Justice C.M.,National Human Genome Research Institute |
Yagnik G.,University of California at Davis |
Kim Y.,National Human Genome Research Institute |
Peter I.,Mount Sinai School of Medicine |
And 30 more authors.
Nature Genetics | Year: 2012
Sagittal craniosynostosis is the most common form of craniosynostosis, affecting approximately one in 5,000 newborns. We conducted, to our knowledge, the first genome-wide association study for nonsyndromic sagittal craniosynostosis (sNSC) using 130 non-Hispanic case-parent trios of European ancestry (NHW). We found robust associations in a 120-kb region downstream of BMP2 flanked by rs1884302 (P = 1.13 × 10-14, odds ratio (OR) = 4.58) and rs6140226 (P = 3.40 × 10-11, OR = 0.24) and within a 167-kb region of BBS9 between rs10262453 (P = 1.61 × 10-10, OR = 0.19) and rs17724206 (P = 1.50 × 10-8, OR = 0.22). We replicated the associations to both loci (rs1884302, P = 4.39 × 10-31 and rs10262453, P = 3.50 × 10-14) in an independent NHW population of 172 unrelated probands with sNSC and 548 controls. Both BMP2 and BBS9 are genes with roles in skeletal development that warrant functional studies to further understand the etiology of sNSC. © 2012 Nature America, Inc. All rights reserved.
Ward K.A.,New South Wales Health |
McAnulty J.M.,New South Wales Health |
Iwasenko J.M.,South Eastern Area Laboratory Services |
Dwyer D.E.,Institute of Clinical Pathology and Medical Research
Emerging Infectious Diseases | Year: 2010
To determine the extent and pattern of influenza transmission and effectiveness of containment measures, we investigated dual outbreaks of pandemic (H1N1) 2009 and influenza A (H3N2) that had occurred on a cruise ship in May 2009. Of 1,970 passengers and 734 crew members, 82 (3.0%) were infected with pandemic (H1N1) 2009 virus, 98 (3.6%) with influenza A (H3N2) virus, and 2 (0.1%) with both. Among 45 children who visited the ship's childcare center, infection rate for pandemic (H1N1) 2009 was higher than that for influenza A (H3N2) viruses. Disembarked passengers reported a high level of compliance with isolation and quarantine recommendations. We found 4 subsequent cases epidemiologically linked to passengers but no evidence of sustained transmission to the community or passengers on the next cruise. Among this population of generally healthy passengers, children seemed more susceptible to pandemic (H1N1) 2009 than to influenza (H3N2) viruses. Intensive disease control measures successfully contained these outbreaks.
Caramins M.,South Eastern Area Laboratory Services |
Colebatch J.G.,Prince of Wales Hospital |
Colebatch J.G.,Neuroscience Research Australia |
Bainbridge M.N.,Baylor College of Medicine |
And 10 more authors.
Human Molecular Genetics | Year: 2013
Weundertook a gene identification and molecular characterization project in a large kindred originally clinically diagnosed with SCA-X1. While presenting with ataxia, this kindred also had some unique peripheral nervous systemfeatures. Theimplicated regionontheXchromosomewas delineated using haplotyping. Large deletions and duplications were excluded by array comparative genomic hybridization. Exome sequencing was undertaken in two affected subjects. The single identified X chromosome candidate variant was then confirmed to co-segregate appropriately in all affected, carrier and unaffected family members by Sanger sequencing. The variant was confirmed to be novel by comparison with dbSNP, and filtering for a minor allele frequency of <1% in 1000 Genomes project, and was not present in the NHLBI Exome Sequencing Project or a local database at theBCMHGSC. Functional experiments on transfected cells were subsequently undertaken to assess the biological effect of the variant in vitro. The variant identified consisted of a previously unidentified non-synonymous variant, GJB1 p. P58S, in the Connexin 32/Gap Junction Beta 1 gene. Segregation studies with Sanger sequencing confirmed the presence of the variant in all affected individuals and one known carrier, and the absence of the variant in unaffected members. Functional studies confirmed that the p. P58S variant reduced the number and size of gap junction plaques, but the conductance of the gap junctions was unaffected. Two X-linked ataxias have been associated with genetic loci, with the first of these recently characterized at the molecular level. This represents the second kindred with molecular characterization of X-linked ataxia, and is the first instance of a previously unreported GJB1 mutation with a dominant and permanent ataxia phenotype, although different CNS deficits have previously been reported. This pedigree has also been relatively unique in its phenotype due to the presence of central and peripheral neural abnormalities. Other X-linked SCAs with unique features might therefore also potentially represent variable phenotypic expression of other known neurological entities. © The Author 2013. Published by Oxford University Press. All rights reserved.
