Surgery (RMH) - Research Publications
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ItemNo Preview Available"Iodide mumps" after angioplasty(Elsevier, 2000-02-01)Vascular surgeons are increasingly performing endo- vascular fluoroscopy-guided procedures. We report a rare complication of radiographic contrast exposure (iodide-induced sialadenitis or “iodide mumps”), which has significance in the postoperative observation and management of patients after these procedures.
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ItemNo Preview AvailableVascular endothelial growth factor d is dispensable for development of the lymphatic system(AMER SOC MICROBIOLOGY, 2005-03)Vascular endothelial growth factor receptor 3 (Vegfr-3) is a tyrosine kinase that is expressed on the lymphatic endothelium and that signals for the growth of the lymphatic vessels (lymphangiogenesis). Vegf-d, a secreted glycoprotein, is one of two known activating ligands for Vegfr-3, the other being Vegf-c. Vegf-d stimulates lymphangiogenesis in tissues and tumors; however, its role in embryonic development was previously unknown. Here we report the generation and analysis of mutant mice deficient for Vegf-d. Vegf-d-deficient mice were healthy and fertile, had normal body mass, and displayed no pathologic changes consistent with a defect in lymphatic function. The lungs, sites of strong Vegf-d gene expression during embryogenesis in wild-type mice, were normal in Vegf-d-deficient mice with respect to tissue mass and morphology, except that the abundance of the lymphatics adjacent to bronchioles was slightly reduced. Dye uptake experiments indicated that large lymphatics under the skin were present in normal locations and were functional. Smaller dermal lymphatics were similar in number, location, and function to those in wild-type controls. The lack of a profound lymphatic phenotype in Vegf-d-deficient mice suggests that Vegf-d does not play a major role in lymphatic development or that Vegf-c or another, as-yet-unknown activating Vegfr-3 ligand can compensate for Vegf-d during development.
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ItemGlutamate weighted imaging contrast in gliomas with 7 Tesla magnetic resonance imaging(ELSEVIER SCI LTD, 2019)INTRODUCTION: Diffuse gliomas are incurable malignancies, which undergo inevitable progression and are associated with seizure in 50-90% of cases. Glutamate has the potential to be an important glioma biomarker of survival and local epileptogenicity if it can be accurately quantified noninvasively. METHODS: We applied the glutamate-weighted imaging method GluCEST (glutamate chemical exchange saturation transfer) and single voxel MRS (magnetic resonance spectroscopy) at 7 Telsa (7 T) to patients with gliomas. GluCEST contrast and MRS metabolite concentrations were quantified within the tumour region and peritumoural rim. Clinical variables of tumour aggressiveness (prior adjuvant therapy and previous radiological progression) and epilepsy (any prior seizures, seizure in last month and drug refractory epilepsy) were correlated with respective glutamate concentrations. Images were separated into post-hoc determined patterns and clinical variables were compared across patterns. RESULTS: Ten adult patients with a histo-molecular (n = 9) or radiological (n = 1) diagnosis of grade II-III diffuse glioma were recruited, 40.3 +/- 12.3 years. Increased tumour GluCEST contrast was associated with prior adjuvant therapy (p = .001), and increased peritumoural GluCEST contrast was associated with both recent seizures (p = .038) and drug refractory epilepsy (p = .029). We distinguished two unique GluCEST contrast patterns with distinct clinical and radiological features. MRS glutamate correlated with GluCEST contrast within the peritumoural voxel (R = 0.89, p = .003) and a positive trend existed in the tumour voxel (R = 0.65, p = .113). CONCLUSION: This study supports the role of glutamate in diffuse glioma biology. It further implicates elevated peritumoural glutamate in epileptogenesis and altered tumour glutamate homeostasis in glioma aggressiveness. Given the ability to non-invasively visualise and quantify glutamate, our findings raise the prospect of 7 T GluCEST selecting patients for individualised therapies directed at the glutamate pathway. Larger studies with prospective follow-up are required.
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ItemDoes early exercise attenuate muscle atrophy or bone loss after spinal cord injury?(NATURE PUBLISHING GROUP, 2016-02)OBJECTIVES: To systematically identify and assess the evidence on the efficacy of exercise initiated early after traumatic spinal cord injury (SCI). METHODS: A comprehensive search (Any-2014) of eleven databases identified studies evaluating exercise interventions initiated within 12 weeks after SCI on muscle and bone loss in paralyzed limbs and comparing with standard care or immobilization. Two reviewers assessed methodological quality. One reviewer extracted data and critiqued results according to the Spinal Cord Injury Rehabilitation Evidence body of evidence framework. RESULTS: A total of 2811 titles were screened. Eleven studies were included: five randomized controlled trials, four cohort studies and two within-subject control studies. All provided level II evidence with a moderate risk of bias. Two studies found significant positive effects of high-load FES-resisted stance on physiological measures of muscle. Three reported positive effects of 3 months of Functional Electrical Stimulation (FES) on muscle size. Two studies found positive effects of 6-month body-weight supported treadmill training or FES on trabecular bone using pQCT. CONCLUSION: We found consistent evidence of positive effects of early exercise on muscle, possibly related to load intensity of the protocol. However, the heterogeneity of interventions and outcomes makes this determination speculative. Evidence for the effectiveness of early exercise on bone is scant and confined to measures of trabecular bone mineral density via pQCT. Transparent reporting of methods and variability of data, combined with standardization of valid and sensitive measures of muscle atrophy and bone loss, could facilitate future meta-analysis on this topic.
