stanford medicine




Evolution’s plucky pisces


To the uninitiated, the threespine stickleback might look like nothing more than a scruffy anchovy with an attitude. But this tough little fish, with its characteristic finny mohawk, is a darling of evolutionary biologists.

That’s because it exhibits some of the most dramatic, adaptive changes of any animal alive today. Flourishing in fresh water or salty, appearing armored or sleek, light-skinned or dark, it’s the ultimate changeling. Naturalists initially classified it as more than 50 separate species.

Now researchers at Stanford and the Broad Institute have figured out which regions of the fish’s genome are responsible for the variations. The findings reverberate far beyond the stickleback: They may help scientists understand how the whale lost its hind limbs when it returned to the sea, for example, or how early humans evolved variations in skin colors.

Studying the whole-genome sequence of 21 of the fish from around the world revealed that the animals — despite their different haunts — repeatedly developed the same traits through changes in similar regions of their genomes. Specifically, the researchers identified 147 regions that varied consistently among freshwater and marine sticklebacks. About 80 percent of the changes involved regulatory regions, controlling when, where and how genes are expressed.

“This addresses a classic debate in evolutionary biology,” says professor of developmental biology David Kingsley, PhD, the senior author of the study, which was published April 5 in Nature. “How do new traits evolve in natural populations? Do they arise through mutations in the coding regions of genes, which alter the structure and function of encoded proteins? Or are new traits the result of modifications in the regulatory regions of genes, which control where and when already-established proteins are expressed?”

In sticklebacks, at least, the balance is tilted toward the regulatory regions.
— Krista Conger


Cancer drug redux

A tweak to the structure of the naturally occurring cancer-curing protein interleukin-2 could overcome its major limitation: terrible side effects. It cures many cancers, but it also causes fluid to build up in the lungs and severe difficulty in breathing.

Christopher Garcia, PhD, professor of molecular and cellular physiology, and his group produced a vast variety of mutated versions of the protein, eventually obtaining one, dubbed Super-2, which in laboratory tests outperformed natural IL-2 by a wide margin in halting tumor growth. Moreover, in an animal model, Super-2 caused much less fluid buildup in the lungs. They published their study April 26 in Nature.

A group at the National Institutes of Health is now testing Super-2 further, in the hope of fast-tracking its development as a new therapy. — Bruce Goldman

Campaign for Stanford Medicine

Stanford University President John Hennessy in May announced the launch of the $1 billion Campaign for Stanford Medicine, half of which already has been committed.

The campaign will help fund the construction of a new Stanford Hospital and make investments in research and teaching. The new hospital, to be built on the current site, will replace aging facilities, incorporate advanced technologies and bring the medical center up to state seismic standards. The hospital will also greatly expand its space for treating major trauma and other emergencies.

“Providing the most advanced health care possible to people — locally, nationally and globally — will be one of the great challenges of this century,” Hennessy said at the announcement. “The Campaign for Stanford Medicine draws upon our particular strengths — the proximity of the university to its hospitals and clinics — to focus on this issue and better serve the public. It will allow us to seek solutions to some of medicine’s most daunting problems, and it will begin in our own community with the new Stanford Hospital.”

Three funda-mental partners have made gifts of $50 million each to the campaign: Tashia and John Morgridge, Anne and Robert Bass, and the Redlich family. In addition, seven companies — Apple, eBay, Hewlett-Packard, Intel, Intuit, Oracle and NVIDIA — have committed a total of $175 million.

While a major portion of the campaign — $700 million — will support the new hospital, the remaining $300 million will fund research and teaching initiatives at the School of Medicine. A parallel fundraising campaign supports child health programs and an expansion of Lucile Packard Children’s Hospital, which will eventually double in size. — Ruthann Richter

Altitude adjustment


“A really nasty hangover” is how Grant Lipman, MD, describes the feeling of acute mountain sickness. So it shouldn’t be surprising that a widely used hangover remedy, ibuprofen, prevents altitude sickness.

