Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 881098 | A comparison of a new slow release aspirin ("slow aspirin") with plain aspirin in the trea | 1977 | In a single centre double-blind crossover study in eighteen patients with established rheumatoid disease, a new slow release aspirin ("slow aspirin") was compared with plain aspirin with respect to patient tolerability and gastric mucosal damage as observed at gastroscopy. "Slow aspirin" was significantly better than plain aspirin with regard to gastroscopic findings. With "slow aspirin", the gastric mucosal appearances were definitely better in eight patients, worse in two, and eight showed no difference. There was a high incidence of gastric ulceration or erosions in the groups as a whole (39%) but few patients complained of dyspepsia. There was little difference in the ability of both plain and "slow aspirin" in controlling the patients' joint symptoms. Evidence has been provided to suggest that "slow aspirin" is less injurious to the gastric mucosa. In an attempt to reduce gastric mucosal damage due to prolonged aspirin treatment it is therefore concluded that "slow aspirin" merits consideration in the management of chronic rheumatoid disease. | |
| 7416125 | Portal hypertension in Felty's syndrome. | 1980 Apr | Idiopathic portal hypertension, usually with esophageal varices, minimal but definitely abnormal liver tests and subtle or no changes on percutaneous liver biopsy has been reported in only a few patients. A case associated with Felty's syndrome in a 65-year old woman with a 44-year history of rheumatoid arthritis is reported in which the liver tests and liver biopsy were normal. Portal hypertension, varices and a patent portal venous system were documented. No surgical procedure was undertaken and she has done well in the 18 months since these studies were performed. A conservative approach is probably warranted in such cases. | |
| 795579 | In vitro effect of thymosin on T-lymphocyte rosette formation in rheumatic diseases. | 1976 Dec | The in vitro effect of calf thymosin fraction 5 on T-rosette forming cells (E-RFC) was studied in Sjögren's syndrome (SS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). The baseline percent E-RFC in sixteen normal controls was67-2 +/- 6-9. E-RFC was significantly decreased in SLE (42-6 +/- 17-0, P less than 0-0001) and SS (51-8 +/- 16-9, P less than 0-002) but not in RA (59-7 +/- 14-1). Ten of twenty-five SS patients and two of eleven RA patients had less than 50% E-RFC, and all showed a significant increase after incubation with thymosin (+ 16-5 +/- 6-5%, P less than 0-0001, and + 11 +/- 4-9%, P less than 0-001, respectively). Eleven of sixteen SLE patients had less than 50% E-RFC. Their response to thymosin was less dramatic but still statistically significant (+ 5-3 +/- 6-0%, P = 0-03). There was no response to thymosin in control subjects or in patients with baseline E-RFC greater than 50%. No increase in E-RFC was seen after incubation with calf spleen fraction 5 or known stimulators of cyclic-AMP. Sera from four active SLE patients, as well as the supernatant obtained from overnight culture of the lymphocytes from one SLE patients, were able to block T-rosette formation by normal lymphocytes, even after exposure to thymosin. Two 'blocking' sera were fractionated by sucrose density gradient ultracentrifucation. In one, the blocking capacity was found to reside in the 19S region containing IgM. In the second, the blocking capacity was in the 7S region containing IgG. Four 'blocking' lupus sera were depleted of IgG or IgM by immunoabsorption with goat anti-human IgG or goat anti-human IgM sepharose 4B. The blocking ability in three sera was partially decreased by depletion of either IgG or IgM, and in a fourth, only by removing IgG. The percent of lymphocytes staining with fluorescein labelled goat anti-human immunoglobulin antisera was increased in SLE patients (35-9 +/- 20-2 vs 21-7 +/- 5-9 in controls, P = 0-02). After overnight culture, the percent of staining cells decreased to normal values. These results suggest that thymosin can stimulate the differentiation of T-lymphocytes in patients with SS, SLE, and RA when the baseline E-RFC is decreased. Furthermore, the decreased percent E-RFC in SLE is probably due to cell-bound anti-lymphocyte antibodies that block sheep erythrocyte receptors on the T-cell and, possibly, thymosin receptors on undifferentiated lymphocytes. | |
