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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.
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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
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journal’s mission is to communicate information about the research and clinical
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To access Baylor’s physicians, clinical services, or educational programs, contact
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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
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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
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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.
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DW. Computer-assisted assignment of functional domains in the nonstructural polyprotein of hepatitis E virus: delineation of an additional
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2. Gupta DN, Smetana HF. Th e histopathology of viral hepatitis as
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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
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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
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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
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Khuroo MS, Teli MR, Skidmore S, Sofi MA, Khuroo MI. Incidence and
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Kamar N, Garrouste C, Haagsma EB, Garrigue V, Pischke S, Chauvet C,
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P, Dalton HR, Santella R, Kanaan N, Essig M, Mousson C, Radenne S,
Roque-Afonso AM, Izopet J, Rostaing L. Factors associated with chronic
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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
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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
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27. Antecol DH, Roberts WC. Sudden death behind the wheel from natural disease in drivers of four-wheeled motorized vehicles. Am J Cardiol
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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.
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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.
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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.
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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.
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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.
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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,
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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.
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in the early history of animals. Science 2011;334(6059):1091–1097.
Baylor University Medical Center Proceedings
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17. Ridley M. Genome: The Autobiography of a Species. New York: HarperCollins, 1999.
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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):
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20. O’Donnell CJ, Nabel EG. Genomics of cardiovascular disease. N Engl J
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21. Baillie JK, Barnett MW, Upton KR, Gerhardt DJ, Richmond TA, De
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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
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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
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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
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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
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13.
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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.
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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.
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19.
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8.
188
22.
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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. Statistical methods in epidemiology.
In Lovric M, ed. International Encyclopedia of Statistical Science. Berlin,
Germany: Springer-Verlag, 2011:1444–1447.
123. Fleming NS, Culler S, McCorkle R, Ballard DJ. Financial and nonfinancial costs associated with electronic health record implementation
in the primary care setting. Health Aff 2011;30(3):481–489.
124. Ginsberg LD, Oubre AY, Daoud YA. L-methylfolate plus SSRI or SNRI
from treatment initiation compared to SSRI or SNRI monotherapy in a
major depressive episode. Innov Clin Neurosci 2011;8(1):19–28.
2011 publications of the Baylor Health Care System medical and scientific staff
191
125. Good VS, Saldaña M, Gilder R, Nicewander D, Kennerly DA. Largescale deployment of the Global Trigger Tool across a large hospital system:
refinements for the characterisation of adverse events to support patient
safety learning opportunities. BMJ Qual Saf 2011;20(1):25–30.
126. Harrington L, Kennerly D, Johnson C. 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. Arch Intern Med
2011;171(14):1238–1243.
136. Swim R. The value of automated data mining. Biomed Instrum Technol
2011;45(2):124–125.
137. Tietze MF, Doughty P, Alberico JG, Bailey P, Jacob B, Sanborn MD,
Scribner LH. Deep vein thrombosis/pulmonary embolism: a survey of
self-reported prevention practices among hospitals. J Healthc Qual 2011
Apr 25 [Epub ahead of print].
HEPATOLOGY
Note: See also Transplantation.
138. Curto TM, Lagier RJ, Lok AS, Everhart JE, Rowland CM, Sninsky JJ;
HALT-C Trial Group. Predicting cirrhosis and clinical outcomes in patients with advanced chronic hepatitis C with a panel of genetic markers
(CRS7). Pharmacogenet Genomics 2011;21(12):851–860.
139. Di Bisceglie AM, Stoddard AM, Dienstag JL, Shiffman ML, Seeff LB,
Bonkovsky HL, Morishima C, Wright EC, Snow KK, Lee WM, Fontana
RJ, Morgan TR, Ghany MG; HALT-C Trial Group. Excess mortality
in patients with advanced chronic hepatitis C treated with long-term
peginterferon. Hepatology 2011;53(4):1100–1108.
140. 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. Chronic viral hepatitis: epidemiology, molecular
biology, and antiviral therapy. Front Biosci 2011;16:225–250.
