RESEARCH
ROUNDUP
Transplant
Cardiologists on Controlling Hypertension
Scientists
and physicians studying heart failure should focus on crucial questions
surrounding the control of hypertension and other vascular risk
factors, say two experts in heart disease at Penn's School of Medicine,
writing in the May 15 issue of the New England Journal of Medicine.
In
their review of heart failure therapies,
Dr. Mariell Jessup, and Dr. Susan
Brozena, say that controlling those
aspects of heart disease represents
the best method of staving off the
most common forms of heart failure
in patients. The researchers acknowledge,
however, that the illness will always
remain "the final pathway for
myriad diseases that affect the heart."
In
their review, Dr. Jessup and Dr. Brozena
examined national data from clinical
trials, and mortality statistics for
patients with both systolic heart
failure (resulting from disease-weakened
left ventricles), and diastolic heart
failure (in which the heart contracts
normally but cannot fully relax between
beats).
The
researchers, both members of the Heart
Failure/Transplant Program at HUP,
note in their review the dichotomy
that exists between clinical study
findings and overall mortality outcomes
for the nation's heart-failure
patients.
Formal
clinical studies indicate a significant
drop in mortality rates for patients
admitted to hospitals with heart failure
and dilated cardiomyopathy (disease-enlarged
hearts); the lower death rates result
from advances in drugs and other medical
interventions, including beta-blockers,
biventricular pacemakers, coronary
bypass surgery and multi-disciplinary
heart-failure teams.
For
the same period, however, statistics
from large epidemiological surveys
show no meaningful change overall
in heart-failure death rates. The
Penn researchers note: "Symptomatic
heart failure continues to confer
a prognosis worse than the majority
of cancers in this country, averaging
a 45 percent one-year mortality."
They
say the disparity between clinical
findings and national statistics results,
in part, because most patients enrolled
in investigational drug trials have
been, until recently, middle-aged
white men with ischemic cardiomyopathy,
which is loss of blood to part of
the heart because of a constriction
or blockage in blood vessels. They
also note that therapies are not given
to all heart-failure patients, and
that for some patients, therapy is
discontinued.
Heart
failure is largely preventable through
controlling blood pressure and other
vascular risks, but until recently
the factors that render a patient
at-risk for heart failure had not
been clearly identified or publicized.
New
diagnostic guidelines for the American
College of Cardiology and the American
Heart Association have addressed the
latter issue. They classify four progressive
stages of heart failure, from Stage
A, which identifies a patient with
high risk but no apparent structural
abnormality of the heart, to Stage
D, in which the patient has end-stage
symptoms of heart failure that do
not respond to standard treatment.
They
say intervention should begin with
Stage A patients, noting: "Results
from trials have shown that the effective
treatment of hypertension decreases
the occurrence of left ventricular
hypertrophy and cardiovascular mortality,
as well as reducing the incidence
of heart failure by 30 to 50 percent."
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Immersive
Experience Without 3-D Goggles
Penn
has installed a virtual reality system that allows a participant
full-body interaction with a virtual environment without the hassle
of bulky, dizzying 3-D glasses.
Key
to the installation, dubbed LiveActor,
is the pairing of an optical motion
capture system to monitor the body's
movements with a stereo projection
system to immerse users in a virtual
environment. The combination lets
users interact with characters embedded
within virtual worlds.
"Traditional
virtual reality experiences offer
limited simulations and interactions
through tracking of a few sensors
mounted on the body," said Dr.
Norman I. Badler, professor of computer
and information science and director
of Penn's Center for Human Modeling
and Simulation.
LiveActor
users wear a special suit that positions
30 sensors on different parts of the
body. As the system tracks the movement
of these sensors as an actor moves
around a stage roughly 10 feet by
20 feet in size, a virtual character--such
as a dancing, computer-generated Ben
Franklin can recreate the user's
movements with great precision and
without a noticeable time lag. The
system can also project images onto
the array of screens surrounding the
LiveActor stage, allowing users to
interact with a bevy of virtual environments.
While
stereo projection systems have in
the past been limited to relatively
static observation and navigation--such
as architectural walk-throughs, games
and medical visualizations--LiveActor
can be used to simulate nearly any
environment or circumstance, chart
user reactions and train users to
behave in new ways.
LiveActor
was made possible through a grant
from the NSF with matching funding
by SEAS as well as equipment grants
from Ascension Technology Corporation
and EON Reality.
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Producing
Mouse Eggs from Embryonic Stem Cells
Researchers
at Penn have created the first mammalian gametes grown in vitro
directly from embryonic stem cells. The work, in which mouse stem
cells placed in Petri dishes--without any special growth or transcription
factors--grew into oocytes and then into embryos, will be reported
this week on the web site of the journal Science.
