8
Although many parents and even some physicians believe headaches — including migraines — are an uncommon occurrence in the pediatric population, in fact they are a frequent complaint. According to Soe Mar, MD, a pediatric neurologist at St. Louis Children’s Hospital, of children under age 3, 3 – 8 percent present with headaches. At age 5, the percentage jumps to around 20 percent, and by the age of 15, 50 – 80 percent of teenagers suffer from headaches. Of those percentages, half are classified as migraines. “Migraine headaches are associated with severe, sometimes throbbing pain that may be accompanied by nausea, vomiting, photophobia and phonophobia. In some cases, prior to the onset of the headache children experience a visual, sensory or motor aura — blurry vision, flashing lights in the eyes, numbness, weakness, even vertigo and confusion,” says Dr. Mar. “For young children who can’t adequately verbalize their pain, they may grab their head, avoid light or noise, stop activity and seek out a dark room to sleep.” Even though the exact pathophysiology of migraine headaches remains unknown — vasodilation, cortical spreading depression, dural plasma protein extravasation, dysfunction of neuromodulatory structures in the brainstem are theories— they do run in families. Usually they occur intermittently, with patients having periods of time when they do not develop migraines. But for parents of children who have frequent migraines, their concern often is whether the headaches are a symptom of something more serious such as a brain tumor. Looking for red flags “A good evaluation of children with migraine headaches includes looking for the ‘red flags’ that may indicate a more serious underlying problem,” explains Dr. Mar. “One of these is increasing frequency and severity of the migraine headaches over a short period. If the headaches steadily worsen over a couple of months, coming every day and becoming severe, further testing is needed.” Another red flag is when the recurring migraines wake children from their sleep. “Although children sometimes can be awakened by a migraine, normally these headaches get better when a patient sleeps,” says Dr. Mar. “Especially during nighttime sleep, pressure in the brain naturally builds slowly. If this pressure increases the severity of a child’s headache to the point where he or she regularly awakens with nausea and vomiting, this likely is not a migraine.” Increasing frequency of intense nausea or vomiting associated with a headache is another cause for concern, as are behavior regression and slipping grades. Doctor’s Digest Clinical Focus | Migraine Headaches: A Common Diagnosis in Children and Teens FEBRUARY 2010 In this issue 3 SLCH Aims at Becoming a National Leader in Low-Dose Radiology 5 COPE Preceptor Profile: Eleanor Shaw, MD 7 Gene Mutation May Reveal Clues for Treating Lung Diseases A MONTHLY NEWSLETTER FOR ST. LOUIS CHILDREN’S HOSPITAL ATTENDING AND REFERRING MEDICAL STAFFS SLC5XXX 2/10 continued on next page

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Although many parents and even some physicians believe headaches—including migraines—are an uncommon occurrence in the pediatric population, in fact they are a frequent complaint. According to Soe Mar, MD, a pediatric neurologist at St. Louis Children’s Hospital, of children under age 3, 3 – 8 percent present with headaches. At age 5, the percentage jumps to around 20 percent, and by the age of 15, 50 – 80 percent of teenagers suffer from

headaches. Of those percentages, half are classified as migraines.

“Migraine headaches are associated with severe, sometimes throbbing pain that may be accompanied by nausea, vomiting, photophobia and phonophobia. In some cases, prior to the onset of

the headache children experience a visual, sensory or motor aura—blurry vision, flashing lights in the eyes, numbness, weakness, even vertigo

and confusion,” says Dr. Mar. “For young children who can’t

adequately verbalize their pain,

they may grab their head, avoid light or noise, stop activity and seek out a dark room to sleep.”

Even though the exact pathophysiology of migraine headaches remains unknown—vasodilation, cortical spreading depression, dural plasma protein extravasation, dysfunction of neuromodulatory structures in the brainstem are theories—they do run in families. Usually they occur intermittently, with patients having periods of time when they do not develop migraines. But for parents of children who have frequent migraines, their concern often is whether the headaches are a symptom of something more serious such as a brain tumor.

