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Biomedical subjects

R D Sturrock

Publications and source records attributed to R D Sturrock.

At least 19 recordsLinked to original sources
PubMed2006

TLR4 mutations (Asp299Gly and Thr399Ile) are not associated with ankylosing spondylitis.

BACKGROUND: Immunoregulatory genes and Gram negative gut bacteria are thought to be important in disease expression in ankylosing spondylitis (AS). OBJECTIVE: To compare the frequency of two common and functional TLR4 mutations (Asp299Gly, and Thr399Ile) between patients with AS and HLA-B27 healthy controls. METHODS: The TLR4 genotypes of patients and healthy HLA-B27 controls were determined using allele-specific PCR and restriction fragment length polymorphism analysis. Asp299Gly genotype was determined in 193 patients and 125 HLA-B27 positive controls and Thr399Ile genotype in 184 patients and 113 HLA-B27 controls. Allele frequencies were compared using a chi(2) test of association. RESULTS: 29/193 (15%) patients with AS had a polymorphism in the Asp299 site compared with 18/125 (14.4%) healthy HLA-B27 controls. Of the patients genotyped for the Thr399Ile allele, 29/184 (15.8%) carried the polymorphism compared with 19/113 (16.8%) HLA-B27 controls. No significant difference between the frequencies of the Asp299Gly genotype or the Thr399Ile genotype between patients with AS and healthy HLA-B27 controls was found. No significant difference in allele frequency was found at either site. CONCLUSION: Two common TLR4 polymorphisms, which cause a functional deficiency in host immune response to Gram negative bacteria, are not overrepresented in patients with AS.

Case-Control Studies↗
PubMed2005

ASAS/EULAR recommendations for the management of ankylosing spondylitis.

OBJECTIVE: To develop evidence based recommendations for the management of ankylosing spondylitis (AS) as a combined effort of the 'ASsessment in AS' international working group and the European League Against Rheumatism. METHODS: Each of the 22 participants was asked to contribute up to 15 propositions describing key clinical aspects of AS management. A Delphi process was used to select 10 final propositions. A systematic literature search was then performed to obtain scientific evidence for each proposition. Outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. The effect size, relative risk, number needed to treat, and incremental cost effectiveness ratio were calculated. On the basis of the search results, 10 major recommendations for the management of AS were constructed. The strength of recommendation was assessed based on the strength of the literature evidence, risk-benefit trade-off, and clinical expertise. RESULTS: The final recommendations considered the use of non-steroidal anti-inflammatory drugs (NSAIDs) (conventional NSAIDs, coxibs, and co-prescription of gastroprotective agents), disease modifying antirheumatic drugs, treatments with biological agents, simple analgesics, local and systemic steroids, non-pharmacological treatment (including education, exercise, and physiotherapy), and surgical interventions. Three general recommendations were also included. Research evidence (categories I-IV) supported 11 interventions in the treatment of AS. Strength of recommendation varied, depending on the category of evidence and expert opinion. CONCLUSION: Ten key recommendations for the treatment of AS were developed and assessed using a combination of research based evidence and expert consensus. Regular updating will be carried out to keep abreast of new developments in the management of AS.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

A clinical procedure to predict the value of temporary occlusion therapy in keratoconjunctivitis sicca.

PURPOSE: To evaluate the effects of dissolvable collagen punctal plugs on the symptoms, tear stability and volume in aqueous deficient dry eyes. METHODS: Sixty-two aqueous deficient dry eye patients of mixed aetiology underwent lacrimal punctal occlusion with dissolvable collagen plugs. The subjects were randomly allocated to one of two treatment groups: group I (n = 36) had their lower puncta occluded and group II (n = 26) had both their upper and lower puncta occluded. The effectiveness of this treatment was clinically assessed by (1). scoring subject symptoms and (2). measuring the tear parameters of tear thinning time (TTT) and tear meniscus height (TMH) as indicators of tear stability and volume, respectively. Following baseline measurements, patients were reviewed at time intervals of 5 and 12 days post-occlusion. A group of age- and gender-matched normals (n = 45) was recruited for comparison (group III). RESULTS: Tear volume and stability were significantly higher in group III compared with I and II at baseline. In the treated groups on both days 5 and 12: (1). symptom score reduced significantly from a median value of 7 to 3 (p = <0.001); (2). tear stability increased significantly from a median value of 3 to 5 s by day 5 (p <or= 0.001); reduced between days 5 and 12 (p < 0.05) and remained below the stability in group III at all times; (c). tear volume increased significantly by day 5 in both treatment groups from a median value of 0.13 to 0.20 mm (p<or=0.001), remained stable by day 12 in group II but reduced in group I (p < 0.05); (d). the increase in tear volume was negatively correlated with pre-treatment tear volume; (e). symptom score correlated with both baseline tear volume and stability. CONCLUSION: Collagen plugs improved tear status in the aqueous deficient dry eyes. Occluding both upper and lower puncta with temporary collagen plugs offers no practical beneficial gain compared with occluding just the lower punctum.

