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AnesthesiaNews
Summer 2011 | Vol. 9.1
Newsletter of the Department of Anesthesia and Perioperative Care | University of California, San Francisco
The Essential Role of
Nurse Anesthetists
CRNAs Leigh-Ann Langford
and Mary Connolly working
at Mt. Zion Hospital
T
here were no anesthesiologists in Waxahachie, Texas where Leigh-Ann Langford
grew up. At the region’s small hospital – a satellite of Baylor Medical Center –
certified registered nurse anesthetists (CRNAs) were the sole anesthesia providers.
One of the CRNAs, Dale Stevenson, was a close friend of Langford’s father.
“For a very long time, my dad didn’t know that anyone other than CRNAs gave
anesthesia,” says Langford, who today is a CRNA at UCSF Medical Center.
Waxahachie’s anesthesia story is especially relevant today, because as UCSF Medical
Center – like many of its counterparts – copes with increased demands for anesthesia
and mandated cuts in residents’ hours, it is turning to CRNAs to help fill the gap.
A Long History of Qualified Care
In the United States, nurse anesthetists have been providing anesthesia care since the
mid-nineteenth century and, today, CRNAs are either masters-prepared or doctoralprepared in anesthesia care. Their training and history signify that what went on in
Waxahachie is hardly unusual, especially in rural areas.
continued on page 4
A New Era in Pain Management | Tracking Sepsis | Ask the Expert | Peer Reviewed Publications
AnesthesiaNews
Summer 2011 | Vol. 9.1
1 The Essential Role of
Nurse Anesthetists
2 From the Chairman
3 Tracking the ICU’s
Serial Killer
4 A New Era in Pain
Management
6 Resident Voices
7 Profile: Bradley Immanuel
8 Honors, Awards,
Appointments
9 Ask the Expert:
Jacqueline M. Leung, MD
10 Active Research Grants
12 Peer Reviewed Publications
2010-2011
16 Upcoming Events
DEPARTMENT CHAIR
EDITOR-IN-CHIEF
Mervyn Maze, MB ChB
EXECUTIVE EDITOR:
Marge O’Halloran
EDITOR:
Morgen Ahearn
DESIGNER:
Laura Myers Design
PRINCIPAL WRITER:
Andrew Schwartz
PHOTOGRAPHERS:
Christine Jegan, Brad Immanuel,
Marco Sanchez, Brant Ward
Anesthesia News is published by
the UCSF Department of Anesthesia
and Perioperative Care
521 Parnassus Avenue
Room C 450, Box 0648
San Francisco, CA 94143-0648
415/476-2131
FROM THE CHAIRMAN
W
hatever the flaws or merits of health care reform (Patient Protection and
Affordable Care Act), the ongoing debate has focused my attention on the
concept of health care value: optimally addressing patients’ presenting
complaints, avoiding excess services, seamless transitions amongst care providers,
preventing new health concerns, returning patients to functional lives, and averting
readmissions. This renewed emphasis on value has powerful implications for
anesthesiologists.
Consider the case of a patient
whose arthritic knee has caused her
debilitating pain for months to the
extent that her shopping tasks are no
longer performed without assistance.
After entering the hospital, her surgeon
completes a terrific knee replacement
and she leaves relatively pain-free, with
a knee able to move in all the right
directions. By traditional measures,
that’s high value care in which
surrogate markers have been used to
measure outcome.
But what if the care plan – from
pre-op through post-discharge care –
didn’t fully account for a variety of
patient risk factors? What if the patient
left the hospital cognitively impaired,
and became more dependent on
others to accomplish the activities of
daily living? Is the patient better off
than when she entered the hospital?
Have costs or efficiency improved if the
episode initiated an escalating need for
other health care services?
In the hospital, anesthesiologists are the care providers best positioned to enhance
value by orchestrating the episode of surgical care and taking a holistic view of the
outcome. Many of the articles in this issue of the newsletter make clear why we must
assume this responsibility.
Sepsis, pain, and the onset of cognitive dysfunction result from a complex set of
factors that are beyond the reach of neat care silos. If anesthesiologists don’t guard
against them across the entire hospital stay, no one will. We can work more closely
with primary care providers before admission, bring together the plans of other care
providers into one comprehensive plan, and communicate more effectively so that all
of us are cognizant of the risks that need to be mitigated before, during, and after each
surgical procedure. At an academic medical center like UCSF, we also can see that
our resources and educational programs are geared towards creating value.
Of course, for many of us, the commitment to value is not new. But if we are to
continue to meet that commitment effectively, we have to adapt to an evolving system.
For anesthesiologists, that means accepting more responsibility for orchestrating each
surgical patient’s entire episode of hospital care and linking these episodes seamlessly
to primary care.
http://anesthesia.ucsf.edu
Send all inquiries to
ahearnm@anesthesia.ucsf.edu
©2011 The Regents of the
University of California
Mervyn Maze, MB ChB
Professor and Chair
2 UCSF Department of Anesthesia and Perioperative Care
Tracking the ICU’s Serial Killer
I
n the intensive care unit – where UCSF
anesthesiologist Judith Hellman, MD,
does her clinical work – sepsis is the
most feared and prolific killer. It’s no
surprise then that Hellman spends her
research hours tracking how the interactions between microorganisms and the
body’s innate immune system lead to
shock and organ dysfunction in sepsis.
Hellman, the UCSF Department of
Anesthesia and Perioperative Care’s
Associate Director of Research, is
particularly focused on activity in the
endothelium, the thin layer of cells
that lines the interior of blood vessels.
A recipient of an NIH RO1 grant funded
through the ARRA program, as of this
writing Hellman has a major paper on
endothelium and sepsis in the January
2011 issue of the Journal of Immunology.
A Career Spent
Homing in on Sepsis
Though she grew up in New York City,
her family’s San Francisco roots
eventually drew Hellman to UC Berkeley
where she majored in microbiology;
she then attended medical school at
Columbia. “I thought I wanted to do
medical research, but when I walked
through the ICU during a medical school
surgery rotation, I became excited about
what goes on there, and eventually
decided to become an ICU physician,”
she says.
Then, she completed residencies
at the heart of sepsis-induced organ
in both internal medicine at Oregon
failure.”
Health Sciences University and
That insight led to her current projects,
anesthesia at Massachusetts General
where Hellman is studying the role of
Hospital. At Mass General, her
Toll-like receptor 2 (TLR2) and TLR2
department chair discovered
agonists. TLRs are proteins
her microbiology background
that serve as surface
and referred her to the lab of
receptors on many cells,
H. Shaw Warren, MD, an
including leukocytes and the
infectious disease physician
endothelium; they recognize
and sepsis researcher.
parts of bacteria – the TLR
“It all sort of came together
agonists – and decide how
at that point – microbiology,
to react. This sets off a
intensive care, sepsis,” says
complex inflammatory
Hellman. After an intensive
cascade, which leads to
care fellowship, also at Mass
coagulopathy, vascular leak,
Judith Hellman
General, Hellman moved on
and, eventually, sepsisto do post-doctoral work in
induced organ failure.
Warren’s lab on a T-32 training grant.
Defining these cellular and chemical
interactions is complicated enough,
A Convoluted, Contradictory
but the challenge for Hellman is to then
Disease Process
make sense of their effects on human
health. On the one hand many responses
As she began her own research career,
Hellman originally focused on lipoproteins in sepsis have important roles in clearing
infection and healing; on the other hand
that are present in the bacteria that
they can initiate fatal shock and organ
cause sepsis and get released when
failure. Hellman hopes to understand
infections are present.
the cellular interactions well enough to
“Then, in my clinical work, I was
target the harmful effects, without
struck by the complex bleeding and
undermining beneficial effects, such as
clotting derangements that occur in
eradication of the infection.
patients with sepsis,” says Hellman.
“You can’t get paralyzed by the
“I couldn’t help but think that processes
complexity,” she says. “You just have to
that occur in the endothelium, which is
accept it can take many years to achieve
important in coagulation homeostasis
the goal.”
and is activated in sepsis, might be
“I couldn’t help
but think that processes
that occur in the endothelium,
which is important in
coagulation homeostasis
and is activated in sepsis,
might be at the heart of
sepsis-induced organ failure.”
Anesthesia News | Summer 2011 3
The Essential Role of
Nurse Anesthetists
continued from front page
Since 2009, California has been an “opt out” state allowing CRNAs
to practice without physician supervision. At UCSF, however, hospital
policy dictates that they practice under the “medical direction” of an
anesthesiologist. At UCSF, CRNAs administer both general and regional
anesthesia in the OR as well as in non-OR settings that include MRI,
neuro-angiography, the endoscopy suite, the cardiac catheterization lab,
and the electrophysiology lab. The ratio of CRNAs to anesthesiologists
during a shift is typically 2:1.
The only areas where CRNAs do not practice at UCSF are the
intensive care unit, obstetrics, open-heart surgery, liver transplant, and
the pain services. “Some of what limits our practice at a teaching hospital
is that these other services offer more of the experiences residents need,”
says CRNA Ann Crowley.
Pleasures and Challenges
Both Crowley and Langford enjoy their work, but also know they face
significant challenges, as any anesthesiologist can attest. “Surgical
anesthesia requires that we maintain the patient’s homeostasis in a
profoundly altered state. That’s our job, but it can be very stressful,”
says Crowley.
“Also, many patients don’t even know we exist,” laughs Langford.
“Frequently we have to explain what our profession is, despite it being
over a century old. Although, this gets old after awhile, it is an opportunity
to educate the community about the CRNA profession.”
