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PMID	Title	PublicationDate	abstract
8081671	Treatment of rheumatoid arthritis with blackcurrant seed oil.	1994 Sep	The objective of this study was to assess the clinical efficacy and side effects of blackcurrant seed oil (BCSO), in a randomized, double-blind, placebo controlled, 24-week trial in patients with RA and active synovitis. BCSO is rich in gammalinolenic acid (GLA) and alphalinolenic acid (ALA). Both GLA and eicosapentaenoic acid which derives from ALA suppress inflammation and joint tissue injury in animal models. Treatment with BCSO resulted in reduction in signs and symptoms of disease activity in patients with RA (P < 0.05). In contrast, patients given a placebo showed no change in disease. Overall clinical responses (significant change in four measures) were no better in the treatment group than in the placebo group. No patients withdrew from BCSO treatment because of adverse reactions. However, many patients withdrew because BCSO and its placebo had to be administered in 15 large capsules daily. Nonetheless, the study indicates that BCSO is a potentially effective treatment for active RA. However, means must be found to reduce the size and number of capsules taken, so that larger studies of longer duration in RA patients can be done.
1593572	Lactate dehydrogenase activity and its isoenzymes in serum and synovial fluid of patients	1992 Apr	By determining the total activity of total lactate dehydrogenase (LDH-T) and its isoenzymes in serum and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and osteo-arthritis (OA) we demonstrated in RA serum increased (p less than 0.02) activity of hepatic LDH (LDH-H) and a shift of the LDH isoenzymatic profile towards the M forms; in rheumatoid SF increased (p less than 0.001) activity of the total LDH-T and LDH-H which makes possible the use of these markers of inflammation in assessing RA activity. Values for LDH-T and LDH-H of 400-700 U/l and 300-500 U/l, respectively, correspond to moderate disease activity, while values exceeding 750 U/l and 550 U/l, respectively, correspond to high RA activity. The anaerobic isoenzymatic distribution of LDH in rheumatoid SF results in a significant (p less than 0.001) decrease in LDH1 and LDH2 and an increase (p less than 0.001) in LDH4 and LDH5.
9007615	Serum copper/zinc superoxide dismutase levels in patients with rheumatoid arthritis.	1996	Rheumatoid arthritis is characterized by a chronic hypertrophic synovitis leading to destruction of connective tissue and functional damage of cartilage and bone structures. Reactive oxygen species play an important role in tissue injury in this disease. To clarify the role of the cellular antioxidant system in the protection against oxygen free radicals, we examined the levels of copper/zinc superoxide dismutase in the sera of patients with rheumatoid arthritis. We used an enzyme-linked immunosorbent assay which determines the concentration of copper/zinc superoxide dismutase independently from its enzymatic activity. We found that patients with rheumatoid arthritis have higher serum copper/zinc superoxide dismutase levels than control subjects. Copper/zinc superoxide dismutase also correlated positively with serum levels of both neopterin and rheumatoid factor, sensitive markers for disease activity in rheumatoid arthritis. These results support the hypothesis that the increased amount of copper/zinc superoxide dismutase is probably inadequate to exert an effective antioxidant protection but can result in a pro-inflammatory, pathogenic effect enhancing tissue damage. Furthermore, copper/zinc superoxide dismutase might be used as a marker of inflammatory activity in rheumatoid arthritis.
