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Baylor University Medical Center Proceedings Volume 25 Number 2 April 2012 The peer-reviewed journal of Baylor Health Care System, Dallas, Texas Baylor University Medical Center Proceedings Articles 115 Unilateral absence of a pulmonary artery: a rare disorder with variable presentation D. L. Glancy, E. B. Hanna, and C. C. Ilie D. W. Reading and U. Oza 119 Hepatitis E infection Images in Medicine 161 Paget’s disease of the calcaneus causing right foot pain P. Patel, G. Schucany, P. B. Wood, and D. Hurst Vincent C. Kuo 121 Fatal aortic rupture from nonpenetrating chest trauma M. M. Benjamin and W. C. Roberts 163 Ruptured cerebral arteriovenous malformation presenting as intraventricular hemorrhage A. F. Saad, M. J. Opatowsky, A. Y. Nixon, S. C. Gilbert, and I. C. Thacker 124 High energy deficit in an ultraendurance athlete in a 24-hour ultracycling race R. Bescós, F. A. Rodríguez, X. Iglesias, A. Benítez, M. Marina, J. M. Padullés, P. Torrado, J. Vázquez, and B. Knechtle 129 The de novo diagnosis of systemic lupus erythematosus and lupus nephritis during pregnancy Volume 25, Number 2 • April 2012 Baylor University Medical Center, Dallas, Texas Electrocardiographic Report 159 Irregular cardiac rhythm in a woman with asthma T. Patel, A. Fenves, and G. Colbert Tributes 165 Tributes to George Boswell, MD P. Neubach and W. Snoots Book Reviews 166 Amyloidosis: Diagnosis and Treatment Reviewed by S. A. Gurevitz and M. J. Stone The Greater Journey 132 A rare case of intraneural ganglion cyst involving the tibial nerve Reviewed by Fran Roberts Willard P. Patel and W. G. Schucany 136 Jorge Felix Saucedo, MD, MBA: a conversation with the editor on optimizing antiplatelet and antithrombotic therapy in patients having percutaneous coronary intervention for acute coronary syndromes From the Editor 174 Facts and ideas from anywhere William C. Roberts Miscellany J. F. Saucedo and W. C. Roberts 139 Darwinian natural selection: its enduring explanatory power Gregory G. Dimijian Pages 113–204 Departments Baylor Sammons Cancer Center at Dallas Site Tumor Conference 152 Extraadrenal pheochromocytoma and vagal paraganglioma A. W. Jennings, J. T. Preskitt, and R. D. Vallera To access Baylor’s physicians, clinical services, or educational programs, contact the Baylor Physician ConsultLine: 1-800-9BAYLOR (1-800-922-9567) Dermatology Report 155 Widespread dermal ulcerations and bullae J. Wofford, M. Patel, A. Readinger, and A. Menter 114 118 128 148 158 160 164 169 Clinical research studies enrolling patients 2011 Ralph R. Tompsett Writing Award winner Selected quotes Baylor news Avocations: Photograph by Dr. Solis Acknowledgment of contributors In memoriam Reader comments: “Irreducible complexity” or “delightful challenge”? (C. R. Boland); Further discussion on Darwinism (D. Hansen, C. E. Jones, J. M. Guileyardo, J. Hoppenstein); Author response (J. A. Kuhn); Kudos (J. Hoppenstein) 184 Selected published abstracts of Baylor researchers 188 2011 publications of the Baylor Health Care System medical and scientific staff www.BaylorHealth.edu/Proceedings Indexed in PubMed, with full text available through PubMed Central Baylor University Medical Center Proceedings The peer-reviewed journal of Baylor Health Care System, Dallas, Texas Volume 25, Number 2 • April 2012 Editor in Chief William C. Roberts, MD Associate Editor Michael A. E. Ramsay, MD Associate Editor Andrew Z. Fenves, MD Founding Editor George J. Race, MD, PhD Bradley R. Grimsley, MD Carson Harrod, PhD H. A. Tillmann Hein, MD Daragh Heitzman, MD Priscilla A. Hollander, MD, PhD Ronald C. Jones, MD Göran B. Klintmalm, MD, PhD Sally M. Knox, MD John R. Krause, MD Joseph A. Kuhn, MD Zelig H. Lieberman, MD Jay D. Mabrey, MD Michael J. Mack, MD Gavin M. Melmed, JD, MBA, MD Robert G. Mennel, MD Dan M. Meyer, MD Michael Opatowsky, MD Joyce A. O’Shaughnessy, MD Dighton C. Packard, MD Gregory J. Pearl, MD Robert P. Perrillo, MD Daniel E. Polter, MD Irving D. Prengler, MD Chet R. Rees, MD Randall L. Rosenblatt, MD Lawrence R. Schiller, MD W. Greg Schucany, MD Jeffrey M. Schussler, MD S. Michelle Shiller, DO Craig T. Shoemaker, MD Michael J. Smerud, MD Marvin J. Stone, MD C. Allen Stringer Jr., MD William L. Sutker, MD Gary L. Tunell, MD Harold C. Urschel Jr., MD Beverlee Warren, MA, MS Wilson Weatherford, MD Lawrence S. Weprin, MD F. David Winter Jr., MD Larry M. Wolford, DMD Scott W. Yates, MD, MBA, MS [email protected] Editorial Board Jenny Adams, PhD W. Mark Armstrong, MD Joanne L. Blum, MD, PhD C. Richard Boland Jr., MD Jennifer Clay Cather, MD Evangeline T. Cayton, MD Barry Cooper, MD R. D. Dignan, MD Gregory G. Dimijian, MD Michael Emmett, MD Giovanni Filardo, PhD Adrian E. Flatt, MD Dennis R. Gable, MD D. Luke Glancy, MD L. Michael Goldstein, MD Paul A. Grayburn, MD Editorial Staff Managing Editor Cynthia D. Orticio, MA, ELS Administrative Liaison JaNeene Jones, RN, FACHE Residents/Fellows Wende N. Gibbs, MD Brittany D. Shoemake, MD Victoria M. Stager, MD Anumeha Tandon, MD Design and Production Aptara, Inc. [email protected] Baylor University Medical Center Proceedings (ISSN 0899-8280), a peer-reviewed journal, is published quarterly (January, April, July, and October). Proceedings is indexed in PubMed and CINAHL; the full text of articles is available both at www.BaylorHealth.edu/Proceedings and www.pubmedcentral.nih.gov. The journal’s mission is to communicate information about the research and clinical activities, continuing education, philosophy, and history of the Baylor Health Care System. Guidelines for authors are available at http://www.baylorhealth.edu/Research/ Proceedings/SubmitaManuscript/Pages/default.aspx. Funding for the journal is provided by the following: Advertising is accepted. Acceptance of advertising does not imply endorsement by Baylor University Medical Center. For information, contact Cindy Orticio at [email protected]. • Baylor Health Care System Foundation • Helen Buchanan and Stanley Joseph Seeger Endowment for Surgery Funding is also provided by donations made by the medical staff and subscribers. These donations are acknowledged each year in the April issue. For more information on supporting Proceedings and Baylor Health Care System with charitable gifts and bequests, please call the Foundation at 214-820-3136. Statements and opinions expressed in Proceedings are those of the authors and not necessarily those of Baylor Health Care System or its board of trustees. Articles and reader comments should be e-mailed to cynthiao@ BaylorHealth.edu. Subscriptions are offered free to libraries, physicians affiliated with Baylor, and other interested physicians and health care professionals. To add or remove your name from the mailing list, call 214-820-9996 or e-mail Cynthia.Orticio@ BaylorHealth.edu. POSTMASTER: Send address changes to Baylor Scientific Publications Office, 3500 Gaston Avenue, Dallas, Texas 75246. Permission is granted to students and teachers to copy material herein for educational purposes. Authors also have permission to reproduce their own articles. Written permission is required for other uses. Copyright © 2012, Baylor University Medical Center. All rights reserved. Printed in the United States of America on acid-free paper. Press date: March 8, 2012. To access Baylor’s physicians, clinical services, or educational programs, contact the Baylor Physician ConsultLine: 1-800-9BAYLOR (1-800-922-9567). 113 Clinical research studies enrolling patients through Baylor Research Institute Currently, Baylor Research Institute is conducting more than 800 research projects. Studies open to enrollment are listed in the Table. To learn more about a study or to enroll patients, please call or e-mail the contact person listed. Table. Clinical research studies conducted through Baylor Research Institute that are enrolling patients Research area Specific disease/condition Contact information (name, phone number, and e-mail address) Chronic obstructive pulmonary disease, asthma (adult) Idiopathic pulmonary fibrosis Breast, ovarian, endometrial, prostate, brain, lung, bladder, colorectal, pancreatic, and head and neck cancer; hematological malignancies, leukemia, multiple myeloma, nonHodgkin’s lymphoma; melanoma vaccine Type 1 and type 2 diabetes, neuropathy, cardiovascular events, inhaled insulin Pancreatic islet transplantation Rose Boehm, RRT, RCP, AE-C Randall Rosenblatt, MD 214-820-9772 [email protected] Grace Rivera 214-818-8472 [email protected] Erica Lusk 214-818-7074 [email protected] Transplant Department 214-820-2050 Crohn’s disease Dian Johnson, MSN, RN 214-818-9687 [email protected] Merielle Boatman 214-820-2273 [email protected] Deborah Devlin 817-922-2575 Claudia Mattil 214-820-7548 [email protected] Liver disease Cheryl Sandbach, RN 214-820-6267 Bryan King, LVN Cheryl Sandbach, RN 214-823-2533 [email protected] 214-820-6267 [email protected] Nancy Hawkins, RN 214-818-9688 [email protected] Neurosurgery Prenatal/amniocentesis HIV/AIDS Hepatitis C, hepatitis B Homocysteine and kidney disease, dialysis fistulas, urine/protein disorders in cancer patients Stroke Multiple sclerosis Cerebral aneurysms Pregnancy Rheumatology (9900 N. Central Expressway) Rheumatoid arthritis, psoriatic arthritis, lupus, gout Spine Vertebral compression fractures Bone marrow, blood stem cells Solid organs Spinal cord injury Obesity Dion Graybeal, MD Annette Okai, MD Kennith Layton, MD Mara Vecchio John J. Cush, MD Kathryn Dao, MD Kennith Layton, MD Grace Rivera Cheryl Sandbach, RN Ann Marie Warren, PhD Erica Lusk 214-820-4561 214-820-4655 214-820-4745 214-820-9626 214-987-1253 214-987-1249 214-820-4745 214-818-8472 214-820-6267 214-820-4460 214-818-7074 Asthma and pulmonary disease Cancer Diabetes Gastroenterology Heart and vascular disease (Dallas campus) Heart and vascular disease (Fort Worth campus) Heart and vascular disease (Plano campus) Hepatology Infectious disease Nephrology Neurology Transplantation Trauma Weight management Aneurysms, coronary artery disease, hypertension, intermittent claudication, heart attack, heart disease, cholesterol disorders, heart valves, prevention of pain post procedures, stem cells, critical limb ischemia, repair of AAA, TAA, and dissections with endografts Heart attack, atrial fibrillation, carotid artery stenting Valve repair/replacement, coronary artery disease, arrhythmias, aneurysm repair, peripheral vascular disease, limb ischemia 214-820-6856 [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] Baylor Research Institute is dedicated to providing the support and tools needed for successful clinical research. To learn more about Baylor Research Institute, please contact Kristine Hughes at 214-820-7556 or [email protected]. 114 Proc (Bayl Univ Med Cent) 2012;25(2):114 Unilateral absence of a pulmonary artery: a rare disorder with variable presentation David W. Reading, MS, and Umesh Oza, MD Unilateral absence of a pulmonary artery (UAPA) is a rare condition with an estimated prevalence of 1 in 200,000 young adults. Most commonly, UAPA occurs in conjunction with cardiovascular abnormalities such as tetralogy of Fallot or cardiac septal defects, but it can also occur in an isolated manner. Patients with isolated UAPA can remain asymptomatic into late adulthood but usually report symptoms such as dyspnea or chest pain or suffer from hemoptysis or recurrent infections. Diagnosis can be difficult due to the rarity of the condition and its nonspecific presentation. We present a case of a 61-year-old man who presented for lung transplant evaluation and was found to have UAPA. Typical findings on chest radiograph, strategies for diagnosis, and available treatments are discussed. CASE PRESENTATION An obese 61-year-old man with a body mass index of 38 kg/m2 was referred to Baylor University Medical Center at Dallas with a diagnosis of a restrictive lung disease of unknown etiology. The patient reported a long history of exercise intolerance, recently complicated by dyspnea at rest. He also had hypertension, hypercholesterolemia, and diabetes mellitus type 2, but denied past or present use of tobacco products. A computed tomography (CT) pulmonary angiogram showed asymmetric lung fields, with a left hemithorax that was smaller than the right. The left lung also appeared hyperlucent, while the right lung appeared plethoric. The left hemidiaphragm was elevated. Cross-sectional CT images demonstrated a hypoplastic left lung and an absent left main pulmonary artery. No evidence of embolic occlusion or surgical changes was present. Distal intrapulmonary branches of the left pulmonary artery were visible, and some of these vessels could be seen communicating across the pleura with bronchial and intercostal vessels arising from the distal thoracic aorta (Figures 1–4). Ventilation perfusion scanning demonstrated absent perfusion of the left lung (Figure 5). Perfusion to the right lung was normal. The Xenon-133 wash-in images revealed decreased left lung volume and homogenous filling of the right lung (Figure 6). There was no abnormal Xenon-133 retention during the washout phase. Based on the Xenon-133 early wash-in phase, the right lung contributed 68% to ventilation, while the left lung Proc (Bayl Univ Med Cent) 2012;25(2):115–118 Figure 1. Coronal CT of the chest with intravenous contrast in a lung window shows a hypovascular and hypoplastic left lung. The left hemidiaphragm is elevated. Figure 2. Transaxial CT of the chest with intravenous contrast in a soft tissue window shows an absent left pulmonary artery. The main pulmonary artery measures 3.7 cm, compatible with pulmonary hypertension. The left lung is hypoplastic, and the mediastinum is shifted to the left. There is no evidence of chronic pulmonary embolism, obstructing malignancy, or surgical changes. There are large extrapleural collateral vessels in the left posterior hemithorax. From the University of Texas Southwestern Medical School at Dallas (Reading) and the Department of Radiology, Baylor University Medical Center at Dallas (Oza). Corresponding author: Umesh Oza, MD, Department of Radiology, Baylor University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, Texas 75246 (e-mail: [email protected]). 115 Figure 3. Coronal CT of the chest with intravenous contrast in a soft tissue window shows large, tortuous intercostal arteries in the patient’s left chest wall. Figure 6. Xenon-133 wash-in images show decreased left lung volume and homogenous filling of the right lung. There was no abnormal Xenon-133 retention during the washout phase (not shown). The patient’s pulmonologist was informed of the diagnosis of unilateral absence of a pulmonary artery (UAPA), and subsequent examinations were scheduled. Unfortunately, the patient failed to report for testing and was ultimately lost to follow-up. DISCUSSION UAPA is a rare condition, with an estimated prevalence of 1 in 200,000 young adults (1). Most commonly, UAPA occurs in conjunction with cardiovascular abnormalities such as tetralogy of Fallot or cardiac septal defects, but it can also occur in an isolated manner (1, 2). Isolated UAPA involves the right lung in about two thirds of cases (3). Due to embryologic Figure 4. Transaxial CT of the chest with intravenous contrast in a lung window relationships, UAPA commonly occurs on the side of the chest shows distal branches of the left pulmonary artery that inappropriately comopposite the aortic arch (although that was not the case in our municate across the pleura with intercostal arteries. Once again, no proximal patient) (4). The exact embryologic cause of UAPA is a matter left pulmonary artery is noted. The left lung is hypoattenuating compared to a of debate and is likely different in left- vs. right-sided UAPA. In plethoric right lung. both cases, however, altered development of a sixth aortic arch segment is thought to result in a ductal origin to a pulmonary artery that leads to the proximal interruption of that vessel when the ductal tissue regresses at the time of birth (4). Distal intrapulmonary branches of the affected artery usually remain intact and can be supplied by collateral vessels from bronchial, intercostal, internal mammary, subdiaphragmatic, subclavian, or even coronary arteries (5, 6). Patients with isolated UAPA can Figure 5. Anterior and posterior technetium 99m macroaggregate albumin perfusion images with a segmental reference show the complete absence of perfusion to the left lung. Perfusion to the right lung is normal without present in a variety of ways. A 2002 evidence of segmental defect. review of 108 cases of UAPA revealed a median age of presentation of 14 contributed 32%. Based on the geometric mean analysis of years (3). The combination of chest pain, pleural effusion, anterior and posterior images, the right lung received 100% of and recurrent infections was present in 37% of patients, while pulmonary perfusion. dyspnea or exercise intolerance was present in 40% of patients. 116 Baylor University Medical Center Proceedings Volume 25, Number 2 Pulmonary hypertension was found in 44% of patients that were tested for the disorder. Hemoptysis occurred in about 20% of patients, and high-altitude pulmonary edema was seen in approximately 10% of patients (3). Seven deaths were noted in the case series and included mortality from massive pulmonary hemorrhage, right heart failure, respiratory failure, pulmonary hypertension, and high-altitude pulmonary edema. Only 14 of 108 patients with isolated UAPA were asymptomatic at the time of their diagnosis and throughout variable follow-up (3). At the time of our patient’s presentation, he reported dyspnea at rest and exercise intolerance. UAPA could definitely be a cause of his dyspnea, and it should be noted that his left lung received 32% of total ventilation on his ventilation perfusion scan but no detectable perfusion, resulting in a large amount of dead space. Pulmonary hypertension could also be a cause for the patient’s dyspnea, and indeed, the patient’s main pulmonary artery was enlarged, measuring 3.7 cm on his CT pulmonary angiogram (Figure 2). However, that study showed no signs of secondary right heart strain. An echocardiogram was ordered but not performed before the patient was lost to follow-up. Other possible causes of dyspnea and exercise intolerance include obesity and deconditioning. Mechanisms have been proposed for many of the common sequelae of UAPA. Pulmonary hypertension may result from blood flow directed away from the absent pulmonary artery to the remaining pulmonary artery. Increased blood flow in the contralateral pulmonary artery leads to shear stress on the endothelium, which results in the release of vasoconstrictive compounds such as endothelin (7). Chronic vasoconstriction of the pulmonary arterioles may lead to remodeling that will cause increased resistance in the pulmonary vasculature and pulmonary hypertension (7). Patients who have developed pulmonary hypertension as a result of UAPA may present with symptoms such as shortness of breath, weight gain, and poor exercise tolerance. Signs of pulmonary hypertension detected on exam may include a loud P2, tricuspid insufficiency, or a parasternal heave. If the pulmonary hypertension has led to right heart failure, jugular venous distension, peripheral edema, hepatojugular reflux, and ascites may also be present. The etiology of recurrent infections observed in patients with UAPA is likely multifactorial. Lack of arterial blood flow to the affected lung may result in poor delivery of inflammatory cells to sites of inflammation and impair ciliary function (5). In addition, poor blood flow to the affected lung may result in alveolar hypocapnia, leading to secondary bronchoconstriction and mucous trapping (5). Chronic infection can lead to bronchiectasis in some patients (5, 8). Hemoptysis is a potentially serious complication of UAPA. Hemoptysis appears to be caused by large collateral circulations that subject venous systems to unusually high pressures. While hemoptysis can be chronic and self-limited, cases of massive hemoptysis have been reported in the literature (5, 9, 10). Diagnosing UAPA can be difficult, but important clues are present in chest radiographs. The chest radiograph of patients with UAPA typically shows asymmetric lung fields, with an April 2012 ipsilateral small hemithorax holding a hyperlucent lung (1, 8). The mediastinum will be shifted towards the affected side, and the hilar vasculature on that side will be absent or greatly diminished. The ipsilateral hemidiaphragm may be elevated. Extensive transpleural collateral circulation in the apices of the lung may mimic tuberculosis by producing an appearance known as pulmonary pseudofibrosis (1). The contralateral lung may be hyperinflated beyond the midline and appear plethoric due to increased blood flow. When suspicious findings are noted on a chest radiograph, the diagnosis of UAPA can be definitively made by CT, magnetic resonance imaging (MRI), or transthoracic echocardiogram. On cross-sectional imaging, the absent pulmonary artery will typically terminate within 1 cm of its expected origin from the main pulmonary artery (1). Other findings that may be noted on CT or MRI include intact peripheral branches of the pulmonary artery, variable collateral circulation, mosaic parenchymal changes, and bronchiectasis secondary to recurrent infections (1, 5, 8). Transthoracic echocardiogram can also be used to diagnose UAPA and is advantageous because the examiner can look for coexisting cardiac malformations at the same time. Angiography is considered the gold standard for the diagnosis of UAPA but is invasive and typically unnecessary, unless it is being used as a preoperative test for a patient who has developed hemoptysis or severe infection (8). Ventilation perfusion scanning is not necessary for the diagnosis of UAPA, but if done will show normal or diffusely diminished Xenon-127 uptake during the wash-in and equilibrium phase, coupled with absent or greatly diminished perfusion in the affected lung (1). Xenon washout typically shows no delay (1). There is currently no consensus concerning treatment of patients with UAPA. Some authors have recommended using serial echocardiography to monitor asymptomatic adults for the development of pulmonary hypertension (11). Patients who develop pulmonary hypertension can be treated medically with vasodilator therapy (3, 7). Alternatively, revascularization of peripheral branches of the affected pulmonary artery to the pulmonary hilum can be attempted, and there are reports of successful revascularization procedures, mostly in the pediatric population (2, 12, 13). Hemoptysis may be treated with embolization, lobectomy, or pneumonectomy (9, 10). Embolization is a relatively safe procedure with few side effects and is a viable alternative to pneumonectomy in patients experiencing hemoptysis (9). Severe infections may require lobectomy or pneumonectomy, and any pulmonary surgery in a patient with UAPA may be complicated by the presence of systemic collaterals (5). 1. 2. 3. Bouros D, Pare P, Panagou P, Tsintiris K, Siafakas N. The varied manifestation of pulmonary artery agenesis in adulthood. Chest 1995;108(3):670– 676. Presbitero P, Bull C, Haworth SG, de Leval MR. Absent or occult pulmonary artery. Br Heart J 1984;52(2):178–185. Ten Harkel AD, Blom NA, Ottenkamp J. Isolated unilateral absence of a pulmonary artery: a case report and review of the literature. Chest 2002;122(4):1471–1477. Unilateral absence of a pulmonary artery: a rare disorder with variable presentation 117 4. 5. 6. 7. 8. Pfefferkorn JR, Löser H, Pech G, Toussaint R, Hilgenberg F. Absent pulmonary artery. A hint to its embryogenesis. Pediatr Cardiol 1982;3(4):283–286. Kadir IS, Thekudan J, Dheodar A, Jones MT, Carroll KB. Congenital unilateral pulmonary artery agenesis and aspergilloma. Ann Thorac Surg 2002;74(6):2169–2171. Bockeria LA, Makhachev OA, Khiriev TK, Abramyan MA. Congenital isolated unilateral absence of pulmonary artery and variants of collateral blood supply of the ipsilateral lung. Interact Cardiovasc Thorac Surg 2011;12(3):509–510. Shostak E, Sarwar A. A 50-year-old woman with dyspnea, lower extremity edema, and volume loss of the right hemithorax. Chest 2009;136(2): 628–632. Griffin N, Mansfield L, Redmond KC, Dusmet M, Goldstraw P, Mittal TK, Padley S. Imaging features of isolated unilateral pulmonary artery 9. 10. 11. 12. 13. agenesis presenting in adulthood: a review of four cases. Clin Radiol 2007;62(3):238–244. Reñé M, Sans J, Dominguez J, Sancho C, Valldeperas J. Unilateral pulmonary artery agenesis presenting with hemoptysis: treatment by embolization of systemic collaterals. Cardiovasc Intervent Radiol 1995;18(4):251–254. Bekoe S, Pellegrini RV, DiMarco RF Jr, Grant KJ, Woelfel GF. Pneumonectomy for unremitting hemoptysis in unilateral absence of pulmonary artery. Ann Thorac Surg 1993;55(6):1553–1554. Turner DR, Vincent JA, Epstein ML. Isolated right pulmonary artery discontinuity. Images Paediatr Cardiol 2000;4:24–30. Welch K, Hanley F, Johnston T, Cailes C, Shah MJ. Isolated unilateral absence of right proximal pulmonary artery: surgical repair and follow-up. Ann Thorac Surg 2005;79(4):1399–1402. Toews WH, Pappas G. Surgical management of absent right pulmonary artery with associated pulmonary hypertension. Chest 1983;84(4): 497–499. 2011 Ralph R. Tompsett Writing Award winner D r. William C. Roberts, editor in chief, announced that Teresa R. Kroeker, MD, is the winner of the 11th Ralph R. Tompsett Writing Award. Dr. Kroeker published two articles in 2011: “Carotid resection and reconstruction associated with treatment of head and neck cancer” with John C. O’Brien, MD, and “Parathyroid adenoma on the ipsilateral side of thyroid hemiagenesis,” with Kevin M. Stancoven, MD, and John T. Preskitt, MD. Dr. Kroeker completed her surgical residency at Baylor University Medical Center at Dallas in June 2011 and is currently a fellow at Mount Sinai Hospital in Toronto. The Proceedings staff thanks all the residents and fellows who were first authors on articles in 2011: 118 Erin M. Bowman, MD, Adam M. Falcone, MD, Poorya Fazel, MD, Justin M. Goldfarb, DO, Stacy A. Gurevitz, MD, Peter T. W. Kim, MD, Vincent C. Kuo, MD, Steven M. Lilly, MD, Thomas H. Louis, MD, Jepsin Maliyil, MD, Janneth Momiy, MD, M. Jordan Ray, MD, Syed Abdul Sarmast, MD, Brian G. Schwartz, MD, Anumeha Tandon, MD, Vibha Thomas, MD, Jason Wachsmann, MD, and Prescilla B. Wood, MD. The Ralph R. Tompsett Writing Award was initiated in 1999 to encourage medical residents and fellows to write for the journal and to acknowledge outstanding contributions. The award is named in honor of Dr. Tompsett, who was the chief of internal medicine at Baylor Dallas from 1957 to 1979. Baylor University Medical Center Proceedings Volume 25, Number 2 Hepatitis E infection Vincent C. Kuo, MD H epatitis E usually presents as a self-limiting viral hepatitis. It is not commonly seen in the United States and is more prevalent in endemic areas. Signs and symptoms are similar to those of other acute viral hepatitis infections. Here a case is presented of a man who recently returned from India and was found to have acute viral hepatitis E infection. CASE PRESENTATION A 63-year-old Indian man presented to the emergency department with fever, nausea, chills, and generalized abdominal pain that had been present for 2 weeks. The patient had been in India for the past 3 months and began to feel ill during the last week of his visit. He was seen by a local physician and was found to have abnormal liver function tests and was treated with sparfloxacin and silibinin. Upon his return, the patient’s symptoms persisted, with fevers up to 102°F, and he began to have emesis. He was admitted for further workup. The patient had a past medical history of allergic rhinitis and gastroesophageal reflux disease. He took omeprazole for his reflux and had taken the sparfloxacin and silibinin given to him while in India. He had no known drug allergies. He did have a significant drinking history: in addition to having 3 to 4 drinks of brandy per day, he engaged in heavy binge drinking during his trip to India. He did not smoke or have a history of illicit drug use. The patient had a low-grade temperature of 100°F on admission with normal blood pressure and heart rate. On physical examination, he had significant scleral icterus. His abdomen was soft and mildly distended with no appreciable ascites or hepatosplenomegaly. He had some generalized discomfort to deep palpation diffusely but no guarding or rebound tenderness. He had no spider angiomas, gynecomastia, or asterixis. His admission laboratory values were significant for a total bilirubin of 9.4 mg/dL with a direct bilirubin of 6.5 mg/dL, alkaline phosphatase of 198 U/L, aspartate aminotransferase (AST) of 560 U/L, and alanine aminotransferase (ALT) of 303 U/L. His complete blood count showed a white blood cell count of 11.8 K/uL, hemoglobin of 13.1 g/dL, hematocrit of 37.1%, and platelet count of 331 K/uL. Prothrombin time was 14.4 seconds with an international normalized ratio of 1.4. Viral hepatitis serologies revealed IgG antibodies to hepatitis A virus, a positive hepatitis B surface antibody with negative Proc (Bayl Univ Med Cent) 2012;25(2):119–120 core antibody, and a negative hepatitis C antibody and polymerase chain reaction (PCR) test. The patient was found to have positive hepatitis E IgM and IgG antibodies in a stool sample and was also positive for hepatitis E RNA on PCR. Abdominal Doppler sonography revealed patency of all hepatic vessels, a normal liver appearance, and no ascites. The patient was diagnosed with acute hepatitis secondary to hepatitis E virus and was treated with conservative measures in the hospital. He never developed any signs of fulminant hepatic failure and, at the time of discharge, his liver enzymes were normalizing and symptoms were improving. DISCUSSION Hepatitis E virus is a single-stranded RNA virus in the family Herpesviridae (1). The first documented infection was in 1955 in New Delhi, India, and the highest incidence of infection is in Asia, Africa, Central America, and the Middle East (2, 3). Hepatitis E is enterically transmitted, spread by contaminated water in endemic areas. The highest attack rates occur in adults between the ages of 15 and 40 (4). Most cases in developed nations follow travel to areas that are endemic for the virus (5). In the United States, serologic evidence for hepatitis E has been as high as 21%, but most individuals have no clinical signs of acute hepatitis infection. One possibility for this discrepancy is that in the United States, the exposure is due to the less virulent genotype 3 of the hepatitis E virus (6). This has been linked to swine and is considered to be a zoonotic infection. Hepatitis E infection presents similarly to other forms of acute viral hepatitis. Patients may be jaundiced from cholestasis and have generalized malaise, anorexia, nausea, vomiting, abdominal pain, and fever. The incubation period for hepatitis E infection can range from 15 to 60 days. If fulminant hepatitis occurs, the fatality rate ranges from 0.5% to 3%. Laboratory values usually reflect an elevated bilirubin, AST, and ALT. These levels can remain elevated up to 6 weeks after onset of illness (7–9). From the Department of Internal Medicine, Baylor University Medical Center at Dallas. Corresponding author: Vincent Kuo, MD, Resident, Department of Internal Medicine, Baylor University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, Texas 75246 (email:[email protected]). 119 Certain patient populations can have more adverse clinical courses or are at higher risk for hepatitis E infection. It is known that pregnancy carries a higher risk of fulminant hepatic failure for reasons not well understood. Patients who are immunosuppressed appear to have a higher incidence of infection and can evolve to chronic hepatitis E infection, which has otherwise not been described (10–12). Hepatitis E infection is best diagnosed by detection of viral RNA by PCR or by IgM antibodies to the virus found in serum or stool samples (13). The incubation period after exposure is 4 to 5 weeks, and patients can have persistent viremia for up to 4 months (14). IgM antibodies appear in the early phase and gradually disappear over several months. The IgG antibodies appear after the IgM response and in some case reports can persist for as long as 14 years (15). Treatment of acute hepatitis E is supportive and involves watching for signs of hepatic failure. There have been case reports of using ribavirin as a potential treatment for acute hepatitis E infection and even chronic infection (16). Pegylated interferon has also been shown to be successful in treating hepatitis E infection in some liver or kidney transplant patients (17, 18). In certain settings, a hepatitis E vaccine can be used to prevent infection (19). 1. Koonin EV, Gorbalenya AE, Purdy MA, Rozanov MN, Reyes GR, Bradley DW. Computer-assisted assignment of functional domains in the nonstructural polyprotein of hepatitis E virus: delineation of an additional group of positive-strand RNA plant and animal viruses. Proc Natl Acad Sci U S A 1992;89(17):8259–8263. 2. Gupta DN, Smetana HF. Th e histopathology of viral hepatitis as seen in the Delhi epidemic (1955–56). Indian J Med Res 1957;45 (Suppl):101–113. 3. Emerson SU, Purcell RH. Running like water—the omnipresence of hepatitis E. N Engl J Med 2004;351(23):2367–2368. 4. Gust ID, Purcell RH. Report of a workshop: waterborne non-A, non-B hepatitis. J Infect Dis 1987;156(4):630–635. 5. Centers for Disease Control and Prevention (CDC). Hepatitis E among U.S. travelers, 1989–1992. MMWR Morb Mortal Wkly Rep 1993;42(1): 1–4. 6. Kuniholm MH, Purcell RH, McQuillan GM, Engle RE, Wasley A, Nelson KE. Epidemiology of hepatitis E virus in the United States: results from the Third National Health and Nutrition Examination Survey, 1988–1994. J Infect Dis 2009;200(1):48–56. 120 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. Favorov MO, Fields HA, Purdy MA, Yashina TL, Aleksandrov AG, Alter MJ, Yarasheva DM, Bradley DW, Margolis HS. Serologic identification of hepatitis E virus infections in epidemic and endemic settings. J Med Virol 1992;36(4):246–250. Bryan JP, Tsarev SA, Iqbal M, Ticehurst J, Emerson S, Ahmed A, Duncan J, Rafiqui AR, Malik IA, Purcell RH, et al. Epidemic hepatitis E in Pakistan: patterns of serologic response and evidence that antibody to hepatitis E virus protects against disease. J Infect Dis 1994;170(3):517–521. Centers for Disease Control (CDC). Enterically transmitted non-A, nonB hepatitis—East Africa. MMWR Morb Mortal Wkly Rep 1987;36(16): 241–244. Khuroo MS, Teli MR, Skidmore S, Sofi MA, Khuroo MI. Incidence and severity of viral hepatitis in pregnancy. Am J Med 1981;70(2):252–255. Kamar N, Garrouste C, Haagsma EB, Garrigue V, Pischke S, Chauvet C, Dumortier J, Cannesson A, Cassuto-Viguier E, Thervet E, Conti F, Lebray P, Dalton HR, Santella R, Kanaan N, Essig M, Mousson C, Radenne S, Roque-Afonso AM, Izopet J, Rostaing L. Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants. Gastroenterology 2011;140(5):1481–1489. Ollier L, Tieulie N, Sanderson F, Heudier P, Giordanengo V, Fuzibet JG, Nicand E. Chronic hepatitis after hepatitis E virus infection in a patient with non-Hodgkin lymphoma taking rituximab. Ann Intern Med 2009;150(6):430–431. Takahashi M, Kusakai S, Mizuo H, Suzuki K, Fujimura K, Masuko K, Sugai Y, Aikawa T, Nishizawa T, Okamoto H. Simultaneous detection of immunoglobulin A (IgA) and IgM antibodies against hepatitis E virus (HEV) is highly specific for diagnosis of acute HEV infection. J Clin Microbiol 2005;43(1):49–56. Koshy A, Grover S, Hyams KC, Shabrawy MA, Pacsa A, al-Nakib B, Zaidi SA, al-Anezi AA, al-Mufti S, Burans J, Carl M, Richards AL. Short-term IgM and IgG antibody responses to hepatitis E virus infection. Scand J Infect Dis 1996;28(5):439–441. Khuroo MS, Kamili S, Dar MY, Moecklii R, Jameel S. Hepatitis E and long-term antibody status. Lancet 1993;341(8856):1355. Mallet V, Nicand E, Sultanik P, Chakvetadze C, Tessé S, Thervet E, Mouthon L, Sogni P, Pol S. Brief communication: case reports of ribavirin treatment for chronic hepatitis E. Ann Intern Med 2010;153(2):85–89. Kamar N, Abravanel F, Garrouste C, Cardeau-Desangles I, Mansuy JM, Weclawiak H, Izopet J, Rostaing L. Three-month pegylated interferonalpha-2a therapy for chronic hepatitis E virus infection in a haemodialysis patient. Nephrol Dial Transplant 2010;25(8):2792–2795. Haagsma EB, Riezebos-Brilman A, van den Berg AP, Porte RJ, Niesters HG. Treatment of chronic hepatitis E in liver transplant recipients with pegylated interferon alpha-2b. Liver Transpl 2010;16(4):474–477. Shrestha MP, Scott RM, Joshi DM, Mammen MP Jr, Thapa GB, Thapa N, Myint KS, Fourneau M, Kuschner RA, Shrestha SK, David MP, Seriwatana J, Vaughn DW, Safary A, Endy TP, Innis BL. Safety and efficacy of a recombinant hepatitis E vaccine. N Engl J Med 2007;356(9):895–903. Baylor University Medical Center Proceedings Volume 25, Number 2 Fatal aortic rupture from nonpenetrating chest trauma Mina Mecheal Benjamin, MD, and William Clifford Roberts, MD A 22-year-old man died following a side impact blow in an automobile accident. Necropsy showed a large tear in the posterior wall of the aorta approximately 12 mm distal to the insertion of ligamentum arteriosum (Figures 1 and 2). Subadventitial hemorrhage was prominent in the descending thoracic aorta. The left pleural space contained large quantities of blood. Traumatic aortic rupture is the second most common cause of death in victims of blunt chest trauma from motor vehicle accidents (1–3). Death usually (85%) occurs at the crash scene (2–4). Aortic rupture was responsible for about 15% of the deaths due to automobile accidents until seat belts and air bags were introduced. Seat belts seem to be more effective than air bags in reducing traumatic aortic injury (TAI) after blunt frontal motor vehicle crashes (5). Data from the National Automotive Sampling System Crashworthiness Data System between 1993 and 1998 indicated that seat belts reduced the incidence of TAI from 2.66% to 0.49% in crashes where an airbag did not deploy. Airbags alone do not significantly reduce TAI in survivors of frontal motor vehicle crashes. Airbags are more effective in those using seat belts, together reducing the incidence from 0.49% to 0.29% (5). According to Christopher and colleagues Figure 1. Most common pattern of full-thickness aortic rupture in motor vehicle accidents. (6), among patients with TAI, 71% were driAlthough motor vehicle accidents are responsible for about vers, 23% were front-seat passengers, and 6% were back-seat 80% of the cases of TAI (9), other causes include, though much passengers (6). Although most reports focused on frontal impact less frequently, falls from heights and crushes, penetrating crashes, side impact accidents also are a major cause of TAI, especially after the introduction of seat belts (7, 8). The direction of the crash impact was known in 672 patients from the From the Department of Internal Medicine (Benjamin) and the Baylor Heart and National Automotive Sampling System registry between 1998 Vascular Institute (Roberts), Baylor University Medical Center at Dallas. and 2002; among those, 57% were frontal, 18% were at the Corresponding author: William Clifford Roberts, MD, Baylor Heart and Vascular driver’s side, 16% at the passenger’s side, 2% in the rear, and Institute, 3500 Gaston Avenue, Suite H-030, Dallas, Texas 75226 (e-mail: 6% in a nonhorizontal direction (6). [email protected]). Proc (Bayl Univ Med Cent) 2012;25(2):121–123 121 by hyperflexion of the spine leading to sudden chest compression and traction on the aortic isthmus, the point at which the mobile aortic arch meets the fixed proximal descending thoracic aorta (16–22). Another theory suggests a “shoveling effect,” as a lower thoracic impact results in cranial displacement of the mediastinum and torsion of the isthmus (22). The “osseous pinch” theory suggests that the proximal descending aorta is pinched between the sternum, upper ribs, and clavicles anteriorly and the vertebral column posteriorly (23). A less favorable theory suggests a “water-hammer” effect, where an acute rise in aortic pressure exerts maximum stress on the aortic isthmus (20). Rupture of the aorta is of course not the only type of cardiovascular injury from blunt chest trauma: rupture of the right or left ventricular free wall or ventricular septum (24), left ventricular aneurysm (25), and cardiac valve regurgitation (26) are some other cardiac consequences of blunt chest trauma. Fatal cardiac arrest has been reported in a number of drivers of motorized vehicles. Usually, the driver becomes aware of the cardiac arrhythmia, pulls to the side of the road, and is then found pulseless slumped over the steering wheel without a crash into another vehicle or into a stationary structure on the side of the road (27). Figure 2. The site of the aortic tear in the patient described. 1. 2. 3. 4. 5. 6. Figure 3. The mechanism of aortic aneurysm formation in the isthmic area after partial tear of the aorta. (gunshot/stab) wounds, and iatrogenic causes (during interventional catheterization). If the rupture is not transmural, a partial tear may lead to an aneurysm (Figure 3). In about 80% of reported cases of TAI, the site of the aortic tear is at the aortic isthmus between the ostium of the left subclavian artery and the ostium of the third pair of intercostal arteries (10–15). The isthmus segment of the proximal descending aorta is the least mobile portion of the thoracic aorta, being “held down” by its attachment to the pulmonary trunk via the ligamentum arteriosum. A much less common site of rupture is the ascending aorta (12). Several mechanisms have been postulated as to why the isthmus portion is the most common site of aortic rupture. The most widely accepted theory suggests that in nonpenetrating chest traumas, sudden high-velocity deceleration is accompanied 122 7. 8. 9. 10. 11. 12. 13. 14. Parmley LF, Marion WC, Mattingly TW. Nonpenetrating traumatic injury of the heart. Circulation 1958;18(3):371–396. Greendyke RM. Traumatic rupture of aorta; special reference to automobile accidents. JAMA 1966;195(7):527–530. Symbas PN, Tyras DH, Ware RE, DiOrio DA. Traumatic rupture of the aorta. Ann Surg 1973;178(1):6–12. Fabian TC, Richardson JD, Croce MA, Smith JS Jr, Rodman G Jr, Kearney PA, Flynn W, Ney AL, Cone JB, Luchette FA, Wisner DH, Scholten DJ, Beaver BL, Conn AK, Coscia R, Hoyt DB, Morris JA Jr, Harviel JD, Peitzman AB, Bynoe RP, Diamond DL, Wall M, Gates JD, Asensio JA, Enderson BL. Prospective study of blunt aortic injury: Multicenter Trial of the American Association for the Surgery of Trauma. J Trauma 1997;42(3):374–380. Brasel KJ, Quickel R, Yoganandan N, Weigelt JA. Seat belts are more effective than airbags in reducing thoracic aortic injury in frontal motor vehicle crashes. J Trauma 2002;53(2):309–312. Michetti CP, Hanna R, Crandall JR, Fakhry SM. Contemporary analysis of thoracic aortic injury: importance of screening based on crash characteristics. J Trauma 2007;63(1):18–24. Ben-Menachem Y. Rupture of the thoracic aorta by broadside impacts in road traffic and other collisions: further angiographic observations and preliminary autopsy findings. J Trauma 1993;35(3):363–367. Katyal D, McLellan BA, Brenneman FD, Boulanger BR, Sharkey PW, Waddell JP. Lateral impact motor vehicle collisions: significant cause of blunt traumatic rupture of the thoracic aorta. J Trauma 1997;42(5):769– 772. Keen G, Bradbrook RA, McGinn F. Traumatic rupture of the thoracic aorta. Thorax 1969;24(1):25–31. Osborn GR. Findings in 262 fatal accidents. Lancet 1943;2:277–284. Strassman G. Traumatic rupture of the aorta. Am Heart J 1947;33(4):508– 515. Parmley LF, Mattingly TW, Manion WC, Jahnke EJ Jr. Nonpenetrating traumatic injury of the aorta. Circulation 1958;17(6):1086–1101. Zehnder MA. Delayed post-traumatic traumatic rupture of the aorta in a young healthy individual after closed injury: mechanical-etiological considerations. Angiology 1956;7(3):252–267. Spencer FC, Guerin PF, Blake HA, Bahnson HT. A report of fifteen patients with traumatic rupture of the thoracic aorta. J Thorac Cardiovasc Surg 1961;41:1. Baylor University Medical Center Proceedings Volume 25, Number 2 15. Conroy C, Hoyt DB, Eastman AB, Holbrook TL, Pacyna S, Erwin S, Vaughan T, Sise M, Kennedy F, Velky T. Motor vehicle-related cardiac and aortic injuries differ from other thoracic injuries. J Trauma 2007;62(6):1462–1467. 16. Sutorius DJ, Schreiber JT, Helmsworth JA. Traumatic disruption of the thoracic aorta. J Trauma 1973;13(7):583–590. 17. Lundevall J. The mechanism of traumatic rupture of the aorta. Acta Pathol Microbiol Scand 1964;62:34–46. 18. Feczko JD, Lynch L, Pless JE, Clark MA, McClain J, Hawley DA. An autopsy case review of 142 nonpenetrating (blunt) injuries of the aorta. J Trauma 1992;33(6):846–849. 19. Shkrum MJ, McClafferty KJ, Green RN, Nowak ES, Young JG. Mechanisms of aortic injury in fatalities occurring in motor vehicle collisions. J Forensic Sci 1999;44(1):44–56. 20. Giulini SM, Bonardelli S. Post-traumatic lesions of the aortic isthmus. Ann Ital Chir 2009;80(2):89–100. 21. Siegel JH, Belwadi A, Smith JA, Shah C, Yang K. Analysis of the mechanism of lateral impact aortic isthmus disruption in real-life motor vehicle crashes using a computer-based finite element numeric model: with simulation of prevention strategies. J Trauma 2010;68(6):1375–1395. April 2012 22. Siegel JH, Yang KH, Smith JA, Siddiqi SQ, Shah C, Maddali M, Hardy W. Computer simulation and validation of the Archimedes Lever hypothesis as a mechanism for aortic isthmus disruption in a case of lateral impact motor vehicle crash: a Crash Injury Research Engineering Network (CIREN) study. J Trauma 2006;60(5):1072–1082. 23. Crass JR, Cohen AM, Motta AO, Tomashefski JF Jr, Wiesen EJ. A proposed new mechanism of traumatic aortic rupture: the osseous pinch. Radiology 1990;176(3):645–649. 24. Mason DT, Roberts WC. Isolated ventricular septal defect caused by nonpenetrating trauma to the chest. Proc (Bayl Univ Med Cent) 2002;15(4):388–390. 25. Glancy DL, Yarnell P, Roberts WC. Traumatic left ventricular aneurysm. Cardiac thrombosis following aneurysmectomy. Am J Cardiol 1967;20(3):428–433. 26. Chang JP, Chu JJ, Chang CH. Aortic regurgitation due to aortic root intimal tear as a result of blunt chest trauma. J Formos Med Assoc 1990;89(1):41–43. 