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Biomedical subjects

P V Lawford

Publications and source records attributed to P V Lawford.

At least 19 recordsLinked to original sources
PubMed2006

Characterisation of the haemodynamics of the superior mesenteric artery.

In contrast to its prevalence in the surrounding vasculature, occurrence of primary atherosclerotic disease in the superior mesenteric artery (SMA) is rare (Glagov et al., 1988. Hemodynamics and atherosclerosis, Insights and perspectives gained from studies of human arteries. Archives of Pathology and Laboratory Medicine 112(10), 1018-1031; Hansen et al., 2004. Mesenteric artery disease in the elderly. Journal of Vascular Surgery 40(1), 45-52). We hypothesise that this sparing might be attributed to more favourable haemodynamic characteristics in the SMA than in other vessels locally. Dynamic magnetic resonance imaging (MRI) images established that the SMA is highly mobile (Jeays, 2006. Investigation of blood flow in the superior mesenteric artery and its potential influence on atheroma and gut ischaemia. Ph.D. Thesis, University of Sheffield), and thus that an analysis based on rigid geometry might be inappropriate. This paper describes an efficient methodology for the construction of a patient-specific, time-dependent model of an arterial segment and reports the results of a haemodynamic characterisation of the SMA for one individual. A transient computational fluid dynamic (CFD) model was constructed by morphing a parametric mesh constructed from simple geometric primitives. This process has the merit that it is easy to control the element size distribution mapped onto the original geometric primitives. It is robust in operation, and is ideally suited to the generation of dynamic CFD meshes of arterial systems that are free from major pathology. Flow boundary conditions were determined based on phase contrast MRI velocity measurements. Comparative studies with rigid walls and with moving walls, based on the transient data, indicated that, despite the significant motion of the SMA (radial dilation of the order of 10% and translation of the order of the radius), the maximum (spatially and temporally-resolved) wall shear stresses changed by no more than 21.6% of a global norm, and the average change was less than 2.1%.

Hemorheology↗
PubMed2006

Computer modelling study of the mechanism of optic nerve injury in blunt trauma.

AIM: The potential causes of the optic nerve injury as a result of blunt object trauma, were investigated using a computer model. METHODS: A finite element model of the eye, the optic nerve, and the orbit with its content was constructed to simulate blunt object trauma. We used a model of the first phalanx of the index finger to represent the blunt body. The trauma was simulated by impacting the blunt body at the surface between the globe and the orbital wall at velocities between 2-5 m/s, and allowing it to penetrate 4-10 mm below the orbital rim. RESULTS: The impact caused rotations of the globe of up to 5000 degrees /s, lateral velocities of up to 1 m/s, and intraocular pressures (IOP) of over 300 mm Hg. The main stress concentration was observed at the insertion of the nerve into the sclera, at the side opposite to the impact. CONCLUSIONS: The results suggest that the most likely mechanisms of injury are rapid rotation and lateral translation of the globe, as well as a dramatic rise in the IOP. The strains calculated in the study should be sufficiently high to cause axonal damage and even the avulsion of the nerve. Finite element computer modelling has therefore provided important insights into a clinical scenario that cannot be replicated in human or animal experiments.

Computer Simulation↗
PubMed2005

A computational study of the passive mechanisms of eye restraint during head impact trauma.

A finite element model of the eye and the orbit was used to examine the hypothesis that the orbital fat provides an important mechanism of eye stability during head trauma. The model includes the globe, the orbital fat, the extra-ocular muscles, and the optic nerve. MRI images of an adult human orbit were used to generate an idealized geometry of the orbital space. The globe was approximated as a sphere 12 mm in radius. The optic nerve and the sclera were represented as thin shells, whereas the vitreous and the orbital fat were represented as nearly incompressible solids of low stiffness. The orbital bone was modelled as a rigid shell. Frontal head impact resulting from a fall onto a hard floor was simulated by prescribing to the orbital bone a triangular acceleration pulse of 200 g (1962 m/s(2)) peak for a duration of 4.5 ms. The results show that the fat provides the crucial passive mechanism of eye restraint. The mechanism is a consequence of the fact that the fat is incompressible and that its motion is restricted by the rigidity of the orbital walls. Thus, the acceleration loads of short duration cannot generate significant distortion of the fat. In contrast, the passive muscles provide little support to the globe. When the connection between the orbital fat and the eye is absent the eye is held mainly by the optic nerve. We discuss the possible role that this loss of contact may have in some cases of the evulsion of the eye and the optic nerve.

