Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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531446 | Comparisons of tolerability findings in international clinical trials. | 1979 | This report summarizes tolerability results from over 30 000 patients treated with diclofenac in clinical trials in rheumatic and other indications in 21 countries. Comparative trials indicates that 75-150 mg daily of diclofenac is better tolerated than similar doses of indomethacin and 1.5-5 g daily of aspirin, and at least as well tolerated as 600-1200 mg of ibuprofen and 500 mg daily of naproxen. In general practice populations unwanted effects can be expected in about 18% of patients and will result in discontinuation in about 4%. Gastrointestinal disturbances were the most frequent unwanted effects with diclofenac, occurring in about 8% of patients. Mild CNS effects also occurred infrequently in about 1.5% and dermatological effects in about 1%; cardiovascular effects also occurred in about 1%. As over 80% of unwanted effects and all of the discontinuations for intolerability occurred in the first six months, the tolerability of diclofenac does not decrease with time. | |
759520 | The dilute whole blood clot lysis assay: a screening method for identifying postoperative | 1979 Jan | A dilute whole blood clot lysis assay was used to identify patients with a high incidence of DVT. Of 191 orthopedic and urologic patients who underwent surgery, the over-all incidence of DVT as determined by 125I-fibrinogen leg scan was 35% in the 92 individuals with abnormal assays and 1% in the 99 patients with normal assays. The likelihood that an individual patient might have developed DVT increased progressively with the number of abnormal assays (p less than 0.001). The incidence of DVT increased from 28% in patients who had one abnormal assay, to 35% in patients with two abnormal assays, to 56% in patients with three abnormal assays. These studies establish the clot lysis assay as a simple means to screen for patients with a high incidence of DVT. A normal assay can eliminate patients from consideration for more extensive studies (venography, fibrinogen scan, impedance plethysmography), whereas those patients with one or more abnormal assays should be seriously considered for these additional studies. | |
3925539 | Quantitative absorption of interleukin-2 by peripheral blood and synovial fluid lymphocyte | 1985 | Peripheral blood (PBL) and synovial fluid lymphocytes (SFL) from 18 patients with definite rheumatoid arthritis (RA) and from one patient with Reiter's disease (RD) were examined for their capacity to absorb quantitatively interleukin-2 (IL-2) from a standardized, lectin-free IL-2 source. For comparison normal ConA blasts and PBL from various inflammatory and noninflammatory diseases as well as from healthy control persons were studied. IL-2 activity was quantitated by measuring 3H-thymidine-2-deoxyriboside uptake in the IL-2 dependent murine T cell line CTL6. ConA blasts exhibited a high IL-2 absorption capacity and served as a positive control for calibrating the absorption assay. In a population of normal PBL at least 5-10% of ConA blasts were required to detect IL-2 absorption. Significant absorption was assumed if more than 50% of IL-2 activity was removed from 200 microliters of a lectin-free IL-2 standard following incubation with 5 X 10(6) lymphoid cells for 2 h at 4 degrees C; this criterion was fulfilled with 8 out of 20 SFL and 4 out of 14 PBL preparations from RA patients. As a rule SFL absorbed more IL-2 than PBL. Control PBL did not absorb significant quantities of IL-2. PBL from the RD patient apparently produced an IL-2 inhibitor during incubation with the IL-2 standard. IL-2 absorption by ConA blasts and SFL was fully inhibited by preincubation of the absorbing cells with monoclonal anti-TAC antibody, a reagent known to react with the human IL-2 receptor. The results are discussed in view of current concepts of antigen/mitogen induced T cell activation. | |
