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Biomedical subjects

R D Sturrock

Publications and source records attributed to R D Sturrock.

At least 37 records · Page 2Linked to original sources
PubMed1999

Oral carriage of staphylococci in patients with rheumatoid arthritis.

OBJECTIVE: To determine the prevalence of oral staphylococcal carriage in patients with rheumatoid arthritis compared with healthy controls. METHODS: Fifty healthy adults, 25 healthy elderly volunteers and 25 patients with rheumatoid arthritis were studied. An oral rinse, tongue swab and nasal swab were collected for culture on blood agar and a range of selective agars. Isolates of staphylococci were identified and antibiotic sensitivity profiles determined by standard methods. RESULTS: Staphylococci were isolated from the mouths of 94% of the healthy adults, 24% of whom carried Staphylococcus aureus. All the healthy elderly carried oral staphylococci and 36% were colonized with S. aureus. Staphylococci were isolated from 96% of the rheumatoid arthritis patients and this group had the highest carriage rate of S. aureus (56%), significantly higher than the healthy adults (P < 0.05). In all three groups, Staphylococcus epidermidis was isolated from the mouths of > 80%. No methicillin-resistant strains of S. aureus were isolated. CONCLUSION: Oral carriage of S. aureus appears to be common in patients with rheumatoid arthritis and studies of the mouth as a source of infection in septic arthritis would be merited.

Adolescent↗
PubMed1999

Clinical aspects, outcome assessment, disease course, and extra-articular features of spondyloarthropathies.

Much has been written over the years regarding the clinical aspects and disease course of the spondyloarthropathies, but publications relating to outcome assessment that attempt to relate measures of process with outcome are few. Extra-articular features of the spondyloarthropathies, eg, uveitis, colitis, and aortitis, are well described, but in the past few years there has been an increasing interest in the incidence of osteoporosis in this group of patients, particularly those with ankylosing spondylitis. In rheumatoid arthritis functional indices have been developed, such as the Health Assessment Questionnaire score, which has been shown to be robust in monitoring response to therapy, but the situation is quite different in a condition such as ankylosing spondylitis. In the last few years a number of functional indices have been developed that are now beginning to be applied to monitor response to treatment in the spondyloarthropathies. The impact of ankylosing spondylitis in women is an area that has been neglected in the past, and a recent review addresses the effects of the disease on the reproductive capacity in women. This overall review of the past year's publications from the clinical aspects of ankylosing spondylitis confirms that clinical research still has much to contribute to this fascinating group of disorders.

Aortitis↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