School of Medicine

Wayne State University School of Medicine
Research shows anti-HIV medicines can cause damage to fetal hearts
In Headlines on November 19, 2014
Steven Lipshultz, M.D.

Steven Lipshultz, M.D.

A study by a Wayne State University School of Medicine and Children’s Hospital of Michigan, Detroit Medical Center, research team is shedding new light on the troubling question of whether the drugs often given to HIV-positive pregnant women can cause significant long-term heart problems for the non-HIV-infected babies they carry.

The study recently published in the journal AIDS shows that while the HIV medications have been successful in helping to prevent the transmission of the virus from mother to infant, they are associated with persistently impaired development of heart muscle and reduced heart performance in non-HIV-infected children whose mothers received the medicines years earlier.

“What our study indicates is that there’s potentially a long-term price to be paid for protecting the children of HIV-infected mothers from the virus,” said Steven Lipshultz, M.D., pediatrician-in-chief at the Children’s Hospital of Michigan and chair of pediatrics for the School of Medicine. Dr. Lipshultz is a specialist in the study of long-term toxic cardiac effects among children affected by cancer and HIV drug therapies.

“These medicines have been very effective at reducing the rate of transmission of HIV from mother to child,” added Dr. Lipshultz, the lead author of the study, “but the findings we’ve just published show clearly that further investigation of their long-term impact on the heart health of the children involved is needed.

“Thanks to the new anti-HIV medications, the rate of transmission has been lowered from 26 percent to less than 1 percent during the past few decades, and that has been a miracle of life for the children involved. Still, we don’t want to be protecting these children from one disease, only to give them another one.”

The study compared heart development and long-term heart functioning in 428 uninfected children of HIV-infected mothers to children who had not been exposed to HIV from 2007 to 2012. The results pointed to a significant association between lagging heart muscle development and impaired pumping ability in the children of the HIV-infected mothers who had received the medications.

“These findings clearly indicate the need for further study,” said Dr. Lipshultz, while pointing to one of the study’s key conclusions: “Subclinical differences in left ventricular structure and function with specific in-utero antiviral exposures indicate the need for a longitudinal study to assess long-term cardiac risk and cardiac monitoring recommendations.”

Dr. Lipshultz, a nationally recognized expert on pediatric cardiac care who 20 years ago led the effort to found the nation’s only registry of pediatric cardiomyopathy, said the study is a “compelling example of how clinical research can be effective in helping to shed light on complex problems in pediatric health care.”

The Children’s Research Center of Michigan team, located at the Children’s Hospital of Michigan, involved with this National Institutes of Health-supported multicenter study includes James Wilkinson, M.D., associate director of the center and professor of pediatrics, and research assistant Joslyn Westphal, M.P.H.

Dr. Wilkinson stressed the study “raises the question of how much do we know about the long-term safety of drugs given to children?” He is concerned that “pediatric drug studies remain particularly limited. The lack of information about the long-term safety of drugs prescribed for children is a special worry, both for drugs that may be used for decades for chronic conditions and for drugs for which short-term use may be found to harm children’s growth and development months or years later. Although these are effective medicines for children, in order to understand their safety, long-term pediatric safety studies are needed to potentially allow future options for improvement if serious safety risks are identified.”

“At the end of the day, our goal at the Children’s Hospital of Michigan is to provide the very best possible care for our patients,” Dr. Lipshultz said.  “Studies like this one are crucially important for meeting that challenge.”

The PHACS (Pediatric HIV/AIDS Cohort Study) is the largest U.S. government study of pediatric HIV and AIDS, with more than 30 centers. It is a trans-National Institutes of Health study with 10 NIH institutes and centers participating and funding PHACS. Since PHACS's inception more than a decade ago, Dr. Lipshultz has been the NIH-funded cardiology leader of PHACS, a member of its scientific leadership group, and the inaugural and only chair of the NIH PHACS Cardiovascular Task Force, the group which led this study.

Researchers find children, energy drinks a dangerous combination
In Headlines on November 17, 2014
Steven Lipshultz, M.D.

Steven Lipshultz, M.D.

More than 40 percent of reports about energy drinks to U.S. poison control centers involved children younger than 6, with some suffering serious cardiac and neurological symptoms, according to research by a Wayne State University School of Medicine physician-researcher presented Nov. 17 at the American Heart Association’s Scientific Sessions 2014 in Chicago.

