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ID PMID Title PublicationDate abstract
1550400 Validity of single variables and composite indices for measuring disease activity in rheum 1992 Feb There is no agreement as to which variable best mirrors disease activity in rheumatoid arthritis (RA) and no studies have been performed on the validity of disease activity variables. In this study the validity of 10 commonly used single variables and three composite indices was tested. All patients participated in a large follow up study in two clinics. The patients (n = 233) had classical or definite RA and a disease duration of less than one year at entry. The mean follow up time was 30 months; the follow up frequency was once every four weeks; 6011 records were used in the analysis. The validation criteria included correlations with the other variables (correlational validity), with the physical disability (criterion validity I), and with the radiographically determined damage of hands and feet (construct validity). The judgment of a group of rheumatologists in clinical practice was also used as a model of criterion validity (II). In this comparison the disease activity score and Mallya index showed the best validity. The best single variable was the number of swollen joints. The validity of most single variables was poor and these variables were not suitable as single endpoint measures in clinical trials.
8814219 Identification of monoclonal antibodies that recognize different disulfide bonded forms of 1996 Sep 5 Thrombospondin 1 (TSP1) is a multidomain glycoprotein from platelets and cells which functions in cell-cell and cell-matrix interactions. The structure of TSP1 is regulated by sulfhydryl-disulfide interchange in the carboxy-terminal Ca2(+)-binding loops and globular domain which markedly influence its interaction with cell surface integrins and its inhibition of neutrophil enzymes. We have identified murine monoclonal antibodies that recognized different disulfide-bonded forms of TSP1, made by preparing TSP1 in buffers containing either 0.1 mM or 2 mM Ca2+. Antibody HB8432 recognizes TSP1 prepared in buffers containing either 0.1 or 2 mM Ca2+, while antibodies D4.6 and A65M recognized only TSP1 prepared in buffers containing 0.1 mM Ca2+. The antibodies recognize these different TSP1 preparations either adsorbed to plastic or extracellular matrix. Immunohistochemistry of human rheumatoid synovial tissue using HB8432 resulted in staining of numerous blood vessel walls and matrix cells, while D4.6 and A65M stained a subset of the HB8432 positive blood vessels and only occasionally stained matrix cells. These results suggested that different disulfide-bonded forms of TSP1 were being expressed in different areas of inflamed tissue.
7531793 Expression of vascular cell adhesion molecule-1 mRNA and protein in rheumatoid synovium de 1995 Feb BACKGROUND: Vascular cell adhesion molecule-1 (VCAM-1) is expressed in synovial tissue of patients with rheumatoid arthritis. VCAM-1-protein has been demonstrated in nonvascular cells beside a vascular expression of this molecule. There are conflicting results about the nonvascular cell types expressing VCAM-1. EXPERIMENTAL DESIGN: For the evaluation of VCAM-1 expression in rheumatoid synovium, this molecule has been demonstrated by alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. Furthermore, VCAM-1 mRNA has been demonstrated by in situ hybridization to evaluate de novo synthesis of this molecule in vivo. To elucidate the nature of the cell types expressing VCAM-1 mRNA, this molecule has been shown by combined in situ hybridization for VCAM-1 and immunohistochemistry in the same tissue section. Double labeling has been performed with anti-collagen type IV monoclonal antibodies to delineate endothelial cells and pericytes and with anti-CD68 antibodies to elucidate the expression of VCAM-1 mRNA in fibroblast-like (type B) or macrophage-like (type A) synoviocytes. RESULTS: Although it has been reported that VCAM-1 occurs on endothelial cells after cytokine stimulation, we show that vascular expression of VCAM-1 mRNA and protein was minimal and restricted to small vessels beneath the lining cell layer. Further expression of VCAM-1 mRNA could be demonstrated in pericytes outside the collagen type IV containing vascular basement membrane. With respect to the expression of VCAM-1 in the synovial lining layer, we could clearly demonstrate by combined in situ hybridization and immunohistochemistry that CD68 positive cells of the monocyte/macrophage lineage in the lining layer (type A cells) do not express VCAM-1 mRNA and that the expression of VCAM-1 mRNA in the lining layer was restricted to fibroblast-like synoviocytes (type B cells). Scattered stromal cells revealing VCAM-1 mRNA were also CD68 negative. CONCLUSIONS: The strong expression of VCAM-1 in the fibroblast-like cells of RA synovium and the lack of expression in the vascular endothelium suggest that the major role of VCAM-1 appears to be associated with the proliferating synovial cells prone to attach and subsequently invade articular cartilage.
