Impregnation of the the polymeric graft with adhesives molecules, typically oligopeptides or glycoprotein improves retention.
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Biomedical subjects
Publications and source records attributed to George Hamilton.
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In patients requiring coronary or peripheral vascular bypass procedures, autogenous vein is currently the conduit of choice. If this is unavailable, then a prosthetic material is used. Prosthetic graft is liable to fail due to occlusion of the graft. To prevent graft occlusion, seeding of the graft lumen with endothelial cells is undertaken. Recent advances have also looked at developing a completely artificial biological graft engineered from the patient's cells with properties similar to autogenous vessels. This review encompasses the developments in the two principal technologies used in developing hybrid coronary and peripheral vascular bypass grafts, that is, seeding and tissue engineering.
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The aim of sodding prosthetic grafts with endothelial cells (EC) is to establish a functioning antithrombogenic monolayer of EC. Application of basement membrane proteins improves EC adherence on ePTFE grafts. Their addition to a biodurable compliant poly(carbonate-urea)urethane graft (CPU) was studied with respect to EC adherence. Preclot, fibronectin, gelatin, and collagen were coated onto CPU. RGD peptide, heparin, and both RGD and heparin were chemically bonded to CPU. Human umbilical vein EC (HUVEC) labeled with 111-Indium oxine were sodded (1.8 x 10(6) EC/cm(2)) onto native and the modified CPU. The grafts were washed after 90 min and EC retention determined. The experiments were repeated six times. EC retention on native CPU was 1.0 +/- 0.2 x 10(5) EC/cm(2). The application of preclot, fibronectin, gelatin, and collagen did not improve EC retention, which was 0.8 +/- 0.1, 0.4 +/- 0.1, 0.3 +/- 0.08, and 0.5 +/- 0.2 x 10(5) EC/cm(2), respectively. Bonding RGD, heparin, and both RGD and heparin significantly improved EC retention to 1.9 +/- 0.6, 1.7 +/- 0.5, and 2.6 +/- 0.6 x 10(5) EC/cm(2), respectively (p < 0.01). Bonding of RGD, heparin, and both RGD and heparin accelerates and enhances EC retention onto CPU. Simple coating of basement membrane proteins confers no advantage over native CPU.
Tissue engineering of endothelial cells (EC) and chemical engineering with anticoagulant moieties has been undertaken in order to improve prosthetic graft patency and thrombogenicity. This was done by covalently bonding a compliant poly(carbonate-urea)urethane graft (MyoLink) with arginine-glycine-aspartate (RGD) or/and heparin (Hep) to ascertain whether EC retention could be improved. The retention of these moieties and EC was assessed after exposure to pulsatile flow. We covalently bonded RGD, Hep, and RGD/Hep onto the luminal surface of MyoLink using spacer arm technology. Narrow-beam X-ray photoelectron spectroscopy was carried out to check the efficiency of the bonding. EC were radiolabeled and seeded onto native MyoLink and with 1) RGD-, 2) Hep-, and 3) RGD/Hep-bonded grafts and exposed to shear stress in a physiological flow circuit for 6 h, which reproduces femoral artery flow waveforms and pulsatility. Results were recorded on a gamma camera imaging system. Viability of cells was tested with a modified Alamar Blue assay (ABA) and scanning electron microscopy for morphological appearance of seeded cells. Experiments were repeated (n=6). RGD, Hep, and RGD/Hep were bonded together in a uniform distribution on the luminal surface of each graft type, and bioactivity of each moiety covalently bonded was very high. In the flow circuit, there was exponential cell retention for the first 60 min of flow for all the grafts, but after 6 h of exposure to pulsatile flow the RGD/Hep-bonded graft had a significantly better cell retention rate than native MyoLink (75.7%+/-2.3 vs. 60.5+/-10.1, P<0.05). ABA test showed that all the seeded cells postexposure to flow were viable, and significantly higher metabolic activity was recorded on a RGD/Hep-bonded graft than with MyoLink-seeded graft (P<0.01). Using RGD/Hep covalently bonded onto graft surfaces improves cell retention and provides an antithrombogenic surface for initial blood flow in vivo until full EC activity develops postseeding. This would allow the development and further improvement of hybrid grafts.
