|| DukeMedNews || Alcohol and Sleep May Not Be a Healthy Mix

This week on MedMinute: Alcohol and Sleep May Not Be a Healthy Mix

For many folks, a nightcap is part of their ritual before retiring for the evening. But an expert says consuming alcohol too close to bedtime may interfere with peaceful slumber and could lead to chronic sleep problems.

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Research shows that alcohol in moderation can provide health benefits. Many people use alcohol as an aid to help them get to sleep, but William Wohlgemuth, clinical psychologist and assistant clinical professor at Duke University Medical Center, says this can be a mistake.

“When the alcohol is metabolized in the body, you have to go to the bathroom more, which can wake you up. Also, sleep becomes a little bit more light after consuming alcohol. So if you have a drink to help you go to sleep at nighttime, it may help you go to sleep, but it’s going to mess up your sleep later in the night.”

Wohlgemuth warns against consuming alcohol too close to bedtime.

“One drink two hours before would probably be out of your system before you went to bed, but two shots of Scotch 30 minutes before you went to bed as a nightcap to help you go off to sleep would be too much and can interfere with the sleep process.”

This is National Sleep Awareness Week, a good time to learn about steps we can take to improve our sleep and our health.

|| DukeMedNews || Positive Outlook Linked to Longer Life in Heart Patients

This week on MedMinutes: Positive Outlook Linked to Longer Life in Heart Patients

A long-term study compared survival rates for heart patients based on their positive and negative emotions and outlooks. Patients reporting more positive emotions and fewer negative ones had a significant reduction in the risk of death.

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Here’s some health advice to take to heart: if you want to live longer, stay happy. A recent study of more than 800 heart patients found that those who reported more positive emotions such as happiness, optimism and joy were 20 percent more likely to be alive after 11 years than those who more often experienced negative emotions like sadness and anger. Beverly Brummett, assistant research professor in the Department of Psychiatry at Duke University Medical Center, conducted the study.

“It could just be that the people that are experiencing more positive emotions just by definition are having a lower frequency of negative emotions and that’s what’s driving the reduction in mortality.”

Brummett says that the adverse health effects of negative emotions are well known, but that researchers may also want to look more closely at the benefits of positive emotions.

“It could be that there’s something very unique about the physiological things that go on when we experience positive emotions – something in the serotonin system, something going on about blood pressure, heart rate, those sorts of things. This is such a new area of research that we just don’t really know.”

Cardiac MRI Finds Small Areas of Heart Cell Death Missed By Nuclear Imaging Techniques

DURHAM, N.C. — Researchers from Duke University Medical Center and Northwestern University Medical School have demonstrated that cardiac magnetic resonance imaging (MRI) technology can detect small areas of heart muscle death that cannot be detected by commonly used imaging techniques.

Their finding is important, the researchers said, because these small areas of muscle cell death, known as infarcts, can be early indicators of future, more severe heart problems.

In their study involving 91 patients with known or suspected coronary artery disease, the researchers found that the traditional nuclear imaging technique, “single photon emission computed tomography” (SPECT) detected only 53 percent of these microinfarcts that were detected by cardiac MRI. Additionally, 13 percent of study patients with microinfarcts were shown to have none when SPECT alone was used.

The findings of the study were reported today (Feb. 1, 2003) in the journal Lancet.

“While both cardiac MRI and SPECT are extremely accurate in detecting large infarcts, our study shows that only cardiac MRI systemically detected smaller infarcts that are missed by SPECT,” said lead researcher Robert Judd, Ph.D., co-director of the Duke Cardiovascular Magnetic Resonance Center (DCMRC). “The smaller the infarct, the more likely that SPECT will miss it.”

Heart attacks occur when blood flow to an area of the heart is cut off or blocked, depriving those muscle cells of needed oxygen and nutrients. When these cells die, they tend to die from the inside of the heart’s pumping chamber and move outward. In a large heart attack, the area of cell death can cover the entire thickness of the chamber’s wall.

