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

Being a parent these days is anxious business, with an onslaught of news reports telling you what might be good or bad for your child’s health and development. In many cases, these claims are based on scientific evidence that is preliminary at best, studied only in small subject pools or retrospectively. To comprehensively confirm a link between, say, breast-feeding and body weight or living near a smokestack and asthma, a large epidemiological study that tracks thousands of children from before birth to adulthood is necessary. But that kind of study is very expensive, thanks to costs associated with recruitment, data collection, and analysis over decades of time.

As such, it’s better to do one enormous study of many factors that potentially influence child health rather than several independent and costly experiments. Enter the $5 billion National Children’s Study, a federally-funded project that hopes to track over 100,000 American children from their mother’s womb to age 21 in order to test possible influences - genetic and environmental, positive and negative - to their health. Already 11 years in the making, the study is just completing its warm-up phase, hoping to start the main event in April 2012. But as Daniel Johnson and Angela DeBello presented at the University of Chicago Medical Center Pediatric Grand Rounds earlier this month, the study is already teaching researchers valuable lessons.

“We have a very ambitious agenda,” said Johnson, an associate professor of pediatrics at the Medical Center involved in the Chicago branch of the study. “We’re kind of learning how to do this as we’re going along.”

The Children’s Health Study was authorized as part of the Children’s Health Act of 2000, alongside improvements to child mental health care, anti-violence programs, and day care provider training. While many of the other initiatives have long been implemented, the CHS has taken more time to reach the launchpad due to the mind-boggling logistics involved. In order to break down the roughly 4 million U.S. births each year into a manageable study cohort, the project will collect medical and survey data on growing kids from 105 different counties reflecting almost every region of the country.

It’s a beautiful plan on paper, but executing the recruitment and retention of 100,000 children around the country is immensely difficult. Debello, the vice president and associate director of public health research at the National Opinion Research Center (one of the organizations charged with administering the CHS), said that pilot studies have revealed just how difficult it is to even find pregnant mothers eligible for the study. Researchers have tried surveying homes for women expecting children or trying to have children, working with medical providers who can direct eligible women to the study, and mailed surveys to try and find the right subjects. But the up-to-date numbers presented at grand rounds indicated the low hit rate of this full court press: of 28,000 households originally contacted in Cook County, only 67 women were found to be eligible for the study (and only 49 provided consent to participate).

“It’s pretty overwhelming…the numbers are going to get big very quickly as this study progresses,” DeBello said. “Not surprisingly, it was far more expensive than we expected it to be.”

Hence that large price tag, which Johnson admitted is high, while also suggesting that it could be a bargain in the end. Any costs spent on conducting the study should be weighed against the potential health care costs saved with the information it collects. There’s a lot of room to work with in child health costs, he pointed out - a study in the journal Health Affairs calculated that environmentally-mediated diseases caused by lead exposure, air pollution, and other toxins produced $76 billion in medical costs in 2008 alone. Johnson also pointed out that the results of a similarly large project, the Framingham Heart Study, has prevented an estimated 800,000 deaths despite only being 1/20th the size of the CHS.

“It’s still not clear how successful this study will be,” Johnson said. “But we think that the goals and aspirations are certainly strong reasons to drive us forward.”

read more

In evolutionary biology today, it’s the ugly guys who get famous. But that hasn’t always been the case. When paleontologists were assembling a library of prehistoric life in the 19th century, they wanted to find the fossils they could easily categorize. The freaks, the weirdos, and the oddities were less well received, square pegs that wouldn’t fit in the round holes on a tree of life. However, today, it’s those hard to categorize fossils that tell the richest stories to biologists seeking to map evolutionary history, with all of its strange tributaries.

When Ramsay Heatley Traquair first described a 332-million-year-old fossil of a holocephalan (a relative of sharks and rays), he gave it a name that marked it as an outcast: Chondrenchelys problematica. Both parts of the name revealed his frustration with finding the right category for the ancient fish - Chondrenchelys means “cartilage eel” (a kind of oxymoron), and problematica is obvious. But the same features that made it so hard to classify in 1935 - plus a frightful new feature never observed before - made the long extinct species especially interesting to John Finarelli and Michael Coates of the University of Chicago.

