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ID PMID Title PublicationDate abstract
8724190 Radiographic evaluation of the upper cervical spine in rheumatoid arthritis: a retrospecti 1996 We analysed retrospectively 295 lateral roentgenograms of the cervical spine in 150 patients with classic or definite rheumatoid arthritis. In addition to measuring the atlantodental interval, measurements of the different vertical parameters described by McGregor, Ranawat and Redlund-Johnell and a new measurement method with high reproducibility were described and their results compared statistically. As a control group we analysed 100 lateral roentgenograms of the cervical spine in patients with no inflammatory disease, posttraumatic lesion, tumour or osseous deformity.
7876045 Malondialdehyde as a sensitive marker of inflammation in patients with rheumatoid arthriti 1994 Oct Malondialdehyde (MDA) levels in the serum were estimated by MDA-TBA (Thiobarbituric Acid) spectro colorimetric assay method in 23 rheumatoid arthritis (RA) patients and were compared with those in 18 healthy subjects. It was found that the mean levels of MDA (265.15 +/- 68.8 n moles/100 ml) in patients with RA were found to be significantly elevated when compared to the mean of that of controls (128.76 +/- 37.8 n moles/100 ml). This study reveals that MDA assessment appears to be a sensitive marker of inflammation in this chronic auto immune disorder and would help in understanding the nature of inflammatory damage at a cellular level.
7878694 Methotrexate in rheumatoid arthritis--a limited sampling strategy for estimation of the ar 1994 Dec A limited sampling strategy for determination of the area under the plasma concentration versus time curve (AUC) of methotrexate (MTX) in patients with rheumatoid arthritis (RA), treated with weekly oral doses, has been validated. Stepwise linear regression analysis was used for optimal inclusion of data points in mathematical models to estimate AUC. A new plot for evaluation of the accuracy and precision of the estimated AUC values was introduced in the present study. By plotting the ratio of determined/estimated AUC values versus estimated AUC values, the influence of number of sampling points on the precision and accuracy of estimated AUC values was easily validated. Our results show that AUC values of MTX in RA patients can be estimated from a single plasma sample at 3 h or preferably, due to increased precision, by additional samplings at 5 and 1 h. A further increase of the number of sampling points increased the precision of the AUC estimates only to a minor extent. The accuracy of the estimated AUC values was independent of the number of sampling points. A limited sampling procedure can now be used for further studies on the relationship between MTX levels and its effects.
8475681 [Radiosynovectomy with dysprosium-165 iron hydroxide]. 1993 Treatment of chronic rheumatoid synovitis (RS) is directed to control the inflammatory process causing pain and disability. Radiation synovectomy is suggested to be an alternative to surgical treatment, but its clinical use has been restricted because of significant leakage (> 10%) associated with the use of the standard radionuclide 90-Yttrium (used as 90-Yttrium silicate colloid) and because of its long physical half-life of 64 hours prolonging the patients' stay in the hospital. 165-Dysprosium possesses promising nuclear properties for the treatment of patients suffering from RS. The maximum soft tissue penetration of its beta-particles is 5.7 mm which is the range being necessary to penetrate the inflamed synovia. Using as carrier ferric hydroxide macroaggregates (DFH) 165-Dy is expected to minimize the cumulative radiation dose to non-target organs by its very low leakage. Animal studies were performed in 13 rats and 6 rabbits to obtain the rationale and safety data for its clinical evaluation. These studies revealed that 98.2 +/- 0.6% of the injected dose remained in the joint with a nontarget organ uptake of less than 0.1%. Clinical results were obtained from 8 patients with rheumatoid arthritis. 24 hours after injection scintigraphy was performed over the treated joint and the liver region revealing no detectable leakage of the injected activity from the joint. Blood pool activity was also assessed revealing a leakage of 0.02% of the dose injected in the knee 24 hours after injection.(ABSTRACT TRUNCATED AT 250 WORDS)
7799339 Progression of erosion and joint space narrowing scores in rheumatoid arthritis assessed b 1994 Sep OBJECTIVE: To determine whether the first order kinetics model or the function proportional to the square root of disease duration better represents the progression of radiographic damage according to the disease duration than a linear model in rheumatoid patients. METHODS: Two hundred twenty-eight patients assessed at a single time point were studied by using 2 nonlinear models of radiographic damage. In 44 patients a second radiographic analysis was taken within a 3-year period. RESULTS: In this data set, both models reveal the highest rate of progression in the first 3 years of the disease. The square root of the disease duration seems to better depict the whole disease course. CONCLUSION: Nonlinear models should be compulsory in the assessment of radiographic damage, especially when slow acting antirheumatic drug effects after 5 years of disease duration are studied.