Looking for red flags“A good evaluation of children with migraine headaches includes looking for the ‘red flags’ that may indicate a more serious underlying problem,” explains Dr. Mar. “One of these is increasing frequency and severity of the migraine headaches over a short period. If the headaches steadily worsen over a couple of months, coming every day and becoming severe, further testing is needed.”

Another red flag is when the recurring migraines wake children from their sleep. “Although children sometimes can be awakened by a migraine, normally these headaches get better when a patient sleeps,” says Dr. Mar. “Especially during nighttime sleep, pressure in the brain naturally builds slowly. If this pressure increases the severity of a child’s headache to the point where he or she regularly awakens with nausea and vomiting, this likely is not a migraine.”

Increasing frequency of intense nausea or vomiting associated with a headache is another cause for concern, as are behavior regression and slipping grades.

Doctor’s Digest

Clinical Focus | Migraine Headaches: A Common Diagnosis in Children and Teens

february 2010

In this issue3 SLCH Aims at Becoming a National Leader in Low-Dose Radiology

5 COPE Preceptor Profile: Eleanor Shaw, MD

7 Gene Mutation May Reveal Clues for Treating Lung Diseases

a monthly newsletter for st. louis Children’s hospital attending and referring mediCal staffs

SLC5XXX 2/10

continued on next page

Page 2: Doctor's Digest

New guides listing contact information for St. Louis Children’s Hospital physicians are now available. To request copies, contact Children’s Direct at 800.678.HELP (4357).

“Children with these severe symptoms may need to undergo brain scans to

determine if there is a tumor or other abnormality in the brain. In some cases,

a spinal tap may be needed to determine if there is a build-up of pressure in the brain,”

says Dr. Mar.

Treating with medications, changing lifestyles

For children and teens who don’t have “red flag” symptoms and whose visual and neurological exams are normal, Dr. Mar recommends beginning treatment with a combination of medication and lifestyle changes.

“With medication, we begin by prescribing the highest possible effective dose of ibuprofen to be administered at the onset of a headache,” says Dr. Mar. “We don’t recommend using ibuprofen more than two days a week, however. If medication is needed more often, then we consider prescribing preventive medications. It’s a matter of choosing the right medication for the right child by looking at the co-morbidities and side effects, and then thoroughly explaining the treatment to families.”

Abortive therapy is designed to stop the migraine headache once it starts. These medications include the triptans, which are serotonin receptor agonists; names include Imitrex, Zomig, Maxalt, Relpax, etc.

“As with many pediatric medications, we have to rely on adult studies to know the efficacy and side effects of the drugs. For that reason, we usually prescribe those that have been around longer because we know what we are looking for in terms of tolerability and side effects,” says Dr. Mar.

Dr. Mar notes that most of the drugs used as preventive medicines—which have the goal of lessening the frequency and severity of migraine attacks—have been in existence

a long time. “The most recent drug approved for prevention of headaches was the antiseizure drug, Topamax, but we also prescribe antidepressants, antihistamines and blood pressure medications,” she says. “With any of these drugs, we advise parents and pediatricians to give them time to work. You need to start with a small dose and slowly build up to make sure that patients can tolerate it. It may take a month or two for any preventive medication to start working. Parents need to understand that this is not ‘magic’ preventive medicine that works immediately.”

An essential part of controlling migraines is evaluating a child’s lifestyle and changing those aspects that may serve as triggers for the onset of headaches. Eliminating as much as possible fatty foods and those with artificial preservatives, chocolate and caffeinated soda, coffee and tea can help lessen the risk. Sleep hygiene is another important factor to evaluate.

“Sleep deprivation is a major trigger for migraines. Very young children need 11 or 12 hours of sleep; often they get only eight hours. Teenagers need eight or nine hours of sleep, and they usually only get five or six,” says Dr. Mar. “And when children and teens go to bed, they need all stimuli turned off. That means no bright lights, no cell phones or computers, no television, radio or stereo. The most they should do is read for a while to help them drift off.” Regular exercise and biofeedback also have positive effects on headaches.