This disproportionate representation of children is concerning given the number of reports of serious cardiac and neurological symptoms, said Steven Lipshultz, M.D., the study’s senior author and professor and chair of pediatrics at Wayne State University and pediatrician-in-chief at Children’s Hospital of Michigan in Detroit.

Researchers analyzed the October 2010-September 2013 records of the American Association of Poison Control Centers’ National Poison Data System, which contains information about calls from the public and health care providers to 55 poison control centers in the United States. “Exposure calls” are defined as those that involve actual or suspected contact with any substance that has been ingested, inhaled, absorbed, applied to or injected into the body, regardless of toxicity or clinical manifestation. Researchers found:

• Of the 5,156 reported cases of energy drink exposure, 40 percent were unintentional, (i.e. unforeseen or unplanned) exposures by young children.

• Moderate to major outcomes were reported in 42 percent of cases involving energy drinks that had been mixed with ethanol (alcohol) and in 19 percent of energy drinks that did not contain alcohol.

• Among cases across all age groups with major outcomes, cardiovascular effects (including abnormal heart rhythm and conduction abnormalities) were reported in 57 percent of cases, and neurologic effects (seizures, including status epilepticus) in 55 percent.

“Energy drinks have no place in pediatric diets,” Dr. Lipshultz said, “And anyone with underlying cardiac, neurologic or other significant medical conditions should check with their health care provider to make sure it’s safe to consume energy drinks.”

Energy drinks may contain pharmaceutical-grade caffeine and additional caffeine from natural sources that may cause the heart to race and blood pressure to increase. Energy drinks with multiple caffeine sources were tied to a higher rate of side effects, typically involving the nervous, digestive or cardiovascular systems.

Some energy drinks contain up to 400 milligrams of caffeine per can or bottle, compared to 100 to 150 mg in a typical cup of coffee, Dr. Lipshultz said. Caffeine poisoning can occur at levels higher than 400 mg a day in adults, above 100 mg a day in adolescents and at 2.5 mg per kilogram (2.2 pounds) of body weight in children younger than 12, he said.

Researchers don’t yet know whether compounds other than caffeine in the drinks contribute to the ill effects. Many of the added ingredients have never been tested for safety and have never been tested in combination.

In 2010, the U.S. Food and Drug Administration banned pre-packaged energy drinks that contain alcohol. Since then, calls to poison control centers about such drinks fell sharply, which supports the effectiveness of education and the combination ban. But some people might custom mix alcohol-energy brews, Dr. Lipshultz said.

Reports to poison control centers vastly underestimate the problem because many people who become ill from energy drinks don’t call the hotlines and emergency room visits are not included. “The reported data probably represent the tip of the iceberg,” Dr. Lipshultz said.

Researchers called for improved labeling of caffeine content and potential health consequences, as well as continued efforts to decrease children’s exposures to the products.

Co-authors of the study are Steven Seifert, M.D., University of New Mexico; Kristopher Arheart, Ph.D., University of Miami; Vivian Franco, M.P.H., University of Miami; Alvin Bronstein, M.D., Colorado School of Medicine; Stacy Fisher, M.D., University of Maryland; Brandon Warrick, M.D., University of New Mexico; and Sara Seifert, M.D., University of Miami.

Medical student Adam Milam wins AAMC's 2014 Herbert W. Nickens Scholarship
In Headlines on November 14, 2014
Adam Milam, Ph.D., Class of 2016.

Adam Milam, Ph.D., Class of 2016.

Wayne State University School of Medicine medical student Adam Milam, Ph.D., received the Herbert W. Nickens Medical Student Scholarship at the Association of American Medical Colleges’ annual meeting Nov. 10 in Chicago.

The $5,000 scholarships are given annually to five outstanding students entering their third year of medical school who have shown leadership in efforts to eliminate inequities in medical education and health care, and in addressing educational, societal and health care needs of racial and ethnic minorities.

“I could not have been more excited and honored. The award is encouraging in that the AAMC believes that medical students can make substantial contributions to addressing inequities in health and education,” Milam said.

The Baltimore native completed degrees in mental and public health studies, including a doctorate in mental health, at Johns Hopkins University before moving to Detroit for medical school in 2012.

“I have always tried to be an active part of the community and have taken a special interest in addressing health inequities,” he said.

