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Cardiovascular Medicine

Behavioral Science, Cardiovascular Medicine, Neuroscience, Research, Stanford News

Scientists zero in on brain’s sigh-control center

Scientists zero in on brain's sigh-control center

sighWhy do we sigh?

(Sigh…) How should I know? Don’t I already have enough on my mind?

As we all well know, sighing is a long, deep involuntary inhalation accompanying sensations of yearning, sadness, relief, boredom, exhaustion, or (see above) exasperation. Fewer of us know (at least I didn’t, but now I do!) that the typical person also sighs spontaneously about every five minutes or so.

If you’re a mouse, you do it much more often – as much as 40 times per hour. (Nobody said it would be easy, little mousie.)

Those spontaneously sighs (and all the other ones), it’s thought, may be helping to keep our half-billion or so alveoli – the tiny sacs through which our lungs exchange oxygen and carbon dioxide with the atmosphere that surrounds us – pumped up and operating efficiently.

That could be, at least in part, why we sigh. But Mark Krasnow, MD, PhD, Stanford biochemist and molecular biologist and Howard Hughes Medical Institute Investigator, has figured out how.

In a series of experiments described in a Nature study, Krasnow’s team, along with colleagues at Stanford and UCLA, painstakingly employed genetic, pharmacological and surgical techniques to map out a precise set of nerve circuits in the brain that are essential to the act of sighing. They showed that a sigh results when inhalation-initiating nerve impulses generated rhythmically within these circuits double up: One impulse effectively laps another and rides piggyback on top of it, producing a deeper, drawn-out inhalation.

The experiments were performed in mice. But the brain circuits involved are sufficiently ancient that our common ancestors no doubt had them, too – and therefore we (probably) do, too, or at least very similar ones.

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Cardiovascular Medicine, Patient Care, Pediatrics, Pregnancy, Stanford News

World-first treatment for rare heart defect saves baby born at Packard Children’s

World-first treatment for rare heart defect saves baby born at Packard Children's

Group shot Liam and doctorsLinda Luna was five months pregnant with her first child when she got the bad news: Ultrasound scans showed a deadly defect in her baby boy’s heart. He had a 90 percent chance of dying before or just after birth. But thanks to a groundbreaking treatment at Lucile Packard Children’s Hospital Stanford, two-month-old baby Liam, who just went home to San Jose last week, is beating those odds.

He is the first baby in the world successfully treated with prenatal maternal hyper-oxygenation for his rare heart defect: congenital Ebstein’s anomaly. This week, several local news outlets report on the success of Liam’s case.

The problem at diagnosis? Due to severe leaks in two heart valves, blood flowed backward through the right half of Liam’s heart. His heart became dangerously enlarged. Too little blood reached his lungs and the rest of his body. Left untreated, the defect would cause irreparable heart and lung damage.

“Once you see type of leakage Liam had, it’s usually a progressive process,” said Theresa Tacy, MD, the fetal cardiology specialist who treated Liam in concert with his mom’s high-risk obstetrician, Katherine Bianco, MD, and a team of other specialists from across the hospital. “It just gets worse,” Tacy said. “The fetus eventually develops heart failure and dies.”

The team gave expectant mom Luna 12 hours per day of oxygen therapy for the last three weeks of her pregnancy. The idea was to relax Liam’s lung blood vessels with the extra oxygen he’d get from his mom. This would make it easier for his heart to pump blood forward into his lungs and, the doctors hoped, let him survive until birth and surgery.

Ebsteins vs normal by Tacy“We were trying to offer Liam’s parents hope but also remain realistic that their baby had a very high chance of not making it,” said cardiologist David Axelrod, MD, who cared for Liam in the cardiovascular intensive care unit after he was born. “We knew that even if he made it through pregnancy, his risk of dying during his first few days of life was very high.”

Immediately after his Nov. 22 birth, the doctors put Liam on an ECMO machine that delivered oxygen to his blood. Cardiothoracic surgeon Frank Hanley, MD, also closed a blood vessel near the heart to help Liam’s blood to flow forward. Finally, 11 days later, Liam was strong enough for a Dec. 3 surgery in which Hanley fully repaired his heart.