Despite their obscurity today, holocephalans are an important group to scientists looking at the origins of jawed vertebrates - a group that would eventually include us. The holocephalans, including still-existing oddballs such as ratfish, the rabbit fish, and the elephant shark, split off from the rest of the fish world 400 million years ago, and have evolved in their own direction ever since. Studying the biology of modern holocephalans can tell us about some of our earliest ancestors, and studying holocephalan fossils gives the field even more direct insight into the early days of vertebrates.

“It represents an awful lot of vertebrate evolutionary history, that’s why it’s important,” said Finarelli, a research associate professor in the Department of Organismal Biology and Anatomy (OBA). “You’re getting down to a fundamental split at a very early point in the vertebrate family tree with what’s around today.”

“You look at these specimens to see what kind of insight you can get into the very general properties or conditions of how to make a jawed vertebrate, because you’re getting this independent pipeline,” said Coates, professor of OBA and senior author of the study.

Yet Chondrenchelys problematica lingered in obscurity until two new specimens were unearthed in the Mumbie Quarry in Scotland, described for the first time last week in the Proceedings of the Royal Society B. More complete than previously described fossils of the species, Finarelli and Coates noticed something unusual and unexpected about the long, skinny fish’s dental structure that sets it apart from other creatures, alive or extinct.

“It’s got teeth where you shouldn’t have teeth. Imagine a full set of teeth in your lips - that’s what this thing has,” Finarelli said. “They’re just fundamentally different from everything else we’ve ever seen in the jaw.”

To confirm that they didn’t just stumble upon mutant representatives of the species, the researchers went back and looked at the older Chondrenchelys fossils. Their re-examination confirmed that the unusual teeth was present in those less well preserved specimens as well, meaning the extra set of choppers was a standard feature for the species - and for no other species seen before or since.

The researchers haven’t yet commissioned an artist to reconstruct the face - “It would be pug ugly,” Coates said - but its homeliness is useful to scientists. Chondrenchelys existed at a time when holocephalans were exploding in diversity and the species newly-discovered weirdness only adds to the possible forms the group can take.

read more

A large portion of medical research is dedicated to designing and testing new and better drugs for treating disease. But what if we could improve treatments with the drugs we already have - and potentially cut costs at the same time? That’s the proposal made in an editorial this week in the Journal of the American Medical Association written by the Medical Center’s M. Eileen Dolan and Vanderbilt University’s Russell Wilke. Their article, “Genetics and Variable Drug Response,” is an optimistic snapshot of the current state of pharmacogenetics, the use of genetic information to improve the use of pharmaceuticals.

Though individualized or personalized medicine has been a goal of physicians and researchers for several years, the science (as it tends to do) is moving slowly. But as Dolan and Wilke write, promising pharmacogenetics examples are beginning to accumulate, from genes for enzymes found to influence the metabolism of chemotherapy and anti-clotting drugs to genetic variants that predict severe side effects from various agents. Some of these discoveries have already made it to the clinic, such as the genetic test (developed at the University of Chicago by Mark Ratain) for a variant that affects the response to the cancer drug irinotecan. Physicians can use the test to lower the dose in patients found to carry the variant associated with severe side effects at the normal dose.

Dolan and Wilke dream even bigger about pharmacogenetics. Currently, the standard drug dose is set by the average response of a large population, hoping to capture a level where people get the most benefit at the least risk. But as more information about the genetics of drug response are revealed, those doses can be better shaped to each patient according to their own personal risk-benefit. This could bring some drugs deemed “too dangerous” back to common use, if some patients have a genetic profile that enables them to endure the treatment safely.

“For drugs with a narrow therapeutic index, pharmacogenetic studies may hold the potential to resurrect treatments previously withdrawn from the market, particularly for agents designed to fill underserved clinical niches,” they write.

If smarter dosing can truly bring effectiveness up and toxicity down, it would be a benefit to both patients and the health care system in general. One suggestion by the authors is to start building gene-based drug dosing into electronic medical records, creating alerts for doctors about “drug-gene interactions” similar to current alarms for potentially dangerous drug-drug interactions. The future of medication may be more complicated than “take two of these,” but smart implementation may save dollars and lives.

