UPMC Physician Resources

Experts to Present at Digestive Disease Week 2013

Posted by UPMC Physician Resources on Monday, May 20th 2013     

Experts from the Division of Gastroenterology, Hepatology, and Nutrition will have a strong presence at Digestive Disease Week 2013, with UPMC physicians and researchers making 16 oral presentations and 35 poster presentations. Preview of the key findings to be presented at the conference:

Uncontrolled Therapeutic Observations in IBD

Confocal Endomicroscopy, Enhanced Endscopy, and Other Emerging Technologies II

Upper GI Small Bowel Imaging: Polyps, Biopsies, Endoscopy Histology

Nutrient Digestion, Absorption, and Metabolism

Are you attending DDW?

To learn more about our clinical programs, research efforts, and fellowship opportunities, visit us at DDW booth 1533, May 18 to 21.

category: Gastroenterology, UPMC
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Pitt Transplant Experts Challenge Assumption, Describe Biological Pathway That Leads To Organ Rejection

Posted by andrewsj3 on Wednesday, May 15th 2013     
PITTSBURGH, May 15, 2013 – Transplant researchers at the University of Pittsburgh School of Medicine challenge a long-held assumption about how biologic pathways trigger immune system rejection of donor organs in a report published online today in the Journal of Clinical Investigation. Their study, sponsored by the National Institutes of Health, suggests a different paradigm is needed to develop better anti-rejection therapies.
Immune system troops called T-cells migrate to transplanted organs, fighting the foreign tissue, explained senior author Fadi Lakkis, M.D., Frank & Athena Sarris Chair in Transplantation Biology, professor of surgery, Pitt School of Medicine, and scientific director of theThomas E. Starzl Transplantation Institute. Until now, scientists have thought these T-cells were beckoned to the site by chemokines, proteins secreted by cells in the lining of the blood vessels, or endothelium, of the organ when it becomes inflamed.
“The prevailing view was that when the endothelium gets inflamed, it gets a little sticky, so T-cells that are zipping by in the bloodstream begin to slow down and bind to chemokines that trigger their arrest and migration into the affected tissue,” Dr. Lakkis said. “We decided to test that hypothesis and found out to everyone’s surprise that’s not the way it works.”
If the chemokine receptors on T-cells were blocked, the researchers reasoned, the cascade of immune events would not happen, stalling rejection. So two days after mice received a heart or kidney transplant, they received T-cells treated with pertussis toxin, which irreversibly binds to a key molecule in the receptor to inhibit its activity, and presumably prevent the migration of memory and effector T-cells already sensitized to recognize the foreign proteins of the donor tissue.
Using a technique called two-photon microscopy, which allows real-time visualization of living tissue, they found that pertussis-treated T-cells invaded the donor organs just as they did if they were untreated, leading to organ rejection.
“This showed us that chemokines are not necessary to start the rejection response,” Dr. Lakkis said. “So then we wondered which cells were sounding the alarm to the immune system.”
The sophisticated microscopy technique revealed that  the donor kidney’s dendritic cells, which identify antigens or foreign proteins and present them on their cell surfaces to be recognized by other immune cells, “stick their feet,” as Dr. Lakkis put it, in the bloodstream, thereby exposing donor surface antigens to the recipient’s immune system.
“So, anti-rejection therapies that target chemokine responses have very little effect,” he said. “But novel drugs that interfere with antigen presentation by the endothelium or the dendritic cells could be very helpful.”
Co-authors include lead author and M.D./Ph.D. student Jeff Walch, and researchers from the Starzl Transplantation Institute and the departments of Surgery, Immunology and Medicine at Pitt School of Medicine; and Yale University School of Medicine.
The project was funded by NIH grants AI064343, AI049466 and AI74490.

