Research Notes

If you want to avoid allergies or asthma, scientists at the Medical School suggest you start paying more attention to what's in your gut.

Cells from an area of allergic lung inflammation in mice from the study treated with antibiotics and colonized with C. albicans in the gut (above). The inflammatory cell infiltrate is mainly composed of eosinophils. Some of the granules shown in eosinophils contain many compounds, such as histamine, that mediate allergy symptoms Below, photomicrograph of the yeast, Candida albicans—a common inhabitant of the human GI tract—which proliferates during antibiotic treatment (Photos by Mari Noverr, Medical School).

In the January 2005 issue of Infection & Immunity, researchers report new evidence suggesting that changes in the normal mixture of microflora—bacteria and fungi in the gastrointestinal tract—can intensify the immune system's reaction to common allergens, like pollen or animal dander, in the lung and increase the risk of developing chronic allergies or asthma.

"Our research indicates that microflora lining the walls of the gastrointestinal tract are a major underlying factor responsible for the immune system's ability to ignore inhaled allergens," says Gary Huffnagle, associate professor of internal medicine and of microbiology and immunology. "Change the microflora in the gut and you upset the immune system's balance between tolerance and sensitization."

To test their hypothesis, Huffnagle and Mairi C. Noverr, a post-doctoral fellow, have developed the first mouse model designed to mimic how humans develop allergies following antibiotic therapy. In Infection & Immunity, they report results of new experiments linking changes in GI tract microflora to an overzealous allergic response in the lung.

Noverr and Huffnagle suspect that changes in gut microflora caused by widespread use of antibiotics and a modern high-fat, high-sugar, low-fiber diet could be responsible for a major increase, during the last 40 years, in cases of chronic asthma and allergies in Western industrialized countries.

To read the full story, visit http://www.med.umich.edu/opm/newspage/2004/gut.htm.

Noverr and Huffnagle's research is funded by the National Institutes of Health and a New Investigator Award from the Burroughs-Wellcome Fund. Other U-M collaborators were Nicole R. Falkowski and Rod A. McDonald, research associates.
—By Sally Pobojewski, Medical School Communications

Workers with carpal tunnel find relief with splinting

A new study finds that nocturnal rest can do a world of good for your hands and wrists, especially if you are one of the millions of American workers just beginning to feel the common pain and discomfort linked to carpal tunnel syndrome (CTS).

The findings, made by a team of researchers with the U-M Health System (UMHS) and the VA Ann Arbor Healthcare System, show that night-time splinting can lessen hand and wrist discomfort for active workers with early symptoms of CTS. The results are published in the January issue of the Archives of Physical Medicine and Rehabilitation.

Those in the study who used a splint saw significant improvement in hand/wrist discomfort, and participants who initially reported higher levels of discomfort at the start of the study saw the greatest improvements with splint use.

While carpal tunnel syndrome is a common work-related disorder and a major cause of impairment and disability in the workplace, the use of initial medical treatment protocols for the disorder—wrist splints, modification of hand activity, non-steroidal anti-inflammatory medication, diuretics and steroid injections—have varied widely across the United States and Western Europe, says lead author Dr. Robert A. Werner, professor in the Department of Physical Medicine and Rehabilitation (PM&R). He also is the chief of physical medicine and rehabilitation at the VA Ann Arbor Healthcare System and an associate research scientist with the U-M Center for Ergonomics.

In addition to Werner, the study was co-authored by Dr. Alfred Franzblau, associate professor in the UMHS Department of Emergency Medicine, associate research scientist at the Center for Ergonomics and professor in the Department of Environmental Health Sciences (EHS) at the School of Public Health; and Nancy Gell, a research associate in PM&R and EHS. The study was funded by the UAW-GM National Joint Committee on Health and Safety.
—Krista Hopson, UMHS Public Relations

Religious ritual evolved with society in Mexico

U-M archaeologists have demonstrated that religious ritual and social organization evolved together among Mexico's prehistoric Zapotec Indians.

Their study, published in the Proceedings of the National Academy of Sciences, provides some of the first physical evidence supporting the assumption that religious ritual co-evolved with social complexity.

Their findings suggest that rituals evolved along with changes in social organization from nomadic hunter-gatherers to permanent village dwellers and eventually stratified societies.

