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ID PMID Title PublicationDate abstract
11724645 Differential roles of nitric oxide and oxygen radicals in chondrocytes affected by osteoar 2001 Dec Osteoarthritis and rheumatoid arthritis are characterized by focal loss of cartilage due to an up-regulation of catabolic pathways, induced mainly by pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFalpha). Since reactive oxygen species are also involved in this extracellular-matrix-degrading activity, we aimed to compare the chondrocyte oxidative status responsible for cartilage damage occurring in primarily degenerative (osteoarthritis) and inflammatory (rheumatoid arthritis) joint diseases. Human articular chondrocytes were isolated from patients with osteoarthritis or rheumatoid arthritis, or from multi-organ donors, and stimulated with IL-1beta and/or TNFalpha. We evaluated the oxidative stress related to reactive nitrogen and oxygen intermediates, measuring NO(-)(2) as a stable end-product of nitric oxide generation and superoxide dismutase as an antioxidant enzyme induced by radical oxygen species. We found that cells from patients with osteoarthritis produced higher levels of NO(-)(2) than those from patients with rheumatoid arthritis. In addition, IL-1beta was more potent than TNFalpha in inducing nitric oxide in both arthritides, and TNFalpha alone was almost ineffective in cells from rheumatoid arthritis patients. We also observed that the intracellular content of copper/zinc superoxide dismutase (Cu/ZnSOD) was always lower in rheumatoid arthritis chondrocytes than in those from multi-organ donors, whereas no differences were found in intracellular manganese SOD (MnSOD) or in supernatant Cu/ZnSOD and MnSOD levels. Moreover, intracellular MnSOD was up-regulated by cytokines in osteoarthritis chondrocytes. In conclusion, our results suggest that nitric oxide may play a major role in altering chondrocyte functions in osteoarthritis, whereas the harmful effects of radical oxygen species are more evident in chondrocytes from patients with rheumatoid arthritis, due to an oxidant/antioxidant imbalance.
11148718 Amyloid precursors and amyloidosis in inflammatory arthritis. 2001 Jan Recent data demonstrating the multifunctional role of serum amyloid A (SAA) in the pathogenesis of amyloidosis have yielded important insights into this potentially fatal consequence of chronic inflammation. SAA has been shown to participate in chemotaxis, cellular adhesion, cytokine production, and metalloproteinase secretion and is thus integrally involved in the disease process. In addition to its production by the liver as part of the acute phase response, SAA is also expressed by several pathologic tissues such atherosclerotic plaques, rheumatoid synovitis and in the brains of patients with Alzheimer disease. Its constitutive production in normal tissue suggests a role for SAA in host defense and tissue turnover. Many pathways are involved in the regulation of SAA, and as more becomes known about these, potential therapeutic targets may be identified. However, the prevention of secondary amyloidosis is best achieved by early and adequate treatment of patients with chronic inflammatory disorders. Suppression of the acute phase response and normalization of SAA levels are likely to significantly impact on the incidence of amyloidosis in inflammatory arthritis.
11508443 Inhibitor of nuclear factor kappaB kinase beta is a key regulator of synovial inflammation 2001 Aug OBJECTIVE: Inhibitor of nuclear factor kappaB kinase beta (IkappaB kinase beta, or IKKbeta) has emerged as a key regulator of the transcription factor nuclear factor kappaB (NF-kappaB). Since IKKbeta could have both pro- and antiinflammatory activity, we examined whether its constitutive activation was sufficient to cause a chronic inflammatory disease such as rheumatoid arthritis. METHODS: Normal Lewis rats were evaluated for paw swelling by plethysmometry and histologic assessment after intraarticular injection of an adenoviral construct encoding the IKKbeta wild-type gene (Ad.IKKbeta-wt); controls received an adenoviral construct encoding green fluorescent protein (Ad.GFP). The rats were killed after 7 days. Additionally, rats were killed 48 hours after intraarticular injection of Ad.IKKbeta-wt or Ad.GFP for studies of IKK activity and NF-kappaB binding. For studies of the effects of inhibition of IKKbeta activity, Lewis rats were immunized with Mycobacterium tuberculosis in mineral oil. The ankle joints were injected on day 12 with an adenoviral construct encoding IKKbeta K-->M (dominant negative, IKKbeta-dn) or Ad.GFP. We evaluated paw swelling and NF-kappaB expression on day 25. RESULTS: Intraarticular gene transfer of IKKbeta-wt into the joints of normal rats resulted in significant paw swelling and histologic evidence of synovial inflammation. Increased IKK activity was detectable in the IKKbeta-wt-injected ankle joints, coincident with enhanced NF-kappaB DNA binding activity. Intraarticular gene transfer of IKKbeta-dn significantly ameliorated the severity of adjuvant arthritis, accompanied by a significant decrease in NF-kappaB DNA expression in the joints of Ad.IKKbeta-dn-treated animals. CONCLUSION: IKKbeta plays a key role in rodent synovial inflammation. Intraarticular gene therapy to inhibit IKKbeta activity represents an attractive strategy for the treatment of chronic arthritis.
