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

ID PMID Title PublicationDate abstract
2166360 Exacerbation of isoniazid induced peripheral neuropathy by pyridoxine. 1990 May Mycobacterium kansasii was isolated from an area of cavitating pneumonia in a man with rheumatoid arthritis. Standard antituberculosis treatment, including isoniazid 300 mg daily, had to be stopped because of peripheral neuropathy. The patient, a slow acetylator, subjectively deteriorated despite withdrawal of isoniazid and treatment with pyridoxine 150 mg daily. Improvement occurred only after the pyridoxine had also been withdrawn. Pyridoxine may cause peripheral neuropathy and this case illustrates the need for caution in the use of this vitamin in the prevention and treatment of isoniazid induced peripheral neuropathy.
2917229 The effect of continuing penicillamine and gold treatment on the course of penicillamine a 1989 Feb The effect of continuing penicillamine or gold treatment was examined in 53 patients with biopsy proven penicillamine (32) or gold (21) nephropathy. Thirty-two patients stopped penicillamine or gold treatment as soon as proteinuria was detected whilst 21 patients continued treatment for periods of 2-11 months. The 24-hour creatinine clearance and urinary protein excretion were measured serially for a median period of 6 years. No significant differences were observed in the initial or maximum proteinuria, the duration of the proteinuria or in the initial or latest creatinine clearances between the groups of patients. These results indicate that penicillamine or gold treatment may be continued for short periods under close supervision despite moderate proteinuria without causing permanent renal damage. As several alternative non-nephrotoxic agents are available for the treatment of rheumatoid arthritis, continued treatment with penicillamine or gold despite proteinuria is seldom indicated.
3102659 Erythropoietin titers in anemic, nonuremic patients. 1987 Apr Erythropoietin titers when related to the hematocrit percentage and measured by bioassay in 33 normal volunteers and in 61 patients with anemias not complicated by renal or chronic disease were found to overlap with titers measured by radioimmunoassay in 20 normals and 28 patients with similar anemias. Erythropoietin titers measured by radioimmunoassay in 34 patients with rheumatoid arthritis, 25 patients with sickle cell anemia (58 separate samples), and 28 patients with erythroid hypoplasia caused by hematologic malignancies were compared with those in the control group of patients with uncomplicated anemias and found not to differ significantly from titers in this group. Erythropoietin titers measured by bioassay in 12 patients with aplastic anemia also fell within the range of those in the control group. Consequently, erythropoietin titers in these anemias appear to be determined primarily by the degree of anemia and not by any specific effect of these illnesses on the production of erythropoietin.
3581696 Cytotoxic drug treatment of reactive amyloidosis in rheumatoid arthritis with special refe 1987 Mar Twenty-two patients with amyloidosis secondary to rheumatoid arthritis were randomised and followed prospectively in order to determine whether treatment with cytotoxic drugs could postpone the development of end-stage renal failure. The diagnosis of amyloidosis was based on albuminuria, amyloid-positive rectal and/or abdominal fat aspiration and/or renal biopsies. Renal function was followed by repeated 51Cr-EDTA measurements of the glomerular filtration rate (GFR). Urinary albumin and serum-creatinine were found unreliable as predictors of renal function. GFR declined more rapidly in the patient group receiving only symptomatic drugs and no cytotoxic drugs (NT-group). After an initial decline, the GFR in the cytotoxic drug treatment group (T-group), mean treatment quotient 79%, levelled off and remained constant for a considerable time. The mean observation time was 45.7 months in the NT-group and 53.5 months in the T-group. Seven out of eleven patients in the NT-group developed end-stage renal disease, compared to two out of eleven patients in the T-group. The cumulative proportion of survivors in the NT-group at 36 and 60 months was 71% and 27% respectively. The corresponding figures in the T-group were 89% and 89%. The difference in favour of the cytotoxic drug-treated group was significant (p less than 0.04).
