PubMed Health⌕ Search

Biomedical subjects

O FitzGerald

Publications and source records attributed to O FitzGerald.

At least 37 records · Page 2Linked to original sources
PubMed2001

Corticotropin-releasing hormone signaling in synovial tissue from patients with early inflammatory arthritis is mediated by the type 1 alpha corticotropin-releasing hormone receptor.

OBJECTIVE: Elevated levels of corticotropin-releasing hormone (CRH) are produced locally in inflamed human synovial tissue, and previous observations indicate a role for CRH in the pathogenesis of inflammatory joint disease. To further elucidate the biologic role of CRH at peripheral sites, we examined the expression of known CRH receptor subtypes in inflamed human synovium and compared the expression patterns in normal synovium. METHODS: Immunohistochemical analysis was used to confirm enhanced expression of specific CRH receptor subtypes in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) synovium. Immunofluorescence double-labeling was used to further characterize CRH receptor-expressing cells. Reverse transcriptase-polymerase chain reaction analysis was performed to examine CRH receptor subtype messenger RNA (mRNA) expression in RA, PsA, and normal synovial tissue. In addition, CRH receptor expression was examined in isolated synovial endothelial cells and synoviocytes. RESULTS: Selective up-regulation of CRH receptors in inflamed synovial tissue indicated that CRH functions locally, in an autocrine/paracrine receptor-mediated manner. Immunoreactive CRH receptor type 1 (CRH-R1) was expressed abundantly on vascular endothelial cells and discrete perivascular cell populations, identified as mast cells. In all samples of inflamed synovium studied, CRH-R1alpha mRNA was detected; however, we were unable to identify CRH-R1beta or any CRH-R2 isoforms in samples from the same cohort of, patients. CRH receptor subtype expression in separated synovial cell populations revealed a pattern of staining similar to that seen in vivo. In contrast, neither CRH receptor subtype was expressed in normal synovial tissue. CONCLUSION: Our findings suggest that CRH signaling, via CRH-R1alpha, may play a role in both the vascular changes and the pathologic mechanisms associated with joint inflammation in human arthritis.

Arthritis, Psoriatic↗
PubMed2001

Disease mechanisms in psoriasis and psoriatic arthritis.

Any hypothesis that tries to explain disease mechanisms in psoriasis and psoriatic arthritis (PsA) must take into account the containment of the inflammatory process to three specific sites: the skin, synovium, and enthesis. This article reviews the recent literature that advances our understanding of disease mechanisms at these specific sites. Additional progress will be achieved by research that focuses on common pathogenic pathways at these sites, in particular when searching for foreign candidates or auto-antigens triggering the T-cell-mediated immune response.

Arthritis, Psoriatic↗
PubMed2001

The effects of treatment with interleukin-1 receptor antagonist on the inflamed synovial membrane in rheumatoid arthritis.

OBJECTIVE: To evaluate the effects of treatment with interleukin-1 receptor antagonist (IL-1Ra) on synovial tissue in rheumatoid arthritis (RA). METHODS: Twelve patients with RA entering a randomized clinical trial of human recombinant IL-1Ra underwent synovial biopsies before and after treatment. Cellular infiltration and adhesion molecule expression were evaluated after immunohistochemical staining. RESULTS: There was a notable reduction in intimal layer macrophages and subintimal macrophages and lymphocytes after treatment with IL-1Ra at 150 mg/day (n=3). Increased cellular infiltration was observed in all patients receiving placebo (n=3); variable changes were observed after IL-1Ra 30 mg/day (n=6). In a limited study of adhesion molecule expression, down-regulation of E-selectin and vascular cell adhesion molecule-1 was observed after treatment with IL-1Ra 150 mg/day, but not after IL-1Ra 30 mg/day or placebo. The apparent arrest of progressive joint damage seen in four patients after treatment with IL-1Ra was associated with reduced intimal layer macrophage accumulation in all patients. CONCLUSION: Treatment of RA with IL-1Ra resulted in reduced mononuclear cell infiltration of synovial membrane, which may represent the in vivo inhibition of biologically relevant IL-1ss-mediated pathogenic effects.

Adolescent↗
PubMed2001

The role of ultrasonography in the diagnosis and management of idiopathic plantar fasciitis.

