As another year comes to a close we’d like to look back at the fascinating research breakthroughs and inspiring patient stories from 2011. ScienceLife ran 168 posts this year, and while we wish we could highlight all of them, here are a handful of our favorites from each month.

January

Patrick Wilson found out that the H1N1 virus could end up helping us fight all types of flu. Stephen Pruett-Jones studied how some male birds mimic the sounds of predators to pick up the ladies (with an audio clip). We interviewed David Gozal about his study on the link between childhood obesity and lack of sleep, and took a look at NCAA regulations mandating sickle cell testing for athletes.

February

Harold Pollack gave a lecture on why violent crime in urban, minority communities should be considered a public health epidemic. Siri Atma Greeley studied the actual medical benefit of widespread genetic testing. Stacy Lindau wanted to know why so few women get help for sexual problems after surviving cancer. We talked to Bana Jabri about the causes of celiac disease, and Sliman Bensmaïa showed us how the brain processes the basic elements of touch very much like it handles visual information.

March

Sola Olopade educated women in Nigeria about using clean-burning stoves to prevent indoor pollution. Stefano Allesina and Jonathan Levine looked at how rock-paper-scissors helps explain evolution. Joshua Miller went to Yellowstone Park to see what stories the ghostly bones of animals can tell, and Scott Eggener questioned the wisdom of indiscriminate prostate cancer screening.

Photo by Gerald Waddell

Andrea King studied the wide range of responses to drinking alcohol, and why it can be fun for some people and a bummer for others. Cheryl Reed took a ride in a helicopter with our UCAN nurses. Kamal Sharma looked at the genes that control animals’ gait, and Ningqi Hou studied how urban environments can dictate how much exercise people get.

May

Daniel McGehee looked at the long-term effects of nicotine on the brain. Habibul Ahsan went to Bangladesh to study the health impacts of accidental exposure to arsenic in drinking water. The brain’s overlooked supporting cells got their due at a conference on neuroscience, and we remembered a landmark discovery about a once popular drug taken during pregnancy that we now know can cause cancer.

June

As we headed into summer, Diana Lauderdale used Google to track MRSA. We learned about an extraordinary transplant where a man received a new heart, liver AND kidney. Daniel Geynisman gave us the rundown on whether or not cell phones are killing us (they’re not, as long as you don’t use them in the car), and some UChicago undergrads studied what happens to gorillas on the birth control pill.

July

We spoke to Donald Jensen and Andrew Aronsohn about the new outlook for patients with hepatitis C. Igor Schneider made a time machine to find the genetic switch for limb development. Farr Curlin led a study about the benefits of addressing spiritual needs alongside medical care, and Adam Cifu looked at the phenomenon of scientific study reversals.

August

Stefano Allesina dug into the long, shady history of nepotism in academia in Italy. John Schneider talked about his work addressing sexual health and stigma in India. Michael Becker discovered a new treatment for the Royal Disease, and we had the rare chance to name check a Spiderman villain in a post.

September

Martha McClintock and Suzanne Conzen studied the connection between social isolation, stress and breast cancer. Gallego Romero traveled to India to search for the origins of lactose intolerance. Stephanie Dulawa developed a mouse model for OCD, and Paul Vezina looked at a different kind of obsession, compulsive gambling.

October

Arshiya Baig started a pilot project to help people learn about life with diabetes through pictures. Manyuan Long found that some of the youngest genes are in the brain. Jens Ludwig and Stacy Lindau published a landmark study about the connection between neighborhood poverty and health, and Issam Awad studied a rare brain disease that soon could be treated with a drug instead of surgery.

November

Cathy Pfister and Tim Wootton figured out how to use seashells to track climate change over the years. Lianne Kurina found a link between loneliness and sleep quality. Shantanu Nundy, Monica Peek and Marshall Chin developed a program to send text message reminders to people with diabetes, and Pan Chen looked at the links between childhood abuse and aggressive behavior in adults.

December

Inbal Ben-Ami Bartal, Jean Decety and Peggy Mason discovered that rats can show empathy for their fellow rats in distress. Maciej Lesniak performed a scary but amazing brain surgery on a patient who was awake. Cathryn Nagler searched for the source of food allergies within our bodies, while Stafano Guandalini uncovered the challenges in educating doctors about one of those allergies, celiac disease.

Whew. Hope you were able to click through at least a few of those. We look forward to another great year of research in 2012. We’re taking a break next week, but we’ll be back on January 5. Happy holidays!

When scientists picture the miniature machines that live inside cells, they often have to settle for indirect evidence and a bit of imagination. Proteins on the nanoscale - one million times smaller than a millimeter - can’t be seen with your typical microscope, so scientists turn to electrical measurements, genetic mutations, and chemical assays to deduce a rough sketch of their target’s structure. More recently, tools such as X-ray crystallography and electron microscopes have allowed scientists to see cellular proteins. But both techniques require steps that change the natural environment of the protein, and can only offer a single photograph rather than a “movie” of its dynamic changes in shape.

So when Joanna Gemel, a research associate assistant professor in the laboratory of Eric Beyer, decided to look at the structure of cellular proteins called connexins and the channels they form, she wanted a different option. Connexins are found within the membrane of a cell in groups of 6, called connexons or hemichannels. When two cells come into contact, their connexons “dock” with each other to form a pathway between the two cells called a gap junction channel. In organs such as the heart or smooth muscle, gap junctions play an important role by facilitating the rapid passage of ions and small molecules from cell to cell.

“Gap junctions are critical for the propagation of electrical impulses in the heart. Abnormalities or mutations in them can cause a lot of problems, such as arrhythmias and atrial fibrillation,” said Gemel, author of a recent paper in The Journal of Biological Chemistry. “We decided that we would like to do something different. Since we never see channels, we asked what would be the best way to see channels and learn more about them?”

