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

ID PMID Title PublicationDate abstract
6742906 Mononuclear phagocytes in rheumatoid arthritis: Fc-receptor expression by peripheral blood 1984 Jun Fc receptor expression by enriched monocytes from rheumatoid arthritis (RA) patients and age and sex matched controls (healthy subjects) was compared by measuring the uptake of IgG on monocytes in a competitive radioassay. The association constant (Ka) between IgG and the monocytes and the number of Fc binding sites per cell was calculated from Scatchard plots of 4 degrees C binding data. RA monocytes had increased expression of Fc receptors as compared with those of controls. This increase was particularly pronounced in those RA patients affected by extra-articular disease. There were significant correlations between the numbers of Fc receptors on monocytes and both C1q binding and anticomplementary activity but none between monocyte Fc receptor numbers and serum rheumatoid factors (IgG and IgM). It is considered that monocyte handling of circulating immune complexes is unimpaired in RA and that monocytes make an adaptive response to increased levels of immune complexes.
6325342 Rheumatoid synovial cell hormone responses modulated by cell-cell interactions. 1984 Mar Cellular interactions within the rheumatoid synovium are likely to be responsible for the destructive properties of this tissue. The responses to hormones which regulate connective tissue metabolism may also be influenced by these cell-cell interactions. To determine the effect of cellular interactions on responses to hormones, human peripheral blood mononuclear cells were cocultured with adherent rheumatoid synovial cells. Coculture resulted in a decrease in response to prostaglandin E2 as assessed by a reduction in the magnitude of the acute prostaglandin-induced cyclic AMP response. In contrast, coculture resulted in an increase in the magnitude of the acute parathyroid hormone-induced cyclic AMP response. The decrease in response to prostaglandin was reversed by the presence of indomethacin during the preincubation, whereas indomethacin had no effect on the cyclic AMP response to parathyroid hormone. Increases in endogenous synovial cell prostaglandin production (stimulated by soluble factors released by the mononuclear cells) accounted for the subsequent decrease in the response to exogenous prostaglandin. The increase in cyclic AMP response to parathyroid hormone could not be explained by a soluble factor and was independent of ambient prostaglandin levels.
6368088 An immunoelectron-microscopic study of the immunoglobulin-synthesizing cells of the rheuma 1984 May Immunoglobulin (Ig)-synthesizing cells were examined in the transitional areas of rheumatoid synovial membrane infiltrates, which are rich in lymphocytes undergoing blastic transformation, by an electron-microscopic immunoperoxidase-labeling technique. Peroxidase reaction products, indicating the presence of Ig, were initially observed in the perinuclear cisternae of lymphoblasts. These products were subsequently observed in the rough endoplasmic reticulum in parallel to cellular maturation. In highly differentiated plasma cells Ig was rarely seen in the endoplasmic reticulum. Blastic lymphocytes containing Ig in transitional areas were in close association with macrophages, indicating that the transitional area is a major site of immunologic induction of Ig synthesis in rheumatoid synovial membrane.
4338011 Virus antibody levels in systemic lupus erythematosus. 1972 May Antibody titers to a group of viral antigens have been determined in sera from patients with systemic lupus erythematosus (SLE), control groups with inflammatory diseases and normals. Mean titers in SLE sera for all viruses tested were significantly greater than in four control groups, but not greater than in active tuberculosis, both by the complement‐fixation (CF) and hemagglutination‐inhibition (HI) methods. By the CF method, only measles virus showed significantly higher titers in SLE than in all control groups; by the HI method, measles antibody titers were higher in SLE than in all groups but tuberculosis. There was no correlation between antibody titers and gammaglobulin levels. The results indicated a moderate though variable overall hypereactivity in SLE to the viral antigens tested.
341276 [Treatment of rheumatic polyarthritis with levamisole in 26 patients]. 1977 Nov Twenty-six patients with rheumatic polyarthritis (serologically positive) were treated with levamisole at a daily dosage of 150 mg. Treatment was continuous for 3 months and 2 days weekly afterwards. Although improvement may appear from the 1st month onwards, it is more frequent between the 1st and 3rd month (13 good or very good results among the 16 patients still treated) and may even improve afterwards (11 good or very good results among the 11 patients still treated in the 6th month). However, the value of levamisole, which appears to be an active drug against rheumatic polyarthritis, is limited by the frequency of side-effects. In 17 cases the trial had to be discontinued for this reason. The most serious side-effects were of haematological nature (2 leukopenias, 1 thrombocytopenia), but in these patients agranulocytosis was not found.
