Paediatrics (RCH) - Research Publications

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    Stability of combined Le Fort I maxillary advancement and mandibular reduction.
    Arpornmaeklong, P ; Shand, JM ; Heggie, AA (Walter de Gruyter GmbH, 2003-11)
    BACKGROUND: There have been reports that correction of severe Class III abnormality by single jaw surgery may invite relapse in the long-term. The purpose of this study was to retrospectively evaluate the stability of combined Le Fort I maxillary advancement and bilateral sagittal split osteotomies for mandibular reduction. METHODS: Thirty patients with a skeletal Class III malocclusion underwent bimaxillary surgery using rigid fixation and interpositional bone grafting of the maxilla. The average age was 24.4 years, and the mean follow-up period was 20 months (Range: 12-63 months). Post-operative changes were measured on lateral cephalometric radiographs using an anatomical best-fit technique. RESULTS: The maxilla was advanced, on average, 6.1 mm (SD: 1.8 mm) and repositioned superiorly at PNS 1.9 mm (SD: 2.1 mm). The mandible was repositioned posteriorly 5.6 mm ISD: 4.2 mm) at menton, which also auto-rotated superiorly. At follow-up, the maxilla relapsed horizontally 0.6 mm (SD: 1.1 mm, p < 0.01) with no significant vertical change. The maxillary central incisors were proclined and the interincisal angle was reduced. Menton relapsed anteriorly 1.4 mm (SD: 2.7 mm, p < 0.01), and gonion rotated superiorly 1.5 mm (SD: 2.3 mm, p < 0.001). In 67 per cent of cases menton moved anteriorly less than 2.5 mm. The overjet and overbite did not change significantly. CONCLUSIONS: The data show that 12-months post-operatively, maxillary advancement combined with mandibular setback was relatively stable in the horizontal and vertical planes.
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    Normal skeletal development of mice lacking matrilin 1:: Redundant function of matrilins in cartilage?
    Aszódi, A ; Bateman, JF ; Hirsch, E ; Baranyi, M ; Hunziker, EB ; Hauser, N ; Bösze, Z ; Fässler, R (AMER SOC MICROBIOLOGY, 1999-11)
    Matrilin 1, or cartilage matrix protein, is a member of a novel family of extracellular matrix proteins. To date, four members of the family have been identified, but their biological role is unknown. Matrilin 1 and matrilin 3 are expressed in cartilage, while matrilin 2 and matrilin 4 are present in many tissues. Here we describe the generation and analysis of mice carrying a null mutation in the Crtm gene encoding matrilin 1. Anatomical and histological studies demonstrated normal development of homozygous mutant mice. Northern blot and biochemical analyses show no compensatory up-regulation of matrilin 2 or 3 in the cartilage of knockout mice. Although matrilin 1 interacts with the collagen II and aggrecan networks of cartilage, suggesting that it may play a role in cartilage tissue organization, studies of collagen extractability indicated that collagen fibril maturation and covalent cross-linking were unaffected by the absence of matrilin 1. Ultrastructural analysis did not reveal any abnormalities of matrix organization. These data suggest that matrilin 1 is not critically required for cartilage structure and function and that matrilin 1 and matrilin 3 may have functionally redundant roles.
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    Analysis of the assembly profiles for mitochondrial- and nuclear-DNA-encoded subunits into complex I
    Lazarou, M ; McKenzie, M ; Ohtake, A ; Thorburn, DR ; Ryan, MT (AMER SOC MICROBIOLOGY, 2007-06)
    Complex I of the respiratory chain is composed of at least 45 subunits that assemble together at the mitochondrial inner membrane. Defects in human complex I result in energy generation disorders and are also implicated in Parkinson's disease and altered apoptotic signaling. The assembly of this complex is poorly understood and is complicated by its large size and its regulation by two genomes, with seven subunits encoded by mitochondrial DNA (mtDNA) and the remainder encoded by nuclear genes. Here we analyzed the assembly of a number of mtDNA- and nuclear-gene-encoded subunits into complex I. We found that mtDNA-encoded subunits first assemble into intermediate complexes and require significant chase times for their integration into the holoenzyme. In contrast, a set of newly imported nuclear-gene-encoded subunits integrate with preexisting complex I subunits to form intermediates and/or the fully assembly holoenzyme. One of the intermediate complexes represents a subassembly associated with the chaperone B17.2L. By using isolated patient mitochondria, we show that this subassembly is a productive intermediate in complex I assembly since import of the missing subunit restores complex I assembly. Our studies point to a mechanism of complex I biogenesis involving two complementary processes, (i) synthesis of mtDNA-encoded subunits to seed de novo assembly and (ii) exchange of preexisting subunits with newly imported ones to maintain complex I homeostasis. Subunit exchange may also act as an efficient mechanism to prevent the accumulation of oxidatively damaged subunits that would otherwise be detrimental to mitochondrial oxidative phosphorylation and have the potential to cause disease.
