Medical Education - Research Publications
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ItemNasal Resistance Is Elevated in People with Tetraplegia and Is Reduced by Topical Sympathomimetic Administration(AMER ACAD SLEEP MEDICINE, 2016)STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is common in individuals with tetraplegia and associated with adverse health outcomes. The causes of the high prevalence of OSA in this population are unknown, but it is important to understand as standard treatments are poorly tolerated in tetraplegia. Nasal congestion is common in tetraplegia, possibly because of unopposed parasympathetic activity. Further, nasal obstruction can induce OSA in healthy individuals. We therefore aimed to compare nasal resistance before and after topical administration of a sympathomimetic between 10 individuals with tetraplegia (T) and 9 able-bodied (AB) controls matched for OSA severity, gender, and age. METHODS: Nasal, pharyngeal, and total upper airway resistance were calculated before and every 2 minutes following delivery of ≈0.05 mL of 0.5% atomized phenylephrine to the nostrils and pharyngeal airway. The surface tension of the upper airway lining liquid was also assessed. RESULTS: At baseline, individuals with tetraplegia had elevated nasal resistance (T = 7.0 ± 1.9, AB = 3.0 ± 0.6 cm H2O/L/s), that rapidly fell after phenylephrine (T = 2.3 ± 0.4, p = 0.03 at 2 min) whereas the able-bodied did not change (AB = 2.5 ± 0.5 cm H2O/L/s, p = 0.06 at 2 min). Pharyngeal resistance was non-significantly higher in individuals with tetraplegia than controls at baseline (T = 2.6 ± 0.9, AB = 1.2 ± 0.4 cm H2O/L/s) and was not altered by phenylephrine in either group. The surface tension of the upper airway lining liquid did not differ between groups (T = 64.3 ± 1.0, AB = 62.7 ± 0.6 mN/m). CONCLUSIONS: These data suggest that the unopposed parasympathetic activity in tetraplegia increases nasal resistance, potentially contributing to the high occurrence of OSA in this population.
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ItemDiacetylbis(N(4)-methylthiosemicarbazonato) Copper(II) (CuII(atsm)) Protects against Peroxynitrite-induced Nitrosative Damage and Prolongs Survival in Amyotrophic Lateral Sclerosis Mouse Model(AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2011-12-23)Amyotrophic lateral sclerosis (ALS) is a progressive paralyzing disease characterized by tissue oxidative damage and motor neuron degeneration. This study investigated the in vivo effect of diacetylbis(N(4)-methylthiosemicarbazonato) copper(II) (CuII(atsm)), which is an orally bioavailable, blood-brain barrier-permeable complex. In vitro the compound inhibits the action of peroxynitrite on Cu,Zn-superoxide dismutase (SOD1) and subsequent nitration of cellular proteins. Oral treatment of transgenic SOD1G93A mice with CuII(atsm) at presymptomatic and symptomatic ages was performed. The mice were examined for improvement in lifespan and motor function, as well as histological and biochemical changes to key disease markers. Systemic treatment of SOD1G93A mice significantly delayed onset of paralysis and prolonged lifespan, even when administered to symptomatic animals. Consistent with the properties of this compound, treated mice had reduced protein nitration and carbonylation, as well as increased antioxidant activity in spinal cord. Treatment also significantly preserved motor neurons and attenuated astrocyte and microglial activation in mice. Furthermore, CuII(atsm) prevented the accumulation of abnormally phosphorylated and fragmented TAR DNA-binding protein-43 (TDP-43) in spinal cord, a protein pivotal to the development of ALS. CuII(atsm) therefore represents a potential new class of neuroprotective agents targeting multiple major disease pathways of motor neurons with therapeutic potential for ALS.
