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ID PMID Title PublicationDate abstract
9150071 HLA-DRB1, DQA1, and DQB1 genotypes and risk of vasculitis in patients with rheumatoid arth 1997 May OBJECTIVE: To investigate the association of rheumatoid vasculitis (RV) with the expression of the shared epitope, HLA-DRB1*04, DQA1, and DQB1 alleles. METHODS: A case-control study was designed to compare the frequency of the shared epitope, DRB1*04 alleles, DQA1, and DQB1 alleles of 31 patients with RV with that of 76 patients with rheumatoid arthritis (RA) without vasculitis. RV cases were discerned in subgroups according to presence or absence of minor skin vasculitis and major organ lesions. HLA-DRB1, DQA1, and DQB1 typing was performed by a polymerase chain reaction amplification and oligonucleotide hybridization. RESULTS: Overall, no associations were found between RV and the shared epitope, the DRB1*04 alleles, DQA1, or DQB1 alleles. The risk of developing RV with minor skin vasculitis (i.e., purpura or petechiae) was 10-20-fold increased in patients with DRB1*04, in particular in those homozygous for DRB1*04, and also in those with DRB1*0401. No such association was found for patients with major organ lesions. CONCLUSION: The occurrence of vasculitis in RA is not associated with the shared epitope. DQA1, or DQB1 alleles. However, the risk of minor skin vasculitis is higher in patients carrying DRB1*04.
9805180 Echocardiographic findings, 24-hour electrocardiographic Holter monitoring in patients wit 1998 Electrocardiographic (ECG) and echocardiographic examinations and 24-h ECG Holter monitoring were carried out in 100 patients (age < 65 years) with rheumatoid arthritis (RA) of stages II-IV according to Steinbrocker's criteria. One hundred patients with osteoarthrosis, spondyloarthrosis and painful shoulder matched for age, sex and body surface area constituted the control group. All patients with myocardial infarction, hypertension, rheumatic fever or a history of diabetes were excluded. Cardiac involvement, evaluated by echo-Doppler cardiography, 24-h ECG Holter monitoring and an ECG at rest, occurred in 52 (52%) patients with RA and in 23 (23%) control group patients (p < 0.0005). In the RA group ECG examination, 1 mm ST depression in at least two consecutive leads was observed more frequently, and occurred statistically more frequently for the highest stage of RA according to Steinbrocker's criteria, highest level of functional index and longer duration of disease. The 24-h Holter ECG monitoring did not show any differences in frequency of rhythm disorders between the RA group and the control group. However, silent myocardial ischaemia episodes appeared more often in the RA group. An ECG examination revealed more cases of valvular heart disease, especially mitral insufficiency, in RA patients than in the control group. A mitral valve prolapse was noted in 6% of patients and a pericardial effusion in 4% of patients. Patients with RA were noted to have a larger diastolic left ventricular diameter and aortic root diameter, and smaller ejection fraction, mean velocity of circumferential fibre shortening and fractional shortening. The results of the examinations show that RA is associated with cardiac involvement in a significant proportion of cases.
10413698 Incidence of corneal melting in association with systemic disease in the Yorkshire Region, 1999 Aug AIMS: To estimate the incidence of corneal melting or necrotising keratitis in association with systemic disease in the Yorkshire Region and to determine the type and duration of the systemic association. METHODS: In a prospective study, vigorous attempts were made to identify all patients presenting with newly diagnosed corneal melting over a 3 year period. RESULTS: 27 patients were identified during the study period. Rheumatoid arthritis and Wegener's granulomatosis were the most common disease associations. Corneal melting was a late complication of rheumatoid arthritis, but usually occurred during early and overt systemic disease in patients with Wegener's granulomatosis. CONCLUSION: The annual incidence of corneal melting in the Yorkshire Region is 3.01/million/year (95% CI = 0.7-9.6).
9617465 High levels of soluble IFN gamma receptor alpha chain in the plasma of rheumatoid arthriti 1998 Soluble receptors for hormones and cytokines have been described. They can serve as natural blockers of their respective ligands. The natural soluble interferon gamma receptor (sIFN gamma R) has been isolated and characterized only in urine. Chromatography of human (hu) plasma from rheumatoid arthritis (RA) patients and controls on immobilized hu IFN gamma or antibodies against IFN gamma R alpha chain permitted us to isolate the sIFN gamma R. The receptor isolated from one control is a protein with a molecular weight between 60-67 kDa depending on the presence of reducing agents. We detected a significantly higher level of plasma sIFN gamma R in patients with rheumatoid arthritis than in apparently healthy subjects.
