Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8810667 | Tyrosine phosphorylation in neutrophils from synovial fluid of patients with rheumatoid ar | 1996 Sep | The priming of neutrophils is associated with an increase in the level of tyrosine phosphorylation of cytosolic proteins, specifically of proteins with mol. wts of 42 and 74 kDa. We show here, using dot blots and Western blotting, that neutrophils isolated from rheumatoid synovial fluid have increased tyrosine phosphorylation of these target proteins. The level of tyrosine phosphorylation within neutrophils in the synovial fluid was increased when compared with neutrophils from the blood of the same patients, normal blood or neutrophils from the synovial fluid of patients without rheumatoid arthritis. Neutrophils from the rheumatoid synovial fluid were also more active and were unable to be further primed by exogenous primers. These data suggest that this elevation of tyrosine phosphorylation was the result of the action of local priming agents within the rheumatoid synovial fluid. | |
| 8834057 | The promise of a new clinical trial--intra-articular IL-1 receptor antagonist. | 1996 Jan | Most rheumatic diseases resist traditional therapeutic interventions. Novel biologicals show considerable promise as antirheumatic agents but do not lend themselves to delivery as drugs. Gene therapy promises to harness the therapeutic potential of proteins by acting as a biological drug delivery system. Considerable progress has been made in the use of genes to treat animal models of RA, and a human trial of this technology is scheduled to begin this year. | |
| 9387389 | HLA-DRB1 alleles genotyping in patients with rheumatoid arthritis in Chinese. | 1996 Dec | OBJECTIVE: To explore the role of HLA-DRB1 genes in the development of rheumatoid arthritis (RA) and the correlations between HLA-DR alleles and clinical manifestations of patients with RA. METHODS: 86 patients with rheumatoid arthritis and 106 race matched controls were studied in whom HLA-DR typing was performed by the method of DNA amplification with sequence-specific primers (PCR-SSP). The subtypes of HLA-DR4 were determined by the method of hybridization of PCR products with sequence-specific oligonucleotides (PCR-SSO). The absence or presence of HLA-DR4 and its subtypes was correlated with the clinical and serological characteristics of the patients. RESULTS: Compared with controls, an increased gene frequency of HLA-DR4 (48.8% vs 17.9%, P < 0.001) and a decreased frequency of HLA-DR7 (16.3% vs 27.4%, P = 0.06) were found. The DRB1* 0405 account for 61.9% of DR4+RA patients and 21.1% of DR4+ controls (P < 0.01). There was no difference between the DR4+ and DR4- patients with respect to age, sex, duration of disease, rheumatoid factor (RF), extra-articular manifestations including secondary Sjogren's syndrome. According to the wrist X-ray stage, the patients of DR4+ were more severe than that of DR4- (P < 0.05). CONCLUSION: HLA-DR4 and DR4 subtype of DRB1*0405 are related to the development of RA in Chinese. HLA-DR4 can be a useful prognostic marker in the patients with RA. | |
| 8129459 | Influence of previous exposure to human parvovirus B19 infection in explaining susceptibil | 1994 Feb | OBJECTIVES: To assess the association between exposure to parvovirus B19 and susceptibility to rheumatoid arthritis (RA). METHODS: One hundred and fifty five twin pairs (76 monozygotic (MZ) and 79 dizygotic (DZ)), discordant for RA, were tested for the presence of IgG antiparvovirus antibodies using ELISA. The data obtained were analysed using conditional logistic regression, from which odds ratios and 95% confidence intervals were calculated. RESULTS: Overall, there was no association between exposure to parvovirus and RA (OR = 1.2, 95% CI: 0.7-1.7). However, in two subgroups there was a suggestion of an association. These were: (1) pairs where the affected twin was rheumatoid factor (RF) seronegative (OR = 2.0, 95% CI: 0.9-12.4) and (2) in opposite-sexed twin pairs where the affected twin was female (OR = 3.0, 95% CI: 0.9-11.6). CONCLUSION: Previous exposure to parvovirus infection did not explain disease susceptibility in both MZ and DZ discordant pairs with rheumatoid arthritis. This infection, however, might be relevant in some subgroups. | |
