Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 6426836 | A method of comparing the toxicities of disease suppressive agents: possible application t | 1984 | A general method for calculating incidences of the more common adverse reactions during long-term therapy with disease suppressive agents is presented. With D-penicillamine treatment, the incidence of proteinuria rises during 6-12 months and then declines, but with aurothiomalate treatment the incidence of proteinuria and rash progressively decline. Low-dose chloroquine treatment was associated with a much lower withdrawal rate due to adverse reactions compared to D-penicillamine. However, the efficacy at mean doses of chloroquine less than 250 mg day-1 has not been formally evaluated. A formal, well-controlled trial comparing D-penicillamine, at current dosage, and of chloroquine, at low dosage, seems warranted in order to place the usefulness of D-penicillamine in perspective. | |
| 871299 | A unifying concept for the role of matrix vesicles and lysosomes in the formal pathogenesi | 1977 Apr | The cells of the connective tissues contain lysosomes with enzymes capable of degrading intercellular substances (collagen, elastin, proteoglycans) and release their enzymes in membrane-bound or in free form into their intercellular substance. In this way extracellularly located lysosomes (= matrix lysosomes) can be detected by morphological and enzymatic means as well as by their metal concentrating property. This function of such matrix-lysosomes is in connection with the two step-degradation of the connective tissue and is thought to be the main part for the fibrocytic fibrolysis, chondrocytic chondrolysis, osteocytic osteolysis and myocytic mediolyses in the vessel wall. The cells of the mesenchymal tissues thus control the turnover and transformation of their own ground substance. Inflammatory and immunologic processes are suggested to be superimposed on this lysosomal action. If the lysosomal enzyme system in the connective tissues and the vessel wall gets out of control, the consequences can be dangerous as e.g. in case of relapsing polychondritis and arterial aneurysms. In this enzyme system proteolytic activators as well as proteolytic decomposable inhibitors are present. The corresponding proteolytic processes are of lysosomal nature and are subordinated to other regulatory mechanisms. | |
| 7053442 | Aspirin and analgesic nephropathy. | 1982 Jan 1 | To assess the effects of long-term aspirin ingestion on renal function, we studied all of the patients at the Massachusetts General Hospital Arthritis Clinic who had been taking aspirin continuously for ten or more years. Aspirin ingestion was documented by multiple, random, unannounced blood salicylate levels. Most of these 46 patients had seropositive rheumatoid arthritis. All creatinine and BUN levels were normal. Maximum recorded specific gravities were greater than 1.019 in 43 of 46 patients. These data suggest that long-term salicylate ingestion does not cause renal damage. | |
| 1099512 | Preoperative and postoperative management: the role of allied health professionals. | 1975 Jul | The success of a coordinated team approach is dependent upon respect and communication among all members, all directed toward the individual patient's goal. Standardized forms can be developed by each discipline and used as a formal mode of communication. These can be available in each patient's record for all the professional staff to read. Unitization has established an atomosphere for informal ongoing communication: i.e. allied health team members have been assigned to the same patient care unit. The same allied health members are therefore working together with the same patient on a day by day basis. Greater efficiency and communication tend to develop spontaneously within such a system. Full inpatient coverage seven days a week by the therapist as well as the nurses has improved continuity of care. Since these changes in staff distribution have taken place, a study of a significant number of patients undergoin total knee or toal hip procedures has shown that there has been a reduction in the average length of stay for the hospitalization, from two days for a total knee replacement to five days for a patient undergoing total hip replacement. Weekly or twice weekly meetings of allied health members, surgeons, and rheumatologists greatly facilitate the progression and coorination of the treatment program. Medical and nursing audits on patients with total hip procedures document a remarkably low rate of surgical complications. Early discharge planning has fostered a smooth transition of the patient to his home and ultimately to work. | |