9890676 Knee and/or hip joint destruction in rheumatoid arthritis is associated with HLA-DRB1*0405 1998 To determine the prognostic factors for knee and/or hip joint destruction in rheumatoid arthritis (RA) patients, we typed 379 RA patients for HLA-DRB alleles and analysed the antigen frequencies. The DRB1*0405 antigen frequency in RA patients who underwent total knee replacement and/or total hip replacement was significantly higher than in those who did not have replacements, which meant that DRB1*0405 was associated with knee and/or hip joint destruction. This finding may be of value for predicting knee and/or hip joint destruction in RA.
10627714 Drug treatment for rheumatoid arthritis. 1999 Sep The general goals of drug treatment for patients with rheumatoid arthritis are to reduce morbidity and mortality. Because rheumatoid arthritis is a potentially devastating disease, a more aggressive treatment approach has emerged in the last decade. The modern treatment pyramid consists of nonsteroidal antiinflammatory drugs and glucocorticoids for symptomatic relief, and disease modifying antirheumatic drugs for reducing disease activity in the short term and joint damage in the long term. There is increasing evidence that a reduction of disease activity by disease modifying antirheumatic drugs alters the course of rheumatoid arthritis and that patients benefit from early installation of these compounds. The major problem with disease modifying antirheumatic drugs is their low efficacy to toxicity ratio, leading to marked reduction of the length of time a patient is taking a given drug. The new treatment strategies, including combination regimens and new drugs that are being investigated, promise better efficacy and tolerance in the near future. A step in this direction is the development of biologic agents targeting specific mechanisms in the immune response. Early results in clinical trials with antitumor necrosis factor-alpha monoclonal antibodies are encouraging.
9204260 Mechanisms of cartilage destruction and novel nonsurgical therapeutic strategies to retard 1997 May Although there are excellent rationales for the use of biologic agents, no published novel therapeutic strategy in patients with early or late rheumatoid arthritis has thus far been proven in controlled clinical studies to prevent or retard cartilage destruction. Although T-cell-specific therapies in chronic rheumatoid arthritis have some success, the percentage of patients responding and the degree of clinical improvement are disappointing, and cartilage injury can neither be prevented nor retarded. Similarly, attempts to interrupt the cytokine loops and inhibit adhesion molecules are only modestly successful. The alternative approach of solely controlling the effector side by direct or indirect metalloproteinase inhibition seems attractive because it would circumvent the cytokine networks while theoretically still preventing the final consequences of inflammation on cartilage. One therapeutic strategy that inhibits metalloproteinses-tetracyclines or chemically transformed tetracyclines-cannot be considered a breakthrough with respect to either reduction of disease activity or prevention or retardation of cartilage injury in rheumatoid arthritis. It is likely that combination therapy will be further developed in the future. The most promising agents today, such as the anti-tumor necrosis factor-alpha antibodies, must be combined with other current strategies as well as with newly developed disease-specific biologic agents. To affect multiple sites in the underlying inflammatory process and to target the delivery of the agents could be one of the goals. The efficacy and effectiveness of any new strategy depends on its ability to alter the function of the aggressive and transformed synovial fibroblasts within the pannus and to protect the articular chondrocytes and early cartilage injury.
9236674 Immunolocalization of inducible nitric oxide synthase in synovium and cartilage in rheumat 1997 Jun Nitric oxide has been implicated as a mediator of inflammatory arthritis, and recent work has shown that pro-inflammatory cytokines stimulate NO production in vitro by activation of the inducible nitric oxide synthase (iNOS) pathway. In order to identify the cellular sources of NO production within the joint, we have used immunohistochemical techniques to study the distribution of iNOS in synovium and cartilage from normal and diseased joints. iNOS was most strongly expressed in the synovial lining layer, subsynovium, vascular smooth muscle and chondrocytes from patients with rheumatoid arthritis (RA). Analysis of serial sections, coupled with double immunofluorescent staining, showed that the CD68+ macrophages in the synovial lining layer and, to a lesser extent, fibroblasts were the predominant source of iNOS within synovium, whereas T cells, B cells and neutrophils were negative. A similar pattern of iNOS staining was seen in osteoarthritis, but fewer cells were iNOS positive and the intensity of staining, particularly in cartilage, was much weaker than in RA. In contrast, no evidence of iNOS was detected in non-inflammatory synovium or in cartilage derived from normal joints (fractured neck of femur). In conclusion, these data support the hypothesis that synovium and cartilage are important sources of increased NO production in patients with inflammatory arthritis. Localization of iNOS at these sites within the inflamed joint raises the possibility that increased local production of NO may contribute to the pathogenesis of inflammatory arthritis by increasing synovial blood flow and by modulating cellular function within synovium and articular cartilage.
