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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
11329057 Vasoactive intestinal peptide prevents experimental arthritis by downregulating both autoi 2001 May Rheumatoid arthritis (RA) is a chronic and debilitating autoimmune disease of unknown etiology, characterized by chronic inflammation in the joints and subsequent destruction of the cartilage and bone. We describe here a new strategy for the treatment of arthritis: administration of the neuropeptide vasoactive intestinal peptide (VIP). Treatment with VIP significantly reduced incidence and severity of arthritis in an experimental model, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of VIP was associated with downregulation of both inflammatory and autoimmune components of the disease. Our data indicate VIP as a viable candidate for the development of treatments for RA.
10381485 Sicca symptoms, saliva and tear production, and disease variables in 636 patients with rhe 1999 Jul OBJECTIVES: (1) To estimate the prevalence of ocular and oral sicca symptoms (SISY) or reduced saliva and tear production; (2) to relate SISY and sicca signs to measures of disease activity, damage, and health status; and (3) to examine the relation between symptoms and objective signs of tear and saliva production in a large sample of representative patients with rheumatoid arthritis (RA). METHODS: From an unselective county RA register 636 patients (age 20-70 years) were examined with Schirmer-I test (ST), unstimulated whole saliva (UWS), questions on SISY and measures of disease activity, damage and health status. RESULTS: Ocular sicca symptoms were reported in 38%, oral sicca symptoms in 50%, and a combination of both in 27%. Reduced tear production was present in 29%, and reduced saliva production in 17%. The minimum frequency of secondary Sjögren's syndrome was 7%. Measurements of exocrine disease manifestations were to variable extents bivariately correlated to disease activity measures, physical disability, pain, fatigue, and use of xerogenic drugs, but were not related to deformed joint count. Multivariate analyses revealed significant associations between disease activity and reduced saliva production. Only weak associations between SISY and tear or saliva production were observed. CONCLUSION: SISY, reduced tear and saliva production were frequent extra-articular manifestations in RA, but were only weakly intercorrelated. High disease activity and at least two SISY were independent predictors of reduced saliva production, but ocular and oral dryness did not seem to be closely related to disease duration, disease activity, damage or health status.
9584363 Arthritis of the forefoot. A review from a rheumatologic and medical perspective. 1998 Apr Pain in the forefoot indicative of metatarsophalangeal synovitis often heralds the presence of significant inflammatory disease, and may be the initial presenting symptom of various systemic disorders. A review of these disorders and their rheumatologic, nonsurgical management is described.
11740752 Periprosthetic tibial fractures after cementless low contact stress total knee arthroplast 2001 Dec Periprosthetic fractures are a recognized complication of total knee arthroplasty. Fractures may occur intraoperatively or postoperatively, and risk factors have been identified that may predispose an individual to such a complication. We report 7 cases of periprosthetic tibial fractures after low contact stress total knee arthroplasty, a complication encountered by the senior author (D.E.B.) only after a change in practice from a cemented implant to a cementless one. In light of this previously unreported complication in our unit, we attempted to identify common features within this group of patients that may have contributed to fracture occurrence. Statistical analysis revealed a highly significant (P<.005) risk of periprosthetic tibial fracture in patients with a preoperative neutral or valgus knee. Age, gender, and diagnosis did not appear to increase the risk of fracture significantly. All patients displayed evidence of reduced bone mineral density in the lumbar spine and femoral neck regions on dual-energy x-ray absorptiometry scanning. Patients with a preoperative neutral or valgus knee and local evidence of osteopenia represent a high-risk group, in whom particular care in alignment should be taken. In this group, it may be preferable to have the tibial component inserted with cement fixation.
