Clinical School (Austin Health) - Research Publications
Now showing items 1-12 of 61
Positron Emission Tomographic Imaging in Stroke Cross-Sectional and Follow-Up Assessment of Amyloid in Ischemic Stroke
(LIPPINCOTT WILLIAMS & WILKINS, 2016-01-01)
BACKGROUND AND PURPOSE: Cardiovascular risk factors significantly increase the risk of developing Alzheimer disease. A possible mechanism may be via ischemic infarction-driving amyloid deposition. We conducted a study to determine the presence of β-amyloid in infarct, peri-infarct, and hemispheric areas after stroke. We hypothesized that an infarct would trigger β-amyloid deposition, with deposition over time. METHODS: Patients were recruited within 40 days of acute ischemic stroke and imaged with computed tomographic or magnetic resonance imaging and Pittsburgh compound B (11C-PiB) positron emission tomographic scans. Follow-up positron emission tomographic scanning was performed in a subgroup ≤18 months after the stroke event. Standardized uptake value ratios for regions of interest were analyzed after coregistration. RESULTS: Forty-seven patients were imaged with (11)C-PiB positron emission tomography. There was an increase in (11)C-PiB accumulation in the stroke area compared with a reference region in the contralesional hemisphere, which was not statistically significant (median difference in standardized uptake value ratio, 0.07 [95% confidence interval, -0.06 to 0.123]; P=0.452). There was no significant increase in the accumulation of (11)C-PiB in the peri-infarct region or in the ipsilesional hemisphere (median difference in standardized uptake value ratio, 0.04 [95% confidence interval, -0.02 to 0.10]; P=0.095). We repeated (11)C-PiB positron emission tomography in 21 patients and found a significant reduction in accumulation of (11)C-PiB between regions of interest (median difference in standardized uptake value ratio, -0.08 [95% confidence interval, -0.23 to -0.03]; P=0.04). CONCLUSIONS: There was no significant increase in (11)C-PiB accumulation in or around the infarct. There was no increase in ipsilesional hemispheric (11)C-PiB accumulation over time. We found no evidence that infarction leads to sustained or increased β-amyloid deposition ≤18 months after stroke.
Comparative Evaluation of Crystalloid Resuscitation Rate in a Human Model of Compensated Haemorrhagic Shock
(LIPPINCOTT WILLIAMS & WILKINS, 2016-08-01)
INTRODUCTION: The most effective rate of fluid resuscitation in haemorrhagic shock is unknown. METHODS: We performed a randomized crossover pilot study in a healthy volunteer model of compensated haemorrhagic shock. Following venesection of 15 mL/kg of blood, participants were randomized to 20 mL/kg of crystalloid over 10 min (FAST treatment) or 30 min (SLOW treatment). The primary end point was oxygen delivery (DO2). Secondary end points included pressure and flow-based haemodynamic variables, blood volume expansion, and clinical biochemistry. RESULTS: Nine normotensive healthy adult volunteers participated. No significant differences were observed in DO2 and biochemical variables between the SLOW and FAST groups. Blood volume was reduced by 16% following venesection, with a corresponding 5% reduction in cardiac index (CI) (P < 0.001). Immediately following resuscitation the increase in blood volume corresponded to 54% of the infused volume under FAST treatment and 69% of the infused volume under SLOW treatment (P = 0.03). This blood volume expansion attenuated with time to 24% and 25% of the infused volume 30 min postinfusion. During fluid resuscitation, blood pressure was higher under FAST treatment. However, CI paradoxically decreased in most participants during the resuscitation phase; a finding not observed under SLOW treatment. CONCLUSION: FAST or SLOW fluid resuscitation had no significant impact on DO2 between treatment groups. In both groups, changes in CI and blood pressure did not reflect the magnitude of intravascular blood volume deficit. Crystalloid resuscitation expanded intravascular blood volume by approximately 25%.
