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

ID PMID Title PublicationDate abstract
3174225 Total elbow replacement. 1988 Sep The historic development of prosthetic total elbow arthroplasty is traced and results of constrained, semiconstrained, and nonconstrained designs reported. The authors' personal experience with the semiconstrained total elbow replacement, surgical indications with an emphasis on careful patient selection, and highlights of operative technique are discussed. Pain, instability, ankylosis, and arthritic degeneration of the elbow have inspired many surgical attempts to improve function and relieve pain. The most sophisticated surgical options now include total elbow replacement. This paper reviews the development of total elbow arthroplasty and assesses the experience with semiconstrained total elbow replacements performed at the New York University Medical Center over the last eight years.
3489273 Pokeweed mitogen-induced secretion of IgG- and IgM-rheumatoid factors by synovial fluid an 1986 Lymphocytes from patients with rheumatoid arthritis (RA) were assayed for their ability to secrete Ig and rheumatoid factors (RF) upon polyclonal activation in vitro. B lymphocytes secreting IgM-RF and IgG-RF were enumerated using hemolytic plaque forming cell (PFC) assays. The sensitivity of RF-PFC formation was similar to that of a reverse PFC assay detecting all cells secreting Ig. Blood mononuclear cells from RA patients generated a median of 12 IgM-RF and 15 IgG-RF-secreting cells/10(6) after 6 days culture with pokeweed mitogen (PWM). Thus a median of approximately 0.5% of IgM- and IgG-secreting cells were identified as RF-PFC. Synovial fluid B lymphocytes co-cultured with autologous blood T lymphocytes in the presence of PWM generated higher numbers of RF-secreting cells; medians of 43 IgM-RF and 441 IgG-RF secreting cells/10(6) were found. Thus, 8-9% of IgM- and IgG-secreting cells from synovial fluid were identified as RF-PFC. In co-cultures containing synovial fluid T cells, PWM-induced RF secretion was low. The data indicate that both blood and SF B cells have the potential for RF secretion.
2225539 Methotrexate and trimethoprim-sulphamethoxazole--a potentially hazardous combination. 1990 Sep A 74-year-old woman had been treated with methotrexate over 2 years for rheumatoid arthritis. She was admitted to the hospital because of non-healing leg ulcers. After being treated with trimethoprim-sulphamethoxazole for a urinary-tract infection, she developed severe pancytopenia, followed by pneumonia and septic shock. The patient died shortly after. Concomitant treatment with methotrexate and sulphonamides should be strongly discouraged.
3963028 Flurbiprofen in the treatment of rheumatoid arthritis. A comparison with aspirin. 1986 Mar 24 This large-scale, double-blind study compared 200 mg per day of flurbiprofen (Ansaid, Upjohn) with 4,000 mg per day of aspirin in 822 patients with definite or classical rheumatoid arthritis who were evaluated for up to 52 weeks. Overall response to therapy was similar in both groups. By the end of the study, however, significantly more patients remained in the flurbiprofen (54 percent) than in the aspirin group (40 percent). Significant differences were also found in the incidence and severity of adverse reactions: 36 percent of flurbiprofen-treated and 63 percent of aspirin-treated patients reported side effects. Severe adverse reactions occurred in 6.7 percent of the flurbiprofen-treated patients compared with 16.5 percent of the aspirin-treated patients. Withdrawals that were due at least in part to adverse reactions were more than twice as frequent in the aspirin group (21.4 percent) than in the flurbiprofen group (10.2 percent). Laboratory data collected throughout the study showed no clinically significant abnormalities in either group. This study suggests that flurbiprofen effectively controls the pain and other symptoms of rheumatoid arthritis, and is superior in safety to aspirin in the treatment of patients with acute and chronic disease.
