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Biomedical subjects

George Hamilton

Publications and source records attributed to George Hamilton.

At least 37 records · Page 2Linked to original sources
PubMed2004

Prevention of contrast-induced nephropathy in vascular patients undergoing angiography: a randomized controlled trial of intravenous N-acetylcysteine.

OBJECTIVE(S): Apart from proper hydration, only oral N-acetylcysteine (NAC) has shown efficacy in reducing radiographic contrast media (RCM)-induced acute renal failure, though its benefit has been challenged. We investigated the effect of intravenous (i.v.) NAC on renal function in patients with vascular disease receiving RCM for angiography. METHODS: Single-center, randomized, double-blind, placebo-controlled trial. Based on a previous study, a trial with 44 patients each in placebo and treatment arms would give at least 80% power to show a statistically significant difference at the 5% level. Vascular patients undergoing angiography were consented and segregated into those whose serum creatinine (SC) level was normal or raised (men >1.32 mg/dl; women >1.07 mg/dL). All patients received 500 mL i.v. normal saline 6 to 12 hours prior to and then after angiography. Groups with normal SC and raised SC were randomly assigned to either 1 g of NAC with normal saline before and after angiography or nothing (placebo). Main outcome measures were change in SC and creatinine clearance (CrCl) as measured 1, 2, and 7 days postangiography (with comparison between active and placebo groups using unpaired t test) and incidence of acute renal decline (>25% or 0.5 mg/dL rise in SC) at 48 hours (with comparison between active and placebo using the Fisher exact test). RESULTS: Forty-six patients received NAC (29 normal SC, 17 raised SC), and 48 received placebo (27 normal SC, 21 raised SC). There was no significant difference in postangiography SC or CrCl at any of the time points measured between NAC and placebo in patients with either normal or raised SC. In the raised SC group, 3 patients from both the NAC and placebo groups suffered acute renal declines. Importantly, at 48 hours, the impaired SC group had a significant reduction in CrCl (-14% +/- 41% vs +18% +/- 58%: P = .0142) and a significant rise in SC (+7.0 +/- 25% vs -1.6% +/- 10%; P = .0246) when compared with the normal SC group. CONCLUSIONS: NAC (i.v. at 1 g) precontrast and postcontrast does not confer any benefit in preventing RCM-induced nephropathy in vascular patients. Patients with pre-existing raised SC have an increased risk of renal impairment as defined by a fall in CrCl and a rise in SC post-RCM when compared with patients with normal SC who appear to benefit from hydration.

Acetylcysteine↗
PubMed2004

The use of animal models in developing the discipline of cardiovascular tissue engineering: a review.

Cardiovascular disease remains one of the major causes of death and disability in the Western world. Tissue engineering offers the prospect of being able to meet the demand for replacement of heart valves, vessels for coronary and lower limb bypass surgery and the generation of cardiac tissue for addition to the diseased heart. In order to test prospective tissue-engineered devices, these constructs must first be proven in animal models before receiving CE marking or FDA approval for a clinical trial. The choice of animal depends on the nature of the tissue-engineered construct being tested. Factors that need to be considered include technical requirements of implanting the construct, availability of the animal, cost and ethical considerations. In this paper, we review the history of animal studies in cardiovascular tissue engineering and the uses of animal tissue as sources for tissue engineering.

Animals↗
PubMed2004

Shear-stress preconditioning and tissue-engineering-based paradigms for generating arterial substitutes.