146. Gonzalez SA, Keeffe EB. Diagnosis of hepatocellular carcinoma: role of
tumor markers and liver biopsy. Clin Liver Dis 2011;15(2):297–306.
147. Gonzalez SA, Keeffe EB. IL-28B as a predictor of sustained virologic
response in patients with chronic hepatitis C virus infection. Gastroenterol
Hepatol (N Y) 2011;7(6):366–373.
148. Gonzalez SA, Keeffe EB. Liver transplantation. In Friedman LS, Keeffe
EB, eds. Handbook of Liver Disease, 3rd ed. Philadelphia: Elsevier, 2011:
420–433.
149. Kronfol Z, Litman HJ, Back-Madruga C, Bieliauskas LA, Lindsay KL,
Lok AS, Fontana RJ; HALT-C Trial Group. No increase in depression
with low-dose maintenance peginterferon in prior non-responders with
chronic hepatitis C. J Affect Disord 2011;129(1–3):205–212.
150. Lambrecht RW, Sterling RK, Naishadham D, Stoddard AM, Rogers
T, Morishima C, Morgan TR, Bonkovsky HL; HALT-C Trial Group.
Iron levels in hepatocytes and portal tract cells predict progression and
outcomes of patients with advanced chronic hepatitis C. Gastroenterology
2011;140(5):1490–1500.e3.
151. Lok AS, Everhart JE, Di Bisceglie AM, Kim HY, Hussain M, Morgan TR;
HALT-C Trial Group. Occult and previous hepatitis B virus infection are
not associated with hepatocellular carcinoma in United States patients
with chronic hepatitis C. Hepatology 2011;54(2):434–442.
152. McGarry LJ, Pawar VS, Parekh HH, Rubin JL, Davis GL, Younossi ZM,
Capretta JC, O’Grady MJ, Weinstein MC. Economic model of a birth
cohort screening program for hepatitis C virus. Hepatology 2011 Dec 2
[Epub ahead of print].
153. Nazario H, Landaverde C, Perrillo R. Do all patients with chronic hepatitis B who are treatment candidates need an assessment of fibrosis? In
Jensen D, ed. Current Controversies in Hepatology: The Experts Analyze
Both Sides. Thorofare, NJ: Slack, 2011:33–42.
154. Nazario HE, Lepe R, Trotter JF. Metastatic breast cancer presenting as
acute liver failure. Gastroenterol Hepatol (N Y) 2011;7(1):65–66.
155. O’Brien TR, Everhart JE, Morgan TR, Lok AS, Chung RT, Shao Y, Shiffman ML, Dotrang M, Sninsky JJ, Bonkovsky HL, Pfeiffer RM; HALT-C
Trial Group. An IL28B genotype-based clinical prediction model for
treatment of chronic hepatitis C. PLoS One 2011;6(7):e20904.
156. O’Bryan JM, Potts JA, Bonkovsky HL, Mathew A, Rothman AL; HALTC Trial Group. Extended interferon-alpha therapy accelerates telomere
length loss in human peripheral blood T lymphocytes. PLoS One 2011;
6(8):e20922.
157. Perrillo R. Measurement of HBsAg concentration during antiviral therapy
of hepatitis B: who, when, and why. Am J Gastroenterol 2011;106(10):
1774–1776.
158. Perrillo RP. Reactivated hepatitis B due to medical interventions: the
clinical spectrum expands. Antivir Ther 2011;16(7):947–949.
159. Perrillo RP, Hann HW, Schiff E, Mutimer D, Willems B, Leung N, Lee
WM, Dixon S, Woessner M, Brosgart CL, Condreay LD, Gardner SD.
Extended treatment with lamivudine and adefovir dipivoxil in chronic
hepatitis B patients with lamivudine resistance. Hepatol Int 2011;5(2):
654–663.
160. Schlitt HJ, Mornex F, Shaked A, Trotter JF. Immunosuppression and
hepatocellular carcinoma. Liver Transpl 2011;17(Suppl 2):S159–S161.