3488155 Lymphocytotoxic antibodies in rheumatoid arthritis: relation to HLA-DR2 and rheumatoid fac 1986 Apr During a Swiss multicenter study on HLA-antigens in rheumatoid arthritis (RA), the patients sera were tested for cytotoxic, complement fixing antibodies against autologous B- and T-lymphocytes (LCA). LCA were found in about 25% of the patients. Anti-B and cold-reacting LCA were more frequent than were anti-T and LCA reacting at 37 degrees. Most patients with anti-B had anti-T LCA as well. Among patients with LCA, 46.4% had the HLA-DR2 antigen as opposed to 21.2% of the patients without such antibodies (p = 0.0004). There was no difference between the two groups in regard to the other HLA-DR antigens. The patients with LCA had higher titers of rheumatoid factors and of antinuclear antibodies than those without these antibodies. There was no significant difference between the patients with LCA and those without in regard to severity of disease (radiological stage in relation to duration of disease), extra-articular involvement, the amount of circulating immune complexes, and erythrocyte sedimentation rate.
2384297 The protective effects of cell-free fluid exudate on cartilage degradation in vitro. 1990 In a short-term culture system, polymorphonuclear neutrophils (PMNs) were shown to cause significant loss of glycosaminoglycan (GAG) from cartilage. In addition, a lysate of these cells, and in particular cells stimulated with a phorbol ester, greatly enhanced this loss of GAG. This loss could be partially or completely inhibited by the addition of cell-free fluid exudate to the system. In other long-term culture experiments, IL-1a was shown to enhance fibroblast-induced GAG loss from cartilage. In this system too the breakdown was inhibited by cell-free fluid exudate. Initial characterization of the protective agent or agents shows them to be heat-stable at 56 degrees C and to be non-dialysable. It is proposed that in the chronic inflammatory joint disease, rheumatoid arthritis, the fluid phase of an inflammatory response may have a protective effect against the underlying pathological processes.
1757123 Circulating phospholipase A2 activity associated with sepsis and septic shock is indisting 1991 Oct Elevation of circulating phospholipase A2 (PLA2) activity is associated with sepsis and septic shock. Elevated levels of PLA2 activity also are seen in association with chronic inflammatory disorders such as rheumatoid arthritis. The relationship between these phospholipases is unclear. We have developed a highly specific enzyme-linked immunosorbent assay (ELISA) capable of measuring human synovial PLA2 in plasma, using monoclonal antibodies raised to recombinant synovial PLA2. This ELISA has been used to quantitate circulating PLA2 levels in patients clinically diagnosed with sepsis. These elevated levels positively correlated with the elevation seen in plasma PLA2 enzyme activity. The antibodies also have been used to purify immunoreactive PLA2 from plasma of patients with sepsis, thus enabling characterization of the purified protein by amino-terminal sequence analysis. We conclude from this study that the increase in PLA2 activity seen in association with sepsis and septic shock results from a dramatic elevation in levels of a circulating PLA2 enzyme. This inflammatory PLA2 is indistinguishable, both immunologically and chemically, from that associated with rheumatoid arthritis. Therapeutic agents directed towards inhibition of this inflammatory PLA2 enzyme may have utility in the treatment of both chronic and acute inflammatory disease.
3098196 Lymphocytes bearing Fc gamma receptors in rheumatoid arthritis. IV. Increased numbers and 1986 Nov Mononuclear cells expressing Fc gamma receptors that form Facb rosettes are increased in the peripheral blood of patients with rheumatoid arthritis compared with controls. Healthy individuals with a positive skin response to tuberculin showed a marked increase in numbers of circulating Facb-R+ cells three days after challenge, returning to baseline after seven days. No response was observed in subjects showing a negative skin test. A similar increase in Facb-R+ cell numbers was measured after intramuscular injection of another specific antigen, tetanus toxoid. In addition to this enhancement of Facb-R+ cell numbers, evidence has been obtained that these cells are in an activated state postimmunisation as judged by acquisition of low density and increased expression of class II MHC antigens. Apparently identical changes in Facb-R+ cell numbers and activation may be induced in vitro either by culturing sensitised mononuclear cells with specific antigen for three days or by an overnight incubation of normal cells with gamma-interferon (gamma-IFN). By analogy, therefore, the increased numbers of Facb-R+ cells in patients with rheumatoid arthritis are probably induced by gamma-interferon generated as part of an antigen driven immune response. In this context it is interesting that patients with Felty's syndrome, in whom neutropenia increases susceptibility to infections leading to the possibility of further stimulation of the immune system by micro-organisms, have particularly high levels of circulating Facb-R+ cells.
