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

ID PMID Title PublicationDate abstract
3941296 Removal of hyaluronic acid from the circulation in rheumatoid disease and primary biliary 1986 Jan Recent evidence from metabolic studies in animals and from measurement of plasma and serum hyaluronic acid (HA) levels in humans indicates that the liver is the organ mainly responsible for the clearance of circulating HA. The clearance of HA from the bloodstream was therefore studied with tritium-labeled material of high specific activity in patients with rheumatoid arthritis or primary biliary cirrhosis (PBC). In patients with rheumatoid arthritis, HA clearance was similar to that reported in normal subjects and approached the range of hepatic blood flow. HA metabolism was also rapid. In patients with PBC, clearance was inversely related to the preexisting plasma HA levels and severity of disease. Renal excretion of HA remained low despite the slower decay of plasma concentrations. Metabolic degradation was not significantly impaired. Most of the injected material was accounted for as tritiated water within 24 hours. Taken with data from other species and with the raised plasma HA levels observed in a variety of liver diseases, our findings indicate that the liver may also be the major site for the uptake of circulating HA in humans. High levels of plasma HA in the absence of hepatic dysfunction can be taken as evidence of an increased input from the tissues.
2159579 [Sequential Tc 99m pyrophosphate scintigraphy of the kidneys and joints in patients with r 1990 Apr The proposed method of sequential scintigraphy of the kidneys and joints in a single administration of 99mTc-pyrophosphate permits obtaining objective information on function and topography of the kidneys and pyodestructive processes in the joints. Dynamic scintigraphy helps to assess visually renal hemodynamics and the antomotopographic position of the kidney and to obtain exhaustive information on accumulative-evacuatory function of each kidney individually. Scintigraphy also helps to investigate all the joints and to detect pyoinflammatory changes in them. The proposed method considerably reduces the time of investigation and lessens radiation exposure of patients, permitting repeated investigations to assess and correct the treatment of patients with rheumatic arthritis.
1871516 [Role of collagen conformation in type II anticollagen immunity in rheumatoid polyarthriti 1991 Jan Type II anticollagen (CII) autoimmunity is a frequently reported, but non-specific, phenomenon in rheumatoid arthritis (RA). The authors show that in 88 sera samples from patients suffering from RA, the incidence of antibodies targeted against endogenous human CII was the same as that found for 149 control blood donors (14.8% versus 11.4%). However, a significant difference was found for the incidence of antibodies targeted against the alpha-chains of CII (26.1% versus 6.0%, p less than 0.001). As a result of investigating the specificity of the anti-CII antibodies in greater detail by means of an immunoprinting of the CII peptide fragments obtained after splitting the molecule by cyanogen bromide, the authors have demonstrated that the largest CII peptides (CB10 and CB11) were better recognized than the smaller peptides (CB8, CB9.7), with no significant difference between PR and control plasmas. Using competitive methods, evidence was obtained in support of heterogeneous recognition by the anti-CII antibodies: some recognize conformational determinants only, whereas others are targeted against the primary sequences of the alpha-1 (II) chain.
3811488 [Initial experiences with the cementless PM endoprosthesis]. 1986 Sep A follow up of 40 cementless fixed endoprostheses type PM showed good results, similar to cement fixed prostheses. In cementless fixation seem to be more early complications and less late complications, so these results are encouraging what concerns cementless fixation.
1659424 Increased proteolytic activity on the surface of monocytes from patients with rheumatoid a 1991 Nov Studies on the expression and localization of the urokinase receptor on peripheral blood monocytes of patients with rheumatoid arthritis (RA), patients with osteoarthritis, and healthy volunteers showed a significant increase in the total number of urokinase receptors on monocytes of patients with RA, compared with osteoarthritis patients or with healthy subjects. The increase in the total number of urokinase receptors in RA was due to an elevation in the number of endogenously occupied urokinase receptors. These data provide evidence that increased proteolytic activity might contribute to the pronounced degradation of cartilage and connective tissue in patients with RA.
3947145 Comparison of urinary glycosaminoglycan excretion in rheumatoid arthritis, osteoarthritis, 1986 Feb Urinary glycosaminoglycan (GAG) excretion was measured in 24 patients with active rheumatoid arthritis (RA) before and after treatment with conventional second-line agents. Urinary GAG excretion was also measured in normal controls, patients with osteoarthritis (OA), and patients with acute myocardial infarction (MI). Total GAG excretion was increased in the RA group and fell after second-line therapy (p less than 0.01). More low than high molecular weight GAG was excreted in the active RA group, and this pattern was reversed after treatment. Excretion of total, high and low molecular weight GAG in the OA group did not differ significantly from controls. Total GAG excretion was increased in the MI group when compared with controls (p less than 0.02) and consisted mainly of high molecular weight GAG. The serial measurement of urinary GAG provides a further index of disease activity and may help to monitor response to treatment.
