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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
7552063 Genetic epidemiology of rheumatoid disease. 1995 Apr The aetiology of rheumatoid arthritis (RA) has both genetic and environmental origins. However, the relationship of these with each other and with RA disease is complicated as both genes and environment may be protective or render individuals susceptible. Diagnostic certainty and disease heterogeneity have posed serious hurdles for investigating RA. Patients with similar disease phenotypes may have different aetiologies and it may now be more appropriate to investigate genetic susceptibility with respect to disease process or characteristic immunopathology. Disease concordance studies have been a classical approach to estimating the upper threshold of the genetic contribution to RA and recent studies have approximately halved the much quoted figure of 32% reported by Lawrence for RA concordance in monozygotic twins. However, the interpretation of twin data has to be treated with caution as MZ twins can differ in terms of somatic rearrangement/mutation of immunoglobulin and T cell receptor genes, X chromosome inactivation in females, genomic imprinting and in utero immune relationship. Calculations based on heritability put the genetic component in RA much higher. HLA is an important genetic factor in RA and risk is thought to be associated with a consensus sequence of amino acids within the third hypervariable region of certain DRB1 alleles. It is now clear that HLA is not particularly associated with onset of synovitis but is more associated with progression and severity of the disease process. The HLA-DRB1*0401/0404 genotype is particularly associated with severe, erosive and seropositive RA. Clear differences in RA susceptibility exist between males and females and this may be attributed to hormonal status. Males have a higher threshold requirement for developing RA and this may explain why RA in males is more associated with HLA risk alleles. We have now reached a critical time for the investigation of RA aetio-pathology. Recent advances in molecular biology and automated microsatellite gene scanning technology are making it possible to map disease susceptibility genes over the whole genome in common disorders such as RA. This will require large numbers of well characterised multiplex affected families. It is anticipated that some of the genes identified will fit in with our current concepts of which inflammatory and immune processes are pathologically important in RA. However others may be a major surprise.
8024612 Circulating and synovial fluid hyaluronan levels. Effects of intraarticular corticosteroid 1994 Jul OBJECTIVE: To assess the effect of intraarticular (IA) corticosteroid on hyaluronan (HA) concentrations in synovial fluid (SF) and serum and the clearance of 131I-labeled albumin from the joints of patients with rheumatoid arthritis (RA), osteoarthritis (OA), and ankylosing spondylitis (AS). METHODS: SF and serum were collected before and 2 weeks and 2 months after IA steroid injection. The HA concentration was assessed using an enzyme-linked immunosorbent assay and 131I-albumin clearance from joints was assessed using an external gamma counter. RESULTS: In RA patients, HA concentrations in the SF were increased following IA steroids, while the serum concentrations were decreased. In OA patients, HA concentrations in SF tended to increase initially (decreasing thereafter), and were associated with increased HA concentrations in serum. There were less marked alterations in the AS patients. Albumin clearance rates were decreased significantly (2 weeks postinjection) only in the RA patients. Estimated HA flux revealed discrepancies between the HA concentration and the rate of flux in RA and AS patients. CONCLUSIONS: These findings suggest that IA steroid injection is associated with a restoration in the relationship between SF and serum HA concentrations toward normal levels.
8624636 Agalactosyl IgG in aggregates from the rheumatoid joint. 1996 Apr It has been postulated that agalactosyl immunoglobulin G (IgG) self-associates to form pathological aggregates in the rheumatoid joint. To examine this hypothesis, IgG aggregates from synovial fluid (SF) of 22 patients with RA were prepared by precipitation with polyethylene glycol (PEG) 6000. The PEG precipitates and SFs were reduced with 2-mercaptoethanol (2ME) and bound to protein G. This procedure isolated the IgG in the PEG precipitates from other contaminating glycosylated proteins. The levels of galactose and N-acetylglucosamine (GlcNAc) residues present on the reduced IgG were quantified by their ability to bind the lectins Ricinus communis (RCA)120 and Bandeiraea simplicifolia (BS) II. Proportionally less galactose (expressed as a ratio of bound RCA120 to BS II) was present on the IgG from the PEG precipitates than on the IgG in the paired SF (P = 0.001). However, in many cases more RCA120 as well as BS II bound to IgG from PEG precipitates than from the corresponding SF. It is considered that agalactosyl IgG occurs preferentially in RA SF PEG precipitates and that this IgG may also exhibit increased Fab glycosylation.
