Search PubMed⌕ Search

Biomedical subjects

Richard L Leask

Publications and source records attributed to Richard L Leask.

At least 19 recordsLinked to original sources
PubMed2006

Normal wound healing in mice deficient for fibulin-5, an elastin binding protein essential for dermal elastic fiber assembly.

Extracellular matrix proteins play a critical role in dermal wound healing by mediating matrix-cell interactions and re-establishing the dermal architecture and environment. Fibulin-5 is an elastin-binding protein essential for elastic fiber development in vivo, and it has recently been shown to inhibit angiogenesis in vitro. Here, we use mice deficient for the fibulin-5 gene (fbln5) to examine the role of fibulin-5 and the effect of the loss of elastic fibers in dermal wound healing. Fbln5 is upregulated in the granulation tissue 14 days after full-thickness wounding in wild-type mice, before the formation of elastic fibers. Although wounded fbln5(-/-) skin showed enhanced neovascularization compared to the wild-type skin, no difference in the rate of wound closure was observed between mutant and wild-type mice. In addition, a breaking strength test revealed that there was no difference in breaking stress or strain between wild-type and fbln5(-/-) wounded skin. These results suggest that fibulin-5 and elastic fibers are not directly involved in short-term wound healing. Clearly, the long-term effect of the absence of fibulin-5 on the function and integrity of regenerated skin needs to be further addressed.

Animals↗
PubMed2006

Morphological findings in 192 surgically excised native mitral valves.

INTRODUCTION: Mitral valve disease (MVD) is a significant clinical problem that is becoming more common in the 21st century. The pathogenesis of MVD seems to be changing and is not well understood. PATIENTS AND METHODS: The present study details the morphological findings in 192 native mitral valves excised over a one-year period at the Toronto General Hospital, Toronto, Ontario. The mean patient age was 59.7+/-12.3 years at operation. RESULTS: There were 106 men (55.2%) and 86 women (44.8%) in the present study. The most frequent changes in the surgically excised valvular leaflets were fibrosis (78.6%) and thickening (66.2%). Fusion (32.3%) and calcification (25.2%) were common changes at the commissures. Chordae tendineae most often showed evidence of thickening (47.9%) and fibrosis (37.0%). In total, 110 valves showed mitral incompetence (57.3%), 72 showed mitral stenosis (37.5%), and 10 showed a combination of stenosis and incompetence (5.2%). CONCLUSIONS: In the present series, MVD was most frequently caused by postinflammatory (rheumatic) valve disease (RVD) (35.9%), followed by myxomatous degeneration (33.3%). Patients with RVD were usually female (66.7%), while those with myxomatous degeneration were more likely to be male (76.6%). RVD remains a significant problem even though the incidence of acute rheumatic fever with cardiac involvement has declined in Canada. This most likely reflects the current sociodemographic composition of the referral population.

Adolescent↗
PubMed2005

Human saphenous vein coronary artery bypass graft morphology, geometry and hemodynamics.

Coronary artery bypass graft (CABG) failure has been linked to graft hemodynamics, in particular wall shear stress. This study characterizes the morphology, geometry and wall shear stress patterns in human CABGs. The intimal thickness (IT) in 49 human saphenous vein CABGs was measured by digital light microscopy. The geometry of six saphenous vein CABGs was replicated by post-mortem infusion of Batson's #17 anatomical corrosion casting compound. Graft hemodynamics were evaluated in two flow models, fabricated from the casts, under steady (Re = 110) and pulsatile flow (Re = 110, alpha = 2) conditions. Saphenous vein CABGs in situ for more than 2 months had, on average, the greatest IT on the hood and suture sites of the distal anastomosis. Floor thickening was highly variable and significantly less than IT at the hood, suture site and graft body. All casts showed an indentation along the floor and 5/6 casts displayed a sharp local curvature on the hood. In both flow models, a large increase in wall shear rate occurred on the hood, just proximal to the toe. The local geometry of the hood created this large spatial gradient in wall shear stress which is a likely factor in hood intimal hyperplasia.