He coordinated the Black Medical Association’s most recent Reach Out to Youth event for Detroit children interested in medical careers. The event is held annually at the School of Medicine. He has volunteered as an HIV testing counselor and was an epidemiologist for the Baltimore City Health Department. He also assisted principal investigators at the United States Centers for Disease Control and Prevention’s Center for the Prevention of Youth Violence/Maryland Safe and Supportive Schools Project of Johns Hopkins Bloomberg School of Public Health. His doctoral dissertation on alcohol outlets and behavioral outcomes in minors has been cited in local and state legislation aimed at reducing crime.

The Class of 2016 M.D. candidate was astonished to learn he was selected for the Nickens scholarship, which is named after the founding vice president of the AAMC’s Diversity Policy and Programs unit. Milam considers himself in good company – Wayne State University President M. Roy Wilson, M.D., received the Herbert W. Nickens Award in 2007.

“The awards named after the late Dr. Herbert Nickens are among the most prestigious that the AAMC can bestow. To our knowledge, he is the first Wayne State University School of Medicine student to receive the honor,” said Silas Norman, M.D., associate dean of Admissions, Diversity and Inclusion. “He is an excellent student and very active in the School of Medicine and community service activities. Members of our staff were there to support him in this historic event.”

Dr. Norman, along with Interim Director for the Office of Diversity and Inclusion D’Andrea Wiggins, D.R.E.; Assistant Dean of Student Affairs and Career Development Lisa MacLean, M.D.; Assistant Dean of Basic Science Education Matthew Jackson, Ph.D.; and Assistant Professor of General Medicine Eric Ayers, M.D.; are among the faculty, staff and administration Milam thanked for their support.

“I would also like to thank the members of the Wayne State University School of Medicine Black Medical Society, who have been partners in my outreach efforts and have encouraged and inspired me. Lastly, I would like to thank my family, friends and mentors, who have always pushed me to follow my dreams,” he said.

The AAMC required a personal statement assessing his leadership efforts. Milam discussed his education, outreach and research in Baltimore, and his time in Detroit.

“My passion to address health disparities first sprouted during my employment at the emergency department as a clinical technician at Johns Hopkins Hospital, where I witnessed patients who were gravely ill from preventable health conditions. Many of the patients relied on the emergency department for all of their medical needs and their health often did not improve even with arguably the best medical care in the country,” he said. “My experiences, education and volunteerism … provide a glimpse into my commitment and leadership to ensuring all people have the opportunity to attain their full health potential. Growing up in Baltimore and now living in Detroit, I am able to see health disparities first-hand and I am committed to addressing these disparities.”
WSU, Detroit's Make Your Date program gives moms-to-be and babies help and hope
In Headlines on November 12, 2014

In observance of November as Prematurity Awareness Month and World Prematurity Day (Nov. 17), Wayne State University and the Detroit Medical Center are encouraging area mothers-to-be to take advantage of a powerful and free nonprofit program that is helping mothers throughout Detroit deliver healthy full-term babies on or after their due date.

Premature babies can face serious health challenges throughout their lives. The city’s Make Your Date program provides a consistent approach among local health care providers in how they deliver support and care to expectant mothers to help them carry their babies to full term. The initiative was launched in May by Mayor Mike Duggan, Wayne State University, Detroit’s leading health systems and other key partners.

Sign up is easy: Visit www.makeyourdate.org or call 313-577-1000.

The Make Your Date campaign asks expectant mothers to do three simple things:

• Make a doctor’s appointment to begin regular checkups.

• Work with their Make Your Date health care provider to develop a healthy mother, healthy baby plan, which includes everything from testing and treatment to nutrition and rest.

• Join group prenatal care or pregnancy education classes, where they can share questions, ideas and concerns, and learn more about their pregnancy.

In celebration of Prematurity Awareness Month, individuals and organizations are encouraged to further the mission and donate to Make Your Date. Go to www.makeyourdate.org/donate/ to make a tax-deductible contribution.

"The Make Your Date program already has shown its effectiveness in getting women connected to help them carry their babies to full term. Every at-risk expectant mother should take advantage of the medical and peer support this wonderful program provides," Duggan said.

