RA, notably in 60% of the seronegative patients and 80% of the early phase patients. Therefore, it was suggested that augmentation of the abnormal IgG in sera was highly specific to patients with RA and that this novel serum test could be very useful for an accurate diagnosis of this disease.
11145032 Relative contributions of the components of the American College of Rheumatology 20% crite 2000 Dec OBJECTIVE: To evaluate factors that influence the responses defined by the American College of Rheumatology (ACR) 20% criteria for improvement in rheumatoid arthritis (RA). METHODS: ACR 20% and 50% response rates were calculated from data collected for the intervals 0-6, 0-12, and 0-24 months for 180 RA patients participating in the Western Consortium of Practicing Rheumatologists long-term observational study of early seropositive RA (mean +/- SD duration of RA at study entry 6.0 +/- 3.4 months). Analyzable cases were patients with paired data for tender and swollen joint counts plus at least 3 of the following criteria: physician's and patient's global assessments of disease activity and patient's score for pain (by visual analog scale), physical function score on the Health Assessment Questionnaire (HAQ), and levels of an acute-phase reactant. Response rates were then recalculated by 3 different methods: 1) using only cases with complete paired data for all criteria, 2) sequentially assuming no improvement in each of the 5 secondary criteria, and 3) substituting grip strength for HAQ scores. RESULTS: Using 464 paired observations for all analyzable cases, ACR 20% (50%) improvement rates were 52.6% (33.0%), compared with 55.6% (34.8%) for 365 paired observations from the cases with complete data. Decreases in ACR response rates when secondary criteria were sequentially set at "no improvement" ranged from 11.7% (pain at 0-6 months) to 1.2% (C-reactive protein at 0-12 months), but these were not statistically different by the kappa statistic. Overall numerical rankings of the relative contributions of the secondary criteria to the ACR 20% or 50% response rates were physician's global assessment, pain, HAQ, patient's global assessment, and acute-phase reactant. Only 7.8% of paired grip strength observations showed > or =20% improvement, compared with 71% of paired HAQ observations. CONCLUSION: The use of all "analyzable" cases (paired data for tender and swollen joint counts plus > or =3 of the 5 secondary criteria) increases the number of subjects and only slightly decreases the ACR response rate compared with analyses limited to cases with complete data. The contributions of the secondary criteria are not statistically different, supporting their equal weighting in the ACR definition of improvement. The ACR 20% response rates are higher when the HAQ, rather than grip strength, is used to measure physical function.