September 9, 2011
NIH Podcast Episode #0142
Balintfy: Welcome to episode 142 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, and coming up in this episode: a new tool that may reduce the burden of the third leading cause of death in the U.S.; a global perspective of mental health; how exercise and a positive environment can impact mental health; and how science is saving science – the preservation of important historical documents created by a Nobel prize-winner, written in pen. But first, this news update.
Balintfy: A large clinical trial has shown that patients at a high risk for a second stroke who received intensive medical treatment had fewer strokes and deaths than patients who received a brain stent in addition to the medical treatment. Inserting a brain stent, also called intracranial stenting is a way to open blocked or narrowed arteries in the brain. A blockage or narrowing of brain arteries called stenosis, accounts for more than 50,000 of the nearly 800,000 strokes that occur annually nationwide. This study, funded by the NIH, was stopped in April because early data showed significantly more strokes and deaths occurred among the stented patients compared to the group who received the medical management alone. Researchers had hypothesized that compared to intensive medical therapy alone, the addition of an intracranial stenting system would decrease the risk of a stroke or death. Now they emphasize that this study shows, stroke patients with recent symptoms and intracranial arterial blockage of 70 percent or greater should be treated with aggressive medical therapy alone. For details on the results of this study, which appear in the New England Journal of Medicine, visit www.ninds.nih.gov.
News updates are compiled from information at www.nih.gov/news. Coming up later in the program: a couple features on mental health – we’ll hear about the top concerns world-wide, and how exercise and positive environments may change the brain and reduce stress-related depression; plus combating COPD – that’s next on NIH Research Radio.
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Commonly prescribed antibiotic reduces acute COPD attacks
Balintfy: An NIH-funded study has found that a commonly prescribed antibiotic lowers the frequency and severity of chronic obstructive pulmonary disease flare-ups. The study results, which appear in the New England Journal of Medicine, show the antibiotic may reduce the burden of chronic obstructive pulmonary disease or COPD and improve the quality of life for patients. COPD is a disease of the lungs that makes it harder and harder to breath over time. Dr. James Kiley at the National Institutes of Health says COPD is now the third leading cause of death in the United States.
Kiley: It is estimated that 12 million people have COPD; and probably what is even more revealing is that maybe another 12 million people have it but they don’t even know it. So we have a prevalence of almost 24 million people with this disease and it is one that kills a lot of people.
Balintfy: Part of the problem is exacerbations or flare-ups, which are sudden onsets of worsened symptoms, including cough, wheezing, and labored breathing. Dr. Kiley explains that many patients, particularly those who have more severe COPD, will have relatively regular exacerbations especially during flu season. He adds that some exacerbations can lead to hospitalizations.
Kiley: Severe acute exacerbations of chronic obstructive pulmonary disease are oftentimes devastating. They can be life-threatening. So anything you can do to try to reduce the numbers of those acute exacerbations would be very, very important from a health, quality of life, and economic as well the overall lifesaving kinds of measures.
Balintfy: There is currently no cure for COPD, though a combination of drugs and lifestyle changes can help manage the symptoms. And now, a new study is showing that adding a common antibiotic to the usual daily treatment regimen for COPD can reduce the occurrence of acute exacerbations and improve quality of life.
Kiley: And we think that it is a very important finding because it's a first time that we've been able to show on a large clinical trial that adding this antibiotic to usual care treatment regimen improves overall quality of life, reduces symptoms, and keeps people out of the hospital.
Balintfy: The clinical trial included more than one-thousand participants. The antibiotic is azithromycin.
Kiley: It's called a macrolide antibiotic. It's in a class of drugs that's used for other things like strep throat and other kinds of infections. The interesting piece of this study that adds a little bit more is that besides the antimicrobial effects of this antibiotic, there have been suggestions that it may have anti-inflammatory type of properties.
Balintfy: Dr. Kiley explains that those anti-inflammatory properties are helpful because in the lungs of patients who have COPD there's some ongoing inflammation. But he warns that more research is needed to identify more approaches, strategies, and treatment interventions that will address this disease.
