Research notes

Updated 4:00 PM July 28, 2003

Research Notes

Researchers seek to increase strength and mobility of the elderly

(Photo by Marcia Ledford, U-M Photo Services)

As they grow older, many people find the tasks they used to take for granted, such as putting groceries away or lifting their grandchildren, become increasingly difficult because aging muscles lose their ability to generate power and force. A group of U-M researchers aims to reverse that trend by investigating ways to boost muscle power and speed of movement in the elderly. The project is funded in part by a three-year, $3.8 million grant from Michigan’s Life Sciences Corridor.
Bruce Carlson, director of the Institute of Gerontology and a professor of cell and developmental biology, heads the team. Researchers are using biopsies to examine muscle fibers at the molecular level, and using instrumentation designed to record muscle power, to measure the success of weight training in study participants. A group of 96 study subjects, ranging from their 20s to older than 70, began training in the spring.

While weight training is known to increase muscle strength, scientists are seeking a better understanding of the process because of new abilities to analyze the biological changes brought about by weight training. Ultimately, analysis at the cellular level should provide insight into the most effective strategies to maintain and restore strength, and increase the speed of movements. Speed of movement is as important as the person’s strength because developing faster movement can help prevent certain types of falls among the elderly, Carlson says.

In addition to Carlson, the team includes: Neil Cole, president of Dexter-based Bio-Logic Engineering; Neil Alexander, associate professor of geriatric medicine and associate research scientist with the Institute of Gerontology; James Ashton-Miller, distinguished senior research scientist in mechanical engineering, biomedical engineering and Institute for Gerontology, and director of the Biomechanics Research Laboratory; Paul Cederna, assistant professor of surgery and assistant research scientist with the Institute of Gerontology; John Faulkner, professor of physiology and director of the Nathan Shock Center for Basic Biology on Aging at the Institute of Gerontology; and Jeffrey Horowitz, assistant professor of kinesiology.
—Colleen Newvine, News Service

Extra risk for prostate cancer in Blacks may be genetic

Doctors know that Black men face a much higher risk of prostate cancer than whites and a higher risk of dying from the disease. While research is zeroing in on answers, too few African American men have been involved enough in research to determine if a promising genetic finding applies to African American as well as Caucasian men.

Now, a study by U-M Health System (UMHS) researchers has found that the gene, macrophage scavenger receptor 1, or MSR1, indeed plays a role in prostate cancer in African American men. The study, published in the July 1 issue of the American Association for Cancer Research journal Cancer Research, came from a larger project called the Flint Men’s Health Study, aimed at identifying risk factors for prostate cancer in African American men. It is a rare effort to recruit large numbers of African Americans in a population-based research study.

“African American men have the highest incidence of prostate cancer in the world. The severity is higher and they tend to die more quickly after diagnosis,” says Dr. Kathleen Cooney, associate professor of internal medicine and surgery at the Comprehensive Cancer Center and senior author of the study. “We don’t know why this is, but part of the difficulty is that African American men are underrepresented in most genetics studies.”

Dr. David Miller, a resident in urology at the Medical School, was lead author of the report. Aruna Sarma, assistant research scientist in the Department of Urology, was the coordinator of the Flint study. The Flint Men’s Health Study was funded by a U-M Specialized Program of Research Excellence, or SPORE, grant in prostate cancer. Additional funding came from the U-M Office of Research and Minority Health, the Department of Urology and several Flint-based community organizations: FAITH, the Genesee County Health Department and QUEST Laboratories.
—Nicole Fawcett, UMHS Public Relations

Sleep disorders may be linked to faulty brain chemistry

The first tantalizing clues that chemical imbalances in the brain may be partly to blame for certain life-disrupting sleep disorders are being reported in two new studies by U-M Health System (UMHS) researchers.

In two papers in the July 8 issue of the journal Neurology, the team reports apparent links between deficits in brain chemistry and obstructive sleep apnea and REM sleep behavior disorder (RBD). Both are relatively common sleep problems that disturb the slumber and daytime behavior of millions of Americans.

The new findings were made using two types of neurochemical brain scans and detailed sleep studies in 13 patients with multiple system atrophy (MSA), a rare and fatal degenerative neurological disease almost always accompanied by severe sleep disorders. Their results from the MSA patients, who all had both sleep apnea and REM behavior disorder, were very different from those of 27 healthy control subjects.

