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ID PMID Title PublicationDate abstract
9666800 Acute myeloid leukemia after azathioprine treatment for autoimmune diseases: association w 1998 Jul 15 Azathioprine is used as an immunosuppressant in a variety of clinical situations, and its prolonged use is associated with an increased risk of solid malignancies. Three patients (one with rheumatoid arthritis and two with systemic lupus erythematosus) treated with azathioprine for 3 to 7 years developed acute myeloid leukemia (AML). The total cumulative doses of azathioprine varied from 89-260 g. An antecedent prolonged pancytopenic phase suggestive of myelodysplasia developed in all the cases. Morphological analysis showed AML with trilineage myelodysplastic features in residual marrow cells in all the cases. Karyotypic analysis showed deletion of the long arm of chromosome 7 (7q-) in one case and monosomy 7 (-7) in two cases. These were chromosomal aberrations typically associated with mutagen- or therapy-related AML. Fluorescence in situ hybridization with a chromosome-7-specific DNA probe was used to investigate the distribution of the monosomy 7 clone in two cases. Monosomy 7 was demonstrated in both the leukemic blasts and the residual myeloid cells of various stages of differentiation. This finding indicated that the leukemia had evolved from a mutated clone that was capable of terminal differentiation, which was consistent with the biological characteristics of the myelodysplastic syndromes. These cases represented therapy-related AML, as evidenced by clincopathological features, karyotypic aberrations of 7q-/-7, and demonstration of leukemic evolution from an underlying clonal myeloid disorder. The data support the hypothesis that azathioprine might be directly mutagenic.
10380046 Neutrophilic lobular (pustular) panniculitis associated with rheumatoid arthritis: a case 1999 Jun Rheumatoid nodules, which affect the subcutis around joints, are the most frequent specific cutaneous lesions of rheumatoid arthritis (RA). Panniculitis is a rarely reported and nonspecific complication of RA. We report a 42-year-old woman with seropositive RA who presented with a 2-month history of lower leg panniculitis. Biopsy of a leg nodule showed a lobular neutrophilic infiltrate with lipophages and central basophilic necrosis. In addition, focal changes of lipomembranous fat necrosis indicative of ischemic damage were identified at the margins of the lobular infiltrate. Neutrophilic lobular panniculitis is commonly detected in panniculitis secondary to bacterial infections, pancreatitis, and factitial causes. However, this pattern of panniculitis has also been reported in some cases of erythema nodosum-like lesions found in Behçet disease or bowel bypass syndrome and in rare cases of seropositive RA. These reported histologic findings fall into the spectrum of neutrophilic vascular reactions described by Jorizzo and Daniels for RA-associated dermatoses. In view of these findings. RA and related neutrophilic dermatoses (e.g., Behçet disease) should be included in the differential diagnosis of neutrophilic lobular panniculitis.
10366120 Musculoskeletal manifestations in a population-based cohort of patients with giant cell ar 1999 Jun OBJECTIVE: To define musculoskeletal manifestations occurring in a population-based cohort of patients with giant cell (temporal) arteritis (GCA). METHODS: The records of 128 patients with GCA diagnosed over a 42-year-period (1950-1991) in Olmsted County, MN, were reviewed for the presence and type of musculoskeletal manifestations, their relationship to the onset and course of GCA, and their response to treatment. RESULTS: Fifty-three patients (41%) developed polymyalgia rheumatica: 23 before, 17 concurrently with, and 13 after the diagnosis of GCA. Thirty patients (23%) developed 1 or more peripheral musculoskeletal manifestations. These included peripheral synovitis in 23 patients (6 of whom fulfilled criteria for rheumatoid arthritis), distal extremity swelling with pitting edema in 13, distal swelling without pitting in 5, tenosynovitis in 6, and carpal tunnel syndrome in 2. Fifty-seven episodes of peripheral manifestations occurred in the 30 patients at different times during the course of GCA. In most, the onset of PMR and peripheral manifestations was within 2 years of the diagnosis of GCA. CONCLUSION: Musculoskeletal symptoms in GCA are common and varied. Most appear linked temporally to the underlying GCA, indicating that the nature of this illness and its clinical expression are broader than often considered.
