Search PubMed⌕ Search

Biomedical subjects

P A Brogan

Publications and source records attributed to P A Brogan.

14 recordsLinked to original sources
PubMed2006

Systemic vasculitis: a cause of indeterminate intestinal inflammation.

OBJECTIVES: Indeterminate intestinal inflammation may result from a variety of inflammatory conditions in addition to ulcerative colitis and Crohn disease. The primary systemic vasculitides may present with intestinal inflammation and an indeterminate colitis. We set out to describe a series of children with primary systemic vasculitis who initially presented with clinical features suggestive of inflammatory bowel disease (IBD) to establish criteria that might help discriminate between IBD and primary systemic vasculitis. METHODS: Ten children (6 boys, median age at presentation 8.9 years, range 0.9-14.5 years) satisfied inclusion criteria. RESULTS: All had abdominal pain, weight loss, diarrhea (6 of 10 bloody) and laboratory evidence of a severe acute phase response. Extraintestinal clinical features included vasculitic rash, renal impairment, myalgia, testicular pain and polyarthritis. Endoscopy showed vascular changes or other macroscopic findings suggestive of vasculitis in 5 of 10 patients. Gut histology revealed indeterminate chronic inflammatory mucosal changes and one patient with small artery fibrinoid necrosis in the submucosal vessels. Extraintestinal biopsy was performed in 6 patients and had a higher yield for the demonstration of vasculitis than intestinal biopsy. The results of selective visceral angiography was suggestive of vasculitis in all patients, but was normal in 7 cases of treatment-unresponsive classic IBD. Treatment comprised corticosteroid and azathioprine in all patients. Cyclophosphamide was given to 7 of 10 patients. CONCLUSIONS: Extraintestinal manifestations and inflammatory responses that may be disproportionate to the degree of intestinal inflammation provide clues to the presence of an underlying primary systemic vasculitis, and these data suggest that selective visceral angiography plays a key role in the diagnosis of vasculitis in this context. It is important to identify and treat any vasculitic component because failure to do so may result in consequential morbidity or mortality.

Abdominal Pain↗
PubMed2004

Vbeta-restricted T cell adherence to endothelial cells: a mechanism for superantigen-dependent vascular injury.

OBJECTIVE: To investigate the potential for endothelial cells to operate as superantigen-presenting cells for T cells and the potential for such an interaction to cause endothelial cell activation and injury. METHODS: Class II major histocompatibility complex (MHC)-positive human umbilical vein endothelial cells (HUVECs) were cocultured for 4 hours with purified T cells and the superantigens staphylococcal enterotoxin B (SEB) or toxic shock syndrome toxin 1 (TSST-1). After staining with fluorescence-conjugated monoclonal antibodies, flow cytometric analysis was performed on the HUVECs and T cells to examine V(beta)-restricted T cell adherence to the endothelial cell monolayer, V(beta)-restricted T cell activation (CD69 up-regulation), surface expression of endothelial cell activation markers, and generation of endothelial microparticles (EMPs). RESULTS: Coculture of purified T cells with class II MHC-positive HUVECs and either TSST-1 or SEB resulted in V(beta)-restricted CD69 up-regulation by CD4 and CD8 cells (V(beta)2 activation for TSST-1; V(beta)3, V(beta)5.1, and V(beta)12 activation for SEB). Additionally, there was CD4 and CD8 T cell V(beta)-restricted adherence to the HUVEC monolayer at 4 hours. Expression of intercellular adhesion molecule 1, E-selectin, and vascular cell adhesion molecule 1 was up-regulated on the class II MHC-positive HUVECs following exposure to superantigen in the presence of T cells, and there was increased EMP release from activated HUVECs, which occurred earlier and was of greater magnitude than that observed in response to tumor necrosis factor alpha. CONCLUSION: Class II MHC-positive endothelial cells operate as competent superantigen-presenting cells for CD4 and CD8 lymphocytes in vitro. Dual signaling between endothelial cells and T cells results in V(beta)-restricted activation and adherence to endothelial monolayers and endothelial cell activation and release of EMPs expressing inducible cell adhesion molecules. It is proposed that this mechanism could account in part for the vascular injury associated with superantigen-mediated diseases including Kawasaki disease.

