UPMC Physician Resources
Doctor’s Choice of Words May Influence Family’s Decision to Permit CPR if Critically Ill Patient’s Heart Stops
Child Neurodevelopmental and Mental Health Disabilities on the Rise, Children’s Hospital of Pittsburgh of UPMC Study Finds
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.
- 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.
PITTSBURGH, April 17, 2013 – Stem cells and tissue-specific cells can be grown in abundance from mature mammalian cells simply by blocking a certain membrane protein, according to scientists at the University of Pittsburgh School of Medicine and the National Institutes of Health (NIH). Their experiments, reported today in Scientific Reports, also show that the process doesn’t require other kinds of cells or agents to artificially support cell growth and doesn’t activate cancer genes.
Scientists hope lab-grown stem cells and induced pluripotent stem (iPS) cells, which have the ability to produce specialized cells such as neurons and cardiac cells, could one day be used to treat diseases and repair damaged tissues, said co-author Jeffrey S. Isenberg, M.D., associate professor, Division of Pulmonary, Allergy and Critical Care Medicine, Pitt School of Medicine.
“Even though stem cells are able to self-renew, they are quite challenging to grow in the lab,” he said. “Often you have to use feeder cells or introduce viral vectors to artificially create the conditions needed for these cells to survive and thrive.”
In 2008, prior to joining Pitt, Dr. Isenberg was working in the National Cancer Institute (NCI) lab of senior author David D. Roberts, Ph.D., using agents that block a membrane protein called CD47 to explore their effects on blood vessels. He noticed that when cells from the lining of the lungs, called endothelium, had been treated with a CD47 blocker, they stayed healthy and maintained their growth and function for months.
Dr. Roberts’ NIH team continued to experiment with CD47 blockade, focusing on defining the underlying molecular mechanisms that control cell growth.
They found that endothelial cells obtained from mice lacking CD47 multiplied readily and thrived in a culture dish, unlike those from control mice. Lead author Sukhbir Kaur, Ph.D., discovered that this resulted from increased expression of four genes that are regarded to be essential for formation of iPS cells. When placed into a defined growth medium, cells lacking CD47 spontaneously formed clusters characteristic of iPS cells. By then introducing various growth factors into the culture medium, these cells could be directed to become cells of other tissue types. Despite their vigorous growth, they didn’t form tumors when injected into mice, a major disadvantage when using existing iPS cells.
“Stem cells prepared by this new procedure should be much safer to use in patients,” Dr. Roberts noted. “Also, the technique opens up opportunities to treat various illnesses by injecting a drug that stimulates patients to make more of their own stem cells.”
According to Dr. Isenberg, “These experiments indicate that we can take a primary human or other mammalian cell, even a mature adult cell, and by targeting CD47 turn on its pluripotent capability. We can get brain cells, liver cells, muscle cells and more. In the short term, they could be a boon for a variety of research questions in the lab.”
In the future, blocking CD47 might make it possible to generate large numbers of healthy cells for therapies, such as alternatives to conventional bone marrow transplantation and complex tissue and organ bioengineering, he added.
“These exciting findings provide a rationale for using CD47 blocking therapies to increase stem cell uptake and survival in transplanted organs, matrix grafts, or other applications,” said Mark Gladwin, M.D., professor and chief, Division of Pulmonary, Allergy and Critical Care Medicine, Pitt School of Medicine. “This continues a strong and productive collaboration between investigators at the NCI and the University of Pittsburgh’s Vascular Medicine Institute.”
Co-authors of the paper include David R. Soto-Pantoja, Ph.D., Michael L. Pendrak, Ph.D., Alina Nicolae, M.D., Ph.D., Zuqin Nie, Ph.D., and David Levens, M.D., Ph.D., of the National Cancer Institute (NCI); Erica V. Stein, B.S., M.Ed., of NCI and George Washington University; Chengyu Liu, Ph.D., of the National Heart, Lung and Blood Institute; Abdel G. Elkahloun, Ph.D., of the National Human Genome Research Institute (NHGRI); and Satya P. Singh, Ph.D., of the National Institute of Allergy and Infectious Diseases.