| 1357169 | No association between rheumatoid arthritis and insulin dependent diabetes mellitus: an ep | 1992 Jun | To acquire more information on the controversial question of a possible association between rheumatoid arthritis (RA) and insulin dependent diabetes mellitus we searched for insulin dependent diabetes mellitus among patients hospitalized due to RA in 2 rheumatism hospitals in Finland. Nine subjects with insulin dependent diabetes mellitus were found among an annual number of 1460 patients admitted to one of the hospitals due to RA. These figures give a frequency of insulin dependent diabetes mellitus in patients with RA of 0.6% (95% confidence interval 0.2-1.0%), which does not exceed the prevalence of insulin dependent diabetes mellitus among the middle aged population of Finland in general (0.5-0.6%). Accordingly, no overrepresentation of homozygosity for HLA-DR4 was found among the total number of 25 patients with RA as well as insulin dependent diabetes mellitus, though the opposite might be expected as these diseases have a common DR4 association--RA with DR4 and DR1 and insulin dependent diabetes mellitus with DR4 and DR3. Instead, an increased frequency of DR1 (p less than 0.0002) and the antigen combination DR1/4 (p less than 0.01) was found in the subjects with both RA and insulin dependent diabetes mellitus compared with the subjects with insulin dependent diabetes mellitus alone. | |
| 7709183 | [Parvovirus B19-induced arthritis/arthropathy--an important differential diagnosis of chro | 1995 Feb 25 | INTRODUCTION/AIMS: The differential diagnosis of rheumatoid arthritis (RA) and parvovirus-B19-induced arthritis/arthropathy (PBA) can be difficult, but is of importance because of the different therapeutic implications. The purpose is to describe characteristic features serving to differentiate between chronic PBA and RA, based on 6 personal cases and the literature. METHODS/PATIENTS: 6 patients presenting with acute (3 cases) or chronic PBA (3 cases) over the last 5 years are described. RESULTS/CONCLUSIONS: The demonstration of anti-parvovirus-B19-immunoglobulins (Ig)M in addition to anti-parvovirus-B19-IgG is the most important diagnostic finding. Measurement of IgM must be done within the first months after onset, as it disappears later on. Furthermore, history of disease (exposure, prodromi and acute onset of arthritis), clinical examination (rash) and further investigations (normal ESR and CRP, typical hematologic findings, examination of synovial tissue and fluid without inflammatory changes, demonstration of the genome of parvovirus B19 by polymerase chain reaction, no erosions on radiographs) support the diagnosis of PBA. 2 of the 3 patients with chronic PBA fulfilled the criteria for classification of RA. Therapeutic approaches in PBA are discussed. In contrast to the favourable effect in RA, immunosuppressive agents may prolong persistence of virus and disease in PBA. | |
| 8833052 | The costs of rheumatoid arthritis: absolute, incremental, and marginal estimates. | 1996 Mar | We determined the average medical and indirect costs of rheumatoid arthritis (RA) from clinical and community based samples and compared those costs to those experienced by similar persons without RA. We reviewed the literature and analyzed the UCSF RA Panel Study and the National Health Interview Survey for the years 1989-91. The annual medical care costs of RA ranged from $4,300 to $5,700 in 1994 terms in the clinical samples, with hospital admissions accounting for half to two-thirds of the total. Indirect costs in the clinical samples exceeded direct costs and ranged from just under $10,000 to more than $16,000 a year. Medical care costs of RA are highly skewed, with persons in the 90th percentile experiencing costs more than 100 times as large as those in the 10th. In the national community based sample, the costs of RA amounted to $8.74 billion, of which more than half was due to medical care. In this sample, the increment of costs experienced by persons with RA compared to those without was $3.07 billion, with 80% of the excess the result of indirect costs due to wage losses. | |
