Among the many benefits of living in St. Louis is the caliber of our medical care. Our top-ranked hospitals and innovative medical schools conduct research to share around the world. Read about the latest innovations here.
veterans who volunteer
Going from serving in a war zone to functioning as a civilian is a big change. That’s why The Mission Continues was started. The national nonprofit deploys veterans on six-month volunteer service missions with community agencies. Founded here in 2007 by now-Governor Eric Greitens, the effort has shown impressive results.
Monica Matthieu, Ph.D., lead author of the study and assistant professor of social work at Saint Louis University, says, “This study tells us that formal volunteering in a civic service program is one option to aid veterans in their transition. Some may call it a gap year. I call it a fulfillment year.”
The study, published in the February 2017 journal Psychiatric Research, looked at 346 veterans who completed The Mission Continues program in 2011 through 2014, volunteering 20 hours a week on specific projects for six months. Before starting, 50 percent said they had symptoms of PTSD, and nearly one-fifth reported symptoms of depression. Half were receiving treatment for mental health conditions. At the end of their volunteer service, many reported it was easier to perform normal activities, and the number of vets with probable PTSD dropped from 50 percent to 43 percent.
Says Matthieu, “The actual mechanism for why volunteering helped isn’t entirely clear. One theory is that stepping outside our own lives to focus on the needs of others causes positive things to come together.” She says the number of veterans with symptoms of depression also decreased, and they reported feeling less isolated.
exercise in a pill
Well, sort of. Multiple grants from the Department of Defense and the National Institutes of Health (NIH) will enable Saint Louis University researchers to impact the epidemics of diabetes and obesity, armed with two nuclear receptors, REV-ERB and ERR. These control muscle metabolism, mimicking the beneficial effects of exercise in people who can’t exercise or who exercise ineffectively.
Right now, both receptor studies are in animal-model testing. Thomas Burris, Ph.D., chair of pharmacology and physiology at Saint Louis University, and his department colleague, John Walker, Ph.D., say earlier studies in animals show that a drug that targets REV-ERB appears to act as an exercise mimic; studies with ERR suggest it has the same potential.
Burris and Walker study nuclear receptor-signaling molecules that sense different hormone levels and regulate gene expression based on the signal they receive. Says Burris: “In many cases of illness, signaling is off. We can correct signals by dialing the hormone messages up or down, mimicking hormones or blocking them. The current studies aim to optimize drug compounds to dial up muscle metabolism.”
Diabetes, obesity, age-related muscle changes and even muscular dystrophy stand to benefit from a drug like this, Burris says, adding: “Diabetes and obesity are a public health crisis, and our research shows we can significantly slow the muscle-wasting process.”
you itch, i itch
Researchers at Washington University School of Medicine have confirmed in mouse studies that some behaviors are hardwired into our circuitry, like yawning and itching.
“Sometimes, all you have to do is mention itching and someone will scratch. But it is not a form of empathy,” reports Zhou-Feng Chen, Ph.D., the principal investigator and director of the Washington University Center for the Study of Itch.
After seeing mice scratch when they saw a mouse scratch on a computer screen, researchers identified the suprachiasmatic nucleus (SCN), a brain region that controls when animals fall asleep or wake up. The SCN was highly active after the mouse watched the video of the scratching mouse. They also discovered that when active, the SCN secretes a chemical substance called gastrin-releasing peptide (GRP), which, in 2007, Chen identified as a key transmitter for itch signals between the skin and spinal cord.
He explains: “The mouse doesn’t see another mouse scratching and then think it might need to scratch, too. Instead, its brain sends out itch signals using GRP as a messenger.” When Chen’s team blocked GRP or the receptor it binds to, the mice did not scratch when they saw other mice scratch. But they were still able to scratch when exposed to itch-inducing irritants.
Chen explains that itching is widespread in the animal kingdom, and it has a protective function. GRP in humans can serve as an important mediator in dermatitis, eczema and morphine painkillers.
He says the goal of these findings is to develop transformational clinical studies on compounds to block GRP pathways to combat uncontrollable itching.
better angioplasty
Coronary angioplasty, a method to open clogged arteries supplying blood and oxygen to the heart muscle, can be lifesaving. A change in technique is taking it to the next level. Currently, many physicians use the deeper femoral artery in the groin to access the coronary arteries, but switching access to a more superficial artery in the wrist allows patients to be discharged the same day. A study published in the Feb. 20 issue of Journal of the American College of Cardiology showed that shifting only 30 percent of angioplasties to the new technique could save the U.S. $300 million a year.
Dr. Amit P. Amin, first author of the study and assistant professor of medicine at Washington University, says, “We have unequivocal evidence that we have better outcomes when we perform radial angioplasty through a blood vessel in the wrist.” He says there is less bleeding, fewer complications, less pain and discomfort, higher patient satisfaction, shorter hospital stays and lower costs.