The question led them to the Center for Nanomedicine, a laboratory run by Michael Allen, a research associate assistant professor in the Department of Medicine. Allen’s tool of choice is atomic force microscopy, a technology invented in the mid-1980’s that remains useful for the visualization of the very, very small. The method, known as AFM for short, uses a strategy similar to an old record player: an extremely tiny needle (2 nanometers at its tip) moves slowly across the surface of a sample, creating a topographic map of the molecular landscape.

“AFM is really good at measuring height, the resolution in the z-axis,” Allen said. “With AFM we can look at 3-dimensional architecture, and in the z-axis the resolution is a tenth of a nanometer.”

But before tapping the potential of AFM, Gemel had to first create a stretch of membrane containing only the connexin she wanted to study, a form called connexin40 that is expressed in certain regions of the heart. Through painstaking transfection, purification, and reconstitution, Gemel produced a layer as thin as a cell membrane, swarming with connexin proteins. After imaging with the microscope, the researchers produced images (like the one posted above) that resembled dense mountain ranges viewed from an airplane, bumps floating in a dark field. Remarkably, the individual subjects and even the channel opening - narrow enough to pass individual atoms - were visible, not unlike the cartoon representation of gap junctions seen in textbooks.

With the extremely fine resolution of the AFM needle, Allen and Gemel set about measuring the heights of individual objects in their sample. Even though they knew that connexin40 was the only protein present in the membrane, their images contained particles of two different heights: some “bumps” were roughly 2.5 nanometers tall, and others were approximately 4 nanometers in height. They subsequently showed that the two different-sized bumps corresponded to whether the asymmetric hemichannels were facing inward or outward in the membrane.

“While it was something that we did not expect, it was an accomplishment to be able to monitor channels from both sides,” Gemel said.

read more

By John Easton

Let’s start with a statistic: almost 2,000 citations a year. One paper by Paul Meier, the Ralph and Mary Otis Isham Distinguished Service Professor emeritus of statistics, pharmacological and physiological sciences, medicine, and the college, has been cited more often, by a wide margin, than any other paper in the field. At last count it was the fifth most cited research paper of all time, in any field. With about 34,000 citations to date, Kaplan, E. L., and Meier, P. (1958), “Nonparametric Estimation from Incomplete Observations,” has been cited by another scientific publication about once, on average, for every day of Meier’s long life—he was born in 1924—and still counting.

Sadly, however, that ratio can only increase. Citation counting will continue, but the numbering of days stopped on Sunday, August 7th, when Professor Meier, a world-class statistician who made “extraordinary contributions to statistics and to society,” according to Columbia University - and everyone else - passed away peacefully at his Manhattan home.

The Kaplan-Meier estimator is used ubiquitously in medical studies to estimate and depict the fraction of patients living for a certain amount of time after treatment. This is not as simple as it sounds. Survival curves are complicated by the uncooperative way in which research subjects often behave. Some leave a study part of the way through. Others elect not to die before the study ends. These are known as “censored observations.” The Kaplan-Meier estimate is a simple way to compute the survival curve despite such troublesome behavior.

There was almost a Kaplan estimator and a Meier estimator. Each had submitted a separate manuscript to the Journal of the American Statistical Association, but the editor recommended that their papers be combined into one. It took them four years. “At one place he solved a problem that I couldn’t solve,” Meier later recalled in an interview [pdf]. “Other places I solved problems he couldn’t.” Finally published in 1958, it was only cited 25 times over the next ten years. Then, boosted by statisticians’ increased computing power, it caught on. It has since been applied to data from clinical trials of therapies for every disease from cancer to cardiology to concussion.

Friends and colleagues point out that this was only one of Meier’s fundamental contributions. He published many more studies, was a persistent and outspoken advocate for randomization in clinical studies, helped design some of the 20th Century’s most important clinical trials and trained many of the leaders in the field.

“Paul was a friend and colleague as well as one of the most influential statisticians of an important era,” recalled Stephen Stigler, the current chair of statistics at the University of Chicago. “He left an indelible mark on us, and through his research on the world’s clinic analytical practice. He will be missed and cannot be replaced.”

“I have been so fortunate and privileged to know this truly great, wonderful, helpful, kind man who was always so generous with his skills and wise advice,” said toxoplasmosis expert Rima McLeod, professor of ophthalmology and visual sciences at the University. “He is one of the founding fathers and giants of statistics in the past century. He was at the same time simply a modest, helpful, supportive and warm colleague who only let you know how special he was by the quality and content of what he said and wrote.”

read more

Ozzie Rivero (left) stands ready with a cardiogenic flush as Mark Russo, MD, preps the heart for transport

By Dianna Douglas

Ozzie Rivero found out early Tuesday afternoon that a young patient at a community hospital in Chicago had died on life support. The patient’s heart was still beating as a machine filled his lungs with air, but he would never open his eyes again. In their grief, his family was willing to give his organs to others.

The University of Chicago Medical Center had a patient near the same age with the same blood type at the top of the list for a heart.

Ozzie Rivero had to get that heart from a dead patient to a barely living one.

Rivero is a manager of organ procurement, part of the team that coordinates the collection of hearts, lungs, kidneys, livers, and pancreases from deceased donors for transplant at the Medical Center.

The community hospital told Rivero that he could come for the heart in a few hours, when an operating room was available. Maybe 10:30 p.m. At the moment, the ER was crowded with people suffering through the summer heat wave and all the ORs were full.

Two surgeons prepared to perform heart surgery at the same time: Mark Russo, MD, would go to the community hospital with Rivero to remove the heart and Jai Raman, MD, would put the heart into his patient.

A nurse called Raman’s patient and explained that there was a possibility of getting a heart. But only a possibility. Raman’s patient came to the Medical Center, and got ready for surgery.

At 8:30 p.m., the community hospital delayed Rivero - more major trauma cases were in their operating rooms, and the procurement would have to wait until at least midnight.

At 9:30 p.m., the hospital delayed Rivero again, this time until after 1 a.m.

Raman’s patient waited, along with the nurses, anesthesiologists, physician assistants, transporters, and residents who stood ready for one of the most complex surgeries performed at the Medical Center.