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ItemFactors Associated with Long-Term Functional and Psychological Outcomes in Persons with Moderate to Severe Traumatic Brain Injury(Medical Journals Sweden, 2016-05-01)Objective: To examine factors impacting long-term functional and psychological outcomes in persons with moderate-severe traumatic brain injury. Methods: A prospective cross-sectional study (n = 103) assessed the long-term (up to 5 years) impact of traumatic brain injury on participants’ current activity and restriction in participation using validated questionnaires. Results: Participants’ median age was 49. 5 years (interquartile range (IQR) 20. 4–23. 8), the majority were male (77%), and 49% had some form of previous rehabilitation. The common causes of traumatic brain injury were falls (42%) and motor vehicle accidents (27%). Traumatic brain injury-related symptoms were: pain/headache (47%), dizziness (36%), bladder/bowel impairment (34%), and sensory-perceptual deficits (34%). Participants reported minimal change in their physical function and cognition (Functional Assessment Measure: motor (median 102, IQR 93–111) and cognition (median 89, IQR 78–95)). Participants were well-adjusted to community-living; however, they reported high levels of depression. Factors significantly associated with poorer current level of functioning/well-being included: older age (≥ 60 years), presence of traumatic brain injury-related symptoms, a lack of previous rehabilitation and those classified in “severe disability categories” at admission. Caregivers reported high levels of strain and burden (55%). Conclusion: Cognitive and psychosocial problems are more commonly reported than physical disability in the longer-term. A greater focus on participation and ageing with disability in these persons is needed.
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ItemSCIPA Switch-On: A Randomized Controlled Trial Investigating the Efficacy and Safety of Functional Electrical Stimulation-Assisted Cycling and Passive Cycling Initiated Early After Traumatic Spinal Cord Injury(SAGE PUBLICATIONS INC, 2017-06)Background. Substantial skeletal muscle atrophy after spinal cord injury (SCI) carries significant repercussions for functional recovery and longer-term health. Objective. To compare the efficacy, safety, and feasibility of functional electrical stimulation-assisted cycling (FESC) and passive cycling (PC) to attenuate muscle atrophy after acute SCI. Methods. This multicenter, assessor-blinded phase I/II trial randomized participants at 4 weeks post-SCI to FESC or PC (4 sessions per week, 1 hour maximum per session, over 12 weeks). The primary outcome measure was mean maximum cross-sectional area (CSA) of thigh and calf muscles (magnetic resonance imaging), and secondary outcome measures comprised body composition (dual energy X-ray absorptiometry), anthropometry, quality of life, and adverse events (AEs). Results. Of 24 participants, 19 completed the 12-week trial (10 FESC, 9 PC, 18 male). Those participants completed >80% of training sessions (FESC, 83.5%; PC, 85.9%). No significant between-group difference in postintervention muscle CSA was found. No significant between-group difference was found for any other tissue, anthropometric parameter, or behavioral variable or AEs. Six participants experienced thigh hypertrophy (FESC = 3; PC = 3). Atrophy was attenuated (<30%) in 15 cases (FESC = 7; PC = 8). Conclusions. Both cycle ergometry regimens examined were safe, feasible, and well tolerated early after SCI. No conclusions regarding efficacy can be drawn from our data. Further investigation of both modalities early after SCI is required.