Dr. Mar recommends pediatricians refer children and teenagers to a pediatric neurologist whenever they feel it is necessary, whether at the onset of migraines or after several treatments have been tried. “Everyone’s comfort level is different, and we are happy to see these patients whenever pediatricians think it’s necessary,” she says.

To schedule a patient for an appointment with Dr. Mar at her headache clinic, call Children’s Direct at 800.678.HELP (4357).

2 |

Share Your Ideas Should you have ideas or suggestions you would like brought before the Children’s Medical Executive Committee (CMEC), contact one of your CMEC private physician representatives:

Jean E. Birmingham, MD 314.918.8827

Peter Putnam, MD 314.965.5437

Isabel L. Rosenbloom, MD 314.291.7766

Kathie Wuellner, MD 618.474.1711

Let Us Hear From You If you have comments or suggestions regarding Doctor’s Digest, or if you would like to share information about your activities as a physician, contact:

Amy Connelly Marketing and Communications St. Louis Children’s Hospital 600 South Taylor Ave. Suite 202 St. Louis, MO 63110 Mailstop 90.94.210

314.286.0324 fax: 314.286.0420 [email protected]

Doctor’s DigestPublished for the attending and referring medical staffs of St. Louis Children’s Hospital.

Lee F. Fetter President

Alison Nash, MD Medical Staff President

Perry Schoenecker, MD Medical Staff President-Elect

SLCH News | 2010 Physician Guides Available

Physician’s Guide to sPecialty services

2010

Page 3: Doctor's Digest

The pediatric radiologists and radiologic technologists at the Joe Buck Imaging Center at St. Louis Children’s Hospital are aiming to become a national leader in low-dose radiology for one important reason: the welfare of their patients.

“When you are dealing with children, it isn’t ‘one size fits all,’” says Elissa Rogers, RT(R), supervisor, ancillary services for the imaging center. “At Children’s, we provide radiology services to premature infants weighing less than a pound to 18 year olds weighing 200 pounds. Our goal is to use the least amount of radiation to produce quality images that provide physicians with the information they need for diagnosis and treatment. This is especially critical because many of the pediatric patients we see have chronic illnesses that require multiple imaging studies over time.”

The imaging center adheres to the ALARA radiation safety principle: keeping radiation as low as reasonably achievable. It also supports the efforts of Image Gently, an initiative of the Alliance for Radiation Safety in Pediatric Imaging that has the goal of changing practice by increasing awareness of opportunities to lower the radiation dose in the imaging of children.

“Our first advantage over other imaging centers is that our equipment is calibrated exclusively to the pediatric population. We aren’t using adult machines adjusted for children,” says Rogers. “All of our radiation technologists are registered with the American Registry of Radiologic Technologists, but beyond that they receive in-depth training in how to image children. Each patient’s radiation dose is calculated based on the child’s age, weight and health. For instance, the radiation dose for a child with cystic fibrosis would be different than that of a healthy child of the same age and weight. We do this for every patient, even for those who have reached what would be considered their full growth.”

To ensure that the lowest radiation doses possible are used, ongoing quality improvement projects continually improve upon existing knowledge. “As an example, we are currently watching doses on head and facial CT scans to determine if we can lower the dosage but still obtain a quality image,” says Rogers. “The volume of patients we see allows us to gather the kind of statistical data we need to make improvements.”

That volume leads to another advantage of SLCH’s imaging center—experience. In 2009, the imaging center served more than 7,000 patients needing CT scans, 68,000 needing plain X-rays and approximately 1,200 undergoing nuclear medicine imaging. Within the imaging center’s new interventional radiology suite, 1,000 patients underwent procedures.

