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Biomedical subjects

George Hamilton

Publications and source records attributed to George Hamilton.

At least 19 recordsLinked to original sources
PubMed2007

Addressing thrombogenicity in vascular graft construction.

Thrombosis is a major cause of poor patency in synthetic vascular grafts for small diameter vessel (< 6 mm) bypass. Arteries have a host of structural mechanisms by which they prevent triggering of platelet activation and the clotting cascade. Many of these are present in vascular endothelial cells. These mechanisms act together with perpetual feedback at different levels, providing a constantly fine-tuned non-thrombogenic environment. The arterial wall anatomy also serves to promote thrombosis as a healing mechanism when it has been severely injured. Surface modification of synthetic graft surfaces to attenuate the coagulation cascade has reduced thrombosis levels and improved patency in vitro and in animal models. Success in this endeavor is critically dependent on the methods used to modify the surface. Platelets adhere to positively charged surfaces due to their own negative charge. They also preferentially attach to hydrophobic surfaces. Therefore synthetic graft development is concerned with hydrophilic materials with negative surface charge. However, fibrinogen has both hydrophilic and hydrophobic binding sites-amphiphilic materials reduce its adhesion and subsequent platelet activation. The self-endothelializing synthetic graft is an attractive proposition as a confluent endothelial layer incorporates many of the anti-thrombogenic properties of arteries. Surface modification to promote this has shown good results in animal models. The difficulties experienced in achieving spontaneous endothelialisation in humans have lead to the investigation of pre-implantation in vitro endothelial cell seeding. These approaches ultimately aim to result in novel synthetic grafts which are anti-thrombogenic and hence suitable for coronary and distal infrainguinal bypass.

Arteries↗
PubMed2006

Incorporation of a lauric acid-conjugated GRGDS peptide directly into the matrix of a poly(carbonate-urea)urethane polymer for use in cardiovascular bypass graft applications.

Gly-Arg-Gly-Asp-Ser (GRGDS) was modified by conjugation to lauric acid (LA) to facilitate incorporation into the matrix of a poly(carbonate-urea)urethane (PCU) used in vascular bypass grafts. GRGDS and LA-GRGDS were synthesized using solid phase Fmoc chemistry and characterized by high performance liquid chromatography and Fourier transform infrared spectroscopy. LA-GRGDS was passively coated and incorporated as nanoparticle dispersion on the PCU films. Biocompatibility of the modified surfaces was investigated. Endothelial cells seeded on LA-GRGDS coated and incorporated PCU showed after 48 h and 72 h a significant (p < 0.05) increase in metabolism compared with unmodified PCU. The platelet adhesion and hemolysis studies showed that the modification of PCU had no adverse effect. In conclusion, LA-conjugated RGD derivatives, such as LA-GRGDS, that permit solubility into solvents used in solvent casting methodologies should have wide applicability in polymer development for use in coronary, vascular, and dialysis bypass grafts, and furthermore scaffolds utilized for tissue regeneration and tissue engineering.

Blood Platelets↗
PubMed2006

Statins and peripheral arterial disease: potential mechanisms and clinical benefits.

Peripheral arterial disease (PAD) is a manifestation of widespread atherosclerosis. Lipid modification (especially with statins) is a component of the treatment of patients with PAD since this condition is considered a coronary heart disease equivalent. This review considers the mechanism of action of statins in PAD. Statins have been shown to reduce the incidence of new coronary events in patients with PAD. However, surveys suggest that many such patients remain undertreated. Statins can also increase walking distance in patients with PAD. There is also evidence that statins can improve renal function in these patients. Several other actions of statins are considered in this review. PAD patients have an increased morbidity and mortality, largely due to myocardial infarction and stroke. Recognizing and treating these high-risk patients as early as possible should be a priority.

Animals↗
PubMed2006

Polyhedral oligomeric silsequioxane-polyurethane nanocomposite microvessels for an artificial capillary bed.