10228036 Regulation of inflammatory responses by oncostatin M. 1999 May 1 Oncostatin M (OM) is a pleiotropic cytokine produced late in the activation cycle of T cells and macrophages. In vitro it shares properties with related proteins of the IL-6 family of cytokines; however, its in vivo properties and physiological function are as yet ill defined. We show that administration of OM inhibited bacterial LPS-induced production of TNF-alpha and lethality in a dose-dependent manner. Consistent with these findings, OM potently suppressed inflammation and tissue destruction in murine models of rheumatoid arthritis and multiple sclerosis. T cell function and Ab production were not impaired by OM treatment. Taken together these data indicate the activities of this cytokine in vivo are antiinflammatory without concordant immunosuppression.
11557653 Benchmarking: the five year outcome of rheumatoid arthritis assessed using a pain score, t 2001 Oct BACKGROUND: Treatment, and therefore outcome, of rheumatoid arthritis (RA) will improve in the next few years. However, improvement in outcome can only be judged against the probability of certain outcomes with current conventional treatment. AIM: To document the five year outcome of RA in the late 1990s. SETTING: Norfolk Arthritis Register (NOAR). DESIGN: Longitudinal observational cohort study. METHODS: 318 patients with recent onset inflammatory polyarthritis recruited by NOAR in 1990-91 completed five years of follow up. Four groups were assessed: the whole cohort, all those referred to hospital, those who satisfied criteria for RA at baseline, and those referred to hospital who satisfied criteria for RA at baseline. Outcome was assessed with a visual analogue scale for pain, the Health Assessment Questionnaire (HAQ), and the Short Form-36 (SF-36). RESULTS: Of the RA hospital attenders, 50% had a visual analogue scale pain score of 5 cm or less and an HAQ score of 1.125 or less. SF-36 scores were reduced in all domains. Results are presented as cumulative percentages. CONCLUSIONS: These results can be used for comparison and to set targets for improvement.
9510855 Chondrex: new marker of joint disease. 1998 Mar Chondrex, a major secretory protein of human chondrocytes and synovial fibroblasts, is increased in serum of patients with joint and cartilage disease. We have developed a sandwich-type ELISA for quantifying chondrex in serum. The interassay CVs were 2.8-3.7% and the average within-run and total CVs were 3.6% and 5.4%, respectively. The limit of detectability by linear dilution was 20 micrograms/L, recovery upon dilution was 102% +/- 5%, and analytical recovery (of added analyte) was 98% +/- 11%. The reference interval (central 90% interval) for chondrex in healthy adults was 25-95 micrograms/L. Chondrex values for patients with active rheumatoid arthritis or osteoarthritis were significantly greater than in healthy adults, inactive rheumatoid arthritis patients, and diabetes patients (P < 0.05). In patients treated with disease-modifying antirheumatic drug therapy, decreasing chondrex values reflected the clinical improvement observed in responders, whereas the values were maintained or increased in nonresponders. In conclusion, chondrex may be a useful marker in the clinical investigation of arthritis.