Jim Duncan, MD, PhD, interventional radiologist with the Mallinckrodt Institute of Radiology, compares the experience

of pediatric radiologists and radiologic technologists at the imaging center with that of a professional musician.

“An experienced musician can ‘name that tune’ after three or four notes, while someone without that background needs to hear a whole verse before recognizing the song,” he says. “Pediatric radiologists and pediatric interventional radiologists work with and think about children every day. As a result, they can determine whether they have enough information to make

a diagnostic decision much more quickly than those who don’t have that expertise. That results in lower doses of radiation for pediatric patients across the board.”

Dr. Duncan has used his expertise in pediatric interventional radiology to help imaging center staff members further their efforts in studying and implementing low-dose radiation procedures. Among those efforts is establishing the means to track the amount of radiation patients receive over time.

“The pediatric interventional radiology equipment we use indicates how much radiation is being used second to second and how much is used for the whole procedure. We are beginning to use the same process for CT exams so that we have an easily accessible, accurate record for each patient,” says Dr. Duncan. “For any radiologic procedure, the basic principle should be that we have a radiation budget. For each patient, we need to spend our radiation wisely, live within the budget and always try to reduce the amount of radiation which in turn improves the long-term result.”

Children’s Direct Line 800.678.4357 StLouisChildrens.org

| 3

Medical Update | SLCH Aims at Becoming a National Leader in Low-Dose Radiology

Page 4: Doctor's Digest

The Adolescent Center is an outpatient resource developed to assist health care providers in the prompt

assessment and care of patients 12 – 21 through consultations, evaluation, treatment and education. The center may be reached at 314.454.2468. Health care providers who would like to be added to the e-mail distribution list for the Adolescent Update newsletter may contact Dr. Katie Plax at [email protected].

Adolescent male reproductive health remained a nebulous entity until the early 1990s, when observations emerged regarding the beneficial effects on teen pregnancy and STI transmission from increased condom usage in adolescent males. This spurred more research toward defining male sexual reproductive health, independent of female reproductive health. Adolescent male health was then targeted as a way of “improving the lives of young adults, as well as mitigating various types of disadvantage.” (Lindberg et al).

Out of these studies emerged four cornerstones of male sexual reproductive health education (SRH):

1. A broad definition of male SRH, including social and physical components.

2. Services need to expand beyond physical exams and tests to include counseling and preventive education.

3. Male SRH must be examined independent of female issues to address male quality of life and social structure.

4. Availability and attractiveness of programs must be improved to foster the participation of males.

Due to recent implementation of sexual education in the past 20 years, sexual activity among adolescent males has been on the decline. Between 1995 and 2002, the percentage of unmarried adolescent males who had engaged in sexual intercourse decreased from 55 percent to 46 percent (Lindberg et al). These declines were not uniform throughout all racial groups, however. The Hispanic adolescent population saw no change, and among Caucasians there was a much smaller decrease. African-American adolescent males still had a higher percentage of sexual activity. Furthermore, research shows a recent leveling off of these values, indicating a potential pending increase in sexual activity among male adolescents.

Adolescent males over the past several years report being given very little guidance in sexual education. With the advent of abstinence-only programs with the last federal administration, sexual education programs in schools have declined. Sexual education then falls to the responsibility of parents. However, recent reports show that only 55 percent of adolescent males reported any conversation with their parents regarding sexual education, and that the majority of those focused on prevention of STIs without mention of birth control. The availability of clinical services providing sexual education remains limited as well. One report showed that despite 2 out of 3 adolescent males having a physical exam in the past year, only 20 percent received counseling on sexual education (Lindberg et al).

Many barriers exist toward adequate SRH education for adolescents, particularly males. The obstacles vary from the concrete such as available youth-specific facilities to the abstract, such as the male role in society. Through further research and advocacy, we hopefully can provide the opportunity for adolescent males to develop into healthy adults who can lead responsible lives.