27. Antecol DH, Roberts WC. Sudden death behind the wheel from natural disease in drivers of four-wheeled motorized vehicles. Am J Cardiol 1990;66(19):1329–1335. Fatal aortic rupture from nonpenetrating chest trauma 123 High energy deficit in an ultraendurance athlete in a 24-hour ultracycling race Raúl Bescós, PhD, Ferran A. Rodríguez, MD, PhD, Xavier Iglesias, PhD, Adolfo Benítez, MSc, Míchel Marina, PhD, Josep M. Padullés, PhD, Priscila Torrado, MSc, Jairo Vázquez, MSc, and Beat Knechtle, MD, PhD This case study examined the nutritional behavior and energy balance in an official finisher of a 24-hour ultracycling race. The food and beverages consumed by the cyclist were continuously weighed and recorded to estimate intake of energy, macronutrients, sodium, and caffeine. In addition, during the race, heart rate was continuously monitored. Energy expenditure was assessed using a heart rate–oxygen uptake regression equation obtained previously from a laboratory test. The athlete (39 years, 175.6 cm, 84.2 kg, maximum oxygen uptake, 64 mL/kg/min) cycled during 22 h 22 min, in which he completed 557.3 km with 8760 m of altitude at an average speed of 25.1 km/h. The average heart rate was 131 beats/min. Carbohydrates were the main macronutrient intake (1102 g, 13.1 g/kg); however, intake was below current recommendations. The consumption of protein and fat was 86 g and 91 g, respectively. He ingested 20.7 L (862 mL/h) of fluids, with sport drinks the main fluid used for hydration. Sodium concentration in relation to total fluid intake was 34.0 mmol/L. Caffeine consumption over the race was 231 mg (2.7 mg/kg). During the race, he expended 15,533 kcal. Total energy intake was 5571 kcal, with 4058 (73%) and 1513 (27%) kcal derived from solids and fluids, respectively. The energy balance resulted in an energy deficit of 9915 kcal. U ltraendurance competitions are held as solo events in an attempt to challenge the limits of human endurance. These events are defined as an endurance performance of more than 6 hours (1). Careful race preparation is mandatory for all competitors, and the successful accomplishment of such a race depends on many factors, among which nutrition is one of the most important. Adequate nutritional intake is important not only to maintain or improve performance but also to avoid disturbances in the athletes’ health. Several studies have reported on the nutritional behavior and demands of cyclists during ultraendurance competitions of several days, such as the Race Across America (2, 3). However, only one case study published in the 1980s has examined the nutritional demands and nutritional behavior of cyclists during events lasting for 24 hours (4). The popularity of these competitions during the past few years has become evident, and with the increase in the number of competitions, information is needed on the nutritional demands in these events (5). Accordingly, the aim of this case study was to describe the nutritional behavior 124 (ingestion of macronutrients, fluids, sodium, and caffeine) and to assess the energy balance of one cyclist during a 24-hour ultracycling race. METHODS Participant and race The physical and physiological characteristics of the cyclist are shown in Table 1. Before testing, the participant was informed of the risks associated with the study and provided written informed consent in accordance with the local ethical committee. The race consisted of completing the greatest possible distance during 24 hours (from 7:00 pm on July 3, 2009, through Table 1. Physical and physiological characteristics of the cyclist Variable Value Age (years) 39 Height (cm) 175.6 Body mass (kg) 84.2 Body mass index (kg/m2) 26.4 Body fat (%) 11.6 VO2max ( mL/kg/min) 64.0 Wmax (watts/kg) 5.5 HRmax (beats/min) 199 VT HR (beats/min) 159 RCP HR (beats/min) 173 VO2max indicates maximum oxygen uptake; Wmax, maximum power output relative to body mass in watts; HRmax, maximum heart rate; VT HR, heart rate at ventilatory threshold; RCP HR, heart rate at respiratory compensation point. From Instituto Nacional de Educación Física de Barcelona, Spain (Bescos, Rodríguez, Iglesias, Benítez, Marina, Padullés, Torrado, Vázquez); and Gesundheitszentrum St. Gallen, St. Gallen, Switzerland (Knechtle). Corresponding author: Raúl Bescós García, Instituto Nacional de Educación Física de Barcelona (INEFC), Av. de l´Estadi s/n, 08038 Barcelona, Spain (e-mail: [email protected]). Proc (Bayl Univ Med Cent) 2012;25(2):124–128 7:00 pm on July 4) on a closed-road circuit that was 3790 m in length and 60 m of elevation per lap. The time and velocity to complete each lap was recorded. During the race, the ambient air temperature was 27.5ºC (range, 24.6–31.0); the relative humidity, 53.9% (range, 33.0–72.0); and the mean velocity of wind, 1.7 m/s (range, 0.6–3.0). Preliminary testing One week before the competition, the athlete reported to a physiology laboratory under controlled conditions (22 ± 1ºC, 40%–60% relative humidity, 760–770 mm Hg) to perform an incremental maximum oxygen uptake (VO2max) test. The test was performed on an electronically braked cycle ergometer (Excalibur Sport, Lode, The Netherlands) modified with clipon pedals. The exercise protocol started at 25 watts and was increased 25 watts every minute until exhaustion. The number of revolutions was individually chosen in the range of 70 to 100 revolutions per minute. During the test, the respiratory response was measured, breath by breath, using a computerized gas analyzer (Cosmed Quark PFT Ergo, Italy). Before the test, the ambient condition was measured and the gas analyzers and inspiratory flowmeter were calibrated using high-precision calibration gases (16.00 ± 0.01% O2 and 5.00 ± 0.01% CO2; Scott Medical Products, USA). After the test, all respiratory data were averaged at 30-second intervals to determine VO2max, taken as the highest average value. In addition, heart rate (HR) was continuously recorded using a portable HR monitor (Polar RS800 SD, Finland). HRmax was defined as the HR at the point of exhaustion. Data collection during the race Within the circuit, all the athletes had a box where they could stop during racing to recover, sleep, eat, and repair bicycle breakdowns. In the other points of the circuit, riders could not receive any assistance. Nutritional data were collected by four trained investigators who remained in the box of the rider, weighing and recording all the food and fluid ingested. Nutritional data were analyzed for nutrient composition using nutritional software (CESNID 1.0, Barcelona University, Spain). Information about the nutritional content of foods not available in the computer program was obtained from the manufacturer. All the food was weighed on a digital scale (Soehnle 8020, Spain) with a precision of 1 g increments up to 1 kg and 2 g between 1 and 2 kg. We divided the input of energy derived from solid and liquid food, classified as products that did not need mastication. In addition, during the competition, HR was continuously monitored, beat by beat, using a portable HR monitor (Polar RS800 SD, Finland) that was properly programmed with gender, age, and weight following the manufacturer’s instruction. Later, all HR data were averaged at 10-second intervals. The linear relationship between HR and VO2 obtained during the laboratory test was used to estimate the oxygen costs and energy expenditure of racing (r2 = 0.988). Taking the average of HR during the competition and the maximal HR obtained during the laboratory test, we calculated the ratio of HRmean/HRmax. April 2012 RESULTS The cyclist successfully completed the race, cycling for 22 h 22 min, in which he completed 557.3 km with 8760 m of altitude at an average speed of 25.1 km/h, finishing in third place. He reported no gastrointestinal disturbances during the race. The average HR during the event was 131 beats/min, with a ratio of HRmean/HRmax of 0.69. He made a total of seven stops lasting 1 h 38 min. During the race, he expended 15,533 kcal of energy, corresponding to 647 kcal/hour. As shown in Table 2, during the event, solid foods provided 73% (4058 kcal) of the total energy, and the remaining 27% (1513 kcal) was provided by fluids such as sport drinks. Carbohydrates were the main macronutrient he ingested (1102 g; 13.1 g/kg). Overall consumption of fluids and sodium during the event was 20.7 L (862 mL/h) and 16,182 mg (34.0 mmol/L), respectively. Fluids comprised 86% (13,878 mg) of the total sodium intake, and solids comprised 14% (2355 mg). During the second half of the event (7–19 h), the cyclist increased consumption of caffeinated drinks, with total caffeine intake of 231 mg (2.7 mg/kg); consumed low amounts of branched chain amino acids in pill form during the rest periods; and ingested one ibuprofen pill after 9 h of competition and two aspirin pills at 18 h. After the event, the athlete lost 2.6 kg of total body mass (prerace, 84.2 kg; postrace, 81.6 kg). A total deficiency of 9915 kcal resulted after the race, so that a higher proportion (64%) of energy was obtained from endogenous fuel stores. DISCUSSION The main finding of this study was the high energy deficit of this cyclist. He ingested only 36% of the energy expended through the event, thus providing the remaining 64% of the energy from endogenous fuel stores. To the best of our knowledge, these data represent the highest energy deficit reported in ultraendurance events of 24 hours or longer. Previous studies showed an energy intake and expenditure ratio between 0.50 and 0.65 (2, 4, 6). However, it is worth mentioning that the method used in this study to estimate energy expenditure (relationship between HR and VO2) has several limitations. For instance, during longer events, HR can be influenced by environmental conditions such as temperature and humidity, which can favor dehydration and an increase of HR without associated changes in VO2 (7). Currently, the method of doubly labeled water is considered the reference method to estimate energy expenditure. Another feasible method to estimate energy expenditure in cycling is the analysis of power output (8). However, neither of these methods was at our disposal during the current study. For this reason and similar to other recent studies (6, 9–11), we estimated energy expenditure using the HR-VO2 method. Compared with the doubly labeled water method, this method is inexpensive and easy to perform. Additionally, monitoring of HR also provides information on the amount of time spent at different levels of exercise intensity, which may also be useful for the assessment of physical activity rather than energy expenditure. Furthermore, it has been reported that energy expenditure estimated using the High energy deficit in an ultraendurance athlete in a 24-hour ultracycling race 125 Table 2. Nutritional analysis of foods and fluids ingested by the cyclist during the event Variable 0–6 h 6–12 h 12–18 h 18–24 h Total – 224 133 200 557 Ingested Solid food (g) Pasta with olive oil Sport bars 252 137 101 65 555 Fruit – 513 – 243 756 Chicken – – – 70 70 Cured ham – – 43 – 43 Bread – – 40 – 40 – – 2292 5714 8006 1806 1830 1279 – 4915 – – – 3080 3080 Fluids (mL) Sport drinks (0% carbohydrate) Sport drinks (1.4% carbohydrate) Sport drinks (7% carbohydrate) Water 1241 932 – – 2173 Caffeinated drinks – 250 330 580 1160 Water in food 8 601 178 365 1152 Juice – 250 – – 250 Supplementation and medication Branched chain amino acids (mg) – – 1000 1500 2500 Ibuprofen (mg) – – 600 – 650 Aspirin (mg) – – – 200 200 Solids 1357 918 675 1108 4058 Fluids 121 211 388 793 1513 Total 1478 1129 1063 1901 5571 Solids 260 164 106 192 722 Fluids 28 52 102 198 380 Total 288 216 208 390 1102 Percent of total energy 77.9 76.5 78.3 82.1 79.1 g/min 0.8 0.6 0.6 1.1 0.8 Solids 23 19 15 29 86 Percent of total energy 6.2 6.7 5.6 6.1 6.2 Carbohydrate/protein ratio 12.5 11.4 13.9 13.4 12.8 26 21 19 25 91 15.6 16.7 16.1 11.8 14.7 Caffeine (mg) – 82 35 113 231 Sodium (mg) 2201 2101 4752 7128 16,182 Analysis Energy (kcal) Carbohydrates (g) Protein (g) Fat (g) Solids Percent of total energy 126 Baylor University Medical Center Proceedings HR method compared with the method of doubly labeled water is overestimated by ~10% (12). If we accounted for this by reducing the energy expenditure estimated in this study by 10%, the energy deficit would be decreased only 4%, from 64% to 60%. Therefore, although the doubly labeled water method could be used under field conditions, the high cost and the inability to obtain an activity pattern does not always make it ideal. Based on the athlete’s average intensity of 69% HRmax, it is estimated that approximately two thirds of the total energy required was met by fat oxidation, with carbohydrate oxidation providing one third (13). However, fat oxidation is not a limitation for providing fuel during longer events (13, 14). The estimation of anthropometric characteristics in the current athlete indicated that he had ~9.8 kg of subcutaneous adipose tissue that could provide >88,000 kcal. Based on that, the athlete should consume a high amount of carbohydrates during the event due to his limited glycogen stores (13). The recommended amount of carbohydrate intake to optimize the oxidation rates has been reported to be between 1.0 and 1.2 g/min (15). The current athlete ingested amounts of carbohydrates below these recommendations during threequarters of the event; only during the last 6 h, when fatigue symptoms were more pronounced and the glycogen stores were possibly depleted, did he meet the carbohydrate consumption threshold of >1.0 g/min. Additionally, although protein is not considered a primary energy source for athletes, it has been suggested to play an important role during longer events. An adequate ratio of carbohydrate/protein may reduce a negative protein balance (16, 17) and may enhance aerobic endurance performance (18). Volume 25, Number 2 An optimal rate (g) between carbohydrate and protein intake seems to be 4:1 (18). Applying these recommendations in the present case study, and assuming that the athlete had ingested the recommended carbohydrate rate (~1.1 g/min), protein intake would have had to have been ~400 g (4.7 g/kg of body mass), representing more than threefold the actual amount of protein intake by the cyclist during the event. Accordingly, this amount of protein seems to be excessive and, independent of the supposed benefits of carbohydrate and protein combination, it should also be taken into account that protein intake is associated with greater satiety and a reduced ad libitum energy intake in humans. Thus, higher protein consumption during longer events can be associated with a reduction of food intake, as well as an increase of the risk of gastrointestinal disturbances. Further studies are needed to analyze whether an increase of protein intake above the current recommendations (1.2 –1.7 g/ kg of body mass/day) may induce benefits in longer and highintensity sport events. Furthermore, the hydration pattern is one of the nutritional keys in ultraendurance events. While the current athlete ingested the high amount of 20.7 L of fluids during the race, the hydration strategy was not in agreement with current recommendations (19, 20). He should have prioritized the consumption of isotonic fluids containing carbohydrates (sucrose, maltose, or maltodextrins) at ~3% to ~8% weight/volume during the race (21). Thus, the strategy of hydration followed by the cyclist substantially reduced the amount of carbohydrate intake. If he had prioritized the consumption of isotonic fluids (7% of carbohydrates), he would have obtained ~900 g extra carbohydrates, reaching values within the carbohydrate recommendations for longer events (15). Related to the hydration pattern, one of the most common medical complications during long-distance events is exerciseassociated hyponatremia (22), defined as a serum plasma or sodium concentration <135 mmol/L-1. To prevent exerciseassociated hyponatremia, the athlete ingested higher amounts of sodium, mainly during the second half of the event when the environmental conditions were harsher. Nevertheless, although some hydration guidelines recommend consuming fluids with a high content of sodium (30–50 mmol/L) (21), currently there is insufficient evidence to determine whether sodium intake prevents or decreases the risk of exercise-associated hyponatremia (23). On the contrary, some risks of excessive sodium supplementation in combination with overhydration have been documented (24). There are at least two ways to reduce the risk of excessive fluid retention: 1) drink only according to thirst and 2) monitor body weight so as to avoid weight gain during exercise. In the present study, the cyclist showed no weight gain; he lost 2.6 kg of body mass over the race. However, in ultraendurance events such as an Ironman triathlon, it has been reported that part of fluid losses, at least 2 kg, could be derived from reduction of fat stores, skeletal muscle mass, glycogen, and the metabolic water stored in glycogen (25, 26). In conclusion, this case study shows one of the highest energy deficits in the scientific sports literature. To minimize the energy deficit, athletes should receive nutritional training beApril 2012 fore the event so that the digestive system can adapt to higher amounts of food and fluids while physical exercise is performed. In addition, they should begin the event with their meals and fluids planned and prepared beforehand according to their preferences. The present findings highlight the importance of the support provided by sports dieticians and sports physiologists in helping athletes plan and monitor their food and fluid intake during longer events. Acknowledgments This study was funded by the National Institute of Physical Education of Barcelona, Polar Iberica, and RPM Events. The authors appreciate the technical support of the Research Group of Applied Nutrition–Department of Nutrition and Bromatology (University of Barcelona). In addition, we are indebted to Víctor Cervera for his support in data collection during the study. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. Zaryski C, Smith DJ. Training principles and issues for ultra-endurance athletes. Curr Sports Med Rep 2005;4(3):165–170. Knechtle B, Enggist A, Jehle T. Energy turnover at the Race Across AMerica (RAAM)—a case report. Int J Sports Med 2005;26(6):499–503. Lindeman AK. Nutrient intake of an ultraendurance cyclist. Int J Sport Nutr 1991;1(1):79–85. White JA, Ward C, Nelson H. Ergogenic demands of a 24 hour cycling event. Br J Sports Med 1984;18(3):165–171. Knechtle B, Knechtle P, Lepers R. 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Energy expenditure and dietary intake of athletes during an ultraendurance event developed by hiking, cycling and mountain climbing. J Sports Med Phys Fitness 2010;50(3):296–302. Livingstone MB, Coward WA, Prentice AM, Davies PS, Strain JJ, McKenna PG, Mahoney CA, White JA, Stewart CM, Kerr MJ. Daily energy expenditure in free-living children: comparison of heart-rate monitoring with the doubly labeled water (2H2(18)O) method. Am J Clin Nutr 1992;56(2):343–352. Maughan RJ. Nutritional aspects of endurance exercise in humans. Proc Nutr Soc 1994;53(1):181–188. Laursen PB, Ahern SM, Herzig PJ, Shing CM, Jenkins DG. Physiological responses to repeated bouts of high-intensity ultraendurance cycling—a field study case report. J Sci Med Sport 2003;6(2):176–186. Jeukendrup AE. Carbohydrate intake during exercise and performance. Nutrition 2004;20(7–8):669–677. Koopman R, Pannemans DL, Jeukendrup AE, Gijsen AP, Senden JM, Halliday D, Saris WH, van Loon LJ, Wagenmakers AJ. Combined ingestion of protein and carbohydrate improves protein balance during ultra-endurance exercise. Am J Physiol Endocrinol Metab 2004;287(4):E712– E720. High energy deficit in an ultraendurance athlete in a 24-hour ultracycling race 127 17. Beelen M, Tieland M, Gijsen AP, Vandereyt H, Kies AK, Kuipers H, Saris WH, Koopman R, van Loon LJ. Coingestion of carbohydrate and protein hydrolysate stimulates muscle protein synthesis during exercise in young men, with no further increase during subsequent overnight recovery. J Nutr 2008;138(11):2198–2204. 18. Ivy JL, Res PT, Sprague RC, Widzer MO. Effect of a carbohydrate-protein supplement on endurance performance during exercise of varying intensity. Int J Sport Nutr Exerc Metab 2003;13(3):382–395. 19. Peters EM. Nutritional aspects in ultra-endurance exercise. Curr Opin Clin Nutr Metab Care 2003;6(4):427–434. 20. American College of Sports Medicine, Sawka MN, Burke LM, Eichner ER, Maughan RJ, Montain SJ, Stachenfeld NS. American College of Sports Medicine position stand. Exercise and fluid replacement. Med Sci Sports Exerc 2007;39(2):377–390. 21. Rehrer NJ. Fluid and electrolyte balance in ultra-endurance sport. Sports Med 2001;31(10):701–715. 22. Rosner MH, Kirven J. Exercise-associated hyponatremia. Clin J Am Soc Nephrol 2007;2(1):151–161. 23. Hew-Butler T, Ayus JC, Kipps C, Maughan RJ, Mettler S, Meeuwisse WH, Page AJ, Reid SA, Rehrer NJ, Roberts WO, Rogers IR, Rosner MH, Siegel AJ, Speedy DB, Stuempfle KJ, Verbalis JG, Weschler LB, Wharam P. Statement of the Second International Exercise-Associated Hyponatremia Consensus Development Conference, New Zealand, 2007. Clin J Sport Med 2008;18(2):111–121. 24. Luks AM, Robertson HT, Swenson ER. An ultracyclist with pulmonary edema during the Bicycle Race Across America. Med Sci Sports Exerc 2007;39(1):8–12. 25. Speedy DB, Noakes TD, Kimber NE, Rogers IR, Thompson JM, Boswell DR, Ross JJ, Campbell RG, Gallagher PG, Kuttner JA. Fluid balance during and after an Ironman triathlon. Clin J Sport Med 2001;11(1):44–50. 26. Knechtle B, Baumann B, Wirth A, Knechtle P, Rosemann T. Male Ironman triathletes lose skeletal muscle mass. Asia Pac J Clin Nutr 2010;19(1): 91–97. Selected quotes From Sir William Osler’s graduation thesis at McGill: “To investigate the causes of death, to examine carefully the condition of organs, after such changes have gone on in them as to render existence impossible, and to apply such knowledge to the prevention and treatment of disease, is one of the highest objects of the physician.” Contributed by Joseph M. Guileyardo, MD, Director of Autopsy Services, Baylor University Medical Center at Dallas. 128 Some additional quotes from William Osler: “Nothing will sustain you more potently than the power to recognize in your humdrum routine, as perhaps it may be thought, the true poetry of life—the poetry of the commonplace, of the ordinary man, of the plain, toil-worn woman, with their loves and their joys, their sorrows and their griefs.” “I have had three personal ideals. One, to do the day’s work well and not to bother about tomorrow. . . . The second ideal has been to act the Golden Rule, as far as in me lay, towards my professional brethren and towards the patients committed to my care. And the third has been to cultivate such a measure of equanimity as would enable me to bear success with humility, the affection of my friends without pride, and to be ready when the day of sorrow and grief came to meet it with the courage befitting a man.” “No man is really happy or safe without a hobby, and it makes precious little difference what the outside interest may be—botany, beetles or butterflies, roses, tulips or irises; fishing, mountaineering or antiquities—anything will do so long as he straddles a hobby and rides it hard.” Baylor University Medical Center Proceedings Volume 25, Number 2 The de novo diagnosis of systemic lupus erythematosus and lupus nephritis during pregnancy Tapan Patel, MD, Andrew Fenves, MD, and Gates Colbert, MD S ystemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue disorder. SLE has marked female predominance, with a 9:1 female-to-male ratio, and generally affects young women of childbearing age. Some women have monthly worsening of symptoms with onset of menses (1). Although some evidence indicates that the increased female prevalence is due to estrogen, it is likely that complex interactions of multiple hormones, including estrogen, prolactin, dehydroepiandrosterone, and testosterone, are involved (2). Fertility is generally preserved in SLE patients, except when renal function is seriously compromised, the disease is very active, or amenorrhea has been induced by cytotoxic therapy such as cyclophosphamide (3). SLE’s effects on pregnancy are controversial.. Although some studies found an increase in the number and severity of SLE flares during pregnancy (4, 5), others found no worsening of flares (6–8). We report two patients who were first diagnosed with SLE during pregnancy and review the interaction of SLE and pregnancy. CASE 1 A 22-year-old African American woman, gravida 2, para 1, presented to another hospital at 6 weeks’ gestation with diffuse joint pain and malar rash. She had no family history of SLE and no past history of miscarriages or blood clot formation. She was found to have positive antinuclear antibodies (ANA) at a titer of 1:2560. The patient also had a positive anti-DNA antibody, low complement factors (C3, 84 mg/dL; C4, 9 mg/dL), leukopenia, and anemia on further workup. She was diagnosed with SLE based on clinical features and laboratory findings and was started on oral prednisone 30 mg daily, which was subsequently decreased to 20 mg daily. At 30 weeks’ gestation, she presented to the maternal-fetal medicine clinic at Baylor University Medical Center at Dallas (BUMC) for an ultrasound. At that time she was taking amlodipine 5 mg daily, prednisone 20 mg daily, and ferrous sulfate 325 mg three times daily and had no known drug allergies. She was found to be hypertensive with a blood pressure of 163/99 mm Hg. She also complained of a mild headache and “dots” in her vision. She denied uterine contractions, vaginal bleeding, or leakage of fluid. Proc (Bayl Univ Med Cent) 2012;25(2):129–131 Her past medical history was signifi cant for preexisting hypertension. She developed chorioamnionitis and preeclampsia during a previous pregnancy and required a cesarean section at 39 weeks. The patient was admitted to BUMC with possible preeclampsia superimposed on chronic hypertension. At admission, urinalysis showed +2 dipstick protein, 30 to 50 white blood cells per high-power field, and microscopic hematuria. Subsequent 24-hour urine contained 1523 mg of protein. Her serum creatinine was 0.6 mg/dL; blood urea nitrogen (BUN), 5 mg/dL; and uric acid, 3.9 mg/dL. Serologic studies included a rheumatoid factor of 8 IU/mL; rapid plasma reagin, nonreactive; C3, 81.1 mg/dL; C4, 8.4 mg/dL; CH50, 267 units; anti-U1 ribonucleoprotein, positive; anticardiolipin IgG, <10 GPL; anticardiolipin IgM, 10.8 MPL; anti-DNA antibody titer, 1:1280; ANA titer, 1:2560; and anti-cyclic citrullinated protein antibody, negative. Prednisone was continued at the dose of 20 mg per day. A renal ultrasound showed that the right kidney was of normal size (12.2 cm length) with mild hydronephrosis likely caused by ureteral compression secondary to the gravid uterus. The left kidney was slightly enlarged (13.3 cm length). Both kidneys had normal cortical echogenicity and thickness. Urine culture was positive for group beta streptococcus, and the patient was treated with amoxicillin. Hydralazine 25 mg twice a day was added to the oral amlodipine dose (5 mg per day), and subsequently the amlodipine dose was increased to 10 mg per day. The condition of both mother and fetus was relatively stable, and the patient’s blood pressure improved. On hospital day 8, the patient was discharged with planned outpatient follow-up by the nephrology and rheumatology services. Her renal function was stable at the time of discharge, with a serum creatinine of 0.6 mg/dL and BUN of 8 mg/dL. Her serum uric acid level was 4.2 mg/dL, and 24-hour urine protein excretion was 803 mg at the time of discharge. From the Division of Nephrology (Patel, Fenves), Department of Internal Medicine (Colbert), Baylor University Medical Center at Dallas. Corresponding author: Tapan Patel, MD, Division of Nephrology, Department of Internal Medicine, Baylor University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, Texas 75246 (e-mail: [email protected]). 129 The patient returned to BUMC 23 days after discharge with preterm rupture of membranes and underwent cesarean section with delivery of a preterm infant. Her renal function was stable at that time (serum creatinine, 0.7 mg/dL). She did not follow up with nephrology or rheumatology after the second discharge. CASE 2 A 21-year-old obese (222-pound) nulliparous Caucasian woman was evaluated at 11 weeks’ gestation and was found to have a serum creatinine of 0.58 mg/dL and BUN of 8 mg/ dL. Her aspartate aminotransferase, alanine aminotransferase, albumin, and urinalysis were all normal. At 13 weeks’ gestation, she developed hypertension with a blood pressure of 155/100 mm Hg. Urinalysis revealed 2+ protein and 10 to 30 red blood cells per high-power field, and her serum creatinine was now 1.38 mg/dL. A 24-hour urine showed a creatinine clearance of 33 mL/min and protein of 3.48 g. A renal sonogram showed that the right kidney was 10.4 cm long and the left kidney, 12.7 cm long. The kidneys had normal shape and echogenicity. No hydronephrosis or mass was detected. Her only medications were prenatal vitamins, and she denied use of nonsteroidal antiinflammatory drugs. She had lost weight during the first trimester, from 222 to 213 pounds. Her past medical history was significant only for two antenatal urinary tract infections that had resolved with ciprofloxacin treatment. There was no family history of hypertension or kidney disease. She was referred to a nephrologist because of these problems, and oral methyldopa was started for hypertension. The patient was admitted to BUMC at 23 weeks’ gestation for monitoring and bed rest due to the high risk of her pregnancy. On admission, her serum creatinine was further increased at 3.2 mg/dL. Focal segmental glomerulosclerosis and membranous nephropathy were in the differential diagnosis for renal failure and proteinuria in this patient. A kidney biopsy performed for diagnosis and potential treatment options showed diffuse proliferative lupus nephritis with crescents (class IV) (Figure). Electron microscopy showed subendothelial, subepi- thelial, and mesangial deposits. Her ANA titer was 1:640, with reportedly low C3 and C4 complement level from an outside laboratory. Oral mycophenolate mofetil 500 mg twice a day and oral prednisone 100 mg daily were started. Subsequently, prednisone was tapered to 60 mg daily, and mycophenolate mofetil was increased to 1 g twice a day. The patient was also started on oral methyldopa and labetalol. At 25 weeks’ gestation, hemodialysis was initiated using a right internal jugular vein–tunneled dialysis catheter. She received daily dialysis treatments for 9 days. Her blood pressure worsened, and at 26 weeks’ gestation, she underwent cesarean section to deliver a boy who subsequently died at the age of 9 months of respiratory failure. After delivery, she was switched from methyldopa to oral enalapril for better control of hypertension. She was discharged 8 days after delivery with a serum creatinine of 3.1 mg/dL. Two weeks after discharge, she remained on prednisone and mycophenolate mofetil. Her serum creatinine remained 3.1 mg/dL, and her BUN was 94 mg/dL. Her blood pressure was 135/82 mm Hg and she weighed 204 pounds, down 45 pounds from her peak weight during pregnancy. This large weight loss was due to delivery and the clearance of accumulated fluid. Seven weeks after delivery, her serum creatinine was 2.11 mg/dL. Fourteen weeks after delivery, her serum creatinine was 1.68 mg/dL; BUN, 16 mg/dL; and albumin, 3.8 mg/dL. Her hemoglobin was reduced to 8.4 mg/dL and hematocrit was 26.2%. Her anemia was presumed to be due to chronic kidney disease. Erythropoiesis-stimulating agent (ESA) was started after confirming sufficient body stores of iron (serum ferritin, 230 ng/mL; serum iron, 65 μg/dL). She weighed 188 pounds and her blood pressure was normal on enalapril 20 mg orally twice a day. She continued oral mycophenolate mofetil 1 g twice a day and was also taking oral hydroxychloroquine 400 mg daily. At 28 weeks after delivery, her serum creatinine was 1.01 mg/dL; BUN, 17 mg/dL; hemoglobin, 12.4 g/dL; and hematocrit, 37.8%. Her urine protein excretion had fallen, as documented by a spot urine protein-creatinine ratio of 1.94 mg/g. ESA therapy was discontinued. Two years after delivery, the patient’s serum creatinine was 0.8 mg/dL, and her SLE was well controlled on low-dose mycophenolate mofetil and prednisone. DISCUSSION In normal healthy women, successful pregnancy depends on adaptation of the maternal immune system that becomes tolerant to fetal antigens of paternal origin. Altered immune regulation induced by pregnancy is manifested mainly at the fetomaternal surface. One of the most important modifications during development of autoimb a mune rheumatic diseases during pregnancy is a Figure. Kidney biopsy results. (a) Light microscopy (hematoxylin and eosin) showing glomerulus with Th1/Th2 shift. It occurs both at the fetoplacental incomplete epithelial crescent and endocapillary hypercellularity. (b) Electron microscopy showing barrier and in maternal circulation and is driven subepithelial and subendothelial immune complex–type deposits and effacement of epithelial foot by physiological increases in progesterone and esprocesses. trogen during pregnancy (9). 130 Baylor University Medical Center Proceedings Volume 25, Number 2 Table. Contraindications to pregnancy in women with systemic lupus erythematosus* • Severe pulmonary hypertension (estimated systolic pulmonary arterial pressure >50 mm Hg or symptomatic) • Severe restrictive lung disease (forced vital capacity <1 L) • Heart failure • Chronic renal failure (creatinine >2.8 mg/dL) • Previous severe preeclampsia or HELLP despite therapy with aspirin and heparin • Stroke within the previous 6 months • Severe lupus flare within the previous 6 months *From Ruiz-Irastorza G, Khamashta MA. Lupus and pregnancy: ten questions and some answers. Lupus 2008;17(5):416–420. Reprinted with permission from Sage. In physiological conditions, it seems that estrogen stimulates both humoral and cellular immune responses (Th1 and Th2 cytokines). Interestingly, at higher than physiological concentrations, such as those reached during pregnancy, it seems that estrogen inhibits cell-mediated immune response (Th1 cytokines), whereas antibody production is induced (Th2 cytokines). The polarization of the Th2 response may explain why the condition of the patient affected by rheumatoid arthritis (Th1 cytokine) generally improves during pregnancy, whereas the condition of the patient with SLE may worsen (Th2 cytokine) (9). Whether pregnancy increases SLE activity has been debated for years. In general, SLE flares during pregnancy are usually not severe. However, data from the Hopkins’ lupus control studies showed an increased risk of SLE nephritis (10). Lupus nephritis during pregnancy is a clinical challenge. Patients with recent active nephritis are at the highest risk, while those in long-standing remission with no past renal disease are at the lowest risk (11). Urinary protein excretion normally rises during pregnancy in women with underlying proteinuria, so an increase does not always indicate active disease (11). Complement levels normally decrease during pregnancy, and this limits their utility as a marker of active lupus. Pregnant women with SLE are at increased risk for preeclampsia and eclampsia (12, 13). Among women with renal disease, the incidence of preeclampsia and eclampsia may be as high as 66% (14). Proteinuria, hypertension, and a decline in renal function can also be seen in preeclampsia; in fact, differentiating between these two conditions is difficult, and they can also coexist. Pregnancy in a patient with SLE is associated with an increased risk of fetal and maternal outcomes, so these patients April 2012 are at high risk. A multidisciplinary therapeutic approach is required for the treatment of the pregnant patient with SLE. Ideally, management of these patients should start before conception. The prognosis of pregnant SLE patients has improved with better diagnosis and treatment. Pregnancy is contraindicated when women have active lupus nephritis. Pregnancy should be avoided until there is a renal remission of at least 6 months’ duration. The Table lists the contraindications to pregnancy in women with SLE. In our two cases, SLE was first recognized during pregnancy. Case 2 developed severe SLE nephritis during her pregnancy but also had marked renal improvement at the end of pregnancy. These two cases demonstrate two main points: • Pregnancy can be associated with the development of fullblown SLE in a previously subclinical patient. • Severe organ involvement, including SLE nephritis, can be the initial manifestation of lupus during pregnancy. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. Petri M, Robinson C. Oral contraceptives and systemic lupus erythematosus. Arthritis Rheum 1997;40(5):797–803. Petri M. Sex hormones and systemic lupus erythematosus. Lupus 2008;17(5):412–415. Doria A, Iaccarino L, Arienti S, Ghirardello A, Zampieri S, Rampudda ME, Cutolo M, Tincani A, Todesco S. Th2 immune deviation induced by pregnancy: the two faces of autoimmune rheumatic diseases. Reprod Toxicol 2006;22(2):234–241. Petri M, Howard D, Repke J. Frequency of lupus flare in pregnancy. The Hopkins Lupus Pregnancy Center experience. Arthritis Rheum 1991;34(12):1538–1545. Ruiz-Irastorza G, Lima F, Alves J, Khamashta MA, Simpson J, Hughes GR, Buchanan NM. Increased rate of lupus flare during pregnancy and the puerperium: a prospective study of 78 pregnancies. Br J Rheumatol 1996;35(2):133–138. Lockshin MD, Reinitz E, Druzin ML, Murrman M, Estes D. Lupus pregnancy. Case-control prospective study demonstrating absence of lupus exacerbation during or after pregnancy. Am J Med 1984;77(5):893–898. Urowitz MB, Gladman DD, Farewell VT, Stewart J, McDonald J. Lupus and pregnancy studies. Arthritis Rheum 1993;36(10):1392–1397. Tandon A, Ibañez D, Gladman DD, Urowitz MB. The effect of pregnancy on lupus nephritis. Arthritis Rheum 2004;50(12):3941–3946. Doria A, Iaccarino L, Sarzi-Puttini P, Ghirardello A, Zampieri S, Arienti S, Cutolo M, Todesco S. Estrogens in pregnancy and systemic lupus erythematosus. Ann N Y Acad Sci 2006;1069:247–256. Petri M. The Hopkins Lupus Pregnancy Center: ten key issues in management. Rheum Dis Clin North Am 2007;33(2):227–235. Day CJ, Lipkin GW, Savage CO. Lupus nephritis and pregnancy in the 21st century. Nephrol Dial Transplant 2009;24(2):344–347. Moroni G, Ponticelli C. The risk of pregnancy in patients with lupus nephritis. J Nephrol 2003;16(2):161–167. Qazi U, Petri M. Auto antibodies, low complement, and obesity predict preeclampsia in SLE: a case-control study. Arthritis Rheum 2007;54(9 Suppl):S264. Hochberg MC, Silman A, et al. Systemic lupus erythematosus—clinical features. In Hochberg MC, Silman A, Smolen JS, Weinblatt ME, Weisman MH, eds. Rheumatology. Edinburgh, UK: Mosby, 2003:1359–1379. The de novo diagnosis of systemic lupus erythematosus and lupus nephritis during pregnancy 131 A rare case of intraneural ganglion cyst involving the tibial nerve Purvak Patel, MD, and William G. Schucany, MD Cystic lesions around the knee are a relatively common occurrence. Several types of cysts have been reported, including synovial, bursal, and ganglion. Ganglion cysts are not lined by synovial cells. Their location is highly variable, with occurrences described in the fat pads near the tibia or femur, muscles, nerves, and arteries. Intraneural ganglia are rare nonneoplastic cysts caused by the accumulation of thick mucinous fluid within the epineurium of peripheral nerves, encased in a dense fibrous capsule. These cysts can cause compression of the adjacent nerve fascicles, resulting in pain, paresthea b sias, weakness, muscle denervation, and atrophy. They are most commonly manifested by local and radiating Figure 1. Axial proton density images with fat saturation demonstrate (a) the tibial nerve (arrow), the pain, but sensory and motor deficits have also been popliteal vein (dashed arrow), and the popliteal artery (dotted arrow) and (b) a multilobulated mass described. Involvement of the tibial nerve is exception- enlarging the tibial nerve (arrow). ally rare, with <15 reported cases in the literature. We present a case of intraneural tibial ganglion cyst in a young woman. We also discuss the imaging features, differential considerations, proposed pathogenesis and anatomic origin, and treatment of this rare entity. CASE REPORT A 34-year-old woman presented with worsening knee pain, which began 5 weeks earlier. She had been driving an all-terrain vehicle the day before but could not recall any distinct injury. She complained of tingling and numbness from the right hip to the foot and had pain that had kept her awake at night. Squatting down exacerbated the pain, whereas standing improved it. The history was also significant for remote anterior cruciate ligament tear involving the right knee. Her physical examination was significant for tenderness to deep palpation along the tibial nerve. She resisted full extension of the knee because it exacerbated the pain, and she had difficulty performing a straight leg test above 30 degrees. Magnetic resonance imaging (MRI) of the right knee demonstrated enlargement of the tibial nerve beginning at the distal thigh and extending into the popliteal fossa as seen on the axial fat-saturated proton density images (Figure 1). Sagittal proton density images demonstrated a multilobulated tubular mass, subadventitial in location, extending along the course of the tibial nerve from the proximal tibial epiphysis to the level of the distal femoral metadiaphysis (Figure 2). A sagittal 132 Figure 2. Sagittal proton density image demonstrates a multilobulated mass with involvement of the tibial nerve (arrow). From the Department of Radiology, Baylor University Medical Center at Dallas. Corresponding author: William G. Schucany, MD, Department of Radiology, Baylor University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, Texas 75246 (e-mail: [email protected]). Proc (Bayl Univ Med Cent) 2012;25(2):132–135 Figure 3. Sagittal T2-weighted image with fat saturation demonstrates a multilobulated tubular cystic mass involving the tibial nerve (arrow). hyperintensity (Figure 3). Axial and sagittal fat-saturated precontrast T1-weighted images demonstrated faint intrinsic T1 contrast (Figure 4). Axial and sagittal T1-weighted intravenous postcontrast T1-weighted fat-saturated images demonstrated peripheral enhancement of the multilobulated tubular cystic mass involving the tibial nerve (Figure 5). The constellation of findings was believed to represent a multilobulated ganglion and was likely contiguous with the posterior joint capsule. Surgical exploration of the popliteal fossa revealed a bubbly longitudinal mass within the sciatic nerve sheath. As this was dissected out of the neurologic sheath, a portion of the mass was entered and the typical sticky jelly-like fluid of a ganglion cyst was encountered. It was not feasible grossly to identify communication with the knee joint, even though the lesion migrated inferior to the popliteal fossa. Whether or not there was nonvisualized communication was uncertain. The portion of the mass that was obtained was then sent to pathology. On gross inspection, a solid portion of the mass was not visible. The appearance was consistent with the MRI scan findings of peripheral enhancement only. DIAGNOSIS: Ganglion cyst without atypical features. DISCUSSION An intraneural ganglion cyst is an uncommon occurrence of the peripheral nerves. The most common type is the peroneal intraneural ganglion cyst. Other reported sites of involvement are the radial, ulnar, median, sciatic, tibial, and posterior interosseus nerves. The first case of intraneural ganglion cyst of the tibial nerve was described in 1967. Since then, about 15 cases a have been reported (1–3). b The differential considerations for cystic Figure 4. (a) Axial and (b) sagittal T1-weighted fat-saturated images before intravenous gadolinium intraneural lesions include cystic nerve sheath contrast demonstrate a faint intrinsic T1 signal (arrow). tumors, atypical Baker’s cyst, and extraneural ganglion. Atypical vascular or lymphatic malformation was also considered in our case. Cystic nerve sheath tumors such as schwannomas and extraneural ganglion can be differentiated from cystic intraneural lesions by MRI. A Baker’s cyst classically is more mass-like, with a characteristic location extending from the tibiofemoral joint to within the confines of the medial head of the gastrocnemius and the muscles of the joint capsule (1, 4–6). Numerous explanations have been proposed for the pathogenesis of intraneural tibial ganglia. a b Early literature described a localized degenerative process of connective and perineural tissue Figure 5. (a) Axial and (b) sagittal T1-weighted fat-saturated images after intravenous gadolinium contrast show peripheral enhancement of the multilobulated tubular mass involving the tibial nerve secondary to chronic mechanical irritation. An alternate theory states that some cysts could (arrows). arise from mucoid or cystic degeneration of forT2-weighted fat-saturated image demonstrated a multilobulated merly solid tumors. Intraneural hemorrhage secondary to traumass within the tibial nerve, which demonstrated T2 signal ma and formation of cysts after resorption of the hemorrhage April 2012 A rare case of intraneural ganglion cyst involving the tibial nerve 133 Figure 6. The anatomy of the superior tibiofemoral joint and the formation of the intraneural ganglion cyst. Reprinted with permission from the Mayo Foundation for Medical Education and Research. All rights reserved. have also been proposed, although the explanation is not convincing since the presence of hemosiderin deposits has been an uncommon finding. Trauma has also been implicated as one of the potential causes of ganglion cyst formation, with sev- eral of the case reports indicating a remote history of trauma. Our patient also had a remote history of trauma to the knee (1). Adn et al favor trauma being a contributing factor rather than a principal causative factor. A more recent explanation based on critical analysis of clinical, operative, and radiologic observations has favored a synovial origin of these intraneuronal ganglion cysts, which is based on a unifying articular theory (6) (Figure 6). The unifying articular theory was initially proposed for the intraneural ganglion cyst arising within the peroneal nerve. It was later extended to include the tibial nerve as well. According to the theory, fluid from the synovial joints—in our case the superior tibiofibular joint—dissects intraepineurally from the joint via articular branches perforating the joint capsule along a path of least resistance. In the case of the tibial intraneural ganglia, the cyst arises from the posterior aspect of the superior tibiofibular joint (as opposed to the anterior origin for the intraneural ganglion cyst involving the peroneal nerve). The articular branch responsible is derived from the oblique descending branch innervating the popliteus muscle. The same authors have also proposed a classification scheme for stages of nerve involvement (Figure 7). Stage 0 represents a cyst within the superior tibiofibular joint. A defect in its posterior capsule allows the cyst to dissect proximally up the articular branch (stage 1). Dissection of the cyst into the popliteal nerve branch is stage 2, extension into the tibial nerve is stage 3, and extension into the tibial division of the sciatic nerve is stage 4 (4). More recent literature has incorporated dynamic aspects of cyst formation due to pressure fluxes to explain various patterns of ascent, cross-over, and descent down terminal nerve branches (6). Classic MRI findings have been proposed to further corroborate the unifying articular theory. However, these imaging findings have been made on a retrospective basis. MRI signs include the “tail sign,” which is seen with a narrow neck or pedicle connecting the intraneural cyst to the joint; denervation of the popliteus muscle and resulting fatty atrophy, i.e., the “popliteus sign”; and the “signet ring sign,” which refers to eccentric Figure 7. Proposed stages of intraneural ganglion growth/migration. Reprinted with permission from the Mayo Foundation for Medical Education and Research. All rights reserved. 134 Baylor University Medical Center Proceedings Volume 25, Number 2 displacement of the tibial nerve fascicles by intraneural cyst. Three-dimensional reformatting can also be helpful in further elucidating the course of the nerve and may be accomplished with high-resolution but nonisotropic planar imaging (5). MR arthrography has also been proposed to detect occult joint communications, especially in recurrent intraneural ganglion cysts (7). Malghem et al described the use of intraarticular injection of contrast in the knee with delayed imaging using computed tomography to demonstrate communication between the ganglion cyst and the articular cavity. Ultrasound imaging can also help delineate the cystic versus solid nature of the lesion (8). More recent literature has mentioned minimally invasive decompression for treatment of symptomatic intraneural ganglion cysts to reduce tibial nerve compression and secondary muscle denervation in patients wanting to avoid an open surgical approach. Ultrasound-guided aspiration can be performed after taking careful measures to avoid injuring the adjacent popliteal artery and the nerve fascicles. However, long-term follow-up studies are needed to determine cyst recurrence (2). An open surgical approach is more definitive treatment, although it is associated with greater risk and technical challenge. The suggested treatment strategy involves decompressing the intraneural ganglion cyst, disconnecting the articular branch (once identified), and resecting the synovium. Failure to disconnect the articular branch can result April 2012 in partial cyst persistence or recurrence. Incomplete resection of the synovium can result in extraneural occurrences (4). 1. 2. 3. 4. 5. 6. 7. 