Specifically, the researchers found that MSA patients had a far lower density of certain brain cells, or neurons, that produce the key chemicals dopamine and acetylcholine. The greater their lack, the worse their sleep problems were.

The patients with the fewest dopamine-producing neurons in the striatum of their brains had the worst RBD symptoms of thrashing, talking and violent flailing while they slept. And patients with the lowest levels of acetylcholine-producing neurons in the brainstem had the most interruptions in their breathing during sleep.

While the researchers are careful to note that their findings to date only can show a correlation, not causation, between brain chemistry and sleep disorders, they plan further research to explore the relationship.

The lead author was Dr. Sid Gilman, the William J. Herdman Professor and chair of the Department of Neurology at the Medical School. The research team also included Robert Koeppe, who directs the Positron Emission Tomography Physics program in the Division of Nuclear Medicine of the Department of Radiology; Dr. Ronald Chervin, an associate professor of neurology who directs the Michael S. Aldrich Sleep Disorders Laboratory; Dr. Flavia Consens, a clinical assistant professor of neurology and sleep disorder specialist; Roderick Little, a professor in the Department of Biostatistics at the School of Public Health; Hyonggin An, a graduate student in biostatistics; Dr. Larry Junck, a professor of neurology; and Mary Heumann, a research associate in the Department of Neurology.

UMHS researchers have been studying sleep disorders for years at the Michael S. Aldrich Sleep Disorders Laboratory. The newly published studies were funded by the National Institute of Neurological Diseases and Stroke.
—Kara Gavin, UMHS Public Relations

Accepting patients from other hospitals may hurt quality rankings

In an era when hospital rankings, report cards and quality surveys steer the nation’s health care decisions, a study finds that major medical centers may be getting penalized on those measures for doing what they do best: taking care of the patients no other hospital can or will treat.

The study, based on four years of data from the U-M Health System’s (UMHS) unique repository of clinical patient information, found that patients transferred to a major center from other hospitals are sicker and more likely to die than others, and that this “transfer effect” is not accounted for by hospital-rating tools. The effect long has been suspected by large private, public and university-affiliated medical centers, but was never fully quantified until now.

The results, published by a UMHS team in the Annals of Internal Medicine, show the effect is enough to damage a hospital’s score on measures that patients, insurers, employers and the government use to make health care choices. The authors call upon those who prepare hospital rankings and reports either to include a hospital’s transfer rate in the statistical analysis of its patient outcomes, or to analyze outcomes with and without transfer patients included. This, they say, will improve the representation of hospital quality that patients and their families can use to guide their health care decisions.

The lead author was Dr. Andrew Rosenberg, an assistant professor of anesthesiology and internal medicine at UMHS who directs research in critical care medicine for the Department of Anesthesiology and treats patients in the Cardiothoracic Intensive Care Unit. He led the study along with Dr. Rodney Hayward, a professor of internal medicine at UMHS and the director of the Health Services Research Center at the Ann Arbor VA Healthcare System, while Rosenberg was a Robert Wood Johnson Clinical Scholar at the Medical School. Dr. Charles Watts, former UMHS chief of clinical affairs and now associate dean for academic affairs at Northwestern University’s Feinberg School of Medicine, co-authored the study. The paper’s authors also include registered nurse Cathy Strachan, who runs the UMHS APACHE database service, and Dr. Timothy Hofer, an associate professor of internal medicine at UMHS.

Hayward and Hofer also are members of the Robert Wood Johnson Clinical Scholars Program, and of the Department of Veterans Affairs Health Services Research & Development Service at the VA Ann Arbor Healthcare System. The study was funded by Rosenberg’s former Robert Wood Johnson Foundation grant, and by VA grants to Rosenberg and Hofer.
—Kara Gavin, UMHS Public Relations

New technique for sorting sperm could improve fertility treatment

A new technique to find the viable sperm in the semen of men with low sperm motility could lead to a new approach for infertility treatment, say U-M Health System (UMHS) researchers.
In a study published online and in the July/August issue of Reproductive BioMedicine Online, UMHS researchers used a microscopic chip divided into two channels to encourage viable, healthy sperm to separate from dead and immature sperm, in order to maximize the potential chances of fertilizing an egg. The research focused on separating the sperm and did not attempt fertilization.