2985325 | Measurement of proteoglycans, elastase, collagenase and protein in synovial fluid in infla | 1985 Mar | The number of leucocytes and the concentrations of protein, proteoglycans (PG), elastase a1 proteinase inhibitor complexes (E-alpha 1 Pi) and collagenolytic activity were measured in the synovial fluid (SF) of 15 patients with rheumatoid arthritis (RA) and 18 with osteoarthritis (OA). The mean levels of protein, E-alpha 1 Pi and collagenase and the number of leucocytes were higher in RA than in OA SF. However, the mean level of PG was higher of OA SF than in RA. In the latter, they were principally in the form of monomers and fragments while in the former they were in the form of aggregates and monomers. There was a direct relationship between the concentration of E-alpha 1 Pi and either the number of white cells or the concentration of synovial proteins, suggesting that the measurement of E-alpha 1 Pi complexes is a biochemical index of the local inflammatory reaction. There was an inverse correlation between the concentrations of PG and E-alpha 1 Pi which may reflect the effect of degradation in PG of elastase and other enzymes released at the same time. Finally, there was a direct relationship between the concentration of E-alpha 1Pi and collagenase which may be the reflection of a simultaneous release of various enzymes from leucocytes and macrophages. | |
7099199 | D-Penicillamine-associated myasthenia gravis: immunological and electrophysiological studi | 1982 Apr | Immunological and electrophysiological features were investigated in a patient with rheumatoid arthritis who developed myasthenic symptoms after 10 months of treatment with D-penicillamine (D-pen). After an initial rise, acetylcholine receptor (AChR) antibodies gradually fell from 24.4 nmole alpha-bungarotoxin bound/liter to 1.8 nmole/liter following withdrawal of the drug, and this was associated with clinical and electrophysiological improvement. Immunoglobuline synthesis by peripheral blood lymphocytes cultured with pokeweed mitogen and D-pen was significantly increased at D-pen concentrations of 10-100 micrograms/ml in 2 patients with D-pen associated myasthenia gravis and 1 out of 3 normal individuals. Furthermore, lymphocytes from 1 myasthenic patient synthesized detectable AChR antibodies in vitro, and the amount of receptor antibody produced was increased in the presence of the drug. This effect was most marked at a concentration of 10 micrograms/ml which is thought to approximate the concentration in vivo. Our results confirm the in vivo findings of others that D-pen may have different effects on immunoglobulin production in different individuals and may also enhance the snythesis of at least 1 autoantibody, the AChR antibody. | |
984064 | The effect of anti-inflammatory agents and inflammation on granulocyte adherence. Evidence | 1976 Nov | Significant inhibition of granulocyte adherence to nylon fiber columns followed the administration of alcohol, aspirin, sodium salicylate, acetaminophen, indomethacin, phenylbutazone, colchicine or prednisone to normal subjects. The addition of salicylates and glucocorticoids to blood in vitro had no effect on adherence, but plasma from volunteer subjects treated with either drug contained a factor which inhibited the adherence of normal granulocytes. The factor is heat stable, nondialyzable and not present in serum; it produces a linear dose response in normal cells. When mixed with the adherence-increasing factor found in inflammatory diseases, it neutralizes the augmenting effect and normal granulocyte adherence results. The effect of anti-inflammatory therapy on inflammatory disease was studied in aspirin-treated patients with rheumatoid arthritis. Their granulocyte adherence fell into two categories based on the clinical control of their disease; patients in good control had only slightly increased granulocyte adherence, but those in poor control had an average adherence more than twice normal. Mean blood aspirin levels were equivalent for the two groups (11.0 mg/100 ml for the well controlled and 13.4 mg/100 ml for those poorly controlled). Thus, clinical response to anti-inflammatory therapy correlates well with granulocyte adherence, not with aspirin levels. The potential pathogenetic role of adherence-modifying factors in inflammatory diseases remains to be determined. | |
6693608 | Cellular atypia in a rheumatoid nodule: a diagnostic pitfall of aspiration biopsy. | 1984 Feb | A 63-year-old cachectic white male developed subcutaneous scalp nodules. Clinically these were felt most likely to represent metastatic tumor, although the patient was known to have rheumatoid arthritis. Aspiration cytology was interpreted as malignant due to the presence of atypical cells, but tissue biopsies demonstrated necrotizing palisading granulomas. The diagnostic hazard of cellular atypia in rheumatoid nodules is discussed. | |