At 12:30 a.m., Rivero walked out of the hospital toward a white SUV idling in a cul-de-sac on 58^th Street, the air conditioning on full blast against the swampy night air. “Hey Herb,” he said to the driver as he opened the back and tossed in a duffel bag and a red cooler full of ice.

The car pulled away from the hospital as Rivero’s cellphone rang—it was Operating Room 16, where all the heart transplants happen. They wanted an update. “You can put the patient to sleep,” Rivero said.

Rivero called Raman, who had gone home in the hope of getting a little time with his family before the marathon surgery began. “They’re putting the patient under,” he said. Raman thanked him for the update and prepared to come back in to the hospital.

Many organ procurements are at night, when ORs are otherwise empty and grieving families have gone home. Rivero skips a lot of sleep in his job, and has seen many of his colleagues give up. “The turnover is high when you never get to meet the recipients or see the success stories,” he said. “We don’t meet the guy who got a new life.” The driver dropped Rivero and the surgeon Mark Russo at the community hospital’s emergency room, and waited outside.

The young man lay on a gurney in a large OR, dead from a traumatic head injury. The air conditioning was broken, and the room got hotter with each person who scrubbed in and gathered around his body. Mark Russo changed into scrubs, washed his hands in a steel sink, tied on a hat and face mask, and pushed open the double doors.

read more

One of the sectors closely monitoring the debt debate in Washington is the medical world, where hospitals, physicians, and patients anxiously await the final agreement on cuts to Medicare and Medicaid. Of particular concern to academic medical centers [pdf] are proposed cuts to graduate medical education, funding used to pay the salary of residents and fellows who are both training as physicians and specialists and working on the front lines of patient care. In a time when a patient’s wait time to see a specialist grows longer and longer, squeezing the bottleneck of physicians-in-training even tighter could have long-term consequences.

This week, the Medical Center’s executive vice president for medical affairs and dean Kenneth Polonsky took to the newspapers to argue against these damaging cuts. In an op-ed letter published by the Chicago Tribune, he expressed concern that the proposed cuts would “would reduce access to doctors, multiply waiting times and do lasting harm to patients in Illinois and nationwide.”

No one questions the need to rein in spending on health care or the obligation of hospitals to do their part. But we need to maintain a high level of patient care, and to make certain that our country has enough physicians in the future. Policymakers in Washington must maintain their support for graduate medical education and find more equitable ways to distribute the budget-cut burden.

Elsewhere…

Speaking of Washington and health care policy, without the Patient Protection and Affordable Care Act, 63-year-old Glenn Bovard of Valparaiso would not have been able to receive life-saving gift this past Father’s Day: a new heart. The Post-Tribune profiled Bovard’s story and surgery, performed by the Medical Center’s Valluvan Jeevanadam and Jai Raman. “The surgery was a cakewalk compared to the heart attack,” Bovard told the paper.

As many as one-third of patients with epilepsy cannot control their seizures with medication. Local newsmagazine Chicago Tonight profiles efforts by Wim van Drongelen, technical and research director of our pediatric epilepsy center, to develop new ways of helping these patients by modeling how seizures begin and spread in the human brain.

At the end of a long, difficult week, many people like to unwind on a Friday evening with a drink? But does alcohol relieve stress, or prolong it? A new study by Emma Childs of the University of Chicago Behavioral Pharmacology Laboratory and written up by the Gannett News Service suggests a double-edged sword - stress reduces the positive effects of alcohol, while a drink may extend the tense feelings produced by a stressful event.

A cautionary tale about when newspapers twist the words of scientists for sensationalist ends - did paleozoologist Darren Naish really say that the Loch Ness Monster was “more fact than fiction?”

Evolution isn’t only a process that happened in the distant past. Carl Zimmer’s wonderful cover story in the Science Times this week follows New York evolutionary biologists as they hunt for signs of urban evolution in progress for mice, fish, ants, and other city-dwelling critters.

To prepare for the grueling 2,200 miles of the Tour de France, cyclists train their muscles at both low and high altitudes. Riding at elevation does more than prepare them for the infamous mountain stages in the Alps, it has a biological effect, increasing the capacity of red blood cells to carry oxygen and improving how their muscles use energy. Though it may seem counter-intuitive, training in the low oxygen conditions found at high altitude is actually beneficial to an athlete’s muscular performance long-term. Could the same be said for another important muscle - the one located inside your skull?

That’s one implication of a new study from University of Chicago researchers on the relationship between the sleep disorder sleep apnea and strokes. Patients with sleep apnea suffer from repeated breathing “pauses” during the night, moments where their brain is briefly deprived of oxygen (known scientifically as “hypoxia”). One or two of these hypoxic episodes may not be dangerous by themselves, but cumulatively, they can be very harmful - sleep apnea has been associated with cognitive impairment, behavioral effects, and cardiovascular disease.

Indeed, sleep apnea increases the danger twice over for one especially serious vascular problem: stroke. Research indicates that patients with the disorder are more likely to suffer a stroke, and if a stroke occurs, it is more likely to cause severe brain damage than in people without sleep apnea. Both sides of this connection have been targeted by investigators from the Department of Pediatrics sleep research group at the University of Chicago Medical Center. In one recent study, led by David Gozal, chair and professor of pediatrics, and Richard Li, assistant professor of pediatrics, the researchers found a mechanism for why putting rats through “intermittent hypoxia” during sleep (an animal model of sleep apnea) can increase the risk of atherosclerosis, the hardening of the arteries involved in many cardiovascular conditions.

But another study, published last month in The Journal of Neuroscience, focused on stroke’s aftermath, testing whether the extra brain damage from a stroke in sleep apnea patients was due to the low-oxygen episodes or an associated risk factor such as obesity. A team led by Yang Wang, associate professor of pediatrics and director of basic research for the sleep medicine laboratory, again simulated sleep apnea in otherwise normal rats with intermittent hypoxia (IH), comparing them with rats that slept in normal oxygen conditions. When a controlled stroke was induced in each of these groups, the resulting damage was very different - the IH rats suffered more damage than controls, indicating a direct effect of hypoxic episodes upon recovery after stroke.