6737380 Arthritis and autoimmune pancytopenia. 1984 Jun We report a patient who developed arthritis and pancytopenia without an underlying systemic disease. Autoantibodies to all lines were demonstrated using an 125I-anti human IgG assay. Elution studies documented cross reactivity of an antibody between erythrocytes and platelets, a pathogenetic variation not previously reported.
3161703 Diflunisal ('Dolobid') once-a-day in the treatment of rheumatoid arthritis. 1985 A 4-week, double-blind, controlled multi-centre study was carried out in 235 patients with active rheumatoid arthritis to compare the efficacy and tolerance of 500 mg or 1000 mg diflunisal per day administered once daily, in the evening, or in divided, twice daily dosage. The results showed that diflunisal given once daily was at least as effective as diflunisal given twice daily. Day pain, morning stiffness, average grip strength and erythrocyte sedimentation rate improved similarly in both groups. Significant differences favouring the once-daily regimen were observed for improvement in night pain, Ritchie index and overall assessments by patient and investigator. Adverse experiences were slightly more common in patients taking diflunisal once daily (24% vs 19%) but this difference was not significant. It is concluded, therefore, that diflunisal once-a-day is an alternative regimen for the treatment of rheumatoid arthritis. It is at least as effective as the twice-daily regimen and may provide additional convenience to the patient and potential enhancement of compliance.
4042480 Infected total knee arthroplasties. 1985 Oct Thirty infected total knee arthroplasties were investigated in 29 patients over an average interval of 42 months. Eleven infections began in the immediate perioperative period. Six developed from postoperative wound-healing problems. The remainder were late infections. Staphylococcus was found in 16 infections, gram-negative agents in five, mixed organisms in five, and other gram-positives in four. Sixteen knees were arthrodesed, six knees were treated by retention of the components, and two above-knee amputations and one resection arthroplasty were performed. Five patients had two-stage revisions to new components. Evidence of persistent infection was present in three arthrodeses, two retained arthroplasties, and one knee that was revised. Perioperative infections were associated with staphylococcal organisms and responded less favorably to conservative treatment. The failure of primary wound healing demands immediate measures to obtain skin coverage. Retention of the arthroplasty components is possible only in selected patients.
6712422 Posterior approach for total hip arthroplasty. A study of postoperative course, early resu 1984 We report a consecutive series of 131 total hip arthroplasties using a prosthesis of Brunswik type and a posterior approach to the hip. Special attention is paid to technical details, postoperative course and early complications. The results are compared with those in published studies in which the lateral transtrochanteric approach has been used. Total hip replacement was performed by a team of four persons. This led to a marked decrease in the average operating time (60 minutes). The amount of blood transfused during and after the operation averaged 761 g. The postoperative course was complicated by one wound infection (0.8%). The immediate results regarding pain and walking capacity were good in 83% of the cases. The use of the posterior approach and a highly trained operating team reduced the time required for the operation, the blood loss and the frequency of postoperative complications, and caused less morbidity in the arthritic patients.
437909 Nephelometric detection of soluble immune complexes: methodology and clinical applications 1979 We have developed a method for the detection of immune complexes by laser nephelometry which is simple, reproducible, suitable for automation, and generally adaptable for diagnostic testing. Light dispersion by antigen-antibody complexes in the test samples is measured after addition of polymeric buffer, which enhances the aggregation of complexes but does not significantly affect unbound immunoglobulins. The method was used to measure immune complexes formed in vitro by incubation of tetanus toxoid with serum from a rabbit previously hyperimmunized with the same antigen, and to compare the levels of immune complexes in human sera obtained from normal adults and from 37 patients with collagen vascular diseases or endocarditis. When precautions were taken to avoid interference produced by the presence of lipoproteins or by freezing of the samples, the results obtained with human sera were consistent with those expected for normal controls and for patients with conditions thought to be associated with the presence of soluble immune complexes.