OBJECTIVE: To compare ultrasonography with bone scintigraphy in the diagnosis of plantar fasciitis and to compare ultrasound-guided injection with palpation-guided injection in the management of idiopathic plantar fasciitis. METHODS: Twenty-three patients with a clinical diagnosis of idiopathic plantar fasciitis in 28 heels underwent ultrasonography and bone scintigraphy of both heels at baseline. The patients were randomized to ultrasound- or palpation-guided injection of triamcinolone hexacetonide and xylocaine into the plantar fascia. The 100 mm visual analogue scale (VAS) of pain, the heel tenderness index (HTI), and ultrasonography were performed at baseline and follow-up (mean=13.4 weeks). RESULTS: The mean thickness (+/-standard error of the mean) of the plantar fascia, measured by ultrasonography, was 5.7+/-0.3 mm in symptomatic heels as compared with 3.8+/-0.2 mm in asymptomatic heels (P<0.001). Ultrasonography findings correlated with bone scintigraphic findings in the diagnosis of plantar fasciitis (P<0.001). Fourteen heels were randomized to ultrasound-guided injection, 10 heels were randomized to palpation-guided injection and four heels were not injected. Ultrasound- and palpation-guided injection resulted in significant mean improvements in VAS [39.6+/-9.2 (ultrasound) vs 41.5+/-8 (palpation)] and HTI [1.35+/-0.2 (ultrasound) vs 1.3+/-0.4 (palpation)]. There was no significant difference in the response rate following corticosteroid injection by either modality (ultrasound=13/14, palpation=8/10). Following injection, the mean thickness of the plantar fascia decreased from 5.7+/-0.3 mm to 4.65+/-0.4 mm (P<0.01). CONCLUSION: Ultrasonography and bone scintigraphy are equally effective in the diagnosis of plantar fasciitis. Ultrasound-guided injection is effective in the management of plantar fasciitis but is not more effective than palpation-guided injection. Ultrasonography may be used as an objective measure of response to treatment in plantar fasciitis.

Fasciitis↗
PubMed2001

Validated measurement of periarticular bone mineral density at the knee joint by dual energy x ray absorptiometry.

OBJECTIVE: The association of inflammatory arthritis with loss of periarticular bone mineral density (BMD) has been well established. However, changes in bone density cannot be quantified by conventional radiography. This study aimed at developing a new technique for measurement of periarticular bone density at the knee joint by dual energy x ray absorptiometry (DXA) and assessing the precision of this technique for selected areas around the knee. METHODS: To validate this technique for bone density assessment in both patient and control subjects, knee joints from healthy subjects and patients with inflammatory arthritis were selected for study. Posteroanterior (PA) and lateral scans of both knees were acquired with the Hologic 4500 elite bone densitometer. Each scan was repeated three times, with repositioning between scans. Knee scans were obtained with the forearm software and evaluated by subregion analysis. Seven femoral and seven tibial subregions of interest (ROIs) were selected on PA scans. Six ROIs were selected on lateral scans. Precision was determined for each ROI selected. RESULTS: 14 knee joints were studied in each group. Precision, expressed as percentage coefficient of variation (CV%), varied widely between subregions. PA scans were most appropriate for measurement of femoral bone density (CV% = 1.89-2.64%), whereas the best value obtained for ROIs within the tibia was on the lateral scan, where CV% for measurement of the proximal 5 mm was 2.67% in the patient group. CV% for BMD of the patella was excellent at 0.84% in the patient group. CONCLUSION: This new application of DXA can be used to measure periarticular bone density at the knee joint. Regions within the distal femur and patella have been identified as the optimal areas to study

Absorptiometry, Photon↗
PubMed2000

Acute-phase serum amyloid A production by rheumatoid arthritis synovial tissue.

Acute-phase serum amyloid A (A-SAA) is a major component of the acute-phase response. A sustained acute-phase response in rheumatoid arthritis (RA) is associated with increased joint damage. A-SAA mRNA expression was confirmed in all samples obtained from patients with RA, but not in normal synovium. A-SAA mRNA expression was also demonstrated in cultured RA synoviocytes. A-SAA protein was identified in the supernatants of primary synoviocyte cultures, and its expression colocalized with sites of macrophage accumulation and with some vascular endothelial cells. It is concluded that A-SAA is produced by inflamed RA synovial tissue. The known association between the acute-phase response and progressive joint damage may be the direct result of synovial A-SAA-induced effects on cartilage degradation.

Acute Disease↗
PubMed1999

Multidisciplinary patient care in rheumatoid arthritis: evolving concepts in nursing practice.