“Being born full term is critical to long-term health,” said Sonia Hassan, M.D., associate dean for Maternal, Perinatal and Child Health for the Wayne State University School of Medicine and co-leader of the Make Your Date program. “Babies born preterm have a higher risk of breathing complications, cerebral palsy and difficulty in school. We want Detroit moms to know they can get the care they need, to give their babies the greatest chance at a healthy start.”

In Detroit, 18 percent of babies are born prematurely, a rate nearly 6 percent higher than the state average. Studies show that low birth weight accounts for almost 50 percent of the city’s infant mortality rate of 14 deaths in every 1,000 births, twice the national average.

Researchers at the Perinatology Research Branch of the of the Eunice Kennedy Shriver National Institute for Child Health and Human Development of the National Institutes of Health, which is housed at Wayne State University and Hutzel Women’s Hospital in the Detroit Medical Center, have made seminal discoveries in the prevention of preterm birth during the past 22 years.

“The prevention of preterm birth is a major priority for the PRB,” said Roberto Romero, M.D., D.Med.Sci, chief of the branch. “We are committed to supporting the efforts to reduce preterm birth in the city of Detroit and abroad.”

Learn how your business or organization can get involved to make a real difference to our mothers, families and neighborhoods. Inquire at info@makeyourdate.org.

The mission of the Make Your Date campaign is to implement evidence-based strategies to reduce the rate of preterm birth. This strategy is executed through education, collaboration and partnerships with health care systems, universities and other established programs. For more information, visit www.makeyourdate.org or call 313-577-1000.
Researcher publishes study showing effectiveness of heart-protecting drug for kids who undergo chemo
In Headlines on November 10, 2014
Steven Lipshultz, M.D.

Steven Lipshultz, M.D.

After nearly three decades of continuing research into how chemotherapy frequently causes toxicity-related damage to the hearts of children who survive cancer, Steven Lipshultz, M.D., Wayne State University chair of pediatrics and pediatrician-in-chief at the Children’s Hospital of Michigan, part of the Detroit Medical Center, has published a breakthrough study demonstrating that a key drug designed to prevent such damage works effectively and safely.

Described by Dr. Lipshultz as “a significant step forward in helping children avoid the heart-damaging side effects that often accompany cancer chemotherapy,” the study in the authoritative Progress in Pediatric Cardiology journal is based in large part on numerous animal model and human clinical trials he performed or directed during the past 25 years.

The article (http://www.sciencedirect.com/science/article/pii/S1058981314000083) answers a recently debated question about the efficacy of the drug dexrazoxane in suppressing the toxic effects of chemotherapy. The bottom-line conclusion: “Studies published since 2011 have confirmed the efficacy of dexrazoxane in preventing or reducing anthracycline-related cardiotoxicity in children with cancer. As a result, we believe that dexrazoxane should be available to children with high-risk cancers to reduce the risk of cardiotoxicity associated with high-dose anthracycline treatment.”

The study findings – many of them obtained by Dr. Lipshultz and his colleagues during their intensive research on cardiac ailments triggered by cancer therapy – also played a large role, he said, in the U.S. Food and Drug Administration’s recent decision to award “Orphan Status” to the drug for the prevention of cardiomyopathy for children and adolescents through 16 years of age treated with anthracyclines. That designation is “extremely important,” he added, in accelerating the process through which major pharmaceutical companies decide to seek FDA approval for and manufacture of the compound.

“I think our study is encouraging because of the way it will help to eventually bring the drug into the clinical setting, where it can protect the hearts of children who are undergoing cancer chemotherapy,” he said.

Dr. Lipshultz, a veteran pediatric cardiologist who 20 years ago led the effort to found the nation’s only registry of pediatric cardiomyopathy cases (the National Institutes of Health-funded North America Pediatric Cardiomyopathy Registry, or PCMR), also noted that the nation’s largest organization of pediatric oncologists, the Children’s Oncology Group, has now recommended the drug to offset toxic effects of chemotherapy in childhood cancer survivors.

Dr. Lipshultz said the study offers “new hope” to the approximately 12,000 American children diagnosed with cancer and treated with chemotherapy each year. About half of those children receive chemotherapy that may eventually result in the development of significant heart problems that can lead to shortened lifespans and reduced quality of life.

“We’ve made terrific progress in the battle against childhood cancer during the past 40 years,” he added, “and the survival rate has more than doubled. But at the same time, we don’t want to be curing these kids of cancer only to see them develop heart problems because of their chemotherapy.

