Can the routine culture of synovial fluid be justified?
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Adolescent↗
Biomedical subjects
R D Sturrock
Publications and source records attributed to R D Sturrock.
Myocrisin-mediated oxidative stress.
This study reports on the ability of myocrisin to mediate in the production and detoxification of oxidants (principally hydrogen peroxide) in the monocyte in-vivo and in-vitro. The hydrogen peroxide produced by the monocyte derived from rheumatoid arthritis patients being treated with myocrisin was found to be 14.9 +/- 1.6 nmoles/10(6) cells and is elevated above levels found in monocytes obtained from patients either being treated with non-steroidal anti-inflammatory drugs (NSAIDs) (11.3 +/- 0.4 nmoles/10(6) cells; P < 0.01) or normal healthy volunteers (11.2 +/- 1.2 nmoles/10(6) cells; P < 0.01). A comparative study on glutathione (GSH) oxidation indicated that levels of monocyte GSH were elevated in myocrisin-treated patients (2.4 +/- 0.49 mmol/l) over normal healthy volunteers (0.83 +/- 0.18 mM; P < 0.01) and that levels of monocyte diglutathione (GSSG) were depressed (myocrisin, 0.97 +/- 0.41 micromol/l; normal, 5.71 +/- 0.73 micromol/l; P < 0.01). The non-inhibition of glutathione reductase and the inhibition of glutathione peroxidase by gold provides the link between these two observations. Thus, gold therapy would seem to elevate monocyte hydrogen peroxide, increase monocyte reduced glutathione and decrease plasma glutathione peroxidase activity. Subsequently, the data from this small group of patients (n = 10) provides an indication that, in-vivo, myocrisin contributes to an increase in oxidative stress.
Anti-Inflammatory Agents, Non-Steroidal↗
Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-alpha production in rheumatoid arthritis.
Tumor necrosis factor-alpha occupies a central role in rheumatoid arthritis (RA) pathogenesis. We now report that interleukin-15 (IL-15) can induce TNF-alpha production in RA through activation of synovial T cells. Peripheral blood (PB) T cells activated by IL-15 induced significant TNF-alpha production by macrophages via a cell-contact-dependent mechanism. Freshly isolated RA synovial T cells possessed similar capability, and in vitro, IL-15 was necessary to maintain this activity. IL-15 also induced direct TNF-alpha production by synovial T cells. In contrast, IL-2 induced significantly lower TNF-alpha production in either cell-contact-dependent or direct culture, and IL-8 and MIP-1 alpha were ineffective. Antibodies against CD69, LFA-1 or ICAM-1 significantly inhibited the ability of T cells to activate macrophages by cell contact.
Arthritis, Rheumatoid↗
Famotidine for healing and maintenance in nonsteroidal anti-inflammatory drug-associated gastroduodenal ulceration.
BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) are strongly associated with gastroduodenal ulceration. How to manage patients with NSAID-associated ulcers is a common clinical dilemma. High-dose famotidine in the healing and maintenance of NSAID-associated gastroduodenal ulceration was therefore evaluated. METHODS: One hundred four patients with rheumatoid or osteoarthritis who had gastroduodenal ulceration received famotidine, 40 mg twice daily. Sixteen patients stopped and 88 continued their NSAID treatment. Ulcer healing was assessed endoscopically at 4 and 12 weeks. Seventy-eight NSAID users with healed ulcers were then randomized to receive 40 mg twice daily famotidine or placebo and underwent endoscopy at 4, 12, and 24 weeks. RESULTS: Cumulative ulcer healing rates at 12 weeks were 89.0% (95% confidence interval [CI], 82.3%-95.7%) for patients who continued NSAID treatment and 100% (95% CI, 82.9%-100.0%) for those who stopped. The subsequent estimated cumulative gastroduodenal ulcer relapse over 6 months for NSAID users who took placebo was 53.5% (95% CI, 36.6%-70.3%). This was reduced to 26.0% (12.1%-39.9%) in patients taking famotidine (P = 0.011). CONCLUSIONS: High-dose famotidine is effective ulcer healing therapy in patients who stop or continue NSAID treatment and significantly reduced the cumulative incidence of gastroduodenal ulcer recurrence compared with placebo when given as maintenance therapy.
Adult↗
Musculoskeletal ultrasound imaging: a new diagnostic tool for the rheumatologist?
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Animals↗
Persistence of Staphylococcus aureus as detected by polymerase chain reaction in the synovial fluid of a patient with septic arthritis.