9577901 [Aspects of quality assurance in a rheumatology clinic. A contribution to the problem of l 1998 Mar In a rheumatological hospital, quality assurance has many aspects. Diagnostic as well as classification criteria are essential; however, they should not be regarded as a strait-jacket. The very important radiological diagnostics require optimal technology. All x-ray-pictures should only be interpreted by experienced rheumatologists. Also of importance is the documentation of all relevant data, sometimes for decades, especially the kind of drugs, their effectiveness and side effects and the assessment of activity, stage, progression and functional ability. Very important is also a close communication with other medical disciplines. Nursing in rheumatology is mostly underestimated quantitatively and qualitatively as well; it cannot be compared with nursing in other patients. Physical and occupational therapy are indispensable parts of treatment of in-patients; under certain conditions, they may have priority in comparison to other treatments. For chronobiological reasons, physical therapy has a definite time requirement. A duration of 3 weeks is necessary to get therapeutically desired adaptation processes. Thus, the duration of stay in rheumatological departments must be longer than in other disciplines. An actual questionnaire, which has been sent to 50 rheumatological departments, asked the question, which reasons and indications will make future in-patient treatment necessary. As main reason, the comprehensive treatment options and induction of a special pharmacotherapy have been mentioned. Also an element of quality assurance in a rheumatological hospital is warmheartedness and humanity.
11296945 Identification of alpha6beta1 integrin positive cells in synovial lining layer as type B s 2001 Mar OBJECTIVE: In rheumatoid arthritis (RA) the synovial lining is responsible for cartilage destruction. Laminin is one of the major matrix molecules surrounding the lining cells. We investigated the laminin adhesion mechanism of synovial lining cells by analyzing the presence of its receptor, alpha6beta1 integrin, on type A and type B synoviocytes. METHODS: The alpha6 integrin subunit and a macrophage marker were simultaneously localized by immunohistochemistry in 29 RA derived, 6 osteoarthritis derived, and 2 healthy synovial samples by light and electron microscopy. We also used enzyme treatments to release cells from synovial tissue samples and localized the same antigens on adherent cells. RESULTS: The alpha6beta1 integrin positive cells were localized in basal areas of the lining layer and many of them were negative for the macrophage markers. By immunolabeling electron microscopy the alpha6 integrin positive cells were confirmed to represent the fibroblast-like type B cells. Further, in freshly isolated synoviocyte cultures the type B cells were positive for alpha6 integrin, whereas all other cell types were negative for this laminin receptor. CONCLUSION: Integrin alpha6beta1 is known to be a laminin receptor of endothelial cells, adipocytes, and macrophages, not usually expressed on fibroblasts. However, in synovial lining layer it is expressed on fibroblastic type B cells, but the macrophage population is negative. The unique characteristics of synovial lining cells distinguish them from other connective tissue cells and must be taken into account in all considerations of the pathogenic mechanisms of rheumatoid disease.
10546599 Unicompartmental knee replacement. A minimum 15 year followup study. 1999 Oct One hundred forty Marmor cemented unicompartmental knee replacements were inserted in 103 patients between 1975 and 1982. Fifty-two patients were women and 51 were men. One hundred twenty-five were medial compartment knee replacements and 15 were lateral knee replacements. At minimum 15 year followup 34 patients with 48 knee replacements were living; only four patients with four knee replacements were lost to followup. Average preoperative and final followup Hospital for Special Surgery knee scores were 57 and 82 points, respectively for the knees of living patients. Average preoperative and final followup Knee Society clinical and Knee Society functional scores were 31 and 42, and 85 and 71 points, respectively. For all knees, 10.2% (14 knees) were revised [4.4% (six knees) for tibial loosening, 5.1% (seven knees) for disease progression, and .7% (one knee) for pain]. For patients living 15 years, 12.5% (six knees) were revised [2.1% (one knee) for tibial loosening, and 10.4% (five knees) for disease progression]. Revision for failure of fixation of these unicompartmental replacements was comparable with that reported for fixed bearing total knee replacement. Disease progression (46%; 62 of 136 knees) and tibial subsidence with wear (10.4%; 15 of 136 knees, five of which required revision) were the major long term problems in this group of patients.