Accidental Falls↗
PubMed2004

A thermal analogy for modelling drug elution from cardiovascular stents.

Restriction of blood flow by the narrowing or occlusion of arteries is one of the most common presentations of cardiovascular disease. One treatment involves the introduction of a metal scaffold, or stent, designed to prevent recoil and to provide structural stability to the vessel. On the occasions that this treatment is ineffective, failure is usually associated with re-invasion of tissue. This can be prevented by local delivery of drugs which inhibit tissue growth. The drug might be delivered locally in a polymer coating on the stent. This paper develops and explores the use of a thermal analogue of the drug delivery process and the associated three-dimensional convection-diffusion equation to model the spatial and temporal distribution of drug concentration within the vessel wall. This allows the routine use of commercial finite element analysis software to investigate the dynamics of drug distribution, assist in the understanding of the treatment process and develop improved delivery systems. Two applications illustrate how the model might be used to investigate the effects of controllable or measurable parameters on the progression of the process. It is demonstrated that the geometric characteristics of the stent can have significant impact on the homogeneity of the dosing in the vessel wall.

Animals↗
PubMed2001

Outlet strut fracture of Björk-Shiley convexo-concave valves: can valve-manufacturing characteristics explain the risk?

BACKGROUND: Björk-Shiley 60 degrees convexo-concave prosthetic heart valves (Shiley, Inc, Irvine, Calif, a subsidiary of Pfizer, Inc) continue to be a concern for approximately 35,000 nonexplanted patients worldwide, with approximately 600 events reported to the manufacturer to date. Fractures of the outlet struts of the valves began to appear in the early 1980s and have continued to the present, but their causes are only partially understood. METHODS: A matched case-control study was conducted evaluating manufacturing records for 52 valves with outlet strut fractures and 248 control subjects matched for age at implantation, valve size, and valve position. RESULTS: In addition to the risk factors recognized as determinants of outlet strut fracture, the United Kingdom case-control study has observed 7- to 9-fold increased risk with performance of multiple hook deflection tests. This test was performed more than once, usually after rework on the valve. Six valves in this study underwent multiple hook deflection tests, of which 4 experienced an outlet strut fracture. Cracks and further rework were noted for these valves. Significant associations were also observed between outlet strut fracture and disc-to-strut gap measurements taken before the attachment of the sewing ring. CONCLUSIONS: It is our view that a combination of factors related to valve design, manufacturing process, and patient characteristics are responsible for outlet strut fractures of Björk-Shiley convexo-concave valves. Multiple hook deflection tests have emerged as a potential new risk factor for outlet strut fracture in both The Netherlands and the United Kingdom. This factor appears to be correlated with the presence of other abnormalities. A further study is needed to investigate the factors correlated with multiple hook deflection tests. On confirmation of risk, the presence of multiple hook deflection tests may be added to equations, quantifying the risk of outlet strut fracture for comparison against risk of mortality and serious morbidity from explant operations.

Analysis of Variance↗
PubMed2000

Glutaraldehyde-induced cross-links: a study of model compounds and commercial bioprosthetic valves.

BACKGROUND AND AIM OF THE STUDY: The treatment of bioprosthetic tissue routinely involves the use of glutaraldehyde, although the specific chemistry of glutaraldehyde fixation is not fully understood. Descriptions of definitive work on this reaction using model compounds are limited. The aim of the present study was to increase our understanding of the chemistry involved in the treatment of collagen-rich tissue with glutaraldehyde. Initially, 6-aminohexanoic acid (6-AHA) was used to model the lysine/hydroxylysine molecules in collagen before studying the more complex chemistry of the tissue. METHODS: The reaction between 0.6% glutaraldehyde and 6-AHA was studied by positive ion electrospray-mass spectroscopy. Untreated, locally treated and commercially produced explanted and non-implanted tissue were hydrolyzed under various conditions and analyzed both directly and after derivatization with 4-chlorophenylhydrazine, 4-bromophenacyl bromide and dansyl chloride by reverse-phase-high performance liquid chromatography-mass spectrometry. RESULTS: The mass spectral data obtained from the reaction of glutaraldehyde with 6-AHA showed the presence of alpha,beta unsaturated aldehydes and their further condensation products involving Michael reactions of glutaraldehyde, Schiff base cross-links and various cyclization products incorporating pyridinium and dihydropyridine ring structures. The only stable cross-link detected was an 'anabilysine'-like compound. Similar structures were present in the tissue, and anabilysine was identified by tandem mass spectrometry. CONCLUSION: The results from the reaction of glutaraldehyde with 6-AHA agree with those published previously. The only detectable stable cross-link definitively identified in treated bioprosthetic tissue was anabilysine. No long-chain polymers of glutaraldehyde were detected.