| 6301658 | Whole body and regional retention of 99mTc-labeled pyrophosphate at 24 hours: physiologica | 1983 | The retention of 99mTc-labeled pyrophosphate (PPi) at 24 h was measured in 235 patients, 119 of whom had a normal bone metabolism. The mean retention in the group of normal subjects is 52% of the injected dose. Reproducibility of the measurement in a given person is 5.5% coefficient of variation (CV). The value depends strongly on sex (higher in males) and age (higher with increasing age, especially in cortical bone). Retention increases slowly with the decrease in glomerular filtration rate (GFR) between 50 and 120 ml/min; it rises very rapidly with values below 50 ml/min. The slowing down of the GFR with age does not account for the increase in PPi retention with age. When expressed as a percentage of the expected value for sex and age, retention is frequently low in osteoporosis (P less than .001), more so when urinary hydroxyproline is low; it is normal or high in osteomalacia, and in some cases rises after vitamin D treatment is started; it is high in hyperparathyroidism (P less than .01). The PPi retention is correlated with bone calcium accretion rate, alkaline phosphatase level, and above all, the urinary hydroxyproline level. The lower the bone mineralization (Ca/hydroxyproline ratio in biopsy), the higher the retention value. We conclude that the PPi retention is an index of bone metabolism when GFR is higher than 50 ml/min. It allows for classification of metabolic bone diseases according to the bone turnover rate. It has the advantage over the usual biologic examinations in that it affords better observation of highly localized bone disorders and can be used in combination with a morphologic record, the bone scintigraphy. | |
| 3876289 | Early rheumatoid-like synovial lesions in rabbits drinking cow's milk. I. Joint pathology. | 1985 | Rheumatoid-like lesions developed in 9 of 25 (36%) Old English rabbits drinking cow's milk for 12 weeks. The incidence of lesions in male and female animals was similar. The majority of rabbits drinking cow's milk developed increased numbers of nucleated cells and raised percentages of T lymphocytes in their synovial fluids, compared to control rabbits. The cell counts and T cell percentages correlated with the severity of the histological lesions. No evidence of glomerulonephritis was observed in any of the experimental animals. | |
| 1085095 | Adjuvant-induced arthritis in four inbred strains of rats. An in vitro study of peripheral | 1976 Feb | The lymphoblastic response (LTT) to non-specific mitogens (PHA, PWM and ConA) of peripheral lymphocytes was investigated at days 0, 7, 14, 21 and 28 after adjuvant injection in four strains of inbred rats: Wistar (WAG), Long Evans (LE), Lewis (LEW) and Brown Norway (BN). LTT was assessed by using 18 hours H3 TdR incorporation in 5 days cultures of whole blood (micromethod). The statistical treatment of data, using principal components multifactorial analysis and analysis of variance showed a striking difference between strains. In control animals the responses to PHA and PWM were correlated and were higher in LE and WAG than in LEW and BN (BN=LEW less than LE=WAG). The response to ConA was independent of that to the other mitogens. It was generally low, but significantly higher in LEW and BN than in WAG and LE. In adjuvant-injected animals the responses to PHA and PWM were still correlated, but modified compared to control: in LE and LEW, but not in WAG and BN, a marked decrease of the response was found, reaching a minimum value within days 7 and 14. In the same time the response to ConA increased in the four strains, later in LE than in the others. However the intensity of the ConA response varied from one strain to another: it was constantly low in LE and WAG compared to LEW and BN. So the most striking modification of LTT were observed in LE and LEW, which both developed the most severe arthritis. However these different behaviours after adjuvant injection were not explained by the initial level of LTT to the different mitogens. These data suggest that the development of intense arthritis is associated with the proliferation and the release into the blood stream of a lymphocyte subpopulation, which exhibits a low response to PHA and PWM and a high response to ConA. These LTT modifications are not paralleled by quantitative variations of B-cells assessed by surface Ig immunofluorescent staining and EAC rosetting. | |
