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

ID PMID Title PublicationDate abstract
3654709 Synovectomy of the rheumatoid knee using intra-articular injection of dysprosium-165-ferri 1987 Sep One hundred and eleven patients who had seropositive rheumatoid arthritis and persistent synovitis of the knee were treated with intra-articular injection of 270 millicuries of dysprosium-165 bound to ferric hydroxide macroaggregates. A two-year follow-up was available for fifty-nine of the treated knees. Thirty-nine had a good result; nine, a fair result; and eleven, a poor result. Of the twenty-five knees that had Stage-I radiographic changes, nineteen had a good result. Of the thirty-four knees that had Stage-II radiographic changes, twenty showed a good result. Systemic spread of the radioactivity from the injected joint was minimum. The mean whole-body dose was calculated to be 0.3 rad and that to the liver twenty-four hours after injection, 3.2 rads. The results indicated that dysprosium-165-ferric hydroxide macroaggregate is an effective agent for performing radiation synovectomy, particularly in knees that have Stage-I radiographic changes. Because of the minimum rate of systemic spread of the dysprosium-165, it offers a definite advantage over agents that previously have been used.
2208871 Animal models of chronic inflammatory arthritis. 1990 Oct The use of animals has been indispensable to the investigation of the etiology, pathophysiology, and treatment of juvenile arthritis. Because of ethical concerns about studying children, the difficulty of obtaining tissue, and the heterogeneous manifestations and protean course of chronic arthritis in childhood, the scope of potential research has been severely limited. This brief review summarizes a few of the animal models most commonly used in chronic inflammatory arthritis research: subcutaneous air pouch, antigen-induced (including arthritogenic infectious agent), and spontaneous models. In the spontaneous and antigen-induced animal models of arthritis, local and systemic immunoregulatory abnormalities clearly play a major role in the pathogenesis of arthritis. By elucidating the immune response to those antigens, as well as the role of genetics and environment, the pathogenesis of juvenile rheumatoid arthritis may be better understood. At the present time, however, the complexity of these models precludes more definitive interpretation and extrapolation to human diseases.
2031149 The presence of anti-protein A antibodies in patients with rheumatoid arthritis. 1991 May Sixteen patients with rheumatoid arthritis (RA) were examined for the presence of anti-protein A antibodies. The F(ab')2 preparations from five RA patients showed significant binding to IgG-free protein A on ELISA. The protein A binding was further examined by immunoblotting. The F(ab')2 preparations of high protein A-binding protein gave a specific reaction with IgG-free protein A on nitrocellulose paper. This demonstrates the presence of anti-protein A antibodies in patients with RA. Those RA patients with anti-protein A antibodies had more active disease as judged by the Lansbury's activity index. The level of serum rheumatoid factor (RAHA) was significantly higher in patients with anti-protein A antibodies than in those without anti-protein A antibodies.
3488089 The ninth complement component in rheumatoid arthritis, Behçet's disease and other rheuma 1986 Aug Using an immunoradiometric assay with two monoclonal antibodies plasma C9 levels were measured in 49 patients with rheumatoid arthritis, eight patients with Behçet's disease, six patients with ankylosing spondylitis, nine patients with psoriatic arthropathy, six patients with systemic lupus erythematosus, five patients with erosive osteoarthritis and four patients with acute gout. Plasma C9 levels were also followed sequentially in four patients with Behçet's disease to show fluctuation during disease activity. The upper limit of normal for plasma C9 was 90 mg/l, 2 standard deviations above the known mean value. Significantly raised levels were found in active rheumatoid arthritis (119.7 +/- 28.3), Behçet's disease (177.9 +/- 26.2) and ankylosing spondylitis (116.1 +/- 23.1). In Behçet's disease the raised C9 levels normalized during disease quiescence suggesting that C9 is a good monitor of disease activity. CRP and ESR values were also measured. In rheumatoid arthritis C9 was more consistently elevated in active disease than CRP or ESR. As there was no association between these measures on mathematical analysis it was concluded that plasma C9 is a better indicator of disease activity in rheumatoid arthritis.
