Roughly 30 million Americans suffer from migraines, and as you might expect, there’s a large pharmaceutical market to prevent or stop these debilitating headaches. Drugs such as Imitrex and Verapamil employ different pharmacological modes of action, reducing migraines by adjusting neurotransmitter levels, blocking ion channels, or simulating the body’s natural painkillers. There’s also a less pharmaceutical migraine treatment strategy, recommended by many headache specialists, that follows the old adage: “Active Body, Active Mind.” One recent study even found that 40 minutes of exercise three times a week can be as effective at preventing migraines as popular anti-migraine medications.

Still, prescribing exercise or environmental enrichment (keeping the mind busy through activities such as reading, crossword puzzles, exercise, or socialization) can strike some doctors and patients as frustratingly vague. Understanding the biological mechanism that makes these activities protective against migraines could help convince doctors and patients of their utility, while also giving researchers the opportunity to translate the factors associated with environmental enrichment into highly effective treatments.  In the laboratory of Richard Kraig, William D. Mabie Professor in the Neurosciences at University of Chicago Medicine, that very effort is underway.

“We are interested in environmental enrichment as a way to stop cognitive decline from aging, injury after stroke, Parkinson’s disease, and cell death after seizures.  With our new work, we apply this search for how the brain protects itself against disease to include migraines,” Kraig said.  ”The ‘why’ of it has sometimes been left in the realm of holistic medicine, with little scientific support.  So establishing the hard science makes it more credible to the psychologists, physiologists, physiatrists, because here’s the chemistry.”

Working with graduate students Yelena Grinberg and Aya Pusic as well as senior technician Heidi Mitchell, Kraig discovered three different natural signals elevated by exercise and environmental enrichment: insulin-like growth factor-1 (IGF-1), interleukin-11 (IL-11), and interferon gamma (IFN-γ). When these “cytokines” are applied to brain slices, they reduce the probability of triggering a spreading depression — a transient wave of reduced brain activity associated with migraines. Understanding how those cytokines stop spreading depression — and the nasal route by which they might be delivered — may revolutionize how migraines and other neurological conditions are treated.

A spreading depression of brain is a chain reaction of dramatic events. After an initial burst of increased neuronal activity, a subsequent ripple of absent activity slowly spreads across involved brain at a rate of about 3 mm per minute — lasting a few minutes overall.  While the event sounds brief, the consequences can last from hours to days, causing harmful oxidative stress, elevated inflammatory factors, moving microglia, and significant pain and discomfort for the migraine sufferer.

Paradoxically, the way to stop this chain reaction may not be to simply reduce or block the byproducts of a spreading depression, but to expose the brain to moderate levels of inflammatory factors, which include the cytokines described above. To interrupt the cycle of repeated migraines, treatments could take place before the process begins or in small steps after the recurrent spreading depression that underlies chronic migraine. While these factors may have negative effects in the short-term, in the long-term they prime the neurons to make antioxidants that are protective against oxidative stress.

“Spreading depression increases oxidative stress in a big fashion — it depolarizes all the brain cells. It’s like an engine kicking out a lot of exhaust, and the exhaust makes the brain hyper-excitable,” Kraig said. “But you have to let the engine run. The engine is running with stimuli that include cytokines that are initially irritative, but then adapt to stop spreading depression.”

The trick, Kraig said, is to mimic the natural cycles of cytokine levels the brain would experience during healthy, active behavior, rather than drowning the system in abnormally high concentrations of the factors that can occur with disease. The cytokines would be delivered to the brain in an on/off pattern rather than chronically, theoretically recreating the rise and fall of natural cytokines during a person’s sleep/wake cycle. By giving just a little bit of a factor normally considered harmful, the treatment could strengthen the brain’s resistance to spreading depression and migraines via the principle of hormesis, or “what doesn’t kill me makes me stronger.”

“The treatment is unique in that it’s the opposite of putting a Band-Aid on something,” Grinberg said. “It’s triggering cells to produce their own antioxidants instead of just providing the antioxidants exogenously. In that way it’s really unique and the opposite of how a lot of people think about medical treatment.”

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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.