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ItemRehabilitation Outcomes In Persons With Spina Bifida: A Randomized Controlled Trial(Medical Journals Sweden, 2015-09-01)Objective: To assess the effectiveness of an interdisciplinary ambulatory rehabilitation programme for persons with spina bifida in an Australian community cohort. Methods: Fifty-four participants randomized to a treatment group (n = 27) for a high-intensity rehabilitation programme (with cognitive behavioural therapy) or a control group (n = 27) comprising usual care. Outcome measures include: Disability: Urogenital Distress Inventory (UDI6), Incontinence Impact Questionnaire-7 (IIQ7), American Urological Association Symptom Index (AUA), Wexner-Faecal Incontinence Score (WFIS), Neurological Disability Scale (NDS); Participation: Depression, Anxiety Stress Scale (DASS), McGill Quality of Life (MQOL), Brief COPE Scale, Genera-lized Self-efficacy Scale (GSE). Assessments were made at baseline and 3-months post-intervention. Results: Adjusted for baseline disease and demographic covariates, the intervention group improved significantly at 3-month follow-up for primary and secondary outcomes, with moderate to large effect sizes (r): urinary/bowel dysfunction (AUA, UDI6, IIQ7, WFIS) (p < 0. 001 for all, r = 0. 4–0. 7); and cognitive function: NDS “cognitive” and “mood” (p < 0. 01, r = 0. 6 for both); DASS “depression”, “anxiety” and “stress” (p < 0. 001 for all, r = 0. 5–0. 7); MQOL total (p = 0. 013, r = 0. 5), “psychological symptoms” (p < 0. 001, r = 0. 8); “active coping” (p = 0. 035) and “self-efficacy” scores (GSE p < 0. 001). No difference between groups was noted in other subscales. Conclusion: Targeted rehabilitation can improve clinical outcomes in persons with spina bifida. Further research is needed for longer-term outcomes related to “ageing” and participation restriction.
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ItemSupportive Care Needs following Cancer Treatment: A Comparison of Breast and Brain Cancer in an Australian Cohort(Hindawi Publishing Corporation, 2014)Objective. To assess and identify patient-reported supportive care needs following definitive treatment in persons with breast cancer (BC) and primary brain tumours (gliomas) (BT) in an Australian community cohort and to assess the commonalities and/or discrepancies of the reported needs in these oncological populations. Methods. A prospective cross-sectional survey of persons with BC () and BT () using questionnaires for supportive care needs, psychological morbidity, and quality of life. Results. BT participants were younger than BC patients (mean ages 51 and 57 years). The median time since diagnosis for both groups was over 2 years. The level of psychological morbidity, mainly depression, was high in both groups: BC (22%) and BT (20%). Participants in both groups reported at least one need (“met” or “unmet”). The BC patients reported higher numbers of “needs” and “unmet” needs compared with BT patients (mean 13.7 versus 11.6 needs; “unmet” needs mean 6.0 versus 4.1). The common “met” and “unmet” needs highlighted by both groups were comparable; the domain for most “met” needs included comprehensive cancer care, while “unmet” needs related to existential survivorship issues. Conclusion. Despite successful treatment many cancer survivors experience unmet supportive care needs in longer term. Understanding the impact of these beyond the acute phase is important as care shifts to community settings. More research in existential survivorship issues is needed.
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ItemAn enriched environmental programme during inpatient neuro-rehabilitation: A randomized controlled trial(Medical Journals Sweden, 2016-05-01)Objective: To assess the effectiveness of an enriched environmental activities programme in an inpatient tertiary neuro-rehabilitation unit. Methods: A total of 103 participants were randomized to an intervention group (n = 52) undertaking an enriched environmental activities programme or a control group (n = 51) receiving usual ward activity. Primary outcome measure: Depression, Anxiety Stress Scale (DASS). Other measures included: Neurological Impairment Scale; Multidimensional Health Locus of Control, Rosenberg Self-Esteem Scale, Montreal Cognitive Assessment (MoCA); Functional Independence Measure (FIM), and Euro-Quality of Life-5D. Questionnaire assessments were performed at admission, discharge and 3-months post-discharge. Results: Mean age of subjects was 62. 5 years (standard deviation 18. 5), 63% were male; 53 had stroke and the remainder had other neurological conditions. Compared with controls, the intervention group showed significant improvement at discharge in: DASS: “total”, “depression”, and “stress” subscales (p < 0. 05 for all, with small effect sizes (η2) = 0. 04–0. 05); MoCA (p = 0. 048, η2 = 0. 04) and FIM motor (total and “self-care”, “mobility” subscales (p < 0. 05 for all, with moderate effect sizes, η2 = 0. 0–0. 08). At 3-month follow-up, significant differences were maintained in most secondary outcomes in the intervention group. Cognitive function and activities improved most in participants with stroke. Conclusion: An enriched environmental programme can produce significant improvements in functional and cognitive ability in inpatient neurological cohorts compared with routine ward activity programmes.
