Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 377958 | Drug therapy reviews: antirheumatic agents. | 1979 May | The pathophysiology, symptoms and drug treatment of rheumatic disease are reviewed. Antirheumatic drugs reviewed are salicylates (including aspirin, sodium salicylate, choline salicylate, choline magnesium salicylate, salsalate), phenylpropionic acid derivatives (fenoprofen, ibuprofen, naproxen), indole derivatives (sulindac, tolmetin and indomethacin), pyrazolone derivatives (phenylbutazone, oxyphenbutazone), gold compounds, penicillamine, antimalarials mefenamic acid, corticosteroids and immunosuppressives. Simple analgesic therapy (acetaminophen, aspirin, propoxyphene) is used in the early stage of the disease. As the disease progresses, aspirin remains the drug of choice for antiinflammatory activity but the phenylpropionic acid or indole derivatives may be preferred in patients unable to tolerate salicylates. If such nonsteroidal antiinflammatory agents are not effective, parenteral therapy with gold compounds or oral penicillamine usually is indicated. Indomethacin or phenylbutazone, then antimalarials, are resorted to next. Corticosteroids or immunosuppressives are reserved for patients who are unsuccessfully controlled or who have major side effects with the other drugs. Mefenamic acid occupies a very secondary place in rheumatoid arthritis treatment. | |
| 369671 | Fibrosing alveolitis. | 1978 Nov 18 | Fibrosing alveolitis is a disease of unknown cause mainly involving the gas-exchanging portions of the lungs. It may occur in isolation and be called cryptogenic or idiopathic, in which case the clinical manifestations are mainly respiratory, or it may be associated with other disorders, such as rheumatoid arthritis. The histopathologic abnormalities of the pulmonary tissue are identical in either instance. Other names used for the disease have included usual interstitial pneumonia, desquamative interstitial pneumonia and the Hamman-Rich syndrome; these terms may describe different stages of the same pathologic process. Many authors in North America and those in the United Kingdom favour the term fibrosing alveolitis when describing chronic interstitial pneumonias. There may be accompanying nonspecific Immunologic abnormalities, which may denote that fibrosing alveolitis is part of the wide spectrum of diseases known as connective tissue disorders. Recently immune complexes have been found in the lung parenchyma; they probably result in the granulocyte destruction and reticuloendothelial proliferation seen in the acute phase of the disease.There are no specific diagnostic tests for the disease apart from lung biopsy, which can be performed at the time of thoracotomy or transbronchially, with the use of a flexible fibreoptic bronchoscope. Lavaged cells from the alveoli have also been obtained via the bronchoscope; in persons with fibrosing alveolitis a high proportion of these cells are neutrophils, and after corticosteroid treatment the proportion decreases. The progress of the disease can be followed by examination of these washings as well as by lung scanning with gallium-67 citrate. Newer methods of treatment using combinations of corticosteroids and immunosuppressant drugs are being evaluated and are initially proving to be successful. | |
| 941300 | The pathogenicity of Mycobacterium fortuitum and Mycobacterium chelonei in man: a report o | 1976 Mar | The clinical records of 7 patients referred to the National Jewish Hospital and Research Center over a 6-year period for evaluation of an abnormal chest x-ray and repeated sputum isolates of rapidly growing mycobacteria (Runyon's Group IV) were reviewed to determine the potential pathogenicity of these organisms. Mycobacterium fortuitum was isolated from 5 patients and Mycobacterium chelonei from 2. Haemoptysis, cough and weight loss were prominent in 6. Three had rheumatoid arthritis. Although two demonstrated cutaneous anergy, lymphocyte responsiveness to PHA was normal. PPD-F was not useful in skin testing or in the in vitro evaluation of lymphocyte function. Histologic examination of the lungs of 2 patients demonstrated caseating granulomata. One patient died of massive pulmonary haemorrhage soon after intiation of therapy. Multi-drug treatment regimens generally resulted in progressive sterilization of the sutum and improvement in the appearance of the chest x-ray. We conclude that some rapidly growing mycobacteria can cause potentially fatal cavitary lung disease and that intensive anti-tuberculosis therapy may successfully alter its course. | |
