Malcolm Brodlie

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RATIONALE Ceramide accumulates in the airway epithelium of mice deficient in cystic fibrosis transmembrane conductance regulator, resulting in susceptibility to Pseudomonas aeruginosa infection and inflammation. OBJECTIVES To investigate quantitatively ceramide levels in the lower airway of people with cystic fibrosis compared with pulmonary hypertension,(More)
Epithelial to mesenchymal transition (EMT) has been implicated in the pathogenesis of obliterative bronchiolitis (OB) after lung transplant. Although TNF-alpha accentuates TGF-beta1 driven EMT in primary human bronchial epithelial cells (PBECs), we hypothesized that other acute pro-inflammatory cytokines elevated in the airways of patients with OB may also(More)
Interleukin (IL)-17 is pivotal in orchestrating the activity of neutrophils. Neutrophilic inflammation is the dominant pathology in cystic fibrosis (CF) lung disease. We investigated IL-17 protein expression in the lower airway in CF, its cellular immunolocalisation and the effects of IL-17 on CF primary bronchial epithelial cells. Immunohistochemistry was(More)
UNLABELLED Maternal diabetes mellitus affects the foetal heart both structurally and functionally. In early gestation, it has a teratogenic effect causing defects of primary cardiogenesis. In late gestation, it causes a unique form of hypertrophic cardiomyopathy. We report an infant of a diabetic mother and an infant where there was presumed gestational(More)
OBJECTIVE To report the oral corticosteroid-sparing effect of omalizumab in children with severe asthma. DESIGN 16-week therapeutic trial. SETTING Tertiary paediatric asthma clinic. PATIENTS 34 children with severe asthma maintained on oral prednisolone (median age 12 years; 15 children <12 years and 19 children ≥12 years). INTERVENTIONS Fortnightly(More)
Therapies to limit or reverse fibrosis have proven unsuccessful, highlighting the need for a greater understanding of basic mechanisms that drive fibrosis and, in particular, the link between fibrosis and inflammation. It has been shown that pro-fibrotic transforming growth factor β1 (TGF-β1)-driven epithelial-to-mesenchymal transition (EMT) can be(More)
Epithelial-to-mesenchymal transition (EMT) has been implicated in the dysregulated epithelial wound repair that contributes to obliterative bronchiolitis (OB) after lung transplantation. Acquisition of Pseudomonas aeruginosa in the transplanted airway has been shown to be a risk factor for the development of OB. We investigated the potential of P.(More)
OBJECTIVES To measure the neonatal autopsy rate at a tertiary referral centre and identify trends over the past decade. To identify factors that may influence the likelihood of consent being given for autopsy. To examine any discordance between diagnoses before death and at autopsy. DESIGN Retrospective review of patients' records. SETTING Tertiary(More)
BACKGROUND Episodic viral wheeze (EVW) associated with viral respiratory tract infections is a common reason for pre-school children to utilise health care resources and for carers to take time away from employment. About a third of children experience a wheezing episode before the age of five years. EVW therefore represents a significant public health(More)