| 7384759 | Perichondrial arthroplasty. A clinical study in twenty-six patients. | 1980 | 26 patients with painful and/or rigid small joints of the extremities have undergone surgery by a new arthroplasty method, utilizing the cartilaginous potential of the perichondrium demonstrated earlier in animal experiments. Perichondrium from the rib has been grafted to the articular surfaces of the affected joint after removal of the remaining ordinary articular cartilage. In 12 cases the joint disease was a sequela after trauma--either fracture involving the joint surfaces, or an open joint injury complicated by a purulent arthritis. In 6 cases there was an idiopathic degenerative joint disease and in 5 the arthritis was of rheumatic origin. In a further 3 cases the indications for operation were various. The follow-up period varied between 3 and 41 months. 13 patients classified as excellent regained range of motion and power and had no pain either at rest or at work. In 3 cases range of motion and power improved, but there was still some pain in the affected joint at work. Ten cases were not improved by the perichondrial arthroplasty and possible reasons for this are discussed. The results indicate that it is possible to restore joint function using free autologous perichondrial grafts from the rib. | |
| 3904436 | Evaluation of the safety of isoxicam. | 1985 Oct 18 | Data collected from more than 1,800 patients with rheumatoid arthritis or degenerative joint disease in Phase 3 clinical studies of isoxicam (Maxicam) indicated that the drug is well tolerated on both a short-term and a long-term basis. The most common type of adverse reaction to all medications (isoxicam, aspirin, and indomethacin) was gastrointestinal: 22.6 percent with isoxicam, at a dosage greater than 200 mg per day; 14.2 percent with isoxicam at 200 mg per day; 31.6 percent with buffered aspirin at 3,600 to 4,800 mg per day; 24.6 percent with indomethacin at 150 mg per day; and 7.2 percent with placebo. The incidence of tinnitus and deafness was significantly greater with buffered aspirin than with isoxicam, and the number of patients who had at least one episode of dizziness, vertigo, or headache was significantly greater with indomethacin than with isoxicam. In open-label, long-term studies, in which approximately 70 percent of the patients participated, the types and frequencies of adverse effects were similar to those observed with isoxicam during the controlled studies. The overall frequency of withdrawal for adverse reactions during the long-term studies was 11.5 percent, similar to that during the controlled studies. At the recommended dosage for isoxicam of 200 mg per day, the incidence of gastrointestinal ulcers was 0.81 percent, well within the range expected among arthritic patients receiving nonsteroidal anti-inflammatory drugs. From the data collected in Phase 3 clinical studies, it may be concluded that isoxicam is better tolerated than either aspirin or indomethacin and should not create unusual problems in the short-term or long-term treatment of rheumatoid arthritis or degenerative joint disease. | |
| 6432412 | Auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis. C | 1984 Mar | Two hundred eight patients were studied in a prospective, controlled, double-blind multicenter trial comparing auranofin (AUR), gold sodium thiomalate (GST), and placebo. One hundred sixty-one patients completed at least 20 weeks of therapy. Response to a variety of measures of efficacy was generally modest for both gold treatment groups although improvement was continuing in both groups at the end of the study. There was statistically significant improvement with both gold preparations compared to placebo for the number of tender joints, the joint tenderness score, and physician assessment of disease severity. GST was also significantly better than placebo for the joint swelling score. GST demonstrated more improvement in patients with anemia and thrombocytosis compared to the other treatment groups and both gold preparations were superior to placebo in improvement of an elevated erythrocyte sedimentation rate. Twenty-seven percent of patients on GST were withdrawn from the study for adverse drug reaction with rash and stomatitis being the predominant cause. Only 6% of patients on AUR were withdrawn for untoward drug effect. The time of onset of the adverse reactions is discussed. The two gold preparations were similar in efficacy although AUR was better tolerated. | |
| 412488 | Gold nephropathy: tissue analysis by X-ray fluorescent spectroscopy. | 1977 Dec | Three patients developed proteinuria following gold therapy for rheumatoid arthritis. The clinical syndrome was a self-limiting proteinuria with normal renal function. By light and electron microscopic appearances the renal lesion was an epimembranous deposit form of membranous glomerulopathy. Immunofluorescent study showed granular deposits of IgG and C3 complement along glomerular basement membranes. By X-ray fluorescent spectroscopic examination, gold was seen to be present within the proximal convoluted tubular cells but was not identified in the glomerular subepithelial deposits. These findings are consistent with an immune-complex form of glomerulopathy in which gold is neither the antigen nor a hapten in the glomerular deposits, and they suggest the hypothesis that antibodies to tubular epithelial antigens induced by gold therapy may be a causative factor in the renal disease associated with gold therapy in rheumatoid arthritis. | |