| 52700 | Some experience with 57Co-labeled bleomycin as a tumor-seeking agent. | 1975 Nov | Bleomycin labeled with 57Co was used as a tumor-localizing agent in 132 patients. In patients with pulmonary tumors the primary localization concentrated radioactivity in 52 of the 54 appropriate cases; out of the 22 clinically known metastases, 19 were visible on the scan; 40 unknown metastases especially in hilus and mediastinum were found by the method and subsequently confirmed. In 22 patients with malignant lymphomas, 18 out of 22 known pathologic lymph glands above the diaphragm were visible on the scan; below the diaphragm the results of scanning in lymph glands and spleen were disappointing, probably because of the disturbing concentration of radioactivity in the kidneys, the bladder, the liver, and sometimes the gut. In 25 patients with various other tumors, 16 out of 22 known localizations above the diaphragm were visible; 2 were uncertain and 4 negative. Below the diaphragm the results were usually negative. In 24 patients with benign lesions, uptake of 57Co-bleomycin was visible on the scintigram in 4 patients with cavitating pulmonary tuberculosis, in 2 with pulmonary infections, in 1 with Caplan lesions of rheumatoid arthritis in the lung, and in 1 with sinusitis ethmoidalis. The significance of these results is discussed. | |
| 1173774 | Chemistry and pharmacology of naproxen. | 1975 Feb | The need for a nonsteroidal anti-inflammatory agent effective in rheumatoid arthritis, osteoarthritis, gout, ankylosing spondylitis and related diseases with reduced side effects when compared to existing drugs led us to develop naproxen: d-2-(6'-methoxy-2'-naphthyl)-propionic acid. This new agent is a highly effective anti-inflammatory, analgetic, and antipyretic agent in the rodent administered orally. In a rat paw edema test for anti-inflammatory activity naproxen was 55 times more active than aspirin. Analgetic activity was assessed by three different assay procedures. In the mouse phenylquinone writhing test naproxen was 7 times as effective as aspirin. In the rat yeast-induced paw edema and the rat carrageenin paw edema analgetic assays the test compound was 10 and 20 times more effective than aspirin, respectively. A yeast-induced pyresis model in the rat indicated that naproxen was 22 times more potent than the standard aspirin. The relative potency of naproxen to phenylbutazone and indometacin is presented. | |
| 135396 | Immunologic considerations in renovascular hypertension. | 1975 | For decases certain diseases, such as glomerulonephritis, polyarteritis nodosa, scleroderma and serum sickness, have been linked with autoimmune pathogenesis. During recent years a host of additional diseases traditionally thought to have some genetic predisposition but with obscure etiology have been suspected of being autoimmune in nature. Rheumatoid arthritis, diabetes, myasthenia gravis and thyroiditis are diseases of widely divergent organ systems, yet may well have common pathways of pathology via immune complexing mechanisms. Herein we present evidence supporting the concept that renal artery stenosis (occurring primarily in association with the middle aortic syndrome or after renal transplantation) is of immune etiology. Although the specific antigenic agent is still to be defined there is growing acceptance of the theory that medium and large vessels are subject to autoimmune vasculitis in many aspects similar to the autoimmune affections of small vessels. Several cases are presented. Some of these suggest an immune reaction by the natural history but without evidence of immunochemical reactants in the involved vessels, presumably because active disease was arrested at the time to study. In other cases immunofluorescent preparations demonstrate reactants in the walls of the vessels to document the hypothesis more convincingly. | |
