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ID PMID Title PublicationDate abstract
1384103 Plasma interleukin-6 and renin substrate in reactive arthritis, rheumatoid arthritis, and 1992 In order to study the role of interleukin-6 (IL-6) in inflammatory disease we monitored plasma levels of IL-6 and acute phase proteins such as C-reactive protein (CRP) and renin substrate (RS) in patients with reactive arthritis (ReA), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Venous plasma samples were collected: (1) during the acute phase or exacerbation of the disease, and (2) several months latter during convalescence. Increased mean [95% confidence intervals (CI)] levels of plasma IL-6 were observed in patients with ReA both in the acute phase and later, 229 (177 to 280) ng/l and 197 (134 to 260) ng/l respectively (P less than 0.001 as compared to controls). The corresponding plasma IL-6 levels in RA patients were 283 (223 to 340) ng/l and 183 (151 to 226) ng/l, respectively (P less than 0.001 as compared to controls). Plasma IL-6 levels in SLE patients were not increased. Plasma RS levels were increased in all patient groups, but no significant correlation to IL-6 or CRP levels was observed, whereas plasma IL-6 and CRP levels showed a positive correlation in ReA and RA patients.
1608484 [Pain in rheumatoid arthritis measured with the visual analogue scale and the Dutch versio 1992 Jun 13 Chronic pain is an important symptom of rheumatoid arthritis (RA). Pain is a complex experience and is not easily measured with a single instrument. Recently a Dutch version of the McGill Pain Questionnaire (MPQ) became available. The MPQ is a measure of the quality of pain as opposed to the traditional measures of pain intensity such as the Visual Analog Scale (VAS). In a study of 415 RA patients both measures of pain were administered. Both pain measures were only weakly related to medical variables. The VAS is easily administered and is reliable. The MPQ offers insight in the sensory experience of pain and gives more information about the quality of life of the patient. The conclusion is that the MPQ is a useful instrument to obtain a better picture of the complexity of the pain experience in RA.
9006234 Pain intensity and health locus of control: a comparison of patients with fibromyalgia syn 1996 Nov The major purpose of this study was to determine if 31 patients with fibromyalgia syndrome (FS) reported different pain intensity and Health Locus of Control (HLC) scores than 30 patients with rheumatoid arthritis (RA). Another purpose was to determine the relationship among experienced actual pain (present, usual, worse, least), recalled prior episodes of pain (worse toothache, headache, and stomach ache), HLC orientation, age and the duration of the actual pain. Visual Analogue Scales were used to measure pain intensity. The Health Locus of Control Scale was used to determine external/internal orientation. The results showed that the FS patients reported significantly more intense actual pain, recalled pain for worse toothache and headache, and were more externally oriented than the RA patients. Present pain intensity was significantly correlated to actual intensity ratings, but not to reported earlier experienced pain, except for worse stomach ache in the RA group. The findings' implications for treatment and education are discussed.
1544227 Regulation of IL-2 production by mononuclear cells from rheumatoid arthritis synovial flui 1992 Mar Products of polyamine oxidation down-regulate IL-2 production by peripheral blood T cells. We show here that the production of IL-2 by rheumatoid arthritis synovial fluid mononuclear cells is inversely correlated with the concentrations of polyamines in these cells. In addition, the inhibition of polyamine biosynthesis or oxidation in cultures of these cells enhances their ability to produce IL-2. Our findings suggest that polyamine oxidation plays an important role in the suppression of T cell function characteristic of rheumatoid arthritis synovial fluids.
1555038 Cytidine deaminase and lactoferrin in inflammatory synovial fluids. Indicators of local po 1992 Apr Cytidine deaminase (CD) is a cytoplasmatic enzyme present predominantly in polymorphonuclear cells (PMNC) in inflamed joints. Lactoferrin is situated in the secondary granules of PMNC and is released by secretory/phagocytic stimuli, whereas CD is released mainly upon cell lysis. To study the release of these molecules in arthritic conditions we measured CD and lactoferrin levels in synovial fluid (SF) drawn from patients with rheumatoid arthritis (RA), crystal pyrophosphate disease (CPPD), psoriatic arthropathy, reactive arthritis, spondylarthropathy, and osteoarthrosis. CD activity was highest in SF from RA and CPPD followed by psoriatic arthropathy, reactive arthritis and spondylarthropathy. Lactoferrin concentrations were highest in CPPD followed by RA, reactive arthritis, psoriatic arthropathy, and spondylarthropathy. Both CD and lactoferrin levels were low in osteoarthrosis SF. Although SF CD activity and lactoferrin levels correlated well in all diagnostic groups, the ratio between CD and lactoferrin was higher for RA, psoriatic arthropathy, and spondylarthropathy compared to reactive arthritis and CPPD. This suggests predominant release by PMNC lysis in the more chronic arthritis groups and more degranulation in the more episodic CPPD and reactive arthritis groups. CD activity and lactoferrin levels correlated significantly with SF cell counts in the RA and psoriatic arthropathy groups.