1812895 Abnormalities in the glycosylation of IgG in spouses of patients with rheumatoid arthritis 1991 Dec Forty-seven members of eight families with a rheumatoid proband were analysed for abnormal glycosylation of IgG. The results (%G(o) which is the percentage of oligosaccharide chains lacking galactose) were corrected for age and expressed as SD units about the mean for the normal population. Seven of 8 probands, 3/8 spouses, 3/5 RA relatives and 4/26 non-RA relatives had %G(o) values greater than 1SD above the age corrected mean for the normal control population (P less than 0.001, less than 0.01, less than 0.005 and greater than 0.5 respectively). A further 13 spouse pairs were studied. Ten of 13 probands and 8/13 spouses had %G(o) values greater than 1SD above the mean (P less than 0.001 and less than 0.001 respectively). Thus in total, a strikingly high number of unaffected spouses had high %G(o) values (11/21). IgM, IgA and IgG rheumatoid factors were studied. While RA patients' sera showed a correlation between IgM and IgA rheumatoid factors and %G(o), (IgM, r = 0.41 0.05 greater than P greater than 0.02, IgA, r = 0.36, P = 0.05), no correlation between IgG RF and %G(o) was noted in the RA patients. No correlation was found between any of the RF classes and %G(o) in spouses and non-RA relatives.
2164400 Altered immune response to glycine-rich sequences of Epstein-Barr nuclear antigen-1 in pat 1990 Jul Prior studies have shown that patients with rheumatoid arthritis (RA) have an increased number of circulating Epstein-Barr virus-infected B lymphocytes and elevated titers of antibody to Epstein-Barr nuclear antigen-1 (EBNA-1), the major nuclear antigen expressed in latently infected B cells. However, it is not known whether antibodies from RA patients recognize the same epitopes as antibodies from normal subjects. are directed at the glycine-alanine repeating region of the molecule. Antibodies specific for this region are also somewhat more prevalent in RA patients than in normal subjects. A panel of synthetic peptides derived from EBNA-1 was used to analyze the immune response to antigenic epitopes outside the glycine-alanine region, using the peptides as solid-phase antigen. Sera from RA patients and from systemic lupus erythematosus patients contained elevated levels of IgG antibodies to 2 non-glycine-alanine peptide and to 3 non-glycine-alanine peptides, respectively. Two of the 3 peptides are glycine-rich, but antibodies that react with them are distinct from each other, as well as from those that react with the glycine-alanine epitope. Eight other peptides from the C-terminal portion of EBNA-1 either do not react with sera or show no difference between normal subjects and patient groups. The antibodies to the glycine-alanine peptide are enriched with kappa light chains, whereas antibodies to epitopes outside the glycine-alanine region are not so restricted among kappa and lambda light chains. Thus, RA patients and systemic lupus erythematosus patients have different antibody responses than do normal subjects, both quantitatively and qualitatively.
2424460 Estimation of the relative avidity of 19S IgM rheumatoid factor secreted by rheumatoid syn 1986 Jun 19S IgM rheumatoid factors (RF) may play an important role in sustaining inflammation in rheumatoid arthritis (RA). As yet, no unique antigenic specificity for RF in RA has been identified. Because the synovium is central to the pathogenic changes in RA, RF produced therein might be pathogenically more important than serum RF. Therefore, we examined the reactivity and relative avidity of 19S IgM-RF in serum and rheumatoid synovial cells (RSC) from 20 patients with seropositive RA. Reactivities were determined by competitive inhibition of serum RF hemolytic activity and RSC RF-plaque-forming cells (PFC) by added soluble antigen, i.e., monomeric human IgG subclasses. Estimation of relative avidities of RSC RF for human IgG subclasses was done by calculation of fractional RF expression in the RSC RF-PFC assay following inhibition by IgG subclasses. RSC RF had greatest reactivity with IgG3 and IgG1, some reactivity with IgG2, and the least reactivity with IgG4. Serum RF reacted most with IgG1 and IgG2, reacted some with IgG4, but reacted poorly with IgG3. The antigenic determinants with which RSC RF reacted were common to many IgG3 molecules. The highest relative avidity of RSC RF was for IgG3. These observations indicate a selective deficiency of serum RF compared with RSC RF and suggest an important pathogenic role for these qualitatively different RSC RF molecules for in situ RF immune complex-mediated inflammation in RA synovial tissue.