8. Adn M, Hamlat A, Morandi X, Guegan Y. Intraneural ganglion cyst of the tibial nerve. Acta Neurochir (Wien) 2006;148(8):885–889. Jose J, Fourzali R, Lesniak B, Kaplan L. Ultrasound-guided aspiration of symptomatic intraneural ganglion cyst within the tibial nerve. Skeletal Radiol 2011;40(11):1473–1478. Friedlander HL. Intraneural ganglion of the tibial nerve. A case report. J Bone Joint Surg Am 1967;49(3):519–522. Spinner RJ, Mokhtarzadeh A, Schiefer TK, Krishnan KG, Kliot M, Amrami KK. The clinico-anatomic explanation for tibial intraneural ganglion cysts arising from the superior tibiofibular joint. Skeletal Radiol 2007;36(4):281–292. Spinner RJ, Hébert-Blouin MN, Maniker AH, Amrami KK. Clock face model applied to tibial intraneural ganglia in the popliteal fossa. Skeletal Radiol 2009;38(7):691–696. Spinner RJ, Amrami KK, Wolanskyj AP, Desy NM, Wang H, Benarroch EE, Skinner JA, Rock MG, Scheithauer BW. Dynamic phases of peroneal and tibial intraneural ganglia formation: a new dimension added to the unifying articular theory. J Neurosurg 2007;107(2):296–307. Spinner RJ, Amrami KK, Rock MG. The use of MR arthrography to document an occult joint communication in a recurrent peroneal intraneural ganglion. Skeletal Radiol 2006;35(3):172–179. Malghem J, Vande berg BC, Lebon C, Lecouvet FE, Maldague BE. Ganglion cysts of the knee: articular communication revealed by delayed radiography and CT after arthrography. AJR Am J Roentgenol 1998;170(6):1579–1583. A rare case of intraneural ganglion cyst involving the tibial nerve 135 JORGE FELIX SAUCEDO, MD, MBA: a conversation with the editor on optimizing antiplatelet and antithrombotic therapy in patients having percutaneous coronary intervention for acute coronary syndromes Jorge Felix Saucedo, MD, MBA, and William Clifford Roberts, MD Figure. Jorge Felix Saucedo, MD, MBA. William Clifford Roberts, MD (hereafter, Roberts): Dr. Saucedo (Figure), I appreciate your coming to Baylor University Medical Center at Dallas to give a cardiology conference (on 5 October 2011) and particularly for the opportunity to talk to you about some of your work. Before focusing on antiplatelet and antithrombotic agents and percutaneous coronary intervention in acute coronary syndromes, could you briefly summarize your early life and describe your parents, siblings, and how you got to Oklahoma City? Jorge Felix Saucedo, MD, MBA (hereafter, Saucedo): It is a pleasure and honor to be here in Dallas in this wonderful medical center. Although her parents were from Lebanon, my 136 mother was born in Mexico City, and my father immigrated to Mexico City from Spain at the age of 17 in 1947. He was a selfmade man. Although not well educated, he worked hard, had a good work ethic, and consequently did quite well in Mexico. He died at the age of 66 from idiopathic pulmonary fibrosis. My mother, a wonderful lady, died at age 77 of lymphoma. Both were Catholics. We were raised as Catholics with strong conservative values. I have a brother and two sisters. My older brother, Fernando, lives in Mexico. Initially, he was in the dress and textile industry, but 5 years ago he franchised four International House of Pancakes. My older sister, Rebecca, age 51, has Down syndrome. She works full-time at a McDonald’s in Mexico, cleaning tables. She can read. She is somewhat independent even though she lives with my younger sister, Myriam, a housewife, with her son in Mexico City. I went to Catholic primary and secondary school and entered medical school right out of high school—the National Autonomous University of Mexico in Mexico City. I went to medical school for 6 years. The fifth year of my medical school was like an internship in the USA. I had a 1-year clinical rotation in Houston, spending a few months at Methodist and Hermann Hospitals and at some other hospitals in the area. That was an important year for me. It was the first year I had lived independently, and it was the year that I met the person who became my wife. Karyn was born in Austin and raised in Houston. She was studying nursing and we were living next door to each other in the same dorm (Favrott Hall) in the middle of the Texas Medical Center. After that 1 year of training in Houston, I returned to Mexico to finish medical school (the sixth year) doing research in the pathology department at the best hospital in Mexico, the National Institute of Nutrition, and arguably one of the best hospitals in Latin America for internal medicine. Roberts: How old were you then? Saucedo: I finished medical school at age 22, and the night before I was to interview for residency I was still trying to decide if I wanted to be a surgeon or an internist. I had interviews for both programs. I finally decided on internal medicine. I like to diagnose. I did my internal medicine training at the National Institute of Nutrition. The training was tremendous. I was very happy there. I worked over 110 hours per week in the wards. We only had a few hours to rest on Saturday evenings and Sunday Proc (Bayl Univ Med Cent) 2012;25(2):136–138 afternoons and began at 5:00 am on Monday through Saturday. I was often called in the middle of the night for my 22 patients. Those years in internal medicine were crucial in my formation and were some of the most fulfilling years of my career. I lived in the hospital taking care of patients day and night. Roberts: When was that? Saucedo: From 1989 to 1992. I knew I wanted to be a cardiologist, and the best place in Mexico was the National Institute of Cardiology in Mexico City. It was founded 60 years ago as the first heart institute in the world by Dr. Chavez. I did 3 years of cardiology training there. I wanted to become an interventional cardiologist, and to accomplish that goal meant coming to the USA for training. I got accepted to do interventional training at the Mayo Clinic and at the University of Michigan Ann Arbor. I decided to go to Michigan. I trained there for 2 years with Eric Bates, Mauro Moscucci, Steve Werns, and David Muller. After the first year, I started getting a little antsy to go to another place that offered the next level of complex interventions and clinical trials. I wrote Martin Leon at the Washington Hospital Center, Washington, DC, interviewed with him, and was accepted. I spent 1.5 years of formal training at the University of Michigan and then 1 year at the Washington Hospital Center. Roberts: What year did you finish your training? Saucedo: June 1996. David Talley, chief of cardiology of the University of Arkansas for Medical Sciences, approached me at an American Heart Association meeting about 3 months before I was planning to return to Mexico. He offered me the directorship of the catheterization lab at the Veterans Administration Hospital and at the University Hospital in Little Rock, Arkansas. I accepted and stayed almost 5 years (1997 until 2001). I ran a busy research organization after Dr. Talley left. We had 15 to 20 research personnel doing a large number of clinical trials. In April 2002 I moved to the University of Oklahoma because of more opportunities, and I have been there since (9+ years). Roberts: Do you still do percutaneous interventions? Saucedo: I am the director of the cath lab. I spend 3 days a week in the cath lab and about 1.5 to 2 days a week in the clinic seeing patients. I am the medical director of the cath lab and the vice chief for the Division of Cardiology. Dwight Reynolds, the chief, is a device expert (defibrillators, pacemakers, etc.). Four years ago he was the president of the Heart Rhythm Society. I have a rather small research operation. About 80% of my time is devoted to seeing inpatients and working in the cath lab. Roberts: You have done a lot of different research involving the cath lab in the past 15 years. What are the investigative accomplishments that you are most proud of? Saucedo: In Little Rock I led a large organization that allowed us to have a strong presence as trialists in the US. While in Little Rock with Robert Letterman, we published a report using angiogenesis for patients with claudication. We injected fibroblast growth factor directly into the common femoral arteries and showed it to be superior to placebo, permitting patients to walk longer with less pain. In collaboration with Dr. Eidt, we were the first group to perform an endovascular repair of an abdominal aortic aneurysm. Also, we were first in the state of Arkansas to have access to some of the newest stents, cath lab April 2012 devices, antiplatelet drugs, and endografts. I also had a small platelet lab and did light transmission aggregometry, a technique I had learned at the University of Michigan working with Dr. Lucchesi of the Department of Pharmacology. In Little Rock I continued with light transmission aggregometry, looking at platelet function, and published a couple of papers on this subject. I started to work with the antiplatelet agent abciximab, an intravenous glycoprotein 2b/3a antagonist. Roberts: What has happened to fibroblast growth factor? Saucedo: The problem with most angiogenesis trials is that most have a very strong placebo effect. Follow-up studies have not been as positive as initial studies. We are doing a few trials on patients with claudication and also those with critical limb ischemia. We hope at some point that there will be a drug, injected intramuscularly, intravenously, or interarterially, that will help produce collaterals to improve outcomes. Roberts: I presume that you are now in the midst of trials on antiplatelet and antithrombotic agents? Which drugs are going to win? Saucedo: For about 14 years we only had two oral antiplatelet agents, other than aspirin, that were approved by the Food and Drug Administration: ticlopidine and clopidogrel. We used clopidogrel as the preferred second oral antiplatelet agent available after aspirin. Two years ago, prasugrel was approved in the US, mainly on the basis of data from the TRITON and TIMI 38 trials. This study showed that in both ST-elevation and non–ST-elevation patients having coronary angioplasty, prasugrel was associated with about a 20% relative risk reduction of death, myocardial infarction, and stroke. There was more bleeding with prasugrel than with clopidogrel. That is one of my passions: getting to that “sweet spot” where there is a perfect balance between reducing myocardial ischemic complications without increasing bleeding risk. Prasugrel is metabolized easier than clopidogrel. The active metabolite of both drugs is similar, but because of the easier metabolism of prasugrel, it is a more active drug. Prasugrel inhibits platelets more rapidly and more intensely than clopidogrel. There is also less variability of its antiplatelet effect compared with clopidogrel. The newest oral antiplatelet agent approved in the US is ticagrelor. This drug is not a thienopyridine like prasugrel and clopidogrel. It acts on the same receptor within the platelet, which is P2Y12, also known as the ADP receptor. This drug was tested in the PLATO trial and compared with clopidogrel. Compared with clopidogrel, ticagrelor reduced myocardial ischemic events, including death, when given to patients presenting with acute coronary syndromes. There is another receptor in the platelets called the “thrombin” receptor or the proteinase-activated receptor (PAR-1), which is activated through thrombin. Investigational drugs such as vorapaxar block the effect of thrombin, thus preventing the platelet from being activated by thrombin. The major clinical trial, TRACER, published in November 2011 in the New England Journal of Medicine showed a minimal efficacy improvement but a significant increased risk of bleeding complications, including intracranial hemorrhage. Roberts: Which antiplatelet agent are you using now? JORGE FELIX SAUCEDO, MD, MBA: a conversation with the editor on optimizing antiplatelets and antithrombotic therapy 137 Saucedo: Prasugrel. In patients with a history of stroke, old age, and those with low body weight, prasugrel should be avoided or used in low doses. Patients <60 kg are given 5 mg rather than 10 mg. Patients >75 years of age bleed more than younger patients, but they benefit from prasugrel as long as they are at high risk for ischemic events, such as those with diabetes mellitus or a history of myocardial infarction. It is my drug of choice for all patients with ST-elevated myocardial infarction and for those with diabetes mellitus. Roberts: With clopidogrel coming off patent, how will the difference in cost affect your choice of antiplatelet agent? Saucedo: It is going to have a profound impact in the market. For the patient with complex coronary anatomy requiring multiple stents and for patients with diabetes, I will still continue to make the case for using the more potent antiplatelet agent, namely prasugrel, because it is metabolized easier, is more bioavailable, and inhibits platelets more potently. Roberts: Are you keeping patients either on clopidogrel or prasugrel longer than 1 year after percutaneous coronary intervention? Saucedo: Yes, I am doing that routinely despite lack of data. The DAPT study—a 30,000+ patient trial sponsored both by the National Institutes of Health and pharmaceutical companies—hopefully will provide that missing data. In this study, after 1 year of dual antiplatelet therapy, patients are randomized to either placebo (aspirin alone) or dual antiplatelet therapy (prasugrel or clopidogrel) in a blinded fashion for another 18 months. Roberts: Routinely how much aspirin are you giving? Saucedo: Either 81 or 162 mg daily, depending on which other drugs I use. Roberts: Is there any reason to use 162 mg over 81? Saucedo: No. A dose of 324 mg is probably too much. Whether 162 or 81 is better is unclear. In Europe they use 100 mg as their standard dose. Roberts: Do you take aspirin yourself? Saucedo: No. I probably need to start taking a statin but I haven’t yet. Roberts: What are your cholesterol numbers? Saucedo: My low-density lipoprotein (LDL) cholesterol is around 145 and my high-density lipoprotein (HDL) cholesterol is about 80 mg/dL. Roberts: Are you positive the HDL is protective? Saucedo: By the guidelines I do not have any risk factors, and the guidelines suggest lipid-lowering drug therapy if the LDL cholesterol needs to be <160 mg/dL. We are talking about risk reduction. By the Framingham risk score I have a 2% risk of 138 a major cardiovascular event in the next 10 years. I have a 98% chance in the next 10 years that I will not have an event, and taking a statin would reduce that to 99%, but there is a cost to it. The cost of saving a life in my case probably would be more than what we deem reasonable, probably more than $50,000 a year. If the statins were a magic pill with absolutely no side effects or cost, every human being should be on them. Nevertheless, I think I will be taking statins in the near future. Roberts: The guidelines, in my view, hinder cardiovascular health. It’s very difficult in my view to be very enthusiastic about lowering cholesterol in your patients if you are not enthusiastic about lowering it in yourself . I believe we should switch gears and forget about “decreasing risk” and switch to “preventing plaques.” If your LDL cholesterol is 145 you are forming plaques right now. Saucedo: You make a good point about preventing plaque. Roberts: You are 47. What are your goals now? Saucedo: I have been a cath lab director for the last 14 years, and I publish close to 10 papers a year. I teach. What is the next challenge? I am not sure I have an answer at this point. Oklahoma has been very good to me. The last year has been a difficult year for our division. We’ve been below budget and feeling pressure from the administration. I love what I am doing and my family is very happy in our current situation, but I still have potential that hasn’t been tapped yet. Roberts: What is your daily schedule? Saucedo: I get up between 4:45 and 5:15 am and work out at a gym for an hour. I usually arrive at work at 7:30 am for a conference and leave about 5:30 to 6:00 pm. Roberts: What time do you go to bed? Saucedo: 10:00 pm. Roberts: Do you have children? Saucedo: Yes, two boys, aged 16 and 14. Roberts: Do you do much professional work at night? Saucedo: Some. I also try to spend time with the family. Roberts: What about weekends? Saucedo: I’m fully dedicated to the family. If I’m not on call, I exercise 2 hours on Saturday, go to the movies, go swimming, watch the kids’ soccer and basketball games, go to church, and have friends over. Roberts: How much time do you take off a year? Saucedo: About 4 weeks. Roberts: How many trips do you take a year? Saucedo: About 20. It has been a pleasure and an honor to spend this time with you. Roberts: Thank you. Baylor University Medical Center Proceedings Volume 25, Number 2 Darwinian natural selection: its enduring explanatory power Gregory G. Dimijian, MD Evolutionary theory has never had a stronger scientific foundation than it does today. In a short review I hope to portray the deep commitment of today’s biologists to Darwinian natural selection and to discoveries made since Darwin’s time. In spite of the scientific advances in the century and a half since the publication of On the Origin of Species, Darwin still remains the principal author of modern evolutionary theory. He is one of the greatest contributors of all time to our understanding of nature. An awesome gulf divides the pre-Darwinian world from ours. Awesome is not too strong a word. . . . The theory of natural selection revolutionised our understanding of living things, furnishing us with a comprehension of our existence where previously science had stood silent. –Helena Cronin (1) The deluge continued day after day on the tiny island of Daphne Major in the Galápagos Islands, 600 miles off the coast of Ecuador. Dusty soil from years of drought washed in torrents down the steep volcanic slopes into the surrounding sea. Plants began to sprout that had lain dormant for years, and vines grew up the tent poles of the researchers on the only flat ground high up near the extinct volcano’s rim. Some plants producing large seeds were smothered by the prolific vines, and others flourished. The finches on the island celebrated by “going crazy,” in the words of one researcher—the males sang, established territory, and mated. The young grew fast on the insects that appeared all over the island, and they began mating at an unusually young age. The findings from this unusual year provided stunning evidence that natural selection was working on every generation of ground finches, changing the calculus of reproductive success and the composition of alleles in the gene pool of the species. The biologists Peter and Rosemary Grant began studying Darwin’s finches in 1973, and their research has continued full-time ever since (2, 3). It is the longest field study in biology other than that of Jane Goodall, who has studied chimpanzees in Tanzania since 1962. Younger biologists have assisted the Grants in their study, so that the ground finches of Daphne Major have been studied in great detail every year since 1973. Proc (Bayl Univ Med Cent) 2012;25(2):139–147 Daphne Major is a volcanic cone with a central crater; the island is only one half mile long (Figure 1). No tourists visit the island because there is no place to land. Steep cliffs encircle almost the entire perimeter, some with reverse slopes and all with waves battering their sides. Embarkation onto the slopes involves maneuvering a small boat next to an area of relatively flat volcanic surface and jumping onto the surface as the wave hovers briefly at the right level. For researchers, this means negotiating the hair-raising landing while carrying tents, food, and research equipment. This inaccessibility has made the island an ideal place for the isolated study of animals that have arrived by water or by air and have established a foothold and reproduced. Island species are free from the competition of innumerable mainland species, but are faced with the challenge of how to exploit the sparse resources of their small world. Ground finches on the island are tame, letting researchers walk up to them at times and even landing on their arms as they are measuring the beak size of one bird with calipers. Because they don’t migrate, they are available for study year Figure 1. An extinct volcanic cone forms the tiny island of Daphne Major in the Galápagos, home of one of the longest studies of natural selection acting on single generations in the wild. Reprinted with permission from Grant PR, Grant BR. How and Why Species Multiply: The Radiation of Darwin’s Finches. Princeton, NJ: Princeton University Press, 2008. From the Department of Psychiatry, The University of Texas Southwestern Medical School at Dallas. Corresponding author: Gregory G. Dimijian (e-mail: [email protected]). 139 round. There is no obstructing vegetation to hamper observations with binoculars. There are no tourists to disturb the fiches or the researchers. For these reasons and more, the island has been described as a natural laboratory. In 2008 the Grants, who teach biology at Princeton, published a scientific volume about their study. Their findings would have been stunning to Charles Darwin, who believed that evolutionary changes brought about by natural selection would become evident only after long periods of time. Instead, every generation of ground finches has produced evidence of changes in morphology and allele frequencies in the population of one ground finch, Geospiza fortis. The birds and their genes were changed by the severe selection pressures of the years of harsh drought; small seeds were scarce, and those individuals with smaller beak depth and smaller body size died. Evolution placed a meaning on death. Through the death of individuals less fit in the prevailing environment, alleles coding for less useful variations became less common in the gene pool. This is nothing less than evolution occurring in real time, measurable in only months, and brought about only by natural selection—the differential survival of alleles that code for more useful traits. The beak of finches is their secret for manipulating seeds. In his superb book about the Grants’ research, The Beak of the Finch, Jonathan Weiner reminded us (4): “Beaks are to birds what hands are to us. They are the birds’ chief tools for handling, managing, and manipulating the things of this world. . . . Each beak is a hand with a single permanent gesture.” Beaks are continually reshaped to maximize their efficiency in crushing seeds of specific sizes and shapes and can be compared to pliers and wrenches (Figure 2). Torrential rains came to the Galápagos in 1983 during the most severe El Niño event in 400 years, as documented in the coral reef fossil record. Research data from this 1 year on Daphne Major required still another year for entering it all into a computer. The final analysis was stunning: birds with large bodies and deeper beaks were dying; small birds with less deep beaks were thriving. Natural selection had reversed its direction. Now on the island small seeds were abundant, and trees producing large seeds were choked by vines. Death of the less fit became an evolutionary “force,” and the gene pool of G. fortis changed again. So did the morphology of the birds, which were now smaller in average body size, with a more pointed beak than in the 1970s. Generation by generation, natural selection could be monitored as it occurred. These findings are robustly documented by elaborate analyses involving 1) beak and body measurements of thousands of birds on the island, 2) observations of behavior, 3) studies of embryonic development, and 4) genetic sequencing of both nuclear and mitochondrial DNA. The issue of fundamental complexity is thus addressed: morphology, behavior, and the genetic code itself changed pari passu with selection pressures. One may argue that this is only correlation, but it is such consistent and remarkable correlation that causation is the only reasonable conclusion. There is no contender for causation other than natural selection. Over the years since these early studies, 140 Figure 2. Bird beaks are like pliers and wrenches, each adapted to its own narrow task, and are constrained in their size and shape by the demands of the ongoing environment in which the bird lives and reproduces. Reprinted with permission from Grant PR, Grant BR. How and Why Species Multiply: The Radiation of Darwin’s Finches. Princeton, NJ: Princeton University Press, 2008. findings have enabled testing through predictions, in which the correlation has remained true. Natural selection is no more, no less, than the changing representation of alleles that code for traits selected for by the environment. It is not a “force,” although “evolutionary force” is an expression that is often used to describe it. It is just the differential survival of alleles in succeeding populations. The environment may be natural or artificial; we know that our artificial environment of antibiotics provides a selective force for alleles in microorganisms that contribute to antimicrobial resistance. There is no fundamental difference in the dynamics of natural and artificial selection. Darwin knew this and began his major opus with a long discussion of the domestication of animals and plants as an excellent analogy to natural selection in the wild. Baylor University Medical Center Proceedings Volume 25, Number 2 The term “islands” refers not only to oceanic islands, but also to freshwater lakes separated from each other (in which innumerable fish species have evolved, for example, the African cichlids), and even to human bodies, in each of which HIV-1 evolves into a smorgasbord of “quasispecies” variants over the course of infection. The field of biological science that addresses geographic diversity is called biogeography. Geographic isolation enables a population to evolve without the intermixing of genes from other populations. Sometimes that proceeds to speciation, or the creation of a new species—reproductively isolated from other species. At other times it may go part of the way, with the creation of variants or subspecies. When I recently visited the White Sands National Monument in Arizona, I learned of a striking example of natural selection on the “islands” of extremely white sand dunes, which are made of gypsum (hydrated calcium sulfate) sand crystals. The dunes are so white that they resemble a snowscape. Three small diurnal (day-active) lizards live in the dunes, having recently evolved from closely related species that live in the brown soils of the surrounding Chihuahuan Desert. The White Sands species are no longer brown but almost white, perfectly mimicking the color of the sands (Figure 3). When mating, they demonstrate a preference for white color morphs if given a choice in laboratory tests. Researcher Erica B. Rosenblum of the University of California at Berkeley has found a genetic basis for this color change, stemming from mutations in the melanocortin-1 receptor gene, which has a key role in producing melanin in vertebrates (5). She explained to me that the change is caused by allelic variants conferring adaptive coloration, not by epigenetic gene silencing or by phenotypic plasticity (variable phenotypic expression without genetic change). It thus represents true genetic differentiation brought about by natural selection operating in a relatively new environment. The fasttrack evolution reminded me of the Galápagos finch study; in fact, the White Sands newspaper sported the headline, “The Galápagos Islands of North America!” Figure 3. The bleached earless lizard, which lives only in White Sands National Monument, New Mexico, has evolved in only 2000 to 6000 years from a darker form living in the surrounding sands of the Chihuahuan Desert. The color change, along with changes in several other traits, has been mapped to gene mutations favored by natural selection. Photograph by Greg and Mary Beth Dimijian. April 2012 Natural selection is one of the pillars of contemporary evolutionary theory. Nevertheless, there are other causes of biotic evolution, some of which were unknown to Darwin. These are addressed after a further elaboration on natural selection. MORE ABOUT NATURAL SELECTION Bricolage is a wonderful French word, the best English translation being “tinkering.” It was first used by François Jacob in 1977 to describe how evolution uses “whatever he [a tinkerer] finds around him whether it be pieces of string, fragments of wood, or old cardboards” to fashion new structures or behavior coded for by genes. Jacob explained: “Evolution does not produce novelties from scratch. It works on what already exists. . . . The appearance of new molecular structures during much of biological evolution must, therefore, have rested on alteration of preexisting ones” (6). Biological structures are thus palimpsests, with layers upon layers of history, like an old scroll erased and written over many times. One example is the vertebral column, which has been tinkered with and modified many times in vertebrate history. In the evolutionary history of whales, there is a stunning discovery: the pelvis becomes detached from the spine, as it is no longer needed to support hind limbs. The whale’s range of spinal motion is thus increased, and tiny hind limbs appear in the soft-tissue areas of fossils as relics of ancestors, destined to disappear completely in modern whales. Other structures in animals are rendered obsolete, such as eyes in some cave-dwelling fishes. The term vestigial has been used to describe these structures; they are remnants of organs once useful to an evolutionary ancestor. Genes are no exception; innumerable examples of vestigial genes, some “rusting away” like submarines on the ocean floor, have been uncovered in animal genomes. For bird lovers, a striking example of bricolage and co-opting of earlier structures is the avian feather. In the past decade paleontologists have found hundreds of fossils of feathered dinosaurs, some with fluffy down, some with simple barbs, still others with hollow filaments. The transition from scales to feathers may have hinged on a relatively simple genetic switch. What adaptive benefits might feathers have conferred on dinosaurs? The same that they confer on birds today: warmth, cryptic coloration, showy patterns used in courtship, and possibly gliding to the ground from low platforms. One chicken-sized dinosaur had feathers on arms, legs, and toes. Even though these feathered dinosaurs were not capable of flight, protofeathers and true feathers may have paved the way for true flight millions of years later. It’s an example of “exaptation,” the assignment of a new adaptive function to a structure that evolved under different selective pressures in an earlier environment. The evolution of vertebrate limbs from the fins of fish is yet another example of a new assignment (by natural selection) to an earlier structure. Fossil finds have recently come one after the other. Tiktaalik, a 375-million-year-old fossil found in 2004, is the colorful name given to a fish skeleton with gills, the first neck, and the first front limbs; the limbs consisted of a functional wrist, elbow, and shoulder—the owner could Darwinian natural selection: its enduring explanatory power 141 “do push-ups.” More recently, in 2011, came the discovery of pelvic-fin muscles in the first fishes to emerge on land (7). Here was evidence of a weight-bearing pelvis, hindlimbs, and their associated musculature—and the “rear-wheel drive” strategy that characterizes terrestrial locomotion in most vertebrates. Play the fossil frames in a movie sequence and you see the emergence of fishes onto land. Even the abrupt Cambrian “explosion” of life 541 million years ago is yielding up its secrets. There is growing evidence from molecular sequences, molecular clocks, and developmental histories that most of the Cambrian fauna originated tens to hundreds of millions of years before the onset of the Cambrian, leaving a clear fossil signature only in the Cambrian (8). Darwin has been vindicated in his prediction that this apparent anomaly would some day be resolved with evidence of ancestral lineages leading up to the explosive appearance of fossils in the Cambrian. Paleontologists stress that it is time to move past the simplistic question, “Where are the missing links in the fossil record of life?” Instead, it is time to accept that 1) the fossil record is now extraordinarily rich, and 2) a seamless record is an impossible goal. Any transition between fossils will always be a “missing link.” If you think the above examples of bricolage are amazing, get ready for this one. The stapes (or stirrup, the innermost of the three middle-ear bones) originated as the hyomandibular bone in fishes, supporting the gills. It later migrated to the hard palate, which it braced against the cranium in jawed fishes and the earliest tetrapods. It made a third change to become the columella in the middle ear of birds and the stapes of the middle-ear bones in mammals. Now a hearing aid, it was once a feeding aid and even earlier a breathing aid. And there is this: When an immature opossum is born, it climbs into its mother’s pouch with its future ear bones still articulating its jaws. The stapes will migrate to the middle ear as the embryo develops. There is hard anatomical evidence supporting these anatomical transitions (9). What better example is there of a “fossil record” in development? Remember that for natural selection to act, there must be 1) genetic variation in a population, 2) occasional mutations, and 3) mixing of genetic entities, either during reproduction (as in eukaryotic sexual reproduction) or in horizontal gene flow (as in bacteria and viruses). Crypsis (hiddenness) is a relatively simple case of natural selection. It refers to camouflaged body color or shape, and to behavior that enhances concealment. We have discussed crypsis in lizards in the White Sands National Monument. Behavioral crypsis is obvious in the immobility and squinted eyes of the Scops Owl on the bare tree branch in the Okavango Delta of Botswana (Figure 4). It is useful for hiding from predators (if you are potential prey) or for remaining unseen by potential prey (if you are a predator). The role of natural selection is inferential, but no other explanation comes close. Alleles arising by chance mutations, which cause crypsis, render an animal less visible to predators or prey. Such alleles are more successful than competitor alleles in getting into the next generation, by virtue 142 Figure 4. Only 8 inches tall, the Scops Owl is almost invisible on the bare branch that is its home, in the Okavango Delta of Botswana. Its extraordinary camouflage includes anatomy and behavior: its breast feathers resemble tree bark, and it remains immobile during the day, keeping its eyes closed so that it is less likely to be spotted by Africa’s diurnal birds of prey. Photograph by Greg and Mary Beth Dimijian. of the benefits they confer. The mutations may be random, but natural selection is anything but random. Mimicry is another relatively simple example of natural selection. If one animal is toxic to predators, and predators learn to avoid it, another animal will benefit from mimicking the same disguise. A hawkmoth caterpillar in a Costa Rican cloud forest displays conspicuous eyespots (its real eyes are tiny) and a soft, fake stinger (Figure 5). Do plants ever “lie”? Consider the passionfruit vine, often parasitized by butterfly eggs that hatch into caterpillars. The caterpillars feed on the leaves. If mutations occur in the plant that produce light-colored spots on the leaves (Figure 6), they might just resemble eggs laid by Heliconius butterflies. Experiments have shown that these butterflies are less likely to lay eggs on host plants that have eggs or egglike plant structures (10). Again, natural selection is the only candidate explanation. What about bacteria and viruses? Even though they don’t reproduce sexually, they both enjoy high levels of horizontal gene transfer (“parasexual reproduction”) and maintain populations with high genetic diversity. There is thus ample variation for selection to act on. Under an antibiotic regime, selection occurs exactly as in Darwin’s finches on the Galápagos. Differential death is the great reaper, eliminating the less fit. Baylor University Medical Center Proceedings Volume 25, Number 2 resistance genes comprising part of fossil bacterial DNA 30,000 years old. Those same genes are found today in modern bacteria, where they encode resistance to beta-lactam, tetracycline, and glycopeptide antibiotics (11). Just think: before Darwin, essentialism was the prevalent view of nature. Each species had an “essence” that was as unchanging as chemical elements in the periodic table. Each plant and animal species was believed to have originated in the same form as we see it today. DOMESTICATION OF ANIMALS Domestication is not just an excellent analogy of natural selection. It’s also a good experiment. –Richard Dawkins (12) Figure 5. Munching on a plant stem in Costa Rica’s Monteverde Cloud Forest Reserve, this Xylophanes caterpillar exhibits fake eyes and stinger. Its real eyes are so tiny that you would need a hand lens to see them. Photograph by Greg and Mary Beth Dimijian. The best experiment ever made in animal domestication (13, 14) is the ongoing study of silver foxes, initiated in the 1950s by the Russian geneticist Dmitry K. Belyaev (Figure 7). On a Siberian fur farm, Belyaev raised silver foxes, Vulpes vulpes, and observed the young of each litter. Without prompting, he and his coworkers noted which juveniles were friendly and which avoided human contact. The friendly “tame” ones were later mated with tame members of other litters, and this mating selection was performed generation after generation. Only tameness was selected for. Now, over 50 years later, the result is a breed of foxes never imagined before: friendly from birth, begging for attention, and with striking anatomical changes: a piebald coat color (with a white patch on the top of the head, seen in border collies, pigs, horses, and cows), short legs, a curled-up tail, and floppy ears. Charles Darwin, who loved dogs and spent much of his life studying domestication, would have been stunned. These changes, which occurred over only 40 generations, reflect changed timing of developmental processes. Childlike traits prolonged into adulthood are an example of neoteny—neo-, “new,” and -teny, “holding onto.” Belyaev’s unique experiment compressed into decades an ancient process that unfolded over Figure 6. Do plants tell lies? Passionflower vine leaves in Costa Rica do, preserving mutations that produce spots closely mimicking eggs of Heliconius butterflies. Plants with the spots are protected from caterpillar predation because butterflies choose to lay their eggs on other plants. Photograph by Greg and Mary Beth Dimijian. Antibiotic resistance occurs not only in modern medicine but also in nature, where microbes, plants, fungi, and insects make their own antimicrobials. It is no surprise to find that these natural antimicrobials must keep evolving in the universal hostpathogen arms race. A study in 2011 demonstrated antibiotic April 2012 Figure 7. A silver fox pup shows tame and affectionate behavior, which results from selective breeding in the longest scientific study of domestication ever made, conceived by the Russian geneticist Dmitry K. Belyaev in the 1950s. Reprinted with permission from Trut LN. Early canid domestication: the farm-fox experiment. American Scientist 1999;87(2):160–169. Darwinian natural selection: its enduring explanatory power 143 centuries. Instead of foxes, wolves are believed to be the ancestral canids that were domesticated into the hundreds of dog breeds that have become our “best friends” (Figure 8). Dog fossils have been found at archeological sites dating from 11,500 to 15,500 years ago (15). It is not surprising that dogs were domesticated long ago. They have served humans as close companions, guard dogs, police dogs, herding dogs, hunting dogs, sled dogs, military dogs, seeing dogs for the blind, and olfactory search dogs. Have dogs domesticated us as well? They may have secured equally important services from us, from feeding to family membership. There is, however, at least one example of a serious disservice we are guilty of: the bulldog’s craniofacial malformation, in which facial shortening has created severe medical problems (Figure 9). In the bulldog’s unfortunate outcome, domestication differs from natural selection. Such a defective phenotype would quickly be eliminated from the reproductive pool by natural selection. Figure 8. Over the past 10,000 to 15,000 years, humans have domesticated the Eurasian wolf and used its natural genetic variation to create hundreds of breeds of domestic dogs. Reprinted with permission from Ellegren H. Genomics: the dog has its day. Nature 2005;438(7069):745–746. Figure 9. The bulldog skull before 1890 (top) and its unfortunate fate through selective breeding in 1935 (bottom). Craniofacial malformation has created serious medical problems, which we would attempt to correct if they occurred in humans. Reprinted with permission from Thomson KS. The fall and rise of the English Bulldog. Amer Scientist 1996;84:220–223. 144 Are we domesticating ourselves? Consider the following features of modern life: • Sanitary sewerage disposal • Clean water • Cooking • Refrigeration • Clothes • Climate control • Modern medical care • “Assisted reproduction”—in vitro fertilization, preimplantation genetic diagnosis, intracytoplasmic sperm injection A more troubling question is: Are we eliminating alleles for “robust” traits from the human gene pool? ENDOGENOUS VIRAL ELEMENTS Viruses, especially bacteriophages (“phages,” viruses that infect bacteria), may be the most numerous and ubiquitous genetic entities on the planet. Genetic sampling techniques show that seawater is a soup of viruses. Bacterial turnover on Earth occurs daily through the most common predator-prey relation known, that of phages and bacteria. Whether or not you choose to consider viruses as living entities, they are visible to natural selection, just as cellular genetic entities are. There is an “archeological record” of past infections by viruses that inserted their genes seamlessly into our DNA (16). These genes are recognized by their sequence similarity to present-day viruses. Many have been found to be degraded, some more than others. Endogenous viral elements (EVEs) constitute a significant portion of our genome—as much as 8%. That’s over 6 times more DNA than is found in all of our 20,000 proteincoding genes. They are replicated in Mendelian fashion every time a cell divides. Most EVEs are retroviruses (which, like HIV-1, convert their RNA to DNA and insert it directly into our genome), but some are nonretroviral, such as Ebola-like and herpesviruslike sequences. Retroviral EVEs are called ERVs (endogenous retroviruses) and HERVs (human endogenous retroviruses). The age of endogenous viruses can be estimated by molecular clock techniques, because they are confined to a host genome and therefore “frozen” in a slower mutational state than freely existing viruses. EVEs constitute direct evidence that modern viral lineages have very ancient roots. Lentiviruses are 2 to 4 million years old; filoviruses, 12 to 30 million years. The science writer Matt Ridley has said: “If you think being descended from apes is bad for your self-esteem, then get used to the idea that you are also descended from viruses” (17). PALEOANTHROPOLOGY During only the past decade, fossil discoveries in Africa, Asia, and the Near East have provided an extraordinary sequence of the transition from arboreal to terrestrial locomotion in early hominins. One of the defining characteristics of hominins is bipedalism, and we are fast approaching an almost seamless fossil record of skeletal adaptations progressing through intermediate stages to fully bipedal, with the requisite changes in foot, ankle, Baylor University Medical Center Proceedings Volume 25, Number 2 knee, pelvis, vertebral column, upper extremities, and forward placement of the foramen magnum. These changes occurred as forests in East Africa were changing into a more open habitat, typical of the “wooded grasslands” of the East African savannah today. Bipedal locomotion enabled a huge increase in efficiency for traveling long distances in search of food and a new habitat, especially when carrying children. The most stunning finding of paleoanthropology, however, has been this: in only 3 million years the hominin body size doubled and the brain tripled in volume to its present size, violating the usual “rules” of allometry. Typically in mammals, if body weight doubles (× 21), brain weight increases not by 21 but by about 23/4 or about 1.7 times. Instead, our intracranial volume increased 3 times, with the neocortex expanding the most. More sophisticated tools, long-distance trade, language, and the earliest art accompanied the encephalization. There can be no better evidence of natural and sexual selection, even though the evidence is “only” inferential and cannot be verified experimentally. Once the stage was set—with hands free to manipulate objects, brain structures capable of complex language, and an omnivore’s gastrointestinal tract providing more efficient energy extraction from a diet of plants and animals—brain expansion progressed steadily and inexorably. Cooperation among kin and tribal members may have contributed significantly to survival of children, who—with their early birth and large brain—required a long period of upbringing. PROCESSES OTHER THAN NATURAL SELECTION THAT CONTRIBUTE TO EVOLUTION, SOME UNKNOWN TO DARWIN Natural selection is not the only process by which life evolves. I have listed other processes and mechanisms below in a short outline. • Sexual selection. Proposed by Darwin and rejected by Alfred Russel Wallace, sexual selection is distinct from natural selection and involves mate choice (intersexual selection) and competition between members of the same sex (intrasexual selection). Even though sexual selection is “natural,” it is not the same as natural selection and may even oppose natural selection, as in the case of male ornaments and bright colors that make the male more vulnerable to predation. • Endosymbiosis. “Endo,” or inside, and “symbiosis,” or living together, refer to the incorporation of a microscopic organism such as a bacterium into a larger cell, such as the protoeukaryotic cell. Mitochondria and chloroplasts have all the identifying traits of bacteria, and they perform crucial functions today (ATP synthesis and photosynthesis, respectively). Most of their genes have migrated to the host cell nucleus and are integrated into the nuclear genome, seamlessly joined in a now obligate partnership—one of the most critical events in the history of the eukaryotic cell. Endosymbiosis is an example of inheritance of acquired characteristics, i.e., Lamarckism. Surprisingly, it is entirely compatible with Darwinian natural selection acting on each partner independently; as with other mutualisms, it confers benefits upon both partners. April 2012 • Major extinctions. Both fit and unfit have perished together in Earth’s great mass extinctions, the latest of which—the “Anthropocene” (also dubbed the “Homogenocene”)—has been proposed as being underway. (Who would doubt this?) • Genetic drift in small populations. Without the buffering effect of large population size, accidents eliminate fit and unfit alike, and gene frequencies would thus change in the population, some at random. • “Accelerated evolution.” An increased mutation rate appears to have occurred in some gene regions of humans—one in neurons playing a key role in the developing cerebral cortex, and another in the FOXP2 gene, involved in human speech. This accelerated mutation rate seems also to occur in some bacterial populations subjected to stress. Something is “tampering” with mutations, providing a surplus when they are needed for a diversity of lottery tickets. The mechanism of this acceleration is unknown, but it sounds as if it may be adaptive—and thus visible to natural selection. • Neutral protein polymorphisms. Different structural forms of a protein that have little or no effect on the phenotype are invisible to natural selection in some environments. • Epigenetics and gene regulation. See discussion immediately below. EPIGENETICS At the interface of gene and environment, epigenetics (epigenomics) addresses heritable changes in gene expression that cannot be explained by changes in DNA sequence. In eukaryotes and prokaryotes, epigenetic changes can activate, reduce, or completely disable a gene’s activity. Epigenetic “marks” control access to DNA by different mechanisms, one of which is methylation of cytosine. Small noncoding RNAs (“noncoding” meaning not coding for proteins) are believed to be another agent of epigenetic change. The terms “epigenetic” and “epigenome” are still somewhat fluid and subject to change. Early in the embryonic development of multicellular organisms, undifferentiated stem cells develop into the many different cells of the developing organism, through the silencing of genes. These changes, also called “epigenetic,” usually last for a lifetime, so that a liver remains a liver. A cancer cell, however, may undergo epigenetic reprogramming, and “epimutations” may contribute to aging. Some epigenetic marks change as the organism responds to environmental change, such as starvation, stress, or disease, and some of these marks may persist for several generations (and are thus called “transgenerational epigenetic inheritance”). Mapping the epigenome has become increasingly important as we realize that the genome holds only a fraction of the information needed to understand development and disease. Genome-wide association studies are uncovering evidence of polygenic (many-genes) predisposition to specific diseases (20). Many of these genetic predispositions involve noncoding DNA that regulates gene expression. Many so-called “genetic” diseases may have their origin in such epigenetic changes. Does epigenetics change our understanding of evolution? Two studies in 2011, one in the plant Arabidopsis thaliana (18) Darwinian natural selection: its enduring explanatory power 145 and the other in the nematode Caenorhabditis elegans (19), showed epimutations that changed the phenotype for only a few generations. The changes, though inherited, were unstable over short time periods. Such cycling is not characteristic of genomic DNA, which remains relatively stable over time. Epigenetically silenced alleles seem to be taken out of the selection pool for short periods of time. This could affect evolution by natural selection on short time scales, but seems unlikely to be the basis of adaptations that are stable over long time periods. Epigenetic silencing of genes appears to be a key defense against transposons, the “jumping genes” discovered by Barbara McClintock. Transposons may be the ultimate “selfish” elements in our genome. A stunning 50% or more of the human genome is derived from retrotransposons, a category of transposons that copy and amplify themselves through RNA intermediates. Retrotransposons pepper our genome, moving to future generations in egg and sperm. Many originate from viruses, and most are strongly mutagenic, inserting themselves inside genes or adjacent to genes. Some 70 human genetic diseases are strongly correlated with mutations caused by the “gymnastics” of these mobile genetic elements. The relevance of epigenetics became apparent when it was found that retrotransposons are heavily methylated and silenced epigenetically, possibly as a defense against their continuous onslaught (21). In summary, epigenetics is of paramount importance in cellular differentiation, disease, and our defenses against endogenous and freely circulating viruses. But our understanding of its full importance in evolution is in its infancy. EARLY LIFE EVOLUTION The ponderous gap between amino acids on the one hand, and cellular organelles, cell membranes, and self-replicating macromolecules on the other, is too great for our current theories. We are very much in the dark about the origin of life. Stanley Miller’s famous experiments in the 1950s with electrical discharges, ammonia, methane, hydrogen, water vapor, and hydrogen sulfide were discounted in the 1990s, but came into favor again in 2008 when heat from hydrothermal vent ecosystems was considered. One current hypothesis states that RNA served as a hereditary template and catalyst, and that the ribosome evolved as a “machine” for building proteins, as it does today. Research suggests that a mineral in common clay may have played a role in the synthesis of RNA. Nevertheless, early life researchers are engaged in formalized guesswork. Darwin thought that the “tree of life” had a last universal common ancestor, now known by the acronym LUCA. Today we believe that the trunk of the tree was a heterogeneous mix of genetic entities that traded genes wantonly by horizontal gene transfer. Vertical inheritance would evolve later. Curiouser and curiouser. INFORMATION When DNA was found to carry the genetic code, it was realized that the information it bears is its only function. This was hard for some biologists to swallow, as it didn’t sound like bio146 chemistry. No one had ever suspected that one organic molecule could code for others, eschewing a chemical function. A digital code was clearly at the root of life. Whereas the English alphabet has 26 letters and the Greek 24, the DNA alphabet has 4 letters. Those letters spell out 3-letter words (codons) which tell the ribosome which amino acids to assemble into proteins. Was it significant—or a stunning historical accident—that binary computer science developed at the same time that we discovered the digital code of life? Here is the heart, the pulsing core of complexity: the informational code that runs the engine of life, the complex calculus that changes under the steady beat of natural selection. The complexity of life is hardly irreducible—we hold it in our hands, and we are learning to manipulate it at the molecular level. With selective death as a portal, evolution changes the information in the gene pool of a species, setting the stage for reproductive isolation and the origin of new species. CONCLUSIONS Across biological disciplines, natural selection has become accepted as a powerful and peerless explanatory principle. It is constantly scrutinizing the smallest differences among competing alleles and their phenotypic expression and has had ample time over Earth’s history to shape the life forms we see around us and in the deep fossil record. The death of the individual has been its portal for changing the gene pool of a species. Through bricolage, or tinkering, it uses old parts and constructs new machines on the palimpsest of its canvas. Biology’s informational code underlies the complex dynamics of life and has only recently yielded secrets that were undreamed of by Charles Darwin. Utterly without the knowledge we have gained since he published On the Origin of Species in 1859, Darwin gave us one of the most profound explanatory principles in the history of science. Acknowledgments The author is grateful to George M. Diggs, Jr., PhD, Professor of Biology, Austin College, and to Kyle E. Harms, PhD, Associate Professor of Biological Sciences, Louisiana State University, for their helpful comments and recommendations. 1. 2. 3. 4. 5. 6. 7. 8. Cronin H. The Ant and the Peacock. New York: Cambridge University Press, 1991:xi. Grant PR, Grant BR. How and Why Species Multiply: The Radiation of Darwin’s Finches. Princeton, NJ: Princeton University Press, 2008. Grant PR, Grant BR. The secondary contact phase of allopatric speciation in Darwin’s finches. Proc Natl Acad Sci U S A 2009;106(48):20141–20148. Available at http://www.pnas.org/content/106/48/20141.full; accessed December 1, 2011. Weiner J. The Beak of the Finch. New York: Vintage Books, 1994:50. Rosenblum EB, Harmon LJ. “Same same but different”: replicated ecological speciation at White Sands. Evolution 2011;65(4):946–960. Jacob F. Evolution and tinkering. Science 1977;196(4295):1161–1166. Cole NJ, Hall TE, Don EK, Berger S, Boisvert CA, Neyt C, Ericsson R, Joss J, Gurevich DB, Currie PD. Development and evolution of the muscles of the pelvic fin. PLoS Biol 2011;9(10):e1001168. Erwin DH, Laflamme M, Tweedt SM, Sperling EA, Pisani D, Peterson KJ. The Cambrian conundrum: early divergence and later ecological success in the early history of animals. Science 2011;334(6059):1091–1097. Baylor University Medical Center Proceedings Volume 25, Number 2 9. 10. 11. 12. 13. 14. 15. Martin T, Lue ZX. Homoplasy in the mammalian ear. Science 2005;307 (5711):861–862. Williams KS, Gilbert LE. Insects as selective agents on plant vegetative morphology: egg mimicry reduces egg laying by butterflies. Science 1981; 212(4493):467–469. D’Costa VM, King CE, Kalan L, Morar M, Sung WW, Schwarz C, Froese D, Zazula G, Calmels F, Debruyne R, Golding GB, Poinar HN, Wright GD. Antibiotic resistance is ancient. Nature 2011;477(7365):457–461. Dawkins R. The Greatest Show on Earth: The Evidence for Evolution. New York: Free Press/Simon & Schuster, 2009. Trut LN. Early canid domestication: the farm-fox experiment. American Scientist 1999;87(2):160–169. Belyaev DK. Destabilizing selection as a factor in domestication. J Hered 1979;70(5):301–308. Pionnier-Capitan M, Bemilli C, Bodu P, Célérier G, Ferrié J-G, Fosse P, Garcia M, Vigne J-D. New evidence for Upper Palaeolithic small domestic dogs in South-Western Europe. Journal of Archaeological Science 2011;38(9):2123–2140. 16. Johnson WE. Endless forms most viral. PloS Genet 2010;6(11): e1001210. 17. Ridley M. Genome: The Autobiography of a Species. New York: HarperCollins, 1999. 18. Becker C, Hagmann J, Müller J, Koenig D, Stegle O, Borgwardt K, Weigel D. Spontaneous epigenetic variation in the Arabidopsis thaliana methylome. Nature 2011;480(7376):245–249. 19. Greer EL, Maures TJ, Ucar D, Hauswirth AG, Mancini E, Lim JP, Benayoun BA, Shi Y, Brunet A. Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans. Nature 2011;479(7373): 365–371. 20. O’Donnell CJ, Nabel EG. Genomics of cardiovascular disease. N Engl J Med 2011;365(22):2098–2109. 