Medicine and Health Sciences Commons^™

A New Perspective On Intervertebral Disc Calcification-From Bench To Bedside, Emanuel Novais, Rajkishen Narayanan, Jose Canseco, Koen Van De Wetering, Christopher Kepler, Alan Hilibrand, Alex Vaccaro, Makarand Risbud

Department of Orthopaedic Surgery Faculty Papers

Disc degeneration primarily contributes to chronic low back and neck pain. Consequently, there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis, ectopic calcification, herniation, or mixed phenotypes. Amongst these phenotypes, disc calcification is the least studied. Ectopic calcification, by definition, is the pathological mineralization of soft tissues, widely studied in the context of conditions that afflict vasculature, skin, and cartilage. Clinically, disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment. It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular …

Sirtuin 6 Activation Rescues The Age-Related Decline In Dna Damage Repair In Primary Human Chondrocytes, Michaela E. Copp, Jacqueline Shine, Hannon L. Brown, Kirti R. Nimmala, Oliver B. Hansen, Susan Chubinskaya, John A. Collins, Richard F. Loeser, Brian O. Diekman

Department of Orthopaedic Surgery Faculty Papers

While advanced age is widely recognized as the greatest risk factor for osteoarthritis (OA), the biological mechanisms behind this connection remain unclear. Previous work has demonstrated that chondrocytes from older cadaveric donors have elevated levels of DNA damage as compared to chondrocytes from younger donors. The purpose of this study was to determine whether a decline in DNA repair efficiency is one explanation for the accumulation of DNA damage with age, and to quantify the improvement in repair with activation of Sirtuin 6 (SIRT6). After acute damage with irradiation, DNA repair was shown to be more efficient in chondrocytes from …

Corneal Wound Healing In The Presence Of Antifibrotic Antibody Targeting Collagen Fibrillogenesis: A Pilot Study, Zeba A. Syed, Tatyana Milman, Jolanta Fertala, Andrzej Steplewski, Andrzej Fertala

Department of Orthopaedic Surgery Faculty Papers

Highly organized collagen fibrils interlacing with proteoglycans form the crucial architecture of the cornea and facilitate its transparency. Corneal scarring from accidental injury, surgery, or infection alters this highly organized tissue, causing severe consequences, including blindness. There are no pharmacological or surgical methods to effectively and safely treat excessive corneal scarring. Thus, we tested the anticorneal scarring utility of a rationally designed anticollagen antibody (ACA) whose antifibrotic effects have already been demonstrated in nonocular models. Utilizing a rabbit model with an incisional corneal wound, we analyzed ACA’s effects on forming collagen and proteoglycan-rich extracellular matrices in scar neotissue. We used …

A Biologic-Device Combination Product Delivering Tumor-Derived Antigens Elicits Immunogenic Cell Death-Associated Immune Responses Against Glioblastoma, Christopher Cultrara, Christopher Uhl, Kenneth Kirby, Essam Abed Elrazaq, Amelia Zellander, David W. Andrews, Charles B. Scott, Lorenzo Galluzzi, Mark A. Exley, Jenny Zilberberg

Department of Neurosurgery Faculty Papers

Background IGV-001 is a personalized, autologous cancer cell-based immunotherapy conceived to deliver a tumor-derived antigenic payload in the context of immunostimulatory signals to patients with glioblastoma (GBM). IGV-001 consists of patient-derived GBM cells treated with an antisense oligodeoxynucleotide against insulin-like growth factor 1 receptor (IGF1R) and placed in proprietary biodiffusion chambers (BDCs). The BDCs are then exposed to 5–6 Gy radiation and implanted at abdominal sites for ~48 hours. IGV-001 has previously been shown to be generally safe with promising clinical activity in newly diagnosed GBM patients.