11453241 Relationship between rheumatoid arthritis and periodontitis. 2001 Jun BACKGROUND: Because of several similar features in the pathobiology of periodontitis and rheumatoid arthritis, in a previous study we proposed a possible relationship between the two diseases. Therefore, the aims of this study were to study a population of rheumatoid arthritis patients and determine the extent of their periodontal disease and correlate this with various indicators of rheumatoid arthritis. METHODS: Sixty-five consecutive patients attending a rheumatology clinic were examined for their levels of periodontitis and rheumatoid arthritis. A control group consisted of age- and gender-matched individuals without rheumatoid arthritis. Specific measures for periodontitis included probing depths, attachment loss, bleeding scores, plaque scores, and radiographic bone loss scores. Measures of rheumatoid arthritis included tender joint analysis, swollen joint analysis, pain index, physician's global assessment on a visual analogue scale, health assessment questionnaire, levels of C-reactive protein, and erythrocyte sedimentation rate. The relationship between periodontal bone loss and rheumatological findings as well as the relationship between bone loss in the rheumatoid arthritis and control groups were analyzed. RESULTS: No differences were noted for the plaque and bleeding indices between the control and rheumatoid arthritis groups. The rheumatoid arthritis group did, however, have more missing teeth than the control group and a higher percentage of these subjects had deeper pocketing. When the percentage of bone loss was compared with various indicators of rheumatoid arthritis disease activity, it was found that swollen joints, health assessment questionnaire scores, levels of C-reactive protein, and erythrocyte sedimentation rate were the principal parameters which could be associated with periodontal bone loss. CONCLUSIONS: The results of this study provide further evidence of a significant association between periodontitis and rheumatoid arthritis. This association may be a reflection of a common underlying disregulation of the inflammatory response in these individuals.
11324929 The first description of rheumatoid arthritis. Unabridged text of the doctoral dissertatio 2001 Mar This unabridged version of the dissertation presented in 1800 by Augustin Jacob Landré-Beauvais for his medical doctorate describes a disease different in many ways from the condition known since Hippocrates as gout. The patients were nine long-term residents of the Salpêtrière hospice in Paris. After reviewing the main features of ordinary or regular gout, Landré-Beauvais points out that the disease he calls "asthenic gout" exhibits several distinctive features, including predominance in women, a chronic course, involvement of many joints from the onset, and a decline in general health. Despite the tentative tone of his title ("Should one recognize...), he clearly is convinced that he is describing an as yet unreported entity, as indicated by the last sentence of his dissertation: "...we must recognize the existence of a new form of gout under the designation primary asthenic gout" And although he stops short of emancipation from the term "gout", which had been used for centuries to designate specific joint manifestations, he makes several keenly discerning observations -- particularly regarding the influence of psychological factors, the need for gentle treatments, and the inappropriateness of bloodletting - thus breaking free from contemporary doctrine. This text is acknowledged as the first description of rheumatoid arthritis. A brief biography of Landré-Beauvais is provided.