7492352 Upregulated expression of IL-4 receptors and increased levels of IL-4 in rheumatoid arthri 1995 Aug The level of IL-4R expression on peripheral lymphocyte subsets from rheumatoid arthritis (RA) patients and controls was studied by flow cytometric analysis of the binding of phycoerythrin-labelled IL-4 (PE-IL-4). In normal lymphocytes, IL-4R is mainly expressed on CD19+ cells, although it was also seen, at lower levels, on CD3+, CD4+ and CD8+ cells. In RA patients, a significantly increased spontaneous expression of IL-4R was observed, compared with controls, in the CD3+, CD4+ and CD19+ cell subsets. No significant differences in IL-4R expression were found between patients receiving steroids and those who were not, suggesting that steroids are not involved in upregulating IL-4R levels in vivo. Because IL-4 is a potent upregulator of IL-4R, we considered the possibility that incremented levels of circulating IL-4 in RA accounted for the high surface expression of IL-4R. By ELISA, we found abnormally high levels of immunoreactive IL-4 in 35.13% of patient serum samples, while it was undetectable in control sera. In addition, we examined IL-4 mRNA expression by polymerase chain reaction (PCR) in the PBMC of patients and controls. IL-4 PCR products were observed in four out of 10 patients studied but in none of the controls. No correlation was observed between the seric concentrations of IL-4 and IL-4R, indicating that activator factors other than IL-4 contribute to the upregulation of IL-4R expression in RA. Since the patients' sedimentation rate and CRP values did not correlate with the concentration of circulating IL-4, we conclude that this lymphokine does not contribute to the deleterious effect of the disease. Rather, due to its antiinflammatory properties, the overproduction of IL-4 in RA may be a compensatory mechanism neutralizing the harmful effect of activated macrophages.
7859417 Human recombinant IL-2 augments immunoglobulin and induces rheumatoid factor production by 1995 Mar Recombinant (r) human IL-2 was administered in vivo to improve homing and engraftment of rheumatoid arthritis (RA) patients' peripheral blood mononuclear cells (PBMC) into severe combined immunodeficient (SCID) mice. Human rIL-2 treatment resulted in augmented human Ig production and induced IgM rheumatoid factor (RF) of human origin in SCID-RA chimeras. The increment of human serum IgG in SCID-RA chimeras after IL-2 treatment ranged between 15 and 43% and for IgM between 50 and 98% during 2-8 weeks postengraftment. Human IgM-RF was detectable after 1 to 2 weeks after engraftment and persisted over a period of 10-13 weeks. No RF was produced in SCID mice engrafted with PBMC from healthy individuals with or without exogenous rIL-2 administration. Thus, human rIL-2 expanded autoreactive clones involved in the production of RF in the SCID-RA chimeras. The present study provides a novel approach to establish an in vivo SCID-RA model to study the cellular and molecular mechanisms involved in the production of RF and development of a RA-like lesion.