21. Baillie JK, Barnett MW, Upton KR, Gerhardt DJ, Richmond TA, De Sapio F, Brennan PM, Rizzu P, Smith S, Fell M, Talbot RT, Gustincich S, Freeman TC, Mattick JS, Hume DA, Heutink P, Carninci P, Jeddeloh JA, Faulkner GJ. Somatic retrotransposition alters the genetic landscape of the human brain. Nature 2011;479(7374):534–537. Editor’s note: Dr. Gregory Dimijian has published several related articles in Baylor University Medical Center Proceedings that may be of interest to our readers: Pathogens and parasites: insights from evolutionary biology. 1999;12(3):175–187. Pathogens and parasites: strategies and challenges. 2000;13(1):19–29. Evolving together: the biology of symbiosis, part 1. 2000;13(3):217–226. Evolving together: the biology of symbiosis, part 2. 2000;13(4):381–390. Evolution of sexuality: biology and behavior. 2005;18(3):244–258. Warfare, genocide, and ethnic conflict: a Darwinian approach. 2010;23(3):292–300; discussion, 24(4):437–438. All articles are freely available on the journal website: www.BaylorHealth.edu/ Proceedings. April 2012 Darwinian natural selection: its enduring explanatory power 147 Baylor news ■ North Texas’ first dedicated cancer hospital opens at Baylor Dallas In February 2012, Baylor University Medical Center at Dallas (BUMC) began opening some areas of the new Baylor Cancer Hospital. The 175,000-square-foot facility is the result of a total renovation of the Collins building and the adjacent building that formerly housed the Baylor Charles A. Sammons Cancer Center. Baylor Cancer Hospital will be home to Baylor Dallas’ inpatient cancer care services, a 24-hour evaluation and treatment center for established cancer patients, and an array of support services for cancer patients, families, and caregivers. ■ BIIR names Ralph Steinman Center for Cancer Vaccines after Nobel Prize–winning physician Medical researchers, physicians, and scientists gathered in January 2012 to name the Ralph Steinman Center for Cancer Vaccines at the Baylor Institute for Immunology Research (BIIR). Dr. Steinman, a 1968 graduate of Harvard Medical School, first observed what would later become known as a dendritic cell several decades ago while working in his university lab. The dendritic cell is an important component of the human immune system that orchestrates our body’s defense against illness. Today, vaccines using dendritic cells are thought to be viable treatments for many diseases, from HIV to cancer. Scientists around the world dedicate their lives to the study of dendritic cell vaccines, including Karolina Palucka, MD, PhD, a BIIR researcher whose work on a melanoma vaccine drew Dr. Steinman’s attention. The two became great friends. In 2007, when Dr. Steinman was diagnosed with an aggressive form of pancreatic cancer, he looked at the diagnosis as an opportunity instead of a roadblock. He and Dr. Palucka designed a pancreatic cancer vaccine based on what they knew from Dr. Palucka’s clinical trials in melanoma, and the vaccine was approved by the Food and Drug Administration for a onetime compassionate use. Dr. Steinman lived for 4½ years after his diagnosis and credited dendritic cell vaccines for his survival. Last fall, 3 days after he lost his battle with the disease, he was awarded the 2011 Nobel Prize in Physiology or Medicine for his discovery of and research on dendritic cells. Medical Center at Grapevine. Hospital officials formally broke ground on the four-story tower on November 9, 2011. The 167,939-squarefoot tower will add more than 100 beds to the 276-bed hospital, making it the third-largest hospital in Baylor Health Care System (BHCS). The neonatal intensive care unit, cardiovascular services, emergency department, intensive care unit, radiology services, and surgical services will benefit from the expansion. The opening is planned for summer 2013. Baylor Grapevine also recently celebrated its 30-year anniversary as a member of BHCS. ■ Becker’s recognizes Baylor heart ■ Baylor Grapevine earns cycle III chest hospitals as Top 50 Becker’s Hospital Review, a bimonthly publication that covers hospitals and health systems, ranked both The Heart Hospital Baylor Plano and Baylor Jack and Jane Hamilton Heart and Vascular Hospital as Top 50 Hospitals with the best patient ratings for quality in the country. Hospitals included on the list are recognized for patient-centered care, medical excellence, and raising the bar for advanced, quality care. The hospitals were among only 50 hospitals with the highest percentage of patients who rated their hospital 9 out of 10 on a scale of 0 (worst) to 10 (best). The data are based on the Hospital Consumer Assessment of Healthcare Providers and Systems Survey, which allows patients to rate line items relating to their patient care experience. pain center accreditation Baylor Regional Medical Center at Grapevine received cycle III chest pain center accreditation from the Society of Chest Pain Centers. The accreditation recognizes the hospital’s expertise in providing quality care to patients who arrive with symptoms of a heart attack. To earn the accreditation, Baylor Grapevine met strict criteria aimed at reducing the time from onset of symptoms to diagnosis and treatment; treating patients more quickly during the critical window of time when the integrity of the heart muscle can be preserved; and monitoring patients when it is not certain they are having a heart attack to ensure they are not sent home too quickly or needlessly admitted to the hospital. ■ Baylor Grapevine breaks ground on a new $100.5 million patient tower A growing population with increasing health care needs fueled the demand for a $100.5 million patient tower at Baylor Regional ACCOLADES Ronald C. Jones, MD, chief of the Department of Surgery at BUMC, was elected to the position of first vice president of the Southern Surgical Association. In this role, he will preside over the scientific session and other conference events in December 2012. Randall L. Rosenblatt, MD, received the Laureate Award from the Texas Chapter of the American College of Physicians. The Laureate 148 Award honors fellows and masters of the college who have demonstrated an abiding commitment to excellence in medical care, education, or research or in service to the college. Robert L. Fine, MD, was recently named a fellow of the American Academy of Hospice and Palliative Medicine, a position currently held by approximately 200 physicians across the country. ■ Baylor Grapevine and Baylor Carrollton Grapevine named ‘Business of the Year’ by chambers of commerce The Northwest Metroport Chamber of Commerce recognized Baylor Regional Medical Center at Grapevine as the 2011 Large Business of the Year for its continued support of the organization and its mission at its annual awards banquet on January 27. The growing hospital was also honored with the community service award for its contributions to the community and unique accomplishments. The Metrocrest area is healthy because of its community neighbor Baylor Medical Center at Carrollton, said the Metrocrest Chamber, which named the hospital Business of the Year for 2011. Baylor Carrollton president and CEO Michael Sanborn, MS, FACHE, accepted the award on February 10, 2012, at the 43rd Annual Metrocrest Chamber of Commerce Awards Banquet. Proc (Bayl Univ Med Cent) 2012;25(2):148–150 RECENT GRANTS • Role and function of prohibitin in intestinal inflammation Principal investigator: Arianne L. Theiss, PhD Sponsor: National Institutes of Health Funding: $146,459 Award period: 2/1/2012–1/30/2013 • North Texas Hepatitis B Consortium: clinical site for the Hepatitis B Network Principal investigator: Robert Perrillo, MD Sponsor: University of Texas Southwestern Medical Center at Dallas/National Institutes of Health Funding: $95,591 Award period: 6/1/2011–5/31/2012 • Molecular mechanisms of plasmacytoid dendritic cell interactions Principal investigator: Yong-Jun Liu, MD, PhD Sponsor: MD Anderson Cancer Center/ National Institutes of Health Funding: $369,477 Award period: 9/13/2011–8/31/2012 • Mechanisms of B-cell responses in autoimmune disease Principal investigator: John Cush, MD Sponsor: Duke University/National Institutes of Health Funding: $177,971 Award period: 5/1/2011–4/30/2012 • Altered T follicular helper cell subsets in active pediatric systemic lupus erythematosus Principal investigator: Hideki Ueno, MD, PhD ■ Baylor Garland’s new discharge lounge eases patient transition A new patient discharge lounge was unveiled November 1, 2011, at Baylor Medical Center at Garland. The discharge lounge is designed to ease long waits for available hospital rooms. It has been taking an average of about 4 hours for patients to leave their hospital rooms after discharge. This means during peak times, patients admitted from the emergency department must wait until a hospital bed becomes available. The goal is to reduce that time to 2 hours by moving discharged patients into the comfortable lounge while they wait for a family member or friend to pick them up. April 2012 • • • • Sponsor: Alliance for Lupus Research Funding: $170,227 Award period: 2/1/2012–1/31/2013 Immune signatures of tuberculosis disease in cynomolgus macaques Principal investigator: Virginia Pascual, MD Sponsor: University of Pittsburgh/Bill & Melinda Gates Foundation Funding: $146,268 Award period: 10/3/2011–8/31/2012 Genetic dissection of systemic lupus erythematosus—from mouse to man Principal investigator: Virginia Pascual, MD Sponsor: University of Texas Southwestern Medical Center at Dallas/National Institutes of Health Funding: $273,017 Award period: 9/1/2011–8/31/2012 Role of mucosal dendritic cell subsets in the control of influenza A virus immunity Principal investigator: A. Karolina Palucka, MD, PhD Sponsor: Mount Sinai School of Medicine/ National Institutes of Health Funding: $95,000 Award period: 7/15/2011–6/30/2012 Selenium colorectal cancer chemoprevention trials Principal investigator: C. Richard Boland, MD Sponsor: The University of Arizona/National Institutes of Health Funding: $51,064 Award period: 8/1/2011–7/31/2012 The lounge, located on the first floor near access services, is staffed by a nurse, tech, and volunteer to ensure the comfort and safety of patients. Patients can use wi-fi, read magazines, or enjoy light snacks while waiting for transportation home. To use the lounge, patients must be able to sit comfortably in a recliner. Orthopedic patients (who typically require a lot of equipment) and mothers with newborns will not be moved from their rooms to the lounge. • Lysosomal disease network Principal investigator: Raphael Schiffman, MD Sponsor: University of Minnesota/National Institutes of Health Funding: $55,000 Award period: 9/1/2011–8/31/2012 • A large population-based study of surgery for abdominal aortic aneurysms Principal investigator: Giovanni Filardo, PhD Sponsor: Agency for Healthcare Research and Quality Funding: $232,136 Award period: 5/1/2012–4/30/2013 • Targeting dendritic cells to block immunosuppression in breast cancer Principal investigator: Yong-Jun Liu, MD, PhD Sponsor: Cancer Prevention and Research Institute of Texas Funding: $274,014 Award period: 9/1/2011–8/31/2012 • Antibody-based combination immunotherapy against prostate cancer Principal investigator: Sangkon Oh, PhD Sponsor: American Cancer Society Funding: $180,000 Award period: 1/1/2012–12/31/2012 prestigious Pathway to Excellence designation from the American Nurses Credentialing Center. The designation identifies the hospitals as having a work environment where nurses can flourish and are empowered to provide outstanding care to patients. The designation also substantiates the professional satisfaction of nurses and identifies the hospitals as one of the best places to work. ■ Baylor ranked one of nation’s top ■ Baylor Garland and Our Children’s House on the Pathway to Excellence Baylor Medical Center at Garland and Our Children’s House at Baylor recently earned the Baylor news integrated health networks BHCS was recently recognized as one of the nation’s “Top 100 Integrated Healthcare Networks” for 2012. Baylor ranked 25th out 149 of nearly 600 health care systems surveyed by IMS, one of the world’s leading providers of health care information, analytic, and technology services with a presence in more than 100 countries. IMS’s rating system takes into account eight factors: integration, integrated technology, contractual capabilities, outpatient utilization, financial stability, services and access, hospital utilization, and physicians. “Advanced technology has rapidly become a pillar of the health care industry and will only increase in importance as federal health care reforms take effect in the coming years,” said Joel Allison, BHCS president and CEO. “Being recognized as one of the top 100 integrated health networks shows how committed Baylor is to maximizing our technological capabilities.” UPCOMING CME PROGRAMS The A. Webb Roberts Center for Continuing Education of Baylor Health Care System is offering the following programs: Wound Care: The Next Generation—Update on Wound Care, Diabetes, and Ethics, April 28, 2012, at Baylor University Medical Center at Dallas Third Annual Latest Advances in Ischemic and Hemorrhagic Stroke Therapy Conference, May 19, 2012, at the Westin Galleria, Dallas, Texas Baylor All Saints Advances in Cardiovascular Conference, October 6, 2012, at the Omni Fort Worth Hotel, Fort Worth, Texas For more information, call 214-820-2317 or visit www.cmebaylor.org PHILANTHROPY NOTES ■ Foundation board chair Erle Nye receives prestigious Linz Award Erle Nye, the chairman of the BHCS Foundation board, has received the 2012 Linz Award, one of the oldest and most prestigious recognitions a Dallasite can receive in honor of extraordinary civic service or humanitarian efforts. In addition to his extensive experience in the corporate world—he was leader at TXU for more than 20 years and now serves as chairman emeritus—Nye has been involved in numerous community, state, and national causes for several decades. He served on the executive boards of the SMU Cox School of Business and the SMU Dedman School of Law, spent 12 years on the Texas A&M University System Board of Regents, and has been chair of the University of Texas Investment Management Company. He also serves as vice chairman of the Governor’s Business Council. He became chairman of the Foundation board in 2010. Nye was nominated for the honor by Joel Allison, president and CEO of BHCS. ■ Gift with ties to Singapore, India supports cancer care in Dallas When the new Baylor Cancer Hospital at BUMC is completely open in spring 2013, 150 cancer patients will have access to a specialized emergency department that will provide people with compromised immune systems safer access to emergency care. The new oncology emergent care clinic waiting room, while located on the BUMC campus, will have a plaque outside its door that reads: “Given generously by Smt. Ginnidevi Radhavallabji Khetan Charitable Trust, Jhunjhunu, India.” The generous $100,000 gift that will name the oncology emergent care clinic waiting room was given through a trust established by Ashok Khetan. Mr. Khetan was looking for a way to honor the memory of his late mother, who fought and lost her battle to cancer but whose generous spirit inspired a family tradition of philanthropy. Mr. Khetan’s nephews, twin brothers Rainer Khetan, MD, and Roger Khetan, MD, are both physicians on staff at BUMC. They suggested to their uncle that he give a gift to Baylor. Mr. Khetan’s gift will fund the oncology patient navigation program at the Baylor Charles A. Sammons Cancer Center. The program provides cancer patients with a nurse who helps ensure they receive timely diagnosis and treatment as well as education, emotional support, and identification of resources needed in the course of their cancer journey. Baylor University Medical Center Proceedings ■ Foundation looks to build on fundraising success While national charitable giving is rising at modest rates consistent with the economic recovery, BHCS Foundation had its best year on record in fiscal year 2011. The Foundation raised more than $36 million for BHCS initiatives, including a $20 million transformational gift from Annette and Harold Simmons for organ transplantation. Over the past 5 years, the Foundation has raised $144 million to support Baylor initiatives. “Baylor has a proud history of philanthropic support, and we continue to earn our community’s support through the value we provide,” said Foundation president Rowland K. Robinson. “This fundraising success offers significant opportunity to redefine health care for our community, as we continue to build upon our national reputation for safety, quality, leadership, and clinically advanced bedside care.” Mr. Robinson added, “The faith that our donors demonstrate in us is inspiring and gratifying, yet we know our work is not complete. To sustain excellence requires innovation and investment. We are building momentum toward something bold that will shape the future of Baylor. We look forward to sharing it with the community in the next year.” Volume 25, Number 2 Proc (Bayl Univ Med Cent) 2012;25(2):151 151 Baylor Sammons Cancer Center at Dallas Site Tumor Conference Extraadrenal pheochromocytoma and vagal paraganglioma Andrew W. Jennings, MD, John T. Preskitt, MD, and Raphaelle D. Vallera, MD P heochromocytomas and catecholamine-secreting paragangliomas, also referred to as extraadrenal pheochromocytomas, are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and sympathetic ganglia. These tumors are uncommon causes of hypertension, accounting for <0.2% of cases (1, 2). While pheochromocytomas are inherently catecholamine-secreting tumors, paragangliomas are less likely to be functional, especially when located in the head and neck. Paragangliomas are rare and widespread tumors, commonly found in the head and neck region. The most common location for head and neck tumors is at the carotid bifurcation, while abdominal tumors are most commonly found in the periaortic-pericaval region (3). While most cases are sporadic, about one fourth of patients with pheochromocytomas are found to have genetic mutations associated with familial disorders, including multiple endocrine neoplasia type 2 syndrome associated with the RET protooncogene, von Hippel-Lindau syndrome associated with the VHL tumor suppressor gene, and mutations in succinate dehydrogenase subunits B and D. These patients typically present at a younger age and are more likely to have bilateral adrenal pheochromocytomas or paragangliomas (4). Paragangliomas are also associated with inherited syndromes caused by genetic mutations in succinate dehydrogenase subunits. Succinate dehydrogenase inactivation has been implicated with the activation of hypoxia-inducible genes involved with tumorigenesis and is an active area of cancer research (5). Rates of malignancy for pheochromocytomas have been reported as 5% to 26%, while reports of malignant paragangliomas are more rare (6, 7). Malignant tumors lack histological and molecular markers that can reliably distinguish them from benign tumors (8). In addition, malignant tumors classified as benign may present at a later time with widely metastatic disease and associated decreased overall survival (9). We present the case of a 51-year-old man with an extraadrenal pheochromocytoma and vagal paraganglioma diagnosed within several months of each other. The patient was successfully treated with surgical excision. While pheochromocytomas and paragangliomas are well documented, to our knowledge there are few if any case reports of an extraadrenal pheochromocytoma and a vagal paraganglioma in the same patient. Therefore, this case report should inform the practitioner of the possibility of 152 multiple primary tumors when treating patients with either condition. CASE PRESENTATION A 51-year-old Caucasian man was initially worked up at an outside institution for severe abdominal and back pain. A computed tomographic (CT) scan of the abdomen and pelvis demonstrated an approximately 4 cm retroperitoneal periaortic mass (Figure 1). The patient was then transferred to our institution for a higher level of care. At presentation to our institution, the patient’s blood pressure was 190/90 mm Hg, and his heart rate was 68 beats per minute with a regular rate and rhythm. The patient was a healthy appearing middle-aged male. No palpable masses were noted on the abdominal exam. Pertinent past medical history included the excision of an abdominal mass at 9 years of age. Figure 1. Heterogeneously enhancing mass on the right side of the retroperitoneum within the aortocaval space. Subsequent excision revealed an extraadrenal pheochromocytoma. From the Division of Surgical Oncology, Department of Surgery (Jennings, Preskitt), and the Division of Endocrinology, Department of Internal Medicine (Vallera), Baylor University Medical Center at Dallas. Corresponding author: John T. Preskitt, MD, FACS, 3410 Worth Street, Suite 235, Dallas, Texas 75246 (e-mail: [email protected]). Proc (Bayl Univ Med Cent) 2012;25(2):152–154 He was told that it was malignant a b but ceased follow-up for a number of years afterwards. In addition, the patient was recently diagnosed with hypertension that had been difficult to control pharmacologically. Otherwise, the patient had no significant medical history. He worked as an intensive care nurse and had no history of alcohol, tobacco, or substance abuse. Family history was negative for any similar familial tuFigure 2. Histology for the two tumors. (a) The retroperitoneum tumor with chromogranin staining. (b) The cervical mors or hypertension. mass with hematoxylin and eosin staining. The patient’s 24-hour urine metanephrines were markedly elevated at 4057 mcg (reference range, a b 0–899), with normetanephrines of 4015 mcg (reference range, 0–599) and a metanephrine-to-creatinine ratio of 2352 (reference range, 0–599). Chromogranin A was also elevated at 1402 ng/mL (reference range, 0–15). Plasma-free normetanephrines were elevated at 9.74 (n < 0.9), and the plasma-free metanephrines were normal. The patient was started on phenoxybenzamine, which normalized his blood pressure. He was subsequently started on Figure 3. Large vascular tumor seen (a) below and (b) extending above the left carotid bifurcation. Subsequent atenolol once his blood pressure excision revealed a vagal paraganglioma. was appropriately blocked with the alpha-blockade. An excision of the retroperitoneal mass this mass several months earlier but had not brought it to a was performed with a multispecialty team, including surgi- physician’s attention, and it had been missed on previous physical oncologists and vascular surgeons. The mass was identi- cal exams. Approximately 15 weeks after the first surgery, the fied at the aortic bifurcation at the organ of Zuckerkandl and patient returned for excision of this mass. Intraoperatively the was successfully excised, including resection of a portion of mass was found to involve not the carotid body, as suspected, but the aortic wall. No significant intraoperative blood pressure the vagus nerve. It was successfully resected, and the patient had variations were noted. Postoperatively, the patient had labile an uneventful postoperative hospital course. Pathology showed blood pressure and initially required vasopressor support. Af- a 4.5 × 2.5 × 2.0 cm paraganglioma, consistent with a primary ter several days, the blood pressure stabilized and the patient tumor based on location and histological findings (Figure 2b). was discharged home on postoperative day 6. Pathology confirmed the diagnosis of a 6.0 × 4.5 × 4.2 cm pheochromocytoma DISCUSSION (Figure 2a), and the patient was followed as an outpatient. Given our patient’s remote history of an abdominal tumor Postoperatively his plasma-free metanephrines showed resection as a child, he likely had a recurrent pheochromocytoa normetanephrine still elevated at 295 (n < 148), and the ma with a concurrent vagal paraganglioma. The paraganglioma metanephrine and chromogranin A were normal. A succinate was diagnosed with CT scan and MIBG scan and presented as dehydrogenase  genetic screen was negative. a palpable mass. This has been shown to be the most common While being followed as an outpatient, a metaiodobenzyl- presenting symptom of benign paragangliomas at 55%, with guanidine (MIBG) scintiscan was obtained, which showed a other presenting symptoms including tinnitus and cranial nerve mass in the left neck. A CT scan of the neck showed a mass palsies. The diagnosis of head and neck paragangliomas is made that appeared to be at the carotid bifurcation, consistent with incidentally in up to 10% of cases when imaging is obtained a carotid body tumor (Figure 3). The patient was referred to a for other reasons. Although head and neck paragangliomas are vascular surgeon for excision. At that time, a palpable mass was less likely to be functional, up to 4% have been shown to be present in the region of the carotid bifurcation in the left neck. functional, and therefore it is recommended that these patients Further questioning of the patient revealed that he had noticed are screened for catecholamine excess (3). Another study showed April 2012 Baylor University Medical Center Proceedings 153 that out of 175 patients with head and neck paragangliomas, 18.9% had multiple lesions and 6.3% were malignant. SDH mutation carriers had an even higher incidence of multiple tumors and malignancy, at 64.7% and 20.6%, respectively. The majority were again carotid body tumors, at 60% of head and neck paragangliomas in this particular series (10). This case demonstrates that patients can present with multiple pheochromocytomas or paragangliomas either concurrently or with a significant time interval between diagnoses. In our case, the patient presented with two separate tumors in different anatomical locations approximately 42 years after surgical excision of his initial tumor. Although these cases are rare, clinicians treating patients with such conditions should maintain close follow-up even in the absence of clinical symptoms and with a history of benign pathology from previous excisions. Special attention should be paid to the head and neck exam, as these lesions can be easily overlooked. Finally, appropriate genetic screening should be considered in patients and families when hereditary syndromes are suspected. 1. 2. 3. 154 Stein PP, Black HR. A simplified diagnostic approach to pheochromocytoma. A review of the literature and report of one institution’s experience. Medicine (Baltimore) 1991;70(1):46–66. Pacak K, Linehan WM, Eisenhofer G, Walther MM, Goldstein DS. Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma. Ann Intern Med 2001;134(4):315–329. Erickson D, Kudva YC, Ebersold MJ, Thompson GB, Grant CS, van Heerden JA, Young WF Jr. Benign paragangliomas: clinical presentation and treatment outcomes in 236 patients. J Clin Endocrinol Metab 2001;86(11):5210–5216. 4. Neumann HP, Bausch B, McWhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, Januszewicz A, Eng C, Smith WM, Munk R, Manz T, Glaesker S, Apel TW, Treier M, Reineke M, Walz MK, Hoang-Vu C, Brauckhoff M, Klein-Franke A, Klose P, Schmidt H, Maier-Woelfle M, Peçzkowska M, Szmigielski C, Eng C; Freiburg-Warsaw-Columbus Pheochromocytoma Study Group. Germline mutations in nonsyndromic pheochromocytoma. N Engl J Med 2002;346(19):1459–1466. 5. Gimenez-Roqueplo AP. New advances in the genetics of pheochromocytoma and paraganglioma syndromes. Ann N Y Acad Sci 2006;1073: 112–121. 6. Eisenhofer G, Bornstein SR, Brouwers FM, Cheung NK, Dahia PL, de Krijger RR, Giordano TJ, Greene LA, Goldstein DS, Lehnert H, Manger WM, Maris JM, Neumann HP, Pacak K, Shulkin BL, Smith DI, Tischler AS, Young WF Jr. Malignant pheochromocytoma: current status and initiatives for future progress. Endocr Relat Cancer 2004;11(3): 423–436. 7. Lee JH, Barich F, Karnell LH, Robinson RA, Zhen WK, Gantz BJ, Hoffman HT; American College of Surgeons Commission on Cancer; American Cancer Society. National Cancer Data Base report on malignant paragangliomas of the head and neck. Cancer 2002;94(3):730–737. 8. Gimenez-Roqueplo AP, Favier J, Rustin P, Rieubland C, Crespin M, Nau V, Khau Van Kien P, Corvol P, Plouin PF, Jeunemaitre X; COMETE Network. Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas. Cancer Res 2003;63(17):5615– 5621. 9. Nomura K, Kimura H, Shimizu S, Kodama H, Okamoto T, Obara T, Takano K. Survival of patients with metastatic malignant pheochromocytoma and efficacy of combined cyclophosphamide, vincristine, and dacarbazine chemotherapy. J Clin Endocrinol Metab 2009;94(8):2850–2856. 10. Papaspyrou K, Mewes T, Rossmann H, Fottner C, Schneider-Raetzke B, Bartsch O, Schreckenberger M, Lackner KJ, Amedee RG, Mann WJ. Head and neck paragangliomas: report of 175 patients (1989–2010). Head Neck 2011 Jun 20 [Epub ahead of print]. Baylor University Medical Center Proceedings Volume 25, Number 2 Dermatology Report Widespread dermal ulcerations and bullae Jay Wofford, Mahir Patel, MD, Allison Readinger, MD, and Alan Menter, MD Bullous pemphigoid is an autoimmune disease of the skin characterized by large, tense bullae resulting in significant morbidity in affected individuals. The diagnosis of bullous pemphigoid may present challenges due to clinical similarities with various other bullous eruptions. Frequently, epidemiological features can provide clues to the diagnosis of bullous pemphigoid, with histologic analysis commonly required for definitive diagnosis. This case study illustrates the typical clinical and histologic findings seen in bullous pemphigoid patients and briefly discusses the differential diagnosis. An in-depth understanding of the intricate pathophysiology is essential in order to educate patients. After diagnosis and appropriate workup, an array of treatment approaches, including topical and systemic corticosteroids, immunosuppressive agents, antibiotics, chemotherapeutic agents, and even monoclonal antibodies, may be utilized individually or in combination to achieve an optimal therapeutic response. extremities, and bilateral lower extremities. Of note, the left neckline showed a 4 cm × 2 cm erythematous, superficial area of ulceration with associated crusting and several 1 cm pustules extending onto the left upper chest (Figure 2). In addition, erythema and diffuse hyperpigmentation were noted in a photo-distributed area around the neck and over the upper back. Large, flaccid bullae were observed over the bilateral lower extremities and the inner thighs (Figure 3). Gentle pressure applied to the edge of a bulla failed to elicit enlargement of the blister or separation of the superficial layers of the skin (negative Nikolsky’s sign). A skin biopsy was taken from the upper back for hematoxylin and eosin (H&E) staining. A second biopsy from an individual bulla on the knee was also obtained for immunofluorescence staining. A provisional diagnosis of bullous pemphigoid was made based on clinical findings, and the patient was prescribed 40 mg prednisone twice a day for 1 month, as well as 500 mg cephalexin three times daily for 10 days. In addition, B ullous diseases are a group of dermatological conditions characterized clinically by fluid-filled blisters of varying sizes and histological depths within the epidermis and dermis. Many of these eruptions have similar presentations and overlapping characteristics. However, key clinical and histopathological differences allow for distinction between these bullous disease subtypes. Here, we discuss a patient who presented to our outpatient clinic with widespread bullae and was subsequently diagnosed with bullous pemphigoid. CASE PRESENTATION A 59-year-old Hispanic man presented to us with a 1-year history of a diffuse, pruritic rash distributed over the entire body, including the buttocks and groin. At the time of presentation, he was not receiving any form of topical or systemic therapy. Past treatments included oral penicillin and corticosteroid injections, with minimal to no relief. The patient reported prior oral lesions but denied any current mucosal or joint involvement. The patient reported no significant past medical history, surgical history, allergies to medications, or a family history of skin disease. Upon physical examination, the patient exhibited multiple superficial ulcerations with purulence and crusting involving the scalp (Figure 1), nose, neck, upper back, bilateral upper Proc (Bayl Univ Med Cent) 2012;25(2):155–158 Figure 1. Superficial ulcerations throughout the scalp with extensive crusting. From Texas Tech University Health Sciences Center, School of Medicine, Lubbuck, Texas (Wofford), and the Division of Dermatology, Department of Internal Medicine, Baylor University Medical Center at Dallas (Patel, Readinger, Menter). Corresponding author: Alan Menter, MD, Division of Dermatology, Department of Internal Medicine, Baylor University Medical Center at Dallas, 3900 Junius Street, Suite 145, Dallas, Texas 75246 (e-mail: [email protected]). 155 Figure 2. Superficial ulceration with secondary crusting on the left medial clavicle, discrete pustules on the left chest, and photodistributed erythema around the neck. Figure 4. Subepidermal separation of the epidermis with reepithelialization of the base of the blister. The dermis shows infiltration by neutrophils and eosinophils. Figure 3. Large, flaccid bullae of the lower extremity and inner thigh. Figure 5. Immunofluorescence shows linear deposition of IgG along the basement membrane zone. the patient was prescribed halobetasol propionate 0.05% ointment for topical application to affected areas. Histologically, the H&E stain showed the presence of subepidermal blister formation with reepithelialization at the base (Figure 4). The blister was filled with serous exudate and red blood cells. In the dermis, collections of perivascular lymphocytes with scattered neutrophils and eosinophils were observed. The immunofluorescence biopsy showed linear deposits of immunoglobulin (Ig) G and C3 along the basement membrane zone (Figure 5). Immunofluorescence was negative for IgA and IgM. Both biopsy specimens confirmed a diagnosis of bullous pemphigoid. DISCUSSION Bullous pemphigoid is an autoimmune blistering skin disease characterized clinically by the presence of large, tense blisters occurring anywhere on the body, but typically seen in preferred locations, including the trunk and flexural regions of the limbs, groin, and lower abdomen. These lesions often ulcerate, become pustular, or rupture with resultant crusting (1). Bullous pemphigoid usually occurs in older patients in the 156 sixth to eighth decades of life, with a predilection for males (2). According to population-based cohort studies in the United Kingdom, the incidence of bullous pemphigoid is 4.3 cases per 100,000 person-years (3). Approximately 10% to 30% of patients with bullous pemphigoid have involvement of the mucous membranes, which is usually transient (4). Bullous pemphigoid, although associated with a relatively low mortality, may cause high morbidity in a percentage of affected individuals (5). Clinically, the cutaneous findings in bullous pemphigoid can be highly variable. In the initial phase of the disease, nonspecific symptoms such as generalized pruritus with or without associated eczematous, excoriated, papular, and/or urticarial lesions may predominate. The bullous phase of the disease follows, being characterized by tense vesicles or bullae containing serous or blood-tinged fluid (4). These blisters can be present on an erythematous base or normal skin, often with associated excoriated papules and/or plaques. The blisters of bullous pemphigoid usually range from 0.5 to 4 cm in diameter, may persist for several days, and frequently rupture, leaving erosions, Baylor University Medical Center Proceedings Volume 25, Number 2 ulcerations, or crusted lesions (1). Blisters in bullous pemphigoid are often symmetrically distributed over the body surface and favor flexural areas, including the groin, axillae, and lower abdomen (4). The bullae of bullous pemphigoid do not extend laterally, thus exhibiting a negative Nikolsky’s sign, and usually heal without scarring. Upon resolution of inflammatory lesions, hyperpigmented or hypopigmented areas of postinflammatory change may be seen (2). Mucous membrane involvement, while uncommon, may affect the oral cavity, eyes, nose, pharynx, esophagus, or anogenital regions and is associated with higher morbidity and mortality (5). Histologically, subepidermal bullae are the characteristic pathological finding. These bullae, as in our case, are caused by linear deposition of circulating IgG antibodies and C3 along the basement membrane zone of the dermal-epidermal junction (1, 4). These IgG antibodies are specifically directed against hemidesmosome-associated proteins located in the basement membrane, known as antigens BP230 and BP180 (6, 7). Once deposited, these IgG antibodies attract complement C3, which, upon deposition, elicits an inflammatory response. An inflammatory cascade results with the additional attraction of neutrophils, lymphocytes, and eosinophils, which deposit in the dermis or within the blister cavity (6, 7). The release of protease enzymes from accumulated neutrophils damages the junctional adhesion complexes responsible for dermal and epidermal cohesion. The end result of this inflammation is the separation of the epidermis from the dermis, resulting in blister formation (8). The early, nonbullous phase of bullous pemphigoid is often clinically nonspecific. Thus, the differential diagnosis of early bullous pemphigoid is broad and includes conditions such as prurigo, urticaria, allergic contact dermatitis, arthropod reactions, pemphigus foliaceus, scabies, and vasculitis. Many of these conditions can be distinguished from bullous pemphigoid based on clinical history. When history and physical examination fail to narrow the diagnosis, biopsy with immunofluorescence analysis will invariably distinguish early bullous pemphigoid from these other conditions (4). In the bullous stage of bullous pemphigoid, multiple disorders need to be differentiated (Table). While the clinical context, especially the nature of the blister, may provide clues to the diagnosis, immunofluorescence analysis is often required for definitive diagnosis, as in our case (1–4). In addition, there is a somewhat controversial association between bullous pemphigoid and underlying internal malignancy. In multiple publications, bullous pemphigoid has been reported to develop with increased frequency in patients with malignant neoplasms of various internal organ systems, including the digestive tract, lung, and urinary bladder (9, 10). An increased risk of lymphoproliferative malignancies has also been suggested (10). However, other studies have shown that patients with bullous pemphigoid do not have an increased incidence of internal malignancy when compared to the general population matched for age and sex (9). Numerous case-control studies indicate that an increased risk of malignancy in bullous pemphigoid patients appears to be marginal and is probably April 2012 Table. Differential diagnosis for the bullous stage of bullous pemphigoid • Pemphigus vulgaris • Bullous lupus erythematosus • Stevens-Johnson syndrome • Porphyria cutanea tarda • Pseudoporphyria • Bullous impetigo • Bullous drug eruption • Cicatricial pemphigoid • Dermatitis herpetiformis • Epidermolysis bullosa • Paraneoplastic pemphigus related to the older age of patients with bullous pemphigoid rather than the disease process itself (4, 10). Currently, extensive studies for underlying internal malignancy should not be the standard of care in patients with bullous pemphigoid, unless history and physical exam indicate otherwise (9). Nevertheless, this blistering disease does appear to develop concomitantly with an underlying neoplasm in rare instances. Therefore, bullous pemphigoid patients with other systemic symptoms or atypical presentations, such as younger age, may require investigative cancer screening (4). Patients with bullous pemphigoid usually carry a favorable prognosis, with spontaneous resolution noted in a small percentage of patients within months to years of initial presentation. However, bullous pemphigoid is frequently a chronic disease with exacerbations and remissions. Due to the healing capability of blisters in bullous pemphigoid, mortality is low. More widespread involvement with multiple bullae and ulcerations increases the mortality risk, necessitating immediate intervention (1). Topical and systemic corticosteroids along with other immunosuppressive medications make up the primary treatment regimen for most patients with bullous pemphigoid. In limited or localized cutaneous disease, high-potency topical corticosteroids and/or topical immunomodulators, such as tacrolimus, may be sufficient. However, for more widespread disease, the use of systemic corticosteroids frequently halts further blister formation within days of treatment initiation. Prednisone, dosed at 0.5 to 1.0 mg per kg of body weight daily, is generally considered to be the first-line treatment modality for controlling bullous pemphigoid. In milder cases of bullous pemphigoid, other antiinflammatory medications such as dapsone and tetracyclines have proven effective. Dapsone has been shown to produce a favorable response in treating the mucosal lesions of bullous pemphigoid. In patients with chronic bullous pemphigoid, systemic corticosteroids are commonly used initially to rapidly control the disease, with eventual tapering and introduction of maintenance immunosuppressive medications. In this commonly used regimen, oral prednisone is initiated at a dose of 0.5 to 1.0 mg per kg of body weight per day, leading to no new blister formation within 1 to 2 weeks. Thereafter, the corticosteroid dose is gradually tapered and an immunosuppressive drug such as azathioprine, methotrexate, or mycophenolate mofetil is added for maintenance Widespread dermal ulcerations and bullae 157 therapy (1, 4). A period of medication overlap exists until systemic corticosteroids are eventually discontinued (4, 11). The selection of an immunosuppressive drug for maintenance therapy is often made based on side effect profile, cost, and practicality. For elderly patients, who make up the majority of bullous pemphigoid cases, methotrexate may be the most cost-effective and tolerable option (11). Finally, in clinically severe disease, more aggressive treatment with plasmapheresis or cyclophosphamide may be required for therapeutic success, with intravenous immunoglobulin and rituximab treatment used in highly treatment-resistant cases (1, 4). 1. 2. 3. Nousari HC, Anhalt GJ. Pemphigus and bullous pemphigoid. Lancet 1999;354(9179):667–672. Bickle K, Roark TR, Hsu S. Autoimmune bullous dermatoses: a review. Am Fam Physician 2002;65(9):1861–1870. Langan SM, Smeeth L, Hubbard R, Fleming KM, Smith CJ, West J. Bullous pemphigoid and pemphigus vulgaris—incidence and mortality in the UK: population based cohort study. BMJ 2008;337:a180. 4. Borradori L, Bernard P. Bullous pemphigoid. In Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology, 2nd ed. St. Louis, MO: Mosby Elsevier, 2008:431–445. 5. Wojnarowska F, Kirtschig G, Highet AS, Venning VA, Khumalo NP; British Association of Dermatologists. Guidelines for the management of bullous pemphigoid. Br J Dermatol 2002;147(2):214–221. 6. Zillikens D, Mascaro JM, Rose PA, Liu Z, Ewing SM, Caux F, Hoffmann RG, Diaz LA, Giudice GJ. A highly sensitive enzyme-linked immunosorbent assay for the detection of circulating anti-BP180 autoantibodies in patients with bullous pemphigoid. J Invest Dermatol 1997;109(5):679–683. 7. Mueller S, Klaus-Kovtun V, Stanley JR. A 230-kD basic protein is the major bullous pemphigoid antigen. J Invest Dermatol 1989;92(1):33–38. 8. Liu Z, Giudice GJ, Zhou X, Swartz SJ, Troy JL, Fairley JA, Till GO, Diaz LA. A major role for neutrophils in experimental bullous pemphigoid. J Clin Invest 1997;100(5):1256–1263. 9. Ortíz LJ, Vázquez M, Sánchez JL. Bullous pemphigoid and malignancy. Bol Asoc Med P R 1990;82(10):458–459. 10. Rzany B, Weller N. Epidemiology of autoimmune skin disorders. In Hertl M, ed. Autoimmune Diseases of the Skin. New York: Springer Verlag, 2001:21–38. 11. Patton T, Korman N. Role of methotrexate in the treatment of bullous pemphigoid in the elderly. Drugs Aging 2008;25(8):623–629. Avocations “Red tulips.” Photo © Rolando M. Solis, MD. Dr. Solis is an interventional cardiologist on the medical staff of Baylor Medical Center at Garland. 158 Baylor University Medical Center Proceedings Volume 25, Number 2 Electrocardiographic Report Irregular cardiac rhythm in a woman with asthma D. Luke Glancy, MD, Elias B. Hanna, MD, and Camelia C. Ilie, MD Figure 1. Electrocardiogram obtained at admission. See text for explication. A n obese (height, 62 inches; weight, 252 lb; body mass index, 46.2 kg/m2) 54-year-old woman with longstanding asthma and chronic cigarette smoking came to the hospital with an acute asthma attack manifested by dyspnea, wheezing, and chest tightness. Her electrocardiogram showed an irregular atrial tachycardia (114 P waves/minute) with multiple P-wave morphologies, frequent aberrant ventricular conduction, and one nonconducted P wave (Figure). Thus, the patient had multifocal atrial tachycardia, also called chaotic atrial mechanism (1), chaotic atrial tachycardia (2), or chaotic atrial rhythm (3). As the name implies, multifocal atrial tachycardia has generally been thought to originate from multiple atrial foci, but because variable conduction of impulses from a single focus cannot be excluded, the mechanistically noncommittal term multiform atrial tachycardia has been suggested (4). Proc (Bayl Univ Med Cent) 2012;25(2):159–160 Multifocal atrial tachycardia usually is seen in patients who are severely ill with a noncardiac problem, which often, as in this patient, is an acute exacerbation of chronic lung disease. Beta-adrenergic agonists and theophylline may be contributing factors. Multifocal atrial tachycardia is often mistaken for atrial fibrillation. Although it is a distinct nosological entity, multifocal atrial tachycardia is often preceded or followed by other atrial arrhythmias, such as atrial fibrillation, atrial flutter, and other atrial tachycardias (2, 4). Multifocal atrial tachycardia From the Department of Medicine, Louisiana State University Health Sciences Center, and the Interim Louisiana State University Public Hospital, New Orleans, Louisiana. Corresponding author: D. Luke Glancy, MD, 7300 Lakeshore Drive, #30, New Orleans, Louisiana 70124 (e-mail: [email protected]). 159 usually disappears when the underlying medical problem has been controlled. 2. Phillips J, Spano J, Burch G. Chaotic atrial mechanism. Am Heart J 1969;78(2):171–179. 4. 1. 3. Lipson MJ, Naimi S. Multifocal atrial tachycardia (chaotic atrial tachycardia). Circulation 1970;42(3):397–407. Berlinerblau R, Feder W. Chaotic atrial rhythm. J Electrocardiol 1972;5(2):135–144. Surawicz B, Knilans TK. Chou’s Electrocardiography in Clinical Practice, Adult and Pediatric (5th ed). Philadelphia: W.B. Saunders, 2001:340–341. Acknowledgment of contributors B aylor University Medical Center Proceedings couldn’t exist without writers or without readers, but it also couldn’t exist without financial support. Baylor Health Care System Foundation has been our longest and greatest contributor. Here we wish to acknowledge our individual donors who sent in gifts between February 10, 2011, and February 10, 2012. The 2011/2012 fundraising effort is still in progress this spring. SPECIAL GIFTS ($25,000) William C. Roberts, MD LEADERSHIP GIFTS ($500+) Michael L. Foreman, MD Valentin Gracia, MD Göran B. Klintmalm, MD, PhD Robert G. Mennel, MD Michael A. Ramsay, MD OTHER INDIVIDUAL DONORS Associate ($100 to $499) W. Mark Armstrong, MD C. T. “Sparkey” Beckham C. Richard Boland, MD Barry Cooper, MD D. Luke Glancy, MD Joseph M. Guileyardo, MD Daragh Heitzman, MD Kenneth C. Killen, MD Mrs. Lloyd W. Kitchens Patrick H. Pownell, MD W. Gregory Schucany, MD Glen W. Simons, MD Eric H. Stocker, MD Texas Vascular Associates, PA Harold C. Urschel, MD Carol-Ann Valentine Marguerite G. Wuebker, MD 160 Friend (to $99) Patricia L. Blanton, MD Donna L. Bowers Dick G. Ellis, MD H. A. T. Hein, MD Samuel Jagoda, MD Robert G. Long, MD Thomas W. Newsome, MD Stacey L. Peterson Lawrence R. Schiller, MD Steve P. Schoettle, MD Carl D. Solomon, DPM Curtis L. Studey, MD Crighton Olive Dunn Surgical Group Craig A. Troop, MD Elgin W. Ware, MD Wilson Weatherford, MD Charles W. Zavala, MD The total amount raised this period from individual donors was $31,390. Any additional donations can be sent to the editorial office or the BHCS Foundation office and will be acknowledged in the April 2013 issue. Baylor University Medical Center Proceedings Volume 25, Number 2 Images in Medicine Paget’s disease of the calcaneus causing right foot pain a b c Figure 1. (a) Saggital, (b) axial, and (c) coronal T1-weighted MRI images demonstrate cortical thickening, trabecular disorganization and condensation, as well as patchy marrow abnormality, including multifocal islands of fatty marrow as well as a heterogeneous signal that is intermediate to low on T1. a b c Figure 2. (a) Axial, (b) sagittal, and (c) coronal fat-saturated T2-weighted images also demonstrate a heterogeneous signal, which is intermediate to high on T2, consistent with areas of fibrous replacement of marrow. A 54-year-old woman presented with worsening right heel pain and tingling for several weeks. She denied a history of trauma. Physical examination revealed a normal range of motion at the right ankle joint. No pain was elicited on palpation of the heel. Plantar fasciitis or tenosynovitis were considered potential etiologies for the patient’s heel pain. Magnetic resonance imaging (MRI) of the right ankle was performed for further evaluation. Proc (Bayl Univ Med Cent) 2012;25(2):161–162 MRI of the foot (Figures 1 and 2) revealed a markedly abnormal appearance of the calcaneus. The bone was diffusely enlarged. There was evidence of cortical thickening, trabecular disorganization, and patchy marrow abnormality. The constellation of findings was most compatible with Paget’s disease of the calcaneus. Plain film imaging of the right foot was also obtained to further corroborate the MRI findings. Anteroposterior and lateral 161 views of the foot (Figure 3) revealed an abnormal appearance of the calcaneus. The calcaneus was enlarged with a sclerotic appearance and with a thickened trabecular pattern suggestive of Paget’s disease. There was no evidence of fracture. —Purvak Patel, MD, Greg Schucany, MD, Peter B. Wood, DPM, and David Hurst, MD Departments of Radiology and Podiatry Baylor University Medical Center at Dallas E-mail: [email protected] a b Figure 3. (a) Lateral and (b) anteroposterior views of the right foot reveal an expansile appearance of the calcaneus. There is marked sclerosis and trabecular thickening involving the calcaneus. Other findings include plantar calcaneal spur as well as spurring along the posterosuperior aspect of the calcaneus. 