8850147 [A case of isolated jejunal ulcer and review of the literature]. 1995 Nov The case of a patient with past history of rheumatoid arthritis and chronic use of non-steroidal anti-inflammatory drugs that presented a solitary yeyunal ulcer with perilesional stenosis is described. Clinically it was manifested as intermitent bowel obstruction and the diagnosis was made during the exploratory laparotomy. Literature was reviewed and the importance of the diagnosis, specially the radiological one is emphasized.
8317319 Leukocyte activation and function-associated antigens in inflammatory disease. 1993 Expression of adhesion molecules, CD11a, CD11b and CD18, and of the function-associated molecules CD3, CD4, CD8, CD16, CD19, CD56 and CD57 was assayed on peripheral blood leukocytes from normal control subjects (n = 10), and from patients with adult periodontitis PD (n = 9), ankylosing spondylitis AS (n = 11) and rheumatoid arthritis RA (n = 14). A novel rapid fixation leukocyte preparation technique was used which prevents artefactual up-regulation of surface antigens. In RA patients, the percentage of CD18+ lymphocytes was decreased and that of CD11b+ neutrophils was increased. On lymphocytes the mean fluorescence intensity (MFI) of both CD11b and CD18 was decreased whereas that of CD57 was increased. In AS patients the percentages of CD11b+ lymphocytes and neutrophils were increased and CD18+ lymphocytes and neutrophils were decreased. On lymphocytes the MFIs of CD11b and CD18 were decreased, whilst that of CD16 was increased. On neutrophils the MFI for CD18 was increased. No significant differences (p < 0.01) were seen for the periodontitis patients. It is suggested that the antigen expression on peripheral blood cells from RA and AS patients is consistent with leukocyte activation.
1402268 The Sauvé-Kapandji operation. Technique and results. 1992 Aug For distal radio-ulnar joint disorders, the Sauvé-Kapandji procedure, previously attributed to Lauenstein, of arthrodesis of the joint and distal ulnar pseudarthrosis is a very useful procedure, yet is not often practised. This paper describes the technique and presents the results of 81 procedures in 71 patients. There was excellent patient satisfaction. The procedure is a reliable and effective method of dealing with distal radio-ulnar joint disorders, especially in rheumatoid arthritis and following distal radial fractures. Some changes to previous techniques are emphasized.
8525392 Peripheral ulcerative keratitis in the setting of rheumatoid arthritis: treatment with imm 1995 Aug Peripheral ulcerative keratitis (PUK) is a rare but serious inflammatory eye condition that can complicate rheumatoid arthritis. PUK can be a warning sign of impending vasculitis, and cytotoxic therapy may be necessary to induce remission. We have encountered three patients with PUK in the past year. Two patients had long-standing quiescent rheumatoid arthritis who developed photophobia. Diagnosis was made by slit lamp examination. Treatment with local cyclophosphamide and prednisone resulted in prompt remission of the ulcer within 8 weeks. Cytotoxic therapy was discontinued altogether within 6 months. The third patient was also treated successfully with oral steroids and azathioprine. In all patients, sicca was noted. None of them had any evidence of systemic vasculitis. PUK, when recognized early and treated aggressively, can result in remission of the ulcer and in the prevention of vasculitis. Keratoconjunctivitis sicca can accompany PUK independent of the activity of rheumatoid arthritis.
