Medical Specialties Commons^™

Rituximab Induces Sustained Reduction Of Pathogenic B Cells In Patients With Peripheral Nervous System Autoimmunity., Michael A Maurer, Goran Rakocevic, Carol S Leung, Isaak Quast, Martin Lukačišin, Norbert Goebels, Christian Münz, Hedda Wardemann, Marinos Dalakas, Jan D Lünemann

Department of Neurology Faculty Papers

The B cell-depleting IgG1 monoclonal antibody rituximab can persistently suppress disease progression in some patients with autoimmune diseases. However, the mechanism underlying these long-term beneficial effects has remained unclear. Here, we evaluated Ig gene usage in patients with anti-myelin-associated glycoprotein (anti-MAG) neuropathy, an autoimmune disease of the peripheral nervous system that is mediated by IgM autoantibodies binding to MAG antigen. Patients with anti-MAG neuropathy showed substantial clonal expansions of blood IgM memory B cells that recognized MAG antigen. The group of patients showing no clinical improvement after rituximab therapy were distinguished from clinical responders by a higher load of clonal …

Ketamine As An Adjunct For The Long-Term Sedation And Analgesia Of A Patient With A Left Ventricular Assist Device (Lvad) And An Open Chest, Avni Gupta, Charles S. Kato, Eugene R. Viscusi

Department of Anesthesiology Faculty Papers

Conclusion:

A multimodal sedative and analgesic regimen that incorporates ketamine offers important therapeutic advantages in select patients who require very high doses of opioids and benzodiazepines, but warrants futher study.

Sir William Osler, M.D., C.M., Jonathan Sarik, B.S., Charles J. Yeo, Md, Pinckney J. Maxwell, Iv, Md

Department of Surgery Gibbon Society Historical Profiles

Sir William Osler impacted medical education and the practice of medicine like few other physicians. As a writer, he authored nearly 1500 publications and lent his name to numerous eponyms. As a teacher he educated vast numbers of students and through his legacy impacted countless more. Sir William Osler (Fig. 1) epitomized what a physician should be throughout his professional life.

The Appropriateness Of Long-Term Opioids To Treat Chronic Back Pain, Thomas Watanabe, Michael Salino, Adam Schreiber

Department of Rehabilitation Medicine Faculty Papers

Point/Counterpoint Case Scenario: A 55-year old man presents to a pain clinic upon referral from his primary care physician. His symptom is axial low back pain. His pain started approximately 1 year earlier without a specific inciting event. He denies radiation of pain into the lower extremities. There is no bowel or bladder involvement. There is no directional preference. He reports pain "all the time," with minimal specific exacerbating or relieving factors. There is no medical-legal involvement. His medical history is significant for hypertension, hypercholesterolemia, obesity, and sleep apnea. He is a divorced father of 2 adult children. He is …

Psychostimulant Drug Abuse And Personality Factors In Medical Students, Joshua T. Buchner, Md, Duc M. Vu, Md, Mohammadreza Hojat

CRMEHC Faculty Papers

Purpose:

This study was designed to examine the prevalence of psychostimulant drug abuse among medical students and to test the hypothesis that medical students who use psychostimulant drugs for non-medical reasons are characterized by a sensation seeking and aggressive-hostility personality and exhibit lower empathy.

Dyschronic, A Drosophila Homolog Of A Deaf-Blindness Gene, Regulates Circadian Output And Slowpoke Channels., James E C Jepson, Mohammad Shahidullah, Angelique Lamaze, Drew Peterson, Huihui Pan, Kyunghee Koh

Farber Institute for Neuroscience Faculty Papers

Many aspects of behavior and physiology are under circadian control. In Drosophila, the molecular clock that regulates rhythmic patterns of behavior has been extensively characterized. In contrast, genetic loci involved in linking the clock to alterations in motor activity have remained elusive. In a forward-genetic screen, we uncovered a new component of the circadian output pathway, which we have termed dyschronic (dysc). dysc mutants exhibit arrhythmic locomotor behavior, yet their eclosion rhythms are normal and clock protein cycling remains intact. Intriguingly, dysc is the closest Drosophila homolog of whirlin, a gene linked to type II Usher syndrome, the leading cause …

