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ID PMID Title PublicationDate abstract
19078220 Inhibition of methotrexate-induced rheumatoid nodulosis by colchicine: evidence from an in 1997 Dec Methotrexate is one of the most effective and widely used medications in the treatment of rheumatoid arthritis. One poorly understood side effect of methotrexate is increased rheumatoid nodule formation, a phenomenon which has been reported to occur in some patients despite suppression of synovial inflammation. Using an in vitro model of nodulosis, induction of monocyte differentiation into multinucleated giant cells, we previously found that methotrexate promotes this inflammatory response by a mechanism dependent on adenosine A1 receptor stimulation. In the current study, we tested the effects of an A1 signal inhibitor, the commonly available anti-inflammatory medication colchicine, and found that it markedly inhibited nodulosis in vitro as well as in seven of fourteen patients in a clinical series.
10483269 [Relationship between primary Sjögren's syndrome and autoimmune thyroid disease]. 1999 Aug Primary Sjögren's syndrome (SS) is an autoimmune disorder of the exocrine glands. The immunopathological findings in the thyroid glands of autoimmune thyroid diseases (AITD) and sialadenitis in SS show similarities such as infiltration by activated T cells and expression of HLA-class II molecules on the epithelial cells. To clarify the relationship between SS and AITD, we evaluated the prevalence of AITD in SS patients and that of SS in AITD patients. Chronic thyroiditis was clinically diagnosed in 23 (28%) of 82 patients with SS. Although 16 patients were euthyroid, hypothyroidism was found in 5 cases and hyperthyroidism in one case. The features of SS were found in 12 (27%) of 45 patients with CT and in one of 24 patients with Graves' disease. These results suggest that a common immunological mechanism may be involved in the development of AITD and SS.
9550429 Suppression of TNF-alpha expression, inhibition of Th1 activity, and amelioration of colla 1997 Dec 15 Rolipram is a type IV phosphodiesterase inhibitor that suppresses inflammation and TNF-alpha production. As anti-TNF-alpha therapy is effective in rheumatoid arthritis, we investigated the effect of rolipram on collagen-induced arthritis (CIA), a murine model of rheumatoid arthritis. Rolipram was administered after the onset of clinical arthritis at doses of 0.5, 3, 5, or 10 mg/kg twice daily, with a dose-dependent therapeutic effect on clinical severity and joint erosion. Immunohistochemical analysis of joints of rolipram-treated mice revealed 67% reduction in TNF-alpha-expressing cells compared with control arthritic mice. In vitro studies using bone marrow-derived macrophages confirmed that rolipram directly suppressed TNF-alpha and IL-12 production following stimulation with IFN-gamma and LPS. The effect of rolipram on T cell activity was studied by measuring Th1/Th2 cytokine production by collagen-stimulated draining lymph node cells from arthritic mice treated in vivo with rolipram. Rolipram reduced IFN-gamma production and increased IL-10, indicating that rolipram down-regulated the ongoing Th1 response to type II collagen. Finally, the effect on CIA of combination therapy was studied using rolipram plus either anti-TNF-alpha or anti-CD4 mAbs. Rolipram plus anti-TNF-alpha was not therapeutically additive, whereas rolipram plus anti-CD4 mAb was clearly additive. This result indicates that the therapeutic effects of rolipram overlap with TNF-alpha blockade, but are complementary to anti-CD4 treatment. It is therefore proposed that a major mechanism of action of rolipram in CIA is suppression of TNF-alpha activity. These findings suggest that type IV phosphodiesterase inhibitors may be effective in pathologic conditions, such as RA, with overexpression of TNF-alpha.
10630626 Effect of lupeol and lupeol linoleate on lysosomal enzymes and collagen in adjuvant-induce 1999 Nov Lysosomal enzymes play important roles in the inflammatory process. The pentacyclic triterpenes, lupeol and lupeol linoleate were administered orally (50 mg/kg) for 8 days to arthritic rats, after 11th day of adjuvant injection. The lysosomal enzymes were significantly increased in arthritic condition, which are involved in the destruction of structural macromolecules in connective tissue and cartilage in rheumatoid arthritis. Hence the level of collagen was significantly decreased and the excretion of urinary hydroxyproline, hexosamine, hexuronic acid and glycosaminoglycans were increased in arthritic rats. Treatment of arthritic rats with triterpenes reversed the above changes, which may be due to stabilization of the lysosomal membrane. Out of the two triterpenes tested, lupeol linoleate showed better ameliorating action than lupeol.