8546721 Responsiveness of human T lymphocytes to bacterial superantigens presented by cultured rhe 1996 Jan OBJECTIVE: Type B fibroblastic synoviocytes are abundant in inflamed joints of patients with rheumatoid arthritis (RA), and can secrete cytokines and other mediators of inflammation. The aim of this study was to determine whether cell lines derived from RA type B synoviocytes could also serve as accessory cells for T lymphocyte activation. METHODS: Cells from RA synoviocyte lines, with or without preculture in interferon-gamma (IFN gamma), were cultured with purified peripheral blood T cells, in the presence or absence of superantigens or other accessory cell-dependent T cell mitogens. T cell proliferation was measured by thymidine incorporation, and synoviocyte surface markers were analyzed by flow cytometry. RESULTS: RA type B synoviocyte lines were potent accessory cells for T cell responses to bacterial superantigens or lectins, and direct cell-cell contact was required. Preculture in IFN gamma augmented synoviocyte expression of major histocompatibility complex (MHC) class II molecules and of ligands for some T cell costimulatory receptors, but synoviocyte accessory cell function was evident even in the absence of IFN gamma. Blocking studies using monoclonal antibodies supported the notion of a role CD2, CD11a/CD18 and MHC class II molecules in synoviocyte-dependent T cell activation. Monoclonal antibodies against IFN gamma, interleukin-1 beta (IL-1 beta), IL-6, IL-8, and tumor necrosis factor alpha failed to block the T cell proliferative responses, but anti-IL-2 was strongly inhibitory. CONCLUSION: Cultured RA and type B synoviocytes can perform some of the functions of professional antigen-presenting cells. If such cells have similar properties in vivo, they may be important participants in activation of immune responses, in addition to their previously described synthetic and proinflammatory roles. If RA synovial tissue T cells, like normal peripheral blood T cells, can respond to superantigens presented by synoviocytes, this interaction could be important in the pathogenesis of RA.
1517532 Effects of famotidine on various immunological parameters in patients with rheumatic disea 1992 We examined the effect of famotidine, a histamine-type 2 receptor antagonist, on the immunocompetent cells. The number of DR(+) cells were significantly decreased in patients with systemic lupus erythematosus (P less than 0.05) by parenteral administration of famotidine (40 mg/days for 4 weeks). However, total lymphocyte number and monocyte number did not change. Immunoglobulin levels of patients with rheumatoid arthritis and normal male did not change. Furthermore, phytohemagglutinin induced lymphocyte proliferation was increased by addition of famotidine (10 ng/ml). Nonetheless, famotidine did not have mitogenic function itself to lymphocyte and did not affect IL-2 production.
1457494 Characterizing the meaning of psychological distress in rheumatoid arthritis. 1992 Sep Symptoms of depression are frequently reported by people with rheumatoid arthritis (RA). To advance our understanding of how best to assess and treat these symptoms, their meaning must be elucidated. This article explores two possible meanings for the emotional distress of RA patients reported on the Center for Epidemiological Studies Depression (CES-D) scale: (1) Certain CES-D scale items may inflate actual depressive symptom scores. (2) Depressive symptoms are experienced and/or expressed in unique ways in an RA population due to the presence of chronic physical symptoms. In this study of 988 people with RA, it was found that there is some modest inflation of the CES-D scale due to the items of "having difficulty getting going" and "everything was an effort." However, irrespective of the modest inflation of the scale, there is evidence that distress in RA is not a static concept. Distress in this RA population was expressed differently from that of a community population, and within the RA population, distress was expressed differently over time.
8833053 Cost effectiveness analysis of drug therapies for rheumatoid arthritis. 1996 Mar We know very little about the relative cost effectiveness of commonly used drug treatments for rheumatoid arthritis (RA), largely due to difficulty obtaining appropriate data and the complexity of the required analysis. There is growing interest in combination therapy for RA. However, it is unclear whether combination therapy will be associated with increased benefit compared to monotherapy, and whether the degree of benefit will offset the anticipated increased costs. We show 3 specific examples derived from a longitudinal database of adults with RA in which we compare the cost effectiveness of longterm drug regimens. Functional status serves as our measure of effectiveness, and we use a conservative estimate of the total annual cost of drug therapy. We also consider the analytic complexity of differences in baseline disease activity. These examples illustrate that in addition to variability in baseline disease activity, there is also substantial variability over time in both effectiveness and costs associated with drug treatment. This variability underscores the importance of considering both the relative effectiveness and costs when making treatment decisions. To make progress in the area of cost effectiveness of longterm treatments for RA and other chronic conditions, it is essential that studies of treatment continue for sufficiently long periods and that relevant cost information be collected in conjunction with measures of effectiveness.