Adult↗
PubMed2003

Prospective comparative study of patients with culture proven and high suspicion of adult onset septic arthritis.

OBJECTIVE: To investigate whether patients with acute septic arthritis (SA) diagnosed by positive synovial fluid (SF) culture (Newman grade A) have different clinical and serological features from those with sterile SF in whom there is nonetheless a high suspicion of SA (Newman grades B and C). PATIENTS AND METHODS: A prospective 12 month multicentre hospital based study of adult patients with SA recruited 47 patients with culture positive SA and 35 patients with clinically suspected SA but sterile SF. RESULTS: Patient demography, clinical and laboratory features at presentation were similar irrespective of the underlying diagnosis, SF culture, and the presence of prosthetic joints. Medical and surgical treatment and outcome were comparable in the two patient groups. Patients with both suspected and proven SA were more likely to be from the more socially deprived areas of our community (p<0.0001). CONCLUSION: Patients in whom there is a high clinical suspicion of SA are comparable to those patients with SA with a positive SF culture and have similar morbidity and mortality on follow up. Therefore, if clinical suspicion of SA is high then it is correct to treat as SA in the absence of bacterial proof.

Acute Disease↗
PubMed2002

Ultrasonography of entheseal insertions in the lower limb in spondyloarthropathy.

OBJECTIVE: To compare ultrasonography (US) with clinical examination in the detection of entheseal abnormality of the lower limb in patients with spondyloarthropathy (SpA). METHODS: 35 patients with SpA (ankylosing spondylitis 27; psoriatic arthritis 7; reactive arthritis 1) underwent independent clinical and ultrasonographic examination of both lower limbs at five entheseal sites-superior pole and inferior pole of patella, tibial tuberosity, Achilles tendon, and plantar aponeurosis. US was performed using an ATL (Advanced Technology Laboratories, Bothell, Washington, USA) high definition imaging 3000 machine with linear 7-4 MHz and compact linear 10-5 MHz probes to detect bursitis, structure thickness, bony erosion, and enthesophyte (bony spur). An enthesitis score was formulated from these US findings giving a possible maximum total score of 36. RESULTS: On clinical examination 75/348 (22%) entheseal sites were abnormal and on US examination 195/348 (56%) sites were abnormal. In 19 entheseal sites with bursitis on US, only five were detected by clinical examination. Compared with US, clinical examination had a low sensitivity (22.6%) and moderate specificity (79.7%) for the detection of enthesitis of the lower limbs. There was no significant correlation between the US score of enthesitis and acute phase parameters such as erythrocyte sedimentation rate (ESR) or C reactive protein (CRP). The intraobserver kappa value for analysis of all sites was 0.9. CONCLUSIONS: Most entheseal abnormality in SpA is not detected at clinical examination. US is better than clinical examination in the detection of entheseal abnormality of the lower limbs in SpA. A quantitative US score of lower limb enthesitis is proposed but further studies are required to validate it in SpA.

Achilles Tendon↗
PubMed2001

B cell receptor-stimulated mitochondrial phospholipase A2 activation and resultant disruption of mitochondrial membrane potential correlate with the induction of apoptosis in WEHI-231 B cells.

Cross-linking of the Ag receptors on the immature B cell lymphoma, WEHI-231, leads to growth arrest and apoptosis. We now show that although commitment to such B cell receptor (BCR)-mediated apoptosis correlates with mitochondrial phospholipase A(2) activation, disruption of mitochondrial function, and ATP depletion, it is executed independently of caspase activation. First, we demonstrate a pivotal role for mitochondrial function in determining B cell fate by showing up-regulation of cytosolic phospholipase A(2) expression, induction of mitochondrial phospholipase A(2) activity, arachidonic acid-mediated collapse of mitochondrial transmembrane inner potential (Delta psi(m)), and depletion of cellular ATP under conditions of apoptotic, but not proliferative, signaling via the BCR. Importantly, disruption of Delta psi(m), ATP depletion, and apoptosis can be prevented by rescue signals via CD40 or by Delta psi(m) stabilizers such as antimycin or oligomycin. Second, we show that commitment and postmitochondrial execution of BCR-mediated apoptosis are not dependent on caspase activation by demonstrating that such apoptotic signaling does not induce release of cytochrome c from the mitochondria or activation of effector caspases, as evidenced by poly(ADP-ribose) polymerase or Bcl-x(L) cleavage. Indeed, apoptotic signaling via the BCR in WEHI-231 B cells does not stimulate the activation of caspase-3 and, consistent with this, BCR-mediated disruption of Delta psi(m) and commitment to apoptosis take place in the presence of caspase inhibitors. In contrast, BCR signaling induces the postmitochondrial activation of cathepsin B, and resultant apoptosis is blocked by the cathepsin B inhibitor, (23,35)trans-epoxysuccinyl-L-leucylamindo-3-methylbutane ethyl ester (EST) suggesting a key role for this executioner protease in Ag receptor-driven apoptosis of WEHI-231 immature B cells.