“It seems that something very bad is happening that affects the ability of the cells to survive or to recover after stroke,” Gozal said.

The researchers then focused on a possible mechanism for why intermittent hypoxia leads to more severe strokes, choosing energy metabolism as their primary suspect. When the brain is active - or trying to recover from damage - it needs a lot of fuel. As with the rest of the body, glucose is the first option for providing energy. But like muscles, a healthy brain can also use lactate as an alternative energy source in times of high demand. The gas pump for getting lactate into neurons is a protein called monocarboxylate transporter 2, or MCT2. Wang and colleagues looked at how intermittent hypoxia affected levels of MCT2 and how MCT2 levels affected the severity of stroke.

The pathway fell into place - exposing rats to IH decreased the expression of the MCT2 gene, while decreasing MCT2 activity through various methods increased brain damage after stroke. A transgenic mouse with elevated MCT2 was even created, and found to be protected against a stroke’s damaging effects. Thus, repeated hypoxia events during sleep could disrupt MCT2 and impair the brain’s ability to use lactate for energy - perhaps by “crying wolf” too many times. Gozal used the metaphor of a night watchman repeatedly running up the stairs for minor smoke alarms, only to be too tired to respond when the big fire starts.

“I think we have dissected in a very careful way, with a lot of work, the mechanisms that may explain why patients with sleep apnea are not only at increased risk of stroke, but also why when that stroke hits, they have a risk of not really recovering,” Gozal said.

The study also raised an intriguing idea about how to prevent this elevated sensitivity to stroke in sleep apnea patients.

read more

By John Easton

Salt is bad for you. According to a 2010 article in the New England Journal of Medicine, lowering dietary salt intake by 3 grams per day could “reduce the annual number of deaths from any cause by 44,000 to 92,000.”

Or maybe not. A 2011 meta-analysis of seven clinical studies of salt reduction, published this week in the American Journal of Hypertension, found “no strong evidence that salt reduction reduced all-cause mortality.” One of the seven studies showed that a low-sodium diet was associated with an increase in the risk of death for certain patients.

Studies of diet–eggs, caffeine and sugar; of screening tests–annual mammograms, PSA testing and lung scans for smokers; even topics as diverse as circumcision or drinking eight glasses of water a day, have all produced conflicting results. How can this happen? How often does this happen?

“We call them reversals,” said Adam Cifu, associate professor of medicine and co-author of a recent research letter on the phenomenon, published in the Archives of Internal Medicine. “Some new therapies are replacements,” he said. “They are better than what came before, as demonstrated by large, well designed, controlled studies.” Other new approaches arrive expecting to become replacements, but biology, complexity and, over time, better studies transform them into reversals.

“They make sense in the laboratory,” Cifu said. “Doctors are eager to try things that should work, based on what we understand about the biology. But the human body is complicated; things that made perfect sense in theory may not work in quite the same way in the clinic. We wanted to find out how often this happened.”

So Cifu and colleague Vinay Prasad, a former Pritzker student and now internal medicine resident at Northwestern, turned to the leading American medical publication, the New England Journal of Medicine. They focused on the 124 articles that appeared in 2009 involving investigation of a new medical practice or a practice already in adoption. Of those 124 articles, 16 could be characterized as a reversal. So 13 percent, one out of eight, contradicted an emerging or accepted medical practice.

The reversals included medical therapies such as tight control of blood sugars for patients in an intensive care unit, invasive procedures such as efforts to reopen clogged arteries for patients with chronic total artery occlusion, and predictive tests such as randomized prostate cancer screening.

One resounding reversal involved back-to-back studies in the August 6, 2009, issue that took a close look at vertebroplasty, a treatment for pain caused by compression fractures of the spine, a common problem for older women. The procedure, which had been widely used for more than a decade, involved injecting bone cement through a small hole in the back into a fractured vertebra. “We spent billions of dollars on this,” Cifu said. Several small early studies implied good results, but there had never been a blinded, placebo-controlled, randomized trial.

However, once NEJM published results from the first such trials, the party was over. One study found “no beneficial effect of vertebroplasty over a sham procedure at 1 week or at 1, 3, or 6 months.” The other reported that results for patients treated with vertebroplasty were “similar to the improvements in a control group.” An editorial in the same issue predicted the procedure, “virtually always considered to be successful,” would now be “considered no better than placebo.”

Cifu and colleagues developed a Why-We-Got-It-Wrong-Initially chart summarizing the reasons behind each reversal.

read more

Popular Mechanics typically offers step-by-step guides for changing your oil or building a bookcase. But in a recent feature they seriously upped the instructional ante with an “Extreme How-To” - How to Perform Open Heart Surgery. The expert chosen to guide their readers through this don’t-try-this-at-home process was Medical Center cardiac and thoracic surgeons Jai Raman and Shahab Akhter who helped develop a new technique in heart surgery called the “wrap procedure.” The surgeons do a great job of explaining how the surgery has changed over the years, particularly in the materials used for repairing the heart and sternum after surgery to speed recovery and decrease scarring. “You’ve got to get comfortable putting stitches into a beating heart,” is just some of the sage advice that Raman offers in the piece.

The end of the academic year always brings a bounty of teaching honors, voted on by medical students, residents, and faculty peers. For the 2010-2011 year, more than two dozen awards were handed out by the Pritzker School of Medicine, the Biological Sciences Division, and departments of the Medical Center. For an awards roundup from both sides of campus, visit this article at the University of Chicago News Site.

The pediatric cancer patients at Comer were treated to a celebrity visit last weekend, though their parents and staff may have recognized her more by voice than by sight. Delilah, the easy listening disc jockey known for her “Love Someone” radio dedications, visited families at Comer before making 3-year-old leukemia patient Atia Lutarewych her “Brave Child of the Week.” You can listen to her segment on the visit here [mp3].