1411795 [Lobenzarit disodium (CCA)--induced diabetes insipidus in a patient with rheumatoid arthri 1992 Aug A 44-year-old female with 16-year history of rheumatoid arthritis visited Akiru Hospital with complaints of a thirst, a dry mouth and a general fatigue. One week prior to admission, the patient manifested excessive thirsty feeling, a body weight loss and a sleepless by the polyuria. She has been given 5-10 mg of prednisolone and 240 mg of lobenzarit disodium (CCA) in a day for 11 months. A hematologic examination showed no abnormality, and the examination of her serum showed the following values: BUN, 9.3 mg/dl; creatinine, 0.9 mg/dl; sodium, 139 mEq/l; chloride, 102 mEq/l; potassium, 3.9 mEq/l; osmolality, 290 mOsm/l. Plasma antidiuretic hormone (ADH) level increased slightly (6.0 pg/ml). Examination of her urine revealed specific gravity, 1.005; no trace of glucose, protein, blood and ketones; normal sediment; and osmolality, 209 mOsm/l. The patient was given exogenous ADH (10 units of vasopressin tannate in oil, intramuscularly) to obtain a diagnosis, and she was found to be unable to concentrate her urine more than 1.008 in the specific gravity. A water restriction, as a test for diabetes insipidus, also failed to concentrate her urine in the specific gravity and in the osmolality. Together with these findings, the patient was diagnosed to be a diabetes insipidus, and CCA was seemed to account for the disease. This unfavorable effect of CCA appeared to be reversible, since the patient recovered her urinary concentrating ability after the medication of CCA was discontinued.
1471839 Beneficial effects of continuous passive motion after total condylar knee arthroplasty. 1992 Nov A randomised, controlled study of the use of postoperative continuous passive motion (CPM) and immobilisation regimen after total condylar knee arthroplasty was performed. CPM resulted in a significant increase in both the early and late range of knee flexion. This increase occurred in both rheumatoid and osteoarthritic patients. The improvement of 10 degrees at 12 months allowed additional important function to be attained. CPM resulted in significantly earlier discharge from hospital. It did not increase the clinical incidence of wound healing problems, nor did it significantly increase the postoperative fixed flexion deformity or the extension lag. CPM can be recommended as a safe and effective modality to achieve more rapid and more successful postoperative rehabilitation after knee arthroplasty.
7712745 Calcareous corneal degeneration: report of two cases. 1995 Jan Band keratopathy, calcium salts in Bowman's membrane, is the most classic form of corneal calcification seen in clinical practice. However, calcareous degeneration, calcium deposition involving the full corneal thickness, is rare. We reviewed the clinical and histopathological records of two patients with severe dry eyes and calcareous corneal degeneration. In each case, complete ophthalmic examination and histopathological study were performed. Both patients had severe dry eyes, case 1 secondary to graft-versus-host disease and case 2 secondary to rheumatoid arthritis, and a persistent epithelial defect and anterior segment chronic inflammation. Both patients underwent repeated penetrating keratoplasties. Histological examination of the corneal buttons showed that calcareous corneal degeneration and band keratopathy were coincident in both cases. Both patients received postoperative medications for high-risk grafting. The mechanisms of corneal calcification may be the same in calcific band keratopathy and calcareous corneal degeneration.