7762425 Lactoferrin and the inflammatory response. 1994 Polyclonal antibodies were prepared to purified breast milk lactoferrin and used in an ELISA to measure plasma concentrations in investigations of various aspects of the inflammatory response. They were also used, in situ, to evaluate granulocyte lactoferrin content in disease states. The first series of studies addressed the putative role of lactoferrin in the pathogenesis of the hypoferremic, hyperferritinemic response to acute inflammation. Dissociation between the lactoferrin response and the iron related changes in rheumatoid arthritis and after alpha-interferon administration suggested that the relationship observed in acute and chronic bacterial infection may reflect coincidental effects of inflammatory cytokines. That lactoferrin does not mediate the inflammatory hypoferremic response was established by the finding that bone marrow transplant recipients, post-myeloablation, developed a hypoferremic response during septic episodes despite virtually undetectable plasma lactoferrin concentrations. The second series of investigations employed the plasma lactoferrin concentration as an index of granulocyte activation and function in a number of inflammatory conditions. Markedly increased initial plasma concentrations in acute pneumonia reflecting profound intravascular granulocyte activation were documented to predict sepsis related mortality. Plasma and granulocyte lactoferrin studies established that viral infection is associated with an acquired granulocyte lactoferrin deficiency. Plasma measurements indicated that asthmatics, even when clinically asymptomatic, have evidence of persistent granulocyte activation.
8252313 Cytokine and prostaglandin production by monocytes of volunteers and rheumatoid arthritis 1993 Dec In this study, dietary supplements of blackcurrant seed oil (BCO) rich in the n-6 polyunsaturated fatty acid (PUFA) gamma-linolenic acid were fed to both RA patients and healthy volunteers with sunflower seed oil being fed to control subjects. A significant improvement in morning stiffness was noted in the RA patients receiving BCO. Monocytes were isolated from all subjects and cultured in the presence of lipopolysaccharide. It was observed that the production from the cultured monocytes of the cytokines IL-1 beta, TNF alpha and IL-6 as well as the prostaglandin PGE2 was markedly altered in those subjects given BCO. The results suggest that the numerous beneficial effects of PUFAs in inflammatory diseases such as RA may be due to a reduction in the secretion of the inflammatory cytokines IL-1 beta and TNF-alpha via redirection of eicosanoid metabolism although the possibility cannot be excluded that the PUFAs may be altering cytokine release directly through an effect on monocyte membranes.
7591992 Glycobiology: 'the function of sugar in the IgG molecule'. 1995 Oct Immunoglobulin G (IgG) is glycosylated in both the Fc and the Fab regions of the protein with a heterogeneous ensemble of structures (glycoforms) that is both highly reproducible (i.e. nonrandom) and site specific. In normal IgG, the 2 highly conserved oligosaccharides of the Fc region are found buried between the CH2 domains, forming specific protein-saccharide interactions with the Fc protein surface. One of the functions attributed to the Fc oligosaccharides of normal IgG is to maintain the conformational arrangements of the Fc domains as well as the hinge regions. These structural features are necessary for Fc effector functions such as Clq and monocyte binding. A hallmark of rheumatoid arthritis (RA) patients is a dramatic increase in the presence of serum IgG containing Fc oligosaccharides lacking an outer arm galactose residue (termed 'G0' glycoforms). The increased level of G0 has been shown to be directly related to the pathogenesis of RA. Nuclear magnetic resonance relaxation studies of the Fc region from normal and RA IgG, as well as examination of x-ray structures, show that the G0 oligosaccharides have an increased mobility resulting from the loss of binding between the G0 oligosaccharide and the Fc protein surface. From these observations it follows that regions of the protein surface that are normally covered by the oligosaccharide are revealed. The newly accessible protein surface could have lectin-like activity and also be inherently antigenic. In addition, the more mobile G0 oligosaccharide can be recognised by mannose binding protein. As the mannose binding protein can activate complement, and the Fc oligosaccharide would not normally be accessible to protein recognition, this finding might suggest a specific role for the G0 glycoform in inflammation when the appropriate IgG glycoforms are clustered.