Methods Mouse (m) or human (h) variants of IGV-001 …

Loss Of Function Mutation In Ank Causes Aberrant Mineralization And Acquisition Of Osteoblast-Like-Phenotype By The Cells Of The Intervertebral Disc, Takashi Ohnishi, Victoria Tran, Kimheak Sao, Pranay Ramteke, William Querido, Ruteja A. Barve, Koen Van De Wetering, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Pathological mineralization of intervertebral disc is debilitating and painful and linked to disc degeneration in a subset of human patients. An adenosine triphosphate efflux transporter, progressive ankylosis (ANK) is a regulator of extracellular inorganic pyrophosphate levels and plays an important role in tissue mineralization. However, the function of ANK in intervertebral disc has not been fully explored. Herein we analyzed the spinal phenotype of Ank mutant mice (ank/ank) with attenuated ANK function. Micro-computed tomography and histological analysis showed that loss of ANK function results in the aberrant annulus fibrosus mineralization and peripheral disc fusions with cranial to caudal progression in …

Microbubble Cavitation Restores Staphylococcus Aureus Antibiotic Susceptibility In Vitro And In A Septic Arthritis Model, Neil Zhao, Dylan Curry, Rachel E Evans, Selin Isguven, Theresa A. Freeman, John R. Eisenbrey, Flemming Forsberg, Jessica M Gilbertie, Sophie Boorman, Rachel Hilliard, Sana S. Dastgheyb, Priscilla Machado, Maria Stanczak, Marc I. Harwood, Antonia F Chen, Javad Parvizi, Irving Shapiro, Noreen J. Hickok, Thomas P Schaer

Department of Orthopaedic Surgery Faculty Papers

Treatment failure in joint infections is associated with fibrinous, antibiotic-resistant, floating and tissue-associated Staphylococcus aureus aggregates formed in synovial fluid (SynF). We explore whether antibiotic activity could be increased against Staphylococcus aureus aggregates using ultrasound-triggered microbubble destruction (UTMD), in vitro and in a porcine model of septic arthritis. In vitro, when bacterially laden SynF is diluted, akin to the dilution achieved clinically with lavage and local injection of antibiotics, amikacin and ultrasound application result in increased bacterial metabolism, aggregate permeabilization, and a 4-5 log decrease in colony forming units, independent of microbubble destruction. Without SynF dilution, amikacin + UTMD does …

Lysosomal Lipid Peroxidation Regulates Tumor Immunity, Monika Bhardwaj, Jennifer J Lee, Amanda M Versace, Sandra L Harper, Aaron R Goldman, Mary Ann S Crissey, Vaibhav Jain, Mahendra Pal Singh, Megane Vernon, Andrew E. Aplin, Seokwoo Lee, Masao Morita, Jeffrey D Winkler, Qin Liu, David W Speicher, Ravi K Amaravadi

Department of Surgery Faculty Papers

Lysosomal inhibition elicited by palmitoyl-protein thioesterase 1 (PPT1) inhibitors such as DC661 can produce cell death, but the mechanism for this is not completely understood. Programmed cell death pathways (autophagy, apoptosis, necroptosis, ferroptosis, and pyroptosis) were not required to achieve the cytotoxic effect of DC661. Inhibition of cathepsins, or iron or calcium chelation, did not rescue DC661-induced cytotoxicity. PPT1 inhibition induced lysosomal lipid peroxidation (LLP), which led to lysosomal membrane permeabilization and cell death that could be reversed by the antioxidant N-acetylcysteine (NAC) but not by other lipid peroxidation antioxidants. The lysosomal cysteine transporter MFSD12 was required for intralysosomal transport …

Glut1 Is Redundant In Hypoxic And Glycolytic Nucleus Pulposus Cells Of The Intervertebral Disc, Shira N. Johnston, Elizabeth S. Silagi, Vedavathi Madhu, Duc H. Nguyen, Irving M. Shapiro, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Glycolysis is central to homeostasis of nucleus pulposus (NP) cells in the avascular intervertebral disc. Since the glucose transporter, GLUT1, is a highly enriched phenotypic marker of NP cells, we hypothesized that it is vital for the development and postnatal maintenance of the disc. Surprisingly, primary NP cells treated with 2 well-characterized GLUT1 inhibitors maintained normal rates of glycolysis and ATP production, indicating intrinsic compensatory mechanisms. We showed in vitro that NP cells mitigated GLUT1 loss by rewiring glucose import through GLUT3. Of note, we demonstrated that substrates, such as glutamine and palmitate, did not compensate for glucose restriction resulting …

