Science Life - A blog of news and ideas in Biomedicine

A Nasal Path to Migraine Relief

Posted at 12:28 pm CT on February 1, 2012

800px-action_photo_of_nasal_spray_on_a_black_backgroundRoughly 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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Posted by - Rob Mitchum

Professionalism and Ethics, Day Two: Prize and Prejudice

Posted at 12:27 pm CT on November 17, 2011

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By John Easton

Even in the court of ethics and medical professionalism, there’s nothing wrong with the occasional honor or award. On day two of the conference, the Maclean Center awarded its first Prize in Clinical Ethics and Health Outcomes - at $50,000, the largest such prize in the ethics field - to John Wennberg, the Peggy Y. Thomson Professor for Evaluative Clinical Sciences at Dartmouth Medical School and founding editor of The Dartmouth Atlas of Health Care.

In 2007, the journal Health Affairs named Wennberg as “the most influential health policy researcher of the past 25 years.” Fitzhugh Mullan, former director of the Bureau of Health Professions in the U.S. Department of Health and Human Services, described Wennberg as “both the Christopher Columbus and the Johnny Appleseed of clinical variation,” meaning he not only discovered the field but also brought it to the attention of the medical and health policy communities.

“While John Wennberg is regarded as a health services researcher,” said Mark Siegler, MD, director of the MacLean Center, “his fundamental work on patient preferences and shared decision making highlight his contributions to the field of clinical medical ethics.”

The Dartmouth Atlas examines the patterns of medical resource intensity and utilization in the United States, with special emphasis on end-of-life care, inequities in the Medicare reimbursement system and the under-use of preventive care.

From the start, it has brought surprises, according to Kenneth Polonsky, dean of the Division of the Biological Sciences and the Pritzker School of Medicine at the University of Chicago, who introduced Wennberg. The report comprehensively documented the “striking differences” in the amount of health care provided in different regions, adding the provocative observation that the amount or cost of care delivered did not correlate with good outcomes.

Joking that “when you get paid so much to give a lecture, you get a little nervous,” Wennberg spoke about the early days of the Atlas and how their studies of practice variation in the mid-1970s “challenged the notion that science was driving utilization.” Instead, decisions about surgical treatment for benign prostate hyperplasia revealed what the researchers called “surgical signatures,” patterns of practice based on the beliefs of individual surgeons.

When Wennberg’s team developed short, balanced videos to show to patients, explaining the risks and benefits of surgical treatment and showing taped interviews with two physicians who had made different decisions, patients were much less likely to choose surgery. “This was the first evidence,” he said, “that engagement of patients could lead to the right utilization rate.”

However, only about 25 percent of medical care turns out to be so “preference-sensitive,” forming what Wennberg calls “little islands of rationality.” Studies of end-of-life care found a far more limited role for shared decision making between patients and their caregivers. Instead, demand for resources appears to be driven by supply. Empty hospital beds and unused capacity strongly correlate with increased medical care late in life. For example, more than twice as many patients were admitted to an intensive care unit in the last six months of life at UCLA compared to Dartmouth.

Wennberg described the four goals of the Atlas’s end-of-life team for the next five years: to better inform patient choices, improve the science behind these decisions, promote organized care and constrain undisciplined capacity spending. At this point, he said, “we don’t need more research, we need more action.”

Another session at the conference focused on a very different book, not an atlas but a historical novel, based on true events and real people. Open Wound: The Tragic Obsession of Dr. William Beaumont, by former ethics fellow Jason Karlawish, a professor of medicine and medical ethics at the University of Pennsylvania, examines the professional and ethical issues raised by William Beaumont, a 19th-century surgeon who cared for - and experimented on - a patient with a shotgun-blast-induced hole in his stomach. Beaumont saved the patient’s life, but then used this wound, which never quite healed, as a window to decipher the mysteries of digestion.

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Posted by - Rob Mitchum

The Many Faces of Medical Professionalism

Posted at 1:35 pm CT on November 16, 2011

siegler-scopeEvery patient wants their doctor to be a professional. But the broader concept of “medical professionalism” is not a cut-and-dry matter, as it opens the door to debates over how physicians interact with politics and society, the regulation of doctors’ ethical and legal behavior, and the role of the physician in the new world of health care. Those are large enough questions to warrant a year of discussion in the MacLean Center for Clinical Medical Ethics Seminar Series, and a centerpiece slot at the 23rd annual Dorothy J. MacLean Fellows Conference, held last week.

