Browse

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

ID PMID Title PublicationDate abstract
8918562 Persistent reduction in IL-6 mRNA in peripheral blood mononuclear cells of patients with r 1996 Nov There is persistent excessive production of a number of pro-inflammatory cytokines in patients with rheumatoid arthritis (RA). A number of experimental therapies have been found to be effective in the treatment of RA, although the effects of these therapies on cytokine production have not been evaluated. One such experimental therapy involves administration of a MoAb to intercellular adhesion molecule-1 (ICAM-1) that has been shown to be clinically beneficial in approximately 60% of the patients, with some patients responding for up to 11 months. The current studies were carried out to determine whether the success of this therapy was associated with changes in mRNA levels for pro-inflammatory and other monocyte-derived cytokines in peripheral blood mononuclear cells (PBMC). Cytokine mRNA levels were assessed in freshly isolated unstimulated PBMC by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) after minimal in vitro manipulation of the cells. Anti-ICAM-1 MoAb administration was followed by an increase in IL-1 beta, IL-8, and tumour-necrosis factor-alpha (TNF-alpha) mRNA detected at 2 or 24 h after the initial infusion in the clinical responders, but no persistent change in these cytokine mRNA levels were observed that correlated with clinical benefit. By contrast, IL-6 mRNA levels declined immediately after the first MoAb infusion and reached pretreatment values variably after the 5 day treatment course. IL-6 mRNA levels remained significantly reduced in patients responding to therapy 1 months after treatment. Fluctuations in monocyte numbers within the PBMC after treatment did not account for the observed changes in cytokine mRNA levels. The results suggest that a decline in IL-6 mRNA levels is a pharmacological action of the MoAb to ICAM-1. Moreover, persistently diminished IL-6 mRNA levels induced by anti-ICAM-1 MoAb might be associated with the long-term benefit of this therapy. In addition, monitoring the activation status of monocytes in circulating PBMC may be useful in predicting response to therapy and warrants further investigation in a larger study population.
8620638 The effect of preoperative exercise on total knee replacement outcomes. 1996 May This study compared the effects of preoperative physical therapy of general cardiovascular conditioning exercises with the routine procedure of no preoperative physical therapy on patients undergoing primary total knee replacement. Thirty patients were randomly assigned to 1 of 3 groups. Group 1 was the control group. Group 2 participated in a physical therapy program designed to strengthen the upper and lower limbs and improve knee range of motion. Group 3 participated in a cardiovascular conditioning program, consisting of arm ergometry, cycle ergometry, aquatic exercises, and aerobic activity. All patients were evaluated preoperatively and postoperatively using the Hospital for Special Surgery Knee Rating, the Arthritis Impact Measurement Scale, and the Quality of Well Being instrument. Both experimental groups tolerated their respective exercise protocols extremely well. All 3 groups showed significant improvement postoperatively as measured by the Hospital for Special Surgery Knee Rating, the Arthritis Impact Measurement Scale and the Quality of Well Being measurement scales. However, neither type of preoperative exercise added to the degree of improvement after surgery at any of the postoperative evaluations.
8151587 Incidence, prevalence and possible risk factors for pneumonitis in patients with rheumatoi 1994 Jan OBJECTIVE: Methotrexate (MTX) is being used increasingly to treat rheumatoid arthritis (RA). Pneumonitis is a serious side effect of MTX therapy (P-MTX). Our aim was to determine in patients with RA the incidence and prevalence of P-MTX in Western Australia and identify risk factors for the development of this adverse reaction. METHODS: Patients with P-MTX were identified by (a) direct communication with rheumatologists in Western Australia, (b) use of a computerized clinical database, (c) questionnaire inquiry of all other rheumatologists in Australia. Possible risk factors for P-MTX were examined using age/sex matched case controls selected from the computerized clinical database. RESULTS: Ten definite and 3 probable cases of P-MTX were identified. Local incidence of P-MTX was 1/35.4 patient years MTX treatment; if definite and probable cases are included (1/49.6 patient years MTX treatment for definite cases alone). Twelve patients with P-MTX were compared with 24 age/sex matched controls. A shorter duration of MTX treatment and a higher incidence of preexisting lung disease were observed in P-MTX cases but these differences were not statistically significant. No difference was observed between the P-MTX and control patients with respect to rheumatoid factor, duration of RA, use of tobacco, dose of MTX, serum creatinine, creatinine clearance or concurrent treatment with aspirin, nonsteroidal antirheumatic drugs or prednisolone. CONCLUSION: Our results indicate that in hospital clinic patients with RA pneumonitis is a common adverse reaction. They suggest that hypersensitivity is probably responsible for most cases of pneumonitis associated with MTX, but preexisting lung disease may confer increased risk.