1696191 The antiperinuclear factor. I. Clinical and serologic associations. 1990 May The antiperinuclear factor (APF) test raises two main problems: the unpredictability of the cells used as substrate and the difficulty in expressing the results. We propose that 10% of the cells have to be stained by a given serum in order for it to be considered positive. APF were found to be present in 76% of rheumatoid arthritis (RA) patients, 3% of healthy controls and occasionally in disease controls. The production of APF was significantly (p less than 0.01) related to the presence of rheumatoid factor in RA, and IgG antibody was predominant in the APF test.
2100875 Levels of SC5b--9 complement complex in plasma and synovial fluid of patients with rheumat 1990 Oct Activation of the terminal complement pathway leads to formation of the C5b--9 complex. The main effects of C5b--9 generation are tissue injury by cell lysis or by stimulation of proinflammatory mediators. In a study carried out in 42 patients, using polyclonal antibodies against C5b--9 neoantigens and C9 in an ELISA assay, we found significantly higher levels of SC5b--9 complex in plasma from the 18 patients with active systemic lupus erythematosus than those found in 10 healthy controls (p less than 0.005). In the 18 patients presenting rheumatoid arthritis and the 6 with progressive systemic sclerosis the plasma levels of SC5b--9 complex did not differ significantly from those in controls. The SC5b--9 levels found in the synovial fluid samples from the 16 rheumatoid arthritis patients were higher than the corresponding plasma ones. The ratio between synovial fluid and plasma levels was 1.2. Immunoperoxidase staining for C5b--9 was intense in three rheumatoid synovial membranes and absent in two normal synovial membranes obtained during meniscectomy. Increased levels of plasma and synovial fluid SC5b--9 reflect pathologic systemic or local activation of the complement carcase in systemic lupus erythematosus and respectively rheumatoid arthritis. Synovial membrane deposits of C5b--9 are indicative for the lytic and proinflammatory effects of complement activation.
2302883 Periprosthetic fractures in patients with total knee arthroplasties. 1990 Mar Ten patients with total knee arthroplasties sustained periprosthetic fractures. Nine of these were supracondylar fractures, and one occurred in the middle one-third of the tibia. These patients were treated with conservative methods in two cases and internal fixation with plate and screws in three cases. The remaining five patients were treated with intramedullary fixation using a specially designed revision prosthesis with long intramedullary stems. The best results wer achieved through the revision arthroplasty, based on walking ability, range of motion, and early rehabilitation.
2945697 Decreased expression of C3b receptor (CR1) on erythrocytes of patients with systemic lupus 1986 Expression of the C3b/C4b receptor (CR1) on erythrocytes is decreased in patients with systemic lupus erythematosus (SLE) compared to normal individuals, and the CR1 antigen is absent from podocytes in severe diffuse proliferate nephritis of SLE. In the present study, we examined the relationship between the number of CR1 on erythrocytes and the occurrence and severity of SLE nephritis, and assessed the expression of CR1 on erythrocytes and the occurrence and severity of SLE nephritis, and assessed the expression of CR1 on erythrocytes in non-SLE nephritis and other systemic inflammatory diseases by measuring the binding of 125I-labeled rabbit F(ab')2 and murine monoclonal IgG anti-CR1 antibodies to erythrocytes of normal individuals and patients in a French population. The number of binding sites for monoclonal anti-CR1 antibody on erythrocytes of 116 normal individuals was 743 +/- 22 (mean +/- SEM) with a range of 169-1,333, and the frequency distribution of this number in the population was bimodal. In 112 patients with SLE, the mean number of CR1 sites on erythrocytes was decreased to 62% of the mean for normal individuals (p less than 0.001). No correlation was found between CR1 expression on erythrocytes and the presence or immunohistopathological type of glomerulonephritis in biopsy specimens from these patients. The mean number of CR1 on erythrocytes of 29 patients with non-SLE glomerulonephritis was slightly decreased to 89% of the normal mean (p greater than 0.05), which could not be attributed to glomerular immune complex disease or vasculitis.(ABSTRACT TRUNCATED AT 250 WORDS)
2649543 Soft tissue metacarpophalangeal reconstruction for treatment of rheumatoid hand deformity. 1989 Mar The long-term results of soft tissue metacarpophalangeal reconstruction without articular resection were reviewed in 16 hands of 12 patients with painful ulnar deviation-subluxation deformity. No splinting was used beyond 3 weeks. Patients had either lupus or rheumatoid arthritis. The mean age at operation was 66 years, with mean disease duration of 15.9 years before operation. At follow-up (mean, 81 months), complete pain relief occurred in 88% of patients and 56 degrees and 64 degrees mean active metacarpophalangeal and proximal interphalangeal range of motion was present, respectively. Ulnar drift was corrected to 6 degrees on the average. The first semiobjective grading scale for metacarpophalangeal reconstruction was introduced. There were 82% good or excellent results.