| 8866922 | Lack of interaction between flucloxacillin and methotrexate in patients with rheumatoid ar | 1996 Mar | 1. The aim of the study was to examine the potential pharmacokinetic interaction between methotrexate and flucloxacillin. 2. Ten rheumatoid arthritis patients participated in the interaction study. Subjects were allocated to either methotrexate alone (5-15 mg per week) or methotrexate plus flucloxacillin (500 mg four times a day 48 h prior to sampling) in a random order. 3. There was a statistically, but not clinically, significant decrease in methotrexate AUC (1307 +/- 389 vs 1212 +/- 394 micrograms l-1 h) in the presence of flucloxacillin. Cmax and tmax parameters for methotrexate were not significantly altered in the presence of flucloxacillin. 4. Data from an additional 10 rheumatoid arthritis patients, starting on methotrexate, were added to the data from the placebo arm of the interaction study and a model dependent pharmacokinetic analysis was performed. The plasma concentration profiles were best described by a two-compartment model with a mean clearance of 11.9 (+/- 1.7) l h-1 and an initial volume of distribution of 31.2 (+/- 2.6) l. The pronounced intersubject variability in the pharmacokinetic parameters was not related to any of the available covariate information. 5. Our findings suggest that no important clinical interaction occurs between flucloxacillin and methotrexate in patients with rheumatoid arthritis. | |
| 8882047 | Sulfasalazine therapy for juvenile rheumatoid arthritis. | 1996 Feb | OBJECTIVE: To determine the safety and therapeutic potential of sulfasalazine (SSZ) in the treatment of a large cohort of patients with juvenile rheumatoid arthritis (JRA). METHODS: All patients who required the addition of a second line agent were offered SSZ and assessed at regular intervals. Thirty patients took SSZ as their sole drug therapy. One hundred thirty-nine patients with an average age of 11.5 yrs (range 1.5-21.8 yrs) took the medication. The duration of symptoms at the start of treatment was 30 mo (1-130 mo). All subtypes of JRA were included in the study group. Patients were treated for a mean of 13 mo (1-42 mo) with 31 mg/kg/day of SSZ. Significant improvement was defined as 50% decrease in the number of joints with active arthritis; or 50% decrease in the number of joints with effusion; or 50% decrease in total degrees of joint contractures; or normalization of an elevated erythrocyte sedimentation rate within 12 months of starting treatment. Data on adverse reactions, remissions, and treatment failure were also collected. RESULTS: One hundred two patients (73%) had significant improvement after starting SSZ. Fifty-six patients (40%) were able to stop all other medication at an average of 9.5 mo. Thirty-nine patients (28%) remitted and discontinued all medication. Twenty-three patients (17%) discontinued the drug for adverse reactions. All reactions resolved completely when the drug was discontinued. CONCLUSION: SSZ is safe and appears to be an effective primary or second line therapy for JRA, and should be studied further in a multi-institutional, placebo controlled study. | |
| 1348938 | Differences in T cell receptor restriction fragment length polymorphisms in patients with | 1992 Apr | OBJECTIVE: The purpose of this study was to determine whether a T cell receptor (TCR) polymorphism, either by itself or in combination with particular HLA polymorphism, leads to susceptibility to rheumatoid arthritis (RA). METHODS: Eight restriction fragment length polymorphisms (RFLPs) detected with TCR gene segments were investigated in 46 individuals with RA and were compared with data from normal control subjects. RESULTS: A statistically significant difference in the genotype frequencies of a Taq I RFLP detected with the TCR alpha constant region (C alpha) gene was noted. In addition, when the DR4+ subpopulations were examined, the allelic frequency of a 2-kb Bam HI fragment detected with a V beta 8 gene was increased in the samples from RA patients (P less than 0.0086). CONCLUSION: The results of this study suggest that germline differences in the TCR repertoire may be associated with RA, and that there is a contributory effect of DR4+ haplotypes with certain TCR haplotypes in susceptibility to RA. | |
| 1564458 | Custom total shoulder arthroplasty in inflammatory arthritis. Preliminary results. | 1992 Mar | Twenty-three patients with inflammatory arthritis and rotator cuff deficiency have undergone 27 custom-fit total shoulder arthroplasties. The design used included a short-stem humeral component and a metal-backed glenoid component with an offset keel. The glenoid component was custom-fit to provide maximum coverage of the glenoid surface. The average age of the patients at the time of surgery was 55 years (range, 20-75 years). All patients had inflammatory arthritis, 16 were on steroids, and all had some degree of rotator cuff involvement ranging from small to complete tears. The average length of follow-up study was 5 years (range, 3-7 years). The average preoperative shoulder