8212922 [Cartesian dualism or alchemy of medical routine practice]. 1993 Jul Whereas alchemy postulated the unity of body and soul as early as in the 15th century, René Descartes developed an artificial separation of the body from the soul in the 17th century, a challenge that today's doctors continue to face. This problematic nature of dualism seems to be suitable for complicating the doctor's relationship with patients of different age groups. With the help of a screening technique and a semi-standardized interview 100 patients (25 women with RA aged > 65; 25 women with RA aged < 55; 25 women aged < 65 without RA and 25 women aged < 55 without RA) were examined with regard to their basic needs in the relationships with their doctor. The patients older than 65 showed characteristic psychophysical particularities and, as compared with patients younger than 55, 86% of them articulated the needs for security as primary need in the relationship with their doctor. Seventy-six percent of the younger patients articulated the need for passing on of information as primary need. To understand the world of the elderly means the handling of pseudo-morbidity, reduced capability, social death and disease as normality, means the acceptance of the need for a mainly emotional doctor-patient relationship. From the results efficient psycho-therapeutical findings can be recommended for the doctor's practical work with regard to "pitfalls," as well as for use as the basis for talks and for a method to use in dealing with elderly people.
1411195 [Dermatopolymyositis induced by D-penicillamine in rheumatoid polyarthritis. Apropos of 1 Treatment of rheumatoid arthritis (RA) with D-penicillamine (DP) is associated with development of dermatopolymyositis (DPM) in 0.2 to 1.2% of cases. A case of DPM which developed after four years DP therapy in a 58-year-old female with RA is reported. The favorable outcome after discontinuation of DP and administration of corticosteroids and the absence of recurrence or malignant disease after 4 years 9 months follow-up demonstrated the causal relationship between DP therapy and development of DPM. An analysis of 34 previously published cases of DP-induced DPM (DP/DPM) showed the following: development of DPM was not influenced by the dosage or duration of DP therapy; reported cases of DP/DPM were clinically identical with primary DPM but had a different outcome, with permanent recovery of DP/DPM occurring 1.5 to 6 months after withdrawal of DP; patients with DP/DPM had immune disorders, including antinuclear antibodies in 14 of 34 patients; the high prevalence of the B18, B35, DR4 haplotype in these patients denotes immunogenetic differences with primary DPM patients (B8-DR3) and DP-induced myasthenia (DR1).
8453799 Serum osteocalcin and calcitropic hormones in a homogeneous group of patients with rheumat 1993 Jan Different mechanisms may play a role in the pathogenesis of the generalized osteopenia found in rheumatoid arthritis (RA). We measured the calcium, osteocalcin (BGP), parathyroid hormone (PTH), calcitonin (CT) and 25(OH)D3 levels as well as urine 24 hr calcium, Ca/Cr and OHP/Cr in a homogeneous group of 30 non-disabled patients (10 men, 8 premenopausal women and 12 postmenopausal women) recently diagnosed as having RA (disease duration 4 to 6 months). They had normal serum levels of vitamin K, were not on previous or present treatments known to interfere with calcium metabolism, and were not pregnant if females of fertile age. The group was compared with an age-matched control group of 32 healthy subjects (10 men, 8 premenopausal women and 14 postmenopausal women). We observed significantly decreased levels of 25(OH)D3 (29.9 +/- 9.9 vs 48.7 +/- 12.1 ng/mL; p < 0.005) and significantly increased levels of urine OHP/Cr (2.24 +/- 0.71 vs 1.56 +/- 0.82 mg/mg; p < 0.001) in the RA group. No differences in these two parameters were found between the three subgroups of RA patients. Male RA patients showed decreased levels of serum BGP (7.3 +/- 1.0 vs 8.2 +/- 1.7 ng/mL; p < 0.01). The remaining parameters did not differ significantly between RA patients and controls. These data suggest that the generalised osteopenia found in RA may be a consequence of increased bone resorption without a concomitant increase in bone formation, perhaps related to mechanisms inherent to the disease.