“However, in these smaller microinfarcts, the cell death may only travel a short distance,” Judd explained. “Since the spatial resolution of SPECT is roughly equivalent to the thickness of the heart chamber wall, it can only detect those infarcts that have traversed a good portion of the chamber wall.”

The spatial resolution of cardiac MRI is 60 times greater than SPECT, Judd said, allowing it to pick up these microinfarcts.

During a cardiac MRI examination, which is non-invasive and radiation-free, a patient is guided through the cavity of a large doughnut-shaped magnet. The magnet causes hydrogen nuclei in cells to align, and when perturbed by radio waves, they give off characteristic signals, which are then converted by computers into three-dimensional images of the heart and its structures. While MRI technology itself is 20 years old, only in the past few years has technology improved to the point where accurate images of moving tissues can be taken.

SPECT technology creates a series of “slices” of the area to be studied, with a computer assembling the slices to create an image. Patients are usually given a radioisotope, which provides information about blood flow and metabolism of tissues being studied. In the study, both groups of patients were given a contrast-enhancement agent.

To verify the findings on human subjects, the researchers then performed the same tests on a series of animals, some without heart disease and others with known disease; and then analyzed the heart tissue after testing. The scientists performed the confirming studies in the animals to ensure that the smaller areas detected by cardiac MRI were actual areas of cell death, and not something else.

“In the animals, cardiac MRI and SPECT detected infarcts involving greater than 75 percent of the chamber wall,” Judd said. “However, for infarcts involving less than 50 percent of the chamber wall, cardiac MRI detected 92 percent, while SPECT detected only 28 percent.”

Judd said that further studies are needed to establish the role of cardiac MRI in the diagnosis of heart disease.

“If we see these spots on cardiac MRI, the patient likely has coronary artery disease,” Judd said. “However, if they don’t have spots, we can’t say for certain they don’t have coronary artery disease.”

Duke cardiologists estimate that about 30 percent of patients with heart disease find that conventional methods for imaging the heart fall short in providing accurate information by which to guide treatment. They said that MRI provides crisp 3-D views of cardiac anatomy with no interference from adjacent bone or air.

The image quality of cardiac MRI also surpasses that of echocardiography — another common imaging technique, Judd said. Cardiac MRI can better show physicians how well the heart muscle is contracting, as well as precisely reveal areas of damaged tissue.

“It wasn’t until a few years ago that engineers developed scanners fast enough to clearly capture a beating heart,” Judd said. “The discipline is still defining itself. We want to advance the field by improving existing cardiovascular imaging techniques and also by creating entirely novel ways to look at the heart and its vessels.”

The experiments reported in this study were conducted at Northwestern University. Some team members have since come to Duke to establish the DCMRC earlier this year, including Judd, co-director Raymond Kim, M.D., Anja Wagner, M.D., and Heiko Mahrholdt, M.D. Team members still at Northwestern are Thomas Holly, M.D., Michael Elliott, M.D., Matthias Regenfus, M.D., Michele Parker, Francis Klocke, M.D., and Robert Bonow, M.D.

The study was funded by grants from National Institutes of Health, the Deutsche Forschungsgemeinschaft and the Robert Bosch Foundation.

Gene Linked to Infertility in Mice; Findings May Apply to Humans

DURHAM, N.C. – A cell biologist at Duke University Medical Center has published a new study in mice that offers another possible genetic explanation for infertility in men: a gene called miwi.

The research has not yet been conducted using human tissue, but Haifan Lin, Ph.D., an associate professor of cell biology at Duke and senior author of the study, suspects that the human counterpart of miwi, called hiwi, is probably also associated with infertility in men. The study could eventually lead to genetic testing for the human form of the miwi gene, Lin said.

Piwi and miwi stem from the piwi family of genes known to be associated with the division of reproductive stem cells, which are the immature cells that can proliferate and mature to become adult sperm cells.

