New insight into how brain cells die in Alzheimer's and FTD

(Epi)genetic hallucinations induced by loss of LSD1 resemble Alzheimer's. Another surprise: LSD1 aggregates in Alzheimer's brain, looking like Tau Read more

2B4: potential immune target for sepsis survival

Emory immunologists have identified a potential target for treatments aimed at reducing mortality in sepsis, an often deadly reaction to Read more

EHR data superior for studying sepsis

Analysis of EHR data says sepsis rates and mortality have been holding steady, contrary to what is suggested by after-the-fact Read more

A shift in how geneticists study complex diseases

An Emory project studying schizophrenia genetics is a good example of how geneticists are shifting from examining small, common mutations to “rare variants” when studying complex diseases.

From studies of twins, doctors have known for a long time that heredity plays a big role in causing schizophrenia. But dissecting out which genes are the most important has been a challenge.

Three landmark studies on schizophrenia genetics published this summer illustrate the limitations of “genome wide association” studies. New York Times science reporter Nicholas Wade summarized the results in this way:

“The principal news from the three studies is that schizophrenia is caused by a very large number of errant genes, not a manageable and meaningful handful.”

The limitations from this type of study comes from the type of markers geneticists are looking at, says Steve Warren, chair of the human genetics department at Emory.

Genome wide association studies usually follow SNPs — single nucleotide polymorphisms. This is a one-letter change somewhere in the genetic code that is found in a fraction of the population. It’s not a big change in the genome, and in many cases, it will have a small effect on disease risk.

Researchers looking for the genes behind complex diseases such as schizophrenia and autism are starting to shift their efforts away from genome wide association studies, Warren says.

Think of a SNP like a misspelling of a word in a certain place in a book, he says. In contrast, the “rare variants” geneticists are starting to study more intensively are more like printers’ errors or missing pages. The rapid sequencing technology that allows scientists to investigate these changes easily is just now coming on line, he says.

One example of these rare variants is DiGeorge syndrome, a deletion that gets rid of dozens of genes on one copy of chromosome 22. Children who have this chromosomal alteration often have anatomical changes to their heart and palate. But it also substantially increases the risk of schizophrenia – to about 25% lifetime risk. That’s a lot more than any of the SNPs identified this summer.

Working with several Emory colleagues, researcher Brad Pearce is planning to examine the genes missing in DiGeorge syndrome in several groups of patients: people with DiGeorge, patients with “typical” schizophrenia and people at high risk of developing schizophrenia.

An article in this spring’s Emory Health describes genetic research on autism. Several of the researchers mentioned there, such as geneticist Joe Cubells and psychiatrist Opal Ousley, are involved in this schizophrenia project as well, because deletions on chromosome 22 also lead to an increased risk of autism.

Pearce’s project is funded through American Recovery and Reinvestment Act money from the NIH.

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Manage stress to your advantage

Recently Charles Raison, MD, assistant professor, Emory Department of Psychiatry and Behavioral Sciences, wrote a blog for the Atlanta Journal-Constitution on stress. As clinical director of the Emory Mind-Body Program and director of the Behavioral Immunology Program, he has been studying stress.

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Raison says stress is everywhere today, both in our private and public lives, but also relentlessly in print, with discussion after discussion regarding what it is and what can be done to ease it.

He notes that you should think of stress like a sandwich. One trick for dealing with stress is to try to stay in the middle of the stress sandwich in the meat of life – the optimal challenge. The basic idea, he comments, is that you see what’s in front of you as a challenge, neither boring nor threatening, difficult enough to keep you fully engaged, easy enough for you to accomplish your goals.

You can read more by Raison by visiting the Atlanta Journal-Constitution Doctor Is In blog online.

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Gaining better medicine in translation

 

David Stephens, MD

David Stephens, MD

Translational research has traditionally been thought of as the process of moving a discovery in one direction – from the laboratory to the patient. More recently, though, researchers have recognized the importance of community engagement in the biomedical discovery process. That’s because involving the community makes for better medical care for patients.

The Atlanta Clinical and Translational Science Institute (ACTSI) is a partnership of educational, research, and health care institutions that involves the community in clinical research that translates laboratory discoveries into advanced treatments for patients. The ACTSI is part of the Clinical and Translational Science Awards (CTSA) of the National Center for Research Resources (NCRR) of the National Institutes of Health.

