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ID PMID Title PublicationDate abstract
11084948 Optimizing glucocorticoid therapy in rheumatoid arthritis. 2000 Nov Glucocorticoids have a profound effect on the immune system and also on the HPA axis. Present insights into these mechanisms are discussed. Glucocorticoid resistance and clinical efficacy in the treatment of RA are reviewed. There is growing evidence for a positive effect of low-dose glucocorticoids on the retardation of erosive joint damage. Side effects of glucocorticoids on bone are now better controlled. Some guidelines to optimize glucocorticoid therapy in RA are given regarding dosage, timing, managing of side effects, and (new) types of glucocorticoids.
9426828 Cartilage protective agent (CPA) Ro 32-3555, a new matrix metalloproteinase inhibitor for 1998 CPA was well tolerated at all dose levels (10-150 mg) following single oral dose administration to healthy male volunteers. There was no relationship between the intensity, duration and number of adverse events reported and the dose of CPA. There was a dose-related increase in exposure as measured by AUC0-infinity and Cmax. Administration of 10 mg CPA following food resulted in a delayed tmax, and a significant decrease in Cmax but not AUC0-infinity.
9188202 Dangers of low-dose corticosteroid therapy in rheumatoid arthritis. 1997 Jun Corticosteroids, even in low doses, have substantial side effects. In addition, once they are instituted for RA it is unlikely that they will ever be stopped. Therefore, the decision to employ this therapy requires careful thought by the physician and informed consent from the patient.
10319029 Use of complementary therapies by patients attending musculoskeletal clinics. 1999 Jan Patients with musculoskeletal disorders commonly seek treatment outside orthodox medicine (complementary therapy). In patients attending hospital clinics we investigated the prevalence of such behaviour and the reasons for it. Patients attending rheumatology and orthopaedic clinics who agreed to participate were interviewed on the same day by means of a structured questionnaire in three sections: the first section about demographic characteristics; the second about the nature and duration of the complaint, the length of any treatment and whether the patient was satisfied with conventional treatment; and the third about the use of complementary medicine, the types of therapy that had been considered and the reasoning behind these decisions. The data were examined by univariate and bivariate analysis as well as logistic regression multivariate analysis. 166 patients were interviewed (99% response rate) and the predominant diagnosis was rheumatoid arthritis (22.3%). 109 patients (63%) were satisfied with conventional medical treatment; 63 (38%) had considered the use of complementary therapies, and 47 (28%) had tried such a therapy. 26 of the 47 who had used complementary therapy said they had gained some benefit. Acupuncture, homoeopathy, osteopathy and herbal medicine were the most popular types of treatment to be considered. Patients of female gender (P = 0.009) and patients who had expressed dissatisfaction with current therapies (P = 0.01) were most likely to have considered complementary medicine. These results indicate substantial use of complementary therapy in patients attending musculoskeletal disease clinics. The reasons for dissatisfaction with orthodox treatment deserve further investigation, as does the effectiveness of complementary treatments, which must be demonstrated before they are integrated with orthodox medical practice.
9493031 [Comparative study of DNA-repair ability of lymphocytes from systemic lupus erythematosus 1997 Dec Induction of DNA breaks with 4-NQO and their resynthesis in the cultivated lymphocytes of peripheral blood of 23 patients with systemic lupus erythematosus (SLE) and 12 patients with rheumatoid arthritis (RA) were studied by the method of hydroxyapatite column chromatography of cell lysates. The number of spontaneous DNA breaks was shown to increase in 48% of patients with SLE and in 42% of patients with RA, compared to that in the control. Inhibition of the repair process was observed in 35% of patients with SLE and in 17% of patients with RA. Complete repair of DNA breaks was observed in 67% of patients with RA and only in 26% of patients with SLE.
9231508 [Methotrexate and non-steroidal anti-inflammatory agent combination in rheumatoid arthriti 1997 Mar It is well known that methotrexate (MTX), used at high dosage in cancer patients, must not be combined with a non-steroidal anti-inflammatory drug (NSAID) because of high risk of side effects; prescribed at low dosage (< or = 15 mg per week) in rheumatoid arthritis patients, MTX is often combined with an NSAID. Some cases reported in the literature underline the potential toxicity of the association of low dose MTX with an NSAID, but most of the pharmacological studies do not confirm this hypothesis. Except for salicylates, NSAIDs do not affect the absorption, distribution, protein binding, area under the curve, half-life, or the elimination of MTX. Therefore, if necessary, MTX (< or = 15 mg per week) can be combined with an NSAID during the treatment of rheumatoid arthritis.