8834013 Effects of antirheumatic agents on cytokines. 1996 Feb A review of the literature concerning the effects of traditional antirheumatic drugs on cytokines and the cytokine and anticytokine approaches already used in the therapy of rheumatoid arthritis (RA) is presented. Many antirheumatic drugs are capable of cytokine modulation in vitro. Corticosteroids inhibit the transcription of a broad spectrum of genes including those encoding monocyte, T cell-derived cytokines and several hemopoietic growth factors, whereas drugs such as cyclosporin A and D-penicillamine interfere with T cell activation more specifically by suppressing interleukin 2 (IL-2) production. The in vivo effects of drug therapy on cytokines in RA patients are less well established. Gold compounds reduce circulating IL-6 levels and the expression of monocyte-derived cytokines, such as IL-1, tumor necrosis factor (TNF), and IL-6, in the rheumatoid synovium. Decreases in circulating IL-6, soluble IL-2 (sIL-2R), and TNF receptors and in synovial fluid IL-1 levels have been reported with methotrexate. Reductions in circulating IL-6 and sIL-2R concentrations have also been observed with cyclosporin and corticosteroids, whereas azathioprine reduces IL-6 but not sIL-2R. Studies on sulfasalazine are conflicting and the in vivo effects of D-penicillamine and antimalarials have not been studied yet. Interferon gamma therapy is not effective in RA but may prove a useful antifibrotic for systemic sclerosis. Colony stimulating factors improve the granulocytopenia associated with Felty's syndrome or drug toxicities but can induce arthritis flares and should be reserved to treat infectious complications. Promising results are being obtained with selective antagonism of TNF and IL-1 in RA, and combinations of anticytokine strategies with traditional antirheumatic drugs have been already envisaged. These should preferably be based in a broader knowledge of the effects of antirheumatic agents on the cytokine network.
8624487 High DNA-binding activity of transcription factor NF-kappa B in synovial membranes of pati 1995 Nov Our objective was to clarify the DNA-binding activity of transcription factor NF-kappa B as related to cytokine induction in the synovium of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Synovial membranes were obtained during arthroplasty of the knee from 7 patients with RA and 4 patients with OA. Nuclear extracts obtained from the synovial membranes were examined by electrophoretic mobility shift assay to determine the DNA-binding activity of NF-kappa B. Markedly high DNA-binding activity of NF-kappa B was detected in the synovial membranes of RA patients, while virtually no activity was observed in those of OA patients. These results suggest that the high induction of NF-kappa B in the nuclear extracts may be relatively specific to synovial membranes in RA. NF-kappa B may regulate the production of cytokines at the site of synovial inflammation.
7774098 Elevated serum interleukin-6 levels associated with active disease in systemic connective 1995 Jan OBJECTIVE: It is well established that connective tissue diseases such as systemic lupus erythematosus (SLE) are associated with a weak or absent acute phase response, although elevated serum interleukin 6 levels have been described. In this study, we have sought to correlate serum levels of IL-6 with standard laboratory and clinical assessments of disease activity in two connective tissue diseases, namely SLE and systemic sclerosis (SSc), and, for comparative purposes, rheumatoid arthritis (RA). METHODS: Serum IL-6 levels were determined by bioassay and also, in some sera, by immunoradiometric assay. They were compared with two inflammatory parameters, serum C-reactive protein (CRP) and plasma viscosity (PV), and with appropriate clinical measurements in the various patient groups, including BILAG in SLE, the skin score in SSc, and the Ritchie index in RA. RESULTS: Serum IL-6 (SeIL-6) levels were elevated in active SLE, SSc, and RA. This was poorly correlated with the acute phase response in SLE and SSc, but there was a strong relationship of SeIL-6 to disease activity in these conditions. In SLE, the BILAG disease activity index correlated best with SeIL-6 levels while there was only a weak relationship between CRP and IL-6, and no relationship between CRP and disease activity. In SSc there was a relationship of disease activity to SeIL-6 but not between SeIL-6 and either CRP or PV. In a small RA group there was a much stronger relationship of SeIL-6 to CRP and PV, as has been previously described. CONCLUSION: The determination of SeIL-6 may be a useful indicator of disease activity in those patients groups, including SLE and SSc, in which a normal acute phase response by the liver is often lacking. The mechanism underlying this hepatic impairment requires further investigation, but is clearly not due to a failure to generate the appropriate cytokine signal. Excessive local or systemic production of IL-6 in connective tissue diseases could play an important pathogenic role in these conditions, for example through stimulating autoantibody synthesis.