8457225	Enhanced chondrocyte destruction by lymphokine-activated killer cells. Possible role in rh	1993 Apr	OBJECTIVE: The lysis of chondrocytes, the parenchymal cells of cartilage, by lymphocytes may provide a potent mechanism by which the immune system participates in sustaining joint damage in rheumatoid arthritis (RA). We studied the capability of lymphocytes from healthy individuals and patients with arthritis to lyse chondrocytes. METHODS: Peripheral blood mononuclear cells (PMBC) were tested for their ability to lyse chondrocytes in a 51Cr-release assay. Enhancement of the chondrolytic activity was determined by preincubating the cells with T cell growth factor (TCGF) or recombinant interleukin-2 (rIL-2) before cytotoxic testing. RESULTS: PBMC from healthy individuals possessed a low ability to lyse chondrocytes, whereas cells from the synovial fluid of patients with RA displayed higher chondrolytic activity. In RA, modulating factors must come into play because not all synovial fluid sample cells showed high chondrolytic activity and cells from synovial tissue had little or no lytic action on chondrocytes. Chondrolytic activities of cells from all sources, including PBMC from healthy subjects and patients with arthritis and cells isolated from synovial fluid or from the synovial tissue of RA patients, were greatly increased by incubating the cells with TCGF or rIL-2. In contrast, treatment of chondrocytes with interferon-gamma, which enhances major histocompatibility complex gene expression, decreased the susceptibility of chondrocytes to lysis. CONCLUSION: These observations suggest a mechanism for joint damage in which the destruction of chondrocytes by lymphocytes is controlled by cytokines released during the inflammatory process in arthritic diseases.
8697665	Sex hormones, proto-oncogene expression and apoptosis: their effects on rheumatoid synovia	1996 Jan	Programmed cell death (apoptosis), is a non-random physiological process characterized by cell fragmentation without leakage of the cellular contents into the extracellular space. Apoptosis is especially important in the immune system. On the other hand the capacity of cells to proliferate and to show local invasiveness, as in cancer cells or the "tumor-like" synoviocytes in rheumatoid arthritis (RA), seems to be controlled by a group of genes called "proto-oncogenes". The early metabolic events in cell apoptosis and proliferation are remarkably similar. The primary location of apoptotic cells in RA synovial tissue is at the level of the synovial lining, varying from rare positive cells to > 50% positive cells. C-jun, c-fos and c-myc oncoproteins seem to be largely restricted to the synovial cells attached to the sites of cartilage and bone destruction. Ovarian follicle atresia could serve as a useful model to study the hormonal regulation of apoptosis in different endocrine tissues. Based on ovarian studies it seems that estrogens generally prevent apoptosis whereas androgens induce apoptosis. The binding of steroids to their receptors forms a complex wherein the receptors are transformed, so that they can then pass through the nuclear membrane and associate with specific recognition sites on DNA. In the majority of cases, the steroid receptors mediate the rapid regulation of the nuclear proto-oncogene transcription. Therefore, they may serve as important "early" regulatory genes and as excellent universal markers in all tissues in steroid hormone action. Since the macrophages are considered to be target cells for sex hormones, we recently evaluated c-myc expression in cytocentrifuge preparations obtained from primary cultures of RA synovial macrophages treated with estrogens, and observed a marked upregulation. Further studies of the influence of sex hormones on synoviocyte apoptosis and proto-oncogene expression should offer new perspectives on the pathogenesis and therapy of synovitis in RA and other rheumatic diseases.
7497893	[Rheumatoid arthritis, neutropenia and splenomegaly: the Felty syndrome].	1995 Dec 8	HISTORY AND FINDINGS: A 59-year-old asymptomatic man, first diagnosed to have rheumatoid arthritis 27 years ago, was admitted to hospital because of splenomegaly and neutropenia, first noted 2 years ago. Physical examination confirmed splenomegaly and also revealed pretibial hyperpigmentation, but no evidence of active rheumatoid arthritis. EXAMINATIONS: Biochemical tests showed relative and absolute neutropenia (white blood cell count 2200/microliters; 1% neutrophils), thrombocytopenia and polyclonal hypergammaglobulinaemia. He also had increased erythrocyte sedimentation rate (38/92), a high titre of rheumatic factor (2128 IU/ml) and increased circulating immune-complexes (74%). Thoracic and abdominal computed tomography provided no evidence of malignant tumor. The spleen measured 15 x 7 x 10 cm. Bone-marrow biopsy from the iliac crest revealed abnormal maturation of granulopoiesis and marked lymphoid infiltration. The clinical triad of rheumatoid arthritis, splenomegaly and neutropenia are diagnostic of Felty's syndrome. As the patient was asymptomatic there was no indication for treatment. CONCLUSION: Felty's syndrome is a rare condition demanding considerable effort in differential diagnosis.