11318597 Cell surface CD28 levels define four CD4+ T cell subsets: abnormal expression in rheumatoi 2001 May CD28 is a costimulatory receptor expressed in most CD4(+) T cells. Despite the long-standing evidence for up- and downregulation of surface CD28 expression in vitro, and the key regulatory role assigned to the upregulation of CD28 counterreceptor [the CD152 (CTLA-4) molecule], in vivo CD28 induction has attracted little attention. We studied CD28 and CD152 expression and function in 33 rheumatoid arthritis (RA) patients, 20 clinically active and 13 inactive, and in 24 healthy donors. Four subsets of CD28(-), CD28(low), CD28(int), and CD28(high) peripheral blood human CD4(+) T cells were defined using three-color flow cytometry. The three CD28(+) subsets displayed a one-, two-, or threefold quantitative difference in their relative number of CD28 antibody binding sites, respectively (P < 0.01). RA patients, whether active or inactive, showed a distinct phenotype when compared to healthy donors: (i) the percentage of CD4(+)CD28(high) cells was increased twofold and the CD4(+)CD28(low) subset was reduced twofold (P < 0.01) and (ii) the CD4(+)CD28(high) cells from RA patients showed an in vivo activated phenotype, CD45RO(+)CD5(high)IL-2Ralpha(+) (P < 0.01). Active RA patients were different from inactive patients. They showed a twofold increase in mean CD28 expression (P < 0.05), whereas each of the CD28(+) subsets in the inactive RA patients showed reduced expression when compared to healthy donors. Notably, both active and inactive RA patients showed abnormal CD28 upregulation when T cells were activated in vitro with CD3 antibodies, but only inactive RA patients showed a hypoproliferative response to TCR/CD3 triggering when compared to healthy donors (P < 0.01). This defective proliferation was normalized by concurrent crosslinking with CD28 antibody. No differences were noted in the expression of CD152 or CD80, a CD28 and CD152 shared ligand. The disregulated in vivo expression of CD28 was related to the RA patients' disease activity and suggests that modulation of CD28 surface levels may be an additional mechanism to finely tune the delicate responsiveness/tolerance balance.
9486005 Transforming growth factor beta 1 and interleukin 4 induced alpha smooth muscle actin expr 1997 Jul OBJECTIVE: To discover if alpha smooth muscle actin expression and myofibroblastic differentiation are induced in synovial fibroblasts by cytokines found in the inflamed RA joint. METHODS: Immunofluorescent microscopy and western blotting were used to examine different cultures of human synovial fibroblasts for expression of alpha actin in the presence of the cytokines transforming growth factor beta (TGF beta 1), interleukin 1 alpha (IL1 alpha), IL4, IL6, tumour necrosis factor alpha (TNF alpha), and basic fibroblast growth factor (FGF). RESULTS: A small but significant population of cells (14.4 +/- 12.9%) expressed alpha actin under standard culture conditions. Upon treatment with TGF beta 1 there was a pronounced increase in the number of cells expressing alpha actin (68.1 +/- 5.49%), accompanied by a change in morphology to a myofibroblast-like phenotype. Other cytokines found within the inflamed joint such as IL1, TNF alpha, IL6, and basic FGF failed to induce alpha actin expression. However, IL4, which is normally absent or only present at low concentrations in the RA joint had a similar effect to TGF beta 1. It was also found that basic FGF inhibited the induction of alpha actin expression by TGF beta 1 and IL4. CONCLUSION: In the presence of TGF beta 1 or IL4, fibroblasts derived from synovial tissue or synovial fluid are induced to differentiate into myofibroblast-like cells containing the alpha smooth muscle form of actin. This differentiation is inhibited by basic FGF. It is suggested that the balance between these particular cytokines may be important in the modulation of fibroblast behaviour, which could have significant effects on joint repair mechanisms and the generation of fibrous tissue within the rheumatoid joint.