| 7380852 | Results with the constrained total knee prosthesis in treating severely disabled patients | 1980 | Fifty-fix constrained total knee replacements (forty Guepar and sixteen Herbert prostheses) were performed in forty-nine severely disabled arthritic patients and they were followed for two to four years. Seventeen of these knees were operated on to salvage a failed prosthesis. Good relief of pain was achieved in 64 per cent of the knees but there was less improvement in walking and function. The over-all range of motion increased because of a reduction in preoperative flexion contractures. The results in the salvage group were less successful than in those patients who underwent a primary operation. Between six months and one year postoperatively, pain had developed in 17 per cent of the fifty-six knees, 9 per cent had walking difficulties, and 7 per cent lost function. Patellofemoral pain accounted for the unfavorable pain ratings in over half of the knees. Zonal roentgenographic analysis of each knee indicated high incidences of radiolucent lines at the cement-bone interface (75 per cent), cement-metal lucencies (68 per cent), and cement deficiencies (73 per cent). Forty-three per cent of the knees showed excessive posterior placement of the prosthesis of more than five millimeters, resulting in flexion contractures of as much as 5 degrees. Complications requiring reoperation developed in nine knees (16 per cent). There was one case of loosening and three knees had deep infections. Chronic postoperative effusions were present in 48 per cent of the knees. The use of either a cemented metal-on-metal hinged knee replacement or a metal-on-polyethylene hinge type of prosthesis was found to result in a relatively high incidence of failures and complications, and did not solve the problem of treating patients with a failed knee prosthesis. | |
| 6946553 | Clinical effects of indomethacin and additive clinical effect of indomethacin during salic | 1981 | Studies on the therapeutic effect of nonsteroidal anti-inflammatory agents in relation to doses or plasma concentrations have been relatively rare. We have investigated the clinical effects of indomethacin in daily doses of 45, 75 and 105 mg compared with placebo. The treatments were given double blind in two-week periods to eight rheumatic patients. There was a statistically significant therapeutic effect on parameters related to pain but no effect was detected on the activity of the disease by technetium scintigraphy. There was no clear association between dose or plasma concentration of indomethacin and therapeutic response in the actual patients with the dose range used. In a subsequent study ASA was given double blind in daily doses of 2 and 4.5 g in two three-week periods to twelve rheumatic patients. Placebo and indomethacin were given as suppositories at night and the clinical effect was evaluated by articular index and subjects rating of morning stiffness and pain. Prostaglandin release from platelets was assessed by a RIA method. It was found that both doses of ASA suppressed the PGF2alpha release totally. Indomethacin had a significant additive effect during 2 g ASA therapy as estimated by articular index and subjective ratings of pain and morning stiffness. On the 4.5 g ASA dose there was a significant improvement only for articular index. Thus the release of PGF2alpha cannot be used as a measure of antirheumatic effect and the clinical practice to combine these drugs seems justified. As the dose of ASA was increased from 2 to 4.5 g daily the total salicylate concentration increased up to 5 times. The unbound and pharmacologically active concentration increased up to 24 times. This disproportionality reflects the combined effect of capacity limited metabolism and capacity limited protein binding of salicylate. | |
| 6616954 | Evidence for a disease specific antigen in circulating immune complexes in ankylosing spon | 1983 Sep | The presence of circulating immune complexes (CIC) has been documented in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and ankylosing spondylitis (AS) by various investigators. It has been suggested that these may be used as probes to identify antigens playing a role in these pathological processes. Using a solid-phase cross-reaction assay to establish if these complexes reacted with each other in specific disease groups, it was found that polyethylene glycol (PEG) precipitates of six AS patients cross reacted in 29 of 36 tests, but reacted with SLE and RA PEG precipitates in only two of 24 tests in each case. SLE PEG precipitates cross-reacted in four of 14 tests and reacted with none of the six AS and four RA precipitates. Similarly, RA PEG precipitates did not cross-react (none of 16 tests), nor did they react with AS (none of 24 or SLE precipitates (none of 16). Similar results were observed when IgG, obtained after acid dissociation on sucrose density gradients of CIC isolated by PEG precipitation and staphylococcal protein A chromatography, was used as the solid phase component. F (ab')2 fragments with similar antibody specificity were obtained by pepsin digestion of isolated CIC from three of six AS patients. These bound radiolabelled AS PEG precipitates (2.02-2.40%) significantly more than SLE (0.22-0.28%) or RA (0.29-0.35%) precipitates. These studies demonstrate the feasibility of obtaining F (ab')2 fragments with antibody activity from isolated CIC and the presence of a disease specific antibody specificity in AS CIC. The nature of the antigen involved remains to be elucidated. Such a cross-reactive antibody specificity was not found in RA nor SLE CIC. | |