In situ tissue engineering using shear-stress preconditioning and adhesive biomolecules is a new approach to autologous tissue engineering. In the present study, novel tissue-engineering grafts (TEGs) were preconditioned within an in vitro pulsatile flow circuit, with and without the addition of fibronectin (FN), to establish whether low-shear-stress conditions promoted endothelial cell (EC) retention and differentiation. TEGs ( n =24) were generated by the contraction and compaction of collagen(I) by porcine aortic smooth-muscle cells (SMCs) on to a compliant polyester graft scaffold. ECs were radiolabelled with [(111)In]indium tropolonate and seeded on to the luminal surface of the TEGs. Following organ culture in a bioreactor (7 days), TEGs were split into four groups ( n =six TEGs per group): Group A acted as controls with TEGs unmodified and seeded with radiolabelled ECs; Group B underwent luminal pre-coating with FN (75 microg/ml) prior to EC seeding; Group C underwent preconditioning within a pulsatile flow circuit at 10-20 microN (1-2 dyn)/cm(2) for 7 days prior to EC seeding, and Group D TEGs were preconditioned for 7 days at 1-2 dyn/cm(2), followed by luminal pre-coating with FN prior to EC seeding. The resistance to physiological shear stress of the seeded ECs was assessed using a gamma-radiation counter within a physiological flow circuit producing an arterial waveform with a mean shear stress of 93.2 microN (9.32 dyn)/cm(2). Environmental scanning electron microscopy (ESEM) was used to determine the distribution and degree of differentiation of the attached Ecs, and tissue-type-plasminogen-activator (tPA) assays provided a measure of function and viability. EC resistance to shear stress at 93.2 microN/cm(2) was significantly enhanced by a period of preconditioning (Group C) at 10-20 microN/cm(2), surface modification with FN (Group B), or both (Group D) when compared with control grafts (Group A). However, TEGs coated with FN whether preconditioned (Group D) or not (Group B) demonstrated the best results for EC retention. ESEM demonstrated near-confluent differentiated flattened ECs in both these cases. EC function was demonstrated by a steady increase in tPA production. Low-shear-stress preconditioning of TEGs enhances EC retention in vitro with an additional advantage demonstrated by pre-treatment with FN prior to endothelialization. These findings may be exploited in the development of tissue-engineered constructs to maintain a confluent endothelial lining.

Adaptation, Physiological↗
PubMed2004

Role of the Thrombelastograph as an adjunctive test in thrombophilia screening.

The Thrombelastograph (TEG) provides a global assessment of haemostatic function. We have investigated the potential role of TEG in thrombophilia testing by studying 87 consecutive patients (all with personal or family history of thrombosis). For each patient, routine thrombophilia screening tests and TEG were performed in parallel. In keeping with previous reports, at least one thrombophilic trait was identified in 34% of the patients. Among those patients with previous thrombosis, the yield from screening was higher (54% with prothrombotic trait). Overall, a hypercoaguable TEG was demonstrated in 45% of patients. However, TEG and standard thrombophilia testing did not necessarily identify the same subset of individuals. Of 39 patients with hypercoaguable TEG, only 17 had a demonstrable thrombophilic trait. Conversely, of 30 patients with proven thrombophilia, 17 also had a hypercoaguable TEG. We conclude that TEG cannot be used as a sole initial screening test in patients referred for thrombophilia testing, as it fails to identify 43% of underlying thrombophilic traits. However, TEG may be a useful adjunctive test, particularly in patients in whom the regular thrombophilia screen proves unremarkable. Prospective studies are warranted to determine whether a hypercoaguable TEG can be used to predict a subset of patients at increased risk for recurrent thrombotic events.

Adolescent↗
PubMed2003

Surface functionalization and grafting of heparin and/or RGD by an aqueous-based process to a poly(carbonate-urea)urethane cardiovascular graft for cellular engineering applications.