The ACTSI’s goal of supporting more effective clinical and translational research has led to a broader definition of translation: discovering what new healthcare tools, diagnostic tests and therapies a community needs and then taking that information back to the laboratory or conducting clinical research to find ways to meet those needs.

David Stephens, MD, is principal investigator of the ACTSI. Stephens says community engagement brings together leaders who discuss the health care needs of their respective communities. Researchers can then periodically meet with leaders, and let them know what progress is being made in the laboratory.

The ACTSI also brings together laboratory scientists with clinical investigators, community clinicians, professional societies and industry collaborators in a wide variety of research projects.

The ACTSI is led by Emory University, along with Morehouse School of Medicine, the Georgia Institute of Technology, Children’s Healthcare of Atlanta, and Kaiser Permanente Georgia. Other partners include the Centers for Disease Control and Prevention, Grady Health System, the Georgia Research Alliance, Georgia Bio, the Atlanta Veterans Affairs Medical Center, and the American Cancer Society.

To hear Stephens’ own words about translational research and the ACTSI, listen to Emory University’s Sound Science podcast.

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H1N1 pediatric flu vaccine clinical trials underway

Emory doctors discuss H1N1 flu vaccine testing

Emory doctors discuss H1N1 flu vaccine testing

Clinical trials are underway at Emory and Children’s Healthcare of Atlanta testing an investigational H1N1 flu vaccine along with the seasonal flu vaccine. Emory will enroll about 100 children, ages six months to 18 years, and up to 650 children nationally will participate in the study.

The study will look at the safety of and measure the body’s immune response to the H1N1 flu vaccine. In addition, it will help determine how and when the vaccine should be given with the seasonal flu vaccine to make it most effective.

Another important factor is learning if there are any potential problems by giving the vaccines together, such as whether one vaccine will undermine the protective power of the other.

The answer is important because experts are predicting that both strains of flu will circulate this fall and winter.

The clinical trial is part of the Vaccine and Treatment Evaluation Units (VTEUs), supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH). At Emory, this team is led by Mark Mulligan, MD, executive director of the Hope Clinic of the Emory Vaccine Center.

The Emory pediatric clinical trial is taking place at the Emory-Children’s Center. It is led by Emory VTEU co-directors Harry Keyserling, MD, professor of pediatric infectious diseases at Emory School of Medicine and Paul Spearman, MD, chief research officer for Children’s Healthcare of Atlanta and vice chair of research for Emory’s Department of Pediatrics, along with Allison Ross, MD, Emory assistant professor of pediatric infectious diseases.

Keyserling says that because children and young adults are considered among the most vulnerable populations for new and emerging strains of influenza, such as the current H1N1 pandemic, it is critically important that testing for a vaccine is quick and efficient.

The pediatric trial follows the launch of a VTEU-led adult clinical trial of the H1N1 and seasonal flu vaccines, which began at Emory’s Hope Clinic on Aug. 10 and will continue with followup visits for the next six weeks by a group of more than 170 volunteers.

Posted on by sgoodwin in Immunology 1 Comment

New tool in the fight for scarce donor organs

With so many men, women and children desperately awaiting a life-saving donor liver through traditional means – those donated by a deceased individual – transplant surgeons at Emory University Hospital looked for ways to improve the odds. transplantcenterlogo

Recently, Emory doctors were the first in Georgia to perform a rare “domino” liver transplant procedure – in effect saving two lives with one donor organ. The doctors had a opportunity to discuss the procedure at a media briefing held a few days ago.

The United Network for Organ Sharing (UNOS) says there are currently more than 16,000 Americans currently awaiting a liver transplant.

Domino liver transplant procedures are aptly named for the sequential, one-after-the-other nature of the process in which a viable liver from a deceased donor is transplanted into the first recipient, and the first recipient’s organ is then transplanted into a second recipient. The procedure is still extremely unusual, with fewer than 100 done in the United States since the first in 1996.

