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Biomedical subjects

S Y Ho

Publications and source records attributed to S Y Ho.

At least 73 records · Page 4Linked to original sources

Bone morphogenetic proteins-2 and -4 attenuate apoptosis in a cerebellar primitive neuroectodermal tumor cell line.

Similarities between primitive neuroectodermal tumors and central nervous system (CNS) progenitor cells have evoked interest in the response of these tumors to endogenous growth factors. The bone morphogenetic proteins (BMPs) have recently been found to regulate survival and differentiation of CNS progenitor cell populations. In this study, we investigated the effects of BMP-2, BMP-4, and BMP-6 on the undifferentiated cerebellar primitive neuroectodermal tumor or medulloblastoma cell line DAOY. Analysis by reverse transcriptase-polymerase chain reaction showed that mRNAs for type IA and type II BMP receptors were present in control cultures. In cultures treated with BMP-2, mRNAs for BMP receptor type IB and the activin R-I receptor became evident. Cultures were analyzed for total cell counts, proliferating cell nuclear antigen (PCNA), and apoptotic DNA fragmentation. There was a significant increase in total cell number in the BMP-2 and BMP-4 treatment groups, without any change in PCNA reactivity, and a dramatic decrease in the proportion of apoptotic nuclei at concentrations of BMP-2 and BMP-4 above 5 ng/ml (P<0.001). These effects were not observed with BMP-6, TGF-beta1 or GDNF. These results suggest that the increase in total cell number is due to the attenuation of apoptosis by BMP-2 and BMP-4. The anti-apoptotic effect of BMP-2 and BMP-4 on this neuroectodermal cell line has potential clinical implications for neuroectodermal tumors.

Apoptosis↗

Distribution of the Purkinje fibres in the sheep heart.

The aim of the present study was to advance our knowledge regarding the anatomy of the purkinje fibres from their origin, at the bundle branches, till their termination within the myocardium. Indian ink injections of the purkinje fibres were carried out in the left ventricle of 25 fresh sheep hearts and in the right ventricle of 20 hearts. Numerous samples were taken from the walls and papillary muscles of the two ventricles for histological analysis and determination of the mode of termination of the fibres. The ventricular conduction system could be injected as far proximally as the bundle branches, thus illustrating the bifascicular nature of the left bundle branch, with numerous interfascicular communications. The purkinje fibres were observed to form an extensive subendocardial network, forming a polygonal arrangement in the left ventricle with a characteristic pattern around the papillary muscles. Deep myocardial branches took origin from this network which penetrated the ventricular wall to reach the epicardium. Histological analysis demonstrated the characteristic features of the purkinje cells, and confirmed the presence ofa perifascicular sheath of connective tissue which surrounded the purkinje fibres until their transition with working cardiomyocytes. The perifascicular connective tissue sheath is important in organising the contraction of the myocardium by preventing lateral spread of conduction and by permitting transmission of the impulse only at the termination of the purkinje fibre. The sheath may also protect the fibres from the stresses and strains originating from contraction of the surrounding myocardium.

Animals↗

Deep vein thrombosis in elderly Hong Kong Chinese with hip fractures detected with compression ultrasound and Doppler imaging: incidence and effect of low molecular weight heparin.

Seventy-eight patients of average age 78 years suffering from an unilateral non-pathological hip fracture underwent compression ultrasound and pulsed and colour Doppler examination of both legs. Twenty-three patients were randomly placed on low molecular weight heparin (LMWH). Twenty-nine (37%) suffered deep venous thrombosis (DVT). There was no statistically significant difference in the incidence of DVT between the control and LMWH groups, and the incidence of DVT in elderly Chinese patients after hip replacement for a hip fracture is similar to that in other studies in Caucasians. There were, however, some differences, namely the contiguous nature of the thrombi rather than focal segmental clots, and the absence of propagation or tail formation. Although the numbers are small, this could possibly represent a population difference. There was a significantly increased occurrence of DVTs on the operated side in both groups. Serial ultrasound examination supports evidence that DVTs occur in the 1st week postoperatively, but there were also a number of patients who developed DVTs in the 2nd week. There was no statistically significant difference in overall incidence of DVT between patients on prophylactic heparin and the control group. Patients on prophylactic heparin had no thigh DVTs in comparison to the control group. LMWH may thus be effective in preventing thigh DVTs and pulmonary emboli.