An aqueous-based process is reported for surface functionalization and grafting of anticoagulant and cell attachment moieties, such as heparin and/or arginine-glycine- aspartate (RGD) onto the lumenal surface of a prefabricated cardiovascular graft (5 mm i.d.) made of poly(carbonate- urea)urethane (MyoLink). It is a three-stage process, all aqueous: (1) hydroxylation using an azobis compound, particularly 2,2'-azobis(2-methylpropionamidine)dihydrochloride, which abstracts hydrogen via an electron transfer process from the polyurethane surface (strong oxygen purging); (2) grafting using the as-generated hydroxide groups to allow attachment of an acrylamide monomer using a conventional ceric ion technique (strong nitrogen purging); and (3) moiety attachment, preactivated with [1-ethyl-3-(3-dimethylaminopropyl)carbodiimide] in acidic solution. The technique was validated by attaching heparin and RGD/heparin to the MyoLink polymer. Following bonding, the graft segments were exposed to prolonged physiologic shear force in a flow circuit (10 h). The grafts first were analyzed by X-ray photoelectron spectroscopy (XPS) to determine the degree of attachment of the moieties and then by materials methods to assess whether any degradation of the graft material itself had occurred since polyurethanes with carbonate amorphous segments are readily susceptible to hydrolytic degradation following functionalization processes. XPS showed the moieties were present on the surface at a concentration of 10%. The S2p(3/2) states of sulfur indicated that there were high degrees of ionic covalent bonding, indicating high degrees of moiety bioactivity. Heparin was found to be present from the sulfur signal, namely NSO(3). RGD was found to be present from the nitrogen signal present at the binding energy of 399 eV. Macroscopic analysis and ESEM showed no signs of polyurethane degradation or small protuberances indicative of microgel formation. Quality control (QC) showed that the internal diameters and wall thicknesses of all the respective grafts postbonding remained within normal batch release limits (5 +/- 0.1mm, i.d.; 0.9 +/- 0.05 mm, wall thickness). Gel permeation chromatography (GPC) showed there were no statistical differences between the control, which was nonbonded (MN 45,300, MW 98,500, D 2.17) and all of the bonded samples, respectively (MN 41,800, MW 104,000, D 2.45). Radial tensile strength (RTS) analysis also showed that all of the respective samples postbonding (1.48N/mm) remained within batch release specifications (>1N/mm). A simple aqueous polymer surface functionalization and grafting technique has been developed for covalent bonding of anticoagulant and cell-attachment moieties onto poly(carbonate-urea)urethane(s) and has been validated by surface and materials analyses. The moieties were attached uniformly and were bioactive at a high surface density. No degradation in terms of a loss in mechanical properties was evident following bonding of the polyurethane.

Chromatography, Gel↗
PubMed2003

Differential diagnosis, investigation, and current treatment of lower limb lymphedema.

HYPOTHESIS: The causes and management of lower limb lymphedema in the Western population are different from those in the developing world. OBJECTIVE: To look at the differential diagnosis, methods of investigation, and available treatments for lower limb lymphedema in the West. DATA SOURCE: A PubMed search was conducted for the years 1980-2002 with the keyword "lymphedema." English language and human subject abstracts only were analyzed, and only those articles dealing with lower limb lymphedema were further reviewed. Other articles were extracted from cross-referencing. RESULTS: Four hundred twenty-five review articles pertaining to lymphedema were initially examined. This review summarizes the findings of relevant articles along with our own practice regarding the management of lymphedema. CONCLUSIONS: The common differential diagnosis in Western patients with lower limb swelling is secondary lymphedema, venous disease, lipedema, and adverse reaction to ipsilateral limb surgery. Lymphedema can be confirmed by a lymphoscintigram, computed tomography, magnetic resonance imaging, or ultrasound. The lymphatic anatomy is demonstrated with lymphoscintigraphy, which is particularly indicated if surgical intervention is being considered. The treatment of choice for lymphedema is multidisciplinary. In the first instance, combined physical therapy should be commenced (complete decongestive therapy), with surgery reserved for a small number of cases.

Diagnosis, Differential↗
PubMed2003

In vivo biostability of a poly(carbonate-urea)urethane graft.