“It was a huge operation for a tiny baby fighting for his life,” Luna said. “The seven-hour wait during surgery was the longest wait of my life, but when they finally wheeled him out, he was a different baby. We were so thankful.”

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Big data, Cardiovascular Medicine, Health and Fitness, Obesity, Research

High BMI and low fitness linked with higher hypertension risk

High BMI and low fitness linked with higher hypertension risk

USMC-120412-M-UY543-003Unfit adolescents who have a high body mass index are more likely to suffer from hypertension when they are older than their peers, according to a new study from researchers at Stanford and Lund University in Sweden.

The paper, the first to discover this connection, was published today in JAMA Internal Medicine.

Lead author Casey Crump, MD, PhD, who recently left Stanford to join the Mount Sinai School of Medicine in New York, and his colleagues tapped a unique data source to uncover the relationship: the Swedish military. In the past in Sweden, all males had to join the military at age 18, and Crump and his team examined fitness and health records from more than 1.5 million military conscripts between 1969 and 1997. Thanks to the Swedish national health-care system, they were also able to obtain follow-up information to see when and if adults were diagnosed with hypertension.

I exchanged emails about the study with Crump, who is vice chair for research in the Department of Family Medicine and Community Health; below is our conversation.

Why did you decide to look at this?

Low physical fitness and obesity are very common, modifiable, and have an enormous public health impact.

What is the primary lesson from this work?

We found that both overweight/obesity and low aerobic fitness at age 18 were linked with higher long-term risk of hypertension in adulthood. Importantly, low aerobic fitness was a strong risk factor for hypertension even among those with normal body mass index (BMI). These findings suggest that interventions to prevent hypertension should begin early in life and include not only weight control but also aerobic fitness, even among persons with normal BMI.

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Cardiovascular Medicine, Patient Care, Pediatrics, Stanford News, Transplants

NBC Dateline to explore the “extraordinary situation” facing one Packard Children’s transplant family

NBC Dateline to explore the "extraordinary situation" facing one Packard Children's transplant family

Bingham family - 560

It’s a story that seems a bit hard to believe.

Stacy and Jason Bingham of Haines, Oregon, have five beautiful children — Sierra, Megan, Lindsey, Hunter, and Gage. Unfortunately, as written about on Scope previously, three of the kids have been hit with cardiomyopathy, a life-threatening disease of the heart muscle that reduces the heart’s ability to pump blood effectively. Two other children are being monitored for heart irregularities.

The result? The eldest, 16-year-old Sierra, has received two heart transplants at Lucile Packard Children’s Hospital Stanford, one in 2006 and a replacement in 2015. Lindsey, 12, had a heart transplant in 2013. Gage, 7, was recently placed on a Heartware ventricular assist device in order to support his failing heart. He is now awaiting placement on the transplant list. Meanwhile, cardiologists are keeping an eye on any potential problems that could be faced by Megan, 14, and Hunter, 9.

“This is an incredibly strong and wonderful family, and they’re facing an extraordinary situation,” said David Rosenthal, MD, director of the pediatric heart failure program at Packard Children’s.

This Sunday, January 17, at 9 PM Pacific, Dateline NBC will be presenting their second national broadcast looking at the personal and medical journey the Binghams have faced, along with the many challenges ahead. In addition, the program will reveal some of the advanced therapies for heart failure offered by the Heart Center at Stanford Children’s Health.

The first Dateline NBC program on the Bingham family, which aired in 2013, can be viewed here.

Robert Dicks is senior director of media relations for Lucile Packard Children’s Hospital Stanford.

Previously: Ventricular assist device helps teen graduate from high schoolStem cell medicine for hearts? Yes, please, says one amazing family and Packard Children’s heart transplant family featured tonight on Dateline
Photo by Norbert von der Groeben

Biomed Bites, Cardiovascular Medicine, Research, Videos

The birth of Bio-X: A behind-the-scenes tale from its first director

The birth of Bio-X: A behind-the-scenes tale from its first director

Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative biomedical researchers.

Before all things “x”, there was Bio-X, Stanford’s groundbreaking interdisciplinary facilitator. But did you know it got its start thanks to a quest to understand myosin, the molecular motor that drives cellular movement?