303188 Butazolidin suppository medication in rheumatism; a clinical study in general practice. 1977 One hundred and seventeen patients with various rheumatic conditions were admitted by eighteen general practitions to a multicentre open clinical trial of the acceptability, effectiveness and tolerability of Butazolidin Suppositories. Dosage was one or two suppositories (= 250 mg or 500 mg phenylbutazone) per day for up to eight weeks. Of the 117 patients entered onto the register for the study, 10 patients refused suppository medication and 8 had local conditions contra-indicating their use. Of the 99 patients starting the trial proper, half had excellent symptomatic relief and tolerance. Sixteen patients discontinued because of poor response. The remainder (34) whilst having significant improvement as shown by mean symptom scores, discontinued treatment. The majority who discontinued did so because of minor local discomfort or minor gastric symptoms, suggesting that acceptability of medication was at least as important as intolerance. No patient had a serious or persistent adverse effect. Comparison with previous studies suggests that gastro-intestinal tolerance to phenylbutazone is improved when it is administered by suppository.
4131162 Enhancement of human lymphocyte transformation by aggregated human gamma globulin. 1974 Apr The effect of heat-aggregated human gamma globulin (aggFII) on the induction of in vitro lymphocyte transformation, measured by the uptake of tritiated thymidine into newly synthesized DNA, was studied with peripheral blood lymphocytes derived from 12 patients with rheumatoid arthritis (RA), six with ankylosing spondylitis (AS), two with systemic lupus erythematosus (SLE), and seven normal subjects. It was found that 200 mug aggFII induced significant transformation of the lymphocytes of eight patients with RA, five with AS, one with SLE, and one normal subject. Neither deaggregated FII nor heat-aggregated human serum albumin induced significant transformation of the lymphocytes of any subject tested. A source of complement appeared necessary to support aggFII-induced blastogenesis, since enhanced transformation occurred only in the presence of fresh plasma. Heat-inactivated plasma and fetal calf serum (FCS), and FCS devoid of hemolytic complement, failed to support enhanced blastogenesis in the presence of aggFII. Since substrates similar to those employed in these studies are present in vivo in the rheumatoid joint, it is suggested that aggFII may enhance intra-articular lymphocyte transformation in subjects with RA.
132693 Gastrointestinal blood loss on phenylbutazone and feprazone. 1976 May Feprazone, a new anti-inflammatory drug, is a useful antirheumatic preparation which causes little gastrointestinal upset. This short cross-over study shows no significant gastrointestinal blood loss with either feprazone or phenylbutazone by the red-cell chromium-51 labelling method.
89333 Antithyroid-antibody activity in the snyovial fluid of patients with various arthritides. 1979 Aug 4 Microsomal and thyroglobulin autoantibody activity has been detected in synovial fluid from 34 of 50 patients with various arthritides (rheumatoid arthritis, ankylosing spondylitis, osteoarthrosis, and gout). Serum from only 4 of these patients showed thyroid-autoantibody activity, and the serum titres were considerably lower than the synovial-fluid titres. This suggests that thyroid autoantibody is produced locally in the joints of these patients.
6732373 Sustained improvement in drug documentation, compliance, and disease control. A four-year 1984 Jun We analyzed the effectiveness of an intervention program involving a clinical pharmacist and nurse clinician in improving drug documentation in medical records, patient compliance, and disease control. Medical records and prescription files were reviewed for patients in a rheumatology and renal clinic. Compliance was estimated by examining prescription refill patterns. Reviews were performed before intervention (control group), nine months after intervention (study group 1), and four years nine months after our intervention program began (study group 2). A six-month retrospective analysis at each review point demonstrated a significant improvement in drug documentation, compliance, and disease control--BP--for both study groups. A significant correlation was found between compliance (refill patterns) and BP control--correlation coefficient phi for the control group, 67 for study group 1, and .89 for study group 2. Cost reductions associated with our intervention program suggest that this program is cost-effective.
7342695 In vitro study of complement dependent active adherence on SLE and RA leukocytes. 1981 Immunological disorders may cause altered motility or attachment of leukocytes. Active adherence of buffy cost cells derived from normal subjects and with autoimmune diseases patients and complement dependency of this process was studied on glass surfaces. The adherence of leukocytes of both normal persons and of SLE and RA patients was decreased in the presence of normal human serum compared to serum-free medium. The effects of native and heat inactivated human sera on leukocytes of SLE and RA patients were compared. Adherence of SLE leukocytes was higher, whereas that of RA leukocytes was lower in unheated serum compared to heat inactivated human serum. Supernatants of leukocytes of SLE, RA patients and control subjects were harvested after incubation in serum-free medium. The C3 levels of supernatants were determined by rocket electrophoresis. Surface attached C3 was detected with immunofluorescence mainly on SLE leukocytes. The cellular effects of supernatants on control leukocytes, were consistent with the changes observed with leukocytes derived from SLE, RA or control patients.