“This study presents the first definitive evidence that the piwi gene family has an essential function in the mammalian male reproductive system,” said Lin, who is senior author of the paper in the June 7, 2002, issue of Developmental Cell.

In a related paper that appears in the June 6, 2002 issue of Oncogene, Lin describes the connection between the human homologue of piwi, called hiwi, and testicular cancer. (Please visit /news/article.php?id=5555 for a news release featuring the Oncogene paper.)

There are a number of genes linked to male infertility, but only two, which includes miwi and crem, have been directly linked to sperm production as master regulators, Lin said.

When the miwi gene is defective or missing, it can lead to complete sterility in mice, he said.

“We show that this gene, miwi, instructs the making of a protein that binds to messenger RNAs to control their life span,” Lin said. Messenger RNAs, which constitute the genetic instructions for proteins, are copied from DNA to be used to direct the cell’s protein-making machinery.

“In turn, these messenger RNAs control the process of sperm production. In short, the protein MIWI, which is encoded by this gene is a master protein responsible for turning genes on and off during the process of sperm formation,” he said.

The testes of mice with a defective miwi gene were, on average, 29 percent smaller by weight and did not produce any sperm.

The research, which was funded by the National Institutes of Health and the David and Lucile Packard Foundation of Los Altos, California, uses gene knockout technology in which Lin bred a mouse lacking the miwi gene, which was linked to chromosome 5.

The miwi gene is a member of the piwi gene family identified by Lin in 1997. The piwi genes were first isolated in Drosophila, or fruit flies, and have since been linked to reproductive stem cell function, ovarian tumors and infertility in fruit flies. Lin found that by removing the gene in fruit flies, the reproductive stem cells, called germline stem cells, would be depleted.

Now, the same family of genes has been linked to infertility in male mice. Lin is confident that the gene infertility link he found in mice, will one day apply to humans.

“In Developmental Cell, we show that without this gene, or if there is an underactive form of the gene, infertility in mice is the end result. We’ve also shown this in fruit flies and nematodes. Given the evolutionary closeness between mice and humans, it is very likely that a defective hiwi gene will affect humans in the same manner as well,” Lin said.

According to the National Institute of Child Health and Human Development (NICHD), there are approximately 2.6 million infertile married couples in the U.S. Male infertility is a factor in approximately 40 percent of those cases.

The study was co-authored by Wei Deng, a postdoctoral fellow in the Lin laboratory.
For more information about male infertility, please visit the NICHD Web site at http://www.nichd.nih.gov/default.htm.

|| DukeMedNews || Low-dose HRT Could Cut Women’s Health Risk

This week on MedMinute … Hormone replacement therapy (HRT) can build bone strength in women. But HRT is linked to increased risk of heart disease and breast cancer. A small-scale study suggests that using a lower dose and different type of hormone may reduce those health risks.

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After much controversy, the confusion about hormone replacement therapy continues. Last year, a Women’s Health Initiative study found that HRT lowered the risk for osteoporosis but increased the risk for heart disease and breast cancer. Now a new study finds that a low-dose estrogen therapy might offer the benefits of HRT, without the risk.

Dr. Tracy Gaudet is director of the Center for Integrative Medicine at Duke University Medical Center.

“It looks very promising that a lower dose of estrogen and different type of estrogen can be very good for bone. They compared people not on the hormone to people on the hormone, and the people on the hormone clearly had better bone density.”

Gaudet says the size and duration of the study were limited, but the results show promise. Women taking estrogen had no more health problems than those not taking it, and bone density increased.

“We do know that estrogen is useful in that way. One of the important questions is: Could we use lower dose and/or a different type of estrogen and get the benefit without the risk? That’s a question we still don’t have the answer to.”

I’m Cabell Smith for MedMinute.

Study says not enough time for prevention

DURHAM, N.C. — Primary care physicians do not have the time to offer needed preventive health care to their patients, says a new Duke University Medical Center study.