7744133 Double-blind comparison of the efficacy of diclofenac/misoprostol and diclofenac in the tr 1994 A double-blind, randomised, parallel-group study was conducted in eight countries to compare the efficacy of a fixed combination of diclofenac sodium (50 mg) and misoprostol (200 mcg) with a fixed combination of diclofenac sodium (50 mg) and placebo in treating the signs and symptoms of rheumatoid arthritis (RA). A total of 346 patients with RA who had been stabilised on diclofenac for at least 30 days were randomly assigned to receive either diclofenac/misoprostol BID or TID (n = 177) or diclofenac/placebo BID or TID (n = 169) for 12 weeks. Primary analyses of efficacy, made upon admission and at 4-week intervals, consisted of physician's global assessment of the arthritic condition, patient's global assessment of the arthritic condition, patient's global assessment of joint tenderness/pain, and physician's assessment of joint swelling. In this study, the fixed combination tablet of diclofenac sodium 50 mg/misoprostol 200 mcg administered BID or TID demonstrated no statistically significant difference in efficacy in the treatment of the signs and symptoms of RA compared with diclofenac sodium 50 mg/placebo administered BID or TID.
7775805 Immunotherapeutic strategies targeting rheumatoid synovial T-cell receptors by DNA inocula 1994 Immunotherapy against autoreactive T-cell receptors (TCRs) has been reported to have promise in several animal models of autoimmune diseases. Facilitated DNA inoculation has many potential advantages as a modality for development of specific immune responses. Specifically, this technology is able to deliver exogenous antigens for processing via both the endogenous pathway, with subsequent presentation by class-I major histocompatibility (MHC) antigens, and the exogenous pathway, with subsequent presentation by class-II MHC antigens. This allows for induction of both arms of the cellular immune system. These cellular immune responses may be particularly important in targeting and controlling pathogenic cell populations. The application of this technology to the treatment of human autoimmune diseases depends on the availability of readily manipulated systems for the evaluation of specific interventions. Here we report the full length cloning and expression of TCRs from rheumatoid arthritis synovial tissue. These were developed by recombinant polymerase chain reaction, cloning and retroviral transduction into a TCR-alpha/beta-negative murine T-cell hybridoma. Reconstitution of CD3 expression was confirmed by flow cytometry. Similar constructs have been developed for TCR-based immunotherapy by facilitated inoculation of DNA intramuscularly. Preliminary analysis of immune responses in mice indicates that these constructs elicit anti-TCR responses. These studies indicate the ability to reconstitute expression of potentially autoreactive human TCRs in a model system wherein specific immune responses elicited against these TCRs by various immunogens can be evaluated.
7777827 The risk of cancer in rheumatoid patients in Japan. 1995 In order to clarify the risk of cancer development in patients with rheumatoid arthritis (RA), the incidence of malignant tumors during a follow-up period was investigated in RA patients at the Center for Adult Diseases, Osaka, Japan. Six hundred and fifty-five eligible rheumatoid patients (131 males, 524 females) who were admitted to our institute between 1980 and 1989 were matched against the files of the Osaka Cancer Registry. Among them, a total of 26 patients (5 males, 21 females) were noted to have developed some kinds of cancer. The female RA patients demonstrated a significantly higher incidence of all cancers than the general population, with an observed/expected (O/E) ratio of 1.71 (95% confidence interval = 1.06-2.62). Cancer of the buccal cavity/pharynx and thyroid cancer also showed a higher incidence in female RA patients, with O/E ratios of 12.93 and 2.74, respectively.