1972633 Tolerability of enteric-coated sulphasalazine in rheumatoid arthritis: results of a co-ope 1990 Jun One thousand three hundred and eighty-two patients with rheumatoid arthritis requiring second-line therapy at 108 centres were entered into an open 6-months prospective tolerability study of enteric-coated sulphasalazine 2 g/day (Salazopyrin EN-tabs). Clinical and laboratory variables were measured, any adverse reactions and the reasons for withdrawal of medication were recorded. The outcome of therapy was known in 87.5% of patients entered of whom 65% continued with sulphasalazine beyond the 6-month study period. 3.2% withdrew for reasons unrelated to treatment, 5% for lack of effect and 26.8% due to an adverse event; gastrointestinal/central nervous 66.6%, rash 15.4%, haematological 5.1%, hepatic 4.7% and miscellaneous 8.1%. 1.2% of patients experienced potentially serious reactions: anaphylactic, haematological and hepatic. The majority of adverse events occurred early and were reversible upon cessation of medication. No clear relationship between withdrawal due to an adverse event attributed to sulphasalazine and the nature of the concomitant non-steroidal anti-inflammatory drug was identified.
3041245 Hepatotoxicity of methotrexate in rheumatic diseases. 1988 May Methotrexate-induced hepatotoxicity is well recognised in the treatment of leukaemia, psoriasis and rheumatoid arthritis. The pathological lesions are non-specific, consisting of fatty change, nuclear pleomorphism, hepatocyte necrosis, portal chronic inflammatory infiltrate, fibrosis and cirrhosis. The mechanism of liver injury is poorly understood; intracellular accumulation of methotrexate polyglutamate and consequent folate depletion are suspected to play a role. Early studies in psoriasis clearly established a relationship of the hepatic injury with the frequency of methotrexate administration. With weekly low dose therapy, however, consensus is lacking regarding the incidence of hepatotoxicity because studies have had disparate control groups, used variable dosage regimens and often failed to document pre-existing liver disease or categorised patients at risk, i.e. elderly patients, alcoholics and obese diabetics. Moreover, current methods of assessing the degree of hepatic injury are subjective, relying on interpretation by an experienced histopathologist. Preliminary evidence suggests less frequent and less severe hepatotoxicity occurs in patients with rheumatoid arthritis, probably as a result of lower methotrexate doses and better patient selection. Nevertheless, until the risk of serious liver disease is better defined it is recommended that patients have a pretreatment liver biopsy, a follow-up biopsy after a cumulative dose of 1500 mg, and then biopsies approximately every 2 years in the absence of other evidence of liver disease or risk factors.
3233039 Proposed digital arthroplasty critical study of the preliminary results. 1988 In view of the results of Swanson implants, particularly the long-term course of silicone implants, the authors studied and developed semi-constrained sliding arthroplasty designed for metacarpo-phalangeal and proximal interphalangeal joints. The preliminary study on bones and then on cadaver hands and finally on the knee of the rabbit allowed the design and experimentation of a prototype which led to the creation of a semi-constrained arthroplasty for which the elastic diaphyseal anchoring is ensured without cement and which possesses sliding surfaces composed of a metallic (proximal piece)--polyethylene (distal piece) interface. We therefore describe the principles of functioning of this arthroplasty, its technique of insertion, dorsal trans-tendon incision, its accessory (drill for diaphyseal preparations), its anatomical requirements (preservation of the palmar plate and lateral ligaments, bone section) and the postoperative course. To date, 52 arthroplasties have been inserted and we present the results of the first 36 cases for which the follow-up is equal to or a greater than one year (20 MP-16 PIP), indicating the technical modalities according to the various aetiologies (21 cases of rheumatoid arthritis--15 post-traumatic cases) and the complications. The average gain in mobility is 40 degrees with a mean range of movement of 64 degrees. In terms of pain, none of the arthroplasties were associated with pain apart from pain on cold in certain post-traumatic cases. The global and thumb-finger prehensile forces were evaluated to be an average of 90% in relation to the healthy side. Radiological assessment demonstrated fixation of the pieces in every case. Lastly, we discuss the outcome of this arthroplasty and its current indications in relation to the problems of instability essentially occurring in dislocated MP joints of rheumatoid arthritis.