9408954 Orthopedic and interventional applications at low field MRI with horizontally open configu 1997 Oct The recently introduced horizontally open configuration imagers allow imaging of knee, hip or shoulder during whole range of motion, which is not possible in conventional MR imagers. Special joint motion devices can be used to provide accurate and reproducible studies. In cervical spine, functional MR imaging may be useful in evaluating alarligament stability in patients with late sequelae of a whiplash injury, and in patients with rheumatoid arthritis who are clinically suspected of having a cervical myelopathy or superior migration of the odontoid process. In shoulder, full range of motion abduction study may be helpful in assessing the supraspinatus tendon impingement. To evaluate patellofemoral malalignment, quadriceps loading is recommended since associated contracting muscles and related soft tissue structures can be evaluated. The position of the femoral head relative to the acetabulum during different positions can be assessed. Open-configuration scanners provide an access to patients during scanning procedure, and therefore permit interventional procedures to be monitored with MRI. Such interventions include aspiration cytology/biopsy and different drainage procedures.
9780474 [Efficacy and tolerability of methotrexate in the treatment of rheumatoid arthritis]. 1998 Mar OBJECTIVE: To verify, in an open study, the efficacy and safety of long-term administration of low weekly doses (5 mg) of methotrexate (MTX) i.m. in different stage rheumatoid arthritis patients. PATIENTS AND METHODS: The study has been performed for 24 months in 42 patients (37 females and 5 males), fulfilling the ARA criteria for rheumatoid arthritis. Main functional parameters, main serological data and some immunology indexes were periodically monitored (after 1, 3, 6, 12 and 24 months of therapy); moreover, some instrumental exams (X-ray of involved joints, liver ultrasound, respiratory function tests) have been performed. RESULTS: Thirty of 42 enrolled patients completed the whole 24 month therapy, and 22 are still using methotrexate. Results were as follows: therapeutic remission in one patient, marked improvement in 12 cases, moderate improvement in 16 and worsening in 1. Among the 12 remaining patients, 2 refused further treatment; 6 and 4 patients were withdrawn from the study because of inefficacy and toxicity, respectively. A significant improvement was observed in all of the main efficacy parameters taken into consideration. Moderate and reversible side effects were registered in 23 patients. CONCLUSIONS: Our results confirm the value of MTX in the treatment of rheumatoid arthritis. In our opinion this drug is very effective even in a relatively early stage of the disease, mainly in patients whose genetic and clinical markers may predict a more aggressive and severe outcome.
11568349 Painful multifocal arthritis: therapy with rhenium 186 hydroxyethylidenediphosphonate ((18 2001 Oct Eight patients (77 joints) with polyarthritis were treated systemically with 570 MBq (15.4 mCi) of rhenium 186 ((186)Re) hydroxyethylidenediphosphonate (HEDP). Pain and disease activity were assessed monthly. In six (75%) of eight patients, a single injection of (186)Re HEDP led to an improvement in disease activity. Systemic low-dose treatment with (186)Re HEDP can reduce pain and disease activity in patients with polyarthritis.
11359452 Prophylactic and therapeutic effects of a humanized monoclonal antibody against the IL-2 r 2001 Apr CIA in the rhesus monkey is an autoimmune-based polyarthritis with inflammation and erosion of synovial joints that shares various features with human rheumatoid arthritis (RA). The close phylogenetic relationship between man and rhesus monkey makes the model very suitable for preclinical safety and efficacy testing of new therapeutics with exclusive reactivity in primates. In this study we have investigated the prophylactic and therapeutic effects of a humanized monoclonal antibody (Daclizumab) against the alpha-chain of the IL-2 receptor (CD25). When Daclizumab treatment was started well after immunization but before the expected onset of CIA a significant reduction of joint-inflammation and joint-erosion was observed. A therapeutic treatment, initiated as soon as the first clinical signs of CIA were observed, proved also effective since joint-degradation was abrogated. The results of this study indicate that Daclizumab has clinical potential for the treatment of RA during periods of active inflammation and suppression of the destruction of the joint tissues.