In peripheral and coronary bypass surgery, the patency of prosthetic grafts is inferior to autologous vein, mainly due to intimal hyperplasia caused in part by compliance mismatch between rigid graft and elastic host artery. We have developed a compliant poly(carbonate-urea)urethane vascular graft "MyoLink" which was biostable in vitro degradation studies. To further investigate the biostability of this material, we report a long-term in vivo study on 8 beagle dogs (15+/-3 kg) implanted with this graft (ID 5mm) in the aorta-iliac position; three grafts were harvested at 18 months to assess short-term biodegradation, with one animal having died from an unrelated infection. The 4 remaining grafts were harvested at 36 months for analysis by: (1) histology, (2) compliance measurements and (3) environmental scanning electron microscopy (ESEM); gel permeation chromatography (GPC); attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and radial tensile strength analysis. There was no infection or inflammation of the grafts or surrounding tissues. Histological analysis showed a well-developed neointima but only at the distal anastomosis. There were no significant differences in compliance pre- and post-implantation and no evidence of material curvature, radial expansion or chemical breakdown, ESEM and GPC showed no signs of degradation. Peak height analysis with ATR-FTIR of the 1740 cm(-1) (C=O of carbonate) and 1253 cm(-1) bands (C-O-C of CO-O-C) showed a loss of carbonate carbonyl but was not statistically significant. Radial tensile strength remained within batch release specifications.This polyurethane graft retains its compliance post-implantation, whilst exhibiting only a minor hydrolysis of the amorphous segment, confirming its biostability in vivo up to 3 years.

Anastomosis, Surgical↗
PubMed2003

The influence of peripheral vascular disease on the carotid and femoral wall mechanics in subjects with abdominal aortic aneurysm.

AIM: Aortic and carotid stiffness is elevated in patients with abdominal aortic aneurysm (AAA). Peripheral vascular disease (PVD) frequently coexists with AAA and may further impair the arterial wall mechanics and increase the cardiovascular load. We therefore studied the elastic carotid and muscular femoral biomechanical properties and intima-media thickness (IMT) in this group of patients. METHODS: The elastic indices and IMTs of the common carotid and common femoral arteries were determined in 30 patients with AAA (15 with PVD) with a duplex scanner coupled with a wall tracking system. Fasting plasma creatinine level, glucose and lipid concentrations, and their physiologic variables known to influence the arterial wall mechanics were also assessed. RESULTS: Patients with AAA and PVD have significantly stiffer carotid (Petersen's elastic modulus, 2207 +/- 905 mm Hg versus 1268 +/- 432 mm Hg; P =.001; stiffness index, 22.73 +/- 9.63 versus 12.60 +/- 4.24; P =.001] and femoral (Petersen's elastic modulus, 4906 +/- 4057 mm Hg versus 2599 +/- 1169 mm Hg; P =.043; stiffness index, 49.02 +/- 40.04 versus 26.07 +/- 13.22; P =.044) arteries than subjects with AAA alone. Although patients with PVD have thicker carotid and femoral IMTs, no statistical difference was seen between the two groups. The subjects were matched for age, body mass index, heart rate, systolic and diastolic blood pressures, total vascular risk score, plasma creatinine level, and fasting lipid and glucose concentrations. CONCLUSION: Subjects with PVD and AAA have significantly stiffer carotid and femoral arteries, which may indicate increased cardiovascular load and may account for the highest mortality rate seen in these patients in the UK Small Aneurysm Trial. Therefore, treatment of associated cardiovascular risk factors is important and may have to be tailored on an individual basis according to the findings of the arterial wall mechanics.

Aged↗
PubMed2002

In vitro stability of a novel compliant poly(carbonate-urea)urethane to oxidative and hydrolytic stress.