3698327 Benign lymphoepithelial lesion: a less than benign disease. 1986 Feb The precise clinical correlate of the benign lymphoepithelial lesion is unclear. Thirty-six cases of benign lymphoepithelial lesions (BLL), reported to the British Salivary Gland Tumour Panel between 1971 and 1984, have been reviewed. Eighty per cent arose in the parotid gland and 20% were bilateral; 83% were in females and the mean age at presentation was 55.26 years. Only 50% presented with, or developed, symptoms of sicca complex, Sjogren's syndrome or related autoimmune disease. Two cases of BLL had, or went on to develop, extra salivary lymphomas and 5 cases of BLL had lymphomatous change in the initial biopsy. A further case had carcinoma within the benign lymphoepithelial lesion. None of those who developed lymphoma had sicca or Sjogren's syndrome but 3 of them had rheumatoid arthritis. The incidence of lymphomas (salivary or extra-salivary) in this series is very much higher than that reported in Sjogren's patients and amounted to 20% overall.
3347339 Autoimmunity in multiple sclerosis. 1988 Mar Multiple sclerosis reportedly coexists with disorders of autoimmune origin. The prevalence with which such disorders occur in the MS population has not been adequately investigated. We reviewed the medical records of 828 patients with definite MS and found that 4.8% had a past or present associated disorder in which autoimmune mechanisms presumably play a role. The cumulative prevalence of these disorders was no higher than that estimated for the general population. Serum from 105 patients, without clinical evidence of an associated autoimmune disorder, was tested for the presence of antinuclear, thyroid, parietal cell, smooth muscle, and mitochondrial antibodies. A significantly higher prevalence (p less than 0.01) of generally low titers of one or more autoantibodies was found in serum from the MS group, compared with a control group of 105 patients with other neurologic disorders. The increased frequency of serum autoantibodies probably reflects the existence of a nonspecific B cell overactivity in MS.
3731279 Fibronectin and retinyl acetate effects on attachment and spreading of normal and rheumato 1986 Jul The action of two effectors - fibronectin (FN) and retinyl acetate (RA) - on cell attachment and spreading of human synoviocytes was investigated by adding these two drugs to the cell culture medium. No relationship was observed between the level of the effectors (FN = 20-80 micrograms/well, RA = 0.50-2 micrograms/well) and the biological effects studied. For normal human synoviocytes, fibronectin was less effective on the adhesion than fetal calf serum (FCS) present in the control culture medium; retinyl acetate, a drug acting on glycoprotein synthesis, led to similar effects to those observed for FCS-treated cells. In the case of rheumatoid synovial cells, the degree of adhesion was similar for drug- and FCS-treated cultures. Moreover, FN and RA had little effect on the spreading compared to FCS. Given these results, it would appear that synoviocytes differ in their behaviour from usual fibroblastic models.
2606513 Heterogeneity of ribosomal autoantibodies from human, murine and canine connective tissue 1989 Nov Antiribosomal auto-antibodies (anti-Rib.Ab) have been studied in connective tissue diseases (human, dog and mouse) by immunoblotting after one-dimensional (1D) or two-dimensional (2D) gel electrophoresis of rat ribosomes. Anti-Rib.Ab could be found in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other connective tissue diseases (progressive systemic sclerosis, PSS; Sjögren syndrome, SjS; mixed connective tissue disease, MCTD; and dermatomyositis, DM with the frequencies 41.7%, 54.6% and 33%, respectively. Immunoblotting after 1D gel electrophoresis showed the great heterogeneity of ribosomal proteins recognized by the anti-Rib.Ab. In the SLE, however, the most frequent antibodies stained bands of the 40S subunit: 30 kDa (34% of positive sera), 19.5 kDa (24.5%) and 43 kDa (17%). In RA, the 25-kDa band of the 60S subunit was the most common (54% of positive sera). In the other human connective tissue diseases, there was no particular predominance. In the MRL/1, anti-Rib.Ab were very frequent (92.6%). The 43-kDa band of the 40S subunit was found in 100% of positive sera. Seventeen out of nineteen dogs with SLE gave positive results on immunoblot, and all of them stained the 43-kDa band of the 40S subunit. 2D gel electrophoresis gave identification of Po, L7, L5, Sb, S19, S13 and L2 proteins in SLE, S3 and SjS, L35a and L37a in RA, and L7, S6 and/or L7a in MRL/1.