Cohen Video

The American Society of Clinical Oncology recently filmed a short video with Medical Center associate professor of medicine Ezra Cohen, where he talks about how he decided to treat cancer patients while working as a small-town family physician. It’s a nice piece about how doctors are inspired to do their work and the connection between laboratory research and clinical care. If you want to see more videos with Dr. Cohen, he discussed head-and-neck cancer with ScienceLife almost exactly one year ago.

Elsewhere…

Right after his very cool study on the genetic origins of limb development was published, evolutionary biologist Neil Shubin departed for his annual expedition to the Canadian Arctic in search of fossils from the earliest limbed creatures. If you want to follow along with the hunt, Shubin’s teammate (and Tiktaalik co-discoverer) Ted Daeschler is blogging from the dig for the Philadelphia Inquirer! Read about how their remote site on Devon Island is “almost like Mars,” and how the expedition is already finding interesting fossils two days into the trip.

read more

The odds of acquiring a disease are often portrayed as a tug of war between two foes: genes and environment. The battle is not always evenly matched. A disease such as cystic fibrosis is entirely genetic - if a child inherits the mutated CFTR gene from both parents, no environment will prevent the condition. On the other hand, environment can trump genetics for many other diseases, such as the relationship between exposure to the toxic substance arsenic and the cancer mesothelioma. But in most places, the tug of war is a more balanced contest, with the genetic factors controlling risk competing with a range of environmental factors from diet and exercise to education and climate.

Scientists have traditionally kept score on these competitions using a measure called heritability, the percentage of a phenotype (a disease or characteristic) that is determined by genetic factors. One way to measure heritability is with twin studies, which assemble data from thousands of pairs of identical or fraternal twins as a natural experiment of whether genes or environment win out. But a new study from University of Chicago psychiatry researchers shows that the blanket term of “environment” does not have to mean things outside the body - it can also refer to the biological state inside the body.

For the paper, published last month in Behavioral Genetics, a team led by post-doc Terrie Vasilopoulos set out to test the relationship between two health conditions: hypertension and cognitive decline. Previous research examining this link established hypertension as a risk factor for the loss of cognitive ability late in life, producing decreases in performance similar to those seen in Alzheimer’s disease and other forms of dementia. Meanwhile, heritability research revealed that genetics play a large part in a person’s risk of cognitive decline in their golden years. So does the “internal environment” of hypertension - and whether it is treated - move the tug-of-war of heritability for cognitive issues toward genes or environment?

To test this hypothesis, the team used data from the Vietnam Era Twin Study of Aging - over 1,200 male-male twin pairs who served in the military between 1965 and 1975. With an age range between 51 and 60, the researchers looked at an important time in a man’s cognitive lifetime before the first signs of dementia typically set in, Vasilopoulos said.

“We really think we are capturing a very important developmental period with the guys that we’re studying, especially for cognitive phenotypes,” said Vasilopoulos, a researcher in the laboratory of Kristen Jacobson, assistant professor of psychiatry. “The groundwork for these bad things that are happening to you later in life are being laid when you’re much younger. By finding these mechanisms early in life, we can start to figure out better game plans of trying to protect people and help people make smarter choices when younger so we don’t see these bad effects when they’re older.”

The men were divided into three groups: those with hypertension receiving treatment, those with untreated hypertension, and those without hypertension. On overall measures of cognitive ability, the three groups showed no differences in performance, suggesting that the researchers were indeed looking at an age before any noticeable decline begins. But when the heritability of different cognitive measures was examined, a relationship with hypertension and anti-hypertension medication emerged.

For two measures - episodic memory and visual-spatial ability - the heritability of how a person performed on the tests actually decreased in those with untreated hypertension, relative to the other two groups. That is, in men with high blood pressure not taking medication, the “internal environment” of the disease outweighed the influence of genetics on two early warning signs of cognitive problems.

