Medicine and Health Sciences Commons^™

Imaging Of Glioma Tumor With Endogenous Fluorescence Tomography, Dax S. Kepshire, Summer L. Gibbs-Strauss, Julia A. O'Hara, Michael Hutchins, Niculae Mincu, Frederic Leblond, Mario Khayat, Hamid Dehghani, Subhadra Srinivasan, Brian W. Pogue

Dartmouth Scholarship

Tomographic imaging of a glioma tumor with endogenous fluorescence is demonstrated using a noncontact single-photon counting fan-beam acquisition system interfaced with microCT imaging. The fluorescence from protoporphyrin IX (PpIX) was found to be detectable, and allowed imaging of the tumor from within the cranium, even though the tumor presence was not visible in the microCT image. The combination of single-photon counting detection and normalized fluorescence to transmission detection at each channel allowed robust imaging of the signal. This demonstrated use of endogenous fluorescence stimulation from aminolevulinic acid (ALA) and provides the first in vivo demonstration of deep tissue tomographic imaging …

Differences In Responses Of Platelets To Fluid Shear Stress In Patients With Peripheral Artery Disease (Pad) And Coronary Artery Disease (Cad)., Vijay Nambi, Kay T Kimball, Paul Bray, Angela L Bergeron, Shawna L Johnson, Joel D Morrisett, Changyi Chen, Peter H Lin, Alan B Lumsden, Christie M Ballantyne, Jing-Fei Dong

Cardeza Foundation for Hematologic Research

Information on differences in platelet function between patients with peripheral arterial disease (PAD) and patients with coronary artery disease (CAD) is limited. We sought to examine the differences in the platelets response to shear stress in patients with PAD compared to those with CAD. Men with symptomatic PAD (ankle brachial index [ABI] < 0.9; n = 29) were compared with similarly aged men with CAD (post coronary artery bypass grafting; n = 40) but without PAD. All participants were on aspirin, and none were on clopidogrel. We measured changes in shear-induced platelet aggregation (SIPA) and shear-induced P-selectin expression (SIPE) under fluid shear rates of 5000 and 10,000 s(-1)which are typically found in arterioles and stenosed arteries, respectively. Aggregation was also induced by a combined stimulation of collagen, fluid shear stress, and adenosine diphosphate (ADP) or epinephrine using a platelet function analyzer (PFA-100) as well as optical aggregometry (arachidonic acid, collagen and epinephrine). Analyses of covariance adjusted for age, aspirin dose, and statin use were used to estimate differences between the groups. Values of SIPA at fluid shear rates of 5000 and 10,000 s(-1) were significantly higher in the PAD group, while there were no differences between the PAD and CAD groups in SIPE at both fluid shear rates. However, baseline shear-induced P-selectin expression was higher in patients with PAD than CAD (mean fluorescence intensity [MFI] = 2.93 +/- 1.37 vs.1.94 +/- 0.67; p = 0.01), while the percentage increases in SIPA and SIPE at fluid shear rates of 5000 and 10,000 s(-1) were significantly higher in patients with CAD when compared to PAD (p < 0.001 for all comparisons). Although there were several similarities in platelet function between men with PAD and men with CAD, significant differences in platelet responses to shear stress were observed in men with PAD when compared to those with CAD. Although the mechanism for these observed differences are not clear, we hypothesize that in vivo platelet activation in PAD patients may contribute to the differences and will need to be further investigated.

Genome Based Cell Population Heterogeneity Promotes Tumorigenicity: The Evolutionary Mechanism Of Cancer., Christine J. Ye, Joshua B. Stevens, Guo Liu, Steven W. Bremer, Aruna S. Jaiswal, Karen J. Ye, Ming-Fong Lin, Lesley Lawrenson, Wayne D. Lancaster, Markku Kurkinen, Joshua D. Liao, C. Gary Gairola, Malathy P. V. Shekhar, Satya Narayan, Fred R. Miller, Henry H. Q. Heng