Aminocaproic Acid↗
PubMed1999

An inexpensive sensor for measuring surface geometry.

A technique to measure surface geometry using a conductive ink sensor is described. In the human system distorted cylinders are common, and geometry can be reconstructed from local measures of curvature. An algorithm is presented to reconstruct the shape of a surface from a series of curvature measurements. The Abrams Gentile Entertainment patented bend sensor was evaluated as a curvature transducer. The sensor was tested at the extremes of the likely measurement range, from curvatures below 0.01 mm(-1) up to a curvature of 0.1 mm(-1). The upper curvature limit proved beyond the design specification of the sensor. The technique was applied at the lower curvature range to reconstruct one quadrant of the chest of a volunteer and record breathing movement. The bend sensor is inexpensive and can be applied to obtain an approximate reconstruction of surface geometry in the human system.

Adult↗
PubMed1996

Formaldehyde replaces glutaraldehyde in porcine bioprosthetic heart valves.

BACKGROUND AND AIMS OF THE STUDY: In the production of porcine bioprostheses, the initial glutaraldehyde treatment is often followed by a short incubation in formaldehyde to ensure sterility of the valve. It is assumed that the glutaraldehyde cross links are stable and that the formaldehyde step does not alter the glutaraldehyde incorporated. The objective of this study was to determine whether the formaldehyde interacts with the tissue to cause changes in the glutaraldehyde composition. MATERIALS AND METHODS: Two methods of tissue treatment were investigated: (i) fresh porcine leaflet tissue was treated with glutaraldehyde, followed by storage in formaldehyde, (ii) tissue processed in glutaraldehyde and transferred to formaldehyde for six hours was returned to glutaraldehyde for storage. The content of the two aldehydes was estimated by high performance liquid chromatography (HPLC), using an adaptation of the method developed by Hughes et al, which measures the acid labile Schiff bases formed between the collagen and the aldehyde. RESULTS: The initial content of glutaraldehyde in the tissue declined from 63 +/- 10 nmol/mg dry weight to 21 +/- 4 nmol/mg dry weight when the leaflets were placed in formaldehyde for 24 hours. The initial uptake of formaldehyde was 800 +/- 144 nmol/mg dry weight after 24 hours and this declined to 370 +/- 33 nmol/mg dry weight over a 16 week period of storage in formaldehyde. By this stage, the level of glutaraldehyde had decreased to 2.4 +/- 0.2 nmol/mg dry weight. There was a sharp decline in the glutaraldehyde concentration from 89 +/- 6 nmol/mg dry weight to 14 +/- 1 nmol/mg dry weight when the tissue was placed in 4% formaldehyde solution for six hours. The formaldehyde uptake was 770 +/- 54 nmol/mg dry weight. After return to 0.625% glutaraldehyde solution the formaldehyde concentration declined whilst the glutaraldehyde concentration initially increased. CONCLUSIONS: These results show that the formaldehyde reacts with the epsilon amino groups of lysine which had not reacted with glutaraldehyde, probably for steric reasons; and that formaldehyde replaces some glutaraldehyde in the tissue by a mass action effect. The tissue concentration of both aldehydes subsequently declined over the study period.

Animals↗
PubMed1996

The use of enzyme activated milk for in vitro simulation of prosthetic valve thrombosis.

