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Biomedical subjects

T David

Publications and source records attributed to T David.

At least 19 recordsLinked to original sources

Imaging the local density of states of optical corrals.

This paper reports the experimental observation, at optical frequencies, of the electromagnetic local density of states established by nanostructures corresponding to the recently introduced concept of optical corral [G. Colas des Francs et al., Phys. Rev. Lett. 86, 4950 (2001)]. The images obtained by a scanning near-field optical microscope under specific operational conditions are found in agreement with the theoretical maps of the optical local density of states. A clear functionality of detection by the scanning near-field optical microscope is thereby identified since the theoretical maps are computed without including any specific tip model.

Journal Article↗

A mathematical model of post-canalization thrombolysis.

During the initial phase of lysis of an occlusive thrombus using lytic agents such as tissue plasminogen activator, blood flow through the centre of the clot is established (the process of recanalization). Following canalization, the clot remains on the vessel wall and further lysis is required. This paper develops a multi-species mathematical model to describe the bulk chemical reactions in the bloodstream and the convective and diffusive transport of chemical species to and from the clot surface in conditions following canalization. For the steady state case, the model indicates that the process of clot lysis following initial recanalization is dominated by surface chemical reactions and the bulk reactions play little role in the lytic process. Lytic rate is dependent on the clot geometry and flow conditions. The rate of clot dissolution is greatest at the upstream end of the clot and decreases steadily downstream due to lytic agent being removed from the flowing blood as it binds to the clot surface. This model may be further developed and used to simulate and compare different lytic regimes.

Animals↗

Numerical models of auto-regulation and blood flow in the cerebral circulation.

A two-dimensional time-dependent computational fluid dynamics model of the Circle of Willis has been developed. To simulate, not only the peripheral resistance of the cerebrovascular tree but also its auto-regulation function, a new "active" boundary condition has been defined and developed using control theory to provide a model of the feedback mechanism. The model was then used to simulate different common abnormalities of the Circle of Willis while a pressure drop, simulating a rapid compression of the right internal carotid artery, was imposed. Test results using a simple tube compared excellently with experiment. The total time-dependent flux for each efferent artery was tabulated and showed the important relationship between geometrical variations in the Circle of Willis and the auto-regulation of blood flow by vascular vaso-dilation and contraction. From this study, it was found that the worst case seemed to be that of a missing or dysfunctional right A1 segment of the anterior cerebral artery. The use of valid physiological models of the peripheral resistance allows for more realistic models of the blood flow in the Circle whilst allowing an easy extension to 3D patient specific simulations.

Blood Flow Velocity↗

Activation and extinction models for platelet adhesion.

Adherent platelets are an important part of both thrombus formation and in certain stages of atherogenesis. Platelets can be activated by potent chemicals released from adherent platelets and adhere far more readily than unactivated ones. An analytical and numerical model is presented utilising high Peclet number for the activation and adhesion of platelets in shear flows. The model uses a similarity transformation, which characterises the relationship between convective, diffusive transport and the bulk platelet activating reaction mechanism. A first order surface reaction mechanism is used to model platelet adhesion at the wall (cell) surface. The reduced Damköhler number, M, characterises the importance of the bulk reaction and includes both convective and diffusive terms. For a high rate of blood flow (M-->0) the activation of platelets can effectively be terminated. In contrast, for (M-->infinity) an inner layer of activated platelets exists with an infinitesimally thin reaction sheet separating activated and non-activated platelets. This characterisation by the Damköhler number highlights results found clinically, in that thrombus forms in areas of low shear (high M) and in some cases an increased blood flow (low M) can inhibit the activation of platelets completely. The model shows the critical balance that exists between convection, diffusion and reaction.

Humans↗

Adhesion of leukocytes under oscillating stagnation point conditions: a numerical study.

Leukocyte recruitment from blood to the endothelium plays an important role in atherosclerotic plaque formation. Cells show a primary and secondary adhesive process with primary bonds responsible for capture and rolling and secondary bonds for arrest. Our objective was to investigate the role played by this process on the adhesion of leukocytes in complex flow. Cells were modelled as rigid spheres with spring like adhesion molecules which formed bonds with endothelial receptors. Models of bond kinetics and Newton's laws of motion were solved numerically to determine cell motion. Fluid force was obtained from the local shear rate obtained from a CFD simulation of the flow over a backward facing step.In stagnation point flow the shear rate near the stagnation point has a large gradient such that adherent cells in this region roll to a high shear region preventing permanent adhesion. This is enhanced if a small time dependent perturbation is imposed upon the stagnation point. For lower shear rates the cell rolling velocity may be such that secondary bonds have time to form. These bonds resist the lower fluid forces and consequently there is a relatively large permanent adhesion region.

