Category: Cardiology

CSI-House teams could make better medical diagnoses

On June 28, 2012

In Biology, Cardiology, Computers/Technology, Genetics/Genomics, Lecture, Medicine

By Ashley Yeager

Comparing a child's DNA to his parents' could help with identification of hard-to-diagnose genetic diseases. Credit: Henrik Jonsson/iStockphoto

Dr. Gregory House, star of House, M.D., and the lab techs on CSI never fail at their jobs. But that’s Hollywood. In real life, diagnosing illnesses and sequencing DNA isn’t so straightforward. It doesn’t always lead to a happy ending either, especially for children who are sick but can’t be diagnosed, even by gifted, real-life doctors.

That’s exactly why geneticist David Goldstein has teamed with pediatrician Vandana Shashi to combine a little House and CSI to identify apparent genetic diseases and quickly end some families’ diagnostic odysseys.

So far, the team has provided likely genetic diagnoses in six of 12 children it has worked with, said Goldstein at a Cardiovascular Research Center Seminar Series talk on June 27.

The children were referred to Shashi for a pilot study where she would record their symptoms, or phenotypic behavior, much like House. Then, Goldstein and his team at the Center for Human Genome Variation collected DNA samples from the children and both of their biological parents.

Using next-generation genetic sequencers, as well as traditional DNA scanners, Goldstein and his team looked for genetic variations between the children’s and parents’ complete genome. Like looking at DNA to identify a criminal, Goldstein and his genetics team are scouring the sequences for genetic fingerprints of the diseases disrupting the children’s lives.

Once variations were identified, the entire team looked for known diseases with similar gene mutations and symptoms. Goldstein explained that the study not only pinpointed the undiagnosed congenital diseases in some patients but also presented new genes that could also be linked to the illnesses. The study’s success has led to the creation of the Genome Sequencing Clinic.

The clinic will begin to help the families of the 50,000 children (out of the four million) born each year in the US with difficult-to-diagnose genetic diseases. These types of studies will likely be the “earliest drivers for large-scale genetic sequencing,” Goldstein said.

But, he cautioned, “there’s a whole lot of junk,” or variation, in DNA. Every genome has the narrative potential for devastating diseases, and that means that House-CSI teams, like Shashi and Goldstein’s, need to be extremely careful when making diagnoses, especially if the results will influence treatment, he said.

Citation: Clinical application of exome sequencing in undiagnosed genetic conditions. Need, A. et. al. 2012. J. Med Genet. 49:6 353-361. doi:10.1136/jmedgenet-2012-100819

New Blogger Nonie: Joining the Team

By sa160@duke.edu

On March 1, 2012

In Cardiology, Genetics/Genomics, Students

By Nonie Arora

Hello there,

This is Nonie Arora, a freshman A.B. Duke Scholar from Novi, MI. I am excited to join the Duke Research Blog team.

I’ve been involved in research since my freshman year of high school. Back then, I was obsessed with the concept of “superbugs” and antibacterial resistance. I ordered E. coli out of a catalog with my chemistry teacher and tested its resistance to common household substances, like soap and bleach. My research interests evolved as I started working in a lab at the Wayne State University Medical School. For three years, I studied genes in a yeast, C. albicans, that contribute to antifungal drug resistance.

My research took me to different science fairs, such as the International Science & Engineering Fair (ISEF) and the Intel Science Talent Search. At ISEF, being in a hall with 1500 other students from around the world – who were all enthusiastic about research – was incredibly motivating. I was eager for more research exposure. The wide variety of research present at Duke, from basic science to behavioral economics to clinical trials, is incredible. Being able to interact with renowned faculty as a freshman is a privilege.

Last semester, I was part of the Genomics FOCUS program and took classes with Hunt Willard and Bob Cook-Deegan. The captivating teaching styles of my professors coupled with a better understanding of how science affects society increased my passion for genomics. This semester, I am working in the Kontos lab studying protein interactions that may explain how endothelial cells maintain a resting state, which is relevant to cardiovascular disease.