| 389405 | Post-therapeutic acute leukemia. | 1979 Dec | This study reports 35 cases of posttherapeutic acute leukemia and reviews the literature on this subject. These AL's are characterized by a high incidence of anemia, in particular refractory anemia, preceding the hematological disorder by several months, by the frequent finding of myelofibrosis, by the essentially granulocytic nature of the AL, and by the low rate of remission and the, in general, extremely short sruvival of a few months. These leukemias may develop following continuous chemotherapy with an alkylating agent, radiotherapy of various extent, or most commonly following intensive treatment with extensive irradiation and polychemotherapy as in the management of Hodgkin's disease. In view of these therapeutic hazards, the present objectives are the modification of alkylating agent therapy by the use of other drugs and sequential administration, and a reduction in the dose and field of irradiation and the duration of polychemotherapy, as in Hodgkin's disease; all present protocols are orientated in this direction. | |
| 281638 | Indomethacin-associated peptic ulceration. | 1978 Dec 13 | A review has been made of the hospital case notes of 32 patients with indomethacin-associated peptic ulceration seen over a four year period in Dunedin. Ulceration attributed to indomethacin therapy was found to particularly involve elderly women, in contrast to a predominance of males and a younger mean age at diagnosis in non-drug associated ulceration seen over the same period. The indomethacin-associated ulcer patients were more frequently complicated by haematemesis or melaena (two-thirds of cases compared to one-quarter for the group not on drugs) and relative hypochlorhydria was frequently noted at the time of gastroscopy in this group as compared to the other cases. It is suggested that patients warranting prolonged treatment with indomethacin require regular reassessment for any evidence of dyspepsia or anaemia, and that barium meal or gastroscopy are indicated for the presence of even mild abnormality of these types. | |
| 1243806 | [The effect of so-called basic therapeutics and symptomatically effective antirheumatic dr | 1975 | Investigation of DNA-synthesis and DNA-repair are important for evaluating mutagenic effects of drugs. Among the tested non steroidal antirheumatic drugs metiacinic acid, ketoprofene, and azapropazone do not show any effect on these mechanisms. Tolmetin and indometacine, however, inhibit DNA-synthesis only, whereas naproxene, oxyphenylbutazone, and flufenamic acid inhibit both DNA synthesis and repair. Gold does not influence DNA synthesis or repair, D-penicillamine inhibits DNA-synthesis only. However, Chloroquine and metabolised cyclophosphamide respecitvely impair both DNA-synthesis and repair. This effect may be also caused by azathioprine in high dosage. Application of two repair- inhibitors or of one DNA-repair-inhibitor and one directly mutagenic acting drug, e.g. cyclophosphamide, should therefore be avoided. | |
| 6217535 | Characterisation of blood and synovial fluid lymphocytes from patients with rheumatoid art | 1982 | Mononuclear cell preparations from peripheral blood (PBL) and synovial fluid (SFL) of 27 Patients with rheumatoid diseases (15 patients with definite rheumatoid arthritis (RA), 10 with other inflammatory joint diseases (OJD), 1 with sarcoid arthritis (SA) and 1 with traumatic arthritis (TA) were examined for lymphocyte subpopulations determined by monoclonal antibodies of the OKT series and by the dot-like, acid alpha-naphthyl esterase staining (ANAE) activity. In patients with classic, active RA, blood T cells carrying the OKT8+ (suppressor/killer) phenotype were significantly reduced leading to an elevated OKT4/OKT8 ratio of 4.1 +/- 0.4 compared with 2.1 +/- 0.1 in healthy controls. In 10 patients with OJD this diminution of OKT8+ cells in peripheral blood was less pronounced or