Antigen-Presenting Cells↗
PubMed2004

Endothelial and platelet microparticles in vasculitis of the young.

OBJECTIVE: Microparticles are released from endothelial cells in response to a variety of injurious stimuli and recently have been shown to be increased in a number of diseases associated with endothelial dysfunction. This study examined endothelial microparticle (EMP) and platelet microparticle (PMP) profiles in children with systemic vasculitis to test the hypothesis that EMPs may provide a noninvasive means of examining endothelial activation or injury. METHODS: The study cohort comprised 39 children with systemic vasculitis at various stages of disease activity, 24 control children with febrile disease, and a control group of 43 healthy subjects. Plasma was ultracentrifuged at 17,000g for 60 minutes, and the microparticle pellets were examined using flow cytometry. RESULTS: Plasma from patients with active systemic vasculitis contained significantly higher numbers of E-selectin-positive EMPs compared with that from patients in remission, healthy controls, or febrile disease controls (P = 0.000 for each). A similar result was obtained for the numbers of EMPs expressing the marker CD105. There was also a significant increase in PMPs expressing CD42a in the active vasculitis group as compared with the other groups, but this difference was not significant for PMPs expressing P-selectin. The EMP counts correlated with the Birmingham Vasculitis Activity Score and the acute-phase reactant levels in the patients with systemic vasculitis, but there was a poor correlation overall between EMP counts and the acute-phase reactant levels in the febrile disease controls. CONCLUSION: EMPs may provide a window to the activated endothelium and could provide important pathophysiologic insights into the vascular injury associated with vasculitis of the young.

Acute-Phase Proteins↗
PubMed2003

T cell Vbeta repertoires in childhood vasculitides.

Superantigens (SAgs) are potent stimulators of T cells bearing specific Vbeta T cell receptors (TCR) and may play a role in the aetiopathogenesis of systemic vasculitis, although this remains contentious. To investigate the possible aetiological role of SAgs, this study examined peripheral blood T cell Vbeta repertoires in children with systemic vasculitis. FACS analysis of 17 different peripheral blood T cell Vbeta families was performed in 20 healthy control children, 27 disease control children with nonvasculitic inflammatory disease, 25 children with primary systemic vasculitis, six patients with Kawasaki disease (KD) and six patients with Henoch-Schönlein purpura (HSP). There was a significantly increased variance of CD4 Vbeta12 and Vbeta17, and CD8 Vbeta1 in the primary systemic vasculitis group compared to control and disease controls. Moreover, 80% of the primary systemic vasculitis children had one or more CD4 Vbeta expansions or deletions, compared with 30% of controls (P < 0.002), and 37% of the disease controls (P < 0.002). In the KD group, the mean percentage of CD4 Vbeta2 T cells was higher than in controls or disease controls. In the HSP group, there was no consistent skewing of the T cell Vbeta repertoire. We have observed changes in the T cell Vbeta repertoire in children with vasculitis over and above those observed in disease controls. While these data provide impetus for further research into this contentious field, they do not resolve unequivocally the question of the role of SAgs in childhood vasculitic syndromes.

Adolescent↗
PubMed2002

Kawasaki disease: an evidence based approach to diagnosis, treatment, and proposals for future research.

This article proposes a clinical guideline for the diagnosis and treatment of Kawasaki disease in the UK based on the best available evidence to date, and highlights areas of practice where evidence is anecdotal or based on retrospective data. Future research as proposed by the London Kawasaki Disease Research Group is outlined, and clinicians are invited to prospectively enroll their suspected cases into this collaborative research project.