But there are many rewards as well. For one, “I think our faculty enjoy
working with us,” says Crowley.
“And UCSF is a vibrant university medical center, with a lot to learn –
and everyone is interested in teaching,” says Langford. “In that environment,
you don’t have to make as big of an effort to seek out cutting edge
anesthesia practice. It’s all right here.”
“Many patients don’t even know we
exist. Frequently we have to explain
what our profession is, despite it
being over a century old.”
4 UCSF Department of Anesthesia and Perioperative Care
A New Era
T
he past decade has seen significant advances in the management
of both acute and chronic pain,
as physicians scramble to respond to
patients’ pain complaints, safety and
regulatory demands, and the need to
reduce hospital readmissions.
“Effective pain management has
come front and center,” says Director
of Pain Medicine Mark Schumacher,
PhD, MD, from the UCSF Department
of Anesthesia and Perioperative
Care. “Yet pain management is
notoriously complex, often touching
on multiple sub-specialty areas across
care settings.”
To address that complexity and
ensure all patients receive the highest
quality care and outpatient follow
up, Schumacher and Chair of the
Department of Anesthesia and
Perioperative Care Mervyn Maze, MB
ChB, are working both within Anesthesia
and with other departments to craft a
unified approach to pain management.
The initial effort will include Interventional
Radiology, Neurology, Neurosurgery,
Obstetrics-Gynecology, Orthopedics,
Osher Center for Integrative Medicine,
Palliative Care and Pharmacy.
“Effective pain management
has come front and center.
Yet pain management is
notoriously complex,
often touching on multiple
sub-specialty areas across
care settings.”
in Pain Management
“The goal is to create a Pain Medicine
Consortium that will coordinate pain
management across all medical
center services – outpatient, inpatient,
and follow-up care – both now, and
at the future Women’s, Children’s
and Cancer Centers at Mission Bay,”
says Schumacher.
More Effective Use of Pain
Management Expertise
As at many other institutions, UCSF
pain management services have grown
in response to patient needs. At the
Parnassus and Mount Zion hospitals,
what began as a post-operative acute
pain service now includes inpatient
chronic pain management for patients
admitted or readmitted due to poorly
controlled pain.
In theory, the outpatient UCSF
Pain Management Center – with its
dedicated, multidisciplinary faculty –
complements the two inpatient services
but, understandably, the services can
overlap. In an effort to more effectively
deploy the department’s expertise,
Schumacher has refocused the
Parnassus and Mount Zion pain services
towards acute post-operative care,
while making a team of dedicated faculty many of them developed or advanced in
from the outpatient Pain Management
part at UCSF. Among them: gabapentin
Center available at both inpatient
for neuropathic and post-operative
hospitals for chronic pain management
pain; the use of capsaicin for blocking
care and consultations.
pain at its source, including
“The chronic pain team
cancer pain; use of
fosters continuous care,
low-dose ketamine for
either by working with
patients who have built a
referring physicians on a
resistance to narcotic
long-term plan or by following
analgesics; and intravenous
patients back to the Pain
lidocaine for post-operative
Management Center,” says
pain reduction.
Schumacher. “And as efforts
“Whether through
proceed to unify pain
optimizing more established
medicine at UCSF, the
regional and interventional
Mark Schumacher
multi-modality Center
techniques or integration
will continue to provide an
of novel non-narcotic pain
important anchor for patients suffering
management strategies, we will more
from chronic painful conditions.”
safely and effectively manage patients’
pain complaints,” says Schumacher.
Translating Research,
To that end, he believes that
Disseminating Knowledge
centralizing pain management expertise
will also help disseminate that expertise
“Perhaps the most exciting part of
to others. “There’s no way one
forming a Pain Medicine Consortium is
physician or team can manage all pain
how it can help bring the work of the
patients at UCSF, but we can now
many world-class pain researchers at
do a better job of working with other
UCSF directly to patients’ bedsides,”
physicians, physician trainees, nurses,
says Schumacher.
and pharmacists on emerging pain
That work includes a number of
management strategies.”
unconventional, non-opioid therapies,
Anesthesia News | Summer 2011 5
ResidentVoices
The UCSF Department of Anesthesia
and Perioperative Care offers a
unique educational experience
for residents and fellows, with
options to pursue a variety of tracks.
Below, in their own voices, are
two physicians in the Anesthesia
Research Scholars program and two
enrolled in the UCSF-wide Global
Health Clinical Scholars program.
Paul Riegelhaupt
Intern, Research Scholars Track
I’ve always been a math
and science nerd. I went to
Albert Einstein College of
Medicine for an MD/PhD,
more to be a scientist than
a doctor, but then fell in
love with being a doctor, and decided
I wanted both.
I found anesthesia while studying
the GABA receptor for my thesis project.
My work was focused on the molecular
structure of protein transporters on
membranes, which certainly come into
play in anesthesia, so it was an easy
transition for me.
I came to UCSF because they put it
all together here: research, clinical
excellence, and a great place to live.
They understand what it takes to get
started as a clinical scientist and they
foster your growth with outstanding
people and more long-term support than
other residency programs. The department believes that research matters and
they’re dedicated to supporting it.
In my med school essay, I told a story
of a guy who keeps jumping into the
water to save people from drowning....
I want to be the guy who figures out
who’s throwing all the people in the
water; I’m really turned on by figuring out
the mechanisms of disease and using
that to fuel medical innovation.
Catherine Chen
Intern, Research Scholars Track
My dad is an oncologist
and I always wanted to be
a doctor. But in my senior
year at Rice (BA in English),
I decided not to apply to
medical school right away;
instead I went to New York and spent
three years doing investment banking.
Within the first year, I knew being a physician better matched my gifts and interests.
I wound up getting into Johns
Hopkins, where I had a surgeon mentor
(Marty Makary, MD, MPH) who does a lot
of research on patient safety and
outcomes. While I was writing a book
chapter for him, I realized that anesthesiologists have been doing this patient
safety/quality of care thing longer than
other specialties. Also, I had done my
anesthesia rotation early – and loved it.
I was attracted to UCSF Anesthesia
because of all the research history and
because of the research track. The way
the track is integrated throughout your
residency lets you develop relationships
over time, rather than starting from
scratch on day one of a fellowship.
And I like that this internship year has
been balanced and doable; I really
appreciate the thought given to the
rotations, electives and schedules.
I would like to focus my research on
the perioperative setting – and look
at the system as a whole to see what
types of things can make patients safer.
There are so many subtleties and niches
in patient safety that I don’t know where
I’ll end up, but one goal is to come up
with new ways to measure quality and the
impact of the interventions we propose.
Kristine Breyer
Global Health Scholar
My interest in global
health began as an undergraduate at the University of
Colorado. Then, I attended
medical school at Loyola
University in Chicago, which
really promotes working with underserved
populations and gave me the opportunity
to work at a free clinic on Chicago’s
West Side and go on a medical trip to
rural Guatemala.
I initially came to UCSF in 2006 as
a plastic surgery resident, but made a
career change into anesthesia in 2009.
The Anesthesia Department has given
me the opportunity to take part in the
Global Health Scholars Program, a
unique program through UCSF’s Institute
of Global Health where residents and
graduate students participate in course
work and develop research projects in
the global health sciences.
For my project I want to combine my
backgrounds in surgery and anesthesia
training to look at perioperative trauma
outcomes and create systems changes
6 UCSF Department of Anesthesia and Perioperative Care
to improve those outcomes, because
injury from trauma is a leading cause of
morbidity and mortality in developing
countries. My long-term goals are to
investigate and use systems changes
and education to improve our ability to
care for all perioperative patients in
developing countries.
UCSF has a strong relationship with
a university hospital in Uganda and we
are in touch with a network of people in
Uganda who are excited to collaborate
with us. We will begin with an observational study and then work together to
design systems change that could help
improve perioperative trauma outcomes.
We are not going to Uganda to impose
changes on their medical system, but as
collaborative partners. It’s their hospital,
their country.
Sarah Gebauer
Global Health Scholar
I grew up in Texas and was
a Spanish major at Emory
University, in part because I
knew I wanted to do global
health work. My grandmother
had done medical and legal
work in Guatemala, and that made us
think about helping people outside of our
small bubble. Then I went to Stanford for
medical school, where I had some great
mentors who took me to Guatemala to
work with local health promoters.
I chose anesthesiology, because
I really like the people and it offers a
good mix of hands-on activities:
critical care, pain medicine – there are
lots of options, lots of ways for your life
to look. I’m looking forward to my
palliative care fellowship at San Diego
Hospice next year.
I chose UCSF, because I was very
impressed by the quality of the clinical
training and the interest of the faculty in
the projects they were doing. When I came
here, I was hoping to continue my interest
in global health and the program directors
were nice enough to let me apply.
(Before I became pregnant), I was
planning a project looking at cleft palate
repair in Nepal, with Dr. (George) Gregory,
looking at complication rates and other
outcomes there. Now I’ll fulfill my requirements by creating an online education
module for the Global Health Education
Consortium. I still plan to make global
health an important part of my career.
Profile: Bradley Immanuel
In challenging economic times, Bradley
Immanuel oversaw dramatic change in the
Department of Anesthesia and Perioperative
Care’s information technology operations.
An amateur photographer who takes about
30,000 photos each year – and an avid bicyclist
– Immanuel lives in San Francisco with his
wife Catherine and his two sons Lucas, 7,
and Jonah, 3.
How did you come to be director of IT
for the UCSF Department of Anesthesia
and Perioperative Care?