absent. As regards SFL subpopulations, patients with RA and OJD exhibited a similar distribution pattern with an elevation of OKT8+, Ia+ and ANAE negative cells and a similar OKT4/OKT8 ratio of 1.5 +/- 0.3 and 1.6 +/- 0.4, respectively. Similar results were also obtained in the only patient with TA, whereas the patient with SA and one RA patient with relapse after surgical synovectomy exhibited high OKT4/OKT8 ratios, both in synovial fluid and peripheral blood. Neither the OKT markers nor the dot-like ANAE staining pattern were significantly correlated to parameters of systemic or local disease activity as estimated by erythrocyte sedimentation rate and a local disease activity index. | |
| 170094 | Purification of rheumatoid synovial collagenase and its action on soluble and insoluble co | 1975 Jun | 1. The neutral collagenase released into the culture medium by explants of ehrumatoid synovial tissue has been purified by ultrafiltration and column chromatography, utilising Sephadex G-200, Sephadex QAE A-50 and Sephadex G-100 superfine. 2. The final collagenase preparation had a specific activity against thermally reconstituted collagen fibrils of 312 mug collagen degraded min-1 mg enzyme protein-1, representing more than a 1000-fold increase over that of the active culture medium. 3. Electrophoresis in polyacrylamide disc-gels with and without sodium dodecyl sulphate showed the enzyme to migrate as a single protein band. Elution experiments from polyacrylamide gels and chromatography columns have provided no evidence for the existence of more than one collagenase. 4. The molecular weight of the enzyme, as determined by dodecylsulphate-polyacrylamide gel electrophoresis, was 33000. 5. Data obtained from sutdies with the ion-exchange resin and from gel electrophoresis in acid and alkaline buffer systems suggested a basically charged enzyme. 6. It did not hydrolyse the synthetic collagen peptide Pz-Pro-Leu-Gly-Pro-D-Arg and non-specific protease activity was absent. 7. The collagenase attacked undenatured collagen in solution at 25 degrees C resulting in a 58% loss of viscosity and producing the two characteristic products TCA(3/4) and TCB(1/4). 8. At 37 degrees C and pH 8.0 both reconstituted collagen fibrils and gelatin were degraded to peptides of less than 10000 molecular weight. 9. As judged by the release of soluble hydroxyproline peptides and electron microscopic appearances the enzyme degraded human insoluble collagens derived from tendon and soft juxta-articular tissues although rates of attack were less than with reconstituted fibrils. 10. The data suggests that pure rheumatoid synovial collagenase at 37 degrees C and neutral pH can degrade gelatin, reconstituted fibrils and insoluble collagens without the intervention of non-specific proteases. 11. The different susceptibilities of various collagenous substrates to collagenase attack are discussed. | |
| 161058 | A review of spontaneously reported adverse drug reactions with diclofenac sodium (Voltarol | 1979 | The author reviews the worldwide picture of adverse reactions reported with diclofenac during the four-year period ending in December 1977, at which point he estimates that some ten million patients had received treatment with the drug. A total of 447 unwanted effects were reported in 194 patients, the most frequently reported side-effects being gastrointestinal in nature, followed by dermatological and central nervous system effects. Thirteen cases of liver function abnormality were reported, although there was reason to believe that 11 of these were not ascribable to diclofenac. Twenty haematological effects were reported, including two cases of agranulocytosis and two cases of fatal aplastic anaemia; one patient in each of these groups was taking concomitant pyrazolone compounds. Evaluation of adverse reactions reported with diclofenac suggest a profile in which gastrointestinal side-effects predominate; however, the risk of serious side-effects of this nature is slight, and the impression of good tolerability which emerges from this review is confirmed by the findings of comparative clinical trials. | |
| 7001487 | Double-blind clinical trial of protacine versus oxyphenbutazone in rheumatic disorders. | 1980 | A double-blind trial wa carried out in 30 in-patients, mainly with rheumatoid disorders, to compare the efficacy and tolerance of protacine with those of oxyphenbutazone. Patients were given oral doses either of 150 mg protacine or 200 mg oxyphenbutazone 3-times daily for 21 days. Clinical symptoms were assessed by semiquantitative scoring at 5-days' intervals. The same was done for side-effects. Protacine globally reduced the symptom scores by 55% and oxyphenbutazone by 34% (p < 0.001). Frequency and severity of side-effects were significantly less and less severe during protacine than during oxyphenbutazone treatment (p < 0.01). Physiological parameters did not vary during either treatment. Good efficacy, good tolerance and a convenient dose schedule suggest that protacine may well be suited also for long-term treatment. | |