References

1. Lindberg L et al. Reassessing Adolescent Male Sexual and Reproductive Health in the United States: Research and Recommendations. American Journal of Men’s Health 2008; 2; 40-56.

2. Marcell et al. Masculine Beliefs, Parental Communication, and Male Adolescents’ Health Care Use. Pediatrics 2007; 110; pp 966-975.

3. Lindberg C et al. Barriers to Sexual and Reproductive Health Care: Urban Male Adolescents Speak Out. Issues in Comprehensive Pediatric Nursing 2006; 29; 2; 73-88.

Adolescent Update | Adolescent Male Reproductive Health by Kevin T. Barton, MD; edited by Katie Plax, MD, director of the SLCH Adolescent Center

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Page 5: Doctor's Digest

A native of St. Louis, Eleanor Shaw’s connections to what is now BJC HealthCare began with her birth at St. Louis Maternity Hospital, a building now a part of Barnes-Jewish Hospital. Then at age 11 she became a patient at St. Louis Children’s Hospital. She remembers a very different atmosphere than exists today.

“My memories are of everything being white and institutional looking,

nothing like today’s bright, beautiful hospital,” she says. “And the quality of care that now exists at Children’s Hospital is just outstanding.”

During high school (Mehlville for those who are curious), Dr. Shaw’s first career ambition was to become a secretary. But during her senior year, a physical education teacher convinced her college would be a more suitable choice. Dr. Shaw enrolled at the University of Missouri – Columbia and decided to become a physician during her freshman year.

“I worked throughout college and medical school, and those experiences helped me make decisions about what career paths to choose. During college, the wife of one of my bosses was a family physician, and she spent time talking with me about the pros and cons of a medical career,” says Dr. Shaw. “During medical school, I worked for the pharmacology department, and I washed lab dishes for a pediatrician researching cystic fibrosis. His work was fascinating, and it sparked my interest in working with children.”

Dr. Shaw completed her pediatric internship and residency at the University of Texas School of Medicine in San Antonio. She then returned to St. Louis and worked at various times as an HMO pediatrician, a house pediatrician at DePaul Health Center, and as a locum tenens for St. Louis Children’s Hospital. In 1992, she went into private practice in Belleville, Illinois, with Robert Kellow, MD.

“I think I am typical of most pediatricians in that what I like most is watching my patients grow up—with the hope that I’ve had some influence on them becoming wonderful adults,” says Dr. Shaw. “I also like that it is a profession in which you are always learning. For instance, a number of illnesses we treated in the past have almost disappeared thanks to preventative-care vaccinations, of which I am a strong proponent. But now other problems have come forward, like obesity that causes children to develop diabetes and heart and joint problems. We are also seeing more behavioral issues like attention deficit disorder that were much less common 20 years ago.”

The ever-changing aspect of pediatric care is one of the reasons Dr. Shaw has served as a COPE preceptor for more than 15 years.

“I want to learn something new every day, and the residents from St. Louis Children’s Hospital help me to do that. They are always willing to answer my questions about new treatment techniques at the same time that I’m teaching them about community pediatrics,” she says. “That kind of back and forth is so beneficial for us both.”

Dr. Shaw’s main goal is to provide residents with an understanding of how important it is to always see that there is a person behind the illness. “With some patients and parents, you really need to take a little more time because they may be really nervous about problems that may seem trivial to us as medical professionals,” she explains. “Residents need to view their patients and families as people who live next door to them in the community and treat them accordingly.”

Dr. Shaw and her husband, Dave have two children. Their son, Steven, 19, is a history major at McKendree University in Lebanon, Illinois. Their daughter, Karen, 18, attends Augustana College in Rock Island, Illinois, and plans on becoming a veterinarian—a helpful profession for a family that includes four rescue dogs.