UPMC Launches First-Ever Gastrointestinal Dermatology Clinic

Posted by andrewsj3 on Monday, May 13th 2013     
PITTSBURGH, May 13, 2013 – Today, UPMC opened the nation’s first-ever gastrointestinal dermatology clinic to provide coordinated care to inflammatory bowel disease (IBD) and celiac disease patients with associated dermatologic conditions.
Up to 30 percent of patients with IBD and celiac disease have cutaneous (skin-related) manifestations of their disease, yet until now there has not been a specialty clinic devoted specifically to these patients.
IBD, which affects as many as 1.4 million people in the U.S., primarily includes Crohn’s disease and ulcerative colitis. Crohn’s is a severe and chronic disease that causes inflammation, ulcers and bleeding in the digestive tract. Crohn’s often affects the end portion of the small intestine, but can affect any part of the gastrointestinal tract. Ulcerative colitis is another type of IBD which affects the colon (large intestine) and rectum. IBD differs from irritable bowel syndrome, which does not cause ulcers or inflammation and does not damage the bowel. Celiac disease is a digestive disorder which damages the small intestine and interferes with the absorption of nutrients from food. People with celiac cannot tolerate gluten, a protein found in wheat, barley and rye.
The clinic, located on the fifth floor of the Falk Medical Building in the Oakland area of Pittsburgh, will initially be open the first Monday of each month, though hours may change depending on demand. Patients must first be referred from UPMC-based gastroenterology departments.
“This is a novel service that we can provide to our patients,” said Lisa Grandinetti, M.D., assistant professor of dermatology at theUniversity of Pittsburgh and dermatologist at UPMC, who will be leading the new clinic. “We’re excited to open the first-ever specialty clinic to address the needs of IBD patients.”
Dermatologic manifestations of gastrointestinal (GI) diseases can occur as both the skin and the GI tract can be affected by the same conditions. Making the correct diagnosis of these conditions requires the ability of physicians to recognize the dermatological presentations of certain GI diseases. For example, dermatitis herpetiformis, or severely itchy small blisters on the elbows, knees and buttocks, is diagnostic for the GI condition known as celiac disease.
Other conditions that will be addressed by this clinic include, but are not limited to:

 

  • Erythema nodosum
  • Pyoderma gangrenosum
  • Aphthous ulcers/aphthous stomatitis
  • Dermatitis herpetiformis and celiac disease
  • TNFα associated psoriasiform dermatoses
  • Nutritional deficiency dermatoses

Dr. Grandinetti joined UPMC in 2009, and has since been receiving referrals from gastroenterologists for patients with IBD who have skin-related problems. Her interest in cutaneous manifestations of GI disease began after medical school, during her residency at the Cleveland Clinic.

“I saw firsthand how patients’ quality of life was significantly affected by their skin condition, often when their GI disease was under control,” noted Grandinetti. “With time, experience and a growing number of patients with cutaneous manifestations of GI diseases, I felt it was a good time to create a specialized clinic that would provide dermatologic and gastroenterologic coordinated care to patients with IBD and other GI issues.”

 

Doctor’s Choice of Words May Influence Family’s Decision to Permit CPR if Critically Ill Patient’s Heart Stops

Posted by andrewsj3 on Thursday, May 9th 2013     
PITTSBURGH, May 9, 2013 – A physician’s choice of words when talking with family members about whether or not to try cardiopulmonary resuscitation (CPR) if a critically ill patient’s heart stops may influence the decision, according to a study by University of Pittsburgh researchers in the June edition of Critical Care Medicine and now available online.
“It’s long been known that the way a choice is framed can influence people’s decisions,” noted Amber E. Barnato, M.D., M.P.H., M.S., lead author of the study and associate professor of clinical and translational science at the University of Pittsburgh School of Medicine. “Our study shows that the words physicians use may play an important role in determining critical end-of-life decisions.”
For this first-of-its-kind study, Dr. Barnato and her team recruited more than 250 adult children or spouses in eight cities: Boston, Atlanta, New York, Los Angeles, San Francisco, Dallas, Denver and Pittsburgh.
The participants took part in a Web-based survey involving a hypothetical situation in which a loved one was in the intensive care unit with a 40 percent chance of dying from sepsis, a dangerous bacterial infection. Some subjects were shown a photo of their loved ones to help them imagine the situation and heighten the emotional response. An actor portrayed a physician who held a virtual, interactive meeting with the family member. The “doctor’s” responses varied, using different words for the same scenarios. Additionally, some offered emotional support, and others offered only clinical information.
A key finding was that when participants were asked to choose between having their loved ones receive CPR if their hearts should stop — a treatment with a 10 percent chance of successfully reviving them — or the alternative, a “Do Not Resuscitate” (DNR) order, 60 percent chose CPR. When the alternative was described as to “allow natural death” instead of a DNR order, the number choosing CPR dropped to 49 percent.
When the actor cited “his own experience” about how most others handled such a situation, family members were more likely to choose what they believed was the common approach. Using more empathic language did not influence CPR choice.
“Simple changes of words and perceptions about social norms resulted in large differences in CPR choices,” said Dr. Barnato. “The change in terminology from ‘DNR’ to ‘allow natural death’ already has been implemented in a health system in Texas. This study suggests that the change isn’t just window dressing — it makes a real difference in the choices that people make. We expect that it also may reduce feelings of guilt for choosing against CPR by making family members feel like they are doing something positive to honor their loved one’s wishes at the end of life, rather than taking something away from them.”
Robert M. Arnold, M.D., chief, section of palliative care and medical ethics at the University of Pittsburgh School of Medicine, co-authored the study.
The work was funded by the National Institute of Nursing Research.