Fabricating artificial vascularised tissue would involve tissue-engineering techniques, but current technology limits this as cultured cells depend on growth media in vitro and on diffusion in vivo. Therefore, there is a need to construct a synthetic microvascular network, which would sustain these cultured cells in a similar manner to normal tissue. This is again hampered by the poor patency rates of current microvascular grafts. Based on our previous work on polyhedral oligomeric silsesquioxane-polyurethane nanocomposites, which have shown the unique ability to repel coagulant proteins whilst still allowing endothelialisation, we have now developed a new generation of microvascular prosthesis using this polymer. Using these dip-coated nanocomposite microvessels, we have shown that it is possible to mimic the hydraulic conductivity and pressure-responsive radial compliance characteristics of biological microvessels. This would allow nutrient exchange across its walls as well as minimise compliance mismatch throughout the physiological pressure range thus reducing intimal hyperplasia in the long term. This microvessel would have the following implications: (1) as a microvascular substitute to vein grafts and (2) in the future as a component of a microvascular network.

Biocompatible Materials↗
PubMed2006

Recognition and management of abdominal compartment syndrome in the United Kingdom.

OBJECTIVE: Abdominal compartment syndrome(ACS) is a condition associated with high mortality if undiagnosed and untreated. ACS is seen in patients managed in intensive care units. Very little is known on the causes, diagnosis and treatment of this condition in the United Kingdom. DESIGN: Questionnaire study. SETTINGS: 222 intensive care units in the UK dealing with acute abdominal condition. RESULTS: 127 (57.2%) questionnaires were returned (32 from teaching hospitals and 95 from district general hospitals. Among these, 96.9% of teaching hospitals and 72.6% of district general hospitals had seen cases of ACS. The conditions most frequently associated with ACS were small and large bowel surgery (67%), vascular surgery (62%) and trauma (60%). ACS was suspected mainly when there was a distended abdomen (98.6%), oliguria (94.5%) and increased ventilatory support (72.2%). The diagnosis was confirmed either clinically (68.4%) or by measuring intra-abdominal pressure (83.7%). The commonest method for measuring intra-abdominal pressure was the intra-vesical route. The pressure threshold for diagnosing the condition was variable, with a range of 11-50 mmHg. There was a large variation in the number of patients who were decompressed. CONCLUSION: Fewer patients are diagnosed with ACS in district general hospitals compared with teaching hospitals. The threshold for the diagnosis of ACS is variable in the UK, as were the numbers of patients who were decompressed, suggesting that many doctors are still reluctant to accept this condition. This study would suggest that there is a need for standardisation of diagnostic threshold and protocols regarding decompression in ACS.

Compartment Syndromes↗
PubMed2006

Critical parameter of burst pressure measurement in development of bypass grafts is highly dependent on methodology used.

BACKGROUND: Because of the low patency rate of currently available vascular bypass grafts, researchers are working towards the development of alternative bypass grafts, ranging from synthetic prostheses to wholly biologic living grafts. The philosophy of measurement required by regulatory agencies such as the United States Food and Drug Administration (FDA) as well as to gain the Conformité Européene (CE) mark is to test above and beyond the limits that would be expected physiologically. The critical parameter of burst pressure is needed for Conformité Européene (CE) mark or United States Food and Drug Administration (FDA) approval before clinical trials can proceed. An accurate measurement of burst pressure in potential porous vascular bypass grafts is, therefore, of utmost importance to ensure adequate strength on implantation in animals and subsequent clinical use. A wide range of methods to measure burst pressure have been used. We tested the burst pressure of a new polyurethane-based nanocomposite vascular prosthesis by using different methods to assess whether the method used affected the results. METHODS: Water was infused at flow rates of 0.2, 50, and 100 mL/min through a syringe pump into latex sleeve-lined porous prostheses manufactured from a poly(carbonate-urea)urethane nanocomposite incorporating silsesquioxane. At the lowest infusion rate, the inflation was done with and without a nonporous inner lining sleeve. A pressure transducer was used to record the peak pressure achieved. RESULTS: Using a nonporous sleeve resulted in a higher burst pressure (428 mm Hg vs 341 mm Hg) at a flow rate of 0.2 mL/min. A lower infusion rate (0.2 mL/min) produced a lower burst pressure than 50 mL/min (428 mm Hg vs 451 mm Hg). No significant difference was found in burst pressure using infusion rates of 50 mL/min and 100 mL/min. CONCLUSIONS: The use of a nonporous sleeve removes the potential weakness presented by the pores themselves. A continuous high infusion rate consistently overestimates burst pressure. These methods may not reflect the physiologic state. Care needs to be taken in interpretation of methodology for burst pressure measurement, and the rate of infusion should be stated in any description of the method. CLINICAL RELEVANCE: The poor patency of small-caliber vascular bypass prostheses has stimulated a large body of research into alternative graft materials. This includes synthetic and, more recently, tissue-engineered hybrid products. Acceptance for international standards requires demonstration of a rigorous mechanical testing regimen, including graft strength, which has on the whole involved burst strength measurement. However, the methods used to measure burst strength have varied with respect to apparatus used and rate of graft inflation. We show that these variables lead to markedly different results. In particular, fast infusion rates may overestimate the actual burst pressure, leading to a false sense of security.

