Medicine & Health

Publication Search Results

Now showing 1 - 10 of 138
  • (2009) Packham, Deborah; Ward, Robyn L; Lin, Vita Ap; Hawkins, Nicholas J; Hitchins, Megan P
    Journal Article
    Abstract: Activating mutations of the BRAF and KRAS genes cause constitutive stimulation of an important cell-signaling pathway promoting tumorigenesis, and are increasingly recognized as determinants of response to targeted cancer therapies. The V600E mutation accounts for most of the BRAF mutations in cancer, and KRAS mutations are predominantly encoded by nucleotide substitutions within codons 12 and 13. We designed novel pyrosequencing assays for the detection of the common ‘‘hotspot’’ mutations in these genes, which demonstrated analytical sensitivities of Z10% in titrations of mutant cell AQ1 lines. The KRAS pyrosequencing assay has the ability to simultaneously identify all potential nucleotide changes within the mutation cluster at codons 12 and 13, with a sequence output in the sense direction to facilitate results interpretation. These assays were used to determine the mutation status in a prospective series of 1198 sporadic colorectal cancers. The BRAF V600E mutation was detected in 13.2% of the colorectal cancers. The frequency of KRAS mutations in our cohort was 32.4%, with G>A transitions at position 2 of codons 12 and 13 being most prevalent. Both assays proved highly sensitive and specific when applied to clinical specimens, and were applicable to both fresh-frozen and formalin-fixed paraffin-embedded archival tissues. These assays would serve as a suitable platform for large-scale mutation detection in cancer specimens where the facility for pyrosequencing is available.

  • (2009) Gao, Steven; Lees, Justin; Wong, Jennifer; Croll, Tristan; George, Peter; Cooper-White, Justin; Tuch, Bernard
    Journal Article
    Human embryonic stem cells (hESCs) have previously been cultured on three dimensional (3D) biodegradable polymer scaffolds. Although complex structures were formed from the hESCs, very little is known about the mechanism of adhesion of these cells to the surfaces of the scaffolds. In this study, we achieved the efficient adhesion of pluripotent hESCs to 3D poly(lactic-co-glycolic acid) (PLGA) scaffolds based on our data from a novel two dimensional (2D) model that imitates the surface properties of the scaffolds. In the 2D model, single cell preparations of pluripotent hESCs adhered efficiently and predominantly to PLGA surfaces coated with laminin in comparison to collagen I, collagen IV, or fibronectin-coated surfaces. Flow cytometry analysis revealed that almost all of the pluripotent single cells expressed the integrin 6, with a small percentage also expressing 3ß1, which facilitates adhesion to laminin. This data was then translated into the 3D environment, with the efficient binding of single pluripotent hESCs to PLGA scaffolds coated with laminin. The utility of this system was shown by the directed differentiation of single hESCs seeded within laminin-coated scaffolds toward the endoderm lineage.

  • (2009) Chen, Hui; Morris, Margaret
    Journal Article
    Maternal obesity due to long-term high-fat diet (HFD) consumption leads to faster growth in offspring during suckling, and increased adiposity at 20 days of age. Decreased expression of the orexigenic neuropeptide Y (NPY) and increased anorexigenic proopiomelanocortin (POMC) mRNA expression were observed in the fed state. However, hunger is the major drive to eat and hypothalamic appetite regulators change in response to meals. Therefore it is important to compare both satiated and fasting states. Female Sprague Dawley rats (8 weeks old) were fed a cafeteria-style HFD (15.33kJ/g) or chow for 5 weeks before mating, with the same diet continuing throughout gestation and lactation. At postnatal day 20, male pups were killed either after overnight fasting or in the fed state. Pups from obese dams were hyperphagic during both pre- and post-weaning periods. Pups from obese dams had higher hypothalamic mRNA expression of POMC and NPY Y1 receptor, but lower hypothalamic melanocortin-4 receptor (MC4R) and its downstream target single-minded gene 1 (Sim1), in the fed state. Overnight fasting reduced circulating glucose, insulin, and leptin and increased hypothalamic NPY Y1 receptor mRNA in pups from both lean and obese dams. Hypothalamic NPY and agouti-related protein were only increased by fasting in pups from obese dams; reductions in MC4R and Sim1 were only seen in pups from lean dams. At weaning, the suppressed orexigenic signals in offspring from obese dams were normalized after overnight fasting, while anorexigenic signaling appeared impaired in these animals. This may contribute to their hyperphagia and faster growth.

  • (2009) Gorrie, Catherine; Waite, PME; Rogers, LJ
    Journal Article
    Cortical asymmetries are well established in humans for language and motor regions and correlate with handedness. Here the authors investigate structural differences in the hemispheres of left- and right-handed common marmosets using surface photography and histology. The hand preferences of 11 marmosets were assessed over their adult life span using a simple reaching task. A significant correlation was found between the length of the right lateral sulcus/brain weight and the % right-hand preference (r = .86, p = .001). Cortical thickness on the superior bank of the right lateral sulcus posteriorly was also positively correlated with % right-hand preference (r = .69, p = .025). Comparison of this site with previously published functional maps of the marmoset cortex show this area corresponds to SII, a region involved in tactile processing and somatosensory discriminations. It is suggested that the correlation between SII thickness and right-hand preference would be consistent with the fact that right-handed marmosets are more proactive than left-handers in exploring novel objects by touch. Enlargement of a cortical area involved tactile discriminations could be a precursor to the evolution of right-handedness as a population bias.