Septic arthritis commonly occurs in the rheumatoid arthritis population. The diagnosis is frequently delayed and the associated mortality is high. In this brief report, we present a patient with rheumatoid arthritis and prosthetic knee joints who developed septic arthritis and had persisting evidence of Staphylococcus aureus DNA in synovial fluid, from his knees, which was detected by polymerase chain reaction (PCR) and a gene probe. This was detected until 10 weeks of therapy despite adequate antibiotic treatment and a sterile synovial fluid. In the future, it may be found that PCR of the synovial fluid will be a valuable investigation for the diagnosis and management of septic arthritis.
Aged↗
Role of certain virulence factors in a murine model of Staphylococcus aureus arthritis.
The susceptibility of male Swiss white mice (MF1) to Staphylococcus aureus-induced arthritis was investigated with wild-type strain allelic replacement mutants. Comparison was made with a known mouse arthritogenic strain. The development and severity of arthritis were dependent both on the numbers of live bacteria injected intravenously and also on the mutant used; the ID50 ranged from (5 X 10(6))-(1 x 10(8)) cfu. The results indicate that expression of the genes associated with virulence, including those for protein A and alpha-haemolysin, play a major role in the pathogenesis of staphylococcal septic arthritis. When either virulence component was carried by the S. aureus variant, a greater degree of inflammation, pannus formation and cartilage destruction was detected histologically. Loss of one or more virulence factors lowered the septic arthritis severity score based on clinical and histological parameters.
Animals↗
Production of nitric oxide in the synovial membrane of rheumatoid and osteoarthritis patients.
We have demonstrated spontaneous nitric oxide (NO) production by primary synovial cultures from rheumatoid (RA) and osteoarthritis patients. Increased NO production followed addition of staphylococcal enterotoxin B. Immunochemical double staining with specific anti-human inducible NO synthase (iNOS) and nonspecific esterase (NSE), or anti-CD68 (markers for tissue macrophages) showed that although many lining layer cells in RA synovium expressed iNOS, most (approximately 90%) were NSE- and CD68-, with only a minor population (approximately 10%) which were iNOS+, CD68+/NSE+. These data demonstrate the capacity for high output of NO by human synovial tissue and show that, although human macrophages can express high levels of iNOS, the majority of cells expressing iNOS are fibroblasts. We also report that synoviocytes, and macrophage cell lines, cultured with the NO donor, S-nitroso-acetyl penicillamine, produced high concentrations of tumor necrosis factor (TNF)-alpha. These results suggest that NO may mediate pathology in RA through the induction of TNF-alpha production.
Adult↗
Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal antiinflammatory drugs.
BACKGROUND: Acid suppression with famotidine, a histamine H2-receptor antagonist, provides protection against gastric injury in normal subjects receiving short courses of aspirin or naproxen. The efficacy of famotidine in preventing peptic ulcers in patients receiving long-term therapy with nonsteroidal antiinflammatory drugs (NSAIDs) is not known. METHODS: We studied the efficacy of two doses of famotidine (20 mg and 40 mg, each given orally twice daily), as compared with placebo, in preventing peptic ulcers in 285 patients without peptic ulcers who were receiving long-term NSAID therapy for rheumatoid arthritis (82 percent) or osteoarthritis (18 percent). The patients were evaluated clinically and by endoscopy at base line and after 4, 12, and 24 weeks of treatment. The evaluators were unaware of the treatment assignment. The primary end point was the cumulative incidence of gastric or duodenal ulceration at 24 weeks. RESULTS: The cumulative incidence of gastric ulcers was 20 percent in the placebo group, 13 percent in the group of patients receiving 20 mg of famotidine twice daily (P = 0.24 for the comparison with placebo), and 8 percent in the group receiving 40 mg of famotidine twice daily (P = 0.03 for the comparison with placebo). The proportion of patients in whom duodenal ulcers developed was significantly lower with both doses of famotidine than with placebo (13 percent in the placebo group, 4 percent in the low-dose famotidine group [P = 0.04], and 2 percent in the high-dose famotidine group [P = 0.01]). Both doses of famotidine were well tolerated. CONCLUSIONS: Treatment with high-dose famotidine significantly reduces the cumulative incidence of both gastric and duodenal ulcers in patients with arthritis receiving long-term NSAID therapy.
Adult↗
The role of interleukin-15 in T-cell migration and activation in rheumatoid arthritis.