Pitt’s Serendipitous Scientific Discovery Holds Potential in Destroying Drug-Resistant Bacteria

Posted by andrewsj3 on Tuesday, May 7th 2013     
PITTSBURGH, May 7, 2013 – Through the serendipity of science, researchers at the University of Pittsburgh have discovered a potential treatment for deadly, drug-resistant bacterial infections that uses the same approach that HIV uses to infect cells.
The National Institutes of Health-supported discovery will be described in the June issue of the journal Antimicrobial Agents and Chemotherapy. It is especially promising in the development of a potential treatment for lung infections in people with cystic fibrosis.
“The discovery of this new antibiotic was an unexpected result of basic research on HIV proteins,” said senior author Ronald Montelaro, Ph.D., professor and co-director of Pitt’s Center for Vaccine Research (CVR). “As a result of studying these proteins, we discovered novel structures that turn out to work very well against bacterial infections, including the complicated bacterial populations in lung infections in cystic fibrosis patients.”
Cystic fibrosis is a genetic disorder that leads to thick, viscous secretions in the lungs and other organs in about 30,000 children and adults in the United States, according to the Cystic Fibrosis Foundation. Lung infections resistant to antibiotics often are deadly for people with cystic fibrosis. About 80 percent of cystic fibrosis patients have at least one antibiotic-resistant infection in their lungs by age 18.
“Infections with progressively resistant bacteria in the lung shorten the lives of people with cystic fibrosis,” said Joseph M. Pilewski, M.D., co-director of the Adult Cystic Fibrosis Center at UPMC. “What happens is the genetic defect predisposes patients to infections that drive the production of mucus that then blocks the airways and makes it difficult to breath.”
Dr. Montelaro and his colleagues found that a particular sequence of amino acids on the tail end of HIV allow the virus to “punch into” and infect cells. The team manufactured a synthetic and more efficient version of this sequence – called engineered cationic antimicrobial peptides, or “eCAPs” – that laboratory tests have shown to rapidly destroy bacteria that are otherwise resistant to most standard antibiotics.
The eCAPs can be assembled in a laboratory setting from the amino acids arginine and tryptophan and manufactured to the shortest effective length, giving the resulting antibiotic treatment maximum potency while reducing costs.
The discovery was featured in April at two prestigious gatherings intended to put scientists in touch with business developers — the BIO International Convention in Chicago, and the University Research & Entrepreneurship Symposium (URES) in Boston.
“At both symposia, we received a lot of interest from pharmaceutical-related companies,” said co-author Jonathan Steckbeck, Ph.D., M.B.A., post-doctoral associate at CVR. “It was a particular honor to be recognized at URES as one of the year’s 10 breakthroughs in life sciences.”
Pitt has taken out several U.S. and international patents on this discovery.
“We have an unmet clinical need for treatment of hospital-acquired infections where the bacteria are extremely resistant to antibiotics,” said co-author Yohei Doi, M.D., Ph.D., assistant professor of medicine in Pitt’s School of Medicine. “We have patients with no treatment options left. The fact that these eCAPs are completely engineered puts them at an advantage because they can be manufactured easily, and they give us some hope for a quick-acting treatment in these dire circumstances.”
Traditional antibiotics typically work by poisoning important metabolic processes after being taken up by the target bacteria, a process that may take hours, or days, to clear a bacterial infection.  In contrast, the eCAPs are specifically attracted to the surface of target bacteria where they disrupt the bacterial membrane, causing death within seconds, or minutes.
Laboratory tests indicate that the eCAPs work well against biofilms, which are bacterial communities that develop very high levels of resistance to antibiotics by working together to protect the film’s inner bacteria from traditional treatments. The eCAPs seem to push through the outer layers of biofilms to destroy the entire bacterial community.
“It’s like a pin bursting a balloon; it’s a very rapid action,” said Dr. Montelaro. “While cystic fibrosis patients are our initial target and a very high-priority target, we also could look at infections associated with burns or indwelling medical devices, such as venous catheters. We could even look to the biodefense realm, in terms of a rapid, handheld nebulizer treatment that soldiers could use in the case of exposure to a bioterrorism agent.”
Additional co-authors are Berthony Deslouches, M.D., Ph.D., and Jodi Craigo, Ph.D., both of Pitt’s Center for Vaccine Research; and Timothy A. Mietzner, Ph.D., of the Lake Erie College of Osteopathic Medicine at Seton Hill.
Funding for this study was provided by NIH award P30CA047904.
Watch the Youtube video of researchers discussing the eCAPs.