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Countless campaigns have been launched to steer schoolchildren toward healthy habits, and yet rates of childhood obesity and diabetes continue to soar. Celebrity endorsements, catchy catchphrases, and food pyramid redesigns have struggled to combat the allure of fast food and television in the battle for child health in the United States. But with childhood obesity rates tripling in the last 30 years and type 2 diabetes showing up earlier in life, there’s an urgent need for more effective programs to promote nutrition and exercise in kids. One strategy is to create more relevant programs, locally focused and tailored to the culture of the children the program is trying to help.

That approach inspired not one but two child diabetes prevention programs created by Medical Center researchers and tested with our neighbors on Chicago’s South Side. The two programs - called Reach-Out and Power-Up - are siblings, with similar designs, goals, and measures, but in slightly different populations and venues. The pilot studies, both published in recent months, demonstrate the challenges faced by researchers in creating effective, reproducible programs with a local focus…and also offer hope that a successful intervention is possible.

Before the programs could be designed, the first step was to listen. The research team, led by Deborah Burnet, professor of medicine and pediatrics, organized focus groups with overweight children and their parents to learn about their specific obstacles to improving health and gather ideas about the types of physical activity and classes that would appeal to them. For example, the African-American children said they would like to try martial arts and yoga, so instructors for those activities were recruited. The conversations laid the groundwork for programs that would take the unique circumstances of families on the South Side of Chicago into account.

“Nutrition and exercise are both behaviors we do in a social context; in a place, in a neighborhood, in the context of certain social mores and expectations and cultural factors,” Burnet said. “Food, especially - who cooks, where we learn how to cook, how do our tastes get shaped in what we like to eat - those occur in social and cultural contexts.”

While both programs were designed to improve the health and behavior of children, the targets were both the kids and their parents. In Reach-Out, families gathered at a local YMCA for 14 weeks, splitting into separate parent and child groups for the first part of each session and then reconvening for a combined activity. Sessions included grocery store tours, exercise training, cooking classes, and even a family basketball game. Scavenger hunts, relay races, and Family Feud-style review quizzes were used to keep the kids and their parents engaged. But addressing the family’s cooking and eating habits could also be a sensitive topic.

“Feeding is all bound up with caring and love, so it’s very complicated - if you tell grandma she’s not cooking for her grandchildren right, her feelings get hurt,” Burnet said. “So how do you do that in a constructive way so that grandma is valued, but also moves in this healthy direction?”

At the end of the Reach-Out pilot study, published in the Journal of the National Medical Association, the program earned glowing reviews from participants, who said that it helped reduce food intake, steered them toward new fruits and vegetables, and encouraged increased physical activity. However, the clinical improvements were modest, including slight dips in BMI z-score (which scales the measure to child age) and glucose-to-insulin ratio. The incremental changes might mean that very heavy kids need more help to get back to healthy habits, Burnet said: “Kids who are this big probably need a more intensive treatment and intervention than a weekly community-based program.”

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Teaching with Treadmills

Inside the Biological Sciences Learning Center on the Medical Center campus is a laboratory that looks more like a gymnasium. Six state-of-the-art treadmills and six futuristic exercise bikes sit around the room, each connected to a computer alongside modified oxygen masks and suction cup sensors. Instead of dissecting frogs or mixing chemicals, students show up to lab sections in shorts and running shoes, prepared to sweat for science. In Mark Osadjan’s “Metabolism and Exercise” course, part of a two-quarter Exercise and Nutrition sequence, there’s no sitting on the sidelines.

Since joining the University of Chicago as a senior lecturer in 2003, Osadjan has designed courses that teach undergraduates about biology by connecting with what most college students care about: keeping fit, and sex. As part of the UChicago core curriculum, every undergraduate must fulfill a biology requirement, even if their interests lie in political science, music theory, or philosophy. With his “Metabolism and Exercise” and “The Biology of Gender” courses, Osadjan has met these science-shy students halfway, filtering instruction on evolution, physiology, and genetics through their own personal hobbies and interests. The efforts have been such a success that Osadjan’s courses fill up soon after registration is opened.

Today, Osadjan was announced as one of this year’s recipients of the Quantrell Award for Excellence in Undergraduate Teaching, an esteemed UChicago honor that goes back to 1938. Last week I met with Mark to talk about his award and his career path, from a graduate student studying Antarctic fish to an instructor of graduate-level science to his current position, teaching predominantly undergraduate non-biology majors.