Interleukin 15 (IL-15) is a novel cytokine with interleukin-2-like activity. It is also a potent T-lymphocyte chemoattractant. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the presence of activated T lymphocytes, macrophages and synoviocytes in the synovial membrane. The mechanisms of T-cell activation in RA are currently unclear. We report the presence of high concentrations of IL-15 in rheumatoid arthritis (RA) synovial fluid and have demonstrated its expression in the synovial membrane lining layer by immunohistochemistry. RA synovial fluids were found to contain chemotactic activity, which was attributable in part to the presence of IL-15. Moreover, in a murine model, injection of recombinant IL-15 was found to induce a local tissue inflammatory infiltrate consisting predominantly of T lymphocytes. Synovial fluid T lymphocytes proliferate in response to IL-15, demonstrating that continued responsiveness to IL-15 is a feature of T cells after entry into the synovial compartment. These data suggest that IL-15 can recruit and activate T lymphocytes in the synovial membrane, thereby contributing to RA pathogenesis.
Aged↗
Cervical spondylodiscitis in a patient with ankylosing spondylitis.
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Cervical Vertebrae↗
CAMPATH-1H, a humanized monoclonal antibody, in refractory rheumatoid arthritis. An intravenous dose-escalation study.
OBJECTIVE: To evaluate the biologic response, tolerability, and potential clinical effect of a humanized antilymphocyte monoclonal antibody, CAMPATH-1H, in patients with rheumatoid arthritis (RA). METHODS: Forty adult patients with active, refractory RA were treated with CAMPATH-1H, given intravenously, in a multicenter, open, single-dose-escalation study. Patients were assigned to dose groups of 1, 3, 10, 30, 60, and 100 mg CAMPATH-1H. RESULTS: There was a profound, immediate, and sustained reduction of the peripheral lymphocyte count; the most susceptible were the levels of CD4+ and CD8+ cells, which remained depressed during the study period. Sixty-three percent of patients developed antibodies to CAMPATH-1H. Side effects occurred frequently throughout the first 24 hours following infusion, and included fever, headache, nausea, vomiting, and hypotension. All of the immediate drug toxicities resolved within the initial 24-hour postdosing period. One patient developed a reactivation of Mycobacterium xenopi infection 10 weeks following infusion. Sixty-five percent of patients developed a clinical response; the mean duration of response was 2 weeks. CONCLUSION: CAMPATH-1H is a lymphocyte-depleting antibody that is biologically potent even after single-dose therapy. There was no correlation between biologic effect and clinical response. Sustained lymphocyte suppression was observed. Acute infusion toxicities were observed in most patients. The role of depleting monoclonal antibodies in the treatment of RA should be reevaluated.
Adult↗
The effect of the hypermobility syndrome on knee joint proprioception.
Proprioceptive sensory feedback is utilized by the central nervous system for conscious appreciation of the position and movement of the body and limbs. In patients with the hypermobility syndrome (HMS), it has been suggested that there is alteration of proprioceptive acuity. Proprioceptive performance of the knee joint was investigated in 10 female subjects who suffered from HMS using a threshold detection paradigm (accurate determination of the onset and direction of knee joint displacement at constant angular velocity). Compared to age- and sex-matched controls, HMS subjects showed significantly higher detection levels at starting knee flexion angles of 30 degrees P < 0.001) and 5 degrees (P < 0.001). Control subjects showed no significant difference in threshold acuity between the sexes (at 5 degrees P = 0.63, at 30 degrees P = 0.48). The increased acuity in proprioception observed towards full extension in the control population (P < 0.001) was absent in the HMS subjects (P = 0.596). Findings reported here suggest that HMS subjects have poorer proprioceptive feedback than controls. Reduced sensory feedback may lead to biomechanically unsound limb positions being adopted. Such a mechanism may allow acceleration of degenerative joint conditions, and may account for the increased prevalence of such conditions seen with HMS subjects.
Adult↗
T-cell clonality in synovial fluid from rheumatoid joints before and after culture in interleukin-2.
T-cell receptor (TCR) gamma gene rearrangements which have been amplified in polymerase chain reactions (PCRs) and analysed by high resolution polyacrylamide gel electrophoresis have been used to investigate the clonal diversity of T-cells in joint effusions from 16 patients with rheumatoid arthritis, one with systemic lupus erythematosus and one with psoriatic arthropathy. Polyclonality was found in every case but an oligoclonal subset of dominant rearrangements was also demonstrated in all but the patient with psoriasis. Marked changes in the relative preponderance of the various clonotypes were observed in 29 of 48 paired tests from 12 cases before and after culture in media containing interleukin-2 (IL-2) showing that SF mononuclear cells cultured in vitro with IL-2 are not representative of those present in vivo.