“Current methods of isolating sperm for in vitro fertilization work, but not perfectly,” says study author Gary Smith, associate professor of obstetrics and gynecology at the Medical School and director of the Assisted Reproductive Technologies Laboratory.

“One method for separating sperm is centrifugation, which requires spinning the sample at high speeds. Yet when this is done, live sperm are pelleted with dead sperm that release substances like free oxygen radicals that can damage the good sperm. That’s a drawback to the current method. This new alternative has the potential to be a good way of getting motile sperm away from dead sperm without causing any damage.”

Smith and colleagues are encouraged by their recent finding, yet they note that it will take several years of development before their approach can be used efficiently and safely in a clinical setting.

The new method involves microfluidics, a new area of biomedical engineering that deals with the microscopic flow of fluids. It currently is used in applications such as gene sequencing and sorting cell cultures. In this case, a device about the size of a penny was built with two channels that flowed together into parallel streams and eventually diverged. Sperm were sent through one channel and a saline solution through another channel. When the channels met, the motile, or healthy, sperm were able to cross over to the other stream and exit through the second channel, while the nonmotile sperm stayed their course through the first channel.

Other authors of the study were Shuichi Takayama, assistant professor of biomedical engineering and macromolecular science and engineering; Timothy Schuster from the Department of Urology, Laura Keller from the Department of Obstetrics and Gynecology, and Brenda Cho from the Biomedical Engineering Department.
—Nicole Fawcett, UMHS Public Relations

Researchers devise new way to control motion of tiny particles

Nanotechnology researchers soon may be able to design new types of tiny shuttles or conveyor belts that could be used to deliver medications to specific cells or to replace wires in molecular-sized electronic devices.

An international team of investigators, including a physicist from U-M, has devised a method that could help researchers with one of the most challenging problems in nanotechnology: controlling the motion of tiny particles, both in artificial nanodevices and biological systems such as ion channels in cell membranes.

Tiny particles exhibit disordered motion, also known as Brownian motion, because they are subject to thermal noise. Learning how to transform this disordered wandering of molecules and small particles into ordered, directed motion is a major thrust in nanotechnology research.

In a paper in Physical Review Letters, a multinational research team has proposed a novel way to control the motion of tiny particles. The paper, by Sergey Savel’ev (Institute of Physical and Chemical Research, RIKEN, Japan), Fabio Marchesoni (Physics Department, Universita di Camerino, Italy and RIKEN) and Franco Nori (Center for Theoretical Physics, U-M and RIKEN), shows how adding “auxiliary” particles that interact with the primary “target” particles can control and enhance the flow for both.
To read this article, visit http://www-personal.engin.umich.edu/~nori/mixture/PRL_4_July_2003.pdf.
—Judy Steeh, News Service

American adults often fail to get recommended care

A new RAND Health study—the largest and most comprehensive examination ever conducted of health care quality in the United States—has found that adults fail to receive recommended health care nearly half the time.

Researchers at RAND Health—the nation’s largest independent health-policy research organization—and the U-M Health System noted that the deficiencies in care they found pose “serious threats to the health of the American public” that could contribute to thousands of preventable deaths in the United States each year.

The researchers said their findings shatter the widely held perception that health care quality is not a problem in the United States. In reality, the study found that many people are not receiving appropriate treatment. According to the researchers, these findings are the best estimates ever provided of the seriousness of the quality problem in this country.
The study—which examined preventive care as well as the management of 30 common health problems such as diabetes, asthma, high blood pressure and heart disease—was published June 26 in the New England Journal of Medicine.

“Most of us take health care quality for granted,” says lead study author Elizabeth McGlynn, associate director of RAND Health. “This study shows that we can’t. There is a tremendous gap between what we know works and what patients are actually getting. Virtually everyone in this country is at risk for poor care.”

The study co-author was Dr. Eve Kerr, assistant professor of internal medicine at the Medical School. Other collaborators on the study were Dr. Steven Asch (RAND, Veterans Affairs Greater Los Angeles Health Care System, University of California, Los Angeles); John Adams (RAND); Joan Keesey (RAND); Jennifer Hicks (RAND); and Alison DeCristofaro (RAND).
The study was funded by The Robert Wood Johnson Foundation. Drs. Asch and Kerr were supported by the Veterans Affairs Health Services Research and Development program.
—RAND Health