score was 36 points (range, 15-50 points) with an average pain score of 7 (of 30) points. Postoperatively, the shoulder score improved to 85 points with a pain score of 28 points. Twenty-one shoulders scored a good to excellent result. Two patients required reoperation, both for recurrent rotator cuff tears, one of which occurred after a fall. Radiographic analysis revealed no incidence of humeral radiolucency and six cases of glenoid radiolucency. Only two of these were progressive and both were associated with irreparable rotator cuff tears. Thus, in the early follow-up, this design of glenoid has decreased the incidence of glenoid radiolucency in this difficult patient population. | |
| 1512771 | Splenectomy as treatment for nonhealing soft tissue defect after total knee arthroplasty i | 1992 Jul | We describe the apparent remarkable effect of splenectomy on wound healing in a patient with rheumatoid arthritis and Felty's syndrome. The patient had previously undergone a knee replacement with 4 months of failure of the surgical wound site to heal or close. The wound, which had broken down and dehisced on 3 separate occasions after plastic surgical attempts at closure, healed cleanly and without recurrence within 3 weeks of splenectomy and plastic repair at the same operation. | |
| 8571264 | [The effect of basic therapy on the morphological picture of the rectal mucosa in patients | 1995 | 140 rectal mucosa biopsies were obtained from 86 patients with rheumatoid arthritis (RA), from 54 RA patients prior to or after a year basic therapy with either methotrexate or sulfa drug (sulfasalazine or salazopyridazine). 80% of the examinees exhibited large macrophages, lymphoid follicules, IgM- and IgG-containing cells. The knowledge of the initial morphologic changes in the rectal mucosa from RA patients helps predict efficacy of methotrexate or sulfonic drug treatment. Rectoromanoscopy with biopsy proved important diagnostic tool in RA capable of differentiating the disease variants, prompting valid therapeutic approach with control of the treatment results. | |
| 8495256 | The frequency of extremely low serum pepsinogen, indicative of corpus gastritis with sever | 1993 May | The aim of this study was to assess the frequency of corpus gastritis with severe atrophy (CGA), pernicious anaemia and combined severe atrophy of antrum and corpus by non-invasive methods (i.e. determination of low serum pepsinogen A (PgA) and serum gastrin) in outpatients with RA (n = 249), compared to outpatients with other rheumatic diseases (n = 181) and outpatients with chronic non-rheumatic diseases (n = 429). In addition we investigated whether NSAIDs could cause or prevent CGA. A low serum PgA level (< 17 micrograms/l), indicating pentagastrin-refractory achlorhydria in patients without gastric resection, was found in 13 patients (5.2%; 95% Confidence Interval (CI) 2.4-8.0) with RA, in 11 (6.1%; 95% CI 2.6-9.5) with other rheumatic diseases and in 12 patients (2.8%; 95% CI 1.2-4.4) with chronic non-rheumatic diseases (NS). Low serum PgA values were more frequent in older patients (P < 0.005) and females (P < 0.05). Pernicious anaemia occurred in RA in 1.2% (95% CI 0-2.6) of the patients while for other rheumatic diseases the frequency was 1.7% (95% CI 0-3.5) and for chronic non-rheumatic diseases 0.2% (95% CI 0-3.6) (NS). In patients with a serum PgA below 17 micrograms/l, normal serum gastrin levels (< 90 ng/l) as an indication of combined severe atrophy of antrum and corpus, were found in 1/13 patients with RA, in 3/11 with other rheumatic diseases and 2/12 with chronic non-rheumatic diseases (NS). The frequency of low serum PgA levels was no different between patients on NSAIDs 17/355 (4.8%) and those without NSAIDs 19/502 (3.8%).(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 1431056 | Application of two-color immunofluorescence staining to demonstration of T-cells and HLA-D | 1992 Nov | We studied the localization of T-cells and HLA-DR antigen-bearing (DR+) cells in rheumatoid synovitis by employing an improved two-color immunofluorescent staining (TCIF) technique. With this technique we have successfully identified DR+ activated T-cells in the inflammatory synovium. T-cells expressed HLA-DR antigen when they were in contact with DR+ antigen-presenting cells (APC). In addition, activated T-cells showed characteristic distribution within the synovium: they were found around high endothelial venules, within lymphoid follicles, and in hyperplastic synovial lining, suggesting their involvement in the development of rheumatoid synovial lesions via interaction with synovial DR+ APC lineage cells. These findings may contribute to better understanding of the role of activated T-cells in the histogenesis of rheumatoid synovitis, a typical chronic inflammatory lesion. | |