“It’s always a trick to figure out how to teach with enough enthusiasm, such that it spills over to the students,” Osadjan said. “It’s our challenge not only to teach these students a certain number of facts, but to show them why those facts are important, relevant, and worth thinking about throughout life.”

You can read more about Osadjan and the other Quantrell winners in the award package at The University of Chicago news site.

Elsewhere…

Most college students spend their summers traveling the country or working an internship, but 20-year-old Rachel Garneau had other plans: donating a kidney. On Tuesday morning, Garneau came to the Medical Center and made the rare gift of an altruistic kidney donation, triggering a kidney swap chain that helped patients in need of the organ in New York and Madison. Neil Steinberg at the Chicago Sun-Times followed the story before and during the surgery, and got some great play-by-play commentary from Yolanda Becker, professor of surgery and director of the kidney and pancreas program.  For instance: “‘The pancreas is the bitch of the abdomen,” she confided.’”

Are clinical trials handicapped by their own success? A new analysis from Anup Malani and Tomas Philipson of the University of Chicago Law School finds that trial enrollment for a given disease plummets when a treatment is found to be effective, using AIDS clinical trials after the approval of anti-retroviral therapy to illustrate the point. Richard Schilsky, professor and section chief of hematology/oncology at the Medical Center, agreed with the findings at Nature News: “There are so many options that patients are not flocking to get into clinical trials like they used to.”

Read how turtles move to warm areas to bask - even in their own eggs as embryos. Adorable photos and interesting commentary (are they determining their own sex?) at Not Exactly Rocket Science.

That news about the World Health Organization adding cell phones to their list of possible carcinogens? Here’s an article from Cancer Research UK to reassure your fears. Another reassuring fact: it was placed by the WHO into the same risk category [pdf] as coffee, dry cleaning, and pickled vegetables.

Can jazz musicians tell the difference between another musician improvising or following composed music? A new study finds the answer, and a ScienceNOW article gives you the chance to test yourself.

Did you know UChicago evolutionary biologist Neil Shubin does a regular science news roundup on local newsmagazine show Chicago Tonight called Scientific Chicago? Well he does, and the latest edition discussed a story familiar to readers of the blog: the mass extinction 360 million years ago that ended “The Age of Fishes.” Watch the video here.

It’s a challenge to watch TV for any length of time these days without coming across a commercial for drinks like Gatorade and Red Bull, beverages usually marketed with adrenalized advertisements featuring athletes and daredevil feats. Though these commercials always feature adults, the tone and pacing is clearly aimed at a younger audience more susceptible to quick-cut, extreme-sports salesmanship. The message appears to be connecting, as a 2003 study found that more than half of adolescents use sports drinks and nearly half used energy drinks. Simultaneously, such beverages are becoming more and more accessible to kids, as some schools removing soda from their vending machines for health reasons are replacing them with sports drinks.

But are their dangers for kids ingesting sports or energy drinks? And how should parents treat their child’s consumption of these beverages? Guidance was provided this week in the journal Pediatrics by a panel of physicians co-led by Holly Benjamin, associate professor of pediatrics at the Medical Center. Their report is a stern warning, particularly on the effects of caffeine-packed energy drinks in young consumers and the casual use of sports drinks intended for replenishment after rigorous exercise. Here are the main take-home points from the report:

1) Sports Drinks ≠ Energy Drinks

A common misconception on the part of both parents and children is equating sports drinks such as Powerade with energy drinks such as Monster, despite their very different ingredients and purpose. While sports drinks purport to rehydrate and restore electrolytes after a long run or game of basketball, energy drinks are high-calorie and filled with stimulants such as caffeine, ginseng, and guarana. Despite these differences, adolescents often mix up the two beverages, expecting thirst-quenching and energy boosts from either one - a misconception encouraged by the  advertising for the various brands of drinks, the report concludes.