Aged↗
PubMed2005

Image based biomechanics of coronary plaque.

In this chapter we present recent developments in the modeling of coronary artery biomechanics. We first introduce the pathology and localization of lesions in the circulatory system. Recent fluid and structural modeling of CAD is presented and discussed. At the end of the chapter, we present recent effort in coupling these two modeling domains using fluid-structure interaction (FSI).

Coronary Artery Disease↗
PubMed2004

Intimal thickness is not associated with wall shear stress patterns in the human right coronary artery.

OBJECTIVE: Low wall shear stress has been implicated in atherogenesis throughout the arterial tree, including the right coronary artery (RCA). The objective of this study was to determine the level of covariation of intimal thickness and wall shear stress in the human RCA. METHODS AND RESULTS: Postmortem histological measurements of intimal thickness were compared with wall shear stresses calculated from computational flow modeling in 4 human right coronary arteries. A statistically significant correlation between intimal thickness and wall shear stress was found in only 1 of the 4 arteries studied. CONCLUSIONS: Wall shear stress does not appear to be related to intimal thickness in the 4 RCAs studied.

Adult↗
PubMed2004

Hemodynamic effects of clot entrapment in the TrapEase inferior vena cava filter.

PURPOSE: The TrapEase vena cava filter has a symmetric design. Emboli can be trapped in the outlet conical section (superior cone) or between the filter and vessel wall at the inlet end (inferior cone). The purpose of this in vitro study is to investigate the hemodynamic effects of clot entrapment by the TrapEase filter and to examine the possibility of flow-induced filter thrombosis. MATERIALS AND METHODS: Velocity and wall shear stress maps were determined for steady flow with use of the photochromic flow visualization technique. Experiments were done for a filter without clot and for three other cases: an asymmetric clot in the inferior zone, a symmetric clot in the superior zone, and a filter with both zones partially occluded. Each simulated clot was 1500 mm(3) and the vessel diameter was 2 cm. RESULTS: The unoccluded filter did not significantly affect the flow field. However, for a partially occluded filter, flow stagnation/recirculation and turbulence developed downstream from the clot. The greatest effect was noted when the clot was against the vessel wall in the inferior trapping region. CONCLUSIONS: The tendency for clots to be trapped between the filter and the vessel wall in the inferior (inlet) region may play an important role in the performance of the TrapEase filter. A clot in this configuration will generate a large region of flow stagnation/recirculation that is considered to be prothrombotic. In addition, a significant amount of the filter wire will be embedded in this region, which may also promote thrombosis.

Blood Flow Velocity↗
PubMed2003

The relationship between wall shear stress distributions and intimal thickening in the human abdominal aorta.

PURPOSE: The goal of this work was to determine wall shear stress (WSS) patterns in the human abdominal aorta and to compare these patterns to measurements of intimal thickness (IT) from autopsy samples. METHODS: The WSS was experimentally measured using the laser photochromic dye tracer technique in an anatomically faithful in vitro model based on CT scans of the abdominal aorta in a healthy 35-year-old subject. IT was quantified as a function of circumferential and axial position using light microscopy in ten human autopsy specimens. RESULTS: The histomorphometric analysis suggests that IT increases with age and that the distribution of intimal thickening changes with age. The lowest WSS in the flow model was found on the posterior wall inferior to the inferior mesenteric artery, and coincided with the region of most prominent IT in the autopsy samples. Local geometrical features in the flow model, such as the expansion at the inferior mesenteric artery (common in younger individuals), strongly influenced WSS patterns. The WSS was found to correlate negatively with IT (r2 = 0.3099; P = 0.0047). CONCLUSION: Low WSS in the abdominal aorta is co-localized with IT and may be related to atherogenesis. Also, rates of IT in the abdominal aorta are possibly influenced by age-related geometrical changes.

Adult↗
PubMed2003

Endothelium and valvular diseases of the heart.