Advanced-Stage Melanoma At Presentation Following The Peak Of The Pandemic: A Covid-19 Cancer Canary In A Coal Mine, Ryan Lamm, Md, Walker Lyons, Md, Winnie So, Rn, Alliric I. Willis, Md, Facs, Msph

Department of Surgery Faculty Papers

Background: For melanoma patients, timely identification and tumor thickness are directly correlated with outcomes. COVID-19 impacted both patients' ability and desire to see physicians. We sought to identify whether the pandemic correlated with changes in melanoma thickness at presentation and subsequent treatment timeline.

Methods: Retrospective chart review was performed on patients who underwent surgery for melanoma in an academic center surgical oncology practice from May 2019 to September 2021. Patients were split into two cohorts: "pre-pandemic" from May 2019 to May 2020 and "pandemic," after May 2020, representing when these patients received their initial diagnostic biopsy. Demographic and melanoma-specific variables …

The Cgas-Sting Pathway Affects Vertebral Bone But Does Not Promote Intervertebral Disc Cell Senescence Or Degeneration, Olivia K. Ottone, C. James Kim, John A. Collins, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

The DNA-sensing cGAS-STING pathway promotes the senescence-associated secretory phenotype (SASP) and mediates type-I interferon inflammatory responses to foreign viral and bacterial DNA as well as self-DNA. Studies of the intervertebral disc in humans and mice demonstrate associations between aging, increased cell senescence, and disc degeneration. Herein we assessed the role of STING in SASP promotion in STING gain- (N153S) and loss-of-function mouse models. N153S mice evidenced elevated circulating levels of proinflammatory markers including IL-1β, IL-6, and TNF-α, showed elevated monocyte and macrophage abundance in the vertebral marrow, and exhibited a mild trabecular and cortical bone phenotype in caudal vertebrae. Interestingly, …

Long-Term Treatment With Senolytic Drugs Dasatinib And Quercetin Ameliorates Age-Dependent Intervertebral Disc Degeneration In Mice, Emanuel J Novais, Victoria Tran, Shira N Johnston, Kayla R Darris, Alex J Roupas, Garrett A Sessions, Irving Shapiro, Brian O Diekman, Makarand V Risbud

Department of Orthopaedic Surgery Faculty Papers

Intervertebral disc degeneration is highly prevalent within the elderly population and is a leading cause of chronic back pain and disability. Due to the link between disc degeneration and senescence, we explored the ability of the Dasatinib and Quercetin drug combination (D + Q) to prevent an age-dependent progression of disc degeneration in mice. We treated C57BL/6 mice beginning at 6, 14, and 18 months of age, and analyzed them at 23 months of age. Interestingly, 6- and 14-month D + Q cohorts show lower incidences of degeneration, and the treatment results in a significant decrease in senescence markers p16INK4a, …

Impaired Meningeal Lymphatic Vessel Development Worsens Stroke Outcome, Pavel Yanev, Katherine Poinsatte, Devon Hominick, Noor Khurana, Kielen R. Zuurbier, Marcus Berndt, Erik J. Plautz, Michael T. Dellinger, Ann M. Stowe

Neurology Faculty Publications

The discovery of meningeal lymphatic vessels (LVs) has sparked interest in identifying their role in diseases of the central nervous system. Similar to peripheral LVs, meningeal LVs depend on vascular endothelial growth factor receptor-3 (VEGFR3) signaling for development. Here we characterize the effect of stroke on meningeal LVs, and the impact of meningeal lymphatic hypoplasia on post-stroke outcomes. We show that photothrombosis (PT), but not transient middle cerebral artery occlusion (tMCAo), induces meningeal lymphangiogenesis in young male C57Bl/J6 mice. We also show that Vegfr3^wt/mut mice develop significantly fewer meningeal LVs than Vegfr3^wt/wt mice. Again, meningeal lymphangiogenesis occurs in …

Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito

Physiology Faculty Publications

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of …

What Are Biofilms?, Noreen J. Hickok

Department of Orthopaedic Surgery Faculty Papers

No abstract provided.