2) Boring is Still Best

Of the two types of drinks, sports drinks pose fewer health risks than the energy drink side of the aisle. But the claims made by sports drinks - to replenish electrolytes, provide muscle-repairing protein, and rehydration - are just as effectively, if not better, performed by plain old water and a balanced diet, the authors write. Sufficient amounts of the electrolytes sodium and potassium, which are important for brain and muscle activity, are provided by a healthy diet (the kind to be promoted by the new USDA “plate” on Thursday), and are only significantly depleted after lengthy or intense exercise. As such, “sports drinks offer little to no advantage over plain water,” the authors write. But they do offer a significant disadvantage compared to H20 - calories. Even the relatively low calories-per-serving of a sports drink (10 to 70 calories, the report says) can increase a child’s daily carbohydrate intake. In the absence of the exercise the drink is intended to offset, that could contribute to the risk of a child being overweight or obese.

3) A Dangerous Buzz

The calorie count of energy drinks is even higher - as high as 270 calories per serving, and often served in multiple-serving cans or bottles. But the even scarier figure cited by the report is the 500 milligrams of caffeine that some cans and bottles of energy drinks contain. To put that amount in perspective, it’s equivalent to roughly 14 cans of caffeinated soda! Energy drinks can also hide their stimulant content behind unusual ingredients other than caffeine. Each gram of guarana, which is included in drinks such as Rockstar and Power Trip, is equivalent to 40mg of caffeine.

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It’s no big secret that one of the keys to good health is getting regular exercise. Yet good intentions are often thwarted by factors outside of one’s control. A person might decide to jog or bike several times a week, but if the neighborhood outside their door is not conducive to physical activity, it can be easier said than done. Whether you live out in the country or deep in the heart of the city, the design of the neighborhood around you can have an effect on your ability to exercise out of doors.

To clarify that relationship between neighborhood streets and physical activity, epidemiologist Ningqi Hou used data from one of the largest longitudinal studies of cardiovascular health in the United States, the CARDIA study. As a graduate student at the University of North Carolina, Hou and her colleagues analyzed the frequency of physical activity in over 5,000 CARDIA participants alongside characteristics of the “street networks” where they live. Hou, now a postdoctoral researcher in the Department of Health Studies at the Medical Center, looked at the density of intersections, the connectivity of streets, and the type of roads in each participant’s neighborhood.

Their hypothesis was that the “built environment,” the infrastructure surrounding a person’s home, has an invisible influence on their behavior that could conflict with their exercise plans.

“Although there are a lot of physical activity interventions, a lot of them don’t actually work. For example, you have an education program to tell people how beneficial physical activity could be, but over time, that effect is going to fade,” Hou said. “However, your built environment is really just existing there for you, and you are passively receiving its influences. To build a sustainable intervention, you need to know what works in that environment.”

The results of the analysis, published in December in Health & Place, were more complex than just “more roads, more exercise.” In areas of low urbanicity - rural and exurb regions with small, spread out populations - more connected street networks did indeed promote walking, jogging, and bicycling. Specifically, a higher density of intersections was associated with more outdoor exercise, suggesting that long, country roads are better suited to physical activity when they are connected instead of remote. That information could be valuable for civic planners looking to build “exurban” neighborhoods that promote health, instead of sprawling suburbs filled with meandering drives and cul de sacs.

“For the ongoing projects we can still influence that process and hopefully help planners to build a more physical activity-friendly environment,” Hou said. “Sometimes when I see the cookie-cutter communities, they have a very suburban style of being spread out, and it kind of worries me. But I think our result may do some good in informing policymakers to change the design for new communities.”

But in more densely packed areas of high urbanicity, the street network effect reversed for women. The higher the density of local roads, the less often female residents biked, jogged, or walked on average (men were unaffected). This unexpected result suggested that other factors associated with high population and street density - such as crime, or socioeconomics - could counteract the exercise benefits of a more connected neighborhood, Hou said. It also suggests that changing urban neighborhoods to promote physical activity may be more complex than adding intersections.

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The benefits of measuring body mass index (BMI) are clear: a physician who knows a patient’s BMI is more likely to counsel her on lifestyle changes, and people are more likely to try diet and exercise on a doctor’s advice. But in the often-rushed environment of the clinic, even the quick calculations required to know a patient’s BMI can get lost in the shuffle.

Internal medicine residents at the Medical Center noticed that almost none of their patients had a BMI recorded on their charts, but many of their patients seemed overweight and obese.