Poly(ester)urethane and poly(ether)urethane vascular grafts fail in vivo because of hydrolytic and oxidative degradative mechanisms. Studies have shown that poly(carbonate)urethanes have enhanced resistance. There is still a need for a viable, nonrigid, small-diameter, synthetic vascular graft. In this study, we sought to confirm this by exposing a novel formulation of compliant poly(carbonate-urea)urethane (CPU) manufactured by an innovative process, resulting in a stress-free. Small-diameter prosthesis, and a conventional poly(ether)urethane Pulse-Tec graft known to readily undergo oxidation in a variety of degradative solutions, and we assessed them for the development of oxidative and hydrolytic degradation, changes in elastic properties, and chemical stability. To simulate the in vivo environment, we used buffered solutions of phospholipase A(2) and cholesterol esterase; solutions of H(2)O(2)/CoCl(2), t-butyl peroxide/CoCl(2) (t-but/CoCl(2)), and glutathione/t-butyl peroxide/CoCl(2) (Glut/t-but/CoCl(2)); and plasma fractions I-IV, which were derived from fresh human plasma centrifuged in poly(ethylene glycol). To act as a negative control, both graft types were incubated in distilled water. Samples of both graft types (100 mm with a 5.0-mm inner diameter) were incubated in these solutions at 37 degrees C for 70 days before environmental scanning electron microscopy, radial tensile strength and quality control, gel permeation chromatography, and in vitro compliance assessments were performed. Oxidative degradation was ascertained from significant changes in molecular weight with respect to a control on all Pulse-Tec grafts treated with t-but/CoCl(2), Glut/t-but/CoCl(2), and plasma fractions I-III. Pulse-Tec grafts exposed to the H(2)O(2)/CoCl(2) mixture had significantly greater compliance than controls incubated in distilled water (p < 0.001 at 50 mmHg). No changes in molecular weight with respect to the control were observed for the CPU samples; only those immersed in t-but/CoCl(2) and Glut/t-but/CoCl(2) showed an 11% increase in molecular weight to 108,000. Only CPU grafts treated with the Glut/t-but/CoCl(2) mixture exhibited significantly greater compliance (p < 0.05 at 50 mmHg). Overall, results from this study indicate that CPU presents a far greater chemical stability than poly(ether)-urethane grafts do.

Biocompatible Materials↗
PubMed2002

A review of the carotid and femoral intima-media thickness as an indicator of the presence of peripheral vascular disease and cardiovascular risk factors.

Peripheral vascular disease (PVD) is a common condition often associated with cardiovascular risk factors and events. With the aid of B-mode ultrasound scanning, evidence is emerging that these risk factors and events are significantly related to an increased carotid and femoral intima-media thickness (IMT). More importantly, treatment of these risk factors is associated with a decrease or a diminished progression of the IMT, paralleled by a reduction in cardiovascular events and an improvement in the symptoms associated with PVD. This evidence is particularly strong for lipid lowering therapy. Additional predictors of cardiovascular risk like the IMT, could now influence the decision to intervene with medication.

Age Factors↗
PubMed2002

Impaired carotid and femoral viscoelastic properties and elevated intima-media thickness in peripheral vascular disease.

BACKGROUND: We undertook a study to determine whether peripheral vascular disease of the lower extremity (PVD) per se affects the arterial viscoelastic properties and intima-media thickness (IMT) of the carotid and femoral arteries. METHODS: Thirty-five patients with PVD, 35 age- and gender-matched control subjects were examined with ultrasound scan wall tracking system, with the simultaneous measurement of blood pressure for carotid and femoral IMT and viscoelastic properties. RESULTS: Subjects with PVD have significantly impaired carotid elastic properties including compliance (mean (SD): 6.50 (2.39) vs 9.93 (4.07) %mmHg(-1)x10(-2), P<0.001), Petersen's elastic modulus (1.77 (0.69) vs 1.19 (0.63) mmHg x 10(3), P=0.001) and stiffness index (17.92 (7.21) vs 12.10 (6.17), P=0.001) when compared to non-PVD controls. They also have significantly altered femoral elastic properties including Petersen's elastic modulus (5.94 (4.98) vs 3.64 (3.27) mmHg x 10(3), P=0.025) and stiffness index (58.42 (47.76) vs 36.96 (33.43), P=0.033). The carotid (0.85 (0.35) vs 0.59 (0.23) mm, P<0.001) and femoral (1.05 (0.39) vs 0.69 (0.31) mm, P<0.001) IMTs are also significantly elevated in PVD patients. After adjustment for the presumed cardiovascular load assessed on the basis of a cumulative total vascular risk score, as well as age, systolic and diastolic pressure, the carotid viscoelastic indices and the carotid and femoral IMTs remained highly significant. However, the difference in femoral elastic variables was no longer evident. CONCLUSION: PVD per se affects the femoral and carotid wall mechanics and morphology similarly to other cardiovascular risk factors and events. These parameters may provide further information for cardiovascular risk assessment in addition to the classical risk factors and the Framingham equation. Indeed, some guidelines have suggested that additional factors such as the carotid scan may influence the clinician's decision to intervene with therapy.