8651970 Malignancy in systemic lupus erythematosus. 1996 Jun OBJECTIVE: To estimate the risk of cancer in patients with systemic lupus erythematosus (SLE). METHODS: Patients with SLE (n = 724) have been followed prospectively, for 24 years, at the University of Toronto Lupus Clinic. The diagnosis of cancer was confirmed by histologic or autopsy reports. Standardized rates of cancer and standardized incidence rates (SIR) (ratio of observed-to-expected cancers) were used to estimate the risk for cancers. RESULTS: Twenty-four cancers were identified in 23 SLE patients (3.2%) during 7,233 patient-years of followup. Compared with the Ontario population, the overall estimated risk for all cancers was not increased in the lupus cohort (SIR 1.08, 95% confidence interval 0.70-1.62). A 4.1-fold increased risk for hematologic cancers was observed, due mainly to an increased risk of non-Hodgkin's lymphoma. The risk for cancer was significantly lower in the SLE cohort compared with patients with rheumatoid arthritis (RA) and systemic sclerosis (SSc). CONCLUSION: SLE is associated with a lower risk of all cancers compared with RA and SSc, but an increased risk for non-Hodgkin's lymphoma compared with the general population.
8945509 Organ-specific disease provoked by systemic autoimmunity. 1996 Nov 29 Rheumatoid arthritis (RA) is a chronic joint disease characterized by leukocyte invasion and synoviocyte activation followed by cartilage and bone destruction. Its etiology and pathogenesis are poorly understood. We describe a spontaneous mouse model of this syndrome, generated fortuitously by crossing a T cell receptor (TCR) transgenic line with the NOD strain. All offspring develop a joint disease highly reminiscent of RA in man. The trigger for the murine disorder is chance recognition of a NOD-derived major histocompatibility complex (MHC) class II molecule by the transgenic TCR; progression to arthritis involves CD4+ T, B, and probably myeloid cells. Thus, a joint-specific disease need not arise from response to a joint-specific antigen but can be precipitated by a breakdown in general mechanisms of self-tolerance resulting in systemic self-reactivity. We suggest that human RA develops by an analogous mechanism.
7687941 [Evaluation of the efficacy of intra-articular administration of somatostatin in rheumatoi 1993 May The above study was undertaken in order to evaluate the efficacy of intra-articular somatostatin in rheumatoid arthritis. Twelve patients were enrolled and all of them concluded the experiment of three consecutive intra-articular somatostatin injections of 750 mcg at two-weekly intervals. All patients reported a statistically significant reduction in painful symptomatology, particularly of pain during active movement, pain at climbing stairs, and morning stiffness. In one patient, telethermography revealed complete subsidence of articular inflammation. There were neither local nor systemic side effects.
8591652 Antimicrobial therapy for rheumatoid arthritis. 1995 Nov New interest in the use of antibiotics in the treatment of arthritis was stimulated by two factors: (1) observations that, in some forms of chronic arthritis, microbial antigens persist in the synovial membrane, and (2) the increasing knowledge of the anti-inflammatory and immunosuppressive effects of antibiotics. Recently, several published controlled studies reported a beneficial effect of tetracyclines on RA and reactive arthritis. Whether the anti-arthritic activity of the tetracyclines investigated is mediated by the antimicrobial, anti-inflammatory or immunomodulatory properties remains to be determined. It may be concluded from these studies that tetracyclines have a beneficial effect on RA, especially when laboratory parameters are considered. The effect on the clinical parameters is not unequivocal. The adverse effects seem to be mild but the long-term efficacy and safety of tetracyclines as disease-modifying antirheumatic drugs remain to be demonstrated.