9256613 [Severe left ventricular dysfunction in a patient with primary Sjögren's syndrome]. 1997 Jun A 43-year-old woman was admitted to our hospital for evaluation of shortness of breath and palpitation on exertion. She had a 20-year history of dry mouth and a 10-year history of recurrent pneumonia. She had been diagnosed as having primary Sjögren's syndrome with interstitial pneumonia at 42 years of age. On admission, cardiac ultrasonography revealed reduced left ventricular systolic function. Complications that would elicit cardiac manifestations such as viral myocarditis, amyloidosis, sarcoidosis, and ischemic heart disease, were excluded. Oral corticosteroid therapy was effective for alleviating symptoms. In this patient, it appears that primary Sjögren's syndrome is involved in the reduced left ventricular systolic function.
9365085 Predictors of total body bone mineral density in non-corticosteroid-treated prepubertal ch 1997 Nov OBJECTIVE: To determine the extent of significant osteopenia in prepubertal patients with juvenile rheumatoid arthritis (JRA) not treated with corticosteroids and to identify variables that are highly related to bone mineralization in this population. METHODS: In a cross-sectional study, 48 JRA patients and 25 healthy control subjects ages 4.6-11.0 years were evaluated. Total body bone mineral density (TB BMD) was determined by Hologic dual energy x-ray absorptiometry. All patients were prepubertal (Tanner stage I or II) and had never taken corticosteroids. For comparison, JRA patients were divided into "low" TB BMD (Z score < or =-1) or "normal" TB BMD (Z score >-1). RESULTS: The overall mean +/- SD TB BMD scores did not differ between the JRA subjects (0.75 +/- 0.06 gm/cm2) and controls (0.73 +/- 0.07 gm/cm2; P > 0.30). However, 29.2% of the JRA patients had low TB BMD, whereas only 16% would be expected to have low TB BMD based on the standard normal distribution (goodness of fit chi(2) = 4.84, P = 0.01). The mean Z score for the JRA patients with low TB BMD was -1.43, and for those with normal TB BMD, it was 0.32. The JRA subjects with low TB BMD were significantly younger, had more active articular disease, greater physical function limitation, higher erythrocyte sedimentation rate, higher joint count severity score, lower body mass index, lower lean body mass, less participation in organized sports, and more protein and vitamin D in their diet compared with JRA patients with normal TB BMD (all P < 0.05). Using logistic regression, a model including age at JRA onset, Juvenile Arthritis Functional Assessment Report (JAFAR) score, triceps skin-fold percentiles, percentage US recommended daily allowance for dietary magnesium intake, and serum 1,25-dihydroxyvitamin D levels was able to accurately segregate 79.6% of the JRA subjects into either the low or normal TB BMD groups (chi(2) = 20.5, P = 0.001). CONCLUSION: This study demonstrated that in a mildly to moderately ill prepubertal JRA population that had never been exposed to corticosteroids, almost 30% had significantly low TB BMD. The patients with low TB BMD had more active and severe articular disease and greater physical function limitation. Disease-related parameters in JRA appear to exert a negative effect on bone mineralization even in prepubertal children, which can be demonstrated despite the exclusion of corticosteroid-treated patients.
10638775 Localised hyaline vascular type of Castleman's disease mimicking adult-onset Still's disea 1999 A previously healthy 18-year-old boy presented with daily spiking fever, polyarthritis, and evanescent skin rashes, as well as hepatomegaly and Raynaud's phenomena for 2 months. He was initially diagnosed with adult-onset Still's disease (AOSD). During the period of follow-up, intermittent fever and migratory polyarthritis persisted and an insidiously growing mass over the right axillary region was noted 1 year after the diagnosis of AOSD. Excisional biopsy of the mass revealed a group of lymph nodes with histological features of the hyaline vascular type of Castleman's disease. The patient's symptoms disappeared soon after excision of the lymph nodes. evanescent rash, lymphadenopathy, hepatosplenomegaly and serositis [5]. A clinical picture compatible with the diagnosis of AOSD has not been described in the localised hyaline vascular type of Castleman's disease. We report such a case in an 18-year-old male patient who presented prolonged fever and polyarthritis with an initial diagnosis of AOSD. The diagnosis of hyaline vascular type of Castleman's disease was made 1 year later, when the patient developed an insidiously growing mass over the right axilla.
10563164 [Recurrent acute pericarditis associated with adult-onset Still's disease treated with per 1999 Oct Recurrent acute pericarditis associated with adult onset Still's disease is an unusual feature. We present a case with recurrent episodes of acute pericarditis with cardiac tamponade which only improved with corticosteroid therapy. Because of the severe and frequent recurrences and corticodependence development, a subtotal pericardiectomy was performed with a good outcome after a 12-month observation period.