Journal Articles: Biochemistry & Molecular Biology

Cancer progression represents an evolutionary process where overall genome level changes reflect system instability and serve as a driving force for evolving new systems. To illustrate this principle it must be demonstrated that karyotypic heterogeneity (population diversity) directly contributes to tumorigenicity. Five well characterized in vitro tumor progression models representing various types of cancers were selected for such an analysis. The tumorigenicity of each model has been linked to different molecular pathways, and there is no common molecular mechanism shared among them. According to our hypothesis that genome level heterogeneity is a key to cancer evolution, we expect to reveal …

Plant Vaccines: An Immunological Perspective., Douglas C. Hooper

Department of Cancer Biology Faculty Papers

The advent of technologies to express heterologous proteins in planta has led to the proposition that plants may be engineered to be safe, inexpensive vehicles for the production of vaccines and possibly even vectors for their delivery. The immunogenicity of a variety of antigens of relevance to vaccination expressed in different plants has been assessed. The purpose of this article is to examine the utility of plant-expression systems in vaccine development from an immunological perspective.

Upregulation Of Pip3-Dependent Rac Exchanger 1 (P-Rex1) Promotes Prostate Cancer Metastasis., Jianbing Qin, Yan Xie, Bo Wang, Mikio Hoshino, Dennis W. Wolff, Jing Zhao, Margaret A. Scofield, Frank J. Dowd, Ming-Fong Lin, Yaping Tu

Journal Articles: Biochemistry & Molecular Biology

Excessive activation of G-protein-coupled receptor (GPCR) and receptor tyrosine kinase (RTK) pathways has been linked to prostate cancer metastasis. Rac activation by guanine nucleotide exchange factors (GEFs) plays an important role in directional cell migration, a critical step of tumor metastasis cascades. We found that the upregulation of P-Rex1, a Rac-selective GEF synergistically activated by Gbetagamma freed during GPCR signaling, and PIP3, generated during either RTK or GPCR signaling, strongly correlates with metastatic phenotypes in both prostate cancer cell lines and human prostate cancer specimens. Silencing endogenous P-Rex1 in metastatic prostate cancer PC-3 cells selectively inhibited Rac activity and reduced …

U2os Cells Lacking Chk1 Undergo Aberrant Mitosis And Fail To Activate The Spindle Checkpoint, Laura Carrassa, Yolanda Sanchez, Eugenio Erba, Giovanna Damia

Dartmouth Scholarship

Chk1 is a conserved protein kinase originally identified in fission yeast, required to delay entry of cells with damaged or unreplicated DNA into mitosis. The requirement of Chk1 for both S and G2/M checkpoints has been elucidated while only few studies have connected Chk1 to the mitotic spindle checkpoint. We used a small interference RNA strategy to investigate the role of Chk1 in unstressed conditions. Chk1 depletion in U2OS human osteosarcoma cells inhibited cell proliferation and raised the percentage of cells with a 4N DNA content, which correlated with accumulation of giant polynucleated cells morphologically distinct from apoptotic cells, while …

Vesicles In Poiseuille Flow, Gerrit Danker, Petia M. Vlahovska, Chaouqi Misbah

Dartmouth Scholarship

Blood microcirculation critically depends on the migration of red cells towards the flow centerline. We identify theoretically the ratio of the inner over the outer fluid viscosities λ as a key parameter. At low λ, the vesicle deforms into a tank-treading ellipsoid shape far away from the flow centerline. The migration is always towards the flow centerline, unlike drops. Above a critical λ, the vesicle tumbles or breaths and migration is suppressed. A surprising coexistence of two types of shapes at the centerline, a bulletlike and a parachutelike shape, is predicted.