1482807 Stevens-Johnson-type reaction with vancomycin treatment. 1992 Dec OBJECTIVE: To report a case of Stevens-Johnson syndrome caused by vancomycin. CASE SUMMARY: Stevens-Johnson syndrome is an acute mucocutaneous process characterized by epidermal and mucosal desquamation. Its pathogenesis is poorly understood. Mortality rates have ranged from 30 to 100 percent. We describe a case of Stevens-Johnson syndrome related to the use of vancomycin in a 71-year-old woman with rheumatoid arthritis receiving treatment for an infected cervical fusion site. Classic "target" lesions distributed throughout the trunk and extremities along with erosive lesions involving the oral and vaginal mucosae were observed in this patient. DISCUSSION: A number of agents have been implicated in the etiology of Stevens-Johnson syndrome. Serious cutaneous reactions to vancomycin, however, have been uncommon. Cessation of vancomycin treatment in our patient led to eventual resolution of her symptoms. CONCLUSIONS: Vancomycin is a potential causative agent of Stevens-Johnson syndrome.
1402934 Porous-coated anatomic (PCA) knee arthroplasty. 3-year results. 1992 Sep During 1984-1986, the authors used the PCA total knee replacement system on 92 knees in 86 patients who were followed for an average of 3.2 years (range, 2.2-4.5 years). Of the 92 knees, 42 were treated due to rheumatoid arthritis (RA) and 50 due to primary or secondary osteoarthrosis (OA). The average age of the patients was 60 years (range, 32-78 years). Seventy-one of the 92 prostheses were inserted without the use of methyl methacrylate cement. Fixation screws for the tibial plate were used in eight cases. One knee was revised due to ligamentous laxity by inserting a thicker tibia plate. Radiographically, there was radiolucency of more than 2 mm below two tibial plates (both RA), and four patellar components (2 RA, 2 OA; 4.3% of total) showed a radiolucent zone of 1 mm or more. Clinically, there were no evident loosenings. According to the Weinfeld scale, 80 knees (37 RA, 43 OA; P = NS) had an excellent result, 10 (6 OA, 4 RA) good, and 2 (1 OA, 1 RA) satisfactory. In comparison, the Hungerford scale gave 47 excellent, 30 good, 14 satisfactory, and 1 poor result. These results reflect that cementless PCA total knee replacement also appears to provide good fixation in both OA and RA knees.
7545872 Mast cells are a major source of basic fibroblast growth factor in chronic inflammation an 1995 Sep Mast cells play an essential role during development of inflammation after chemical and immunological insults and have been implicated in tissue fibrosis and angiogenesis. The exact contribution of mast cells to these conditions is largely unknown. In this study, we found that a potent angiogenic and mitogenic polypeptide, basic fibroblast growth factor (bFGF), is localized to the majority of mast cells from normal skin and lung and in tissue samples characterized by fibrosis, hyperplasia, and neovascularization. Using specific antibodies to mast cell tryptase, tissue macrophage, and bFGF, we demonstrate that cytoplasmic bFGF immunoreactivity is localized to 96.8 +/- 9.6% of tryptase-positive cells in human fibrotic lung tissue (n = 10), 82.3 +/- 6.9% of tryptase-positive cells in rheumatoid synovia (n = 6), and 93.1 +/- 4.8% of tryptase-positive cells in skin hemangioma (n = 5). Moreover, these tryptase-positive cells comprise a major portion (86 to 97%) of nonvascular cells exhibiting cytoplasmic bFGF staining in these tissues. In contrast, macrophage-like cells contribute less than 10% of the bFGF-positive cells in the same samples. The specificity of the immunostaining results was supported by the finding that cultured human mast cells (HMC-1) express both bFGF mRNA and protein. Our data indicate that mast cells, a primary source of heparin, also serve as a significant source of a heparin-binding growth factor, bFGF, in these disease processes. These observations suggest that mast cells may contribute to these pathological conditions by releasing this polypeptide.
8335336 [Rheumatoid arthritis--current research perspectives]. 1993 Jun No other chronic inflammatory disease is currently receiving more attention from basic scientists than rheumatoid arthritis (RA). Topics of intense research are HLA disease association, peculiarities of the synovial T- and B-cell repertoire, changes of synoviocytes and cytokine profiles as well as animal models and new therapeutic strategies.