9201307 Arthritis susceptibility in mice expressing human type II collagen in cartilage. 1997 Jun Collagen type II (CII) induced arthritis (CIA) in mice is an experimental model for rheumatoid arthritis. Induction with non-self (e.g. human) CII induces severe arthritis whereas the mice are less susceptible to induction with self CII (i.e. mouse). To analyse whether an autoimmune response to human CII can develop and is pathogenic the authors have established transgenic mice expressing human CII in cartilage and backcrossed them into two different gene backgrounds susceptible to CIA (DBA/1 and C3H.Q). The transgenic human CII expression was restricted to cartilage and did not disturb cartilage morphology or lead to chondrodystrophy. In addition, development of stress-induced arthritis was not affected by the transgene. The cartilage specific expression of human CII reduced, but did not eliminate, the susceptibility to CIA irrespective of the species source (human, bovine, chick, rat) of CII used for immunization. A common denominator between these heterologous CII in comparison with mouse CII is the previously defined CII 256-270 epitope. An expression level dependent T-cell tolerance was seen in this epitope as well as to the entire CII. However, all human transgenic mouse lines could still mount significant autoreactive T- and B-cell responses. Approximately 10% of the transgenic mice developed arthritis after immunization with human CII. These findings show, therefore, that cartilage-located human CII induce tolerance but can nevertheless be a target for development of arthritis.
9150098 Measures of physical function and emotional well being for young adults with arthritis. 1997 May We investigated whether it is necessary to adapt measures of functional status as used with adults with rheumatoid arthritis when measuring physical function in young adults between 16 and 30 years of age with arthritis, and which aspects of emotional well being are important outcomes in young adults with arthritis. A questionnaire as filled in by 196 young adults with arthritis and 117 healthy peers of same age and sex. Functional status was measured with the 17 item Young Adults Disability Inventory (YADI), which includes the 8 item Modified Health Assessment Questionnaire (M-HAQ). Four aspects of emotional well being were assessed: depression, anxiety, loneliness, and self-esteem. The mean score of the patients on the YADI was significantly higher than that on the M-HAQ. YADI scores correlated significantly higher with a measure of disease symptoms than the scores on the M-HAQ with disease symptoms. Anxiety was not strongly correlated with functional status, disease symptoms, or self-reported Thompson joint score. Depression, loneliness, and self-esteem were moderately correlated with functional status and disease symptoms and weakly correlated with the Thompson score. There were no significant difference in emotional well being between patients and their healthy peers. Patients with severe symptoms were significantly more depressed than their healthy peers. It seems that the YADI is more appropriate measure of functional status in young adults with arthritis than the M-HAQ. Depression seems to be an important emotional outcome for young adults with arthritis. Anxiety does not seem to be a severely affected area of emotional well being.
9805190 Methicillin-resistant Staphylococcus aureus septic arthritis: urgent and emergent. 1998 A 71-year-old male rheumatoid patient presented with MRSA septic arthritis. The impact of this organism on musculoskeletal practice is discussed.
9046967 Oral tolerance for the treatment of autoimmune diseases. 1997 Orally administered autoantigens suppress autoimmunity in animal models, including experimental allergic encephalomyelitis, collagen and adjuvant-induced arthritis, uveitis, and diabetes in the non-obese diabetic mouse. Low doses of oral antigen induce antigen-specific regulatory T-cells in the gut, which act by releasing inhibitory cytokines such as transforming growth factor-beta, interleukin-4, and interleukin-10 at the target organ. Thus, one can suppress inflammation at a target organ by orally administering an antigen derived from the site of inflammation, even if it is not the target of the autoimmune response. Initial human trials of orally administered antigen have shown positive findings in patients with multiple sclerosis and rheumatoid arthritis. A double-blind, placebo-controlled, phase III multi-center trial of oral myelin in 515 relapsing-remitting multiple sclerosis patients is in progress, as are phase II clinical trials investigating the oral administration of type II collagen in rheumatoid arthritis, S-antigen in uveitis, and insulin in type I diabetes.