Physical And Functional Interaction Between The Dopamine Transporter And The Synaptic Vesicle Protein Synaptogyrin-3, Loreto A Egaña, Rolando A Cuevas, Tracy B Baust, Leonardo A Parra, Rehana K Leak, Sarah Hochendoner, Karina Peña, Marisol Quiroz, Weimin C Hong, Mario M Dorostkar, Roger Janz, Harald H Sitte, Gonzalo E Torres

Faculty, Staff and Student Publications

Uptake through the dopamine transporter (DAT) represents the primary mechanism used to terminate dopaminergic transmission in brain. Although it is well known that dopamine (DA) taken up by the transporter is used to replenish synaptic vesicle stores for subsequent release, the molecular details of this mechanism are not completely understood. Here, we identified the synaptic vesicle protein synaptogyrin-3 as a DAT interacting protein using the split ubiquitin system. This interaction was confirmed through coimmunoprecipitation experiments using heterologous cell lines and mouse brain. DAT and synaptogyrin-3 colocalized at presynaptic terminals from mouse striatum. Using fluorescence resonance energy transfer microscopy, we show …

Characterization Of Conserved Properties Of Hemagglutinin Of H5n1 And Human Influenza Viruses: Possible Consequences For Therapy And Infection Control, Veljko Veljkovic, Nevena Veljkovic, Claude P. Muller, Sybille Müller, Sanja Glisic, Vladimir Perovic, Heinz Köhler

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: Epidemics caused by highly pathogenic avian influenza virus (HPAIV) are a continuing threat to human health and to the world's economy. The development of approaches, which help to understand the significance of structural changes resulting from the alarming mutational propensity for human-to-human transmission of HPAIV, is of particularly interest. Here we compare informational and structural properties of the hemagglutinin (HA) of H5N1 virus and human influenza virus subtypes, which are important for the receptor/virus interaction.

RESULTS: Presented results revealed that HA proteins encode highly conserved information that differ between influenza virus subtypes H5N1, H1N1, H3N2, H7N7 and defined an …

Primary Cardiac Tumors., Suraj Maraj, Md, Gregg S. Pressman, Md, Vincent M. Figueredo, Md

Division of Cardiology Faculty Papers

Primary cardiac tumors are a rare entity compared to tumors that metastasize to the heart. Patients with such tumors may be asymptomatic. Many cases are found incidentally during evaluation of an unrelated medical condition. It is important for the clinician to have a high index of suspicion when evaluating a patient presenting with signs and systemic symptoms concerning possible malignancy, plus cardiac specific symptoms or complications. These can include new onset dyspnea, congestive heart failure, arrhythmias or murmurs varying with body positions. Imaging, particularly the use of echocardiography, remains the cornerstone of diagnosis, and may be combined with new imaging …

A Study Of Micrornas In Silico And In Vivo: Diagnostic And Therapeutic Applications In Cancer., Scott A Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

There is emerging evidence of the production in human tumors of abnormal levels of microRNAs (miRNAs), which have been assigned oncogenic and/or tumor-suppressor functions. While some miRNAs commonly exhibit altered amounts across tumors, more often, different tumor types produce unique patterns of miRNAs, related to their tissue of origin. The role of miRNAs in tumorigenesis underscores their value as mechanism-based therapeutic targets in cancer. Similarly, unique patterns of altered levels of miRNA production provide fingerprints that may serve as molecular biomarkers for tumor diagnosis, classification, prognosis of disease-specific outcomes and prediction of therapeutic responses.

Long-Distance Delivery Of Bacterial Virulence Factors By Pseudomonas Aeruginosa Outer Membrane Vesicles, Jennifer M. Bomberger, Daniel P. Maceachran, Bonita A. Coutermarsh, Siying Ye, George A. O'Toole, Bruce A. Stanton, Frederick M. Ausubel

Dartmouth Scholarship

Bacteria use a variety of secreted virulence factors to manipulate host cells, thereby causing significant morbidity and mortality. We report a mechanism for the long-distance delivery of multiple bacterial virulence factors, simultaneously and directly into the host cell cytoplasm, thus obviating the need for direct interaction of the pathogen with the host cell to cause cytotoxicity. We show that outer membrane–derived vesicles (OMV) secreted by the opportunistic human pathogen Pseudomonas aeruginosa deliver multiple virulence factors, including β-lactamase, alkaline phosphatase, hemolytic phospholipase C, and Cif, directly into the host cytoplasm via fusion of OMV with lipid rafts in the host plasma …

