Princess Margaret Hospital for Children

About: Princess Margaret Hospital for Children is a healthcare organization based out in Perth, Western Australia, Australia. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 1501 authors who have published 2068 publications receiving 75773 citations. The organization is also known as: Perth Children's Hospital & PMH.

Genome-Wide Association Study to Identify the Genetic Determinants of Otitis Media Susceptibility in Childhood

Abstract: Background: Otitis media (OM) is a common childhood disease characterised by middle ear inflammation and effusion. Susceptibility to recurrent acute OM (rAOM; ≥3 episodes of AOM in 6 months) and chronic OM with effusion (COME; MEE ≥3 months) is 40-70% heritable. Few underlying genes have been identified to date, and no genome-wide association study (GWAS) of OM has been reported. Methods and Findings: Data for 2,524,817 single nucleotide polymorphisms (SNPs; 535,544 quality-controlled SNPs genotyped by Illumina 660W-Quad; 1,989,273 by imputation) were analysed for association with OM in 416 cases and 1,075 controls from the Western Australian Pregnancy Cohort (Raine) Study. Logistic regression analyses under an additive model undertaken in GenABEL/ProbABEL adjusting for population substructure using principal components identified SNPs at CAPN14 (rs6755194: OR = 1.90; 95%CI 1.47-2.45; Padj-PCA = 8.3×10-7) on chromosome 2p23.1 as the top hit, with independent effects (rs1862981: OR = 1.60; 95%CI 1.29-1.99; Padj-PCA = 2.2×10-5) observed at the adjacent GALNT14 gene. In a gene-based analysis in VEGAS, BPIFA3 (PGene = 2×10-5) and BPIFA1 (PGene = 1.07×10-4) in the BPIFA gene cluster on chromosome 20q11.21 were the top hits. In all, 32 genomic regions show evidence of association (Padj-PCA<10-5) in this GWAS, with pathway analysis showing a connection between top candidates and the TGFβ pathway. However, top and tag-SNP analysis for seven selected candidate genes in this pathway did not replicate in 645 families (793 affected individuals) from the Western Australian Family Study of Otitis Media (WAFSOM). Lack of replication may be explained by sample size, difference in OM disease severity between primary and replication cohorts or due to type I error in the primary GWAS. Conclusions: This first discovery GWAS for an OM phenotype has identified CAPN14 and GALNT14 on chromosome 2p23.1 and the BPIFA gene cluster on chromosome 20q11.21 as novel candidate genes which warrant further analysis in cohorts matched more precisely for clinical phenotypes.

Antenatal antecedents of moderate and severe cerebral palsy.

Abstract: Summary Aetiological relationships between cerebral palsy, preterm birth, small-for-gestational-age (SGA) birth and selected feto-maternal factors were investigated in a case-control study of all moderate and severe cerebral palsy cases born in Western Australia between 1980 and 1986 (n= 215) Cases were individually matched to three controls of the same gender and plurality born in the same year Two of the controls were matched to the index cases for gestational age, one of which was also matched for birthweight Pre-eclampsia and urinary tract infections were not significantly associated with cerebral palsy The significant association of antepartum haemorrhage with cerebral palsy was accounted for by its associations with preterm birth Congenital malformations and non-cerebral palsy neurological disorder were significantly associated with cerebral palsy; these associations were only partially accounted for by adjusting for preterm birth and small-for-gestational-age birth This study shows that some of the risk of cerebral palsy associated with the antenatal antecedents of some common feto-maternal factors is mediated through preterm birth, confirming the importance of interrelationships between antenatal antecedents in the aetiology of some cerebral palsy Perinatal and post-neonatal causes now account for only around 20% of all cerebral palsy Future reductions in cerebral palsy incidence may therefore depend on acquiring greater knowledge of inter-relationships between antenatal antecedents

Topical 0.1% rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: a pilot study of four patients.

Abstract: Tuberous sclerosis complex (TSC) is an autosomal dominant genodermatosis characterised by the development of hamartomatous tumours in multiple organs including the brain, skin, kidneys, heart and lungs. Facial angiofibromas are the most visible and unsightly of the cutaneous manifestations of TSC, often resulting in stigmatisation for both the affected individuals and their families. Current treatments include vascular laser, ablative lasers and other destructive techniques such as shave excision and electrodessication. For the best outcome these treatments have to be repeated throughout childhood and teenage years, necessitating multiple general anaesthetics. We report a pilot study of topical rapamycin in four children with TSC and facial angiofibromas. Two patients were trialled on 0.1% rapamycin in petrolatum and the other two patients with 0.1% rapamycin solution (Rapamune) applied topically. Both preparations were rapidly and equally effective, however the 0.1% in petrolatum was much better tolerated. Younger patients with smaller angiofibromas had the best response with near complete clearance. Both preparations were more cost effective than pulsed dye laser under general anaesthesia. Although larger studies are needed, this treatment shows a potential to be a first-line management for facial angiofibromas in TSC and appears safe to start in early childhood.

Celiac disease and eosinophilic esophagitis: a true association.

Abstract: Background and aim Celiac disease (CD) and eosinophilic esophagitis (EE) are distinct disorders with specific clinico-pathological characteristics. Recent reports suggest an association between the 2. The aim of this study was to estimate the prevalence of EE among children diagnosed with CD in our institution in the last 8 years. Materials and methods Princess Margaret Hospital in Western Australia is the state's only pediatric referral center and the Department of Anatomic Pathology handles almost all of the pediatric gastrointestinal biopsy specimens. All of the children who had histological confirmation of CD between January 2000 and November 2007 were identified. Among this cohort, those who had concurrent esophageal biopsies performed were obtained and those with histology consistent with EE identified. The slides of all of these cases were reviewed. Case notes of children with CD and EE were reviewed for demographic details, symptoms, endoscopic findings, and follow-up data. Results Among the total of 250 children diagnosed with CD during the study period, 121 had concurrent esophageal biopsies. Ten children had histological findings consistent with EE, although only 7 had endoscopic findings suggestive of EE. Median eosinophil count in these esophageal biopsies was 52 per high power field (range 23-80). Four children had follow-up endoscopies and all 4 demonstrated recovery of duodenal mucosa but persistent esophageal eosinophilia on gluten-free diet. In 3 children resolution of EE occurred after specific treatment of EE. Conclusions The prevalence of EE in this cohort of children with CD is at least 4%. This is likely to be an underestimation because only 121 of 250 children had concurrent esophageal biopsies. Coexistent EE should be kept in mind in children undergoing endoscopy for suspected CD, and esophageal biopsies should be obtained, irrespective of whether esophageal mucosa appears normal or abnormal at endoscopy.