| 8205404 | Changes in stiffness following short- and long-term application of standard physiotherapeu | 1994 Jun | A computer-controlled MCP joint arthrograph was developed to measure the stiffness of finger joints objectively. This was used to study the short-term (one application) and long-term (multiple applications over 6 weeks) effects of several physiotherapeutic methods on the reduction in joint stiffness. The techniques used were hot wax baths, pulsed ultrasound alone, wax baths plus pulsed ultrasound and exercise. In the short-term (i.e. after each application) wax plus ultrasound produced a statistically significant reduction in elastic torque range (P < 0.01) and dissipated energy (P < 0.05). However, the reductions in these stiffness parameters were temporary. Long-term no significant reductions in stiffness were measured. In other words, stiffness was reduced by each therapy session, but it then increased again before the next session. Wax, ultrasound alone or exercise produced no short- or long-term effects. | |
| 7699678 | Pharmacokinetics and renal function in patients with rheumatoid arthritis receiving a stan | 1995 Jan | OBJECTIVE: To determine the pharmacokinetics of a standard oral dose of 7.5 mg in a cohort of patients beginning methotrexate (MTX) and continuing the drug over 24 months. METHODS: Twenty-one patients underwent pharmacokinetic testing after receiving a dose of 7.5 mg of oral MTX and concomitant nonsteroidal antiinflammatory drug (NSAID) therapy. Studies were performed at the time of MTX initiation, and after 6 and 24 months of therapy. RESULTS: No significant differences with time were observed in area under the serum concentration versus time curve (AUC), maximal MTX concentration achieved postdosing (Cmax) or time to maximal MTX concentration (Tmax). Renal clearance of MTX at 6 months decreased by a mean (+/- SD) of 23.8 (40.3) cc/min (p = 0.014). Creatinine clearance decreased by 8.6 cc/min (17.2) (p = 0.033) at 6 months. CONCLUSION: No differences in AUC, Tmax, or Cmax were observed over a 2 year period in patients with rheumatoid arthritis on a standard 7.5 mg dose of MTX. Renal clearance and creatinine clearance both decreased significantly after 6 months of treatment. This effect may be clinically relevant in certain individuals as MTX is renally excreted. | |
| 7651257 | Second-line agents for rheumatoid arthritis. | 1995 Aug 21 | Second-line agents (disease-modifying agents or slow-acting antirheumatoid drugs) are well established for synovitis that persists despite treatment with non-steroidal anti-inflammatory agents. Indications for their use in the elderly are similar to those in younger people, but the elderly are at higher risk of adverse reactions. Therefore, lower doses, more cautious patient selection and more frequent monitoring for adverse reactions are recommended. Low dose corticosteroids are often effective in the elderly and obviate the need for second-line agents. | |
| 7637310 | [A case of necrotic scleromalacia during the course of rheumatoid arthritis]. | 1995 Jan | Necrotic scleromalacia occurred in both eyes of patient, 80, with rheumatoid arthritis lasting for 00 years. The authors report the clinical course of the disease during a 2.5 year follow-up, methods of treatment and compared their own observations with those of others. | |
| 8810131 | Superoxide dismutase activity in arthropathy: its role and measurement in the joints. | 1996 Jun | The electron spin resonance (ESR) method was used to measure the superoxide dismutase (SOD) activity in synovial fluids from the knee joints of 73 patients with rheumatoid arthritis (RA), and the results were compared with those of 50 patients with osteoarthritis (OA) and posttraumatic arthritis (PA). The SOD activity in RA and OA knee joint fluids was higher than in the control patients with PA. Patients with moderate RA (grade III or IV according to Larsen's classification of rheumatoid knee radiographs) showed higher SOD activities in joint fluids than patients with early (grade I or II) and terminal (grade V) stages of RA. Our results suggest that the SOD activity in joint fluids is a valid index of articular destruction and repair. |