“In recent decades, there has been a renewed focus in medical education on professionalism being seen as a way to improve patient care, strengthen the doctor-patient relationship, reduce conflict of interest, improve physician self-regulation and ultimately to strengthen the alliance between medicine, patients, and society,” said Mark Siegler, Director of the MacLean Center, in his opening remarks.

If professionalism is too abstract, the themes on the first day of the conference could be simplified as what a doctor should and should not do in today’s tumultuous health care waters. Driving that instability is the ever-growing chunk of the world economy eaten up by the health care industry, said the conference’s first speaker, Arthur Rubenstein of the University of Pennsylvania (and formerly of UCMC). The United States spent $2.3 trillion on health care in 2009, he said, roughly equivalent to the GDP of France. With economies slowing around the world, those costs are unsustainable, and physicians must come together as a profession to work with patients and policymakers to find solutions that benefit all parties.

“We need to do something about that as a medical profession. If we don’t, the future is going to be quite problematic,” Rubenstein said. “If in the financial crisis which we are now surely in, at both the state and national level, the medical profession puts their own interests before those of patients - particularly the poor and elderly patients - our now privileged position in society will be given up, and our contract with society will be changed for the worse, and we may not recover in the foreseeable future.”

Participation was also one take-home message of Christine Cassel’s talk, which emphasized how the classical definition of the medical professional would have to evolve in the new health care landscape envisioned by last year’s Affordable Care Act. Cassel, the president and CEO of the American Board of Internal Medicine (and another former UChicagoan), said that the three primary goals of health care reforms are affordability, access, and quality. Creating a system that addresses all three will require balancing the intrinsic motivations of physicians to help patients with the extrinsic motivations of financial and regulatory oversight. A new kind of medical professionalism that accepts a health care system based around technology and teamwork will help the field achieve that balance with a minimum of pain, Cassel said.

“To my mind it’s a new kind of professionalism that leaves behind these old ideas of what the nostalgic profession was, and becomes committed to collaboration, evidence, measurement, and transparency so that it’s not at odds with accountability, but in fact becomes accountability,” Cassel said. “This is a challenge for many of us, and it’s going to take change.”

A case study of how that change can happen was presented by Troy Brennan, Chief Medical Officer for the pharmacy chain CVS. Brennan recapped efforts over the last decade to eliminate gifts from pharmaceutical companies to physicians at academic medical centers. While this practice was once thought to be innocuous by many physicians, others argued that it created a conflict of interest. In an example of extrinsic regulation to alter physician behavior, the American Board of Internal Medicine proposed that academic medical centers regulate these interactions between Big Pharma and physicians - an initiative supported by medical students. As a result, physician-industry relationships dropped, though a CVS study is still collecting data on whether that has affected prescription behavior, driving more doctors toward prescribing generics instead of brand name drugs.

Preserving physicians’ integrity and reputation is important for the role of the medical professional proposed by Paul Starr of Princeton University. In a time of ideological polarization and lack of trust in public institutions, it’s important for professionals to bring trustworthy knowledge to the public debate, Starr said, citing the recent Republican debate where candidate Michele Bachmann claimed a link between the HPV vaccine and mental disability.

“When prominent political figures make uninformed statements on national television about the effects of a vaccine, or distort the findings of researchers on a cancer screening test, then politicians may have a real, substantial impact on public understanding,” Starr said. “It is just at those moments when the scientific community should hold its ground and insist on abiding by the evidence.”

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Posted by - Rob Mitchum

Finding the Muslim View on Medicine

Posted at 2:13 pm CT on August 15, 2011

sultanahmed_kneelMuslims are the fastest-growing religious minority in the United States, with over 7 million Americans declaring themselves as followers of Islam and more than 2,000 mosques nationwide. But in spite of the numbers, little data has been collected about American Muslims’ beliefs about health and disease, or their experience in the U.S. health care system. One reason for this also lies within the demographics, as American Muslims are a particularly diverse minority, containing South Asians, Arabs, and African-Americans, as well as both recent immigrants and long-term, multiple-generation natives. With such a wide variety of members from different ethnic, racial, and socioeconomic backgrounds, how does one pin down the health care experience of American Muslims?

The only way, thought Aasim Padela, was to talk to all of them - or at least representatives from each of the major groups in the American Muslim community. For his recent report, “Meeting the Healthcare Needs of American Muslims,” Padela and his colleagues at the Institute for Social Policy & Understanding went to the rich Muslim community of southeastern Michigan, one of the largest Muslim populations in the United States. Reaching out to multiple mosques and holding focus groups with over a hundred participants, the group looked for common denominators of people who share the Islamic faith, but perhaps little else.