| 6961426 | Antibodies to distinct polypeptides of RNA polymerase I in sera from patients with rheumat | 1982 Dec | Sera from patients with rheumatic autoimmune diseases were screened for antibodies directed against RNA polymerase I by using a solid-phase radioimmunoassay. Significant levels of the antibodies were detected in the sera of all patients with either systemic lupus erythematosus or mixed connective tissue disease and in 78% of the individuals with rheumatoid arthritis. No detectable anti-RNA polymerase I antibodies were found in the sera from healthy subjects. Individuals taking hydralazine, three of whom exhibited symptoms of drug-induced lupus, had barely detectable levels of the antibodies. Immunoglobulins obtained from sera containing anti-RNA polymerase I antibodies, as determined by the radioimmunoassay, could inhibit RNA polymerase I activity in vitro. Sera from patients with systemic lupus erythematosus contained immunoglobulins directed against the polymerase I-associated polypeptide of Mr 65,000 as well as against the polypeptides of Mr 120,000 or Mr 25,000, or both. Sera from individuals with rheumatoid arthritis reacted with the polypeptide of Mr 65,000 only. The antibodies in the sera of patients with mixed connective tissue disease were directed against the Mr 42,000 polypeptide or a combination of the Mr 65,000, 42,000, and 25,000 polypeptides. These data suggest that the production of anti-RNA polymerase I antibodies may be a unique characteristic of individuals with rheumatic autoimmune diseases and that the production of antibodies against specific polypeptides of RNA polymerase I may be indicative of the particular class of disease. | |
| 8838 | Clinical study of a new anti-inflammatory and analgesic compound, benorylate, in rheumatic | 1975 | Benorylate is obtained by esterification of acetylsalicylic acid and N-acetyl p-aminophenol (4-acetamidophenyl 2-acetoxybenzoate). Experimentally, this new product has been shown to be a good analgesic and anti-inflammatory agent. A clinical trial was carried out in order to study the efficacy, side effects and tolerance of this new product. In a group of 49 hospitalised patients aged from 20 to 70 years who were treated with this new product, 15 had ankylosing spondylitis, 11 had chronic progressive rheumatoid arthritis, 4 had Reiter's syndrome, 4 had psoriatic arthropathy, 8 had osteoarthrosis of the hip and 7 had various forms of rheumatism. The drug was administered orally in suspension form, initially three times per day, then twice, the total daily doses being 15 ml (6 g) or 20 ml (8 g). Treatment was regarded as effective in 62% of the cases, and of these 62%, 46% good and very good results were obtained. In 88% of the patients, tolerance was satisfactory and of these, it was excellent in 80%. Only in 2 cases did treatment have to be discontinued on account of side effects. From the biological point of view, uricaemia was significantly reduced in 7 patients, and in 6 patients uricuria increased. With regard to the level of salicylate in the blood assays showed that it is the same for 6 g benorylate and for 4 g aspirin. Benorylate has been shown to be an effective treatment for both inflammatory and degenerative rheumatic disorders. The results of its use can be compared with those obtained by acetylsalicylic acid, but is better tolerated. In addition, in chronic disorders it is better to have to take the product only twice per day. | |
| 4020134 | Immune response to nucleic acid antigens and native DNA by human peripheral blood lymphocy | 1985 Sep | The immunogenicity of DNA fragments (either oligonucleotide (oligo) or total DNA digest) covalently linked to keyhole limpet hemocyanin (oligo-KLH or DNA-KLH) was tested with peripheral blood lymphocytes (PBL) from 63 systemic lupus erythematosus patients (SLE) in vitro. PBL from 10 normal individuals and 11 rheumatoid arthritis (RA) patients served as controls. Antibodies to three nucleic acid antigens (oligo, denatured DNA (d-DNA), and native DNA (n-DNA] were assayed in supernatants of cultured lymphoid cells by a sensitive solid-phase radioimmunoassay. More than 50% of SLE and RA patient lymphoid cells formed spontaneous antibodies to one or several nucleic acid antigens. In contrast, only two normals did. After in vitro challenge with oligo-KLH or DNA-KLH, cultured