According to Stuart Knechtle, MD, professor of surgery in the Emory School of Medicine and director of the Emory liver transplant program, domino transplants are a rare but effective way of overcoming the national shortage of organs available for transplant. In most cases of domino liver transplants, one of the donated livers is transplanted from a patient with another type of disorder that does not affect the organ recipient.

“This successful domino liver transplant is something that simply does not start or end in a hospital operating room,” says Knechtle.

Liver recipient Bob Massie discusses his “miracle.”

Liver recipient Jean Handler discusses being “thankful and shocked.”

“This procedure, which saved two lives,” says Knechtle, “and will impact both families for many years to come, is the end result of a long chain of special events, starting with the decision by one person to donate the gift of life upon his untimely demise, which in turn allowed the recipient of that person’s organ to then donate hers to another patient.”

You can view the full briefing at this web site.

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Jeff Koplan discusses H1N1 on panel

Experts on H1N1 influenza are collaborating all across the country to learn more about the virus and how to prevent its transmission. In a race against time, Emory studies are taking place in the lab and in human clinical trials to help find a vaccine that can be used in the near weeks to come.

Recently, Emory’s Jeff Koplan, MD, vice president for global health and past CDC director, participated in a Breakthroughs panel sponsored by Big Think, Pfizer and Discover to discuss the latest issues in pandemic and genomic science, fields that have not only made big headlines recently but also promise to be two of the most pressing topics in global science and medicine in coming years.

Jeffrey P. Koplan, MD, MPH

Jeffrey P. Koplan, MD, MPH

The panel focused on the real-time, round-the-clock scientific mission to understand the history, significance, and future of the new strain of flu that emerged suddenly this spring. Panelists included Koplan; Barry Bloom, Joan L. and Julius H. Jacobson Professor of Public Health at Harvard; Peter Palese, chairman of the microbiology department at Mt. Sinai Medical Center; and Michael Worobey, ecologist and evolutionary biologist at the University of Arizona.

View: Superbug – Are We Prepared for The Next Great Plague?


Emory began signing up several hundred interested volunteers several weeks ago for a clinical trial of the H1N1 vaccine along with the seasonal flu vaccine. About 170 adults have now been vaccinated in the trial, which will last about nine weeks and involve several vaccinations and blood tests. A clinical trial testing the H1N1 vaccine in children will begin at Emory and Children’s Healthcare of Atlanta in the next few days, followed by another adult clinical trial adding an adjuvant to the H1N1 vaccine.

In addition, a multi-pronged attack against the H1N1 virus by Emory researchers is using a new method of rapidly producing highly targeted monoclonal antibodies to develop a diagnostic test as well as a temporary therapy to stave off the H1N1 virus. The antibodies, which can be isolated from a small amount of the blood of humans infected with the virus, could be targeted against H1N1 and rapidly reproduced to detect or attack the virus.

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Biomaterials used for hips and knees

Orthopaedics is a constantly evolving subspecialty where medical technology and research drives the development of new products used for reconstruction of body parts, specifically for hip and knee replacements.

Emory has been on the forefront of investigating and using three materials for these replacements: ceramic on ceramic surfaces, metal on metal surfaces, or highly cross-linked polyethylene. These newer biomaterials can reduce wear rates by over 99 percent compared to previous materials, thus enhancing the life of the new hip or knee.

Adult reconstruction or hip and knee arthritis surgery delivers quality outcomes that make a dramatic improvement in a patient’s quality of life. At the first post-operative visit, patients are more comfortable, have less pain and are even more functional than before their surgery.

Orthopeadic surgeon James R. Roberson, MD, chairman, Department of Orthopaedics in Emory School of Medicine, and professor of orthopaedic surgery specializes in adult reconstructive surgery of the hip and knee.

Roberson has been involved in clinical research for more than 20 years to solve difficult problems of the arthritic hip and knee. He pioneered a minimally invasive surgery technique for knee replacement that allows him to use smaller incisions in certain patients who have uncomplicated conditions.

Visit Emory University Orthopaedics & Spine Center and Emory University Orthopaedics & Spine Hospital to learn more about orthopaedic services and watch a video about the hospital.

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Pediatric liver disease on the rise

Miriam Vos, MD with patient.

Miriam Vos, MD with patient.

