Warren symposium follows legacy of geneticist giant

If we want to understand how the brain creates memories, and how genetic disorders distort the brain’s machinery, then the fragile X gene is an ideal place to start. That’s why the Stephen T. Warren Memorial Symposium, taking place November 28-29 at Emory, will be a significant event for those interested in neuroscience and genetics. Stephen T. Warren, 1953-2021 Warren, the founding chair of Emory’s Department of Human Genetics, led an international team that discovered Read more

Mutations in V-ATPase proton pump implicated in epilepsy syndrome

Why and how disrupting V-ATPase function leads to epilepsy, researchers are just starting to figure Read more

Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more

Research

Initial Results of Heart Valve Study Encouraging

 

Emory heart patient, Glenrose Gay of Vidalia was the first person in GA to receive a new aortic valve via catheter. Pictured here in 2007 with Emory cardiologists, Drs. Peter Block (left) and Vasilis Babaliaros.

Since October 2007, Emory University Hospital has been one of approximately 20 hospitals nationwide, and the only site in Georgia, studying a new non-surgical treatment option for patients with failing aortic valves. The life threatening heart condition,aortic stenosis, affects tens of thousands of Americans each year when the aortic valve tightens or narrows, preventing blood from flowing through normally.

As part of the Phase II clinical trial, researchers have been performing transcatheter aortic valve implantation (TAVI) comparing this procedure with traditional, open-heart surgery or medical therapy in high-risk patients with aortic stenosis.

During the TAVI procedure, doctors create a small incision in the groin or chest wall and then feed the new valve, mounted on a wire mesh on a catheter, and place it where the new valve is needed. This offers a non-invasive way for doctors to treat patients who are too ill or frail to endure the traditional open-heart surgical approach.

The study, published Wednesday in The New England Journal of Medicine (NEJM) followed 358 patients who received either catheter-delivered valves or standard non-surgical treatment.

The findings showed that patients who had replacement heart valves delivered by catheter were more likely to survive a year than patients who were treated without replacing their original valves. According to the authors, catheter-delivered valves “should be the new standard of care” for patients who are not able to undergo surgery.

“These results show great promise for patients with severe aortic stenosis and help us make a giant step forward in our battle against this common disease,” says Peter Block, MD, professor of medicine, Emory School of Medicine and principal investigator of the study at Emory. “They are especially important since the number of people with failing valves is expected to greatly increase as baby boomers continue to age.”

Aortic valve stenosis often occurs with age, most commonly among elderly patients over 70 years of age, but can surface earlier in life in those with rheumatic heart disease or congenital abnormalities of the valve.

Approximately 90 patients have received new valves at Emory since the clinical trial started in 2007. Researchers hope to receive FDA approval in late 2011.

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Global health: from autism screening to neglected tropical diseases

A partnership of more than 40 universities, the Consortium of Universities for Global Health held its second annual meeting at the University of Washington in Seattle this week, with a wide range of presentations centered on the theme Transforming Global Health: The Interdisciplinary Power of Universities.  Emory Global Health Institute presentations ranged from neglected tropical diseases to autism in Chinese populations to changes in medical school curricula.

Carlos Franco-Paredes, MD

Emory’s Carlos Franco Paredes, MD, MPH, associate professor of medicine (infectious disease) talked about a troublesome global health issue—one that hits close to home—the effect of neglected tropical diseases in the immigrant and refugee communities living in Atlanta. Neglected tropical diseases are disabling, disfiguring, and deadly diseases impacting more than one billion people worldwide, says Paredes. Atlanta’s immigrant populations show a high prevalence of intestinal parasitic infections, schistosomiasis, strongyloidiasis, and hepatitis B.

Meanwhile, Joseph Cubells, MD, associate professor of human genetics at Emory, shared his experience with the Mandarin Chinese Autism Spectrum Screening Questionnaire in urban Mandarin Chinese-speaking communities. Cubells says large-scale, community-based studies of autism spectrum disorders require effective tools for screening potential cases. So, to meet the need for such tools in Chinese populations, he and his colleagues translated and back-translated The Autism Spectrum Screening Questionnaire, a 27-item parental checklist originally published in English.

And what about incorporating global health education into the medical curriculum as a way of transforming universities’ role in advancing global health? Emory’s Henry Blumberg, MD, professor of infectious disease and his colleagues have done just that. Now, global health is a part of Emory’s innovative new medical curriculum, which was launched in 2007. After all, global health is becoming ever more important to the world at large, garnering more interest from future physicians.


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Reading the blood: metabolomics

In the Star Trek series, Dr. McCoy could often instantly diagnose someone’s condition with the aid of his tricorder. Medicine on 21st century Earth has not advanced quite this far, but scientists’ ideas of how to use “metabolomics” are heading in this direction.