To chart the evolution of ancient religious practices, U-M anthropologists Joyce Marcus and Kent Flannery used radiocarbon dating to date ritual buildings and features found in the Oaxaca region. They found that the earliest ritual feature, a cleared area resembling a Native American dance ground, dated to about 8,600 years ago.

At this time, the population was nomadic, and most rituals were performed when the maximum number of families came together to participate. With the advent of an agriculture-based society centered in permanent villages, the researchers found that rituals and temples became less accessible to all, echoing the increase in social inequality. In addition, some rituals began to be performed at specific times each year.

"In the days when people lived by hunting wild animals and collecting wild plants, major rituals were held during those times when the largest number of people lived together, usually the season of abundance," says Marcus, professor of anthropology and curator of Latin American Archeology at the University's Museum of Archaeology.

"The rest of the year, people were so nomadic that they didn't have a quorum. It looks as if these ad hoc rituals were open to everyone."
—Diane Swanbrow, News Service

How to measure patient safety at children's hospitals?

In recent years, children's hospitals have joined in the national push to improve patient safety and avoid preventable problems. It has been hard to measure progress, however, because of uncertainty about whether standard patient safety measurement tools apply to their patients, who are younger, smaller and on average sicker than those at other hospitals.

But now, a new study of data from 67 children's hospitals in 31 states shows that many of the same indicators used in adult hospitals can be used to measure preventable complications and problems in children's hospital patients, from post-procedure infections and dangerous blood clots to bedsores.

The measurement tools, from the federal Agency for Healthcare Research and Quality (AHRQ), formally are called AHRQ Patient Safety Indicators (PSIs).

The researchers find, however, that two of the AHRQ PSIs are inaccurate for measuring children's care. And they say none of the measures should be used to compare children's hospitals with one another, though the indicators can be useful in pinpointing individual patients' charts that need to be reviewed.

The study, published by the journal Pediatrics, evaluated information about 1.92 million children's hospital stays during four years, compiled by the National Association of Children's Hospitals and Related Institutions (NACHRI). The team was led by Dr. Aileen Sedman, professor emerita of pediatrics at the Medical School and former associate chief of clinical affairs at the U-M Health System. She led the analysis with Vinita Bahl of U-M and colleagues from C.S. Mott Children's Hospital, NACHRI, AHRQ and the Children's Hospital of Wisconsin.

The analysis shows that children's hospitals could do a better job in areas such as preventing hospital-acquired infections, clots in intravenous lines and bedsores. These three potentially avoidable problems affected 3.5, 5.7 and 17 patients, respectively, out of every 1,000 applicable children treated at the hospitals in the study.

In two other categories, the analysis appeared to reveal a disturbingly high preventable death rate among young patients. But when the researchers dug deeper into the data and looked at each case individually, they found that the standards, not the hospitals, were to blame, and that the death rates were inaccurate.
—Kara Gavin, UMHS Public Relations

Many use prescription drugs as stimulants for non-medical purposes

Seven percent of college students have used prescription stimulants for non-medical purposes during their lifetimes and 4 percent have used in the past year, according to a study of students at 119 four-year colleges and universities nationwide published in the January issue of the journal Addiction.

The study, based on data from the Harvard School of Public Health College Alcohol Study, found that past year rates ranged from none to 25 percent at individual colleges and universities. Students attending three historically Black colleges reported the lowest rate (none) of non-medical prescription stimulant use. Reported use was higher among students who were male, white and members of fraternities. The study also showed that abuse of non-medical prescription stimulants was higher among women who were members of sororities.

And students who use prescription stimulants non-medically are more likely to abuse other substances such as alcohol, marijuana, ecstasy and cocaine, researchers found.

"They are also more likely to engage in other risky behaviors such as driving after heavy drinking," says Sean Esteban McCabe, lead author of the study and assistant research scientist at U-M's Substance Abuse Research Center. The study's co-author is Henry Wechsler, lecturer, Department of Society, Human Development and Health at the Harvard School of Public Health and director of the College Alcohol Study.

The highest rates of non-medical use of prescription stimulants are on college campuses in the Northeastern region of the United States, schools with highly competitive admissions criteria and those college campuses with higher rates of binge drinking, the study found.