1373738 Increased binding of synovial T lymphocytes from rheumatoid arthritis to endothelial-leuko 1992 May The infiltration of the synovial membrane (SM) by mononuclear cells, mostly T cells, is a typical histopathological feature associated with rheumatoid arthritis (RA). The entry of T lymphocytes into the SM is believed to be mediated by a number of molecules in the endothelium that are induced in response to a series of inflammatory mediators. In this study, we have investigated the adhesion of synovial T cells from RA patients to two endothelial ligands: endothelial-leukocyte adhesion molecule-1 (ELAM-1), the only selectin known to function as a vascular addressin for T cells, and vascular cell adhesion molecule-1 (VCAM-1), the cellular ligand of VLA-4. Our results clearly demonstrate that synovial T cells isolated from both SM and synovial fluid (SF), bearing an activated and memory phenotype, displayed an enhanced capacity to interact with these two endothelial molecules as compared with T cells from peripheral blood (PB) either of the same RA patients or healthy donors. A further enhancement of VLA-4-mediated T cell binding to VCAM-1 and fibronectin could be observed when already in vivo-activated synovial T cells were stimulated in vitro with phorbol esters, suggesting the existence of several cellular affinity levels for both very late activation-4 (VLA-4) ligands. Moreover, both PB and synovial T cells from RA patients exhibited strong proliferative responses when they were cultured with either fibronectin or VCAM-1 in combination with submitogenic doses of anti-CD3 mAb. This increased endothelial binding ability of synovial T lymphocytes together with their proliferation in response to the interaction with VCAM-1 and fibronectin may represent important mechanisms in the regulation of T cell penetration and persistence in the chronically inflamed SM of RA.
1341793 [Juvenile systemic rheumatoid arthritis and adult-onset Still's disease: comparison of cli 1992 Jun The course of systemic juvenile rheumatoid arthritis (JRA) and that of Still's disease in the adult is unpredictable. The clinical course of 14 patients with JRA and 7 adults with Still's disease 6 months after onset was classified into 4 forms according to the persistence of joint manifestations after the cessation of systemic signs. a) monocyclic systemic form (5 children and 2 adults); b) polycyclic systemic form (3 children and 1 adult); c) monocyclic chronic joint form (3 children and 2 adults) and d) polycyclic chronic joint form (3 children, 2 adults). Seven of the 21 patients (5 children and 2 adults) developed joint sequelae, 5 with the polycyclic chronic joint form and 2 with the monocyclic chronic joint form. None of the patients with systemic forms, mono or polycyclic, developed sequelae. Thus, the course of patients with JRA and Still's disease may be used to predict development of joint sequelae.
7771343 Basic mechanisms in rheumatoid arthritis: the role of T lymphocytes in rheumatoid synoviti 1994 Undoubtedly, synovitis is a cell-mediated process involving various cell types, such as T cells, B cells, APC, monocytes/macrophages, synoviocytes, chondrocytes, and cytokines. Therefore, it is difficult to clarify the cell type that plays the central role in the inflammatory process. Despite this difficulty, there is strong evidence that T cells mediate the disease in collaboration with APC that bear specific antigenic peptides. The mediators released could perpetuate an ongoing inflammatory process in the joints irrespective of the nature of the initiating agents. Therefore, many approaches to a more specific immunotherapy for RA have been developed, directed toward the modulation of T cell function. Thus far, various forms of chemical and biologic treatment have been used, such as cyclosporin A and monoclonal antibodies directed against T-cell epitopes and IL-2 receptor, with some beneficial effects on the course of RA. The development of a more specific immunotherapy using reagents directed against the T-cell receptor and vaccination with specific T cells await further studies, since we still do not know the inciting antigen(s) in RA. Nevertheless, we are hopeful that the ongoing search for the still unknown antigen(s) will be successful, thus providing new and better treatment regimens for a still uncurable disease.
