Surgery (RMH) - Research Publications
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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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ItemAAV-Mediated CRISPR/Cas Gene Editing of Retinal Cells In Vivo(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016-06)PURPOSE: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) has recently been adapted to enable efficient editing of the mammalian genome, opening novel avenues for therapeutic intervention of inherited diseases. In seeking to disrupt yellow fluorescent protein (YFP) in a Thy1-YFP transgenic mouse, we assessed the feasibility of utilizing the adeno-associated virus 2 (AAV2) to deliver CRISPR/Cas for gene modification of retinal cells in vivo. METHODS: Single guide RNA (sgRNA) plasmids were designed to target YFP, and after in vitro validation, selected guides were cloned into a dual AAV system. One AAV2 construct was used to deliver Streptococcus pyogenes Cas9 (SpCas9), and the other delivered sgRNA against YFP or LacZ (control) in the presence of mCherry. Five weeks after intravitreal injection, retinal function was determined using electroretinography, and CRISPR/Cas-mediated gene modifications were quantified in retinal flat mounts. RESULTS: Adeno-associated virus 2-mediated in vivo delivery of SpCas9 with sgRNA targeting YFP significantly reduced the number of YFP fluorescent cells of the inner retina of our transgenic mouse model. Overall, we found an 84.0% (95% confidence interval [CI]: 81.8-86.9) reduction of YFP-positive cells in YFP-sgRNA-infected retinal cells compared to eyes treated with LacZ-sgRNA. Electroretinography profiling found no significant alteration in retinal function following AAV2-mediated delivery of CRISPR/Cas components compared to contralateral untreated eyes. CONCLUSIONS: Thy1-YFP transgenic mice were used as a rapid quantifiable means to assess the efficacy of CRISPR/Cas-based retinal gene modification in vivo. We demonstrate that genomic modification of cells in the adult retina can be readily achieved by viral-mediated delivery of CRISPR/Cas.
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ItemTwo decades of percutaneous transjejunal biliary intervention for benign biliary disease: a review of the intervention nature and complications.(Springer Science and Business Media LLC, 2011-10)OBJECTIVE: To assess outcomes of percutaneous transjejunal biliary intervention (PTJBI) in terms of success and effectiveness in patients with a Roux-en-Y hepaticojejunostomy for benign biliary strictures and stones. METHODS: Clinical and radiographic records of 63 patients with a Roux-en-Y choledochojejunostomy or hepaticojejunostomy for benign disease who underwent at least one PTJBI between 1986 and 2007 were reviewed. Effectiveness was determined by successful access rate, rates of stricture dilatation and/or stone extraction, morbidity, complications and hospitalisation. RESULTS: PTJBI was attempted 494 times. Successful access to the Roux-en-Y was accomplished in 93% of interventions. After access to the Roux-en-Y was granted, all strictures were effectively dilated. Ninety-seven percent of extraction attempts of intrahepatic calculi were successful. The median number of interventions per patient was five. The median interval between interventions was 51.5 weeks (range 2.7-1,279.6 weeks). The early complication rate was 3%. Morbidity, measured in terms of cholangitis episodes was 14%, in 25 out of 63 patients. Mean hospitalisation was 4.1 nights per year. CONCLUSION: PTJBI is safe and effective in treating benign biliary strictures and/or calculi. High success rates and short hospitalisation periods, together with few complications make it a well-accepted and integral part of managing complex biliary problems.