8994013	Evaluation of the effectiveness of a metacarpophalangeal ulnar deviation orthosis.	1996 Oct	Rheumatoid arthritis (RA) causes structural damage that precipitates joint deformity, including metacarpophalangeal (MCP) joint ulnar drift (UD). Orthoses have been designed in order to maintain hand function by improving joint alignment, restoring biomechanical balance and reducing stress on supporting diseased tissues. This study investigated the impact an MCP UD (MUD) splint had on: pain, hand function, grip strength, and passive correction of UD when worn for function by RA patients. Twenty seven hands (26 subjects) were evaluated and performances compared with and without the splint. Results showed anatomic alignment improved significantly in all except the index finger. The mean difference for all fingers combined was 10 degrees. Observable correction of subluxation was identified from x-ray film and noted in 14.8% of index fingers, 18.5% of middle fingers, 33.3% of ring fingers, and 48.1% of little fingers. Three point pinch showed a statistically significant change, the mean difference being an improvement of 15% while wearing the splint. There was no significant change in hand function score, pain score, gross grip strength, and lateral pinch. Subjects' perceptions of the MUD splint gained from a questionnaire showed a high acceptance: 79.2% reporting minimal interference in ADL, 95.8% satisfied with cosmesis, 87.5% satisfied with comfort, and 95.8% reported continued use of the orthosis.
8066865	[Fish oils and rheumatoid arthritis].	1994 Jun 6	Dietary supplementation with polyunsaturated fatty acids--n-3 PUFA or fish oils--has gained increasing interest among patients suffering from rheumatoid arthritis. The biochemical background for the beneficial effects of fish oils in modulating the inflammatory response is briefly described and is partly based on findings from experimental animal models. Ten published double-blind studies evaluating the effect of a daily supplement with three to six grams of n-3 PUFA to patients with active rheumatoid arthritis are reviewed. The studies support a modest effect of fish oil on patient-reported disease parameters without serious side effects. Future research should evaluate effect, tolerance and side effects in long term studies with different daily intakes of n-3 PUFA and should also focus on the effect of n-3 PUFA in combination with standard therapy in patients with rheumatoid arthritis.
8596143	Human T-cell leukemia virus type I tax transactivates the interleukin-6 gene in human rheu	1995 Nov	OBJECTIVE: To determine the effect of the human T cell leukemia virus type I (HTLV-I) tax gene on interleukin-6 (IL-6) production and gene transcription in synovial cells, we established the synovial cell line, E-11, from a patient with rheumatoid arthritis. METHODS: E-11 cells were transfected with tax expression vector using the calcium phosphate coprecipitation method. IL-6 production and gene expression were investigated by ELISA and Northern blot analysis, respectively. To clarify how tax induces IL-6 gene expression, we used deletion analysis and chloramphenicol acetyltransferase (CAT) assay, and electrophoretic mobility shift assay (EMSA). RESULTS: Transfection of the tax gene induced markedly high levels of IL-6 mRNA. Furthermore, the tax gene strongly transactivated IL-6 gene promoter activity assayed by CAT assay. By using deletion and site specific mutations, we have identified a nuclear factor (NF)-kappa B sequence (positions -73 to -63) which is essential for tax transaction. EMSA demonstrated the induction of specific binding of nuclear extracts to the NF-kappa B sequence by HTLV-I tax. CONCLUSION: The HTLV-1 tax gene may transactivate IL-6 gene in the synovial cells through NF-kappa B and may contribute in the pathophysiology of HTLV-I associated arthritis.