3291821 Fibrositis, fibromyalgia, and musculoskeletal disease: the current status of the fibrositi 1988 Jul Fibrositis (fibromyalgia) is a common disorder, but is often not considered or diagnosed by clinicians. It is characterized by widespread musculoskeletal pain and aching, disturbed sleep, fatigue, morning stiffness, and local tenderness. The presence of multiple (seven or more) tender points and widespread pain or aching are necessary and sufficient conditions for diagnosis. Fibrositis occurs in a "primary" form, but most commonly in association with other rheumatic diseases where it is a concomitant condition. The designation "myofascial pain syndrome" has replaced older concepts of localized fibrositis, and is considered a separate entity.
3954461 Palindromic rheumatism with rheumatoid nodules: a case report with ultrastructural studies 1986 Jan Rheumatoid nodules developed on the finger tips of a patient with palindromic rheumatism. The patient had no bone cysts or erosions and had no rheumatoid factor. A light microscopic and ultrastructural study of a nodule showed a necrotic centre with fibrin, collagen, and granular material surrounded by large histiocytes, fibrocytes, lymphocytes, and vessels with adjacent mast cells as has been seen with nodules in classical rheumatoid arthritis (RA). We describe the first immunoperoxidase studies on a rheumatoid nodule and have identified reaction products for immunoglobulins and C3 in perivascular and endothelial cell vacuoles and in the necrotic centre.
3559588 A critical analysis of alignment factors influencing functional results following trispher 1986 In a study of the impact of selected patient factors and alignment variables on functional results of total wrist arthroplasty, functional score and range of motion were found to be improved and incidence of component shift and progressive radiolucent lines decreased by proper positioning of the implant center of rotation and restoration of carpal height. Angulation of the implant stems was secondary in importance to the other positioning variables with respect to overall function and durability. A neutral alignment range for this implant arthroplasty was proposed. Within this neutral range, functional score averaged 94 points and range of motion averaged 68 degrees. There were no reoperations, component shifting, or progressive radiolucent lines, and all wrists rated an excellent score.
3149007 Partial amino acid sequence analysis and variable subgroup determination (VH and VL) of a 1988 Continuous cell lines secreting monoclonal rheumatoid factors (RF) were derived from rheumatoid arthritis (RA) patients by cloning Epstein-Barr virus (EBV) transformed B cells and by hybridoma techniques. We studied five different clones with stable RF secretion. All were IgM, 4 kappa and 1 lambda. One of these clones, RFAN was extensively studied, and the partial amino acid sequences of the variable regions of both heavy and light chains were determined. After affinity purification, the IgM lambda RF antibody derived from the EBV clone was run under reducing conditions on SDS-polyacrylamide gel electrophoresis. The separated heavy and light chains were blotted and then sequenced by a gas-phase sequenator. The N-terminal sequence of the lambda light chain corresponded to that of the V lambda III subgroup. The heavy chain of the same IgM RF clone had a blocked N-terminus, but a cyanogen bromide peptide starting after methionine at position 82 showed a sequence typical of the VHIII subgroup. Heavy and light chains were also prepared by gel filtration after reduction and carboxymethylation from the same EBV clone made into a hybridoma. After this preparation, the heavy chain was not blocked and the N-terminal sequence confirmed that the heavy chain variable region belonged to the VHIII subgroup. We believe this to be the first amino acid sequence study of a monoclonal RF derived from the repertoire of an RA patient.