Biocompatible Materials↗
PubMed2006

The effect of shear stress on human endothelial cells seeded on cylindrical viscoelastic conduits: an investigation of gene expression.

The present study assesses the effect of physiological shear stress on gene expression from human ECs (endothelial cells) seeded on a small-diameter cylindrical bypass graft constructed from nanocomposite based on poly(carbonate-silsesquioxane-bridge-urea)urethane. ECs were seeded on to 5-mm-diameter conduits, placed in a physiological flow circuit and exposed to 1 or 4 h of shear stress at 1.4+/-0.3 Pa. Subsets of conduits were incubated at 37 degrees C and 5% CO2/95% O2 for a further 4 h to determine if gene expression returned to basal levels. PCR was conducted for glyceraldehyde-3-phosphate dehydrogenase, TGFbeta-1 (transforming growth factor beta-1), COL-1 (collagen-1) and PECAM-1 (platelet/EC adhesion molecule-1). Increases in gene expression were seen following flow in nanocomposite conduits. These were significant at 4 h for TGFbeta-1, COL-1 and PECAM-1. After a 4 h recovery period, there were no significant differences in gene intensity, suggesting that this change is transient. These data prove that mRNA can be obtained from ECs seeded on tubular conduits and exposed to shear stress and that gene-expression studies can be successfully carried out. We believe this is a substantial improvement on studies based on flat sheets.

Biomimetic Materials↗
PubMed2006

Vitreous cryopreservation maintains the viscoelastic property of human vascular grafts.

Assess the effects of cryopreservation (cryo) and vitrification (vitro) on the viscoelastic properties of blood vessels. Human external Iliac artery vessels were harvested from liver organ donors (n=8). In each case the vessel was segmented into 3 equal parts, which were randomly placed in one of 3 categories: Fresh (stored in 4 degrees C UW for 6 h), Cryo (Placed in 10% Dulbecco's modified Eagle medium (DMEM) and slowly frozen to -196 degrees C), or Vitro (Placed in 40% DMEM and rapidly cooled to -196 degrees C). A pulsatile flow circuit was used to perfuse arterial segments at physiological pulse pressure and flow. Intraluminal pressure was measured using a Millar Mikro-tip catheter transducer, and vessel wall motion was determined with duplex ultrasonography coupled with a novel echo-locked vessel wall tracking system. Diametrical compliance (DC), Petersons elastic modulus (Ep), and stiffness index (beta) were then calculated for each of the three groups over 3 mean pressure ranging from 40 to 80 mmHg. The change in the viscous component of arterial wall (lag phase angle, theta) was calculated from hysteresis plots. No significant changes were observed in the elastic properties of fresh and vitrified vessels (P>0.05 for each of DC, Ep, and beta). Similarly, variation in the wall viscosity between fresh and vitrified vessels appeared to be nonsignificant (theta=12.60+/-4.04 vs. 17.60+/-1.14, respectively). In contrast, statistical analysis of results obtained for cryopreserved vessels to the fresh vessels showed significant reduction in elastic parameter values. There was also a significant increase in the phase angle theta of the cryopreserved vessels (theta=24.30+/-6.32; P<0.001) compared with fresh vessel. Results suggest that vitrification maintains both elastic and viscous components of the mechanical properties of vascular grafts, which is positively correlated with their functional patency. In contrast, damage caused during cryopreservation significantly affects the overall tensile strength and elasticity of the vessel (i.e., Ep and beta), the dynamic properties (DC), and appears to significantly affect the viscous component of the vessel wall (theta), which is likely reduce the patency of the graft for transplantation purposes.