3091203 [Induction of arthritis in mice by injection of homologous type II collagen]. 1986 Immunization with heterologous type II collagen (CII) induces arthritis in DBA/1 mice, a strain genetically susceptible to this disease. In order to develop an experimental model of autoimmunity more adequate for the study of human Rheumatoid Arthritis, DBA/1 mice were injected with homologous native CII. About 6 weeks later, the animals developed a chronic progressive polyarthritis assessed by clinical observations and histologic examination. The incidence of arthritis as well as the severity of the disease are clearly higher in males. Conversely, the secretion of autoantibodies raised against mouse CII is correlated neither with sex nor with activity score of the arthritis.
3447280 [Topical use of Rheumon-Gel in the combined treatment of patients with rheumatoid arthriti 1987 Rheumon-Gel was used for therapy of 51 patients with rheumatoid arthritis. It has been shown that the drug has a marked antiinflammatory and analgesic action, a positive effect on a number of subjective (pain in the joints and constrained movements in the morning), objective (body temperature, edema and joint function), and laboratory (leucocyte count, ESR, C-reactive protein, titer of antistreptolysin-O and antistreptohyaluronidase) indices and therefore it can be recommended for multimodality therapy of rheumatic patients, particularly of those with rheumatoid arthritis combined with G. I. tract diseases when the use of most of the antirheumatic drugs is counterindicated.
3303286 [Specific antibodies of soluble nuclear antigens in autoimmune vasculitis]. 1987 Jun In order to assess the clinical value of antinuclear antibody (ANA) assays in classifying vasculitis, 136 sera from 28 patients with cutaneous vasculitis alone, and 80 patients with vasculitis associated with a connective tissue disease or an unclassified arthritis were tested. ANAs were assayed by indirect immunofluorescence, anti-ENA and anti-histone antibodies were tested by immunodiffusion. ANAs are seldom in patients with cutaneous vasculitis alone (1 positive serum/28 = 3.5%). ANAs are more generally observed in vasculitis associated with systemic lupus erythematosus (SLE) (15 positive sera/16 vasculitis associated with SLE = 94%), rheumatoid arthritis (RA) (8 positive/30 RA with vasculitis = 27%), or a Sjögren syndrome (SS) (9 positive/19 vasculitis with SS = 47%). ANAs in SS are correlated with vasculitis or Raynaud's phenomenon. ANAs are not detected in vasculitis associated with other connective tissue diseases or unclassified arthritis. Anti-ENA antibodies are only found in vasculitis associated with SLE (11 positive sera/13 = 85%) or SS (3 positive sera/19 = 16%). Contrasting with the findings of other groups, our results show no anti-ENA antibodies in RA with vasculitis. Anti-RNP in SLE are correlated with cutaneous vasculitis (p less than 0.005). An antibody different from anti-Ro (SS-A) antibodies but precipitating with a trypsinized human spleen extract was observed in 2/11 sera from RA with vasculitis and not in other sera. Its significance is not established yet; this antibody would have a clinical interest only if further studies showed a high prevalence in rheumatoid vasculitis.
2161600 D-penicillamine induced pemphigus treated with methylprednisolone pulse therapy. 1990 A patient with severe rheumatoid arthritis received d-penicillamine treatment for 16 months. She developed mild pruritus 6 months after d-penicillamine initiation, and severe pemphigus 10 months after d-penicillamine was changed to azathioprine. Subsequent methylprednisolone pulse therapy resulted in a transient clinical remission of pemphigus. A literature review of d-penicillamine induced pemphigus and high dose methylprednisolone pulse therapy is presented.
2238861 [The HLA system and rheumatoid arthritis]. 1990 Jul Recent developments in molecular biology allow a more detailed description of and insight into the interaction between T-cell receptor, antigen/peptide, and MHC gene products. These advances also provide a better approach to understanding the molecular genetics of susceptibility to certain diseases. This review tries to interpret MHC structure/function relationships, using rheumatoid arthritis as a paradigm. The following aspects are of special importance: Most likely MHC class-II gene products are directly involved in the pathogenic process and are not only to be considered as "markers". Susceptibility to rheumatoid arthritis is not associated with a single serologically defined HLA-specificity (e.g., HLA-DR4). However, there is substantial evidence that shared functional epitopes on different MHC molecules (e.g., HLA-DR1 and HLA-DR4 subtypes) confer risk for rheumatoid arthritis.