Adenosine Triphosphate↗
PubMed2001

A prospective 2-year study of 75 patients with adult-onset septic arthritis.

AIMS AND METHODS: To assess the clinical features of septic arthritis and characterize therapeutic strategies and outcome in a prospective study of 75 patients selected by positive synovial fluid culture. RESULTS: Underlying joint disease was present in 46 patients, 25 of whom had rheumatoid arthritis and 15 osteoarthritis. Eleven patients were i.v. drug abusers. Fifty-six per cent of cases involved the knee, 15% involved two or more joints, and staphylococci and streptococci were cultured in >90%. Seventy-eight per cent of patients lived in areas of high social deprivation. Fever was present in 64% and the white cell count (WCC) was normal in 38%. The C-reactive protein was elevated in 98%. Leg ulcers were present in 11% of all patients but in 38% of patients who died (P<0.006). Median duration of antibiotic therapy was 15 days i.v. with subsequent oral treatment for 21 days. Thirty-seven per cent of cases required surgical intervention. Mortality was 11%. A raised WCC at presentation (P<0.02) and the development of abnormal renal function (P<0.015) were predictors of poor prognosis.

Age of Onset↗
PubMed2001

Metacarpophalangeal joints in rheumatoid arthritis: laser Doppler imaging--initial experience.

Laser Doppler imaging is a noninvasive method yielding a spatial perfusion map. With use of a near-infrared laser, elevated perfusion associated with the metacarpophalangeal joints was detectable in patients with active rheumatoid arthritis. Findings at laser Doppler imaging correlated with pain scores and synovitis detected at ultrasonography, whereas the power Doppler sign (red pixels inside the active green box) did not. Laser Doppler imaging has the potential to help assess soft-tissue inflammation.

Adult↗
PubMed2000

Novel use of laser Doppler imaging for investigating epicondylitis.

OBJECTIVE: This investigation evaluated a novel form of tissue perfusion measurement, laser Doppler imaging (LDI), in a case of lateral epicondylitis to establish if it might have applications in assessing soft tissue lesions. LDI was used in conjunction with ultrasonography to provide information about tissue oedema as well as the power Doppler signal as an alternative method of assessing blood flow. METHODS: A laser Doppler imager with a near-infrared (NIR) laser source was used to improve tissue penetration and yield measurements of perfusion (flux) from structures under the skin. Skin temperature over the lateral epicondylar region was also measured. Ultrasonography was used in both grey-scale and power Doppler modes. LDI, temperature measurements and ultrasonographic data were obtained before treatment and serially after local injection of methylprednisolone. RESULTS: Before treatment there was increased perfusion and skin temperature and the presence of a power Doppler sign associated with the right lateral epicondyle as well as oedema at the extensor origin. None of these was present at the asymptomatic contralateral epicondylar region. Twenty-four hours after methylprednisolone administration, both perfusion and skin temperature had increased, and they declined over the subsequent 48 h. Although skin temperature had declined to normal (referenced to the contralateral epicondyle) by the third day after injection, it took until the eleventh day after injection for perfusion to normalize. CONCLUSIONS: LDI using an NIR laser source appears to be an effective non-invasive method for the examination of inflammatory responses in soft tissue, with greater sensitivity than thermally based methods. In addition, LDI was found to correlate with power Doppler ultrasonography.

Anti-Inflammatory Agents↗
PubMed2000

Inflamed retrocalcaneal bursa and Achilles tendonitis in psoriatic arthritis demonstrated by ultrasonography.