Cigarette Smoke Initiates Oxidative Stress-Induced Cellular Phenotypic Modulation Leading To Cerebral Aneurysm Pathogenesis., Robert M. Starke, John W. Thompson, Muhammad S. Ali, Crissey L. Pascale, Alejandra Martinez Lege, Dale Ding, Nohra Chalouhi, David M. Hasan, Pascal Jabbour, Gary K Owens, Michal Toborek, Joshua M. Hare, Aaron S. Dumont

Department of Neurosurgery Faculty Papers

OBJECTIVE: Cigarette smoke exposure (CSE) is a risk factor for cerebral aneurysm (CA) formation, but the molecular mechanisms are unclear. Although CSE is known to contribute to excess reactive oxygen species generation, the role of oxidative stress on vascular smooth muscle cell (VSMC) phenotypic modulation and pathogenesis of CAs is unknown. The goal of this study was to investigate whether CSE activates a NOX (NADPH oxidase)-dependent pathway leading to VSMC phenotypic modulation and CA formation and rupture.

APPROACH AND RESULTS: In cultured cerebral VSMCs, CSE increased expression of NOX1 and reactive oxygen species which preceded upregulation of proinflammatory/matrix remodeling genes …

Effect Of Hemiepiphysiodesis On The Growth Plate: The Histopathological Changes And Mechanism Exploration Of Recurrence In Mini Pig Model., Jing Ding, Jin He, Zhi-Qiang Zhang, Zhen-Kai Wu, Fang-Chun Jin

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Hemiepiphysiodesis has been widely used to correct angular deformity of long bone in immature patients. However, there is a limited knowledge about the biomechanical effect of this technique on the histopathological changes of the growth plate and the mechanism of recurrence of malformation after implant removal. We aimed to evaluate the biomechanical effect of hemiepiphysiodesis on the histopathological changes of the growth plate and the mechanism of recurrence of malformation after implant removal in Bama miniature pigs, and to explore the role of asymmetric stress during this procedure.

Methods: Eight 3-month-old male Bama miniature pigs sustained surgeries on the …

Tnf-Α Promotes Nuclear Enrichment Of The Transcription Factor Tonebp/Nfat5 To Selectively Control Inflammatory But Not Osmoregulatory Responses In Nucleus Pulposus Cells., Zariel I. Johnson, Alexandra C. Doolittle, Joseph W. Snuggs, Irving M. Shapiro, Christine L. Le Maitre, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Intervertebral disc degeneration (IDD) causes chronic back pain and is linked to production of proinflammatory molecules by nucleus pulposus (NP) and other disc cells. Activation of tonicity-responsive enhancer-binding protein (TonEBP)/NFAT5 by non-osmotic stimuli, including proinflammatory molecules, occurs in cells involved in immune response. However, whether inflammatory stimuli activate TonEBP in NP cells and whether TonEBP controls inflammation during IDD is unknown. We show that TNF-α, but not IL-1β or LPS, promoted nuclear enrichment of TonEBP protein. However, TNF-α-mediated activation of TonEBP did not cause induction of osmoregulatory genes. RNA sequencing showed that 8.5% of TNF-α transcriptional responses were TonEBP-dependent and …

Posttranscriptional Regulation Of Parg Mrna By Hur Facilitates Dna Repair And Resistance To Parp Inhibitors, Saswati N. Chand, Mahsa Zarei, M. J. Schiewer, Akshay R. Sanan, Carmella Romeo, Shruti Lal, Joseph A. Cozzitorto, Avinoam Nevler, Laura Scolaro, Eric R. Londin, Wei Jiang, Nicole Meisner-Kober, Michael J. Pishvaian, Karen E. Knudsen, Charles Yeo, John M Pascal, Jordan M. Winter, Jonathan R. Brody