(Iv) Managing Bone Loss Of The Femur And Tibia In Revision Total Knee Arthroplasty, Glenn J. Kerr, M.D, Joseph A. Karam, M.D., Javad Parvizi, M.D., Frcs

Rothman Institute Papers

The number of primary and revision knee arthroplasty procedures performed yearly is steadily increasing. The management of bone loss at the time of revision surgery will play an integral role in the longevity and function of these knees into the future. There are a variety of options for addressing these defects varying from the use of polymethylmethacrylate bone cement, metal augments, sleeves, cones and large allograft replacements. This manuscript discusses the evaluation, classification and management of bone loss of the distal femur and proximal tibia.

Frontal Sinus Osteoma Removal With The Ultrasonic Bone Aspirator., Eric Ehieli, Jaemi Chu, Eli Gordin, Edmund A Pribitkin

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Osteomas, the most common skull tumors, are typically excised through either an open or endoscopic ostectomy using a high-speed drill, a technically challenging procedure that can result in injury to adjacent soft tissue structures. Osteoma removal through ultrasonic bone emulsification and aspiration (UBA) offers the advantages of decreased blood loss, preservation of adjacent soft tissue structures, and precise bone removal. UBA was used to successfully remove a forehead osteoma without injury to adjacent nerves and with a satisfactory cosmetic outcome. We describe skull osteoma removal with an ultrasonic bone aspirator, which offers potential advantages over conventional bone removal techniques.

Frontal Sinus Osteoma Removal With The Ultrasonic Bone Aspirator., Eric Ehieli, Jaemi Chu, Eli Gordin, Edmund A. Pribitkin

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Osteomas, the most common skull tumors, are typically excised through either an open or endoscopic ostectomy using a high-speed drill, a technically challenging procedure that can result in injury to adjacent soft tissue structures. Osteoma removal through ultrasonic bone emulsification and aspiration (UBA) offers the advantages of decreased blood loss, preservation of adjacent soft tissue structures, and precise bone removal. UBA was used to successfully remove a forehead osteoma without injury to adjacent nerves and with a satisfactory cosmetic outcome. We describe skull osteoma removal with an ultrasonic bone aspirator, which offers potential advantages over conventional bone removal techniques.

Robotic-Assistance Does Not Enhance Standard Laparoscopic Technique For Right-Sided Donor Nephrectomy., Xiaolong S Liu, Hadley W Narins, Warren R Maley, Adam M Frank, Costas D. Lallas

Department of Urology Faculty Papers

OBJECTIVE: To examine donor and recipient outcomes after right-sided robotic-assisted laparoscopic donor nephrectomy (RALDN) compared with standard laparoscopic donor nephrectomy (LDN) and to determine whether robotic-assistance enhances LDN.

MATERIALS & METHODS: From December 2005 to January 2011, 25 patients underwent right-sided LDN or RALDN. An IRB-approved retrospective review was performed of both donor and recipient medical charts. Primary endpoints included both intraoperative and postoperative outcomes.

RESULTS: Twenty right-sided LDNs and 5 RALDNs were performed during the study period. Neither estimated blood loss (76.4 mL vs. 30 mL, P = .07) nor operative time (231 min vs. 218 min, P = …

Thickened Ascending Aortic Wall Mimicking Intramural Hematoma., Kentaro Yamane, Hitoshi Hirose, Benjamin A. Youdelman, James Diehl

Department of Surgery Faculty Papers

A 45-year-old Hispanic woman presented with a 3-day history of ‘‘burning’’ chest pain. A computed tomo- graphic angiogram of the chest revealed the ascending aorta had a maximum diameter of 40 mm with marked thickening of the aortic wall (Figure 1), which we con- cluded was an intramural hematoma. On entering the pericardium, a milky-white plaque-like area on the ascending aorta was encountered (Figure 2). The ascending aorta was firm to palpation. Intraoperative transesophageal echocardiography and epiaortic ultra- sound showed a hyperechoic aortic wall with no find- ings compatible with aortic dissection. The ascending aorta had an irregular surface contour, …