Aged↗
PubMed2002

Thermo-mechanical analysis of a compliant poly(carbonate-urea)urethane after exposure to hydrolytic, oxidative, peroxidative and biological solutions.

AIMS: To date, there is still a great need for a fully viable small diameter (< 6 mm) polymeric vascular graft. Currently in such low flow locations, non-elastic expanded polytetrafluoroethylene (ePTFE) is the best available but it is quite inferior to autologous saphenous vein since it fails due to intimal hyperplasia caused by compliance mismatch between the graft and elastic host artery. Recently, a novel compliant poly(carbonate-urea)urethane vascular graft whose trade name is MyoLink has been developed. In this article, we report the findings of a thermo-mechanical analysis of the polymers chemistry postexposure to in vitro solutions comprised of hydrolytic, oxidative, peroxidative and biological media. METHODS AND MATERIALS: The following degradative solutions were used in vitro: plasma fractions I-IV; phospholipase A2 (PLA); cholesterol esterase (CE) and solutions of H2O2/CoCl2, t-butyl peroxide/CoCl2 (t-but/CoCl2) and glutathione/t-butyl peroxide/ CoCl2 (glut/t-but/CoCl2). The MyoLink graft was compared against a conventional poly(ether)urethane (Pulse-Tec). All the graft specimens were 100 mm in length (5.0 mm ID) and were incubated in the latter solutions at 37 degrees C for 70 days in total. The following thermo-mechanical methods were used to analyse both graft types: thermo-mechanical analysis (TMA) and dynamic mechanical thermal analysis (DMTA). RESULTS: Incubation of Pulse-Tec in plasma fractions I-IV, PLA and CE reveals only one observable modification: an increase in the size of the low temperature, melting phase. But incubation in H2O2/CoCl2, and t-but/CoCl2 leads to an increase in the polymeric phase separation coupled with an enlargement in the size of the low temperature melting crystalline phase in Pulse-Tec. The glut/t-but/CoCl2 solution leads to a phase separation between the hard and soft segment domains, coupled with an increase of the internal order within the hard segment domains in Pulse-Tec. The only system in which MyoLink degraded was glut/t-but/CoCl2. In this system, an increase of the phase separation coupled with a simultaneous increase of the crystal size of the low-temperature melting crystalline phase occurred. CONCLUSION: This study shows dramatic changes in the chemistry of the soft and hard segments occurred in the case of the conventional poly(ether)urethane Pulse-Tec graft material. Such changes were not manifested in the majority of solutions in the case of MyoLink but a hydrolytic-led degradation of the carbonate soft segment was evidenced only in the glut/t-but/CoCl2 system.

Blood Vessel Prosthesis↗
PubMed2002

New prostheses for use in bypass grafts with special emphasis on polyurethanes.

Vascular bypass procedures using traditional prosthetic grafts such as polytetrafluoroethylen (PTFE) and polyethylene tetraphthlate (Dacron) are prone to failure when used in low flow states such as in below knee bypass and when the diameter of the graft is less than 6 mm. A major factor in this is compliance mismatch between the graft and the diseased vessel, which may cause intimal hyperplasia at the distal anastomosis. PTFE and Dacron are rigid grafts with poor compliance. By improving the compliance of the prosthetic graft it is hoped that patency will improve. Recent advances in polyurethane chemistry have developed materials that do not degrade and which allow compliance matching of the graft to the patient's vasculature. It is now possible to manufacture biologically and haemodynamically compatible grafts with small diameter from these polyurethane graft materials. This review will focus on the lack of compliance in current vascular bypass grafts and the promise of the new polyurethane polymers in a new generation of small-bore bypass grafts.

Biocompatible Materials↗