9858207 Composition and function of peripheral blood stem and progenitor cell harvests from patien 1998 Dec High-dose chemotherapy with autologous stem cell rescue has been proposed as an intensive therapy for severe rheumatoid arthritis (RA). In view of previous observations of abnormal haemopoiesis in RA patients, the composition and function of peripheral blood stem cell harvests (PBSCH) was investigated. Compared with PBSCH from healthy allogeneic donors mobilized with the same dose of G-CSF (filgrastim; 10 microg/kg/d, n = 14), RA PBSCH (n = 9) contained significantly fewer mononuclear cells (375 v 569 x 10(6)/kg, P = 0.03) and CD34+ cells (2.7 v 5.8 x 10(6)/kg, P = 0.003). However, there were increased proportions of CD14+ cells (P = 0.006) and CD14+ CD15+ cells (the phenotype of previously described 'abnormal' myeloid cells, P = 0.002) in the RA PBSCH which translated into 3.5- and 7-fold increases respectively on a per CD34+ cell basis. There were no differences in T-cell activation status as judged by proportions of CD4+ and CD8+ expressing CD45RA, CD45RO, HLA-DR and CD28 (RA PBSCH, n = 7, donor PBSCH, n = 5, P = 0.2-0.7). Phytohaemagglutinin responses determined fluorocytometrically with induction of CD69 expression were reduced in CD4+ and CD8+ cells following filgrastim administration in 3/3 RA patients tested. Compared with bone marrow as a potential source of CD34+ cells, PBSCH contained 11-fold more T cells (P < 0.0005), 8-fold more B cells (P < 0.0005) and 4-fold more monocytes (P = 0.02). In short-term methylcellulose culture there were no differences in colony counts (CFU-GM, CFU-GEMM, BFU-E) per CD34+ cell from PBSCH from RA patients (n = 11) and healthy donors (n = 10). Long-term culture initiator cells were cultured successfully from cryopreserved PBSCH from RA patients (n = 9). In conclusion, PBSCH from RA patients differed significantly in composition from normal individuals, but in vitro studies support normal stem and progenitor cell function. Changes in T-cell function occur during mobilization in RA patients. This work provides reassurance for the use of PBSCH as haematological rescue and baseline data for clinical trials of graft manipulation strategies in patients with RA.
10830256 Benefits and risks of minocycline in rheumatoid arthritis. 2000 May Rheumatoid arthritis is a chronic inflammatory disease affecting about 1% of the adult population. The pathophysiology of rheumatoid arthritis remains incompletely understood. An infectious aetiology of the disease has long been postulated, but not proved. Despite insufficient evidence for the infectious nature of this disorder, several antibacterials, such as sulfa compounds, tetracyclines and rifampicin, have been investigated in the treatment of rheumatoid arthritis. In the last few years, minocycline, a semi-synthetic derivative of tetracycline, has been extensively studied as a therapeutic agent for rheumatoid arthritis. The antirheumatic effect of minocycline can be related to its immunomodulatory and anti-inflammatory, rather than to its antibacterial properties. Its efficacy in rheumatoid arthritis has been reported in 2 open trials and in 3 double-blind controlled studies. The first 2 double-blind studies, 1 in The Netherlands and 1 in the US, were performed in patients with advanced disease. Both studies showed a modest, but statistically significant improvement in the clinical parameters of disease activity and in the erythrocyte sedimentation rate in the minocycline-treated patients. The US study also reported that patients in the minocycline group developed fewer erosions than those in the placebo group. This finding supports the role of minocycline as a disease modifying agent. The common adverse effects of minocycline reported in these 2 studies included gastrointestinal adverse effects, dizziness, rash and headaches. Less common adverse effects were intracranial hypertension, pneumonitis, persistent skin and mucosal hyperpigmentation, lupus-like syndrome and acute hepatic injury. The third double-blind study enrolled only seropositive rheumatoid arthritis patients with early disease (less than 1 year duration), and showed very encouraging results of significant improvement in the disease activity parameters in the minocycline treated group of patients. The same authors later reported that about half of these patients were in or near remission after 3 years of follow up. No adverse effects were reported in this study. Summarising the data of these 3 double-blind studies, we may conclude that minocycline may be beneficial in patients with rheumatoid arthritis, especially when given early in the disease course or in patients with a mild disease.