2124096 Association of serum IgM kappa monoclonicity in patients with Sjögren's syndrome with an 1990 Nov Minor salivary gland biopsy specimens from 11 patients with primary Sjögren's syndrome with circulating monoclonal IgM kappa cryoglobulins, seven without cryoglobulins, and four patients with rheumatoid arthritis and Sjögren's syndrome (one with monoclonal and three with polyclonal cryoglobulins) were examined by the peroxidase antiperoxidase bridge technique, using antihuman kappa and lambda antibodies. In 6/11 patients with primary Sjögren's syndrome and in one patient with Sjögren's syndrome and rheumatoid arthritis with monoclonal cryoglobulins a predominance of plasma cells containing intracytoplasmic kappa light chains was found (kappa:lambda greater than 3:1). Two of those seven patients had immunohistological features of immunocytomas. In the other five patients with circulating monoclonal cryoglobulins the kappa:lambda ratio of positive cells did not exceed 3:1, while six out of seven patients without cryoglobulins and the patients with rheumatoid arthritis and Sjögren's syndrome with polyclonal cryoglobulins had almost equal numbers of kappa and lambda stained cells. One of seven patients with primary Sjögren's syndrome without cryoglobulins had an increased number of lambda light chain positive cells, indicating a non-secretory lambda monoclonal population. These findings suggest that the main area of B cell monoclonal expansion in primary Sjögren's syndrome may be the affected exocrine glands.
2807785 Renal transplantation in amyloid nephropathy. 1989 Renal transplantation was performed in 2 patients with end-stage renal disease due to AA-type amyloidosis. One patient with amyloidosis of rheumatoid arthritis (RA) origin died twelve months after renal transplantation in cardiogenic shock. AA-amyloid deposits were demonstrated in the graft even though there were excellent function and no proteinuria. The second patient with amyloid nephropathy due to familial Mediterranean fever (FMF) showed no impairment of graft function 24 months after transplantation. These 2 cases are compared to an additional 31 cases of renal transplantation for amyloid nephropathy described in the literature. Proteinuria was reported in 32.3% and amyloid was detected in the functioning graft in 41.4%. The function was excellent even when small amyloid deposits were present in the graft. Renal transplantation is indicated in cases of amyloid nephropathy of the AA-type, provided life threatening amyloid involvement of other organs is not present.
2735960 Methotrexate in rheumatoid arthritis. Toxic effects as the major factor in limiting long-t 1989 Jun In an effort to understand the prognostic features that may influence the probability of a patient's continuing to take methotrexate (MTX) over time, we studied 152 rheumatoid arthritis patients treated with MTX between 1981 and 1986. The overall probability of continuing to take MTX was 71.2% at 1 year, 55.5% at 3 years, 50% at 5 years, and 49% at 6 years. By univariate analysis, patients who started MTX therapy later in the study, American blacks, younger patients, those with less severe disease, and those with less frequent or less severe toxic events appeared to have a better probability of continuing the drug therapy. When these parameters were evaluated by multivariate analysis, only the time when MTX was started and the occurrence of toxic effects independently influenced the probability of continuing MTX. Thus, by current practice standards, toxic effects emerge as the main reason for MTX discontinuation.
2533393 [Immunomodulating basic therapy of rheumatoid arthritis using ciamexone]. 1989 Dec 9 Ciamexone, a 2-cyanoaziridine derivative, had been shown previously in animal studies to inhibit the proliferation of autoreactive lymphocytes dose dependently, without affecting the reaction against foreign antigens. To extend the experimental models of ciamexone's in vitro effects to the clinical level, we performed a pilot study to evaluate the clinical efficacy of ciamexone therapy. We further studied its influence on the systemic inflammatory activity and T-lymphocyte subsets in the peripheral blood of 10 patients with active rheumatoid arthritis (RA). Following 6 months' treatment with ciamexone all patients showed a significant decrease of both the clinical and biochemical scores. Concerning the T-lymphocyte subsets analysis, a relatively decreased rate of the activated T-lymphocytes was observed concurrently. Minor side effects included rash (n = 1), hepatotoxicity (n = 1) and diarrhea (n = 1). The study thus documents the clinical efficacy of ciamexone in patients with RA, but also indicates the agent's potential toxicity.