9357141 Taming TNF: strategies to restrain this proinflammatory cytokine. 1997 Oct Recent studies have demonstrated the essential role of tumor necrosis factor alpha (TNF-alpha) in rheumatoid arthritis and Crohn's disease. This article discusses agents known to suppress the formation or activity of TNF-alpha, and summarizes clinical studies using anti-TNF-alpha antibodies.
9546814 HLA-DR and the development of rheumatoid arthritis. 1997 Susceptibility to develop Rheumatoid arthritis (RA) maps to a highly conserved amino acid motif ("the shared epitope") expressed in the third hypervariable region of different HLA-DRB1 alleles. This motif, namely QKRAA, QRRAA or RRRAA helps the development of RA by an unknown mechanism. However, it is now established that the shared epitope can 1. Shape the T cell repertoire. 2. Interact with 70 kD heat shock proteins.
11324931 Relationship of ankle joint involvement with subtalar destruction in patients with rheumat 2001 Mar AIMS: In the present study we evaluated radiographically involvement of the ankle joint and its relationship to destruction of the subtalar joint in rheumatoid arthritis (RA). METHODS: An inception cohort of 103 patients with seropositive RA was followed over a period of 20 years. Follow-up examinations were conducted after onset, 1, 3, 8, 15, and 20 years from entry. A total of 83 patients attended the 15-year and 68 patients the 20-year follow-up. Radiographic evaluation was performed using a lateral weight-bearing ankle radiograph. A simplified grading was applied for the talocrural joint, in which the ankles (patients) were divided into three groups: no changes, minor changes and major changes. In the end-point analysis the last radiograph was assigned. Subtalar destruction was recorded (Larsen grade > or = 2). Severity of RA in different groups was evaluated using the Larsen score of 0-100 of hands and feet. Difference between patient groups was evaluated using Cuzick's test. RESULTS: At the endpoint major changes of the ankles were detected in seven patients (7%) only, minor changes were observed in 17 patients (16%). The first minor involvement of the ankle was observed at the three-year follow-up in two patients. First major changes were detected at the 15-year follow-up in three ankles of two patients. Subtalar pathology preceded that of TC joint in all ankles with major changes. In 17 patients with minor changes, simultaneous subtalar pathology was observed in all but two ankles, while preceding subtalar involvement was radiographically manifest in 13 of 21 ankles. The means of Larsen scores of 0-100 were in the three ankle grading groups 40, 54 and 63, respectively. Cuzick's test for the trend was highly significant (P < 0.001). No reconstructive surgery was performed on the ankle joint during the follow-up, whereas the subtalar joint complex was fused cumulatively in 12 patients. CONCLUSIONS: The ankle joint is involved in a late stage of RA and is usually affected only in the patients with severe disease. Subtalar pathology precedes the changes in the talocrural joint almost regularly.
10090187 ACR and EULAR improvement criteria have comparable validity in rheumatoid arthritis trials 1999 Mar We compared the validity of the American College of Rheumatology (ACR) and the European League of Associations for Rheumatology (EULAR) definitions of response in rheumatoid arthritis (RA) clinical trials. US: ACR and EULAR improvement criteria were calculated in 7 large randomized RA clinical trials. The discriminant validity of the response criteria between treatment groups was studied using the Mantel-Haenszel chi-squared value. To compare both sets of criteria the chi-squared ratio was determined for each trial. Europe: In 2 large randomized RA clinical trials, ACR and EULAR criteria were calculated, once with extensive and once with 28 joint counts. The classification of patients with these 4 criteria were compared with each other using cross tables. We further studied the difference in response between treatment groups per trial, the association of response with patient and investigator assessment of improvement, and the association of response with radiological progression. US: The chi-squared ratio for most trials was close to 1. There was no clear pattern suggesting that the discriminant validity of the ACR criteria was stronger than the discriminant validity of the EULAR definition of response or vice versa. Europe: Conflicting results between ACR and EULAR were present in only 3% of patients in both trials. The discriminant validity of all 4 criteria (ACR and EULAR with reduced and extensive joint counts) was comparable. All criteria were related with the overall assessment of improvement by both investigator and patient. The association with radiographic progression was comparable for EULAR and ACR improvement criteria. There is a high level of agreement between ACR and EULAR improvement classification, and their validity is equivalent. The discriminating potential of the criteria between treatment groups is comparable, as is the association with patient's and investigator's overall assessment and with radiographic progression.