8833045 Adrenal and gonadal steroid hormone deficiency in the pathogenesis of rheumatoid arthritis 1996 Mar Rheumatoid arthritis (RA) is a multifactorial disease in which both environmental and genetic factors play a role. Data also suggest that neuroendocrine factors are involved. I briefly summarize observations that support this hypothesis. RA is characterized by striking age-sex disparities. The incidence of disease in women increases steadily from the age of menarche to its maximal incidence around menopause. The disease is uncommon in men under age 45, but its incidence increases rapidly in older men and approaches the incidence in women. These observations strongly suggest that androgens play a major suppressive role, and, in fact, testosterone levels are depressed in most men with RA. Mechanistically, many data indicate that testosterone suppresses both cellular and humoral immune responses. Dehydroepiandrosterone (DHEA), an adrenal product, is the major androgen in women. Its production is strikingly dependent upon age. Peak production is in the 2nd and 3rd decades, but levels decline precipitously thereafter. DHEA levels are low in both men and women with RA, and recent data show that levels of this hormone may be depressed before the onset of disease. The role of DHEA in immune diseases, however, is controversial. The menopausal peak of RA onset suggests estrogen and/or progesterone deficiency play a role in the disease, and many data indicate that estrogens suppress cellular immunity but stimulate humoral immunity, i.e., deficiency promotes cellular (Th1-type) immunity. Recent data also indicate that progesterone stimulates a switch for Th1 to Th2-type immune responses. RA often develops or flares in the postpartum period, particularly if the mother breastfeeds. This is again consistent with gonadal steroid deficiency playing a role in the onset of disease. Breastfeeding is associated with blunted hypothalamic-pituitary-adrenal function and elevated prolactin synthesis. Gonadal and adrenal steroid hormone deficiency, plus elevated prolactin, probably greatly facilitates the expression of Th1-type immunity, which is widely believed to be critical in the pathogenesis of RA. By contrast, RA typically remits during pregnancy, in parallel with the increasing levels of corticosteroids, estrogens, and progesterone. Pregnancy is characterized by a shift in immune function from Th1-type to Th2-type. Oral contraceptives, which generate a condition of pseudopregnancy, also decrease the risk of RA. These data argue that adrenal and gonadal steroid hormones suppress the development of RA. Several studies indicate that corticosteroid production is inappropriately low in patients with RA, and are reminiscent of observations in Lewis rat models of chronic erosive arthritis. In summary, a growing body of data indicate that RA develops as a consequence of a deficiency in both adrenal and gonadal steroid hormone production. This hypothesis clearly has potential clinical implications.
7582702 Discordance between objective and subjective assessment of functional ability of patients 1995 Oct The objectives were to investigate whether there is a discordance between observed and reported functional ability in patients with rheumatoid arthritis (RA) as measured by the Health Assessment Questionnaire (HAQ) and, if so, which demographic, clinical and psychological factors contribute to that discordance. Fifty-one consecutive RA patients of the out-patient clinic were included. Self-reported functional ability was compared with the observed performance of tasks as described by the HAQ. The amount of discordance was computed by subtracting reported scores from observed scores. A positive sign stands for overestimation of functional ability by the patient. The average amount of discordance was low, 0.09 (S.D. 0.39), but showed a large range: -0.88 to 1.00. Multiple regression analysis showed that male patients overestimate their functional ability by 0.21 HAQ units compared with female patients. RA patients overestimate their functional ability with increasing disease duration and severity, while RA patients in the early stage of the disease tend to underestimate their functional ability.