Targeting Apoptosis For Optical Imaging Of Infection, Mathew L Thakur, Kaijun Zhang, Bishnuhari Paudyal, Devadhas Devakumar, Maria Y Covarrubias, Changpo Cheng, Brian D Gray, Eric Wickstrom, Koon Y Pak

Department of Radiology Faculty Papers

PURPOSE: Infection is ubiquitous and a major cause of morbidity and mortality. The most reliable method for localizing infection requires radiolabeling autologous white blood cells ex vivo. A compound that can be injected directly into a patient and can selectively image infectious foci will eliminate the drawbacks. The resolution of infection is associated with neutrophil apoptosis and necrosis presenting phosphatidylserine (PS) on the neutrophil outer leaflet. Targeting PS with intravenous administration of a PS-specific, near-infrared (NIR) fluorophore will permit localization of infectious foci by optical imaging.

METHODS: Bacterial infection and sterile inflammation were induced in separate groups (n = 5) …

Balloon-Occluded Retrograde Transvenous Obliteration For The Treatment Of Gastric Varices., Alia S Dadabhai, Jonathan M Fenkel, Daniel B Brown, Loren Laine

Division of Gastroenterology and Hepatology Faculty Papers

Clinical Perspectives in Hepatology aims to engage two experts with opinions supporting differing perspectives on the management of a case. Typically, the case represents an area of debate or evolving practice in clinical hepatology.

The patient presented below gives us the opportunity to discuss balloon-occluded retrograde transvenous obliteration (BRTO) for treatment of gastric varices. Although described since the mid-1990s and accepted as effective therapy, particularly in Japan, BRTO is used sporadically in the United States and Europe. In fact, it is not mentioned in the U.S. (AASLD) or European (EASL/Baveno V) guidelines. Hopefully, increased awareness of and expertise in this …

Essential Role Of Caveolin-3 In Adiponectin Signalsome Formation And Adiponectin Cardioprotection., Yajing Wang, Xiaoliang Wang, Jean-François Jasmin, Wayne Bond Lau, Rong Li, Yuexin Yuan, Wei Yi, Kurt Chuprun, Michael P. Lisanti, Walter J Koch, Erhe Gao, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Adiponectin (APN) system malfunction is causatively related to increased cardiovascular morbidity/mortality in diabetic patients. The aim of the current study was to investigate molecular mechanisms responsible for APN transmembrane signaling and cardioprotection.

METHODS AND RESULTS: Compared with wild-type mice, caveolin-3 knockout (Cav-3KO) mice exhibited modestly increased myocardial ischemia/reperfusion injury (increased infarct size, apoptosis, and poorer cardiac function recovery; P

CONCLUSIONS: Taken together, these results demonstrated for the first time that Cav-3 plays an essential role in APN transmembrane signaling and APN anti-ischemic/cardioprotective actions.

Expression Of Stem Cell Marker Aldh1 In Cervical Intraepithelial Neoplasia, Ping Gong, Juan Palazzo, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Conclusions:

Cervical dysplasia show positive staining for ALDH1 compared to normal cervical mucosa.

ALDH1 positive cells distribution parallels the dysplastic cells in cervical dysplasia.

CSC, as detected by ALDH1 expression, may play a role in the progression of cervical intraepithelial neoplasia and carcinogenesis.

Loss Of Retinoblastoma (Rb) Tumor Suppressor Expression In Breast Cancer Correlates With Better Response To Neoadjuvant Chemotherapy, Jeanne Mcfalls, Md, Jessica Kline, Ba, Gordon Schwartz, Md, Mba, Facs, Angieszka Witkiewicz, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Conclusions:

Loss of RB tumor suppressor staining in pre-treatment breast cancer biopsies can be used prior to initiation of neoadjuvant chemotherapy to predict good tumor response. This association between RB loss and good neoadjuvant response holds regardless of ER status and across various chemotherapy regimens. Assessment of RB status in the pre-treatment biopsy could be useful clinical tool to define patients who are most likely to benefit from neoadjuvant chemotherapy.