Another inspiring story of pediatric cancer was told in the Chicago Tribune this week, focusing on 6-year-old neuroblastoma patient Theofanis Yianas. After Theo’s hair fell out from chemotherapy treatment, 30 friends and family members shaved their heads in solidarity with the young boy. Theo’s doctor, professor of pediatrics Susan Cohn, comments on the importance of support in a patient’s recovery.

What did St. Vitus’ Dance - the 14th century outbreak of weeks and months-long uncontrolled dancing across Europe - have to do with mirror neurons in the brain? UChicago psychologist John Cacioppo weighs in on this fascinating phenomenon for ABC News.

An interesting plan to create “mystery shoppers” for assessing the primary care shortage in the United States was revealed in the New York Times on Sunday, then disappeared by Tuesday after doctors bristled about “snooping.” The survey, which would have been conducted by the University of Chicago National Opinion Research Center, shows how far the administration will go to collect data on the current health care system…and how stiff the medical field’s resistance can be to being measured.

By Dianna Douglas

Darryl Williams got winded while running an annual 10K race in Oak Park in 1995. Puzzling, since he was in excellent shape. Over the next five years, he had irregular heartbeats and felt strange sensations in his chest. But none of the treatments his doctors tried made a difference.

Allen Anderson, associate professor of medicine and director of the Advanced Heart Failure Program, met Williams in 2000. The arrhythmia was becoming life-threatening. Anderson diagnosed Williams with sarcoidosis of the heart, an inflammatory disease, and began to treat him with medication.

Williams was determined to get better. He followed his doctor’s orders and took his medications, even when they had toxic side effects. “We were able to control it for 10 years,” Anderson said. “He did his part as well, by taking care of himself.”

But Williams’ sarcoidosis continued to grow. The disease, which affects about 18 people per 100,000 annually, spread to his liver. Soon his ailing heart and liver put serious strain on his kidneys. Anderson decided that his only hope was a new heart, liver and kidney. “He was in heart failure and liver failure. He was critically ill. He was going to die.”

The criteria to be considered for a three-organ transplant are stringent. “We have to be very careful about patient selection,” Anderson said. A heart, liver and kidney transplant is a massive surgery. “We have to pick patients who have a good chance of survival.”

Williams’ case was the subject of many multidisciplinary meetings, with hematologists, surgeons, nutritionists, psychiatrists, social workers, infectious disease specialists. “The fundamental question is: are you going to commit organs to this person?” said John Renz, professor of surgery and director of the Liver Transplant Program. “You have to look at all aspects of a patient. And you have to feel that you are committing that precious resource well.”

After multiple screenings, the team was convinced. At 55 years old, Darryl Williams didn’t have any other health problems that would complicate his recovery. He was always careful to follow his doctors’ instructions, and would likely keep taking his medications after a transplant surgery. And, as important as anything, he had a large family and community of friends to support him through the ordeal.

After three months of waiting in the hospital for the transplants, Williams was rolled into an operating room.

“It’s an extraordinary surgery,” said Valluvan Jeevanandam, professor and chief of cardiac and thoracic surgery. “People don’t do well after any open heart surgery without a good functioning liver,” he said. “The liver has to filter out toxins and promote coagulation. Similarly, a new liver won’t do well without a good heart.”

He compares multi-organ heart transplants to “walking a tight rope without a net under you.”

There are other pressures, too. After leaving the deceased donor, the heart is only good for about five hours. A liver can be transplanted for 18 hours, and a kidney can sometimes be good for up to 48 hours. So, the heart goes in first.

“From a technical point of view, all three surgeries have to be perfect,” Jeevanandam said. “The challenging thing is sewing in all three organs in an environment hostile to any transplant procedure.”

The heart transplant was over in about four hours, but the heart was struggling. “We had to maintain his heart until he could get his liver,” Jeevanandam said. The surgeons used inotropes to stimulate the heart and a balloon pump to keep oxygen flowing.

Then Renz and the liver transplant team took over. read more

A Magic 8-Ball for Cardiac Arrest

Cardiac arrest is one of the most common ways that people die, and hospitals need to be constantly vigilant about the threat of heart stoppage in their patients. So physicians have long sought to develop a way of predicting who is most at risk for cardiac arrest when checked into the hospital, such that extra care and surveillance can be taken. At the 2011 international meeting of the American Thoracic Society, held this past week in Denver, two Medical Center fellows presented research refining these early warning systems to make them a more effective hospital tool.

In the first study, pulmonary and critical care fellow Gordon E. Carr connected cardiac arrest with another frequent sight on the hospital ward: pneumonia. Carr’s study found that patients admitted with pneumonia are at elevated risk of cardiac arrest over the next three days after admission, and that almost 40 percent of these cardiac arrests occurred while the patient was outside of the intensive care unit. “We found a compelling signal that some patients with pneumonia may develop cardiac arrest outside of the ICU, without apparent shock or respiratory failure,” Carr said in a press release. “If this is true, then we need to improve how we assess risk in pneumonia.”

Adding extra caution about cardiac arrest to the care of patients with pneumonia is a specific way to improve surveillance. But to apply to more patients, a broader scale is needed, one that can be easily assembled from the vital signs that are already routinely measured in the wards. One such scale, called the Modified Early Warning Score or MEWS was tested by pulmonary and critical care fellow Matthew Churpek as a predictor of cardiac arrest, who found it to be better at predicting a cardiac arrest in the next 48 hours than any individual vital sign. But MEWS was designed for general risk of death, not specifically for cardiac arrest, and Churpek suggested a more specialized risk score could be calculated for use by hospitals. The benefits of such a measure, he said in a press release, would be immense.

“Rapid response teams are a complex and resource-intensive intervention, so providing evidence-based criteria for their activation is crucial,” Churpek said. “Our patients will do better if we can detect who is at high risk early enough to intervene and prevent a cardiac arrest.”