Department of Surgery Faculty Papers

The majority of pancreatic ductal adenocarcinomas (PDAC) rely on the mRNA stability factor HuR (ELAV-L1) to drive cancer growth and progression. Here, we show that CRISPR-Cas9–mediated silencing of the HuR locus increases the relative sensitivity of PDAC cells to PARP inhibitors (PARPi). PDAC cells treated with PARPi stimulated translocation of HuR from the nucleus to the cytoplasm, specifically promoting stabilization of a new target, poly (ADP-ribose) glycohydrolase (PARG) mRNA, by binding a unique sequence embedded in its 3⁰ untranslated region. HuR-dependent upregulation of PARG expression facilitated DNA repair via hydrolysis of polyADP-ribose on related repair proteins. Accordingly, strategies to …

In Vivo Evaluation Of Stem Cell Aggregates On Osteochondral Regeneration., Banupriya Sridharan, Amy D. Laflin, Michael A. Holtz, Donna M. Pacicca, Nicholas K. Wischmeier, Michael S. Detamore

Manuscripts, Articles, Book Chapters and Other Papers

To date, many osteochondral regenerative approaches have utilized varied combinations of biocompatible materials and cells to engineer cartilage. Even in cell-based approaches, to date, no study has utilized stem cell aggregates alone for regenerating articular cartilage. Thus, the purpose of this study was to evaluate the performance of a novel stem cell-based aggregate approach in a fibrin carrier to regenerate osteochondral defects in the Sprague-Dawley rat trochlear groove model. Two different densities of rat bone marrow mesenchymal stem cell (rBMSC) aggregates were fabricated by the hanging drop technique. At 8 weeks, the cell aggregates supported the defects and served as …

Degenerative Changes Of The Canine Cervical Spine After Discectomy Procedures, An In Vivo Study., Peter Grunert, Yu Moriguchi, Brian P Grossbard, Rodolfo J Ricart Arbona, Lawrence J Bonassar, Roger Härtl

Articles, Abstracts, and Reports

BACKGROUND: Discectomies are a common surgical treatment for disc herniations in the canine spine. However, the effect of these procedures on intervertebral disc tissue is not fully understood. The objective of this study was to assess degenerative changes of cervical spinal segments undergoing discectomy procedures, in vivo.

RESULTS: Discectomies led to a 60% drop in disc height and 24% drop in foraminal height. Segments did not fuse but showed osteophyte formation as well as endplate sclerosis. MR imaging revealed terminal degenerative changes with collapse of the disc space and loss of T2 signal intensity. The endplates showed degenerative type II …

Crispr Knockout Of The Hur Gene Causes A Xenograft Lethal Phenotype., Shruti Lal, Edwin C, Cheung, Mahsa Zarei, Ranjan Preet, Saswati N. Chand, Nicole C. Mambelli-Lisboa, Carmella Romeo, Matthew C. Stout, Eric Londin, Austin Goetz, Cinthya Y. Lowder, Avinoam Nevler, Charles Yeo, Paul M. Campbell, Jordan M. Winter, Dan A. Dixon, Jonathan Brody

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related deaths in the United States, whereas colorectal cancer is the third most common cancer. The RNA-binding protein HuR (ELAVL1) supports a pro-oncogenic network in gastrointestinal (GI) cancer cells through enhanced HuR expression. Using a publically available database, HuR expression levels were determined to be increased in primary PDA and colorectal cancer tumor cohorts as compared with normal pancreas and colon tissues, respectively. CRISPR/Cas9 technology was successfully used to delete the HuR gene in both PDA (MIA PaCa-2 and Hs 766T) and colorectal cancer (HCT116) cell lines. HuR deficiency has …