Kiley: We still have a long way to go. I mean the issue here is what can we do to address the mechanisms underlying the properties that this agent provides? We've got a bit more research to do before we're going to start understanding the causes of it and the mechanisms underlying it. So we're making progress and that's what's really important. I think it's good news for the patients, for families, for the public at large that our research is starting to pay off.
Balintfy: He says this recent study, published in the New England Journal of Medicine, shows research is translating findings from clinical trials and basic science to benefit patients.
Kiley: I think the study is an important study from the standpoint of now we have a potentially new agent that we can introduce into the toolbox, if you will, for the physician to care for patients that have chronic obstructive pulmonary disease.
Balintfy: For more information on this study, and COPD, visit www.nhlbi.nih.gov.
Thinking globally to improve mental health
Balintfy: Now a couple stories on mental health. First, a comprehensive, NIH-led effort has identified the top 40 barriers to improving mental health worldwide. Four-hundred, twenty-two experts in fields such as neuroscience, basic behavioral science, mental health services, and epidemiology, are calling for a greater world focus on improving access to care and treatment for mental, neurological, and substance use disorders. Wally Akinso reports on how the panel, with experts from 60 different countries, is also calling for increasing discoveries in research that will enable this goal to be met.
Akinso: A global health initiative aims to improve mental health worldwide.
Collins: The initiative is called Grand Challenges in Global Mental Health.
Akinso: Dr. Pamela Collins is from the National Institutes of Health.
Collins: And this is an initiative that was meant to catalyze investment and research needed to reduce the burden of mental neurological and substance use disorders. And it’s a priority setting intervention. But unlike previous priorities setting exercises in mental health, this one was conducted with the idea of mobilizing a community of funders.
Akinso: The initiative, led by the NIH and the Global Alliance for Chronic Diseases has identified the top 40 barriers to better mental health around the world. To identify those barriers, Dr. Collins explains that an initial list of more than 1,500 research challenges was narrowed down to 154.
Collins: According to the feasibility, the immediacy of impact, the impact on disease burden and disparities reduction.
Akinso: Dr. Collins and colleagues assembled an international panel of experts to identify the research priorities. The panel consisted of more than 400 experts in fields such as neuroscience, basic behavioral science, mental health services, and epidemiology, and represented more than 60 countries. She highlights the top five challenges.
Collins: The top five: they were to integrated screening and core packages of services into routine primary health care; to reduce the cost and improve the supply of effective medications; to provide effective and affordable community based care and rehabilitation; to improve children's access to evidence-based care by trained health care providers in low and middle income countries; and to strengthen the mental health component in training of all health care personnel.
Akinso: According to Dr. Collins, the disorders targeted by the Grand Challenges in Global Mental Health collectively account for more years of life lost to poor health, disability, or early death than either cardiovascular disease or cancer.
Collins: I would say that most important similarity when you look at these initiatives that are focusing on chronic disease like mental disorders, neurological disorders, and substance use disorders, is that they really highlight the need for a range of science, from discovery science to services research, to policy research, and intervention studies. And this whole range is needed to address the needs for management of disease for disease burden reduction of these kinds of illnesses.
Akinso: She adds that addressing these challenges could have far reaching effects, including increasing access to services and ultimately reducing the treatment gap associated with these disorders. For more information, visit www.nimh.nih.gov. This is Wally Akinso at the NIH, Bethesda, Maryland.
Exercise and positive environment can help hedge against stress related depression
Balintfy: Also regarding mental health, NIH investigators are seeing new evidence that suggests exercise and positive environment can help hedge against stress related depression. Jim McElroy talks to two NIH experts about whether it is possible that exercise or other positive changes to our environment can help build up resistance to stress-induced depression.
McElroy: Dr. Michael Lehmann is with a team of National Institute of Mental Health scientists investigating how our brains process the connection between a positive environment and fighting off depression.
Lehmann: What research has shown previously is that environmental enrichment has a number of beneficial effects on the psychology and physiology of animals. Exercise is also known to be a possible antidepressant and exercise also increases adult neurogenesis.