After graduating from Pepperdine University with a political
science degree, I spent five years working for a nonprofit
doing economic development in Russia. But it was a small
operation and I often found myself acting as the computer
fix-it guy. I’ve spent the last nine years in the department’s
IT unit and have really enjoyed it. I was given the chance to
build on successes and learn from failures; I would not have
had that chance in most other organizations.
How does the department’s IT unit
currently operate?
Our group does everything from helping a faculty member
check email to creating programs that facilitate professional
fee billing to serving as liaison to other campus IT groups.
We’re a kind of IT concierge; we make sure Anesthesia faculty
and staff get what they want and need so IT problems don’t
take away from their ability to do world-class patient care,
research and education…. We spend about 50-60 percent of
our time troubleshooting, and the rest creating new systems
or electronic workflows.
Some samples of Brad’s photography
For example?
For example, to help the department more accurately bill,
we’ve created a confirmation solution that downloads data
from the current EMR system. In our system, areas that often
get missed – such as when someone forgets to document an
Anesthesia event – bubble to the top. It also helps us see
which faculty members worked with which residents, so we
can know who is best prepared to do evaluations. There are
also things like the no-fault reporting system we set up with
Dr. Caldwell; for just a few hours of a programmer’s time the
department has received a lot of benefit.
But big changes are on the way?
Yes. The Medical Center’s EMR is changing from PICIS and
UCare to APeX. This will have a big effect on faculty and
residents; our role will largely be to ensure our confirmation
system works with APeX and to help faculty when they need
to access APeX from their office.
The bigger change for IT is the Chancellor’s Operational
Excellence initiative – a response to state budget cuts. Up to
now, IT at UCSF has been a series of small businesses and
Anesthesia has had gold-plated service…Now we have to
figure out how to make excellent service available to others
without degrading our department’s ability to set our own IT
agenda; we want to be able to continue providing specialized
services to our faculty, staff and other department members.
Anesthesia News | Summer 2011 7
HonorsAwardsAppointments
FACULTY HONORS,
AWARDS &
APPOINTMENTS
Jon Matthew Aldrich, MD
ing software and hardware. Dr. Collins
believes that hospital-based in-situ
simulation programs will be a major part
of the educational fabric of the UCSF
and affiliated hospitals.
CAMPUS AWARD:
Adrian Gelb, MB ChB
UCSF Academy of Medical Educators
Excellence in Teaching Award, 2010
EXTRAMURAL AWARD:
CAMPUS AWARD:
Distinguished Service Award, Society for
Neuroscience in Anesthesiology and
Critical Care, 2010
William K. Hamilton Award for Excellence
in Teaching, 2010-2011
Michael Gropper, MD, PhD
CAMPUS APPOINTMENT:
Matthias Braehler, MD
UCSF Department of Anesthesia and
Perioperative Care’s Executive Vice
Chair, 2011
Pedram Aleshi, MD
CAMPUS AWARD:
Ronald D. Miller Award for Excellence in
Junior Faculty Advising and Mentoring of
Residents, 2010-2011
Jan Hirsch, MD
CAMPUS AWARD:
CAMPUS AWARD:
UCSF Academy of Medical Educators
Excellence in Teaching Award, 2010
UCSF Academy of Medical Educators
Excellence in Teaching Award, 2010
Benjamin Houseman, MD, PhD
CAMPUS AWARD:
Neal Cohen, MD
CAMPUS APPOINTMENT:
UCSF Academy of Medical Educators
Excellence in Teaching Award, 2010
Interim Vice Dean for Academic Affairs,
2011
CAMPUS AWARD:
Lee-Lynn Chen, MD
Eric Lin, MD
UCSF Academy of Medical Educators
Excellence in Teaching Award, 2010
Errol Lobo, MD, PhD
CAMPUS AWARD:
UCSF Exceptional Physician Award, 2011
Mervyn Maze, MB ChB
CAMPUS APPOINTMENT:
Adam Collins, MD (above)
as part of a multidisciplinary team including
Leslie Dubbin, RN, and Robert Mackersie, MD
CAMPUS AWARD:
Hearts Grant, SFGH, 2011
A Hearts grant for $92,500 was recently
awarded to a multidisciplinary team at
San Francisco General Hospital to initiate
trauma team training and other courses
to improve the delivery of patient care
to the critically ill at SFGH. The grant
awardees are Leslie Dubbin, RN, Robert
Mackersie, MD, and Adam Collins, MD.
The grant funds will be used to purchase
a Laerdal SimMan 3G with accompany-
The William K. Hamilton, MD,
Distinguished Professorship
Throughout his tenure at UCSF, Bill
Hamilton was determined that while
many anesthesia departments were
held back by the yet undeveloped skills
of anesthesiologists, his Department
would proceed apace with other more
established medical specialties. Not
only did he succeed in this endeavor,
but he was the force behind research
discoveries that were implemented by
all fields of medicine.
A Distinguished Professorship within
the Department of Anesthesia named
for Dr. William K. Hamilton will recognize
his past exemplary service, while
signaling the promise that continued
research, training and clinical care in
anesthesiology at UCSF will spur the
discoveries of tomorrow.
— Text from the William K. Hamilton
Distinguished Professorship brochure
8 UCSF Department of Anesthesia and Perioperative Care
J. Renee Navarro, MD, PharmD
CAMPUS APPOINTMENT:
UCSF’s first Vice Chancellor for Diversity
and Outreach, 2010
Mark Rollins, MD, PhD
CAMPUS APPOINTMENT:
Director of Fetal Anesthesia, UCSF Fetal
Treatment Center, 2011
Arthur Wallace, MD, PhD
CAMPUS APPOINTMENT:
Vice Chair, UCSF Department of
Anesthesia and Perioperative Care, 2011
Chief, San Francisco Veteran’s
Affairs Medical Center, Anesthesiology
Service, 2011
Jenson Wong, MD
CAMPUS APPOINTMENTS:
Medical Director, Health Information
Technology for San Francisco
General Hospital and Trauma Center,
2010
RESIDENT AWARDS
Michele Arnold, MD
CAMPUS AWARD:
Stuart C. Cullen Award for Excellence
during Residency, 2010-2011
Brad Cohn, MD
CAMPUS AWARD:
Julius R. Krevans Award for Clinical
Excellence, SFGH, 2010
Madina Gerasimov, MD
CAMPUS AWARD:
Jeffrey A. Katz Award for Work Ethic and
Professionalism during Residency,
2010-2011
Anuj Malhotra, MD
CAMPUS AWARD:
Mark A. Rosen Award for Scholarship
during Residency, 2010-2011
POST-DOCTORAL
SCHOLAR AWARD
Niccolo Terrando, BSC, PhD
EXTRAMURAL AWARD:
2nd Place, Best Abstract Prize
Competition session at Euroanaesthesia
2010, for “Unraveling the interactions
between postoperative infection, surgery,
and inflammation in post-operative
cognitive dysfunction”
Ask the Expert: Jacqueline M. Leung, MD
What can
anesthesiologists
do to decrease
or prevent the
occurrence of
postoperative
delirium?
Delirium is currently
conceptualized as a geriatric
syndrome, which means that
rather than the cause being
disease in a single organ, a
constellation of events likely
contributes to delirium’s
occurrence.
For example, there are
multiple patient-dependent risk
factors for postoperative
delirium, including: older age,
lower educational level,
impairment of cognitive status
before surgery, and previous
history of a central nervous
system disorder. In addition,
various baseline risk factors,
including events that take place
during the perioperative period,
can be precipitating factors.
Among the most important of
these factors, studies have
identified intraoperative blood
loss, medications such as
opioids, and postoperative pain.
Risk Identification
and Mitigation is Crucial
Therefore, decreasing or preventing the
occurrence of postoperative delirium
begins with rigorous risk identification
during the preoperative evaluation. Since
cognitive status is not routinely evaluated
in the preoperative period, it is probably
indicated to add a limited cognitive screen
such as the mini-cog (an assessment
instrument that combines an uncued
3-item recall test with a clock-drawing
test) to exclude pre-existent cognitive
impairment. When an at-risk patient is
identified, a collaborative, proactive
approach is indicated, which can involve
nursing, geriatrics, surgery, and pharmacy
services. This multi-disciplinary approach
might include:
n early
orientation upon anesthesia
emergence, including having family
members present in the post anesthesia
recovery unit;
n minimization
of sensory deprivation by
providing hearing and visual aids;
n aggressive
management of
postoperative pain; consider the use of
regional techniques for postoperative
analgesia or the use of narcotic
adjuvant to minimize the use of
postoperative intravenous opioids;
n and
avoidance of multiple drugs,
particularly those with central nervous
system effects, such as drugs with
anti-cholinergic properties and
benzodiazepines.
of hemoglobin and renal function in
the early postoperative period are
also indicated for at risk patients since
hypoxemia, anemia and uremia are clearly
avoidable and potentially reversible
precipitating factors for delirium.
The Role of Sleep
Finally, though we have long suspected
that sleep disruption is another major
precipitating factor, routine use of sleep
aids should be avoided. Instead, consider
non-pharmacologic approaches, such as
the practice of early mobilization and
avoiding sleep disruption by minimizing
nighttime vital signs measurements and
procedures. Sleep disruption is particularly prevalent in the intensive care unit
(ICU), and here again, non-pharmacologic
interventions designed to aid a good
night’s sleep may be essential for
ultimately decreasing the occurrence
of delirium.