Child Neurodevelopmental and Mental Health Disabilities on the Rise, Children’s Hospital of Pittsburgh of UPMC Study Finds

Posted by andrewsj3 on Sunday, May 5th 2013     

PITTSBURGH, May 5, 2013 – More children have disabilities now than a decade ago, and the greatest increase is among children of higher-income families, according to a Children’s Hospital of Pittsburgh of UPMC study presented today at the Pediatric Academic Societies(PAS) annual meeting in Washington, DC.

Results of the study, led by Amy Houtrow, M.D., Ph.D., M.P.H., chief, Division of Pediatric Rehabilitation Medicine at Children’s Hospital, also showed that while disabilities due to neurodevelopmental and mental health problems have increased sharply, disabilities related to physical health conditions have decreased. This trend was most noteworthy among children under 6 years of age whose rate of neurodevelopmental disabilities nearly doubled during the study, from 19 cases to 36 cases per 1,000 children.

“A century of health care improvements and social changes have altered the face of childhood chronic disease and disability,” said Dr. Houtrow, who also is an associate professor of physical medicine and rehabilitation and of pediatrics at the University of Pittsburgh School of Medicine. “Nearly six  million kids were considered disabled in 2009 and 2010—almost one million more than in 2001 and 2002.”

Dr. Houtrow said that while previous studies have found an increase in the  prevalence of childhood disability, she and the research team wanted to look more closely at the specific conditions and socio-demographic factors associated with disabilities.

The researchers studied data from the National Health Interview Survey conducted by the U.S. Centers for Disease Control and Prevention from 2001 to 2002 and from 2009 to 2010. Participants included  more than 102,000 parents of children up to age 17.

The research team assembled a composite of disability indicators to identify disabled children and their associated underlying chronic conditions. Conditions were categorized into three groups: physical, neurodevelopmental/mental health, and other.

The overall rate of disability for children under age 18 increased 16.3 percent between the 2001 to 2002 study period and the 2009 to 2010 study period.

Children living in poverty represented the largest numbers of overall children with disability in both time periods but not the highest growth rates. The largest increase in growth rates of disabilities was seen among children living in households with incomes at or above 300 percent of the federal poverty level—about $66,000 a year for a family of four in 2010.

“We are worried that children living in lower income families may be having problems accessing diagnostic and treatment services,” Dr. Houtrow said.

Since the study could not pinpoint why the disability rate is increasing, more research is needed, the author concluded.

Co-investigators were: Kandyce Larson, Ph.D., American Academy of Pediatrics; Paul Newacheck, Dr.P.H., Professor of Pediatrics and Health Policy, University of California San Francisco; Neal Halfon M.D., M.P.H., Professor of Pediatrics, Health Policy and Management, UCLA.

