Gamma interferon and interleukin-10 gene expression in synovial tissues from patients with early stages of Chlamydia-associated arthritis and undifferentiated oligoarthritis and from healthy volunteers.
(17/2657)
Genetically determined differences in interleukin-10 (IL-10) and gamma interferon (IFN-gamma) responses in mice correlate with clearance of Chlamydia pneumonitis infection. We measured the synovial expression of IL-10 and IFN-gamma and additional cytokine genes in patients who had recent-onset Chlamydia-associated arthritis (Chl-AA). IL-10 and IFN-gamma mRNA were relatively abundant in recent-onset Chl-AA. (+info)
Predominance of mononuclear cells expressing the chemokine receptor CCR5 in synovial effusions of patients with different forms of arthritis.
(18/2657)
OBJECTIVE: To study the role of the chemokine receptors CCR5 and CCR2 in patients with arthritis. METHODS: CCR5 expression on peripheral blood leukocytes was compared with the expression on leukocytes isolated from the synovial fluid of 20 patients with different rheumatic joint diseases. Three additional samples were studied for CCR2 expression. The expression of chemokine receptors on blood and synovial fluid leukocytes was determined by 3-color flow cytometry analysis. To test CCR5 receptor down-modulation from the cell surface, leukocytes were incubated in vitro with a RANTES (regulated on activation, normal T cell expressed and secreted) derivative, aminooxypentane (AOP)-RANTES. Patients were genotyped for the delta32 CCR5 deletion by polymerase chain reaction. RESULTS: A high percentage of CCR5-expressing CD4+ and CD8+ T cells (74% and 81%, respectively), monocytes (51%), and natural killer cells (35%) was found in the synovial fluid of all patients, whereas in the peripheral blood, only a small percentage of these cells expressed CCR5 (13%, 32%, 7.8%, and 4%, respectively). Infiltration of CCR5-positive leukocytes was not reduced in CCR5-heterozygous patients. A similar, but less pronounced, distribution was observed for CCR2-positive T cells. In vitro, CCR5 was completely down-modulated on synovial fluid leukocytes by AOP-RANTES. CONCLUSION: The predominance of CCR5-positive mononuclear cells in the synovial effusions of patients with arthritis suggests an important role for CCR5 in the process of joint inflammation, and identifies CCR5 as a possible new target for therapeutic intervention. (+info)
The detection of DNA from a range of bacterial species in the joints of patients with a variety of arthritides using a nested, broad-range polymerase chain reaction.
(19/2657)
OBJECTIVE: Bacteria have been implicated in the pathogenesis of many types of inflammatory arthritides. The aim of this study was to identify any bacterial DNA in synovial fluid (SF) from patients with a range of inflammatory arthritides. METHODS: A highly sensitive, broad-range, nested polymerase chain reaction (PCR) protocol targeting the bacterial 16S rRNA gene was designed and applied to SF from 65 patients with a range of rheumatic diseases. RESULTS: Bacterial DNA was detected in 26 SF samples, including eight from patients with rheumatoid arthritis and five with juvenile arthritides. PCR products were identified by sequencing and searching of bacterial genomic databases; 'best fits' included Haemophilus influenzae, Bordetella and Yersinia. CONCLUSIONS: These finding suggest an association between bacterial infection and inflammatory arthritides in some patients. Further research is required to determine the role of these organisms in the pathogenesis and whether such patients might respond to prolonged antibiotic therapy. (+info)
Granisetron (Kytril) suppresses methotrexate-induced nausea and vomiting among patients with inflammatory arthritis and is superior to prochlorperazine (Stemetil).
(20/2657)
OBJECTIVE: Methotrexate (MTX) is an increasingly popular anti-rheumatic drug with its usefulness limited by toxicity, most commonly gastrointestinal (GI). The aim of the study was to study the effectiveness of the 5-HT3 receptor antagonist granisetron (GR) in the therapy of MTX-induced nausea. METHODS: A single-blind 8 week pilot study with random allocation to either GR 1 mg or prochlorperazine (Stemetil; PCh) 10 mg was undertaken in 13 patients who were taking or had taken MTX for either rheumatoid arthritis (10) or psoriatic arthritis (3). RESULTS: One in six patients treated with PCh completed the 8 week study compared to 7/7 treated with GR. After switching of symptomatic patients, 11 completed the study on GR and median improvement was by two grades (P < 0.001) with a significantly better visual analogue scale score for patient satisfaction compared to PCh. CONCLUSION: Treatment with GR may be useful in establishing and maintaining some patients on MTX where GI toxicity would have precluded such therapy. (+info)
Bibliometric methods for the evaluation of arthritis research.