To that end, our department has
organized a multi-disciplinary clinical
study to address whether sleep disruption
directly contributes to postoperative
delirium in the ICU. Brain monitors will
measure different sleep stages in the
patients, and we will use a standardized
measure for ICU delirium. We hope
that this study will contribute to the
understanding of the pathophysiology
of delirium in the hospital and allow us
to design effective strategies to prevent
or minimize its occurrence.
Other tactics can include monitoring for
dehydration, bladder distention or ileus,
and proactive prevention of falling injury
by use of a “sitter.” Frequent checks
of oxygen saturation and measurements
References
1.Marcantonio ER, Flacker JM, Wright RJ, Resnick NM. Reducing delirium after hip
fracture: a randomized trial. J Am Geriatr Soc. 2001 May;49(5):516-22.
2.Marcantonio ER, Goldman L, Mangione CM, et al. A clinical prediction rule for
delirium after elective noncardiac surgery. JAMA. 1994 Jan 12;271(2):134-9.
3.Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly
persons. Predictive model and interrelationship with baseline vulnerability. JAMA. 1996
Mar 20;275(11):852-7.
4.Vaurio LE, Sands LP, Wang Y, Mullen EA, Leung JM. Postoperative delirium: the
importance of pain and pain management. Anesth Analg. 2006 Apr;102(4):1267-73.
5.Leung JM, Sands LP, Paul S, Joseph T, Kinjo S, Tsai T. Does postoperative delirium
limit the use of patient-controlled analgesia in older surgical patients? Anesthesiology.
2009 Sep;111(3):625-31.
Anesthesia News | Summer 2011 9
ActiveResearchGrants
Christian Apfel
Andrew Gray
Jan Hirsch
Chanhung Lee
Liu, Bin (continued)
Principal Investigator
Principal Investigator
Principal Investigator
Principal Investigator
Principal Investigator
Academic Senate, Individual Grant,
09/01/10–08/31/11
Carl Koller Memorial Research
Grant/American Society of Regional
Anesthesia and Pain Medicine,
Individual Grant, 01/01/11–12/31/12
REAC/Simon E Mem FD, Individual
Grant, 06/01/09–05/31/11
American Heart Association (AHA–
National Office), Individual Grant,
01/01/07–12/31/11
Vaxiion Therapeutics, Individual
Grant, 11/01/09–11/01/11
Smoking Status as a Risk
Factor for Severe Acute
Post-Operative Pain After
Elective Surgery
$34,445
Intravascular Contrast for
Regional Anesthesia
$41,304
Roland Bainton
Zhonghui Guan
Principal Investigator
Principal Investigator
NIH/NIGMS, Individual Grant,
08/01/07–05/31/12
Physiology and Regulation
of Drug Transport Across
the Blood Brain Barrier
$1,450,670
Principal Investigator
UCSF Anesthesia, Individual Grant,
07/01/10–06/30/11
Roland Bainton, 2010 RFA
$100,000
Philip Bickler
Principal Investigator
NIH/NIGMS, Individual Grant,
03/01/07–02/28/12
Intracellular Signaling in
Anesthetic and Hypoxic
Preconditioning of Neurons
$1,238,340
Tobacco Smoke Exposure –
a Predisposing Factor to
Ventilator Induced Lung Injury
and Damage to the Alveolar
Epithelial Type II Cell?
$30,000
Benjamin Houseman
Jae-Woo Lee
Foundation for Anesthesia Education
& Research (FAER), Research Career
Award, 07/01/10–06/30/12
Principal Investigator
Principal Investigator
Contributions of Histone
Acetylation Inflammatory Pain
$175,000
Pharmacologic Dissection
of the P13-Kinase Pathway
in Trauma
$598,050
Principal Investigator
REAC/Cox J Fund, Individual Grant,
07/01/10–06/30/11
Role of Histone Acetylation
Inflammatory Pain
$30,000
Tomoki Hashimoto
Principal Investigator
NIH/NINDS, Individual Grant,
02/01/07–01/31/12
NIH/NIGMS, Research Career Award,
03/01/10–02/28/15
Principal Investigator
Pathophysiology of
Postoperative Delirium in
Older Patients
$2,176,111
Various Industry Sponsors, Other
Clinical Contract, 09/01/86–Present
Principal Investigator
Helen Kim
Marek Brzezinski
Principal Investigator
Northern California Institute for
Research and Education (NCIRE),
Individual Grant, 01/11/09–12/31/11
Judith Hellman
Principal Investigator NIH/NIAID,
Individual Grant,
06/05/09–05/31/11
Is PTSD a Risk Factor for
Medical and Psychiatric
Complications in the
Perioperative Period?
$50,000
TLR2 in Sepsis-Induced
Coagulopathy, Endothelial
Leak, and Pulmonary
Dysfunction
$687,893
Yongmei Chen
Principal Investigator
Principal Investigator
NIH/NINDS, Individual Grant,
09/15/09–08/31/11
Endothelial Progenitor Cells
in Brain Arteriovenous
Malformations
$154,500
Adrian Gelb
Principal Investigator
Abratech Corporation, SubcontractResearch, 01/13/11–08/31/11
UCSF Anesthesia, Individual Grant,
07/01/10–06/30/11
Judith Hellman, 2010 RFA
$50,000
Principal Investigator
Academic Senate, Individual Grant,
01/20/11–06/19/11
Purchase of Electrical
Cell-Substrate Impedance
Sensing (ECIS) System-Shared
Instrument Grant
$35,000
Jacqueline Leung
Development of an
Interdisciplinary, WebBased Trauma Education
Curriculum at San Francisco
General Hospital
$30,000
Principal Investigator
Tomoki Hashimoto, 2010 RFA
$34,982
Mesenchymal Stem Cells for
Treatment of Acute Lung Injury
$608,850
Principal Investigator
Principal Investigator
UCSF Anesthesia, Individual Grant,
07/01/10–06/30/11
NIH/NHLBI, Research Career Award,
08/04/08–07/31/13
UCSF Academy of Medical
Educators–Innovations Funding,
Individual Grant, 07/01/10–06/30/11
Intracranial Aneurysm
Pathogenesis-Roles of
Vascular Remodeling and
Inflammation
$1,346,491
Accuracy of Pulse Oximeters
with Profound Hypoxia
$200,000
Influence of Matrix
Metalloproteinase on Brain
Arteriovenous Malformation
Hemorrhage
$260,000
UCSF Anesthesia, Individual Grant,
07/01/10–06/30/11
Benjamin Houseman, 2010 RFA
$50,000
Principal Investigator
NIH/NIA, Individual Grant,
09/15/09–08/31/14
Lawrence Litt
Principal Investigator
NIH/NIGMS, Individual Grant,
04/01/09–01/31/13
Hypothermia, Anesthesia
and NMR Metabolomics
in Ischemic Neonatal
Brain Slices
$1,401,093
NIH/NINDS, Research Career Award,
07/01/08–06/30/13
Bin Liu
Genetic Influences on
Clinical Outcome in Brain
Arteriovenous Malformations
$782,716
Principal Investigator
Kerstin Kolodzie
Principal Investigator
REAC/Harris Fnd, Individual Grant,
07/10/10–06/30/11
The Effect of General
Anesthesia on the Risk for
Arrhythmia? A pilot study
$29,917
Rondall Lane
Principal Investigator
University of Pittsburgh,
Subcontract-Research,
06/01/09–05/31/11
Isolating Mechanisms
Underlying Hospital Variation
in End-of-Life ICU Use
$43,693
Brain-Activity During Sedation
Predicting Post-Sedation
Explicit-Memory
$138,089
10 UCSF Department of Anesthesia and Perioperative Care
NIH/NCI, Individual Grant,
03/07/06–01/31/12
Human Antibody Targeted
Minicell Drug Delivery Platform
$127,500
Principal Investigator
Pancreas Cancer Program, Individual
Grant, 04/01/10–03/31/11
Developing Recombinant
Tumor and Tumor Stem Cell
Surface Antigens for
Pancreatic Tumor Detection
and Therapy
$26,500
Co-Investigator
Lustgarten Foundation for
Pancreatic Cancer, Individual Grant,
03/01/11–02/28/13
Developing Targeted
Nanoparticles to Interfere with
K-ras Expression Using siRNA
$200,000
Martin London
Principal Investigator
APSF-Anesthesia Patient Safety
Foundation, Individual Grant,
01/01/06–12/31/11
Perioperative Pharmacologic
Prophylaxis for Cardiovascular
Events in the Department of
Veterans Affairs: A Pharmacoepidemic Pilot Project
$75,000
James Marks
Principal Investigator
Fox Chase Cancer Center,
Subcontract-Research,
02/05/07–01/31/12
Mapping a Clinically
Significant Internalizing
Tumor Epitope Space
$1,582,152
Defining the Role of Affinity
in Antibody-Based Tumor
Targeting and Therapy
$638,122
Principal Investigator
Principal Investigator
NIH/NCI, Individual Grant,
12/05/08–11/30/11
Internalizing Antibody-Targeted
Nanosized siRNA Therapeutics
$373,890
Principal Investigator
NIH/NCI, Individual Grant,
02/01/09–01/31/12
Selection of Internalizing
Human Antibodies Targeting
Pancreatic Tumor Cells
in Situ by Laser Capture
Microdissection
$373,890
Principal Investigator
NIH/NCI, Individual Grant,
03/01/10–12/31/13
Identifying Antigens Bound by
Novel scFvs Targeting All