The project was funded by the NIH, NCI and NHGRI intramural programs and grants HL108954-01, HL103455-01, 11BGIA7210001; the Institute for Transfusion Medicine, the Western Pennsylvania Hemophilia Center, and Pitt’s Vascular Medicine Institute.
Children’s Hospital of Pittsburgh of UPMC Study Reveals Success Rate of Minimally Invasive Surgical Approaches in Infants
Pitt, Mount Sinai Team Finds Novel Mechanism Regulating Replication of Insulin-Producing Beta Cells for Diabetes Treatment
PITTSBURGH / NEW YORK, March 26, 2013 – Bringing scientists a step closer to new treatments for diabetes, researchers at the University of Pittsburgh School of Medicine and The Mount Sinai Medical Center have discovered a novel mechanism that regulates the replication of insulin-producing beta cells in the pancreas. The findings were recently published online ahead of print in Diabetes, a journal of the American Diabetes Association.
Regenerating beta cells to restore insulin production has moved to center stage in the quest for therapies for both Type 1 and 2 diabetes, said lead author Nathalie Fiaschi-Taesch, Ph.D., assistant professor, Division of Endocrinology and Metabolism, Pitt School of Medicine.
“Ideally, we would be able to do this by collecting cells from donor pancreatic tissue and growing them in the lab or better yet, giving a patient a pill to stimulate their own beta cells to replicate,” she said. “In the past, this has proven to be very challenging. Our findings provide new insights into how one may be able to do this. ”
After a 2009 paper in which a team led by Dr. Fiaschi-Taesch and Andrew F. Stewart, M.D., formerly of Pitt and now Irene and Dr. Arthur M. Fishberg Professor of Medicine and director of the Diabetes, Obesity and Metabolism Institute at The Mount Sinai Medical Center in New York, successfully induced human beta cells to replicate in the lab by elevating the level of a protein called cdk-6. In two current reports in Diabetes, they continued to examine the workings of the cell cycle proteins involved in the replication machinery.
What they found surprised them. Scientists had assumed the proteins resided in the cell’s nucleus, where they could act upon genes and molecules to stimulate – or in the case of beta cells, prevent – cell replication. Their experiments showed that the cell cycle proteins were actually in the cell’s cytoplasm, the fluid around the nucleus and contained within the cell membrane.
“It’s like looking under the hood of a car for the engine and instead finding all the parts scattered around the back seat: it’s no wonder the car won’t go,” Dr. Stewart explained. “Now we have to find ways to get those parts hooked up and back under the hood so that they can once again function as the engine that drives beta cell replication.”
Increasing levels of cdk-6 led that molecule and other key (or critical) cell cycle proteins to move into the nucleus to foster replication, but in the quiescent or non-replicating cell, the only ones that remained in the nucleus were inhibitors of replication. Understanding how and why those inhibiting proteins block replication could in turn lead to ways to block their activity, providing a novel approach for reviving beta cell regeneration, Dr. Fiaschi-Taesch said.
Dr. Stewart noted that the relocation of cell cycle proteins outside the nucleus in the beta cell might hold true for other kinds of cells.
“It makes me curious about whether we can turn replication back on in other cells that aren’t known to regenerate, such as neurons,” he said. “I’d also like to know why these proteins continue to be produced by the quiescent cell if they aren’t playing a role in cell replication.”
In the second Diabetes paper, the team described the intracellular localization of all the cell cycle proteins in the beta cell, a biochemical atlas that could guide other researchers.
Co-authors include Jeffrey W. Kleinberger, B.S., Fatimah Salim, B.S., Ronnie Troxell, B.S., Rachel Wills, B.S., Mansoor Tanwir, M.D., Gabriella Casinelli, B.S., Amy E. Cox, M.D., and Karen K. Takane, Ph.D., Harish Srinivas, Ph.D., all of the Division of Endocrinology and Metabolism, Pitt School of Medicine; and Donald K. Scott, Ph.D., of Mount Sinai Medical Center.
The project was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health, though grants U-01 DK 089538, R-01 DK55023, R56 DK065149 and T32-07052; the Juvenile Diabetes Research Foundation; the American Diabetes Association, and the University of Pittsburgh.