Aged↗

Ventricular morphology and coronary arterial anatomy in hearts with isometric atrial appendages.

BACKGROUND: Knowledge of the precise anatomy can be advantageous when striving to improve surgical results in patients with visceral heterotaxy. METHODS: We studied the ventricular mass, and its coronary arterial supply, in 125 specimens with isomeric right and 58 with isomeric left appendages. RESULTS: The situation in which each atrium connected to its own ventricle was the most common arrangement in hearts with isomeric left appendages. The pattern with both atriums connecting to the same ventricle was more frequently seen in those with isomeric right appendages. Concordant ventriculoarterial connections were seen in only 4% of cases with isomeric right appendages, but were seen in 45% of those with isomeric left appendages. Abnormal patterns in branching of the coronary arteries were commonly associated with abnormal ventricular architecture. The morphologically right or left ventricular arteries were frequently lacking in those hearts with a dominant ventricle and a rudimentary and incomplete ventricle. A solitary coronary artery was seen in 13%. CONCLUSIONS: Recognition of these abnormalities is of clinical importance if optimal surgical strategies are to be established for patients with visceral heterotaxy.

Coronary Vessels↗

Common arterial trunk associated with double aortic arch.

The combination of common arterial trunk associated with double aortic arch is very rare. We are aware of only four cases ever reported in English literature. We add two cases of this entity and comment on the morphological aspects, the clinical impact of the combined lesions, and their diagnostic and therapeutic implications.

Aorta, Thoracic↗

The nature of the obstructive muscular bundles in double-chambered right ventricle.

OBJECTIVE: Our goal was to establish the morphologic nature of the obstructive muscular lesions in double-chambered right ventricle. METHODS: We based our morphologic observations on 10 normal hearts and on the surgical findings in 26 patients, aged 0.5 to 24 years, with a mean of 6.9 years (SD 5.8 years). In the normal hearts, we measured the distance from the pulmonary valve to the apex of the right ventricle and from the takeoff of the moderator band to the ventricular apex. From angiograms available in 20 patients, using the frontal view, we then measured the distance from the pulmonary valve to the apex of the right ventricle and from the midpoint of the obstructive lesion to the apex of the right ventricle. This permitted calculations of multiple ratios. RESULTS: In the 10 normal hearts, the moderator band took origin at a mean ratio of 0.48 (SD 0.16) of the ventricular length. On the basis of the angiographic findings, we identified 2 basic forms of double-chambered right ventricle. In 9 patients, the obstructive muscular shelf was positioned low and diagonally across the apical component, with a mean ratio of 0.38 relative to the ventricular length (SD 0.02). In the other 11 patients, the obstructive shelf was high and horizontal, with a mean ratio of 0.27 (SD 0.02). The difference was statistically significant (P =.001). Surgical repair was performed successfully in all 26 patients through a right ventriculotomy. CONCLUSIONS: Double-chambered right ventricle is the consequence of a high or low muscular division of the apical component of the right ventricle. The abnormal muscular bundle probably represents accentuated septoparietal trabeculations, rather than always being an abnormal moderator band.

Adolescent↗

Morphologic spectrum of Ebstein's malformation: revisitation relative to surgical repair.

OBJECTIVE: Our aim was to elucidate the morphologic spectrum of Ebstein's malformation of the tricuspid valve with regard to diagnosis and the feasibility of surgical repair, in the light of the currently favored reconstructive techniques. METHODS: We examined 23 autopsied hearts. Taking the displacement of the septal and mural leaflets of the abnormal tricuspid valve as our diagnostic criterion, we focused subsequently on the location of the distorted valvular orifice and the attachment and formation of the anterosuperior leaflet. We also assessed the dimensions of the components of the right ventricle relative to the plane of the displaced valvular orifice. RESULTS: In all hearts, the septal and mural leaflets were hinged at various points within the inlet of the right ventricle. In many cases, however, these leaflets were virtually absent. The plane of the effective tricuspid valvular orifice was displaced anterosuperiorly to varying degrees. In the most severe forms, the valvular mechanism took the form of a 1-leaflet valve. The length of the functional right ventricle when compared with the left ventricle ranged proportionally from 0.6 to 1. 1 (mean, 0.9). CONCLUSIONS: Ebstein's malformation is much more than simple "downward displacement" of the leaflets. In essence, the valvular orifice is formed within the ventricular cavity at the junction of the atrialized inlet and functional ventricular components. When surgical intervention becomes necessary, it is essential to make a detailed assessment of both valvular and ventricular abnormalities.