162 Baylor University Medical Center Proceedings Volume 25, Number 2 Images in Medicine Ruptured cerebral arteriovenous malformation presenting as intraventricular hemorrhage A 64-year-old woman with a history of ovarian carcinoma and cerebrovascular accident presented with the acute onset of a severe throbbing headache with associated nausea and vomiting. The patient described intermittent headaches over the preceding month with associated vision changes during these episodes. She was found to have intraventricular hemorrhage on an initial head computed tomography (CT) scan. Follow-up CT angiography and digital subtraction cerebral catheter angiography were performed. The initial unenhanced head CT (Figure 1) reveals hyperdense hemorrhage layering b a in the frontal horns and atria of the lateral ventricles in addition to suspicious punctuate atrial calcifications. Such calcifications often herald the presence of an arteriovenous malformation (AVM). The CT angiogram (Figure 2) and catheter angiogram (Figure 3) demonstrate an enhancing nidus of blood vessels located in the medial temporal-occipital lobe and atrium of the right lateral ventricle consistent with an AVM. The vascular malformation is fed predominantly through an enlarged posterior communicating and posterior cerebral artery with drainage through both an enlarged basal vein of Rosenthal and enlarged superFigure 1. (a, b) Initial unenhanced axial CT images with diffuse intraventricular hemorrhage (arrows) ficial cortical veins. No intranidal aneurysm was detected. and punctuate AVM calcifications (arrowheads). a b c Figure 2. (a) Axial CT angiogram demonstrates the AVM nidus in the atrium of the lateral ventricle (arrows). (b) Axial reconstructed CT angiogram reveals enlargement of the posterior cerebral and posterior communicating arteries (arrowheads) in addition to an enlarged draining venous varix (arrow). (c) Coronal reconstructed CT angiogram with an enlarged draining vein (short arrow) feeding an enlarged basal vein of Rosenthal (long arrow). Proc (Bayl Univ Med Cent) 2012;25(2):163–164 163 Martin grading system (grades 1 through 5) on the basis of size, location, and venous drainage patterns; higher numbers indicate less favorable surgical and treatment outcomes. The presented case meets criteria for a grade 2 AVM in this system. Treatment options for AVMs include endovascular embolization, surgical resection, and radiosurgery alone or in combination. In AVMs <3 cm in diameter, particularly those that are deeply situated in the brain, stereotactic radiosurgery is the therapy of choice, achieving cure rates of 80% to 90% at 2 to 3 years after treatment. —Amin F. Saad, MD, Michael J. Opatowsky, MD, Amy Y. Nixon, MD, Steven C. Gilbert, MD, and Ike C. Thacker, MD a b Department of Radiology, Baylor University Medical Center at Dallas Figure 3. (a) Anteroposterior and (b) lateral catheter angiogram images show the AVM nidus (arrowheads) with enlargement of the right posterior cerebral and posterior communicating arteries (arrows). True AVMs contain one or more enlarged feeding arteries, a nidus, and enlarged early draining veins with no intervening capillary bed. They are considered a congenital anomaly but typically do not become symptomatic until beyond the third or fourth decade of life. AVMs are classified using the Spetzler- Sources Grossman RI, Yousem DM. Neuroradiology: The Requisites, 3rd ed. St. Louis, MO: Mosby, 2010. van Beijnum J, van der Worp HB, Buis DR, Al-Shahi Salman R, Kappelle LJ, Rinkel GJ, van der Sprenkel JW, Vandertop WP, Algra A, Klijn CJ. Treatment of brain arteriovenous malformations: a systematic review and meta-analysis. JAMA 2011;306(18):2011–2019. Ponce FA, Spetzler RF. Arteriovenous malformations: classification to cure. Clin Neurosurg 2011;58:10–12. In Memoriam George M. Boswell Jr., MD Department of Orthopedic Surgery, Baylor University Medical Center at Dallas Dr. George Boswell (Figure) was born in Dallas in 1920 and received his bachelor’s degree in journalism at Texas Tech University, followed by a master’s degree in psychology from The University of Texas. Figure. George M. Boswell Jr., MD. His adventurous spirit led him to join the US Navy in 1940, prior to the onset of war against Japan. He rose to the rank of lieutenant commander and spent most of the war in the Pacific, where he served as the beach-landing officer in charge at Iwo Jima, Okinawa, and most of the other island battles. At the conclusion of the conflict, he made a major career change, entering medical school at the Southwestern Medical School (which subsequently became The University of Texas 164 Southwestern Medical School). He was awarded his medical degree in 1950. While he was doing a general surgical residency, Dr. Marvin Knight encouraged him to enter orthopedics, and he subsequently made many contributions to that specialty. Dr. Boswell joined the staff of Baylor University Hospital in 1952. In that year he and Dr. Harold Cheek performed the first anterior lumbar fusion done in the South. He also did the first cervical fusion and the first artificial knee at Baylor. For many years, he looked after staff of the Dallas police and fire departments and was commissioned as an officer in both of those organizations. His many outside interests included flying, gardening, and church activities. In 1997, the Prothro-Perkins Foundation established a chair at Baylor University Medical Center at Dallas in honor of Dr. Boswell, who dedicated the chair to “the perpetuation of the art and science of medicine in the practice of orthopedic surgery and to the preservation of the traditional patient-physician relationship.” Professor Boswell continued to see patients and even make house calls even after his retirement. He died on December 5, 2011, at the age of 91. Baylor University Medical Center Proceedings Volume 25, Number 2 Tributes Tributes to George Boswell, MD Paul Neubach, MD I had the honor of knowing Bos for 35 years. He would frequently call the house wanting me to see one of his patients. My wife would answer the phone, and Bos would ask, “Sweetie, is he there?” She would turn to me and say “Dr. Boswell is on the phone.” When I saw one of his patients, I knew to expect a call that evening because he wanted to know what I thought about “his patient.” Bos was a great orthopedist to his patients, but he was so much more than that. He was “their doctor.” He loved each and every one of them just as they adored him. Wynne Snoots, MD When trying to distill nearly 50 years of observation into a few minutes, the limitation of language becomes apparent. I had to go back to some old English lessons. A quick history of my Bos experience starts in the 1960s when I was one of his orthopedic residents at Baylor. My memories are of working day and night, a late night drive in the gull wing Mercedes to the China Clipper Café on McKinney for a snack, and back to the OR for another case. Bos could sleep sitting or standing, between cases. He was a very quick and accomplished surgeon, whose patients all loved him. He was innovative—and always ahead of the curve with new procedures and instrumentation that he soon mastered and turned into mainstream procedures at Baylor. I think he must have taken care of most of the Dallas police and fire department as patients over the years. He pioneered instrumentation in spinal surgery, arthroplasties, and fracture treatment with internal fixation—as well as early mobilization, especially of elderly patients after injury, which returned many to independent function, in contrast to the prolonged bed rest that was the standard at the time. He slowed down a little over the years, but it seems like yesterday I saw him over at the Truett Hospital in his scrubs, checking on patients and growling about how to improve patient care, a little more stooped and bowed over but still quick of mind and spirit. I remember his house calls when I was down and the lift those visits gave to my wife. He continued to see his patients even when he was home in bed. Those who came by to visit him were still patients in his eyes, and his concern for their problems was apparent. Proc (Bayl Univ Med Cent) 2012;25(2):165 This synopsis does not begin to express the ways we have all benefited from his hands. The English language is very expressive but is lacking when trying to articulate those intimate and inner feelings that close interpersonal relationships generate. Nouns are too specific and adjectives help but are still lacking. To say that he was a physician who was outstanding, innovative, caring, likeable, smart, skilled, and so forth does not express what we want to say. We can try metaphors—a diamond for example. The stone’s attributes do have a lot in common with Bos. He was both rough and brilliant, multifaceted, polished, hard, durable, desirable, and valuable, but still not the right picture. Allegory is a similar device but, again, not personal enough. How about testimonials? Our dog, Tess, a border collie, has developed a phobia about storms. During our Texas drought, we had almost forgotten about it. This fall, a rain brought it back into focus. We happened to visit Bos that day and the subject came up. As expected, he had a solution. His dog, Buddie, was under his bed and comfortable in his Thunder shirt. He told us how great it was and where to get it. Every time we would visit, he would ask whether he had gotten the Thunder shirt yet. I had procrastinated when I found out it cost $50 and could not imagine why it would work. Another rainstorm with Tess trying to claw through the bed convinced us to try it. Just as Bos had told us, it works, and if you could speak dog, her testimonial is available. Again helpful but not the answer. The Aggie in me says to keep it simple. How about a simple possessive pronoun or two? How many of you have seen Bos as a patient? How many call him my doctor? That possessive pronoun is earned, not given. In this new health care environment, how many of you still use that term when you describe your “provider”? Bos earned that privilege because he felt you were his patient and treated you that way. Mutual values and communication provide the basis for the trust necessary for a meaningful physician/patient relationship. How can we capitalize on that concept? With a little plagiarism, this succinct declarative statement, with two possessive pronouns, is at least a start at identifying the essence of Dr. Boswell. Our doctor, who art in heaven, We want to thank you for your care. Amen. 165 Book Reviews Amyloidosis: Diagnosis and Treatment edited by Morie A. Gertz, MD, and S. Vincent Rajkumar, MD New York: Humana Press, 2010. Hardcover, 248 pp., $189.00. Reviewed by by Stacy A. Gurevitz, MD, and Marvin J. Stone, MD B ased on the all-inclusive title, you might think this book weighs 5 pounds and will snap your already bowing bookshelf. But you’re wrong: this small volume covers almost everything that you ever wanted to know about amyloidosis. And we mean you, primary care doctor, pathology resident, or subspecialist in various fields. Twenty-eight different proteins can form amyloid, and it is critically important to know which is deposited in the fibrils of each patient. Amyloidosis is thus a generic term describing a final common pathway for protein deposits in tissues. Since nearly all organ systems can be involved in amyloidosis, this volume will be useful in everyone’s collection. For subspecialty clinicians, the book will serve as a great tool to learn more about the other issues that your patient is facing; for example, nephrologists and cardiologists caring for amyloid patients will learn a lot about their patients’ neuropathy. Ophthalmologists will learn something from this book, especially if they can hang on until page 197, where a whole paragraph is devoted to ocular manifestations of transthyretin amyloidosis. Chapter 1 (Fibril Structure and Fibrillogenesis) contains some terms that you might remember from college physics, like thermodynamics and kinetics, but do not let that scare you away. This chapter offers a clearly written review of the pathogenesis of amyloid, which lays the foundation for the rest of the book. How can one rationally approach treatment modalities without an understanding of these diverse disorders? Because amyloid is so varied in its etiology and clinical presentations, it does not behave like most of the diseases with which we are familiar. The illustrations are well done and many are in color. From gross pathology pictures (p. 108) to radiologic studies (p. 22) to electrocardiograms (p. 109), the color is enriching and supportive. There are numerous well-organized diagrams and figures (p. 161, Therapy Algorithm for AL; p. 50, Pathogenic 166 Steps in the Development of Amyloid Diseases). The lack of a photomicrograph in chapter 3 (Diagnosis and Classification) was disappointing, but the Congo red stain on the cover compensated for this omission. The discussion about scintigraphy in chapter 2 highlights the fundamental basics of nuclear medicine and how it is used in staging to localize amyloid deposits. The downside is that this technique is not widely available. Everyone will delve into chapter 3, Diagnosis and Classification, where the authors describe the pitfalls of stains and immunohistochemistry. However, the emerging gold standard for accurate identification of the protein in the fibrillar deposits—mass spectrometry—receives only passing mention. The structure of the book is one factor that makes it useful, but also leads to faults. The monograph is a collection of 15 chapters written by multiple contributors. Each chapter begins with an abstract, which serves as a nice introduction to the subject. Next come keywords, which could be used as search terms in an electronic version of the book. The chapters are brief and crisp (the entire book has only 248 pages). Because the chapters have different authors, the reader gets a change of style for each topic—sometimes an advantage and other times not. The authors were allowed some liberty in the format that they chose. For example, Bajwa and Kelly, authors of chapter 10, use a case vignette to introduce the neurologic manifestations of systemic amyloidosis. The weakness of multiple authorship is repetitiveness. The readers are told on page 155 that “immunoglobulin light chain amyloidosis is associated with a plasma cell dyscrasia,” which was stated by different authors a mere 10 pages earlier. However, this makes the book useful as a resource for those looking for an overview of this complex subject. The references placed after each chapter make them easily accessible; also, they are relatively recent and from peer-reviewed resources. Nearly all chapters conclude with future directions. Treatment of the amyloid diseases is nonoptimal and dependent on the protein in these fibrils. Moreover, the extracellular location and limited solubility of the fibrils make them difficult targets. During the past 2 decades, however, an enormous amount of progress has been made towards understanding the amyloidoses. The editors are to be congratulated on putting this recent information together in a readable and informative volume. Stacy Gurevitz, MD, is a pathology resident at Baylor University Medical Center at Dallas, and Marvin J. Stone, MD, is Director of Oncology Medical Education and Associate Medical Director of the Baylor Charles A. Sammons Cancer Center at Dallas. Proc (Bayl Univ Med Cent) 2012;25(2):166–168 The Greater Journey: Americans in Paris by David McCullough New York: Simon & Schuster, 2011. Hardcover, 558 pp., $37.50. Reviewed by Fran Roberts Willard T o read David McCullough’s absorbing account of a 70-year period in French history is to be swept away in the vivid and inspiring stories of some of the hundreds of Americans who made the migration east to partake in the intellectual and cultural riches of the City of Light. What many of them achieved individually in literature, the arts, and sciences would profoundly influence our own American history. In the 1830s, the first wave of talented and ambitious Americans set sail for Paris with the firm notion that only there would they be able to realize their dreams. Most were well educated and reasonably well off, or at least they had parents able and willing to finance them. Most, though not all, were single men in their 20s, with at least one exception being Elizabeth Blackwell, America’s first female physician. One such young man was Oliver Wendell Holmes, a shy, affable Bostonian, who at 25 years of age had already gained some acclaim for his poem “Old Ironsides,” a tribute to the USS Constitution, which had helped save the Navy from scrapping the historic ship. His compatriots included James Jackson Jr. and Mason Warren, the sons of Boston’s most prominent physicians, James Jackson and John Collins Warren, who had founded the Massachusetts General Hospital. Unlike these two young men, Holmes had not had an easy time convincing his father to fund his most expensive dream to receive medical training in Paris, for not only would it require great sacrifice at home but his preacher father was concerned for his son’s morals. “If he was to be anything better than a rural dispenser of pills and powders,” he had argued, he would need at least 2 years in Paris, the world’s leading center of medicine and medical training at that time. A perilous sea voyage of 3000 miles lay ahead, but Holmes braved the Atlantic in the spring of 1833. Nothing could have prepared him for Paris, a city of 800,000 (four times the size of New York City) and the cultural center of Europe. How old things looked made a deep impression, as did the appalling poverty. And, yet, there were the riches of Paris to be discovered in long, rambling walks. It was impossible not to be impressed with the famous bridges on the Seine and the unique beauty of the numerous gardens and palaces. There was theater and opera and cafes to be enjoyed and, of course, the Louvre, the world’s greatest museum of art. Holmes immediately took to Paris, to the French people and to the language. He chose to live on the Left Bank in the Latin Quarter, settling into a top-floor room in a fifth-floor high-rise. For 40 francs a month ($8), he got not only some basic furnishings but also a porter, who would wake him in the April 2012 mornings, make his bed, wash his clothes, and polish his boots. Better yet, his room was only a few blocks from the École de Médecine; to his delight, he found he could make it to his first lecture each morning in 4 minutes flat. This was the sixth arrondissement and home to the College of the Sorbonne and the School of Law, but, most of all, it was the world of Paris Médicale, whose population rivaled that of a small city. The celebrated medical school drew several thousand students from all over France and much of the world. Here, too, were the shops and homes of the medical booksellers, instrument makers, and medical artists. As a place to learn it was beyond compare, for it was here that the illustrious professors and physicians were advancing the art and science of medicine as nowhere else in the world. There were a number of hospitals serving Paris Médicale. The largest and oldest of the hospitals was Hôtel-Dieu, considered preeminent in surgery and serving more than 15,000 patients a year; as in all Paris hospitals, patients were treated for free. The 800-bed Hôpital de la Pitié was known for its clinical medicine, particularly for the treatment of diseases of the chest, such as tuberculosis. The Hôpital des Enfants-Malades was the first children’s hospital in the world. In 1833, a total of 12 hospitals provided treatment for 65,935 patients; in comparison, the combined number of patients that same year for the Massachusetts Hospital and the McLean Hospital was less than 800. The sheer number of patients and the range of their diseases gave medical students a first-hand experience they would not be able to obtain elsewhere. Although the hospitals were mostly old, the medical school had been founded only about 70 years earlier, and since the Revolution of 1789, all qualified young men, regardless of wealth or family background, were allowed to attend. For this reason, the language of instruction had been changed from Latin to French. Unlike at American medical schools, a college education was required; however, this requirement was waived for American students, as was the tuition. At the École, students would have to select “lines of study” in either surgery or general medicine, which is what Holmes chose. All students, though, would attend lectures in both as part of their training and would make the rounds of the hospitals with both physicians and surgeons, but surgery students would have a different curriculum. One of the medical giants in France was Guillaume Dupuytren, once a battlefield surgeon who had been made a baron by Napoleon. The contraction of the palmar fascia of the hand, known as “Dupuytren’s contracture,” was named after him. Watching Dupuytren march through the wards in his white apron, the diminutive Holmes thought him a “lesser kind of deity.” Dupuytren reportedly spent most nights at one of the better gambling houses at the Palais Royal, and the students assumed his mood each morning revealed whether he had won or lost. On most mornings, his mood was foul. Still, his lectures were not to be missed, and to see him with scalpel in hand was to see un spectacle. He spoke the whole time and loved to “make a show.” There was no anesthesia, and Dupuytren, like other surgeons of the time, did not wash his hands or sterilize Book Review 167 his instruments before surgery, as such precautions were not yet known. Unfortunately, most patients who survived surgery would later die of infection. The teacher and practitioner who seemed to influence the American medical students most profoundly was PierreCharles-Alexandre Louis. Diseases of the chest, particularly tuberculosis, a leading killer of the day, were his forte. That he was married to the sister of Victor Hugo only added to his reputation. His insistence on the need for facts and for “exact observation” in the treatment of disease made him require his students to make slow and careful examinations of patients, to question them at length, to make good use of the stethoscope, which was first introduced in 1819, and to take detailed notes. Holmes embraced the Louis scientific approach and recorded how he would spend 5 hours a day sitting at the bedsides of patients, asking questions and filling his notebook with notes. Another advantage for American medical students studying in Paris was the easy availability of cadavers for dissection, which was not the case in the United States because of both state laws and public attitude. Holmes wrote of sharing the cost of a cadaver with a Swiss student and how by evening they had “cut him into pieces.” These students not only had the opportunity through dissection to study all parts of the body—nerves, muscles, organs, blood vessels, and bones—they also had the chance to examine women patients, who did not share the same attitude as American women, some of whom would rather have died than be examined by a male physician. To mark the end of his first year, Holmes wrote his father: My aim has been to qualify myself so far as my faculties would allow me, not for a new scholar, (or) for a follower of other men’s opinions, (or) for a dependent on their authority, but for the character of a man who has seen and therefore knows, who has thought and therefore arrived at his own conclusions. I have lived among a great and glorious people. I have thrown my thoughts into a new language. I have received the shock of new minds and new habit. I have drawn closer the ties of social relations with the best formed minds I have been able to find from my own country. . . . I hope you do not think your money has been wasted. 168 But it was not enough to persuade his father to let him stay much longer. At the end of his second year, Holmes reluctantly returned to Boston, where he would become the professor of anatomy at Harvard Medical School for 36 years, also serving for part of that time as dean. Meanwhile, more American medical school students kept arriving, totaling nearly 700 by the year 1900. They would also return home to practice medicine and to pass on their knowledge to others. While a whole chapter is devoted to “The Medicals,” McCullough fully explores the varied and rich stories of numerous Americans inspired by their time in Paris, such as James Fenimore Cooper, whose The Last of the Mohicans was the first American novel to garner international readership, and Samuel Morse, who worked diligently on his ambitious project, “The Gallery of the Louvre.” Thinking he had failed as an artist, Morse returned to America and would later become an inventor, revolutionizing the field of communications. He would never have believed that his masterpiece would sell nearly 150 years later for $3 million, the largest sum ever paid—until that time—for an American work of art. These stories of aspiring Americans, including Mary Cassatt, Harriet Beecher Stowe, and Augustus Saint-Gaudens, the sculptor of such memorials as the Farragut, Sherman, and Robert Gould Shaw memorials, serve as an important reminder of how much dedicated work and perseverance are required to realize great talent. McCullough also examines the panoramic changes Paris itself went through during this time, including the Cholera epidemic of 1832, which killed 18,000 people, and the FrancoPrussian War. McCullough’s story of Elihu Washburne, America’s minister to France between 1869 and 1877, serves as a beautiful portrait of a true statesman. Like the other talented Americans, Holmes had made the most of his time in the City of Light. He’d not only received the best medical training to be had in the world, but also now shared the French conviction that art, music, poetry, and good conversation were essential to the enjoyment and meaning of life. So, it is no surprise that he frequently liked to say: “Good Americans, when they die, go to Paris.” The reviewer, Fran Roberts Willard, is a freelance writer in Leesburg, Virginia. Baylor University Medical Center Proceedings Volume 25, Number 2 Reader comments “Irreducible complexity” or “delightful challenge”? I n the January issue of the BUMC Proceedings, Joseph Kuhn, MD, presented his views on evolution in his article “Dissecting Darwinism” (1). In the article, he expresses his personal doubts about contemporary concepts held by most scientists regarding the evolution of life and diverse species on our planet. He offers no alternative explanation, but rather expresses his pessimism that we will ever understand how complex organisms have developed. The essence of his opinion is expressed in his term the “irreducible complexity of cellular systems,” in which he suggests that this issue is just too difficult to understand and that there is no hope that we will ever know how biological systems have evolved. But one man’s “irreducible complexity” is another man’s “delightful challenge.” Why assume that these issues will never be understood? Look at what has transpired in the time since the discovery of the structure of DNA by Watson and Crick in 1953. This field is an extremely active area of science, and our understanding of biological processes continues to increase in a logical, iterative, and immensely interesting way. Why be a pessimist about this? What would Ben Franklin think if we magically transported a laptop computer or cell phone back to the 18th century? Wouldn’t that be a bewildering, complex experience? Do you think he could be convinced that this would be the work of human hands in less than three centuries? In his somewhat rambling narrative (with unnecessary tangents on John Hunter—who briefly confounded our understanding of venereal diseases—and the activities of the Texas State Board of Education in 2010), a number of misconceptions and factual errors were offered by Kuhn. First, many of us were taught the Miller and Urey experiments in high school biology, which demonstrated that complex molecules could be generated from simple ones present in the primordial seas when subjected to pulses of energy, such as ionizing radiation or electrical storms, both ubiquitous in the early life of the earth. So, what were the earliest chemical precursors of life? Since the mid 1980s, evolutionary biologists have realized that RNA—and not DNA—was the likely initial macromolecule of life, a point noted by Kuhn but apparently not completely comprehended. RNA is unique by having the ability to self-replicate, but it also has intrinsic enzymatic activities and can catalyze chemical reactions. Given enough time (and most scientists estimate that the earth is about 4.5 billion years old), it is not surprising that somewhere in the primordial soup of our planet, a variety of complex compounds would spontaneously form. Miller and Urey did not know the full range of compounds that would appear under these circumstances—it was 1953! However, they provided hard evidence that complex compounds could evolve from simple ones in the soup. Again, given immense amounts of time, and the huge “test tube” involved, some of the RNA precursors would eventually Proc (Bayl Univ Med Cent) 2012;25(2):169–173 polymerize into ever larger macromolecules with self-replicating ability in the RNA world. It’s not that complicated. The origin of the biochemical precursors of life did not depend upon a single electrical spark that gave rise to a fully replicating DNA strand or a completely functioning genome. Rather, this occurred over millions of years due to cooperation between strands of nucleic acids, some facilitating strand extension, others facilitating replication. The early RNA strands would replicate simply because it was a chemical possibility. It’s just chemistry. In fact, the ability of RNA strands to spontaneously replicate is reasonably accurate for strands up to 100 ribonucleotide units long. For RNAs to grow longer may seem difficult (or “irreducibly complex”) until you take into account that cooperation takes place between RNA strands in what might be called the “primordial pizza” of life (2), which takes into account that these molecules were not necessarily randomly scattered throughout the early oceans. One strand of RNA can catalyze other reactions through chemical cooperation. Cooperation would positively select for increasingly complex molecules. The intrinsic chemical properties of these macromolecules, plus natural selection, are the driving forces in this wondrous process. Eventually, randomly growing nucleic acid chains would evolve into what we would recognize as primitive genes, and the combination of genes on a single nucleic acid chain would reduce the randomness of their distribution, further increasing the chances for positive interactions among these macromolecules. The issues of biologic cooperation are discussed in detail in Martin Novak’s SuperCooperators (2) and Mark Ridley’s The Cooperative Gene (3), both highly recommended for scientific optimists. Taking the concept of cooperativity further, the organization of complex genomes takes advantage of additional layers of regulation through which a minor change in one genetic element can broadly influence the expression of many other genes. The evolution of highly complex organs such as the eye—an issue that bothered Newton, in fact—became less mysterious when it was discovered that there are classes of genes that can orchestrate the expression of dozens or scores of other genes simultaneously. For example, homeobox genes control the differentiation fates of tissues and organs by influencing the expression of multiple other genes that act in concert with one another to direct complex cellular behaviors. Similarly, microRNAs interact with the untranslated regions of messenger RNAs and can influence the stability and expression of >100 target genes. The human genome has >1000 microRNAs. Increasing the expression of just one of these “master genes” can have an enormous, coordinated effect. One of the insights gained by sequencing the human genome was not that we have more genes than other organisms—we don’t. However, we have a very large number of genes that are involved in the regulation of many others, which can orchestrate complex biological processes. 169 One way to make complex issues seem “irreducibly complex” is to misunderstand or willfully misstate the data involved in the complexity. Kuhn explores the genetic relationship between humans and chimps and makes the erroneous claim that the similarity between human and chimp genomes is 70% to 75% (1). Moreover, the paper cited to support this actually reported that the number of single nucleotide substitutions between the chimp and human is actually 1.23% (making the degree of similarity over 98.7%!) (4). This means that there are 35 million single nucleotide differences, which may seem to be a large number until you divide that by the 3 billion base pairs in our genome and recognize that this occurred over 30 million years of evolutionary time. There are additional differences in the noncoding repetitive sequences between humans and chimps (i.e., in the historically disparaged “junk DNA”), just as there is a large amount of diversity in these sequences between different humans; these are not thought to be of major functional significance. These polymorphisms at repetitive sequences are so common in humans that forensic science can use them to identify each human individually. None of the 67 authors of the chimp genome article is likely to support any of Dr. Kuhn’s interpretations. Also, in the interests of accuracy, the human genome consists of 2.91 billion base pairs (5), not 5 billion (1). Some of the complexity is reduced by getting the facts right. In the words of Alexander Pope from An Essay on Criticism: A little learning is a dang’rous thing; Drink deep, or taste not the Pierian Spring. So, what it comes down to is whether you think that evolutionary biology is “irreducibly complex,” too difficult for anyone to ever comprehend and take a pessimist’s view, or embrace the delightful challenge of learning about the biology of life. Frankly, it’s a fool’s errand to make a case that anything is permanently beyond human comprehension. As for myself, I get considerable enjoyment out of each step forward in the scientific literature and find the journey worth all the effort. —C. Richard Boland, MD, Division of Gastroenterology, Baylor University Medical Center at Dallas 1. 2. 3. 4. 5. Kuhn JA. Dissecting Darwinism. Proc (Bayl Univ Med Cent) 2012;25(1):41–47. Novak MA. SuperCooperators. Altruism, Evolution, and Why We Need Each Other to Succeed. New York: Free Press, 2011. Ridley M. The Cooperative Gene. How Mendel’s Demon Explains the Evolution of Complex Beings. New York: Free Press, 2001. The Chimpanzee Sequencing and Analysis Consortium. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 2005;437(7005):69–87. Venter JC, Adams MD, Myers EW, et al. The sequence of the human genome. Science 2001;291(5507):1305–1351. Further discussion on Darwinism The paper on evolution by Joseph A. Kuhn, MD, can only be referred to as the ramblings of a religious creationist, who 170 believes that god created life, and Darwinian evolution is a fraud. The published paper has nothing at all to do with medical science, but is a thinly veiled, fundamentalist religious attempt to get unscientific biological “facts” into the peer-reviewed literature. If the sadly misguided Dr. Kuhn had bothered to thoroughly read some of the many real scientific references he cites . . . , especially the landmark court ruling Kitzmiller v Dover, he would have found that all his presented “evidence” against evolution by natural selection has been thoroughly debunked by real scientists time and time again. Dr. Kuhn is doing nothing but reheating intelligent design talking points—which science and the law agree are, in fact, religious creationism and a far, far cry from real science. —Dennis Hansen, PhD, Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland Dr. Kuhn is breathtakingly ignorant of basic facts surrounding the data used to support the conclusion that life has evolved, and he is amazingly ignorant of what modern biologists actually think about the origin of life and how evolution works. Dr. Kuhn should at least have had to accurately characterize the state of the art of evolutionary thought. Just as one basic example: his Figure 3 bears no resemblance to what the fossil record says. First, it should have zoomed in to look at roughly 60 million years around the Precambrian-Cambrian boundary (instead of encompassing 600 Myr to make things look as instantaneous as possible), and second, he should have based his figure on one that reflects actual data. The fossil data show that most phyla progressively appear over at least 20 to 30 million years before and after the Precambrian-Cambrian boundary. And really, these data just reflect the first appearances of many phyla of preservable hard parts (as opposed to their genetic differentiation). So, when you add estimates for genetic divergence times derived from molecular clocks, the origin of many of the phyla is pushed back further into the Precambrian, over an even more extended period of time. Instead, Dr. Kuhn avoided the primary literature, or any literature produced by actual experts in paleontology, and drew his Figure 3 from an evangelical website hostile to evolution. One thing I would strongly emphasize is that evolution is a theory that allows scientists to make lots of predictions: about what will be found in the fossil record, about genes we might expect to find in distantly related organisms, and so on. It is the success of evolution in making predictions about what we will find in the future that testifies to the correctness of the conclusion that all life has evolved from earlier common ancestors. If you want examples appropriate for the medical community, how about the Nobel Prizes awarded for medicine for research that never would have been done without evolution proposing that we can look in other organisms for genes that we can do experiments on that would be ethically impossible in humans. Here are a few examples: 1995: Genetic controls of embryonic development in humans (et al.) as derived from the study of fruit flies Baylor University Medical Center Proceedings Volume 25, Number 2 2001: Discovery of key compounds controlling cell division in all eukaryotes (including humans) as derived from yeast and sea urchins 2002: Genetic regulation of organ development and programmed cell death in nematodes, which also applies to humans 2006: RNA interference—gene silencing by double-stranded RNA, based on nematodes, again applicable to humans Virtually any research done on other organisms with a view toward understanding human biology has as its starting point the evolutionary conclusion that humans are biologically related to the rest of life on earth, that we are not a completely separate creation. In contrast, as you would gather from Dr. Kuhn’s summary of intelligent design arguments, intelligent design argues that every organism is too horribly complex to understand except in the context of an intelligent designer designing it. An intelligent design researcher would calculate the astronomically terrible odds that any given aspect of another organism would be so similar to humans as to be worth researching for its potential medical benefit. Thus, no research would get done. Dr. Kuhn’s mischaracterizations of the prebiotic molecules research is decades out of date, and his material on transitional fossils in the fossil record is simply an argument from ignorance: I can’t possibly imagine how B could evolve from A; therefore, it didn’t. —Charles E. Jones, PhD, Department of Geology and Planetary Science, University of Pittsburgh, Pittsburgh, Pennsylvania awakened to the cellular and molecular aspects that must be understood before sweeping concepts of natural selection are used to postulate the very beginning of life on this planet. Having read your paper, I shall be forever changed. I had no idea that you were a student of this science. This paper contains such substance that eclipses the usual papers published or presented at meetings. Congratulations on a job well done. —Jay Hoppenstein, MD, FACS Dallas, Texas Dr. Joseph Kuhn’s recent paper, “Dissecting Darwinism,” cites the title of Charles Darwin’s book as On the Origin of the Species whereas the actual title of this book is On the Origin of Species. This common misconception is probably important since the former suggests a theory concerning the origin of life, whereas the latter is primarily concerned with divergence of species in the process of adaptation and natural selection. Darwin himself attempted to clarify this distinction in the conclusion to later editions (2 through 6) of this book, which ends with the following statement: Response to Dr. Boland 1. Contrary to Dr. Boland’s assessment, I have not expressed “pessimism that we will ever understand how complex organisms have developed,” nor that “there is no hope that we will ever know how biological systems have evolved.” This is an equivocation on the word “complex.” Irreducible complexity is a testable, scientific term that does not mean that something is “too complex to understand,” as proposed by Dr. Boland. It is important for the reader to understand that many cellular functions or systems cannot be built through step-by-step mutational processes, since the intermediate versions are not functional for the designated purpose and offer no survival advantage. The concrete examples of irreducible complexity in my article were too numerous to mention here (2). However, his examples of the laptop or cell phone represent “systems” that did not likely arise one step at a time, nor did they arise through a natural process. I agree that Ben Franklin would be surprised to see a laptop, though I suspect he would not imagine that it arose from boron, polysilicon, gold, and lithium over billions of years. 2. The origin of DNA and the inherent coding information is a major obstacle for step-by-step Darwinian explanations. Although newspapers and high school biology texts often assert (without providing detail) an RNA-world hypothesis, there are strongly dissenting scientists who argue that the essential RNA polymerase enzyme does not form by itself (3). Stephen Meyer listed additional insurmountable obstacles to an RNAfirst hypothesis: 1) the inability to account for the necessary There is grandeur in this view of life, with its several powers, having been originally breathed by the Creator into a few forms or into one; and that, whilst this planet has gone circling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being evolved. —Joseph M. Guileyardo, MD Autopsy Services, Baylor University Medical Center at Dallas Dear Dr. Kuhn: Your article, “Dissecting Darwinism,” published in the January 2012 issue of the Baylor University Medical Proceedings, was astonishing for its clarity and its coherent analysis of a widely accepted theory whose advocates, such as myself, never knew the questions to ask to challenge its cohesiveness. I have been April 2012 Response from Dr. Kuhn I appreciate the opportunity to address the reader comments regarding my article, “Dissecting Darwinism.” There are a few overarching issues. First, the scrutiny or concerns about certain aspects of Darwinian evolution belong to many eminent scientists. In fact, over 800 PhD scientists have signed a letter stating their concerns about the full scope of Darwinian evolution (1). Second, there is no dispute with many aspects of Darwinian evolution, such as natural selection and variation within a species (most of the examples in Dr. Dimijian’s article). Third, a few absolute stumbling blocks remain for even the most impassioned Darwinists: the origin of DNA, the origin of the cell, and the issue of irreducibly complex systems that require numerous essential proteins to accomplish a function. Reader comments 171 nucleotides or ribose molecules (they don’t form spontaneously), 2) the nonfunctional early ribosome, 3) the nonexistent RNA translation and coding system, and 4) the origin of the inherent genetic information. He specifically stated, “RNA-first theories, like their predecessors, had failed to explain the central question of the origin of the ‘information’ that living cells require.” As William Dembski noted, “The origin of information is not a problem of chemistry. Chemistry can be a carrier of information, but it cannot be its source” (4). Dr. Boland stated: “Given enough time, it is not surprising that somewhere in the primordial soup, a variety of complex compounds would spontaneously form.” But modern geochemists doubt that a “primordial soup” existed. He made the mistake that origin-of-life researcher David Abel warned against: “Mere possibility is not an adequate basis for asserting scientific plausibility,” and “just because a hypothesis is possible should not grant that hypothesis scientific respectability” (5). In this case, the odds of producing a self-replicating RNA molecule go beyond the available probabilistic resources. My article, “Dissecting Darwinism,” simply suggested that students and doctors have a right to know that the mechanism proposed by Dr. Boland is not universally supported. Even ardent evolutionists admit that the origin-of-life research is “completely in the dark” (6). 3. Dr. Boland notes the “homeobox genes” as key regulatory genes that orchestrate the expression of dozens of other genes simultaneously. Awareness of many functions of noncoding DNA, including the micro RNA noted by Dr. Boland, has rapidly increased over the past 5 years. Surprisingly, he noted, “These are not thought to be of major functional significance.” However, as we learn more about the role of the human genome, it is exciting and optimistic that we are learning how this remarkable strand of approximately 5 billion nucleotides (2.5 billion base pairs) is responsible for everything, such as development, repair, inhibition, replication, coordination, and interaction with all other biological systems. The DNA also has layering aspects, which allow for coding of more than one protein/RNA molecule during the same transcription. In any case, mutations in homeobox genes cannot explain the origin of body form. As one author in Nature stated, “Homeobox genes are selector genes. They can do nothing if the genes regulated by them are not there. . . . It is totally wrong to imply that an eye could be produced by a macromutation when no eye was ever present in the lineage before” (7). 4. Finally, Dr. Boland’s comment that the characterization of 70% to 75% similarity between human and chimp genomes “willfully misstated the data” is not consistent with the published literature. First, it is important to acknowledge that nearly all DNA is now shown to directly code for either protein or RNA (responsible for numerous regulatory, differentiation, replication, or structural actions) (8). In other words, we must consider the entire human genome and not presume that some of the human genome is useless. The alignment of 2.4 billion nucleotides (chimp) compared to 3.16 billion nucleotides (human) has been calculated to represent an approximate 76% similarity, according to geneticist Richard Buggs (9, 10). A 2007 article in 172 Molecular Biology and Evolution stated: “For about 23% of our genome, we share no immediate genetic ancestry with our closest living relative, the chimpanzee. We conclude that about 1/3 of our genes started to evolve as human-specific lineages before the differentiation of human, chimps, and gorillas took place” (11). Finally, an important article in Nature in 2010 revealed the flaws in the earlier 2005 human-chimp draft report and presented the most species-specific analysis of the Y chromosome (12). The authors found only a 70% similarity. As far as looking at specific genes, the chimp and human Y chromosome had a dramatic difference in gene content of 53%. Regardless of the formula, it should be remembered that even a conservative estimate of 30 million DNA changes from chimp to human would require almost 60 beneficial mutations per generation (20 years) in order to account for a direct lineage from chimp to man in 10 million years. Based on a generation time of 20 years, Haldane’s dilemma predicts that only a few thousand mutations could become fixed into an evolving population during the time period (10 million years) from chimp to man. Response to Dr. Hansen Dr. Hansen chose to use ad hominem arguments, charging that I am a “religious creationist.” His attacks are inaccurate, and any aspersions to my religion are irrelevant, as I did not make any theological arguments. I am just a surgeon with experience in molecular medicine and with respect for objective scientific inquiry. The articles I cited are from mainstream scientific sources. Some Darwinists have a certain degree of indoctrination that makes it difficult for them to accept papers that are critical of their “paradigm.” These papers have raised specific concerns about the ability of Darwinian evolution to explain (a) the origin of DNA, (b) the origin of the cell, and (c) the inability of irreducibly complex systems to form in a step-by-step fashion. Response to Dr. Jones The letter from Dr. Jones, a geologist, wrongly assumes that the paper was promoting intelligent design. No ideological alternative to Darwinian evolution was offered, though scientifically valid arguments have been proposed by theists, agnostics, and atheists who independently question whether stepwise mutation and natural selection could account for DNA, the cell, or irreducibly complex systems (3, 4, 13, 14). In addition, he is incorrect in his assessment of the current state of affairs regarding prebiotic molecules research. I would acknowledge an enormous amount of modern research into molecular chemistry, hydrothermal vents, lipid formation, and many aspects of prebiotic science. But many of these ideas have problems. To take hydrothermal vents, for one, they would serve as a poor location for the origin of life to take place since their high heat would quickly degrade any organic molecules. As William Dembski noted, “Most of origin-of-life research is as relevant to the real problem of life’s origin as rubber-band powered propeller model planes are to the military’s most sophisticated stealth aircraft.” In other words, there is not a single paper that has demonstrated the autoformation of DNA, RNA, or a functioning cell. The Baylor University Medical Center Proceedings Volume 25, Number 2 paper “Dissecting Darwinism” simply summarized the facts and controversy. Dr. Jones’ argument regarding the fossil data being expressed graphically in a manner that emphasizes the abrupt formation of most major animal phyla is accurate and an excellent observation. In addition, molecular clocks have been shown to be a variable and unsteady process, requiring a host of assumptions that are not widely accepted, including the assumption that the organisms are related in the first place. As one paper in Annual Review of Earth and Planetary Sciences recognized, “The second area where molecules and morphology are in serious disagreement concerns the origins of the metazoan phyla. . . . The discord between the two for the animal phyla may be as much as 500 million years,” and concluded, “the idea that there is a universal molecular clock ticking away has long since been discredited” (15). A 2006 article in Biological Therapy stated that a “review of the history on molecular systematics and its claims in the context of molecular biology reveals that there is no basis to the ‘molecular assumption’” (16). Moreover, molecular clocks simply assume that any genetic similarity results from common ancestry; they do not demonstrate that is the case. My article indicated that there are paleontologists who feel strongly that the fossil data do not fully support Darwinian evolution. As Nature editor Henry Gee commented, “To take a line of fossils and claim that they represent a lineage is not a scientific hypothesis that can be tested, but an assertion that carries the same validity as a bedtime story—amusing, perhaps even instructive, but not scientific” (17). Thus, the fossil data remain controversial based on abrupt formation of species, less-than-convincing missing links (transitional species), and variable and assumption-laden conclusions of molecular clocks. The examples of Nobel Prizes in molecular medicine further emphasize the incredible elegance of DNA and actually make it appear even more unlikely that DNA arose through a process of random mutation and natural selection. The inability of mutations to form new DNA or even a single new protein is demonstrated in the real-world experimental stage of bacteria, viruses, and parasites representing hundreds of millions of years of evolutionary study (18). These letters to the editor have shown the following prediction to be true: As the paradigm is questioned, there will be many who will cry “ignorance and heresy” (2). I believe that it is imperative to allow journals and scientists the opportunity to investigate the inability of Darwinism to explain the origin of life, the origin of DNA, the concept of irreducible complexity, and the controversial fossil evidence for speciation. —Joseph Kuhn, MD, FACS Department of Surgery, Baylor University Medical Center at Dallas 1. 