Subtypes of Mesothelioma
$1,250,293
NIH/NIAID, Individual Grant,
08/15/07–07/31/12
Development of botulinum
neurotoxin immunotherapy,
serotypes C, D, F, and G
$3,709,450
Principal Investigator
Xoma, Inc., Subcontract-Research,
02/17/09–09/14/14
Production of Monoclonal
Antibody-Based Therapeutics
for Botulism
$1,595,352
Principal Investigator
UC Irvine, Subcontract-Research,
05/01/09–04/30/14
Evolving Diagnostic Antibodies
for Botulinum Neurotoxins
$1,383,486
James Marks (continued)
Mervyn Maze
Arun Prakash Budde
Hua Su
William Young
Principal Investigator
Principal Investigator
Principal Investigator
Principal Investigator
Program Director
Georgetown University,
Subcontract-Research,
09/03/08–06/30/11
Foundation for Anesthesia Education
& Research (FAER), Fellowship,
01/01/11–01/31/11
UCSF Anesthesia, Individual Grant,
07/01/10–06/30/11
NIH/NINDS, Individual Grant,
02/01/10–01/31/12
NIH/NIGMS, Training Grant,
07/01/07–06/30/12
Adaptive Immunity from
High Affinity Anti-HER2/neu
Monoclonal Antibodies
$244,683
2011 Medical Student
Anesthesia Research
Fellowship Program
Arun Prakash, 2010 RFA
$30,000
Jeffrey Sall
Targeted Gene Expression
in Ischemic Brain by
Intravenous Delivery
$386,250
Comprehensive Anesthesia
Research Training
$921,700
Rachel McKay
Principal Investigator
Principal Investigator
Principal Investigator
Columbia University, SubcontractResearch, 01/13/06–07/31/11
Georgetown University,
Subcontract-Research,
02/02/09–12/31/13
NIH/NIGMS, Research Career Award,
02/01/10–01/31/14
Determinants of Tumor
Sensitivity to EGFR-Targeted
Antibodies
$384,635
Effect of Anesthetic
Choice (Sevoflurane versus
Desflurane) on Speed and
Sustained Nature of Airway
Reflex Recovery in the
Context of Antagonized
Neuromuscular Block
$231,014
Principal Investigator
Principal Investigator
Merrick Pharmaceuticals, URC/
Unfunded Research Collaboration,
05/15/09–05/14/11
Bispecific Antibodies Targeting
Basal Breast Cancers
Principal Investigator
Centers for Disease Control,
Contract, 09/09/09–09/07/11
Monoclonal Antibodies for
Mass Spectrometry Based
Detection of Biothreat Agents
$593,898
Principal Investigator
Functional Genetics, Inc,
Subcontract-Research,
07/01/10–06/30/13
Development of Broad
Spectrum Host Oriented
Therapeutic Antibodies
Against Influenza Infection
$398,854
Principal Investigator
Functional Genetics, Inc,
Subcontract-Research,
07/0/1/10–06/30/13
Discovery of Critical Host
Genes Enabling Resistance
to HIV-1 Infection as
Therapeutic Targets
$400,611
Principal Investigator
Lustgarten Foundation for
Pancreatic Cancer, Individual Grant,
08/01/10–07/31/11
The Lustgarten Foundation
Biomarker Initiative
$116,716
Baxter Healthcare Corp., Contract,
08/05/10–08/04/11
Principal Investigator
Population Health Research Institute
(PHRI), Contract, 10/29/10–04/29/11
An International, PlaceboControlled Factorial Trial to
Assess the Impact of Clonidine
and Aspirin in Patients Undergoing Noncardiac Surgery Who
are at Risk of Perioperative
Cardiovascular Event
$64,000
Volatile Anesthetic Alteration
of Neural Precursor Cell Cycle
and Fate Decisions
$478,440
Principal Investigator
UCSF Anesthesia, Individual Grant,
07/01/10–06/30/11
American Heart Association
(AHA–WSA), Individual Grant,
07/01/10–06/30/12
Induction of Functional
Angiogenesis in the
Ischemic Brain
$140,000
Pekka Talke
Principal Investigator
Mark Schumacher
The Pharmacokinetics and
Pharmacodynamics of
Dexmedetomidine in Patients
with Seizure Disorders
$31,631
NIH/NINDS, Individual Grant,
07/01/09–06/30/13
Capsaicin Receptor Subtypes
in Pain Transduction
$1,195,075
Principal Investigator
UC San Diego, SubcontractResearch, 07/01/10–02/28/11
Hospira, Inc., Clinical Trial,
12/09/10–12/08/12
NIH/NINDS, Individual Grant,
01/01/09–12/31/13
Principal Investigator
Greg Stratmann
Principal Investigator
Masimo Corporation, Contract,
02/04/10–07/31/11
Principal Investigator
Pulse Oximeter Parameter
Performance During Liver
Transplant
$13,904
Principal Investigator
International Anesthesia Research
Society (IARS), Research Career
Award, 01/01/09–12/31/11
Ludmila Pawlikowska
Is Pediatric Anesthesia
Associated with Long-Term
Hippocampal Dysfunction?
$80,000
Principal Investigator
Principal Investigator
NIH/NIDDK, Individual Grant,
03/01/09–02/28/13
Genetic Analysis of Metabolic
Syndrome by Admixture
Mapping in African American
$1,258,469
Principal Investigator
NIH/NINDS, Individual Grant,
02/01/10–01/31/12
Somatic Mutation Detection
in Brain AVM by Massively
High-Throughput Sequencing
$416,973
NIH/NINDS, Program Project Grant,
04/01/09–03/31/14
Principal Investigator
Hospira, Inc., Contract,
09/24/07–12/31/11
Binbin Wang
Intensive Insulin Therapy in
Deceased Donors to Improve
Renal Allograft Function and
Transplanted Allograft
Outcomes
$821,251
James Sonner
Principal Investigator
Principal Investigator
James Sonner, 2010 RFA
$86,368
DHHS/Health Resources and
Services Administration (HRSA
Individual Grant, 09/01/08–08/31/11
Predictors of Spontaneous
Cerebral AVM Hemorrhage
$2,047,332
Julin Tang
UCSF Anesthesia, Individual Grant,
07/01/10–06/30/11
Principal Investigator
Pain Management by an
Endogenous Antihyperalgesic
$136,247
Principal Investigator
Integrative Study of Brain
Vascular Malformations
$6,657,383
A Prospective, Randomized,
Controlled Study on the
Use of Dexmedetomidine
to Facilitate Extubation in
Surgical Intensive-Care
Unit Patients who Failed
Previous Weaning Attempts
Following Prolonged
Mechanical Ventilation
$154,966
Claus Niemann
A Randomized Trial
of Unruptured Brain
Arteriovenous Malformation
(ARUBA)
$162,368
NIH/NINDS, Individual Grant,
07/01/08–06/30/13
Jeffrey Sall, 2010 RFA
$53,050
Principal Investigator
Principal Investigator
Hemodynamics of Cerebral
Arteriovenous Malformations
$1,652,669
Principal Investigator
NIH/NINDS, Multicenter Project
Grant, 09/30/09–06/30/14
Brain Vascular Malformation
Consortium: Predictors of
Clinical Course
$6,095,571
Principal Investigator
UCSF Anesthesia, Individual Grant,
07/01/10–06/30/11
Binbin Wang, 2010 RFA
$1,350
The Leslie Munzer Neurological
Institute, Individual Grant,
01/01/09–12/31/11
Influence of Bone Marrow
Derived Cells in the
Development of Abnormal
Blood Vessels in a Model
of Brain AVM
$25,000
UCSF Anesthesia, Individual Grant,
07/01/10–06/30/11
Greg Stratmann, 2010 RFA
$62,000
Principal Investigator
ReNu Medical, Inc., Clinical Trial,
02/15/11–02/14/12
Accuracy of Pulse Oximeters
in Neonates and Children
Undergoing Cardiac Surgery
$20,000
Anesthesia News | Summer 2011 11
PeerReviewedPublications
Aldrich JM, Gropper MA. Can we predict pulmonary complications after
thoracic surgery? Anesth Analg. May 1;110(5):1261-3, 2010.
Anderson A, Eilers H, Yost CS. Anaphylaxis complicating graft reperfusion
during orthotopic liver transplantation: a case report. Transplant Proc.
Jun;42(5):1967-9, 2010.
Antoine J, Hussain Z, El-Sayed I, Apfel CC. The unrecognised difficult extubation:
a call for vigilance. Anaesthesia. Sep;65(9):946-8, 2010.
Apfel CC, Jalota L. Can central antiemetic effects of opioids counter-balance
opioid-induced nausea and vomiting? Acta Anaesthesiol Scand. Feb;54(2):129-31,
2010.
Apfel CC, Saxena A, Cakmakkaya OS, Gaiser R, George E, Radke O. Prevention
of postdural puncture headache after accidental dural puncture: a quantitative
systematic review. Br J Anaesth. Sep;105(3):255-63, 2010.
Apfel CC, Cakmakkaya OS, Martin W, Richmond C, Macario A, George E,
Schaefer M, Pergolizzi JV. Restoration of disk height through non-surgical spinal
decompression is associated with decreased discogenic low back pain: a
retrospective cohort study. BMC Musculoskelet Disord. Jul 8;11:155, 2010.
Apfel CC, Zhang K, George E, Shi S, Jalota L, Hornuss C, Fero KE, Heidrich F,
Pergolizzi JV, Cakmakkaya OS, Kranke P. Transdermal scopolamine for the
prevention of postoperative nausea and vomiting: a systematic review and
meta-analysis. Clin Ther. Nov;32(12):1987-2002, 2010.