1287822 Self-appraisal and coping in out-patients with chronic disease. 1992 Dec Self-appraisal, coping efforts, muscle function, and activity and severity of disease were examined in out-patients with rheumatoid arthritis, osteoarthrosis or diabetes mellitus. Factor analysis of a 31-item self-appraisal and coping questionnaire yielded eight factors (self-appraisal, acceptance, minimization, planful problem-solving, avoidance, persistence, attribution of responsibility, and support seeking). For the factors of avoidance, minimization, and persistence, as well as for measures of activity and severity of disease, significant differences between the diagnostic groups were found. For patients with rheumatic arthritis, hierarchical regression analysis indicated disease duration to be associated with acceptance and with attribution of responsibility, and disability measures to be associated with self-appraisal. For patients with osteoarthrosis, they showed disability in muscle function to be associated with avoidance, and more negative self-appraisal as well as lower levels of support seeking to be associated with long disease duration. Results are discussed in terms of structural and adaptive defence forms and of adherence to a coping model ("medical model") which tends to foster acceptance and dependency.
8275594 Osteoporosis in rheumatoid arthritis. 1993 Sep Osteoporosis is recognised as a common complication of rheumatoid arthritis, with two characteristic patterns--juxta-articular and generalized bone loss. Increasingly sophisticated means of measuring bone turnover and identifying inflammatory mediators which affect bone resorption have enhanced our understanding of the disease process. The aetiology is multifactorial, involving disease-specific and general factors, but the relative importance of the various risks remains uncertain. The evidence for a protective role for oestrogens and the detrimental effect of low dose corticosteroids will be discussed. Biochemical assessment of bone loss lacks sensitivity and specificity, but the rapid improvement in radiological techniques for measuring bone mineral density have improved our ability to diagnose and assess disease progression. The diagnosis and treatment of specific risk factors, such as testosterone or vitamin D deficiency, may be helpful in a few patients, but the ultimate aim must be the early diagnosis and prevention of this potentially catastrophic complication.
7766499 Epidemiology of the rheumatic diseases. 1995 Mar Epidemiologic studies are important for both understanding and defining rheumatology practice. Controversy still exists over whether the incidence of rheumatoid arthritis is declining, and genetic studies indicate a diversity of HLA haplotypes in rheumatoid arthritis. Large longitudinal osteoarthritis studies have helped define diagnostic criteria and the role of obesity in disease progression. The negative association between osteoarthritis and osteoporosis at specific sites continues to be explored, and the value of long-term estrogen therapy in preventing bone loss has been examined. Both retrospective and prospective population studies have been used to describe the relationship between silicone gel breast implants and connective tissue disease. These and other studies have helped to define the important role of epidemiologic research in the understanding of rheumatic diseases.
8670592 Expression of bcl-2 in rheumatoid arthritis. 1996 Jul Since defective apoptosis has been suggested to play a role in the development of autoimmune diseases, we have investigated the expression of the proto-oncogene bcl-2 in patients with rheumatoid arthritis (RA). The expression of bcl-2 was studied in peripheral blood (PB) and synovial fluid (SF) lymphocytes and synovial tissues (ST) from patients with RA using immunohistochemistry, flow cytometry and nucleic acid hybridization. Patients with reactive arthritis (ReA) or osteoarthritis (OA) and healthy individuals were used as controls. The expression of bcl-2 protein in PB lymphocytes and the expression of bcl-2 mRNA in PB mononuclear cells (PBMC) was similar in healthy controls and patients with RA. However, bcl-2 protein expression was significantly reduced in SF lymphocytes when compared to PB lymphocytes. Similar results were observed with lymphocytes from patients with ReA, and irrespective of whether total lymphocytes, T cells or different T-cell subsets were studied. In the synovial sections, the expression of bcl-2 was restricted to lymphocytes, and bcl-2+ cells were observed in the majority of samples from patients with RA, OA and ReA. These data indicate that the expression of bcl-2 is not increased in the lymphocytes or ST derived from patients with RA. Instead, decreased expression of bcl-2 protein in SF lymphocytes compared to PB lymphocytes was demonstrated. We suggest that bcl-2 does not play a significant role in the pathogenesis of RA.
