July 30, 2010
NIH Podcast Episode #0114
Balintfy: Welcome to the 114th episode of NIH Research Radio with news about the ongoing medical research at the National Institutes of Health—the nation's medical research agency. I’m your host, Joe Balintfy. Coming up in this episode: research helping infants—a new more successful heart surgery procedure and the amount of oxygen to help preterm survival and reduce eye risks—plus, understanding the microbiome. But first, a quick news update.
Balintfy: A team of NIH-funded researchers has successfully regenerated rabbit joints using a cutting edge process to form the joint inside the body. Regenerative procedures like this are performed by stimulating organs or tissues—that previously could not be repaired—to heal themselves. In this study, three-dimensional structures made of special materials in the shape of the tissue, were infused with a protein to promote growth of the rabbit joint. The experiment only demonstrates the feasibility of this approach. Future work could replace arthritic joints in pre-clinical animal models and ultimately in arthritis patients who need total joint replacement.
News updates are compiled from information at www.nih.gov/news. Coming up next helping the hearts and eyes of infants, plus more on the microbiome.
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Newer Heart Surgery for Infants Offers First-Year Survival Benefit over Traditional Procedure
Balintfy: A newer heart surgery for infants offers first-year survival benefit over a traditional procedure. Wally Akinso has the details.
Akinso: Infants born with a severely underdeveloped heart who undergo a newer surgical procedure are more likely to survive their first year and not require a heart transplant. This is according to a report by researchers supported by the National Heart, Lung, and Blood Institute. But the study of 549 newborns suggests that after the first year, the new surgical procedure yields similar results to a more traditional one.
Pearson: This study enrolled newborns who are born with only one functioning pumping chamber of their heart which is called a ventricle.
Akinso: Dr. Gail Pearson is the director of the NHLBI’s Adult and Pediatric Cardiac Research Program.
Pearson: Most of us are born with two functioning ventricles and these infants have a special type of complex heart disease in which they only have one ventricle—this is called hypoplastic left syndrome. So we were targeting enrolling these babies in order to compare two different types of surgical procedures. For the first procedure that they have to help them in their first couple of weeks of life.
Akinso: The Single Ventricle Reconstruction Trial is the largest trial to compare treatment for congenital heart disease, and the first North American, multi-center, randomized trial of surgical therapy for congenital heart disease patients. Dr. Pearson says two procedures were studied.
Pearson: Both procedures were being used to some extent, but surgeons realized that there were pluses and minuses to both of them. And also realized that they wanted to apply some scientific method to this and figure out which surgical procedure might be better.
Akinso: Congenital heart disease is the most common birth defect. Every year, about 1 percent of babies are born with abnormally formed hearts. The trial compared for the first time two surgical procedures that are commonly used to treat babies born with only the right ventricle, which pumps blood to the lung, to determine whether one procedure improves outcomes more than the other. Dr. Pearson explains the two procedures.
Pearson: The more standard one involves the use of what's called a modified Blalock-Taussig shunt and this is one means of getting blood to flow to the baby's lungs in order to provide oxygenated blood to be pumped to the body. The newer variation, instead of having a shunt from the aorta to the pulmonary artery, which is what the modified Blacklock-Taussig shunt is, has a shunt for the blood directly from the right ventricle, which is the baby’s only functioning ventricle to the pulmonary artery.
Akinso: Researchers followed all study patients for at least 14 months. They evaluated the number of deaths and heart transplantations in each group at one year, as well as the number of complications.
Pearson: The overall conclusion was that for the first year of life the newer procedure offers improved survival without needing a heart transplant.
Akinso: Dr. Pearson adds that this study shows great promise for helping not only this high-risk group of patients, but also for improving the health and well being of many more babies and children with heart problems. For more information on this study, visit www.nhlbi.nih.gov. This is Wally Akinso at the National Institutes of Health Bethesda, Maryland.
Higher Oxygen Levels Improve Preterm Survival, Increase Risk for Eye Condition
Balintfy: Two findings from an NIH research network study provide new information on how much oxygen very preterm infants should receive starting on the first day of life and the most effective means to deliver it to them. In this segment, we here from Dr. Rosemary Higgins, Program Scientist at the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The first question Dr. Higgins: why did you undertake this study?
Higgins: Babies born 13 to 16 weeks early often have trouble breathing on their own because their lungs are not fully developed. So it’s common practice to give them oxygen to help them breathe. There isn’t a lot of research to determine exactly how much oxygen they should get, or the best method to provide it to them. We know that if a baby’s blood oxygen levels are too low, they can develop brain or other organ damage, or even die. On the other hand, we know that some babies given 100 percent oxygen are at high risk for a condition known as retinopathy of prematurity. Retinopathy of prematurity can cause vision impairment or blindness. So, lower oxygen levels might help prevent retinopathy of prematurity.