1484414 [A case of rheumatoid arthritis with immunotactoid glomerulopathy]. 1992 Aug The patient was a 64-year-old female who had been treated by a local doctor for rheumatoid arthritis and hypertension for 10 years. Malaise and edema developed since July, 1990, and as proteinuria and renal dysfunction were noted, the patient was admitted to our hospital on November 2. On admission, BUN was 33mg/dl, creatinine was 2.5mg/dl, and proteinuria was about 3g/day. Renal biopsy was performed after admission. Light microscopy revealed nodular lobulation of glomeruli and occlusion of loops. Dylon staining was negative. Immunofluorescent study showed granular deposition of IgG, IgM, C3, C4, Clq in the glomerular basement membrane and mesangial area. Electron microscopy showed a large amount of electron dense deposits in the subendothelium and mesangial area and dense aggregation of tubular structure in the deposit, part of which exhibited a profile of fingerprint deposit. The tubular structures were classified into three major types, which were 120, 100, and 50nm in diameter. From these findings, a diagnosis of immunotactoid glomerulopathy was made. After renal biopsy, plasmapheresis and prednisolone were administered, and the patient has been managed conservatively to date.
1517060 Audit of full blood count monitoring in patients on longterm gold therapy for rheumatoid a 1992 Mar The use of injectable gold in the treatment of rheumatoid arthritis (RA) is hampered by the high incidence of adverse reactions of which myelotoxicity is potentially the most serious. Regular full blood count (FBC) monitoring prior to each injection, a practice which requires much time and effort, has never been fully evaluated. Of 154 patients who were started on gold and followed by the lifetable method for up to 10 years, five patients were withdrawn from treatment because of myelotoxicity, thrombocytopenia in all cases: the two most serious cases occurred early at 3 and 7 months after starting treatment; three mild cases occurred at 17, 37 and 60 months, were of slow onset and reversed spontaneously. Clearly, FBC monitoring is justifiable in the first two years of treatment when the incidence of adverse reaction is highest. Further investigation is required to justify this practice after two years of uncomplicated treatment.
8254101 Improved immunoturbidimetric method for rheumatoid factor testing. 1993 Nov The performance of two immunoturbidimetric modifications for rheumatoid factor (RF) testing, which differ with respect to the means of complement inactivation (heat treatment and inactivation with polyvinyl sulphonate), were compared in serum samples from 87 patients with rheumatoid arthritis (RA) and from 403 healthy subjects. IgM-rheumatoid factor titres were also measured with an enzyme linked immunosorbent assay (ELISA). Both immunoturbidimetric tests gave positive reactions (rheumatoid factor > or = 20 IU/ml) in 74 out of the 87 (85%) RA sera. In cases with high RF concentrations the results after chemical inactivation tended to be slightly higher compared with heat inactivation. In healthy subjects rheumatoid factor was detected in 19/403 (4.7%) sera using heat inactivation and in 22/403 (5.5%) sera with chemical inactivation of complement. Interrun coefficient of variation in the chemical inactivation assay was 4.4%; with the heat inactivation method it was 8.1%. In the ELISA, a marginally better correlation was noted in the results obtained using chemical inactivation. Inactivation of complement by means of polyvinyl sulphonate offers the advantage of easier test performance and better reproducibility, and the results may reflect more accurately true rheumatoid factor concentrations.
1595005 [Lung injury associated with bucillamine therapy]. 1992 Apr We have reported previously a first case of interstitial pneumonitis in rheumatoid arthritis treated with bucillamine in 1989. Thereafter, a dozen cases with lung injury associated with bucillamine therapy have been reported. To explore the similarities among these patients, we tried to carry out a survey concerning the lung injuries in these cases in the present study. We obtained the following results. (1) Patients with lung injury consisted of 7 females and 3 males, aged 65 years on average (59-72). (2) The total amount of bucillamine used was 20-40 g on average (5.1-144 g) during approximately 100 days. (3) Serum rheumatoid factor was positive in 9 of 10 cases. (4) HLA-DR4 was significantly (p less than 0.01) detected in all cases of lung injury associated with bucillamine. (5) Interestingly the effect of bucillamine on rheumatoid disease activity was excellent in most cases. (6) Drug lymphocyte stimulation test (DLST) using bucillamine was performed in 6 cases. Positive DLST was found in 3 of 6 cases. These results suggest that cell-mediated hypersensitivity reaction (Coombs & Gell type IV) may contribute to the development of lung injury associated with bucillamine therapy.