8394794 Macrophages, synovial tissue and rheumatoid arthritis. 1993 May Macrophage-like synoviocytes originate in the bone marrow, like other mononuclear phagocytes, and are constantly replaced via the circulation. In rheumatoid synovium sections, 80-100% of the synovial lining cells are macrophage-like cells functioning as antigen processing- and antigen-presenting cells to T lymphocytes. Monocyte and lymphocyte traffic into the rheumatoid arthritis (RA) synovium is mediated by adhesion molecules such as endothelial-leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecules-1 and -2 (ICAM-1 and ICAM-2), as well as monocyte chemotactic protein 1 (MCP-1) and beta 2 integrins (CD11 a,b,c/CD18). Macrophage-like cells in the RA synovium are highly activated based on their morphology, surface class II HLA antigen expression, and synthesis of cytokines such as interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage CSF, and transforming growth-factor beta (TGF-beta). Evidence for type 1 (higher affinity) and type 2 (lower affinity) androgen (ARs) and estrogen receptors (ERs) on macrophage-like synoviocytes in either male or female synovial samples from both RA patients and controls has been reported. In particular, ERs have also been found on CD8+CD29+ CD45R0+ T lymphocytes (memory), infiltrating rheumatoid synovial tissues. Sex hormones have been found to influence macrophage activity in experimental and clinical conditions such as RA. Generally estrogens have immunostimulatory effects, whereas androgens are immuno-suppressive.(ABSTRACT TRUNCATED AT 250 WORDS)
1491383 Sex hormones in postmenopausal HLA-identical rheumatoid arthritis discordant sibling pairs 1992 Nov Dehydroepiandrosterone sulfate (DHEAS), testosterone, androstenedione, 17-beta estradiol and sex hormone binding globulin have been assayed in 50 HLA-identical postmenopausal rheumatoid arthritis (RA) discordant sibling pairs. The only difference was for DHEAS, siblings with RA having a significantly lower level than their sisters. However, in 68 patients with RA, the level of DHEAS inversely correlated with disease duration, a radiographic grading score, the Health Assessment Questionnaire score, duration of morning stiffness, and a clinical score of disease activity and severity (the Spread/Severity index). These observations, taken with that of previous work on DHEAS, suggest that low levels may be a consequence of RA rather than predisposing to the disease. The role of sex hormones in RA will have to be approached in alternative ways.
8299253 EGF and EGF-r immunoexpression in Sjögren's syndrome secondary to rheumatoid arthritis. C 1993 Nov Minor labial salivary gland biopsies from 25 patients with secondary Sjögren's syndrome (SS) suffering from rheumatoid arthritis and from 11 patients complaining of ocular dryness associated with rheumatoid arthritis without proven SS, were studied for the immunohistochemical expression of Epidermal Growth Factor (EGF) and its receptor (EGF-r). Minor labial salivary glands from 11 healthy individuals were used as the control. Furthermore, the results were correlated with data retrieved from a previous study on EBV expression by the in situ hybridization method in the same specimens. In 16/25 cases of secondary SS the epithelial duct cells expressed both EGF and EGF-r, particularly in the areas of lymphoepithelial lesion and tissue destruction. Eleven of these cases expressed a positive EBV hybridization signal. In contrast, only 3/11 patients with ocular dryness and 2/11 cases from the group of healthy individuals showed immunoreactivity for EGF/EGF-r. A positive EBV signal was detected in 3/11 and 1/11 of these cases, respectively. These results indicate that EGF and EGF-r may play a crucial role in the evolution of the disease under the constant influence of EBV, which seems to up-regulate the expression of the EGF/EGF-r system.
1307491 Evaluation of the role of cytokines in autoimmune disease: the importance of TNF alpha in 1992 Cytokines and growth factors are involved in all important biological processes. Hence it is anticipated that they will be of importance in autoimmune disease. The pathogenesis of autoimmune diseases involves a number of stages, initiation, perpetuation and tissue damage, each of which involves different cell and molecular interactions. In this review, we will discuss an outline of the cytokine involvement in the various stages of autoimmune development, prior to focusing on the analysis of cytokines in rheumatoid arthritis. Cytokines exert their effect via high affinity cell surface receptors. Thus an understanding of cytokines involves the analysis of receptor expression, and also of cytokine inhibitors. Currently there is only adequate knowledge of these aspects in rheumatoid arthritis (RA), and as such the emphasis of this review is on RA. One of the major reasons for being interested in the role of cytokines in autoimmunity is to define possible therapeutic targets. There is now considerable evidence that TNF alpha is such a target in RA, and the effect of anti TNF alpha monoclonal antibody therapy in RA is discussed.