Adrenal Cortex Hormones↗
PubMed2002

Arterial distensibility in children and teenagers: normal evolution and the effect of childhood vasculitis.

BACKGROUND: Polyarteritis nodosa is a necrotising vasculitis of the medium sized and small muscular arteries. The inflammatory and subsequent reparative processes may alter the arterial mechanical properties. The effect of vasculitic damage on arterial distensibility has never been explored however. AIM: To determine the normal values and the effect of childhood vasculitis on arterial distensibility in children and teenagers. METHODS: Distensibility of the brachioradial arterial segment was studied using pulse wave velocity (PWV proportional, variant 1/ radical distensibility), in 13 children with polyarteritis nodosa at a median age of 11.8 (range 4.9-16) years. As a control group, 155 healthy schoolchildren (6-18 years, 81 boys) were studied. PWV was assessed using a photoplethysmographic technique; blood pressure was measured by an automatic sphygmomanometer (Dinamap). Data from patients were expressed as z scores adjusted for age and compared to a population mean of 0 by a single sample t test. Determinants of PWV in normal children were assessed by univariate and multivariate linear regression analyses. RESULTS: Age, height, weight, and systolic blood pressure correlated individually with the brachioradial PWV. Multivariate analysis identified age as the only independent determinant. Ten of the patients were in clinical remission, while three had evidence of disease activity at the time of study. The PWV in the patient group as a whole was significantly greater than those in healthy children (mean z score +0.99). Raised C reactive protein concentration (>2 mg/dl) in the three patients with active disease was associated with a higher PWV when compared to those in remission (z score +2.78 v +0.45). The diastolic blood pressure of the patients was higher than those of the controls (z score +1.04) while the systolic pressure was similar (z score -0.36). CONCLUSIONS: PWV in the brachioradial arterial segment increases gradually during childhood independent of body weight, height, mass, and blood pressure. Increased PWV, and hence decreased distensibility, in this peripheral arterial segment occurs in polyarteritis nodosa and is amplified during acute inflammatory exacerbation.

Adolescent↗
PubMed2000

Vasculitis from the pediatric perspective.

This article reviews the spectrum of vasculitic illness affecting children. Apart from the relatively common vasculitides (Henoch-Schönlein purpura, Kawasaki disease, and in worldwide terms Takayasu disease) there are a number of important but comparatively rare disorders affecting children. As in adults, there is a considerable degree of overlap between the various vasculitic syndromes in childhood. With modern therapeutic agents, the prognosis for many of the childhood vasculitides has improved; however, in spite of this, there remains a not inconsequential morbidity and mortality. It is anticipated that as our knowledge of the immunopathogenesis of this group of disorders expands, classification and treatment of vasculitis in both children and adults will improve.

Adult↗
PubMed2000

The management of fever and petechiae: making sense of rash decisions.

In a retrospective and prospective audit of 55 children presenting to the paediatric assessment unit of a district general hospital with fever and petechial rash, 9% had significant bacterial sepsis. The "ILL criteria" (irritability, lethargy, low capillary refill) for the management of children with fever and petechiae are proposed.

Adolescent↗
PubMed1983

Worker exposure to asbestos during removal of sprayed material and renovation activity in buildings containing sprayed material.

Contents and types of asbestos in fireproofing insulation materials sprayed on ceilings of 127 buildings throughout the U.S. were studied. Asbestos was found to be present in more than 50% of the buildings and chrysotile was the main component identified. Frequency distribution of airborne fiber concentrations was lognormal. During renovation activities by various workers, including sheet-metal workers, carpenters and electricians, average fiber concentrations at workers' breathing zones were less than 2 fibers/cc, but exceeded 0.1 fibers/cc. During removal of sprayed materials, workers were exposed to extremely high concentrations (average 16.4 fibers/cc) when dry methods were used. When wet methods were used during removal, the airborne fiber concentrations were sharply reduced to less than 2 fibers/cc.

Air Pollutants↗