What is metabolomics? Just as genomics means reading the DNA in a person or organism, and assessing it and comparing it to others, metabolomics takes the same approach to all the substances produced as part of the body’s metabolism: watching what happens to food, drugs and chemicals we are exposed to in the environment.

This means dealing with a huge amount of information. Human genomes may be billions of letters (base pairs) in length, but at least there are only four choices of letter!

A recent article in Chemical & Engineering News explores this concept of the “exposome” and quotes Dean Jones. He and his colleagues recently described how they can use sophisticated analytical techniques to resolve thousands of substances in human plasma. Jones is the director of the Clinical Biomarkers Laboratory at Emory University School of Medicine. The paper is in the journal Analyst, published by the Royal Society of Chemistry.

Analytical techniques can discern more than 2500 metabolites from human plasma within 10 minutes

Using a drop of blood, within ten minutes the researchers can discern more than 2,500 substances in a reproducible way. One fascinating tidbit: when they compared the metabolic profiles for four healthy individuals, most of the “peaks” were common between individuals but 10 percent were unique.

The potential uses for this type of technology are staggering.

Jones reports he has been working with researchers at Yerkes National Primate Research Center to discern early signs of neurodegeneration in transgenic monkeys with Huntington’s disease. He has been collaborating with clinical nutrition specialist Tom Ziegler to examine how diet interacts with oxidative stress, and with lung biology to identify markers for fetal alcohol exposure in animal models.

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Preterm infants born at unspecialized hospitals face higher risk of death

Very low-birth-weight (VLBW) and very preterm (VPT) infants not born in highly specialized, level III hospitals have a higher risk of neonatal and pre-discharge death compared to similar infants born at level III hospitals, according to a recent Journal of the American Medical Association (JAMA) study.

Lead study author Sarah Lasswell, MPH, and colleagues at the Rollins School of Public Health conducted a large-scale analysis of previous research to examine the relationship between hospital level at birth and neonatal (generally the first four weeks after birth) or pre-discharge mortality for VLBW (weighing 53 ounces or less) and VPT (32 weeks or less gestation) infants to determine the importance of level of care at birth to survival.

Lasswell and colleagues found that VLBW infants born in non-level III hospitals had a 62 percent increase in odds of neonatal/pre-discharge death compared with VLBW infants born in level III hospitals. In addition, VPT infants born in lower-level hospitals had a 55 percent increase in odds of neonatal/pre-discharge mortality compared with those born in level III facilities.

“The results of this review confirm a primary premise on which perinatal regionalization systems are based: high-risk infants have higher mortality rates when born outside hospitals with the most specialized levels of care,” Lasswell and colleagues write.

“Strengthening perinatal regionalization systems in states with high percentages of VLBW and VPT infants born outside of level III centers could potentially save thousands of infant lives every year.”

About 13 million babies are born prematurely every year – nearly 10 percent of all newborns – and more than 1 million premature babies die each year, according to the March of Dimes.

The study, “Perinatal Regionalization for Very-Low-Birth-Weight and Very Preterm Infants: A Meta-Analysis,” was published in the Sept. 1, 2010, issue of JAMA. It was conducted as part of Lasswell’s graduate research at the Rollins School of Public Health under the direction of Roger Rochat, MD. Lasswell is now a researcher at the U.S. Centers for Disease Control.

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Higher education linked to improved heart disease outcomes in richer countries

A higher level of education is associated with reduced risk of heart disease and stroke for people who live in rich countries, but not for those in low- and middle-income nations, according to the findings of a recent study led by Emory epidemiologist and cardiologist Abhinav Goyal, MD, MHS.

Abhinav Goyal, MD, MHS

The study published in the Sept. 7, 2010, issue of the journal Circulation, a publication of the American Heart Association, is one of the first international studies to compare the link between formal education and heart disease and stroke. It examined data on 61,332 people from 44 countries who had been diagnosed with heart disease, stroke, or peripheral arterial disease, or who had cardiovascular disease risk factors such as smoking or obesity.

Goyal and team found that highly educated men in high-income countries had the lowest level of cardiovascular disease. However, their findings suggest that research conducted in richer nations can’t always be applied to poorer countries.

“We can’t simply take studies that are conducted in high-income countries, particularly as they relate to socioeconomic status and health outcomes, and extrapolate them to low- and middle-income countries,” says Goyal, assistant professor of epidemiology and cardiology at Emory’s Rollins School of Public Health and Emory School of Medicine. “We need dedicated studies in those settings.”

The research team was surprised to find that despite decreased heart disease risk among the higher educated in industrialized nations, nearly half of the highly educated women from high-income countries smoked, compared with 35 percent for those with the least amount of schooling. For men, smoking rates were virtually the same across educational groups in low- and middle-income countries.

