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

ID PMID Title PublicationDate abstract
7827376 Hemophagocytic syndrome in a patient with rheumatoid arthritis. 1994 Oct A 63-year-old female, who had been diagnosed with rheumatoid arthritis (RA) 3 years previously, was admitted due to progressive pancytopenia, lymphadenopathy, fever, and weight loss. The physical and laboratory findings fulfilled all of the American Rheumatism Association (ARA) revised criteria for RA. Her bone marrow aspirate revealed a decreased nuclear cell count (1.8 x 10(4) microliters) and megakarocyte count (0/microliter), and macrophages phagocytizing blood cells (4%), indicating the presence of hemophagocytic syndrome. The serological tests for several viruses revealed no obvious viral etiology. However, a slight Epstein-Barr virus (EBV) reactivation could not be excluded. Administration of 40 mg prednisolone daily improved her abnormal hematological findings and immunological laboratory parameters. This is a case of RA accompanied by hemophagocytic syndrome, which has not been reported previously as a complication of RA.
8187448 A clinical and biochemical assessment of methotrexate in rheumatoid arthritis. 1994 Mar Low-dose methotrexate has gained widespread acceptance as a second-line agent in rheumatoid arthritis (RA). The Leeds Human Model Screening System (LHMSS) is a validated screening mechanism allowing the rapid evaluation of compounds for their potential as anti-rheumatic agents, the results of which have been confirmed in longer term studies. We have evaluated methotrexate in patients with RA using the LHMSS at a maintenance dose of 10mg/week. Significant change occurred in four out of eleven variables over a 24-week period (p < 0.01). This degree of change is greater than that seen with nonsteroidal anti-inflammatory agents but less than with other recognised second-line agents such as D-penicillamine, suggesting that methotrexate may have less potential as a second-line agent than D-penicillamine.
7683880 Increased percentage of CD3+, CD57+ lymphocytes in patients with rheumatoid arthritis. Cor 1993 May OBJECTIVE: To determine whether a small CD3+ lymphocyte population expressing 110-kd CD57 antigens (HNK1) is expanded in patients with rheumatoid arthritis (RA), as it is in patients who have undergone bone marrow transplantation and patients with the acquired immunodeficiency syndrome, and to investigate whether it is involved in the pathogenesis of RA. METHODS: The phenotype of CD3+, CD57+ lymphocytes was analyzed by flow cytometry, and correlations between the percentage of these cells in the blood and various clinical and biologic parameters were investigated. RESULTS: The percentage of CD3+, CD57+ lymphocytes was increased in RA patients compared with controls. These lymphocytes expressed T cell receptor alpha/beta. Eighty percent expressed the CD8 accessory molecule, and 20% expressed the CD4 accessory molecule. The leukocyte common antigen CD45RA isoform was expressed by these CD3+, CD57+ lymphocytes in blood. The HLA-DR antigen was expressed in synovial fluid but not in blood. Finally, the percentage of these lymphocytes in the blood correlated with the duration of RA. CONCLUSION: The expansion of the CD3+, CD57+ lymphocyte population and their activation in the synovial fluid of RA patients suggest that these cells are involved in the inflammatory process.
7716604 Cerebral vasculitis complicating rheumatoid arthritis. 1995 Apr Central nervous system vasculitis is a rarely described complication of rheumatoid arthritis. We report a case of cerebral vasculitis in a 55-year-old woman with a 7-year history of seropositive, nodular rheumatoid arthritis. Striking multifocal abnormalities of the white matter on magnetic resonance imaging led to a suspicion of vasculitis despite lack of clinical evidence of extracranial vasculitis and normal findings on cerebrospinal fluid studies and cerebral angiography. After institution of treatment with glucocorticoids and azathioprine, she survived in stable condition for 14 months from the onset of symptoms. Postmortem examination of the brain revealed vasculitis and chronic ischemic changes.