8879864 Chloroquine neuromyopathy. 1996 Sep A 59-year-old woman with rheumatoid arthritis was treated with prednisone and 250 mg of chloroquine diphosphate (CQ) daily. Though there was improvement in her joint symptoms, she began to notice progressive lower limb weakness, later extending to the arms and lasting for 2 months. Electromyography showed fibrillations, polyphasic potentials and high frequency discharges. Biceps brachii biopsy showed that virtually every muscle fiber and multiple small vacuoles surrounded by a basophilic rim. There was variation in fiber diameter and some fibers were atrophic and angulated. ATPase revealed type grouping. Electron microscopy showed, in each muscle fiber, numerous concentric membranous bodies, some with curvilinear profiles, beneath the sarcolemma or among the myofibrils. Some were also observed in endothelial cells of muscle capillaries. CQ was withdrawn, but no significant regression of symptoms had been observed at the time follow-up was discontinued. The patient died of cardiac insufficiency and bronchopneumonia. The case illustrates a rare complication of CQ therapy of rheumatic conditions. It is noteworthy because the drug was administered in therapeutic doses and only for a short period. CQ is known to interfere with lysosomal function, from which presumably the membranous bodies here described originate. Improvement of neuromuscular symptoms has been reported following withdrawal of the drug.
8195989 Person and contextual features of daily stress reactivity: individual differences in relat 1994 Feb We examined the mood-related and pain-related consequences of daily stressors among 74 individuals with rheumatoid arthritis who supplied daily reports for 75 days. Meta-analyses of time series regression coefficients disclosed a significant same-day relation between events and mood but no consistent effects of events on same-day pain, next-day mood, or next-day pain. With distributional characteristics of the daily data controlled, Ss with more active inflammatory disease showed a greater positive relation of events with same-day and next-day pain, those with a recent history of more major life stressors showed a greater positive relation of events with next-day pain, and those with less social support showed a greater positive relation of events with next-day mood disturbance. Implications of these and other findings for theories of stress and adaptation and the methodological challenges of daily experience research are discussed.
1333767 Serum catalase as the protective agent against inactivation of alpha 1-proteinase inhibito 1992 Oct Human serum contains catalase activity, which can protect alpha 1-proteinase inhibitor from inactivation by H2O2. The primary source of serum catalase is probably erythrocytic. The enzyme activity correlates with haemoglobin concentration in sera from control subjects but not in sera from patients with rheumatoid arthritis. Catalase is inactivated by oxidants, such as H2O2 and hypochlorous acid and it is suggested that the decrease in catalase/haemoglobin ratio observed in rheumatoid serum is due to oxidant stress associated with inflammation.
7636772 Body image, disfigurement and disability. 1995 Apr The body-related attitudes of groups of women suffering from physical conditions that are commonly regarded as being disfiguring and/or disabling were studied by means of the Body Attitudes Questionnaire. Despite their conditions, the women did not necessarily disparage their bodies. They also seemed to worry less about small changes in weight and shape than did comparable women without physical difficulties, and to have an enhanced sense of their own robustness. There was an indication that development of negative body attitudes might be linked to emergence of a chronic physical condition during adolescence, rather than from birth or during adulthood. If our results are confirmed, they point to the need to pay special attention to the psychological needs of women whose bodies become dysfunctional at this sensitive time.
1294734 Longterm drug therapy for rheumatoid arthritis in seven rheumatology private practices: I. 1992 Dec The probability of continuation of a particular nonsteroidal antiinflammatory drug (NSAID) over 5 years was estimated for 1,775 courses taken by 532 patients with rheumatoid arthritis treated in 7 rheumatology private practices. Similar results were seen for 15 different NSAID--48% of courses were continued at 12 months, 36% at 24 months, and 20% at 60 months. Only acetylated salicylates, other than plain aspirin, were continued significantly longer than any of the other NSAID. The probability of continuation of plain aspirin was similar to other NSAID, including nonacetylated salicylates and nonsalicylate NSAID. The first NSAID taken by an individual patient was continued only marginally longer than the 4th NSAID taken by the same patient. While most NSAID courses were not continued for long periods, 20% were continued for longer than 5 years, suggesting effective longterm results in this minority of courses.