Multidisciplinary patient care is essential in the management of rheumatoid arthritis (RA), a chronic potentially disabling, multisystem disease. Concepts of multidisciplinary care continue to evolve. While all team members can make valuable contributions to patient care, this chapter focuses in particular on continuing and changing aspects of team management. Of the many disciplines associated with rheumatology, nursing has undergone the most radical change in recent years. New roles have been defined and the nursing profession is now emerging with additional skills to support patients and their families. Concepts of patient education also continue to evolve. As the beneficial effects of education are demonstrated, a patient education programme should be seen as essential to the management of rheumatoid arthritis. Finally, the importance of counselling skills is emphasised.

Arthritis, Rheumatoid↗
PubMed1999

Collagenase, cathepsin B and cathepsin L gene expression in the synovial membrane of patients with early inflammatory arthritis.

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.

Adult↗
PubMed1999

Quantitative analysis of synovial membrane inflammation: a comparison between automated and conventional microscopic measurements.

OBJECTIVE: The objective of this study was to quantify selected features of chronic synovial tissue inflammation by computerised image analysis and to validate the results by comparison with conventional microscopic measurements. METHODS: Synovial biopsy samples were obtained from the knee joints of patients with chronic arthritis and prepared for immunohistochemical analysis using standard techniques. Following the development of special software, four parameters of chronic synovial inflammation were evaluated: intimal layer thickness, CD3+ cell infiltration, CD8+ cell infiltration and vascularity. Intimal layer thickness was expressed in microns. The intensity of CD3+ and CD8+ cell infiltration was expressed as the percentage area of the tissue section occupied by positively stained cells. Vascularity was expressed as the percentage area occupied by blood vessels. Conventional quantitative microscopic analysis was also undertaken and the results from both methods compared. RESULTS: Seventy eight tissue sections were selected for study. Measurements of intimal layer thickness by both techniques correlated strongly: r = 0.85, p = 0.0006. Measurements of CD8+ cell infiltration, usually widely dispersed, also correlated well: r = 0.64, p = 0.005. Measurements of CD3+ cell infiltration, often densely aggregated, correlated less well: r = 0.55, p = 0.02. Measurements of vascularity demonstrated no statistically significant correlation: r = 0.41, p = 0.07. Proficiency in the use of computerised image analysis was readily acquired. CONCLUSION: Computerised image analysis was successfully applied to the measurement of some features of synovial tissue inflammation. Further software development is required to validate measurement of blood vessels of variable size.

Arthritis↗
PubMed1999

Predominance of CD8+ T lymphocytes in psoriatic arthritis.

OBJECTIVE: To characterize the synovial fluid (SF) derived T cell populations in psoriatic arthritis (PsA) and compare with similar populations from rheumatoid arthritis (RA). METHODS: Paired peripheral blood (PB) and SF samples were analyzed by 3 color flow cytometry using monoclonal antibodies to CD3, CD4, CD8, HLA-DR, CD25, CD45RA, and CD45RO. RESULTS: There was a significantly increased CD8+ T cell population in PsA SF compared to RA: PsA mean 61% (range 35-93), RA mean 46% (range 6-72) (p < 0.005). This resulted in a reversal of the CD4:CD8 ratio in PsA SF compared to RA SF (p < 0.001). Patients with oligoarticular PsA had the most pronounced differences in SF derived T cell populations compared to RA (p < 0.0005) but these results were not significantly different from PsA patients with a polyarticular disease pattern. PB PsA T cell populations were not different from controls, in contrast to RA, where the CD4+ T cell population was increased (p < 0.0026), giving an exaggerated PB CD4:CD8 ratio. The majority of PsA SF CD8+ T cells expressed CD45RO, mean 73% (range 58-95), and HLA-DR antigen: mean 72% (range 38-94). Low levels of CD25 were detectable in this population, indicating a nonclassical activation pattern: mean 2% (range 0.3-4.4). CONCLUSION: In PsA, activated (HLA-DR+) and mature (CD45RO+) CD8+ T cells predominate in SE Analysis of this population may uncover clues to pathogenesis in this HLA class I mediated disease.

Adult↗
PubMed1999

Ultrasonography in the diagnosis and management of psoriatic dactylitis.

OBJECTIVE: To determine the ultrasonographic features of dactylitis in psoriatic arthritis (PsA). METHODS: Seventeen patients with PsA presenting with a total of 25 dactylitic fingers and toes underwent ultrasonographic examination of the digits with a 7.5 or 10 MHz transducer. RESULTS: Flexor tenosynovitis was present in 96% (24/25) of dactylitic digits. Articular synovitis was present in 52% (13/25) of dactylitic digits. Subcutaneous soft tissue enlargement was present in all digits. The presence of articular synovitis in a dactylitic finger on ultrasonography correlated with the presence of joint space narrowing and periostitis on plain radiography. CONCLUSION: Dactylitis in PsA is due to both flexor tenosynovitis and articular synovitis. Dactylitis in PsA has an increased incidence of articular synovitis, which was associated with the development of articular damage as assessed by plain radiography.