Astrocytes Promote Progression Of Breast Cancer Metastases To The Brain Via A Kiss1-Mediated Autophagy., Natalya Kaverina, Anton V Borovjagin, Zaira Kadagidze, Anatoly Baryshnikov, Maria Baryshnikova, Dmitry Malin, Dhimankrishhna Ghosh, Nameeta Shah, Danny R Welch, Patrik Gabikian, Apollon Karseladze, Charles Cobbs, Ilya V Ulasov

Articles, Abstracts, and Reports

Formation of metastases, also known as cancer dissemination, is an important stage of breast cancer (BrCa) development. KISS1 expression is associated with inhibition of metastases development. Recently we have demonstrated that BrCa metastases to the brain exhibit low levels of KISS1 expression at both mRNA and protein levels. By using multicolor immunofluorescence and coculture techniques here we show that normal adult astrocytes in the brain are capable of promoting metastatic transformation of circulating breast cancer cells localized to the brain through secretion of chemokine CXCL12. The latter was found in this study to downregulate KISS1 expression at the post-transcriptional level …

Chondroinduction From Naturally Derived Cartilage Matrix: A Comparison Between Devitalized And Decellularized Cartilage Encapsulated In Hydrogel Pastes., Emily C. Beck, Marilyn Barragan, Tony B. Libeer, Sarah L. Kieweg, Gabriel L. Converse, Richard A. Hopkins, Cory J. Berkland, Michael S. Detamore

Manuscripts, Articles, Book Chapters and Other Papers

Hydrogel precursors are liquid solutions that are prone to leaking after surgical placement. This problem was overcome by incorporating either decellularized cartilage (DCC) or devitalized cartilage (DVC) microparticles into traditional photocrosslinkable hydrogel precursors in an effort to achieve a paste-like hydrogel precursor. DCC and DVC were selected specifically for their potential to induce chondrogenesis of stem cells, given that materials that are chondroinductive on their own without growth factors are a revolutionary goal in orthopedic medicine. We hypothesized that DVC, lacking the additional chemical processing steps in DCC to remove cell content, would lead to a more chondroinductive hydrogel with …

Targeting Wnt/Β-Catenin Pathway In Hepatocellular Carcinoma Treatment, Valery Vilchez, Lilia M. Turcios, Francesc Marti, Roberto Gedaly

Surgery Faculty Publications

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Liver cancer is generally related to hepatitis B or C infection and cirrhosis. Usually, patients with HCC are asymptomatic and are diagnosed at late stages when surgical treatment is no longer suitable. Limited treatment options for patients with advanced HCC are a major concern. Therefore, there is an urge for finding novel therapies to treat HCC. Liver cancer is highly heterogeneous and involved deregulation of several signaling pathways. Wnt/β-catenin pathway is frequently upregulated in HCC and it is implicated in maintenance of tumor initiating cells, drug …

Enos Transfection Of Adipose-Derived Stem Cells Yields Bioactive Nitric Oxide Production And Improved Results In Vascular Tissue Engineering., Stephen Mcilhenny, Ping Zhang, Thomas Tulenko, Jason Comeau, Sarah Fernandez, Aleksandra Policha, Matthew Ferroni, Elizabeth J Faul, Gabor Bagameri, Irving Shapiro, Paul J. Dimuzio

Department of Surgery Faculty Papers

This study evaluates the durability of a novel tissue engineered blood vessel (TEBV) created by seeding a natural vascular tissue scaffold (decellularized human saphenous vein allograft) with autologous adipose-derived stem cells (ASC) differentiated into endothelial-like cells. Previous work with this model revealed the graft to be thrombogenic, likely due to inadequate endothelial differentiation as evidenced by minimal production of nitric oxide (NO). To evaluate the importance of NO expression by the seeded cells, we created TEBV using autologous ASC transfected with the endothelial nitric oxide synthase (eNOS) gene to produce NO. We found that transfected ASC produced NO at levels …

Iv And Ip Administration Of Rhodamine In Visualization Of Wbc-Bbb Interactions In Cerebral Vessels., Zachary Wilmer Reichenbach, Hongbo Li, John P. Gaughan, Melanie B. Elliott, Ronald Tuma