| 3927925 | Impact of diagnosis-related group-based reimbursement for treatment of rheumatic diseases | 1985 Aug | The impact of Medicare's diagnosis-related group (DRG)-based reimbursement system was examined for care given to 734 rheumatic disease patients discharged from a teaching hospital during a 2-year period. The analysis accounted for length of stay "outliers" as defined by Medicare and distinguished costs from charges. Excluding outliers, DRG reimbursement would result in net revenues to the hospital of +1,126 per DRG 240 patient and $1,794 per DRG 241 patient. The difference between DRGs in cost per patient was significant, indicating that DRGs clearly identify 2 groups of rheumatic disease patients. After excluding outliers, the coefficients of variation in costs for DRGs 240 and 241 were 72% and 80%, respectively, which although high, were average for DRGs at our institution. Mean total charge per patient was different for groups defined by their primary rheumatologic diagnosis in DRG 240 but not DRG 241. For rheumatoid arthritis and systemic lupus erythematosus patients, the total charge per patient did not differ, but the types of services did. The cost of treating outliers would create an average loss per outlier of $18,400 and $16,500, respectively, in DRGs 240 and 241. Outliers accounted for 34.5% and 21.8% of the 2 DRGs' total costs, respectively, but only 6.4% and 3.6% of the total number of patients. Under current DRG reimbursement rates, the cost of care for rheumatology patients would be adequately reimbursed in our hospital: losses from outliers would be offset by net revenues from inliers as long as current Medicare adjustments for capital and medical education costs were continued. | |
| 6978137 | T cell leukemia presenting as chronic polyarthritis. | 1982 Jan | T cell leukemia was detected in a woman who suffered from chronic polyarthritis. The peripheral blood leukocytes were increased in number and consisted of lymphocytes, 95% of which could be identified as T lymphocytes. T cell infiltration was found in the bone marrow, the synovial fluid, and tissue, and in nodules macroscopically resembling rheumatoid skin lesions. Further investigation of these cells by enzyme chemistry, immunohistochemistry, electron microscopy, and cytochemistry revealed that they had irregularly indented nuclei, no alpha-naphthyl acetate esterase activity, and only faint granular acid-phosphatase activity. The cells were negative for Ia-like antigen and surface immunoglobulin. Analysis of the cell surface glycopeptides showed the presence of abnormally enlarged carbohydrate structures. These data suggest that these leukemic T cells are a malignant equivalent of immature T cells. | |
| 7250802 | [Several years' experience with thumb saddle joint prosthesis by the de la Caffinière met | 1980 | This type of endoprosthesis was used for four years in chronically painful idiopathic osteoarthritis of the carpometacarpal joint of the thumb. Our results match exactly those published by the originator of the endoprosthesis CAFFINIERE, i.e. 70% excellent results, nearly 30% problem cases. The problem of loosening of the stem or the cup of the prosthesis seems to depend in our cases on the operative technique rather than on the design or other factors. In the rheumatoid patient as well as in polyarthrotic hands we cannot encourage the prosthetic replacement of the carpometacarpal joint of the thumb. | |
| 921825 | Destruction of joint homografts. An experimental study. | 1977 Nov | The host synovium undergoes a striking transformation at about 26 weeks after joint homografting. Histologically the synovium invaded and destroyed the graft with which it came in contact, becoming markedly hypercellular; the infiltrate consisted mainly of plasma cells and lymphocytes. The synovium at this stage closely resembled a rheumatoid pannus. The cartilage in contact with this invasive synovium lost its staining qualities, failed to take up S-35, and was gradually destroyed. The mechanism causing this transformation remains unclear. It is postulated that these changes could be due to an inflammatory or immune response. | |
| 6421291 | Sjögren's syndrome in MRL/l and MRL/n mice. | 1984 Feb | Six autoimmune murine models (MRL/l, MRL/n, NZB, NZB/NZW, PN, C57BL/6J-lpr/lpr) were compared with normal control C57BL/6J and DBA/2 mice to determine if spontaneous autoimmune disease was associated with evidence of Sjögren's syndrome. Schirmer tests documented dry eyes in NZB/NZW and PN mice; other autoimmune strains and controls had normal tear formation. All autoimmune mice had conjunctivitis, but this abnormality was most severe in the PN strain. Ninety-eight percent of MRL/l and MRL/n mice had mononuclear cell infiltrates in lacrimal glands, and salivary glands were involved to a lesser degree. New Zealand mice and PN mice had smaller gland lesions. The extensive gland destruction in MRL/l and MRL/n mice suggested that these substrains merit further studies as animal models of Sjögren's syndrome. | |