“We looked at American Muslims as a conglomerate and asked what was common,” said Padela, assistant professor of medicine and director of the Initiative on Islam and Medicine at the University of Chicago. “We wanted to talk to each of these three large groups, which we know comprise the majority of American Muslims, and look at what’s similar in terms of health care challenges and beliefs. What we found as similar is something we can attribute to their faith.”

The final product was a fascinating piece of medical anthropology, a snapshot of how American Muslims view their own health or illness, the struggles they face in the U.S. health care system, and their solutions for establishing stronger communication between their faith and their medical caretakers. In an environment where physicians are expected to meet their patients halfway on ways to prevent and cure disease, understanding the perspective of a community that is already large, and growing larger, is an important first step toward improved care.

One primary finding of the report describes the “medical narrative” of American Muslims, their views on where disease comes from and the most effective strategy for fighting it off. Many participants in Padela’s focus groups believed that God takes an active role in health and illness, perceiving conditions from a winter flu to breast cancer as divinely ordained.

“Most participants perceived illness through a religious lens as predestined,” the authors wrote, “a trial from God by which one’s sins are removed, an opportunity for spiritual reward, a reminder to improve one’s health, and sometimes a sign of personal failure to follow Islam’s tenets.”

One might think that treating such a patient would be difficult for a physician, faced with a patient that believes they are being religiously challenged through their illness. But Padela said that a closer understanding of Islam refutes these fatalistic notions, and that most Muslims agree that health issues are best confronted with a combination of spiritual and medical healing.

“God also says to take care of your body, and that means you have to go to people in this world,” said Padela, who conducted the research as a Robert Wood Johnson Foundation Clinical Scholar at the University of Michigan. “Doctors are a part of that, but only a part. Imams play a big role in healing, in the sense that they help you understand disease and illness.”

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Posted by - Rob Mitchum

Medical Ethics Summer School

Posted at 8:26 am CT on August 9, 2011

It has been a couple months since the end of the spring quarter, and the with it the end of many of the Medical Center’s weekly lecture series. But a recent batch of videos posted to the website of the MacLean Center for Medical Ethics brought a whiff of the school year to the dog days of summer. The videos feature a selection of the lectures from the third and final segment of the 2010-2011 theme, “Health Disparities: Local, National, Global,” [pdf] and run the gamut of expert perspectives from libertarian law and the insurance industry to black history and medical education. If you are going through lecture withdrawal or want to get excited for next year’s MacLean Center series (“Medical Professionalism and the Future of American Medicine” [pdf]) beginning in late September, enjoy these videos.

The Case for Health Disparities - Richard Epstein, University of Chicago

Richard Epstein’s annual contribution to the seminar series is always a combustible reaction, where the classically conservative law professor’s market economics conflict with the more liberal lean of the regular audience. This year’s topic was especially flammable - after a couple dozen lectures on the struggle to reduce the health care gap in the United States and around the world, here was Epstein arguing for preserving those very same inequities. Beyond the deliberately provocative title, Epstein’s characteristically off-the-cuff speech recommended that health care reformers should choose a different target - instead of minimizing the health care differences between top and bottom, push policies that support growth and innovation for all patients, rich or poor, while encouraging charity instead of coercive giving.

Future Directions for Health Equity - Anne Beal, Aetna Foundation

The Aetna Corporation is in the business of providing health insurance to Americans. The Aetna Foundation is the charitable arm of that company, dispensing grants and funds to research ways of improving the health care system and reducing costs. Researcher and author Anne Beal is the current president of the Aetna Foundation, and focused her talk on reducing costs and inequalities via improving the quality of health care in America. “Giving people the right care at the right time and preventing disease is an amazing way for us to really rein back a lot of these health care costs,” Beal said. [Original Article]

“Without Health and Long Life All Else Fails”: African-Americans and the History of the Elimination of Racial Disparities in Health and Health Care - Vanessa Northington Gamble, George Washington University

Obviously, racial disparities in health care are not a new phenomenon. Efforts to improve the health of African-Americans also didn’t begin with the civil rights movement, though the strategies employed by the disparity-fighters of the segregation era were very different from today.