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    ANTIGENIC VARIATION IN PLASMODIUM-FALCIPARUM
    BIGGS, BA ; GOOZE, L ; WYCHERLEY, K ; WOLLISH, W ; SOUTHWELL, B ; LEECH, JH ; BROWN, GV (NATL ACAD SCIENCES, 1991-10)
    Antigenic variation of infectious organisms is a major factor in evasion of the host immune response. However, there has been no definitive demonstration of this phenomenon in the malaria parasite Plasmodium falciparum. In this study, cloned parasites were examined serologically and biochemically for the expression of erythrocyte surface antigens. A cloned line of P. falciparum gave rise to progeny that expressed antigenically distinct forms of an erythrocyte surface antigen but were otherwise identical. This demonstrates that antigenic differences on the surface of P. falciparum-infected erythrocytes can arise by antigenic variation of clonal parasite populations. The antigenic differences were shown to result from antigenic variation of the parasite-encoded protein, the P. falciparum erythrocyte membrane protein 1.
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    The Australasian Society for Infectious Diseases guidelines for the diagnosis, management and prevention of infections in recently arrived refugees: an abridged outline
    Murray, RJ ; Davis, JS ; Burgner, DP (WILEY, 2009-04-20)
    About 13,000 refugees are currently accepted for migration into Australia each year, many of whom have spent protracted periods living in extremely disadvantaged circumstances. As a result, medical practitioners are increasingly managing recently arrived refugees with acute and chronic infectious diseases. The Australasian Society for Infectious Diseases has formulated guidelines for the diagnosis, management and prevention of infection in newly arrived refugees. This article is an abridged version of the guidelines, which are available in full at . All refugees should be offered a comprehensive health assessment, ideally within 1 month of arrival in Australia, that includes screening for and treatment of tuberculosis, malaria, blood-borne viral infections, schistosomiasis, helminth infection, sexually transmitted infections, and other infections (eg, Helicobacter pylori) as indicated by clinical assessment; and assessment of immunisation status, and catch-up immunisations where appropriate. The assessment can be undertaken by a general practitioner or within a multidisciplinary refugee health clinic, with use of an appropriate interpreter when required. The initial assessment should take place over at least two visits: the first for initial assessment and investigation and the second for review of results and treatment or referral.
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    Excessive alcohol use and its association with risky sexual behaviour: a cross-sectional analysis of data from Victorian secondary school students
    Agius, P ; Taft, A ; Hemphill, S ; Toumbourou, J ; McMorris, B (WILEY, 2013-02)
    OBJECTIVE: Estimate the prevalence of sexual behaviour and alcohol use and examine the association between excessive alcohol use and risky sexual behaviour in late secondary students in Victoria, Australia. METHOD: The sample of Year 11 students from government and independent schools participating in the 2008 International Youth Development Study (n=450) was representative of the Victorian school population. Logistic regression analyses examined the associations between sexual behaviour, binge and compulsive drinking, adjusting for socio-demographic, school and family factors. RESULTS: Under half (44%) the students had experienced sex in the past year, half (50%) had engaged in binge drinking in the past two weeks and 26% reported compulsive drinking in the past year. Of those who reported sex in the past year (n=197), 34% had sex without a condom at the last sexual encounter and 28% later regretted sex due to alcohol. The likelihood of experiencing sex was increased by binge (OR=2.44, 95%CI 1.44-4.12) and compulsive drinking (OR=2.15, 95%CI 1.29-3.60). For those sexually active, binge drinking increased the risk of having three or more sexual partners (OR=3.37, 95%CI 1.11-10.26) and compulsive drinking increased the likelihood of regretted sex due to alcohol (OR=4.43, 95%CI 2.10-9.31). Excessive drinking was not associated with condom non-use. CONCLUSION AND IMPLICATIONS: Risky sex - multiple sexual partners and regretted sex due to alcohol - and excessive drinking are highly prevalent and co-associated among Victorian late secondary students.
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    Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence
    Gordon, L ; Joo, JE ; Powel, JE ; Ollikainen, M ; Novakovic, B ; Li, X ; Andronikos, R ; Cruickshank, MN ; Conneely, KN ; Smith, AK ; Alisch, RS ; Morley, R ; Visscher, PM ; Craig, JM ; Saffery, R (COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 2012-08)
    Comparison between groups of monozygotic (MZ) and dizygotic (DZ) twins enables an estimation of the relative contribution of genetic and shared and nonshared environmental factors to phenotypic variability. Using DNA methylation profiling of ∼20,000 CpG sites as a phenotype, we have examined discordance levels in three neonatal tissues from 22 MZ and 12 DZ twin pairs. MZ twins exhibit a wide range of within-pair differences at birth, but show discordance levels generally lower than DZ pairs. Within-pair methylation discordance was lowest in CpG islands in all twins and increased as a function of distance from islands. Variance component decomposition analysis of DNA methylation in MZ and DZ pairs revealed a low mean heritability across all tissues, although a wide range of heritabilities was detected for specific genomic CpG sites. The largest component of variation was attributed to the combined effects of nonshared intrauterine environment and stochastic factors. Regression analysis of methylation on birth weight revealed a general association between methylation of genes involved in metabolism and biosynthesis, providing further support for epigenetic change in the previously described link between low birth weight and increasing risk for cardiovascular, metabolic, and other complex diseases. Finally, comparison of our data with that of several older twins revealed little evidence for genome-wide epigenetic drift with increasing age. This is the first study to analyze DNA methylation on a genome scale in twins at birth, further highlighting the importance of the intrauterine environment on shaping the neonatal epigenome.