Neither did I, until I watched this video with James Spudich, PhD, professor of biochemistry. Here he tells the tale, which involves a unique collaboration — and student exchange — between the Departments of Biochemistry and of Physics, and between Spudich and Bio-X co-founder Steven Chu, PhD (the former U.S. Secretary of Energy and Nobel laureate), a partnership that produced insight into the functioning of myosin as well as Bio-X.

“We had to invent new ways to approach the problem in order to understand how these motors really work,” Spudich says in the video above.

Invent new ways, they did. And now, that invention has given birth to scores more.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: Stanford molecular-motor maven Jim Spudich wins Lasker Award, Close-up look at mutinous mutant molecule implicated in hypertrophic cardiomyopathy and They said “Yes”: The attitude that defines Stanford Bio-X

Cardiovascular Medicine, Pediatrics, Transplants

Unusual bridge-to-transplant method helps teen get new heart and lungs

Unusual bridge-to-transplant method helps teen get new heart and lungs

bridge-to-transplant device
Earlier this year, Oswaldo Jimenez’s heart and lungs were failing. He needed a combined heart-lung transplant, but his doctors at Lucile Packard Children’s Hospital Stanford were worried that the 14-year-old from Salem, Oregon might not survive the wait for donor organs.

Stanford physicians have lots of experience with using external and implanted pumps that can support a patient’s failing heart. A few years ago, for instance, an 8-year-old patient spent 229 days with a Berlin Heart pump that moved blood through her body while she awaited a heart transplant.

Oswaldo’s case was different. Although his heart failure was significant, his failing lungs posed the biggest risk to his health. His doctors were concerned that his poor lung function would immobilize him – yet to benefit from transplanted lungs, he needed to stay fairly fit and mobile while he waited.

So the doctors decided to try an unusual bridge-to-transplant procedure called a “pulmonary to left atrial shunt,” which connected Oswaldo’s heart to a portable box outside his body that oxygenated his blood. Essentially, the team gave Oswaldo a temporary, artificial lung.

A press release from the hospital explains how it worked:

The procedure involved the insertion of a tube that redirected blood away from Oswaldo’s lungs into the oxygenator. This, in turn, provided oxygen to the blood and then returned it to his body, with his own heart providing the pump. Reports on this shunt device being able to sustain patients’ lives range from several weeks to six months, depending mostly on being able to prevent the blood from clotting while avoiding complications such as bleeding or stroke.

On July 12, Oswaldo made history by becoming the first child in the western United States to undergo this treatment — it saved his life and bought him time. Then, just one week after receiving the shunt, donor organs became available. Oswaldo received his heart and lung transplant on July 19.

Oswaldo is still recovering at the Ronald McDonald House, and his doctors think he’ll be able to go home close to the New Year. He’s looking forward to being a kid again, and his grateful family is thinking about how his case might benefit other kids in similar situations. “Now the doctors can use this therapy to treat other patients,” said Oswaldo’s mom, Carmen Hernandez.

Previously: Stem cell medicine for hearts? Yes please, says one amazing family, “Liberated from LVAD support”: One patient’s story and Image of the Week: First heart-lung transplant
Image of pulmonary to left atrial shunt courtesy of Lucile Packard Children’s Hospital Stanford

Cardiovascular Medicine, Education, Patient Care, Stanford Medicine Unplugged

Pathology vs. patients: Balancing morbid fascination with heart-felt care

Pathology vs. patients: Balancing morbid fascination with heart-felt care

Stanford Medicine Unplugged (formerly SMS Unplugged) is a forum for students to chronicle their experiences in medical school. The student-penned entries appear on Scope once a week during the academic year; the entire blog series can be found in the Stanford Medicine Unplugged category.

3690107655_eef7c24702_zI recently saw a patient who, against all odds, survived an aortic dissection. Miraculously, he was alive after the wall of his aorta — the largest and most important vessel in the body — began to rip apart. Aortic dissections are so violent and agonizing that a large portion of these patients don’t survive. Yet somehow, my patient was still able to sit upright in his chair and recount his story to me just a day after his surgery, a testimony to how far medicine has advanced and to how lucky he was.