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Posted by - Rob Mitchum

The Stressful Truth Hidden Inside a Reverse Disparity

Posted at 8:40 am CT on May 26, 2011

398px-u-turn_iconsvgOver the year-long discussion of health disparities in the MacLean Center for Clinical Medical Ethics seminar series, the health gaps presented between American whites and blacks have been predominantly a one-way street. On nearly every health measure - from infant mortality to diabetes to cardiovascular disease - higher rates are observed for African-Americans. But there’s one health gap where the racial positions are surprisingly flipped, said James Jackson of the University of Michigan in his visit to the series in early May. Over the course of a provocative talk, Jackson demonstrated how this strange reverse disparity in mental health could be hiding a model explaining the physical health gaps that continue to resist reduction efforts.

In a 2007 study, a survey project led by Jackson measured the lifetime prevalence of major depressive disorder in African-Americans, Caribbean blacks, and white Americans. An almost complete reversal from the normal health disparity was observed, with roughly 18% of whites diagnosed with major depression at some point in their lives, compared to only 10.4% of African-Americans. The data, though replicated several times, was initially greeted with skepticism by observers who were mostly familiar with biased data based on hospital admissions, Jackson said.

“When people noticed this, they really began to contort  the data,” said Jackson, a psychologist and director of the Institute for Social Research at the U. of M. “The argument was that there must be something wrong with the way it was assessed, because everybody knows that African-Americans have to have higher rates of psychiatric disorders than whites.”

But now that the reverse disparity has been verified in many different populations, Jackson has started to ask why these differences exist. His working theory hinges on two other observations: the delayed appearance of physical health disparities over the course of life, and cultural differences in the way people cope with stress. When well-known health disparities on measures such as diabetes or hypertension are broken down by age, there is not a consistent gap between blacks and whites, but a gap that emerges and rapidly grows in middle age (45-64 years old). Putting aside differences in infant mortality rates, some evidence actually suggests that black children are healthier than white children on many measures, Jackson said.

The growing gap in health measures over the life course is paralleled by another growing gap - in the frequency of poor health behaviors. In white populations, smoking rates peak in young adulthood and then decline, while the rate in black populations accelerates with age. The same pattern holds true for heavy alcohol use and drug use, Jackson said, while frequency of vigorous physical activity declines with age faster for black females than white females. Obesity is more complex - it is the only black-white difference observed early in life, at least for females - but this gap also widens over life course, regardless of socioeconomic status.

The core of Jackson’s theory was to cast those physically unhealthy behaviors not as mere vices, but as methods people use to self-medicate themselves against the stress of daily living.

“If you’re having a bad day…you know it. At the end of the day, your stomach is upset, you have a headache. There are palpable things that are present with regard to the stress reaction to the circumstances,” Jackson said. “But if you are growing a tumor for cancer, you don’t know it, until it reaches a certain stage.”

“If you know you’re having these stress-related kinds of problems, this awareness motivates you to action - you are motivated to do something about the physiological and psychological consequences of stressors in your life. And what do you want to do? People eat comfort food to reduce stress, the activity in the chronic stress response network,” Jackson said. “If I’m stressed, a Twinkie makes me feel better.”

Self-regulating stress can also go beyond junk food, Jackson said, to severe drug and alcohol use. All of these coping strategies may help dampen the stress response and protect mental health, but only at the cost of exacerbating physical health problems.

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Posted by - Rob Mitchum

Fighting Disparities During Segregation

Posted at 12:09 pm CT on May 13, 2011

424px-booker_t_washington_retouched_flattened-cropReducing health disparities in the United States has been a top priority for our health care system in these early years of the 21st century. But efforts to narrow the health gap between black and white patients go much farther back, to the start of the previous century when the first African-Americans were graduating from medical schools and Ph.D. programs around the United States. Those early black professionals looked at the state of African-American health at the turn of the 20th century and were appalled, said Vanessa Northington Gamble, professor of medical humanities and history at George Washington University, at her MacLean Center for Clinical Medical Ethics seminar in late April. No less a figure than Booker T. Washington spoke out about the direct link between African-American health and civil rights in the early 1900’s, saying:

“Without health … it will be impossible for us to have permanent success in business, in property getting, [and] in acquiring education …. Without health and long life all else fails.”

The solutions those black intellectuals chose to improve the health of their race, in a time of national segregation, were very different from the options under consideration today. But Gamble said that discussion of those efforts is missing from the conversation about health disparities interventions in today’s society.

“We don’t talk about the history of these disparities - what are some of the programs that came in the past to address these disparities,” Gamble said. “I do think that many people think it’s only been in the past 20 to 25 years… but I want to talk about what the black community did to take care of itself.”