11386777 Wrist arthrodesis with excision of the proximal carpal bones using the Ao/ASIF wrist fusio 2001 Jun We present our series of 17 patients who underwent wrist arthrodesis with excision of the proximal row carpal bones using the AO wrist fusion plate and local bone graft obtained from the excised proximal carpal row. All patients were evaluated using a questionnaire to assess pain, function, ability to perform an occupation and satisfaction with the procedure. The mean follow-up was 17 months, at which time all the fusions had united. Clinical outcome scores showed that 14 and 15 of the 17 patients achieved good or excellent results with regard to their current condition and clinical improvement, respectively. Four patients required secondary surgery, two for fractures and two for instability of the distal radio-ulnar joint unrelated to the wrist fusion.
9364646 Radiosynovectomy's clinical applications and cost effectiveness: a review. 1997 Oct It is apparent that from the work of the authors and many others, including the work of Rivard, Sledge, Zuckerman, among others, that radiosynovectomy has an important role to play in providing effective treatment of affected joints associated with rheumatoid arthritis and other forms of arthritis as well as the hemophiliac joint. The treatment offers relief from the effects of recurrent joint effusion with an approximately 60% to 66% favorable response and from recurrent hemarthrosis in the hemophiliac joint with an approximately 75% to 80% favorable response. The impact of providing radiosynovectomy as an alternative to surgical synovectomy is seen, where postoperative side effects such as joint stiffness are avoided, improved quality of life is repeatedly documented, and the cost savings in health care dollars, particularly evident in the hemophiliac joint in this relatively small population, are potentially enormous. With almost two million people in the United States suffering from rheumatoid arthritis, the potential savings in health care dollars is also enormous. As with any use of in vivo radiopharmaceuticals, the potential for radiation-induced damage exists. However, with a 25 plus year record of use, more optimally configured radiopharmaceuticals, and the addition of maneuvers to minimize potential joint leakage, the risk of radiation induced damage appears to be minimal. It appears as though radiosynovectomy is an effective as well as cost-effective alternative to surgical synovectomy and is becoming the procedure of choice particularly in the hemophiliac patient with recurrent hemarthrosis and synovitis who has failed medical therapy. It is also the procedure of choice in patients for whom surgery is contraindicated because of the presence of clotting factor inhibitors.
11060753 Biological agents: a novel approach to the therapy of rheumatoid arthritis. 2000 Jul Rheumatoid arthritis (RA) is the most common chronic autoimmunopathy, clinically leading to joint destruction as a consequence of the chronic inflammatory processes. The pathogenesis of this disabling disease is not well understood, but molecular events leading to tissue inflammation with cartilage and bone destruction are now defined in more detail. Established therapy, slow acting disease-modifying antirheumatic drugs (DMARDs) as with low-dose methotrexate (MTX) are the accepted 'golden standard' therapies and both lead to a significant improvement of disease symptoms, however are unable to stop joint destruction. Due to these disappointing treatment options and the identification of some inflammatory mediators as therapeutic targets, novel therapeutic agents such as monoclonal antibodies (mAbs), cytokine receptor-human immunoglobulin constructs or recombinant human proteins have been tested in RA with some success. In particular, clinical trials testing anti-TNF-alpha agents either alone or in combination with MTX have convincingly demonstrated the feasibility and efficacy of these novel approaches to the therapy of RA. Importantly, a clinical trial testing combination therapy with chimeric (mouse-human) anti-TNF-alpha mAb cA2 (Remicadetrade mark) and MTX could, for the first time in any RA trial, show that average radiological progression in the cA2/MTX groups could be completely prevented over a 12 month observation period. Similar encouraging results might evoke from trials employing other TNF-alpha-directed agents like the fully human mAb D(2)E7 or the p75 TNF-alpha-receptor-Ig construct, etanercept.
9567205 Surgery of the rheumatoid foot and ankle. 1998 Mar Numerous reconstructive procedures have been used to address the manifestations of rheumatoid arthritis in the foot and ankle. Clinical studies have documented that these procedures relieve pain, however they often sacrifice motion essential to the normal function of the foot. In the forefoot, metatarsophalangeal joint resection arthroplasty shortens the lever arm of the foot, defunctions the toes, and disables the plantar plate and fat pad. Arthrodesis of the ankle and hindfoot alters gait and the effective transmission of weight-bearing stresses through the foot and ankle. These ablative procedures may provoke the deterioration of adjacent joints and may cripple the long-term function of the lower extremity. The introduction of reconstructive procedures designed to preserve motion in joints essential to function and the recognition and treatment of muscle imbalances associated with bone and joint deformities are recent advances in the surgical management of the rheumatoid foot and ankle.
