IN PILOT STUDY, SCREENING DETECTS POTENTIALLY SERIOUS HEART CONDITIONS IN HEALTHY CHILDREN
Science Daily - A pilot study in healthy children and adolescents shows that it is feasible to screen for undiagnosed heart conditions that increase the risk of sudden cardiac arrest (SCA). Adding a 10-minute electrocardiogram (EKG or ECG) to a history and physical examination identified unsuspected cases of potentially serious heart conditions.
Although more research is needed, the preliminary results suggest that a relatively low-cost screening might help identify children who are at risk for sudden cardiac arrest, possibly preventing childhood death.
"In the United States, the current American Heart Association guidelines recommend screening only competitive athletes, not all children, using history and physical examination alone," said the study leader, Victoria L. Vetter, M.D., M.P.H., a pediatric cardiologist at The Children's Hospital of Philadelphia. She noted that in Italy and Japan, which have compulsory screening of all athletes or schoolchildren, researchers have found that adding an ECG to the history and physical increases the likelihood of detecting children at risk for SCA.
"Our pilot study evaluated the feasibility of adding an ECG to cardiac screening of healthy school-aged children," Vetter added. The Children's Hospital research team published their study on March 15 in the American Heart Journal.
In children, sudden cardiac arrest is caused by structural or electrical abnormalities in the heart that frequently cause no symptoms and may go undiagnosed. It results in an estimated 100 to 1,000 or more annual deaths in childhood in the U.S. The current study evaluated 400 healthy subjects, 5 to 19 years old, recruited from Children's Hospital's Care Network. The researchers screened the subjects using a medical family history questionnaire, a physical examination, an ECG and an echocardiogram.
The study team identified previously undiagnosed cardiac abnormalities in 23 subjects, and hypertension in an additional 20. Ten of the 400 subjects (about 2.5 percent) had potentially serious cardiac conditions. Of those 10 subjects, only one had experienced symptoms, and those had previously been dismissed. None of the 10 subjects had a family history of SCA. "In our study, using ECG outperformed the history and physical examination and found previously unidentified potentially serious abnormalities that would not have been identified by history and physical examination alone," the study authors wrote. The authors added that the children in the screening were not all high school athletes, and most would not have undergone athletic cardiac screening. Regular physical examinations by primary care physicians had not detected the cardiac conditions found in the current study
"Performing the ECG and its interpretation added less than 10 minutes to each subject's total evaluation," said Vetter, added that the ECG machines are portable and relatively inexpensive.
"Our pilot study showed that adding ECG to the currently recommended guideline of history and physical examination is feasible for screening children and adolescents, and offers the potential to identify serious cardiovascular abnormalities," said Vetter. "However, our study was not designed to be generalized to a larger population of children at risk for SCA. Larger, more representative studies must be done, as well as cost-effectiveness research." She added that larger pediatric studies may establish better standards for ECG measurements, and determine how broad ECG-screening of school-aged children could best be implemented.
A CHANGE OF HEART: RESEARCHERS REPROGRAM BRAIN CELLS TO BECOME HEART CELLS
ScienceDaily (July 9, 2011) - For the past decade, researchers have tried to reprogram the identity of all kinds of cell types. Heart cells are one of the most sought-after cells in regenerative medicine because researchers anticipate that they may help to repair injured hearts by replacing lost tissue. Now, researchers at the Perelman School of Medicine at the University of Pennsylvania are the first to demonstrate the direct conversion of a non-heart cell type into a heart cell by RNA transfer.
Working on the idea that the signature of a cell is defined by molecules called messenger RNAs (mRNAs), which contain the chemical blueprint for how to make a protein, the investigators changed two different cell types, an astrocyte (a star-shaped brain cell) and a fibroblast (a skin cell), into a heart cell, using mRNAs.
James Eberwine, PhD, the Elmer Holmes Bobst Professor of Pharmacology, Tae Kyung Kim, PhD, post-doctoral fellow, and colleagues report their findings online in the Proceedings of the National Academy of Sciences. This approach offers the possibility for cell-based therapy for cardiovascular diseases.
"What's new about this approach for heart-cell generation is that we directly converted one cell type to another using RNA, without an intermediate step," explains Eberwine. The scientists put an excess of heart cell mRNAs into either astrocytes or fibroblasts using lipid-mediated transfection, and the host cell does the rest. These RNA populations (through translation or by modulation of the expression of other RNAs) direct DNA in the host nucleus to change the cell's RNA populations to that of the destination cell type (heart cell, or tCardiomyocyte), which in turn changes the phenotype of the host cell into the destination cell.
The method the group used, called Transcriptome Induced Phenotype Remodeling, or TIPeR, is distinct from the induced pluripotent stem cell (iPS) approach used by many labs in that host cells do not have to be dedifferentiated to a pluripotent state and then redifferentiated with growth factors to the destination cell type. TIPeR is more similar to prior nuclear transfer work in which the nucleus of one cell is transferred into another cell where upon the transferred nucleus then directs the cell to change its phenotype based upon the RNAs that are made. The tCardiomyocyte work follows directly from earlier work from the Eberwine lab, where neurons were converted into tAstrocytes using the TIPeR process.
The team first extracted mRNA from a heart cell, then put it into host cells. Because there are now so many more heart-cell mRNAs versus astrocyte or fibroblast mRNAs, they take over the indigenous RNA population. The heart-cell mRNAs are translated into heart-cell proteins in the cell cytoplasm. These heart-cell proteins then influence gene expression in the host nucleus so that heart-cell genes are turned on and heart-cell-enriched proteins are made.
To track the change from an astrocyte to heart cell, the team looked at the new cells' RNA profile using single cell microarray analysis; cell shape; and immunological and electrical properties. While TIPeR-generated tCardiomyocytes are of significant use in fundamental science it is easy to envision their potential use to screen for heart cell therapeutics, say the study authors. What's more, creation of tCardiomyoctes from patients would permit personalized screening for efficacy of drug treatments; screening of new drugs; and potentially as a cellular therapeutic.
These studies were enabled through the collaboration of a number of investigators spanning multiple disciplines including Vickas Patel, MD and Nataliya Peternko from the Division of Cardiovascular Medicine, Miler Lee, PhD and Junhyong Kim, PhD from the Department of Biology and Jai-Yoon Sul, PhD and Jae Hee Lee, PhD also from the Department of Pharmacology, all from Penn.