3876290 | Early rheumatoid-like synovial lesions in rabbits drinking cow's milk. II. Antibody respon | 1985 | Thirty-six percent of Old English rabbits fed pasteurized cow's milk developed early rheumatoid-like synovial lesions. All rabbits drinking milk developed high titres of serum and synovial fluid Clq-binding activity. This has been shown to be due to specific antibody to Clq, produced in response to Clq in cow's milk. In addition, these rabbits responded to other bovine proteins present in cow's milk, including conglutinin, beta-lactoglobulin and IgG. There was no correlation between serum or synovial fluid titres of antibody to bovine milk proteins and synovial lesions. | |
6236015 | Eluted rheumatoid synovial tissue T cell subsets and HLA-DR bearing cells at different sta | 1983 Mar | By using monoclonal antibodies of the OK series in the indirect immunofluorescence technique we wanted to enumerate T cell subsets and HLA-DR-bearing cells of patients with classical rheumatoid arthritis after the cells were eluted from rheumatoid synovial tissue and at different stages of two cell fractionation procedures. The procedures were an overnight incubation on plastic flasks or a brief (7 min) fractionation on nylon wool columns, both followed by Isopaque-Ficoll gradient centrifugation. 70-90% HLA-DR+ cells and 15-30% T3+ (T cells) were initially observed. Plastic flask incubation and gradient centrifugation reduced the mediam number of HLA-DR+ cells to 55% while the number of T3+ cells increased to 60-75%, the number of T4+ (helper/inducer T cells) and T8+ (cytotoxic/suppressor T cells) usually being about equal. The other fractionation procedure left essentially the same relative proportions of cells bearing these markers even though the cell yield was 5-10 times greater than for the plastic flask fractionation. About 30% of the T cells were calculated to bear HLA-DR antigens, indicating local activation in vivo. | |
6765393 | Pharmacology, clinical efficacy, and adverse effects of piroxicam, a new nonsteroidal anti | 1982 Mar | Piroxicam, a new non-steroidal anti-inflammatory drug, possesses analgesic, antipyretic, and anti-inflammatory properties and inhibits platelet aggregation in animal models. Its elimination half-life is 38 hours, and hepatic metabolism to inactive metabolites is the primary route of elimination. Less than 10% of a dose appears unchanged in the urine. Clinical studies demonstrate that piroxicam's analgesic and anti-inflammatory properties are useful in the management of rheumatoid arthritis and osteoarthritis. Limited clinical studies suggest that piroxicam may be useful in the management of acute gouty arthritis, ankylosing spondylitis, acute musculoskeletal disorders, and as an analgesic. The gastrointestinal system is the major site of adverse effects. Piroxicam is currently marketed in 20 mg capsules and once daily dosing has proven effective for many patients. | |
4583778 | A naturally occurring human antibody to loops of Henle. | 1973 Aug | A hitherto unreported immunofluorescent staining pattern obtained from human sera is described. Serum from six patients was found to possess specific antibody activity against lining cells of loops of Henle on the kidney of several species including man. All six patients had diseases of supposed immune aetiology, but in only one was any overt disturbance of renal funtion demonstrated and this patient had primary glomerular disease. | |
6836233 | Treatment of finger joints with local steroids. A double-blind study. | 1983 | The study was performed in 24 patients all having rheumatoid arthritis affecting the finger joints. Randomly, and in a double-blind fashion, the inflamed interphalangeal and proximal interphalangeal joints of one hand were injected with either triamcinolone hexacetoide (TH) or methylprednisolone (MP) and those of the other hand vice versa. A total of 120 affected swollen finger joints were injected--59 joints with TH and 61 with MP. The duration of effect and the possible side effects were followed up for a period of 6 months. All injections produced clinically significant effects. There were no significant differences between the two treatment groups at the start of the treatment, but after 6 months the results in the TH group were significantly better. However, there were also more joints with skin and soft tissue atrophy in this group than in the MP group. | |