| 102190 | Immunologically diagnosed malignancy in Sjögren's pseudolymphoma. | 1978 Sep | Studies of lymphocyte markers in a patient with Sjögren's syndrome who exhibited histologically benign lymphoproliferation in the lung revealed a malignant cell clone. T and B cells were quantitated according to their ability to form spontaneous rosettes with sheep erythrocytes and to fluoresce with fluorescein-conjugated antiserums, respectively. Circulating lymphocytes were 66 percent T cells (N = 58 +/- 2 per cent) and 14 percent B cells (N = 22+/- 1 percent), the latter exhibiting normal polyclonal distribution of membrane immunoglobulins. However, lymphocyte suspensions obtained from fresh lymph node and from biopsy specimens from a lymphoid lung nodule revealed 95 percent and 88 percent B cells, with 1 percent and 2 percent T cells, respectively. Moreover, when cryostat-frozen sections from both tissues were reacted with each of the heavy and light chain-specific antiserums, most cells demonstrated the presence of intracytoplasmic mu kappa immunoglobulin exclusively. Twenty-two months later, a clinically and histologically classic lymphoma developed. Repeat marker studies performed on cells freshly isolated and on frozen sections from the histologically malignant lymph node revealed persistence of the monoclonal marker on most cells. | |
| 6772719 | Characterization of immune complexes and immunoglobulin G antibodies reactive with neutrop | 1980 Aug | These studies were performed to determine the relative contribution of immune complexes or antibodies reactive with PMNs to the elevated levels of IgG PMN-binding activity seen with sera from some patients with Felty's syndrome. Twenty-one sera from 19 patients with Felty's syndrome were fractionated by gel filtration on Sephadex G-200. Fourteen of the sera had elevated levels of IgG PMN-binding activity as measured by a sensitive IgG-specific antiglobulin inhibition technique. Ten of the G-200 excluded pools and eight of the G-200 IgG pools had levels of IgG PMN-binding activity greater than 2 S.D. above the mean value for normals.Significant correlations were observed between the levels of IgG PMN-binding activity in the sera and the values for both the G-200 excluded pools (r = 0.51) and the IgG pools (r = 0.69). These data suggested that both soluble immune complexes and antibodies reactive with PMNs contributed to the elevated serum levels of IgG PMN-binding activity seen with sera from some patients with Felty's syndrome. Further evidence for the presence of PMN-binding immune complexes in the sera of patients with Felty's syndrome was the strong correlation between the values of serum IgG PMN-binding activity and the levels of immune complexes as detected by C1q binding (r = 0.71) or analytical ultracentrifugation (r = 0.60). Studies of G-200 excluded samples adsorbed with human IgG coupled to Sepharose 4-B indicated that immune complexes containing rheumatoid factors contributed only in part to the increased levels of IgG PMN-binding activity and of C1q-binding activity. Confirmation of the presence of antibodies reactive with neutrophils was the finding of significantly greater binding to PMN with F(ab')2 fragments of IgG from four sera of patients with Felty's syndrome compared to F(ab')2 from normal sera. Adsorption studies suggested that the PMN-reactive antibodies did not possess rheumatoid factor activity. | |
| 7337970 | Isolation of circulating immune complexes by conglutinin and separation of antigen from di | 1981 Oct | A method for the isolation of complement-fixing immune complexes from human serum and the separation of antigen from antibody is described. In order to isolate the complexes, we used soluble bovine conglutinin in a three-step procedure: (1) serum containing immune complexes is reacted with conglutinin in the presence of 10 mM calcium; (2) the conglutinin-bound immune complexes are precipitated by anti-conglutinin rabbit serum; (3) the precipitate is washed and the complexes are eluted from the precipitate by EDTA (pH 7.5) which chelates calcium and releases C3-associated immune complexes from conglutinin. To separate the antigen from the antibody, the isolated complexes are acid-dissociated (pH 3.0), and the antibody is absorbed to staphylococcal protein A conjugated