2. 3. A Scientific Dissent from Darwinism, 2009. Available at http://www. dissentfromdarwin.org/. Kuhn JA. Dissecting Darwinism. Proc (Bayl Univ Med Cent) 2012;25(1): 41–47. Meyer SC. Signature in the Cell. New York: HarperCollins, 2009: 296–321. April 2012 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. Dembski WA, Wells JA. The Design of Life: Discovering Signs of Intelligence in Biological Systems. Richardson, TX: Foundation for Thought and Ethics, 2007. Abel DL. The universal plausibility metric (UPM) & principle (UPP). Theor Biol Med Model 2009;6:27. Slack G. What neo-creationists get right. The Scientist, June 20, 2008. Available at http://classic.the-scientist.com/news/print/54759/. Szathmary E. When the means do not justify the ends [Book review of Sudden Origins: Fossils, Genes, and the Emergence of Species]. Nature 1999;399(6738):745. Wells J. The Myth of Junk DNA. Seattle, WA: Discovery Institute Press, 2011. Buggs R. Chimpanzee? Available at http://www.refdag.nl/chimpanzee_1_282611. Buggs R. 70% Chimp? Available at http://www.refdag.nl/70_ chimp_1_295967. Ebersberger I, Galgoczy P, Taudien S, Taenzer S, Platzer M, von Haeseler A. Mapping human genetic ancestry. Mol Biol Evol 2007;24(10): 2266–2276. Hughes JF, Skaletsky H, Pyntikova T, Graves TA, van Daalen SK, Minx PJ, Fulton RS, McGrath SD, Locke DP, Friedman C, Trask BJ, Mardis ER, Warren WC, Repping S, Rozen S, Wilson RK, Page DC. Chimpanzee and human Y chromosomes are remarkably divergent in structure and gene content. Nature 2010;463(7280):536–539. Berlinski D. The Devil’s Delusion: Atheism & Its Scientific Pretensions. New York: Basic Books, 2009:10. Monton B. Seeking God in Science: An Atheist Defends Intelligent Design. Peterborough, ON: Broadview Press, 2009. Smith AB, Peterson KJ. Dating the time of origin of major clades: molecular clocks and the fossil record. Ann Rev Earth Planet Sci 2002;30: 65–88. Schwartz JH, Maresca B. Do molecular clocks run at all? A critique of molecular systematics. Biological Theory 2006;1(4):357–371. Gee H. In Search of Deep Time: Beyond the Fossil Record to a New History of Life. New York: Free Press, 1999. Behe MJ. Experimental evolution, loss-of-function mutations, and “the first rule of adaptive evolution.” Q Rev Biol 2010;85(4):419–445. Kudos The January issue of the Baylor University Medical Center Proceedings is the best issue I have read. The medical topics chosen for inclusion in this issue were interesting; however, those article that dealt with subjects of historical content, especially Dr. Kuhn’s article on Dissecting Darwinism, were outstanding. I was pleased to see that Dr. Fenves has become an associate editor. I remember when he first started practice. Proceedings is a wonderful journal and a platform for Baylor physicians to publish their work; however, I believe that the inclusion of other authors outside of the Baylor universe adds to the quality of the publication. I started my general surgical practice at Baylor in 1971 and was chairman of the general surgery department at Presbyterian Dallas at the time of my retirement about 6 years ago. Reading Proceedings keeps me in touch with former colleagues and abreast of the progressive advancement of medicine. I know of no other hospital publication in Texas that compares to Proceedings. —Jay Hoppenstein, MD, FACS Dallas, Texas Reader comments 173 From the Editor Facts and ideas from anywhere WATER SCARCITY Benjamin Franklin stated in his Poor Richard’s Almanac, “When the well is dry we learn the worth of water” (1). Steven Solomon, in his book entitled Water: The Epic Struggle for Wealth, Power and Civilization, stated that “water is overtaking oil as the world’s scarcest critical natural resource” (2). William C. Roberts, MD. He indicated that oil is substitutable, albeit painfully, by other fuel sources, or in extremis can be done without, but water’s uses are pervasive, irreplaceable by any other substance, and indispensable. In his 2010 book he provides numerous observations, some of which are the following. There is hardly an accessible freshwater source or a strategically placed waterway in an economically advanced part of the planet that has not been radically engineered by man. As the world population moves toward 9 million and with so many third world inhabitants moving toward consumption and waste-generation levels of the one fifth living in industrialized nations, demand for more fresh water is soaring. Yet no new breakthrough capable of expanding the usable water supply is anywhere evident. Water scarcity is cleaving an explosive fault line between fresh water-haves and have-nots: among relatively well-watered industrial world citizens and those of water-famished developing countries; among those upriver who control river flows and their neighbors downstream whose survival depends upon receiving a sufficient amount; and among those nations with enough agricultural water to be self-sufficient in food and those dependent upon foreign imports to feed their populations. The new fresh water fault line is fomenting a more divisive competition among interest groups and regions for a greater allocation of limited domestic water resources: between heavily subsidized farmers on the one side and nonsubsidized industrial and urban users on the other; between the well-healed situated within close proximity to fresh water sources and the rural and urban poor remote from water sources; between those able to pay the top price for abundant, wholesome drinking water and the water destitute who glean the dredges; between those who dwell in 174 locations with effective pollution regulations, modern wastewater treatment, and sanitation facilities, and those whose daily lives are contaminated by exposure to impure, disease-plagued water; between the privileged minority living in the planet’s relatively well-watered and forested temporal zones and the largest part of the human race living on water-fragile dry lands, oversaturated tropics, or more exposed to the costly unpredictability of extreme precipitation that causes floods, mudslides, and droughts. Every day across the planet, armies of the water poor, mainly women and children compelled by thirst to forego school and productive work, march barefoot 2 or 3 hours per day transporting water in heavy plastic containers from the nearest clear source for their barest household survivor needs—some 200 pounds per day for a four-person household. This portion of humanity includes over 1.1 billion people, almost one fifth of all humanity, who lack access to at least a gallon per day of safe water to drink. Some 2.6 billion, 2 out of 5 people on earth, are sanitary have-nots lacking the additional 5 gallons needed daily for rudimentary sanitation and hygiene. Far fewer still achieve the minimum threshold of 13 gallons per day for both basic domestic health and well-being, including water for bathing and cooking. The lives of the most abject of water have-nots are chronically afflicted and shortened by diarrhea, dysentery, malaria, dengue fever, schistosomiasis, cholera, and the other conditions that make waterborne diseases human beings’ most prevalent scourge. Half the people in the developing world of Africa, Asia, Latin America, and the Caribbean suffer from diseases associated with inadequate fresh water and sanitation. This side of the humanitarian divide includes the 2 billion human beings whose lives are uprooted catastrophically every decade from inadequate public infrastructure protection from water shocks. By contrast, on the water-have side of the humanitarian divide, industrialized-world citizens use 10 to 30 times more water than their poorest, developing nation counterparts. In the water-wealthy USA, each person uses an average of 150 gallons of water per day for domestic and municipal purposes, including such extravagances as multiple toilet flushes and lawn watering. Water rationing is increasingly commonplace in water have-not societies. So too are internecine conflicts and violent protests over scare supplies and high prices. Inadequate water Proc (Bayl Univ Med Cent) 2012;25(2):174–183 supply commonly manifests itself in the form of insufficient food output, stunted industrial development, and a shortage of energy, which requires copious volumes of water for cooling and power generation. Chronic water scarcity undercuts the political legitimacy of governments, fomenting social instability and failed states. Water rights, bombings, deaths, and other violent warning signs occurred from 1999 to 2005 in conflicts over water in Karachi, Pakistan, in Gujarat, India, in provinces of arid North China, in Cochabamba, Bolivia, between Kenyan tribes, among Somalian villages, and in Darfur, Sudan. The wars in the last century were often about oil; in this century, water. Up to half the world’s wetlands disappeared or were severely damaged in the 20th century’s drive to obtain more arable land and fresh water for agriculture. Worldwide expansion of irrigable farmland is now peaking for the first time in history. Mankind’s withdrawal of useable, renewable fresh water from the surface of the planet is expected to rise about 60% by 2025! In the first decade of the 21st century, an increasing number of nations were so critically water stressed that they could no longer grow all the crops they needed to feed and clothe their populations. Growing crops is a water-intensive enterprise: about three quarters of mankind’s water is used for farm irrigation. Food itself is mainly water. To produce a single pound of wheat requires half a ton or nearly 250 gallons of water; a pound of rice needs between 250 and 650 gallons. Livestock for meat and milk multiplies the water requirements since the animals have to be nourished with huge quantities of grain; up to 800 gallons or over 3 tons of water is needed to produce a single hamburger and some 200 gallons for a glass of cow’s milk. A well-nourished person consumes about 900 gallons of water each day in the food he or she eats. Production of an ordinary cotton t-shirt requires about 700 gallons of water. As water-poor countries fall short of self-sufficiency, they are growing increasingly dependent upon importing grain and other foods from water-wealthier farming nations. By 2025, up to 3.6 billion people in some of the driest, most densely populated and poorer parts of the Middle East, Africa, and Asia will live in countries that cannot feed themselves. The growing bifurcation between water-poor food importers and water-rich exporters is further exacerbated by manmade ruination of crop land from soil erosion and polluting runoff. The upward spiraling international food prices as the era of cheap water and cheap food comes to an end is already causing grave consequences. What is needed is a new Green Revolution, perhaps including the development of genetically modified plant hybrids that grow with less water. Man’s access to this renewable fresh water supply is limited to a maximum of one third, since about two thirds quickly disappears in floods and into the ground, ultimately returning to the sea. Even so, that one third totals enough available renewable water to more than suffice for the planet’s 7 billion people if it were distributed evenly. But it is not. A large share runs off unused in lightly inhabited jungle rivers like the Amazon, the Congo, and the Orinoco, and across Russia’s Siberian expanses toward the Arctic, in the giant Yenisei and Lena Rivers. Thus, the amount of readily available fresh water per person is less April 2012 than the threshold annual 2000 cubic meter measure of water sufficiency. And it is declining sharply as the world population increases. Hot climates suffer much higher losses from evaporation than cool, temperate ones. In Africa, only one fifth of all rainfall transforms into potentially utilized runoff. Thus, each region’s actual water challenge varies enormously by environment, availability, and the population it has to support. Australia, by far the driest continent, has only 5% of the world’s runoff, but it supports the smallest human population— a mere 20 million, or less than one half of 1% of the world’s population. Asia, the largest continent, receives the most renewable water, about one third of the total. Nonetheless, it is the most water-stressed continent because it has to meet the needs of three fifths of humanity, contains some of the world’s arid expanses, and receives over three quarters of its precipitation in the form of hard-to-capture seasonal monsoons. The waterrichest continent is South America, with 28% of the world’s renewable water and only 6% of its population. On a per-person basis, it receives 10 times as much fresh water each year as Asia and 5 times as much as Africa. Yet most of it flows away unused through jungle watersheds, while some high desert regions remain bone dry. North America is water wealthy, with 18% of the world’s runoff and 8% of its population. Europe has only 7% of the world’s water for its 12% share of population, but it is comparatively advantaged in its wet, northern, and central half because much of its water falls year round, evaporates slowly, and runs off in easily accessible navigable small rivers. The planet’s dry lands, encompassing one third of humanity, or over 2 billion people, have only 8% of the world’s renewable supply of water in their surface streams and fast-recharging ground water tables. More than 90% of the dry-land inhabitants live in developing nations, making water famine one of the key vexing challenges of international economic development. It is hardly surprising that the vast dry land belt stretching from North Africa and the Middle East to the Indus Valley is also one of the world’s politically volatile regions. At the other end of the spectrum are super water-have countries such as Brazil, Russia, Canada, Panama, and Nicaragua, with far more water than their populations can ever use. The USA and China have large hydrological imbalances: the modestly populated American far west feels constraints on its rapid growth, and the fertile northern plain of China is one of the most severely water-scarce, environmentally challenged regions on earth. India’s huge population is outstripping the highly inefficient management of its fresh water resources, forcing farmers, industry, and households to pump ground water faster and deeper than prudent. Western European nations have managed successfully because they use their limited water resources more productively, using a higher proportion for industry and cities and less for agriculture. Because water is so heavy and needed in such vast quantities, chronic shortages cannot be permanently relieved by transporting it over long distances. One reliable indicator of water wealth is the amount of water storage capacity each nation has installed per person to buffer it against natural shocks. The storage leaders are the world’s wealthiest nations, while the poorest remain most exposed to the natural caprices of water. Facts and ideas from anywhere 175 Despite its growing scarcity and preciousness to life, water is also man’s most misgoverned, inefficiently allocated, and profligately wasted natural resource in both democracies and authoritarian states. Modern governments routinely maintain monopolistic control over their nation’s supply, pricing, and allocation; commonly, water is distributed as a social good, a political largesse to favored interest groups and to public projects. Governments treat water as if it were a limitless gift of nature to be freely dispensed by any authority with the power to exploit it. In contrast to oil, and nearly every other natural commodity, water is largely exempted from market discipline. Rarely is any inherent value ascribed to the water itself. Only the cost of capturing and distributing it is routinely accounted. Nor is any cost ascribed to the degradation of the water ecosystem from whence it comes and to which, often in a polluted condition, it ultimately returns. By belonging to everyone and being the responsibility of no one, water for most of history has been consumed greedily and polluted recklessly. The result, compounded over time, is a colossal underpricing of water’s full economic and environmental worth. This fact sends an insidious, illusionary economic signal that water supply is endlessly plentiful, promoting wasteful use. Man’s most egregious waste of water came from the distortions caused by the chronic underpricing of water for irrigation. Irrigation farmers in Mexico, Indonesia, and Pakistan paid little more than 10% of the full cost of their water. Because Islamic tradition held that water should be free, many Muslim countries charge little or nothing for it. American government dam water subsidies were grandfathered upon a small number of farmers who cultivated a quarter of the irrigated crop land in the arid lands of the west. Inefficient flood irrigation is still subsidized in many water-poor regions. Underpriced water is also a disincentive to urban conservation. Through leaky infrastructure, thirsty Mexico City loses enough water every day—some two fifths of its total supply—to meet the needs of a city as large as Rome. The world faces a trillion-dollar-plus water infrastructure deficit in the years immediately ahead just to patch the leaks! Water’s peculiar treatment economically was contemplated in the 18th century by Adam Smith. In his Wealth of Nations, he pondered, “Nothing is more useful than water; but it will purchase scarce anything; scarce anything can be had in exchange for it.” Why was water, despite being invaluable to life, so cheap, while diamonds, though relatively useless, so expensive? Smith’s answer was that water is ubiquity and the relatively easy labor required to obtain it accounted for its low price. His theory was superseded within mainstream economics in the late 19th century by a more refined explanation. Water’s price was determined by a sliding scale based on its availability for its least valued uses: watering lawns, filling swimming pools, quenching the thirst of wildlife. Its premium rose as it became scarce for its most precious uses, reaching its zenith as priceless drinking water. The worth of water is now rising and to reflect Smith’s original observation, nothing is more useful. Bottled water is the world’s fastest growing beverage, with annual global sales of over $100 billion, increasing at 10% per year and reaching handsome profits for several corporate giants 176 (Nestle, Coca-Cola, and Pepsi-Cola). The markup is 1700 times over the cost of public tap water. Privatized management of water utilities is another huge global sector, as is wastewater services, dominated by corporate multinationals. In total, water is a fastgrowing, highly fragmented, competitive $400 billion per year industry. Subjecting water to market forces has enormous capacity to stimulate badly needed efficiency gains and innovations. But water is too precious to human life and too politically explosive to be left to the merciless logic of market forces alone. Water scarcity requires nothing less than a comprehensive reevaluation of water’s vital importance as the new oil—a precious resource that has to be consciously conserved, efficiently used, and properly accounted for on the balance sheet: from public health, food production, and energy production to national security and the sustainability of the human civilization. Turn off the faucet! ENERGY DRINKS A June 2011 article in Pediatrics warned that “stimulantcontaining energy drinks have no place in the diets of children or adolescents” (3). In October 2011, the National Federation of State High School Associations cautioned that caffeinated energy drinks—often confused with such products as Gatorade, a fluid replacement drink—should not be consumed before, during, or after physical activity because they could raise the risk of dehydration and increase the chance of potentially fatal heart illnesses. The organization also warned of possible interactions with prescription medications, including stimulants used to treat attention-deficit hyperactivity disorder. The energy drink business is now a $7.7 billion industry. Most best-selling energy drinks (Monster, Red Bull, and Rockstar) contain about 80 mg of caffeine per 8 oz, though they are often sold in containers as large as 20 to 24 oz (Table 1). Other more extreme products abound, some of them in mix-your-own powders or concentrates, in strengths researchers say range from about 50 to 500 mg per serving. At their maximum strength, energy drinks contain about 300 mg more than the 2-oz shots of 5-Hour Energy frequently seen near checkout counters. A 16-oz can of the top-selling energy drinks contain about 160 mg of caffeine. A 16-oz cup of Starbucks’ robust Pike Place Roast contains 330 mg. Some researchers have complained that identifying caffeine content and other ingredients is difficult for consumers because US Food and Drug Administration (FDA) regulations do not require products marketed as dietary supplements—as many energy drinks are—to adhere to the same labeling requirements as food and beverages. Canada, in November 2011, moved to limit caffeine in energy drinks to no more than 180 mg in containers up to 20 ounces. In the USA, cola-type drinks are limited by the FDA to 71 mg of caffeine per 12-oz serving. But no such limit applies to energy drinks marketed as dietary supplements, and manufacturers are not required to list the caffeine content or all ingredients on the label, sometimes opting for the term “energy blend” or “proprietary blend.” Additives, including the herbal supplements guarana, green tea, and yerba mate, can boost the effective level of caffeine. Baylor University Medical Center Proceedings Volume 25, Number 2 Table 1. Approximate caffeine content in selected drinks* Beverage Serving size (oz) Caffeine (mg) Soft drinks Coca-Cola 12 Diet Coke Pepsi Table 2. Estimated new cancer cases and deaths in the USA, 2012* Site New cases Deaths 34 All Oral cavity and pharynx 1,638,910 40,250 577,190 7,850 12 46 Digestive system 284,680 142,510 12 38 Respiratory system 244,180 164,770 Sprite Coffee McDonald’s brewed 12 0 16 100 Bones and joints Soft tissues (including heart) Skin† 2,890 11,280 81,240 1,410 3,900 12,190 Starbucks Caffe latte Starbucks Pike Place Roast Energy drink 16 16 150 330 Breast Genital system Urinary system 229,060 340,650 141,140 39,920 58,360 29,330 Amp 16 160 Eye and orbit 2,610 270 Full Throttle Monster NOS Red Bull Rockstar 16 16 16 16 16 197 160† 260 154 160 Brain and nervous system Endocrine system Lymphoma 22,910 58,980 79,190 13,700 2,700 20,130 Spike Shooter 8.4 300 Myeloma Leukemia Other or unspecified 21,700 47,150 31,000‡ 10,710 23,540 45,900 Wired X 344 Energy shots 5-Hour Energy 16 344 *Adapted from Siegel et al., 2012 (8) with permission. †Excludes 2 207 basal and squamous. ‡Underestimated. *Reprinted with permission from Norwood, 2011 (3). Sources: Product labels, MayoClinic.com, company reports. †Monster energy drinks do not include caffeine content on the label, but company and independent reports put it at about 160 mg per 16-oz serving. Less common additives such as yohimbine and bitter orange can increase heart rate, cause changes in blood pressure, and interact with certain antidepressive medications, according to the National Institutes of Health. Monster, the US leader in sales, does not list the amount of caffeine on its can, although independent sources place it at about 80 mg per 8-oz container, or 240 in Monster’s 24-oz can. So far the FDA has not acted on petitions by academics and other experts to limit caffeine or change labeling requirements for energy drinks. Emergency room visits associated with energy drink use increased more than 10-fold, from 1128 in 2005 to 13,114 in 2009, according to a report released in November 2011 by the federal government’s Substance Abuse and Mental Health Services Administration; in 44% of visits, patients combined energy drinks with other substances such as alcohol, pharmaceuticals, or illicit drugs. Most adverse reactions were in those who consumed two to eight energy drinks or >200 mg of caffeine. A report from the Mayo Clinic by Higgins and colleagues (4) listed the side effects of these energy drinks as insomnia, nervousness, nausea, rapid heartbeat, and in rare cases seizures, cardiac arrhythmias, and cardiac arrest. CANCER ESTIMATES FOR 2012 Each year the American Cancer Society estimates the numbers of new cancer cases and deaths expected in the USA in April 2012 the current year and compiles the most recent data on cancer incidence, mortality, and survival based on data from the National Cancer Institute, the Centers for Disease Control and Prevention (CDC), the North American Association of Central Cancer Registries, and the National Center for Health Statistics (5). A total of 1,638,910 new cancer cases and 577,190 deaths from cancer are projected to occur in the USA in 2012 (Table 2). During the most recent 5 years for which there is data (2004–2008), overall cancer incident rates declined slightly in men (by 0.6% per year) and were stable in women, while cancer death rates decreased by 1.8% per year in men and by 1.6% per year in women. Over the past 10 years (1999–2008), cancer death rates have declined by >1% per year in men and women of every racial/ethnic group with the exception of American Indians/Alaskan Natives, among whom rates have remained stable. The most rapid declines in death rates occurred among African American and Hispanic men (2.4% and 2.3% per year, respectively). Death rates continue to decline for all four major cancer sites (lung, colorectal, breast, and prostate gland), with lung cancer accounting for almost 40% of the total decline in men and breast cancer accounting for 34% of the total decline in women. The reduction in overall cancer death rates since 1990 in men and since 1991 in women translates to the avoidance of about 1,024,400 deaths from cancer. Nevertheless, cancer is still the second leading cause of death in the USA behind heart disease. About 1 in 2 men and 1 in 3 women develop cancer during their lifetimes. The reduction in breast cancer deaths has been attributed to the Facts and ideas from anywhere 177 decreased use of hormone replacement therapy, to earlier detection, and to better treatments. Both colonoscopy screening and mammography screening rates are higher than they were a year ago. Although the frequency of cancer in general is decreasing, seven cancers are increasing: mouth and throat cancers caused by human papillomavirus, the same virus that causes cervical cancer; esophageal adenocarcinoma, which is linked to chronic acid reflux, obesity, and smoking; melanoma, caused by exposure to ultraviolet radiation from the sun and tanning beds; liver cancer, which may be related in part to increases in hepatitis B and C infections; thyroid cancer, for unknown reasons, but maybe because of better detection; kidney cancer, which may be related to rising obesity; and pancreatic cancer, which is linked to smoking, obesity, and family history. Thus, preventing obesity will decrease the frequency of cancers of the esophagus, liver, kidney, and pancreas. Another reason to lose weight. BINGE DRINKING According to a January 2012 report from the CDC, 1 in 6 adults in the USA is a binge drinker, consuming an average of eight drinks per occasion and doing so four times a month (6). The risky behavior exists in all states, causing more than half of the 80,000 deaths and three quarters of the $23 billion in economic cost. Most alcohol-impaired drivers binge drink. Binge drinking means men drinking ≥5 drinks within a short period of time and women drinking ≥4 drinks. The authors analyzed self-reported data collected during 2010 of US adults aged ≥18 in 48 states and in the District of Columbia. The prevalence was twice as likely in men (23%) than women (11%). The highest prevalence of binge drinking was among those aged 18 to 34 years. The highest frequency was among the 65+ group. Those with an income of >$75,000 annually were more likely to binge drink. Those with an income of <$25,000 annually did it most often and drank the most per binge. Most people, however, who binge drink are not alcoholics. STRESS A survey by the American Psychological Association (APA) indicates that the average stress level in the USA in 2011 was 5.2 on a 10-point scale, down from 6.2 in 2007 (7). Among those surveyed, 39% indicated that their stress rose in 2011, 17% said it dropped, and 44% said it stayed the same. According to the APA, until 2011, stress has been rising each year since 2007. The newest survey involved 1226 adults aged 18 and older. Those reporting extreme stress, grade 8, 9, or 10, dropped from 32% to 22%, and 27% of adults said their stress had decreased in the past 5 years. Better economic conditions may be the explanation, because the 10 top causes of stress are money, work, the economy, relationships, family responsibilities, family health, personal health, job stability, housing costs (mortgage or rent), and personal safety. The APA also has recommendations to handle stress: take a break, exercise, laugh, get support, and meditate. Of these, the most successfully used stress management tool is exercise. The APA survey found that adults aged 18 to 32 (the so-called “Millennials”) are less likely than older adults to feel stressed by the economy. Unlike older adults who have watched their nest eggs disappear, younger people have been most affected by the downturn’s impact on jobs. COMPASSION FATIGUE Compassion fatigue is a combination of burnout and secondary traumatic stress from witnessing the suffering of others. The group that is affected the most is nurses, and compassion fatigue can lead to a feeling of sadness and despair that affects their health and well-being (8) (Table 3). A number of hospitals are tackling the problem in the midst of a worsening shortage of nurses. Compassion fatigue has been linked to decreased productivity, lessened empathy, more sick days, and higher turnover, particularly among cancer-care providers. A study led by the University of Nevada’s nursing school in Reno found that about 12% of US registered nurses were not working. Of those, more than 25% cited burnout or stressful work environments. The high Table 3. Symptoms of compassion fatigue* turnover increases the workload on remaining nurses, and that can result in higher death rates Work-related Physical Emotional and lessened patient safety. Compassion fatigue • Mood swings • Headaches • Avoidance or dread of was identified as a special problem for nurses in working with certain • Restlessness • Digestive problems: diarthe early 1990s. The New York State Nurses Aspatients rhea, constipation, upset • Irritability sociation conducted its first compassion-fatigue stomach • Reduced ability to feel • Oversensitivity workshop at a hospital last year and is urging empathy towards • Muscle tension • Anxiety hospitals and nursing schools to offer such propatients or families • Sleep disturbances: • Excessive use of substances: grams. • Frequent use of sick inability to sleep, insomnia, days • Lack of joyfulness *From Landro, 2012 (8). 178 too much sleep • Fatigue • Cardiac symptoms: chest pain/pressure, palpitations, tachycardia nicotine, alcohol, illicit drugs • Depression • Anger and resentment • Loss of objectivity • Memory issues • Poor concentration, focus, and judgment AIRPLANE GERMS It’s a common complaint: fly on a crowded airplane and come home with a cold. Air travelers suffer higher rates of infection than do non–air travelers. A reported number is 20% (9). Air that is recirculated through the cabin is most often blamed. But studies have shown that high-efficiency particulate air filters on most jets today Baylor University Medical Center Proceedings Volume 25, Number 2 capture 99.97% of bacterial and virus-carrying particles. When air circulation, however, is shut down, which sometimes happens during long waits on the ground or for short periods when passengers are boarding or exiting, infections can spread rapidly. A study in 1979 found that when a plane sat 3 hours with its engines off and no air circulating, 72% of the 54 passengers on board got sick within 2 days. The flu strain they had was traced to one passenger. For that reason, the Federal Aviation Administration issued an advisory to airlines in 2003 saying that passengers should be removed from planes within 30 minutes if there is no air circulating, but compliance is not mandatory. Much of the danger comes from the mouths, noses, and hands of passengers sitting nearby. The “hot zone” for exposure is generally two seats beside, in front of, and behind, according to a study in the July 2011 issue of Emerging Infectious Diseases, published by the CDC. A number of factors increase the odds of bringing home a cold from an airplane. The environment at 30,000 feet enables easier spread of disease. Air in airplanes is extremely dry, and viruses tend to thrive in low-humidity conditions. When mucus membranes dry up, they are far less effective at blocking infection. High altitudes also tire the body, and fatigue plays a role in making people more susceptible to catching colds. Also, viruses and bacteria can live for hours on some surfaces; some viral particles have been found to be active up to a day in certain places. Tray tables can be contaminated, and seatback pockets, which get stuffed with used tissues, soiled napkins, and trash, can be particularly dangerous. It is also difficult to know what germs are lurking on airline pillows and blankets. There are some basic precautions passengers can take to keep coughs away. 1) Hydrate: drinking water and keeping nasal passages moist can reduce the risk of infection. 2) Keep hands clean: frequently use an alcohol-based hand sanitizer. We often infect ourselves, touching mouth, nose, or eyes with our own hands that have picked up something. 3) Use disinfectant wipes to clean off tray tables before using. 4) Avoid seatback pockets. 5) Open the air vent and aim it so it passes just in front of your face. Filtered airplane air can help direct airborne contagions away from you. 6) Change seats if you end up near a cougher, sneezer, or someone who looks feverish. 7) Inform the crew if air circulation is shut off for an extended period. 8) Avoid airline pillows and blankets. Fortunately, most people sitting near someone who is ill do not get sick. stops are unrolling initiatives to help truckers slim down, shape up, and improve their health. Employers are holding health seminars, building on-site gyms, bringing in nutritionists and fitness trainers, and offering financial incentives to employees who stop smoking or lose weight. Some drivers are cooking in their rigs, walking or biking around truck stops, and blogging about their experiences at sites like truckingsolutionsgroup.org and safetythruwellness.com. TRUCK DRIVING AND BODY WEIGHT According to a 2007 study in the Journal of the American Diabetic Association, 86% of the estimated 3.2 million truck drivers in the USA are overweight, and most are obese (10). The US Transportation Department requires truck drivers to pass a certifying medical exam every 2 years. Drivers are checked for severe heart conditions, high blood pressure, and respiratory maladies, including sleep disorders. The results are bleak. Driving is a sedentary activity. Most truckers are paid by the mile, so they tend to squeeze every minute out of the 11 hours they are allowed on the road in a 24-hour period. Recently, transportation carriers, industry organizations, and even truck COST OF ASSISTED LIVING As the baby boomer generation grows older, the average life expectancy also increases. In the USA, life expectancy in 2008, the last year available, was 78.1 years. The number of people living in nursing homes nationwide has dropped in the last decade as other services—such as home health care and assisted living—have become more readily available (13). In 2000, 1.72 million lived in nursing homes in the US, and that had dropped to 1.5 million by 2010. Daily rates for rooms in private nursing homes vary across the continental US from <$200 to >$350 per day. The average in Texas is $188 per day and in Alaska, $655 per day. The hourly cost of hiring a home health aide across the April 2012 SLEEP DISORDERS IN POLICE OFFICERS Rajaratnam and colleagues (11) from Boston screened 4957 North American police officers who participated in either an online or an onsite screening and monthly follow-up surveys between July 2005 and December 2007, and 40% screened positive for at least one sleep disorder: 1666 (34%) for obstructive sleep apnea, 281 (6%) for moderate to severe insomnia, and 269 (5%) for shift work disorder. Respondents who screened positive for any sleep disorder had an increased prevalence of physical and mental health conditions, including diabetes mellitus, depression, and cardiovascular disease. Police officers need to be awake. OBESITY AND MEDICARE The US Medicare system recently announced that it will cover intensive behavioral counseling for willing participants with a body mass index of ≥30 kg/m². The plan, expected to cover more than 30% of the Medicare population, will mean 6 months of in-person therapy, extending to 12 months if the beneficiary has successfully lost 3 kg. TREATING LOW BACK PAIN Sherman and associates (12) from Seattle, Washington, and Portland, Oregon, designed a trial to determine whether yoga is more effective than conventional stretching exercises or a self-care book for patients with chronic low back pain. A total of 228 adults with chronic low back pain were randomized to 12 weekly classes of yoga, conventional stretching exercises, or a self-care book. Back-related functional status and bothersomeness of pain at 12 weeks were the primary outcomes. At both 12 weeks and 26 weeks, the outcomes for the yoga group were superior to those of the self-care group but not superior to conventional stretching exercises at any time point. Keep stretching and moving. Facts and ideas from anywhere 179 US varies from $15 to $30 daily. In Texas, the average is $18. Adult day care centers in the US range from $40 to >$100 per day; in Texas the average is $40 per day. Who should consider a long-term care insurance policy? Not the wealthy. Not those of modest means who qualify for Medicare. It is those in between, where paying long-term care expenses would impoverish the spouse. Many people believe Medicare covers long-term care, but generally it does not. One must meet certain conditions for Medicare to pay for these types of care. People are staying in assisted living facilities for a lot longer than in the past. They are a lot less institutional than nursing homes: their appearance is better, they smell nicer, and they offer nice activities, such as live bands every week. CANINE POSTTRAUMATIC STRESS DISORDER By some estimates, more than 5% of the approximately 6050 military dogs deployed by US combat forces are coming down with canine posttraumatic stress disorder (PTSD) (14). Of those, about half are likely to be retired from service. Although veterinarians have long diagnosed behavioral problems in nonhuman animals, the concept of canine PTSD is only about 18 months old, having come into vogue among military veterinarians who have been seeing patterns of troubling behavior among dogs exposed to explosions, gunfire, and other combat-related violence in Iraq and Afghanistan. Like humans with the analogous disorder, different dogs show different symptoms. Some become hypervigilant, others avoid buildings or work areas that they had previously been comfortable in, and some undergo sharp changes in temperament, becoming unusually aggressive with their handlers or clingy and timid. Many stop doing the task they were trained to perform. Treatment can be tricky since the patient (dog) cannot explain what is wrong; veterinarians and handlers must make educated guesses about the traumatizing events. Care can be as simple as taking a dog off patrol and giving it lots of exercise, play, and gentle obedience training. More serious cases receive what is called “desensitization counter conditioning,” which entails exposing the dog at a safe distance to a site or sound that might trigger a reaction—a gunshot, a loud bang, or a vehicle, for instance. If the dog does not react, it is rewarded, and the trigger is moved progressively closer until the dog is comfortable with it. DIABETES MELLITUS AND AMPUTATION About 1 in 10 US adults has diabetes mellitus; it is the seventh leading cause of death in the USA, according to the CDC. A recent study (15) disclosed that the number of diabetic patients aged ≥40 years who had lost a toe, foot, or leg fell from 1988 through 2008 from >11 to 4 per 1000 people. Among nondiabetics during the same period, the frequency of amputation had not changed. Even though the frequency of type 2 diabetes mellitus is continuing to increase in the USA because of the great increase in body weight, some of the other dreaded complications of diabetes including blindness and kidney failure have also decreased during this 20-year period. The exact reason for the decrease in amputations is unclear, 180 but CDC officials believe that improved patient education, earlier diagnosis, better blood sugar monitoring, protective shoes and other medical devices, and better care of feet are paying dividends. PEOPLE HURTING PEOPLE Matthew White, a self-described atrocitologist, necromatrician, and quantifier of hemoclysms, has compiled the most comprehensive, disinterested, and statistically nuanced estimates available of the death tolls of history’s major catastrophes in a book entitled The Great Big Book of Horrible Things (16). His scorn is directed at the stupidity and callousness of history’s great leaders and at the indifference of traditional history to the magnitude of human suffering behind momentous events. The largest numbers of victims in the top 25 events are listed in Table 4. The Second World War heads the list with 60 million fatalities. The American Civil War (1861–1865) resulted in 620,000 soldier fatalities and 75,000 civilian fatalities, and it is listed at number 75 in the all-time list. The Korean War, which resulted in 3 million soldier and civilian fatalities, is number 30. Our enemies in World War II, namely Germany and Japan, now are our best friends internationally. Table 4. The 25 deadliest multicides* No Event 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Second World War (1939–1945) Chinggis Khan (1206–1227) Hao Zedong (1949–1976) Famines in British India (18th–20th centuries) Fall of the Ming Dynasty (1635–1662) Taiping Rebellion (1850–1864) Joseph Stalin (1928–1953) Midwest slave trade (7th–19th centuries) Timur (1370–1405) Atlantic slave trade (1452–1807) Conquest of the Americas (after 1492) First World War (1914–1918) An Lushan Rebellion (755–763) Xin Dynasty (9–24) Congo Free State (1885–1908) Russian Civil War (1918–1920) Thirty-Year War (1618–1648) Fall of the Yuan Dynasty (ca. 1340–1370) Fall of the Western Roman Empire (395–455) Chinese Civil War (1927–1937, 1945–1949) Mahdi Revolt (1881–1898) The Time of Troubles (1598–1613) Aurangzeb (1658–1707) Vietnam War (1959–1975) The Three Kingdoms of China (189–280) Deaths (millions) 66 40 40 27 25 20 20 18.5 17 16 15 15 13 10 10 9 7.5 7.5 7 7 5.5 5 4.6 4.2 4.1 *From White, The Great Big Book of Horrible Things, 2012 (16). Baylor University Medical Center Proceedings Volume 25, Number 2 PROFESSIONAL BASEBALL AND BODY WEIGHT As Matthew Futterman described in a January 27, 2012, piece in The Wall Street Journal, in signing C. C. Sabathia, Albert Pujols, and Prince Fielder (son of big leaguer Cecil Fielder), the New York Yankees, Los Angeles Angels, and Detroit Tigers have committed $590 million to 825 pounds of baseball player (17). The Detroit Tigers reached a reported 9-year, $214 million deal with 71-inch, 275-pound 27-year-old Fielder. Albert Pujols (Prince Albert) is 75 inches tall and weighs 230 pounds at age 31. He signed a 10-year $254 million contract with the Los Angeles Angels. Sabathia at age 31 is 79 inches in height and weighs 290 pounds. He signed a contract extension last year to pitch for the Yankees for 5 more years for $122 million (plus a $25 million option for 2017). All three of these players need a nutritionist. Their late-night meals and free (to them) room service in hotels is too tempting for them. TOMATOES Thomas Jefferson thought they were poisonous, and although he grew many in his yard in Monticello they were for decoration only. Now, 90% of backyard gardens include tomato plants, and in 2009 Americans bought $5 billion worth of commercially grown fresh tomatoes. Barry Estabrook has recently written a book entitled Tomatoland . . . and he asks the question: “What has happened to the good flavor that used to be in tomatoes?” (18). He found that the lack of flavor in today’s crop of tomatoes is the result of science and business working together to create fruits that have a long shelf life and are nearly impervious to bruising or harsh handling. Most tomatoes Americans eat whole (as opposed to in a sauce or ketchup form) are grown in Florida. The Sunshine State’s sandy soil lacks the basic nutrients needed to produce good-tasting fruit, so farmers rely heavily on chemical fertilizers, pesticides, and herbicides to give the plants a boost. The high environmental and human cost of this chemical is a fruit devoid of tomato flavor and one that contains less vitamin C, thiamine, niacin, and calcium and 14 times as much sodium as a tomato grown in the 1960s. The best tomato is the one grown in one’s backyard. If you can’t grow your own, shop at the local farmer’s market or find locally grown in-season tomatoes in the supermarket. Whole Foods sells only “organic” tomatoes that have not been sprayed with chemicals. ERRORS IN NEWSPAPERS Newspapers often focus on reporting errors produced by members of our society, particularly those in prominent positions. The Washington Post publishes its own errors, a total of 875 corrections in its print edition in 2011, a 17% decrease from 1054 in 2010 (19). The 875 number is the lowest for any year since the Post began counting in 2005, when it had >1300 corrections. Good for the Post! EUROZONE GOVERNMENT DEBT European leaders are trying to stop a debt crisis that is threatening to shadow their 12-year-old experiment: a common Euro currency (20). The monetary union has existed April 2012 since the Euro was created in 1999, but the European Union, which includes the 17 Euro nations and 10 others that use their own currencies, has no central authority over taxing and spending. Government debt as a percentage of gross domestic product in 2010 among the European countries ranges from 7% in Estonia to 143% in Greece, and not one of the 17 countries is in the black. The unemployment rate in the 17 nations ranges from 5% (Cyprus) to 20% (Spain). The US cannot provide leadership because we also are broke. Individuals have a hard time saving money without frugality; nations must learn that virtue. FINANCIAL WORTH OF LAWMAKERS ON CAPITOL HILL In the 1970s, the members of Congress included a barber, a pipefitter, and a housepainter, and they organized into what was called the “blue collar caucus” (21). The financial gap between Americans and their representatives in Congress has widened considerably since then, according to an analysis of financial disclosures by The Washington Post. Between 1984 and 2009, the median net worth of a member of the House of Representatives more than doubled, from $280,000 to $725,000 in inflationadjusted 2009 dollars, excluding home equity. Over the same period, the wealth of an American family declined slightly, with the comparable median figure sliding from $20,500 to $20,000 according to the Panel Study of Income Dynamics from The University of Michigan. The growing disparity between Representatives and the represented means that there is greater distance between the economic experience of Americans and those of lawmakers. The growing financial comfort of members of Congress relative to most Americans is consistent with the general trend in the USA toward inequality of wealth. Members of Congress have long been wealthier than average Americans, and in recent decades the wealth of the wealthiest Americans has outpaced that of the average. In 1984, the earliest year for which consistent wealth statistics are available for members of Congress, the 90th percentile of US families had holdings worth 6 times those of the median families; by 2009, the 90th percentile had holdings worth 12 times those of the median families. These figures include home equity. Not only has the median wealth of members of Congress increased, but the proportion of Representatives who have little besides a home has shrunk. In 1984, 1 in 5 House members had 0 or negative net worth, excluding home equity; by 2009 that number had dropped to 1 in 12. Another possible reason for the growing wealth of Congress is that running a campaign has become much more expensive, making it more likely that wealthy people, who can donate substantially to their own campaigns, gain office. Since 1976, the average amount spent by winning House candidates quadrupled in inflation-adjusted dollars, to $1.4 million. The congressional pay is not one of the reasons for the growing disparity between Representatives and their constituents. In inflation-adjusted dollars, a member of Congress in 1977 earned $215,000; today, a member of Congress earns $174,000. The growth of income inequality has tracked closely with Facts and ideas from anywhere 181 measures of political polarization, which has been gauged using the average difference between the liberal/conservative scores for Republican and Democratic members of the House. A person’s financial circumstances affect a person’s political outlook. People identified as lower or middle class have been more likely to see income inequality as a problem and to favor redistribution of income. A Representative’s occupation before being elected influences how liberal or conservative he or she is in voting, according to a study from Duke University. In order from most conservative to most liberal: farm owners; business people such as bankers or insurance executives; private-sector professionals such as physicians, engineers, and architects; lawyers; service-based professionals, such as teachers and social workers; politicians; and blue-collar workers. Although party affiliation is the strongest determiner of voting records, the differences between legislators of different occupational backgrounds are striking. This information was gathered by Peter Whoriskey of The Washington Post. SNOWFLAKES Kenneth Libbrecht, a Cal-Tech physics professor, has been studying snowflakes under the microscope for nearly 2 decades (22). His photos of the frozen crystals of water grace more than 3 billion US postage stamps. He also has authored numerous articles on the molecular dynamics that dictate how ice crystals grow. The shape that snow takes depends on the temperature. From about freezing to 25°F, snow forms as flakes; when the temperature hits about 23°, the snow forms into needles; and at about 22°, into hollow columns. When the temperature drops to 10°, flakes start forming again, but when it gets to –8° or so, it once again turns to columns, and at –30°, snow stops forming altogether. A copy of one of his stellar denFigure. Snowflake. drites is shown in the Figure. PUBLIC-SECTOR PENSIONS An Associated Press survey in 2011 found that the 50 states in the USA have a combined $690 billion in unfunded pension liabilities and just under $420 billion in retiree health care obligations (23). In California it was recently pointed out that a public education teacher there for 40 years can retire at age 59 with a pension of $174,000 a year for the rest of his or her life. Many cities, counties, and states in the US are struggling to pay pension bills, but changes are afoot. In November 2011, San Francisco voters supported a local ballot initiative to raise minimum retirement ages for some city workers. Laws increasing retirement ages for government workers have been signed in Rhode Island and Massachusetts in efforts to address underfunded pension systems. In New Jersey the retirement age was raised from 62 to 65. Most private-sector workers no longer receive defined benefit pensions that will pay them for 182 life. Most must wait until age 65 or 67 to collect their full Social Security benefits or draw from 401k (closed) accounts that are invested in the stock market. MATRIMONY In 1960, 72% of adults 18 and older were married. That fell to 57% in 2000 and to 51% in 2011, according to Pew Researcher D’Vera Cohn (24). The share of marrieds could dip below 50% in a few years as single-person households, single parents, and couples living together outside of legal marriage multiply. The number of new marriages in the USA fell 5% from 2009 to 2010, a fall that may or may not be related to the bad economy. The decline is spread among age groups but is most dramatic among those under 30. Nearly 3 of every 5 adults aged 18 to 29 were married in 1960; but in 2011, it was only 1 in 5. DISPOSING OF ELECTRONICS Electronics contain lead, mercury, cadmium, and other potentially harmful chemicals, but only 25% of discarded devices (by weight) were recycled in 2009, the most recent year for which the Environmental Protection Agency has data (25). Seventeen states have banned electronic waste from landfills, requiring it to be recycled so its toxic materials do not leach into ground water. If we all recycled computers, computer displays, hard-copy devices, keyboards, mice, television sets, and mobile devices, we would all be better off. FIRECRACKER INJURIES Many Filipinos, largely influenced by Chinese tradition, believe that noisy New Year’s celebrations drive away evil and misfortune. But many in the Philippines have carried that superstition to extreme, exploding huge firecrackers and firing guns to welcome the new year despite threats of arrest. Firecrackers in Manila on New Year’s Eve 2011 injured 454, and 18 others were injured by stray bullets (26). The injured revelers included many children and filled hospital emergency rooms in Manila shortly after midnight. About a dozen plane flights, including two from the USA, were diverted or cancelled early New Year’s Day after dark smog caused by a night of firecracker explosions obscured visibility at Manila’s airports. Additionally, firecrackers ignited at least three fires that destroyed several houses in the capital area. Be careful with firecrackers. US DEBT The US debt is now about $16 trillion! The US population now is about 313 million people, and thus the debt for every adult and child amounts to $52,500. Countries in debt appear to be at the mercy of countries not in debt. Baylor University Medical Center Proceedings —William Clifford Roberts, MD 6 February 2012 Volume 25, Number 2 Franklin B. Poor Richard’s Almanack. New York: Peter Pauper Press (77 pp.). 