Doctors Against Ronald McDonald

Childhood obesity is a growing problem in the United States, and doctors point the finger of blame directly at increased consumption of junk food and fast food. Chains such as McDonalds have made noise about making their food healthier, especially for children, by posting calorie counts on menus and offering snacks such as apples and carrots instead of fries. But according to an open letter signed by over 500 health care professionals and placed in newspapers around the country this week, they have not done enough.

read more

Today, nearly everyone is aware of the dangerous health effects of smoking cigarettes. Even fewer people would deny the harmful effects of drinking water contaminated with arsenic. But when these two toxic influences are mixed together, is the sum of their damage more than the individual effect of each? To put it another way: for a person in an area with low, “safe” amounts of arsenic in the groundwater smokes, is their risk of disease increased as though they were drinking unsafely contaminated water?

To study this question, University of Chicago epidemiologist Habibul Ahsan returned to his project studying the consequences of accidental arsenic exposure in the people of Bangladesh. Ahsan’s Health Effects of Arsenic Longitudinal Study (HEALS) has tracked thousands of Bangladeshi citizens who unknowingly consumed well water with high levels of arsenic after health organizations installed wells to reduce water-borne infectious disease. That study, which has expanded to 20,000 subjects, discovered a 70 percent higher risk of death from chronic disease in those drinking water with the highest levels of arsenic. Even people exposed to moderate levels of arsenic, amounts that can be found naturally in some regions of the United States, were at a 20 to 30 percent higher risk of dying from chronic disease.

Ahsan and his team from UChicago, Columbia University, New York University, and Bangladesh, looked at whether the combination of arsenic exposure and smoking made the odds even scarier on one particular mortality endpoint: cardiovascular disease. While arsenic is traditionally thought of as causing different types of cancer and skin lesions, chronic exposure can also produce various heart and circulatory problems such as hypertension and atherosclerosis. Previous studies of these cardiovascular effects have been small, retrospective, and focused on extremely high exposures in Taiwan and Chile. With the Bangladesh study, Ahsan and colleagues could look at a broader spectrum of exposure, and follow subjects carefully over time to isolate the effect of arsenic from other factors.

For the study, published last week in the British Medical Journal, the researchers tracked nearly 12,000 Bangladeshis, taking urine samples to measure arsenic exposure and registering the cause of death in those who died over the time they were tracked (an average of 6.6 years). Overall, 460 subjects died, with nearly half of those (198 people) dying from some form of cardiovascular disease. Associating those deaths with arsenic exposure confirmed the Taiwan and Chile studies on people exposed to high concentrations (as high as 80 times the safe limit of 10 parts per million) of the toxin. But a worrisome trend also emerged for more moderate exposures, with a 50 percent increase in cardiovascular mortality risk observed at levels as low as 2.5 times the safe limit.

“We were able to show that, even at lower doses than previously reported, there seems to be a deleterious effect of arsenic regarding cardiovascular disease mortality, particularly from ischemic and other heart diseases,” Ahsan said.

For those subjects who were smokers - even those who had quit - a deadly synergy emerged. For a current smoker exposed to the high levels of arsenic, the increased risk of dying from cardiovascular disease jumped from 50 percent to 328 percent. Former smokers saw a lower bump in risk, but if exposed to moderate levels of arsenic, they shared the same risk as those exposed to high levels that had never smoked. Ahsan said that the result emphasized the importance of targeting multiple risk factors in improving public health around the world.

“This tells us that there are some individuals who are dying from cardiovascular disease solely because of the presence of both factors, not because of the presence of one or the other,” Ahsan said. “It’s one more reason to pay attention to arsenic exposure, but yet another reason that will underscore the importance of smoking cessation.”

read more

A sickle cell (left) and a normal red blood cell (right). From carnegiescience.edu.

In 2006, Rice University football player Dale Lloyd II collapsed during a practice and later died. The cause of death was acute exertional rhabdomyolysis, a sudden breakdown of muscle tissue into the blood brought on by strenuous exercise. But the trigger for Lloyd’s death may have been sickle cell trait, the name for when a person carries one of the two genes required for full-blown sickle cell disease.

People with sickle cell disease form abnormal red blood cells that can lead to chronic pain, hypertension, stroke, and death, while people with sickle cell trait (approximately 2 million in the U.S.) are generally thought to be symptom-free. But Lloyd’s death drew attention to potentially fatal consequences for athletes with sickle cell trait, and a lawsuit filed by the player’s family led to the NCAA mandating testing for all Division I athletes in 2010.

But is screening for sickle cell trait the best preventive measure for college athletes? That was the topic on the table at the first Department of Pediatrics Grand Rounds of 2011 last week, where both the medical and ethical implications of the NCAA’s new policy were considered. Though mandatory sickle cell trait screening has previously been adopted by the military and the National Football League, the NCAA stance could cause a “trickle-down” effect to high schools and youth sports, leading to millions of tests that might cause more harm and expense than good.

At least fifteen NCAA athletes have died from sickle cell trait-related causes in the last 30 years. But given that there have been approximately 2 million total athletes over that time span, that’s only 1 death for every 400,000 people, said Holly Benjamin, associate professor of pediatrics and surgery. Compared to more common, harmful occurrences such as concussions and spinal cord injuries, that’s an exceedingly rare event.

Which is not to say that it shouldn’t be closely monitored. Sickling, the name for a sickle-cell-related attack, can develop after as little as 2 or 3 minutes of strenuous exercise, and can be exacerbated by heat, altitude, and dehydration, Benjamin said. Parents, coaches, and trainers should be vigilant about athletes who suddenly collapse, giving them fluids and oxygen and transporting them to the nearest emergency department.

But while screening athletes for sickle cell trait might improve the response to an athlete’s collapse, preventing that collapse in the first place would be even more beneficial. As a demonstration, Lainie Ross, professor of pediatrics, surgery, and medicine, used the history of sickle cell trait testing in the American military, which has faced similar tragedies and pressure to screen.

After 4 sickle cell trait-related deaths in 1970, a study found that African-American recruits with the gene were 30 times more likely to die during basic training. In response, the Armed Forces considered screening for carriers of the gene and restricting service in those with positive tests. Meanwhile, another study was started to test whether the danger could be reduced by using the wet-bulb globe temperature (WBGT) index, a measure incorporating temperature, humidity and other factors to determine how dangerous conditions are for physical activity. An intervention based around reducing exertion and increasing rest for basic training recruits on days with a high WGBT index was successful not only in completely eliminating deaths related to sickle cell trait, but reduced deaths in non-carriers as well.