COPE Preceptor Profile | Eleanor Shaw, MD

Children’s Direct Line 800.678.4357 StLouisChildrens.org

| 5

Upcoming Events | Spring CPU Focuses on NeurosciencesSt. Louis Children’s Hospital (SLCH) and Washington University School of Medicine are presenting a one-day educational pediatric neuroscience program on Friday, April 9, 2010, at the Chase Park Plaza Hotel in St. Louis. SLCH physicians will present current clinical strategies for dealing with the neurological, cognitive, social and emotional impairments manifested in children with autism, epilepsy, brain tumors and mild brain trauma.

Topics include:

• MildHeadInjury:Treatment,Long-TermOutcomes& Return to Play

• TheRoleofNeuroimaginginPediatricPractice

• PediatricNeuro-Oncology

• TreatingAutismOvertheLifeCourse

• NeuropsychologicalConsiderationsinPediatricEpilepsy

• MediallyIntractableEpilepsy:Pre-OperativeEvaluation& Neurosurgical Treatment

• PrecociousPuberty:Definitions,Diagnosis&Treatment

• PsychogenicMovementDisordersinChildren&Adolescents

Visit StLouisChildrens.org > For Healthcare Professionals > Education or call Children’s Direct at 800.678.HELP (4357) for more information and to register.

Page 6: Doctor's Digest

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Teresa Vietti, a pediatrician, oncologist, clinical investigator, whose leadership ushered in the era of cooperative clinical trials in childhood cancer, died January 25, 2010. She was 82.

Dr. Vietti, professor emeritus of pediatrics and radiology at Washington University and pediatric oncologist at St. Louis Children’s Hospital, was an internationally recognized pioneer in the clinical investigation of childhood cancer

for over 50 years. Her basic science studies of the mechanisms of action of anti-neoplastic agents and their development as key components to multi-agent therapy in childhood cancer paved the way for an increase in survival in childhood cancer from less than 15 percent to about 80 percent, which has occurred during the past four decades. Dr. Vietti conceived of the multi-institution pediatric cooperative groups and founded the 90-institution Pediatric Oncology Group of which she was the sole chairperson for its first 15 years. Under her leadership, the organization grew to more than 100 institutions and 1500 investigators. She designed and directed over 200 clinical trial investigations in the treatment of childhood cancer and published over 200 research articles.

Born in Fort Worth, Texas, in 1927, Dr. Vietti and her twin sister, Eleanor Ardel, became interested in science and medicine as very young girls. Dr. Vietti attended Rice University and then earned a medical degree from Baylor College of Medicine in Houston in 1953. She arrived at St. Louis Children’s Hospital that same year for an internship and residency in pediatrics.

After further training in hematology, Dr. Vietti returned to

Washington University School of Medicine in 1961 as assistant professor of pediatrics, becoming full professor in 1972. She became chief of the pediatric hematology/oncology division in 1970 and remained in that role until 1986.

“Hundreds of thousands of children with cancer and their families worldwide have experienced life when none would have been possible were it not for Teresa Vietti,” said Alan L. Schwartz, MD, PhD, the Harriet B. Spoehrer Professor of Pediatrics, chair of the Department of Pediatrics and St. Louis Children’s Hospital pediatrician-in-chief.

“Teresa Vietti was a dedicated teacher, compassionate physician, a most generous person, indeed self-effacing, and a model colleague,” Schwartz said. “At a time when pediatric medicine could offer compassion but not cure to children with cancer, Teresa Vietti almost single-handedly developed the approach of laboratory-based studies, translational research and clinical trials. She was truly the mother of multimodality cancer treatment.”

She also was the co-author of the book “Clinical Pediatric Oncology,” which has been one of the premier texts in

its field through its four editions.

In 1994, Dr. Vietti was awarded the Lifetime Achievement Award of the Society for Pediatric Hematology/Oncology. In September 1996, her photograph was featured on the cover of Cancer Research, the leading scientific oncology journal, in tribute to her more than 40 years of pioneering

studies. Among many other awards, in 2007, she received the Second Century Award of Washington

University School of Medicine.

Dr. Vietti had no immediate family or survivors.

