RESEARCHERS TO STUDY TREATMENT OPTIONS FOR HIGH-RISK LUNG CANCER PATIENTS
Researchers at Washington University School of Medicine are recruiting subjects to study patients who have both early-stage lung cancer and breathing problems that limit their treatment options. For these patients, the surgery used to treat early-stage, nonsmall cell lung cancer, the most common type of lung cancer, is risky due to the increased incidence of complications related to their already decreased lung function.
Patients in the study will either undergo a modified type of lung surgery that may reduce complications by removing a smaller portion of the lung than in traditional surgery or have a highly targeted form of radiation therapy that treats the tumor with high-dose radiation while sparing surrounding tissue.
“Our hope is that doctors and patients will embrace this cutting-edge trial so we can clarify the optimal treatment for this group of higher-risk patients,” says study co-investigator Dr. Bryan Meyers, chief of thoracic surgery.
Patients will be followed for five years to evaluate survival rates and quality of life after treatment.
GENETIC TRANSMISSION OF AUTISM EXPLORED
In a recently published study, Washington University researchers showed that they are learning more about how autism is genetically transmitted. The study looked at how autism runs in families between half-siblings, as compared to siblings who have both parents in common.
“We found that autism risk for half-siblings is about half of what it is for full siblings,” says Dr. John Constantino, director of the William Greenleaf Eliot Division of Child and Adolescent Psychiatry at Washington University and psychiatrist-in-chief at St. Louis Children’s Hospital. “Most of the half-siblings we studied had the same mothers. Given that half of the risk of transmission was lost and half was preserved among those maternal half-siblings, mothers and fathers appear to be transmitting risk equally in families in which autism recurs.”
Autism is more common in boys than girls, so researchers were interested in the patterns of genetic transmission from mother to child. The study also shows that autism may be due to the combined effects of many genes instead of just one key gene that codes for the condition.
The study is notable in part for its size: more than 5,000 families were enrolled, and 619 of those included at least one maternal half-sibling. The half-siblings lived with their biological mother, sharing environmental influences in early childhood.
“If transmission of autism risk was occurring equally from unaffected mothers and fathers, you would predict that maternal half-siblings’ risk of autism would be about half of what we saw in full siblings,” Constantino says. “And that’s exactly what we found.”
UNDERSTANDING THE GENETICS OF KIDNEY STONE FORMATION
Ask anyone about the worst pain he or she has experienced, and two things often come up: childbirth and kidney stones. Obviously there’s not much to be done about childbirth other than the palliative options already available, but researchers at Washington University may be on the track of better risk-assessment and treatment for kidney stones.
Using a mouse model, scientists are exploring kidney stones’ specific genetic causes and examining the potential for new treatments. It is known that kidney stones form when minerals in urine crystallize. Causes include dehydration, excessive salt or calcium consumption, age, and genetic predisposition.
The research team has found that a key gene involved in the formation of kidney stones, claudin-14, is activated when other factors, such as not drinking enough water, cause a molecular reaction. Gene activation then causes excess calcium to remain in the urine instead of passing through the kidneys and back into the bloodstream. The resulting stones cause severe pain when they get stuck in the bladder, ureter or urethra. A variation in claudin-14 blocks the ability to properly regulate the gene’s activity and increases likelihood of kidney stones.
Researchers are optimistic that they may someday be able to develop drug therapies to keep claudin-14 activity in check and reduce the risk of kidney stones in people who have the genetic variation.
RESEARCHERS LEARN MORE ABOUT NETWORKS BETWEEN BRAIN REGIONS IN ALZHEIMER’S
Alzheimer’s disease continues to be a conundrum for scientists seeking to understand exactly what causes the condition, how it progresses and what can be done to stop it. Researchers at Washington University are studying how the telltale brain plaques that form in Alzheimer’s disease patients disrupt the brain’s ability to network from one region to another.
“Precise measurement of changes in brain networks are critical to understanding Alzheimer’s and will likely be important in models of other neurodegenerative disorders,” says senior study author Dr. David Holtzman, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. “For example, we can now test whether blocking Alzheimer’s plaques from building up in the mouse brain prevents disruptions in brain networks.”
Studies of brain region connectivity have been conducted in humans using functional magnetic resonance imaging. Holtzman and his colleagues are working on mouse studies that involve testing for similar patterns of networking between brain regions. “Being able to analyze brain function from a similar perspective in animal models, where we have much more freedom to manipulate genes and proteins, should be very helpful in our efforts to understand and treat complex conditions like Alzheimer’s disease,” he says.
NEW TEST TO HELP CREATE CHOLESTEROL MANAGEMENT PLAN
The Mercy Lipid Center is offering a free test for people who have a family history of early heart disease, an intolerance to cholesterol-lowering drugs, or problems making the lifestyle changes needed to lower cholesterol. The test, known as Advanced NMR (nuclear magnetic resonance), measures multiple factors, such as inflammation markers, genetics and specific types of cholesterol-carrying blood particles.