8783420	Immunohistochemical detection of factor XIIIa and factor XIIIs in synovial membranes of pa	1996	In spite of differences in etiology, RA and OA lead to astonishingly similar synovitic alterations. Fibroblastic transformation of the synovial membrane and an increase in monocytes constitute a rare but highly characteristic feature of RA. Monocytes synthesize factor (F) XIII, implying that FXIII (a and s) in synovial tissue might help to differentiate between RA and OA. Biopsies were obtained at open surgery from 98 unselected patients with the clinical diagnosis of RA (n = 54) or OA (n = 44). In a three-stage (ABC) immunoperoxidase technique, polyclonal antisera against factor XIIIa and factor XIIIs were investigated. Compared to OA sections. RA synovium showed more FXIIIa-positive cells-monocytes, fibrocytes, fibroblasts and synovial lining cells. In the subsynovial layer, band-like structure of FXIIIa-stained cells was observed in 27.8% of the RA patients, but in only one OA specimen. Higher proportions of FXIIIa-positive monocytes, macrophages, histiocytes and fibroblasts, as well as positive Langhans giant cells and vascular wall regions (except endothelial cells), were observed in RA. OA specimens revealed more intense FXIIIa labeling of these cells with a lower percentage of stained cells. Overall, labeling with FXIIIs antibody resulted in less intense staining. In conclusion, distinction between synovitis caused by RA and synovitis due to OA is possible, as the former show higher numbers of FXIIIa-positive cells, including monocytes, fibroblasts, fibrocytes and synovial lining cells. Further more, RA tissue is stained less intensely than OA tissue. There is evidence for continuous excretion of FXIII in the synovial membrane by the above-mentioned cell systems.
7881837	Compound heterozygosity of HLA-DR4 and DR1 antigens in Asian Indians increases the risk of	1995 Jan	The relationship of HLA-DR antigens in rheumatoid arthritis (RA) patients with the presence of rheumatoid factor (RF), extra-articular features, joint erosions, functional status and response to disease modifying anti-rheumatic drugs (DMARDs) was studied. Seventy-four patients with RA were serologically typed for class II antigens. Clinical features were recorded before starting DMARDs and during follow-up to assess response and side-effects. HLA-DR1 and DR4 antigens were present more frequently in patients with RA than in the general population. The presence of DR4 correlated with RF seropositivity (P < 0.001) while DR1 was associated with seronegativity (P < 0.02). Ten of the 11 patients with extra-articular features had DR1 and/or DR4. Patients with both DR4 and DR1 had a significantly higher frequency of extra-articular features compared with those with only one of these (P < 0.01). HLA-DR4 and DR1 had no relation with the presence of subcutaneous nodules, erosive changes, deformities, response to drugs and side-effects of DMARDs.
1391934	Progress in understanding the pathogenesis of the anemia of chronic disease.	1992 Oct 1	Improved understanding of the inflammatory response and the identification and characterization of the specific cytokines involved, as well as improved understanding of erythropoiesis, and the availability of recombinant human growth factors such as EPO, have greatly enhanced our appreciation of the pathogenesis of ACD by allowing development of a number of informative models for studying this syndrome. It appears that a variety of cytokines are involved in all aspects of the pathogenesis of ACD, from the inhibition of erythroid progenitors and EPO production to impairment of iron release. A schematic of the contributions of some of these cytokines to the development of ACD is shown in Fig 6. The exact biochemical mechanisms by which these effects occur is still to be determined. The progress outlined in this report has allowed us to develop a more precise understanding of the pathogenesis of this common and important clinical syndrome. In 1983, Hansen subtitled a review of ACD "A Bag of Unsolved Questions." Although this description is still accurate, our understanding of ACD has now developed to the point where we can offer a more defined subtitle: "A Bag of Cytokines."
1352482	The effect of anti-adhesion molecule antibody on the development of collagen-induced arthr	1992 Jul	In order to study how inflammatory cells including autoimmune lymphocytes interact with each other to develop collagen-induced arthritis (CIA), we injected monoclonal antibodies against mouse LFA-1 and ICAM-1 into DBA/1 mice immunized with type II collagen (CII). Both antibodies suppressed the development of CIA. These antibodies showed no effect on anti-CII antibody response, although they both significantly suppressed DTH response. It was suggested that anti-adhesion molecule antibodies suppress CIA mainly through their effect on cell-mediated immunity, without affecting humoral immunity under the conditions used.