McElroy: Neurogenesis is the genesis of new neurons in the brain. In the late 1990s, it became apparent that new neurons are formed in the adult as well as the young brain. Teaming with Dr. Lehmann in studying the role of neurogenesis in brain function is Dr. Robert Schloesser.
Schloesser: Antidepressants have to be given for like several weeks before a robust effect on neurogenesis can be detected. And it's also known in humans, antidepressants have to be given for several weeks before an antidepressant effect is being detected. And this raised the question of a connection...
McElroy: Working with mice, the NIMH scientists needed to come up with a test-something called social defeat stress- that would replicate the type of stress levels experienced by people.
Lehmann: The way we set up our housing situation is that we place two male animals within the same cage but they're separated by a divider. So when we lift this divider the two animals will conflict and there will be a series of social interactions where the animals either win or lose at social interactions. The animal that continues to lose the social interactions will become behaviorally depressed.
McElroy: After 14 days, these animals were then housed either in a barren environment, or an environment with opportunities to explore and exercise. Animals housed in this enriched environment after they have undergone social defeat, stopped acting depressed. The recovery, however, depended on neurogenesis. These researchers showed this using a method involving gene transfer to shut down adult neurogenesis in some of the mice at a specific time in a specific area of the brain.
Lehmann: When we knock out neurogenesis, animals that are exposed to environmental enrichment don't retain the beneficial effects of the enrichment exposure. Whereas animals that have the ability for neurogenesis are able to retain these beneficial effects.
Schloesser: What's new in our study is our study is the first study that can link environmental enrichment and its beneficial effects to neurogenesis and the requirement of neurogenesis. No one had so far linked the two things that are open in the literature- that enrichment can massively increase the survival of newborn neurons and that enrichment can also has this tremendous beneficial effects on mood states and behavioral... behavior as related to mood in rodents.
McElroy: As research continues, this laboratory recently reported on studies that pinpoint an area of the brain that is central to the ability of environmental enrichment to have beneficial effects on stress resiliency. These findings suggest that this area of the brain, a part of the cortex involved in the processing of emotion, could be a target for new medications for depression.
Balintfy: That’s Jim McElroy reporting. For more information on these findings and mental health topics, visit www.nimh.nih.gov. Up next, the importance of preserving an historical document.
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Balintfy: Welcome back to NIH Research Radio. History is a subject we’ve all studied, or are studying as we get back to school this time of year. And we study it because, as experts point out, history fades, in some ways, quite literally. I’m speaking with two experts from the NIH’s National Library of Medicine. They explain that the materials which hold and convey our knowledge, experiences, and memories, are all subject to the laws of nature. I’m joined by Holly Herro, a conservation librarian, and Peter Gabriel, a conservation scientist, not the rock star. I start by asking, why is conservation important? Peter?
Gabriele: I think a lot of it has to do with history and preserving history. You know, with such a digital world today, we sometimes don’t get a chance to touch the documents and see the things that are historically important to whatever subject they might be. They're stuck in a file. They have different file extensions and consequently, you can get to some things, you can't get to others.
Balintfy: We’re talking about one of the most important historical documents of the twentieth century: the first summary of the genetic code created by the American biochemist and 1968 Nobel Laureate, Dr. Marshall Nirenberg. He created a chart back in the mid-1960s to help decipher and document his discovery. And he didn’t use a computer program like Excel.
Gabriele: Yeah. He used ballpoint pen, he used fountain pen, he used pencil, red pencil, which is kind of interesting because he emphasized some of his data with the red pencil and when he hit the leather off the ball so to speak on his analysis, he would put a red box around the data.
Balintfy: So now this document and Dr. Nirenberg’s notes, some 40 years old, are at the National Library of Medicine, which is celebrating its 175th anniversary this year. Holly, what did you see when it arrived?
Herro: Well, I could see by examining the document that there was a shift in the color of the ink and so we needed to find out why. And then determine the best way to store it for the future for future generations.