“They initially wanted to improve obesity rates in patients,” said Vineet Arora, MD, who participates in teaching a quality improvement curriculum to residents and is senior author of a study. “But we needed something feasible. Recording and calculating most patients’ BMI was something they could change.”

Their quality improvement initiative and a study about it, published online in March in the American Journal of Medical Quality, grew out of the quality improvement education that all residents now receive at the University of Chicago.

Neda Laiteerapong, MD, was an internal medicine resident at the University of Chicago Medical Center when she decided that measuring BMI was vital to improving patient care. “We couldn’t even identify who was obese in our clinic. If you don’t identify it, you’re not going to treat it on a patient-by-patient basis,” she said.

Laiteerapong and nine of her fellow residents looked at the triage of patients in the clinic, and decided that they could easily make a few small changes to the vital signs that nurses record when a patient is checked in. “Most clinics weigh people, but they don’t measure height,” Laiteerapong said, noting that the combination of height and weight is usually only measured in children. She also said that asking a patient his height isn’t an accurate way to calculate BMI, since people often overestimate how tall they are.

The residents added rulers in the clinics, height and weight charts in the patient rooms, and a slot on the patient intake form for BMI. The nurses took the measurements, and the residents were responsible for calculating BMI. Within a month, the number of patients with a recorded BMI jumped from 4% to 80%.

Julie Oyler, MD, assistant professor of medicine and associate program director for the internal medicine residency, implemented the quality improvement curriculum for residents in 2006. “I would consider this a successful project,” she said. “Instead of complaining about poor practices in a clinic, the residents are getting experience changing and fixing the clinics.”

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As the call for pitchers and catchers to report goes out in Arizona and Florida, amateur athletes are also getting the itch for warm weather and outdoor activity.  Whether you’re dusting off your baseball glove, your tennis racket, or your golf clubs, it’s not too early to start thinking about avoiding a sports injury that could keep you out of commission for most of this season. On Wednesday, March 2nd, at the Tinley Park Convention Center, the University of Chicago Medical Center will present a free seminar, Stay in the Game, featuring a panel of sports medicine specialists (and a buffet and iPad raffle, to boot).

Among the panelists will be J. Martin Leland, MD, assistant professor of surgery, and ScienceLife’s go-to expert on sports medicine topics. Leland has worked with professional baseball teams, college athletics programs, and youth athletes of all ages to diagnose and treat sports injuries such as torn labrums and ligament sprains, using physical therapy, non-surgical interventions, or surgical procedures whenever appropriate. But Leland also has an interest in preventing those injuries from happening in the first place, and will present tips on avoiding elbow and shoulder damage from various sports at the Tinley Park program.

“Prevention is very different. You’re thinking of very different things in terms of preventing injuries compared to if you’re trying to rehab one,” Leland said. “If you’re trying to rehab a specific injury, you’re going to have a very specific course. Prevention tends to be a broader strategy.”

As such, Leland identified four areas where injury prevention can be strengthened for athletes of all ages: conditioning, equipment, hydration, and mechanics. Though he’ll expand upon those topics at Wednesday’s event - and will, of course, answer attendee’s questions - here’s a sneak preview of his tips for avoiding the disabled list this year.

Conditioning

“I’ve worked with numerous professional baseball players, some of whom are incredibly flexible, to the point where grown men who are centerfielders in Major League Baseball can do a split at the drop of a hat,” Leland said.

That’s testimony to the importance of stretching and flexibility in avoiding sports injuries - a ritual you can personally observe if you ever show up early enough to watch the warm-ups before a baseball game. But amateur athletes should also be sure to stretch their muscles before any type of strenuous activity, even for a sport like golf that seems distinctly low-impact. People can loosen muscles with an activity as simple as jumping jacks, Leland said, but should make sure that all stretches are “slow, gradual, and progressive,” holding the stretch for at least 30 seconds, and avoiding stretches that could actually do more harm than good.

“You’ll see some people when they’re trying to stretch their hamstrings, they’ll bounce up and down,” Leland said. “That actually increases your risk of injury, and you can strain or tear a muscle doing those stretching exercises alone.”