Transperitoneal Robotic-Assisted Laparoscopic Prostatectomy After Prosthetic Mesh Herniorrhaphy., Costas D. Lallas, Mark L. Pe, Jitesh V. Patel, Pranav Sharma, Leonard G. Gomella, Edouard J. Trabulsi

Department of Urology Faculty Papers

BACKGROUND AND OBJECTIVES: We report our institutional experience performing transperitoneal robotic-assisted laparoscopic prostatectomy (RALP) in patients with prior prosthetic mesh herniorrhaphy to assess the feasibility of this procedure in this patient population. METHODS: From October 2005 to January 2008, transperitoneal robotic-assisted laparoscopic prostatectomies were performed and prospectively recorded. We retrospectively reviewed 309 patients. RESULTS: Twenty-seven patients (8.7%) were found to have a history of prior hernia repair with prosthetic mesh placement. The mean age was 55.7, estimated blood loss (EBL) was 228 mL, operative (console) time was 197 minutes, and length of hospital stay (LOS) was 1.62 days. In contrast, …

Drug Abuse Treatment Beyond Prison Walls, Carl Leukefeld, Carrie B. Oser, Jennifer Havens, Michele Staton Tindall, Jennifer Mooney, Jamieson B. Duvall, Hannah Knudsen

Behavioral Science Faculty Publications

The period surrounding release from prison is a critical time for parolees, bearing the potential for a drug-free and crime-free life in the community but also high risks for recidivism and relapse to drugs. The authors describe two projects. The first illustrates the use of a formal Delphi process to elicit and combine the expertise of treatment providers, researchers, corrections personnel, and other stakeholders in a set of statewide guidelines for facilitating re-entry. The second project is a six-session intervention to enable women to protect themselves against acquiring or transmitting HIV in their intimate relationships.

Long-Term Survival After Multidisciplinary Management Of Resected Pancreatic Adenocarcinoma, Matthew H G Katz, Huamin Wang, Jason B Fleming, Charlotte C Sun, Rosa F Hwang, Robert A Wolff, Gauri Varadhachary, James L Abbruzzese, Christopher H Crane, Sunil Krishnan, Jean-Nicolas Vauthey, Eddie K Abdalla, Jeffrey E Lee, Peter W T Pisters, Douglas B Evans

Faculty, Staff and Student Publications

INTRODUCTION: Actual 5-year survival rates of 10-18% have been reported for patients with resected pancreatic adenocarcinoma (PC), but the use of multimodality therapy was uncommon in these series. We evaluated long-term survival and patterns of recurrence in patients treated for PC with contemporary staging and multimodality therapy.

METHODS: We analyzed 329 consecutive patients with PC evaluated between 1990 and 2002 who underwent resection. Each received a multidisciplinary evaluation and a standard operative approach. Pre- or postoperative chemotherapy and/or chemoradiation were routine. Surgical specimens of 5-year survivors were re-reviewed. A multivariate model of factors associated with long-term survival was constructed.

RESULTS: …

Pick1 Deficiency Causes Male Infertility In Mice By Disrupting Acrosome Formation, Nan (Tori) Xiao, Chuen Kam, Chong Shen, Wenying Jin, Junqi Wang, Kwong Man Lee, Liwen Jiang, Jun Xia

All Dugoni School of Dentistry Faculty Articles

Protein interacting with C kinase 1 (PICK1) is a peripheral membrane protein involved in protein trafficking, a function that has been well characterized in neurons. Here, we report that male mice deficient in PICK1 are infertile and have a phenotype resembling the human disease globozoospermia. The primary defect in the testes of Pick1-knockout mice was fragmentation of acrosomes in the early stages of spermiogenesis. This fragmentation was followed by defects in nuclear elongation and mitochondrial sheath formation, leading to round-headed sperm, reduced sperm count, and severely impaired sperm motility. We found that PICK1 interacted with Golgi-associated PDZ- and coiled-coil motif-containing …

Associated Symptoms In The Ten Days Before Diagnosis Of Kawasaki Disease., Annette L. Baker, Minmin Lu, L Luann Minich, Andrew M. Atz, Gloria L. Klein, Rosalind Korsin, Linda Lambert, Jennifer S. Li, Wilbert Mason, Elizabeth Radojewski, Victoria L. Vetter, Jane W. Newburger, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To describe common associated symptoms within the 10 days before diagnosis in subjects enrolled in the Pediatric Heart Network's trial of steroid therapy in Kawasaki disease (KD).