8122120 Late-onset, seropositive, erosive rheumatoid arthritis. 1993 Dec This report describes the natural history, clinical features, and therapeutic requirements of late-onset seropositive and/or erosive rheumatoid arthritis (LORA). One hundred twenty-nine patients with mean disease duration of 6 years and mean age of disease onset of 66 years were studied. All patients met American Rheumatism Association criteria for rheumatoid arthritis (RA). Ninety-one percent were seropositive for rheumatoid factor, 83% had erosive disease, and 58% had significant medical problems. Therapeutically, most patients required sequential use of multiple second-line agents. Functional classification did not change significantly despite treatment, and complete remissions were unusual even with remittive therapy. It is concluded that a subset of LORA patients have seropositive aggressive, destructive disease.
7575719 Emergence of oligoclonal T cell populations following therapeutic T cell depletion in rheu 1995 Sep OBJECTIVE: To examine the compartment of CD4+ T cells in patients with rheumatoid arthritis (RA) who have developed persistent lymphopenia following antibody-mediated T cell depletion and to investigate why T cell depletion is of limited therapeutic efficacy. METHODS: Circulating T lymphocytes from 10 patients with seropositive RA treated with the monoclonal antibody (MAb) CAMPATH-1H were longitudinally monitored by fluorescence-activated cell sorter analysis with MAb. To assess the molecular diversity of repopulating T cells, random samples of T cell clones from the peripheral blood of 3 patients were analyzed by sequencing the T cell receptor (TCR) beta chains. At the time of recurring disease, the synovial tissue was examined by immunohistochemistry, and the repertoires of peripheral and synovial tissue T cells were compared by TCR beta-chain sequencing and by semiquantitative hybridization with oligonucleotides specific for the V-D-J beta junctional region of selected clones. RESULTS: The reconstitution of the peripheral T cell compartment was very slow. A mean CD4+ T cell count of 105/microliters was reached 34 weeks following MAb treatment. After treatment, the percentage of CD4+ T cells with the CD45RO+ phenotype was significantly increased (P = 0.001), indicating the expansion of antigen-primed memory T cells. TCR beta-chain sequences revealed a marked restriction in the diversity of repopulating T cells with the emergence of dominant clonotypes. Despite the low counts of peripheral CD4+ T cells, the synovial tissue was infiltrated by CD4+ T cells to a similar extent as that in RA patients not treated with MAb. Selected clonotypes that had emerged in the peripheral blood compartment dominated the repertoire of tissue-infiltrating T cells in the synovium. CONCLUSION: In patients with RA, T cell depletion induces a long-term imbalance in T cell homeostasis. Clonal proliferation of CD4+ T cells severely restricts the diversity of available T cell specificities and results in the emergence of dominant clonotypes, which accumulate in the synovial tissue despite peripheral lymphopenia.
8280401 Methotrexate in juvenile rheumatoid arthritis. Do the benefits outweigh the risks? 1993 Nov Juvenile rheumatoid arthritis (JRA) is a heterogeneous group of autoimmune diseases resulting in chronic idiopathic peripheral arthritis. The aetiology of JRA is unclear, and current pharmacotherapy is ameliorative rather than curative. Nonsteroidal anti-inflammatory drugs are given initially, but only one-third to one-fourth of patients are managed adequately with these agents. Advanced therapeutic drugs, frequently referred to as disease-modifying antirheumatic drugs or second-line agents, are given to the child with aggressive or resistant disease. Among these, the antimetabolite methotrexate has proven to be the most effective in alleviating articular disease manifestations and reducing laboratory parameters of inflammation. When given orally in low dosages (10 to 15 mg/m2/week), methotrexate is well tolerated, without evidence of substantial bone marrow suppression or severe hepatotoxicity. Extensive long term tolerability data are not yet available for children, but longitudinal studies in adult patients with rheumatoid arthritis suggest that the drug may be given safely for extended periods in many patients. Paediatric rheumatologists are beginning to give higher dosages of methotrexate (up to 1 mg/kg/week) parenterally with some success. The long term consequences of higher dose methotrexate in children are unknown. Methotrexate has now become, and will probably remain for some time, the drug of first choice for children with recalcitrant JRA.