3490895 Fibronectin binding with immunoglobulin aggregates and its association with rheumatic diso 1986 Nov Fibronectin was shown to bind heat-aggregated, but not monomeric, human IgG, suggesting that fibronectin may bind directly to IgG immune complexes. The presence of material both binding and already containing fibronectin was demonstrated in polyethylene glycol precipitates of sera and synovial fluids from patients with rheumatoid arthritis (RA) and gout, but not normal sera. By contrast, complement-fixing complexes contained fibronectin in RA synovial fluids and sera, but not in sera and synovial fluids from other rheumatic disorders. It is considered that fibronectin binds to immune complexes in RA synovial fluids and sera but that some other, as yet unidentified material, is effective in binding fibronectin in sera and synovial fluids from patients with osteoarthritis and crystal synovitis.
3735273 Prevalence of rheumatoid arthritis, osteoarthritis, chondrocalcinosis and gouty arthritis 1986 Jun The prevalence of rheumatic diseases was studied in representative subsamples by interview (n = 134), and by physical (n = 89) and radiographic (n = 81) examination in a representative sample of 79-year-olds in Göteborg, Sweden. The prevalence of rheumatoid arthritis (3-8 ARA criteria) was 10%. Radiographic osteoarthritis (OA) was diagnosed in wrists and/or finger joints of 65% of the probands and in knee joints of 14%. The first metacarpophalangeal (MCP I) joint was more frequently involved in males than in females (p less than 0.05). In females palpable enlargement of distal (DIP) and proximal interphalangeal finger joints correlated (p less than 0.01) to radiographic OA. The degree of heavy work in previous occupations was correlated to radiographic OA of DIP II-V in females (p less than 0.05 and of MCP I in males (p less than 0.05) but not to radiographic or clinical OA in knee joints. Symptoms of OA were reported by 6.1% in the knee and in 4.5% in hip joints. The prevalence of chondrocalcinosis averaged 15% (23% of females and 6% of males). Chondrocalcinosis of the hands occurred in 21% of females but in no males. The prevalence of hyperuricemia was 15% (women 6%, men 29%), and gouty arthritis was found in one woman.
2567150 A double blind comparative study of sulphasalazine and hydroxychloroquine in rheumatoid ar 1989 May In a double blind, single observer, 48 week study the effects of sulphasalazine (2 g daily) and hydroxychloroquine (400 mg daily months 0-6, thereafter 200 mg daily) were compared in 60 patients with definite or classical rheumatoid arthritis. They had not been treated previously with second line drugs. The onset of response with sulphasalazine was earlier than with hydroxychloroquine. After 48 weeks a comparison of the treatments showed no statistically significant differences in disease activity variables. Adverse reaction was the main reason for withdrawal in the sulphasalazine group and lack of efficacy in the hydroxychloroquine group. All adverse reactions, one being agranulocytosis after eight weeks of sulphasalazine treatment, appeared in the first three months of treatment and were completely reversible.
2169063 The effect of dietary fish oil supplement upon the content of dihomo-gammalinolenic acid i 1990 May Patients (n = 23) with definite or classical rheumatoid arthritis were given 18 g/day fish oil in gelatin capsules which provided 3.2 g/day EPA and 2.0 g/day DHA. The treatment period was 12 weeks followed by a 4 week washout period. Fish oil supplementation to the diet resulted in a substantial increase in the content of EPA and DHA in each of the plasma fractions examined (PL, TG, and CE). Little change was seen in the AA level of the TG and CE fractions but a modest decrease in AA was seen in PL. However the intake of fish oil caused a significant depression in the content of DGLA in the PL (p less than 0.005) and CE (p less than 0.01) fractions relative to baseline values. All changes had reverted to near baseline levels 4 weeks after dietary intervention. Since DGLA is the precursor of PGE1, which has been shown to be anti-inflammatory, our findings suggest that the anti-inflammatory effects of fish oil consumption could be mitigated by an associated reduction in DGLA.