to Sepharose leaving the antigen in solution. The antibody bound to Sepharose-protein A is recovered by elution with 3.5 M magnesium chloride. This procedure permitted the isolation of immune complexes from sera of hepatitis B surface antigen (HBsAg) positive chronic active hepatitis. In addition, immune complexes were isolated from sera of patients with rheumatoid arthritis, systemic lupus erythematosus and primary biliary cirrhosis. The isolated immune complexes contained IgG, IgM, C3 and albumin. Specific antibodies such as rheumatoid factors, anti-nuclear antibodies and antimitochondrial antibodies in varying titres have been found to be present in the isolated immune complexes. The conglutinin method has proven to be a useful technique for the isolation of immune complexes and for the identification of antibody and could be applied to the identification of the antigen in immune complexes. | |
| 3873326 | Reduction in gastric mucosal hemorrhage and ulceration with chronic high-level dosing of e | 1985 Jun | When administered on a chronic high-dosage regimen, enteric-coated aspirin granules produced significantly less gastric damage than plain aspirin or aspirin-antacid combinations. Clinically meaningful damage occurred in all subjects receiving plain aspirin, 93% of those receiving aspirin-antacid combination and only 27% and 20% of those receiving enteric-coated aspirin granules qid and bid, respectively. All three aspirin formulations were taken as 1 g qid (4 g/day) and an additional group received enteric granules administered as 2 g bid (4 g/day). Gastric damage was assessed by means of endoscopy carried out after seven days of treatment. Enteric granules are equally safe when administered on a bid or qid regimen (at same total daily dosage) and, in a bid regimen, should provide a compliance advantage for patients on high-dose therapy for diseases such as rheumatoid arthritis. | |
| 6480071 | The immunological basis of inflammatory diseases. | 1984 Jun | Most immunologically-mediated diseases are inflammatory in nature, as assessed by cellular infiltrates at the lesion site. Recent immunohistological studies using monoclonal antibodies on tissue sections and synovial or cerebrospinal fluid reveal that B- and T-lymphocytes (predominantly T) participate in this reaction, together with monocytes and macrophages. The etiopathogenesis of inflammatory diseases of immunological origin can be discussed at two levels. (1) Lesions may be secondary to the cytopathic effect of antibodies, either by direct cytolysis or by opsonization, antigenic modulation, or blockage of functionally-relevant molecules. Immune complexes formed in the circulation or locally at the lesion site may intervene. Direct cellular mechanisms are probably involved, as suggested by evidence in hepatitis (indirect) and in juvenile insulin-dependent diabetes (direct). K-cells may act by antibody-dependent cytotoxicity, particularly in autoimmune diabetes and thyroiditis where lymphocyte-dependent antibodies are demonstrated. Unfortunately, the absence of adequate markers does not permit adequate detection of K-cells in inflammatory reaction sites. (2) Etiological factors are multiple in a given disease and even in a single patient. Deficiency of suppressor T-cells, assessed using monoclonal anti T-cell antibodies, represents a major predisposing factor, although suppressor cell deficit may be restricted to some antigens (EBV) in certain patients. The deficiency of interleukin-2 production in lupus and rheumatoid arthritis is intriguing but the mechanism and its relationship to disease etiology are unknown. Other immunological factors include intrinsic B-cell hyperactivity, anti-T-cell auto-antibodies, and complement deficiencies, whereas non-immunological factors such as viruses, drugs or sex hormones are important but ill-defined.