161. Trotter JF. Hot-topic debate on hepatitis C virus: the type of immunosuppression matters. Liver Transpl 2011;17(Suppl 3):S20–S23.
IMMUNOLOGY
Note: Some publications of the BRI/BIIR staff are listed under Neurology, Dermatology, and Transplantation.
162. Bentebibel SE, Schmitt N, Banchereau J, Ueno H. Human tonsil B-cell
lymphoma 6 (BCL6)-expressing CD4+ T-cell subset specialized for B-cell
help outside germinal centers. Proc Nat Acad Sci U S A 2011;108(33):
E488–E497.
Baylor University Medical Center Proceedings
Volume 25, Number 2
163. Buglio D, Khaskhely NM, Voo KS, Martinez-Valdez H, Liu YJ, Younes
A. HDAC11 plays an essential role in regulating OX40 ligand expression
in Hodgkin lymphoma. Blood 2011;117(10):2910–2917.
164. Butterfield LH, Palucka AK, Britten CM, Dhodapkar MV, Håkansson
L, Janetzki S, Kawakami Y, Kleen TO, Lee PP, Maccalli C, Maecker HT,
Maino VC, Maio M, Malyguine A, Masucci G, Pawelec G, Potter DM,
Rivoltini L, Salazar LG, Schendel DJ, Slingluff CL Jr, Song W, Stroncek
DF, Tahara H, Thurin M, Trinchieri G, van Der Burg SH, Whiteside TL,
Wigginton JM, Marincola F, Khleif S, Fox BA, Disis ML. Recommendations from the iSBTc-SITC/FDA/NCI Workshop on Immunotherapy
Biomarkers. Clin Cancer Res 2011;17(10):3064–3076.
165. Cobb A, Roberts LK, Palucka AK, Mead H, Montes M, Ranganathan
R, Burkeholder S, Finholt JP, Blankenship D, King B, Sloan L, Harrod AC, Lévy Y, Banchereau J. Development of a HIV-1 lipopeptide
antigen pulsed therapeutic dendritic cell vaccine. J Immunol Methods
2011;365(1–2):27–37.
166. Corrigan CJ, Wang W, Meng Q, Fang C, Eid G, Caballero MR, Lv Z, An
Y, Wang YH, Liu YJ, Kay AB, Lee TH, Ying S. Allergen-induced expression of IL-25 and IL-25 receptor in atopic asthmatic airways and late-phase
cutaneous responses. J Allergy Clin Immunol 2011;128(1):116–124.
167. Eapen M, Le Rademacher J, Antin JH, Champlin RE, Carreras J, Fay J,
Passweg JR, Tolar J, Horowitz MM, Marsh JC, Deeg HJ. Effect of stem
cell source on outcomes after unrelated donor transplantation in severe
aplastic anemia. Blood 2011;118(9):2618–2621.
168. Garcia-Romo GS, Caielli S, Vega B, Connolly J, Allantaz F, Xu Z, Punaro
M, Baisch J, Guiducci C, Coffman RL, Barrat FJ, Banchereau J, Pascual V.
Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus. Sci Transl Med 2011;3(73):73ra20.
169. Guo Y, Audry M, Ciancanelli M, Alsina L, Azevedo J, Herman M, Anguiano E, Sancho-Shimizu V, Lorenzo L, Pauwels E, Philippe PB, Pérez
de Diego R, Cardon A, Vogt G, Picard C, Andrianirina ZZ, Rozenberg
F, Lebon P, Plancoulaine S, Tardieu M, Valérie Doireau, Jouanguy E,
Chaussabel D, Geissmann F, Abel L, Casanova JL, Zhang SY. Herpes
simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity. J Exp Med
2011;208(10):2083–2098.