At the time, black patients faced segregated hospitals and racist theories, such as those put forth by statistician Frederick L. Hoffman in his book, “Race Traits and Tendencies of the American Negro.” Hoffman, an actuary for Prudential insurance, argued that the company should not cover African-Americans because they were destined to die out due to unchangeable biological factors of their race. To refute those claims, W.E.B. Du Bois published his 1906 study, “The Health and Physique of the Negro American,” which pinpointed socioeconomic factors, rather than biology, as the cause of poor health in the black community.

“Du Bois agreed that the health status of African-Americans was worse than that of white Americans,” Gamble said. “Where there was disagreement was on what were the causes of what we would now call health disparities or inequities…for example, he said the high infant mortality rate in Philadelphia was not a ‘Negro affair,’ but an index of social conditions.”

In the wake of that research, black professionals united to try to beat back higher rates of infant mortality, pneumonia, and tuberculosis - the latter of which Du Bois called “the greatest enemy of black people.” One of the best strategies, in the face of segregated hospitals and discrimination from white physicians, was to establish black hospitals to improve access to health care. One example on the South Side of Chicago was Provident Hospital, founded in 1891 by Emma Reynolds and Daniel Hale Williams, who would go on to perform the first successful open-heart surgery there. Similarly, black doctors formed the National Medical Association in 1895, because of their difficulties in joining the American Medical Association. Playing along with segregation wasn’t unanimously popular in the black population of the time; in fact, Gamble said one minister prayed Provident would burn to the ground because it catered to racism.

“You have to look at [black hospitals] in the context of segregation,” Gamble said. “Many black physicians said we wish we didn’t have to start black hospitals, but if we wait for integration, the health of the race would suffer.”

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Posted by - Rob Mitchum

Disparities Across the Ocean and Next Door

Posted at 9:44 am CT on March 23, 2011

Like the rest of campus, the MacLean Center for Clinical Medical Ethics seminar series is on spring break, resuming in early April with a talk from provocative economist Richard Epstein. So now’s a good chance to get caught up on the previous quarter’s seminars, covering topics under the umbrella of health disparities from the biological factors of breast cancer to the relationship between crime and public health to some of the exciting projects from the Urban Health Initiative. Hopefully, the ScienceLife coverage has kept interested readers informed about the valuable contents of this unique seminar series, but if you prefer a more visual experience, the MacLean Center website has posted several of the lectures in video form. Here’s a recap of the Winter Quarter sessions that are currently available for viewing.

Eliminating Global Disparities in Breast Cancer - Olufunmilayo Olopade Jim Fackenthal, University of Chicago

Unfortunately, Dr. Olopade was unable to deliver her talk due to a last-minute conflict, but Jim Fackenthal, research associate assistant professor in her laboratory, was able to provide emergency relief. The disparity in the survival rates of white women and black women in the United States with breast cancer remains wide, and while some of this gap can be explained by socioeconomic factors, biology also plays a role. Fackenthal talks about the evidence for more aggressive and harder to treat forms of breast cancer in women of West African origin here and abroad. The group’s research projects span from laboratory experiments on genetics and epigenetics to blood testing and screening in Nigeria.

Births to Arab-American Women Before and After 9/11: Evidence of Stress Effects - Diane Lauderdale, University of Chicago

The terrorist attacks of September 11, 2001 were stressful for all Americans, but possibly most challenging for Arab-Americans who experienced discrimination in the wake of the events. Lauderdale, a professor of epidemiology, wanted to look at whether one could measure a negative health impact of this discrete period of stress, choosing premature or underweight births as a health outcome potentially sensitive to discrimination. It wasn’t an easy task, as Lauderdale and her collaborators first had to develop an algorithm to find names in California’s birth registry that are likely of Arab origin. But the results of the study were striking, as Lauderdale was able to measure a spike in babies born underweight to Arab-American mothers in the months after 9/11, without any significant changes among other ethnicities.

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Posted by - Rob Mitchum

Linkage 3/11: Panspermia, Kidney Swaps, and Genetic Tests

Posted at 12:09 pm CT on March 11, 2011

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Alien Life & Scientific Skepticism: The Sequel

In a bit of deja vu this week, a new paper stirred up fevered online debate about the existence of aliens among us - and the traditions of scientific publications. This time, ground zero for the debate was not the bacteria of arsenic-laced Mono Lake, but microscopic filaments on a rare group of meteorites collected in Antarctica in the 80’s and 90’s. In a paper published last Friday by the Journal of Cosmology, NASA scientist Richard Hoover argued that these filaments are bacterial fossils, of species that fell to Earth with the meteorite - a conclusion that was breathlessly reported by Fox News with the lede “We are not alone in the universe.”