Coronary angioplasty is done to alleviate chest pain or shortness of breath caused by clogged coronary arteries. By threading a small catheter into either the wrist or groin artery, the cardiologist can view the narrowed heart artery, deliver an inflatable balloon to open it, and place a stent to keep it open. So why aren’t all angioplasties performed through the wrist? Amin says the femoral artery is bigger and offers a straighter route to the coronary arteries, so many physicians have not yet mastered the new technique.
“The American College of Cardiology stated it’s easier on patients than a tooth cleaning. Patients are 80 percent awake. They walk around within 2 hours and then go home,” he says.
heartburn meds & kidney failure
Chronic heartburn is rampant in this country. Doctors breathed a sigh of relief when a class of drugs called Proton Pump Inhibitors (PPIs) proved extremely effective for controlling it. PPIs include Nexium, Prevacid, Prilosec and Protonix. The problem is too much of a good thing. More than 15 million Americans suffering from heartburn, ulcers and acid reflux disease get prescriptions from their doctors for PPIs, and millions more buy them over the counter.
Dr. Ziyad Al-Aly is senior author of a new study and an assistant professor of medicine at Washington University School of Medicine. The study, published in the Feb. 22 issue of Kidney International, evaluated the use of PPIs in 125,000 patients. It showed that patients on long-term use (more than 90 days) had a greatly increased risk of chronic kidney disease and kidney failure. “The problem is that these drugs have been considered safe, and the doctor just keeps refilling the prescription,” Al-Aly says. “It’s viewed as a maintenance drug.”
That needs to change. He says that even over-the-counter versions caution patients not to take them for more than four weeks, but people still do. The study demonstrated that early kidney problems like low urine output or swelling in the legs and ankles were absent in more than half the patients, so they aren’t aware of the damage until it becomes chronic.
Al-Aly says doctors must pay careful attention to kidney function in patients who use PPIs, even in the face of no symptoms. More important, PPIs should not be the first line of treatment for heartburn; instead, diet, exercise, and reducing risk factors like smoking and alcohol should come first. PPIs should be used short-term only, one to four weeks,” he notes. Patients who take PPIs need to tell their doctors so other solutions can be found and they can be monitored for effects.
new drugs reverse alzheimer’s
According to the Alzheimer’s Association, one in three seniors dies with Alzheimer’s or some other form of dementia. Research on finding a cure is picking up speed, and one target is tau protein in the brain. Normal tau protein contributes to healthy, functioning brain neurons. But in some people, it collects into toxic tangles that damage brain cells. Researchers at Washington University School of Medicine have shown in animal studies that a synthetic molecule can reduce levels of tau protein and neurologic damage.
The study in mice and monkeys came out Jan. 25 in Science Translational Medicine. Timothy Miller, M.D., Ph.D., professor of neurology and the study’s senior author, explains that the synthetic molecule, an antisense oligonucleotide, may treat neurodegenerative diseases based on abnormal tau. Oligonucleotides interfere with instructions for building proteins. They can bind to RNA, a messenger molecule that carries those instructions, and target it for destruction before the bad protein can be built. Oligonucleotides can be designed to target RNA for almost any protein, good news for those identified as problematic in Alzheimer’s patients.
Miller says the particular molecule that targets tau protein reduction probably will be most effective in a specific population of people who have a tau gene mutation. He says they hope to have human trials within a year or so. Such trials are already underway for oligonucleotides to treat Huntington’s disease and amyotrophic lateral sclerosis (ALS).
jump-start weight loss
For significantly overweight people, aspiration therapy helps rid their bodies of excess calories before they are even absorbed. Developed by researchers at Washington University School of Medicine, this device can help patients lose up to 14 percent of their body weight while learning healthier ways to eat and exercise.
The aspiration device is a tube with holes along the surface that is implanted about 5 inches into the stomach. The end of the tube protrudes slightly from the skin but is undetectable under a shirt. During a meal, the patient must eat very slowly and chew food well, combining it with lots of water. Then, 30 to 60 minutes after eating, they hook the tube up to a reservoir of tap water to flush into the stomach and withdraw the pureed food, removing about one-third of it.
Dr. Vladimir Kushnir, director of the Bariatric Endoscopy Center at Washington University and Barnes-Jewish Hospital, was involved in early clinical trials and has been following patients for about three years. Kushnir says, “People must learn to eat smaller portion sizes and consume fewer calories. Eating differently is a big part of the weight loss. Most patients perform aspiration therapy once or twice a day after their largest meals.” He sees the device as an aid in helping patients eventually gain more control over consumption.
The advantage of this therapy over surgical procedures like lap band or gastric bypass is that it is minimally invasive with little downtime, and it doesn’t make permanent changes to the body. He says the best time to remove it is when it’s used only once a day and weight has been stable for months.