Three dimensional models in uro-oncology: a future built with additive fabrication
PURPOSE: Three-dimensional (3D) printing was invented in 1983 but has only just begun to influence medicine and surgery. Conversion of digital images into physical models demonstrates promise to revolutionize multiple domains of surgery. In the field of uro-oncology, researchers and clinicians have recognized the potential of this technology and are working towards making it an integral part of urological practice. We review current literature regarding 3D printing and other 3D technology in the field of urology. METHOD: A comprehensive assessment of contemporary literature was performed according to a modified PRISMA analysis for the purposes of this narrative review article. Medical databases that were searched included: Web of Science, EMBASE and Cochrane databases. Articles assessed were limited only to English-language peer-reviewed articles published between 1980 and 2017. The search terms used were "3D", "3-dimensional", "printing", "printing technology", "urology", "surgery". Acceptable articles were reviewed and incorporated for their merit and relevance with preference given for articles with high impact, original research and recent advances. RESULTS: Thirty-five publications were included in final analysis and discussion. CONCLUSIONS: The area of 3D printing in Urology shows promising results, but further research is required and cost reduction must occur before clinicians fully embrace its use. As costs continue to decline and diversity of materials continues to expand, research and clinical utilization will increase. Recent advances have demonstrated the potential of this technology in the realms of education and surgical optimization. The generation of personalized organs using 3D printing scaffolding remains the 'holy grail' of this technology.
Surgical outcomes of trabeculectomy and glaucoma drainage implant for uveitic glaucoma and relationship with uveitis activity
IMPORTANCE: This study provides ophthalmologists who manage uveitic glaucoma with important information on factors that can affect the success of surgical management of this challenging disease. BACKGROUND: This study examines surgical outcomes of trabeculectomy and glaucoma device implant (GDI) surgery for uveitic glaucoma, in particular the effect of uveitis activity on surgical outcomes. DESIGN: Retrospective chart review at a tertiary institution. SAMPLES: Eighty-two cases with uveitic glaucoma (54 trabeculectomies and 28 (GDI) surgeries) performed between 1 December 2006 and 30 November 2014. METHODS: Associations of factors with surgical outcomes were examined using univariate and multivariate analysis. MAIN OUTCOME MEASURES: Surgical outcomes as defined in Guidelines from World Glaucoma Association. RESULTS: Average follow up was 26.4 ± 21.5 months. Overall qualified success rate of the trabeculectomies was not statistically different from GDI, being 67% and 75%, respectively (P = 0.60). Primary and secondary GDI operations showed similar success rates. The most common postoperative complication was hypotony (~30%). Active uveitis at the time of operation was higher in trabeculectomy compared with GDI group (35% vs. 14%). Active uveitis at the time of surgery did not significantly increase risk of failure for trabeculectomies. Recurrence of uveitis was significantly associated with surgical failure in trabeculectomy group (odds ratio 4.8, P = 0.02) but not in GDI group. CONCLUSIONS AND RELEVANCE: Surgical success rate of GDI was not significantly different from trabeculectomy for uveitic glaucoma in this study. Regular monitoring, early and prolonged intensive treatment of ocular inflammation is important for surgical success particularly following trabeculectomy.
Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease
(BAISHIDENG PUBLISHING GROUP INC, 2016-09-21)
AIM: To determine if manipulation of dietary advanced glycation end product (AGE), intake affects non-alcoholic fatty liver disease (NAFLD) progression and whether these effects are mediated via RAGE. METHODS: Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol (HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mRNA were determined. RESULTS: Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content (a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE(-/-) animals developed NASH of similar severity to RAGE(+/+) animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION: In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD.
The academic tweet: Twitter as a tool to advance academic surgery
(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2018-06-01)
Social media, Twitter in particular, has emerged as an essential tool for surgeons. In the realm of academic surgery, it enables surgeons to advance the core values of academic surgery, as outlined by the Association for Academic Surgery: inclusion, leadership, innovation, scholarship, and mentorship. This article details the ways in which surgeons are using Twitter to embody these values and how the Twitter account for the Association of Academic Surgeons accomplishes its goal of inspiring and developing young academic surgeons.