7699619 Does a muscle strength index provide complementary information to traditional disease acti 1994 Dec OBJECTIVE: To develop a muscle strength index (MSI) and determine whether it provides complementary information to traditional disease activity variables in patients with rheumatoid arthritis (RA). METHODS: The MSI was developed on the basis of practical and empirical aspects and statistical considerations. Intra and interobserver reliability was assessed on the data from 3 observers on 2 strength measurements in each of 10 patients. The association of the MSI with variables of disease activity and severity was assessed in univariate analysis. The contribution of the MSI in the explanation of physician's global disease activity after accounting for the effect of traditional measures of disease activity was assessed in multiple linear regression models. RESULTS: Eight strength measurements (extension and flexion of knee and elbow joints) obtained with a hand held pull gauge were aggregated into the MSI as the mean of the standardized scores. In 65 patients with RA, the MSI had a high internal consistency (Cronbach's alpha 0.95) and intra and interobserver reliability (Pearson correlation coefficient 0.94 each). The MSI correlated moderately with traditional measures of disease activity and strongly with physical functional disability and radiological damage. In contrast to grip strength, the MSI explained additional variation of physician's global assessment of disease activity if added to variables of pooled activity indices. CONCLUSION: The MSI is a reliable and valid measure of disease activity and severity and may improve the content validity of pooled disease activity indices.
7966064 Evaluation of a German version of the physical dimensions of the Health Assessment Questio 1994 Jul OBJECTIVE: Our objective was to translate and adapt the disability section of the health assessment questionnaire (HAQ) into German (HAQ-G) to suit Swiss-German conditions and to test its metric properties, reliability, and validity. METHODS: We tested 62 consecutive patients with rheumatoid arthritis (RA) attending the outpatient Clinic of the Department of Rheumatology, University Hospital Zurich. All patients fulfilled the American Rheumatism Association 1987 revised criteria for RA. The translation was done by 2 translators aware of the objective of the questionnaire and some questionable items were discussed and resolved in a panel by 4 rheumatologists including one bilingual clinical researcher. Test-retest reliability was assessed with Pearson's correlation coefficient on the scores of 2 questionnaire mailed in a 10-day interval. The internal consistency was assessed with Cronbach's coefficient alpha. To assess the construct validity, we compared the HAQ scores to clinical, laboratory, and radiological variables of disease activity and outcome. To assess criterion validity, we compared physicians' assessment of functional class (observed disability) to the HAQ (referred disability). The content validity was assessed in a multivariate model explaining HAQ scores with a variety of other measurements of disease activity and outcome. RESULTS: The test-retest reliability was 0.94; the internal consistency was 0.92; the criterion validity was 0.76; and correlations with other disease variables ranged from 0.39 (Larsen radiological score) to 0.66 (grip strength). CONCLUSION: The HAQ-G is a reliable and valid instrument for measuring functional disability in a German speaking population with RA.
8948298 Quantified neurological examination with emphasis on motor and sensory functions in patien 1996 Nov A controlled study of quantified clinical neurological examination, including psychophysical assessment of sensory thresholds, in patients with rheumatoid arthritis (RA) was carried out. Fifty-five women with seropositive RA living in North Norway and 83 healthy controls underwent clinical neurological examination quantified by neurological symptom score (NSS) and neurological deficit score (NDS). Vibration threshold (VT), warm-cold detection threshold (limen) as well as heat pain detection threshold (HPDT) were performed to evaluate afferent myelinated and unmyelinated fibre functions. Higher scores on NSS and NDS were seen in RA patients compared with the controls. Higher index finger and big toe VT was demonstrated in the patients, while results from warm-cold limen and HPDT were not significantly different in the two groups. Among the disease-related variables, the most prominent finding was a positive association of index finger VT with disease duration in the patients (P = 0.01). Maximum walking time (15 m) was a significant predictor of big toe VT in the patient group (P = 0.0001). This study suggests impaired peripheral nerve function in afferent myelinated fibres. However, involvement of dorsal column fibres cannot be excluded, although patients with radiological atlantoaxial subluxation were not included in this study.