“These are the two types of cognitive domains that are first affected by age-related cognitive decline,” Vasilopoulos said. “In Alzheimer’s disease or other types of neurodegeneration or just regular aging, those are the most affected or first affected. So we really think we are honing in on the mechanisms of why hypertension is bad for cognitive performance late in life.”

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

In a typical clinical trial, the results are reported in purely medical or biological terms. Did the patients in the treatment group live longer than those in the control group? Did the drug shrink the tumor or reduce symptoms? Were clinical measures such as blood pressure or cell counts affected? These are the details that the Food & Drug Association and the physician community look for when they decide to approve or prescribe new therapies. But looking at a new treatment’s effects in a medical vacuum might miss critical details about its actual usefulness out in the real world, where patients have different priorities and health care dollars are finite.

To create a more well-rounded and practical clinical trial, medical researchers need to reach outside of their discipline for expertise. Or, they can bring those experts into the hospital fold, as was recently done with the establishment of the University of Chicago Program in the Economics of Cancer. Led by Ya-Chen Tina Shih, an economist who specializes in the economic aspects of cancer care, the program has a unique premise: to study the economics of a disease that produces estimated yearly costs of $270 billion and rising in the United States. In a field where new treatments, devices, and procedures appear with startling frequency, Shih’s group aims to weigh the costs and benefits of these new technologies so that patients receive the best, most logical care rather than just the hot, new, often-pricey thing on the market.

“I see it as a place to bring researchers together to look at economic issues in cancer,” Shih said. “The issues to be addressed can be large policy issues or a cost-effectiveness analysis comparing two different treatments. What we would like to do is provide an environment where if there are oncologists who want to study those questions, they don’t have to try to learn everything themselves. They can team up with economists or people in operation research or health services research, and can work on issues together. Similarly, people with no medical training who are interested in exploring those questions can find their clinical collaborators here.”

Calculating the cost of cancer is harder than it might seem. A diligent researcher could, with much effort, simply total up all the money spent on drugs, procedures, doctor’s appointments, and devices, and calculate a price tag for cancer or cancer treatment. But one must also take into account the indirect cost of missing work, either temporarily due to illness, side effects, or surgery, or permanently due to death. Other factors are even harder to convert into dollars, such as quality of life under different treatments, while still others are politically fraught, such as cost-effective analysis to determine whether a new treatment is a significant enough improvement over the current standard of care to justify coverage by insurance companies.

Economists can estimate these figures retrospectively, after a given treatment has been out on the market for a few years or more, but at that point the horse is long out of the barn. If a new treatment is given to patients for three years, then found to be less cost-effective than the standard of care it replaced, it could unnecessarily cost society millions or billions of dollars. Shih hopes that the Program in the Economics of Cancer will help cancer researchers design clinical trials with such economic questions in mind, so that information about costs can be gathered before the widespread diffusion of a new technology that provides a very small benefit at substantial cost.

“You don’t at the conclusion of a trial say ‘let’s add a cost-effectiveness analysis to that.’ By then, it’s way too late,” Shih said. “The idea is to get more people interested in collecting this data at early timepoints, so by the time they really want to answer a question, they have the data to answer it.”

read more

Cancer used to be a black box, a disease that physicians could only monitor through surgical biopsies and indirect measures. But for the last thirty years, the use of computed tomography imaging, better known as CT scans, has allowed oncologists and cancer researchers to keep close watch on the growth or shrinkage of a tumor for many different types of cancer. A patient with a lung tumor, for example, can be scanned every few months in order to see whether their therapy is working - and if it’s not, doctors may choose to switch treatments. Clinical trials of new therapies for cancer also make use of CT scans, using the increase or decreased size of the tumor as a primary data point.

But for all the benefits of scans over surgeries to monitor tumor size, flaws remain for CT scans. A new study published this week in the Journal of Clinical Oncology shines a harsh light on one of the primary problems - the technology’s variability. Patients usually are given CT scans months apart, and trained radiologists measure the tumors to see whether they are growing or receding. But how much of those changes can be attributed to random error from the imperfect resolution of the scan or the breathing of the patient?