3175573 [Low-dose oral methotrexate in the treatment of rheumatoid polyarthritis]. 1988 Sep 10 28 patients with severe rheumatoid arthritis were treated with pulse weekly oral methotrexate over a mean follow-up of 24 months (6-36 months). Within one month the patients improved significantly by all clinical standards of efficacy and erythrocyte sedimentation rate. Maximum improvement tended to occur after 6 months' therapy and was maintained for up to 36 months in most patients. 11 patients discontinued treatment because of adverse effects. It is concluded that this trial confirms the efficacy of methotrexate in rheumatoid arthritis. Careful baseline and follow-up monitoring is recommended due to frequent adverse reactions.
3262460 Cytokines in synovial fluid. I. The presence of biologically active and immunoreactive IL- 1988 Jun Using a sensitive IL-1-dependent T cell clone we estimated interleukin 1 (IL-1)-like activity in a variety of synovial fluids (SF). Although we demonstrate that SF contains potent inhibitors of endogenous and exogenous IL-1 we were able to estimate that samples from rheumatoid arthritis, osteoarthritis and other arthritides contain the equivalent of tens or hundreds of picograms of IL-1 per millilitre, when compared to a standard IL-1 preparation. Although there was some correlation between these results and those obtained using a radio-immunoassay (RIA) for IL-1 beta, the RIA indicated that IL-1 was present in the nanogram range. The results suggest that the importance of inhibitors of IL-1 in SF merits particular attention and that it is also important to consider the bioactivity of cytokines which may be detected by physical methods.
2904761 Molecular genetic studies of rheumatoid arthritis. 1988 Dec 23 Bam HI DR-beta and DQ-beta restriction fragment length polymorphisms (RFLPs) were found with increased frequency in white persons with seropositive rheumatoid arthritis as compared with control subjects. DR-beta 4.8-, 5.2-, and 7.0-kilobase (kb) RFLPs were observed in 86.5 percent of rheumatoid arthritis patients and in 56 percent of control subjects (p = 0.001, relative risk [RR] = 5.0). The 6.0-kb RFLP was present in 79 percent of rheumatoid arthritis patients and 32 percent of control subjects (p = 0.0002, RR = 8.0). The 4.8-, 5.2-, and 7.0-kb RFLPs correlated with DR4, -7, -9, and -w53 phenotypes and the 6.0-kb RFLP correlated only with DR4. Thus, these RFLPs do not appear to be disease-specific. A DQ-beta 3.2-kb RFLP was found in 63.5 percent of rheumatoid arthritis patients and in 38.0 percent of control subjects (p = 0.01, RR = 2.8). This fragment was frequently found in persons expressing DR1 and DQw1 phenotypes. Probes consisting of the first exon of the DR-beta-I and DR-beta-IV genes, respectively, only hybridized with the 5.2- and 6.0-kb RFLPs. These data suggest that more than one gene within the major histocompatibility complex contributes to susceptibility to seropositive rheumatoid arthritis in white persons.
2016523 Differential synthesis of 5-lipoxygenase in peripheral blood and synovial fluid neutrophil 1991 Apr 15 In order to investigate 5-lipoxygenase enzyme regulation in neutrophils during an inflammatory reaction, we studied 5-lipoxygenase mRNA levels, as well as de novo enzyme synthesis, in resting and activated neutrophils isolated from normal individuals and patients with rheumatoid arthritis. The approach used was to analyze these activities in resting peripheral blood neutrophils of normal individuals on the one hand and in peripheral blood and matched synovial fluid neutrophils isolated from patients with rheumatoid arthritis on the other hand. Our first observation was that resting peripheral blood neutrophils of either normal individuals or patients show detectable levels of 5-lipoxygenase mRNA and are able to synthesize the enzyme de novo. Our second observation was that inflammatory activated neutrophils from synovial fluid reveal lower 5-lipoxygenase mRNA levels and enzyme synthesis than do the patient-matched peripheral blood cells. This is in spite of the fact that, for other proteins, synovial fluid neutrophils are equally or more active than their peripheral blood counterparts. We conclude that peripheral blood neutrophils are capable of synthesizing the enzyme, thus ensuring the turnover of the protein. Furthermore, complex regulatory mechanisms appear to take place in response to inflammation as it occurs in synovial fluids of patients with rheumatoid arthritis, leading to decreased mRNA levels and enzyme synthesis. Possible mechanisms of regulation are discussed and are presently under investigation.
2809229 An improved enzyme-linked immunosorbent assay of anti-collagen antibodies in human serum. 1989 Nov 13 An improved enzyme-linked immunosorbent assay (ELISA) for the determination of anti-collagen antibodies in human serum has been developed. The method is based on the use of serum samples diluted to 1/50 with heat-inactivated normal rabbit serum adjusted to pH 8.0 with solid Tris (0.05 M), NaCl (0.15 M) and 2 M HCl. The use of normal rabbit serum minimizes non-specific adsorption of immunoglobulin G onto the plastic surface of microtiter plate. The applicability of the method for the quantitation of anti-collagen antibodies in human serum is demonstrated with 290 specimens of sera from normal controls (194) and patients with rheumatoid arthritis (96).