The study was supported by grants from the Robert Wood Johnson Foundation and the National Institute on Drug Abuse.
—Joel Seguine, Office of the Vice President for Communications

Stock investors' returns are lower than they think

Stock market investors are getting poorer overall returns than they realize, says a U-M business professor.

This is because stock returns historically have been measured on a buy-and-hold basis, which does not account for different returns that occur at different points in time.

A study by Ilia Dichev, associate professor of accounting at the Stephen M. Ross School of Business, contends that traditional buy-and-hold returns fail to assess the return experiences of stock investors because they ignore the timing effects of capital flows in and out of securities.

Instead, Dichev suggests using a new, more accurate measure that involves the dollar-weighting of returns (i.e., the returns generated by bigger investment amounts receive greater weighting than the returns from smaller investment amounts) and, therefore, properly reflects the effect of investors' timing.

"The compounding of buy-and-hold returns reflects the investing experience of passive buy-and-hold investors and assumes an equal weighting of returns over time," Dichev says. "However, most investors are actively trading or otherwise engaging in stock-capital transactions.

"As a result, they are consciously or unconsciously timing particular stocks or the market as a whole, and varying their net investment exposure over time. Thus, while buy-and-hold returns provide a good benchmark to track the investment performance of stocks, they can be a poor measure of the actual return experience of investors, if capital-flow timing affects stock returns."
—Bernie DeGroat, News Service

Synthetic biology: Researchers mass-produce genes on a chip

Imagine that the bricks used to build a house cost $1,000 each; that would make building a home cost-prohibitive. Similarly, the bricks to build living organisms—genes and genetic assemblies—can cost thousands of dollars to make in the lab, which also is cost-prohibitive.

But now, scientists have developed a way to make the materials for genes on a microchip in mass quantities for a fraction of the current cost.

The technology enabled scientists to make an important part of the genome for an E-coli bug, and to reproduce the instructions for making proteins. This has significant applications in vaccine production, gene therapy, and DNA sensors and diagnostics.

"The significance of our paper is that for the first time, we have a mechanism for us to make the genes in high accuracy, very inexpensively, and to make those genes containing the information for the protein factory in an organism" that synthesize all other proteins in the body, says Erdogan Gulari, the Donald L. Katz Collegiate Professor of Chemical Engineering and co-author of a paper on the topic that appeared in the Dec. 23 Nature.

"This is the starting point to making a complete functioning organism that can produce energy, neutralize toxins and produce medically useful proteins, for the benefit of human health and quality of life."

The paper, entitled "Accurate multiplex gene synthesis from programmable DNA microchips," was co-authored by researchers from the College of Engineering, Harvard University, University of Houston and Atactic Technologies Inc. The technology currently is licensed to Atactic, a company founded by CoE alum Xiaochuan Zhou, professor Xiaolian Gao of the University of Houston, and Gulari.
—Laura Bailey, News Service

Study investigates value of 'center of excellence' designation

A new study by U-M Health System researchers says cancer surgery performed at a medical center designated by the National Cancer Institute (NCI) as a "center of excellence" is associated with less risk of death soon after surgery than if performed at a high-volume surgery center, but finds no difference in five-year survival rates.

The full study will be published in the Feb. 1 issue of Cancer, a peer-reviewed journal of the American Cancer Society.

In 1971 the NCI created a program to award cancer centers special designation as centers of regional excellence if they demonstrated excellence in three areas: research, cancer prevention and clinical services. Although these centers often advertise their superior outcomes, say the study's authors, to date their relative performance has not been examined.

Nancy J. O. Birkmeyer, associate professor of surgery at the Medical School, and her colleagues investigated whether this designation actually improves survival. Perioperative mortality was significantly lower at NCI-designated medical centers for four of six procedures to partially or completely remove the diseased organ: colectomy, pulmonary resection, gastrectomy and esophagectomy. No significant difference in mortality was observed in patients treated with cystectomy or pancreatic resection at either type of institution.

Among patients surviving surgery, however, five-year survival rates for all six procedures did not differ significantly between NCI-designated cancer centers and control cancer centers for any of the procedures.

"Our study suggests that NCI cancer center designation should be weighted less heavily than other factors in deciding where to undergo major cancer surgery," the authors conclude.

This study was supported by grants from the NCI and the Agency for Healthcare Research and Quality.
—Cancer, Feb. 1 issue