1079212 | Scientific methodology applied. | 1975 Apr | The subject of this symposium is naproxen, a new drug that resulted from an investigation to find a superior anti-inflammatory agent. It was synthesized by Harrison et al. in 1970 at the Syntex Institute of Organic Chemistry and Biological Sciences. How can we chart the evolution of this or any other drug? Three steps are necessary: first, chemical studies (synthesis, analysis); second, animal pharmacology; third, human pharmacology. The last step can additionally be divided into four phases: metabolism and toxicology of the drug in normal volunteers; dose titration and initial clinical trials with sick subjects (pharmacometry); confirmatory clinical trials when the drug is accepted on the market and revaluation (familiarization trials). To discover the truth about naproxen, we must all participate actively with a critical mind, following the principles of scientific methodology. We shall find that the papers to be presented today all deal with the third step in the evaluation process--clinical pharmacology. It is quite evident that the final and most decisive test must be aimed at the most valuable target: the human being. The end product of this day's work for each of us should be the formation of an opinion based on solid scientific proofs. And let us hope that we will all enjoy fulfilling the symposium in its entire etymological meaning this evening. In vino veritas. | |
6287560 | Serum deoxyribonuclease I and clinical activity in systemic lupus erythematosus. | 1981 | Serum deoxyribonuclease I (DNase I) activity in systemic lupus erythematosus (SLE) patients was shown to be lower than that of healthy laboratory personnel, rheumatoid arthritis, and scleroderma patients (P less than 0.001). The decrease in DNase I activity in SLE sera was not due to the effect of various autoantibodies or to heat labile DNase I inhibitor. A relationship between serum DNase I activity and active SLE was demonstrated. Patients with active lupus nephritis had the lowest levels of enzymatic activity. | |
324748 | Fenoprofen: a review of its pharmacological properties and therapeutic efficacy in rheumat | 1977 Apr | Fenoprofen1 (dl-2-[3-phenoxyphenyl]propionic acid) is a new non-steroidal anti-inflammatory, antipyretic, analgesic agent advocated for use in rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis and gout. Published data suggest that in rheumatoid arthritis, fenoprofen 2.4 g daily is comparable in effectiveness with moderate doses of aspirin (3.6 to 4 g daily), but generally causes fewer and milder side-effects at the dosages used. In published comparisons with other non-steroidal anti-inflammatory agents of the same chemical group, it is closely comparable with naproxen in effectiveness but tends to cause more minor side-effects than naproxen. However, as no one of the non-steroidal anti-inflammatory agents is the most suitable drug for all patients requiring such therapy, fenoprofen should be considered along with the other drugs of its type in the initial treatment of the arthritic patient. Fenoprofen has compared favourably with phenylbutazone in osteoarthrosis of the hips and with aspirin in osteoarthrosis of the shoulders, hips, knees and spine. Its exact place in the management of gout and ankylosing spondylitis remains to be determined. | |
160348 | A controlled clinical study comparing sulindac with ibuprofen and aspirin in the treatment | 1979 | Forty-six patients (seventeen male, twenty-nine female) with musculo-skeletal disease were put on a controlled clinical study comparing sulindac with ibuprofen and soluble aspirin. Twenty patients were treated with sulindac 200 mg twice daily, twelve received sulindac 100 mg twice daily, eight had ibuprofen 400 mg thrice daily and six treated with soluble aspirin 600 mg thrice daily. All patients did well on these drugs, but the ones on sulindac 200 mg twice daily showed better response than sulindac 100 mg twice daily. It proved to have the same efficiency as ibuprofen and soluble aspirin; but had less side-effects and also patients required to take the drug only twice daily to get relief because of its prolonged duration of action. | |