Arteriosclerosis↗

Optical analogy to electronic quantum corrals.

We describe full multiple-scattering calculations of localized surface photonic states set up by lithographically designed nanostructures made of a finite number of dielectric pads deposited on a planar surface. The method is based on a numerical solution of the dyadic Dyson's equation. When the pads are arranged to form a closed circle, we find field patterns that look like the electronic charge density recently observed above quantum corrals. We propose two experimental techniques that could be used to observe these electromagnetic modes in direct space.

Journal Article↗

Platelet deposition in stagnation point flow: an analytical and computational simulation.

A mathematical and numerical model is developed for the adhesion of platelets in stagnation point flow. The model provides for a correct representation of the axi-symmetric flow and explicitly uses shear rate to characterise not only the convective transport but also the simple surface reaction mechanism used to model platelet adhesion at the wall surface. Excellent agreement exists between the analytical solution and that obtained by the numerical integration of the full Navier--Stokes equations and decoupled conservation of species equations. It has been shown that for a constant wall reaction rate modelling platelet adhesion the maximum platelet flux occurs at the stagnation point streamline. This is in direct contrast to that found in experiment where the maximum platelet deposition occurs at some distance downstream of the stagnation point. However, if the wall reaction rate is chosen to be dependent on the wall shear stress then the analysis shows that the maximum platelet flux occurs downstream of the stagnation point, providing a more realistic model of experimental evidence. The analytical formulation is applicable to a large number of two-dimensional and axi-symmetrical surface reaction flows where the wall shear stress is known a priori.

Arterial Occlusive Diseases↗

The General Medical Council's Performance Procedures: peer review of performance in the workplace.

The General Medical Council procedures to assess the performance of doctors who may be seriously deficient include peer review of the doctor's practice at the workplace and tests of competence and skills. Peer reviews are conducted by three trained assessors, two from the same speciality as the doctor being assessed, with one lay assessor. The doctor completes a portfolio to describe his/her training, experience, the circumstances of practice and self rate his/her competence and familiarity in dealing with the common problems of his/her own discipline. The assessment includes a review of the doctor's medical records; discussion of cases selected from these records; observation of consultations for clinicians, or of relevant activities in non-clinicians; a tour of the doctor's workplace; interviews with at least 12 third parties (five nominated by the doctor); and structured interviews with the doctor. The content and structure of the peer review are designed to assess the doctor against the standards defined in Good Medical Practice, as applied to the doctor's speciality. The assessment methods are based on validated instruments and gather 700-1000 judgements on each doctor. Early experience of the peer review visits has confirmed their feasibility and effectiveness.

Clinical Competence↗

Numerical models for the simulation of flexible artificial heart valves: part I--computational methods.

A numerical model of the coupled motion of a flexing surface in a high Reynolds number flow is presented for the simulation of flexible polyurethane heart valves in the aortic position. This is achieved by matching a Lagrangian dynamic leaflet model with a panel method based flow solver. The two models are coupled via the time-dependent pressure field using the unsteady Bernoulli equation. Incorporation of sub-cycling in the dynamic model equations and fast pre conditioning techniques in the panel method solver yields efficient convergence and near real-time simulations of valve motion. The generality of dynamic model allows different material properties and/or geometries to be studied easily and interactively. This interactivity is realized by embedding the models within a design environment created using the software IRIS Explorer. Two flow domains are developed, an infinite domain and an internal domain using conformal mapping theory. In addition bending stress on the valve is computed using a simple stress model based on spline and circle equation techniques.

Biomechanical Phenomena↗

Population of the vessel wall by leukocytes binding to P-selectin in a model of disturbed arterial flow.