“Unfortunately, there is no other drug to protect the hearts of children with cancer, which is why it’s so important that we develop dexrazoxane as a powerful tool that can accomplish that task. And it’s very encouraging to know that much of the research allowing that to happen has been performed by investigators right here at the Children’s Hospital of Michigan and Wayne State University. This new study provides a perfect example of how research conducted at the bedside, in a clinical setting, is crucial to accomplishing our mission of providing the very best possible care for patients.”

Said Dr. Lipshultz, who has received commendations from both the NIH and the U.S. Congress for his research in pediatric cardiology. “For a pediatrician whose passion is helping sick kids get better and go on to healthy lives, the publication of a study like this one is very rewarding indeed.”

Kresge's vision workshop highlights research, engages vision community
In Headlines on November 7, 2014
Mary Elizabeth Hartnett, M.D., presented the Clinical Translational Lectureship.

Mary Elizabeth Hartnett, M.D., presented the Clinical Translational Lectureship.

Renu Kowluru, Ph.D., led the organizing committee.

Renu Kowluru, Ph.D., led the organizing committee.

The Kresge Eye Institute, in association with the Wayne State University School of Medicine’s Department of Anatomy and Cell Biology, presented its inaugural Vision Research Workshop on Oct. 15 at the Robert S. Jampel, M.D., Ph.D., Auditorium in Detroit to highlight the research accomplishments of KEI’s graduate students, postdoctoral fellows, residents and clinical fellows.

The workshop, a by-product of a vision research retreat held last March, provided an opportunity for Wayne State’s vision community to interact with each other and exchange ideas for possible collaboration. Sessions on inflammation and eye diseases, ocular diseases and retina pathophysiology were presented.

Seventeen abstracts were accepted for oral presentations and 15 for poster presentations, with the top three presentations receiving awards. Deepa Talreja won first place for “Toll-like Receptor 2 Mediates Retinal Pigmented Epithelial (RPE) Cell Innate Responses to Candida Albicans." Cui Li received second place for "IL-17 Regulates MerTK+ Cells in P. aeruginosa Keratitis," tying with Pawan Kumar Singh for "Bioactive lipid mediator resolvin D1 (RvD1) promotes the resolution of inflammation in bacterial endophthalmitis via TLR2-signaling." "Intracellular Ca++ Shapes Transient Signaling in a Subset of Depolarizing Bipolar Cells in the Mouse Retina," by C.B. Hellmer, and "Characterization of the Müller glial response during adult retinal regeneration,” by Alexandra H. Ranski, placed third.

“The faculty was happy to learn what others are doing, and how they can collaborate with others, and our trainees were happy to get a platform to present their work,” said Renu Kowluru, Ph.D., chair of the organizing committee and professor of Ophthalmology, Endocrinology and of Anatomy and Cell Biology.

Dr. Kowluru was supported by co-committee members Linda Hazlett, Ph.D., distinguished professor and chair of the Department of Anatomy and Cell Biology; KEI Director Mark Juzych, M.D., M.H.S.A., the David Barsky, M.D. Endowed Chair and professor of Ophthalmology; Ophthalmology clinical fellow Sonia Rana, M.D.; postdoctoral fellow Pawan Kumar Singh, Ph.D.; and doctoral student Bing Xu.

The event was organized and run by trainees, postdoctoral fellows and graduate students, giving them additional experience in the defense and presentation of their research at local, national and international meetings, and hands-on training in organizing and running scientific meetings.

“Overall, the presentations were thorough and the discussions were constructive. Our trainees really worked hard in putting on a great show,” Dr. Kowluru added. “A number of participants have already indicated that they are looking forward to next year’s conference.”

As part of the workshop, adult and pediatric retina surgeon Mary Elizabeth Hartnett, M.D., presented “Retinopathy of Prematurity: The Effects of VEGF in Health and Pathology,” the second annual Kresge Eye Institute Clinical Translational Lectureship. Dr. Hartnett is a professor of Ophthalmology at the University of Utah and the John A. Moran Eye Center. Her research focuses on understanding the mechanisms of aberrant angiogenesis in age-related macular degeneration and retinopathy of prematurity. She is chair of the Diseases and Pathophysiology of the Visual System Study Section of the National Eye Institute. Dr. Hartnett is a fellow of the American College of Surgeons and of the Association for Research in Vision and Ophthalmology.

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