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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