According to the study published in the April 2003 issue of the American Journal of Public Health, providing the recommended preventive maintenance for patients would take an estimated 7.4 hours out of a primary care physician’s day, leaving approximately 30 minutes for critical and chronic disease care.

“We know that prevention is very important for the health of our nation,” said Kimberly Yarnall, M.D., lead author of the study. “But what our study showed was that given the large number of recommendations — everything from cancer screening to lifestyle counseling — coupled with the large number of patients that most physicians are responsible for, it is simply not possible for physicians to deliver all those services to their patients. It’s a big problem.”

Yarnall said that the average patient in a family practice waiting room needs 25 preventive services that have been recommended by the U.S. Preventive Services Task Force. Recommended services vary depending on age, sex, chronic disease status and gestation. Frequency of the services also varies from patient to patient.

Using these recommendations, the Duke researchers assigned conservative time values to the tasks. They estimated the average number of patients a physician sees in a year to be 2,500 and used U.S. Census figures to model a patient panel with an age and sex distribution similar to that of the U.S. population, including children. Chronic disease statistics and pregnancy rates were also factored into the model. The calculations dramatically showed what Yarnall said doctors and patients have been reporting for years: that there is not enough time for all of the recommendations.

“Most would assume that the answer is to pare down the recommendations,” said Yarnall, “but even if we slashed the recommendations in half, it would still take half of every day, or half of every visit, to do half of what is now recommended. Prevention is critical, particularly since chronic disease rates in American adults and children are on the rise.”

Yarnall also said that the problem will become worse as baby boomers age and as new genetic tests become available.

Lloyd Michener, M.D., senior author on the study and chair of Duke University Medical Center’s department of community and family medicine, said that the solution to the problem of inadequate time for preventive care lies in creating a new health-care model that uses a team of caregivers.

The team approach, which Duke has been using for more than 20 years, ensures that patients receive the preventive care they need in addition to acute care and chronic disease management, said Michener. Health-care providers on the team would include nurse practitioners, physician’s assistants, nutritionists and health educators.

“By working together, we can offer the patient better care,” said Michener. “When we relieve physicians of the sole responsibility for prevention, we can free them up to handle more complicated disease management and acute care. Patients will have more time to discuss complex issues of care, while still receiving the quality preventive care that they need.”

The Duke researchers cited as an example of a team approach the management of a patient at risk for heart disease. The patient has high cholesterol and a father who had a heart attack before age 55. Rather than take the estimated eight minutes reported in the study to discuss the importance of a healthy diet with the patient, the doctor might refer the patient to a nutritionist or to a nutrition class. The doctor then has time to discuss any acute care issues, the patient has time to ask questions, and the nutritionist will offer a much more comprehensive explanation of the diet on cholesterol and heart disease.

“It’s win-win for everyone,” said Yarnall. “We believe preventive maintenance is extremely important; no one would argue that. But doctors do not have the time to do it all. With this model, patients get the information they need and we can all feel confident that people are getting the care and attention they need to develop and keep healthier lifestyles.”

|| DukeMedNews || MedMinutes

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|| DukeMedNews || Treatment to repair torn cartilage could soon include liposuction.

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Researchers at Duke University Medical Center have found a way to turn ordinary fat cells into cartilage cells. Farshid Guilak is director of orthopedic research and senior member of the research team. He says he took what are called undifferentiated stem cells, or cells that have not yet been assigned a task by the body, and gave them the information they needed to become cartilage cells. Guilak says the procedure could be extremely beneficial.

“We envision being able to take a set of cells from the patient, manipulating them outside the body to grow a replacement piece of cartilage or to produce cells that can form cartilage and then placing them back into the injured site where they can help repair or regenerate the cartilage that’s been damaged due to a sports injury or a car accident, for example.”

Guilak says there are also possibilities that the procedure could be used to grow specialized fat cells that would help in plastic or reconstructive surgery following a mastectomy. It will still be three to five years before the procedure could be available to the general public. I’m Tom Britt.