170. Hambleton S, Salem S, Bustamante J, Bigley V, Boisson-Dupuis S, Azevedo J, Fortin A, Haniffa M, Ceron-Gutierrez L, Bacon CM, Menon G,
Trouillet C, McDonald D, Carey P, Ginhoux F, Alsina L, Zumwalt TJ,
Kong XF, Kumararatne D, Butler K, Hubeau M, Feinberg J, Al-Muhsen
S, Cant A, Abel L, Chaussabel D, Doffinger R, Talesnik E, Grumach A,
Duarte A, Abarca K, Moraes-Vasconcelos D, Burk D, Berghuis A, Geissmann F, Collin M, Casanova JL, Gros P. IRF8 mutations and human
dendritic-cell immunodeficiency. N Engl J Med 2011;365(2):127–138.
171. Igyártó BZ, Haley K, Ortner D, Bobr A, Gerami-Nejad M, Edelson BT,
Zurawski SM, Malissen B, Zurawski G, Berman J, Kaplan DH. Skin-resident murine dendritic cell subsets promote distinct and opposing antigenspecific T helper cell responses. Immunity 2011;35(2):260–272.
172. Lande R, Ganguly D, Facchinetti V, Frasca L, Conrad C, Gregorio J,
Meller S, Chamilos G, Sebasigari R, Riccieri V, Bassett R, Amuro H,
Fukuhara S, Ito T, Liu YJ, Gilliet M. Neutrophils activate plasmacytoid
dendritic cells by releasing self-DNA-peptide complexes in systemic lupus
erythematosus. Sci Transl Med 2011;3(73):73ra19.
173. Mathian A, Gallegos M, Pascual V, Banchereau J, Koutouzov S. Interferon-␣ induces unabated production of short-lived plasma cells in
pre-autoimmune lupus-prone (NZB×NZW)F1 mice but not in BALB/c
mice. Eur J Immunol 2011;41(3):863–872.
174. McNab FW, Berry MP, Graham CM, Bloch SA, Oni T, Wilkinson
KA, Wilkinson RJ, Kon OM, Banchereau J, Chaussabel D, O’Garra
A. Programmed death ligand 1 is over-expressed by neutrophils in the
blood of patients with active tuberculosis. Eur J Immunol 2011;41(7):
1941–1947.
175. Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L,
Zurawski G, Foucat E, Dullaers M, Oh S, Sabzghabaei N, Lavecchio
EM, Punaro M, Pascual V, Banchereau J, Ueno H. Human blood
CXCR5+CD4+ T cells are counterparts of T follicular cells and contain spe-
April 2012
cific subsets that differentially support antibody secretion. Immunity 2011;
34(1):108–121.
176. Oh MH, Oh SY, Yu J, Myers AC, Leonard WJ, Liu YJ, Zhu Z, Zheng
T. IL-13 induces skin fibrosis in atopic dermatitis by thymic stromal
lymphopoietin. J Immunol 2011;186(12):7232–7242.
177. Palucka K, Ueno H, Banchereau J. Recent developments in cancer vaccines. J Immunol 2011;186(3):1325–1331.
178. Palucka K, Ueno H, Fay J, Banchereau J. Dendritic cells and immunity
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179. Palucka K, Ueno H, Roberts L, Fay J, Banchereau J. Dendritic cell subsets
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180. Pedroza-Gonzalez A, Xu K, Wu TC, Aspord C, Tindle S, Marches F, Gallegos M, Burton EC, Savino D, Hori T, Tanaka Y, Zurawski S, Zurawski
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181. Quartier P, Allantaz F, Cimaz R, Pillet P, Messiaen C, Bardin C, Bossuyt
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182. Sancho-Shimizu V, Pérez de Diego R, Lorenzo L, Halwani R, Alangari A,
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184. Ueno H, Fay J, Palucka AK, Banchereau J. Harnessing myeloid dendritic
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185. Ueno H, Klechevsky E, Schmitt N, Ni L, Flamar AL, Zurawski S,
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186. Wieckowski E, Chatta GS, Mailliard RM, Gooding W, Palucka K,
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187. Zhang Z, Kim T, Bao M, Facchinetti V, Jung SY, Ghaffari AA, Qin J,
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188. Zhang Z, Yuan B, Bao M, Lu N, Kim T, Liu YJ. The helicase DDX41
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189. Zhang Z, Yuan B, Lu N, Facchinetti V, Liu YJ. DHX9 pairs with IPS-1
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190. Zitvogel L, Palucka K. Antibody co-targeting of DCs. Blood 2011;118(26):
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INFECTIOUS DISEASES
191. Kannan TR, Hardy RD, Coalson JJ, Cavuoti DC, Siegel JD, Cagle
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192. Kannan TR, Coalson JJ, Cagle M, Musatovova O, Hardy RD, Baseman JB. Synthesis and distribution of CARDS toxin during Mycoplasma
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193. Tagliabue C, Techasaensiri C, Torres JP, Katz K, Meek C, Kannan TR,