2. Solomon S. Water: The Epic Struggle for Wealth, Power and Civilization. New York: HarperCollins, 2010 (596 pp.). 3. Norwood R. Young athletes, energy drinks: A bad mix? USA Today, December 2–4, 2011. 4. Higgins JP, Tuttle TD, Higgins CL. Energy beverages: content and safety. Mayo Clin Proc 2010;85(11):1033–1041. 5. Siegel R, Naishadham D, Jernal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62(1):10–29. 6. Lloyd J. “Dramatic” findings on binge drinking. USA Today, January 11, 2012. 7. Jones S. Yeah, we’re STRESSED but dealing with it. USA Today, January 11, 2012. 8. Landro L. When nurses catch compassion fatigue, patients suffer. Wall Street Journal, January 3, 2012. 9. McCartney S. Where germs lurk on planes. A survival guide. Wall Street Journal, December 20, 2011. 10. Ellin A (New York Times). Truckers driven to shape up. Dallas Morning News, November 27, 2011. 11. Rajaratnam SM, Barger LK, Lockley SW, Shea SA, Wang W, Landrigan CP, O’Brien CS, Qadri S, Sullivan JP, Cade BE, Epstein LJ, White DP, Czeisler CA; Harvard Work Hours, Health and Safety Group. Sleep disorders, health, and safety in police officers. JAMA 2011;306(23):2567–2578. 12. Sherman KJ, Cherkin DC, Wellman RD, Cook AJ, Hawkes RJ, Delaney K, Deyo RA. A randomized trial comparing yoga, stretching, and a self-care book for chronic low back pain. Arch Intern Med 2011;171(22):2019–2026. 1. April 2012 13. Yip P, Alcott K. The cost of growing old. Dallas Morning News, December 19, 2011. 14. Dao J. Our furriest solders get PTSD, too. Dallas Morning News, December 5, 2011. 15. Li Y, Burrows NR, Gregg EW, Albright A, Geiss LS. Declining rates of hospitalization for nontraumatic lower-extremity amputation in the diabetic population aged 40 years or older: U.S., 1988–2008. Diabetes Care 2012;35(2):273–277. 16. White M. The Great Big Book of Horrible Things. New York: WW Norton, 2012 (669 pp.). 17. Futterman M. Will cholesterol kill baseball? Wall Street Journal, January 27, 2012. 18. Harris M. What happened to tomatoes? Erickson Living, January 2012. 19. Pexton PB. The year in corrections. Washington Post, January 1, 2012. 20. Act or face collapse, eurozone is warned. Dallas Morning News, November 29, 2011. 21. Whoriskey P. Congress looks less like rest of America. Washington Post, December 27, 2011. 22. Weise E. Wondering about snowflakes. USA Today, December 19, 2011. 23. Pear R. Hefty price tag thwarts payroll tax deal, others. Dallas Morning News, December 5, 2011. 24. Associated Press. Fewer Americans wedded to the idea of matrimony. Dallas Morning News, December 21, 2011. 25. Koch W. More states ban disposal of electronics in landfills. USA Today, December 19, 2011. 26. Gomez J. Philippines New Year firecrackers injure nearly 500. Huffington Post, January 1, 2012. Facts and ideas from anywhere 183 Selected published abstracts of Baylor researchers AMERICAN JOURNAL OF CARDIOLOGY Presence of a congenitally bicuspid aortic valve among patients having combined mitral and aortic valve replacement Roberts WC, Janning KG, Vowels TJ, Ko JM, Hamman BL, Hebeler RF Jr Am J Cardiol 2012;109(2):263–271. Reprinted with permission from Elsevier. Although bicuspid aortic valve occurs in an estimated 1% of adults and mitral valve prolapse in an estimated 5% of adults, occurrence of the 2 in the same patient is infrequent. During examination of operatively excised aortic and mitral valves because of dysfunction (stenosis and/ or regurgitation), we encountered 16 patients who had congenitally bicuspid aortic valves associated with various types of dysfunctioning mitral valves. Eleven of the 16 patients had aortic stenosis (AS): 5 of them also had mitral stenosis, of rheumatic origin in 4 and secondary to mitral annular calcium in 1; the other 6 with aortic stenosis had pure mitral regurgitation (MR) secondary to mitral valve prolapse in 3, to ischemia in 2, and to unclear origin in 1. Of the 5 patients with pure aortic regurgitation, each also had pure mitral regurgitation: in 1 secondary to mitral valve prolapse and in 4 secondary to infective endocarditis. In conclusion, various types of mitral dysfunction severe enough to warrant mitral valve replacement occur in patients with bicuspid aortic valves. A proper search for mitral valve dysfunction in patients with bicuspid aortic valves appears warranted. Aortic medial elastic fiber loss in acute ascending aortic dissection Roberts WC, Vowels TJ, Kitchens BL, Ko JM, Filardo G, Henry AC, Hamman BL, Matter GJ, Hebeler RF Jr Am J Cardiol 2011;108(11):1639–1644. Reprinted with permission from Elsevier. The cause of acute aortic dissection continues to be debated. One school of thought suggests that underlying aortic medial cystic necrosis is the common denominator. The purpose of the present study was to determine if there was loss and, if so, how much loss of medial elastic fibers in the ascending aorta in patients with acute aortic dissection with the entrance tear in the ascending aorta. We examined operatively excised ascending aortas in 69 patients having acute dissection with tears in the ascending aorta. Patients with previous aortotomy, healed dissection, and connective tissue disorders were excluded. The 69 patients’ ages ranged from 31 to 88 years (mean 56); 49 were men and 20 were women. Loss of aortic medial elastic fibers was graded as 0 (no loss), 1+ (trace), 2+ (mild), 3+ (moderate), and 4+ (full thickness loss). Of these 69 patients, 56 (82%) had 0 or 1+ elastic fiber loss; 13 patients (18%), 2+ to 4+ loss including 4 with 2+, 6 with 3+, and 2 with 4+. Nearly all patients (97%) had a history of systemic hypertension and/or had received antihypertensive drug therapy. In conclusion, most patients (82% in this study) having acute aortic dissection with entrance tears in the ascending aorta have normal numbers or only trace loss of aortic medial elastic fibers. 184 Thus, underlying abnormal ascending aortic structure uncommonly precedes acute dissection. Accuracy of two-dimensional echocardiography in determining aortic valve structure in patients >50 years of age having aortic valve replacement for aortic stenosis Ayad RF, Grayburn PA, Ko JM, Filardo G, Roberts WC Am J Cardiol 2011;108(11):1589–1599. Reprinted with permission from Elsevier. We sought to measure the accuracy of 2-dimensional transthoracic echocardiography in determining aortic valve structure in patients with aortic stenosis (AS) undergoing aortic valve replacement (AVR). Few studies have compared aortic valve structure determined by echocardiogram to that determined by examination of the operatively excised stenotic aortic valve. Two-dimensional echocardiograms were reviewed and interpreted by an expert echocardiographer in blinded fashion in 100 patients >50 years of age (mean 70) who had undergone AVR for isolated AS ± aortic regurgitation and the aortic valve structure (unicuspid, bicuspid, tricuspid) was compared to that from examination of the operatively excised stenotic valve. After excluding 14 cases in which echocardiograms were uninterpretable because of heavy calcium and/or poor image quality, congenitally malformed valves were present in 44 patients (51%) and tricuspid valves in 42 of the 86 patients (49%). Ten of the 14 patients (71%) with uninterpretable echocardiograms had congenitally malformed valves. Valve structure by echocardiogram was concordant with morphologic interpretation in 57 of 86 patients (66% accuracy, kappa = 0.33). Accuracy trended toward improvement as degree of AS decreased. In patients with valve areas similar to those enrolled in the recent transcatheter aortic valve implantation trial (PARTNER; 0.7 ± 0.2 cm2), aortic valve structure was accurately determined by echocardiography in 21 of 35 patients (60%). In conclusion, aortic valve structure was interpretable by transthoracic echocardiogram in 86 of 100 patients and accurate in 57 of these 86 patients (66%). Effect of body mass index on survival in patients having aortic valve replacement for aortic stenosis with or without concomitant coronary artery bypass grafting Roberts WC, Roberts CC, Vowels TJ, Ko JM, Filardo G, Hamman BL, Matter GJ, Henry AC, Hebeler RF Jr Am J Cardiol 2011;108(12):1767–1771. Reprinted with permission from Elsevier. The purpose of this report is to describe the effect of body mass index (BMI) on 30-day and late outcome in patients having aortic valve replacement (AVR) for aortic stenosis (AS) with or without concomitant coronary artery bypass grafting. From January 2002 through June 2010 (8.5 years), 1,040 operatively excised stenotic aortic valves were submitted to the cardiovascular laboratory at Baylor University Medical Center at Dallas. Of the 1,040 cases 175 were eliminated because they had a previous cardiac operation. The present study included 865 adults whose AVR for AS was their first cardiac operation. Propensityadjusted analysis showed that 30-day and late mortality were strongly Proc (Bayl Univ Med Cent) 2012;25(2):184–187 and significantly associated with BMI. Decreased risk of 30-day and long-term mortality was observed for patients with BMI in the low 30s compared to patients with BMI in the mid 20s or >40 kg/m2. In conclusion, the findings in this study indicate a strong and significant adjusted association between BMI and 30-day and long-term mortality in patients having AVR for AS with or without concomitant coronary artery bypass grafting. Better survival was observed in patients with BMIs in the low 30s compared to patients with BMIs in the mid 20s and >40 kg/m2. of immunosuppressive interventions, such as cancer chemotherapy, anti-rejection drugs and the use of tumour necrosis factor-α inhibitors and monoclonal antibody to B-cell antigen. It now appears reasonable to consider transarterial chemoembolization (TAC) for hepatocellular carcinoma as an additional medical intervention associated with hepatitis B reactivation. Pre-emptive antiviral treatment of hepatitis B surface antigen (HBsAg) carriers can prevent serious complications arising from immunosuppressive-induced viral reactivation. Specific recommendations for antiviral prophylaxis in HBsAg carriers undergoing TAC should be added to international management guidelines. ANNALS OF ALLERGY, ASTHMA, AND IMMUNOLOGY Randomized placebo-controlled trial of the bradykinin B2 receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial CLINICAL REVIEWS IN BONE AND MINERAL METABOLISM Uric acid nephrolithiasis: a systemic metabolic disorder Wiederkehr MR, Moe OW Lumry WR, Li HH, Levy RJ, Potter PC, Farkas H, Moldovan D, Riedl M, Li H, Craig T, Bloom BJ, Reshef A Clinic Rev Bone Miner Metab 2011;9:207–217. Reprinted with permission from Humana Press. Ann Allergy Asthma Immunol 2011;107(6):529–537. Reprinted with permission from Elsevier. Uric acid nephrolithiasis is characteristically a manifestation of a systemic metabolic disorder. It has a prevalence of about 10% among all stone formers, the third most common type of kidney stone in the industrialized world. Uric acid stones form primarily due to an unduly acid urine; less deciding factors are hyperuricosuria and a low urine volume. The vast majority of uric acid stone formers have the metabolic syndrome, and not infrequently, clinical gout is present as well. A universal finding is a low baseline urine pH plus insufficient production of urinary ammonium buffer. Persons with gastrointestinal disorders, in particular chronic diarrhea or ostomies, and patients with malignancies with a large tumor mass and high cell turnover comprise a less common but nevertheless important subset. Pure uric acid stones are radiolucent but well visualized on renal ultrasound or computed tomography. A 24 h urine collection for stone risk analysis provides essential insight into the pathophysiology of stone formation and may guide therapy. Management includes a liberal fluid intake and dietary modification. Potassium citrate to alkalinize the urine to a goal pH between 6 and 6.5 is essential, as undissociated uric acid deprotonates into its much more soluble urate form. Background: The For Angioedema Subcutaneous Treatment (FAST)-3 study was a phase III, randomized, double-blind, placebo-controlled study of icatibant (bradykinin B2 receptor antagonist) in subjects with hereditary angioedema (HAE) resulting from C1-INH deficiency or dysfunction (type I/II). Objective: To investigate icatibant efficacy and safety in subjects with acute HAE attacks. Methods: Subjects with moderate to very severe cutaneous or abdominal symptoms received icatibant (n = 43) or placebo (n = 45). Five subjects with laryngeal (mild-to-moderate) first attacks received icatibant (n = 3) or placebo (n = 2), and 5 subjects with severe laryngeal first attacks received open-label icatibant. Results: Cutaneous or abdominal attacks: icatibant significantly reduced median times (vs placebo) to 50% or more reduction in symptom severity (2.0 vs 19.8 hours; P < .001, primary endpoint), onset of primary symptom relief (1.5 vs 18.5 hours; P < .001, key secondary endpoint), or almost complete symptom relief (8.0 vs 36.0 hours; P = .012) and provided a shorter time to initial symptom relief (0.8 vs 3.5 hours; P < .001). For laryngeal attacks, median time to 50% or more reduction in symptom severity was 2.5 hours (icatibant) and 3.2 hours (placebo). No icatibant-treated subject required rescue medication before symptom relief occurred. The incidence of adverse events (AEs) was similar in icatibant- and placebo-treated subjects (41% and 52%, respectively). All icatibant-treated subjects experienced injection site reactions, but none reported clinically relevant changes in safety parameters or serious AEs. Conclusions: FAST-3 demonstrated that icatibant was effective and generally well tolerated in subjects with acute HAE attacks. ANTIVIRAL THERAPY Reactivated hepatitis B due to medical interventions: the clinical spectrum expands Perrillo RP Antivir Ther 2011;16(7):947–949. Reprinted with permission from International Medical Press. Reactivated hepatitis B is a potentially serious disorder that can result in liver failure and death. It has been described with a wide variety April 2012 ISLETS Establishment of a prolonged pancreas preservation model for islet isolation research in mice Itoh T, Sugimoto K, Shimoda M, Chujo D, Takita M, Iwahashi S, Kanak M, Yoshiko T, Naziruddin B, Levy MF, Matsumoto S Islets 2011;3(6):376–380. Reprinted with permission. Establishing a prolonged pancreas preservation model in a small animal is important for islet isolation research. Use of a rat pancreas model has been reported, but no published reports have used a mouse pancreas for prolonged cold preservation prior to islet isolation. For the model, a mouse is preferred over a rat because of its small size, well-known immune characterization, and variety of gene-modulated models. In the present study, we established a prolonged pancreas preservation model in a mouse for islet isolation research. The collagenase solution was injected successfully after 24 and 48 h cold preservations in University of Wisconsin solution, and islets could be isolated from both groups of preserved pancreata. The islet yields from the control, 24 h preserved, and 48 h preserved pancreata were 183.9 ± 13.9, 128.5 ± 15.5, and 24.6 ± 12.9 per pancreas, respectively. The propidium iodide-positive Selected published abstracts of Baylor researchers 185 area assay was significantly increased in both preserved groups, and insulin secretion levels in response to 20.0 mM glucose and stimulation indices were significantly decreased in the 48 h preserved group. Inflammation-related gene mRNA levels were significantly upregulated in the 24 h preserved group, as previously shown in the human model. Thus, this model might be useful for prehuman islet isolation screening research, reserving research using human pancreata for the most promising approaches. JOURNAL OF BIOLOGICAL CHEMISTRY Early alterations of brain cellular energy homeostasis in Huntington disease models Mochel F, Durant B, Meng X, O’Callaghan J, Yu H, Brouillet E, Wheeler VC, Humbert S, Schiffmann R, Durr A J Biol Chem 2012;287(2):1361–1370. Reprinted with permission from the American Society for Biochemistry and Molecular Biology. Brain energy deficit has been a suggested cause of Huntington disease (HD), but ATP depletion has not reliably been shown in preclinical models, possibly because of the immediate post-mortem changes in cellular energy metabolism. To examine a potential role of a low energy state in HD, we measured, for the first time in a neurodegenerative model, brain levels of high energy phosphates using microwave fixation, which instantaneously inactivates brain enzymatic activities and preserves in vivo levels of analytes. We studied HD transgenic R6/2 mice at ages 4, 8, and 12 weeks. We found significantly increased creatine and phosphocreatine, present as early as 4 weeks for phosphocreatine, preceding motor system deficits and decreased ATP levels in striatum, hippocampus, and frontal cortex of R6/2 mice. ATP and phosphocreatine concentrations were inversely correlated with the number of CAG repeats. Conversely, in mice injected with 3-nitroproprionic acid, an acute model of brain energy deficit, both ATP and phosphocreatine were significantly reduced. Increased creatine and phosphocreatine in R6/2 mice was associated with decreased guanidinoacetate N-methyltransferase and creatine kinase, both at the protein and RNA levels, and increased phosphorylated AMPdependent protein kinase (pAMPK) over AMPK ratio. In addition, in 4-month-old knock-in Hdh(Q111/+) mice, the earliest metabolic alterations consisted of increased phosphocreatine in the frontal cortex and increased the pAMPK/AMPK ratio. Altogether, this study provides the first direct evidence of chronic alteration in homeostasis of high energy phosphates in HD models in the earliest stages of the disease, indicating possible reduced utilization of the brain phosphocreatine pool. JOURNAL OF BONE AND JOINT SURGERY Changes in gait following the Scandinavian Total Ankle Replacement Brodsky JW, Polo FE, Coleman SC, Bruck N J Bone Joint Surg Am 2011;93(20):1890–1896. Reprinted with permission from JBJS (http://www.jbjs.org/). Background: There is a resurgence of popularity with regard to total ankle arthroplasty, although there are limited data documenting the effect of total ankle arthroplasty on ankle joint motion, gait, or ankle function. The purpose of this study was to perform a prospective 186 evaluation of the effect of the Scandinavian Total Ankle Replacement on gait. Methods: We prospectively studied 50 consecutive patients with advanced ankle arthritis who underwent unilateral total ankle arthroplasty with the Scandinavian Total Ankle Replacement ankle prosthesis. Three-dimensional gait analysis was performed with use of a 12-camera digital-motion capture system. Kinetic parameters were collected with use of two force plates. Temporal-spatial measurements included stride length and cadence. The kinematic parameters that were measured included the sagittal plane range of motion of the ankle, knee, and hip. The kinetic parameters that were studied included ankle plantar flexion-dorsiflexion moment and sagittal plane ankle power. The mean period of follow-up was 49 months (range, 24 to 108 months). Results: Temporal-spatial analysis showed that walking velocity increased as a function of increases in both cadence and stride length, and to significant levels for each. Kinematic analysis showed that ankle range of motion increased from a mean of 14.2° to 17.9° (P < 0.001), with the increase coming from increased plantar flexion. Increased motion was also measured at the hip and knee. Significant increases were found in ankle power (from 0.69 to 1.00 W/kg [P < 0.001]) and ankle plantar flexion moment (from 0.88 to 1.09 Nm/kg [P < 0.001]). Conclusions: This study demonstrated that, at the time of intermediateterm follow-up and in comparison with the effects of ankle arthrodesis on gait as reported in previous studies, total ankle arthroplasty was associated with a more normal ankle function and a more normal gait, both kinetically and in terms of temporal-spatial parameters. More importantly, the study demonstrated marked improvement in multiple, objective parameters of gait following total ankle arthroplasty as compared with the patient’s own preoperative function. The long-term maintenance of the gait improvements will require further study. JOURNAL OF EXPERIMENTAL MEDICINE Targeting self- and foreign antigens to dendritic cells via DCASGPR generates IL-10–producing suppressive CD4+ T cells Li D, Romain G, Flamar AL, Duluc D, Dullaers M, Li XH, Zurawski S, Bosquet N, Palucka AK, Le Grand R, O’Garra A, Zurawski G, Banchereau J, Oh S J Exp Med 2012;209(1):109–121. ©2012 Li et al. Rockefeller University Press. doi: 10.1084/jem.20110399 Dendritic cells (DCs) can initiate and shape host immune responses toward either immunity or tolerance by their effects on antigen-specific CD4+ T cells. DC-asialoglycoprotein receptor (DC-ASGPR), a lectinlike receptor, is a known scavenger receptor. Here, we report that targeting antigens to human DCs via DC-ASGPR, but not lectin-like oxidized-LDL receptor, Dectin-1, or DC-specific ICAM-3-grabbing nonintegrin favors the generation of antigen-specific suppressive CD4+ T cells that produce interleukin 10 (IL-10). These findings apply to both self- and foreign antigens, as well as memory and naive CD4+ T cells. The generation of such IL-10–producing CD4+ T cells requires p38/extracellular signal-regulated kinase phosphorylation and IL-10 induction in DCs. We further demonstrate that immunization of nonhuman primates with antigens fused to anti-DC-ASGPR monoclonal antibody generates antigen-specific CD4+ T cells that produce IL-10 in vivo. This study provides a new strategy for the establishment of Baylor University Medical Center Proceedings Volume 25, Number 2 antigen-specific IL-10–producing suppressive T cells in vivo by targeting whole protein antigens to DCs via DC-ASGPR. Cochran VY, Blair B, Wissinger L, Nuss TD pathologic finding of preservation injury on liver biopsies taken at the time of transplant and within the first week of transplant (B-cell, P = 0.0032; T-cell, P = 0.0289). In summary, a positive crossmatch had no significant impact on patient survival or graft outcome. However, there was a significantly higher incidence of preservation injury in primary LT recipients with a positive crossmatch. This finding is important for a broader understanding of preservation injury, which may include a significant immunologic component. J Nurs Adm 2012;42(1):40–46. Reprinted with permission from Lippincott Williams & Wilkins. POPULATION HEALTH MANAGEMENT JOURNAL OF NURSING ADMINISTRATION Lessons learned from implementation of postdischarge telephone calls at Baylor Health Care System Postdischarge telephone calls can enhance patient satisfaction, outcomes, and care continuity. The authors describe the Dallas–Fort Worth-based Baylor Health Care System standardized process for placing emergency department discharge telephone calls to patients. The metrics and guidelines related to the process as well as lessons learned, models of care, the future state of the postdischarge telephone calls, and findings are discussed. LIVER TRANSPLANTATION Implications of a positive crossmatch in liver transplantation: a 20-year review Ruiz R, Tomiyama K, Campsen J, Goldstein RM, Levy MF, McKenna GJ, Onaca N, Susskind B, Tillery GW, Klintmalm GB Liver Transpl 2011 Dec 5 [Epub ahead of print]. Reprinted with permission from the American Association for the Study of Liver Diseases and John Wiley and Sons. Whether a positive crossmatch result has any relevance to liver transplantation (LT) outcomes remains controversial. We assessed the impact of a positive crossmatch result on patient and graft survival and posttransplant complications. Over a 20-year period, 2723 LT with a crossmatch result were identified: 2479 primary LT and 244 retransplants. The incidence of a positive B-cell and T-cell crossmatch was 10.1% and 7.4%, respectively, among primary LT recipients and 14.6% and 6.4%, respectively, for retransplants (P = 0.0494 for Bcell crossmatch). Across all primary transplants, females (P < 0.0001) and patients with autoimmune hepatitis (P < 0.005) had a greater frequency of a positive crossmatch. There was no effect from race or age. For both primary transplants and retransplants, patient and graft survival were not affected by the presence of a positive crossmatch. With regard to posttransplant complications, there was no difference in rejection episodes (hyperacute, acute, or chronic) or technical complications (biliary and vascular) between the crossmatch-negative and -positive groups. However, there was a significant difference in the Electronic health record use to classify patients with newly diagnosed versus preexisting type 2 diabetes: infrastructure for comparative effectiveness research and population health management Kudyakov R, Bowen J, Ewen E, West SL, Daoud Y, Fleming N, Masica A Popul Health Manag 2011 Aug 30 [Epub ahead of print]. Reprinted with permission from Mary Ann Liebert, Inc. Publishers. Use of electronic health record (EHR) content for comparative effectiveness research (CER) and population health management requires significant data configuration. A retrospective cohort study was conducted using patients with diabetes followed longitudinally (N = 36,353) in the EHR deployed at outpatient practice networks of 2 health care systems. A data extraction and classification algorithm targeting identification of patients with a new diagnosis of type 2 diabetes mellitus (T2DM) was applied, with the main criterion being a minimum 30-day window between the first visit documented in the EHR and the entry of T2DM on the EHR problem list. Chart reviews (N = 144) validated the performance of refining this EHR classification algorithm with external administrative data. Extraction using EHR data alone designated 3205 patients as newly diagnosed with T2DM with classification accuracy of 70.1%. Use of external administrative data on that preselected population improved classification accuracy of cases identified as new T2DM diagnosis (positive predictive value was 91.9% with that step). Laboratory and medication data did not help case classification. The final cohort using this 2-stage classification process comprised 1972 patients with a new diagnosis of T2DM. Data use from current EHR systems for CER and disease management mandates substantial tailoring. Quality between EHR clinical data generated in daily care and that required for population health research varies. As evidenced by this process for classification of newly diagnosed T2DM cases, validation of EHR data with external sources can be a valuable step. If you are a Baylor researcher and would like your published abstract to be included in this section, please e-mail the PubMed citation to [email protected]. April 2012 Selected published abstracts of Baylor researchers 187 2011 publications of the Baylor Health Care System medical and scientific staff ANESTHESIOLOGY AND PAIN MANAGEMENT 1. 2. 3. 4. 5. 6. 7. Aufderheide TP, Nichol G, Rea TD, Brown SP, Leroux BG, Pepe PE, Kudenchuk PJ, Christenson J, Daya MR, Dorian P, Callaway CW, Idris AH, Andrusiek D, Stephens SW, Hostler D, Davis DP, Dunford JV, Pirrallo RG, Stiell IG, Clement CM, Craig A, Van Ottingham L, Schmidt TA, Wang HE, Weisfeldt ML, Ornato JP, Sopko G; Resuscitation Outcomes Consortium (ROC) Investigators. A trial of an impedance threshold device in out-of-hospital cardiac arrest. N Engl J Med 2011;365(9):798–806. Bulger EM, May S, Kerby JD, Emerson S, Stiell IG, Schreiber MA, Brasel KJ, Tisherman SA, Coimbra R, Rizoli S, Minei JP, Hata JS, Sopko G, Evans DC, Hoyt DB; ROC investigators. Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock: a randomized, placebo controlled trial. Ann Surg 2011;253(3):431–441. Caputo TD, Ramsay MAE, Rossmann JA, Beach MM, Griffiths GR, Meyrat B, Barnes JB, Kerns DG, Crump B, Bookatz B, Ezzo P. Evaluation of the SEDline to improve the safety and efficiency of conscious sedation. Proc (Bayl Univ Med Cent) 2011;24(3):200–204. Potapov E, Meyer D, Swaminathan M, Ramsay M, El Banayosy A, Diehl C, Veynovich B, Gregoric ID, Kukucka M, Gromann TW, Marczin N, Chittuluru K, Baldassarre JS, Zucker MJ, Hetzer R. Inhaled nitric oxide after left ventricular assist device implantation: a prospective, randomized, double-blind, multicenter, placebo-controlled trial. J Heart Lung Transplant 2011;30(8):870–878. Ramsay M. Cardiopulmonary disease in the liver transplant patient: the role of Doppler echocardiography. In Fleming R, ed. Doppler Echocardiography. Rijeka, Croatia: InTech Open Access Publisher, 2011. Ramsay M. Liver transplantation and portopulmonary hypertension. In Milan Z, ed. Cardiovascular Diseases and Liver Transplantation. New York: Nova Biomedical Books, 2011:83–97. Stiell IG, Nichol G, Leroux BG, Rea TD, Ornato JP, Powell J, Christenson J, Callaway CW, Kudenchuk PJ, Aufderheide TP, Idris AH, Daya MR, Wang HE, Morrison LJ, Davis D, Andrusiek D, Stephens S, Cheskes S, Schmicker RH, Fowler R, Vaillancourt C, Hostler D, Zive D, Pirrallo RG, Vilke GM, Sopko G, Weisfeldt M; ROC Investigators. Early versus later rhythm analysis in patients with out-of-hospital cardiac arrest. N Engl J Med 2011;365(9):787–797. CARDIOLOGY/CARDIAC, VASCULAR, AND THORACIC SURGERY Ayad RF, Bhella PS, Dockery WD, Schussler JM. Patency of vein graft anastomoses facilitated with the hexalon device. Ann Thorac Surg 2011;91(3):894–898. 9. Ayad RF, Grayburn PA, Ko JM, Filardo G, Roberts WC. Accuracy of two-dimensional echocardiography in determining aortic valve structure in patients >50 years of age having aortic valve replacement for aortic stenosis. Am J Cardiol 2011;108(11):1589–1599. 10. Benoit E, O’Donnell TF Jr, Iafrati MD, Asher E, Bandyk DF, Hallett JW, Lumsden AB, Pearl GJ, Roddy SP, Vijayaraghavan K, Patel AN. The role of amputation as an outcome measure in cellular therapy for critical limb ischemia: implications for clinical trial design. J Transl Med 2011;9:165. 11. Bhella PS, Pacini EL, Prasad A, Hastings JL, Adams-Huet B, Thomas JD, Grayburn PA, Levine BD. Echocardiographic indices do not reliably track changes in left-sided filling pressure in healthy subjects or 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 8. 188 22. 23. 24. 25. patients with heart failure with preserved ejection fraction. Circ Cardiovasc Imaging 2011;4(5):482–489. Bonow RO, Maurer G, Lee KL, Holly TA, Binkley PF, Desvigne-Nickens P, Drozdz J, Farsky PS, Feldman AM, Doenst T, Michler RE, Berman DS, Nicolau JC, Pellikka PA, Wrobel K, Alotti N, Asch FM, Favaloro LE, She L, Velazquez EJ, Jones RH, Panza JA; STICH Trial Investigators. Myocardial viability and survival in ischemic left ventricular dysfunction. N Engl J Med 2011;364(17):1617–1625. Bose R, Schussler JM. Use of Angio-Seal closure device when the arteriotomy is above or below the common femoral artery. Clin Cardiol 2011;34(11):700–702. Braunlin EA, Harmatz PR, Scarpa M, Furlanetto B, Kampmann C, Loehr JP, Ponder KP, Roberts WC, Rosenfeld HM, Giugliani R. Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis and management. J Inherit Metab Dis 2011;34(6):1183–1197. Brinkman W. Repair of thoracic aortic aneurysms: strategy before tactics. EuroIntervention 2011;7(5):539–540. Edgerton JR, Mahoney C, Mack MJ, Roper K, Herbert MA. Long-term monitoring after surgical ablation for atrial fibrillation: how much is enough? J Thorac Cardiovasc Surg 2011;142(1):162–165. Falcone AM, Bose R, Stoler RC, Kim M, Laible E, Kang L, Waters K, Dunkerley J, Choi JW. The AmBulatory Closure Device Percutaneous Intervention (ABCD-PCI) study: a single-center experience. Proc (Bayl Univ Med Cent) 2011;24(3):192–194. Fazel P, Schussler JM, Berbarie RF, Hamman BL, Fenves AZ. Embolization of a stent from an arteriovenous graft into the right ventricle in a patient on chronic hemodialysis. Proc (Bayl Univ Med Cent) 2011;24(2):94–95. Feldman T, Foster E, Glower DG, Kar S, Rinaldi MJ, Fail PS, Smalling RW, Siegel R, Rose GA, Engeron E, Loghin C, Trento A, Skipper ER, Fudge T, Letsou GV, Massaro JM, Mauri L; EVEREST II Investigators. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med 2011;364(15):1395–1406. Filardo G, Grayburn PA, Hamilton C, Hebeler RF Jr, Cooksey WB, Hamman B. Comparing long-term survival between patients undergoing off-pump and on-pump coronary artery bypass graft operations. Ann Thorac Surg 2011;92(2):571–577. Filardo G, Nicewander D, Ballard DJ. Changes over 6 years in administration of aspirin and beta blockers on arrival, and timely reperfusion in patients with acute myocardial infarction. Am J Cardiol 2011;107(10):1421–1425. Fonarow GC, Albert NM, Curtis AB, Gheorghiade M, Heywood JT, Liu Y, Mehra MR, O’Connor CM, Reynolds D, Walsh MN, Yancy CW. Associations between outpatient heart failure process-of-care measures and mortality. Circulation 2011;123(15):1601–1610. Friedewald VE, Ballantyne CM, Davidson MH, Gotto AM Jr, Ridker PM, Roberts WC. The editor’s roundtable: JUPITER follow-up. Am J Cardiol 2011;107(10):1549–1557. Friedewald VE, Boden WE, Stone GW, Yancy CW, Roberts WC. The editor’s roundtable: role of percutaneous coronary intervention and drugeluting stents in patients with stable coronary heart disease. Am J Cardiol 2011;108(10):1417–1425. Friedewald VE, Emmett M, Gheorghiade M, Roberts WC. The editor’s roundtable: pathophysiology and management of hyponatremia Proc (Bayl Univ Med Cent) 2012;25(2):188–204 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. and the role of vasopressin antagonists. Am J Cardiol 2011;107(9): 1357–1364. Friedewald VE, Emmett M, McCullough P, Yancy CW, Roberts WC. The editor’s roundtable: anemia and cardiovascular disease. Am J Cardiol 2011;107(11):1630–1635. Friedewald VE, Fonarow GC, Olshansky B, Yancy CW, Roberts WC. The editor’s roundtable: implantable cardioverter-defibrillators in primary prevention of sudden cardiac death and disparity-related barriers to implementation. Am J Cardiol 2011;107(4):583–590. Friedewald VE, Goldfarb S, Laskey WK, Vetrovec GW, Roberts WC. The editor’s roundtable: contrast agents and risk for contrast-induced nephropathy. Am J Cardiol 2011;107(12):1848–1855. Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Kay GN, Le Huezey JY, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann LS, Smith SC Jr, Priori SG, Estes NA 3rd, Ezekowitz MD, Jackman WM, January CT, Lowe JE, Page RL, Slotwiner DJ, Stevenson WG, Tracy CM, Jacobs AK, Anderson JL, Albert N, Buller CE, Creager MA, Ettinger SM, Guyton RA, Halperin JL, Hochman JS, Kushner FG, Ohman EM, Stevenson WG, Tarkington LG, Yancy CW; American College of Cardiology Foundation/American Heart Association Task Force. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. Circulation 2011;123(10):e269–e367. Gable D. Role of total endoluminal superficial femoral artery bypass. J Cardiovasc Surg (Torino) 2011;52(5):683–700. Garner JB, Grayburn PA, Yancy CW. Best clinical trials reported in 2010. Am J Cardiol 2011;108(1):162–168. George BA, Ko JM, Lensing FD, Kuiper JJ, Roberts WC. “Repaired” tetralogy of Fallot mimicking arrhythmogenic right ventricular cardiomyopathy (another phenocopy). Am J Cardiol 2011;108(2):326–329. Gharacholou SM, Hellkamp AS, Hernandez AF, Peterson ED, Bhatt DL, Yancy CW, Fonarow GC. Use and predictors of heart failure disease management referral in patients hospitalized with heart failure: insights from the Get with the Guidelines program. J Card Fail 2011;17(5):431–439. Goldstein LB, Whitsel LP, Meltzer N, Schoeberl M, Birnbaum J, Nelson S, Gardner TJ, Yancy CW, Gibbons RJ, Sacco RL, Hiratzka L; American Heart Association (AHA) Advocacy Coordinating Committee; Council on Cardiovascular Nursing, AHA; Council on the Kidney in Cardiovascular Disease, AHA; Council on Cardiovascular Radiology and Intervention, AHA; Council on Cardiovascular Surgery and Anesthesia, AHA; Council on Clinical Cardiology, AHA; Council on Cardiovascular Disease in the Young, AHA; Council on Cardiopulmonary, Critical Care, Perioperative, and Resuscitation, AHA; Council on Peripheral Vascular Disease, AHA; Council on Arteriosclerosis, Thrombosis and Vascular Biology, AHA; Council on Epidemiology and Prevention, AHA; Council on Nutrition, Physical Activity and Metabolism, AHA; Interdisciplinary Council on Functional Genomics and Translational Biology, AHA. American Heart Association and nonprofit advocacy: past, present, and future. A policy recommendation from the American Heart Association. Circulation 2011;123(7):816–832. Grayburn PA. The importance of regurgitant orifice shape in mitral regurgitation. JACC Cardiovasc Imaging 2011;4(10):1097–1099. Grayburn PA, Roberts BJ, Aston S, Anwar A, Hebeler RF Jr, Brown DL, Mack MJ. Mechanism and severity of mitral regurgitation by transesophageal echocardiography in patients referred for percutaneous valve repair. Am J Cardiol 2011;108(6):882–887. Hammill BG, Curtis LH, Fonarow GC, Heidenreich PA, Yancy CW, Peterson ED, Hernandez AF. Incremental value of clinical data beyond claims data in predicting 30-day outcomes after heart failure hospitalization. Circ Cardiovasc Qual Outcomes 2011;4(1):60–67. Head SJ, Ko J, Singh R, Roberts WC, Mack MJ. 3-year durability of a Smeloff-Cutter ball-caged mitral valve. Ann Thorac Surg 2011;91(2): 606–608. Henry CL, Ko JM, Henry AC, Roberts WC, Matter GJ. Aortic valve replacement for stenosis with or without coronary artery bypass grafting after 2 previous isolated coronary artery bypass grafting operations. Proc (Bayl Univ Med Cent) 2011;24(1):6–8. April 2012 40. Hicks TD, Kedora JC, Shutze WP. Treatment of an ilioenteric fistula with an Amplatzer Vascular Plug. J Vasc Surg 2011;54(5):1495–1497. 41. Kaul S, Miller JG, Grayburn PA, Hashimoto S, Hibberd M, Holland MR, Houle HC, Klein AL, Knoll P, Lang RM, Lindner JR, McCulloch ML, Metz S, Mor-Avi V, Pearlman AS, Pellikka PA, DeMars Plambeck N, Prater D, Porter TR, Sahn DJ, Thomas JD, Thomenius KE, Weissman NJ. A suggested roadmap for cardiovascular ultrasound research for the future. J Am Soc Echocardiogr 2011;24(4):455–464. 42. Kowal RC. PVI’s inconvenient truths: lights out for dormant reconnection? J Cardiovasc Electrophysiol 2011 Nov 14 [Epub ahead of print]. 43. Lilly SM, Schussler JM, Stoler RC. Anomalous origin of the right coronary artery from the left sinus of Valsalva associated with syncope in a young athlete. Proc (Bayl Univ Med Cent) 2011;24(1):13–14. 44. Mack MJ. Coronary artery disease: how should the STICH trial results affect clinical practice? Nat Rev Cardiol 2011;8(8):427–428. 45. Mack MJ. Risk scores for predicting outcomes in valvular heart disease: how useful? Curr Cardiol Rep 2011;13(2):107–112. 46. Mack MJ, Banning AP, Serruys PW, Morice MC, Taeymans Y, Van Nooten G, Possati G, Crea F, Hood KL, Leadley K, Dawkins KD, Kappetein AP. Bypass versus drug-eluting stents at three years in SYNTAX patients with diabetes mellitus or metabolic syndrome. Ann Thorac Surg 2011;92(6):2140–2146. 47. Momiy J, Vasquez J. Iatrogenic vertebral artery pseudoaneurysm due to central venous catheterization. Proc (Bayl Univ Med Cent) 2011;24(2): 96–100. 48. O’Connor CM, Albert NM, Curtis AB, Gheorghiade M, Heywood JT, McBride ML, Inge PJ, Mehra MR, Reynolds D, Walsh MN, Yancy CW, Fonarow GC. Patient and practice factors associated with improvement in use of guideline-recommended therapies for outpatients with heart failure (from the IMPROVE HF trial). Am J Cardiol 2011;107(2):250–258. 49. Pearl GJ, Gable DR. Treatment of superficial femoral artery occlusive disease. In Eskandori M, Marasch M, Pearce W, Yao J, eds. New Findings in Vascular Surgery. Shelton, CT: People’s Medical Publishing House, 2010:83–94. 50. Roberts WC. Natural history, clinical consequences, and morphologic features of coronary arterial aneurysms in adults. Am J Cardiol 2011;108(6): 814–821. 51. Roberts WC. Prophylactic replacement of a dilated ascending aorta at the time of aortic valve replacement of a dysfunctioning congenitally unicuspid or bicuspid aortic valve. Am J Cardiol 2011;108(9):1371–1372. 52. Roberts WC. The congenital bicuspid aortic valve. In Edwards BS, Meller JH, eds. Jesse E. Edwards, His Legacy to Cardiovascular Medicine. Stamford, CT: Science International Corporation, 2011. 53. Roberts WC, de Lemos J, Libby P. Which is more important: plaque quantity or plaque rupture? Medical Roundtable: Cardiovascular Edition 2011(Winter);2:41–47. 54. Roberts WC, Gotto AM Jr, Guyton J, LaRosa J, Viggiani R. The editor’s roundtable: closing the clinical practice gap–using evidence-based treatments for managing lipids. Am J Cardiol 2011;107(2):230–242. 55. Roberts WC, Karia SJ, Ko JM, Grayburn PA, George BA, Hall SA, Kuiper JJ, Meyer DM. Examination of isolated ventricular noncompaction (hypertrabeculation) as a distinct entity in adults. Am J Cardiol 2011;108(5): 747–752. 56. Roberts WC, Roberts CC, Vowels TJ, Ko JM, Filardo G, Hamman BL, Matter GJ, Henry AC, Hebeler RF Jr. Effect of body mass index on survival in patients having aortic valve replacement for aortic stenosis with or without concomitant coronary artery bypass grafting. Am J Cardiol 2011;108(12):1767–1771. 57. Roberts WC, Varughese CA, Ko JM, Grayburn PA, Hebeler RF Jr, Burton EC. Carcinoid heart disease without the carcinoid syndrome but with quadrivalvular regurgitation and unsuccessful operative intervention. Am J Cardiol 2011;107(5):788–792. 58. Roberts WC, Vowels TJ, Kitchens BL, Ko JM, Filardo G, Henry AC, Hamman BL, Matter GJ, Hebeler RF Jr. Aortic medial elastic fiber loss in acute ascending aortic dissection. Am J Cardiol 2011;108(11): 1639–1644. 2011 publications of the Baylor Health Care System medical and scientific staff 189 59. Roberts WC, Vowels TJ, Ko JM, Filardo G, Hebeler RF Jr, Henry AC, Matter GJ, Hamman BL. Comparison of the structure of the aortic valve and ascending aorta in adults having aortic valve replacement for aortic stenosis versus for pure aortic regurgitation and resection of the ascending aorta for aneurysm. Circulation 2011;123(8):896–903. 60. Sarmast SA, Schussler JM. Monozygotic twins with identical cardiac conditions. Proc (Bayl Univ Med Cent) 2011;24(2):104–106. 61. Schussler JM. Effectiveness and safety of transradial artery access for cardiac catheterization. Proc (Bayl Univ Med Cent) 2011;24(3):205–209. 62. Schwartz BG, Daulat S, Kuiper J. The Kounis-Zavras syndrome with the Samter-Beer triad. Proc (Bayl Univ Med Cent) 2011;24(2):107–109. 63. Schwartz BG, Schussler JM, Rosenthal RL. Tumor-like coronary atheroma: a modern coronary evaluation with a historical perspective. Tex Heart Inst J 2011;38(3):275–278. 64. Shoemake BD, Patterson BA, Schussler JM. Clinical significance of a single coronary artery arising from the right sinus of Valsalva with the left anterior descending anterior to the pulmonary artery and a retro-aortic left circumflex. Am J Cardiol 2011;108(8):1196. 65. Tandon A, Simpson L, Assar MD. Unusual origin of type 1 atrioventricular block with comments on Wenckebach’s contribution. Proc (Bayl Univ Med Cent) 2011;24(1):9–12. 66. Thomas KL, Hernandez AF, Dai D, Heidenreich P, Fonarow GC, Peterson ED, Yancy CW. Association of race/ethnicity with clinical risk factors, quality of care, and acute outcomes in patients hospitalized with heart failure. Am Heart J 2011;161(4):746–754. 67. Urschel HC Jr. Thoracic outlet syndrome. BMJ Point of Care [website, updated 2011]. Available at www.pointofcare.bmj.com. 68. Urschel HC Jr. Thoracic outlet syndromes. In Cameron JL, Cameron AM, eds. Current Surgical Therapy, 10th ed. Philadelphia: Elsevier Saunders, 2011:834–841. 69. Urschel HC Jr, Montano R. Thoracic outlet syndromes [website, updated 2011]. Available at http://thoracicoutletsyndromes.com. 70. Velazquez EJ, Lee KL, Deja MA, Jain A, Sopko G, Marchenko A, Ali IS, Pohost G, Gradinac S, Abraham WT, Yii M, Prabhakaran D, Szwed H, Ferrazzi P, Petrie MC, O’Connor CM, Panchavinnin P, She L, Bonow RO, Rankin GR, Jones RH, Rouleau JL; STICH Investigators. Coronaryartery bypass surgery in patients with left ventricular dysfunction. N Engl J Med 2011;364(17):1607–1616. 71. Wann LS, Curtis AB, Ellenbogen KA, Estes NA 3rd, Ezekowitz MD, Jackman WM, January CT, Lowe JE, Page RL, Slotwiner DJ, Stevenson WG, Tracy CM, Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Kay GN, Le Heuzey JY, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann LS, Jacobs AK, Anderson JL, Albert N, Creager MA, Ettinger SM, Guyton RA, Halperin JL, Hochman JS, Kushner FG, Ohman EM, Stevenson WG, Yancy CW. 2011 ACCF/ AHA/HRS focused update on the management of patients with atrial fibrillation (update on dabigatran). Heart Rhythm 2011;8(3):e1–e8. [Also published in Circulation 2011;123(10):1144–1150.] 72. Wann LS, Curtis AB, January CT, Ellenbogen KA, Lowe JE, Estes NA 3rd, Page RL, Ezekowitz MD, Slotwiner DJ, Jackman WM, Stevenson WG, Tracy CM; 2006 Writing Committee Members, Fuster V, Rydén LE, Cannom DS, Le Heuzey JY, Crijns HJ, Lowe JE, Curtis AB, Olsson SB, Ellenbogen KA, Prystowsky EN, Halperin JL, Tamargo JL, Kay GN, Wann LS; ACCF/AHA Task Force Members, Jacobs AK, Anderson JL, Albert N, Hochman JS, Buller CE, Kushner FG, Creager MA, Ohman EM, Ettinger SM, Stevenson WG, Guyton RA, Tarkington LG, Halperin JL, Yancy CW. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline). Heart Rhythm 2011;8(1):157–176. [Also published in J Am Coll Cardiol 2011;57(2):223–242 and Circulation 2011;123(1):104–123.] 73. Yancy CW. Is ideal cardiovascular health attainable? Circulation 2011;123(8): 835–837. 74. Yancy CW, Wang TY, Ventura HO, Piña IL, Vijayaraghavan K, Ferdinand KC, Hall LL; CREDO Advisory Group. The coalition to reduce racial and ethnic disparities in cardiovascular disease outcomes (CREDO): why CREDO matters to cardiologists. J Am Coll Cardiol 2011;57(3):245–252. 190 DERMATOLOGY 75. American Academy of Dermatology Work Group, Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, Gottlieb A, Koo JY, Lebwohl M, Leonardi CL, Lim HW, Van Voorhees AS, Beutner KR, Ryan C, Bhushan R. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidencebased conclusions. J Am Acad Dermatol 2011;65(1):137–174. 76. Dy LC, Whiting DA. Histopathology of alopecia areata, acute and chronic: Why is it important to the clinician? Dermatol Ther 2011;24(3): 369–374. 77. Farley E, Menter A. Psoriasis: comorbidities and associations. G Ital Dermatol Venereol 2011;146(1):9–15. 78. Hudson CP, Kempers S, Menter A, Papp K, Smith S, Sofen H, Colón LE, Johnson LA, Gottschalk R. An open-label, multicenter study of the efficacy and safety of a weekday/weekend treatment regimen with calcitriol ointment 3 microg/g and clobetasol propionate spray 0.05% in the management of plaque psoriasis. Cutis 2011;88(4): 201–207. 79. Joyce CE, Zhou X, Xia J, Ryan C, Thrash B, Menter A, Zhang W, Bowcock AM. Deep sequencing of small RNAs from human skin reveals major alterations in the psoriasis miRNAome. Hum Mol Genet 2011;20(20):4025–4040. 80. Kamili QU, Miner A, Hapa A, Menter A. Infliximab treatment for psoriasis in 120 patients on therapy for a minimum of one year: a review. J Drugs Dermatol 2011;10(5):539–544. 81. Kimball AB, Gordon KB, Langley RG, Menter A, Perdok RJ, Valdes J; ABT-874 Study Investigators. Efficacy and safety of ABT-874, a monoclonal anti-interleukin 12/23 antibody, for the treatment of chronic plaque psoriasis: 36-week observation/retreatment and 60-week open-label extension phases of a randomized phase II trial. J Am Acad Dermatol 2011;64(2):263–274. 