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ItemPeripheral neuropathy in the hands of people with diabetes mellitus(ELSEVIER IRELAND LTD, 2016-09)AIMS: Peripheral sensorimotor neuropathy is a recognised complication of diabetes mellitus however little attention has been given to its development in the hands. The aim of this study was to determine the prevalence of sensory impairment in the hands of participants with diabetes, the agreement between two measurement tools for assessing sensation and the association between hand sensibility, age, glycaemic control and end-organ damage. METHODS: A total of 162 participants were recruited and divided into two cohorts based on a diagnosis of diabetes. Participants were tested for the presence of hand neuropathy using Semmes-Weinstein monofilaments and the AsTex™. Medical records of participants with diabetes were accessed retrospectively to determine glycaemic control and diabetes complications. RESULTS: A highly statistically significant association was found between neuropathy and diabetes status (P<0.001) on monofilament testing. The prevalence of neuropathy was 64% compared to ∼10% amongst participants without diabetes. Age, male gender and diabetic retinopathy were associated with neuropathy. The AsTex™ identified participants with diminished protective sensation on monofilament testing. CONCLUSIONS: This study demonstrates a relationship between diabetes and upper limb neuropathy. Age, male gender and retinopathy were associated with diminished hand sensation. The AsTex™ may have a role as a screening tool for identifying clinically significant hand neuropathy.
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ItemInduction monotherapy with sirolimus has selected beneficial effects on glomerular and tubulointersititial injury in nephrotoxic serum nephritis(DOVE MEDICAL PRESS LTD, 2014)BACKGROUND: The study aimed to test the hypothesis that therapeutic treatment with a mammalian target of rapamycin complex 1 inhibitor reduces renal cell proliferation and attenuates glomerular and tubulointerstitial injury in the early phase of nephrotoxic serum nephritis (NSN) in rats. METHODS: Male Wistar-Kyoto rats received a single tail-vein injection of sheep anti-rat glomerular basement membrane serum (day 0) and were treated with vehicle or sirolimus (0.25 mg/kg/day by subcutaneous injection) from day 1 until day 14. RESULTS: Treatment with sirolimus attenuated kidney enlargement by 41% (P<0.05), improved endogenous creatinine clearance by 50% (P<0.05), and reduced glomerular and tubulointerstitial cell proliferation by 53% and 70%, respectively, (P<0.05 compared to vehicle) in rats with NSN. In glomeruli, sirolimus reduced segmental fibrinoid necrosis by 69%, autologous rat immunoglobulin G deposition, glomerular capillary tuft enlargement, and periglomerular myofibroblast (α-smooth muscle actin-positive cells) accumulation (all P<0.05) but did not significantly affect glomerular crescent formation (P=0.15), macrophage accumulation (P=0.25), or the progression of proteinuria. In contrast, sirolimus preserved tubulointerstitial structure and attenuated all markers of injury (interstitial ED-1- and α-smooth muscle actin-positive cells and tubular vimentin expression; all P<0.05). By immunohistochemistry and Western blot analysis, sirolimus reduced the glomerular and tubulointerstitial expression of phosphorylated (Ser 235/236) S6-ribosomal protein (P<0.05). CONCLUSION: Induction monotherapy with sirolimus suppressed target of rapamycin complex 1 activation, renal cell proliferation, and injury during the early stages of rodent NSN, but the degree of histological protection was more consistent in the tubulointerstitium than the glomerular compartment.