1307690	Chloroquine levels in blood during chronic treatment of patients with rheumatoid arthritis	1992	Blood levels of racemic chloroquine and its main metabolites desethylchloroquine and bisdesethylchloroquine were measured in 29 patients treated chronically for rheumatoid arthritis. In six patients, the concentrations were followed during a one day dosage interval. There was considerable intersubject variability in the steady state blood concentrations of chloroquine (range 36.6 to 3895 ng.ml-1) and its two main biotransformation products; the latter represented, respectively, 47.7% and 12.9% of the concentration of chloroquine. This finding shows the need for further studies in view of the known toxic effects of chloroquine and the inevitable accumulation due to the exceptionally long residence time of the compound and its metabolites. The main requirement, which has not yet been met, for adding chloroquine to the list of drugs for which therapeutic drug monitoring is useful, is the lack of information about its mechanism of action, and consequently the dose-effect relationships of its therapeutic and toxic actions. Regular ophthalmic examination, in particular, is strongly recommended. The relatively high concentrations of desethylchloroquine and bisdesethylchloroquine found during chronic treatment show the need for more information about the therapeutic value and adverse effects of the metabolites.
7551662	Comparison of the validity and reliability of self-reported articular indices.	1995 Aug	Our objective was to compare the validity and reliability of three formats for self-administered articular indices assessing pain (PAI) or swelling (SAI). Fifty-five patients with rheumatoid arthritis were asked to mark the degree of pain on a list of 16 joints (PAI list), to mark 'painful joints' on a mannequin presenting 42 joints (PAI diagram), and to mark 'swollen or tender joints' on a mannequin presenting 38 joints (SAI diagram). The test--retest reliability (intraclass correlation coefficient) ranged from 0.63 (SAI diagram) to 0.67 (PAI diagram) and 0.85 (PAI list). The correlation with clinical parameters was strongest for the PAI list and the SAI diagram. The association of the SAI diagram with clinical parameters increased with omission of the less reliable toe joints and/or weighting for joint size according to Lansbury. As expected, the short and weighted SAI diagram correlated more strongly with the physician-derived swollen joint count (r = 0.49), C-reactive protein (r = 0.49) and erythrocyte sedimentation rate (r = 0.41) than did the PAI list whereas the PAI list correlated more strongly with physician-derived tender joint count (r = 0.43), global pain measured on a numerical rating scale (r = 0.57) and the Health Assessment Questionnaire (r = 0.49) than did the SAI diagram. We concluded that patients' rating of tender and swollen joints on a mannequin diagram and calculation of a 26-joint and weighted articular index produces an excellent estimate of total joint inflammation, which may be useful in clinical, health services and epidemiological research. An articular index calculated from ratings of pain degree of 16 joints or joint groups may provide complementary information.
7831943	[Perspectives in gene therapy in rheumatic and degenerative diseases of the spine and join	1994 Nov	Rheumatoid degenerative conditions of the spine and other joints are most common in elderly patients. Data by the "National Center for Health Statistics" state that approximately 500 in 1000 persons above 65 are affected. Numbers for Germany should be in the same range. Although a lot of research has been dedicated to these conditions many of the actual causes remain unclear. There is consensus about the involvement of Interleukin-1 in the development of rheumatoid arthritis RA. Recent results point towards a more refined understanding and a gene therapy approach utilizing synovial cells. The synovium will in this strategy be the locus of drug (eg hormone) synthesis antagonizing the rheumatoid disease. We believe that this new approach will have a major impact on the treatment of RA.