“What this shows is that effective intervention does not require the identification of sickle cell trait,” Ross said.

read more

ScienceLife ran 219 posts in 2010, and choosing the best of them is as hard as picking a favorite gene.  So here’s a month-by-month scan of a busy year at the University of Chicago Medical Center, full of exciting discoveries in the laboratory and the clinic. The impact of some of this research is already being felt by patients receiving improved, evidence-based medical care. For other studies, the clinical benefit may be years in the future, and may take unpredictable forms. As a closing message for 2010, we’ll re-quote the recently departed Eugene Goldwasser, whose laboratory research isolating and purifying the hormone erythropoietin has helped millions of people worldwide.

“It is a particularly impressive example of how basic research can pay a dividend that could not be anticipated at the start,” Goldwasser wrote about his life’s work, “and it is a pity that the lesson still has not been learned by those who control public funding of science.”

January: Tong Chuan-He looked at how cancer may result from cells who don’t want to grow up. Scientists studied how sleep affects the language learning skills of starlings (with painstakingly acquired video of the experiment!). Richard Jones combined two laboratory staples - Western blots and DNA micro-arrays - to develop a new method for studying protein networks. While physicians such as Tammy Utset treat patients with lupus, UChicago scientists are looking for the genetic origins of the autoimmune disorder.

February: Many Medical Center employees returned from volunteering with relief efforts in Haiti, and we filmed video interviews with Rex Haydon, Tiffany Cupp, Richard Cook, and Dima Awad on their experiences. Most of the human genome is “junk” between protein-encoding regions, but Marcelo Nobrega developed a way to find important regulatory elements in that genetic sea. Like birds, human learning can be affected by sleep, and Leila Kheirandish-Gozal reported on the impact of obstructive sleep apnea upon learning in children. Can a single protein in the brain create behaviors associated with drug addiction in rats?

March: Everyone knows air travel is stressful, but did you know that eastbound flights cause stronger cortisol changes than westbound trips? The laboratory of Milan Mrksich found a way to direct stem cells to form fat or bone by shaping them into stars or flowers, a brilliant example of bioengineering. Computational neuroscientists discovered how touch is like vision in the brain, knowledge that could be used to someday re-engineer Luke Skywalker’s robot hand. Dartmouth president and Partners in Health co-founder Jim Yong Kim visited to talk about a new, needed area of research: health care delivery.

April: Researchers at the Field Museum and the University of Chicago teamed up for the Emerging Pathogens Project, an effort to find new viruses in animals before they jump to humans. Cardiologist Martin Burke tested out a new type of internal defibrillator device that can go under the skin, instead of into the heart (the clinical trial, reported in May, was a success). In a lecture to the MacLean Center of Clinical Medical Ethics, transplant surgeon J. Michael Millis described his efforts to bring American organ transplant practices to China.

May: A trial testing the erectile dysfunction drug Viagra for a rare, untreatable lung disease failed, but pulmonologist Imre Noth found a silver lining. Lauren Sallan and Michael Coates uncovered evidence of a previously unappreciated mass extinction event 360 million years ago that changed the path of life on Earth. Researchers from the University of Chicago and around the world presented science at the frontier of biotechnology at the annual BIO conference.

June: In a study that is literally the size of an entire country, epidemiologist Habibul Ahsan measured the toll of a tragic, accidental exposure of millions to arsenic in Bangladesh. Putting a gene from fireflies into the pancreas of mice isn’t mad science, it’s an imaging tool that will help study cures for diabetes. Epigenetics, the modifications that turn genes on and off, took off in 2010, and cardiologists Stephen Archer and Jalees Rehman linked one epigenetic factor to pulmonary artery hypertension.

July: Scientists don’t often get to see the fruits of their research in the flesh, but the Celebrating the Miracles gathering of diabetic children weaned off injected insulin thanks to genetic research was a moving exception (video of the event can also be viewed). Another hot topic in science and medicine this year was the use of computational analysis to sift through rapidly accumulating data, topics explored by Gary An and Andrey Rzhetsky. Or you can build a computer model of a brain network to study the dynamics of epilepsy, like neurologist Wim van Drongelen.

August: Air pollution is a problem indoors as well as outdoors in developing countries where dung and firewood are used to cook food - a problem being tackled in a project led by Sola Olopade. A study of the hormonal changes induced by a stressful test revealed a surprising protective effect of marriage and long relationships. Microbiologist Olaf Schneewind’s laboratory developed two new strategies against MRSA, the most-wanted cause of hospital-acquired infections.

September: To study multiple sclerosis, neurologist Brian Popko’ s laboratory developed a new mouse model that can replicate the disease, then spontaneously recover. Meanwhile, a new drug to treat MS, originally isolated from fungus found in wasps, was approved by the FDA and is being studied for broader uses at the Medical Center. The micro-organisms that live in humans were analyzed as part of a “microbiome” study looking at the protective effects of breast-feeding against a intestinal disease.

October: Common wisdom on quitting smoking says to stay away from cigarette-associated cues, but research from psychiatrist Harriet de Wit’s laboratory revealed that abstinence could make craving even worse. A study of how getting a good night’s rest affects dieting results suggested that “sleeping off the pounds” isn’t merely a fantasy. Graduate student Daniel Matute solved a 100-year-old riddle about how quickly new species become reproductively incompatible with each other.

November: In perhaps our favorite study of the year, geneticist George Perry found a way to acquire the genomic information of endangered species from…poop. The evolutionary biologist Leigh Van Valen passed away, but his Lewis Caroll-inspired Red Queen Hypothesis lives on. Sometimes statistics don’t tell the whole truth, as in the curious case of the aspirin paradox - why the cardio-protective drug may actually predict worse outcomes after heart attack.