6795630 Mechanism of stimulation of prostaglandin synthesis by a factor from rheumatoid synovial t 1981 Aug Rheumatoid synovial cell monolayers, with [1-14C]arachidonic acid ([1-14C]AA) incorporated into cell lipids, are stimulated by a factor (RSF) produced by explant cultures of rheumatoid synovial tissue to produce up to 50-fold increases in [1-14C]prostaglandin E2 and [1-14C]prostaglandin I2. In contrast, levels of free [1-14C]AA released from RSF-stimulated cells are generally lower than [1-14C]AA levels in cultures of untreated cells. These observations are inconsistent with a mechanism of prostaglandin stimulation consisting of an increase in phospholipase activity, because this mechanism would increase free AA levels as well as prostaglandins. A mechanism is proposed in which free AA is maintained at low steady-state levels by reacylation of free AA into phospholipids at a rate more rapid than its reaction with cyclooxygenase to form prostaglandins. In this mechanism, stimulation of the rate of the cyclooxygenase step by RSF accounts for increased prostaglandin synthesis as well as the decreased release of AA. On the basis of data previously reported by others, it is suggested that this mechanism may also be applicable to the stimulation of prostaglandin synthesis by several other agents. Preliminary characterization of the RSF indicates that it is a protein, and molecular seive chromatography indicates that its molecular weight is about 18,000. The production of RSF by rheumatoid synovial tissue is suppressed to undetectable levels by 1 microM dexamethasone.
7353130 Gastroscopic evaluation of anti-inflammatory agents. 1980 Jan 12 Gastroscopy was performed in 164 patients with rheumatoid arthritis (RA) and 85 with osteoarthritis (OA) to assess the effects of anti-inflammatory agents on the stomach. The main criterion for entry into the trial was the absence of active gastric lesions on pretreatment endoscopy. The patients were divided into groups to receive one of 12 anti-inflammatory drugs or combinations of these. Gastroscopy repeated at three to six and at 12 months disclosed gastric lesions in 78 cases (31%), patients in both disease categories being similarly affected. Lesions occurred in 41 of the 177 patients (23%) receiving a single drug and in 37 of the 72 (51%) receiving combined treatment. All the anti-inflammatory drugs caused gastric damage, the greatest offender being aspirin (13 out of 26 patients) and the least sulindac and diflunisal (two out of 19 (11%) and two out of 20 (10%) patients respectively). Corticosteroids caused gastric damage in only three out of 21 patients (14%), a lower incidence than expected.The indiscriminate prescribing of anti-inflammatory drugs to patients with OA is to be deplored. A lack of correlation between the patients' subjective complaints of gastric discomfort and the gastroscopic findings emphasises the unreliability of patients' complaints and the importance of gastroscopy in assessing gastric tolerance. It was not possible to assess minimal prescribing doses or minimum periods of treatment below which gastric damage may be guaranteed not to occur.
445955 Absorption and excretion of tolmetin in arthritic patients. 1979 Jul The absorption, kinetics, biotransformation, and excretion of tolmetin and its metabolites were studied in patients with rheumatoid arthritis (RA) to evaluate the effects of the disease on tolmetin disposition. Five RA patients were stabilized on tolmetin sodium (300 mg, 4 times daily for 14 days) before receiving a single oral solution dose of tolmetin-14C sodium (300 mg as the acid) on day 15. Tolmetin was rapidly and completely absorbed (peak time, 20 to 60 min) and eliminated rapidly from plasma with a biphasic decay curve (t1/2beta congruent to 2.1 hr). MCPA, the oxidative metabolite, appeared more slowly (peak time, 40 to 90 min) but was eliminated rapidly in a biphasic manner (t1/2beta congruent to 1.7 hr). The terminal elimination phases for both tolmetin and MCPA demonstrated a curvature which suggested possible nonlinearity in the kinetic disposition of the drug. There were no apparent effects of the disease on the kinetics of tolmetin or MCPA. Tolmetin, MCPA, and tolmetin glucuronide were recovered quantitatively in urine (0 to 72 hr) with most of the exretion occurring in the 0- to 24-hr period. A significant increase, relative to data on normal subjects, in the renal clearance of both tolmetin and MCPA was noted. Concomitant increase in the apparent volume of distribution secondary to reported decreases in the plasma protein binding of tolmetin appeared to be the reason for increased renal clearance of tolmetin.
4665356 Radioimmunoassay of the A prostaglandins. 1972 Jul