“This test is a great opportunity for patients to get more details about their heart risk factors related to cholesterol,” said Dr. Denise Janosik, cardiologist with Mercy Clinic Heart and Vascular. “Individuals who appear to be at goal with their cholesterol numbers might learn that there are additional ways to reduce their risks and highlight factors that otherwise wouldn’t have been addressed.”
Test results provide the basis for a customized plan to help control and minimize heart disease risk through cholesterol management.
EXISTING DRUGS MAY BOOST VIRAL IMMUNITY
Washington University researchers are screening large numbers of existing drugs to determine which ones could help activate the body’s immune system and fight viral infections.
“Over many years of research, we have developed a good understanding of the human body’s own mechanisms to fight viruses,” says the study’s first author Dr. Dhara Patel, a postdoctoral research scholar. “Instead of targeting the virus itself, which most current antiviral drugs do, we have designed a strategy to look for chemical compounds that will enhance this innate antiviral system.”
Of particular interest to researchers is the drug idarubicin, used to treat leukemia, lymphoma and breast cancer. The screening found that this drug significantly increases cells’ interferon signaling pathway, an important part of immune response to viruses.
“While idarubicin is not something you would give to a patient who has the flu, we are continuing to screen more drugs,” Patel says. “We’re starting to find compounds from different drug classes that are not so toxic and that have similar properties in enhancing interferon signaling. We’re still validating them, but we’re very excited about what we’re finding.”
NEW OPTION FOR HEART VALVE REPLACEMENT PATIENTS
For patients with severe heart valve disease who are not good candidates for heart surgery, a new procedure uses catheters to replace a faulty aortic valve. Transcatheter aortic valve replacement (TAVR) is being performed by specialists at Mercy Heart and Vascular Hospital.
A bovine heart valve is attached to a mesh stent and delivered via a catheter inserted into the groin and then threaded through the femoral artery to the heart. Surgeons can implant the new valve without opening the chest or using a heart bypass machine during the procedure. “The procedure is easier on patients than traditional surgery and recovery time is greatly diminished,” says Dr. Anthony Sonn, a cardiologist with Mercy Clinic. “TAVR will improve the quality of life and extend life expectancy for those who are not able to withstand open heart surgery.”
LIMITED HAND FUNCTION RESTORED TO QUADRIPLEGIC PATIENT
Washington University specialists recently published a case study in which a quadriplegic patient regained some hand function following an innovative new procedure and a year of intensive physical therapy.
The patient suffered a spinal cord injury at the lowest vertebra in the neck. Nerves from the upper arm join the spinal cord above the point of injury, and surgeons rerouted these working nerves to allow for brain signals to the hand. Now able to pinch with his thumb and forefinger, the patient can feed himself small pieces of food and write with assistance.
“This procedure is unusual for treating quadriplegia because we do not attempt to go back into the spinal cord where the injury is,” says Dr. Ida Fox, assistant professor of plastic and reconstructive surgery at Washington University. “Instead, we go out to where we know things work—in this case, the elbow—so that we can borrow nerves there and reroute them to give hand function.”
To detour around the block in this patient’s spinal cord injury and return hand function below the level of the injury, surgeons operated in the upper arms. There, the working nerves that connect above the injury and the non-working nerves that connect below the injury run parallel to each other, making it possible to tap into a functional nerve and direct those signals to a non-functional neighbor. The subsequent physical therapy was crucial in retraining the brain to send signals that will result in a pinching motion rather than an elbow-flexing motion.
BABIES WITH BETTER IMMUNE RESPONSE HAVE FEWER COLDS IN FIRST YEAR
Some babies are born with better immunity than others, and those who have higher immunity have fewer viral respiratory illnesses in their first year, according to researchers at Washington University.
“Viral respiratory infections are common during childhood,” says Dr. Kaharu Sumino, assistant professor of medicine and first author of the study. “Usually they are mild, but there’s a wide range of responses— from regular cold symptoms to severe lung infections and even, in rare instances, death. We wanted to look at whether the innate immune response—the response to viruses that you’re born with—has any effect on respiratory infections during the baby’s first year.”
Sumino and her research colleagues measured an immune response to viruses by testing infants’ umbilical cord blood for the response when exposed to viral infection. They looked for a substance in the blood that is released by immune cells to prevent virus replication.
While 88 percent of the infants had at least one cold during their first year, the average was four colds for the babies. Those who had a more robust immune response, as evident in their cord blood lab tests, suffered fewer colds. The researchers hope that their findings will help with efforts to create drugs to protect against viral infections.
EARLY DRUG USE CORRELATED TO LESS EDUCATION
Taking drugs or abusing alcohol at a young age correlates to lower levels of educational attainment, according to Washing - ton University researchers. They found that among 6,242 male twins who served in the military during the Vietnam era, those who took drugs or drank as early teens or developed dependencies were less likely to earn a college degree.
“We can’t say that substance dependence or early substance use causes lower educational achievement, but we do see a strong association,” says lead author Dr. Julia Grant, research assistant professor of psychiatry. “Drugs and alcohol affect many lifetime milestones such as marriage, parenthood and employment,” she says. “These events in later life all are influenced by early substance use, and this study provides further evidence that as a society, we need to continue our public-health efforts to reduce underage drinking, smoking and use of drugs.”