Equipment

One of the most important precautions against injuries on the playing field is simply making sure the playing field is as safe as possible. Many youth baseball leagues have started to transition to new magnetic breakaway bases, Leland said, replacing the more common rigid, locked-in-place versions that can cause ankle and leg injuries during slides.

“When you slide into them really hard, the breakaway bases will move out of the way and it’s not like you’re basically sliding into a brick wall,” Leland said.

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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.

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Losing weight can be described at its simplest as a matter of counting calories during the daytime. Consume fewer calories and burn more through activity and exercise, and you’re likely to lose weight. Eat more high-calorie foods and sit on the couch all day watching football, and you get the opposite effect. But according to a new study from University of Chicago Medical Center researchers, another number should be taken into account by dieters: hours of sleep.

Given people generally do not eat or exercise while asleep (aside from some Ambien users), the link between weight and sleep may seem unlikely. But previous research at the University of Chicago found that sleep loss can wreak havoc with a person’s endocrine system, the hormones that control appetite and metabolism. In a 2004 study, men limited to only four hours of sleep a night reported increased appetite and showed hormonal changes consistent with increased hunger - increased ghrelin, which signals hunger, and decreased leptin, which signals satiety. But the long-term influence of those sleep pattern changes on weight gain or loss remained to be studied.

Monday, an experiment testing that connection was published by Plamen Penev, assistant professor of medicine, and colleagues in the Annals of Internal Medicine. And this was no easy experiment: 10 subjects had to spend two 14-day periods essentially living in a laboratory, so that scientists could control their diet, their daily activity, and the amount of sleep. But the small study reached a compelling, unexpected conclusion.

On the surface, the results may look disappointing. Subjects were allowed 8-1/2 hours in bed during one two-week period, and limited to 5-1/2 hours in bed the other two weeks. Diet and exercise were kept the same between the two periods, so that the effect of sleep alone could be isolated. But when the researchers looked at weight loss during the two periods, it was almost identical. Subjects lost about 3 kilograms, or 6 pounds, over the two weeks, whether they were getting a long night’s sleep or the reduced amount.

But not all weight loss is created equal. When the researchers looked more closely at what kind of weight was lost over the two-week periods, an important difference was revealed. With adequate sleep time, more than half of what was lost was fat. But when sleep was limited to less than 5-1/2 hours, only a quarter of the lost weight was due to reduced fat, suggesting that important protein and muscle were being shed instead of unsightly flab.

“If your goal is to lose fat, skipping sleep is like poking sticks in your bicycle wheels,” Penev said. “Cutting back on sleep, a behavior that is ubiquitous in modern society, appears to compromise efforts to lose fat through dieting. In our study it reduced fat loss by 55 percent.”

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Attaining a healthy weight is often billed as an individual pursuit, with television commercials eagerly encouraging customers to take hold of their habits. But for all the calorie-counting and exercise schedules you can give a person, their struggle with weight doesn’t occur in isolation. Family members and friends can negatively influence your diet, whether it’s meals at home or dining out, and your activity levels - encouraging a night at the bar instead of an hour on the treadmill.

But those external influences can also be harnessed for good, as a front page article by Julie Deardorff in the Chicago Tribune showed yesterday. Deardorff focused on the Maudsley Approach, a family-based treatment for anorexia and bulimia that involves the parents or other relatives in encouraging the patient to eat. That strategy is a shift from the traditional treatment for eating disorders, which usually involves a one-on-one inpatient program designed to convince the patient to regain healthy eating habits. But the Maudsley Approach, designed in part by University of Chicago psychiatrist Daniel Le Grange, has evidence on its side: trials, such as this one, that showed better outcomes with family-based treatment compared to traditional psychotherapy.

I spoke to Le Grange about the Maudsley Approach and other research trends for our Dr. FAQ video series in March; here’s the video that most directly focuses on family-based treatment.

While family appears to be a useful tool for positively changing the diet of someone with an eating disorder, there is also a dark side to the familial influence on food habits. Study after study has found that obesity runs in families, through an as-yet-undetermined interaction of genetics and environmental factors. Even in families where one member undergoes a surgical procedure for their obesity such as gastric bypass, the ripple effects through their family remain.