Cryopreservation↗
PubMed2006

Is there an alternative to systemic anticoagulation, as related to interventional biomedical devices?

To reduce the toxic effects, related clinical problems and complications such as bleeding disorders associated with systemic anticoagulation, it has been hypothesized that by coating the surfaces of medical devices, such as stents, bypass grafts, extracorporeal circuits, guide wires and catheters, there will be a significant reduction in the requirement for systemic anticoagulation or, ideally, it will no longer be necessary. However, current coating processes, even covalent ones, still result in leaching followed by reduced functionality. Alternative anticoagulants and related antiplatelet agents have been used for improvement in terms of reduced restenosis, intimal hyperphasia and device failure. This review focuses on existing heparinization processes, their application in clinical devices and the updated list of alternatives to heparinization in order to obtain a broad overview, it then highlights, in particular, the future possibilities of using heparin and related moieties to tissue engineer scaffolds.

Anticoagulants↗
PubMed2006

Vulnerability assessment of New Jersey's food supply to invasive species: the New Jersey IMPORT project.

The United States' environment and economy have been severely impacted by unintentionally introduced biological organisms for the last 100 years. Our ecosystems and biological reserves of conservation importance are regularly invaded by non-indigenous species. To help prevent future invaders from entering the ports, this project undertaken at the Port of Elizabeth proposed to: 1. Catalog the different vegetable and fruit crops entering this country; 2. Evaluate the potential risk to New Jersey crops that an introduced exotic pest might pose; and 3. Evaluate the potential that imported crops entering the U.S. have for harboring exotic pests. The New Jersey IMPORT report, or Invasive Management Promoting Open and Responsible Trade project, details a newly designed ecological risk assessment tool to evaluate entry potential of invasive pests at the Port of Elizabeth. Risk designations were assigned to shipments of four fruits; seven vegetables; and two field/forage crops based on: i) Country of origin; ii) Amounts of commodities imported; and iii) Endemic pests present in exporting countries. Between 5,000 and 180,000 tons of crops were imported into the Port of Elizabeth from October 2001 to 2003. Pest risk analyses were drafted for twenty-five intercepted insects taken from the Port Information Network. In addition, eighteen pest risk analyses were drafted for invasive fungi, bacteria, and viruses of global concern as alerted by ProMed Digest. It was concluded that three crops imported remain at high risk: apples, peppers, and tomatoes. Peaches, soybeans, lettuce, sweet corn, potatoes, squash, and eggplant imported were considered moderate risk. Blueberries, cranberries, and alfalfa were considered low risk.

Animals↗
PubMed2005

Cardiovascular tissue engineering: state of the art.

In patients requiring coronary or peripheral vascular bypass procedures, autogenous arterial or vein grafts remain as the conduit of choice even in the case of redo patients. It is in this class of redo patients that often natural tissue of suitable quality becomes unavailable; so that prosthetic material is then used. Prosthetic grafts are liable to fail due to graft occlusion caused by surface thrombogenicity and lack of elasticity. To prevent this, seeding of the graft lumen with endothelial cells has been undertaken and recent clinical studies have evidenced patency rates approaching reasonable vein grafts. Recent advances have also looked at developing a completely artificial biological graft engineered from the patient's cells with surface and viscoelastic properties similar to autogenous vessels. This review encompasses both endothelialisation of grafts and the construction of biological cardiovascular conduits.

Animals↗
PubMed2005

Current status of prosthetic bypass grafts: a review.

Polymers such as Dacron and polytetrafluoroethylene (PTFE) have been used in high flow states with relative success but with limited application at lower flow states. Newer polymers with greater compliance, biomimicry, and ability to evolve into hybrid prostheses, suitable as smaller vessels, are now being introduced. In view of the advances in tissue engineering, this makes possible the creation of an ideal off-the-shelf bypass graft. We present a broad overview of the current state of prosthetic bypass grafts.

Animals↗
PubMed2005

Development of an RNA isolation procedure for the characterisation of human endothelial cell interactions with polyurethane cardiovascular bypass grafts.