“Everyone needs to be educated about the risk of heart disease in particular, and counseled to adopt healthy lifestyles and to quit smoking,” Goyal says.

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Old-school medicine: relief of skin irritation with gentian violet

In the September issue of the Journal of the American Academy of Dermatology, Jack Arbiser and colleagues describe the use of gentian violet to provide some relief to a patient who came to the emergency room with a painful skin irritation. Arbiser is a professor of dermatology at Emory University School of Medicine.

A coal-tar dye which is inexpensive and available over the counter, gentian violet was first synthesized in the 19th century. It has been used as a component of paper ink, a histological stain, and an antibiotic or antifungal agent, especially before the arrival of penicillin.

“Clinicians should not forget about gentian violet for immediate pain relief and antibiotic coverage,” the authors conclude in their case report.

Biopsy of the patient's irritated skin shows that the gene angiopoetin-2 (dark brown) is turned on

In addition to its antibiotic properties, Arbiser reports that gentian violet has antiinflammatory effects, possibly because of its inhibition of the enzyme NADPH oxidase and the gene angiopoetin-2.

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A family of troublemakers known as XMRV

A long-delayed paper on the connection between chronic fatigue syndrome and XMRV (xenotropic murine leukemia virus-related virus) finally surfaced last week in PNAS. Astute readers may recall that XMRV has also been linked to prostate cancer.

Detecting XMRV in prostate tissue. A variety of assays (neutralizing antibodies, polymerase chain reaction or fluorescence in situ hybridization) may be used to look for XMRV

The twist from last week’s paper is that the NIH/FDA team, led by Harvey Alter, didn’t find viruses all with the same sequence in chronic fatigue patients. Instead, they found a cluster of closely related, but different, viruses. While confusing, these results may explain why tests for the presence of the virus that are based on viral DNA sequences may have generated varying (and conflicting) results. An alternative assay based on antibodies, such as the one urologist John Petros and colleagues at Emory developed, may be useful because it casts a wider net.

Pathologist Hinh Ly has been diving into the XMRV field, with a recent paper in Journal of Virology describing what “gateway” (receptor) molecule the virus uses to sneak into cells and what kinds of cells in the prostate it can infect.

In a collaboration with Ila Singh at the University of Utah, antiviral drug expert Raymond Schinazi has found that a number of drugs active against HIV also stop XMRV. This offers some hope that if doctors can detect members of the XMRV family, and figure out what they’re up to, they might be able to combat the troublemakers as well.

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When bone marrow goes bad

Plasma cells live in our bone marrow. Their job: to make antibodies that protect us from bacteria and viruses. But if those plasma cells grow unchecked, that unchecked growth leads to multiple myeloma.

Sagar Lonial, MD

Multiple myeloma is a type of cancer that results in lytic bone disease, or holes in the bones. What’s more, the cancerous cells crowd out normal bone marrow resulting in anemia or a low white count, leaving a person vulnerable to infections.

Sagar Lonial, MD, an oncologist at Winship Cancer Institute, Emory University, treats people with multiple myeloma. The prognosis for people with this type of cancer is poor; however, researchers are gaining on the disease. Twenty years ago, the survival rate was two to three years; now, it’s four to five.

Lonial says one of the keys to improving patients’ prognosis is increasing their enrollment in clinical trials and better access to life-extending drugs.

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Stem cell research center gets NSF support

Stem cell research is on the verge of impacting many elements of medicine, but scientists haven’t yet worked out the processes needed to manufacture sufficient quantities of stem cells for diagnostic and therapeutic purposes.

Todd McDevitt and Robert Nerem

The National Science Foundation (NSF) has awarded $3 million to Georgia Tech to fund a center that will develop engineering methods for stem cell production. The program’s co-leaders are Todd McDevitt, PhD, an associate professor in the Georgia Tech/Emory Department of Biomedical Engineering and Robert Nerem, director of the Emory/Georgia Tech Center for Regenerative Medicine (GTEC), which will administer the award.

“Successfully integrating knowledge of stem cell biology with bioprocess engineering and process development is the challenging goal of this program,” says McDevitt.

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New drug strategy against fragile X

Even as clinical trials examining potential treatments for fragile X syndrome gain momentum, Emory scientists have identified a new strategy for treating the neurodevelopmental disorder.

In a paper recently published in Journal of Neuroscience, a team led by cell biologist Gary Bassell shows that PI3 kinase inhibitors could restore normal appearance and levels of protein production at the synapses of hippocampal neurons from fragile X model mice. The next steps, studies in animals, are underway.

“This is an important first step toward having a new therapeutic strategy for fragile X syndrome that treats the underlying molecular defect, and it may be more broadly applicable to other forms of autism,” he says.

A recent Nature Biotechnology article describes pharmaceutical approaches to autism and fragile X.

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