December: Evolution textbooks may need a rewrite after geneticist Manyuan Long’s laboratory discovered that new genes can be just as essential as old genes. A study by neurobiologist Nicholas Hatsopoulos proved that the only thing better than a thought-controlled device is a thought-controlled device equipped with a robot arm. Ripped from the headlines: microbiologist Jack Miller weighed in on the hype over arsenic-based bacteria, and ethicist/physician/friar Daniel Sulmasy discussed the Presidential Bioethics Commission’s report on synthetic biology.

All told, it was a great year of science and medicine. Let’s do it again in 2011! Regular posting will resume Jan. 3rd. Happy Holidays.

Ultrasound imaging is best known for pictures of developing fetuses; 3D is typically associated with monster movies. But when you put the two together and aim the technology at the heart, they create a valuable tool that is changing the way heart disease is treated. Three-dimensional echocardiography is a cutting edge imaging technique used to obtain a detailed look at a patient’s heart in motion, figure out what may be wrong, and determine the best way to fix it.

The high-definition images collected by “3D Echo” can detect holes in the heart, problems with the valves that let blood pass between chambers, and irregularities in muscle contraction and blood flow. Information gathered during an echocardiogram can help surgeons create detailed plans for procedures to correct heart problems and can give them immediate feedback in the operating room after the surgery to make sure it was successful. For the increasing number of procedures that can be performed with cardiac catheterization instead of open heart surgery, a 3D echocardiogram provides live information to help guide cardiologists in their repairs.

“This is progressing very quickly and in many diseases, it really, really changes the way that people think about cardiology,” said Roberto Lang, professor of medicine and the director of the Noninvasive Cardiac Imaging Lab at the University of Chicago Medical Center. “We can look at the heart and tell the surgeon what he or she is going to encounter at the time of surgery.”

At this month’s American Heart Association meeting in Chicago, Lang presented research and participated in panels on the latest uses of 3D echocardiography. Since its submarine-sonar-inspired origin in 1953, the sonogram has been applied to cardiac function in many ways, through 2D images (similar to today’s fetal ultrasounds), through 3D reconstructions built from 2D data, to today’s instantaneous 3D view. Though real-time 3D imaging was only made possible 8 years ago, it is rapidly sweeping into the hospitals around the world, and new uses are still being discovered as the technology improves further.

During the AHA meeting, Lang presented what he calls “fusion imaging,” a combination of 3D Echo and computed tomography (CT) scanning to help determine the best place to implant a pacemaker for restoring normal heart contraction. Another presentation focuses on how 3D Echo can collect information about problems with the mitral valve - the portal between the left atrium and left ventricle of the heart. The precise location of leaks and other abnormalities can be mapped from the same angle the surgeon will see during surgery, Lang said, minimizing surprises on the operating table.

The best way to grasp the value of 3D echocardiograms is to see one, and last year, a production company came to the Medical Center and filmed Lang at work and talking about his field. Watch the results below.

“When we do these studies, we use all the different modalities and integrate them into a simple study,” Lang says in the video. “You want to be a detective and find out exactly what is happening to the patient, so you use all the technologies available and integrate them in order to come up with a good question or a good answer.”

[Thanks to Philips and Tomorrow Media for the video footage.]

Originally developed in 1897 as a painkiller, aspirin has become a valuable cardiology tool in the 21st century for preventing and treating cardiovascular disease. Because of the drug’s ability to reduce blood clotting, doctors commonly recommend a daily aspirin to patients at high risk or with a history of heart attacks, strokes, and other cardiovascular ailments. Extensive research has largely supported the drug as a cheap and effective way to prevent these life-threatening events and to help nullify what remains the leading cause of death in the United States.

But in 2000, a group of Boston cardiologists trying to identify risk factors that might predict poor outcomes after a heart attack made a strange discovery. Most of the predictive risk factors they discovered and ultimately incorporated into their well-known 7-point “TIMI risk score” made perfect sense. For example, if you came to the emergency room with chest pain and had an abnormal electrocardiogram or elevated levels in the blood signaling heart damage, you were more likely to be at risk for future adverse events. But the team also discovered one risk factor for predicting worse outcomes that was far from expected: the prior use of aspirin. According to their analysis, patients who were taking aspirin to prevent cardiovascular disease actually did worse after suffering a heart attack.

“It seemed to make little sense, because aspirin had clearly proven itself in other settings to be protective against heart attacks,” said Jonathan Rich, an instructor of medicine in the section of cardiology at the University of Chicago Medical Center. “If you suffered a heart attack, to prevent you from having another, your doctor invariably puts you on aspirin. So this unexpected discovery caught everyone’s attention. Did this mean that aspirin use could actually be hurting people?”

Dubbed the “aspirin paradox,” this observation did not deter doctors from continuing to prescribe aspirin for the prevention of cardiovascular disease. But the mystery caused some to wonder whether there was a biological reason for aspirin’s unexpected role as a risk factor, such as “aspirin resistance” in some patients, or if there was instead an epidemiological or statistical explanation. While working in Boston with the TIMI study group, Rich took charge of an effort to comb through the data for a way to explain the paradox.

The research ultimately led to a study, published last month in the Journal of the American College of Cardiology, which seems to take aspirin off the hook. When researchers controlled for a long list of potential confounding variables such as age, sex, smoking, and previous history of cardiovascular events, the association of prior aspirin use with a higher chance of post-event mortality entirely disappeared. Aspirin, they concluded, was not directly causing worse outcomes after a heart attack. Instead, it was simply a common drug that people with previous cardiovascular disease - by definition, a population at high risk for poorer outcomes, were frequently taking.

“Aspirin is probably an innocent bystander,” Rich said. “The reason people who take aspirin do worse than those not taking aspirin is because those taking aspirin have already suffered a heart attack, a stroke, or have heart failure for which they were prescribed the drug. In actuality, when we looked closer at the heart attacks that people suffered, those who were taking aspirin actually had less severe heart attacks than those not taking aspirin, suggesting that perhaps aspirin was indeed beneficial, but simply insufficient to prevent the heart attack entirely.”

read more