To test this baseline error, researchers from Memorial Sloan-Kettering Cancer Center got a little tricky. Instead of taking two scans from a patient months apart, they took two scans in quick succession, within 15 minutes. The scans were then handed off to experienced radiologists, who were told to measure the change in tumor size without knowing how much time had elapsed between the images. The results were sobering - despite the tumor being biologically identical between the two near-simultaneous scans, the radiologists found changes in size of 1mm or more in more than half of the samples and a 10 percent error range in either direction overall. Although the criteria for tumor progression is an increase in size of 20 percent or more, that 10 percent error could considerably distort the data when clinical and research decisions are made using normally-spaced scans.

The result doesn’t render CT scans obsolete, but offers new caution about the method’s shortcomings.

“It’s the sense of, ‘Really? Is this first happening now?’” Michael Maitland, assistant professor of medicine at the Medical Center, commented to Reuters Health about the study findings. “This is telling us scientifically how much noise is naturally there without any treatment or the cancer getting worse. It’s an important thing to do whenever you are going to use any kind of marker for a disease.”

In an accompanying editorial in the Journal of Clinical Oncology, Maitland went further, writing with his co-authors that it was time for oncologists to rely less upon CT scans alone and move toward integrating those images with other measures to create more precise monitoring technologies. As cancer edges toward more personalized treatment strategies, developing better diagnostic tools will become even more important, they argued.

“It is time to cast away familiar conventions and turn to better methods of evaluating malignant disease therapeutics,” they wrote. “It is time to replace these systems with more innovative, quantitative approaches that have the potential to define relationships between solid tumors, disease progression, and therapeutic outcomes in patients.”

Elsewhere…

It might have come out a few days late for the 4th of July, but Travis Carter’s study of the effects of seeing the American flag on political beliefs is still timely. If the Booth Business School researcher is right, we’ll all be slightly more Republican for at least the next 8 months. Ed Yong at Not Exactly Rocket Science did a great writeup that was featured on the Colbert Report this week (and also wrote up our own Neil Shubin’s study on the origin of limb genetic programs this week as well).

read more

A patient in the hospital receives a long line of visitors, from physicians to nurses to medical students to other staff members. The conversations with most of these personnel tends to be mostly business - answering clinical questions or following instructions, with maybe a little bit of small talk squeezed in between temperature measurements and pill swallowing. Deeper conversations of a religious or spiritual nature may be left to hospital chaplains or religious representatives visiting the patient. But with only about two-thirds of hospitals providing pastoral care - and with tightening hospital budgets potentially threatening to push that number even lower - is it possible to measure the value of these spiritual discussions?

That was the aim of a new study by the research group of Farr Curlin, associate professor of medicine at the University of Chicago Medical Center. In an analysis led by medical student Joshua Williams, the team measured how many of over 3,000 patients in a survey reported having a spiritual or religious discussion while they were in the hospital, who that conversation was with, and most importantly, how it affected the patient’s opinion of their experience in the hospital. Published recently in the Journal of General Internal Medicine, the study found that a little bit of attention to a patient’s spiritual concerns boosted patients’ satisfaction with doctors, confidence and trust in their physicians, their feelings about the teamwork between doctors and nurses, and their rating of the overall care received.

“Our data is the strongest data so far that having these issues addressed, even having them brought up, is something that people experience as very positive,” Curlin said. “What’s interesting is it didn’t matter whether the patient said they wanted it, just having had it was associated with higher rates of satisfaction across four different measures.”

Surprisingly, the source of the spiritual or religious conversation was less important than the content. The benefits were the same whether patients talked with a chaplain, a physician, or even a religious figure from outside the hospital, Curlin said. Furthermore, while most of spiritual discussions were originated by chaplains (61 percent), the patient satisfaction figures suggested the good vibes were contagious, spreading out to improve patients’ feelings about the other members of their health care team.

“It was the whole experience: the physicians, the clinical team that took care of them,” Curlin said. “The care they received at the hospital was rated more highly if someone talked to them about spiritual concerns.”