82. Menter A, Sofen H, Smith S, Papp K, Kempers S, Hudson CP, Colón LE, Johnson LA, Gottschalk R. An open-label, multicenter study of the efficacy and safety of an AM/PM treatment regimen with clobetasol propionate spray 0.05% and calcitriol ointment 3 microg/g in the management of plaque psoriasis. Cutis 2011;88(1):46–51. 83. Roberson ED, Liu Y, Ryan C, Joyce CE, Duan S, Cao L, Martin A, Liao W, Menter A, Bowcock AM. A subset of methylated CpG sites differentiate psoriatic from normal skin. J Invest Dermatol 2011 Nov 10 [Epub ahead of print]. 84. Ryan C, Leonardi CL, Krueger JG, Kimball AB, Strober BE, Gordon KB, Langley RG, de Lemos JA, Daoud Y, Blankenship D, Kazi S, Kaplan DH, Friedewald VE, Menter A. Association between biologic therapies for chronic plaque psoriasis and cardiovascular events: a meta-analysis of randomized controlled trials. JAMA 2011;306(8):864–871. 85. van de Kerkhof P, Barker J, Griffiths CE, Menter A, Leonardi C, Young M, Kemeny L, Pincelli C, Bachelez H, Katsambas A, Ståhle M, Horn EJ, Sterry W; International Psoriasis Council. Improving clinical trial design in psoriasis: perspectives from the global dermatology community. J Dermatolog Treat 2011;22(4):187–193. 86. Whiting DA. How real is senescent alopecia? A histopathologic approach. Clin Dermatol 2011;29(1):49–53. 87. Wittkowski KM, Leonardi C, Gottlieb A, Menter A, Krueger GG, Tebbey PW, Belasco J, Soltani-Arabshahi R, Gray J, Horn L, Krueger JG; International Psoriasis Council. Clinical symptoms of skin, nails, and joints manifest independently in patients with concomitant psoriasis and psoriatic arthritis. PLoS One 2011;6(6):e20279. 88. Young MS, Horn EJ, Cather JC. The ACCEPT study: ustekinumab versus etanercept in moderate-to-severe psoriasis patients. Expert Rev Clin Immunol 2011;7(1):9–13. EMERGENCY MEDICINE/TRAUMA 89. Cook A, Osler T, Gaudet M, Berne J, Norwood S. Blunt cerebrovascular injury is poorly predicted by modeling with other injuries: analysis of NTDB data. J Trauma 2011;71(1):114–119. Baylor University Medical Center Proceedings Volume 25, Number 2 90. Matsushima K, Cook A, Tollack L, Shafi S, Frankel H. An acute care surgery model provides safe and timely care for both trauma and emergency general surgery patients. J Surg Res 2011;166(2):e143–e147. 91. Min W, Ding BC, Tejwani NC. Comparative functional outcome of AO/ OTA type C distal humerus fractures: open injuries do worse than closed fractures. J Trauma 2011 Sep 15 [Epub ahead of print]. 92. Norwood S, Cook AD, Berne JD. Level I verification is associated with a decreased mortality rate after major torso vascular injuries. Am Surg 2011;77(1):32–37. 93. O’Keeffe T, Thekkumel JJ, Friese S, Shafi S, Josephs SC. A policy of dedicated follow-up improves the rate of removal of retrievable inferior vena cava filters in trauma patients. Am Surg 2011;77(1):103–108. ENDOCRINOLOGY See also Transplantation for articles on islet cell transplantation and Health Care Research and Improvement for articles on improving diabetes care. 94. Aronne LJ, Finer N, Hollander PA, England RD, Klioze SS, Chew RD, Fountaine RJ, Powell CM, Obourn JD. Efficacy and safety of CP945,598, a selective cannabinoid CB1 receptor antagonist, on weight loss and maintenance. Obesity (Silver Spring) 2011;19(7):1404–1414. 95. Chaudhuri A, Rosenstock J, Digenio A, Meneghini L, Hollander P, McGill JB, Dandona P, Ilgenfritz J, Riddle M. Comparing the effects of insulin glargine and thiazolidinediones on plasma lipids in type 2 diabetes: a patient-level pooled analysis. Diabetes Metab Res Rev 2011 Nov 12 [Epub ahead of print]. 96. Davidson MB, Raskin P, Tanenberg RJ, Vlajnic A, Hollander P. A stepwise approach to insulin therapy in patients with type 2 diabetes mellitus and basal insulin treatment failure. Endocr Pract 2011;17(3):395–403. 97. Dunn FL, Higgins LS, Fredrickson J, DePaoli AM; INT131-004 study group. Selective modulation of PPARγ activity can lower plasma glucose without typical thiazolidinedione side-effects in patients with type 2 diabetes. J Diabetes Complications 2011;25(3):151–158. 98. Garber A, Henry RR, Ratner R, Hale P, Chang CT, Bode B; LEAD-3 (Mono) Study Group. Liraglutide, a once-daily human glucagon-like peptide 1 analogue, provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetes. Diabetes Obes Metab 2011;13(4):348–356. 99. Hollander P, Raslova K, Skjøth TV, Råstam J, Liutkus JF. Efficacy and safety of insulin detemir once daily in combination with sitagliptin and metformin: the TRANSITION randomized controlled trial. Diabetes Obes Metab 2011;13(3):268–275. 100. Hollander PL, Li J, Frederich R, Allen E, Chen R; CV181013 Investigators. Safety and efficacy of saxagliptin added to thiazolidinedione over 76 weeks in patients with type 2 diabetes mellitus. Diab Vasc Dis Res 2011;8(2):125–135. FAMILY MEDICINE Note: Most family medicine and internal medicine articles are subclassified by specialty, even if generalists were among the authors. 101. Evans R, Moss S, Montoya CC. Clinical inquiries. Which nutritional therapies are safe and effective for depression? J Fam Pract 2011;60(2):99– 100, 100a–100c. 102. Maliyil J, Caire W, Nair R, Bridges D. Splenic abscess and multiple brain abscesses caused by Streptococcus intermedius in a young healthy man. Proc (Bayl Univ Med Cent) 2011;24(3):195–199. GASTROENTEROLOGY Note: See also Oncology for research on colon cancer. 103. Laroui H, Theiss AL, Yan Y, Dalmasso G, Nguyen HT, Sitaraman SV, Merlin D. Functional TNF␣ gene silencing mediated by polyethyleneimine/ TNF␣ siRNA nanocomplexes in inflamed colon. Biomaterials 2011;32(4): 1218–1228. 104. Molloy JW, Mallat DB. Novel use of the Soehendra stent extractor for pancreatic stone lithotripsy. Gastrointest Endosc 2011;74(3):725–726. 105. Pak CY, Sakhaee K, Moe OW, Poindexter J, Adams-Huet B, Pearle MS, Zerwekh JE, Preminger GM, Wills MR, Breslau NA, Bartter FC, Brater April 2012 DC, Heller HJ, Odvina CV, Wabner CL, Fordtran JS, Oh M, Garg A, Harvey JA, Alpern RJ, Snyder WH, Peters PC. Defining hypercalciuria in nephrolithiasis. Kidney Int 2011;80(7):777–782. 106. Schiller LR. Chronic idiopathic diarrhea. In Guandalini S, Vaziri H, eds. Diarrhea: Diagnostic and Therapeutic Advances. New York: Humana Press, 2011:311–324. 107. Schiller LR. Malabsorption. In Bope ET, Kellerman R, Rakel RE, eds. Conn’s Current Therapy 2011. Philadelphia: Elsevier Saunders, 2011:553–559. 108. Schiller LR. Diarrhea following small bowel resection. In Bayless TM, Hanauer SB, eds. Advanced Therapy in Inflammatory Bowel Disease, 3rd ed. Shelton, CT: People’s Medical Publishing House, 2011:845–850. 109. Schiller LR. What is the role of antidiarrheal agents in patients with IBS? In Lacy BE, ed. Curbside Consultations in IBS. Thorofare, NJ: Slack, 2011:203–206. 110. Theiss AL, Laroui H, Obertone TS, Chowdhury I, Thompson WE, Merlin D, Sitaraman SV. Nanoparticle-based therapeutic delivery of prohibitin to the colonic epithelial cells ameliorates acute murine colitis. Inflamm Bowel Dis 2011;17(5):1163–1176. 111. Theiss AL, Sitaraman SV. The role and therapeutic potential of prohibitin in disease. Biochim Biophys Acta 2011;1813(6):1137–1143. 112. van Dinter TG Jr, Schmidt JF, Tarnasky PR. Obstructive jaundice caused by intraductal hepatocellular carcinoma. Clin Gastroenterol Hepatol 2011;9(9):e94–e95. GYNECOLOGY 113. Johns A. The Lump: A Gynecologist’s Journey with Male Breast Cancer. Austin, TX: Live Oak Book Company. 114. Luciano DE, Exacoustos C, Johns DA, Luciano AA. Can hysterosalpingocontrast sonography replace hysterosalpingography in confirming tubal blockage after hysteroscopic sterilization and in the evaluation of the uterus and tubes in infertile patients? Am J Obstet Gynecol 2011;204(1):79. e1–e5. 115. Sikirica V, Bapat B, Candrilli SD, Davis KL, Wilson M, Johns A. The inpatient burden of abdominal and gynecological adhesiolysis in the US. BMC Surg 2011;11:13. HEALTH CARE RESEARCH AND IMPROVEMENT Note: This section represents primarily the publications of the IHCRI staff, although some of those publications are included under Cardiology and other areas. 116. Aliberti S, Peyrani P, Filardo G, Mirsaeidi M, Amir A, Blasi F, Ramirez J. Association between time to clinical stability and outcomes after discharge in hospitalized patients with community-acquired pneumonia. Chest 2011;140(2):482–488. 117. Allison JT. Enhancing care, one community at a time. Hosp Health Netw 2011;85(5):52. 118. Ballard DJ, Leonard BM. National Priorities Partnership focus on eliminating overuse: applications to cardiac revascularization. Am J Med Qual 2011;26(6):485–490. 119. Bentley S, Hermes A, Phillips D, Daoud YA, Hanna S. Comparative effectiveness of a prenatal medical food to prenatal vitamins on hemoglobin levels and adverse outcomes: a retrospective analysis. Clin Ther 2011;33(2):204–210. 120. Clark N, Brenner J, Johnson P, Peek M, Spoonhunter H, Walton J, Dodge J, Nelson B. Reducing disparities in diabetes: the alliance model for health care improvements. Diabetes Spectrum 2011;24(4):226–230. 121. da Graca B, Filardo G. Vascular bioprinting. Am J Card 2011;107(1):141– 142. 122. Filardo G, Adams AJ, Ng HK. 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Safety issues related to the electronic medical record (EMR): synthesis of the literature from the last decade, 2000–2009. J Healthc Manag 2011;56(1):31–43. 127. Kahraman S, Hu P, Stein DM, Stansbury LG, Dutton RP, Xiao Y, Hess JR, Scalea TM. Dynamic three-dimensional scoring of cerebral perfusion pressure and intracranial pressure provides a brain trauma index that predicts outcome in patients with severe traumatic brain injury. J Trauma 2011;70(3):547–553. 128. Kennerly D, Richter KM, Good V, Compton J, Ballard DJ. Journey to no preventable risk: the Baylor Health Care System patient safety experience. Am J Med Qual 2011;26(1):43–52. 129. Kudyakov R, Bowen J, Ewen E, West SL, Daoud Y, Fleming N, Masica A. Electronic health record use to classify patients with newly diagnosed versus preexisting type 2 diabetes: infrastructure for comparative effectiveness research and population health management. Popul Health Manag 2011 Aug 30 [Epub ahead of print]. 130. Morrow JR Jr, Bain TM, Frierson GM, Trudelle-Jackson E, Haskell WL. Long-term tracking of physical activity behaviors in women: the WIN Study. Med Sci Sports Exerc 2011;43(1):165–170. 131. Rayan N, Baird R, Masica A. Rapid response team interventions for severe hyperkalemia: evaluation of a patient safety initiative. Hosp Pract (Minneap) 2011;39(1):161–169. 132. Rice D, Roberts WL, Collinsworth A, Fleming N. An accountable care approach to diabetes management. Clinical Diabetes 2011;29(2)70–72. 133. Rice D, Roberts WL, Collinsworth A, Fleming N. Diabetes and the case for accountable care. Endocrine Today 2011;9(4). Available at http://www. endocrinetoday.com/view.aspx?rid=82773. 134. Ringo K, Taylor K, Bair JD. Impact of omega-3 fatty acids on energy expenditure in GVHD. Oncology Nutrition Connection 2011;19(3):3–10. 135. Stauffer BD, Fleming N, Ogola G, Fullerton C, Herrin J, Ballard DJ. Effectiveness and cost of a transitional care program. 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Freedman ND, Curto TM, Lindsay KL, Wright EC, Sinha R, Everhart JE; HALT-C Trial Group. Coffee consumption is associated with response to peginterferon and ribavirin therapy in patients with chronic hepatitis C. Gastroenterology 2011;140(7):1961–1969. 141. Ghany MG, Kim HY, Stoddard A, Wright EC, Seeff LB, Lok AS; HALTC Trial Group. Predicting clinical outcomes using baseline and follow-up laboratory data from the hepatitis C long-term treatment against cirrhosis trial. Hepatology 2011;54(5):1527–1537. 142. Gonzalez SA. Consensus interferon: tailored therapy and the impact of adherence. Dig Dis Sci 2011;56(3):631–634. 143. Gonzalez SA. Transplant hepatology: opportunities in an emerging field. Gastrointest Endosc 2011;73(4):799–801. 192 144. Gonzalez SA, Keeffe EB. Acute liver failure. In Friedman LS, Keeffe EB, eds. Handbook of Liver Disease, 3rd ed. Philadelphia: Elsevier, 2011: 20–33. 145. Gonzalez SA, Keeffe EB. 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Brachytherapy 2011;10(Suppl 1): S53–S54. 373. Wood PB, Parikh SR, Krause JR. Extranodal NK/T-cell lymphoma, nasal type. Proc (Bayl Univ Med Cent) 2011;24(3):251–254. 374. Wu Y, Amonkar MM, Sherrill BH, O’Shaughnessy J, Ellis C, Baselga J, Blackwell KL, Burstein HJ. Impact of lapatinib plus trastuzumab versus singleagent lapatinib on quality of life of patients with trastuzumab-refractory HER2+ metastatic breast cancer. Ann Oncol 2011;22(12):2582–2590. 375. Xu CF, Bing NX, Ball HA, Rajagopalan D, Sternberg CN, Hutson TE, de Souza P, Xue ZG, McCann L, King KS, Ragone LJ, Whittaker JC, Spraggs CF, Cardon LR, Mooser VE, Pandite LN. Pazopanib efficacy in renal cell carcinoma: evidence for predictive genetic markers in angiogenesis-related and exposure-related genes. J Clin Oncol 2011;29(18):2557–2564. 376. Young JL, Koon EC, Kwong J, Welch WR, Muto MG, Berkowitz RS, Mok SC. Differential hRad17 expression by histologic subtype of ovarian cancer. J Ovarian Res 2011;4(1):6. 377. Zurita AJ, George DJ, Shore ND, Liu G, Wilding G, Hutson TE, Kozloff M, Mathew P, Harmon CS, Wang SL, Chen I, Chow Maneval E, Logothetis CJ. Sunitinib in combination with docetaxel and prednisone in chemotherapynaive patients with metastatic, castration-resistant prostate cancer: a phase 1/2 clinical trial. Ann Oncol 2011 Aug 5 [Epub ahead of print]. ORAL AND MAXILLOFACIAL SURGERY/DENTISTRY 378. Cotter J, McCann A, Schneiderman E, DeWald J, Campbell P. Factors affecting the performance of oral cancer screenings by Texas dental hygienists. J Dental Hygiene 82(4):326–334. 379. Hu J, Jham BC, Ma T, Friedman ER, Ferreira L, Wright JM, Accurso B, Allen CM, Basile JR, Montaner S. Angiopoietin-like 4: a novel molecular hallmark in oral Kaposi’s sarcoma. Oral Oncol 2011;47(5):371–375. 380. Naidu A, Wright JM. The role of the human papillomavirus in oropharyngeal cancer. Tex Dent J 2011;128(5):447–454. 381. Ray JM, Triplett RG. What is the role of biofilms in severe head and neck infections? Oral Maxillofac Surg Clin North Am 2011;23(4):497–505. 382. Wolford LM, Dhameja A. Planning for combined TMJ arthroplasty and orthognathic surgery. Atlas Oral Maxillofac Surg Clin North Am 2011;19(2): 243–270. 383. Wolford LM, Perez D, Stevao E, Perez E. Airway space changes after nasopharyngeal adenoidectomy in conjunction with Le Fort I osteotomy. J Oral Maxillofac Surg 2011 Jun 17 [Epub ahead of print]. 384. Wolford LM, Rodrigues DB. Autogenous grafts/allografts/conduits for bridging peripheral trigeminal nerve gaps. Atlas Oral Maxillofac Surg Clin North Am 2011;19(1):91–107. 385. Wolford LM, Rodrigues DB, Limoeiro E. Orthognathic and TMJ surgery: postsurgical patient management. J Oral Maxillofac Surg 2011;69(11): 2893–2903. ORTHOPAEDIC SURGERY 386. Brodsky JW, Polo FE, Coleman SC, Bruck N. Changes in gait following the Scandinavian Total Ankle Replacement. J Bone Joint Surg Am 2011;93(20):1890–1896. 387. Burkhead WZ Jr. A history of the rotator cuff before Codman. J Shoulder Elbow Surg 2011;20(3):358–362. 388. Garofalo R, Castagna A, Borroni M, Krishnan SG. Arthroscopic transosseous (anchorless) rotator cuff repair. Knee Surg Sports Traumatol Arthrosc 2011 Oct 20 [Epub ahead of print]. 2011 publications of the Baylor Health Care System medical and scientific staff 199 389. Krishnan SG, Reineck JR, Bennion PD, Feher L, Burkhead WZ Jr. Shoulder arthroplasty for fracture: does a fracture-specific stem make a difference? Clin Orthop Relat Res 2011;469(12):3317–3323. 390. McCain KJ, Smith PS, Polo FE, Coleman SC, Baker S. Excellent outcomes for adults who experienced early standardized treadmill training during acute phase of recovery from stroke: a case series. Top Stroke Rehabil 2011;18(4): 428–436. 391. Riad J, Coleman S, Lundh D, Broström E. Arm posture score and arm movement during walking: a comprehensive assessment in spastic hemiplegic cerebral palsy. Gait Posture 2011;33(1):48–53. OTOLARYNGOLOGY 392. Ducic Y, Coimbra C. Minimally invasive transfrontal sinus approach to resection of large tumors of the subfrontal skull base. Laryngoscope 2011;121(11):2290–2294. 393. Ducic Y, Marra DE. Metastatic basal cell carcinoma. Am J Otolaryngol 2011;32(6):455–458. 394. Ducic Y, Young L. Improving aesthetic outcomes in pediatric free tissue oromandibular reconstruction. Arch Facial Plast Surg 2011;13(3): 180–184. 395. Lee M, Inman J, Ducic Y. Central segment harvest of costal cartilage in rhinoplasty. Laryngoscope 2011;121(10):2155–2158. 396. Sawhney R, Young L, Ducic Y. Mylohyoid advancement flap for closure of composite oral cavity defects. Laryngoscope 2011;121(11): 2313–2316. PHARMACOLOGY 397. Roth JM. Recombinant tissue plasminogen activator for the treatment of acute ischemic stroke. Proc (Bayl Univ Med Cent) 2011;24(3):257–259. 398. Sears E, Steimel T. New drugs approved in 2010. Proc (Bayl Univ Med Cent) 2011;24(2):146–152. PHYSICAL MEDICINE AND REHABILITATION 399. Allen DN, Thaler NS, Ringdahl EN, Barney SJ, Mayfield J. Comprehensive trail making test performance in children and adolescents with traumatic brain injury. Psychol Assess 2011 Nov 21 [Epub ahead of print] 400. Barney SJ, Allen DN, Thaler NS, Park BS, Strauss GP, Mayfield J. Neuropsychological and behavioral measures of attention assess different constructs in children with traumatic brain injury. Clin Neuropsychol 2011;25(7): 1145–1157. 401. de Leon JM, Driver VR, Fylling CP, Carter MJ, Anderson C, Wilson J, Dougherty RM, Fuston D, Trigilia D, Valenski V, Rappl LM. The clinical relevance of treating chronic wounds with an enhanced nearphysiological concentration of platelet-rich plasma gel. Adv Skin Wound Care 2011;24(8):357–368. 402. Nakase-Richardson R, Sherer M, Seel RT, Hart T, Hanks R, Arango-Lasprilla JC, Yablon SA, Sander AM, Barnett SD, Walker WC, Hammond F. Utility of post-traumatic amnesia in predicting 1-year productivity following traumatic brain injury: comparison of the Russell and Mississippi PTA classification intervals. J Neurol Neurosurg Psychiatry 2011;82(5): 494–499. 403. Rackley C, Allen DN, Fuhrman LJ, Mayfield J. Generalizability of WISCIV index and subtest score profiles in children with traumatic brain injury. Child Neuropsychol 2011 Nov 22 [Epub ahead of print]. 404. Reynolds CR, Mayfield JW. Neuropsychological assessment in genetically linked neurodevelopmental disorders. In Goldstein S, Reynolds CR, eds. Handbook of Neurodevelopmental and Genetic Disorders in Children, 2nd ed. New York: Guilford Press, 2011. 405. Thaler NS, Barney SJ, Reynolds CR, Mayfield J, Allen DN. Differential sensitivity of TOMAL subtests and index scores to pediatric traumatic brain injury. Appl Neuropsychol 2011;18(3):168–178. 406. Yablon SA, Brin MF, VanDenburgh AM, Zhou J, Garabedian-Ruffalo SM, Abu-Shakra S, Beddingfield FC 3rd. Dose response with onabotulinumtoxinA for post-stroke spasticity: a pooled data analysis. Mov Disord 2011;26(2):209–215. 200 PLASTIC SURGERY 407. Ahmad J, Eaves FF 3rd, Rohrich RJ, Kenkel JM. The American Society for Aesthetic Plastic Surgery (ASAPS) survey: current trends in liposuction. Aesthet Surg J 2011;31(2):214–224. 408. Bailey SH, Saint-Cyr M, Oni G, Wong C, Maia M, Nguyen V, Pessa JE, Colohan S, Rohrich RJ, Mojallal A. The low transverse extended latissimus dorsi flap based on fat compartments of the back for breast reconstruction: anatomical study and clinical results. Plast Reconstr Surg 2011;128(5):382e–394e. 409. Brandt FS, Cazzaniga A, Baumann L, Fagien S, Glazer S, Kenkel JM, Lowe NJ, Monheit GD, Narins RS, Rendon MI, Rohrich RJ, Werschler WP. Investigator global evaluations of efficacy of injectable poly-L-lactic acid versus human collagen in the correction of nasolabial fold wrinkles. Aesthet Surg J 2011;31(5):521–528. 410. Brown SA, Rohrich RJ, Baumann L, Brandt FS, Fagien S, Glazer S, Kenkel JM, Lowe NJ, Monheit GD, Narins RS, Rendon MI, Werschler WP. Subject global evaluation and subject satisfaction using injectable poly-L-lactic acid versus human collagen for the correction of nasolabial fold wrinkles. Plast Reconstr Surg 2011;127(4):1684–1692. 411. Burns PB, Rohrich RJ, Chung KC. The levels of evidence and their role in evidence-based medicine. Plast Reconstr Surg 2011;128(1):305–310. 412. Chang S, Pusic A, Rohrich RJ. A systematic review of comparison of efficacy and complication rates among face-lift techniques. Plast Reconstr Surg 2011;127(1):423–433. 413. Eaves FF, Haeck PC, Rohrich RJ. Breast implants and anaplastic large cell lymphoma: using science to guide our patients and plastic surgeons worldwide. Plast Reconstr Surg 2011;127(6):2501–2503. 414. Graham DW, Heller J, Kurkjian TJ, Schaub TS, Rohrich RJ. Brow lift in facial rejuvenation: a systematic literature review of open versus endoscopic techniques. Plast Reconstr Surg 2011;128(4):335e–341e. 415. Hanke CW, Rohrich RJ, Busso M, Carruthers A, Carruthers J, Fagien S, Fitzgerald R, Glogau R, Greenberger PE, Lorenc ZP, Marmur ES, Monheit GD, Pusic A, Rubin MG, Rzany B, Sclafani A, Taylor S, Weinkle S, McGuire MF, Pariser DM, Casas LA, Collishaw KJ, Dailey RA, Duffy SC, Edgar EJ, Greenan BL, Haenlein K, Henrichs RA, Hume KM, Lum F, Nielsen DR, Poulsen L, Shoaf L, Seward W, Begolka WS, Stanton RG, Svedman KJ, Thomas JR, Sykes JM, Wargo C, Weiss RA. Facial soft-tissue fillers conference: assessing the state of the science. J Am Acad Dermatol 2011;64(4 Suppl):S66–S85, S85.e1–136. 416. Lee MR, Unger JG, Rohrich RJ. Management of the nasal dorsum in rhinoplasty: a systematic review of the literature regarding technique, outcomes, and complications. Plast Reconstr Surg 2011;128(5):538e–550e. 417. Mojallal A, Ouyang D, Saint-Cyr M, Bui N, Brown SA, Rohrich RJ. Dorsal aesthetic lines in rhinoplasty: a quantitative outcome-based assessment of the component dorsal reduction technique. Plast Reconstr Surg 2011;128(1):280–288. 418. Mojallal A, Wong C, Shipkov C, Ho Quoc C, Recchiuto J, Brown S, Rohrich RJ, Saint-Cyr M. Redefining the vascular anatomy and clinical applications of the sartorius muscle and myocutaneous flap. Plast Reconstr Surg 2011;127(5):1946–1957. 419. Oni G, Saint-Cyr M, Maia M, Colohan S, Rohrich RJ. Secondary techniques in breast reconstruction refinement: the periareolar advancement flap. Plast Reconstr Surg 2011;128(5):1015–1024. 420. Rohrich RJ. Current concepts in wound healing: update 2011. Plast Reconstr Surg 2011;127(Suppl 1):1S–2S. 421. Rohrich RJ, Ahmad J. Rhinoplasty. Plast Reconstr Surg 2011;128(2): 49e–73e. 422. Rohrich RJ, Ghavami A, Mojallal A. The five-step lower blepharoplasty: blending the eyelid-cheek junction. Plast Reconstr Surg 2011;128(3): 775–783. 423. Rohrich RJ, Hanke CW, Busso M, Carruthers A, Carruthers J, Fagien S, Fitzgerald R, Glogau R, Greenberger PE, Lorenc ZP, Marmur ES, Monheit GD, Pusic A, Rubin MG, Rzany B, Sclafani A, Taylor S, Weinkle S, McGuire MF, Pariser DM, Casas LA, Collishaw KJ, Dailey RA, Duffy SC, Edgar EJ, Greenan BL, Haenlein K, Henrichs RA, Hume KM, Lum F, Nielsen DR, Poulsen L, Shoaf L, Seward W, Begolka WS, Stanton RG, Baylor University Medical Center Proceedings Volume 25, Number 2 Svedman KJ, Thomas JR, Sykes JM, Wargo C, Weiss RA. Facial soft-tissue fillers conference: assessing the state of the science. Plast Reconstr Surg 2011;127(4 Suppl):22S. 424. Rohrich RJ, Taylor NS, Ahmad J, Lu A, Pessa JE. Great auricular nerve injury, the “subauricular band” phenomenon, and the periauricular adipose compartments. Plast Reconstr Surg 2011;127(2):835–843. 425. Sullivan D, Chung KC, Eaves FF 3rd, Rohrich RJ. The level of evidence pyramid: indicating levels of evidence in Plastic and Reconstructive Surgery articles. Plast Reconstr Surg 2011;128(1):311–314. 426. Trussler AP, Hatef DA, Rohrich RJ. Management of hypertension in the facelift patient: results of a national consensus survey. Aesthet Surg J 2011;31(5):493–500. 427. Veber M, Vaz G, Braye F, Carret JP, Saint-Cyr M, Rohrich RJ, Mojallal A. Anatomical study of the medial gastrocnemius muscle flap: a quantitative assessment of the arc of rotation. Plast Reconstr Surg 2011;128(1):181–187. 442. Prater S, Rees CR, Bruner A, Savage C. Determination of minimum effective height of transparent radiation face shielding for fluoroscopy. Health Phys 2011;101(Suppl 3):S135–S141. 443. Ray MR, Shaw CJ, Opatowsky MJ, Layton KF. Emergent surgical and endovascular repair of a level III carotid arterial gunshot injury. Proc (Bayl Univ Med Cent) 2011;24(2):101–103. 444. Wachsmann J, Oza U, Latifi H. Positron emission tomography-computed tomography of esophageal adenocarcinoma with vascular invasion and tumor thrombus. Proc (Bayl Univ Med Cent) 2011;24(4):359–361. RHEUMATOLOGY 445. Kavanaugh A, Cush JJ. Proceedings of the 2011 Rheumatology Winter Clinical Symposia. Semin Arthritis Rheum 2011;40(5):479–481. 446. Kavanaugh AF, Mayer LF, Cush JJ, Hanauer SB. Shared experiences and best practices in the management of rheumatoid arthritis and Crohn’s disease. Am J Med 2011;124(4 Suppl):e1–e18. PULMONOLOGY/SLEEP MEDICINE 428. Alex RM, Bashaboyina A, Al-Abed MA, Bhave G, Iyer S, Watenpaugh D, Zhang R, Burk JR, Behbehani K. Quantitative variation of blood pressure dynamics during sleep apnea. Int J Med Implants Dev 2011;5(2):115. 429. Gower RG, Busse PJ, Aygören-Pürsün E, Barakat AJ, Caballero T, DavisLorton M, Farkas H, Hurewitz DS, Jacobs JS, Johnston DT, Lumry WR, Maurer M. Hereditary angioedema caused by C1-esterase inhibitor deficiency: a literature-based analysis and clinical commentary on prophylaxis treatment strategies. World Allergy Org J 2011;4(2):S9–S21. 430. Lumry WR. Hereditary angioedema: a case of near fatal laryngeal swelling in a 41-year-old woman. Allergy Asthma Proc 2011;32(Suppl 1):13–15. 431. Lumry WR, Li HH, Levy RJ, Potter PC, Farkas H, Moldovan D, Riedl M, Li H, Craig T, Bloom BJ, Reshef A. Randomized placebo-controlled trial of the bradykinin B2 receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial. Ann Allergy Asthma Immunol 2011;107(6):529–537. 432. Watenpaugh DE, Burk JR. Periodic limb movement disorder. In Domino FJ, ed. The 5-Minute Clinical Consult, 20th ed. Philadelphia: Lippincott Williams and Wilkins, 2011:980–981. 433. Watenpaugh DE, Burk JR. Restless legs syndrome. In Domino FJ, ed. The 5-Minute Clinical Consult, 20th ed. Philadelphia: Lippincott Williams and Wilkins, 2011:1136–1137. 434. Watenpaugh D, Burk JR, Zhang R, Behbehani K. Investigation of end tidal carbon dioxide and heart rate variations during apnea. Int J Med Implants Dev 2011;5(2):115. RADIOLOGY Note: See also Oncology and other departments in which radiologists were coauthors. 435. Bowman EM, Oza UD, Latifi HR. Utility of pattern recognition in the detection of unsuspected additional primary malignancies on positron emission tomography–computed tomography. Proc (Bayl Univ Med Cent) 2011;24(3):210–215. 436. Carter BW, Khorashadi L, Lichtenberger JP III. A tracheal lesion simulating an aneurysmal bone cyst. Proc (Bayl Univ Med Cent) 2011;24(4): 354–355. 437. Cura M, Elmerhi F, Bugnogne A, Palacios R, Suri R, Dalsaso T. Renal aneurysms and pseudoaneurysms. Clin Imaging 2011;35(1):29–41. 438. Harshman LK, Latifi HR, Griffeth LK. Visualization of discrete sacral foramina as an ancillary sign of superscan. Clin Nucl Med 2011;36(1): 21–24. 439. Louis TH, Sanders JM, Stephenson JS, Harbour LN, Ford KF III. Splenic hemangiomatosis. Proc (Bayl Univ Med Cent) 2011;24(4):356–358. 440. Marichal DA, Anwar T, Kirsch D, Clements J, Carlson L, Savage C, Rees CR. Comparison of a suspended radiation protection system versus standard lead apron for radiation exposure of a simulated interventionalist. J Vasc Interv Radiol 2011;22(4):437–442. 441. Marichal DA, Barnett DW, Meler JD, Layton KF. Fiducial marker placement for intraoperative spine localization. J Vasc Interv Radiol 2011;22(1): 95–97. April 2012 SURGERY Note: See also Oncology, Cardiology, and surgical subspecialties. 447. Kroeker TR, Stancoven KM, Preskitt JT. Parathyroid adenoma on the ipsilateral side of thyroid hemiagenesis. Proc (Bayl Univ Med Cent) 2011;24(2):92–93. 448. Liechty J, Wood R. Operative management of pulmonary abscess due to spontaneous perforation of diffuse intramural esophageal pseudodiverticulosis. Proc (Bayl Univ Med Cent) 2011;24(3):216–219. 449. Preskitt JT. Sports hernia: the experience of Baylor University Medical Center at Dallas. Proc (Bayl Univ Med Cent) 2011;24(2):89–91. TRANSPLANTATION (ORGAN AND PANCREATIC CELLS) 450. Anazawa T, Matsumoto S, Yonekawa Y, Loganathan G, Wilhelm JJ, Soltani SM, Papas KK, Sutherland DE, Hering BJ, Balamurugan AN. Prediction of pancreatic tissue densities by an analytical test gradient system before purification maximizes human islet recovery for islet autotransplantation/allotransplantation. Transplantation 2011;91(5):508–514. 451. Busque S, Cantarovich M, Mulgaonkar S, Gaston R, Gaber AO, Mayo PR, Ling S, Huizinga RB, Meier-Kriesche HU; PROMISE Investigators. The PROMISE study: a phase 2b multicenter study of voclosporin (ISA247) versus tacrolimus in de novo kidney transplantation. Am J Transplant 2011;11(12):2675–2684. 452. Chinnakotla S, Klintmalm GB, Kim P, Tomiyama K, Klintmalm E, Davis GL, Trotter JF, Saad R, Landaverde C, Levy MF, Goldstein RM, Stone MJ. Long-term follow-up of liver transplantation for Budd-Chiari syndrome with antithrombotic therapy based on the etiology. Transplantation 2011;92(3):341–345. 453. Chujo D, Matsumoto S. Pancreas and islet transplantation for type 1 diabetes. J Japan Diabetes Soc 2011;53(4):260–262. 454. Chujo D, Takita M, Tekin Z, Matsumoto S. Chronic graft dysfunction in allogenic islet cell transplantation. In Belgaris J, Savarese AN, eds. Cell Transplantation: New Research. Hauppauge, NY: Nova Science Publishers, 2011. 455. Fujita Y, Takita M, Shimoda M, Itoh T, Sugimoto K, Noguchi H, Naziruddin B, Levy MF, Matsumoto S. Large human islets secrete less insulin per islet equivalent than smaller islets in vitro. Islets 2011;3(1):1–5. 456. Gaber AO, Mulgaonkar S, Kahan BD, Woodle ES, Alloway R, Bajjoka I, Jensik S, Klintmalm GB, Patton PR, Wiseman A, Lipshutz G, KupiecWeglinski J, Gaber LW, Katz E, Irish W, Squiers EC, Hemmerich S. YSPSL (rPSGL-Ig) for improvement of early renal allograft function: a double-blind, placebo-controlled, multi-center phase IIa study. Clin Transplant 2011;25(4):523–533. 457. Hatanaka N, Takita M, Yamaguchi T, Kami M, Matsumoto S. Development of a novel scale to assess the quality of life in type 1 diabetic patients for beta cell replacement therapy. Diabetology Internat 2011;2(2):55–64. 458. Ikemoto T, Sugimoto K, Takita M, Shimoda M, Noguchi H, Naziruddin B, Levy MF, Shimada M, Matsumoto S. Japanese herbal medicine TJ-48 prevents autoimmune diabetes in NOD mice. Am J Chin Med 2011;39(4): 1–14. 2011 publications of the Baylor Health Care System medical and scientific staff 201 459. Irish WD, Arcona S, Bowers D, Trotter JF. Cyclosporine versus tacrolimus treated liver transplant recipients with chronic hepatitis C: outcomes analysis of the UNOS/OPTN database. Am J Transplant 2011;11(8):1676–1685. 460. Itoh T, Chujo D, Matsumoto S. Islet cell transplantation research for curing diabetes. In Belgaris J, Savarese AN, eds. Cell Transplantation: New Research. Hauppauge, NY: Nova Science Publishers, 2011:1–19. 461. Itoh T, Iwahashi S, Shimoda M, Chujo D, Takita M, SoRelle JA, Naziruddin B, Levy MF, Matsumoto S. High-mobility group box 1 expressions in hypoxia-induced damaged mouse islets. Transplant Proc 2011;43(9): 3156–3160. 462. Itoh T, Sugimoto K, Shimoda M, Chujo D, Takita M, Iwahashi S, Kanak M, Yoshiko T, Naziruddin B, Levy MF, Matsumoto S. Establishment of a prolonged pancreas preservation model for islet isolation research in mice. Islets 2011;3(6):376–380. 463. Kim PTW, Chinnakotla S, Davis G, Jennings LW, McKenna GJ, Onaca N, Ruiz RM, Goldstein R, Levy MF, Klintmalm GB. Renal-sparing immunosuppressive protocol using OKT3 after liver transplantation: a 19year single-institution experience. Proc (Bayl Univ Med Cent) 2011;24(4): 287–294. 464. Klintmalm GB. Immunosuppression, generic drugs and the FDA. Am J Transplant 2011;11(9):1765–1766. 465. Klintmalm GB. Treat patients, not statistics. Am J Transplant 2011 Dec 17 [Epub ahead of print]. 466. Klintmalm GB, Davis GL, Teperman L, Netto GJ, Washburn K, Rudich SM, Pomfret EA, Vargas HE, Brown R, Eckhoff D, Pruett TL, Roberts J, Mulligan DC, Charlton MR, Heffron TG, Ham JM, Douglas DD, Sher L, Baliga PK, Kinkhabwala M, Koneru B, Abecassis M, Millis M, Jennings LW, Fasola CG. A randomized, multicenter study comparing steroid-free immunosuppression and standard immunosuppression for liver transplant recipients with chronic hepatitis C. Liver Transpl 2011;17(12): 1394–1403. 467. Lai JC, Verna EC, Brown RS Jr, O’Leary JG, Trotter JF, Forman LM, Duman JD, Foster RG, Stravitz RT, Terrault NA; Consortium to Study Health Outcomes in HCV Liver Transplant Recipients (CRUSH-C). Hepatitis C virus-infected women have a higher risk of advanced fibrosis and graft loss after liver transplantation than men. Hepatology 2011;54(2): 418–424. 468. Lawrence MC, Naziruddin B, Levy MF, Jackson A, McGlynn K. Calcineurin/ nuclear factor of activated T cells and MAPK signaling induce TNF-alpha gene expression in pancreatic islet endocrine cells. J Biol Chem 2011;286(2): 1025–1036. 469. Matsumoto S. Autologous islet cell transplantation to prevent surgical diabetes. J Diabetes 2011;3(4):328–336. 470. Matsumoto S. Clinical allogeneic and autologous islet cell transplantation: update. Diabetes Metab J 2011;35(3):199–206. 471. Matsumoto S. Progress in pancreatic islet isolation method. J Japan Pancreas Soc 2011;26:176–182. 472. Matsumoto S, Hatanaka N. Islet transplantation from live related donor. In Kandeel F, ed. Islets: Biology, Immunology, and Clinical Transplantation. New York: Springer, 2011. 473. Matsumoto S, SoRelle JA, Shimoda M. Regenerative medicine and tissue engineering for the treatment of diabetes. In Eberli D, ed. Tissue Engineering for Tissue and Organ Regeneration. Rijeka, Croatia: InTech, 2011. 474. Matsumoto S, Takita M, Chaussabel D, Noguchi H, Shimoda M, Sugimoto K, Itoh T, Chujo D, Sorelle J, Onaca N, Naziruddin B, Levy MF. Improving efficacy of clinical islet transplantation with iodixanol based islet purification, thymoglobulin induction and blockage of IL-1-beta and TNF-alpha. Cell Transplant 2011 Mar 8 [Epub ahead of print]. 475. Matsumoto S, Takita M, Shimoda M, Chujo D, Itoh T, Iwahashi S, Sorelle JA, Tamura Y, Rahman A, Purcell K, Naziruddin B, Onaca N, Levy MF. Insulin independence by supplemental islet transplantation 5 years after initial islet transplantation. J Diabetes 2011;3(4):353–355. 476. Matsumoto S, Takita M, Shimoda M, Itoh T, Iwahashi S, Chujo D, SoRelle JA, Tamura Y, Rahman A, Purcell K, Onaca N, Naziruddin B, Levy MF. Usefulness of the secretory unit of islet transplant objects 202 (SUITO) index for evaluation of clinical autologous islet transplantation. Transplant Proc 2011;43(9):3246–3249. 477. McKenna GJ, Klintmalm GB. The question of induction? Maybe not all antibodies are equal. . . . Transpl Int 2011;24(7):637–639. 478. McKenna GJ, Trotter JF, Klintmalm E, Onaca N, Ruiz R, Jennings LW, Neri M, O’Leary JG, Davis GL, Levy MF, Goldstein RM, Klintmalm GB. Limiting hepatitis C virus progression in liver transplant recipients using sirolimus-based immunosuppression. Am J Transplant 2011;11(11): 2379–2387. 479. Noguchi H, Kobayashi N, Matsumoto S. Technologies to improve human islet transplantation. In Soto-Gutierrez A, Navarro-Alvarez N, Fox IJ, eds. Methods in Bioengineering: Methods in Cell Transplantation. Norwood, MA: Artech House, 2011. 480. O’Leary JG, Kaneku H, Susskind BM, Jennings LW, Neri MA, Davis GL, Klintmalm GB, Terasaki PI. High mean fluorescence intensity donorspecific anti-HLA antibodies associated with chronic rejection postliver transplant. Am J Transplant 2011;11(9):1868–1876. 481. O’Leary JG, Landaverde C, Jennings L, Goldstein RM, Davis GL. Patients with NASH and cryptogenic cirrhosis are less likely than those with hepatitis C to receive liver transplants. Clin Gastroenterol Hepatol 2011;9(8):700–704.e1. 482. O’Leary JG, Trotter JF. Is MELD fit enough? Gastroenterology 2011;140(7): 1871–1874. 483. O’Leary JG, Trotter JF, Neri MA, Jennings LW, McKenna GJ, Davis GL, Klintmalm GB. Effect of tacrolimus on survival in hepatitis C– infected patients after liver transplantation. Proc (Bayl Univ Med Cent) 2011;24(3):187–191. 484. Paterno F, Khan A, Cavaness K, Asolati M, Campsen J, McKenna GJ, Onaca N, Ruiz R, Trotter J, Klintmalm GB. Malpositioned transjugular intrahepatic portosystemic shunt in the common hepatic duct leading to biliary obstruction and liver transplantation. Liver Transpl 2011;17(3):344–346. 485. Qin H, Matsumoto S, Klintmalm GB, De Vol EB. A meta-analysis for comparison of the two-layer and University of Wisconsin pancreas preservation methods in islet transplantation. Cell Transplant 2011;20(7):1127– 1137. 486. Ranjan D, Klintmalm G, Roberts J; Members of the Critical Care Task Force, ASTS. American Society of Transplant Surgeons’ White Paper: impact of closed ICUs on transplant patients’ care. Am J Transplant 2011;11(4): 670–671. 487. Reich DJ, Magee JC, Gifford K, Merion RM, Roberts JP, Klintmalm GB, Stock PG; ASTS Fellowship Training Committee. Transplant surgery fellow perceptions about training and the ensuing job market—are the right number of surgeons being trained? Am J Transplant 2011;11(2):253–260. 488. Ruiz R, Tomiyama K, Campsen J, Goldstein RM, Levy MF, McKenna GJ, Onaca N, Susskind B, Tillery GW, Klintmalm GB. Implications of a positive crossmatch in liver transplantation: A 20-year review. Liver Transpl 2011 Dec 5 [Epub ahead of print]. 489. Saxena V, Lai JC, O’Leary JG, Verna EC, Brown RS Jr, Stravitz RT, Trotter JF, Krishnan K, Terrault NA; for the ConsoRtiUm to Study Health Outcomes in HCV Liver Transplant Recipients (CRUSH-C). Donorrecipient race mismatch in African-American liver transplant patients with chronic hepatitis C. Liver Transpl 2011 Dec 5 [Epub ahead of print]. 490. Shafer TJ, Schkade D, Schkade L, Geier SS, Orlowski JP, Klintmalm G. Zero risk tolerance costs lives: loss of transplantable organs due to human immunodeficiency virus nucleic acid testing of potential donors. Prog Transplant 2011;21(3):236–247. 491. Sher L, Jennings L, Rudich S, Alexopoulos SP, Netto G, Teperman L, Kinkhabwala M, Brown RS Jr, Pomfret E, Klintmalm G; HCV-3 Study Group. Results of live donor liver transplantation in patients with hepatitic C virus infection: the HCV 3 trial experience. Clin Transplant 2011 Dec 12 [Epub ahead of print]. 492. Shimoda M, Itoh T, Sugimoto K, Takita M, Chujo D, Iwahashi S, SoRelle JA, Naziruddin B, Levy MF, Grayburn PA, Matsumoto S. An effective method to release human islets from surrounding acinar cells with agitation in high osmolality solution. Transplant Proc 2011;43(9):3161–3166. Baylor University Medical Center Proceedings Volume 25, Number 2 493. SoRelle JA, Naziruddin B.  cell replacement therapy. In Wagner D, ed. Type 1 Diabetes. Rijeka, Croatia: InTech, 2011:503–526. 494. Strait RT, Hicks W, Barasa N, Mahler A, Khodoun M, Köhl J, Stringer K, Witte D, Van Rooijen N, Susskind BM, Finkelman FD. MHC class I-specific antibody binding to nonhematopoietic cells drives complement activation to induce transfusion-related acute lung injury in mice. J Exp Med 2011;208(12):2525–2544. 495. Takasaki Y, Watanabe M, Yukawa H, Sabarudin A, Inagaki K, Kaji N, Okamoto Y, Tokeshi M, Miyamoto Y, Noguchi H, Umemura T, Hayashi S, Baba Y, Haraguchi H. Estimation of the distribution of intravenously injected adipose tissue-derived stem cells labeled with quantum dots in mice organs through the determination of their metallic components by ICPMS. Anal Chem 2011;83(21):8252–8258. 496. Takita M, Matsumoto S, Noguchi H, Shimoda M, Chujo D, Itoh T, Sugimoto K, Sorelle JA, Onaca N, Naziruddin B, Levy MF. Cluster analysis of self-monitoring blood glucose assessments in clinical islet cell transplantation for type 1 diabetes. Diabetes Care 2011;34(8):1799–1803. 497. Takita M, Matsumoto S, Qin H, Noguchi H, Shimoda M, Chujo D, Itoh T, Sugimoto K, Onaca N, Naziruddin B, Levy MF. Secretory Unit of Islet Transplant Objects (SUITO) Index can predict severity of hypoglycemic episodes in clinical islet cell transplantation. Cell Transplant 2011 Jun 9 [Epub ahead of print]. 498. Takita M, Matsumoto S, Shimoda M, Chujo D, Itoh T, Iwahashi S, SoRelle JA, Onaca N, Naziruddin B, Levy MF. Association between the secretory unit of islet transplant objects index and satisfaction with insulin therapy among insulin-dependent islet recipients. Transplant Proc 2011;43(9):3250–3255. 499. Takita M, Naziruddin B, Matsumoto S, Noguchi H, Shimoda M, Chujo D, Itoh T, Sugimoto K, Onaca N, Lamont J, Lara LF, Levy MF. Implication of pancreatic image findings in total pancreatectomy with islet autotransplantation for chronic pancreatitis. Pancreas 2011;40(1): 103–108. 500. Takita M, Naziruddin B, Matsumoto S, Noguchi H, Shimoda M, Chujo D, Itoh T, Sugimoto K, Tamura Y, Olsen GS, Onaca N, Lamont J, Lara LF, Levy MF. Body mass index reflects islet isolation outcome in islet autotransplantation for patients with chronic pancreatitis. Cell Transplant 2011;20(2):313–322. 501. Trotter J, Everhart JB. Outcomes among living liver donors. Gastroenterology 2011 Dec 21 [Epub ahead of print]. 502. Trotter JF, Gillespie BW, Terrault NA, Abecassis MM, Merion RM, Brown RS Jr, Olthoff KM, Hayashi PH, Berg CL, Fisher RA, Everhart JE; Adult-to-Adult Living Donor Liver Transplantation Cohort Study Group. Laboratory test results after living liver donation in the adultto-adult living donor liver transplantation cohort study. Liver Transpl 2011;17(4):409–417. 503. Yukawa H, Noguchi H, Hayashi S. Embryonic body formation using the tapered soft stencil for cluster culture device. Biomaterials 2011;32(15): 3729–3738. ETHICS AND PALLIATIVE CARE 504. Corporon K. Comfort and caring at the end of life: Baylor’s doula program. Proc (Bayl Univ Med Cent) 2011;24(4):318–319. 505. Fine RL. Rationing or stewardship in pursuit of just medical reform. Am J Bioethics 2011;11(7):22–23. HISTORY 506. Cooper B. The origins of bone marrow as the seedbed of our blood: from antiquity to the time of Osler. Proc (Bayl Univ Med Cent) 2011;24(2): 115–118. 507. Millard MW. Can Osler teach us about 21st-century medical ethics? Proc (Bayl Univ Med Cent) 2011;24(3):227–235. 508. Stone MJ. The humanities are the hormones. Proc (Bayl Univ Med Cent) 2011;24(1):17–20. 509. Stone MJ. History of myeloma. CancerUpdate 2011;2(2):4. 510. Stone MJ. On William Osler: the old art and the new science. ASCO Post 2011;2(10):1, 4. April 2012 511. Urschel HC Jr. War and medicine: the good, the bad, and the ugly. Uniformed Services University of the Health Sciences. Military Surgery Heritage, July 2011. 512. Wolford LM. History of the Baylor oral and maxillofacial surgery program, Dallas, TX. J Oral Maxillofac Surg 2011;69(11):2883–2892. INTERVIEWS 513. Grayburn PA, Roberts WC. Paul A. Grayburn, MD, on percutaneous mitral repair with the MitraClipTM device: a conversation with the editor. Am J Cardiol 2011;108(2):277–284. 514. Krause JR, Roberts WC. John Richard Krause, MD: a conversation with the editor. Proc (Bayl Univ Med Cent) 2011;24(2):119–130. 515. Urschel HC III, Roberts WC. Harold Clifton Urschel III, MD: an interview with the editor on his passion to prevent and cure addiction. Proc (Bayl Univ Med Cent) 2011;24(4):325–338. EDITORIALS, BOOK REVIEWS, AND MISCELLANEOUS 516. Aryangat AV, Chakmakjian ZH. Review of Diabetes and the Brain (Biessels and Luchsinger). Proc (Bayl Univ Med Cent) 2011;24(1):56. 517. Bentz ML, Ahmad J, Rohrich RJ. Fundraising and philanthropy in plastic surgery: an essential tool for academic excellence. Plast Reconstr Surg 2011;127(5):2108–2112. 518. Boland CR. Speed kills. Clin Gastroenterol Hepatol 2011;9(4):290–292. 519. Carethers JM, Goel A. Our new AGA institute president—C. Richard Boland, M.D. Gastroenterology 2011;140:1675–1679. 520. Chapman BJ. Unraveling the conflicts to preserve research integrity. Proc (Bayl Univ Med Cent) 2011;24(3):224–226. 521. Dihn TA, Rosner BI, Boland CR, Gruber SB, Burt RW. Screening for Lynch syndrome in the general population—response. Cancer Prev Res (Phila) 2011;4:472. 522. Eaves FF 3rd, Rohrich RJ. So you want to be an evidence-based plastic surgeon? A lifelong journey. Aesthet Surg J 2011;31(1):137–142. 523. Hasse JM. Editor’s note. Nutr Clin Pract 2011;26(4):373. 524. Hasse JM. Obesity. Editor’s note. Nutr Clin Pract 2011 Oct;26(5):509. 525. Inzer RW. Review of Amenorrhea (Santoro and Neal-Perry). Proc (Bayl Univ Med Cent) 2011;24(3):266. 526. Jones RC, Lieberman ZH, O’Brien JC, Stone MJ. Remembrances of Dr. Billie Aronoff. Proc (Bayl Univ Med Cent) 2011;24(4):346–347. 527. Mack MJ. Invited commentary. Ann Thorac Surg 2011;91(3):714–715. 528. Matthews CM. Gene therapy: available now! Proc (Bayl Univ Med Cent) 2011;24(3):247. 529. Matthews CM. Nurturing your divine feminine. Proc (Bayl Univ Med Cent) 2011;24(3):248. 530. Roberts WC. Facts and ideas from anywhere. Proc (Bayl Univ Med Cent) 2011;24(1):57–73. 531. Roberts WC. Facts and ideas from anywhere. Proc (Bayl Univ Med Cent) 2011;24(2):154–162. 532. Roberts WC. Facts and ideas from anywhere. Proc (Bayl Univ Med Cent) 2011;24(3):268–279. 533. Roberts WC. Facts and ideas from anywhere. Proc (Bayl Univ Med Cent) 2011;24(4):365–374. 534. Roberts WC. From-the-editor columns by William C. Roberts, MD, in the American Journal of Cardiology 1982–2011. Am J Cardiol 2011;108:1517–1520. 535. Roberts WC. Good books in cardiovascular diseases appearing in 2010. Am J Cardiol 2011;107:1250–1251. 536. Roberts WC. Piercing the impact factor and promoting the Eigenfactor™. Am J Cardiol 2011;108(6):896–898. 537. Roberts WC. Proceedings of the editorial board meeting of The American Journal of Cardiology, April 3, 2011. Am J Cardiol 2011;107:1864–1865. 538. Rohrich RJ. Introduction to the facial soft-tissue fillers conference supplement. J Am Acad Dermatol 2011;64(4 Suppl):S47–S49. 539. Rohrich RJ. So you want to be an international plastic surgeon? Plastic and Reconstructive Surgery visits China. Plast Reconstr Surg 2011;127(2):981–985. 540. Rohrich RJ, Pessa JE. Discussion. Aging of the facial skeleton: aesthetic implications and rejuvenation strategies. Plast Reconstr Surg 2011;127(1): 384–385. 2011 publications of the Baylor Health Care System medical and scientific staff 203 541. Rohrich RJ, Sullivan D. So you want to be like Leonardo da Vinci or Michelangelo? Which one are you? Plast Reconstr Surg 2011;128(6): 1309–1311. 542. Rohrich RJ, Sullivan D, Tynan E, Abramson K. Introducing the new PRS iPad app: the new world of plastic surgery education. Plast Reconstr Surg 2011;128(3): 799–802. 543. Solis R. Avocations: Photographs. Proc (Bayl Univ Med Cent) 2011;24 (4):353. 544. Sullivan D, Rohrich RJ. Authorship and medical ghostwriting: Plastic and Reconstructive Surgery policy. Plast Reconstr Surg 2011;127(6):2496–2500. 545. Surgery Journal Editors Group. Consensus statement on the adoption of the COPE guidelines. J Hepatobiliary Pancreat Sci 2011;18(1):125–126. 546. Sutton SW, Guillen MA, Hebeler RF, Hamman BL. A tribute to John Capehart, MD, “Sooner proud” and 1961 National Spelling Bee champion. Proc (Bayl Univ Med Cent) 2011;24(4):343–345. 547. Vanderpool D. Journey to the Borderland: Baylor’s Faith in Action Initiative’s donation of medical equipment to Ukraine. Proc (Bayl Univ Med Cent) 2011;24(4):312–317. 204 548. Warren B. Review of The Heart Manual (Fuster). Proc (Bayl Univ Med Cent) 2011;24(3):267. 549. Warren B, Warren TS. Review of The Price of Everything (Porter). Proc (Bayl Univ Med Cent) 2011;24(4):364. 550. Winter FD. Review of Notes of a Medical Maverick (Weisse). Proc (Bayl Univ Med Cent) 2011;24(3):266–267. 551. Yancy CW. A bald fade and a BP check: Comment on “Effectiveness of a barbershop-based intervention for improving hypertension control in black men.” Arch Intern Med 2011;171(4):350–352. Note: This list (finalized on February 13, 2012) was based on submissions from medical and allied health staff and on PubMed searches. Although the list is representative of the year’s publications, some articles and book chapters were undoubtedly missed, since only a small percentage of researchers respond to the request for publications. Staff are encouraged to submit their publications each year. For more information or to submit publications for this list, please contact Cynthia Orticio ([email protected]). Baylor University Medical Center Proceedings Volume 25, Number 2 Baylor University Medical Center Proceedings Volume 25 Number 2 April 2012 The peer-reviewed journal of Baylor Health Care System, Dallas, Texas Baylor University Medical Center Proceedings Articles 115 Unilateral absence of a pulmonary artery: a rare disorder with variable presentation D. L. Glancy, E. B. Hanna, and C. C. Ilie D. W. Reading and U. Oza 119 Hepatitis E infection Images in Medicine 161 Paget’s disease of the calcaneus causing right foot pain P. Patel, G. Schucany, P. B. Wood, and D. Hurst Vincent C. Kuo 121 Fatal aortic rupture from nonpenetrating chest trauma M. M. Benjamin and W. C. Roberts 163 Ruptured cerebral arteriovenous malformation presenting as intraventricular hemorrhage A. F. Saad, M. J. Opatowsky, A. Y. Nixon, S. C. Gilbert, and I. C. Thacker 124 High energy deficit in an ultraendurance athlete in a 24-hour ultracycling race R. Bescós, F. A. Rodríguez, X. Iglesias, A. Benítez, M. Marina, J. M. Padullés, P. Torrado, J. Vázquez, and B. Knechtle 129 The de novo diagnosis of systemic lupus erythematosus and lupus nephritis during pregnancy Volume 25, Number 2 • April 2012 Baylor University Medical Center, Dallas, Texas Electrocardiographic Report 159 Irregular cardiac rhythm in a woman with asthma T. Patel, A. Fenves, and G. Colbert Tributes 165 Tributes to George Boswell, MD P. Neubach and W. Snoots Book Reviews 166 Amyloidosis: Diagnosis and Treatment Reviewed by S. A. Gurevitz and M. J. Stone The Greater Journey 132 A rare case of intraneural ganglion cyst involving the tibial nerve Reviewed by Fran Roberts Willard P. Patel and W. G. Schucany 136 Jorge Felix Saucedo, MD, MBA: a conversation with the editor on optimizing antiplatelet and antithrombotic therapy in patients having percutaneous coronary intervention for acute coronary syndromes From the Editor 174 Facts and ideas from anywhere William C. Roberts Miscellany J. F. Saucedo and W. C. Roberts 139 Darwinian natural selection: its enduring explanatory power Gregory G. Dimijian Pages 113–204 Departments Baylor Sammons Cancer Center at Dallas Site Tumor Conference 152 Extraadrenal pheochromocytoma and vagal paraganglioma A. W. Jennings, J. T. Preskitt, and R. D. Vallera To access Baylor’s physicians, clinical services, or educational programs, contact the Baylor Physician ConsultLine: 1-800-9BAYLOR (1-800-922-9567) Dermatology Report 155 Widespread dermal ulcerations and bullae J. Wofford, M. Patel, A. Readinger, and A. Menter 114 118 128 148 158 160 164 169 Clinical research studies enrolling patients 2011 Ralph R. Tompsett Writing Award winner Selected quotes Baylor news Avocations: Photograph by Dr. Solis Acknowledgment of contributors In memoriam Reader comments: “Irreducible complexity” or “delightful challenge”? (C. R. Boland); Further discussion on Darwinism (D. Hansen, C. E. Jones, J. M. Guileyardo, J. Hoppenstein); Author response (J. A. Kuhn); Kudos (J. Hoppenstein) 184 Selected published abstracts of Baylor researchers 188 2011 publications of the Baylor Health Care System medical and scientific staff www.BaylorHealth.edu/Proceedings Indexed in PubMed, with full text available through PubMed Central