To date no reliable method has been developed for the isolation of RNA from cells seeded onto cylindrical vascular grafts. This study was performed in order to develop a reliable methodology for isolating RNA from cylindrical conduits made from poly(carbonate-urea)urethane (PU). Human umbilical vein EC were seeded onto PU vascular grafts and an Alamar blue assay performed to assess cell viability. Cells were prepared for RNA extraction by trypsinisation, cell scraping and direct application of cell lysis buffer. In all cases RNA was extracted using a "Qiagen RNeasy" kit. Alamar blue showed viable cells were present on all of the seeded PU vascular grafts. Levels of RNA extracted from the cells removed from the graft by the trypsinisation yielded 0.130 microg/microl, by scraping 0.078 microg/microl and by direct lysing 0.093 microg/microl of RNA, respectively. RTPCR was conducted successfully for GAPDH and TGF-beta1. Trypsinisation prior to RNA extraction provided the highest RNA yield and attained near complete cell removal ensuring that gene expression obtained was representative.

Biocompatible Materials↗
PubMed2005

Measurement of critical lower limb tissue hypoxia by coupling chemical and optical techniques.

It has been a long-term goal to develop non-invasive methods that can detect critical levels of tissue hypoxia to help in the management of chronic lower limb ischaemia. In the present study, skeletal muscle oxygenation was measured using a new Clark-type TCPO2 [transcutaneous PO2 (partial pressure of O2)]/PCO2 (partial pressure of CO2) monitoring system and optical NIRS (near-infrared spectroscopy) at graded levels of hypoxaemia using a rabbit model (n=6). The TCPO2/PCO2 probe was placed on the shaved hindlimb to record SPO2 (skin PO2) and SPCO2 (skin PCO2) continuously. A pair of NIRS probes were placed on the limb to monitor HbO2 (oxyhaemoglobin) and Hb (deoxyhaemoglobin). Graded hypoxaemia was achieved by stepwise reductions of FiO2 (fraction of inspired O2) from 30% to 6%. Animals were allowed to recover after each episode of hypoxia at an FiO2 of 30% as indicated by normalized arterial blood PO2. There was a significant (P<0.05) decrease in SPO2 with all grades of hypoxaemia and no significant changes in SPCO2. There was a significant (P<0.05) increase in muscle Hb with all grades of hypoxaemia and a significant (P<0.05) decrease in HbO2 when FiO2 was below 15%. A significant correlation was found between the SPO2 and HbO2 (r=0.92, P<0.001) and both were significantly correlated with arterial blood PO2 (P<0.001). The new TCPO2/PCO2 system, in addition to its application for the assessment of conditions such as chronic venous insufficiency where alteration in skin oxygenation occurs solely, also has potential in conditions such as peripheral vascular disease where both skin and muscle oxygenation may be affected.

Animals↗
PubMed2005

Single stage cell seeding of small diameter prosthetic cardiovascular grafts.

Small-diameter prosthetic cardiovascular bypass grafts have high occlusion rates. Thrombogenicity caused by the lack of endothelial cells (ECs) on the luminal surface of the grafts is one of the main reasons for its occlusion. One strategy to improve the clinical performance of cardiovascular prosthetic grafts has been to seed its luminal surface with a monolayer of the patient's own ECs. In this strategy a "two stage" seeding procedure is utilized whereby cells obtained from a vein are amplified in cell culture, then seeded onto a fibrin-arginine-glycine-aspartate (RGD) tripeptide-enriched expanded polytetrafluoroethylene (ePTFE) graft in a rotating bioreactor for one week, after which it is surgically implanted. This achieves patency rates approaching those of vein grafts. The disadvantage of two stage seeding is that it requires culture facilities, a large amount of RGD, which is expensive and is confined to elective cases because of the delay between cell cultivation, seeding, and graft implantation. A single stage seeding using freshly extracted ECs that is transplanted onto the graft at the same time frame of the bypass operation without the need for cell cultivation would be an ideal answer for the disadvantages of two stage seeding. Animal trials have been successful but human trials of single stage seeding have been disappointing. It has been hypothesized that extracted ECs are scarce, furthermore, they are washed off the graft surface once exposed to blood flow. This review examines the various techniques/technologies to improve endothelial cell extraction from various sources and retention onto the luminal surface of prosthetic cardiovascular grafts in order to develop a clinically applicable strategy for single stage seeding.

Animals↗