11197302 Genetic analysis of multiplex rheumatoid arthritis families. 1999 Sep To examine the genetic contribution of HLA and non-HLA genes in the etiopathogenesis of rheumatoid arthritis (RA), 60 Caucasian multiplex families were identified and DNA analyzed for over 52 markers including DRB1, DQA1 and DQB1 alleles. Many of the markers were chosen because of close proximity to candidate genes suggested by previous studies or models of pathogenesis. Sibling pair analysis (SIBPAL), relative pair analysis (RELPAL) and linkage studies using two different models of inheritance suggested linkage for the MHC and two additional chromosomal regions: chromosome 2 (D2S443 near CD8 and IGk; 2p13-2p11.1), and chromosome 15 (CYP19-estrogen synthase; 15q15). No support was found for two chromosomal regions, 1p36 and 3q13, recently suggested by other studies. We used transmission disequilibrium testing (TDT), conditional logistic regression, and segregation analysis to study the contributions that the shared epitope and TNF-c have in contributing to risk for RA. These studies provide additional evidence that the association of HLA alleles in RA patients from multiplex families is similar to that observed in sporadic disease, suggest candidate regions for further analysis and find additional support for an association of TNF-c alleles with RA susceptibility.
10653854 IL-6 inhibits the proliferation of fibroblastic synovial cells from rheumatoid arthritis p 2000 Feb IL-6 and tumor necrosis factor (TNF)-alpha have been proven to play an important role in the development of rheumatoid arthritis (RA). It is well known that TNF-alpha induces IL-6 production from synovial cells as well as their proliferation. The effect of IL-6 on synovial cells, however, is not clear. An in vitrostudy was performed to determine the effect of IL-6 on the proliferation of synovial cells. Fibroblastic synovial cells isolated from the synovial tissues of eight RA patients were employed after the third to sixth passages. IL-6 in the presence of soluble IL-6 receptor (sIL-6R) inhibited the proliferation of synovial cells in a dose-dependent manner in seven cases without increasing the number of necrotic or apoptotic cells, while TNF-alpha increased synovial cell proliferation in all cases. The inhibitory effect of IL-6 was observed only in the presence of sIL-6R although small amounts of IL-6R were detected in these cells by RT-PCR analysis. However, anti-IL-6R or anti-gp130 mAb treatment increased spontaneous growth of synovial cells in all eight cases, suggesting that endogenous IL-6 and a small amount of IL-6R expressed in synovial cells suppressed their growth without exogenous IL-6 or sIL-6R. In addition, the IL-6-sIL-6R complex reduced the TNF-alpha-induced proliferation of synovial cells while TNF-alpha induced their IL-6 production. These data suggest that IL-6 may act as a negative feedback factor for TNF-alpha-induced synovial cell growth.
9825750 Cost-effectiveness and cost-utility of combination therapy in early rheumatoid arthritis: 1998 Oct OBJECTIVE: Assessment of the cost-effectiveness and cost-utility of early intervention in rheumatoid arthritis (RA) patients, with combined step-down prednisolone, methotrexate and sulphasalazine, compared to sulphasalazine alone. METHODS: Multicentre 56 week randomized double-blind trial with full economic analysis of direct costs and utility analysis with rating scale and standard gamble measurement techniques. RESULTS: The combined-treatment group included 76 patients and the sulphasalazine group 78 patients. The mean total costs per patient in the first 56 weeks of follow-up were $5519 for combined treatment and $6511 for treatment with sulphasalazine alone (P = 0.37). Out-patient care, in-patient care and non-health care each contributed about one-third to the total costs. The combined-treatment group appeared to generate savings in the length of hospital stay for RA, non-protocol drugs and costs of home help, but comparisons were not statistically significant. Protocol drugs and monitoring were slightly more expensive in the combined-treatment group. Clinical, radiographic and functional outcomes significantly favoured combined treatment at week 28 (radiography also at week 56). Utility scores also favoured combined treatment. CONCLUSION: Combined treatment is cost-effective due to enhanced efficacy at lower or equal direct costs.