PubMed | Sydney Childrens Hospital Randwick, South Eastern Area Laboratory Services and University of New South Wales
Type: Journal Article | Journal: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] | Year: 2016
Faecal elastase-1 (FE1) is a sensitive marker for exocrine pancreatic enzyme insufficiency. Pancreatic insufficiency (EPI) leads to maldigestion and subsequent poor weight gain. Thus, FE1 is performed as work-up for children with failure to thrive (FTT). However, EPI in the paediatric population outside of cystic fibrosis (CF) is rare. This study aimed to identify the indications for FE1 testing and their diagnostic yield in children. The secondary aim was to evaluate the cost per case of EPI detected for the various indications.All FE1 tests performed on children (0-18 years) at a tertiary paediatric hospital in Sydney, Australia between 2010 and 2013 (inclusive) were identified. A retrospective chart audit was performed to identify the indication for testing FE1. The diagnostic yield based on FE1 cut-offs <200 and<100g/g were assessed.The most common indication for testing FE1 was FTT only (71/216, 32.9%), however, in this cohort of patients, FE1 was least likely to be positive with only 2 out of the 71 (2.8%) patients returning a positive result. In comparison, CF was the second most common indication for testing (60/216, 27.8%), but nearly half (48.8%) of tests returned a positive result in this cohort. The cost per case detected (FE1 <200g/g) reflected the test yield with an average cost per positive test of $262.50 (AUD2015) for FTT with short-gut syndrome and $420.00 (AUD2015) for CF-related indications.Our study shows that for patients with isolated failure to thrive, FE1 testing is low yield and costly.
PubMed | Prince of Wales Hospital, South Eastern Area Laboratory Services and Sydney Childrens Hospital
Type: Journal Article | Journal: Molecular neurobiology | Year: 2016
Astrogliosis and microgliosis in hippocampal sclerosis (HS) are widespread and are postulated to contribute to the pro-excitatory neuropathological environment. This study aimed to establish if seizure burden at the time of surgery or post-surgical outcome were correlated with the extent of gliosis in HS. As a secondary aim, we wanted to determine if the degree of gliosis could be predicted by pre-operative neuroimaging.Children and adults who underwent epilepsy surgery for HS between 2002 and 2011 were recruited (n=43), and age-matched autopsy controls obtained (n=15). Temporal lobe specimens were examined by DAB immunohistochemistry for astrocytes (glial fibrillary acidic protein (GFAP)) and microglia (CD68). Cell counting for GFAP and CD68 was performed and quantitative densitometry undertaken for GFAP. Seizure variables and outcome (Engel) were determined through medical record and patient review. Seizure frequency in the 6months prior to surgery was measured to reflect the acute seizure burden. Duration of seizures, age at onset and age at operation were regarded to reflect chronic seizure burden. Focal, lobar and generalized atrophy on pre-operative MRI were independently correlated with the degree of cortical gliosis in the surgical specimen.In HS, both acute and chronic seizure burden were positively correlated with the degree of gliosis. An increase in reactive astrocyte number in CA3 was the strongest predictor of poor post-operative seizure outcome at 1 and 3years post-operatively in this cohort. Changes in lower cortical astrocyte and upper cortical microglial number also correlated with post-operative outcome at 1year. Post-surgical seizure outcome (1, 3 and 5years) did not otherwise correlate with GFAP immunoreactivity (GFAP-IR) or CD68 immunoreactivity (CD68-IR). Increased microglial activation was detected in patients with pre-operative bilateral convulsive seizures, compared to those without convulsive seizures. Furthermore, focal, lobar and generalized atrophy on pre-operative neuroimaging were independently correlated with the degree of cortical gliosis in the surgical specimen.
Li-Kim-Moy J.P.,Sydney Childrens Hospital |
Tobias V.,South Eastern Area Laboratory Services |
Day A.S.,University of Otago |
Leach S.,University of New South Wales |
Lemberg D.A.,Sydney Childrens Hospital
Journal of Pediatric Gastroenterology and Nutrition | Year: 2011
Background and Objective: Eosinophilic esophagitis (EE) is characterized by marked esophageal mucosal eosinophilia on histological examination. Although the clinical and histological features of EE are increasingly recognized, the overlap of clinical symptoms and histological findings with gastroesophageal reflux disease (GERD) can lead to diagnostic difficulty. In children with EE we sought to define the frequency of subepithelial fibrosis and define the clinical correlates of this feature. The specificity of this finding in EE was obtained by comparison with a matched group of children with GERD, to ascertain its usefulness as a histological aid in differentiating between the 2 diagnoses. Patients and Methods: Comparison was made between 27 patients with EE and 24 patients with GERD, whose endoscopic biopsy specimens included subepithelial tissue. Demographic data, symptoms, endoscopic findings, and other histological findings were also compared. Results: In contrast to patients with GERD, those with EE more commonly reported longer periods of symptoms (especially dysphagia) and were more likely to have endoscopic abnormalities. Subepithelial fibrosis was present in 89% of patients with EE and 37.5% of patients with GERD (P < 0.0001). The features of fibrosis in EE included uniformity and hyalinization, whereas the fibrosis in GERD was predominantly associated with lymphoid tissue. Conclusions: Subepithelial fibrosis commonly occurs in children with EE and is associated with increased age and length of symptoms. We propose that along with mucosal eosinophilic infiltration the presence of subepithelial fibrosis is a feature of EE. Copyright © 2011 by European Society for Pediatric Gastroenterology.