7909272 Sulphasalazine-induced systemic lupus erythematosus in a patient with erosive arthritis. 1994 Feb An unusual case of a lady with seropositive erosive RA, treated for 5 yr with sulphasalazine. She then developed SLE which resolved after stopping the drug. This case is reported with a short review of the literature.
8100384 Immuno-electron microscopic analysis of the distribution of ICAM-1 in human inflammatory t 1993 An immuno-electron microscopic analysis was undertaken to determine ICAM-1 expression on vascular endothelium in human tonsils and in synovia from patients with rheumatoid arthritis. ICAM-1 was preferentially expressed on high endothelial venules (HEV) located in the parafollicular regions of the tonsils and HEV located in the villous processes of the synovia. On both tissues, these areas contained the greatest number of perivascular lymphocytes. In contrast, ICAM-1 was only weakly expressed on the low endothelium lining capillaries, venules and sinusoids. In both tonsils and synovia, ICAM-1 was confined to the luminal and lateral surfaces of the endothelial cells and absent from the abluminal surfaces adjacent to the basement membrane. We propose that in inflammatory tissues, ICAM-1 mediates the interaction of circulating lymphocytes with the high endothelial cells, but may not have a major role in promoting their migration through the whole thickness of the blood vessel wall.
7779117 Correlation between gold-induced enterocolitis and the presence of the HLA-DRB1*0404 allel 1995 Jun OBJECTIVE: In recent years we have treated 4 rheumatoid arthritis (RA) patients who developed gold-induced enterocolitis, a well-recognized, although rare, complication of chrysotherapy. The aim of the present study was to seek any genetic predisposition for this complication. METHODS: HLA DNA typing was done on fresh white blood cells from the 4 patients. RESULTS: Three of the 4 patients (75%) exhibited the DRB1*0404 allele, whereas the prevalence of this allele among the Ashkenazi Jewish population of RA patients without colitis was 9.2% and 10.2% in 2 different studies. CONCLUSION: The results indicate that the DRB1*0404 may be associated with risk for the development of gold-induced enterocolitis in this population and suggest that HLA DNA typing should be considered in Jews who may be undergoing chrysotherapy.
8346482 Occipitocervical fixation in nontraumatic upper cervical spine instability. 1993 Sep Ten patients requiring occipitocervical fixation were reviewed: five were unstable secondary to rheumatoid arthritis, one had Klippel-Feil, and four had neoplastic disease. Patients with nonneoplastic disease improved, having decreased pain, decreased paresthesias, and increased ambulation. Patients with neoplastic disease improved significantly after the surgery, but eventually died from different tumors. The technique found to be most efficient was the placement of an intraoperatively contoured Luque rectangle wired from the occiput to appropriate cervical spine levels.
8053953 Decreasing incidence and prevalence of rheumatoid arthritis in Pima Indians over a twenty- 1994 Aug OBJECTIVE: To evaluate temporal trends in the incidence of rheumatoid arthritis (RA). METHODS: Incident cases of RA were identified among a population-based cohort of Pima Indians in Arizona over the period 1965-1990. RESULTS: Among 2,894 subjects, 78 incident cases of RA were identified. The age-adjusted incidence declined by 55% in men (Ptrend = 0.225), and by 57% in women (Ptrend = 0.017) after controlling for oral contraceptive or estrogen use and for pregnancy experience. During the same period, age-adjusted prevalence rates of active RA decreased by 29% in men (Ptrend = 0.63) and by 40% in women (Ptrend = 0.02). Fewer than 17% of subjects with known RA were taking slow-acting antirheumatic drugs (SAARDs) in 1990. CONCLUSION: The decrease in incidence and prevalence of RA in this population over such a short period implicates the involvement of an environmental factor(s), other than exogenous estrogens, in the pathogenesis of the disease. However, the possibility that the observed decrease might be explained by an increased use of SAARDs in subjects with RA cannot be excluded.