Ballard PL, Lee JW, Fang X, Chapin C, Allen L, Segal MR, Fischer H, Illek B,
Gonzales LW, Kolla V, Matthay MA. Regulated gene expression in cultured
type II cells of adult human lung. Am J Physiol Lung Cell Mol Physiol.
Jul;299(1):L36-50, 2010.
Behrends M, Martinez-Palli G, Niemann CU, Cohen S, Ramachandran R,
Hirose R. Acute hyperglycemia worsens hepatic ischemia/reperfusion injury in rats.
J Gastrointest Surg. Mar;14(3):528-35, 2010.
Bickler PE, Fahlman CS. Enhanced hypoxic preconditioning by isoflurane:
signaling gene expression and requirement of intracellular Ca2+ and inositol
triphosphate receptors. Brain Res. Jun 22;1340:86-95, 2010.
Bickler PE, Fahlman CS, Gray JJ. Hypoxic preconditioning failure in aging
hippocampal neurons: impaired gene expression and rescue with intracellular
calcium chelation. J Neurosci Res. Dec;88(16):3520-9, 2010.
Bidlingmaier S, Wang Y, Liu Y, Zhang N, Liu B. Comprehensive analysis of
yeast surface displayed cDNA library selection outputs by exon microarray to
identify novel protein-ligand interactions. Mol Cell Proteomics. Mar;10(3):
M110.005116, 2011.
Bidlingmaier S, Liu B. Construction of yeast surface-displayed cDNA libraries.
Methods Mol Biol. 729:199-210, 2011.
Bidlingmaier S, Liu B. Identification of protein/target molecule interactions using
yeast surface-displayed cDNA libraries. Methods Mol Biol. 729:211-23, 2011.
Blobner M, Eriksson LI, Scholz J, Motsch J, Della Rocca G, Prins ME. Reversal of
rocuronium-induced neuromuscular blockade with sugammadex compared with
neostigmine during sevoflurane anaesthesia: results of a randomised, controlled
trial. Eur J Anaesthesiol. Oct;27(10):874-81, 2010.
Boyd BS, Wanek L, Gray AT, Topp KS. Mechanosensitivity during lower extremity
neurodynamic testing is diminished in individuals with Type 2 Diabetes Mellitus and
peripheral neuropathy: a cross sectional study. BMC Neurol. Aug 28;10:75, 2010.
Broadhurst MJ, Leung JM, Kashyap V, McCune JM, Mahadevan U, McKerrow JH,
Loke P. IL-22+ CD4+ T cells are associated with therapeutic trichuris trichiura
infection in an ulcerative colitis patient. Sci Transl Med. Dec 1;2(60):60ra88, 2010.
Brzezinski M, Lee A, Holak EJ, Pagel PS. A simple method for obtaining a
“ramped” laryngoscopy position after anesthetic induction. J Cardiothorac Vasc
Anesth. Jun;24(3):537-9, 2010.
Brzezinski M, Kukreja J, Mitchell JD, Pagel PS, Tassone RF. Sudden Onset of
Atrial Flutter During Continuous Venovenous Hemodialysis. J Cardiothorac Vasc
Anesth. Jan 11Jan 11. [Epub ahead of print], 2011.
Carvalho B, Aleshi P, Horstman DJ, Angst MS. Effect of a preemptive femoral
nerve block on cytokine release and hyperalgesia in experimentally inflamed skin of
human volunteers. Reg Anesth Pain Med. Nov;35(6):514-9, 2010.
Choukalas CG, Walter J, Glick D, O’Connor MF, Tung A, Dinwiddie SH, Nunnally
ME. Mask ventilation, hypocapnia, and seizure duration in electroconvulsive
therapy. J Clin Anesth. Sep;22(6):415-9, 2010.
12 UCSF Department of Anesthesia and Perioperative Care
Choy DF, Modrek B, Abbas AR, Kummerfeld S, Clark HF, Wu LC, Fedorowicz G,
Modrusan Z, Fahy JV, Woodruff PG, Arron JR. Gene expression patterns of
Th2 inflammation and intercellular communication in asthmatic airways.
J Immunol. Feb 1;186(3):1861-9, 2011.
Cohen JM, Gray AT. Functional deficits after intraneural injection during
interscalene block. Reg Anesth Pain Med. Jul-Aug;35(4):397-9, 2010.
Cohen JM, Gray AT. Reply to drs. Bigeleisen, chelly, and filip. Reg Anesth Pain
Med. Jan-Feb;36(1):95-7, 2011.
Cohen MJ, Serkova NJ, Wiener-Kronish J, Pittet JF, Niemann CU. 1H-NMR-based
metabolic signatures of clinical outcomes in trauma patients – beyond lactate and
base deficit. J Trauma. Jul;69(1):31-40, 2010.
Cohen NH. Critical care medicine in the United States: what we know, what we
do not, and where we go from here. Crit Care Med. Jan;38(1):304-6, 2010.
Cohen NH. The real reasons not to rely on severity scores. Crit Care Med.
Jan;38(1):334-5, 2010.
Coursin DB, Cohen NH, Murray MJ. Refrain from exclusionary training.
Crit Care Med. Sep;38(9):1919-20, 2010.
Darragh MR, Schneider EL, Lou J, Phojanakong PJ, Farady CJ, Marks JD,
Hann BC, Craik CS. Tumor detection by imaging proteolytic activity.
Cancer Res. Feb 15;70(4):1505-12, 2010.
Delaloy C, Liu L, Lee JA, Su H, Shen F, Yang GY, Young WL, Ivey KN, Gao FB.
MicroRNA-9 coordinates proliferation and migration of human embryonic stem
cell-derived neural progenitors. Cell Stem Cell. Apr 2;6(4):323-35, 2010.
Desalvo MK, Mayer N, Mayer F, Bainton RJ. Physiologic and anatomic
characterization of the brain surface glia barrier of Drosophila. Glia. Feb 23.
doi: 10.1002/glia.21147. [Epub ahead of print], 2011.
Dong J, Thompson AA, Fan Y, Lou J, Conrad F, Ho M, Pires-Alves M, Wilson BA,
Stevens RC, Marks JD. A single-domain llama antibody potently inhibits the
enzymatic activity of botulinum neurotoxin by binding to the non-catalytic
alpha-exosite binding region. J Mol Biol. Apr 9;397(4):1106-18, 2010.
Dougherty RH, Sidhu SS, Raman K, Solon M, Solberg OD, Caughey GH,
Woodruff PG, Fahy JV. Accumulation of intraepithelial mast cells with a unique
protease phenotype in T(H)2-high asthma. J Allergy Clin Immunol.
May;125(5):1046-1053.e8, 2010.
Drasner K. Anesthetic effects on the developing nervous system: if you
aren’t concerned, you haven’t been paying attention. Anesthesiology. Jul;113(1):
10-2, 2010.
Drasner K. Local anesthetic systemic toxicity: a historical perspective.
Reg Anesth Pain Med. Mar-Apr;35(2):162-6, 2010.
Drummond DC, Noble CO, Guo Z, Hayes ME, Connolly-Ingram C, Gabriel BS,
Hann B, Liu B, Park JW, Hong K, Benz CC, Marks JD, Kirpotin DB. Development
of a highly stable and targetable nanoliposomal formulation of topotecan.
J Control Release. Jan 4;141(1):13-21, 2010.
Dubowitz G, Detlefs S, McQueen KA. Global anesthesia workforce crisis:
a preliminary survey revealing shortages contributing to undesirable outcomes
and unsafe practices. World J Surg. Mar;34(3):438-44, 2010.
Dubowitz G. Global health and global anesthesia. Int Anesthesiol Clin.
Spring;48(2):39-46, 2010.
Eberspächer E, Blobner M, Werner C, Ruf S, Eckel B, Engelhard K, Schmahl W,
Gelb AW. The long-term effect of four hours of hyperventilation on neurocognitive
performance and lesion size after controlled cortical impact in rats. Anesth Analg.
Jan 1;110(1):181-7, 2010.
Eger EI 2nd. After you, please: the second Annual John W. Severinghaus Lecture
on Translational Science. Anesthesiology. Apr;112(4):786-93, 2010.
Eger EI 2nd. Cost in several flavors. Anesth Analg. Feb 1;110(2):276-7, 2010.
Eilers H, Liu KD, Gruber A, Niemann CU. Chronic kidney disease: implications
for the perioperative period. Minerva Anestesiol. Sep;76(9):725-36, 2010.
Eilers H, Cattaruzza F, Nassini R, Materazzi S, Andre E, Chu C, Cottrell GS,
Schumacher M, Geppetti P, Bunnett NW. Pungent general anesthetics
activate transient receptor potential-A1 to produce hyperalgesia and neurogenic
bronchoconstriction. Anesthesiology. Jun;112(6):1452-63, 2010.
Eilers H, Larson MD. The effect of ketamine and nitrous oxide on the
human pupillary light reflex during general anesthesia. Auton Neurosci.
Jan 15;152(1-2):108-14, 2010.
Erickson SE, Vasilevskis EE, Kuzniewicz MW, Cason BA, Lane RK, Dean ML,
Rennie DJ, Dudley RA. The effect of race and ethnicity on outcomes among
patients in the intensive care unit: A comprehensive study involving socioeconomic
status and resuscitation preferences. Crit Care Med. Mar;39(3):429-435, 2011.
Eriksson LI. Advancing medical science and practice in anesthesiology:
Karolinska. Anesthesiology. Dec;113(6):1258-9, 2010.