I admit that I was more fascinated by his cardiovascular travails than I was concerned by his suffering and the long road of recovery awaiting him. After all, it was only a few months prior that we learned the pathophysiology of aortic dissections. And now in front of me was a real life case study accompanied by authentic lab values, imaging, and physical exam findings, all of which were free for me to probe.

Had I encountered him prior to medical school, I would have spent more time to express words of support and sympathy — he’s a survivor and he needed any and all means of encouragement to return to some semblance of normalcy.

Once we have reached the end of the journey, the patient himself is buried underneath our medical knowledge and the disease has seized all our attention.

But medical school, for better or worse, changes your perception of patients and their plights. Despite all the efforts in the curriculum to teach us to view the patient as a whole, the endless nights and sacrificed weekends of burying ourselves in textbooks and scrambled jargon eventually dehumanizes patients and forces the spotlight on the pathology.

Call it insensitivity or callousness, but this morbid fascination with human illness is one of the paradoxes in medicine — that we must sympathize with the patient as well as with the disease that is harming him and may eventually kill him.

And for better or worse, becoming a competent doctor requires some modicum of this perverse curiosity, a veritable double-edged sword. Anyone who lacks it would simply not be able to survive four years of college dedicated mostly to studying basic biology, another four years of medical school to studying clinical presentations, and then finally another handful of years to specialize, all the while taking on hundreds of thousands of dollars in debt and sacrificing young adulthood. Yet, insidiously, once we have reached the end of the journey, the patient himself is buried underneath our medical knowledge and the disease has seized all our attention.

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Cardiovascular Medicine, Chronic Disease, Dermatology, Research, Stanford News

Limb compression device reduces skin infections caused by lymphedema

Limb compression device reduces skin infections caused by lymphedema

Key among the nasty problems caused by lymphedema, a common cardiovascular disease that causes limb and trunk swelling, is the risk of skin infection. Lymphedema causes the skin to thicken and become inelastic, which open the doors for infection to enter more easily; according to Stanford’s Stanley Rockson, MD, about 25 percent of lymphedema patients experience recurring infections that can result in hospitalization.

Thus the results of a recent study published in JAMA Dermatology offers some exciting news, says Rockson, a world renowned expert in lymphedema.

The fact that we saw dramatic reductions in the incidence in rate of infections… is very noteworthy

In the study, an advanced model of a pneumatic compression device used to treat lymphedema was found to reduce skin infections from the disease by nearly 80 percent. Rates of cellulitis, the medical term for such skin infections, were lowered from 21 percent to 4.5 percent in the people with lymphedema due to cancer and from 28.8 percent to 7.3 percent in individuals whose lymphedema was not due to cancer.

Pneumatic compression devices, which have been in use for decades, are inflatable garments that when applied to the swollen area of the skin inflate and deflate in cycles to help drain lymph fluid build up. Most of these devices simply apply an increasing degree of pressure from the garment, but the model used in this study goes a step further. As Rockson, a co-author on the study, explains in a podcast accompanying the journal article:

This device works not just by adding pressure… It actually intends to simulate the intervention used by physical therapists when they do manual lymphatic massage. It places very low pressure stress on the skin increasing the filling of the lymphatic capillaries and thereby stimulating intrinsic contractility.

The idea is that the distribution of the pressure can be relegated and the treatment more targeted, he says.

“The fact that we saw dramatic reductions in both the incidence in rate of infections as well as the decreases in cost-related to care, ER visits, hospitalizations, intravenous antibiotics, is very noteworthy,” Rockson concludes.

The research was conducted at the University of Minnesota School of Public Health in collaboration with Vanderbilt University School of Nursing.

Previously: Home health care treatments for lymphedema patients cut costs and improve care; New Stanford registry to track lymphedema in breast cancer patients.

Cardiovascular Medicine, Patient Care, Surgery

61-year-old grandfather gets new heart valve at Lucile Packard Children’s Hospital Stanford

61-year-old grandfather gets new heart valve at Lucile Packard Children's Hospital Stanford

Dr. George Lui, M.D., Dr. Dan Murphy, M.D., Mr. Sang Hee Yoon, Mrs. Min Wha Yoon, and Dr. Katsuhide Maeda, M.D. at Stanford Children’s Health Care on Tuesday, October 6, 2015. ( Norbert von der Groeben/ Stanford School of Medicine )One little-known fact about children’s hospitals: A number of their patients are not children.