1294742 Fibroblast growth factors released by wounded endothelial cells stimulate proliferation of 1992 Dec We demonstrated that vascular endothelial cells mechanically wounded by scraping from the substratum were able to release growth promoting factors for synovial cells as well as for endothelial cells. The wounded endothelial cell conditioned medium stimulated the proliferation of synovial cells derived from different human donors dose dependently and induced transit of growth arrested synovial cells (predominant in the G0 and G1 phases), through the S phase and into the G2 and M phases. When the wounded endothelial cell conditioned medium was applied to heparin-sepharose columns, mitogenic activity was eluted with 2.0 M NaCl. The mitogenic activity in wounded endothelial cell conditioned medium, which was heat sensitive, was inhibited by protamine sulfate and a specific mouse monoclonal antibody against basic fibroblast growth factor (bFGF). Our results are evidence that the wounded endothelial cell conditioned medium contained growth promoting factors for synovial cells, including bFGF. We also showed the presence of bFGF in the endothelial cells of the small blood vessels and stromal synovial fibroblast-like cells in patients with rheumatoid arthritis (RA). Our results suggest that the endothelial cells in the luxuriant capillaries in the synovial tissues from patients with RA may have a critical role in the stimulation of neighboring synovial cell proliferation, resulting in pronounced synovial hyperplasia.
7586974 Vitamin D3 metabolism in patients with rheumatic diseases: low serum levels of 25-hydroxyv 1995 Jul 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) has been shown to modulate lymphocyte activation in vitro. Through binding to specific receptors 1,25-(OH)2 D3 inhibits proliferation, immunoglobulin production and the release of cytokines. Moreover, 1,25-(OH)2 D3 is efficiently produced by activated monocytes. These findings suggest that 1,25-(OH)2 D3 may play a role as a regulator of immunological activation. Consequently, we found it of interest to study the serum levels of the two major metabolites of vitamin D3 in patients with systemic lupus erythematosus (SLE) (n = 21), rheumatoid arthritis (RA) (n = 29) and osteoarthritis (n = 12). In patients with SLE the levels of 25-OH D3 were below those of the healthy controls (p = 0.0008) and OA (p = 0.0168). The levels 1,25-(OH)2 D3 corresponded to normal levels. There were no significant correlations between 25-OH D3 levels and clinical or paraclinical disease manifestations. Further, the phenotypic distribution of Gc-globulin, which binds vitamin D3 metabolites in circulation, was normal. The serum concentrations of 1,25-(OH)2 D3 and 25-OH D3 in patients with RA and OA corresponded to those of the controls. Although the cause of the reduced 25-OH D3 levels in SLE patients is unclear, possible beneficial effects of administration of vitamin D to these patients should be considered.
8361160 Quantification of soft-tissue imbalance in condylar knee arthroplasty. 1993 Jul Soft-tissue balance has been debated in recent publications in connection with the long-term survival of the 'condylar-type' knee prostheses. Present methods of assessment have all assumed that the soft tissues around the knee are inelastic strings. The authors have developed two instruments to quantify soft-tissue imbalance, at the time of the operation, with the assumption that the soft tissues are viscoelastic structures. These two soft-tissue balancing devices were consequently used on 121 patients undergoing condylar knee arthroplasties at the Derbyshire Royal Infirmary and Bretby Hall Orthopaedic Hospital. The first instrument consisted of two flat plates separated by four standard compression springs and provided a qualitative measure of imbalance assuming that the soft tissues were viscoelastic. It was used on 55 patients before being replaced by the quantitative measure of the second instrument. The authors have redefined soft-tissue imbalance, to take into account the viscoelastic nature of the soft tissues, as the resultant trapezoidal geometry of the knee after the bony cuts have been made and when the knee is tensed by equal forces both medially and laterally. The second balancer eliminates the requirement to quantify the individual tensions in the medial and lateral structures by introducing to the system a low-friction, central pivot in the coronal plane. Once the pivot is situated at the centre of the knee, an equilibrium position is achieved where the clockwise and counter-clockwise moments are equal. The tensions exerted by soft tissues can be assumed to be equal and opposite as their moment arms are the same.(ABSTRACT TRUNCATED AT 250 WORDS)