OBJECTIVE: To demonstrate the use of high resolution ultrasound measurements and power Doppler mode in the diagnosis and follow up of a patient with psoriatic arthritic with retrocalcaneal bursitis and Achilles tendonitis. METHODS: An outpatient based ATL HDI 3000 ultrasound equipment was used with a CL10-5 MHZ 26 mm probe and musculoskeletal software. Real time B mode and power Doppler mode were used to detect changes in structure and blood flow. RESULTS: Unilateral retrocalcaneal bursitis and Achilles tendonitis were demonstrated by sonography. Power Doppler mode was useful to demonstrate an increased blood flow around an abnormal retrocalcaneal bursa. A follow up examination showed marginal thickening of the Achilles tendon without any bursitis. CONCLUSIONS: Ultrasonography is an objective method in the confirmation of clinical diagnosis after physical examination. During the examination it is possible to gain not only qualitative but also quantitative data. A comparative study with quantitative data is possible in longitudinal studies.

Achilles Tendon↗
PubMed1999

Neutrophils, Helicobacter pylori, and nonsteroidal anti-inflammatory drug ulcers.

BACKGROUND & AIMS: Gastric injury by nonsteroidal anti-inflammatory drugs (NSAIDs) is minimal in neutropenic animals. This study examined peptic ulcer development in the presence or absence of gastric neutrophils in patients requiring long-term use of NSAIDs. METHODS: Gastric histology, neutrophils, and Helicobacter pylori were assessed in 120 patients randomized to receive placebo or 20 or 40 mg famotidine twice daily as prophylaxis against NSAID-related ulcers and who underwent endoscopy at 0, 4, 12, and 24 weeks. RESULTS: In 43 patients without gastric neutrophils, ulcers developed in 1 of 14 (7.7%) taking placebo, 2 of 16 (12.5%) taking 20 mg famotidine, and none of 13 taking 40 mg famotidine. However, in 77 patients with neutrophils, ulcers developed in 13 of 28 (47. 4%) taking placebo (P < 0.001), 3 of 26 (12.6%) taking 20 mg famotidine, and 3 of 23 (13%) taking 40 mg famotidine. Eight of 46 patients (17%) without H. pylori had neutrophils compared with 69 of 74 (93%) with both H. pylori and neutrophils (P < 0.001). CONCLUSIONS: Gastric neutrophils increase the incidence of ulceration in long-term NSAID users. Because neutrophils exist with H. pylori, eradicating this infection might prevent NSAID-related peptic ulcers.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

An investigation of factors limiting aerobic capacity in patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) has been shown to produce exercise limitation and breathlessness. The purpose of this study was to investigate factors which may be responsible for limiting aerobic capacity in patients with AS. Twenty patients with no other cardio-respiratory disease performed integrative cardiopulmonary exercise testing (CPET). The results were compared to 20 age and gender matched healthy controls. Variables that might influence exercise tolerance, including pulmonary function tests (body plethysmography), respiratory muscle strength (MIP, MEP) and endurance (Tlim), AS severity assessment including chest expansion (CE), thoracolumber movement (TL), wall tragus distance and peripheral muscle strength assessed by maximum voluntary contraction of the knee extensors (Qds), hand grip strength and lean body mass (LBM), were measured in the patients with AS and used as explanatory variables against the peak VO2 achieved during CPET. As subjects achieved a lower peak VO2 than controls (25.2 +/- 1.4 vs. 33.1 +/- 1.6 ml kg-1min-1, mean +/- SEM, P = 0.001). When compared with controls, ventilatory response (VE/VCO2) in AS was elevated (P = 0.01); however gas exchange indices, transcutaneous blood gases and breathing reserve were similar to controls. AS subjects developed a higher HR/VO2 response (P < 0.01) on exertion but without associated abnormalities in ECG, blood pressure response or anaerobic threshold. The AS group experienced a greater degree of leg fatigue (P < 0.01) than controls at peak exercise. Although the breathlessness scores (BS) were comparable to controls at peak exercise, the slopes of the relationship between BS and work rate (WR) [AS 0.054 (0.1), Controls 0.043 (0.06); P < 0.05] and BS and % predicted oxygen uptake [AS 0.084 (0.18), Controls 0.045 (0.06); P < 0.01] were steeper in the AS subjects. There was weak association between peak VO2 and vital capacity (r2% 12.0), MIP (11.8) but no association between Tlim, CE, Wall tragus distance or TL movement. The strongest association with aerobic capacity was between measurements of peripheral muscle strength (Qds; r = 0.75; hand grip; r = 0.47) accounting for 53% (P < 0.001) and 23.5% (P < 0.01) of the total variance in peak VO2, respectively. The addition of LBM to Qds in the regression model significantly improved the explained variance to 78.3% (P < 0.001). This study shows that peripheral muscle function is the most important determinant of exercise intolerance in AS patients suggesting that deconditioning is the main factor in the production of the reduced aerobic capacity.

Case-Control Studies↗