In a study led by Lipman, a clinical assistant professor of emergency medicine, 58 men and 28 women ascended California’s White Mountains to test ibuprofen’s impact on the condition, which in severe cases can be fatal if untreated. They started at 4,100 feet, taking either 600 milligrams of ibuprofen or a placebo at 8 a.m., and headed up in cars to 11,700 feet, where they had a second dose at 2 p.m. Then they hiked to 12,570 feet and had a third dose at 8 p.m., before spending the night on the mountain.

Ibuprofen cut the incidence of altitude sickness by 26 percent and reduced symptoms overall. The study was published in the June issue of Annals of Emergency Medicine. — John Sanford

Stop lecturing me

Despite dramatic changes in the medical world over the past century, medical education still relies on the traditional lecture format. It’s time for that to change, say the authors of “Lecture halls without lectures,” in the New England Journal of Medicine. In the May article, co-author Charles Prober, MD, senior associate dean for medical education, proposes replacing most lectures with short online videos, which would free up class time for more interactive education.

“Teachers would be able to actually teach, rather than merely make speeches,” the authors write.

Stanford’s core biochemistry class tested the method this year: Students watched short videos on their own time and used classes to discuss clinical vignettes highlighting the biochemical bases of diseases.

“Student reviews of the course improved substantially from the previous year, and class attendance increased from 30 to 80 percent, even though class attendance was optional,” they write. — Tracie White

Low-cost cancer scan


Tens of thousands of people die needlessly each year in developing countries from mouth cancers that could have been detected early with regular dental checkups. But with fewer than one dentist per 100,000 people in the world’s rural areas, that’s not an option. Now an ultra-low-cost device being developed at Stanford and tested this summer in India may enable early diagnosis.

Invented by Manu Prakash, PhD, assistant professor of bioengineering, and his team, the device attaches to a smartphone’s built-in camera, providing a high-resolution, panoramic image of the inside of a mouth. Illuminated by a blue fluorescent light, malignant cancer lesions show up as dark spots on the image, which could be sent to dentists or oral surgeons wirelessly.

The scanner is designed for mass production, with an estimated material cost of just a few dollars. — Kris Newby

Zombies among us


New Stanford research shows that about 3.6 percent of American adults — or around 8.4 million — are prone to sleepwalking. The study is the first to use a large, representative sample of the U.S. general population to demonstrate the number of sleepwalkers (19,136 adults in 15 states were surveyed), and the researchers say the findings underscore the fact that sleepwalking is much more prevalent in adults than previously appreciated.

Maurice Ohayon, MD, DSc, PhD, a professor of psychiatry and behavioral sciences, and his colleagues also found an association between nocturnal wanderings and certain psychiatric disorders, such as depression and anxiety. They published their study May 15 in the journal Neurology. — Michelle L. Brandt

Heart-test excess

Left ventriculography, an invasive imaging procedure that measures heart function, is dramatically overused, according to a new Stanford study. The procedure adds both risk and cost, says co-author Ronald Witteles, MD, assistant professor of cardiovascular medicine, calling the rates of unnecessary use of the test “shockingly high.”

The procedure was developed 50 years ago to assess heart function by measuring its ejection fraction — the percentage of blood in the heart’s left ventricle that gets squeezed out with each beat. But over the years, several less-invasive and often superior methods of measuring ejection fraction have emerged, such as echocardiograms and nuclear cardiac imaging.

For the new study, the researchers examined a national database of about 96,000 patients who in 2007 had a coronary angiography — a procedure for imaging the coronary arteries. During a coronary angiography, cardiologists insert a catheter into a blood vessel in the patient’s arm, groin or neck, thread it into a coronary artery, and fill it with dye to release in the bloodstream. Cardiologists perform left ventriculography, which costs about $300, as an add-on to angiography, advancing a catheter from the artery into the left ventricle.

Suspecting that left ventriculography was overused, the researchers zeroed in on the 37,000 coronary angiography patients who had previously undergone one of the new methods of measuring ejection fraction. Surprisingly, 88 percent of those patients went on to get a left ventriculography.

“If a patient recently had an echocardiogram or a nuclear study, it didn’t make them less likely to have the left ventriculography procedure — it made them more likely,” Witteles says. “That is impossible to explain from a medical justification standpoint.”

The study was published in the American Heart Journal in April. — Tracie White








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