The effect was not limited to patients with strong religious beliefs, or even those who sought out a patient ear for their spiritual thoughts. Forty-one percent of patients said they wanted to discuss such concerns, but even patients who weren’t seeking spiritual counsel but were approached anyway demonstrated the same positive influence upon their experience in the hospital. Curlin said that a benefit even for non-religious patients indicated that the effects of talking to a chaplain (or a physician, or a friendly custodian) were more about being recognized as a person instead of a patient.

read more

It’s one of the most significant events in Earth’s history: the moment when a sea creature first stepped - or more likely wriggled - onto land. The momentous occasion 400 million years ago opened up a whole new habitat where life on Earth could evolve and spread out, and made that first bold pioneer and its peers the ancestor to everything from dinosaurs to birds to humans. Obviously, scientists would love to know more about what that brave explorer looked like, and have long hunted for their fossils. But genetics offers another way to journey back in time and look at the biology of the first fish to leave the water, and a study published today by University of Chicago scientists suggests that the genetic tools to make those first historic steps were present long before they actually occurred.

In this case, the genetic hunt was inspired by a famous fossil find, the 2004 discovery of Tiktaalik by a team led by University of Chicago evolutionary biologist Neil Shubin. Tiktaalik was described by its discoverers as a “fishapod” - a transitional species between fish and the four-limbed land-dwelling tetrapods. Though Tiktaalik and its cousins had fin-like appendages, the skeletal structure within those fins was more complex than typically seen for an aquatic species, featuring wrist and hand-like compartments that may have allowed it to do “push-ups” and drag itself slowly across land. Such a sophisticated structure probably didn’t develop overnight, leading Shubin to wonder just how far back the genetic program for developing a limb might have existed in fish.

“This is really a case where knowing something about the fossils and the morphology led us to think about genetic experiments,” said Shubin, the Robert R. Bensley Professor of Organismal Biology and Anatomy and senior author of the study in the Proceedings of the National Academy of Sciences. “Tiktaalik and its cousins showed us that this limb compartment is not an utter novelty in tetrapods, as was thought for a long time. So an antecedent of that program must exist.”

To answer that question, Igor Schneider, a postdoctoral research in Shubin’s laboratory, assembled a genetic “time machine” to look at the origin of a genetic switch for limb development. A genetic switch controls the expression of genes - where and when they are turned on during embryonic development. Schneider took the human sequence of a genetic switch called CsB that controls limb development and looked for similar sequences in a diverse group of animals: mouse, chicken, frogs, zebrafish, and the skate. Though very different today, the animals all share a common ancestor some 400 million years in the past, millions of years before Tiktaalik. Looking at what the CsB switches share in common between those distant relatives today offers a glimpse at the biology of their great-great-great-(repeat 100 million times)-grandfather.

Just looking at the sequences revealed many similarities between the CsB switches of fish species and tetrapods. But the real test was to determine whether the switches performed similar functions despite 400 million years of divergent evolution. To test this required a little bit of mad science: swapping gene sequences across species. First, the CsB switch from a mouse was put into a zebrafish embryo, where it was shown to activate gene expression in the distal fin. The reverse experiment - zebrafish CsB into mouse embryo - was even more exciting, as the primitive fish switch successfully activated gene expression in the developing mouse paw (seen at right).

“The genetic switches that drive the expression of genes in the digits of mice are not only present in fish, but the fish sequence can actually activate the expression in mice,” Schneider said. “This tells us how the antecedents of the limb go back in time at every level, from fossils to genes.”

In both experiments, the gene that the switches activated was merely a reporter gene that told researchers where and when the switch was flipped on. The actual genes that cause an appendage to form the skeletal structure for a limb or fin were not present. But could a transplant of the mouse switch and the relevant genes into a fish embryo produce a lab-grown fishapod?

read more

By John Easton

At 1:30 pm, on Monday, December 12, at its Annual Meeting and Exposition in San Diego, The American Society of Hematology will recognize Janet Rowley of the University of Chicago Medical Center, and Brian Druker of Oregon Health & Science University, with the 2011 Ernest Beutler Lecture and Prize for their significant advances in the diagnosis and treatment of chronic myeloid leukemia (CML), a cancer of the blood characterized by an overproduction of white blood cells.

This is a great honor - and a storage problem.