9106936 NMR monitoring of rheumatoid arthritis patients receiving anti-TNF-alpha monoclonal antibo 1997 The aim of this study was to investigate if dynamic gadolinium-DTPA-supported magnetic resonance (MR) imaging can monitor the therapeutic effect of a fast-acting immuno-modulating drug like anti-tumour necrosis factor alpha (anti-TNF-alpha) monoclonal antibody (moab) in patients with rheumatoid arthritis (RA). Dynamic MR imaging was performed on 64 joints in a total of 18 patients before and after infusion with either a placebo or 1 or 10 mg/kg of anti-TNF-alpha moab. Additionally, treating the placebo group and reinfusing the verum group with either 3 or 10 mg/kg was monitored by quantitative nuclear magnetic resonance (NMR). Time-dependent signal intensity changes were then correlated with a total of five Paulus criteria and with ESR and C-reactive protein (CRP). No changes in either the gadolinium uptake or clinical parameters were seen after the infusion of a placebo. Therapy with 1 mg/kg anti-TNF-alpha moab resulted in a significant decrease in clinical disease activity, as well as in gadolinium-DTPA uptake in dynamic NMR studies. However, correlations between singal intensity changes and Paulus criteria were only demonstrated for the variable "doctor's evaluation of disease activity". Patients given 10 mg/kg moab demonstrated a very significant improvement in all clinical manifestations of their disease, as well as a high significant reduction in gadolinium uptake (P = 0.004). In addition, the latter group showed significant correlations between time-dependent signal intensity changes and five Paulus criteria: "number of swollen joints", "number of painful joints", "duration of morning stiffness", "doctor's evaluation of disease activity" and "patient's evaluation of disease activity". No differences and correlations were seen for ESR and CRP. We concluded that dynamic NMR studies are suitable to monitor inflammatory activity in RA patients under therapy with biological response modifiers such as anti-TNF-alpha moab.
10366125 An aggressive form of polyarticular arthritis in a man with CD154 mutation (X-linked hyper 1999 Jun Hyper-IgM syndrome (HIM) is a rare immunodeficiency disorder that has been associated with the development of symptoms and clinical features characteristic of rheumatoid arthritis (RA). We describe a patient with HIM and severe erosive arthritis with prominent nodules in the absence of detectable serum rheumatoid factor. Because HIM results from defects in either T cell CD154 (CD40 ligand) expression or abnormal CD40 signaling, the molecular basis of the patient's disease was analyzed. Activated CD4+ T cells failed to express surface CD154 protein, and molecular analysis of CD154 complementary DNA revealed a nucleotide transversion resulting in the nonconservative amino acid substitution G-D at amino acid 257. This case indicates that defective CD154-dependent CD40 signaling can be associated with susceptibility to a severe inflammatory arthritis that has both similarities to and differences from idiopathic RA.
11300392 One way to ventilate patients during fibreoptic intubation. 2001 Apr Occasionally anaesthesiologists find themselves in situations where ventilation during intubation with a fibreoptic bronchoscope (FOB) is desirable. In order to ventilate the patient during the FOB intubation, we used a 90 degree angle swivel connector, normally used for fibreoptic bronchoscopia in an intubated patient. After a nasotracheal tube is placed with the tip in the oropharynx, ventilation of the patient is possible via this tube by closing the mouth and other nostril. The fibrescopic procedure is done through the right-angle connector with suction port and the tube is used to guide the tip of the FOB to the aditus laryngis. The method has been used in 7 patients who were impossible to intubate with a conventional procedure. In all patients ventilation was possible and intubation was performed in 5 min (range 1-15).
10025862 Peripheral ulcerative keratitis--an extracutaneous neutrophilic disorder: report of a pati 1999 Feb The term peripheral ulcerative keratitis represents a spectrum of inflammatory diseases, characterized by cellular infiltration, corneal thinning, and ulceration. Neutrophilic dermatoses are rarely associated with peripheral ulcerative keratitis. To date, peripheral ulcerative keratitis has only been reported in patients with pyoderma gangrenosum. Separate episodes of pyoderma gangrenosum, Sweet's syndrome, and pustular vasculitis developed in a 60-year-old patient with rheumatoid arthritis over an 8-year period. Over the past 2 years, 3 episodes of peripheral ulcerative keratitis occurred. Cyclosporine (4 mg/kg/d) treatment was started on confirmation of pyoderma gangrenosum. Over the ensuing 2 years, it became evident that the activity of her ocular and skin diseases, as well as her arthritis, paralleled the administration or cessation of cyclosporine therapy. Dermatologists should be aware of the association of Sweet's syndrome, pyoderma gangrenosum, and pustular vasculitis with peripheral ulcerative keratitis. This rare ocular manifestation and the serious sequelae when left untreated make recognition crucial. Cyclosporine proved to be a very effective treatment for all of our patient's diseases.