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ItemImplications of laparoscopic inguinal hernia repair on open, laparoscopic, and robotic radical prostatectomy.(Elsevier BV, 2014-03)PURPOSE: There have been anecdotal reports of surgeons having to abandon radical prostatectomy (RP) after laparoscopic inguinal hernia repair (LIHR) due to obliteration of tissue planes by mesh. Nodal dissection may also be compromised. We prospectively collected data from four experienced prostate surgeons from separate institutions. Our objective was to evaluate the success rate of performing open RP (ORP), laparoscopic RP (LRP) and robotic assisted RP (RALRP) and pelvic lymph node dissection (PLND) after LIHR, and the frequency of complications. METHODS: A retrospective analysis of prospectively maintained databases of men who underwent RP after LIHR between 2004 and 2010 at four institutions was undertaken. The data recorded included age, preoperative prostate-specific antigen, preoperative Gleason score, and clinical stage. The operative approach, success or failure to perform RP, success or failure to perform PLND, pathological stage, and complications were also recorded. RESULTS: A total of 1,181 men underwent RP between 2004 and 2010. Fifty-seven patients (4.8%) underwent RP after LIHR. An ORP was attempted in 19 patients, LRP in 33, and RALRP in 5. All 57 cases were able to be successfully completed. Ten of the 18 open PLND were able to be completed (55.6%). Four of the 22 laparoscopic LND were able to be completed (18.2%). Robotic LND was possible in 5 of 5 cases (100%). Therefore, it was not possible to complete a LND 56.8% of patients. Complications were limited to ten patients. These complications included one LRP converted to ORP due to failure to progress, and one rectourethral fistula in a salvage procedure post failed high intensity focused ultrasound. CONCLUSIONS: LIHR is an increasingly common method of treating inguinal hernias. LIHR is not a contra-indication to RP. However PLND may not be possible in over 50% of patients who have had LIHR. Therefore, these patients may be under-staged and under treated.
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ItemImaging characteristics of nodal metastases in paraganglioma, ameloblastoma and olfactory neuroblastoma: case reports and literature review(BRITISH INST RADIOLOGY, 2016)Paraganglioma, ameloblastoma and olfactory neuroblastoma are uncommon primary head and neck tumours. When nodal metastases from these tumours occur, they may present later than and with different imaging characteristics compared with squamous cell carcinoma (SCC), demonstrating appearances similar to the primary tumour type rather than features typical of metastatic nodal SCC. We present three cases in which imaging characteristics of nodal metastases in paraganglioma, ameloblastoma and olfactory neuroblastoma mimicked the primary tumour and discuss their implications for clinicoradiological follow-up.
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ItemA Brassica exon array for whole-transcript gene expression profiling.(Public Library of Science (PLoS), 2010-09-16)Affymetrix GeneChip® arrays are used widely to study transcriptional changes in response to developmental and environmental stimuli. GeneChip® arrays comprise multiple 25-mer oligonucleotide probes per gene and retain certain advantages over direct sequencing. For plants, there are several public GeneChip® arrays whose probes are localised primarily in 3' exons. Plant whole-transcript (WT) GeneChip® arrays are not yet publicly available, although WT resolution is needed to study complex crop genomes such as Brassica, which are typified by segmental duplications containing paralogous genes and/or allopolyploidy. Available sequence data were sampled from the Brassica A and C genomes, and 142,997 gene models identified. The assembled gene models were then used to establish a comprehensive public WT exon array for transcriptomics studies. The Affymetrix GeneChip® Brassica Exon 1.0 ST Array is a 5 µM feature size array, containing 2.4 million 25-base oligonucleotide probes representing 135,201 gene models, with 15 probes per gene distributed among exons. Discrimination of the gene models was based on an E-value cut-off of 1E(-5), with ≤98% sequence identity. The 135 k Brassica Exon Array was validated by quantifying transcriptome differences between leaf and root tissue from a reference Brassica rapa line (R-o-18), and categorisation by Gene Ontologies (GO) based on gene orthology with Arabidopsis thaliana. Technical validation involved comparison of the exon array with a 60-mer array platform using the same starting RNA samples. The 135 k Brassica Exon Array is a robust platform. All data relating to the array design and probe identities are available in the public domain and are curated within the BrassEnsembl genome viewer at http://www.brassica.info/BrassEnsembl/index.html.