BACKGROUND AND AIM OF THE STUDY: Thrombosis remains a serious risk for patients with artificial heart valves and may be attributed in part to adverse blood flow patterns. Although the final assessment of a valve must follow years of clinical experience, in vitro flow analyses give valuable information prior to implantation. Laser Doppler velocimetry and computational fluid dynamics enable quantitative flow analyses to be made in vitro. Whilst these techniques highlight features such as areas of stasis, turbulence and high shear which may predispose to thrombus formation, the complex and time varying nature of the flow through valves makes it difficult to predict accurately potential sites of thrombus deposition and accumulation. METHODS: A technique is described which uses enzyme activated milk as a coagulable blood analogue to indicate flow related clotting. Milk flowing past a test valve or object was activated to clot downstream of the test piece after a certain time period. Milk clot was deposited clot at sites determined by the local flow disturbances. Milk clotting patterns produced on and around standard objects were compared with the transient flow patterns predicted around identical configurations to test the validity of computational flow analyses for predicting flow disturbances leading to clotting. Milk clots on valves were compared with examples of thrombus found on explanted valves of the same design. RESULTS: The sites of deposition were consistent with the predicted flow patterns around the two configurations of flow obstruction studied. Milk clotting patterns on valves corresponded with the early stages of thrombus on explanted valves of the same design. CONCLUSIONS: Whilst a coagulable milk mixture may be used to evaluate the risk of flow induced clot adherence, care must be taken when extrapolating to the clinical situation as other factors such as material properties, blood chemistry and concomitant disease must also be considered.

Animals↗
PubMed1994

Elective removal of convexo-concave Björk-Shiley valves.

Replacement has been an accepted method for treating advanced cardiac valvular disease for more than 25 years. However, the perfect prosthesis has yet to be developed, judging by the number of devices available. A prosthesis that initially appears promising may cause problems in due course, and indeed some devices have been modified or withdrawn from clinical use. A notable example of a prosthetic valve that has give problems is the Björk-Shiley convexo-concave prosthesis, some models of which have undergone mechanical failure due to strut fracture. We report the elective removal of such a valve and the subsequent examination of the prosthesis. The results of this examination suggest that a policy of elective removal is justified.

Adult↗
PubMed1994

In vitro heart valve testing: steady versus pulsatile flow.

The design of artificial heart valves has traditionally been based on the development of a prototype device which was then subjected to extensive laboratory testing in order to confirm its suitability for clinical use. In the past the in vitro assessment of a valve's performance was based principally on the measurement of parameters such as pressure difference, regurgitation and, more recently, energy losses. Such measurements can be defined as being at the 'macro' level and rarely show any clinically significant differences amongst currently available prostheses. The analytical approach to flow through heart valves has previously been hampered by difficulties experienced in solving the relevant equations of flow particularly in the case of pulsatile conditions. Computational techniques are now available which enable appropriate solutions to be obtained for these problems and consequently provide an opportunity for detailed examination of the 'micro' level of flow disturbances exhibited by the different valves. This present preliminary study is designed to illustrate the use of such an analytical approach to the flow through prosthetic valves. A single topic has been selected for this purpose which is the comparative value of steady versus pulsatile flow testing. A bileaflet valve was chosen for the analysis and a mathematical model of this valve in the aortic position of the Sheffield Pulse Duplicator was created. The theoretical analysis was carried out using a commercially available Computational Fluid Dynamics package, namely, FIDAP, on a SUN MICROSYSTEMS 10-30 workstation.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗
PubMed1991

Validation of the orifice formula for estimating effective heart valve opening area.

Interest in the Gorlin formula for estimating heart valve effective orifice area (EOA) has recently been rekindled and the formula itself has been challenged. In this validation study, explanted native heart valves, unimplanted mechanical prostheses, unimplanted bioprostheses and explanted bioprostheses have been tested in vitro in a pulsatile flow simulator. Pressures have been measured 30 mm upstream and 100 mm downstream from the plane of the valve sewing ring (to give pressure drop, pd in kPa). Flow (Q in 1 min-1) has been measured directly by electromagnetic flowmeter and orifice areas have either been taken from manufacturer supplied data (mechanical valves) or have been digitised from video images at maximum orifice (biological valves). The formula EOA = Q/(6.96 x pd 1/2) - 0.7 fitted the data with good correlation, r = 0.96 (n = 179). The orifice assumption on which this formula is based (cf. Gorlin formula) is confirmed though it is recommended that the formula should be modified to account for (i) the pressure recovery phenomenon and (ii) the fact that forward flow through a valve only occurs over a portion of the cycle in pulsatile flow. Heart rates used in the study ranged from 40 to 140 min-1, stroke volumes ranged from 20 to 114.3 ml, cardiac outputs from 2.0 to 8.0 1 min-1 and peripheral resistance from 0.1 to 1.6 kPa 1-1 min (1 - 12 mmHg l-1 min). Application of the formula was independent of the flow conditions.