9476924 Fluorine-18-fluorodeoxyglucose uptake in rheumatoid arthritis-associated lung disease in a 1998 Feb An 18F-fluorodeoxyglucose (FDG) whole-body PET scan was performed on a thyroid cancer patient with long-standing rheumatoid arthritis who presented with pulmonary nodules. A recent diagnostic radioiodine whole-body scan was negative. However, the 18F-FDG scan demonstrated intense uptake in the chest lesions as well as in several joints affected by rheumatoid arthritis. Fine-needle aspiration of a pulmonary nodule revealed inflammatory reaction and absence of malignant cells, fungus and tuberculous infection. A repeat chest CT scan after 7 mo of steroid therapy showed a marked decrease in the size and number of nodules. In thyroid cancer patients, 18F-FDG uptake in the lung may not necessarily represent pulmonary metastases. This case illustrates a benign, unrelated pathology namely, rheumatoid arthritis-associated lung disease.
11034770 Thermotherapy for treating rheumatoid arthritis. 2000 BACKGROUND: Heat and cold therapy are often used as adjuncts in the treatment of rheumatoid arthritis by rehabilitation specialists. OBJECTIVES: To evaluate the effects of heat and cold on objective and subjective measures of disease activity in patients with rheumatoid arthritis. SEARCH STRATEGY: We searched Medline, Embase, PEDro, Current Contents, Sports Discus and CINAHL up to June 2000. The Cochrane Field of Rehabilitation and related therapies and the Cochrane Musculoskeletal Review Group were also contacted for a search of their specialized registers. Handsearching was conducted on all retrieved articles for additional articles. SELECTION CRITERIA: Randomized or controlled clinical trials of ice or heat compared to placebo or active interventions in patients with rheumatoid arthritis and case-control and cohort studies were eligible. No language restrictions were applied. Abstracts were accepted. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified potential articles from the literature search. These reviewers extracted data using pre-defined extraction forms. Consensus was reached on all data extraction. Quality was assessed by two reviewers using a 5 point scale that measured the quality of randomization, double-blinding and description of withdrawals. MAIN RESULTS: Three studies (79 subjects) met the inclusion criteria. There was no effect on objective measures of disease activity (including inflammation, pain and x-ray measured joint destruction) of either ice versus control or heat versus control. Patients reported that they preferred heat therapy to no therapy (94% like heat therapy better than no therapy). There was no difference in patient preference for heat or ice. No harmful effects of ice or heat were reported. REVIEWER'S CONCLUSIONS: Since patients enjoy thermotherapy, and there are no harmful effects, thermotherapy should be recommended as a therapy which can be applied at home as needed to relieve pain. There is no need for further research on the effects of heat or cold for RA.
10381487 Anti-inflammatory effects of systemic anti-tumour necrosis factor alpha treatment in human 1999 Jul OBJECTIVES: To evaluate in vivo the contribution of tumour necrosis factor alpha (TNFalpha) to the chimeric transfer model of human rheumatoid arthritis synovial membrane into SCID mice (hu/mu SCID arthritis), systemic anti-TNFalpha treatment was performed and the clinical, serological, and histopathological effects of this treatment assessed. METHODS: Animals were treated with the rat-antimouse TNFalpha monoclonal antibody V1q, starting on day 1 after hu/mu engraftment, twice weekly for 12 weeks. Joint swelling, serum concentrations of human and murine interleukin 6 (IL6), and serum amyloid P (SAP) were measured. Histopathological and immunohistochemical analyses of the joints were also performed at the end of treatment. RESULTS: Neutralisation of murine TNFalpha induced the following effects: (a) reduction of extent and duration of the acute arthritis phase, with significant reduction of joint swelling at two weeks; (b) decrease of murine SAP concentrations after the first antibody administration; and (c) increase of murine IL6 in the serum. At the end of treatment, there was a significant reduction of the inflammatory infiltration in the engrafted joints. Because of the mild degree of joint erosion, no treatment effects could be demonstrated on the destructive process. CONCLUSION: In the lymphocyte independent hu/mu SCID arthritis, anti-TNFalpha treatment reduces local and systemic signs of inflammation.
11056676 Cytokine, activation marker, and chemokine receptor expression by individual CD4(+) memory 2000 IL-10, IL-13, IFN-gamma, tumor necrosis factor (TNF)-alpha, LT-alpha, CD154, and TNF-related activation-induced cytokine (TRANCE) were expressed by 2-20% of rheumatoid arthritis (RA) synovial tissue CD4(+) memory T cells, whereas CD4(+) cells that produced IL-2, IL-4, or IL-6 were not detected. Expression of none of these molecules by individual CD4(+) cells correlated with the exception of TRANCE and IL-10, and TRANCE and TNF-alpha. A correlation between expression of IL-10 and CCR7, LT-alpha and CCR6, IFN-gamma and CCR5, and TRANCE and CXCR4 was also detected.