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ItemEGFR signaling promotes self-renewal through the establishment of cell polarity in Drosophila follicle stem cells.(eLife Sciences Publications, Ltd, 2014-12-01)Epithelial stem cells divide asymmetrically, such that one daughter replenishes the stem cell pool and the other differentiates. We found that, in the epithelial follicle stem cell (FSC) lineage of the Drosophila ovary, epidermal growth factor receptor (EGFR) signaling functions specifically in the FSCs to promote the unique partially polarized state of the FSC, establish apical-basal polarity throughout the lineage, and promote FSC maintenance in the niche. In addition, we identified a novel connection between EGFR signaling and the cell-polarity regulator liver kinase B1 (LKB1), which indicates that EGFR signals through both the Ras-Raf-MEK-Erk pathway and through the LKB1-AMPK pathway to suppress apical identity. The development of apical-basal polarity is the earliest visible difference between FSCs and their daughters, and our findings demonstrate that the EGFR-mediated regulation of apical-basal polarity is essential for the segregation of stem cell and daughter cell fates.
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Item'Please don't call me Mister': patient preferences of how they are addressed and their knowledge of their treating medical team in an Australian hospital.(BMJ, 2016-01-06)OBJECTIVES: To investigate how patients prefer to be addressed by healthcare providers and to assess their knowledge of their attending medical team's identity in an Australian Hospital. SETTING: Single-centre, large tertiary hospital in Australia. PARTICIPANTS: 300 inpatients were included in the survey. Patients were selected in a sequential, systematic and whole-ward manner. Participants were excluded with significant cognitive impairment, non-English speaking, under the age of 18 years or were too acutely unwell to participate. The sample demographic was predominately an older population of Anglo-Saxon background. PRIMARY AND SECONDARY OUTCOME MEASURES: Patients preferred mode of address from healthcare providers including first name, title and second name, abbreviated first name or another name. Whether patients disliked formal address of title and second name. Secondarily, patient knowledge of their attending medical team members name and role and if correct, what position within the medical hierarchy they held. RESULTS: Over 99% of patients prefer informal address with greater than one-third having a preference to being called a name other than their legal first name. 57% of patients were unable to correctly name a single member of their attending medical team. CONCLUSIONS: These findings support patient preference of informal address; however, healthcare providers cannot assume that a documented legal first name is preferred by the patient. Patient knowledge of their attending medical team is poor and suggests current introduction practices are insufficient.
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ItemDisruption of MEF2C signaling and loss of sarcomeric and mitochondrial integrity in cancer-induced skeletal muscle wasting(IMPACT JOURNALS LLC, 2012-02)Cancer cachexia is a highly debilitating paraneoplastic disease observed in more than 50% of patients with advanced cancers and directly contributes to 20% of cancer deaths. Loss of skeletal muscle is a defining characteristic of patients with cancer cachexia and is associated with poor survival. The present study reveals the involvement of a myogenic transcription factor Myocyte Enhancer Factor (MEF) 2C in cancer-induced skeletal muscle wasting. Increased skeletal muscle mRNA expression of Suppressor of Cytokine Signaling (Socs) 3 and the IL-6 receptor indicative of active IL-6 signaling was seen in skeletal muscle of mice bearing the Colon 26 (C26) carcinoma. Loss of skeletal muscle structural integrity and distorted mitochondria were also observed using electron microscopy. Gene and protein expression of MEF2C was significantly downregulated in skeletal muscle from C26-bearing mice. MEF2C gene targets myozenin and myoglobin as well as myokinase were also altered during cachexia, suggesting dysregulated oxygen transport capacity and ATP regeneration in addition to distorted structural integrity. In addition, reduced expression of calcineurin was observed which suggested a potential pathway of MEF2C dysregulation. Together, these effects may limit sarcomeric contractile ability and also predispose skeletal muscle to structural instability; associated with muscle wasting and fatigue in cachexia.