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Last October, a group of Illinois legislators visited the University of Chicago Medical Center for two days of education and discussion about cardiovascular medicine and health care reform, part of a nationwide “Legislator in the Lab” program. In addition to laboratory tours and panel discussions, the legislators and their staffs heard a series of brief, informative lectures on different cardiology topics, from prevention of sudden cardiac death to the use of stem cells for heart tissue regeneration. Many of these lectures were videotaped and posted to the Medical Center’s YouTube channel, and I thought I’d share a couple of them here today.

Dr. Matthew Sorrentino on Risk Factors for  Cardiovascular Disease

Everyone knows a little bit about risk factors for heart disease, such as obesity, age, family history, and tobacco use. But it’s important to remember that these factors don’t exist in isolation - instead, they interact in a way that can dramatically increase a person’s risk for heart attack or stroke. As such, cardiologists keep a scoresheet on their patients, adding up risk factors to determine a patient’s risk for heart attack. Matthew Sorrentino, professor of medicine in the section of cardiology, breaks down how doctors use these risk assessments, and how they can guide interventions that offer fast, powerful risk reduction.

Dr. Rupa Mehta on Heart Disease in Women

The undisputed leaders in the arena of women’s health awareness are breast cancer organizations, which routinely organize charity walks and fundraisers that draw thousands of participants and light city buildings pink. But as Rupa Mehta, assistant professor of medicine in the section of cardiology, reminded the audience in her talk, breast cancer and other diseases trail far behind cardiovascular disease as a killer of women. 460,000 women in the United States die from heart disease each year, which breaks down to about one death a minute. Mehta talks about the challenges that face physicians and patients in recognizing and treating heart disease in women, including watching out for the different set of symptoms - including fatigue, sleep disturbances, and shortness of breath - that signal an oncoming heart attack in females.

General internal medicine might seem like an awfully vague term. But assuming the health care reform bill signed by President Obama in March will be fully implemented, the general internists will finally have their day. Many of the bill’s provisions are focused on a reshuffling of the American medical landscape, which is currently dominated by sub-specialists focused on one organ system. In recent years, fewer medical students have chosen to pursue lower-paid and less glamorous careers in internal medicine, leaving a worrisome shortage in primary care doctors and hospitalists just as 32 million uninsured Americans are about to go on the books. The spotlight is about to focus on internal medicine.

“About time,” would probably be the response from most of the doctors assembled in Minneapolis last week for the 2010 Society for General Internal Medicine national meeting. Over three days, thousands of internists met in discussion groups and research panels to chart the course for a new age of American medicine. Though some fears were expressed about how an already overwhelmed system would be able to deal with the new influx of patients, the conference was more focused on seizing the opportunity to rehabilitate U.S. primary care and bring medical services to those who are traditionally underserved. The urgency of the moment was expressed right in the caps-lock and exclamation point of the meeting’s theme: “Value(s)-based generalism: THE TIME IS NOW!”

Of course, many of these efforts to expand the net of primary care didn’t start when Obama used 22 pens to sign the health care bill on March 23rd. Many of the presentations by University of Chicago faculty at the conference discussed pilot programs already being tested to improve the care of those who have traditionally fallen through the health care cracks, efforts to reduce disparity that may be instructive as the reform measures fall into place.

A workshop moderated by Marshall Chin, professor of medicine, presented four examples of programs funded by Finding Answers, Chin’s Robert Wood Johnson Foundation-supported group for studying racial and ethnic health disparities. Chin said the mission was to “evaluate interventions that reduce racial and ethnic disparities,” and the short presentations showed the breadth of that mission. Projects using cultural awareness training, electronic medical record software, and pay-for-performance programs were all discussed as potential solutions, with researchers from Harvard, Brigham and Women’s Hospital and Baylor outlining projects currently underway. One fascinating approach, described by Barbara Turner from Penn, employed African-American patients who had successfully controlled their high blood pressure as “peer coaches” to help fellow patients struggling to adhere to treatment - an elegant way of using community bonds to spread healthy messages.