10025109 [Need and possibilities for quality management in drug therapy of patients with rheumatic 1998 Dec Only during recent years have intensive attempts been made to install a program for more objectively based quality criteria instead of the traditional subjectively and empirically determined therapeutic decisions for the application of DMARDs. The optimized quality management for this treatment should focus on factors such as: diagnosis as early as possible (basic for the introduction of DMARD therapy), reliable assessment of the individual long-term prognosis (as an important aid in the choice of the appropriate drug), prompt determination and establishment of the chosen therapy, and an optimal long-term application of this treatment (including competent control of effectiveness, tolerance, and compliance). Instrumentation for these purposes have been so far only partly available, e.g., diagnostic criteria and control guidelines. Besides the partially missing appropriate measures, maximum quality management is presently opposed by insufficient rheumatological specialist care for many RA patients--caused by the lack of specialists and a dilatory attitude towards involving them, respectively. Nevertheless, there is hope that in the course of new developments the gap between needs and benefits of quality management will grow smaller.
9135222 Detection of oncostatin M in synovial fluid from patients with rheumatoid arthritis. 1997 Mar OBJECTIVE: To measure oncostatin M (OSM) in synovial fluid from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: 20 samples of synovial fluid from patients with RA and 10 samples from patients with OA were examined using an OSM specific sandwich ELISA. RESULTS: OSM was detected at concentrations ranging from 2.36 to 901.82 pg/ml in 18 (90%) of 20 samples of synovial fluid from RA patients. There was no detectable OSM in synovial fluid from OA patients. In the RA patients, the OSM concentration in synovial fluid correlated significantly with the synovial fluid white blood cell count (r = 0.67, p < 0.01), but not with other laboratory parameters of disease activity. CONCLUSION: These findings suggest that OSM may contribute to joint inflammation in RA.
10432191 Discrimination of osteoarthritic and rheumatoid human synovial cells in culture by nuclear 1999 Jun Rheumatoid arthritic (RA) and osteoarthritic (OA) synovial cells in culture differ in their metabolic and proliferative behaviour. To assess links between these properties and nuclear changes, we used image analysis to study chromatin texture, together with nuclear morphometry and densitometry of OA and RA cells in primary culture. Chromatin pattern at the third day (D3) was heterogeneous and granular with chromatin clumps whereas at the final stage (D11) of culture a homogeneous and finely granular chromatin texture was observed. This evolution indicates global chromatin decondensation. These characteristics were more marked for RA than for OA nuclei. At each culture time, RA nuclei could be discriminated with high confidence from OA ones from parameters evaluating the organization of the chromatine texture. Nuclear image analysis is thus a useful tool for investigating synovial cell biology.
9467197 Orthopaedic manifestations of systemic disease. 1998 Jan Nuclear medicine studies can be initiated to detect or evaluate systemic diseases such as inflammatory arthritis or Paget's disease. This is usually because of the strengths of nuclear medicine studies such as high sensitivity, an ability to easily image the whole body, and typical diagnostic patterns of abnormalities. In other instances, a systemic disease may be incidentally suggested by a scintigram such as osteoporosis or hyperparathyroidism; or a focal abnormality such as a vascular necrosis may be detected that should indicate a systemic condition should be sought. Although most nuclear medicine studies have high sensitivity for disease, specificity is often less and, for a particular scan abnormality, several conditions may have to be considered. Familiarity with the varying patterns of abnormality associated with different disease is therefore vital to correct assessment.
11051018 [Significance of sagittal stability in knee prosthesis implantation--an analysis of 76 cas 1999 Jul ISSUE: How does the sagittal stability influence the outcome in unconstrained knee arthroplasty? METHOD: In order to clarify this aspect, 76 arthroplasties (10 male, 66 female, 39x gonarthrosis, 37x rheumatoid arthritis) in 61 patients with unconstrained primary knee arthroplasty were examined with a mean follow-up of 4 years. The determined values were the HSS-Score, the Knee-Society-Score, the range of motion, the flexion contracture as well as the posterior and anterior drawer with the KT 1000. The laxity was defined as the sum of the anterior and posterior drawer. RESULTS: The mean values measured were 2.9 mm for the anterior drawer, 1.9 mm for the posterior drawer and 4.8 mm for the laxity. The total patient population reached 81.3 points in the Knee Score, 70.9 points in the Function-Score and 80.7 points in the HSS-Score. The medium range of motion was determined as 103.5 degrees, the medium flexion contracture as 3.5 degrees. For an anterior drawer of > 6 mm and a posterior drawer of < 1 mm the results deteriorated significantly. A laxity of 8-11 mm gave the best score results. CONCLUSION: An anterior drawer of < 6 mm, a posterior drawer of 2-5 mm and a laxity of 8-11 mm seem to be recommendable for unconstrained knee arthroplasty.