2474900 Quantification by ELISA of erythrocyte-bound C3 fragments expressing C3d and/or C3c epitop 1989 A sensitive ELISA assay for quantifying erythrocyte (E) bound C3 fragments was developed. The assay employs a double-antibody sandwich technique, using polyclonal anti-C3d or anti-C3c antibodies to quantify C3 fragments, expressing C3d and/or C3c epitopes in washed, detergent-solubilized E. The assay detected 50-120 molecules of C3d per E in healthy individuals. Antigens reacting with anti-C3c antibodies were also detected on E from normal individuals, but the density of C3c-epitopes was 0.9-2.4 times lower than that of C3d-epitopes. In 2 patients with congenital factor I deficiency significantly increased density of E-bound C3c- as well as C3d-antigen was observed. Plasma infusion in one of the patients induced a loss of E-bound C3c-antigens, indicating cleavage of E-bound C3b to iC3b and further to C3c and E-bound C3d. Loss of C3c-antigens also occurred following in vitro treatment with normal human serum of E from one of the patients. Two thirds of 22 patients with systemic lupus erythematosus (SLE) and of 18 patients with rheumatoid arthritis had significantly increased density of E-bound C3d, the highest density being 490 C3d molecules/E in an SLE patient. The density of E-bound C3d correlated with the plasma-C3d concentration, indicating that the coating of E with C3d reflects the degree of complement activation.
1940933 Evaluation of micromotion in cemented vs uncemented knee arthroplasty in osteoarthrosis an 1991 Sep Twenty-four patients (25 knees) with osteoarthrosis (OA) and 19 patients (20 knees) with rheumatoid arthritis (RA) were operated with bi-tricompartmental knee arthroplasty. The patients were randomized to cemented or cementless fixation of the tibial component. The fixation of the tibial components was examined with roentgen stereophotogrammetric analysis (RSA) up to 24 months after operation. The following parameters representing tibial component micromotion were measured: (1) maximum migration of the prosthetic edge (maximum total point motion, MTPM); (2) distal migration of the prosthetic center (subsidence); (3) maximum proximal movements of the prosthetic edge ("lift-off"); and (4) prosthetic rotations, corresponding to internal/external rotation, adduction/abduction, and forward/backward tilt of the tibial component. All prostheses displayed significant micromotions, which tended to decrease 3-6 months after the operation. The average migration after 2 years, when measured as maximum single axis rotation, and MTPM were about 0.9 degrees-1.5 degrees and 1.0-1.5 mm, respectively, in all four groups. There were no statistically significant differences between cemented and cementless prostheses in either the OA or the RA group. The fixation in the RA patients did not significantly differ from that of the OA patients, perhaps because the RA patients had lower weight and were living a more sedentary life.
2202549 A comparison of two formulations of indomethacin ('Flexin Continus' tablets and 'Indocid' 1990 A multi-centre, double-blind, crossover study was carried out in 80 patients with rheumatoid arthritis to compare the efficacy and side-effect profiles of two formulations of indomethacin. Patients were allocated at random to receive 75 mg indomethacin per day either as 1 controlled-release tablet at night or as 1 immediate-release capsule given 3-times a day for a period of 4 weeks before being crossed over to receive the alternative treatment for a further 4 weeks. Pain scores, daily symptomatology and the requirement for escape analgesia recorded by both investigator and patient indicated that controlled-release indomethacin tablets, 75 mg given at night, was as efficacous as immediate-release indomethacin capsules given 3-times daily. However, the controlled-release formulation had a superior side-effect profile with a reduced incidence of abdominal/epigastric pain compared to the immediate-release preparation.
2805607 Low-dose methotrexate treatment of rheumatoid arthritis; long-term observation of efficacy 1989 Sep Forty-one patients with rheumatoid arthritis (RA) were treated with a weekly low-dose of methotrexate for a mean period of 32 months (range, 5-81 months) and were given a mean total dose of 954 mg (range, 145-2000 mg). Eighty-three percent of the patients improved. Of these 39% (16 patients) had a complete clinical remission and 17% (7 patients) showed marked improvement, 27% (11 patients) showed moderate improvement and 17% (7 patients) were unchanged. Patients responding to methotrexate therapy maintained the improvement as long as the therapy continued, unless severe infections occurred. Seven patients withdrew during the study including two, who died of myocardial infarction. Methotrexate was withdrawn because of adverse drug reactions in two patients, fear of toxicity in two and for administrative reasons in one patient. Adverse reactions developed in 25 patients (61%). In all but two cases these reactions were mild and reversible. Pancytopenia, a major side effect, was present in two patients: in one patient in association with pneumonia and in the other patient associated with an acute infectious enteritis (after three years treatment in the first and six years in the second patient); both recovered when methotrexate was discontinued. Age, sex, duration of treatment did not remarkably influence the outcome of therapy or the occurrence of adverse reactions.