P53 Expression In Oropharyngeal Squamous Cell Carcinoma In Increased In Hpv Positive Smokers, Madalina Tuluc, Voichita Bar-Ad, Zi-Xuan Wang, Joseph Curry

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background and Objectives

High risk HPV is associated with oropharyngeal SCC (OSCC) and is responsible for the increasing incidence of this cancer type among younger patients.

Patients with HPV positive oropharyngeal SCC have a better prognosis when compared with HPV negative, tobacco induced SCC.

HPV E6 inactivates p53 leading to low expression of p53; tobacco induced oropharyngeal SCC is characterized by p53 overexpression, resistance to treatment and poor prognosis. However, in many cases of HPV OSCC, there is a history of current or remote smoking, making this disease a multifactorial process. We expect that smoking will influence the level of …

A Progressive Postresection Walking Program Significantly Improves Fatigue And Health-Related Quality Of Life In Pancreas And Periampullary Cancer Patients., Theresa Yeo, Sherry A Burrell, Patricia K Sauter, Eugene P Kennedy, Harish Lavu, Benjamin E Leiby, Charles Yeo

College of Nursing Faculty Papers & Presentations

BACKGROUND: As patients with pancreas and periampullary cancer (PPC) experience improved survival rates and longevity, the focus shifts toward living life while surviving cancer. Fatigue is the most commonly reported symptom in all cancer patients. Exercise has been found to effectively decrease fatigue levels and improve physical functioning in cancer patients.

STUDY DESIGN: One hundred two patients with resected PPC consented to participate in this study and were randomized to either an intervention group (IG) or a usual care group (UCG). Subjects completed visual analog scales, the FACIT-Fatigue Scale and the Short Form-36v2 after surgery and again 3 to 6 …

Aberrant Expression Of Cd56 On Granulocytes And Monocytes In Myeloproliferative Neoplasm And Myelodysplastic Syndrome, Ping Gong, Md, Fernanco Metrebian, Md, Alina Dulau-Florea, Md, Zi-Xuan Wang, Phd, Renu Bajaj, Phd, Stephen C Peiper, Jerald Z. Gong, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Conclusions:

Aberrant CD56 expression on granulocytes is seen in all aubtypes MPN and high grade MDS. CD56 expression in MPN correlated with bone marrow morphology, BCR/ABL transcript, and bone marrow engraftment study following treatment. Identification of abnormal CD56+ granulocytes and monocytes is helpful in both the initial diagnosis and long-term follow up of patients with MPN and MDS.

P16/Rb Correlations In Oropharyngeal Squamous Cell Carcinoma (Oscc), Madalina Tuluc, Voichita Bar-Ad, David Cognetti

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The objective of this study is to explore the patterns of Rb expression in p16 positive and negative OSCC, in relation to patient's smoking history.

Effect Of Obstructive Sleep Apnea On Mitral Valve Tenting., Gregg S. Pressman, Vincent M. Figueredo, Abel Romero-Corral, Ganesan Murali, Morris N Kotler

Division of Cardiology Faculty Papers

Obstructive apneas produce high negative intrathoracic pressure which imposes an afterload burden on the left ventricle. Such episodes might produce structural changes in the left ventricle over time. Doppler echocardiograms were obtained within 2 months of attended polysomnography. Patients were grouped according to apnea-hypopnea index (AHI): mild/no OSA (AHI < 15) and mod/severe OSA (AHI ≥ 15). Mitral valve tenting height and area, left ventricular (LV) long and short axis, and LV end-diastolic volume (LVEDV), were measured along with tissue Doppler parameters. Comparisons of measurements at baseline and follow up between and within groups were obtained; correlations between absolute changes (deltas) in echocardiographic parameters were also performed. After a mean follow up of 240 days mitral valve tenting height increased significantly (1.17 ± 0.12 cm to 1.28 ± 0.17 cm, p=0.001) in mod/severe OSA as did tenting area (2.30 ± 0.41 cm² to 2.66 ± 0.60 cm², p=0.0002); delta tenting height correlated with delta LVEDV (rho 0.43, p=0.01) and delta tenting area (rho 0.35, p=0.04). In mild/no OSA patients there was no significant change in tenting height; there was a borderline significant increase in tenting area (2.20 ± 0.44 cm …