11004866 [Lung changes during the course of non-Hodgkin's lymphoma in a patient with rhematoid arth 2000 A case of 51 years old woman with 12-years history of rheumatoid arthritis and secondary Sjoegren's syndrome, who developed EBV-associated diffuse large B-cell lymphoma (Lymphomatoid granulomatosis type) involving lungs, lymph nodes and bone marrow was described.
10329496 On the edge: the physiological and pathophysiological role of chemokines during inflammato 1999 Apr Most, if not all, chemokines bind to seven transmembrane spanning G protein-coupled receptors and activate cellular migration. Stimulated chemokine expression is essential for directing leukocyte emigration from the circulation into sites of inflammation and tissue damage. In contrast, constitutive chemokine expression plays a role in the development of lymphoid cells, organs, and tissues. The present review examines rheumatoid arthritis and transplantation rejection as two examples of pathological conditions where chemokine directed leukocyte infiltration aids in the pathogenesis of the disease. We further discuss insights into leukocyte trafficking gained by chemokine and chemokine receptor transgenic and null mutant mice.
11197934 [Radiologic quantification of joint changes. A methodological overview]. 2000 Dec Osteoarthritis as well as rheumatoid arthritis lead to chronical progressive destruction of diseased joints. As aggressive new treatments need to be evaluated, plenty of (semi-) quantitative methods for the radiological joint evaluation had been developed. They lack sufficient reproducibility due to their low objectivity. Modern approaches of computer-assisted radiological quantification should increase the reproducibility and efficiency of radiological scoring. Automatically calculated, computer-assisted measurements of joint space, cartilage- and synovial volume, periarticular assessment of bone mineral density and quantitative analysis of the subchondral plate will have major impact on the radiological routine of the future.
9741814 Connective tissue markers of rheumatoid arthritis. 1998 Jul Rheumatoid arthritis (RA) is a common systemic autoimmune disorder of unknown aetiology. The most common outcome of RA is a progressive development of joint destruction and deformity. Early introduction of disease-modifying antirheumatic drugs seems important for prevention of the long term injuries of articular cartilage and bone. Early diagnosis and selection of patients with rapidly progressive disease therefore is of clinical significance. Routine laboratory tests are valuable in monitoring for renal, hepatic and haematological side effects of medical treatment. Determination of rheumatoid factor contributes to the classification of arthritis as RA, and acute phase reactants are useful for quantifying and comparing the level of inflammatory activity in the course of a given patient. There is, however, a lack of sensitive and specific biochemical markers for RA, and frontline biochemical research is devoted to characterizing molecules which are of diagnostic and prognostic value, as well as molecules which are indicators of the degree of joint cartilage and bone destruction. The present survey summarizes current knowledge concerning possible tissue-specific marker molecules of RA.
9361159 Methotrexate use in miscellaneous inflammatory diseases. 1997 Nov Methotrexate has proven to be a safe, effective, long-term therapy for rheumatoid arthritis. Its property as a corticosteroid-sparing drug in rheumatoid arthritis has been recognized and its potential has been explored in other inflammatory and autoimmune diseases. This article describes and analyzes the use of methotrexate for a wide variety of diseases, some of which are not the usual province of rheumatologists, to provide some guidance concerning its role for treatment. Methotrexate therapy seems promising for systemic lupus erythematosus, inflammatory myopathy, inflammatory eye disease, inflammatory bowel disease, and some manifestations of sarcoidosis. Its role in other diseases is not as well defined.