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ItemBedside quantification of fat-free mass in acute spinal cord injury using bioelectrical impedance analysis: a psychometric study(NATURE PUBLISHING GROUP, 2018-04)STUDY DESIGN: Psychometric. OBJECTIVES: Assess the validity of bioimpedance-based measures of fat-free mass (FFM) in acute SCI and of current definitions of obesity based on body mass index (BMI). SETTING: Australia. METHODS: All admissions within eight weeks of a new traumatic SCI were screened. 29% were eligible. 71% of those consented. Twenty participants (18 male) completed deuterium dilution (DD) and bioimpedance-based measurements of FFM. Thirteen also underwent dual-energy x-ray absorptiometry. Strength of relationships and agreement were examined using Lin's concordance coefficient and limits of agreement analysis, respectively. Sensitivity and specificity were calculated for three BMI cutoffs for obesity, using percentage fat mass (%FM) obtained from DD as reference. RESULTS: Median time since injury was 41 days (IQR 28-48). FFM from DD and DXA were highly correlated but not identical. Concordance and agreement between DD and seven bioimpedance-based predictive equations are presented. The best-fitting equation demonstrated a low bias (+0.6 kg) and moderate dispersion (±5.2 kg). The cutoff for overweight in able-bodied people (BMI ≥25 kg/m2) provided sensitivity of 43.8%, compared to 25% for the cut-off for obesity (BMI ≥30 kg/m2). FM from bioimpedance gave the highest sensitivity (88.9%). CONCLUSIONS: BMI demonstrates poor specificity to classify obesity in acute SCI. Present findings support the utility of bioimpedance-based measurements for estimating FFM in acute SCI for group comparisons. These results are generalizable to traumatic SCI 4-8 weeks post injury; however, the present data reflect a high proportion of high cervical injuries. Further research is indicated to establish validity for assessment of individuals and for longitudinal monitoring. SPONSORSHIP: The present study was funded by a grant from the Institute for Safety, Compensation and Recovery Research (ISCRR Project #NGE-E-13-078). M Panisset was supported by an Australian Postgraduate Award. K Desneves was supported by the Austin Medical Research Foundation.
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ItemA novel neuromodulation technique for the rehabilitation of balance and gait: A case study(ELSEVIER SCI LTD, 2018-08)Cranial-nerve non-invasive neuromodulation (CN-NINM) through the tongue has been proposed as an adjuvant intervention to improve efficacy of rehabilitation. However, CN-NINM effects have only been explored in multiple sclerosis and stroke populations. In this report we used CN-NINM during a 2-week (2 × 1.5 h sessions daily) physiotherapy program for the rehabilitation of a 57 y/o woman presenting with balance and gait impairments after a surgical resection of a fourth ventricular ependymoma. Clinical and instrumented balance and gait assessments showed improved performance in all tests and without adverse effects This study shows the beneficial effects and feasibility of combined physiotherapy and CN-NINM in this patient.
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ItemMicroarray analysis of human leucocyte subsets: the advantages of positive selection and rapid purification.(Springer Science and Business Media LLC, 2007-03-05)BACKGROUND: For expression profiling to have a practical impact in the management of immune-related disease it is essential that it can be applied to peripheral blood cells. Early studies have used total peripheral blood mononuclear cells, and as a consequence the majority of the disease-related signatures identified have simply reflected differences in the relative abundance of individual cell types between patients and controls. To identify cell-specific changes in transcription it would be necessary to profile purified leucocyte subsets. RESULTS: We have used sequential rounds of positive selection to isolate CD4 and CD8 T cells, CD19 B cells, CD14 monocytes and CD16 neutrophils for microarray analysis from a single blood sample. We compared gene expression in cells isolated in parallel using either positive or negative selection and demonstrate that there are no significant consistent changes due to positive selection, and that the far inferior results obtained by negative selection are largely due to reduced purity. Finally, we demonstrate that storing cells prior to separation leads to profound changes in expression, predominantly in cells of the myeloid lineage. CONCLUSION: Leukocyte subsets should be prepared for microarray analysis by rapid positive selection.
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ItemNo Preview AvailableStreamlined genetic education is effective in preparing women newly diagnosed with breast cancer for decision making about treatment-focused genetic testing: a randomized controlled noninferiority trial(NATURE PUBLISHING GROUP, 2017-04)PURPOSE: Increasingly, women newly diagnosed with breast cancer are being offered treatment-focused genetic testing (TFGT). As the demand for TFGT increases, streamlined methods of genetic education are needed. METHODS: In this noninferiority trial, women aged <50 years with either a strong family history (FH+) or other features suggestive of a germ-line mutation (FH-) were randomized before definitive breast cancer surgery to receive TFGT education either as brief written materials (intervention group (IG)) or during a genetic counseling session at a familial cancer clinic (usual-care group (UCG)). Women completed self-report questionnaires at four time points over 12 months. RESULTS: A total of 135 women were included in the analysis, all of whom opted for TFGT. Decisional conflict about TFGT choice (primary outcome) was not inferior in the IG compared with the UCG (noninferiority margin of -10; mean difference = 2.45; 95% confidence interval -2.87-7.76; P = 0.36). Costs per woman counseled in the IG were significantly lower (AUD$89) compared with the UCG (AUD$173; t(115) = 6.02; P < 0.001). CONCLUSION: A streamlined model of educating women newly diagnosed with breast cancer about TFGT seems to be a cost-effective way of delivering education while ensuring that women feel informed and supported in their decision making, thus freeing resources for other women to access TFGT.Genet Med 19 4, 448-456.