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METABOLIC DISEASES
194. Benko W, Ries M, Wiggs EA, Brady RO, Schiffmann R, Fitzgibbon EJ.
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195. Bernard G, Chouery E, Putorti ML, Tétreault M, Takanohashi A,
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196. Chan A, Holleran WM, Ferguson T, Crumrine D, Goker-Alpan O,
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197. Chan YM, Broder-Fingert S, Paraschos S, Lapatto R, Au M, Hughes
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198. Durant B, Forni S, Sweetman L, Brignol N, Meng XL, Benjamin ER,
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199. Gough MS, Morgan MA, Mack CM, Darling DC, Frasier LM, Doolin
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200. Mochel F, Durant B, Durr A, Schiffmann R. Altered dopamine and
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201. Mochel F, Durant B, Meng X, O’Callaghan J, Yu H, Brouillet E, Wheeler
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202. Prust M, Wang J, Morizono H, Messing A, Brenner M, Gordon E, Hartka
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203. Ramos-Roman MA, Sweetman L, Valdez MJ, Parks EJ. Postprandial changes in plasma acylcarnitine concentrations as markers of fatty acid flux in
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204. Seaver LH, He XY, Abe K, Cowan T, Enns GM, Sweetman L, Philipp M,
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NEPHROLOGY
207. Daugirdas JT, Finn WF, Emmett M, Chertow GM; Frequent Hemodialysis Network Trial Group. The phosphate binder equivalent dose. Semin
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208. Emmett M. Bartter and Gitelman syndromes. In Sterns RH, ed. UpToDate. Waltham, MA: UpToDate, 2011.
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210. Emmett M. Etiology and diagnosis of type 1 and type 2 renal tubular acidosis. In Sterns RH, ed. UpToDate. Waltham, MA: UpToDate, 2011.
211. Emmett M. Pathophysiology of renal tubular acidosis and the effect
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218. Kuo VC, Fenves AZ, Mehta AN. Multiple myeloma presenting as acute
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219. Wiederkehr MR, Moe OW. Uric acid nephrolithiasis: a systemic metabolic disorder. Clinic Rev Bone Miner Metab 2011:9(3):207–217.
NEUROLOGY/NEUROSURGERY
220. Chimowitz MI, Lynn MJ, Derdeyn CP, Turan TN, Fiorella D, Lane BF,
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221. Chimowitz MI, Lynn MJ, Turan TN, Fiorella D, Lane BF, Janis S,
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222. Freitag FG. Sumatriptan needle-free subcutaneous (Sumavel® DosePro™)
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223. Giller CA. Feasibility of identification of gamma knife planning strategies
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224. Klineberg E, Schwab F, Ames C, Hostin R, Bess S, Smith JS, Gupta
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225. Lafage V, Schwab F, Vira S, Hart R, Burton D, Smith JS, Boachie-Adjei
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226. Lafage V, Smith JS, Bess S, Schwab FJ, Ames CP, Klineberg E, Arlet
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227. Lipton RB, Silberstein S, Dodick D, Cady R, Freitag F, Mathew N, Biondi DM, Ascher S, Olson WH, Hulihan J. Topiramate intervention to
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229. Phillips JT, Fox E, Grainger W, Tuccillo D, Liu S, Deykin A. An openlabel, multicenter study to evaluate the safe and effective use of the singleuse autoinjector with an AvonexR prefilled syringe in multiple sclerosis