(21/2657)
This study uses bibliometric methods to evaluate the magnitude and quality of publications in arthritis research in the UK and compare this with that of other countries. Arthritis research was defined by publication in a specialist journal or by specific title key words or address. Outputs from 13 countries between 1988 and 1995 were analysed by number, research level (from clinical to basic) and potential impact on other researchers (from low to high). The UK has a strong presence in arthritis research and the highest relative commitment of all the countries studied. UK output was more clinical than that of other countries, except Spain, and was of relatively high impact. A second study examined UK arthritis papers supported by different funding sources, including government, private-non-profit and industry. Papers with funding acknowledgements were of significantly higher impact and less clinical than those without. The Arthritis Research Campaign was the leading funder in the UK with high-impact papers which, over the 8 yr period, have become more clinical than those supported by other funding sources, except hospital trusts. (+info)
Collagenase, cathepsin B and cathepsin L gene expression in the synovial membrane of patients with early inflammatory arthritis.
(22/2657)
OBJECTIVE: To examine the expression of the matrix metalloproteinase, MMP-1, and the cysteine proteases, cathepsin B (CB) and cathepsin L (CL), in the synovial membrane (SM) of patients with early inflammatory arthritis. METHODS: Samples of SM were obtained by blind needle biopsy or needle arthroscopy from inflamed knees of 28 patients with early inflammatory arthritis (mean disease duration 10.2 months, range 2 weeks-18 months). Sixteen patients had rheumatoid arthritis (RA), nine psoriatic arthritis and there was one each with ankylosing spondylitis, gout and an undifferentiated arthritis. Comparison was made with tissue from two patients with established erosive RA and three normal synovial tissue samples. In situ hybridization was performed using digoxigenin-labelled RNA probes. RESULTS: MMP-1, CB and CL were expressed in all patients with early arthritis and in established erosive RA, whereas normal synovium showed only scanty expression. The three proteases were prominent in perivascular infiltrates and endothelial cells of early arthritis tissue. MMP-1 was observed primarily in the lining layer, but was also evident in the sublining area. CB and CL were expressed to a lesser extent in the lining layer, and were present mainly in the subintima. The three proteases were not found in lymphoid aggregrates. No differences were observed between the disease categories. CONCLUSIONS: The detection of MMP-1, CB and CL in the synovium shortly after symptom onset implies that the potential for joint destruction exists at a very early stage in the disease. In addition, the perivascular and endothelial cell expression suggests a role for these proteases in mononuclear cell influx to the inflamed synovium and in angiogenesis. (+info)
Gene therapy of arthritis.
(23/2657)
Genes encoding anti-arthritic products can be transferred to intra-or extraarticular sites where their expression suppresses various aspects of the pathophysiology of arthritis. A variety of viral and non-viral vectors can be used for the in vivo or ex vivo delivery of such genes. Promising pre-clinical data have resulted from the application of these strategies in several animal models of disease. Genes showing efficacy in this way include these encoding interleukin (IL) -1Ra, IL-1sR, TNFsR, transforming growth factor beta (TGF-beta), IL-13, Fas L, IL- 10 and vIL-10. Two human arthritis gene therapy protocols are underway in the USA and Germany. Both studies involve the ex vivo transfer of an IL-1Ra cDNA to the metacarpophalangeal joints of patients with rheumatoid arthritis. Progress in developing gene treatments for arthritis has been rapid, and permits optimism about their ability eventually to improve the treatment of this group of diseases. (+info)
Angiogenesis and arthritis.
(24/2657)
Indices of angiogenesis are increased in synovia from patients with arthritis, and vascular proliferation may contribute to the pathogenesis of synovitis, pannus growth, bone and cartilage destruction, and osteophyte formation. Pharmacological inhibition of angiogenesis therefore has potential as a therapeutic strategy in human arthritis. However, vascular growth is also essential for normal development, female reproduction and tissue repair. Selective inhibition of undesirable angiogenesis requires an understanding of the different regulatory mechanisms in pathological and physiological angiogenesis. This review outlines the evidence that the rate of angiogenesis is increased in the inflamed human synovium, and possible approaches to, and consequences of, the modulation of vascular growth. (+info)