Opinions, hopes and concerns regarding pharmacogenomics: a comparison of healthy individuals, heart failure patients and heart transplant recipients.

It is not yet known whether healthy individuals and patients with a chronic disease have similar attitudes towards pharmacogenomics. Thus we conducted a survey of 175 healthy volunteers, 175 heart failure (HF) patients and 100 heart transplant recipients to compare their opinions on this subject. Most participants (>90%) stated that they would accept pharmacogenomic testing and expressed high hopes regarding its potential applications. Overall, interest for pharmacogenomics was shared equally among the three groups. In contrast, after adjusting for age, gender, education and income, healthy individuals were more likely to voice concerns about potential employment (P=0.008 vs HF, odds ratio (OR)=2.93, confidence interval (CI)=1.33-6.47; P=0.010 vs Transplant, OR=2.46, CI=1.24-4.90) and insurance discrimination (P=0.001 vs HF, OR=5.58, CI=2.01-15.48; P<0.001 vs Transplant, OR=4.98, CI=2.03-12.21) and were possibly more worried by confidentiality issues. These findings highlight the need for strict legislation and proper educational strategies directed at the general population to facilitate the clinical implementation of pharmacogenomics.

In vivo evaluation of ammonia plasma modified ePTFE grafts for small diameter blood vessels replacement. A preliminary report.

BACKGROUND: Today, saphenous veins are most frequently used to reconstruct occluded or diseased small diameter vessels (< or =6 mm in diameter). However, these veins are unavailable in 30-40% of patients. In such a situation, prosthetic grafts provide the only alternative. Since an endothelial cell (EC) lining, important for maintaining a haemostatic-thrombotic balance, does not develop onto the intima of implanted grafts in humans, these grafts occlude within a short period of time. The failure of vascular grafts is attributed to their characteristics which are nonconducive towards endothelial cell adhesion, spreading and growth. In order to examine whether the patency of vascular grafts can be improved by the surface modification of grafts' intima, small diameter grafts were modified by a novel ammonia plasma treatment to enhance their interactions with EC. METHODS: Through laparotomy, ammonia plasma treated ePTFE (4 mm in diameter) grafts (n=3) and control untreated grafts (n=6) were implanted into the distal infrarenal aorta of rabbits. At appropriate time, grafts and adherent tissue were removed, fixed, stained and embedded in Poly/Bed 812. Light microscopic examination of thin sections cut from the proximal and distal anastomatic and midportion segments of explanted grafts was carried out. RESULTS: In control group studies, all animals developed lower limb paraplegia within seven days of implantation. Light microscopic examination of explanted control grafts showed that control grafts were obstructed by thrombosis/intimal hyperplasia. However, ammonia plasma modified explanted grafts, after one month of transplantation, revealed an endothelial cell-like lining that covered the grafts' inner surfaces. Accordingly, these grafts remained patent in animals. CONCLUSIONS: The grafts' surfaces that are made conducive to EC adhesion and proliferation and host response may influence endothelial regeneration. It is hoped that the combination of angiogenic molecules (i.e. endothelial cell specific growth factors such as VEGF) with ammonia plasma modified grafts may provide further insight into the development of ideal small diameter prosthesis.

Enhanced growth of animal and human endothelial cells on biodegradable polymers.

Biodegradable polymers such as poly(L-lactic acid) (PLLA), poly(glycolic acid) (PGA) and PGA coated with PLLA are being employed for cell transplantation and for in vivo regeneration of vascular tissue. Ingrowth and organization of fibrovascular tissue inside polymer scaffolds lead to the occlusion of the regenerated blood vessel. In order to provide regulatory mechanisms to control the development of an inner capsule, endothelialization of these materials is necessary. To achieve this, we employed a novel ammonia plasma technique to surface modified PLLA substrates. Human endothelial cell (HUVEC) and rabbit microvascular endothelial cell (RbMVEC) growth was studied on modified PLLA and control PLLA. Our studies show that modified PLLA and fibronectin (Fn)-coated modified PLLA exhibited statistically significant improvement in HUVEC and RbMVEC growth (P<0.001) when compared to PLLA and Fn-coated PLLA. Therefore, ammonia plasma treatment gives us the unique capability of modifying prosthetic biomaterials of various constructs with the eventual transplantation of mammalian cells to be used in tissue engineering or as biological implants.