8587173 [Acute myeloid leukemia (M1) following chemotherapy for Ki-1 lymphoma complicated with rhe 1995 Dec A 58-year-old woman complicated with rheumatoid arthritis (RA) was admitted to our hospital with right axillar lymphadenopathy and splenomegaly in November 1992. She was diagnosed as an anaplastic large-cell lymphoma (Ki-1 +) (stage IIIB) on the histological findings of the right axillar lymph nodes. She was treated with 11 courses of CHOP regimen between February 1992 and May 1993, and with mitoxantrone, etoposide (VP-16) and predonisolone in April 1992 and May 1993. The right axillar lymph nodes and spleen were irradiated at a dose of 36Gy in October 1992 and May 1993 respectively. In May 1993, peripheral blood showed WBC 89,000/microliter with 96% myeloblasts, Hb 8.3 g/dl, and Plt 124,000/microliter. Bone marrow aspirate revealed hypercellularity with 90% myeloblasts, which were positive for CD13 and HLA-DR. She was diagnosed as AML (M1). The karyotype showed normal. Southern blot analysis did not reveal the rearrangement of the MLL gene. She received the BHAC-DMP regimen and obtained complete remission. However, she relapsed during consolidation therapy, and died of cerebral bleeding. An autopsy revealed absence of a residual tumor. The mean interval from exposure to alkylating agent to the onset of secondary leukemia has been reported to be about 5 years, in contrast to a shortened interval of about 2 years for VP-16-induced leukemia. In our patient, it took only 1 year to have AML following chemotherapy for Ki-1 lymphoma. This suggests that her AML might be induced not only by treatments for RA and Ki-1 lymphoma, but also by immunological background such as RA.
8553806 Microscopy and tomography of erosive changes in the temporomandibular joint. An autopsy st 1995 Oct Thirty-nine temporomandibular joint autopsy specimens were examined by microscopy and tomography for erosive changes. We found two types of erosive changes, an extensive type with complete loss of cartilage and a local type with retained articular cartilage. On microscopic examination nearly twice as many temporal components as condyles were eroded. The erosions were generally more extensive in the condyle. Erosions in the condyle were evenly distributed. In the temporal component there was a slight predominance of erosions located to the lateral part of the tubercle. The radiologic investigation underestimated both the presence and the extent of the erosions. Positive predictive values and negative predictive values were 0.70 and 0.83, respectively, for erosions in the condyle and 0.91 and 0.68 for erosions in the temporal component. It is suggested that the initial event in osteoarthrosis of the TMJ can occur as a subarticular hard-tissue change. The need for more accurate diagnostic tools than radiography should be stressed.
9010086 Prognostic value of contrast enhanced Gd-DTPA MRI for development of bone erosive changes 1996 Dec Conventional radiograms have been used to quantitate the progression of rheumatoid arthritis, mainly through the assessment of bone erosions, but this approach has many limitations. It has been suggested that an advantage of contrast-enhanced Gd-DTPA MRI over radiography may be its prognostic value due to its ability to show the natural history of active destructive to inactive fibrous pannus. The aim of this study was to evaluate the possible prognostic value of MRI for future development of bone erosive changes in small hand joints in patients with RA. The results of the study confirm that in joints in which inflammatory active pannus is shown by contrast-enhanced MRI, progression of bone-destructive changes can be expected.
1540042 Interplay between environmental factors, articular involvement, and HLA-B27 in patients wi 1992 Jan Medical records of 138 patients with psoriatic arthritis and 138 with rheumatoid arthritis were reviewed for the occurrence of an environmental factor triggering arthritis. Twelve (9%) of the patients with psoriatic arthritis had had an acute disorder immediately preceding onset of arthritis (an operation in four cases, articular trauma in three, abortion in two, myocardial infarction, thrombophlebitis, and phosphoric ester intoxication in one case each). Peripheral arthritis occurred in all these patients. Among the rheumatoid patients, an acute event immediately preceding the onset of the disease was recorded in two cases (1%) only (chi 2 = 7.52; p = 0.006). No significant association was found in the arthritic patients between the incidence of acute events preceding arthritis onset and positivity of the HLA-B27 phenotype.