It has become increasingly evident that the endothelium plays a critical role in the pathogenesis of valvular heart disease. The endothelium helps regulate vascular tone, inflammation, thrombosis, and vascular remodeling. Dysfunction of the endothelial cells has been linked to many vascular disorders including atherosclerosis. Common valvular diseases such as senile degenerative valve disease, myxomatous (or floppy) valves, rheumatic valves, and infective endocarditis valves show changes in the synthetic, morphologic, and metabolic functions of the valvular endothelial cells. These diseases are active processes related to endothelial cell dysfunction. Endothelial cell dysfunction is caused by mechanical forces, bacterial infection, autoantibodies, and circulating modulators of endothelial cell function. This study reviews the role of endothelial cell dysfunction in the more common valvular diseases. Continued research on endothelial cell dysfunction is crucial to our understanding of valvular heart diseases and may elucidate novel treatment and prevention strategies.

Aged↗
PubMed2003

Genetic abnormalities of the endothelium.

Endothelial cell dysfunction plays an important role in the development and progression of cardiovascular and other disease. The purpose of this review is to discuss some of the genetic diseases known to adversely affect endothelial function. Although the list is exhaustive, we focus our discussion on primary pulmonary hypertension, diabetes mellitus, Alzheimer's disease, Crohn's disease, Von-Hippel-Lindau disease, familial Mediterranean fever, thrombotic microangiopathy, and key vascular malformations. Endothelial dysfunction results from a complex interplay between genetic and environmental factors. This review highlights some of the growing body of evidence implicating endothelial dysfunction as an important mediator of diverse diseases.

Alzheimer Disease↗
PubMed2003

Primary cardiac sarcoma involving the pulmonary artery and valve.

Primary pulmonary artery neoplasms are rare and lethal. Those involving the pulmonary valve are even rarer with only a few reported cases in the literature. The poor prognosis of these neoplasms, despite attempted multimodal therapy, is largely related to delay and difficulty in diagnosis. The case of a 53-year-old woman is described who within one month of suddenly developing shortness of breath was found to have a mass arising from the pulmonary valve and extending through the pulmonary vasculature, requiring extensive surgical resection. She died two weeks postoperatively. The morphological findings of this primary pulmonary artery sarcoma are presented. Diagnosis, treatment, prognosis and literature are reviewed, and consideration of this tumour in the differential diagnosis of other pulmonary diseases is emphasized.

Echocardiography, Transesophageal↗
PubMedDate not supplied

Morphological findings in explanted Toronto stentless porcine valves.

BACKGROUND: Stentless porcine valves have many documented advantages over stented valves. Since its introduction in 1991, the Toronto stentless porcine valve (T-SPV) has shown excellent hemodynamic performance. METHODS: A total of 332 T-SPVs have been implanted at our institution up to December 2003, 25 of which have been explanted at surgery. Herein, we report a study of 30 explanted T-SPVs seen at our institution over a 5-year period. RESULTS: The mean patient age at explant was 61.2+/-11.8 years with a mean implant duration of 100.7+/-27.8 months (after excluding one valve removed early postoperatively for infective endocarditis). Twenty-seven of 30 valves (90%) showed structural deterioration characterized by tissue degeneration, cusp tears, calcification, and lipid insudation. Eight valves (26.7%) showed evidence of calcification on gross inspection and a total of 23 valves (76.7%) showed at least one microscopic focus of calcification, located primarily in the basal and commissural regions of the cusp. Twenty valves (66.6%) showed cusp tears. Pannus was visible grossly on the surface of 27 of 30 valves (90%), while histologically, at least some degree of pannus was observed on both the inflow and outflow surfaces of all but two valves. Twelve T-SPV (40.0%) showed calcification in the porcine aortic tissue, four of which involved calcification of the porcine muscle shelf in the right coronary cusp. Two T-SPV showed no significant structural deterioration. Their clinical reason for explantation was incompetence or infective endocarditis. CONCLUSION: With a freedom from reoperation of about 87.0% at up to 10 years, the T-SPV shows excellent durability. The majority of explanted valves show structural valve deterioration similar to that seen in other porcine heart valves.

Animals↗