338021 | Radiation-induced chromosome damage in human lymphocytes. | 1977 Nov | ABSTRACT Analysis for chromosome aberrations in human peripheral blood lymphocytes has been developed as an indicator of dose from ionising radiation. This paper outlines the mechanism of production of aberrations, the technique for their analysis and the dose-effect relationships for various types of radiation. During the past ten years the National Radiological Protection Board has developed a service for the UK in which estimates of dose from chromosome aberration analysis are made on people known or suspected of being accidentally over-exposed. This service can provide estimates where no physical dosemeter was worn and is frequently able to resolve anomalous or disputed data from routine film badges. Several problems in the interpretation of chromosome aberration yields are reviewed. These include the effects of partial body irradiation and the response to variations in dose rate and the intermittent nature of some exposures. The dosimetry service is supported by a research programme which includes surveys of groups of patients irradiated for medical purposes. Two surveys are described. In the first, lymphocyte aberrations were examined in rheumatiod arthritis patients receiving intra-articular injections of colloidal radiogold or radioyttrium. A proportion of the nuclide leaked from the joint into the regional lymphatic system. In the second survey a comparison was made between the cytogenetic and physical estimates of whole body dose in patients receiving iodine 131 for thyroid carcinoma. | |
6993665 | Long-term safety of benoxaprofen. | 1980 | Adverse experiences were monitored in 1,681 patients with rheumatoid arthritis (RA) or osteoarthritis to evaluate the safety of benoxaprofen at daily doses up to 1,000 mg during long-term therapy. Gastrointestinal side effects with benoxaprofen compared favorably to those reported during aspirin and ibuprofen therapy, with peptic ulcers reported in 0.4% of the patients or 1 ulcer for 200 patient years. The incidence of photosensitivity or onycholysis was 9%. Laboratory examinations revealed no significant changes in BUN, hematocrit, hemoglobin, SGOT, and SGPT values. The only trend toward abnormal values was seen in the LDH in patients with RA. | |
6217996 | Indoprofen in rheumatic patients with acute episodes: a multicentre trial. | 1982 | The results are reported of an open multicentre trial in 228 rheumatic patients with flare-ups. Fourteen centres adopting the same investigational protocol collaborated in the study. Indoprofen was administered for 1 week at a daily dosage of 1000 mg according to a treatment schedule used with success in acute gouty arthritis: a 400 mg i.v. bolus was followed by 200 mg (1 tablet) t.i.d. Subjective (pain) and objective variables were used for reliable assessment of activity. Marked reduction of pain intensity was already noticeable on day 1 of treatment and was followed by progressive improvement in subjective and objective variables for all the diagnoses considered. According to the patients' own overall assessments, results were good or very good in more than 50% of cases. The best outcomes were obtained in low back pain, acute gout and psoriatic arthritis. At the end of treatment only 7.4% of patients experienced no change or deterioration of symptoms. Adverse reactions, consisting mostly of mild and reversible gastrointestinal disturbances, were reported by 9.2% of patients, but only in 1.8% was treatment discontinued. Indoprofen administered according to the above schedule is an appropriate treatment for acute episodes of rheumatic diseases. | |
300118 | New antirheumatic agents: Fenoprofen calcium (Nalfon), naproxen (Naprosyn), and tolmetin s | 1977 Mar 21 | The new antirheumatic agents, fenoprofen calcium, naproxen, and tolmetin sodium, are effective in the management of rheumatoid arthritis. Their efficacy is comparable, but not superior, to that of aspirin in usual oral doses. These agents also may be useful in degenerative joint disease and ankylosing spondylitis and as analgesics and antipyretics; however, there are insufficient data available to establish their efficacy and dosages for these uses. The incidence of adverse reactions, including gastrointestinal bleeding, is lower with these agents than with aspirin; thus, these drugs may be useful substitutes in patients who cannot tolerate the gastrointestinal effects of aspirin. |