  • (2009) Leong, G; Gorrie, Catherine; Ng, K; Rutkowski, S; Waite, P.M.E
    Journal Article
    Study Design : Prospective experimental Objectives : To investigate inter-rater and intra-rater reliability of electrical perceptual threshold (EPT) testing in assessing somatosensory function in healthy volunteers. Setting: Spinal Injuries Unit, Royal North Shore Hospital, Sydney, NSW, Australia Methods: Cutaneous electrical stimulation of 4 dermatomes at American Spinal Injuries Association (ASIA) sensory key points (C3, T1, L3, S2) was performed on 40 control subjects. The lowest ascending stimulus intensity at which sensation was perceived was recorded as the EPT. Mean EPT values for each dermatome, as determined by 2 testers at two time points, were examined and plotted against a normative template. Differences and associations between intra- and inter-rater measurements, and left-right measurements were investigated. EPT results for 2 people with spinal cord injuries were also examined. Results : EPT measurements from left and right sides, obtained from the two time points and two testers, were found to be strongly associated, with the exception of left and right side measurements at the S2 dermatome. No significant differences in the mean EPT for tester or time period were found. The intra- and inter-rater reliability was good for all dermatomes tested. Mean EPT measurements fell within the range of a normative template at each of the 4 dermatomes tested. Conclusion : EPT is an objective, reproducible and quantifiable method of assessing sensation in a control group. However, caution should be applied in certain dermatomes such as S2 where there was large variation between left and right side measurements. Sponsorship : New South Wales Office of Science and Medical Research

  • (2009) Nielssen, O.; Large, M.; Westmore, B.; Lackersteen, S.
    Journal Article
    Objective: To examine the circumstances of homicides of children in New South Wales from 1991 to 2005. Design and setting: Retrospective analysis of all identified child homicides in NSW from 1991 to 2005, based on data on offenders and victims obtained from crime statistics, documents located by systematic searches of legal databases and media reports, and medicolegal reports of offenders who committed child homicides during psychotic illness. Main outcome measures: Demographic characteristics of homicides and a history of prior psychiatric treatment among offenders with psychosis. Results: We located documents describing 165 homicides by 157 offenders. Fifty-nine deaths were a consequence of child abuse, including those of five children who died from methadone overdoses. Both the offenders and the victims in fatal child abuse were significantly younger than in other forms of child homicide. The courts found that 27 child homicides had been committed by 26 offenders during the acute phase of psychotic illness, and 15 of these offenders had never been treated with antipsychotic medication. Conclusions: Earlier identification and treatment of psychotic illness in mothers, and changes in the way methadone is provided to opiate-dependent parents, might result in a small overall reduction in the number of child deaths. More lives could be saved by measures that reduce the incidence of child abuse, including the prohibition of corporal punishment of children.

  • (2009) Large, M.; Nielssen, O.
    Journal Article
    Objective: To examine the relationship between the numbers of psychiatric hospital beds and prisoners using recent statistics. Design: An analysis of published data from 158 countries. Methods: Multiple linear regression techniques were used to examine the relationship between per capita measures of income and numbers of psychiatric hospital beds and the dependant variable of per capita prison populations, in high and low-and-middle-income countries. Results: Prison and psychiatric populations were positively correlated in low-and-middle-income countries. There was no relationship between the number of psychiatric hospital beds and prison populations in high-income countries. Conclusions: In low-and-middle income countries the association between prison and psychiatric hospital populations may depend on the ability of governments to pay for custodial institutions as well as differences in cultural attitudes towards abnormal and criminal behaviour. In high-income (HI) countries psychiatric and prison populations are not related and probably determined by separate social and political factors.

  • (2009) Short, Alison; Holdgate, Anna; Ahern , Nicole; Morris, Jennifer
    Journal Article
    The interdisciplinary context of the emergency department encompasses diverse clinical presentations requiring teamwork by doctors, nurses and allied health workers to achieve optimal patient care. This interdisciplinary focus is extended by adding a research perspective. This project sought to systematically examine the current research capacity of emergency department staff at a major Australian tertiary urban hospital and to derive information about further research-related needs with a view to enhancing research capacity. The mixed method project utilized a department-wide staff survey followed by focus groups and individual interviews. Adequate response rates to the two phases were achieved (n¼67, n¼17 respectively). Not surprisingly, 89% of participants reported that they needed help with developing their research skills. Clinicians reported little or no experience with (i) finding literature (35%) and critical review (50%), (ii) research skills and techniques, both qualitative (72%) and quantitative (63%), and (iii) research output: publishing (68%), writing & presenting (34%). Data from focus groups and individual interviews yielded themes around developing research skills, communication, meaningfulness, team work and interdisciplinary strategies, forming part of the Dimensional Enhancing Research Capacity (DERC) model. This project highlighted not only interdisciplinary needs for research but also the way that research may additionally assist with building interprofessional linkage.

  • (2009) Ekholm , Jodie; Short, Alison
    Journal Article
    Background: Responding to an imposed health area merger, all those involved in nurse education were required to amalgamate their activities across the newly created larger and diverse health area. Methods: This reflective paper outlines issues arising as a result of the merger, puts forward responses of ED nurse education staff based on a simple questionnaire, and reviews changes implemented as a result of the merger. Results: Whilst there was some initial resistance, strategies were developed from within the educator staff involved in order to facilitate the merger process. The questionnaire indicated that initial concerns were gradually overcome during the transition process. Ultimately, a successful merger occurred, leading to a range of educational benefits. Conclusions: Although difficult, a successful merger transitional process led to the development of a broad, systemised career pathway for ED nurses. Further benefits were ultimately apparent as a result of the merger, including issues of resource allocation, cost-savings, and potential staff retention.

  • (2009) Senadheera, S.; Markus, I.; Bertrand, R. L.; Liu, L.; Morris, M. .J.; Bertrand, P. P
    Conference Paper