8348359 Carpal instability in rheumatoid arthritis. 1993 Aug The authors examined prospectively the prevalence of and relations among patterns of carpal instability in 52 patients with proven rheumatoid arthritis. Posteroanterior, lateral and oblique radiographs of both wrists were obtained. Nineteen patients exhibited one or more patterns of instability. The most common isolated pattern was volar intercalated segmental instability, apparent in six patients. Five patients showed more than one pattern, most commonly a combination of ulnar translocation and volar carpal subluxation. Patients with active erosions or changes in the distal radioulnar joint were more likely to exhibit instability than those without such findings. Carpal instability is a frequent mechanical complication of rheumatoid arthritis. The radiologist should be aware of this possibility, so that a diagnosis can be made promptly and appropriate clinical management begun.
8162637 Three-colour flowcytometric examination of CD4/CD45 subsets reveals no differences in peri 1994 Jan Reactive arthritis (ReA) and rheumatoid arthritis (RA) are inflammatory joint diseases which differ in several clinical and immunological aspects. In both diseases locally activated T cells are considered important for pathogenesis. Subsets of T cells are demonstrated by staining with monoclonal antibodies recognizing isotypes of the common leukocyte antigen: CD45RA, which is considered to be a marker of native T cells, and CD45RO a marker of primed T cells; a third subset was also identified according to the staining intensity of CD45RB: CD45RBbright and CD45RBdim. The expression of these and the surface markers CD3, CD4, CD8, CD14 and CD56 was studied in synovial fluid (SF) and peripheral blood (PB) of patients with ReA (n = 11), RA (n = 10) and normal controls (n = 10) by three-colour immunocytometry. Significantly more CD45RBbright were found in the PB of patients with ReA (64.1%) and RA (63.5%) than in the SF of ReA (36.8%) and RA (40.6%) patients. However, when analyzed in relation to CD45RO, the CD45RO/CD45RBbright population was not significantly different between the SF and PB of patients with ReA (32.2% vs. 26.8%) and RA (30.6% vs. 28.1%), respectively. Among the three cellular subtypes of CD4+ lymphocytes demonstrated in this study (CD45RA/RBbright, CD45RO/CD45RBbright and CD45RO/CD45RBdim) none, in contrast to previous results of other groups, showed marked differences between ReA and RA in either of the compartments examined.
7882703 Investigation into the duration of action of sustained-release ibuprofen in osteoarthritis 1994 The duration of action of sustained-release ibuprofen ('Brufen Retard') was investigated in a 14-day double-blind study involving 14 osteoarthritis and 10 rheumatoid arthritis patients. The recommended once-daily dosage of this preparation (1600 mg taken in the evening) provided effective control of arthritic symptoms for both patient groups, with significant overall improvements in pain and stiffness compared to baseline. Substitution of placebo for a single dose of the active treatment resulted in a trend towards worsening of pain and stiffness in the rheumatoid group; however, the only statistically significant change involved impaired quality of sleep (p = 0.03) during the night after placebo administration, over 24-hours after the previous dose of active medication. In this particular study, symptom control was also clearly achieved for the osteoarthritis patients, as this group showed no deterioration within the same period. The 24-hour clinical action underlying these findings is consistent with ibuprofen plasma profiles obtained with the sustained-release preparation in earlier pharmacokinetic studies. It is likely that the greater sensitivity of rheumatoid patients to withdrawal of a single day's active treatment in this study reflects a more severe inflammatory disease process than that of the osteoarthritis patients.
8843860 The presence of interleukin-13 in rheumatoid synovium and its antiinflammatory effects on 1996 Oct OBJECTIVE: To study the production of interleukin-13 (IL-13) in rheumatoid synovium and the effects of recombinant IL-13 on the phenotype and function of synovial fluid (SF) macrophages and T cells derived from patients with rheumatoid arthritis (RA). METHODS: The presence of IL-13 in SF was studied using an IL-13-specific enzyme-linked immunosorbent assay (ELISA); the production of IL-13 was studied in SF mononuclear cells (SFMC) by reverse transcriptase-polymerase chain reaction. The effects of recombinant IL-13 on cytokine production by and phenotype of SFMC were evaluated using cytokine-specific ELISAs and flow cytometry, respectively. The effect of IL-13 on the proliferation of SFMC was determined by 3H-thymidine incorporation. The production and the effects of IL-13 were compared with those of IL-4. RESULTS: IL-13 was present in 27 of 28 SF samples, and IL-13 messenger RNA (mRNA) was detectable in SFMC. Importantly, IL-13 levels were significantly higher than those of IL-4, and IL-13 protein and mRNA were expressed in several samples, although IL-4 synthesis was undetectable. Recombinant IL-13 significantly reduced the production of IL-1 beta and tumor necrosis factor alpha and the expression of CD16 and CD64 by SF macrophages, whereas the expression of HLA-DR and CD23 was increased. These effects on SF macrophages were similar to those observed with IL-4, but in contrast to IL-4, IL-13 had no growth-promoting effect on SF T cells. CONCLUSION: IL-13 is consistently present in rheumatoid synovium. The ability of exogenous IL-13 to decrease the production of proinflammatory cytokines by SFMC suggests that it may have therapeutic potential in the treatment of patients with RA.