1295608	Cytomorphological, ultrastructural and immunological characteristics of the ovialsyn fluid	1992 Jul	Experiments have been performed on 15 samples of synovial fluid (SF) from patients with seropositive rheumatoid arthritis (RA) (Latex 1/280 and Waaler Rose 1/1024) versus 10 SF samples from patients with hydroarthrosis, used as control. By cytomorphologic studies, we determined the cellularity, ragocytosis and synoviocytogram of the SF cellular pellet and found out that rheumatoid SF is characterized by cytosis (9953/mm3), ragocytosis (70%) and polynucleosis (73%) whereas hydroarthrotic SF is characterized by lymphocytosis (54.6%). Ultrastructurally, rheumatoid SF ragocytes present numerous intracytoplasmic inclusions and phagolysosomes, a fact that certainly evidences an endocytotic activity. At the level degenerative of PMN cells, (6%), the experiments evidenced the presence of some lysis cytoplasmic plateau associated with the absence of cellular organelles, as well as an alteration of the granulofibrillar structure of the nucleus. We also noticed cellular debris consisting of partially destroyed cellular organelles. By immunologic studies we obtained seric pathologic values for CIC (mean = 108.05 U), IgM (mean = 420 Ul/ml), IgG (mean = 355 Ul/ml), anti DNA antibodies (mean = 405 U) and anti collagen II antibodies (mean = 558 U). As regards the seric complement activity of C1q and C3 fractions, it was higher (mean = 18.87 mg% and mean = 109.94 mg%, respectively) than in the SF (mean = 5.78mg% and mean = 30.83 mg%, respectively). Corroborating the cytomorphological, ultrastructural and immunological data, we could better explain the lesional types examined and emphasize the importance of the immunomorphological changes in RA diagnosis.
8285007	[Our method of arthrodesis of the wrist].	1993	The authors emphasize the importance of a stable pain-free carpus for the function of fingers. Reflections on their own type of osteosynthesis are based on anatomical and biomechanical findings. They emphasize the functional concept of the central pillar of the wrist where maximum flexion and extension takes place. In this very line formed by the distal portion of the radius, os lunatum, os capitatum and the base of the third metacarpal bone they apply the splint. The splint is as compared with classical AO splints low (only 2.8 mm), L-shaped and in its cross section slightly convex dorsally. It follows thus the natural arching of the carpal and metacarpal bone and does not increase the tension of soft structures and the overlying skin. By the localization of oval openings it makes slight self-compression possible and ensures adequate, three-point fixation of the metacarpal region. The oval opening in the short branch of the splint serves location of the centre of the transverse section of the second metacarpal bone and ensures correct placement of the screw. It makes plastic operation of extensors possible which in rheumatic synovialis and destruction of the carpal bone are frequently impaired. The authors present the results of 21 operations. Adequate healing of bone was achieved in all patients, on average after 3.5 months. In all the height of the carpal index (CHI) was increased and the hand grip improved. In nine patients they found rupture of the extensors and repaired it. In all instances they performed synovectomy and resection of the head of the ulna. Two patients have bilateral arthrodesis.(ABSTRACT TRUNCATED AT 250 WORDS)
8088079	An unusual clinical manifestation of secondary SjÃ¶gren's syndrome and concomitant Paterso	1994 Jun	We describe the case of a female patient who presented with rheumatoid arthritis accompanied by severe dysphagia that led to prostration. The clinical picture and a barium contrast swallowing study suggested neoplastic proliferation at the borderline between the hypopharynx and the oesophagus. A comprehensive examination, however, did not confirm neoplasm. Dysphagia was caused rather by mucoso-fibrotic changes at the borderline between the hypopharynx and the oesophagus, representing the simultaneous presence of the Paterson-Kelly syndrome and secondary SjÃ¶gren's syndrome.
7567185	Physical fitness in children with juvenile rheumatoid arthritis and other chronic pediatri	1995 Oct	This article discusses the importance of physical fitness and exercise in healthy adults and children, and differentiates the terms "physical fitness" and "physical activity". The benefits of physical activity for adults and children with chronic illnesses and rheumatic diseases are emphasized.