Adult↗
Effect of cyclosporin A on interleukin-6 and soluble interleukin-2 receptor in patients with rheumatoid arthritis.
OBJECTIVE: To investigate the effect of cyclosporin A (CyA) therapy on circulating concentrations of interleukin-6 (IL-6) and soluble interleukin-2 receptor (sIL-2R) in patients with rheumatoid arthritis (RA). METHODS: Twenty four RA patients with active disease were studied. Plasma was collected before and after 16 weeks of CyA treatment. IL-6 was measured by B9 bioassay and sIL-2R by enzyme linked immunosorbent assay (ELISA). RESULTS: The initial median IL-6 concentration of 165 IU/ml decreased significantly to 71 IU/ml after 16 weeks (p < 0.05). Similarly, the initial median plasma sIL-2R value of 665 U/ml decreased significantly to 570 U/ml (p < 0.05). This decrease was accompanied by an improvement in clinical parameters of disease activity. Some association between sIL-2R, IL-6, haemoglobin, and platelets was also observed. CONCLUSIONS: This study has demonstrated that, in vivo, CyA therapy in RA can significantly reduce circulating concentrations of IL-6 and sIL-2R. Modulation of both T and non-T cell derived cytokines may be one mechanism by which CyA improves rheumatoid disease. Whether this is a direct effect of CyA on the cells within the rheumatoid joint producing these cytokines or an indirect effect mediated by other cytokines which can influence IL-6 and Il-2R values remains to be determined.
Adult↗
Mucosal erosions in longterm non-steroidal anti-inflammatory drug users: predisposition to ulceration and relation to Helicobacter pylori.
The importance of erosions in longterm non-steroidal anti-inflammatory drug (NSAID) users, their relevance to ulceration and their relation to Helicobacter pylori are unclear. This study assessed the incidence of peptic ulcers in the presence or absence of erosions or H pylori in a group of longterm NSAID users (n = 50), undergoing endoscopy at 0, 4, 12, and 24 weeks while continuing with NSAIDs. Ulcers diagnosed at baseline endoscopy were excluded. Ulcers developed in nine of 23 patients (39%) with pre-existing erosions compared with six of 27 (22%) without erosions (p < 0.05). The group infected with H pylori (n = 30) had a total of 18 patients (60%) with erosions, a total of 12 ulcers (40%), and eight ulcers (27%) complicating previous erosions, compared with five (25%, p < 0.01), three (15%, p < 0.05), and one (5%, p < 0.01) respectively in patients not infected with H pylori (n = 20). Ulcer development was not influenced by the initial number of erosions but strongly associated with H pylori positive duodenal erosions. It is concluded that ulcers are more likely to develop in longterm NSAID users who have mucosal erosions or H pylori, or both.
Adult↗
Slow-acting antirheumatic drugs. Drug interactions of clinical significance.
The slow-acting antirheumatic drugs (SAARDs) are being used in an increasing proportion of patients with rheumatoid arthritis (RA). The potential toxicity of each drug is well recognised. Many patients with RA will be on other medications and the potential for adverse drug interactions with SAARDs is not so well publicised. There have, over the years, been numerous reports of possible drug interactions with SAARDs but few of these are clinically relevant. It is, however, vitally important that the physician is aware of a number of potentially life-threatening interactions, particularly those associated with methotrexate. The SAARDs are a very useful group of drugs for the treatment of RA and, by being aware of their potential toxicity and drug interactions, hopefully they can be used safely and effectively.
Antirheumatic Agents↗
Microwave thermography as a noninvasive assessment of disease activity in inflammatory arthritis.
Microwave thermography is the technique of measuring natural thermal radiation from body tissues of clinical interest. It is safe, requires no control of environmental conditions and exposes the patient to no ionising radiation. In this study, we found that microwave thermography of the knee joints showed weak correlation with some global parameters of disease activity. Bed rest alone for three days had no significant effect on microwave thermographic index (MTI). Intra-articular steroid injection, however, was associated with a marked fall in MTI both in the injected knee and the contra-lateral knee. We conclude that microwave thermography can measure inflammatory activity in the knee joints of patients with inflammatory arthritis and can respond to clinical change brought about by major treatment intervention.
Adrenal Cortex Hormones↗