9068288 Fasting enhances mucosal antigen specific B cell responses in rheumatoid arthritis. 1997 Feb OBJECTIVE: To evaluate the influence of fasting on the antigen specific immune responsiveness in patients with rheumatoid arthritis and healthy volunteers. METHODS: Seven rheumatoid arthritis patients and 17 healthy volunteers were immunised perorally or parenterally with influenza virus vaccine after a three to six day long period of total energy deprivation (water fast). The subsequent antigen specific antibody mediated immune response was recorded in the blood at the single cell level by the ELISPOT method. RESULTS: Short term starvation induced an enhanced antigen specific mucosa derived B lymphocyte response in rheumatoid arthritis patients and healthy volunteers. In contrast, the systemic B cell responses were not significantly altered by a total energy deprivation. CONCLUSIONS: Short term starvation increases the mucosa derived B cell responsiveness, while systemic responsiveness is largely unaffected. The similar pattern of response in rheumatoid arthritis patients and healthy volunteers indicates that fasting alters the mucosal immune response independently of medical treatment.
11136883 Rheumatology telephone helplines: an activity analysis. South and West of England Rheumato 2000 Dec BACKGROUND: Anecdotal evidence suggests that the services offered by rheumatology telephone helplines in the UK vary widely between NHS Trusts because of the lack of national or European guidelines. OBJECTIVE: To conduct an activity analysis of six NHS Trust rheumatology telephone helplines in the south and west of England. METHODS: Serial data were collected on the first 100 calls received on or after 1 January 1999 by six rheumatology helplines in the south and west of England. Background information was gathered on the management, availability, setting and purpose of each helpline. Data on the time taken to manage these calls and patient satisfaction were not collected. RESULTS: Patients with rheumatoid arthritis were the major users and no significant differences were found in the outcome of their calls between centres, but wide variations were revealed in the management of the helplines, the populations they serve and the services they offer. CONCLUSION: The rheumatology helpline services in six NHS Trusts in the south and west of England were shown to be the same in name only. They lacked uniformity in the delivery of care and accessibility to relevant patient groups. The geographical variation in service delivery may result in patient dissatisfaction and confusion if a number of hospitals are attended over the course of a patient's chronic disease. Further research is required to identify the helpline needs of the broader rheumatology population, patient satisfaction, outcomes and system costs, and to progress towards the development of national and European guidelines.
9826720 Perturbation of the T cell repertoire in rheumatoid arthritis. 1998 Nov 24 Aberrations in the T cell repertoire with the emergence of oligoclonal populations have been described in patients with rheumatoid arthritis (RA). However, the extent of the repertoire perturbations as well as the underlying mechanisms are not known. We now have examined the diversity of the peripheral CD4 T cell repertoire by determining the frequencies of arbitrarily selected T cell receptor (TCR) beta-chain sequences. Healthy individuals displayed a highly diverse repertoire, with a median frequency of individual TCR beta-chain sequences of 1 in 2.4 x 10(7) CD4 T cells. In RA patients, the median TCR beta-chain frequency was increased 10-fold, indicating marked contraction of the repertoire (P < 0.001). The loss in TCR diversity was not limited to CD4 memory T cells but also involved the compartment of naive T cells, suggesting that it reflected an abnormality in T cell repertoire formation and not a consequence of antigen recognition in the synovium. Also, control patients with chronic inflammatory disease such as hepatitis C expressed a diverse repertoire indistinguishable from that of normals. Telomere length studies indicated an increased replicative history of peripheral CD4 T cells in RA patients, suggesting an enhanced turnover within the CD4 compartment. Compared with age-matched controls, terminal restriction fragment sizes were 1.7 kilobases shorter (P < 0.001). These data demonstrate an altered CD4 T cell homeostasis in RA that may contribute to the autoimmune response as well as to the immunodeficiency in these patients.