8574626 A study of ovarian function in rheumatoid arthritis. 1995 Oct Ovarian function was evaluated prospectively in 16 female rheumatoid arthritis patients in the childbearing age. None of the patients was using oral contraceptives. The control group included 31 women with tubal sterility. Serum levels of estrone, 17 beta-estradiol and progesterone were assayed and used to determine an estrogen index and a luteal index. An ovulatory score was calculated as the sum of the estrogen and luteal indices. Estrogen levels were lower in the rheumatoid arthritis group than in the control group, but the difference was not significant. No statistically significant difference was found for progesterone levels, suggesting that luteal function was normal in the rheumatoid arthritis patients. The rheumatoid arthritis group had a significantly lower mean ovulatory score reflecting a decreased likelihood of ovulation as compared with the control group (p < 0.01). This abnormality may explain why fertility is reduced in women with rheumatoid arthritis.
8833055 Chloroquine combined with cyclosporine in rheumatoid arthritis: more than the addition of 1996 Mar Combination therapy in rheumatoid arthritis (RA) with 2 or more disease modifying antirheumatic drugs (DMARD) is theoretically attractive if the drugs exert additional or even synergistic effects and have different toxicity patterns to avoid cumulative toxicity. The combination of cyclosporin A (CsA) with chloroquine has shown in in vitro studies a synergistic ability to inhibit the proliferation of peripheral blood mononuclear cells and clonal T cells and the production of interferon gamma by clonal T cells. This synergy is probably based on different mechanisms of action of the 2 drugs: CsA primarily inhibits the production of interleukin 2 (IL-2) (and other cytokines) at the level of transcription, whereas chloroquine primarily inhibits the responsiveness of T cells to IL-2 stimulation. To evaluate whether these in vitro data can be extrapolated in vivo, a large 2 phase trial has been initiated in the Netherlands in which the combination of CsA with chloroquine is evaluated in patients with RA.
8712878 Course and characteristics of anaemia in patients with rheumatoid arthritis of recent onse 1996 Mar OBJECTIVE: To describe the incidence, cause, and course of anaemia in rheumatoid arthritis (RA). METHODS: Medical records of 225 patients who received a diagnosis of RA between 1990 and 1992 were reviewed longitudinally for mention of anaemia. Anaemia was classified as anaemia of chronic disease if ferritin concentrations reflected adequate body iron stores. Among iron depleted anaemic patients, iron deficiency anaemia was identified using the response to iron supplementation. RESULTS: Anaemia developed in 64% of the patients, mostly within 18 months of follow up, but disappeared again in 54% of those patients. The prevalence of anaemia varied from 39% to 53% throughout follow up. Iron depletion was found in 38% of anaemic patients; 40% of them did not recover from their anaemia after iron supplementation and were classified as having anaemia of chronic disease. Anaemia of chronic disease thus caused 77% and iron deficiency anaemia 23% of observed anaemia. Recovery from anaemia occurred in 42% of the patients with anaemia of chronic disease and in 72% of iron depleted patients after iron supplementation. Anaemic patients, particularly those with anaemia of chronic disease, had a significantly greater number of the American College of Rheumatism criteria for RA, significantly more erosive joint damage, and significantly increased concentrations of serum rheumatoid factor than patients without anaemia. CONCLUSION: Anaemia appeared as a frequent and dynamic manifestation. Recovery and recurrence of anaemia was observed throughout follow up, leading to a longstanding and relatively high prevalence of the condition. Iron deficiency was diagnosed frequently and follow up revealed a considerable overlap with anaemia of chronic disease, making this the most important cause of anaemia in RA. Recovery from anaemia occurred more frequently in iron depleted anaemic patients than in those with anaemia of chronic disease. Anaemic patients, particularly those with anaemia of chronic disease, seemed to have a more serious course of their RA compared with non-anaemic patients.