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  • 1
    Electronic Resource
    Electronic Resource
    The in Vivo Effect of Doxycycline Treatment on Matrix Metalloproteinases in Reactive Arthritis (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 732 (1994), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1994.tb24776.x
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  • 2
    Electronic Resource
    Electronic Resource
    Cell-Mediated Immune Response in the Diseased Joints in Patients with Reactive Arthritis (1986)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 23 (1986), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: To evaluate the level of lymphocyte activation in reactive and rheumatoid arthritis, density gradient-isolated, synovial fluid mononuclear cells were stained with a panel of antisera directed at lymphocyte activation markers using an avidin-biotin-peroxidase complex (ABC) method. More specifically, we studied the expression of immune response-associated class II HLA antigen (la), of receptors for interleukin 2 (Tac) and transferrin (T9), as well as of gp 40/80 glycoprotein (4F2). Although Ia+ cells formed about 60% of all the synovial fluid mononuclear cells in both disease conditions, the proportion of Tac+ (33±4% vs 3±1%, P〈0.001), T9+ (34±4% vs 5±2%, P〈0.001), and 4F2+ (48±6% vs 3±2%, f〈0.001) cells was high only in reactive arthritis. All the patients who had reactive arthritis followed a favourable clinical course during the 4-month-long prospective follow-up, whereas disease activity was stable in patients with rheumatoid arthritis. These findings suggest that the diseased joints in reactive arthritis are a site for an active, but normally down-regulated, cell-mediated immune response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1986.tb02005.x
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  • 3
    Electronic Resource
    Electronic Resource
    DNA synthesis in CD4- and CD8-positive cells in synovial fluid of patients with reactive and rheumatoid arthritis (1989)
    Springer
    Rheumatology international 8 (1989), S. 269-272 
    Details
    ISSN: 1437-160X
    Keywords: Activated lymphocytes ; Autoradiography ; Immunohistochemistry ; Cytotoxic lymphocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The occurrence of MHC class I antigens and microbial antigens derived from the triggering infection of the diseased joints in reactive arthritis (ReA) seems to set the stage for local immune activation. In this report activated lymphocytes are demonstrated by using an avidin-biotin-peroxidase complex (ABC) method combined with autoradiography that identifies DNA synthesis and, thus, activation. Most of the activated T lymphocytes in reactive arthritis were found to belogn to the CD8 suppressor/cytotoxic T-lymphocyte subset. In striking contrast, the majority of the activated T lymphocytes detected in rheumatoid arthritis (RA) synovial fluid belonged to the CD4 helper/inducer subset. These findings agree well with the assumption that CD8-positive cells identify the foreign antigen in the context of class I antigens, whereas CD4-positive cells are found to be associated with the recognition of MHC locus II coded HLA antigens.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00270983
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  • 4
    Electronic Resource
    Electronic Resource
    Phenotypic characterization of 3H-thymidine incorporating cells in rheumatoid arthritis synovial membrane (1986)
    Springer
    Rheumatology international 6 (1986), S. 269-271 
    Details
    ISSN: 1437-160X
    Keywords: Autoradiography ; Immunoperoxidase ; Rheumatoid arthritis ; Synovial membrane ; 3H-thymidine incorporating cells ; Monoclonal antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tritiated-thymidine incorporating cells in synovial tissue samples from ten patients with definite or classic rheumatoid arthritis (RA) were studied by combining two techniques. Tritiated-thymidine-labelled cells were seen in autoradiography and simultaneously the subtype of them was determined with immunoperoxidase staining using monoclonal antibodies. Tritiated-thymidine-labelled cells comprised 0.8±0.4% of all the inflammatory cells in RA synovial membrane. Of all 3H-thymidine-labelled cells 34±17% were positive for OKT8 and 19±8% for OKT4 monoclonal antibodies. OKM1-positive cells comprised 7±3% of all 3H-thymidine labelled cells, whereas only a few (3±4%) of them were positive for pan-B monoclonal antibody. This study emphasizes the importance of activated OKT8 lymphocytes in RA synovial membrane.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00541318
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  • 5
    Electronic Resource
    Electronic Resource
    T cell subsets in the blast cell population in phytohemagglutinin-stimulated peripheral blood in vitro and in rheumatoid arthritis synovial fluid in vivo (1987)
    Springer
    Rheumatology international 7 (1987), S. 67-70 
    Details
    ISSN: 1437-160X
    Keywords: Rheumatoid arthritis ; Synovial fluid ; Lymphocyte activation ; Immunoregulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The immunomodulatory T4/T8 ratio was studied in the total and activated lymphocyte populations by a method combining visualisation of 3H-thymidine incorporating blasts with autoradiography (AR) with simultaneous identification of the respective lymphocyte subsets using monoclonal antibodies in avidin-biotin-peroxidase complex (ABC) staining. In rheumatoid arthritis synovial fluid the activated T4/T8 ratio (calculated from T cells in the S phase of the cell cycle) was significantly different from the total T4/T8 ratio (calculated for all the T cells) (0.45±0.05 versus 0.69±0.05, P〈0.01). Similarly, the activated and total T4/T8 ratios were also significantly different in the phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cell cultures at days 3 and 5.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00270309