Balintfy: Holly, so you would say in this day and age of computers that saving actual documents like these, rather than just storing their images and content digitally, is important?
Herro: Yes. Oftentimes, people will visit historical libraries to see documents, they want to be next to the history. Peter and I were involved with the sickle cell symposium in the fall of last year and there were researchers from all over the world and had come -- and we had the first patient's medical records there -- and one gentleman walked up and said, we had copies on them on the table, he goes, “I don’t want to see the copy, I want to see the original.” It was in the exhibit case so I pointed him toward the case and he literally almost ran over to the case, he was so excited to see the original. So it's that kind of emotion that you see in people when they see an original very important document such as the Nirenberg chart.
Gabriele: You know, that's a great word, emotion. That's really what it was because I was almost in tears when you first showed me the documents? I couldn't believe that after all my studies, I'm standing, I'm touching, I'm in possession of Dr. Nirenberg's work. I mean there is just another level in the human spirit when you come in contact with these things. It's the reason people visit Rome and look at the great sculptures or go to the museums and look at the great artists. It's still very important for us to appreciate the emotion that is represented in that document.
I mean for one thing when you look at it you can see the activity, you can see where they concentrated this week on a whole bunch of stuff. It's the living, breathing history and I know that's if it's in history, it's not living and breathing. That's the oxymoron of this whole thing is that when you're looking at these historic documents, the science jumps out of that, you know, the effort jumps out. It's very exciting. It's a --
Herro: Another extension of the work is we're looking at artwork. We've talked to an artist who does a lot of his work in ballpoint pen ink, Larry Lebby, an African-American gentleman from the south. So we've got one of his pieces here and we're going to be analyzing that as well in kind of comparison.
Balintfy: To the Nirenberg chart?
Gabriele: Yeah. He's very excited. I spoke with him a couple of weeks ago. And we gravitated to the ink and the next think you know he wants to be involved in some of the information exchange that we get involved in.
I think the really neat part about this is that it shows that there's a bridge between science and art. Not only in the content of the documents, Larry's work being the work of an artist, Dr. Nirenberg's work being the work of the scientist, but that the ink bridged the combined interests.
Balintfy: Holly, you're nodding.
Herro: My very first interest was conserving a John F. Kennedy letter and I was working with some folks at Library of Congress and they said you just have to store it properly, which now we know was improperly, but that's a whole another subject, and wait for science to catch up. Then I was conserving some World War I posters that had some ink on it and the ink wasn't stable, but I needed to wash them. And so that's when I started my conversations with Peter. So there's a huge puzzle that needs to be solved – it’s a huge puzzle.
Gabriele: And one of the interesting things about this is that while the objects may seem distinctly different from each other, artwork versus science versus a letter or whatever, it's still the photochemistry of oxidation that not only affects these documents but affects us. It affects our world, our materials and everything. So if you know nature, the second law of thermodynamics is entropy and everything breaks down. But I think the other thing that accelerated this was the fact that Kennedy used ball ink.
Herro: That’s right. I forgot to mention that.
Gabriele: And --
Herro: His signature.
Balintfy: And whether it’s the Nirenberg chart, a presidential signature, or an artwork, you’re saying conservation is much more that just saving that?
Gabriele: From my perspective, I think there should be serious consideration to developing forensic conservation where we use the traditional tools of analytical science and forensic analysis to help understand what's happening to these documents.
Herro: To use the word again -- deciphering the puzzle of the ink and the interaction with the environment and how we're going to store the Nirenberg charts long term.
Balintfy: Holly Herro and Peter Gabriel with the NIH’s National Library of Medicine, thank you very much. For more about the Nirenberg chart and other NLM historical documents visit www.nlm.nih.gov.
Balintfy: And that’s it for this episode of NIH Research Radio. Please join us again on Friday, September 23 when our next edition will be available. If you have any questions or comments about this program, please let me know. Best to reach me by email—my address is firstname.lastname@example.org. I'm your host, Joe Balintfy. Thanks for listening.
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