| 4416752 | Tuberculosis as a continuing cause of renal amyloidosis. | 1974 Sep 28 | In 40 patients with renal amyloidosis seen in a ten-year period tuberculosis was the major preceding disease in 20, though it was active in only two at diagnosis. Most patients presented with renal failure, and only two survived for five years. This experience (at least, in the west of Scotland) conflicts with the generally accepted view that rheumatoid arthritis is the commonest cause of renal amyloidosis. | |
| 7281690 | [Serum hydroxyproline parameter of collagen metabolism (author's transl)]. | 1981 Mar 6 | The serum hydroxyproline level enables a clinical assessment to be made of bone metabolism. A clinical-chemical method, which is described in detail, was applied in 50 control persons as well as in 76 patients with diseases of bones and/or joints. This method, which is a modification of the standard ion-exchange method of Goverde and Veenkamp for the determination of free hydroxyproline in serum, is readily applicable to mass routine laboratory usage and may be repeated ad libitum, thereby facilitating control follow-up of therapeutic response. The mean value of serum free hydroxyproline in the normal control group was 11.9 mu mol/1 (range: 6.86 to 16 mu mol/1), i.e. 1.56 mg/1 (range: 0.9 to 21 mg/1). The upper limit of normal values was calculated to be 15.5 mu mol/1 (2.0 mg/1), allowing a clear-cut differentiation from pathologically raised levels above this value. | |
| 6460402 | [Reactive SH-groups in clinical practice. Methodological notes]. | 1981 | Experimental investigations have been performed in order to point out the extrinsic factors influencing the results of -SH group determination. It has been observed that the anticoagulants normally used to obtain plasma samples, influence the serum -SH groups; in particular, heparin increases and citrate depresses the levels; the most reproducible data were obtained in serum samples. In addition it has been shown that the exposure to light for 6-8 hours lowered the serum -SH groups, whereas darkness prevented these changes. Serum-SH groups were not influenced by the administration of non steroidal anti-inflammatory agents, whereas D-Penicillamine and Tiopronin induced an increase of the -SH levels, ranging between 15-20%. The levels returned to the basal values within two hours from the drug intake. Following the methodological criteria here described it is possible to obtain a good information about the -SH group reserve, which free radicals generated in several diseases could consume. The practical usefulness of the serum -SH group determination in oxidative-peroxidative processes in discussed. | |
| 796535 | [Comparative pathology of the microcirculatory bed]. | 1976 Nov | This paper presents an analysis of publications, mostly by Soviet authores, on clinical studies and morphological examinations of the microcirculatory bed in different pathology. It is concluded that the microcirculatory bed should be regarded as an integral system responding to the pathological effects by a local and general reaction of its structural components and by changing the rheological properties of blood. Two types of changes develop in the microcirculatory system -- sterotyped ones, typical for extreme states (various kinds of shock, hypertensive crisis, stress situations), and those specific for certain diseases (diabetes melitus, essential hypertension, athersclerosis, collagenoses, etc.). In all the above diseases the pathological process affects the functional structures of microcirculation that undergo a rearrangement in accordance with the requirements of the body. In the initial period of the disease this re-arrangement is of a compensatory nature and passes ahead of the clinical manifestations. A comparison of the pictutrs obtained by biomicroscopy of the bulbconjunctiva of the eye and of other mucosae with film preparations of the serosae demonstrates their complete similarity. Therefore, the method of biomicroscopy of the eyeball and of the mucosae as a method reflecting the state of microcirculation in the body as a whole should become an integral part of the clinical examination of patients. |