Errando CL, Pérez-Caballero P, Gelb AW, Sigl JC. Methodology, human factors,
and incidence of intraoperative awareness. Acta Anaesthesiol Scand.
Jul;54(6):781-3, 2010.
Fagerlund MJ, Kåhlin J, Ebberyd A, Schulte G, Mkrtchian S, Eriksson LI.
The human carotid body: expression of oxygen sensing and signaling genes of
relevance for anesthesia. Anesthesiology. Dec;113(6):1270-9, 2010.
Fahlenkamp AV, Peters D, Biener IA, Billoet C, Apfel CC, Rossaint R, Coburn
M. Evaluation of bispectral index and auditory evoked potentials for hypnotic
depth monitoring during balanced xenon anaesthesia compared with sevoflurane.
Br J Anaesth. Sep;105(3):334-41, 2010.
Fan QW, Cheng C, Hackett C, Feldman M, Houseman BT, Nicolaides T,
Haas-Kogan D, James CD, Oakes SA, Debnath J, Shokat KM, Weiss WA. Akt and
autophagy cooperate to promote survival of drug-resistant glioma. Sci Signal.
Nov 9;3(147):ra81, 2010.
Fan Y, Shen F, Frenzel T, Zhu W, Ye J, Liu J, Chen Y, Su H, Young WL, Yang GY.
Endothelial progenitor cell transplantation improves long-term stroke outcome in
mice. Ann Neurol. Apr;67(4):488-97, 2010.
Fang X, Neyrinck AP, Matthay MA, Lee JW. Allogeneic human mesenchymal stem
cells restore epithelial protein permeability in cultured human alveolar type II cells
by secretion of angiopoietin-1. J Biol Chem. Aug 20;285(34):26211-22, 2010.
Feiner JR, Bickler PE, Mannheimer PD. Accuracy of methemoglobin detection
by pulse CO-oximetry during hypoxia. Anesth Analg. Jul;111(1):143-8, 2010.
Feiner JR, Bickler PE. Improved accuracy of methemoglobin detection by pulse
CO-oximetry during hypoxia. Anesth Analg. Nov;111(5):1160-7, 2010.
Flexman AM, Ng JL, Gelb AW. Acute and chronic pain following craniotomy.
Curr Opin Anaesthesiol. Oct;23(5):551-7, 2010.
Franck M, Radtke FM, Apfel CC, Kuhly R, Baumeyer A, Brandt C, Wernecke KD,
Spies CD. Documentation of post-operative nausea and vomiting in routine clinical
practice. J Int Med Res. May-Jun;38(3):1034-41, 2010.
Gabarrós A, Young WL, McDermott MW, Lawton MT. Language and motor
mapping during resection of brain arteriovenous malformations: indications,
feasibility, and utility. Neurosurgery. Mar;68(3):744-52, 2011.
Gabriel RA, Kim H, Sidney S, McCulloch CE, Singh V, Johnston SC, Ko NU, Achrol
AS, Zaroff JG, Young WL. Ten-year detection rate of brain arteriovenous malformations in a large, multiethnic, defined population. Stroke. Jan;41(1):21-6, 2010.
Gao P, Chen Y, Lawton MT, Barbaro NM, Yang GY, Su H, Ling F, Young WL.
Evidence of endothelial progenitor cells in the human brain and spinal cord
arteriovenous malformations. Neurosurgery. Oct;67(4):1029-35, 2010.
Garcia-Rodriguez C, Geren IN, Lou J, Conrad F, Forsyth C, Wen W, Chakraborti S,
Zao H, Manzanarez G, Smith TJ, Brown J, Tepp WH, Liu N, Wijesuriya S, Tomic MT,
Johnson EA, Smith LA, Marks JD. Neutralizing human monoclonal antibodies
binding multiple serotypes of botulinum neurotoxi Protein Eng Des Sel.
Mar;24(3):321-31, 2011.
George E, Hornuss C, Apfel CC. Neurokinin-1 and novel serotonin antagonists for
postoperative and postdischarge nausea and vomiting. Curr Opin Anaesthesiol.
Dec;23(6):714-21, 2010.
Gomez-Sjoberg R, Leyrat AA, Houseman BT, Shokat K, Quake SR. Biocompatibility
and Reduced Drug Absorption of Sol-Gel-Treated Poly(dimethyl siloxane) for
Microfluidic Cell Culture Applications. Anal Chem. Oct;82:8954-8960, 2010.
Gray AT, Drasner K. Safety of ultrasound-guided regional anesthesia.
Anesthesiology. Jun;112(6):1538-9, 2010.
Guffey PJ, McKay WR, McKay RE. Case report: epidural hematoma nine days
after removal of a labor epidural catheter. Anesth Analg. Oct;111(4):992-5, 2010.
Guo L, Gelb AW. False negatives, muscle relaxants, and motor-evoked potentials.
J Neurosurg Anesthesiol. Jan;23(1):64, 2011.
Guo L, Gelb AW. The use of motor evoked potential monitoring during cerebral
aneurysm surgery to predict pure motor deficits due to subcortical ischemia.
Clin Neurophysiol. Apr;122(4):648-55, 2011.
Hao Q, Su H, Palmer D, Sun B, Gao P, Yang GY, Young WL. Bone marrowderived cells contribute to vascular endothelial growth factor-induced angiogenesis
in the adult mouse brain by supplying matrix metalloproteinase-9. Stroke.
Feb;42(2):453-8, 2011.
Hao Q, Zhu Y, Su H, Shen F, Yang GY, Kim H, Young WL. VEGF Induces More
Severe Cerebrovascular Dysplasia in Endoglin than in Alk1 Mice. Transl Stroke Res.
Sep 1;1(3):197-201, 2010.
Hårdemark Cedborg AI, Bodén K, Witt Hedström H, Kuylenstierna R, Ekberg O,
Eriksson LI, Sundman E. Breathing and swallowing in normal man – effects of
changes in body position, bolus types, and respiratory drive. Neurogastroenterol
Motil. Nov;22(11):1201-8, 2010.
He J, Wang Y, Feng J, Zhu X, Lan X, Iyer AK, Zhang N, Seo Y, VanBrocklin HF,
Liu B. Targeting prostate cancer cells in vivo using a rapidly internalizing novel
human single-chain antibody fragment. J Nucl Med. Mar;51(3):427-32, 2010.
Heier T, Caldwell JE, Feiner JR, Liu L, Ward T, Wright PM. Relationship between
normalized adductor pollicis train-of-four ratio and manifestations of residual
neuromuscular block: a study using acceleromyography during near steady-state
concentrations of mivacurium. Anesthesiology. Oct;113(4):825-32, 2010.
Hiller DB, Di Gregorio G, Kelly K, Ripper R, Edelman L, Boumendjel R, Drasner K,
Weinberg GL. Safety of high volume lipid emulsion infusion: a first approximation of
LD50 in rats. Reg Anesth Pain Med. Mar-Apr;35(2):140-4, 2010.
Howard M, Roux J, Lee H, Miyazawa B, Lee JW, Gartland B, Howard AJ, Matthay
MA, Carles M, Pittet JF. Activation of the stress protein response inhibits the STAT1
signalling pathway and iNOS function in alveolar macrophages: role of Hsp90 and
Hsp70. Thorax. Apr;65(4):346-53, 2010.
Hsieh TC, Schiller NB, Joshi RV. Extensive lipomatous hypertrophy of the
interatrial septum with involvement of the right atrium. Anesth Analg.
Mar 1;110(3):725-6; discussion 727, 2010.
Hsieh TC, Katz JA. Images in anesthesiology: thyroid cancer invading the trachea.
Anesthesiology. Oct;113(4):961, 2010.
Huang JJ, Azakie A, Russell IA. Echo rounds: discrete subvalvular aortic stenosis.
Anesth Analg. Apr 1;110(4):1003-5, 2010.
Hyytiä H, Ristiniemi N, Airas L, Pettersson K, Hellman J. Development of an
immunoassay for the detection of cystatin C dimers. J Immunol Methods. Apr
15;355(1-2):14-20, 2010.
Innes AL, McGrath KW, Dougherty RH, McCulloch CE, Woodruff PG, Seibold MA,
Okamoto KS, Ingmundson KJ, Solon MC, Carrington SD, Fahy JV. The H antigen
at epithelial surfaces is associated with susceptibility to asthma exacerbation.
Am J Respir Crit Care Med. Jan 15;183(2):189-94, 2011.
Iyer AK, Su Y, Feng J, Lan X, Zhu X, Liu Y, Gao D, Seo Y, Vanbrocklin HF, Courtney
Broaddus V, Liu B, He J. The effect of internalizing human single chain antibody
fragment on liposome targeting to epithelioid and sarcomatoid mesothelioma.
Biomaterials. Apr;32(10):2605-13, 2011.
Jalota L, Apfel CC. Importance of the Spanish Expert Guidelines for the prevention
and treatment of postoperative nausea and vomiting. Rev Esp Anestesiol Reanim.
Oct;57(8):467-72, 2010.
Josephson SA, Moheet AM, Gropper MA, Nichols AD, Smith WS. Ventilatorassociated pneumonia in a neurologic intensive care unit does not lead to increased
mortality. Neurocrit Care. Apr;12(2):155-8, 2010.
Kåhlin J, Eriksson LI, Ebberyd A, Fagerlund MJ. Presence of nicotinic, purinergic
and dopaminergic receptors and the TASK-1 K+-channel in the mouse carotid body
Respir Physiol Neurobiol. Jul 31;172(3):122-8, 2010.
