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UPMC study finds integrated heart revascularization may be better than traditional bypass 
People with multi-vessel coronary artery disease who need heart bypass may do better if they undergo a combination of minimally invasive bypass surgery followed almost immediately by angioplasty, instead of having traditional open-chest surgery. 
In a study, physicians at the University of Pittsburgh Medical Center (UPMC) found that the combined procedure, called integrated coronary revascularization (ICR), was a safe and potentially lower-cost treatment than traditional open-chest bypass surgery. 
Principal investigator Howard Cohen, M.D., associate chief in the UPMC Presbyterian division of cardiology and director of the UPMC Presbyterian cardiac catheterization labs, will present the study March 30 at the American College of Cardiology’s annual scientific session in Atlanta. 

In ICR, surgeons operate on the blocked arteries while the heart continues to beat, unlike standard bypass  
in which the patient is placed on the heart-lung bypass machine and the heart is stopped. Surgery is done through a single three-inch incision in the chest, under the breast, which makes the stressful procedure of cutting through the breastbone unnecessary. Bypass is performed using the patient’s internal mammary artery which is connected to the left anterior descending artery or one of its major branches. Following bypass surgery the patient may immediately undergo conventional balloon angioplasty to restore blood flow to the remaining arteries. In many cases angioplasty is performed prior to bypass surgery. 
“While the study included only a small number of patients, this new approach is very promising for a potentially large group of people who can benefit from the best of both worlds, that is, the best surgical means of revascularization combined with low-risk, state-of-the-art angioplasty, with stenting whenever possible to reduce the risk of restenosis,” said Dr. Cohen. 
In the study, ICR was performed on 25 patients, eight of whom were considered at very high risk for surgery. Angioplasty was performed on 13 patients the same day as the bypass,  on the following day on five patients and days 2-4 on seven patients. The average length of hospital stay for bypass surgery and angioplasty was three days. At an average follow-up of 4.8 months, all patients are alive and free of ischemic symptoms. 
A previous study at the UPMC found that the total average cost of minimally invasive bypass surgery was $12,885 compared with $21,260 for traditional bypass surgery, and the average hospital stay for traditional bypass patients was 5.9 days. 
“We conclude in this initial pilot study that integrated coronary revascularization is feasible and safe, and potentially lower cost compared to multi-vessel coronary artery bypass,” said Dr. Cohen. “These preliminary data suggest that a randomized clinical trial comparing traditional bypass surgery and ICR is warranted for patients with multi-vessel coronary artery disease.” 
For additional information about UPMC Health System, please access http://www.upmc.edu. 

Altered neural circuitry may contribute to disturbances in cognitive functions in schizophrenia, say Pitt researchers

Study results published by University of Pittsburgh researchers  offer a strong biological explanation for why cognitive processes become disordered in patients with schizophrenia. 
“These results are important because even though psychosis - the delusions and hallucinations associated with this disease is its most striking feature, disturbance in cognitive processing is often the most disabling, persistent and difficult to treat feature of schizophrenia”, commented David A. Lewis M.D., professor of psychiatry and neuroscience and co-author of the study. 
Schizophrenia is a serious and common mental illness that afflicts more than 2 million people in the United States. The onset of the disease usually occurs during late adolescence or early adulthood and frequently leads to a life of disability, and, in 10 to 15 percent of cases, ends in suicide. Families of patients with the illness often bear tremendous emotional and financial burdens related to it. 
Dr. Lewis and his colleagues found that a specific component of the neural circuitry, or connections among brain cells, of the prefrontal cortex is substantially altered in a majority of people with the disorder. The affected component is called a chandelier neuron axon cartridge and plays a major role in controlling other neurons that process information within the prefrontal cortex and then send it to other brain regions. The prefrontal cortex is responsible for complex thinking processes, such as making judgments, formulating plans, organizing speech and other forms of communication. Disturbances in these processes severely affect the ability of an individual with schizophrenia to complete their education, gain employment and function in society. 
The Pitt scientists examined post-mortem brain specimens from a total of 55 subjects whose families consented to the study. Dr. Lewis and his colleagues discovered that the number of chandelier neuron axon cartridges was reduced on average by 40 percent in subjects with schizophrenia compared to both normal controls and subjects with psychiatric disorders other than schizophrenia. Their study indicates that the alterations in chandelier neuron axon cartridges represent a disturbance in brain biology than may be specific to the disease process of schizophrenia. In addition, the findings do not appear to be a consequence of the treatment with antipsychotic medications. 