STUDY DESIGN: Patients with acute KD were enrolled between days 4 and 10 of illness at 8 centers between 2002 and 2004. We defined common associated symptoms as those occurring in >or=10% of patients. Principal clinical criteria for KD were not included in this analysis.

RESULTS: Among 198 patients, irritability was reported in 98 (50%), vomiting in 88 (44%), decreased food/fluid intake in 73 (37%), cough in 55 (28%), diarrhea in 52 …

Laparoscopic Treatment Of Pancreatic Pseudocysts In Children., Suzanne M. Yoder, Steven Rothenberg, Kuojen Tsao, Mark L. Wulkan, Todd A. Ponsky, Shawn D. St Peter, Daniel J. Ostlie, Timothy D. Kane

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Pancreatic pseudocysts are problematic sequelae of pancreatitis or pancreatic trauma causing persistent abdominal pain, nausea, and gastric outlet obstruction. Due to the low volume of disease in children, there is scant information in the literature on the operative management of pseudocysts with minimally invasive techniques. We conducted a multi-institutional review to illustrate several technical variations utilized in achieving laparoscopic cystgastrostomy in the pediatric population.

METHODS: A retrospective review was conducted of all patients who underwent laparoscopic cystgastrostomy in five institutions. Patient data, operative techniques, and postoperative course were analyzed.

RESULTS: There were 13 patients with a mean age of …

The Significance Of Gata3 Expression In Breast Cancer: A 10-Year Follow-Up Study., Vincenzo Ciocca, Constantine Daskalakis, Robin M. Ciocca, Alejandra Ruiz-Orrico, Juan P. Palazzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

GATA3 is a transcription factor closely associated with estrogen receptor alpha in breast carcinoma, with a potential prognostic utility. This study investigated the immunohistochemical expression of GATA3 in estrogen receptor alpha-positive and estrogen receptor alpha-negative breast carcinomas. One hundred sixty-six cases of invasive breast carcinomas with 10-year follow-up information were analyzed. Positive GATA3 and estrogen receptor alpha cases were defined as greater than 20% of cells staining. Time to cancer recurrence and time to death were analyzed with survival methods. Of 166 patients, 40 were estrogen receptor alpha negative and 121 estrogen receptor alpha positive. Thirty-eight (23%) recurrences and 51 …

Thoracoscopy In Children: Is A Chest Tube Necessary?, Todd A. Ponsky, Steven S. Rothenberg, Kuojen Tsao, Daniel J. Ostlie, Shawn D. St Peter, G W. Holcomb Iii

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Historically, a chest tube or drain has been left following a thoracic operation to allow drainage of air or fluid in the postoperative period. However, in patients undergoing thoracoscopy, the tube is often the greatest source of postoperative pain. We began excluding chest tubes several years ago and therefore are reviewing our experience to evaluate the safety and efficacy of this approach.

METHODS: A retrospective review of the medical record was performed on patients undergoing thoracoscopy at two centers from 1993 to 2007. Patients who left the operating room without a chest tube were included in this series. Patient …

Universal Screening For Extracardiac Abnormalities In Neonates With Congenital Heart Disease., Javier H. Gonzalez, Girish S. Shirali, Andrew M. Atz, Sarah N. Taylor, Geoffrey A. Forbus, Sinai C. Zyblewski, Anthony M. Hlavacek