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ItemNovel Use of Ex Vivo Uretero-Pyeloscopy in Autotransplantation: A Systematic Review and Case Report.(Mary Ann Liebert Inc, 2015)BACKGROUND: Autotransplant has been practiced for decades but is regaining popularity in the nephron-sparing era. Initially for benign disease, autotransplantation has a select role in malignant processes that warrants new techniques and ideas to ensure patient safety. We review the use of ex vivo uretero-pyeloscopy and frozen section to ensure kidneys may be utilized in a patient with suspected malignancy. CASE PRESENTATION: A systematic review (PRISMA standard) of ex vivo uretreo-pyeloscopy was undertaken. We then present the case of a 37-year-old Caucasian female who was suspected of having ureteral obstructing malignancy; she had previous treatment of the bladder with bacillus Calmette-Guerin (BCG) for recurrent urothelial malignancy. The lesion biopsies and cytology were suspicious but inconclusive, indicating nephroureterectomy was a likely course of management. RESULTS: On reviewing the literature, we found that the use of ex vivo uretero-pyeloscopy has been described for urolithiasis to remove stones before transplantation but not specifically to exclude malignancy. Ultimately, in this case, the patient underwent a renal autotransplantation for obstruction that was caused by a granuloma on the background of the previous BCG treatment. Intraoperatively, ex vivo uretero-pyeloscopy and frozen section were crucial in guiding this case by allowing for appropriate identification and resection of the ureteral lesion. In addition, the preservation of ureteral length allowed for autotransplantation, which remains effective at follow-up. CONCLUSION: Ex vivo urteroscopy has been used effectively in donor kidneys to treat urolithiasis with minimal complications. We believe that this is the first documented case of ex vivo uretero-pyeloscopy being used effectively in renal autotransplantation to exclude urothelial malignancy.
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ItemRho/ROCK pathway is essential to the expansion, differentiation, and morphological rearrangements of human neural stem/progenitor cells induced by lysophosphatidic acid(ELSEVIER, 2013-05)We previously reported that lysophosphatidic acid (LPA) inhibits the neuronal differentiation of human embryonic stem cells (hESC). We extended these studies by analyzing LPA's effects on the expansion of neural stem/progenitor cells (NS/PC) derived from hESCs and human induced pluripotent stem cells (iPSC), and we assessed whether data obtained on the neural differentiation of hESCs were relevant to iPSCs. We showed that hESCs and iPSCs exhibited comparable mRNA expression profiles of LPA receptors and producing enzymes upon neural differentiation. We demonstrated that LPA inhibited the expansion of NS/PCs of both origins, mainly by increased apoptosis in a Rho/Rho-associated kinase (ROCK)-dependent mechanism. Furthermore, LPA inhibited the neuronal differentiation of iPSCs. Lastly, LPA induced neurite retraction of NS/PC-derived early neurons through Rho/ROCK, which was accompanied by myosin light chain (MLC) phosphorylation. Our data demonstrate the consistency of LPA effects across various sources of human NS/PCs, rendering hESCs and iPSCs valuable models for studying lysophospholipid signaling in human neural cells. Our data also highlight the importance of the Rho/ROCK pathway in human NS/PCs. As LPA levels are increased in the central nervous system (CNS) following injury, LPA-mediated effects on NS/PCs and early neurons could contribute to the poor neurogenesis observed in the CNS following injury.
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ItemStargazin and AMPA receptor membrane expression is increased in the somatosensory cortex of Genetic Absence Epilepsy Rats from Strasbourg(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2011-04)Absence-like seizures in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model are believed to arise in hyperexcitable somatosensory cortical neurons, however the cellular basis of this increased excitability remains unknown. We have previously shown that expression of the Transmembrane AMPA receptor Regulatory Protein (TARP), stargazin, is elevated in the somatosensory cortex of GAERS. TARPs are critical regulators of the trafficking and function of AMPA receptors. Here we examine the developmental expression of stargazin and the impact this may have on AMPA receptor trafficking in the GAERS model. We show that elevated stargazin in GAERS is associated with an increase in AMPA receptor proteins, GluA1 and GluA2 in the somatosensory cortex plasma membrane of adult epileptic GAERS. Elevated stargazin expression is not seen in the epileptic WAG/Rij rat, which is a genetically distinct but phenotypically similar rat model also manifesting absence seizures, indicating that the changes seen in GAERS are unlikely to be a secondary consequence of the seizures. In juvenile (6 week old) GAERS, at the age when seizures are just starting to be expressed, there is elevated stargazin mRNA, but not protein expression for stargazin or the AMPA receptor subunits. In neonatal (7 day old) pre-epileptic GAERS there was no alteration in stargazin mRNA expression in any brain region examined. These data demonstrate that stargazin and AMPA receptor membrane targeting is altered in GAERS, potentially contributing to hyperexcitability in somatosensory cortex, with a developmental time course that would suggest a pathophysiological role in the epilepsy phenotype.