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    Avoiding conflict: What do adolescents with disordered eating say about their mothers in music therapy?
    McFerran, K ; Baker, F ; Kildea, C ; Patton, G ; Sawyer, S (SAGE Publications, 2008-06-01)
    Music therapy is an integral part of the inpatient treatment programme for young women with disordered eating at the Royal Children's Hospital in Melbourne. As part of ongoing clinical audit activities, an investigation was undertaken to analyse retrospectively the lyrics of young women who had participated in the music therapy programme. The¬¬¬¬¬¬ purpose was to monitor and improve local clinical practice and clarify the specific contribution of music therapy to the diagnosis of anorexia nervosa. Results highlighted the role of mothers in the experiences of the young participants, with references to this relationship exceeding those to any other relationships. These findings are discussed in conjunction with an abandoned study where parental consent was not forthcoming for participation in a group music therapy research project. This article promotes a continuing awareness of the importance of the mother-daughter relationship in the treatment of eating disorders.
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    New Mid-Cretaceous (latest Albian) dinosaurs fromWinton, Queensland, Australia.
    Hocknull, SA ; White, MA ; Tischler, TR ; Cook, AG ; Calleja, ND ; Sloan, T ; Elliott, DA ; Sereno, P (Public Library of Science (PLoS), 2009-07-03)
    BACKGROUND: Australia's dinosaurian fossil record is exceptionally poor compared to that of other similar-sized continents. Most taxa are known from fragmentary isolated remains with uncertain taxonomic and phylogenetic placement. A better understanding of the Australian dinosaurian record is crucial to understanding the global palaeobiogeography of dinosaurian groups, including groups previously considered to have had Gondwanan origins, such as the titanosaurs and carcharodontosaurids. METHODOLOGY/PRINCIPAL FINDINGS: We describe three new dinosaurs from the late Early Cretaceous (latest Albian) Winton Formation of eastern Australia, including; Wintonotitan wattsi gen. et sp. nov., a basal titanosauriform; Diamantinasaurus matildae gen. et sp. nov., a derived lithostrotian titanosaur; and Australovenator wintonensis gen. et sp. nov., an allosauroid. We compare an isolated astragalus from the Early Cretaceous of southern Australia; formerly identified as Allosaurus sp., and conclude that it most-likely represents Australovenator sp. CONCLUSION/SIGNIFICANCE: The occurrence of Australovenator from the Aptian to latest Albian confirms the presence in Australia of allosauroids basal to the Carcharodontosauridae. These new taxa, along with the fragmentary remains of other taxa, indicate a diverse Early Cretaceous sauropod and theropod fauna in Australia, including plesiomorphic forms (e.g. Wintonotitan and Australovenator) and more derived forms (e.g. Diamantinasaurus).
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    New Australovenator hind limb elements pertaining to the holotype reveal the most complete Neovenatorid leg.
    White, MA ; Benson, RBJ ; Tischler, TR ; Hocknull, SA ; Cook, AG ; Barnes, DG ; Poropat, SF ; Wooldridge, SJ ; Sloan, T ; Sinapius, GHK ; Elliott, DA ; Dodson, P (Public Library of Science (PLoS), 2013)
    We report new skeletal elements pertaining to the same individual which represents the holotype of Australovenator wintonensis, from the 'Matilda Site' in the Winton Formation (Upper Cretaceous) of western Queensland. The discovery of these new elements means that the hind limb of Australovenator is now the most completely understood hind limb among Neovenatoridae. The new hind limb elements include: the left fibula; left metatarsal IV; left pedal phalanges I-2, II-1, III-4, IV-2, IV-3; and right pedal phalanges, II-2 and III-1. The detailed descriptions are supported with three dimensional figures. These coupled with the completeness of the hind limb will increase the utility of Australovenator in comparisons with less complete neovenatorid genera. These specimens and the previously described hind limb elements of Australovenator are compared with other theropods classified as neovenatorids (including Neovenator, Chilantaisaurus, Fukuiraptor, Orkoraptor and Megaraptor). Hind limb length proportion comparisons indicate that the smaller neovenatorids Australovenator and Fukuiraptor possess more elongate and gracile hind limb elements than the larger Neovenator and Chilantaisaurus. Greater stride lengths to body size exist in both Fukuiraptor and Australovenator with the femur discovered to be proportionally shorter the rest of the hind limb length. Additionally Australovenator is identified as possessing the most elongate metatarsus. The metatarsus morphology varies with body size. The larger neoventorids possess a metatarsus with greater width but shorter length compared to smaller forms.