Department of Neurosurgery Faculty Papers

Epi-illuminescence intravital fluorescence microscopy has been employed to study leukocyte-endothelial interactions in a number of brain pathologies. Historically, dyes such as Rhodamine 6G have been injected intravenously. However, intravenous injections can predispose experimental animals to a multitude of complications and requires a high degree of technical skill. Here, we study the efficacy of injecting Rhodamine 6G into the peritoneum (IP) for the purpose of analyzing leukocyte-endothelial interactions through a cranial window during real time intravital microscopy. After examining the number of rolling and adherent leukocytes through a cranial window, we found no advantage to the intravenous injection (IV). Additionally, we …

Identification Of Experimentally Induced Colitis By In Vitro Nuclear Magnetic Resonance., R H Rolandelli, S H Saul, R G Settle, D O Jacobs, Raymond Singer, G L Wolf, J L Rombeau

Raymond L Singer MD

The present study determined whether in vitro nuclear magnetic resonance could be used to assess experimentally induced colitis in rats. Acute colitis was induced in 6 Sprague-Dawley rats by acetic acid enema, while 6 control animals received saline enemas. All animals were sacrificed 24 hours post-enema, and NMR relaxation times, T1 and T2, of colonic samples were determined on a 10 MHz spin analyzer (RADX, Houston, TX). Colonic water content was determined on the same samples by desiccation. Colitis animals showed significantly higher T1 and T2 relaxation times and tissue water content than controls. T1 and T2 times correlated significantly …

3d Thoracoscopic Ultrasound Volume Measurement Validation In An Ex Vivo And In Vivo Porcine Model Of Lung Tumours, V. Hornblower, E. Yu, A. Fenster, J. Battista, R. Malthaner

Richard A. Malthaner

The purpose of this study was to validate the accuracy and reliability of volume measurements obtained using three-dimensional (3D) thoracoscopic ultrasound (US) imaging. Artificial "tumours" were created by injecting a liquid agar mixture into spherical moulds of known volume. Once solidified, the "tumours" were implanted into the lung tissue in both a porcine lung sample ex vivo and a surgical porcine model in vivo. 3D US images were created by mechanically rotating the thoracoscopic ultrasound probe about its long axis while the transducer was maintained in close contact with the tissue. Volume measurements were made by one observer using the …

3d Thoracoscopic Ultrasound Volume Measurement Validation In An Ex Vivo And In Vivo Porcine Model Of Lung Tumours, V. Hornblower, E. Yu, A. Fenster, J. Battista, R. Malthaner

Richard A. Malthaner

The purpose of this study was to validate the accuracy and reliability of volume measurements obtained using three-dimensional (3D) thoracoscopic ultrasound (US) imaging. Artificial "tumours" were created by injecting a liquid agar mixture into spherical moulds of known volume. Once solidified, the "tumours" were implanted into the lung tissue in both a porcine lung sample ex vivo and a surgical porcine model in vivo. 3D US images were created by mechanically rotating the thoracoscopic ultrasound probe about its long axis while the transducer was maintained in close contact with the tissue. Volume measurements were made by one observer using the …

Development And Implementation Of A Clinical Pathway Approach To Simulation-Based Training For Foregut Surgery., Kiyoyuki W. Miyasaka, Joseph Buchholz, Denise Lamarra, Giorgos C. Karakousis, Rajesh Aggarwal

Student Papers, Posters & Projects

INTRODUCTION: Contemporary demands on resident education call for integration of simulation. We designed and implemented a simulation-based curriculum for Post Graduate Year 1 surgery residents to teach technical and nontechnical skills within a clinical pathway approach for a foregut surgery patient, from outpatient visit through surgery and postoperative follow-up.

METHODS: The 3-day curriculum for groups of 6 residents comprises a combination of standardized patient encounters, didactic sessions, and hands-on training. The curriculum is underpinned by a summative simulation "pathway" repeated on days 1 and 3. The "pathway" is a series of simulated preoperative, intraoperative, and postoperative encounters in following up …