9099931 Characterization of a soluble form of CD58 in synovial fluid of patients with rheumatoid a 1996 Jun Reduced levels of a soluble form of the adhesion receptor and CD2 ligand CD58 (sCD58) were previously described in RA patients. In order to understand the biological significance of this finding we biochemically characterized sCD58 in RA and asked how well sCD58 binds to CD2. sCD58 concentrations were measured in serum and synovial fluid (SF) samples of RA patients by two ELISAs, one detecting domain 1 of CD58 (CD58-D1), and the other one the complete molecule (CD58-D1 + D2). Small amounts of split sCD58-D1 were found in most RA sera, but not SF. In addition, split sCD58-D2 was detected in SF by affinity chromatography, SDS-PAGE, and Western blotting. Gel filtration gave similar peaks at 95-125 kD for RA sera, SF, and normal serum. Binding of SF-sCD58 to the CD2+ Jurkat variant JBB1 or recombinant CD2 was stronger than urinary sCD58 and reached binding of oligomeric recombinant CD58 at low concentrations. In conclusion, sCD58-split products were found in RA sera and SF. At concentrations as they occur in vivo, SF-sCD58 binds to CD2 much more strongly than urinary sCD58. It is conceivable that locally released sCD58 blocks the CD2/CD58 interaction under physiological conditions. Insufficient release of sCD58, e.g. in synovitis, might result in T cell accumulation and perpetuation of inflammation.
8474076 Patient preferences for nonsteroidal antiinflammatory drug related gastrointestinal compli 1993 Feb We conducted a pilot study examining the relative preferences for various nonsteroidal antiinflammatory drug associated adverse gastrointestinal events and misoprostol prophylaxis for these events. Thirty patients with rheumatoid arthritis volunteered to participate. A trained nurse interviewer administered the structured pretested interview. Respondents rated 18 hypothetical health states on a category rating scale with anchors at 0 (immediate death) and 100 (full health for life). Linear contrasts were created to test the null hypotheses of equal preferences, using t tests for correlated means. Our results suggest that respondents place a high value on the avoidance of (in order of decreasing importance) surgery, hospitalization, prophylaxis induced diarrhea and uncomplicated ulcer requiring outpatient treatment. The avoidance of ulcer symptoms (primarily dyspepsia) and the inconvenience of an additional medication taken 4 times daily (in the absence of diarrhea) appeared to be substantially less important from these patients' perspective. Further work is underway to confirm these preliminary findings.
8742871 Late complications in elbow arthroplasty. 1996 Mar The world literature (1986 to 92) reports an amazingly high complication rate of elbow arthroplasty, amounting to 43%. Accordingly, we also find a high revision rate (18% on average) and a considerable rate (15%) of permanent complications. These figures do not correspond to our own experience with the GSB III (Gschwend/Scheier/Bähler) elbow prosthesis, a sloppy hinge with flanges on the lower and anterior part of the distal humerus. Our respective figures of complications are two to four times lower for rheumatoid elbows. When complications are discussed, a clear distinction of the type of prosthesis is mandatory, because linked or nonlinked and nonconstrained or semiconstrained prostheses have specific complications. The following complications are discussed separately: loosening (radiologic and clinical), ulnar neuropathy, infection, dislocation and subluxation, uncoupling, intraoperative bone fractures, and failure of the implant. The possible causes are analyzed, and means to avoid or treat these complications are discussed. We conclude that even in the long term ( > 10 years), results obtained with elbow arthroplasty are approaching those of hip and knee arthroplasty.