Outside of research, I like to run, read the New York Times, and devour law thrillers. When I have the time, I indulge in watching The Big Bang Theory, House, and the Good Wife. At home, I enjoy spending time with my parents and my 11-year old sister. It’s probably easier to answer some of the questions that my professors propose than the ones she does!

I look forward to contributing my perspective on research at Duke.

Big Doctors May Contribute to Big Health Problem

By Karl Bates

On February 12, 2012

In Behavior/Psychology, Cardiology, Medicine

By Ashley Mooney

Sometimes talking about weight loss can be difficult, especially with a doctor who is just as chubby as you.

This is not Dr. Califf.

A recent study by researchers at Johns Hopkins Bloomberg School of Public Health and Medical Institutions found that physicians with higher body mass indexes are less likely to address weight issues in patients.

The researchers surveyed 500 doctors and found that 30 percent of normal-weight doctors were likely to engage patients in discussions of weight loss and exercise, while only 18 percent of overweight or obese doctors did the same.

The study also showed that when physicians perceived that a patient’s body weight met or exceeded their own body weight, 93 percent of physicians would diagnose them with weight issues and likely to recommend obesity care.

Despite findings that overweight doctors are less likely to engage patients in such discussions, some noted that patients might identify better with those who have similar BMI’s.

“I believe that the reaction to one’s weight is highly individual,” said Dr. Robert Califf, Vice Chancellor for Clinical Research and Donald F. Fortin, M.D. Professor of Cardiology at Duke. “Some docs seem to feel better about discussing it if they are overweight because they identify with the patient.”

Califf also noted that his own exercise and health experiences only partially help him in dealing with his patients.

Detecting disease with sound

By Becca Bayham

On September 29, 2011

In Biomedical Engineering, Cancer, Cardiology, Computers/Technology, Engineering, Faculty, Lecture, Medicine, Physics

By Becca Bayham

Most people experience ultrasound technology either as a pregnant woman or a fetus. Ultrasound is also employed for cardiac imaging and for guiding semi-invasive surgeries, largely because of its ability to produce real-time images. And Kathy Nightingale, associate professor of biomedical engineering, is pushing the technology even further.

“We use high-frequency sound (higher than audible range) to send out echoes. Then we analyze the received echoes to create a picture,” Nightingale said at a Chautauqua Series lecture last Tuesday.

According to Nightingale, ultrasound maps differences in the acoustic properties of tissue. Muscles, blood vessels and fatty tissue have different densities and sound passes through them at different speeds. As a result, they show up as different colors on the ultrasound. Blood is more difficult to image, but researchers have found an interesting way around that problem.

“The signal from blood is really weak compared to the signal coming from tissue. But what you can do is inject microbubbles, and that makes the signal brighter,” Nightingale said.

Microbubbles are small enough to travel freely throughout the circulatory system — anywhere blood flows. Because fast-growing tumors require a large blood supply, microbubbles can be particularly helpful for disease detection.

Like most other electronics, ultrasound scanners have gotten smaller and smaller over the years. Hand-held ultrasounds “are not as fully capable as one of those larger scanners, just as with an iPad you don’t have as many options as your computer or laptop,” Nightingale said. However, the devices’ portability has earned them a place both on the battlefield and in the emergency room.

Nightingale’s research explores another aspect of ultrasonic sound — its ability to “push” on tissue at a microscopic scale. The amount of movement reveals how stiff a tissue is (which, in turn, can indicate whether tissue is healthy or not). It’s the same concept as breast, prostate and lymph node exams, but allows analysis of interior organs too.

“We can use an imaging system to identify regions in organs that are stiffer than surrounding tissue,” Nightingale said. “That would allow doctors to look at regions of pathology (cancer or scarring) rather than having to do a biopsy or cut someone open to look at something.”