Left acute neovascular glaucoma after right carotid endarterectomy
(ELSEVIER SCIENCE BV, 2018-06-01)
Carotid endarterectomy is a commonly performed vascular surgical procedure with well-known complications, such as stroke and nerve injury. Neovascular glaucoma (NVG) is an exceedingly rare complication after carotid endarterectomy that can result in loss of vision. All previous reports of NVG after carotid endarterectomy have occurred on the same side as the carotid surgery; in this report, we present a case of left-sided NVG after right carotid endarterectomy for contralateral ocular ischemic syndrome. We aim to emphasize the importance of early recognition and treatment of this serious complication as rapid intervention has the potential to save sight.
Dominant KCNA2 mutation causes episodic ataxia and pharmacoresponsive epilepsy
(LIPPINCOTT WILLIAMS & WILKINS, 2016-11-08)
OBJECTIVE: To identify the genetic basis of a family segregating episodic ataxia, infantile seizures, and heterogeneous epilepsies and to study the phenotypic spectrum of KCNA2 mutations. METHODS: A family with 7 affected individuals over 3 generations underwent detailed phenotyping. Whole genome sequencing was performed on a mildly affected grandmother and her grandson with epileptic encephalopathy (EE). Segregating variants were filtered and prioritized based on functional annotations. The effects of the mutation on channel function were analyzed in vitro by voltage clamp assay and in silico by molecular modeling. KCNA2 was sequenced in 35 probands with heterogeneous phenotypes. RESULTS: The 7 family members had episodic ataxia (5), self-limited infantile seizures (5), evolving to genetic generalized epilepsy (4), focal seizures (2), and EE (1). They had a segregating novel mutation in the shaker type voltage-gated potassium channel KCNA2 (CCDS_827.1: c.765_773del; p.255_257del). A rare missense SCN2A (rs200884216) variant was also found in 2 affected siblings and their unaffected mother. The p.255_257del mutation caused dominant negative loss of channel function. Molecular modeling predicted repositioning of critical arginine residues in the voltage-sensing domain. KCNA2 sequencing revealed 1 de novo mutation (CCDS_827.1: c.890G>A; p.Arg297Gln) in a girl with EE, ataxia, and tremor. CONCLUSIONS: A KCNA2 mutation caused dominantly inherited episodic ataxia, mild infantile-onset seizures, and later generalized and focal epilepsies in the setting of normal intellect. This observation expands the KCNA2 phenotypic spectrum from EE often associated with chronic ataxia, reflecting the marked variation in severity observed in many ion channel disorders.
The genetic basis of music ability
(FRONTIERS MEDIA SA, 2014-06-27)
Music is an integral part of the cultural heritage of all known human societies, with the capacity for music perception and production present in most people. Researchers generally agree that both genetic and environmental factors contribute to the broader realization of music ability, with the degree of music aptitude varying, not only from individual to individual, but across various components of music ability within the same individual. While environmental factors influencing music development and expertise have been well investigated in the psychological and music literature, the interrogation of possible genetic influences has not progressed at the same rate. Recent advances in genetic research offer fertile ground for exploring the genetic basis of music ability. This paper begins with a brief overview of behavioral and molecular genetic approaches commonly used in human genetic analyses, and then critically reviews the key findings of genetic investigations of the components of music ability. Some promising and converging findings have emerged, with several loci on chromosome 4 implicated in singing and music perception, and certain loci on chromosome 8q implicated in absolute pitch and music perception. The gene AVPR1A on chromosome 12q has also been implicated in music perception, music memory, and music listening, whereas SLC6A4 on chromosome 17q has been associated with music memory and choir participation. Replication of these results in alternate populations and with larger samples is warranted to confirm the findings. Through increased research efforts, a clearer picture of the genetic mechanisms underpinning music ability will hopefully emerge.