We implemented a 2-yr program to reduce organophosphorus and carbamate insecticide use and mitigate their associated risks as they relate to peach production in New Jersey and elsewhere. The main thrust integrated mating disruption with ground cover management practices to reduce oriental fruit moth, Grapholita molesta (Busck) (Lepidoptera: Tortricidae), and tarnished plant bug, Lygus lineolaris (Palisot de Beauvois) (Heteroptera: Miridae), abundance and damage. This Reduced Risk Peach Arthropod Management Program was compared with adjacent conventionally managed peach orchards. In 1999, we found 2.3 times fewer L. lineolaris and stink bugs (Euschistus servus (Say), E. tristigmus (Say), Acrostemum hilare (Say) (Heteroptera: Pentatomidae) and 2.0 times less heteropteran damaged peaches in reduced-risk orchards when compared with conventionally managed orchards. In 2000, we observed 4.9 times fewer heteropteran insects in reduced-risk orchards but damage levels were not significantly different between the two programs. In both years, G. molesta mating disruption gave at least 4 mo of noninsecticidal control of this major pest. The reduced-risk program provided a level of pest control that was equal to or better than conventional peach pest management programs while using fewer organophosporus and carbamate insecticides.
The objective of this study was to investigate the effects of lipid-lowering treatment on renal function in patients with peripheral arterial disease (PAD). This was a retrospective study of hyperlipidemic claudicants referred to a vascular surgery and risk modification clinic. Serum creatinine and urate concentrations and the fasting lipid profile were measured pretreatment and after 3-4 months of treatment with 20 mg/day simvastatin. In 103 consecutive patients with PAD (57 men; 46 women), median age 67 years (range: 51 to 83) there was a significant decrease in serum creatinine from a mean (SD) of 87 (12) micromol/L pretreatment to 84 (12) micromol/L post-treatment (p<0.0001). This difference was more marked in the tertile of patients with the highest baseline creatinine levels. There was also a significant reduction in serum urate from 0.37 (0.07) mmol/L to 0.35 (0.07) mmol/L (p<0.0001). Both these effects were independent of the degree of total cholesterol (TC) or low-density lipoprotein (LDL) cholesterol reduction. There was a significant reduction in TC from 6.6 (1.0) to 5.2 (0.8) mmol/L and LDL cholesterol from 4.3 (1.0) to 2.8 (0.7) mmol/L; both p<0.0001. Significant improvement also occurred in the high-density lipoprotein cholesterol and triglyceride levels. Cholesterol lowering with simvastatin 20 mg/day improved indices of renal function after 3-4 months of treatment in hyperlipidemic patients with PAD. Further studies are needed to establish and define the clinical relevance of these findings, especially in patients with different degrees of renal failure.
Peripheral arterial disease (PAD) is underdiagnosed and undertreated. This is despite the high vascular morbidity and mortality rates associated with PAD. There is also evidence that quitting smoking, improving the lipid profile, lowering the blood pressure, and administering antiplatelet drugs reduce the risk of vascular events in these patients. Secondary prevention for patients with PAD is yet to meet the standard of care for those with ischemic heart disease. The authors surveyed 200 claudicants attending a vascular clinic with additional follow-up in a risk modification clinic. After a median follow-up of 28 months (range: 6-65) there was a significant (p = 0.001) improvement in walking distance; 34 patients (17%) had a vascular ischemic event. Of those, 11 patients (5.5%) had worsening intermittent claudication and 9 had a stroke/transient ischemic attack; 9 events (4.5%) were fatal. The lipid targets were met in 76% the patients. Half the smokers quit smoking and 94% of the patients were taking antiplatelet drugs or anticoagulants. Blood pressure reached the accepted target in 87% of the patients. Secondary prevention in patients with PAD may reduce the risk of vascular events. Aggressive risk modification is therefore recommended.