11469449 MTX affects inflammation and tissue destruction differently in the rat AA model. 2001 Jul OBJECTIVE: To investigate the dose response relationships of methotrexate (MTX) therapy in rat adjuvant arthritis (AA), an animal model of rheumatoid arthritis (RA). METHODS: Female Lewis rats were fed a defined diet and were treated with 0, 0.3, 1, 2, 3, 5, and 10 mg MTX per week beginning 3 days after adjuvant injection and lasting 6 weeks. The presence or absence of arthritis, and its degree were measured by hindpaw edema scores, ankle widths, and radiographic and histopathologic scores. RESULTS: The 2, 3, 5, and 10 mg MTX per week doses resulted in deaths before the end of the protocol and suppressed normal body weight gain. Tissue destruction, measured by radiographic and histopathologic scores, was reduced in a dose dependent manner with increasing MTX dose. Suppression of inflammation, measured by ankle widths and radiographic and histopathologic scores, reached a maximum at the 1 mg MTX dose and declined at higher doses. CONCLUSIONS: Suppression of tissue destruction and inflammation in rat AA does not occur in a concerted fashion as the dose of MTX increases. The implications of these findings to human disease remain to be determined.
11201829 [Quality of life in rheumatoid arthritis patients]. 2000 AIM: To study quality of life (QL) in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Questionnaire survey (MCA, BIPQ, AIMS, MHAQ) covered 190 RA patients (mean age 47.7 +/- 1.4 years). Many of them were group II invalids. All the patients had slow-progressive polyarthritis, articular and seronegative RA prevailed. Most of the patients had articular and seronegative RA with first-degree activity, x-ray stage II and third-degree deficiency of the articular function. RESULTS: It is shown that RA patients have subnormal quality of life. Its deterioration was related to clinical parameters: duration of the disease and its activity, invalidity, X-ray stage, articular and locomotor functions, psychological status. Hypochondriac, apathical and neurastenic reactions to the disease occurred most frequently. Euphoric reaction to the disease was a positive factor for QL. Changes in social status were essential for QL in RA patients. CONCLUSION: QL is an integral indicator of health status in RA patients. It can be estimated basing on only one questionnaire--AIMS as it includes all the necessary components.
10450516 Transgenic mouse models of rheumatoid arthritis. 1999 Jun A combined analysis of data available in the literature has demonstrated that the strongest association in rheumatoid arthritis (RA) is with DR genes rather than DQ or DP genes. Functional and structural data of RA-associated DR molecules suggest that selective binding of peptides is the molecular basis for this association. The establishment of functional transgenic mice expressing RA-associated HLA class II molecules has proven to be useful in the delineation of the role of these molecules in immune responses possibly related to RA and in the development of humanized models for this disease. Such humanized mice develop arthritis upon immunization with type II collagen (CII), which shows similarities with RA. Interestingly, the immunodominant T-cell determinant in CII is derived from positions 261-273, which overlap with a previously identified CII T-cell epitope restricted by the mouse Aq molecule, which is associated with collagen-induced arthritis. Studies in collagen transgenic mice have shown that recognition of this peptide may lead either to T-cell tolerance or to an arthritogenic response. It is therefore proposed that the T-cell recognition of the CII peptide bound by DR molecules is one of the molecular interactions of critical importance in the development of RA and accordingly also an important target for prevention and treatment of this disease.
9927230 Perpetuation of inflammation associated with experimental arthritis: the role of macrophag 1998 Rheumatoid arthritis (RA) is characterized by an abnormal cellular and cytokine infiltration of inflamed joints. This study addresses a previously unrecognized interaction between neutrophilic-myeloperoxidase (MPO) and macrophages (Mphi) which could explain the perpetuation of inflammation associated with RA. A monoarticular arthritis was induced in female Lewis rats by injection of streptococcal cell wall extracts (PG-APS). After swelling and erythema subsided, joints were re-injected with one of the following: porcine MPO or partially inactivated MPO (iMPO). Injection with either MPO or iMPO induced a 'flare' of experimental RA. Blocking the Mphi-mannose receptor by mannans, ablated exacerbation of disease. These results indicate that MPO or iMPO can play a pivotal role in the perpetuation but not initiation of this RA model.
