Some 15,000 Americans die each year from AAAs, which are a ballooning or bulging of the aorta, the main artery that carries blood to organs and the lower extremities. Left untreated, the aneurysm will continue to expand until it ruptures unexpectedly and bleeds, causing death in up to 80 percent patients.
“We are combining medical imaging techniques with engineering analyses to develop a non-invasive method of estimating AAA severity,” said David Vorp, Ph.D., assistant professor of surgery and mechanical engineering and director of the Vascular Biomechanics and Vascular Research Lab at the University of Pittsburgh.
“By utilising these models and estimating biomechanical stresses within the aneurysm wall, clinicians may be better able to assess a specific aneurysm's propensity to rupture and make a sound  judgement on whether surgical intervention is warranted. Ideally, surgery is performed only when the associated risks are exceeded by the risk of an AAA rupture. Making this decision is presently very difficult since AAAs  afflict mainly those over 60 years of age”.
The standard surgical procedure to repair an AAA involves a large abdominal incision. The aneurysm is repaired by suturing a Teflon/polyester graft into place inside the AAA. 
Recently, vascular surgeons at UPMC have used a minimally invasive procedure called endovascular surgery in which the aneurysm is repaired from inside the aorta using a cathether. The cathether contains a collapsed polyester tube which is inserted into the patient's femoral artery and moved to the site of the aneurysm. Once inside the aneurysm, a spring-type attachment system hooks the tube to the inside walls of the artery on either end of the aneurysm and is anchored into place. Blood then flows through the implant, effectively depressurizing the aneurysm.
Endovascular surgery is still a new exploratory field and only a small percentage of patients are eligible  for this technique. Therefore, the only option for most patients is to undergo traditional surgical repair, according to Dr. Vorp.
“The decision to repair an aneurysm is usually based on its maximum diameter,” he said. “Surgeons typically will repair an AAA when it exceeds 5 cm (2-1/2 inches) in diameter but this does not take into account important characteristics of individual aneurysms. Some AAAs may have the same maximum diameter, but may have differences in shape, wall thickness, or mechanical properties which have an effect on their growth and potential to rupture.
“From an engineering perspective, the proper definition of  'critical state' for an AAA is when its capacity to withstand forces is about to be breached,” Dr. Vorp said. “That is, a more sound indicator of the severity of a specific aneurysm is to compare the acting wall stresses exceed the strength.”
Dr. Vorp and his team have developed a technique to noninvasively assess the wall stresses acting in individual AAAs based on the patient's blood pressure and the virtual AAA, a three dimensional reconstruction of CT scans taken prior to surgery.
The scans provide cross-sectional images of the AAA which are then processed and refined by computer analyses into a virtual aneurysm.
In his  research, Dr. Vorp also has tested the tensile strength of 150 tissue samples taken at the time of AAA surgery repair and found a 50 percent decrease in the strength of the AAA wall compared to healthy aorta tissue.
“Our next step is to develop a method to noninvasively determine the tensile strength of an individual aneurysm, rather than a patient population, perhaps based on clinical parameters such as the patient's age, gender, body size, etc.,”  Dr. Vorp said.
 

University of Pittsburgh reports novel ways to improve Transplant Acceptance at Transplantation Society Meeting
Genetically altered dendritic cells (DCs) could significantly improve the body's acceptance of a transplanted organ, according to University of Pittsburgh researchers in reports made at the 17th World Congress of the Transplantation Society held July 12-17 in Montreal. Known as the pacemakers of the immune system, DCs are specialised white blood cells that regulate the activity of other immune cells within the body. In the case of organ transplantation, investigators are harnessing DCs to teach T cells to tolerate transplanted organs that would  normally be recognised by the body as foreign.
“DCs can be manipulated to disable the host's T cell response to a new organ,”, noted Angus Thomson, Ph.D., D. Sc., F.R.C.Path., professor of surgery and director  of transplant immunology at the University of Pittsburgh's Thomas E. Starzl Transplantation Institute.
One catch, however, is that donor dendritic cells transplanted together with an organ carry the same tissue markers that spur the host's immune system to reject a new graft. In effect, they could suffer rejection similar to a new organ, according to Dr. Thomson. In an animal transplant model, Pitt researchers circumvented this potential snag by genetically modifying donor-derived dendritic cells to churn out their own local supply of immunosuppressants.
“The benefits are two-fold,” explained Dr. Thomson. “First, by producing their own localised immunosuppressant, dendritic cells buy enough time to each host T cells not to attack and 'evict' the new organ, as it were. Second, the immunosuppressants also dampen the attack of T cells on the new organ. And because these dendritic cells produce immunosuppressants at a local, rather than systemic level, this engineered process minimises side effects such as infection associated with systemic delivery of immunosuppressants.”
In one study, Dr. Thomson's team used  an adenovirus to shuttle the gene for the imunosuppressant protein  transforming growth factor beta (TGFb1) into dendritic cells taken from the bone marrow of one mouse strain. Next, they took these DCs and transplanted them along  with a heart to another immunologically distinct strain of mice. These altered DCs prolonged the survival of the new heart grafts in mice compared with mice  who received donor hearts and DCs that had not been genetically modified with TGFb1.
In another tissue culture study, the Pittsburgh investigators found that DCs genetically altered with an adenovirus to carry a gene for CTLA4-Ig were less likely themselves to be reject by a host's immune system CTLA4-Ig is an immunosuppressant that has been used in clinical trials to treat psoriasis. “This research gives us yet another indication that donor DCs genetically modified to protect themselves are less likely to disappear quickly within a donor body before they have a chance to teach T cells to tolerate a new organ,” said Dr. Thomson. In a related animal study, the researchers found that the CTLA4-Ig protein plus a monoclonal antibody, anti-CD40 ligand, effectively inhibits organ rejection in animal transplant recipients with immune  systems that have been pre-sensitised to reject a new organ. This pre-sensitisation can occur after a previous transplant or after events unrelated to transplantation such as multiple pregnancies or multiple blood transfusions.
“In essence, the immune systems of these transplant recipients are pre-armed to fight off a transplant,” said Dr. Thomson. The Pittsburgh team is currently planning clinical protocols incorporating the use of genetically altered DCs for delivery to patients as they receive organ transplants. They also expect to develop protocols using CTLA4-Ig and anti-CD40 ligand for pre-sensitised, difficult-to-treat transplants recipients. The CTLA4-Ig used in the research was provided by Immunex Inc. of Seattle.
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