11327245 The antiquity of rheumatoid arthritis: a reappraisal. 2001 Apr OBJECTIVE: To demonstrate the existence of rheumatoid arthritis (RA) before the 19th century. METHODS: Survey of primary and secondary references on the history of rheumatic diseases. RESULTS: Paleopathological evidence suggests the existence of RA in America since 8000 BC and in Europe since the 7th century. Descriptions and representations of a symmetric chronic polyarthritis producing characteristic deformities can be found in Rome since 100 BC and India since 500 BC. The first clinical distinction between RA and gout was published in Mexico in 1578. Different historical conditions contributed to lack of recognition of RA by official medicine before 1800. The recognition of RA as a distinct entity in the 19th century was influenced by socioeconomic circumstances. CONCLUSION: RA is not a recent disease. Historical investigation can provide useful clues on its pathogeny.
10339301 Mortality in rheumatoid arthritis: experience in four clinical series compared with the ex 1998 BACKGROUND: Survival curves and decimal Standardized Mortality Ratios (SMRs) were reported in 1994 for four clinical series of patients with Rheumatoid Arthritis (RA), with use of a common data processing system. It was felt to be desirable to compare the excess mortality observed in clinical patients with the excess mortality found in substandard policyholders with RA in the 1983 Medical Impairment Study. RESULTS: The weighted mean SMR was 2.25 for the male RA patients and 2.42 for the females. Although similar in magnitude to the percentage male and female Mortality Ratios (MRs) in the 1983 Medical Impairment Study, the derived Excess Death Rate (EDR) was higher for the clinical RA patients, despite the lower select mortality versus the population mortality, even after adjustment for difference in mean age between the clinical and insurance series. CONCLUSION: The higher EDR in four clinical series of RA patients probably reflects a higher proportion of more severe cases, who are declined for insurance or do not accept a highly rated offer.
9836379 Treatment of rheumatoid arthritis with IL-1 inhibitors. 1998 Extensive evidence from both in vivo and in vitro experiments indicate that IL-1, a prototypic proinflammatory cytokine, is involved in the mechanisms that lead to progressive joint destruction in RA. IL-1Ra, a member of the IL-1 family, binds IL-1 receptors but does not induce any cellular responses. IL-1Ra competitively inhibits the binding of IL-1 to its cell surface receptors and thus, acts as an endogenous antiinflammatory mediator. However, the results of several studies suggest that a relatively deficient production in IL-1Ra as compared to that of IL-1 in RA synovium may predispose to the perpetuation of chronic inflammation. Systemic administration of IL-1Ra, or local delivery into the joint by gene therapy, in different experimental animal models of arthritis attenuated the severity of the inflammatory response and reduced articular destruction. In addition, treatment of rheumatoid patients with IL-1Ra led to an improvement in different clinical and biological parameters and to a reduction in the radiological signs of joint erosions. Encouraging results also have been reported in both in vitro and in vivo experimental animal models of arthritis through using other strategies designed to block the effects of IL-1 at the level of production, prevent the binding of IL-1 to its cell surface receptors, or interfere with the effects of IL-1 at the post-receptor level.
11561108 Expression of chemokines and matrix metalloproteinases in early rheumatoid arthritis. 2001 Sep OBJECTIVE: To compare macrophage infiltration and expression of chemokines and matrix metalloproteinases (MMPs) in synovial tissue between patients with early and long-standing rheumatoid arthritis (RA). METHODS: Knee synovial biopsies were taken from 22 patients with early (<1 yr) and 22 patients with long-standing (>5 yr) RA and immunostained with antibodies specific for CD68; macrophage inflammatory protein (MIP)-1alpha and monocyte chemoattractant protein (MCP)-1; MMP-1 and -3 and the tissue inhibitors of metalloproteinases (TIMP)-l and -2. Immunostaining was quantified using a colour video image analysis system. RESULTS: CD68+ macrophage infiltration and the expression of MIP-1alpha, MCP-1, MMP-1, MMP-3, TIMP-1, and TIMP-2 were observed in synovial tissue of patients with early RA. In long-standing RA, there was a further increase in CD68+ macrophage infiltration and MIP-1alpha expression in the synovial lining layer. CD68 expression correlated with MIP-1alpha (R=0.39, P=0.01), but not with MCP-1 expression. CONCLUSION: Macrophage accumulation, and the expression of chemokines and MMPs in synovial tissue occur in early RA. Targeting chemokines which play a role in the migration of macrophages into the joints may be of therapeutic benefit in RA patients.