9490250 [Results of surgical treatment for Dupuytren contracture]. 1997 Early and late results of surgical treatment for Dupuytren contracture within 53 hands in 47 patients aged 19-72 (mean 58) are presented. Early results depended on magnitude of deformity and late ones (3-7 years after surgery) depended on recurrence of the contracture. In patients who had rheumatoid arthritis or the results were slightly worse; pathological changes within the hand were to blame and not the recurrence of contracture itself. No difference in histopathology of this condition was observed between rheumatoid arthritis-group- and ankylosing spondylitis patients.
11034702 Cyclophosphamide for treating rheumatoid arthritis. 2000 OBJECTIVES: To assess the short-term effects of cyclophosphamide for the treatment of rheumatoid arthritis. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's Register, the Cochrane Controlled Trials Register (issue 3, 2000), Medline and Embase up to and including August 2000. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing oral cyclophosphamide against placebo (or an active drug at a dosage considered to be ineffective) in patients with rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: Data abstraction was carried out independently by two reviewers. The same two reviewers using a validated checklist (Jadad 1996) assessed the methodological quality of the RCTs and CCTs. Rheumatoid arthritis outcome measures were extracted from the publications for baseline and end-of-study. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts. Weighted mean differences (WMDs) were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout. MAIN RESULTS: A total of 70 patients were included in the pooled analysis of two trials, 31 receiving cyclophosphamide. A statistically significant benefit was observed for cyclophosphamide when compared to placebo for tender and swollen joint scores: SMDs were -0.57 and -0.59 respectively. The difference in ESR also favoured the active drug but did not reach statistical significance (-12 mm, 95%CI: -26 to 2.5). One trial reported the number of patients developing new or worse erosions: the OR for cyclophosphamide compared to placebo was 0.17 (95% CI: 0.05 to 0.57). Patients receiving placebo were six times more likely to discontinue treatment because of lack of efficacy than patients receiving cyclophosphamide. Withdrawals from adverse reactions were higher in the cyclophosphamide group (Odds ratio=2.9), although this difference was not statistically significant. Side effects from cyclophosphamide included hemorrhagic cystitis, nausea, vomiting, leucopenia, thrombocytopenia, alopecia, amenorrhea and herpes zoster infections. REVIEWER'S CONCLUSIONS: Cyclophosphamide appears to have a clinically and statistically significant benefit on the disease activity of patients with RA, similar to some disease modifying antirheumatic drugs (DMARDs) such as antimalarials or sulfasalazine, but lower than methotrexate. Toxicity however is severe, limiting its use given the low benefit-risk ratio compared to other antirheumatic agents.
9002040 Nonparametric simulation based linkage statistics for general pedigrees. 1997 Jan A common strategy for testing for linkage without posing a disease model is to test for increased marker similarity among the affected pedigree members. We developed a simulation based statistic, SimIBD, which measures marker similarity in terms of identity-by-descent (IBD) when it can be determined whether or not the alleles are IBD, and in terms of the probability of the alleles being IBD when it cannot be determined. The SimIBD statistic is not only more powerful than its precursor, the affected-pedigree-member (APM) method, but it is also less sensitive to the misspecification of marker allele frequencies.
10444359 Role of cytokines in the pathogenesis of anemia of chronic disease in rheumatoid arthritis 1999 Aug The aim of our study was to evaluate the role of proinflammatory cytokines: tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), as well as the possible contribution of interleukin-10 (IL-10) in anemia of chronic disease (ACD) of rheumatoid arthritis (RA) patients. We measured the serum levels of TNFalpha, IL-1beta, and IL-6 in 105 anemic and 127 nonanemic RA patients. We also investigated the effects of the above cytokines on the development of burst-forming units-erythroid (BFUe) and colony-forming units-erythroid (CFUe) in bone marrow cultures. Anemic patients had significantly higher serum levels of TNFalpha, IL-1beta, and IL-6 compared to nonanemics. Serum IL-10 levels were low and there was no significant difference in IL-10 concentrations between anemic and nonanemic patients. Proinflammatory cytokines inhibited proliferation of BFUe and CFUe. IL-10 did not decrease the erythroid colony growth. Proinflammatory cytokines may play a role in the pathogenesis of ACD in RA patients. Low levels of IL-10 possibly contribute to the development of ACD.