Manuscripts, Articles, Book Chapters and Other Papers

Extracardiac or genetic abnormalities (EGA) represent a factor in the morbidity of patients with congenital heart disease. We evaluated the way neonates with CHD are screened at our institution and determined the yield for the screening tests. We reviewed the charts of 223 neonates with structural CHD. Subjects were categorized into 6 groups: univentricular, left-sided obstructive lesions, right-sided obstructive lesions, septal defects, conotruncal defects (CTD), and other. We reviewed which patients underwent cranial ultrasonogram (CUS), abdominal ultrasonogram (AUS), and/or genetic studies (GS) as well as their results. There was a high prevalence of EGA in each group by CUS (32% …

Comorbidities, Patient Knowledge, And Disease Management In A National Sample Of Patients With Copd, R Graham Barr, Bartolome R Celli, David M Mannino, Thomas Petty, Stephen I Rennard, Frank C Sciurba, James K Stoller, Byron M Thomashow, Gerard M Turino

Faculty, Staff and Student Publications

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States but is often undertreated. COPD often overlaps with other conditions such as hypertension and osteoporosis, which are less morbid but may be treated more aggressively. We evaluated the prevalence of these comorbid conditions and compared testing, patient knowledge, and management in a national sample of patients with COPD.

METHODS: A survey was administered by telephone in 2006 to 1003 patients with COPD to evaluate the prevalence of comorbid conditions, diagnostic testing, knowledge, and management using standardized instruments. The completion rate was 87%.

RESULTS: …

Coronary Steal Syndrome After Coronary Artery Bypass For Anomalous Aortic Origin Of A Coronary Artery., Benjamin A. Youdelman, Glenn J. Pelletier, C Igor Mesia, Marshall L. Jacobs

Department of Surgery Faculty Papers

Anomalous aortic origin of a coronary artery found in a symptomatic 9-year-old boy was initially treated with coronary artery bypass grafting using a left internal mammary artery anastomoses to the left anterior descending coronary artery, but resulted in coronary ischemia, likely from a steal phenomenon. Subsequent transection of the proximal left internal mammary artery with anastomosis to the ascending aorta, and coronary ostial enlargement, resulted in a durable treatment. We recommend caution in choosing coronary artery bypass grafting using a left internal mammary artery pedicle graft for the treatment of anomalous aortic origin of a coronary artery.

Laparoscopic Duodenojejunostomy For Superior Mesenteric Artery Syndrome., Jason D. Fraser, Shawn D. St Peter, Jenevieve H. Hughes, James M. Swain

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Superior mesenteric artery (SMA) syndrome, also called Wilkie's syndrome, is a rare clinical phenomenon believed to be caused by compression of the third portion of the duodenum by the overlying superior mesenteric artery. We present the case of a 32-year-old female who presented with epigastric pain, weight loss, and vomiting.

METHODS: Her workup included a normal upper endoscopy as well as an abdominal CT scan and upper GI contrast study that confirmed the diagnosis of superior mesenteric artery syndrome. The patient was taken to the operating room and underwent successful treatment with laparoscopic duodenojejunostomy.

RESULTS: The patient achieved complete …

Hyperglycemia And Acquired Weakness In Critically Ill Patients: Potential Mechanisms, Leigh Ann Callahan, Gerald S. Supinski

Internal Medicine Faculty Publications

Critical illness polyneuropathy/critical illness myopathy (CIP/CIM) is a major cause of mortality and long-term morbidity in critically ill patients, but the true incidence and prevalence of these syndromes are not known. Hermans and colleagues show that when intensive insulin therapy is used as part of routine clinical practice in the intensive care unit, the incidence of CIP/CIM as determined by electrophysiologic testing is reduced. Our understanding of the mechanisms responsible for inducing prolonged weakness in intensive care unit patients is limited, and the role of hyperglycemia in modulating these processes is unknown. Intensive insulin therapy currently remains the only effective …

Smoking Enhances Risk For New External Genital Warts In Men, Dorothy J. Wiley, David Elashoff, Emmanuel V. Masongsong, Diane M. Harper

Dartmouth Scholarship

Repeat episodes of HPV-related external genital warts reflect recurring or new infections. No study before has been sufficiently powered to delineate how tobacco use, prior history of EGWs and HIV infection affect the risk for new EGWs. Behavioral, laboratory and examination data for 2,835 Multicenter AIDS Cohort Study participants examined at 21,519 semi-annual visits were evaluated. Fourteen percent (391/2835) of men reported or were diagnosed with EGWs at 3% (675/21,519) of study visits. Multivariate analyses showed smoking, prior episodes of EGWs, HIV infection and CD4+ T-lymphocyte count among the infected, each differentially influenced the risk for new EGWs.