Miriam Vos, MD treats a growing number of children with nonalcoholic fatty liver disease. Yet little research has been conducted into the development of the illness. Nonalcoholic fatty liver disease in children, which often is associated with obesity, occurs when fat deposits itself in the liver. It eventually can lead to inflammation, cirrhosis and even liver failure.

In the hopes of preventing the disease in children, Vos, a pediatric hepatologist at Emory University School of Medicine

and Children’s Healthcare of Atlanta, is conducting research into the origins of this disorder in children. She suspects a diet high in sugar and too little exercise are tied to its onset.

In fact, a recent study led by Vos found that Americans are getting more than 10 percent of their daily calories from fructose, used mainly in sugar-sweetened beverages and processed foods.

The study analyzed the amount and sources of dietary fructose consumption among U.S. children and adults from 1988 to 1994. The researchers found that U.S. children and adults consumed 54.7 grams of fructose per day, an almost 50 percent increase from a national study sample conducted in 1977-1978.

Fructose occurs naturally in fruits and vegetables, however, it is added to many processed foods as table sugar (sucrose) and high-fructose corn syrup.

Vos has written a book aimed at helping children and their families shed pounds and achieve better nutrition through changes in lifestyle and diet.

To hear Vos’s own words about nonalcoholic fatty liver disease in children, listen to Emory University’s Sound Science podcast.

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Heated, targeted chemotherapy helps abdominal cancers

Cancer of the colon, ovaries, appendix or other organs within the abdomen often spreads to the lining of the abdominal cavity. Experts call this condition peritoneal surface malignancy. Until recently, treatment options for this form of cancer only provided relief from symptoms.

Emory University Hospital is one of a few facilities nationwide to utilize a new combination therapy to slow or prevent recurrence of this cancer. Hyperthermic intraperitoneal chemoperfusion (HIPEC) is a procedure done immediately following surgery that delivers heated chemotherapy directly into the abdominal cavity where it can penetrate cancerous tissue. Heat at 42 C (107 F) destroys cancer cells and enhances the power of chemotherapy.

The term “intraperitoneal” means that the treatment is delivered to the abdominal cavity. “Hyperthermic chemoperfusion” means that the solution containing chemotherapy is heated to a temperature greater than normal body temperature.

Charles Staley, MD, chief of surgical oncology at the Emory Winship Cancer Institute, says by bathing the abdomen with heated chemotherapy immediately following surgery doctors can administer a higher dose of medication than would normally be tolerated by a patient if given intravenously – the traditional way chemotherapy is administered.

During surgery, Staley removes all visible tumors throughout the abdomen, a procedure known as cytoreductive surgery. Following surgery, while still in the operating room, Staley administers the new treatment, which takes about two hours. Recent studies show improved prognosis in patients treated with HIPEC after the cytoreductive surgery.

Illustration of heated chemo therapy

Illustration of heated, targeted chemotherapy

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New heart valve replacement option under study

A new option for heart valve replacement is under study at Emory University Hospital. Cardiologists at the Emory Heart & Vascular Center are conducting groundbreaking research to study a non-surgical treatment option for patients with severe aortic stenosis, a narrowing of the aortic valve opening that affects tens of thousands of people each year. It is most common 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. Patients often develop symptoms of chest pain, shortness of breath, fainting spells and heart failure.

Peter Block, MD

Peter Block, MD

Emory cardiologists, led by Peter Block, MD, FACC, professor of medicine, Emory School of Medicine, are performing percutaneous aortic valve replacement as part of a clinical trial, comparing this procedure with traditional, open-heart surgery or medical therapy in high-risk patients with aortic stenosis. It provides a new way for doctors to treat patients who are too ill or frail to endure the traditional surgical approach. So far, 115 people have participated in the phase II clinical trial.

In this new procedure, doctors create a small incision in the groin or chest wall and then feed a wire mesh valve through a catheter and place it where the new valve is needed. The standard therapy, which has been used to treat aortic stenosis for more than 30 years, is to remove the diseased valve through open-heart surgery.

Block says the results seen so far in this clinical trial show great promise for this procedure. He says this is especially important since tens of thousands of Americans are diagnosed with failing valves each year and that number is expected to increase substantially in the coming years as baby boomers pass the age of 70.

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