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 6609414 | Differences in the production of and/or the response to interleukin-2 by T lymphocytes fro | 1984 | We have studied the production of and the response to interleukin-2 (IL-2) by blood T lymphocytes from 83 untreated patients with six connective tissue diseases, each patient with a healthy age/sex matched control. SLE patients had markedly decreased production of IL-2, both when elicited with phytohemagglutinin (PHA) and when promoted by autologous mixed lymphocyte reaction (AMLR). They also had decreased response to IL-2. Conversely, patients with scleroderma had normal production of IL-2 with both stimuli and their lymphocytes responded to IL-2 similarly to, or even better than, controls. Patients with mixed connective tissue disease had decreased production of IL-2 upon PHA stimulation but it was normal in AMLR systems. Response to IL-2 was moderately diminished. Patients with rheumatoid arthritis showed moderately decreased production of Il-2 with both stimuli but a normal response to Il-2. Patients with Sjögren's syndrome had similar, but less marked defects than those of SLE. Patients with dermato-polymyositis showed decreased production of IL-2 in AMLR but normal production of IL-2 in response to PHA as well as normal response to IL-2. The differences found between the various connective tissue diseases support the notion that the T cell dysregulation that results from or leads to "autoimmunity" in them is peculiar to each disease. | |
| 6442048 | [Intracellular gold content of circulating blood cells using various gold compounds]. | 1984 | Evidence on the action mechanisms of gold salts in the treatment of rheumatoid arthritis is still inconclusive. The intracellular localization of the place of action is likely. Therefore not only the serum gold levels but also the intracellular concentration of gold are of special interest. We measured the gold concentration in the serum and in the blood cells after in vitro application of aurothiomalate (Tauredon), gold keratinate (Auro-Detoxin) and triethylphosphine-gold (Ridaura) and in blood samples of patients undergoing these gold salts treatments. Cell-bound concentrations were found to vary extensively as a function of the gold compound used. While no or very little gold was present intracellularly after administration of the 2 parenteral drugs, up to 40% of the circulating gold was found to bind to the cells after administration of the triethylphosphine compound for gastro-intestinal absorption. The red cell concentration was more or less the same as that in the extracellular compartment. Gold apparently accumulated in the white cells, because the cell-bound concentration relative to unit volume was up to 20 times higher than the plasma level. The method used did not offer any information on the actual binding site of gold in white cells, i.e. cytoplasm versus nucleus versus cell membrane. | |
| 6359862 | Use of antipyretic analgesics in the pediatric patient. | 1983 Nov 14 | Fever and pain are the most common issues in pediatric patient management. Acetaminophen, aspirin, and dipyrone are the most commonly used drugs and are equivalent in their efficacy. Dipyrone, used in many parts of the world, but not in the United States, is an effective agent; however, it has been implicated in producing agranulocytosis and anaphylactic shock. The salicylates have anti-inflammatory effects making them appropriate for the treatment of patients with juvenile rheumatoid arthritis, but they are gastric irritants, may impair clotting, and, because of saturable kinetics, may lead to accumulation and toxicity. Acetaminophen is an effective antipyretic and analgesic with few side effects that is toxic only in massive overdose. | |
| 6617983 | Effects of intravenous high doses of ketoprofen on blood clotting, bleeding time and plate | 1983 | The effect of ketoprofen (Orudis, Farmitalia) on ADP, epinephrine (EPI) and collagen (COLL) induced platelet aggregation (PlA), simplate bleeding time (SBT), partial thromboplastin time (PTT) and per cent prothrombin activity (PrA) was studied in eleven patients, four males and seven females (median age 59 years) with rheumatoid arthritis (six cases), cancer (four cases) and osteoarthrosis (one case). Tests were performed before and 1, 8 and 24 hours after a single intravenous dose (600 mg) of ketoprofen and on Days 4 and 8 during a 7-day treatment (200 mg i.v. every 8 hours) and 1 day after withdrawal of the drug. PTT and PrA were not affected by the drug. Bleeding time was not significantly modified by the acute treatment, but was prolonged during the subacute course, though it was not different from baseline values at the end of the trial. Significant reduction of platelet aggregation was seen in both acute and subacute conditions with complete or almost complete recovery 36 hours after the last dose. It is concluded that ketoprofen affects platelets with readily reversible inhibition of in vitro aggregation and a slight increase of bleeding time. |