Another successful example of community health intervention was presented in tandem by Deborah Burnet, section chief of internal medicine at the Medical Center, and Lorri McClinton-Powell, a teacher from Woodlawn Elementary School on the southeast side of Chicago. Last year, Burnet and colleagues conducted a pilot study of the POWER-UP program, an anti-obesity effort based around after-school activities for children and parents, with 40 children and their parents at Woodlawn. Fourteen weekly sessions - focused on themes such as “Muscle Mania” and “Stop & Shop” - taught the children about healthy eating, exercise, and behavior at restaurants and grocery stores. Though small, the study’s results held promise, with declines in overall body mass index among all but the heaviest kids at baseline. The group is currently working with Chicago Public Schools on the possibility of expanding the program for a larger study, Burnet said.

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Please welcome Laurel Mylonas-Orwig, author of today’s post and a new contributor to the blog!

Every two years, the best athletes in the world gather to compete in the modern Olympic Games. Against a backdrop of sand or snow, these seemingly superhuman competitors push their bodies to perform feats that would be impossible for the average person. Yet in the past few decades, concerns have mounted over whether some participants have gone beyond what the human body is truly capable of, relying on performance enhancers to reach new heights. In the 2004 Summer Olympics, a record number of athletes tested positive for banned substances, leading to several disqualifications and stripped medals. But in the just-completed 2010 Winter Olympics in Vancouver, drug testing has only caught two athletes thus far.

Despite this low number, experts are skeptical that athletes have stopped looking for illegal ways to gain a competitive edge. Instead, officials suspect that those who want to cheat have found ways around the current doping tests. The biggest elephant currently in the drug-testing room is an enhancement that is not yet reliably detectable, or even proven to be scientifically possible: gene doping.

Gene doping is a new and dangerous frontier in performance enhancement. An offshoot of gene therapy, gene doping may someday allow athletes to produce extra copies of genes that provide a competitive advantage such as increased muscle mass or endurance. At present, however, both gene doping and gene therapy remain largely untested in humans. Although some animal studies have shown promising results, others have demonstrated deadly side effects, leaving the effects of such treatments questionable at best.

Natural Enhancement?

When research into gene therapy began, it was not intended to yield performance-enhancing technology. Gene therapy is designed to treat debilitating or deadly medical conditions via the insertion of corrective genes into the body’s cells. But the theory behind gene therapy indicates that if the right gene were to be spliced into a healthy person’s DNA, a competitive edge could be gained. One example is that of erythropoietin, more commonly known as “Epo.” First purified in the late 1960’s by University of Chicago researcher Eugene Goldwasser, Epo is a hormone that promotes the production of oxygen-carrying red blood cells.

In 1997, a group of University of Chicago scientists led by Dr. Jeffrey Leiden experimented with Epo gene therapy as a treatment for Epo-responsive anemia, a debilitating condition caused by chronic renal failure. The study focused on the safety and efficacy of injecting a virus carrying the gene into the muscles of mice and non-human primates. Overall, the experiments proved successful: researchers were able to establish a threshold dose required for long-term Epo expression, and the elevated hematocrit, or red blood cell volume, in the animals that underwent the treatment led to increased aerobic ability. More importantly, no adverse reactions to the treatment were observed.

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The massive, long-term Diabetes Prevention Program study has now found (twice!) that altering one’s lifestyle in terms of diet and exercise is more effective than a common prescription drug in delaying the onset of the disease. To power this study and its recently published follow-up, dozens of medical centers conducted multiple examinations each year on thousands of patients - 3234 in the first 3-year study, and 2665 in the 10-year follow. It’s impressive - and more clinically useful - to look at the summary data accumulated from this very large population of patients. But what kind of impact does a huge study such as the DPP have on the individual participants?

With help from Margaret Matulik, the DPP program coordinator at the University of Chicago Medical Center, I connected with a couple of the study subjects to hear about the lives behind the data points. Both Katherine Seaberry, 80, and Robert Nolan, 61, are from Chicago, and enrolled in the study in the late 1990’s. Both were also motivated to join the DPP due to their respective families’ experience with diabetes - Nolan’s sister and mother suffered from the disease and died around the age of 60, and Seaberry said her “whole family” has been diagnosed with diabetes.

“It saved me,” Seaberry said of her involvement with the Diabetes Prevention Program. “It’s amazing that I’m the only one in my family that’s not diabetic. If I wasn’t in this study, I think I would be diabetic by now.”

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