For more information on Dr. Houtrow and the Division of Pediatric Rehabilitation Medicine, visit http://www.chp.edu/rehab.

 

 

 

Study Finds Late-Life Depression Associated with Increased Risk for Dementia

Posted by andrewsj3 on Wednesday, May 1st 2013     
PITTSBURGH, May 1, 2013 – Late-life depression is associated with an increased risk for all-cause dementia, Alzheimer’s disease and, most predominantly, vascular dementia, according to the results of a new meta-analysis published today in the British Journal of Psychiatry.
Previous studies have shown an association between depression and Alzheimer’s disease, but this is the first meta-analysis that specifically addresses the risk of Alzheimer’s disease and vascular dementia in older adults with late-life depression.  The study, conducted by researchers at the University of Pittsburgh School of Medicine and the Federal University of Minas Gerais School of Medicine, is also the first to show that late-life depression increases the risk of vascular dementia and that the risk of vascular dementia is greater than the risk of Alzheimer’s disease for older adults with depression.

 

“All-cause dementia” refers to all dementia syndromes, the most common of which is Alzheimer’s disease, accounting for 60 to 80 percent of all dementia cases.  Alzheimer’s disease is associated with memory problems and apathy in early stages, and impaired judgment, confusion, disorientation, behavior changes, and difficulty speaking in later stages.  Vascular dementia is the second most common cause of dementia, and is associated with impaired judgment or ability to plan and complete tasks, as opposed to memory loss that is common in early stages of Alzheimer’s.

 

“An understanding of how late-life depression increases the risk of dementia could lead to better prediction and prevention mechanisms,” said Meryl Butters, Ph.D., associate professor of Psychiatry at the University of Pittsburgh School of Medicine, and corresponding author of the study. “Early diagnosis and prevention of depression could have a major dual public health impact as they could also potentially prevent or delay cognitive decline and dementia in older adults.”
Late-life depression is one of the most common psychiatric illnesses in older adults, affecting 15 percent of adults aged 65+ in the United States, or approximately 6 million people.  Depression in late-life may be a relapse of an earlier depression, or it can be triggered by chronic illness (including degenerative brain diseases such as Alzheimer’s disease), grief, placement in a nursing home, or hospitalization. Late-life depression is associated with poorer general health and higher incidences of cardiovascular disease.

 

Although the symptoms of depression vary, clinical depression is characterized by an inability to function normally or complete daily tasks, over a prolonged period of time.
The research evaluated a total of 23 community-based cohort studies as part of a meta-analysis to calculate the pooled risk of all-cause dementia, Alzheimer’s disease and vascular dementia in older adults with late-life depression.  The findings concluded those with late-life depression are:

 

  • 1.85 times more likely to develop all-cause dementia
  • 1.65 times more likely to develop Alzheimer’s disease
  • 2.52 times more likely to develop vascular dementia

The authors note that preventing depression and improving general health including cardiovascular health should be considered in public health policies associated with preventing and/or delaying the onset of dementia.

“Fortunately, we already know that depression can be prevented and treated,” added Dr. Butters. “Now that we know the risks of dementia, we need to conduct clinical trials to investigate the impact of preventing depression on risk of cognitive decline and dementia in older adults.”

This research was sponsored by the National Institute of Mental Health (NIMH) and the John A. Hartford Foundation Center of Excellence in Geriatric Psychiatry at UPMC.

 

Pitt Team Finds Melatonin Delays ALS Symptom Onset and Death in Mice

Posted by andrewsj3 on Thursday, April 25th 2013     
PITTSBURGH, April 25 – Melatonin injections delayed symptom onset and reduced mortality in a mouse model of the neurodegenerative condition amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, according to a new study by researchers at the University of Pittsburgh School of Medicine. In a report published online ahead of print in the journal Neurobiology of Disease, the team revealed that receptors for melatonin are found in the nerve cells, a finding that could launch novel therapeutic approaches.
 