A memorial service for Dr. Vietti will be held in the spring. Memorial contributions may be made to Washington University School of Medicine, Department of Pediatrics, c/o Alan L. Schwartz, Ph.D., M.D., 660 South Euclid Ave., Campus Box 8116, St. Louis, MO 63110.

Faculty Update | Pediatric Oncology Pioneer Dies at 82

Research Round-Up | Family-Based Weight Loss Study Seeking ParticipantsFocus: The NIH-funded Comprehensive Maintenance Program to Achieve Sustained Success (COMPASS) study is enrolling overweight children in a new study. The study tests different approaches for a weight maintenance program.

Currently Enrolling: The COMPASS study is currently recruiting overweight children who are 7 to 11 years. To be eligible, the child must have a BMI above the 85th percentile and one parent must be overweight.

All parents and children who participate will receive family-based behavioral weight control sessions. The weight control treatment sessions last for four months, followed by eight months of

maintenance sessions. Patients then attend follow up assessments at 18 and 24 months.

Families who complete the study and assessments will receive $225.

Primary Investigator: Denise Wilfley, PhD, professor of psychiatry, medicine, pediatrics and psychology, Washington University School of Medicine.

More Information: Call Holley Boeger, study coordinator at 314.286.0078 or [email protected] to learn more about the study and criteria to participate. This study is funded by the National Institute of Health.

Page 7: Doctor's Digest

by Beth Miller

A genetic mutation found in four children born with multiple abnormalities may provide insight into potential treatments for newborn lung distress and chronic obstructive pulmonary disease (COPD).

The children were born with abnormally developed lungs, gastrointestinal and urinary systems, skin, skull, bones and muscles. In addition, all had cutis laxa, an inherited connective tissue disorder that causes skin to hang loosely from the body. Three of the patients died from respiratory failure before age 2.

Details about the discovery of the mutation, found by researchers from Washington University School of Medicine, McGill University, New York University Langone Medical Center and collaborating institutions, are published in the Oct. 15 online edition of the American Journal of Human Genetics.

Elaine C. Davis, PhD, senior author and associate professor of anatomy and cell biology at McGill University in Montreal, Canada, compared various tissues from a mouse genetically engineered to be missing a form of the LTBP4 gene with skin tissue samples from one of the children. She found remarkable similarities. The mouse, provided by Daniel Rifkin, MD, the Charles Aden Poindexter Professor of Medicine and professor of cell biology at NYU Langone Medical Center, showed similar connective tissue alterations by electron microscopy as the patient. The child had cutis laxa, lethal pulmonary complications and gastrointestinal and urinary disease.

Based on these observations, researchers in the laboratory of Zsolt Urban, PhD, a pediatric geneticist at Washington University School of Medicine, sequenced the LTBP4 gene in the four children and confirmed they had mutations. He determined that the patients were the first described to show severe symptoms of a novel syndrome, which the researchers have named Urban-Rifkin-Davis Syndrome.

The findings have potential implications for newborns with underdeveloped lungs as well as older patients with severe lung diseases, including COPD, says Urban, first author of the paper.

“Many newborns commonly have breathing difficulties,” Dr. Urban says. “Part of the problem is that the lung is not developed properly, especially the alveoli, the tiny sacs at the end of the smallest airways that serve as a place for oxygen uptake and gas exchange. This finding helped us identify a gene essential for the development of alveoli and potentially provide a target for intervention in premature babies.”

Dr. Urban says potential treatments could include introducing the protein product of the LTBP4 gene to the newborn or using existing drugs that can moderate transforming growth factor beta (TGFß), which is overactivated in the tissues of these children. The drug losartan, now in trials for treating Marfan syndrome, another connective tissue disorder, has been shown to limit TGFß and merits further research as a possible treatment.

The researchers now are broadening their research into the new syndrome among other patients with cutis laxa. Dr. Urban, assistant professor of pediatrics, of medicine and of genetics at Washington University School of Medicine, heads the International Center for the Study of Cutis Laxa at St. Louis Children’s Hospital.