7979597 Rheumatoid-susceptible alleles of HLA-DRB1 are genetically recessive to non-susceptible al 1994 Sep OBJECTIVE: To assess the relationship between HLA-DRB1 genotypes and the progression of bone destruction in Japanese patients with RA. METHODS: The HLA-DRB1 alleles were determined by polymerase chain reaction and allele specific oligonucleotide probe techniques in 160 Japanese patients with RA. HLA-DR 0101, 0401, 0404, 0405, 1001 and 1402 were regarded as susceptible alleles of RA according to previous reports. Patients were classified into three groups (S/S, S/N and N/N group), based on the possession of two, one or no susceptible factor. The grading of radio-graphic changes in the wrists and fingers were evaluated by Larsen's criteria. The radiographic grades were first compared with the results of genotyping in the 160 cross sectional cases. A retrospective study was then conducted on a subgroup consisting of 57 cases taken from the 160 cases used for the cross sectional study. RESULTS: In the scatter diagram of the 160 cross sectional cases expressing the relationship between the stage of bone destruction and duration of RA, the regression line and the 95% confidence intervals separated the S/S group from the S/N and N/N groups in the early phase of development of bone destruction. In the retrospective study on the 57 cases the median years taken to development to stage V in the wrists after the onset of symptoms were 13.1 in the patients in the S/S group, 22.7 in the S/N group and 23.0 in the N/N group. The difference observed between the S/S and S/N group, and between the S/S and N/N group were statistically significant (p < 0.01), but that between the S/N and N/N groups was not. Thus the bone destruction in the wrists and fingers progressed more rapidly in the S/S group than in the S/N and N/N groups; and the rheumatoid susceptible alleles of HLA-DRB1 can be considered to be genetically recessive to the non-susceptible alleles in the progression of bone destructions in the wrists and fingers. CONCLUSION: Genotyping of HLA-DRB1 can be a useful prognostic marker in the early phase of RA.
7644787 [Methotrexate treatment of amyloidosis secondary to rheumatoid arthritis]. 1995 Jun Amyloidosis secondary to rheumatoid arthritis is a complication with a poor prognosis and as yet an undefined medical therapy. In the last decades the use of different cytostatics has been advocated to avoid renal function deterioration. The clinical characteristics and course in eight patients with amyloidosis secondary to rheumatoid arthritis are here reported after therapy with low dosage methotrexate. In twelve patients who followed a 12-month therapy a clinical improvement was observed, with a marked decrease in proteinuria; in one of them proteinuria disappeared. These results suggest that methotrexate at low doses might be an alternative in the early treatment of amyloidosis secondary to rheumatoid arthritis in patients with preserved renal function.
1626285 Analysis of cell populations in rheumatoid arthritis synovial tissues. 1992 Jun Knee synovium, taken from patients with rheumatoid arthritis at the time of arthroplasty, was studied immunohistologically. Focal perivascular lymphoid infiltrates of different sizes were examined in detail to evaluate changes in cell populations as the infiltrate size increased. T cells formed the largest component of mononuclear cells of all aggregates. The large grade 3 aggregates contained substantial numbers of B cells arranged around a central venule and cells bearing the CD45RA+ phenotype. In contrast, the small grade 1 aggregates contained few B cells and the T-cell population contained relatively greater numbers of CD8+ cells. Cells bearing the CD45RO+ phenotype exceeded CD45RA+ cells in grade 1 aggregates. Detailed analysis of mononuclear cell aggregates of different sizes in the rheumatoid synovium suggests that the composition of each aggregate depends on the total number of mononuclear cells it contains.