Over the past 30-40 years, many hospitals have started using a new technique for delivering oxygen to preemies. Traditionally, preterm infants are given oxygen through a ventilator. The ventilator tube is placed into the infant’s wind pipe and pulses air into the lungs. The ventilator tube also can administer surfactant into the lungs. That’s a sticky substance that helps to keep the tiny air sacs open. In recent years, some hospitals have supplied oxygen through a CPAP device. CPAP, or C-P-A-P, stands for continuous positive airway pressure. It’s used to treat adults with sleep apnea. With CPAP, a fitting is placed into the babies nostrils, and gently pumps air into the lungs. It’s usually used without surfactant. CPAP has not been directly compared to surfactant prior to the current study.
Balintfy: How did you conduct the study?
Higgins: Researchers in the NICHD Neonatal Research Network observed more than 1,300 infants born at 20 sites. These infants were very premature—born between the 24th and 27th week of pregnancy. They weighed only one to two pounds on average, and many needed respiratory therapy. For one arm of the study, we compared two different oxygen saturation targets: 85-89 percent versus 91-95 percent. The other part of the study compared the methods used to provide oxygen to the infants: ventilator with surfactant or the CPAP device.
Balintfy: What did your studies find?
Higgins: The first study found that the different oxygen levels had different effects on survival and retinopathy of prematurity. More of the infants in the low oxygen level group died than did infants in the higher level group: 19.9 percent versus 16.2 percent. However, fewer of the infants on the lower oxygen level developed severe retinopathy of prematurity: 8.6 percent versus 17.9 percent. It’s important to stress that two-thirds of the cases of severe retinopathy improve without treatment. Of the remaining one-third, these infants can go on to develop severe visual impairment or become legally blind. Some children with milder degrees of retinopathy of prematurity do develop eye and vision problems.
In the second study, we found that infants on CPAP did as well as infants in the ventilator surfactant group. They were more likely to have survived and did not require breathing therapy a week after being born. The CPAP infants were less likely to need steroid treatment for their lungs and spent less time overall on ventilators.
The earliest preterm infants in the study, born at 24 to 25 weeks gestation, were less likely to die if they had received CPAP initially than had they been on a ventilator.
Balintfy: What is the take away message of your study?
Higgins: Oxygen saturation levels are extremely important for preterm infant survival. Higher oxygen levels improve survival, but also increase the chances of retinopathy of prematurity. We also want to emphasize that CPAP appears to be an appropriate first treatment for preterm newborns. CPAP appears to be just as effective as ventilator therapy especially for these very tiny, very preterm infants and is associated with fewer complications.
Balintfy: Thank you very much Dr. Higgins. For more information on this study, visit the website, www.nichd.nih.gov. Coming up next, the Human Microbiome Project—how it’s different from the Human Genome Project. Stay tuned.
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The Human Microbiome Project
Balintfy: Within the body of a healthy adult, microbial cells are estimated to outnumber human cells by a factor of ten to one. These communities, however, remain largely unstudied, leaving almost entirely unknown their influence upon human development, physiology, immunity, and nutrition. In this follow-up interview from episode 88 in July of 2009, I’m talking again to Dr. Julia Segre at the National Human Genome Research Institute. First, what exactly is the microbiome?
Segre: The definition of the microbiome is the DNA of all of the small organisms that live in and on our body. So, those are called microbiota or microflora. Those are organisms that you typically can only see if you look under a microscope.
So, when we are now expanding the definition and the concept of the genetic landscape of a human to include not only the DNA encoded by the human cell DNA, but also the DNA of all of the small organisms that live in and on us, because we now appreciate that a lot of the functions of a human body may actually be carried—or are actually carried out by these small organisms, such as digestion.
Balintfy: So, there’s actually then an impact, not just from the Human Genome Project; there’s also going to be an impact from the Human Microbiome Project. Can you explain a little bit of the similarities and differences in terms of the impact on human health?
Segre: There’s actually two different points that I would want to make. One is from the point of view of medicine. I work on the skin disorders and these diseases, which we think of as human diseases—so, things like psoriasis and eczema—the treatments for them have typically been antibiotics or topical steroids: things that probably have more of an effect on the microbiota than they do on the human cells.
So, we’re really bringing that together, where we’re now conceiving of a human disease like eczema or psoriasis as something that is really about the bacterial organisms that live on our skin.
Now, there is a component of that that is from the human cells, because the human cells provide the environment for these organisms to live on. So, there is this interplay between the human cells and the microbial cells, and what we are now trying to do is combine those two types of information and consider all of that the human genome or the human—and kind of bridge between the human microbiome—and the bacterial and the fungal organisms that live on our body and in our bodies—and that of our human cells, and talk about personalized medicine, maybe using drugs that—or small molecules or—I mean, topical steroids, topical antibiotics, oral antibiotics, oral steroids, and recognizing that we are impacting the microbiota as well as the human cells. And when we think about the use of a drug, to think about how we’re impacting both of those populations and that they are communicating with each other.
