The effect of vessel material properties and pulsatile wall motion on the fixation of a proximal stent of an endovascular graft.

Migration is a serious failure mechanism associated with endovascular abdominal aortic aneurysm (AAA) repair (EVAR). The effect of vessel material properties and pulsatile wall motion on stent fixation has not been previously investigated. A proximal stent from a commercially available stent graft was implanted into the proximal neck of silicone rubber abdominal aortic aneurysm models of varying proximal neck stiffness (ß=25.39 and 20.44). The stent was then dislodged by placing distal force on the stent struts. The peak force to completely dislodge the stent was measured using a loadcell. Dislodgment was performed at ambient pressure with no flow (NF) and during pulsatile flow (PF) at pressures of 120/80 mmHg and 140/100 mmHg to determine if pulsatile wall motions affected the dislodgement force. An imaging analysis was performed at ambient pressure and at pressures of 120 mmHg and 140 mmHg to investigate diameter changes on the model due to the radial force of the stent and internal pressurisation. Stent displacement forces were ~50% higher in the stiffer model (7.16-8.4 N) than in the more compliant model (3.67-4.21 N). The mean displacement force was significantly reduced by 10.95-12.83% from the case of NF to the case of PF at 120/80 mmHg. A further increase in pressure to 140/120 mmHg had no significant effect on the displacement force. The imaging analysis showed that the diameter in the region of the stent was 0.37 mm greater in the less stiff model at all the pressures which could reduce the fixation of the stent. The results suggest that the fixation of passively fixated aortic stents could be comprised in more compliant walls and that pulsatile motions of the wall can reduce the maximum stent fixation.

Engineering silicone rubbers for in vitro studies: creating AAA models and ILT analogues with physiological properties.

In vitro studies of abdominal aortic aneurysm (AAA) have been widely reported. Frequently mock artery models with intraluminal thrombus (ILT) analogs are used to mimic the in vivo AAA. While the models used may be physiological, their properties are frequently either not reported or investigated. This study is concerned with the testing and characterization of previously used vessel analog materials and the development of new materials for the manufacture of AAA models. These materials were used in conjunction with a previously validated injection molding technique to manufacture AAA models of ideal geometry. To determine the model properties (stiffness (beta) and compliance), the diameter change of each AAA model was investigated under incrementally increasing internal pressures and compared with published in vivo studies to determine if the models behaved physiologically. A FEA study was implemented to determine if the pressure-diameter change behavior of the models could be predicted numerically. ILT analogs were also manufactured and characterized. Ideal models were manufactured with ILT analog internal to the aneurysm region, and the effect of the ILT analog on the model compliance and stiffness was investigated. The wall materials had similar properties (E(init) 2.22 MPa and 1.57 MPa) to aortic tissue at physiological pressures (1.8 MPa (from literature)). ILT analogs had a similar Young's modulus (0.24 MPa and 0.33 MPa) to the medial layer of ILT (0.28 MPa (from literature)). All models had aneurysm sac compliance (2.62-8.01 x 10(-4)/mm Hg) in the physiological range (1.8-9.4 x 10(-4)/mm Hg (from literature)). The necks of the AAA models had similar stiffness (20.44-29.83) to healthy aortas (17.5+/-5.5 (from literature)). Good agreement was seen between the diameter changes due to pressurization in the experimental and FEA wall models with a maximum difference of 7.3% at 120 mm Hg. It was also determined that the inclusion of ILT analog in the sac of the models could have an effect on the compliance of the model neck. Ideal AAA models with physiological properties were manufactured. The behavior of these models due to pressurization was predicted using finite element analysis, validating this technique for the future design of realistic physiological AAA models. Addition of ILT analogs in the aneurysm sac was shown to affect neck behavior. This could have implications for endovascular AAA repair due to the importance of the neck for stent-graft fixation.

Detection of adeno-associated virus type 2 in sorted human bone marrow progenitor cells.

Wild-type adeno-associated virus (wtAAV) is a helper-dependent human parvovirus which has the ability to integrate into the genome of a wide variety of human cells, including those of the hemopoietic lineages. Recombinant adeno-associated virus (rAAV) is becoming a good candidate for virally mediated gene therapy. rAAV is likely to be a safe vector in clinical gene transfer, as it has never been associated with any disease despite previous studies showing that up to 70% of adults are seropositive for wtAAV. Seroconversion appears to occur early in life. wtAAV is an upper respiratory tract virus that is gut secreted, but little is known about the integration of latent wtAAV in hemopoietic lineages. Unlike retroviruses, which have been the most common vehicles for gene transfer to date, wtAAV appears to have a preferred integration site in the target cell which has been termed AAVS1. Several studies have shown that wtAAV can only integrate into only one of the pair of chromosome 19 in a cell. This may have implications for the use of rAAV in gene transfer because patients with latent virus would be refractory to further infection with rAAV. We used a polymerase chain reaction (PCR) assay to detect the presence of wtAAV in the bone marrow samples from 106 patients who presented at our institution. We were able to detect the presence of integrated virus in 18 whole marrow samples. Subsequently CD34+ and CD3+ cell subsets were sorted from the cryopreserved marrow of three PCR-positive individuals to assess integration of virus in these cell lineages. In all three samples tested, we were unable to detect wtAAV virus in the CD34+ hematological precursor cells, but a detectable level of integrated viral DNA was demonstrated in the CD3+ cell fraction. Our findings therefore suggest that CD34+ cells might remain a good target for rAAV-mediated gene transfer despite previous wtAAV infection.

Successful treatment of parvovirus B19 infection and red cell aplasia occurring after an allogeneic bone marrow transplant.

Chronic parvovirus B19 infection in the immunocompromised host may cause severe anaemia secondary to failure of erythropoiesis. This has been previously documented in patients with the Acquired Immune Deficiency Syndrome (AIDS), congenital immunodeficiencies and in children with acute lymphoblastic leukaemia during maintenance chemotherapy. We describe persistent parvovirus infection in a 14-year-old boy after HLA-matched sibling allogeneic bone marrow transplantation for acute lymphoblastic leukaemia in second remission.

Recombinant interferon-alpha in inoperable hepatocellular carcinoma: a randomized controlled trial.

To evaluate the clinical efficacy of interferon-alpha in hepatocellular carcinoma, 71 adult Chinese patients with histologically proven inoperable hepatocellular carcinoma were randomized to receive recombinant interferon-alpha 2a (50 x 10(6) IU/m2) intramuscularly three times a week (n = 35) or no antitumor therapy (n = 36). The survival of interferon-alpha-treated patients was significantly better than that of patients who received no antitumor therapy (p = 0.0471); median lengths of survival were 14.5 and 7.5 wk, respectively. Objective tumor regression greater than 50% was observed in 31.4% (11 of 35) of patients receiving interferon-alpha. Interferon-alpha induced tumor regression greater than 50% in 11 (31.4%) patients. Compared with the group receiving no antitumor therapy, the interferon-alpha therapy group had more tumor regression (p < 0.0001) and less tumor progression (p = 0.001). This high-dose interferon-alpha therapy was relatively well tolerated; only 34.3% of patients required reduction of dosage by one third or one half because of persistent fatigue. Two patients with diabetes mellitus (one also had tabes dorsalis) exhibited mental deterioration that might have been partially attributable to interferon-alpha therapy. We conclude that interferon-alpha is useful in a proportion of Chinese patients with inoperable hepatocellular carcinoma, both in prolonging survival and in inducing tumor regression.