7899371 [Rheumatic manifestations of parvovirus B19 infection]. 1995 Jan 28 Parvoviruses are small single-strand DNA viruses. Human parvovirus (PV B19) was isolated in the 1970s and recognized as a pathogen in the 80s. Its role was first demonstrated in acute erythroblastopenia in patients with chronic haemolytic anaemia, then in epidemic megalerythema. More recently PVB19 has been shown to be the aetiologic agent in fetal loss and chronic infection in immunodepressed patients. Further attention has focused on rheumatologic manifestations, particularly in prolonged joint diseases raising the problem of differential diagnosis and a possible pathogenic relationship with rheumatoid arthritis and systemic lupus erythematosus. Clinically, subjects with parvovirus B19 infection have flu-like manifestations of joint pain and myalgia lasting for about 1 week. Generally, the joint pain is symmetrical, of inflammatory type usually involving proximal joints (phalangeal joints in two-thirds of the cases). Acute back pain or associated extra-articular signs are often absent. Signs regress spontaneously in 10 to 15 days although longer periods have been observed. Diagnosis can be confirmed by ELISA identification of specific IgM antibodies. Nonsteroid antiinflammatory drugs are generally effective.
11048621 Growth factors, insulin-like growth factor-1 and growth hormone, in synovial fluid and ser 1996 Dec OBJECTIVE: Synovial fluid (SF) plays an important role in joint function. We evaluated the growth factors, insulin-like growth factor-1 (IGF-1) and growth hormone (GH) in SF and serum from patients with osteoarthritis (OA), rheumatoid arthritis (RA), gout, pseudogout and diffuse idiopathic skeletal hyperostosis (DISH). DESIGN: Standard radioimmunoassay techniques were used to measure concurrent levels of IGF-1 and GH. SF samples and serum samples were obtained concomitantly from 27 patients with OA, 22 patients with RA, nine men with gout, 14 patients with pseudogout and eight men with DISH. RESULTS: In the case of IGF-1, a comparison of serum and SF levels shows that SF levels of IGF-1 are lower than serum levels in all groups. Men and women gave similar values. In contrast, in the case of GH, all groups, except males with RA, had higher GH values in SF when compared with serum values. Individual patients with other forms of arthritis demonstrated similar relationships. CONCLUSION: The finding that IGF-1 is present in levels about one-half as great in SF as compared with serum suggests that IGF-1 may be produced in lesser amounts or is utilized by the patient in customary joint function. The finding that GH is present in SF at values twice as high, or more, of serum levels in inflammatory arthritides suggests that GH may play a role in the pathophysiology of arthritic disorders.
8609945 Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloro 1996 May 16 BACKGROUND: Rheumatoid arthritis is a common disease that causes substantial morbidity and mortality. The responses of patients with rheumatoid arthritis to treatment with a single so-called disease-modifying drug, such as methotrexate, are often suboptimal. Despite limited data, many patients are treated with combinations of these drugs. METHODS: We enrolled 102 patients with rheumatoid arthritis and poor responses to at least one disease-modifying drug in a two-year, double-blind, randomized study of treatment with methotrexate alone (7.5 to 17.5 mg per week), the combination of sulfasalazine (500 mg twice daily) and hydroxychloroquine (200 mg twice daily), or all three drugs. The dose of methotrexate was adjusted in an attempt to achieve remission in all patients. The primary and point of the study was the successful completion of two years of treatment with 50 percent improvement in composite symptoms of arthritis and no evidence of drug toxicity. RESULTS: Fifty of the 102 patients had 50 percent improvement at nine months and maintained at least that degree of improvement for two years without evidence of major drug toxicity. Among them were 24 of 31 patients treated with all three drugs (77 percent), 12 of 36 patients treated with methotrexate alone (33 percent, P < 0.001 for the comparison with the three-drug group), and 14 of 35 patients treated with sulfasalazine and hydroxychloroquine (40 percent), P = 0.003 for the comparison with the three-drug group). Seven patients in the methotrexate group and three patients in each of the other two groups discontinued treatment because of drug toxicity. CONCLUSIONS: In patients with rheumatoid arthritis, combination therapy with methotrexate, sulfasalazine, and hydroxychloroquine is more effective than either methotrexate alone or a combination of sulfasalazine, and hydroxychloroquine.