Balintfy: Another thing that’s connected to the microbiome is the immune system. So, it’s not just how things are being treated, but how the body itself is reacting. Can you explain a little bit about how the immune system is shaped by the microbiome or vice versa?
Segre: What’s amazing there is that if you sample soil or water, you’ll find about 100 different bacterial phylum. Only about seven or eight can live in and on the human. So, there is an enormous selection where seven to eight bacterial phylum—a phylum would be, for example, Firmicutes, and that would actually include staph and strep. And so, the immune system is clearing the vast majority of bacteria that would like to take up residence and can take up residence in the soil and in the water where there is no immune system present.
But on the other hand, the immune system is also shaped by the microbiome. It is educated so that when you see certain types of bacteria, you’re immune system understands those bacteria in the context of what we call the commensals, the healthy bacteria that live on the body.
And our microbiota definitely changes as we go through our lives, so the microorganisms of a baby who is just born and only having formula or breast milk is going to be very different than the baby that starts to eat rice cereal, than the baby that starts to eat food off the table. And at the same time, that baby is going from being held all the time to crawling and exploring the environment to walking and running around. And then as well, as we go through puberty, our skin becomes much oilier. It’s a really different environment.
So, the microbiota can really change, and probably impacts our health given the different places that we live and the different food that we eat and then also the different products that we use. I mean, if you, you know—that’s why some people find that different moisturizers really work well for them and don’t.
Balintfy: So ultimately, when the Microbiome Project is completed, what do you think it’s going to tell us? What do you think we’re going to learn from it that will change or improve our lives?
Segre: So the—one of the real goals of the NIH right now is to produce personalized medicine, which is when you walk into a physician’s office, how is the physician going to determine the best treatment for you to stay healthy and perhaps prevent disease or to treat a disease?
A lot of the drugs that we do use now are things that modulate the bacteria and the fungi—the antibiotics, the steroid creams. But I have to use the example now of eczema, which is the skin disorder that we work on. If a kid walks in with severe eczema, it’s not clear to us whether that patient should be—that kid should be treated with steroids, antibiotics, things to lower the bacterial load, whether that kid really needs to use heavy creams, emollients. And sometimes it’s a process of trial and error.
What we’d like to use is the biomarkers. We’d like to use bacteria, like the bacterial diversity and the microbiota. We would like to use the microbiome as biomarkers to really tailor personalized medicine and say, "You have psoriasis or you have eczema. It looks exactly the same to me, but now I’m going to run this diagnostic test and see if your psoriasis is related to having these five bacteria. If so, you are most likely to benefit from using this steroid or this cream."
And what we’re trying to say is that we have a lot of drugs, we just don’t always know which one is the best one to try first. And it can be very frustrating in our case for the kids and parents of the kids who have eczema when we say, "Try this and if it doesn’t work, come back again in two weeks." What we’re tying to do is to try to tailor better treatment for patients and to do that in real time — point of contact care. A patient walks in and I say, "This is the best drug for you to use."
Balintfy: That kind of covered most of the key questions I had. Is there something that maybe you would want to reemphasize or just basically take a second stab at that’s important for the public, you think, to know about the Microbiome Project?
Segre: So, when we think about the definition of the Microbiome Project, that technically what we are doing is we’re swabbing someone’s skin or taking—swabbing inside their nose and we’re sequencing all of the DNA that we find. And then we have to piece back together what DNA came from which of these different organisms.
It’s as if a spaceship landed in Washington, D.C. and took DNA from everyone who was walking through the intersection at once. And we do understand that that DNA belongs to 100 different people, but we are sampling it as if we’re getting those 100 people all together. And we’re thinking about the bacteria for the first time now not as separate organisms, but how they form a community. Because our human cells all have the same protein encoded potential, the DNA of every human cell is the same, but the DNA of every bacteria could be different.
So, we have to think about it with this layer of complexity that the bacteria and the fungi are really interacting with each other. They’re interacting with the human cells and that it is a community of organisms that are together creating this protein encoding potential that could vastly exceed our own human cells.
Balintfy: Thank you again Dr. Julia Segre from the National Human Genome Research Institute. For more information about the Human Microbiome Project, visit the website: nihroadmap.nih.gov/hmp—again that’s nihroadmap (one word)-dot-nih-dot-gov-slash-hmp.
And that’s it for this episode of NIH Research Radio. Please join us again on Friday, August 13th when our next edition will be available. I’m your host Joe Balintfy, thanks for listening.
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