lymphocytes of more than 50% of SLE patients formed antibodies to one or several nucleic acid antigens. Similar results were obtained in PBL from RA patients. In SLE patients, the response to both antigens was either monospecific or polyspecific, but DNA-KLH appeared to raise a greater proportion of antibody to n-DNA than oligo-KLH. A greater proportion of patients with active disease responded in vitro compared with those with inactive disease. A mixture of oligo together with KLH was not immunogenic in vitro. Oligo-KLH or DNA-KLH did not raise antibody to an irrelevant antigen, ovalbumin. Of particular interest, PBL from seven of 10 normal subjects formed antibody to n-DNA after challenge in vitro with oligo-KLH. The data support the view that DNA fragments could be an important immunogen in SLE. Furthermore, this study provides an in vitro model to test the tolerogenicity of similar fragments of DNA linked to self carrier molecules such as gamma-globulin. | |
| 4567306 | Studies of T- and B-lymphocytes in patients with connective tissue diseases. | 1973 Feb | Peripheral blood lymphocytes from normal subjects as well as patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and active tuberculosis were studied for the relative distribution of bone marrow-derived lymphocytes (B-cells) and thymic-derived T-cells. B-cells were identified by direct immunofluorescence of surface Ig markers; T-cells were studied using rabbit antisera to pooled human fetal thymocytes absorbed with chronic lymphatic leukemia lymphocytes as a source of B-cells. In normal subjects, the sum of percentages of peripheral blood lymphocytes staining for surface Ig (B-cells) plus the percentage of cells staining with the absorbed antithymocyte antiserum closely approximated 100%. The mean value for percent B-cells among 51 normals tested was 22.9%+/-7.1; mean T-cells value was 75.3+/-13.95%. T-cell-specific antiserum stained 18% of normal human bone marrow lymphocytes, 42.5% of lymphocytes from normal spleens, and 98% of cells obtained from thoracic duct drainage of patients with RA. Specificity of antihuman thymocyte antiserum appeared to depend on the use of living cells. When patients with RA were examined, a wide range (14-98%) of peripheral blood T-cell values was found. Values for low percentages of peripheral blood T-cells appeared to correlate to some extent with severe clinical disease. In 11 of 36 RA patients, the sum of identifiable B- plus T-cells accounted for only 34-55% of peripheral blood lymphocytes. The identity of the remaining "null" cells could not be identified.3 of 24 SLE patients studied showed low percentages of peripheral blood T-cells, but no correlation could be drawn between T- to B-cell ratios and clinical disease activity. Among 21 patients with active tuberculosis, one had a low value for identifiable T-cells. No significant differences from normals in range or proportion of B-cells was identified in patients with active tuberculous infection. | |
| 6099287 | Human polymorphonuclear leukocyte collagenase and gelatinase. Comparison of certain enzyma | 1984 | Collagenase and gelatinase of human PMN leukocytes were separated by serial chromatography. The enzymes were shown to be similar in latency, activatability, chromatographic and electrophoretic behavior and the response to inhibitors. They recognize the same peptide linkage for cleavage, only each with a distinct difference in the effect caused by the secondary binding sites of the substrate molecules. | |
| 6888595 | [The "other" advantages of the pill]. | 1983 Jul 16 | ||
| 6603295 | In vitro immunoglobulin synthesis by lymphocytes from patients with rheumatoid arthritis. | 1983 Jun | We have investigated B cell function in nine patients with rheumatoid arthritis (RA) compared to sex and age matched controls in a pokeweed mitogen driven system. Levels of IgG and IgM synthesized in the supernatant were measured by a competition ELISA. We have found that cultured mononuclear cells from RA patients showed a defective Ig synthesis when depleted of monocytes. In contrast RA mononuclear cells not depleted of monocytes produced substantial levels of Ig after stimulation by the mitogen. The percentages of T and B lymphocytes in the peripheral blood of RA patients were normal; however, an increased number of lymphocytes formed rosettes with mouse erythrocytes indicating an abnormality in the B cell pool. These results demonstrate defective in vitro immunoglobulin synthesis by RA lymphocytes and show the importance of monocytes in this culture system. | |