I wrote about one such patient recently, a 61-year-old San Jose grandfather who received a new heart valve at Lucile Packard Children’s Hospital Stanford in May. Sang Hee Yoon was born in South Korea at a time when many babies with heart defects died in infancy. He was one of the first people there to receive a surgical repair for his heart condition, called tetraology of Fallot. The repair worked well for many years, but eventually he needed a replacement for a malfunctioning heart valve.

When the time came, the doctors on our adult congenital heart disease team were here to help. My story explains the unusual challenges of their field, which is growing rapidly as 20,000 teenagers with congenital heart defects “graduate” to adult medical care each year:

“Patients come back at 40 or 50 years old, telling us, ‘My doctor said I was cured,’” said George Lui, MD, medical director of the Adult Congenital Heart Program at Stanford, a collaboration between the Heart Center at Lucile Packard Children’s Hospital and Stanford Health Care. Some patients’ childhood surgical repairs were initially judged so successful that they never expected to return to a cardiologist, said Lui… In other cases, the first surgery was so unusual and risky that the surgeon discouraged the patient from undergoing further operations.

But most adults with repaired congenital heart defects are not cured, doctors have learned. As the discipline has matured, cardiologists have honed their understanding of how to help patients like Yoon navigate the risks of living with lingering heart problems, as well as learning how congenital defects interact with cardiovascular problems people acquire with age.

Mr. Yoon’s new heart valve has made a big difference – he and his wife told me that his health is better than ever before. Prior to his surgery at Stanford, his malfunctioning heart valve meant that his body never quite got enough oxygen. He often felt achy or had tightness in his chest, especially at high altitudes. All that is resolved now. The couple’s four children and 10 grandchildren are thrilled:

“They are so happy about my condition,” [Yoon] said. “Not only family members but everybody I know is saying, ‘You look so healthy!’” The Yoons have already visited Kings Canyon National Park, a destination they chose for its mountainous scenery. “I feel such gratitude that now I can enjoy my new life,” Yoon said.

Previously: Patient is “living to live instead of living to survive” thanks to heart repair surgery, Little hearts, big tools and Surgeon building a heart valve that can grow and repair itself
Photo – of Mr. and Mrs. Yoon with his doctors (from left to right) George Lui, MD, Daniel Murphy, MD, and Katsuhide Maeda, MD – courtesy of Lucile Packard Children’s Hospital Stanford

Cardiovascular Medicine, Public Health, Research, Stroke

In study, work stress linked to stroke risk

In study, work stress linked to stroke risk


High-stress jobs are known to be associated with increased risk of cardiovascular disease. A research study published last week in the journal Neurology now indicates that work stress also increases the risk of stroke, especially for women.

Dingli Xu, MD, and his research team from Southern Medical University in Guangzhou, China performed a comprehensive statistical analysis of six previous research studies on job stress and stroke risk; the studies included a total of 138,782 participants who were followed for three to 17 years. For the work they classified jobs into one of our four categories, based on the amount of control workers have over their jobs and the psychological demand of their jobs:

  • Passive jobs with low control and low demand, such as janitors and other manual laborers
  • Low-stress jobs with high control and low demand, such natural scientists and architects
  • High-stress jobs with low control and high demand, such as waitresses and nursing aids
  • Active jobs with high control and high demand, such as physicians, teachers and engineers

Xu’s team determined that people with high-stress jobs had a 22 percent increased risk of all types of stroke compared to people with low-stress jobs, while there was no increased relative risk of stroke for people with passive or active jobs. The increased risk associated with a high-stress job compared to a low-stress one was found to be even greater at 58 percent for ischemic strokes, the most common type of stroke.

Analyses were also performed separately for women and men, including more than 126,459 women and only 12,323 men. Women with high-stress jobs had a 33 percent higher risk of all types of stroke than women with low-stress jobs. However, no significant increase in relative stroke risk was seen for men with high-stress jobs, most likely due to the limited number of men included in the studies.

Similarly, the researchers calculated the increased incidence of stroke in the population associated with high-stress jobs to be 4.4 percent overall and 6.5 percent for women.

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