7720426 [Follow-up result of 14 cases of the first metatarsophalangeal joint arthroplasty with tit 1994 Sep An 8-year follow-up study of 14 cases (22 feet) of titanium total 1st metatarsophalangeal joint arthroplasty with two designs (type I and type II) is reported. The follow-up period average was 5 years with a range of 3 to 8 years. The rate of subjective satisfaction was 72.7% (16/22), the incidence of complications 31.8% (7/22), and the rate of revision 27.3% (6/22). The results implicate that titanium total hallux MTP joint arthroplasty is a suitable procedure for osteoarthritis, rheumatoid arthritis and hallux rigidus of the 1st MTP joint, and that type II prosthesis seems better than type I prosthesis. In addition, prosthetic designing, surgical technique and postoperative complications are also discussed in detail.
8102057 Increased levels of circulating intercellular adhesion molecule 1 in the sera of patients 1993 Aug OBJECTIVE: We sought to assess whether circulating levels of intercellular adhesion molecule 1 (ICAM-1) in patients with rheumatoid arthritis (RA) are elevated and correlate with clinical measures of disease activity and whether this ICAM-1 originates from the synovium. METHODS: Circulating ICAM-1 (cICAM-1) levels were determined by sandwich enzyme-linked immunosorbent assay of serum from 61 RA, 18 osteoarthritis (OA), and 11 inflammatory arthritis (IA) patients. In addition, paired serum and synovial fluid samples were collected from 17 RA, 9 OA, and 4 IA patients. The stability of cICAM-1 was assessed by overnight incubation at 37 degrees C. Finally, the potential degradative effects of synovial fluid proteases were assessed by incubation of recombinant soluble ICAM-1 with patient synovial fluid. RESULTS: RA sera contained significantly greater (P < 0.001) levels of cICAM-1 compared with RA synovial fluid and compared with sera or synovial fluid from the OA and IA patients. Circulating ICAM-1 levels were unaffected by overnight incubation at 37 degrees C and were unaffected by exposure to RA, OA, or IA synovial fluid. Serum levels of cICAM-1 demonstrated a weak, but significant (P < 0.05) correlation with the joint score and erythrocyte sedimentation rate in 25 RA patients treated with nonsteroidal antiinflammatory drugs. CONCLUSION: The greatest elevations of cICAM-1 were seen in RA patient sera. In both RA and OA, synovial fluid cICAM-1 levels were consistently lower than serum levels, suggesting that cICAM-1 did not originate in the synovium. Because the production of cICAM-1 can be increased by cytokines (e.g., interleukin-1, tumor necrosis factor alpha), elevated levels of circulating ICAM-1 in RA may be reflective of systemic exposure to elevated cytokine levels.
8129796 Exacerbation of established collagen-induced arthritis in mice treated with an anti-T cell 1994 Mar OBJECTIVE: To investigate the effect of T cell depletion on established collagen-induced arthritis (CIA) in mice, using monoclonal antibodies (MAb) to T cell receptor alpha/beta (TCR alpha/beta). In addition, experiments using anti-CD3 MAb were performed for comparison. METHODS: CIA was induced in male DBA/1 mice by immunizing them twice with bovine type II collagen (CII). The arthritis score and anti-CII antibody titers were examined serially. Proportions of T cells were determined by fluorescence-activated cell sorter (FACS) analysis on spleen cells or peripheral blood cells. RESULTS: When anti-TCR alpha/beta MAb was injected on the day of CII priming, no arthritis was detected in association with depressed anti-CII antibody titers. Unexpectedly, however, when MAb was given after arthritis was established, a rapid exacerbation of arthritis was observed, which resulted in ankylosis of most joints. Anti-CII antibody titers were not affected. The addition of anti-TCR gamma/delta MAb had no effect on the augmented arthritis. T cell depletion by anti-CD3 MAb during established CIA also caused an enhancement of arthritis, which was, however, weak and only transient. FACS analysis revealed that the early improvement of arthritis after the transient augmentation seen in the mice treated with anti-CD3 MAb paralleled the early recovery of alpha/beta T cells in the periphery. CONCLUSION: The present results support the concept that alpha/beta T cells, in general, may play a regulatory role in the clinical course of murine CIA after disease onset. Therefore, caution is recommended when using intensive T cell-targeted therapy in patients with rheumatoid arthritis.