Rowley has received many prizes over the course of her career: the Lasker Award, the Gruber Genetics Prize and the American Association for Cancer Research Award for Lifetime Achievement. President Jimmy Carter appointed her to the National Cancer Advisory Board. President Bill Clinton awarded her the National Medal of Science. George W. Bush selected her for his President’s Council on Bioethics. She stood with President Barack Obama when he signed the stem cell research bill and she returned to the Obama White to accept the Presidential Medal of Freedom. Then she moved to a new office with a better view, but less shelf space.

Rowley has long been known for brilliant insights, intellectual rigor, and relentless tenacity, but never for extreme neatness. “Her filing system involved piles,” said MaryBeth Neilly, a senior research technician who works with her. When preparing for the move, “we found awards all over the place,” she said. “We knew we needed a place to put them, and that her office was not that place.”

Thus was born the shrine. “Once we moved, but before we unpacked, we ordered a display case,” said Neilly. She and Rowley sorted through the honors and picked the cream of the crop; those that were the most significant, or that looked really cool. Lots of them, some of the trophies, most of the plaques and the vast majority of honorary doctorates, were transported - lovingly, but in bulk - to the University archives.

The display case soon filled to capacity. “There’s a lot of crystal in there, a lot of shiny metal,” Neilly said, such as the National Cancer Institute’s Rosalind E. Franklin Award for Women in Cancer Research, a big carved glass bowl, or the National Medal of Science, a golden medallion.

A few favorites - for reasons aesthetic or sentimental - wound up in Rowley’s office, including the Lasker, the Presidential Medal of Freedom, a large, twisting crystal chromosome from the Jeffrey M. Trent Lectureship in Cancer Research, and a bronze sculpture from the Leukemia and Lymphoma Society. A few more are at Rowley’s house. Two made of a particularly valuable soft, shiny heavy metal, stay at a local bank. The exact positioning of the Beutler Prize has not yet been determined.

Elsewhere…

Vijay S. Dayal, a longtime fixture of the Medical Center’s otolaryngology department, passed away last week at the age of 74. A head-and-neck surgeon and expert on hearing and balance, Dayal was also known as a skilled inventor, obtaining patents for an artificial voice box and a customized “rotating chair” used to test dizziness and balance. “Testing in the chair is not uncomfortable for the patient,” Dayal said in 1991. “It’s like a mild ride on a merry-go-round and it provides us with information we cannot get any other way.” You can read another obituary for Dr. Dayal at the Chicago Tribune.

What’s it like to be a medical student? Pritzker first-year Akash Parekh narrates a day in his life for US News & World Report. Spoiler alert: there’s not much free time, or sleep.

If parents refuse vaccinations for their child, should pediatricians be allowed to refuse to take them as a patient? That interesting ethical question was the subject of an article by the Chicago Tribune’s Deborah Shelton.

The new Scientific American blog network officially launched this week, and provides a new home to many of my favorite science bloggers. For a taste, check out Lucas Brouwers’ post on the evolution of E. coli, and this interview with John Boswell of Symphony of Science (best known for the Carl Sagan autotune track “A Glorious Dawn”).

The latest cult favorite in the sphere of human genetics is the microbiome, the genes of the bacterial species that live inside and upon the human body. Because bacterial cells outnumber human cells in an adult by approximately ten to one, and tens of thousands of different species make up the human ecosystem, studying this world will be even more of a challenge than the Human Genome Project, which only had to concern itself with a single species: us. But as the microbiome is increasingly discovered to play a role in obesity, diabetes, infant diseases, and hospital-acquired infections, the number of researchers pondering a bacterial angle for their own disease of interest is exploding.

So the microbiome was the ideal topic for the first lecture of the Institute for Translational Medicine seminar series on Advanced Tools, a monthly meeting designed for University of Chicago researchers to share methodological know-how. Leading the discussion was a veteran of the young microbiome scene - Eugene Chang, professor of medicine and an expert on gastroenterology. For several years, Chang has applied the tools of microbiology to the bacterial populations of the human gut, looking for mechanisms involved in digestive diseases. As the techniques for studying the microbiome have evolved, Chang said he has seen the pros and cons of the field’s growth.