Panspermia, the idea that life on Earth may have been seeded by alien organisms that arrived on the backs of meteorites, is a seductive idea. But as the old saying goes: once bitten by reports of alien bacteria, twice shy. Far fewer science reporters fell for the meteorite alien bacteria as they had on the arsenic-based bacteria story of last December, perhaps because of a lesson learned or merely because of the lower-profile journal in which the new paper appeared. And while the criticisms over the arsenic study took a few days to seep from science blogs to mainstream media, the travel time was much shorter this time around - Phil Plait’s skepticism on his Bad Astronomer blog was quickly trailed by an AP story that carried a chorus of criticism. Questions about the qualifications and objectivity of the author and the journal soon followed, as the Columbia Journalism Review recaps.

As with the arsenic story, the meteorite episode was almost more fascinating for what it says about modern scientific communication than what it said about science itself. On the surface, the Journal of Cosmology appeared to take some progressive steps for publishing research, including making the article free and open access and soliciting commentaries from “100 experts” on the findings, 24 of which were published soon after the original article. That move would appear to address one of the critiques of the team that published the arsenic bacteria paper, regarding their attitude that criticism was only valid through traditional (and slow) peer-reviewed channels, instead of online discussion that is able to react more immediately.

However, a very thorough, critical commentary by microbiologist Rosie Redfield (who also sounded the first alarm about the arsenic bacteria research) has not been published by the journal, while some very odd commentaries have, such as one concluding “Hoover’s findings are incompatible with the creationist model of life based on biblical Genesis and Aristotelian philosophy.” The journal has also reacted petulantly to criticism, posting an editorial called “Have the terrorists won?” that claims “Only a few crackpots and charlatans have denounced the Hoover study.” So while the latest alien bacterial invasion of Earth’s media is showing some steps in the right direction, it also signals that the growing pains of adapting scientific discussion to a faster media age are still present.

Elsewhere…

Last week, the Medical Center was part of a four-way kidney swap that spanned the country, from the Bronx to California (we should have a video of the event posted next week). Coincidentally, in a New York Times editorial published Sunday, the Medical Center’s Lainie Ross argued that such swaps or “donor chains” were a better option than proposed revisions to the current organ allocation system that would prioritize younger recipients.

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Posted by - Rob Mitchum

Saving Lives & Lungs with Cleaner Stoves

Posted at 11:05 am CT on March 10, 2011

cooking1Cooking indoors over firewood and dung is a tough habit to break for billions of poor people around the world. But Sola Olopade, MD, professor of medicine and family medicine, found a way. He wanted to stop women from hunching for hours over open fires inside their houses, cooking with babies strapped to their backs. The air in such houses quickly becomes filled with toxins, and the women and children have a host of bad health consequences.

“It’s the most unclean combustion you can get,” Olopade said in his seminar earlier this month at the MacLean Center for Clinical Medical Ethics. “The women and children have coughs, headaches, runny noses, chest tightness.”

Those are just the health problems he could measure. “I wonder what kind of cognitive dysfunction people develop in spaces where the carbon monoxide is so high.”

Unfortunately, the billions of poor people who cook their daily meals over firewood and dung have few other options. Without electricity, Olopade said, “energy poverty drives people to use whatever they can get their hands on.” But Olopade was determined to see whether education and a little technology could make it less dangerous for people to breathe inside their houses.

Olopade, who is clinical director of the University of Chicago Global Health Initiative, went to two small villages in his native Nigeria, ready to distribute energy-efficient ceramic stoves. He believed the simple stoves could make an enormous improvement in the community’s health. His team measured the air quality inside 100 homes, and found heavy metals, carbon monoxide, and particulate matter more than twenty times the World Health Organization acceptable standards. The researchers also educated the community about the dangers of exposure to smoke from using firewood to cook indoors and the benefit of using the new stoves, handing out brochures about cooking in their native dialect.cooking2

“I told them without medical jargon that this was killing people,” Olopade said.

Three months after giving the stoves to the families in the villages, Olopade returned. He took the same air quality measurements, repeated the survey of symptoms and saw a remarkable improvement. Carbon monoxide and particulate matter levels were dramatically lower, much closer to the WHO standards.

“People were very happy with the stoves. They’re very simple. They’re lined with ceramic which retains a lot of heat and promotes more complete combustion of the firewood or biomass fuel,” Olopade explained.

The women were burning the same fuel - cow dung, agricultural waste, and firewood - but the stoves had kept most of the pollutants from pouring into the homes. With this small change, “you can really improve the indoor environment,” Olopade said.