We examined the hypothesis that disturbance of laminar flow promotes the attachment of leukocytes to the vessel wall in regions where the wall shear stress is otherwise too high. Isolated neutrophils, lymphocytes, or monocytes were perfused through chambers with backward-facing steps so that vortices occurred with well-defined reattachment of flow. Wall shear stresses downstream in reestablished flow equaled 0.07 Pa (low shear) or 0.3 Pa (high shear). In chambers coated with P-selectin, adherent leukocytes rolled. By use of a P-selectin-Fc fragment chimera, adhesion was predominantly stationary, enabling definition of initial attachment sites. Neutrophils adhered in all regions of the low-shear chamber, with a local maximum around the reattachment point. However, in the high-shear chamber, adhesion was restricted to the recirculation zone and immediately downstream from the reattachment point. Rolling at high shear stress allowed a population of regions where initial attachment could not occur. At high shear, lymphocytes and monocytes also formed attachments restricted to the region of the reattachment point. The results imply that all types of leukocytes might bind to a capture receptor in high-shear vessels with discontinuities in the wall and might then spread to other regions.

Blood Vessels↗

[Conjunctival in situ carcinoma in a patient with Waldenström's disease].

A 73-year-old male patient was treated for conjunctival in situ carcinoma invading the cornea of his right eye. The patient had been previously operated on for two corneoconjunctival lesions on the same eye (one was a pterygium, the other was simple epithelial hyperplasia) and was regularly followed for a systemic lymphoplasmocytic lymphoma (Waldenström's disease). After a corneoconjunctival excision of the tumor, the histological analysis was performed and established the diagnosis of in situ carcinoma. The tumor recurred a few months later and radiation therapy was then given. No recurrence was observed after this latter treatment.

Aged↗

Dependence of adhesive behavior of neutrophils on local fluid dynamics in a region with recirculating flow.

We have recently described patterns of adhesion of different types of leukocytes downstream of a backward facing step. Here the predicted fluid dynamics in channels incorporating backward facing steps are described, and related to the measured velocities of flowing cells, patterns of attachment and characteristics of rolling adhesion for neutrophils perfused over P-selectin. Deeper (upstream depth 300 microm, downstream depth 600 microm, maximum wall shear stress approximately 0.1 Pa) and shallower (upstream depth 260 microm, downstream depth 450 microm, maximum wall shear stress approximately 0.3 Pa) channels were compared. Computational fluid dynamics (CFD) predicted the presence of vortices downstream of the steps, distances to reattachment of flow, local wall shear stresses and components of velocity parallel and perpendicular to the wall. Measurements of velocities of perfused neutrophils agreed well with predictions, and suggested that adhesion to P-selectin should be possible in the regions of recirculating flow, but not downstream in re-established flow in the high shear channel. When channels were coated with a P-selectin-Fc chimaera, neutrophils were captured from flow and immobilised. Capture showed local maxima around the reattachment points, but was absent elsewhere in the high shear chamber. In the low shear chamber there was depression of adhesion just beyond the reattachment point because of expansion of flow and depletion of neutrophils near the wall. Inside the recirculation zones, adhesion decreased approaching the step because of an increasing, vertically upward velocity component. When channels were coated with P-selectin, neutrophils rolled in all regions, but lifted off the surface as they rolled backwards into low shear regions near the step. Rolling velocity in the recirculation zone was independent of shear stress, possibly because of the effects of vertical lift. We conclude that while local wall shear stress influences adhesive behavior, delivery of cells to the wall and their behavior after capture also depend on components of flow perpendicular to the wall.

Blood Flow Velocity↗

Mesh crural repair of large paraesophageal hiatal hernias.

Surgical repair is indicated in patients with paraesophageal hernias but is associated with a high recurrence rate. Our objective was to assess the safety and efficacy of mesh reinforcement of the crural closure in laparoscopic paraesophageal hernia repair. We conducted a 7-year retrospective review of all patients undergoing laparoscopic paraesophageal hernia repair with or without use of mesh. The main outcome measures were use of mesh, reason for use, age, sex, preoperative symptoms, length of operation, length of hospital stay, postoperative complications, and long-term follow-up conducted by physician interview. Twelve patients were repaired with mesh (Group A) and 12 without (Group B). Age, sex, operating time, length of hospital stay, and postoperative complications were similar in both groups. In Group A two patients required an interposition graft and ten required mesh reinforcement of the crural closure. One Group A patient developed an early recurrence requiring a reoperation, and one Group B patient developed a gastric leak where the fundus was sutured to the crura. The remainder of the patients experienced resolution of their symptoms at 2 weeks follow-up. Long-term follow-up (average 37 months) showed one Group B patient with a recurrence of reflux symptoms, but an upper gastrointestinal study showed no recurrence of hernia. All others remained asymptomatic. We conclude that the use of mesh in laparoscopic repair of large paraesophageal hernias appears safe and may reduce recurrence.