Adolescent↗
PubMed1998

Ultrasound guided injection of recalcitrant plantar fasciitis.

OBJECTIVE: To determine the effect of ultrasound guided injection in recalcitrant idiopathic plantar fasciitis. METHODS: Four patients with a clinical diagnosis of idiopathic plantar fasciitis, who were unresponsive to palpation guided injection with triamcinolone acetonide and local anaesthetic, underwent ultrasonographic examination of the heel. RESULTS: The following ultrasonographic features were noted:- (a) increased thickness of plantar fascia in symptomatic heels compared with asymptomatic heels, (b) loss of distinction of the distal plantar fascia borders, (c) reduced echogenicity of the plantar fascia. Ultrasound guided injection of the enlarged, hypoechoic plantar fascia resulted in complete relief in four of five heels (mean duration of follow up = 24 months) in three cases. One patient developed a recurrence of symptoms after six months. CONCLUSION: Ultrasound allows for confirmation of the clinical diagnosis and ultrasound guided injection produces a good clinical response when unguided injection is unsuccessful. The technique is quick, inexpensive, and entails no radiation exposure.

Anesthetics, Local↗
PubMed1997

Clinical, immunopathogenic, and therapeutic aspects of psoriatic arthritis.

Psoriatic arthritis is a common chronic rheumatic disease that may result in considerable joint damage if left untreated. Recent clinical studies have focused on the identification of poor prognostic factors. Early, aggressive treatment is indicated in patients with significant joint inflammation and certain HLA antigens. Immunopathogenic evidence continues to point toward an HLA class I-mediated disease with perhaps an important role for CD8+ T cells. Although few basic research publications discuss psoriatic arthritis, studies in the areas of spondyloarthropathy and psoriasis continue to shed light on disease mechanisms. Greater collaboration is advocated among researchers in these areas and those interested in achieving a better understanding of the disease pathogenesis of psoriatic arthritis.

Arthritis, Psoriatic↗
PubMed1997

Comparison of the accuracy of steroid placement with clinical outcome in patients with shoulder symptoms.

OBJECTIVE: To study the effect of accuracy on the clinical outcome of local steroid injections to the shoulder. METHODS: 37 patients with shoulder symptoms of at least two months' duration received local injections of a mixture of triamcinolone and radiographic contrast material using a standardised technique. Radiographs of the joint were taken immediately afterwards. Details of the patients' symptoms (assessed by visual analogue scales) and range of movement at the joint were obtained before and two weeks after the injection. At follow up the patients were also assessed by means of a five point global rating scale of maximum and current benefit. RESULTS: 14 of the 38 procedures (37%) were judged to be accurately placed: four of the 14 attempted subacromial injections (29%) and 10 of the 24 attempted glenohumeral injections (42%). There were significant differences in relation to outcome between the accurately placed and the inaccurately placed groups. CONCLUSIONS: Accuracy of steroid placement by injection in patients with shoulder symptoms may significantly affect the clinical outcome.

Adult↗
PubMed1996

Diagnosis and treatment of heel pain in chronic inflammatory arthritis using ultrasound.

The authors examined the role of ultrasound (US) in diagnosis and management of heel pain in chronic inflammatory arthritis. Nineteen patients underwent US examination. Eight patients (2 with previously unsuccessful nonguided injections), had 11 US-guided corticosteroid injections for treatment of retrocalcaneal bursitis (n = 6), plantar fasciitis (n = 3), and posterior tibial tenosynovitis (n = 2). US-demonstrated Achilles tendon rupture (n = 2), Achilles tendinitis (n = 8), posterior tibial tenosynovitis (n = 6), peroneus longus tenosynovitis (n = 2), retrocalcaneal bursitis (n = 13), and plantar fasciitis (n = 4). Loss of smooth bone contour (n = 13) correlated with bone erosions on plain radiographs in all but one case. Ten of 11 guided injections resulted in full resolution of heel pain. The diverse causes of heel pain are highlighted, and the ability of US to provide information with management implications is confirmed. US-guided corticosteroid injection is beneficial, especially after failure of nonguided injection.

Achilles Tendon↗