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  • 6
    Electronic Resource
    Electronic Resource
    Plasma interleukin-6 and renin substrate in reactive arthritis, rheumatoid arthritis, and systemic lupus erythematosus (1992)
    Springer
    Rheumatology international 12 (1992), S. 93-96 
    Details
    ISSN: 1437-160X
    Keywords: Angiotensinogen ; Inflammation ; Interleukin-6 ; Reactive arthritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to study the role of interleukin-6 (IL-6) in inflammatory disease we monitored plasma levels of IL-6 and acute phase proteins such as C-reactive protein (CRP) and renin substrate (RS) in patients with reactive arthritis (ReA), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Venous plasma samples were collected: (1) during the acute phase or exacerbation of the disease, and (2) several months later during convalescense. Increased mean [95% confidence intervals (CI)] levels of plasma IL-6 were observed in patients with ReA both in the acute phase and later, 229 (177 to 280) ng/l and 197 (134 to 260) ng/l respectively (P 〈0.001 as compared to controls). The corresponding plasma IL-6 levels in RA patients were 283 (223 to 340) ng/l and 183 (151 to 226) ng/l, respectively (P 〈0.001 as compared to controls). Plasma IL-6 levels in SLE patients were not increased. Plasma RS levels were increased in all patient groups, but no significant correlation to IL-6 or CRP levels was observed, whereas plasma IL-6 and CRP levels showed a positive correlation in ReA and RA patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00290261
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  • 7
    Electronic Resource
    Electronic Resource
    Anti-collagenolytic mechanism of action of doxycycline treatment in rheumatoid arthritis (1998)
    Springer
    Rheumatology international 17 (1998), S. 175-180 
    Details
    ISSN: 1437-160X
    Keywords: Key words Rheumatoid arthritis ; Doxycycline ; Collagenases ; Matrix metalloproteinases ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tetracyclines exert, independently of their anti-microbial activity, anti-collagenolytic effects by inhibiting activities of human interstitial collagenases and by preventing the oxidative activation of latent pro-collagenases. We tested the clinical response to a 3-month doxycycline in concert with collagenase activity in 12 rheumatoid arthritis (RA) patients. Patients received 150 mg/day of doxycycline for 3 months. Clinical assessments at zero, six and 12 weeks comprised classification of the functional class, joint score index, Hb, CRP, ESR, health assessment questionnaire, visual analogue scale (VAS) of pain, pain disability index, comprehensible psychopathological rating scale (CPRS), SDS-PAGE laser densitometric collagenase activity measurements and Western blots. Significant reductions were seen in joint score index (P〈0.01), pain VAS (P〈0.05) and some CPRS parameters. Furthermore, collagenase activities measured from saliva by quantitative SDS-PAGE electrophoresis were significantly reduced during the 12-week intervention (P〈0.01). Western blots demonstrated intact 75–80 kDa enzyme protein (classic neutrophil collagenase), but also a newly discovered mesenchymal, less glycosylated 40–55 kDa MMP-8 subtype of fibroblast/chondrocytic origin. These results indicate that the documented favourable clinical response may in part be due to in vivo inhibition of classic neutrophil and mesenchymal collagenase/MMP-8 activities produced by doxycycline. This anti-collagenolytic doxycycline effects is mediated through inhibition of the enzyme activity and not through degradation of the enzyme, which may have contributed to the reportedly reduced tissue destruction, as has been seen in clinical studies concerning RA as well as reactive arthritis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002960050030
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  • 8
    Electronic Resource
    Electronic Resource
    Gly-X-Y repeat sequences in the treatment of active rheumatoid arthritis (1999)
    Springer
    Rheumatology international 18 (1999), S. 129-135 
    Details
    ISSN: 1437-160X
    Keywords: Key words Oral tolerance ; Collagen ; Gelatin ; Gly-X-Y repeat ; Arthritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to examine if oral administration of Gly-X-Y repeat sequences alleviates disease activity in rheumatoid arthritis (RA). The study had a randomized, placebo controlled and double blind design with a wash-out/cross-over between the two 3-months long treatment periods. A total of 40 patients entered and 36 patients fulfilled the study, among them 16 started with the active drug and 20 with a placebo. Disease activity score (DAS) was used as the primary outcome measure with several secondary outcome variables. Type I or α error of 0.05 was accepted and the power (=1-β) was set to 80%, which according to the power analysis was also achieved. With active drug treatment, joint swelling score (54 count; P〈0.001), Ritchie's index (P〈0.01) and DAS (P〈0.001) improved. HAQ also improved (P〈0.05), but there was no improvement in the subjective condition of the patients as measured with the self-reported Pain Disability