Aged↗

Analysis of explants and causes of mortality during long-term follow-up of the Toronto stentless porcine valve.

UNLABELLED: The long-term status of stentless porcine valves has not yet been defined. METHODS: 447 patients were followed at 6 IDE sites up to 10 years (total follow-up, 2024.3 pt years; mean, 4.5 years): 35% were over 70 years and 41% underwent concomitant coronary artery bypass grafting. RESULTS: 10 patients underwent reoperation for valve explant (0.5%/pt year) because of severe aortic incompetence (AI) from dilatation of the aorta, sinotubular junction or sinus of Valsalva with torn commissures or cusps (8 patients) and endocarditis with abscess and dehiscence (2 patients). Six of 8 patients with late AI had bicuspid native aortic valves (mean age, 39.8 years). Overall freedom from reoperation was 95.2%. Freedom from structural deterioration was 96.1% at 7 years (98.0% for patients >60 years). Of 49 late deaths (2.5%/pt year), 9 were valve related (0.5%/pt year), 10 cardiac related, and 30 because of noncardiac causes. Valve-related deaths were because of endocarditis (3), CVA (1), redo surgery (1), or unknown reasons (4). Noncardiac deaths were due mainly to cancer (19/30). At seven years, freedom from all cause death was 81.8% and freedom from valve-related death 96.9%. CONCLUSIONS: Late mortality after stentless valve replacement has been primarily because of comorbidities present at surgery or developing later. The Toronto stentless porcine valve is associated with a low rate of reoperation and valve-related death.

Adult↗

Eight-year hemodynamic follow-up after aortic valve replacement with the Toronto SPV stentless aortic valve.

The hemodynamic performance of stentless aortic bioprostheses has been well described during the first few months after surgery. The purpose of the present study was to describe the hemodynamic performance of the Toronto SPV valve (St. Jude Medical, Inc, St. Paul, MN) in a multicenter trial through 8 years. The long-term study of the Toronto SPV valve includes 447 consecutive patients from 6 investigative centers. Echocardiographic follow-up was performed at specified intervals, with quantitative analysis performed at a centralized core laboratory. Mean transvalvular gradient decreased significantly between discharge and 6 months, between 6 months and 1 year, and between 1 year and 2 years after surgery, without further significant change. The effective orifice area increased significantly early after surgery and continued to increase through 6-year follow-up. The left ventricular (LV) stroke volume increased progressively from discharge through 6-year follow-up. The LV mass index decreased significantly from discharge through 3 years after surgery and stabilized through 5 years. There was a gradual increase in LV outflow tract diameter between 1 year and 6 years after surgery. The prevalence of any aortic regurgitation (AR) (including trivial) and > or = mild AR increased significantly between discharge and 6-year to 8-year follow-up. However, the prevalence of > or = moderate AR remained very low at 6 years (2.6%) and 8 years (4.5%) after surgery. In conclusion, the Toronto SPV stentless tissue aortic valve is associated with excellent hemodynamics early after surgery and through 8 years after surgery. LV mass decreases early, and returns to within the range of normal by 1 year after surgery. There is evidence of continued LV mass regression involving the LV outflow tract, potentially contributing to a small but significant late improvement in hemodynamics. The prevalence of significant AR remains low through 8 years.

Adult↗

The assessment of poorly performing doctors: the development of the assessment programmes for the General Medical Council's Performance Procedures.

BACKGROUND: Modernization of medical regulation has included the introduction of the Professional Performance Procedures by the UK General Medical Council in 1995. The Council now has the power to assess any registered practitioner whose performance may be seriously deficient, thus calling registration (licensure) into question. Problems arising from ill health or conduct are dealt with under separate programmes. METHODS: This paper describes the development of the assessment programmes within the overall policy framework determined by the Council. Peer review of performance in the workplace (Phase 1) is followed by tests of competence (Phase 2) to reflect the relationship between clinical competence and performance. The theoretical and research basis for the approach are presented, and the relationship between the qualitative methods in Phase 1 and the quantitative methods in Phase 2 explored. CONCLUSIONS: The approach is feasible, has been implemented and has stood legal challenge. The assessors judge and report all the evidence they collect and may not select from it. All their judgements are included and the voice of the lay assessor is preserved. Taken together, the output from both phases forms an important basis for remediation and training should it be required.

Clinical Competence↗