The health benefits were drastic. Before the intervention, many of the children and most of the mothers suffered from dry cough, runny noses, burning eyes, breathing difficulties, chest tightness, headaches and dizziness. All of these health problems plummeted after they started cooking on the clean stoves.

“Just by engaging the community in partnership, educating them on the dangers of exposure to toxic fumes and giving people efficient stoves, without changing their lives much, the change in symptoms is dramatic,” Olopade concluded.

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Posted by - Dianna Douglas

Linkage 3/4: Budget Backlash, Overprevention, Mass Extinction

Posted at 9:32 am CT on March 4, 2011
Sen. Dick Durbin tours Argonne National Laboratory with Rick Stevens, Professor of Computer Science (photo courtesy of Argonne)

Sen. Dick Durbin tours Argonne National Laboratory with Rick Stevens, Professor of Computer Science (photo courtesy of Argonne)

In Washington, the fight over budget cuts is well underway, as a Republican majority in the House and a Democratic majority in the Senate tussle over the best way to reduce a multi-trillion dollar federal deficit. The first bill of the new House, H.R.1, set federal appropriations for the rest of fiscal year 2011 (ending in September) and snipped $61 billion from the budget, predominantly from discretionary domestic spending. One target of those cuts would be the National Institutes of Health budget, which would lose roughly $1.6 billion of its $32 billion budget for funding scientific research in the United States.

As you might expect, this news was not welcomed by Chicago-area researchers, who turned up in lab coats to support a news conference by Sen. Dick Durbin last Sunday at Northwestern University’s downtown campus. Durbin vowed to fight against the cuts as H.R.1 is discussed in the Senate, saying that interrupting the funding would slow progress toward new treatments for diseases such as AIDS, diabetes, and cancer. (video here)

“When you put these research projects on hold, you can’t ask the laboratory mice to take a nap,” Durbin said. “You can’t ask the cultures to stop growing - we’ll get back to you at the end of the fiscal year. And you can’t expect the professional researchers, the men and women who have dedicated their lives to medical research, to have certainty that next year they’ll have a job.”

Researchers from each of the major Chicago academic hospitals appeared at the conference and talked about how the proposed budget cuts could harm their own projects. Michelle Le Beau, director of the University of Chicago Comprehensive Cancer Center, discussed the biomedical research underway at UChicago thanks to the nearly $300 million in NIH funding received this year and last. Le Beau focused in on her own research examining therapy-related acute myeloid leukemia - a “very cruel and ironic” cancer caused by the chemotherapy and radiation treatment of a prior tumor. Any job losses that follow from NIH cuts could break up the expert team she has formed to study causes and treatment of the disease, she said.

“A lapse in funding will result in dismantling our highly specialized research team, and this leads to a loss of capability, because it takes years to assemble these teams again,” Le Beau said. “These are individuals who have trained for years to apply their extraordinarily unique skills. They have families to support and bills to pay.”

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Posted by - Rob Mitchum

Measuring Discrimination…with 9/11

Posted at 11:57 am CT on January 27, 2011

040909-C-3948H-001It is widely acknowledged that racial or ethnic discrimination can negatively affect a person’s health. But how can a scientist measure this impact? The treatment that a person encounters due to the color of their skin, their language, or their country of origin is likely a chronic stimulus, encountered over their entire life rather than during a discrete period of time. How that person perceives or reacts to discrimination may also vary widely from individual to individual - some may shrug it off or internalize the damage, some may grow angry and lash out. Wrapping one’s statistical arms around such a huge variable is nearly impossible.

One way around this problem is to locate a finite period of elevated discrimination against a particular group, and measure the impact of that event upon health. Diane Lauderdale, professor of epidemiology in the Department of Health Studies, found just such an event in the terror attacks of September 11, 2001, and the brief but intense harassment of Arab-Americans that followed. In her talk for the MacLean Center of Clinical Medical Ethics seminar series in January, Lauderdale detailed how she studied a link between post-9/11 discrimination and birth outcomes for a paper in the journal Demography (pdf).

While it might be hard to pin down the discrimination experienced by people of Arabic origin over the course of their lives in the United States, their life in the months after the attacks was undoubtedly more stressful. According to the American-Arab Anti-Discrimination Committee, more than 700 violent incidents were directed toward persons who were perceived to be Arab in the nine weeks after 9/11. But a massive media and government pushback likely limited the duration of this out-of-control hatred, with the director of the ADC commenting in December 2001 that “My impression is that we are rapidly returning to what one would unfortunately call a normal amount of hate crimes.”