“We can’t determine from this study whether the alterations in chandelier neuron axon cartridges are the primary brain disturbance in schizophrenia, or if they represent the brain’s response to some other abnormality,” continued Dr. Lewis. “But the results do open options for the development of new treatments targeted at improving the cognitive symptoms of this disorder.” 
Co-authors of this study are Tsung-Ung Woo, M.D., Ph.D., formerly of Pitt, now a resident in psychiatry at UCLA and Richard E. Whitehead, B.S., research specialist and Darlene S. Melchitzky, M.S, research principal, from the department of psychiatry, University of Pittsburgh School of Medicine. 
For additional information about UPMC Health System, please access http://www.upmc.edu 

Three institutions combine efforts in first-ever demonstration of long-term function in transplanted human liver cells 

A team of physicians and scientists from three medical centers has combined forces to show that an infusion of liver cells can function more than a year to partially correct a patient’s rare metabolic liver disease. The procedure suggests that cell transplantation may have broader application and be a safer and less invasive treatment than liver transplantation for some patients with disorder of the liver. 
The liver cell infusion took place in April 1997 at the University of Nebraska Medical Center (UNMC) in Omaha and was performed on a 10-year-old girl suffering from Crigler-Najjar Syndrome Type I, a rare disease in which the liver does not make the enzyme that allows bilirubin, a blood cell byproduct, to be normally excreted by the body. 
The team performing the procedure was headed by Ira Fox, M.D., a UNMC transplant surgeon who collaborated with J. Roy-Chowdhury, M.D. and N. Roy-Chowdhury, Ph.D., liver disease experts at the Albert Einstein College of Medicine in Bronx, N.Y., and Stephen Strom, Ph.D., an expert in isolating human liver cells from the University of Pittsburgh. 
“This is an important step forward,” Dr. Fox said. “We now know that factors which have limited the long-term effectiveness of pancreatic islet cell transplants for the treatment of diabetes do not affect the long-term function of transplanted liver cells, at least for some liver disorders.” 
Because the body is unable to conjugate and normally excrete bilirubin, patients with Crigler-Najjar disease develop jaundice and must spend 12 hours a day or longer receiving phototherapy, which helps degrade the bilirubin in the skin, so it can be cleared from the body. 
Other than a liver transplant, there is no cure for Crigler-Najjar disease.  
The oldest living patients with this disease is 31 years old and few people live beyond their teens. 
“This is a very insidious disease,” Dr. Fox said. “Because of the daily need for phototherapy, patients with this disease can’t live a normal life.  
The light therapy becomes less effective as patient get older, and there is an increasing risk that the high level of bilirubin will cause brain damage, especially if the patient develops an infection.” 
Because liver transplantation is not without risk, UNMC surgeons decided to try to do the less-invasive cell transplant procedure.  
The donor liver cells infused into the patient came from a liver that wasn’t suitable for whole organ transplantation, but the liver cells were perfectly fine, Dr. Fox said. 
The liver cells were isolated from the donor liver by Dr. Strom and his team at the University of Pittsburgh and transportated by air carrier to UNMC.  
From there, the cells were infused though a catheter inserted though the skin below the patient’s breast bone while the patient was awake.  
The cells traveled though the catheter into a  major blood vessel leading into the liver. 
Approximately 7 billion cells, comprising about five percent of the liver’s total mass, were infused in the course of a 15-hour period.  
The patient was discharged from the hospital 20 hours after the cell infusion was complete. 
Using methods developed by the Roy-Chowdhurys and their colleagues, the team was able to measure the patient’s enzyme activity in the liver and analyze the function of the transplanted cells. 
Going into the procedure, the patient’s bilirubin level was approximately 27 mg/dl.  
A year after the liver cell transplant, it has been steadily hovering around 12 mg/dl. The normal bilirubin level for most people in less than one. However, keeping the patient’s bilirubin level below 20 mg/dl significantly decreases the risk of brain damage. 
Since the procedure, the patient’s daily photherapy has been reduced from 10 to 12 hours per day to between six to seven hours per day, and she has become significantly less jaundiced.  
Because the donor liver cells are foreign to the patient’s body, she must take immunosuppression drugs to prevent her body from rejecting the cells.  
To date, the authors report no signs of rejection. 
She now has two types of cells in her liver, Dr. Strom said. Most  are her own, which don’t produce the enzyme necessary for the excretion of bilirubin, but a portion of the cells are the transplanted cells, which express the enzyme and are able to conjugate bilirubin, thus reducing its levels on the blood. 
“Human liver cell transplantation had been tried before, but until now it had not been possible to demonstrate the prolonged survival and function of these cells.” Dr. J. Roy-Chowdhury said. “Our studies provide the first unequivocal evidence of the long-term function of transplanted human liver cells.” 
“Now that we know long-term cell functioning is possible, the infusion of additional liver cells may completely free the patient from the need for phototherapy“, 
Dr. Strom said. “Ultimately, it could mean that this disease, and other diseases of the liver, may be cured without the need for whole-organ transplantation.”

 
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