A Role For Caveolin-1 In Desmoglein Binding And Desmosome Dynamics., D Brennan, S Peltonen, A Dowling, W Medhat, K J Green, J K Wahl, F Del Galdo, M G Mahoney

Department of Dermatology and Cutaneous Biology Faculty Papers

Desmoglein-2 (Dsg2) is a desmosomal cadherin that is aberrantly expressed in human skin carcinomas. In addition to its well-known role in mediating intercellular desmosomal adhesion, Dsg2 regulates mitogenic signaling that may promote cancer development and progression. However, the mechanisms by which Dsg2 activates these signaling pathways and the relative contribution of its signaling and adhesion functions in tumor progression are poorly understood. In this study we show that Dsg2 associates with caveolin-1 (Cav-1), the major protein of specialized membrane microdomains called caveolae, which functions in both membrane protein turnover and intracellular signaling. Sequence analysis revealed that Dsg2 contains a putative …

Hyperphosphorylation Of The Cardiac Ryanodine Receptor At Serine 2808 Is Not Involved In Cardiac Dysfunction After Myocardial Infarction., Hongyu Zhang, Catherine A Makarewich, Hajime Kubo, Wei Wang, Jason M Duran, Ying Li, Remus M Berretta, Walter J Koch, Xiongwen Chen, Erhe Gao, Héctor H Valdivia, Steven R Houser

Division of Cardiology Faculty Papers

RATIONALE: Abnormal behavior of the cardiac ryanodine receptor (RyR2) has been linked to cardiac arrhythmias and heart failure (HF) after myocardial infarction (MI). It has been proposed that protein kinase A (PKA) hyperphosphorylation of the RyR2 at a single residue, Ser-2808, is a critical mediator of RyR dysfunction, depressed cardiac performance, and HF after MI.

OBJECTIVE: We used a mouse model (RyRS2808A) in which PKA hyperphosphorylation of the RyR2 at Ser-2808 is prevented to determine whether loss of PKA phosphorylation at this site averts post MI cardiac pump dysfunction.

METHODS AND RESULTS: MI was induced in wild-type (WT) and S2808A …

Increase In Muscle Mitochondrial Biogenesis Does Not Prevent Muscle Loss But Increased Tumor Size In A Mouse Model Of Acute Cancer-Induced Cachexia., Xiao Wang, Alicia M Pickrell, Teresa A Zimmers, Carlos T Moraes

Kimmel Cancer Center Faculty Papers

Cancer-associated cachexia is a complex metabolic condition characterized by the progressive loss of body fat and deterioration of muscle mass. Although the cellular and molecular mechanisms of cachexia are incompletely understood, previous studies have suggested mitochondrial dysfunction in murine models of cancer cachexia. To better understand the metabolic shift in cancer-induced cachexia, we studied the effects of enhanced oxidative capacity on muscle wasting using transgenic mice over-expressing Peroxisome Proliferator-Activated Receptor gamma Co-activator-1α (PGC-1α) in skeletal muscle in a Lewis lung carcinoma-implanted model. Increased mitochondrial biogenesis was observed in the skeletal muscle of tumor-implanted mice. However, these increases did not prevent …

Gender-Sensitive Reporting In Medical Research., Shirin Heidari, Quarraisha Abdool Karim, Judith D Auerbach, Simone E Buitendijk, Pedro Cahn, Mirjam J Curno, Catherine Hankins, Elly Katabira, Susan Kippax, Richard Marlink, Joan Marsh, Ana Marusic, Heidi M Nass, Julio Montaner, Elizabeth Pollitzer, Maria Teresa Ruiz-Cantero, Lorraine Sherr, Papa Salif Sow, Kathleen Squires, Mark A Wainberg