Index and Comprehensible Psychopathological Rating scale questionnaires. Apparently, 5/36 patients had a response of ≥1.2 in DAS and 33/36 changed for the better; DAS impaired only in 3/36 patients during the active drug treatment. When the stringent EU response criteria were applied and the results were compared to the placebo group, the response was not clinically significant. We conclude that Gly-X-Y repeat sequences are not effective as used in the present study. However, this does not definitely disprove the value of the Gly-X-Y repeat sequences, because confounding effects of dosage, concomitant medication and excessive degradation of the linear Gly-X-Y sequences in the stomach, gut or by phagolysosomes could not be adequately controlled. The discrepancy between the favourable effects in the preliminary, open pilot study and the controlled clinical trial emphasizes the value of the DAS, EU response criteria and adequately administered controlled clinical studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002960050071
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  • 9
    Electronic Resource
    Electronic Resource
    Alpha-linolenic acid in the treatment of rheumatoid arthritis. A double-blind, placebo-controlled and randomized study: flaxseed vs. safflower seed (1995)
    Springer
    Rheumatology international 14 (1995), S. 231-234 
    Details
    ISSN: 1437-160X
    Keywords: Dietary intervention ; Alpha-linolenic acid ; Rheumatoid arthritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In rheumatoid arthris s various pro-inflammatory metabolites of arachidonic acid (AA), such as leukotriene B4 (LTB4) and prostaglandin E2 (PGE2), contribute to tissue destruction and pain. In contrast to AA, which is an omega-6 fatty acid, the omega-3 fatty acids, after having been liberated from the cell membrane phospholipids, are further converted into the non-or anti-inflammatory eicosanoids LTB5 and PGI3. AA concentration is an important regulatory step in the synthesis of both prostanoids and leukotriens. Dietary supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has therefore been used to decrease the ratio of AA to EPA or DHA to obtain beneficial clinical effects. EPA and DHA are found in animal fat and are quite expensive compared to their precursor alpha-linolenic acid (alpha-LNA) found in flaxseed oil. We, therefore, performed a placebocontrolled trial with alpha-LNA in 22 patients with rheumatoid arthritis, using a linoleic acid preparation as a placebo. After a 3-month follow-up, the treatment group showed an increased bleeding time, but the clinical, subjective (global assessment, classification of functional status, joint score index, visual analogue scale, pain tendereness score) and laboratory parameters (haemoglobin, erythrocyte sedimentation rate, C-reactive protein) did not show any statistical alterations. AA, EPA and DHA did not change either in spite of a significant increase in alpha-LNA in the treatment group. Thus, 3-month's supplementation with alpha-LNA did not prove to be beneficial in rheumatoid arthritis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00262088
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  • 10
    Electronic Resource
    Electronic Resource
    Availability of iron and degree of inflammation modifies the response to recombinant human erythropoietin when treating anemia of chronic disease in patients with rheumatoid arthritis (1997)
    Springer
    Rheumatology international 17 (1997), S. 67-73 
    Details
    ISSN: 1437-160X
    Keywords: Key words Anemia of chronic disease ; Rheumatoid arthritis ; Erythropoietin ; Iron supplementation ; Inflammation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Forty-six patients with rheumatoid arthritis (RA) and documented anemia of chronic disease (Hb 〈100/110 g/l) were randomized to receive either human recombinant erythropoietin (r-HuEPO, n = 36, 300 U/kg body weight) or placebo (n = 10) for 12 weeks in a multicenter study. An adequate response was defined as elevation of Hb≥120 g/l. Relevant clinical and laboratory assessments were made to evaluate efficacy and secure safety. A significant elevation in Hb from week 10 onwards was noted in twenty-six patients (five drop-outs) out of nine patients receiving placebo (one drop-out) (12±1.2 g/l vs 4±0.5 g/l; Hb elevation from 95 g/l to 107 g/l vs 93 g/l to 97 g/l, P〈0.05). Only 14.6%, however, were considered responders according to preset criteria. In the responders a lower initial CRP, a significant reduction in ESR but not in CRP was seen compared to the remaining r-HuEPO group. A significant elevation of energy level was noted in the r-HuEPO group; otherwise, no differences in clinical variables were seen. No serious adverse effects were noted. When analyzing patients receiving oral iron in combination with r-HuEPO and adding five additional, openly selected patients receiving both adequate iron supplementation and r-HuEPO, there was a significant weekly elevation of Hb from week 8 onwards in favor of combination therapy over the ones only receiving r-HuEPO (18±1.1 g/l vs 7±1.1 g/l, P〈0.05). The initial six responders had now reached ten of whom seven belonged to the combination therapy group. Response to r-HuEPO in RA patients appears to be dependent on availability of iron and on the degree of inflammation. If r-HuEPO treatment is considered, iron deficiency should always be corrected and strenous efforts should have been made to control the disease itself.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002960050011
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