10798603 Does hemopoietic stem cell transplantation have a role in treatment of severe rheumatoid a 2000 Jan Based on animal models and limited clinical experience, there is considerable interest in use of high-dose immunosuppression followed by hemopoietic stem cell transplantation as treatment for severe rheumatoid arthritis. Because of its relatively low treatment-related mortality and morbidity, autologous transplantation is a more attractive option than allogeneic transplantation for initial clinical trials, even though anecdotal reports suggest that allogeneic transplantation has a greater likelihood of bringing about long-term disease control. The approach remains experimental with many unanswered questions such as the value and safety of high-dose therapy without transplantation, the need for T cell purging, the possible deleterious effects of post-transplant hemopoietic growth factors and the potential of "mini" allogeneic transplantation (a process whereby intense immunosuppression is combined with less intense myelosuppression). To achieve quick progress it is essential that clinical trials be carefully designed with all cases being reported to the Autoimmune Disease Stem Cell Project Database.
11324781 An English and Spanish quality of life measure for rheumatoid arthritis. 2001 Apr OBJECTIVE: To develop a rheumatoid arthritis-specific health-related quality of life instrument, translate the English instrument into Spanish, and test the scaling assumptions, reliability, validity, and feasibility of both the English and Spanish versions. METHODS: The development of the Quality of Life-Rheumatoid Arthritis Scale (QOL-RA Scale) involved literature review, consultations with experts, 40 face-to-face interviews, and 5 focus group discussions with multiethnic and multilingual women with rheumatoid arthritis (RA). Translation design facilitated conceptual and linguistic equivalence. Data for the psychometrics came from telephone interviews of a sample of 107 Caucasian/English and 80 Hispanic/Spanish women with RA. The instruments were (a) the Arthritis Impact Measurement Scales 2 (AIMS2), (b) the Lubben Social Network Scale (LSNS), (c) the Center for Epidemiologic Studies-Depression Scale (CES-D), and (d) the QOL-RA Scale. Descriptive statistics, significance tests, Cronbach's alpha technique, correlation, and factor analysis were used. RESULTS: The QOL-RA Scale, an 8-item scale, took 2 to 3 minutes to administer. Psychometric analysis revealed that the psychometric attributes and constructs of both English and Spanish questionnaires are comparable (i.e., equivalent). Both versions demonstrated the following: (a) normal distribution of the QOL-RA Scale, roughly symmetrical distributions of the items, equivalent means and standard deviations across items, and less than 10% floor and ceiling effects, (b) Cronbach's alpha coefficients of 0.87-0.90, (c) significant correlations of the QOL-RA Scale with the AIMS2 subscales, LSNS, and CES-D, ranging from 0.25 to 0.66 (P < or = 0.01), and (d) extraction of 2 factors, namely physio-psychological and socio-psychological, that explained 65% to 73% of the variance in the scale scores. CONCLUSION: The QOL-RA Scale, in both English and Spanish versions, appears to meet the assumptions of a summated rating scale and the criteria of relevance, reliability, validity, feasibility, and adaptability to several languages.
9864838 [Anti-CD4 therapy in treatment of rheumatoid arthritis--have the die been cast?]. 1998 Oct The hypothesis of rheumatoid arthritis (RA) as a T cell mediated disease has led to the development of numerous therapeutic approaches that target the function of T cells. The development of monoclonal antibodies against the T cell surface molecule CD4 has raised hopes to achieve a major progress in the treatment of RA. However, after encouraging results in early open studies, double blind trials were unable to demonstrate the efficacy of anti-CD4-therapy in RA. There are numerous reasons to explain the failure of this treatment approach. Besides the fact that the T cell hypothesis of RA has repeatedly been challenged, pharmacological problems or an inappropriate selection of outcome criteria have to be considered. The final evaluation of anti-CD4 therapy in RA will be possible only after the testing of newly developed non-depleting anti-CD4 antibodies.