10074594 MPO-ANCA necrotizing glomerulonephritis related to rheumatoid arthritis. 1998 Nov Two patients with rheumatoid arthritis (RA) developed necrotizing crescentic glomerulonephritis with high titers of anti-myeloperoxidase antibodies (MPO) in the absence of overt extrarenal vasculitis. We therefore suggest that in some patients with RA, MPO-ANCA necrotizing glomerulonephritis (GN) may occur as a kidney-limited form of rheumatoid vasculitis, and that RA should be added to the list of diseases potentially associated with necrotizing GN with anti-MPO antibodies. These observations also point out the importance of repeatedly evaluating titers of anti-MPO antibodies in the course of RA, especially if renal impairment or abnormal urinary sediment are present.
10817554 Single values of serum transferrin receptor and transferrin receptor ferritin index can be 2000 May OBJECTIVE: To elucidate the use of serum transferrin receptor (sTfR) to distinguish between iron-deficiency anemia (IDA) and anemia of chronic disease (ACD), and to establish an improved scheme to identify functional iron deficiency (FID) in rheumatoid arthritis (RA) patients with anemia. METHODS: We studied 30 anemic RA patients whose iron status was confirmed by bone marrow examination and determination of the sTfR level, serum ferritin level, and sTfR-log ferritin index (TfR-F Index). All patients with diminished or exhausted iron stores (n = 18) received oral iron supplementation. RESULTS: Baseline values of sTfR and the TfR-F Index predicted the response correctly in all patients who received supplementation treatment and were normal in 10 of 11 patients with normal initial iron stores (ACD). CONCLUSION: The results of this study elucidate the roles of sTfR and the TfR-F Index in the differential diagnosis between IDA and ACD and provide direct evidence that these parameters are useful in detecting FID, irrespective of the concurrent iron storage status.
10922468 Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protei 2000 Jul 28 Matrix metalloproteinase (MMP)-19 and MMP-20 (enamelysin) are two recently discovered members of the MMP family. These enzymes are involved in the degradation of the various components of the extracellular matrix (ECM) during development, haemostasis and pathological conditions. Whereas MMP-19 mRNA is found widely expressed in body tissues, including the synovium of normal and rheumatoid arthritic patients, MMP-20 expression is restricted to the enamel organ. In this study we investigated the ability of MMP-19 and MMP-20 to cleave two of the macromolecules characterising the cartilage ECM, namely aggrecan and the cartilage oligomeric matrix protein (COMP). Both MMPs hydrolysed aggrecan efficiently at the well-described MMP cleavage site between residues Asn(341) and Phe(342), as shown by Western blotting using neo-epitope antibodies. Furthermore, the two enzymes cleaved COMP in a distinctive manner, generating a major proteolytic product of 60 kDa. Our results suggest that MMP-19 may participate in the degradation of aggrecan and COMP in arthritic disease, whereas MMP-20, due to its unique expression pattern, may primarily be involved in the turnover of these molecules during tooth development.
9641509 A self-report Thompson articular index: what does it measure? 1998 The aim of this study was to investigate the reliability and validity of the self-report Thompson articular index (ThAI) in Dutch patients with rheumatoid arthritis (RA). A rheumatologist assessed the ThAI in 43 patients with RA. Patients completed the self-report ThAI and the AIMS-2 questionnaire to assess physical function, pain, mood and level of tension. Blood samples were taken to measure the erythrocyte sedimentation rate (ESR). After 4 weeks, patients were sent a questionnaire for a repeat assessment of the self-report AI. The test-retest reliability of the self-report ThAI was adequate (ICC=0.83). There was low agreement between ThAI scores from patients and AI scores assessed by the rheumatologist (ICC=0.44). Self-report ThAI scores (mean=230.5) were significantly higher than the rheumatologist's scores (mean=110.8). Levels of agreement between patients and rheumatologist for individual joints were disappointing, ranging from 49% to 74% (Cohen's kappa from -0.02 to 0.48). The rheumatologist's ThAI scores correlated significantly with ESR (r=0.55) and physical function (r=0.44), but not with pain, mood or level of tension. Patients' scores correlated significantly with physical function (r=0.51), pain (r=0.43), and mood (r=0.36) but not with ESR or level of tension. In regression analyses the only significant predictor of the rheumatologist's ThAI scores was ESR, and for patients' scores physical function, thus showing that patients' responses are not confounded by mood or level of tension. In conclusion, the self-report ThAI is a reliable measure, but the validity is questionable because of the non-significant correlation with ESR and the low level of agreement between patients and rheumatologist. The results indicate that self-reported joint involvement is more closely related to physical function than to arthritic activity.