Adult↗
PubMed1989

Is callus calcium content an indicator of the mechanical strength of healing fractures? An experimental study in rat metatarsals.

Changes in the mechanical properties and the calcium content of healing fracture callus were followed, using rat metatarsals. By 24 weeks post-fracture the mean ultimate tensile stress and elastic modulus were still less than half that of the contralateral unfractured bone, whereas the mean torsional modulus had almost reached that of the unfractured bone. The calcium content of the callus formed immediately between the fractured ends of the bone showed changes which coincided with the increases in mechanical strength and the moduli, thus measurement of callus calcium content would enable the prediction of the strength of a healing fracture.

Animals↗
PubMed1989

Pericardial heterografts: a comparative study of suture pull-out and tissue strength.

The force required to pull sutures out of glutaraldehyde fixed bovine pericardium, for four different suture bites: 0.5 mm, 1 mm, 1.5 mm and 2.0 mm, was compared with the tissue strength. The mean suture pull-out force was significantly lower than the tissue strength for all bites, with a minimum value of 2.86 +/- 1.02 N for the 0.5 mm bite and a maximum value of 6.32 +/- 0.77 N for the 2.0 mm bite. The mean force which produced failure of the chemically modified pericardium was 15.49 +/- 8.48 N. The mean force at pull-out of the sutures lay on a regression line: force at failure = 1.68 + 2.25 x Bite. A video film of the experiments showed that the suture does not cut through the pericardium. It pulls a V-shaped band of collagen fibre bundles through the stationary pericardium. Eventually this band breaks away from the free edge of the tissue specimen. The specimens under uniaxial load failed by laminate debonding of two layers of tissue, rupture of the serosal surface layer followed by shear and fibre slippage. These results indicate that any suture which bears load, during the normal functioning of a heart valve substitute, will be a source of weakness, compared to the overall tissue strength. As a consequence the alignment/holding suture of the Standard Ionescu-Shiley valve and the modified stitch of the low profile valve are likely to be potential sites of fatigue failure.

Biomechanical Phenomena↗
PubMed1988

Pericardial heterografts: why do these valves fail?

Eighteen explanted pericardial heterografts were studied (16 standard Ionescu-Shiley, one Hancock, and one Mitroflow). Regurgitation was the reason given for explantation of all the Ionescu-Shiley valves. The other two valves were removed for technical reasons. All the Ionescu-Shiley valves had commissural tears and there was concomitant gross calcification in 10 of the 16 valves. In addition, an apparent increase in cusp area had caused "leaflet sagging". The explanted leaflets were thicker and stiffer than leaflets from an unimplanted valve. These features were confirmed directly with an animal model of subcutaneous implantation. Examination with an electron microscope revealed that these changes in mechanical properties seemed to be linked to fiber separation and infiltration by an amorphous proteinlike matrix. The durability of the glutaraldehyde-fixed pericardium depended on a number of factors. Early and midterm failure appeared to be stress induced. Predisposition to high mechanical stresses near the stent was exacerbated by the changes induced by the host environment. This problem was aggravated further in the Ionescu-Shiley valves by stress concentrations around the hole associated with the holding suture. In the long term, collagen disruption associated with leaflet flexure was followed by secondary calcification at the boundary between the intact and disrupted material.

Aortic Valve↗
PubMed1987

Experimental study in rat metatarsals to determine whether callus vascularity is an indicator of the mechanical strength of healing fractures.

Changes in the mechanical properties and percentage area of blood vessels of healing fracture callus were followed using rat metatarsals. By 24 weeks after fracture the mean ultimate tensile stress and elastic modulus were still less than half that of the contralateral unfractured bone, whereas the mean torsional modulus had almost reached that of the unfractured bone. The percentage area of blood vessels declined from five days post-fracture and showed no changes which coincided with the increases in mechanical strength or moduli. We conclude that studies of vascularity would not justify a prediction of the strength of a healing fracture.

Animals↗