10543271 Lung function abnormalities and respiratory muscle weakness in children with juvenile chro 1999 Sep In contrast to adult rheumatoid arthritis (RA) little is known about the prevalence, nature and cause of lung function abnormalities in children with juvenile chronic arthritis (JCA). The aim of this study was to determine whether children with polyarticular and systemic onset JCA have lung function abnormalities and if so, whether they are related to pulmonary disease, thoracic and/or muscular involvement. We determined lung function and disability in 31 children with polyarticular and systemic JCA. Respiratory muscle function, thorax expansion and spine mobility were determined in the same patients, as well as in 32 matched healthy children. Peak expiratory flow (PEF) and forced vital capacity (FVC) were significantly reduced in JCA patients, when compared to reference values. Thorax expansion and spine mobility were normal, compared to paired controls. Maximum inspiratory (PI,max) and expiratory (PE,max) pressures were significantly reduced in patients compared to paired control subjects. A positive correlation was found between PE,max and FVC and PEF, an inverse correlation between expiratory pressure and disability. In conclusion, children with polyarticular and systemic juvenile chronic arthritis show a pronounced impairment in respiratory muscle strength, severe enough to cause mild lung function abnormalities and an increase in disability-scores.
9158088 Prevention of collagen-induced arthritis (CIA) by treatment with polyethylene glycol-conju 1997 May Administration of a soluble protein into animals prior to challenge immunization induces immunological tolerance which is specific for the protein. In addition, chemical modification of proteins with polyethylene glycol (PEG) has been reported to convert the immunogenic proteins to become tolerogenic. However, differences in tolerogenic properties between PEG-modified proteins and the native counterparts have never been analysed. The ability of PEG-conjugated type II collagen (PEG-CII) to attenuate CIA, an animal model for rheumatoid arthritis, was compared with the native unconjugated CII. Groups of DBA/1 J mice were treated weekly with i.p. injections with PEG-CII, native CII, or vehicle alone for 3 weeks, before they were challenged with CII in adjuvants. The induction of tolerance was confirmed in both PEG-CII- and CII-pretreated mice when suppression of lymph node T cell proliferation in response to CII was noted. The degrees of suppression of T cell proliferation were comparable between the two pretreated groups. However, induction of arthritis and production of IgG anti-CII antibody were more markedly suppressed in PEG-CII-pretreated mice than in native CII-pretreated mice, although the severity of arthritis and antibody levels in the latter group were also lower than in control mice. IgG2a and IgG2b antibody levels were equally suppressed in the two pretreated groups, whereas the IgG1 level was significantly lower in the PEG-CII-pretreated group than in the native CII-pretreated group. The results provide the first evidence that attachment of PEG to CII renders the protein more tolerogenic.
10467454 The effect of da-fang-feng-tang on treatment of type II collagen-induced arthritis in DBA/ 1999 Da-Fang-Feng-Tang (DFFT), which is believed to be effective for treating human rheumatoid arthritis (RA), was given to DBA/1 mice at the onset of type II collagen-induced arthritis (CIA) to examine its effect. Granules of the crude DFFT extract were administered by gastric gavage at a dose of 1.6 g/kg/day for 12 weeks, starting the day CIA began. The levels of anticollagen IgG antibody were significantly decreased in the sera of the DFFT-treated group compared with the control group from weeks 2 to 7 after the onset of CIA. The severity of arthritis in the DFFT-treated group was markedly alleviated when compared with the control group. In addition, histological examination of the DFFT-treated group showed less cartilage and bone erosion. These results suggest that administration of DFFT suppressed the development of CIA in mice and support the belief that DFFT is effective in treating human RA.
9091585 Collagen-induced arthritis is reduced in 5-lipoxygenase-activating protein-deficient mice. 1997 Mar 17 Collagen-induced arthritis in the DBA/1 mouse is an experimental model of human rheumatoid arthritis. To examine the role of leukotrienes in the pathogenesis of this disease, we have developed embryonic stem (ES) cells from this mouse strain. Here, we report that DBA/1 mice made deficient in 5-lipoxygenase-activating protein (FLAP) by gene targeting in ES cells develop and grow normally. Zymosan-stimulated leukotriene production in the peritoneal cavity of these mice is undetectable, whereas they produce substantial amounts of prostaglandins. The inflammatory response to zymosan is reduced in FLAP-deficient mice. The severity of collagen-induced arthritis in the FLAP-deficient mice was substantially reduced when compared with wild-type or heterozygous animals. This was not due to an immunosuppressive effect, because anti-collagen antibody levels were similar in wild-type and FLAP-deficient mice. These data demonstrate that leukotrienes play an essential role in both the acute and chronic inflammatory response in mice.