| 6607733 | A long-term longitudinal study of anticentromere antibodies. | 1984 Feb | A longitudinal retrospective study of 37 patients previously tested for anticentromere antibodies (ACA) in 1982 was carried out. No ACA were found in stored sera from 22 ACA-negative patients including 1 patient with CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia). All ACA-positive patients, with 1 exception, were found to have ACA in their sera over prolonged periods of time. One patient developed ACA for the first time when the third feature of the CREST syndrome (Raynaud's phenomenon) was noted. Anticentromere antibodies were IgG, and no consistent change in titer over time was found. | |
| 6617077 | Availability of salicylate from salsalate and aspirin. | 1983 Oct | Salicylate availability from salsalate (SSA) and aspirin (ASA) was examined in six rheumatoid arthritis patients in a multiple-dose double-blind crossover study. Doses contained equimolar amounts of salicylic acid. After initial ASA treatment to achieve therapeutic salicylate levels (150 to 300 micrograms/ml) the patients received equimolar doses of SSA or ASA. When steady state was achieved patients were hospitalized, and blood and urine specimens were obtained during three dosing intervals and during the washout period that followed. Thereafter, patients were placed on the alternate medication for at least a week and the in-hospital pattern was repeated. Despite insignificant differences in absorption of the formulations, as measured by urinary salicylate recovery, the plasma salicylic acid AUC was lower after SSA. Evidence indicates that this apparent lower availability of salicylate from SSA is due to incomplete hydrolysis to salicylic acid, the unhydrolyzed SSA being excreted mainly as glucuronide conjugates. | |
| 3995211 | The development of screening tests for D-penicillamine-like antirheumatic activity based o | 1985 May | Injections of labile copper complexes such as copper II bisglycinate [Cu(II)gly] induce marked inflammatory responses in rats in contrast to stable copper complexes like copper II bishistidinate which are nonirritant. The antirheumatic drugs D-penicillamine, mercaptopyridoxine, thiola and captopril, inhibit Cu(II)gly-induced cutaneous vascular permeability when given intravenously and show oral cupriuretic activity. Inhibition of Cu(II)gly inflammation alone or cupriuretic activity alone do not appear predictive of clinical antirheumatic activity since L-cysteine methylester and trien, which are active in the former and latter tests, respectively, are devoid of clinical antirheumatic activity. Indomethacin and aspirin are inactive in these tests, thus discounting the concept that such drugs act in part through their copper complexes. The mechanisms by which labile copper induces inflammation and by which D-penicillamine-like drugs modulate the response are discussed. It is suggested that copper can generate free radicals in vivo and that D-penicillamine may act by neutralization of labile copper complexes and/or by formation of copper complexes with the capacity to catalyse the dismutation of superoxide anion. | |
| 1117023 | The Walldius hinge arthroplasty. | 1975 Feb | Eighty-three Walldius arthroplasties, performed by one surgeon as salvage operation on the knee joint between 1966 and 1972, were independently reviewed. The fifty-seven living patients with sixty-seven arthroplasties were interviewed and examined and the clinical records of the deceased patients were inspected. Sixty-seven arthroplasties (81 per cent) were successful and sixteen failed (19 per cent). Acrylic cement was used to secure the prosthesis on eight occasions only. There were two primary infections (2-4 per cent) and two delayed (2-4 per cent). Major loosening occurred in three arthroplasties (3-6 per cent). Minor loosening was compatible with a good result. Arthrodesis was successful on the two occasions on which it became necessary to remove the implant. There were no disasters. On the basis of these results it is considered that the Walldius arthroplasty can justifiably be offered as an alternative to primary arthrodesis of the knee. | |
| 6525801 | Red blood cell membrane-bound IgG: demonstration of antibodies in patients with autoimmune | 1984 | Immunoglobulin G (IgG) bound in vivo to the surfaces of red blood cells (RBC-IgG) was quantificated by an enzyme-linked immunosorbent assay (ELISA) using the cells themselves as solid phase. The method was applied on RBC from normal subjects, patients with autoimmune haemolytic anaemia (AIHA) and rheumatoid patients with and without circulating immune complexes (CIC). Small amounts of RBC-IgG were detected in normal subjects and rheumatoid patients without CIC. Fifteen out of 16 patients with AIHA had increased RBC-IgG indicating RBC sensitization with IgG antibodies, although only eight patients had a positive direct antiglobulin test (DAT) with anti-IgG. Ten out of 13 rheumatoid patients with a negative DAT and with CIC had increased RBC-IgG suggesting RBC C3 receptor-bound IC. The results provide background for further studies of the significance of RBC-IgG in health and disease. |