Use Of Clopidogrel In The Reduction Of Myocardial Damage During Percutaneous Coronary Intervention, Arijit Dasgupta, Debabrata Mukherjee

Gill Heart & Vascular Institute Faculty Publications

It is estimated that approximately a quarter of patients undergoing coronary intervention may have significant post-procedural creatinine (CK)/creatinine kinase myocardial band (CK-MB) elevations and approximately half may have post-procedural troponin elevations. Current data suggest that periprocedural infarction is associated with short-, intermediate-, and long-term adverse outcomes, most notably mortality. This review examines the role of clopidogrel in decreasing periprocedural myonecrosis following percutaneous coronary intervention (PCI). Clopidogrel is an important pharmacologic agent used to reduce myocardial infarction post-coronary intervention as assessed directly by the evaluation of cardiac biomarkers and indirectly by the evaluation of short-term ischemic events. The optimal dose of …

Dosimetric Evaluation Of Heterogeneity Corrections For Rtog 0236: Stereotactic Body Radiotherapy Of Inoperable Stage I-Ii Non-Small-Cell Lung Cancer., Ying Xiao, Lech Papiez, Rebecca Paulus, Robert Timmerman, William L. Straube, Walter R. Bosch, Jeff Michalski, James M. Galvin

Department of Radiation Oncology Faculty Papers

PURPOSE: Using a retrospective analysis of treatment plans submitted from multiple institutions accruing patients to the Radiation Therapy Oncology Group (RTOG) 0236 non-small-cell stereotactic body radiotherapy protocol, the present study determined the dose prescription and critical structure constraints for future stereotactic body radiotherapy lung protocols that mandate density-corrected dose calculations.

METHOD AND MATERIALS: A subset of 20 patients from four institutions participating in the RTOG 0236 protocol and using superposition/convolution algorithms were compared. The RTOG 0236 protocol required a prescription dose of 60 Gy delivered in three fractions to cover 95% of the planning target volume. Additional requirements were specified …

Analysis Of Carotid Lumen Surface Morphology Using Three-Dimensional Ultrasound Imaging, Bernard Chiu, Vadim Beletsky, J David Spence, Grace Parraga, Aaron Fenster

Medical Biophysics Publications

Carotid plaque surface irregularity and ulcerations play an important role in the risk of ischemic stroke. Ulcerated or fissured plaque, characterized by irregular surface morphology, exposes thrombogenic materials to the bloodstream, possibly leading to life- or brain-threatening thrombosis and embolization. Therefore, the quantification of plaque surface irregularity is important to identify high-risk plaques that would likely lead to vascular events. Although a number of studies have characterized plaque surface irregularity using subjective classification schemes with two or more categories, only a few have quantified surface irregularity using an objective and continuous quantity, such as Gaussian or mean curvature. In this …

Paracrine Sonic Hedgehog Signalling By Prostate Cancer Cells Induces Osteoblast Differentiation, Samantha M Zunich, Taneka Douglas, Maria Valdovinos, Tiffany Chang

Dartmouth Scholarship

Sonic hedgehog (Shh) and components of its signalling pathway have been identified in human prostate carcinoma and increased levels of their expression appear to correlate with disease progression and metastasis. The mechanism through which Shh signalling could promote metastasis in bone, the most common site for prostate carcinoma metastasis, has not yet been investigated. The present study determined the effect of Shh signalling between prostate cancer cells and pre-osteoblasts on osteoblast differentiation, a requisite process for new bone formation that characterizes prostate carcinoma metastasis.