9470915 Nail abnormalities in rheumatoid arthritis. 1997 Dec Many nail abnormalities have traditionally been described in association with rheumatoid arthritis (RA), but their specificity has never been assessed in a controlled study. Our purpose was to evaluate the frequency and the specificity of nail changes associated with RA in a case-controlled study including 50 patients suffering from RA and 50 controls. For each patient, a general skin examination was performed and the 20 nails were examined. The nail features were noted and classified. A chi 2 test or a Fisher test was used to compare the two groups. The only nail abnormalities significantly associated with RA were longitudinal ridging on nine or 10 finger nails (29 patients in the RA group vs. three in the controls, chi 2: P < 0.001) and clubbing on at least one nail (24 patients vs. 10, chi 2: P < 0.01). Other nail changes were noticed but were not frequent enough to be significant. The presence of longitudinal ridging on the finger nails was significantly associated with RA.
11251690 Association of vitamin D receptor genotypes with early onset rheumatoid arthritis. 2001 Feb The presence of certain vitamin D receptor (VDR) genotypes has been associated with low bone mineral density (BMD) in elderly populations as well as with accelerated bone loss in patients with rheumatoid arthritis (RA). In the present study, VDR genotypes from 120 Spanish patients with RA were investigated. Three VDR gene polymorphisms (BsmI, ApaI and TaqI) were investigated using polymerase chain reaction followed by enzymatic digestion. The distributions of VDR allelic frequencies were similar in patients and controls and therefore no influence of VDR polymorphisms on rheumatoid arthritis susceptibility could be demonstrated. However, in an analysis of the clinical features of the different VDR-related genetic subgroups, the BB/tt genotype, defined by the BsmI and TaqI restriction site polymorphisms, was identified to be weakly associated with an early onset RA in female patients. This VDR genotype has been associated with a low BMD level in various studies. When patients were stratified according to the presence of the shared HLA epitope SE, it was found that SE + female patients bearing the BB/tt genotype showed the earliest disease onset. The mechanisms by which the VDR polymorphism is associated with RA is unknown, but they could be related to the immunoregulatory properties of vitamin D.
11099935 Molecular mimicry between HLA-DR alleles associated with rheumatoid arthritis and Proteus 2000 Oct Molecular mimicry is one of the pathological mechanisms proposed to explain the association between microorganisms and autoimmune diseases. This review deals with the association between bacteria and rheumatic diseases with a special emphasis on rheumatoid arthritis where upper urinary tract infection by Proteus mirabilis is the possible cause of this severe, arthritic condition. Prospective trials involving anti-Proteus therapy should be carried out.
11094412 Genetics of rheumatoid arthritis: confronting complexity. 1999 The genetic basis for rheumatoid arthritis (RA) is likely to be extremely complex. Even the role of MHC genes remains to be fully defined, and may involve interactive genetic effects. The difficulty of precisely defining the clinical phenotype, as well as underlying genetic heterogeneity, complicates the problem. In addition, stochastic genetic or physiologic events may contribute to the low penetrance of susceptibility genes. This situation parallels developing paradigms for other autoimmune disorders, in which many different genes each appear to contribute a small amount to overall risk for disease, and where severity and specific phenotypic subtypes are subject to genetic effects. The completion of the human genome project, along with advances in informatics, will be required to reach a deeper understanding of RA. It is likely that this will involve an iterative and interactive process between several different scientific disciplines.