3443453 Glutathione and lymphocyte activation: a function of ageing and auto-immune disease. 1987 Aug A decline in tissue and serum of glutathione (GSH) content and GSH-metabolizing enzymes with age has been implicated in the increasing susceptibility to carcinogens, disease and drugs which occurs with advanced age. Immunological senescence has been directly associated with increased incidence of cancer and infection with age. The auto-immune diseases of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) demonstrate depressed T-cell function together with B-cell hyperactivity. In addition, RA and SLE are chronic inflammatory conditions which have been associated with low serum and erythrocyte GSH concentrations when compared to normal. We hypothesized that augmentation of intracellular GSH concentrations in lymphocytes may enhance immune function in depressed immune states. Our data, using murine animal models for ageing (C57BL/6J) and the RA/SLE-like auto-immune diseases of the MRL/lpr mouse, indicate that intracellular glutathione of splenic lymphocytes does not decline with age or with a chronic inflammatory auto-immune disease. In contrast, immune responsiveness in splenic lymphocytes does decline. We can, however, augment both intracellular GSH concentrations and the immune response of splenic lymphocytes from animals of all ages as well as in those animals with the SLE-like auto-immune disease.
2209706 Structures on the I-A molecule predisposing for susceptibility to type II collagen-induced 1990 Sep The susceptibility to type II collagen (CII)-induced arthritis (CIA) in mice is profoundly influenced by major histocompatibility complex (MHC) class II genes in the H-2 region. Analyses of MHC-congenic strains on the B10 background show that only strains developing an anti-CII antibody response after immunization with autologous CII develop arthritis after induction with CII from various species. The susceptible haplotypes have been found to be H-2q, H-2r, H-2w3 and H-2w17. In addition, these haplotypes respond to different patterns of CII derived from various species suggesting that T cell receptors and CII peptides interact. In contrast, certain haplotypes closely related to H-2q, such as the H-2p and H-2w5 haplotypes, are resistant to induction of CIA and are nonresponders to CII. We have earlier shown that a critical structure on the I-A beta molecule determines the susceptibility differences between the p and q haplotypes. We have now determined the structure of exon 2 of the A beta as well as some of the A alpha genes of the remaining haplotypes in the p, q and r families. The sequences show similarities between the CIA-susceptible haplotypes in the A beta C-terminal part and the A alpha N-terminal part of the first domains forming a large part of the antigenic peptide-binding site. Among the wild mouse-derived haplotypes, the w5 haplotype showed an A beta sequence identical to that of the p haplotype consistent with its nonresponder nature to CII immunization. These findings suggest that (a) structures shared between different class II molecules are of importance for the susceptibility to disease in mouse strains and (b) most likely recognition of different CII peptides is important for development of disease.
2408137 Expression of activation antigens on T cells in rheumatoid arthritis patients. 1990 Feb The aim of our study was to identify differences in cell surface marker expression between T cells taken from the peripheral blood (PB) of healthy individuals and T cells recovered from inflamed joints of rheumatoid arthritis (RA) patients. Out of 118 monoclonal antibodies (MoAbs) directed against activation antigens on haematopoietic cells, 12 MoAbs recognizing nine distinct surface molecules were selected after a screening procedure to study the expression of the corresponding antigens on T cells from the PB, synovial fluid and synovial tissue of RA patients, and also on T cells from PB and spleens of controls. Using two-colour flow cytometry and immunohistology we found the molecules B-C5, CD39, CD40, CD45 R0, CD54, CD76 and potentially 1D11 to be substantially up-regulated on T cells from various body compartments in RA patients. We thus could determine that the cell surface of T cells in RA patients not only differs in MHC class II expression, but also in a number of other activation-associated cell surface molecules from T cells in healthy individuals.
3426301 Molecules controlling lymphocyte-endothelial interactions in lymph nodes are produced in v 1987 Dec In vitro lymphocyte adhesion to, and selective radiosulphate uptake by, endothelial cells has been demonstrated in diseased synovium of patients with rheumatoid disease, osteoarthritis, and the peripheral arthropathy associated with ankylosing spondylitis and ulcerative colitis. These characteristics have been described previously in endothelial cells functionally specialised for promoting lymphocyte traffic from blood to lymph node parenchyma. It is suggested that these observations indicate that some synovial vessels may be responsible, at least in part, for the selective accumulation of lymphocytes in the tissue. Manipulation of the development of this type of vessel may offer a novel way of influencing the progress of inflammatory arthropathies.