Kanematsu Y, Kanematsu M, Kurihara C, Tada Y, Tsou TL, van Rooijen N, Lawton
MT, Young WL, Liang EI, Nuki Y, Hashimoto T. Critical roles of macrophages in the
formation of intracranial aneurysm. Stroke. Jan;42(1):173-8, 2011.
Kanematsu Y, Kanematsu M, Kurihara C, Tsou TL, Nuki Y, Liang EI, Makino H,
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in mice. Hypertension. May;55(5):1267-74, 2010.
Khachi S, Zhu Y, Yang GY. Preparation and analysis of endothelial progenitor cells
associated with angiogenesis. Methods Mol Biol. 621:139-48, 2010.
Kim H, McCulloch CE, Johnston SC, Lawton MT, Sidney S, Young WL. Comparison
of 2 approaches for determining the natural history risk of brain arteriovenous
malformation rupture. Am J Epidemiol. Jun 15;171(12):1317-22, 2010.
Anesthesia News | Summer 2011 13
PeerReviewedPublications
Kong EC, Woo K, Li H, Lebestky T, Mayer N, Sniffen MR, Heberlein U, Bainton RJ,
Hirsh J, Wolf FW. A pair of dopamine neurons target the D1-like dopamine receptor
DopR in the central complex to promote ethanol-stimulated locomotion in
Drosophila. PLoS One. Apr 1;5(4):e9954, 2010.
Koth LL, Cambier CJ, Ellwanger A, Solon M, Hou L, Lanier LL, Abram CL,
Hamerman JA, Woodruff PG. DAP12 is required for macrophage recruitment to
the lung in response to cigarette smoke and chemotaxis toward CCL2. J Immunol.
Jun 1;184(11):6522-8, 2010.
Krasnodembskaya A, Song Y, Fang X, Gupta N, Serikov V, Lee JW, Matthay MA.
Antibacterial effect of human mesenchymal stem cells is mediated in part from
secretion of the antimicrobial peptide LL-37. Stem Cells. Dec;28(12):2229-38, 2010.
Lawton MT, Kim H, McCulloch CE, Mikhak B, Young WL. A supplementary grading
scale for selecting patients with brain arteriovenous malformations for surgery.
Neurosurgery. Apr;66(4):702-13; discussion 713, 2010.
Neal JM, Bernards CM, Butterworth JF 4th, Di Gregorio G, Drasner K, Hejtmanek
MR, Mulroy MF, Rosenquist RW, Weinberg GL. ASRA practice advisory on local
anesthetic systemic toxicity. Reg Anesth Pain Med. Mar-Apr;35(2):152-61, 2010.
Nguyen HP, Zaroff JG, Bayman EO, Gelb AW, Todd MM, Hindman BJ; IHAST-MIDS
and IHAST Investigators. Perioperative hypothermia (33 degrees C) does not
increase the occurrence of cardiovascular events in patients undergoing cerebral
aneurysm surgery: findings from the Intraoperative Hypothermia for Aneurysm
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Niemann CU, Eilers H. Abdominal organ transplantation. Minerva Anestesiol.
Apr;76(4):266-75, 2010.
Niemann CU, Feiner J. Quality improvement in transplant anesthesia: which way
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Niemann CU, Xu F, Choi S, Behrends M, Park Y, Hirose R, Maher JJ. Short
passive cooling protects rats during hepatectomy by inducing heat shock proteins
and limiting the induction of pro-inflammatory cytokines. J Surg Res.
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Little SJ, Van der Heusen F, Thornton KC. Complete intraoperative
transesophageal echocardiogram imaging of the extent of an inferior vena cava
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Osredkar D, Sall JW, Bickler PE, Ferriero DM. Erythropoietin promotes
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May;38(2):259-65, 2010.
Liu J, Litt L, Segal MR, Kelly MJ, Yoshihara HA, James TL. Outcome-related
metabolomic patterns from 1H/31P NMR after mild hypothermia treatments of
oxygen-glucose deprivation in a neonatal brain slice model of asphyxia. J Cereb
Blood Flow Metab. Feb;31(2):547-59, 2011.
Percie du Sert N, Rudd JA, Apfel CC, Andrews PL. Cisplatin-induced emesis:
systematic review and meta-analysis of the ferret model and the effects of 5-HT(3)
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Liu LL, Aldrich JM, Shimabukuro DW, Sullivan KR, Taylor JM, Thornton KC,
Gropper MA. Special article: rescue therapies for acute hypoxemic respiratory
failure. Anesth Analg. Sep;111(3):693-702, 2010.
Perouansky M, Rau V, Ford T, Oh SI, Perkins M, Eger EI 2nd, Pearce RA. Slowing
of the hippocampal θ rhythm correlates with anesthetic-induced amnesia.
Anesthesiology. Dec;113(6):1299-309, 2010.
Logvinova AV, Litt L, Young WL, Lee CZ. Anesthetic concerns in patients with
known cerebrovascular insufficiency. Anesthesiol Clin. Mar;28(1):1-12, 2010.
Pinsonneault RL, Mayer N, Mayer F, Tegegn N, Bainton RJ. Novel models for
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Lou J, Geren I, Garcia-Rodriguez C, Forsyth CM, Wen W, Knopp K, Brown J,
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Politis GD, Schneider WJ, Van Beek AL, Gosain A, Migliori MR, Gregory GA,
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Lu DC, Roeser AC, Mummaneni VP, Mummaneni PV. Nuances of occipitocervical
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Ponomarev I, Rau V, Eger EI, Harris RA, Fanselow MS. Amygdala transcriptome
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Lyon R, Gibson A, Burch S, Lieberman J. Increases in voltage may produce
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Mikhak B, Weinsheimer S, Pawlikowska L, Poon A, Kwok PY, Lawton MT, Chen Y,
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Miller RD, Ward TA, Shiboski SC, Cohen NH. A comparison of three methods of
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Mummaneni PV, Lu DC, Dhall SS, Mummaneni VP, Chou D. C1 lateral mass
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Nakamura JL, Phong C, Pinarbasi E, Kogan SC, Vandenberg S, Horvai AE,
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Dose-dependent effects of focal fractionated irradiation on secondary malignant
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14 UCSF Department of Anesthesia and Perioperative Care
Prakash A, Hellman J. Editorial: Pattern recognition receptors and factor B:
“complement”ary pathways converge. J Leukoc Biol. Oct;88(4):605-7, 2010.
Puntillo KA, Arai S, Cohen NH, Gropper MA, Neuhaus J, Paul SM, Miaskowski C.
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Radke OC, Werth K, Borg-von-Zepelin M, Saur P, Apfel CC. Two serial check
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Reddy S, Shaller CC, Doss M, Shchaveleva I, Marks JD, Yu JQ, Robinson MK.
Evaluation of the Anti-HER2 C6.5 Diabody as a PET Radiotracer to Monitor
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Roux J, Carles M, Koh H, Goolaerts A, Ganter MT, Chesebro BB, Howard M,
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Transforming growth factor beta1 inhibits cystic fibrosis transmembrane
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Rubinsky L, Raichman N, Lavee J, Frenk H, Ben-Jacob E, Bickler PE.
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Sidhu SS, Yuan S, Innes AL, Kerr S, Woodruff PG, Hou L, Muller SJ, Fahy JV.
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Thoma MS, Maa J, Schiller NB, Litt L. Cholecystectomy in the presence of a large
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Vagefi PA, Klein I, Gelb B, Hameed B, Moff SL, Simko JP, Fix OK, Eilers H, Feiner
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Anesthesia News | Summer 2011 15
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Department of Anesthesia and Perioperative Care
University of California, San Francisco
Box 0648
San Francisco, CA 94143-0648
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AnesthesiaNews
Summer 2011 | Vol. 9.1
Upcoming Events
The Changing Practice of Anesthesia
September 22-25, 2011
Hotel Nikko San Francisco / San Francisco, California
COURSE CHAIRS:
Merlin Larson, MD
Professor Emeritus in Residence,
Department of Anesthesia and Perioperative Care
Binbin Wang, MD
Assistant Clinical Professor,
Department of Anesthesia and Perioperative Care
Susan Yoo, MD
Assistant Clinical Professor,
Department of Anesthesia and Perioperative Care
Program and registration information: www.cme.ucsf.edu
UCSF Center for Cerebrovascular Research
CCR/PPG SEMINARS
Presented by the Center for Cerebrovascular Research
Department of Anesthesia and Perioperative Care
University of California, San Francisco
San Francisco General Hospital
For a list of upcoming seminars: http://avm.ucsf.edu/
For a list of past seminars:
http://avm.ucsf.edu/research/recent_seminars.html
UCSF Maintenance of Certification
in Anesthesia Simulator Course
The UCSF Department of Anesthesia Simulation Center is
endorsed by the American Society of Anesthesiologists for meeting
the standards required for conducting ABA MOCA® simulation
courses. This center offers eight hour, single day courses for four
participants. Each participant will play active roles in all four
scenarios, including one scenario as the primary anesthesiologist
and one as the secondary anesthesiologist. Each scenario is
recorded with sound and video, which is used to guide the
debriefing conference that follows.
Dec. 16, 2011 / Feb. 10 / Mar. 9 / Apr. 20 / or May 18, 2012
COURSE CHAIR:
Adam Collins, MD
Associate Professor of Clinical Anesthesia,
Director, UCSF Anesthesia Simulator Center
To reserve a spot, please contact Armando Leiva,
course administrator, at leivaa@anesthesia.ucsf.edu.