Annually about 5,000 people are diagnosed with ALS, which is characterized by progressive muscle weakness and eventual death due to the failure of respiratory muscles, said senior investigator Robert Friedlander, M.D., UPMC Endowed Professor of neurosurgery and neurobiology and chair, Department of Neurological Surgery, Pitt School of Medicine. But the causes of the condition are not well understood, thwarting development of a cure or even effective treatments.
 
Melatonin is a naturally occurring hormone that is best known for its role in sleep regulation. After screening more than a thousand FDA-approved drugs several years ago, the research team determined that melatonin is a powerful antioxidant that blocks the release of enzymes that activate apoptosis, or programmed cell death.
 
“Our experiments show for the first time that a lack of melatonin and melatonin receptor 1, or MT1, is associated with the progression of ALS,” Dr. Friedlander said. “We saw similar results in a Huntington’s disease model in an earlier project, suggesting similar biochemical pathways are disrupted in these challenging neurologic diseases.”
 
Hoping to stop neuron death in ALS just as they did in Huntington’s, the research team treated mice bred to have an ALS-like disease with injections of melatonin or with a placebo. Compared to untreated animals, the melatonin group developed symptoms later, survived longer, and had less degeneration of motor neurons in the spinal cord.
 
“Much more work has to be done to unravel these mechanisms before human trials of melatonin or a drug akin to it can be conducted to determine its usefulness as an ALS treatment,” Dr. Friedlander said. “I suspect that a combination of agents that act on these pathways will be needed to make headway with this devastating disease.”
 
Co-authors of the paper include other scientists from the University of Pittsburgh School of Medicine; Harvard Medical School; Ohio State University; Weifang Medical University; Bedford VA Medical System, Boston; St. Joseph’s Hospital and Medical Center, Phoenix; University of Texas Medical School at Houston; and VA Pittsburgh Health Care System.
 
The project was funded by grants NS051756, NS039324, and NS055072 of the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health; the U.S. Department of Defense; and the Muscular Dystrophy Association.

Mild Blast Injury Causes Molecular Changes in Brain Akin to Alzheimer’s Disease, Pitt-Led Team Says

Posted by andrewsj3 on Wednesday, April 24th 2013     
PITTSBURGH, April 24 – A multicenter study led by scientists at the University of Pittsburgh School of Medicine shows that mild traumatic brain injury after blast exposure produces inflammation, oxidative stress and gene activation patterns akin to disorders of memory processing such as Alzheimer’s disease. Their findings were recently reported in the online version of the Journal of Neurotrauma.
 
Blast-induced traumatic brain injury (TBI) has become an important issue in combat casualty care, said senior investigator Patrick Kochanek, M.D., professor and vice chair of critical care medicine and director of the Safar Center for Resuscitation Research at Pitt. In many cases of mild TBI, MRI scans and other conventional imaging technology do not show overt damage to the brain.
 
“Our research reveals that despite the lack of a lot of obvious neuronal death, there is a lot of molecular madness going on in the brain after a blast exposure,” Dr. Kochanek said. “Even subtle injuries resulted in significant alterations of brain chemistry.”
 
The research team developed a rat model to examine whether mild blast exposure in a device called a shock tube caused any changes in the brain even if there was no indication of direct cell death, such as bleeding. Brain tissues of rats exposed to blast and to a sham procedure were tested two and 24 hours after the injury.
 
Gene activity patterns, which shifted over time, resembled patterns seen in neurodegenerative diseases, particularly Alzheimer’s, Dr. Kochanek noted. Markers of inflammation and oxidative stress, which reflects disruptions of cell signaling, were elevated, but there was no indication of energy failure that would be seen with poor tissue oxygenation.
 
“It appears that although the neurons don’t die after a mild injury, they do sustain damage,” he said. “It remains to be seen what multiple exposures, meaning repeat concussions, do to the brain over the long term.”
Co-authors include researchers from the Safar Center for Resuscitation Research and the University of Pittsburgh School of Medicine; University of California, San Diego; ORA Inc., of Fredericksburg, Va.; Walter Reed Army Institute of ResearchDyn-FX Consulting Ltd, Amherstburg, ON; Uniformed Services University of the Health Sciences, Bethesda, MD; and Integrated Services Group, Inc., Potomac, MD.
 
The project was funded by the Defense Advanced Research Projects Agency.
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