24383559 Nomenclature and classification of juvenile idiopathic arthritis: where to after Durban? 2000 Jun Abstract The Durban classification system for juvenile idiopathic arthritis (JIA) is reviewed in a historical context and in association with a review of problems that have become apparent. These include: (i) a family history of psoriasis as an exclusion factor (oligoarthritis and enthesitis-related arthritis) and as in inclusive factor (psoriatic arthritis); (ii) a family history of HLA-B27-associated disease as an exclusion factor (oligoarthritis) and an inclusive factor (enthesitis-related arthritis); (iii) the requirement of a dermatological opinion for psoriasis; (iv) the absence of HLA-B27 antigen in proband, with the presence of antigen in the family history; (v) the definition of time of onset; (vi) the presence of rheumatoid factor (RF) with oligoarthritis; (vii) HLA-B27-positive males with an onset of arthritis after 8 years of age. Modifications are suggested to maintain the homogeneity of groupings for research, whilst providing a practical scheme for clinicians. Three main modifications are suggested. (A) That the family history be included in descriptors rather than as inclusive or exclusion criteria. (B) Further development of the hierarchical system, which is partly used in the Durban classification. (C) That the following changes be made: rheumatoid-factor-positive oligoarthritis and polyarthritis be classified together; extended oligoarthritis and polyarthritis be classified together; HLA-B27-positive disease be classified with fewer inclusive and exclusion criteria; the criteria for psoriatic arthritis be modified; the classification of the disease in a particular child be changed in the event of relevant changes in the child's disease or laboratory profile. These suggestions are made to stimulate discussion.
11890661 Oncostatin M in the anti-inflammatory response. 2001 Nov Oncostatin M (OM) is a pleiotropic cytokine of the interleukin 6 family, whose in vivo properties and physiological function remain in dispute and poorly defined. These in vivo studies strongly suggest that OM is anabolic, promoting wound healing and bone formation, and anti-inflammatory. In models of inflammation OM is produced late in the cytokine response and protects from lipopolysaccharide (LPS)-induced toxicities, promoting the re-establishment of homoeostasis by cooperating with proinflammatory cytokines and acute phase molecules to alter and attenuate the inflammatory response. Administration of OM inhibited bacterial LPS-induced production of tumour necrosis factor alpha and septic lethality in a dose dependent manner. Consistent with these findings, in animal models of chronic inflammatory disease OM potently suppressed inflammation and tissue destruction in murine models of rheumatoid arthritis and multiple sclerosis. T cell function and antibody production were not impaired by OM treatment. Taken together, these data indicate that the activities of this cytokine in vivo are anti-inflammatory without concordant immunosuppression.
10775080 Hypocomplementemic urticarial vasculitis: report of a pediatric case. 2000 Apr Hypocomplementemic urticarial vasculitis syndrome (HUVS) is well described in adults but is quite rare in children. We report a pediatric case of HUVS initially diagnosed as juvenile rheumatoid arthritis and then as Henoch-Schönlein purpura. Beginning at 3 years of age, our patient developed polyarthritis with hypocomplementemia. She subsequently experienced an intermittent purpuric rash beginning at age 4 years, and she continued to have episodic arthritis and rash for years. Hematuria and proteinuria were noted at 12 years of age; renal biopsy revealed membranoproliferative glomerulonephritis with membranous features. Serum complement evaluation revealed activation of the classical pathway, consistent with HUVS. Therapy with oral dapsone led to improvement in proteinuria. HUVS should be considered in the differential diagnosis of pediatric patients with glomerulonephritis, urticarial rash, arthritis/arthralgias, and obstructive pulmonary disease.
9141265 A nationwide surveillance study of rheumatic diseases among Japanese children. 1997 Apr To estimate the number of children with rheumatic diseases, a questionnaire was distributed to the pediatrics department of 1,290 hospitals in Japan in June 1994. From this survey, 1,606 cases with juvenile rheumatoid arthritis (JRA), 906 cases with systemic lupus erythematosus (SLE), 320 cases with dermatomyositis/polymyositis (DM/PM), 28 cases with scleroderma (PSS), 70 cases with Sjögren's syndrome (Sjs), 93 cases with mixed connective tissue disease (MCTD), 25 cases with aortitis syndrome, 20 cases with polyarteritis (PN) and 51 cases with Behçet disease were reported. The crude annual incidence rates per 100,000 among the childhood population were estimated as JRA, 0.83; SLE, 0.47; DM/PM, 0.16; PSS, 0.01; Sjs, 0.04; MCTD, 0.05; aortitis syndrome, 0.01; PN, 0.01; and Behçet disease, 0.03. The present study reveals that there are more children with rheumatic diseases than are estimated from the reported cases in the literature and the number of children who are receiving Assistance Medical Costs Insurance covered by the Japanese government.