“This is an area that is really hot,” Chang said. “It isn’t coincidental that this interest has coincided with emerging technologies, because the emerging technologies over the last decade have allowed us to look at the microbiome in many different ways….but this is a field where you can be easily consumed by the technology.”

Those techniques have changed alongside the trends of the broader field of microbiology, Chang said. Scientists interested in bacteria were once limited to studying what they could both find and grow in a lab dish, which left the vast majority of species unexplored. But new genetic techniques have brought those hidden worlds into the light, allowing scientists to take a more complete census of the bacteria present in a given sample from the Earth’s environment, or the special environments within the human body. With this added power has come a whole new menu of choices for scientists, from low-cost methods (i.e. T-RFLP) that can take a surface-level snapshot of the most common members of a microbial community to deeper sequencing that can identify rare microbes that may turn out to be relevant to disease (i.e. pyrosequencing).

“We have a number of techniques that have advantages and limitations,” Chang said. “What you use is dependent on what your question is and how deep you need to go.”

In Chang’s laboratory, the questions relate to the origins of inflammatory bowel diseases such as ulcerative colitis. A recent study looked at the microbial diversity within the colon, comparing the bacterial populations present in the mucosa of the proximal colon (near the small intestine) to the distal colon (near the anus). A T-RFLP analysis, which looks at fragments of ribosomal DNA in the mucosal samples, found that the microbes present in the two regions were distinct, with higher “richness” (the number of species present) observed in the proximal versus distal colon.

But to determine the role of the microbes in disease, just taking a census isn’t enough. The newest wave of microbiome research is focused on function, using techniques that find out what those billions of bacteria are actually doing inside our bodies or out in the world. With metagenomics, scientists can analyze all the genes from a given sample of soil, skin, or mucus, then group those genes by their functional role (metabolism, transport, etc.) using a technique developed by Argonne called MG-RAST. Many groups, including Chang’s team, are also interested in measuring host-microbe relationships - how the bacterial population affects the biology of their home organism.

“Sure we can say who’s there, but how do we actually know what’s important?,” Chang said.

read more

The hepatitis C virus has always been an unusual disease. Largely symptom-free in its early stages, many people are unaware for many years that they have contracted the virus. But if left untreated, hepatitis C can eventually cause severe liver damage that may necessitate an organ transplant. Until recently, physicians have had only limited success in combating the hepatitis C virus, administering a lengthy combination of two drugs that completely cured less than half of the patients treated.

However, in recent months the forecast for curing hepatitis C patients became much sunnier. The near simultaneous FDA approval of not one, but two new therapies for the virus - called telaprevir and boceprevir - promises to dramatically improve the cure rate for the disease and prevent serious cases of liver cirrhosis and cancer. The two drugs are members of the same protease inhibitor class that has revolutionized HIV treatment, and adding one to the previous two hepatitis C therapies (forming what’s known as “triple therapy”) promises to increase cure rates to as high as 80 percent.

But new therapies bring loads of new questions and considerations for patients. At the University of Chicago Center for Liver Disease, which takes care of hundreds of hepatitis C patients, physicians Donald Jensen and Andrew Aronsohn organized a series of patient education sessions to address how the new therapies change the landscape of the disease. While many patients have been waiting years for the approval of telaprevir and boceprevir, choosing the right time to begin therapy is no simple decision. Because the therapy still takes between 24 and 48 weeks to complete, and must be closely monitored to make sure the protocol is successfully followed by the patient, hepatitis C clinics can only start treating so many patients at a time. In an editorial for the journal Hepatology, Jensen and Aronsohn explained why the University of Chicago has thus chosen to treat the sickest patients first, asking hepatitis C patients in the earlier, less severe stages of the infection to delay their therapy with the new agents.

To further spread information about these decisions, the basics of hepatitis C, and the impact of the new therapies, Jensen and Aronsohn agreed to film a series of videos for ScienceLife. Watch as the two physicians explain how the new therapies work, what patients can expect from the new treatment protocol, and why it is important for patients and their physician to choose the right time to start therapy.

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.