Department of Medicine Faculty Papers

Sex and gender differences influence the health and wellbeing of men and women. Although studies have drawn attention to observed differences between women and men across diseases, remarkably little research has been pursued to systematically investigate these underlying sex differences. Women continue to be underrepresented in clinical trials, and even in studies in which both men and women participate, systematic analysis of data to identify potential sex-based differences is lacking. Standards for reporting of clinical trials have been established to ensure provision of complete, transparent and critical information. An important step in addressing the gender imbalance would be inclusion of …

Christian Albert Theodor Billroth, M.D., Founding Father Of Abdominal Surgery (1829-1894)., Zhi Ven Fong, B.S., Harish Lavu, Md, Ernest L. Rosato, Md, Charles J. Yeo, Md, Scott W. Cowan, Md

Department of Surgery Gibbon Society Historical Profiles

In the 1800s, the field of surgery was in its infancy, somewhat primitive and embryonic. The technical nature of surgery was the basis for the dividing line between the disciplines of surgery and internal medicine. Sterilization was not a common practice. Radical surgical resections and experimentation in medicine were shunned. With his boldness equaled only by his innovation and resourcefulness, Theodor Billroth would become a pioneer not only in the development of modern surgery, but also in the advancement of its cultural and historical significance.

Theodor Billroth And His Musical Life., Patrick A. Hartendorp, B.S., Charles J. Yeo, Md, Pinckney J. Maxwell, Iv, Md

Department of Surgery Gibbon Society Historical Profiles

Although most widely recognized for the two types of gastric reconstructions that bear his name, Christian Albert Theodor Billroth was one of the most innovative surgeons of his time. His contributions included developing techniques for procedures on the larynx, breast, and esophagus. He pioneered sterility and antisepsis in operating rooms. He also improved surgical education by advocating for longer apprenticeships, which helped create a framework for today’s residency programs. However, what often goes unnoticed was Dr. Billroth’s love for music, a passion that fueled him throughout his life.

Cyclin D1 Induces Chromosomal Instability., Mathew C Casimiro, Richard Pestell

Department of Cancer Biology Faculty Papers

We developed mouse model systems to investigate the potential for cyclin D1 to induce CIN in vivo. In a mammary gland specific Tet-inducible model the acute expression profile regulated by cyclin D1 after 7 days was enriched in genes that rank highly with CIN. We also used a mammary gland targeted model (MMTV) to continuously express cyclin D1. The mice started to develop mammary gland tumors at 400 days and the tumor-free incidence was 40% in MMTV-cyclin D1. The gene expression profile of the tumors showed enrichment for the CIN signature. We next compared cyclin D1 expression and the highest …

Small Non-Coding Rnas Govern Mammary Gland Tumorigenesis., Zuoren Yu, Richard Pestell

Department of Cancer Biology Faculty Papers

Small non-coding RNAs include siRNA, miRNA, piRNA and snoRNA. The involvement of miRNAs in the regulation of mammary gland tumorigenesis has been widely studied while the role for other small non-coding RNAs remains unclear. Here we summarize the involvement of miRNA in breast cancer onset and progression through regulating the cell cycle and cellular proliferation. The regulation of breast cancer stem cells and tumor regeneration by miRNA is reviewed. In addition, the emerging evidence demonstrating the involvement of piRNA and snoRNA in breast cancer is briefly described.

Robotic Surgery Training With Commercially Available Simulation Systems In 2011: A Current Review And Practice Pattern Survey From The Society Of Urologic Robotic Surgeons., Costas D Lallas, John W Davis And Members Of The Society Of Urologic Robotic Surgeons

Department of Urology Faculty Papers

Abstract Objectives: Virtual reality (VR) simulation has the potential to standardize surgical training for robotic surgery. We sought to evaluate all commercially available VR robotic simulators. Materials and Methods: A MEDLINE(®) literature search was performed of all applicable keywords. Available VR simulators were evaluated with regard to face, content, and construct validation. Additionally, a survey was e-mailed to all members of the Endourological Society, querying the pervasiveness of VR simulators in robotic surgical training. Finally, each company was e-mailed to ask for a price quote for their respective system. Results: There are four VR robotic surgical simulators currently available: RoSS™, …