“We are finding that about 70 percent of cutis laxa patients with pulmonary, gastrointestinal and urinary problems have Urban-Rifkin-Davis Syndrome,” Dr. Urban says. “Now we will look at what percentage of cutis laxa patients with only pulmonary problems have the mutation.”

Early developmental problems that are not detectable in childhood may predispose a person to age-related disease such as COPD, Dr. Urban says. Dr. Urban and colleagues are also testing samples collected from patients with COPD for LTBP4 mutations. When lungs are damaged with COPD, alveoli lose their elastic quality, and the walls between them are destroyed as they become thick and inflamed.

“Patients who may have a slightly reduced activity of LTBP4 might be more susceptible to chronic lung diseases later in life,” Dr. Urban says. “Identifying genes that are central for the formation of alveoli may help us devise ways to regenerate alveoli in patients with COPD.”

Urban Z, Hucthagowder V, Schürmann N, Todorovic V, Zilberberg L, Chio J, Sens C, Brown C, Clark R, Holland K, Marble M, Sakai L, Dabovic B, Rifkin D, Davis EC. Mutations in LTBP4 cause a syndrome of impaired pulmonary, gastrointestinal, genitourinary, musculoskeletal and dermal development. American Journal of Human Genetics.

This study was funded in part by the National Institutes of Health, March of Dimes, Phillip Morris USA Inc. and the Canadian Institutes of Health Research.

Research Round-Up | Gene Mutation May Reveal Clues for Treating Lung Diseases

Children’s Direct Line 800.678.4357 StLouisChildrens.org

| 7

Chief Resident Award

Each month, St. Louis Children’s Hospital’s Chief Residents honor a resident who shows exceptional dedication to his or her patients, colleagues or profession. In January, the SLCH Chief Resident Award was presented to Douglas Moeckel, MD, third-year pediatrics resident, in recognition of his ability to lead and unify a care team with his positive attitude, collaborative

communication and utmost professionalism.

Page 8: Doctor's Digest

In this issue1 Migraine Headaches: A Common Diagnosis in Children and Teens

4 Adolescent Male Reproductive Health

6 Pediatric Oncology Pioneer Dies at 82

Non-profitOrganizationU.S. Postage

PAIDSt. Louis, MO

Permit No. 617One Children’s PlaceSt. Louis, MO 63110

Marketing and Communications 314.286.0324Fax: 314.286.0420

St. Louis Children’s Hospital was redesignated as a Magnet® hospital by the American Nurses Credentialing Center’s (ANCC) Magnet Recognition Program®, which recognizes excellence in nursing. The announcement was made January 21.

Only 2 percent of hospitals nationally have achieved Magnet redesignation. Magnet hospitals must continue to achieve rigorous standards to earn another four-year designation. Such high standards enable a

hospital, like a magnet, to attract and retain outstanding nurses, the ANCC reports.

“I am so proud to work with such a great staff and leadership team here,” says Peggy Gordin, MS, RN, NEA-BC, FAAN, vice

president of patient care services. “This achievement followed an intensive two-year application and evaluation process. Everyone’s hard work has paid off, and we are all very excited to have that recognized.”

The Magnet Recognition Program was developed in 1994 by the ANCC, the largest nursing accrediting and credentialing organization in the United States. The program recognizes hospitals that provide quality patient care, nursing excellence and innovations in professional nursing practice. It also provides a forum for nurses around the nation to communicate successful practices and strategies.

“Being a Magnet hospital speaks to the high level of patient care, collaboration and professionalism of our entire organization,” says Lee Fetter, SLCH president. “Magnet hospitals must meet high standards, such as having better patient outcomes and outstanding patient satisfaction. I’m proud of our team for earning this honor, and it inspires all of us to continue to strive to be even better.”

Spotlight | Children’s Hospital Nationally Recognized for Excellence in Nursing