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230. Phillips JT, Giovannoni G, Lublin FD, O’Connor PW, Polman CH,
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231. Phillips JT, Stone L. Use of MRI in the clinical management of multiple
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232. Powers WJ, Clarke WR, Grubb RL Jr, Videen TO, Adams HP Jr, Derdeyn
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239. Daniel K, Cason CL, Shrestha S. A comparison of glomerular filtration rate estimating equation performance in an older adult population
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251. Leeper B. Diabetes and cardiovascular disease. Crit Care Nurs Clin North
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259. Pilcher J. Creative learning ideas from around the U.S. Neonatal Netw
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263. Pilcher J, Bedford LA. Hierarchies of evidence in education. J Contin
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Izatt L, Davidson R, Chu C, Eccles D, Selkirk CG, Daly MB, Isaacs C,
Stoppa-Lyonet D, Buecher B, Belotti M, Mazoyer S, Barjhoux L, VernyPierre C, Lasset C, Dreyfus H, Pujol P, Collonge-Rame MA, Collaborators GS, Rookus MA, Verhoef S, Kriege M, Hoogerbrugge N, Ausems
MG, van Os TA, Wijnen JT, Devilee P, Meijers-Heijboer HE, Blok MJ,
Heikkinen T, Nevanlinna HA, Jakubowska A, Lubinski J, Huzarski T,
Byrski T, Durocher F, Couch FJ, Lindor NM, Wang X, Thomasson M,
Domchek SM, Nathanson KL, Caligo MA, Jernström HC, Liljegren A,
Ehrencrona H, Karlsson P, Ganz PA, Olopade OI, Tomlinson G, Neuhausen SL, Antoniou AC, Chenevix-Trench G, Rebbeck TR. Common
genetic variation at BARD1 is not associated with breast cancer risk in
BRCA1 or BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev
2011 Mar 10 [Epub ahead of print].
364. Stone MJ. Pathogenesis and morbidity of autoantibody syndromes in Waldenstrom’s macroglobulinemia. Clin Lymphoma Myeloma Leuk 2011;11(1):
157–159.
365. Stone MJ, Bogen SA. Management of hyperviscosity syndrome. Blood
2011 Dec 6 [Epub ahead of print].
366. Takahashi M, Koi M, Balaguer F, Boland CR, Goel A. MSH3 mediates sensitization of colorectal cancer cells to cisplatin, oxaliplatin, and a poly(ADPribose) polymerase inhibitor. J Biol Chem 2011;286(14):12157–12165.
367. Thomas V, Dobson R, Mennel R. Primary cutaneous large B-cell lymphoma, leg type. Proc (Bayl Univ Med Cent) 2011;24(4):350–353.
368. Toiyama Y, Yasuda H, Saigusa S, Matushita K, Fujikawa H, Tanaka K,
Mohri Y, Inoue Y, Goel A, Kusunoki M. Co-expression of hepatocyte
growth factor and c-Met predicts peritoneal dissemination established by
autocrine hepatocyte growth factor/c-Met signaling in gastric cancer. Int
J Cancer 2011 Jul 27 [Epub ahead of print].
April 2012
369. Tong AW, Senzer N, Cerullo V, Templeton NS, Hemminki A, Nemunaitis
J. Oncolytic viruses for induction of anti-tumor immunity. Curr Pharm
Biotechnol 2011 Jul 8 [Epub ahead of print].
370. Treon SP, Merlini G, Morra E, Patterson CJ, Stone MJ. Report from the
Sixth International Workshop on Waldenström’s Macroglobulinemia.
Clin Lymphoma Myeloma Leuk 2011;11(1):68–73.
371. Wang Z, Rao DD, Senzer N, Nemunaitis J. RNA interference and cancer
therapy. Pharm Res 2011;28(12):2983–2995.
372. Wilcox B, Senzer N, Filardo G, Reynolds J, Zielsdorf L, Adams J.
Thirteen-year biochemical progression free survival in clinical stage T1-T2
prostate cancer patients treated with permanent seed implantation: Baylor
University Medical Center experience. 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