10587558 Frequency of sepsis after local corticosteroid injection (an inquiry on 1160000 injections 1999 Dec OBJECTIVES: The principal aims of this study were to determine the frequency of sepsis after local corticosteroid injection (SALCSI), to compare the results with those of the literature and to determine the main factors leading to a decrease in the frequency of SALCSI. METHODS: A retrospective study was conducted among 69 rheumatologists in private practice. Sixteen items were studied and are reported. RESULTS: The mean number of years of private practice in rheumatology was 20.9. The total number of CS injections (CSI) was 1160000 for an average of 809 CSI per year and per therapist. The mean number of CSI performed by one rheumatologist was 16 800. Fifteen SALCSI had occurred, which corresponds to a frequency of 1/77300 CSI. The rate of SALCSI for the older rheumatologists was lower than that of their younger colleagues. The frequency of use of corticosteroid packaged in a sterile syringe (CSPSS) was approximately 85%. Nine out of the 15 cases of sepsis had occurred after the use of CS not packaged in a sterile syringe and six after the use of CSPSS. Thus, the frequency of SALCSI was 1/162000 after the use of CSPSS and 1/21000 after the use of CS not packaged in a sterile syringe. CONCLUSIONS: The mean frequency of SALCSI in Paris and the surrounding area was 1/77300 during the last 21 yr, a decrease since the 1960s and 1970s. This decreased incidence is in part due to the greater experience of the rheumatologist, but even more to the use of CSPSS.
9494990 Surgical management of the rheumatoid hip. 1998 Feb Total hip arthroplasty (THA) has improved significantly in the last 30 years since the popularization of the procedure by John Charnley in the late 1960s. The significant advances in THA in the last 20 years have been that it is highly reproducible and durable, has high quality of function and low morbidity, patient satisfaction is high, and salvage is possible when necessary. The main object of this article is to discuss the surgical management of patients who have RA of the hip joint, dealing with indications, surgical techniques, results, and complications.
9098088 Intracellular metabolism of 4-hydroxynonenal in primary cultures of rabbit synovial fibrob 1997 The intracellular metabolism of 4-hydroxynonenal (HNE), a secondary product of lipid peroxidation and mediator of inflammation, which was found in the joints of patients with rheumatoid arthritis, was investigated in primary cultures of rabbit synovial fibroblasts. A consumption rate of 27.3 nmol/min x 10(6) cells was measured for the cultivated fibroblasts. It could be shown, that 4-hydroxynonenal enters the synovial fibroblasts and is metabolized mainly oxidatively to 4-hydroxynonenoic acid, intermediates of the tricarboxylic acid cycle and water and by formation of the glutathione-HNE adduct. The share of protein-bound HNE was about up to 8% of the total added HNE after 10 min of incubation. All metabolites accumulates intracellularly within the incubation time except of 4-hydroxynonenal itself. An increase of 4-hydroxynonenoic acid could be detected also extracellularly during the intracellular metabolism of 4-hydroxynonenal. Therefore, an involvement of synovial fibroblasts in the secondary antioxidant defense system of the joints during conditions of higher HNE concentrations like rheumatoid arthritis is suggested.
10641082 [The ocular manifestations in rheumatoid polyarthritis]. 1999 Systemic diseases as rheumatoid arthritis and ankylosing spondylitis have unknown etiologies, unclear pathogenic mechanisms and multiorgan involvements. Ocular involvement is variable and may effect several levels: sclera, cornea, uvea and conjunctiva. Because an ocular event signify an enhancement of inflammatory-immune reactions, the patient may undergo a complete investigation and general therapy must complete local treatment. The paper showing the ocular manifestation in patients with rheumatic arthritis through a ten-years period.
10036635 Retroviral sequences in rheumatoid arthritis synovium. 1998 There are several relationships between retroviruses and cellular transformation, as well as retroviruses being involved in the development of autoimmune diseases. Retroviruses have been discussed as etiologic agents modulating or triggering certain pathways in the pathogenesis of rheumatoid arthritis (RA). However, none of the currently known retroviruses has been identified as specific for RA. Due to the unique properties of retroviruses, distinct experimental approaches can be used to detect retroviral activity in cells and tissues. Current research in RA using state-of-the-art molecular biology techniques includes both the search for exogenous and endogenous retroviral gene sequences in synovium of patients with RA.