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.” |