The
results demonstrate that even outside
the body embryonic stem cells remain
totipotent, or capable of generating
any of the body's tissues, said
lead researcher Dr. Hans R. Schöler,
professor of reproduction medicine
and director of Penn's Center
for Animal Transgenesis and Germ Cell
Research of the School of Veterinary
Medicine.
"We
found that not only can mouse embryonic
stem cells produce oocytes, but that
these oocytes can then enter meiosis,
recruit adjacent cells to form structures
similar to the follicles that surround
and nurture natural mouse eggs, and
develop into embryos," said Dr.
Schöler.
Dr.
Schöler said oocyte development
in vitro may offer a new way for embryonic
stem cells to be produced artificially,
sidestepping the ethical concerns
articulated by President Bush and
others. Implanting a regular nucleus
from any of the body's cells
into such an oocyte would yield a
totipotent stem cell.
The
Penn scientists pulled off this feat
using a gene called Oct4 as a genetic
marker. After the stem cells were
plated in a regular Petri dish -- densely
but without special feeder cells or
growth factors--the scientists
used fluorescent markers linked to
Oct4 and other telltale genes to assay
oocyte development. After 12 days
in culture, the cells organized into
colonies of variable size. Shortly
thereafter, individual cells detached
from these colonies.
In
the experiment described recently
in Science, both male- and
female-derived stem cells developed
into female gametes. Dr. Schöler
and colleagues now plan to test whether
oocytes developed in vitro can be
fertilized.
Dr.
Schöler was joined in the research
by Karin Hübner, James Kehler,
Rolland Reinbold, Rabindranath de
la Fuente and Michele Boiani of Penn's
School of Veterinary Medicine; Lane
K. Christenson, Jennifer Wood and
Jerome Strauss III from Penn's
School of Medicine; and Guy Fuhrmann
of the Centre de Neurochimie in France.
The work was funded by the NIH, the
Marion Dilley and David George Jones
Funds, the Commonwealth and General
Assembly of Pennsylvania and the Association
pour la Recherche sur la Cancer.
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Accruing
Sleep Debts' With Inadequate Nightly Sleep
Sleep,
don't be too sure you're getting enough of it. Those who believe
they can function well on six or fewer hours of sleep every night
may be accumulating a "sleep debt" that cuts into their
normal cognitive abilities, according to research conducted at Penn's
School of Medicine. What's more, the research indicates, those people
may be too sleep-deprived to know it.
The
study, published in the March 15 issue
of the journal Sleep, found
that chronically sleep-deprived individuals
reported feeling "only slightly
sleepy" even when their performance
was at its worst during standard psychological
testing. The results provide scientific
insight into the daily challenges
that confront military personnel,
residents and on-call doctors and
surgeons, shift workers, parents of
young children, and others who routinely
get fewer than six hours of sleep
each night.
"Routine
nightly sleep for fewer than six hours
results in cognitive performance deficits,
even if we feel we have adapted to
it," said Dr. Hans P.A. Van Dongen,
assistant professor of sleep and chronobiology
in the department of psychiatry and
corresponding author of the study. "This
work demonstrates the importance of
sleep as a necessity for health and
well-being. Even relatively moderate
sleep restriction, if it is sustained
night after night, can seriously impair
our neurobiological functioning."
Dr.
David F. Dinges, professor of psychology
in the department of psychiatry and
chief of the Division of Sleep and
Chronobiology, served as principal
investigator for the study.
Dr.
Dinges, Dr. Van Dongen and their colleagues
looked at the effects of four hours
nightly sleep and six hours nightly
sleep on healthy volunteer subjects
aged 21 to 38, over a two-week period.
They compared the results of the subjects' accumulating
performance deficits, determined by
standard psychomotor vigilance and
other cognitive tests, with similar
test results obtained from subjects
who had gone without sleep for more
than three nights.
The
first group of subjects experienced
increasing lapses in psychomotor vigilance
over days, resulting in a decline
of performance that matched that of
the subjects who went without sleep
for 88 hours. At that level, the subjects
suffered lapses in their ability to
react that would put them at risk
driving or flying an airplane. They
were also less able to multi-task
successfully.
Other
scientists who worked on the study
are Dr. Greg Maislin, also of Penn,
and Dr. Janet M. Mullington, of Beth
Israel Deaconess Medical Center and
Harvard University. The study was
funded by the National Institute of
Nursing Research of the NIH, National
Center for Research Resources and
the National Heart, Lung and Blood
Institute.
Almanac, Vol. 49, No. 34, May 27, 2003
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