2075829 Increased ability of peripheral blood B cells from patients with rheumatoid arthritis to p 1990 Dec Twenty-four patients with rheumatoid arthritis (RA) and 20 normal controls were examined for the ability of their peripheral blood B cells to produce interleukin 1 (IL-1) with or without lipopolysaccharide (LPS). B cells were purified from peripheral blood by negative selection methods (i.e., removal of adherent cells and sheep red blood cell rosette-forming cells, followed by treatment with monoclonal antibodies (OKT3 and OKM1) and complement). The amount of IL-1 in B cell culture supernatants (SN) was measured by thymocyte and fibroblast proliferation assays and an enzyme-linked immunosorbent assay for IL-1 alpha and beta. As a group, cultured B cells from patients with RA, both spontaneously and when stimulated with LPS, produced higher levels of IL-1 than those from normal controls. IL-1 production by RA B cells with LPS had a weak but positive correlation with disease activity. Moreover, RA B cell culture SN with elevated levels of IL-1 had a synergistic effect on the growth of anti-human IgM (anti-mu) stimulated B cells. In separate experiments, the growth of RA B cells was significantly promoted by IL-1 beta both with and without anti-mu stimulation. These results suggest that B cell-derived IL-1 may be involved in the B cell clonal expansion of RA through its own activity as a B cell stimulatory factor.
3608266 Goldsalts, levamisole and D-penicillamine as first choice slow-acting antirheumatic drugs 1987 Apr In the present study, 345 rheumatoid arthritis patients were treated using goldsalts, D-Penicillamine or levamisole as the slow-acting antirheumatic drug of first choice. Goldsalts were given to 182 patients, levamisole to 139 and D-Penicillamine to 24. At the time of the present evaluation, 83 patients were still on goldsalts (44.6%), 63 on levamisole (45.2%) and 11 on D-Penicillamine (45.9%). Adverse reactions required interruption of treatment in 64 patients on goldsalts (35.2%), in 44 on levamisole (31.7%) and in 5 on D-Penicillamine (20.8%). Inefficacy was responsible for withdrawal of 33 patients receiving goldsalts (18.1%), 30 receiving levamisole (21.6%) and 8 receiving D-Penicillamine (33.3%). The duration of treatment was 4.6 years for goldsalts, 3.6 years for levamisole and 3.6 years for D-Penicillamine. In the present analysis none of the compounds was found to have a definite advantage over the others. The rather favourable treatment continuation rates in this study can be attributed to the fact that the slow-acting antirheumatic drugs were given at an early stage of the disease, preferably before the occurrence of radiological lesions.
3955938 Correction of alignment deformities during total knee arthroplasties: staged soft-tissue r 1986 Jan Preoperative evaluation consists of a series of radiographs and a careful analysis of the gait in order to estimate the amount of bone resection and soft-tissue release needed for successful arthroplasty. Graduated, surgical soft-tissue releases were used for realigning arthritic knees during arthroplasty. Medial, lateral, anterior, and posterior releases provide step-by-step correction for realigning markedly deformed joints. The procedure prevents "over-releasing" leading to ligamentous instability. At surgery the mechanical axis of the limb was used for knee realignment by use of a towel clip over the hip joint and palpation of the malleoli at the ankle; the center of the hip, knee, and ankle should be in a straight line. Elimination of abnormal moment (the tendency to produce motion about the normal axis) at the knee with weight-bearing was the goal for realignment. Proper alignment is the key to success and longevity in knee arthroplasty. Soft-tissue releases should be used with any type of instrumentation the surgeon desires. The patella must also be realigned.
3952006 Cardiac conduction abnormalities and atrial arrhythmias associated with salicylate toxicit 1986 Jan Cardiac side effects from aspirin are uncommon; however, severe acid-base imbalance, pulmonary edema, ventricular ectopic activity and cardiopulmonary arrest have been reported in patients with toxic serum salicylate concentrations. We saw a patient with salicylate toxicity who developed a variety of sinus and atrioventricular nodal conduction disturbances and atrial arrhythmias with a relatively low toxic serum salicylate concentration. The cardiac rhythm returned to normal as the serum salicylate concentration decreased, and results of subsequent electrophysiologic testing and Holter monitoring were normal. A low serum albumin level may have resulted in altered salicylate binding in this patient, thereby increasing the availability of unbound (active) drug for toxic effects.