3437420 Plasma glycosaminoglycans in systemic lupus erythematosus. 1987 Dec The glycosaminoglycans (GAG) of plasma were assayed for uronic acid content in 13 female patients with systemic lupus erythematosus (SLE) and in healthy controls and compared with earlier results obtained in patients with rheumatoid arthritis (RA). The GAG were fractionated into a high charge "free" fraction known to contain chondroitin sulfate (CS) as a major and heparan-sulphate (HS) as a minor GAG and a low charge "bound" fraction known to contain low sulphated CS as the only GAG. The concentration of the free GAG was significantly increased in SLE (p less than 0.01); this increase was mainly due to the high concentrations of free GAG in patients with active disease. These patients also had an increased concentration of "bound" GAG (p less than 0.05). However, the plasma GAG concentrations did not correlate with the erythrocyte sedimentation rate, the binding of native DNA or the C4 concentration. Plasma proteoglycans and/or GAG are known to modulate certain immune functions. Whether the increase in free GAG reported here is somehow associated with the disturbed immunoregulation in SLE remains speculative.
2577026 [Periosteal reaction in periarteritis nodosa in children]. 1989 Oct 21 Bone involvement has exceptionally been reported in children with periarteritis nodosa. A 5-year old girl was admitted to hospital for fever and arthralgias. Three months later, myalgias and painful subcutaneous nodules developed on the legs and ankles. Skin biopsy yielded a diagnosis of periarteritis nodosa. X-ray films revealed a bilateral periosteal reaction with images of laminae in the tibia and fibula. After a 4-year remission under corticosteroid therapy, the periosteal reaction persisted.
2053922 The clinical and health status of patients with recent-onset rheumatoid arthritis. 1991 Jun This study was designed to document the clinical and health status of patients with recent-onset rheumatoid arthritis (RA). Three groups were studied: 108 patients who had had RA for greater than 1 year (established RA group), 313 patients who had had RA for less than or equal to 1 year (recent-onset RA group), and 188 healthy friend of the patients with recent-onset RA (no RA group). Clinical status was measured using tender joint count, erythrocyte sedimentation rate, and overall physician assessment. Health status was measured using the physical, psychological, pain, and arthritis impact scores of the Arthritis Impact Measurement Scales. Scores on all clinical and health status measures indicated substantial disease effects in the group with recent-onset RA. For most of these measures, effect size analysis indicated that clinical and health status impacts in the recent-onset RA group were similar in magnitude to those found in the groups with more established disease, with scores in both groups being substantially different from those found in the no RA group. These results document the magnitude of the clinical and health status impacts in recent-onset RA. They lend support to recent arguments advocating aggressive therapy earlier in the course of this frequently disabling disease.
3775335 [Rheumatoid factors of immunoglobulin classes IgA, IgG and IgM: methods of determination a 1986 Sep 20 Routine laboratory tests (Rose-Waaler test, latex fixation test) for the detection of rheumatoid factor (RF) measure IgM RF by its ability to agglutinate sheep red blood cells or latex particles coated with IgG. Recently, solid-phase RIA and ELISA have been developed to detect RF of all major immunoglobulin classes in a sensitive and reproducible manner. In the literature the pathogenetic, diagnostic and prognostic significance of IgA, IgG and IgM RF is discussed. Using a micro-ELISA with human IgG-Fc-fragments as antigens, we have detected IgA RF and/or IgG RF not only in sera from seropositive rheumatoid arthritis (RA) (n = 48), but also in 13 of 22 sera from seronegative RA, which was statistically significant compared with a group of 50 normal controls. There was a good correlation between IgM RF in ELISA and Rose-Waaler titres for agglutinating RF (r = 0.70). No RF were found in patients with psoriatic arthritis (n = 16).
3211088 A question of value: measuring the impact of chronic disease. 1988 The indirect costs of illness--those resulting from lost functional capacity rather than from medical expenditures--have long been measured in quantitative economic terms. A recent survey of rheumatoid arthritics and osteoarthritics employs, however, an alternative method of estimation based on qualitative values. Both the persons with arthritis and the health controls indicated that maintaining social contacts and personal relationships, shopping, running errands, and doing chores for their family and themselves were much more important than work-related activities. Policy efforts should thus target disease interventions toward activity losses assigned the highest personal value rather than attempt to define the dollar value of these losses.