The device is recommended for people with a body mass index (BMI) of 35 to 55, which is considered medically significant obesity. Many who are eligible also have other health problems like diabetes, high blood pressure or sleep apnea. Although FDA approved, it currently is not covered by most insurance plans.
relief for chronic pain
One hundred million American adults suffer with chronic pain at a cost to society of about $600 billion a year. Currently, many patients have the choice of continuing to suffer or taking opioid pain medications, which have a well-publicized addictive potential and horrible side effects. “We have an urgent need for safer, non-addictive pain medications,” says Daniela Salvemini, Ph.D., a professor of pharmacology and physiology at Saint Louis University and principal investigator in a new study. She has been awarded a grant by the Mayday Fund to determine if either of two key molecules can be used as biomarkers for specific types of pain.
In previous work, Salvemini discovered pain pathways, the molecular series of events that lead to it, to help researchers understand how it occurs. The pain pathways are dependent on two molecules, S1PR1 and A3AR. By modulating these molecules, scientists were able to block and reverse pain.
Salvemini explains, “If patients with pain have a high level of these molecules in their blood or tissues, these markers may serve as useful measurements to know if a pain pathway is activated and whether these patients might benefit from a drug that specifically targets these molecules.”
Mouse models confirmed that by modulating these markers, they were able to block and reverse pain. This new grant will allow them to study people and take blood samples and measure levels of these receptors. They may find that some types of pain have increased levels and others don’t, allowing them to identify patients most likely to respond to a particular treatment.
Right now, Salvemini and her team will start by studying patients with pain from chemotherapy-induced neuropathy. Blood samples will be gathered in a pre-clinical phase to identify candidates for therapy. The goal is to find effective targeted treatments.
ptsd & heart health
Young veterans who suffer from post-traumatic stress disorder (PTSD) are being diagnosed with cardiovascular and metabolic conditions like high blood pressure, high cholesterol, diabetes and ischemic heart disease at much higher rates than veterans without PTSD.
Jeffrey Scherrer, Ph.D., Saint Louis University associate professor in family and community medicine, has received a $2.3 million grant to study the effects of treating PTSD on cardiovascular and metabolic health. The four-year study has started and will look at medical data from veterans between the ages of 18 and 70, the majority of whom served in the Iraqi and Afghan conflicts.
Says Scherrer, “The study has two components. Medical chart data extraction looks at 5,960 patient treatment records for V.A. patients being treated for PTSD in clinics that provide cognitive processing therapy or prolonged exposure therapy. Then, that data will be merged wwith the larger number of variables contained in the V.A.’s national patient database and coded for positive cardiovascular behavior like diet classes and smoking cessation treatment.”
The study will equalize factors that may confuse the results by comparing the records with those of 5,960 patients without PTSD complaints. Scherrer wants to know whether patients who get relief from PTSD symptoms through therapy are more able to decrease risky behaviors that harm cardiovascular and metabolic health. Is improving health behaviors enough to lower risk for these conditions, or do these risks remain because of psychological changes caused by PTSD?
“If what our pilot data suggests is true and reductions in PTSD symptoms are associated with improved health behaviors, then physicians and therapists can encourage patients at the start of PTSD treatment to change their health behaviors,” Scherrer says. Otherwise, those patients will require lifelong, aggressive monitoring.
predicting depression
Analyzing functional MRI brain scans of newborns, researchers at Washington University found that the strength and type of connections between certain brain regions predicted which babies developed shyness, anxiety or nervousness by age 2. These symptoms have been linked to clinical depression and anxiety disorders in older children and adults. The research was published in the February issue of the Journal of the American Academy of Child & Adolescent Psychiatry.
By comparing the brain scans of preemies and full-term babies, they found the preemies had weaker connections between the amygdala and the insula and pre-frontal cortex regions of the brain. The amygdala is involved with processing emotions; the insula with consciousness and emotion. The pre-frontal cortex plays roles in planning and decision-making. Those weaker connections appear to increase the risk of early symptoms related to depression and anxiety.
Sixty-five full-term newborns and 57 babies born at least 10 weeks early were studied. Dr. Cynthia Rogers, assistant professor of child psychiatry and primary author on the study, found the findings interesting, but says they want to follow these same babies longer into life and do repeat scans at ages 9 or 10 to see if the brain connections continue to influence the risk of depression and anxiety disorders.
“We want to see if full-term babies and preemies have the same risk caused by the same weak connections and whether, as the children get older, we see a widening gap in disorders between the two groups. We know that pre-term babies are at risk for other problems like ADHD and autism. Connectivity may be a factor in predicting such problems in preterm babies as well.”
Rogers says if they identify brain disruptions early, they can develop treatments to alter how the brain centers function. She says other factors like genetics and stress can influence whether a child develops depression or other cognitive problems. “As we bring the older children back for retesting, we can collect information on the home environment and positive parenting practices to help us understand why some at-risk babies developed normally.”