Lauderdale chose to focus on pregnant women, who are particularly sensitive to stress. High levels of corticotropin-releasing hormone - a peptide increased by stress - can induce early labor, producing babies that are premature and/or underweight. Lauderdale hypothesized that pregnant Arab-American mothers might have given birth to more low birth weight babies in the six months following 9/11 than they had during the same months in the previous year.

One problem: while Lauderdale had access to the birth certificates of more than 1.5 million children born in California from 2000-2002, the certificates categorized race only by black, white, American Indian, Asian, and Other - no Arabic. Fortunately, previous work by Lauderdale and colleagues had developed an algorithm for predicting a person’s Arab origin using their first and last names. While the algorithm was admittedly imperfect, it was able to create enough of an enriched sample to conduct the comparison, Lauderdale said.

Her analysis found that the births of most groups (white mothers, black mothers, foreign born mothers) were unaffected by the events of 9/11, with virtually no difference in the risk of having a low birth weight baby between the two years. But for the 15,000 Californian women with Arabic names analyzed, there was a small but significant spike in low birth weight babies from October 2001 to March 2002. Children born to those mothers were 34 percent more likely to be underweight than babies born to Arabic mothers from October 2000 to March 2001.

To break the Arabic group down even further, Lauderdale looked at whether each child was given a traditionally Arabic name, potentially a sign of stronger ethnic identity. While the number of Arab names given to newborns did not change before and after 9/11, babies with “traditional” names were more than twice as likely to be born underweight in 01-02 compared to the same months in 00-01. Babies with more “American” names, on the other hand, were almost unperturbed, with only a 16% higher chance of being underweight at birth.

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Posted by - Rob Mitchum

MacLean Center Ethics Seminar Videos: The First Batch

Posted at 3:19 pm CT on January 26, 2011

Since late September, ScienceLife has been posting near-weekly recaps of the annual Maclean Center for Clinical Medical Ethics seminar series. The topic for this academic year, “Health Disparities: Local, National, Global” (pdf), has brought together an all-star cast of physicians, biologists, economists, social scientists and other experts to present research on some of the biggest challenges facing health care in the United States and around the world. Most of the sessions have been videotaped, and the first batch of those videos recently went live on the MacLean Center website. Here’s a digest of the first seven seminars available to watch and the ScienceLife posts that briefly summarized the discussions. The videos have also been added to each post.

Rick Kittles (UIC) - “Race, Biomedical Research, and the Politics of Trust”

Rebuilding Trust, Moving Beyond Race

Kathleen Cagney (UChicago) - “The Neighborhood Context of Health Disparities”

Urban Crime and the Waistline

Robert Sampson (Harvard) - “The Social Reproduction of Health Disparities: Lessons from the Chicago Neighborhood Project”

The Invisible Hand of the Neighborhood

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Posted by - Rob Mitchum

Sickle Cell on the Football Field

Posted at 9:56 am CT on January 17, 2011
red-blood-cells

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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Posted by - Rob Mitchum

Year in Review: UChicago Research 2010

Posted at 9:48 am CT on December 27, 2010

mrksich-shapes-1024x4021

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

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

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

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

lukehand-300x1601March: Everyone knows air travel is stressful, but did you know that eastbound flights cause stronger cortisol changes than westbound trips? The laboratory of Milan Mrksich found a way to direct stem cells to form fat or bone by shaping them into stars or flowers, a brilliant example of bioengineering. Computational neuroscientists discovered how touch is like vision in the brain, knowledge that could be used to someday re-engineer Luke Skywalker’s robot hand. Dartmouth president and Partners in Health co-founder Jim Yong Kim visited to talk about a new, needed area of research: health care delivery.

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

3989665583_e680b02fa4May: A trial testing the erectile dysfunction drug Viagra for a rare, untreatable lung disease failed, but pulmonologist Imre Noth found a silver lining. Lauren Sallan and Michael Coates uncovered evidence of a previously unappreciated mass extinction event 360 million years ago that changed the path of life on Earth. Researchers from the University of Chicago and around the world presented science at the frontier of biotechnology at the annual BIO conference.

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

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

friends-chatting-around-stove1August: Air pollution is a problem indoors as well as outdoors in developing countries where dung and firewood are used to cook food - a problem being tackled in a project led by Sola Olopade. A study of the hormonal changes induced by a stressful test revealed a surprising protective effect of marriage and long relationships. Microbiologist Olaf Schneewind’s laboratory developed two new strategies against MRSA, the most-wanted cause of hospital-acquired infections.

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

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

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

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

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

Posted by - Rob Mitchum