Guilak says being able to use such easily obtainable material as fat cells could benefit many patients and improve many treatments.

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“There are possibilities for reconstructive and plastic surgery, for example if we can form a controlled amount of fat for mastectomy patients. The other possibilities are to form other tissues that are of the same origin and we have some preliminary evidence that that can be done. Tissues such as tendons and ligaments or muscle which would also be used for repairing injuries.”

|| DukeMedNews || Drug Fights Fungus That Attacks AIDS Patients

Today on the Newsline: Duke geneticist Joseph Heitman talks about the discovery of an existing class of drugs used to treat organ transplant recipients that may also help fight a type of fungus that infects and often kills AIDS patients and other people with weakened immune systems.

Background: Researchers at Duke University Medical Center have discovered that an existing class of drugs used to treat organ transplant recipients may also help fight a type of fungus that infects and often kills AIDS patients and other people with weakened immune systems. The researchers said the compounds effectively stopped growth of the fungus in test tube studies. They are now testing the most promising compound in animals afflicted with fungal infections.

In the May 15 issue of the EMBO Journal, geneticist Dr. Joseph Heitman, a Howard Hughes Medical Institute investigator; fungus expert Dr. John Perfect of the division of infectious diseases; and their colleagues identified a trait in the fungus Cryptococcus neoformans that allows it to infect people, and suggested a potential new drug target to stop the infection.

In Cut 1, Heitman says the problems in treating these infections are two-fold. The first is that the immune system itself is compromised, so you don’t have assistance from the immune system in fighting the infection.

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C. neoformans is the leading cause of fungal meningitis, a serious and sometimes deadly infection of the thin membrane that covers and protects the brain. The fungus enters the body through the lungs when a person breathes in its airborne spores. In a healthy person, it is mostly harmless, because the immune system effectively combats the organism. However, in people with suppressed immune systems, the organism can evade the host defense and infect the brain. Between 6 percent and 10 percent of AIDS patients develop this life-threatening infection, the researchers said. In about 40 percent of these patients, it is the first infection they develop when their infection progresses to AIDS.

Heitman says there is a pressing need for new anti-fungal agents against Cryptococcus and other fungi because they are identifying an increase both in the number of cases of serious fungal infection and in strains of fungus resistant to current treatments.

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Once an infection is established, treatment options are limited. The most effective anti- fungal drug, called fluconazole, requires lifetime therapy in AIDS patients and has side effects such as nausea and kidney disease.

The researchers found the immunosuppressive drugs cyclosporin and FK506, which are used to treat organ transplant recipients, prevent C. neoformans from growing at body temperature, but not at room temperature.

|| DukeMedNews || Summer is one of the peak periods for children to be taken to the emergency room.

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If this summer is like summers past, children will be rushed to emergency rooms in the U.S. nearly threemillion times for serious preventable injuries. Of that number, some 6,000 will die and more than 100,000 will be permanently disabled. Preventable injuries are the leading killer of children 14 and under. As part of a nationwide effort to prevent those injuries, this week has been designated “National Safe Kids Week.” Local organizations around the country will be holding classes and making presentations to educate parents and kids on the most dangerous activities and how to avoid injuries. Duke University Hospital ER nurse Teresa Cromling says parents and children might think of summer as the season for fun, but she and her colleagues call it trauma season.

“Children are outside more frequently without adult supervision, and they have more time on their hands. Parents are still going to work and doing the things that they do when the children are in school.”

Cromling says the number-one cause of childhood injuries regardless of the season is motor vehicles. Whether inside the vehicle or outside, children require special attention and care. I’m Tom Britt.

Cromling says summer is the time when children get outdoors to explore and experiment, often without adult supervision.

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“The five biggest summer risks would be risks that involve riding in a car, swimming, playing on wheeled play objects like scooters and bikes, walking safely as well as playing safely both outdoors and indoors.”