2959754 Long-term results of total joint arthroplasty in nonambulatory patients. 1987 The authors conducted a long-term follow-up study of 27 patients, all confined to a bed or wheelchair for at least 6 months, who had total joint arthroplasty to relieve rest pain, correct deformity, and enable independent ambulation. The average duration of nonambulatory status before operation was 3 years (mean, 1 1/2 years), with the longest being 15 years. The patients required an average 3-month hospital stay and an average of three major total joint arthroplasties in the lower extremities. All of the patients were ambulatory at the time of discharge but required some sort of aid. After 1 year, 20 patients (74%) were able to launch independently; 9 (33%) could ambulate without aids; and 14 (52%) could ambulate with aids. At follow-up evaluation 3-12.8 years (average, 6.5 years) after operation, nine patients (33%) ambulated without aids, five (19%) required a single crutch or cane, and nine (33%) required bilateral crutches or a walker, for a total success rate of 85%, which did not deteriorate with time.
3664163 The prescribing of chloroquine and hydroxychloroquine by consultant rheumatologists in the 1987 Oct A questionnaire on chloroquine and hydroxychloroquine prescribing was circulated nationally to 212 consultant rheumatologists and 119 replies were analysed. Of all patients receiving second-line drugs, 10% were prescribed antimalarials, with hydroxychloroquine being used four times more frequently than chloroquine. Eighty-five per cent of rheumatologists always used the same dose of hydroxychloroquine or chloroquine. Only 5% considered patient's weight in deciding the dose. Fear of ocular toxicity was expressed by many physicians; 54% had experienced corneal deposits; 4% retinopathy and 40% believed cumulative dose determined toxicity. Much confusion existed over the necessity for and frequency of ophthalmological monitoring. Only 56% requested ophthalmological tests before commencing treatment, although 86% monitored the eyes during therapy. Other side-effects were believed to affect 1-10% of patients, with no anticipated difference between doses of 250 mg chloroquine and 400 mg hydroxychloroquine daily.
2912464 Insulin-like growth factor stimulation of chondrocyte proteoglycan synthesis by human syno 1989 Jan We investigated the role of insulin-like growth factors (IGFs) as regulating factors of cartilage metabolism in human synovial fluid (SF), using a bovine explant culture system that was shown to respond to recombinant IGF-1 in vitro. SF from rheumatoid arthritis (RA) patients and from control patients was found to stimulate chondrocyte proteoglycan synthesis in bovine articular cartilage. A monoclonal antibody directed primarily against IGF-1 (and to some extent, IGF-2) partially blocked the stimulatory action of serum and totally blocked the stimulation by SF. These findings indicate that IGFs are major regulating factors of cartilage proteoglycan synthesis in human SF. In addition, we measured serum and SF levels of IGF-1 in RA patients and control patients, using a radioimmunoassay. No difference in immunoreactive serum IGF-1 was detected between patients and controls. The IGF-1 levels in SF were consistently lower than in serum, for both patient groups. No differences in IGF-1 concentration were found between RA and non-RA SF. The relevance of these data with respect to joint inflammation is discussed.
3598992 Rheumatoid arthritis and its association with HLA-DR antigens. I. Cell mediated immune res 1987 Apr HLA-DR antigens and cellular sensitivity to native bovine type I and type II collagen and proteoglycans were examined in patients with classic rheumatoid arthritis (RA) and normal individuals. Fifty eight percent of patients with RA (n = 88) and 28% of normals (n = 52) were DR4+ (pc less than 0.01). DR4 phenotype was significantly increased in patients with severe disease stages (III-IV), as defined by the ARA criteria, in contrast to those showing mild disease stages (I-II) (p less than 0.05). Furthermore, peripheral blood mononuclear cells from 55 patients and 30 controls were evaluated for the in vitro production of leukocyte inhibitory factor in response to native type I and type II collagen and proteoglycans. By using this assay, cells from the arthritic group exhibited a statistically significant response when stimulated with native type I collagen and proteoglycans. The cellular immune response was not associated with any particular HLA-DR antigens, or to the disease stage or severity.