Vecellio E.,South Eastern Area Laboratory Services |
Georgiou A.,Macquarie University
Studies in Health Technology and Informatics | Year: 2016
Repeat and redundant procedures in medical imaging are associated with increases in resource utilisation and labour costs. Unnecessary medical imaging in some modalities, such as X-Ray (XR) and Computed Tomography (CT) is an important safety issue because it exposes patients to ionising radiation which can be carcinogenic and is associated with higher rates of cancer. The aim of this study was to assess the impact of implementing an integrated Computerised Provider Order Entry (CPOE)/Radiology Information System (RIS)/Picture Archiving and Communications System (PACS) system on the number of XR and CT imaging procedures (including repeat imaging requests) for inpatients at a large metropolitan hospital. The study found that patients had an average 0.47 fewer XR procedures and 0.07 fewer CT procedures after the implementation of the integrated system. Part of this reduction was driven by a lower rate of repeat procedures: the average inpatient had 0.13 fewer repeat XR procedures within 24-hours of the previous identical XR procedure. A similar decrease was not evident for repeat CT procedures. Reduced utilisation of imaging procedures (especially those within very short intervals from the previous identical procedure, which are more likely to be redundant) has implications for the safety of patients and the cost of medical imaging services. © 2016 The authors and IOS Press.
Varettas K.,South Eastern Area Laboratory Services
ANZ Journal of Surgery | Year: 2012
In Australia, there are six Therapeutic Goods Administration-licensed clinical bacteriology laboratories providing bacterial and fungal bioburden testing of allograft musculoskeletal samples sent from 10 tissue banks. Musculoskeletal swab and/or tissue biopsy samples are collected at the time of allograft retrieval and sent to bacteriology laboratories for bioburden testing, in some cases requiring interstate transport. Bacteria and fungi may be present within the allograft at the time of retrieval or contaminated from an external source. The type of organism recovered will determine if the allograft is rejected for transplant, which may include all allografts from the same donor. Bacteriology staff also provides unpaid support of tissue banks through meeting involvement, consultations, licence-related activities, validations and research funded by their organisation and not part of any contractual agreement. Bacteriology laboratories and tissue banks must be compliant to the Code of Good Manufacturing Practice - Human Blood and Tissues and regulated by the Therapeutic Goods Administration. Clinical bacteriology laboratories also require mandatory accreditation to Standards Australia International Organisation for Standardisation (ISO) 15189:2009 medical laboratories - particular requirements for quality and competence, and may also attain Standards Australia/New Zealand Standard ISO 9001:2000 quality management systems certification. Bacteriology laboratories and musculoskeletal tissue banks are integral partners in providing safe allograft musculoskeletal tissue for transplant. © 2012 The Author. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.
Tan Y.L.,St George Hospital |
Kidson-Gerber G.,South Eastern Area Laboratory Services
The Medical journal of Australia | Year: 2016
Haemoglobinopathy screening should be performed in women with microcytic indices, women from high risk ethnic populations and those with unexplained anaemia. Early testing of women and their partners expedites appropriate management prior to and during pregnancy. Haemoglobinopathy screening is a multistep process beginning with a full blood count, ferritin assay, screening tests for haemoglobinopathies (ie, haemoglobin electrophoresis, high performance liquid chromatography, capillary electrophoresis) and assessment of clinical risk. Iron deficiency may obscure the diagnosis of β-thalassaemia trait. If possible, haemoglobinopathy testing should be performed when the woman is iron-replete. Genetic testing can be offered on the basis of the combined risk of the couple; but turnaround times are lengthy at present, hence the emphasis on early pregnancy or pre-conception screening. Screening processes vary between states and local health districts; a uniform approach to screening and genetic testing with a national registry to record results would improve management of this growing problem.
PubMed | South Eastern Area Laboratory Services
Type: | Journal: Cell and tissue banking | Year: 2017
The bioburden screening process of allograft musculoskeletal tissue samples received at the South Eastern Area Laboratory Services includes the routine use of solid agar and cooked meat (CM) broth media. CM has been routinely sub-cultured onto solid agar plates after aerobic incubation at 35C. This study will evaluate whether a visual assessment of CM can replace sub-culture by an in vitro inoculation and a prospective study. Eight challenge organisms were serially diluted and inoculated into CM. The average inoculum of 0.5-5.5CFU produced visible turbidity of CM after 24-h incubation for 7 of the challenge organisms with one organism producing turbidity after 48-h incubation. The prospective study evaluated 222 CM of which 213 were visually clear and no-growth on sub-culture and 9 turbid CM which were culture positive. Broth cultures are an integral part of the bioburden screening process of allograft musculoskeletal tissue and swab samples and visual assessment of CM can replace sub-culture.