1471436 [The mobile rheumatoid health unit--an ambulatory consultation from the viewpoint of the p 1992 The acceptance of a university-based outpatient department (Department of Rheumatology, Hannover Medical School, FRG) has been investigated. Ninety-five former patients with RA, previously treated in the department were interviewed by phone. 312 general practitioners from the city of Hannover received a mailed questionnaire. Patients were asked why they had left outpatient department care; questions for general practitioners dealt with types of referral. Despite high satisfaction with the outpatient unit in both groups, we found several shortcomings which possibly might influence discontinuation of treatment and non-utilization of the department: patients and physicians criticized the scheduling system and waiting times. Both groups complained of frequently changing doctors. The general practitioners wanted more contact with the department and more information about the unit. A small group of patients and referring physicians expressed resignation.
1407356 [A case of intracranial multiple nonspecific granulomas related to rheumatic disease: with 1992 Sep We encountered a rare case of a 48-year-old man with intracranial multiple granulomas secondarily caused by rheumatic disease. This was proven surgically after an 11-year course of remissions and deteriorations. In 1980, at the age of 32 years, the patient was first seen at the clinic of Neurology of the University Hospital, complaining of swelling and arthralgia of the joints of the knee, ankle, and wrist and with remittent fever and visual disturbance. The patient was diagnosed as having possible rheumatoid arthritis, and treated with administration of 30mg/day of prednisolone, which greatly improved the symptoms. The administration of 5 to 10mg/day of prednisolone had been continued after discharge from hospital. In 1985, visual acuity of the left eye decreased, and left facial hypesthesia developed. The patient was rehospitalized at the same clinic, and treated with 100mg/day of prednisolone, which again diminished the symptoms. Computed tomography(CT) on admission showed a high density mass with contrast enhancement in the left cavernous region. In addition to the left cavernous mass, a high density mass was detected by CT in the left parietal lobe, in 1987. Visual acuity of the left eye deteriorated in 1989. Because his response to prednisolone had decreased, the visual symptom was treated with gold sodium, which acted effectiveness. Symptoms deteriorated again in 1990. Early in 1991, CT and magnetic resonance imaging showed a new mass at the right frontal lobe, while the mass in the left cavernous region had increased in size. The patient was transferred to the clinic of Neurosurgery for surgical treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
7981993 Insufficiency fractures of the distal tibia. 1994 Nov Eight patients are described who had sustained insufficiency fractures of the distal tibia, in one case, bilaterally. Seven of the eight patients had RA. Features common to most patients were delay in diagnosis, low body weight, pain and swelling around the ankle joint, steroid therapy, generalized osteopenia and relatively young age. Patients with RA all had ankle joint involvement and impaired mobility.
8418454 Pulmonary manifestations of rheumatic disease. 1993 Jan The lungs are a common target in many rheumatic diseases. Treatment of the primary rheumatic disease is often all that is required to control lung involvement. Physicians must be careful not to attribute lung disease to the underlying rheumatic disorder, because interstitial lung disease can be a complication of drug therapy.
8636447 Identification of clonally expanded T cells in rheumatoid arthritis using a sequence enric 1996 Mar 1 Identification of expanded clones engaged in immune and autoimmune responses is still imperfect, since they are often diluted by irrelevant cells expressing diverse specificities. To efficiently characterize T cell receptors expressed by clonally expanded lymphocytes in rheumatoid arthritis (RA) and other inflammatory conditions, we developed an assay system, termed sequence enrichment nuclease assay (SENA). Key elements of SENA are the efficiency of heat-denatured DNA strand reassociation, which increases exponentially with concentration, and the elimination of unhybridized sequences by single-strand-specific DNase. T cell clonal expansions were identified primarily in synovial fluids, but also in peripheral blood of RA patients. Synovial fluids had more prominent expansions in the CD8 than the CD4 subset, whereas clonal expansions in the CD4 subset predominated among peripheral blood lymphocytes. Dominant clones exhibited diverse sequences with no clear conservation of junctional motifs, although the same amino acid sequence was identified in two patients. In most instances, dominant clones in the blood were discordant to those in the corresponding synovial fluid, suggesting local stimulation or preferential sequestration of T cells displaying particular specifities.