Adolescent↗

Transthoracic 3-dimensional echocardiography in the assessment of subaortic stenosis due to a restrictive ventricular septal defect in double inlet left ventricle with discordant ventriculoarterial connections.

UNLABELLED: To evaluate the accuracy and clinical utility of three-dimensional echocardiography in the assessment of the size and shape of the ventricular septal defect in double inlet left ventricle. METHODS: We validated the technique in an autopsy study, and then performed a clinical investigation. Six autopsied hearts were immersed in a waterbath and examined with 3-dimensional echocardiography. We identified the cross-section within the dataset which optimally displayed the ventricular septal defect "en face", and compared its smallest and largest diameters, as well as its area. The ventricular septal defect was then filled with a silicone sealant and a section prepared for direct measurement. In patients, we measured the diameters and area of the ventricular septal defect in endsystole nad computed the aortic valvar area in endsystole from the cross-section showing the aortic valve "en face". Ten patients with double inlet left ventricle, aged between 2 and 15 years, were studied using rotational or parallel scanning. All patients had undergone banding of the pulmonary trunk at a mean age of 7 (3-36) days, usually at the time of repair of the coarctation. Two patients had undergone surgical enlargement of the ventricular septal defect prior to echocardiographic examination. RESULTS: The correlation between the areas of the ventricular septal defect in the specimens measured directly and by 3-dimensional echocardiography was r=0.98, with limits of agreement between -0.1-0.08 cm2. In the patients, the area of the defect was measured as 3.9+/-2 cm2, whereas the aortic valvar area was 2.6+/-0.9 cm2. The ratio between the areas was 1.5 (0.5-2.3). Three patients with areas of the ventricular septal defect smaller than those of the aortic valve had resting Doppler gradients between double inlet left ventricle and the aorta of 16, 20 and 30 mm Hgs, respectively. CONCLUSIONS: 3-dimensional echocardiography provides accurate assessment of the area of the ventricular septal defect in double inlet left ventricle, and is helpful in identifying patients with subaortic stenosis caused by restrictive defects.

Adolescent↗

A unique case of ventricular isomerism?

Isomerism of the atriums has often been described with various complex cardiac malformations. As far as is known, a case of 'ventricular isomerism' has never been recorded. Described is a specimen where, on the basis of morphological criterions, there are two right ventricles.

Aorta, Thoracic↗

Sudden death in an adult with a small ventricular septal defect and an aneurysmal membranous septum.

An apparently healthy man of 26 years of age suddenly died. He was known to have had a small ventricular septal defect and complete right bundle branch block from early childhood. At post-mortem examination the small ventricular septal defect was found associated with an aneurysm of the membranous septum. Histological examination showed a normal atrioventricular node and bundle, adjacent to the aneurysm. There was fibrous interruption at the commencement of the right bundle branch, which was considered the basis of the bundle branch block. It was also considered that the right bundle branch block was of the hereditary type and that this, rather than the aneurysm of the membranous septum, was responsible for the unexpected death.

Adult↗

Localisation and quantitation of autonomic innervation in the porcine heart I: conduction system.

This study was prompted by the prospect of transgenic pigs providing donor hearts for transplantation in human recipients. Autonomic innervation is important for the control of cardiac dynamics, especially in the conduction system. Our objective was to assess the relative distribution of autonomic nerves in the pig heart, focusing initially on the conduction system but addressing also the myocardium, endocardium and epicardium (see Crick et al. 1999). Quantitative immunohistochemical and histochemical techniques were adopted. All regions of the conduction system possessed a significantly higher relative density of the total neural population immunoreactive for the general neuronal marker protein gene product 9.5 (PGP 9.5) than did the adjacent myocardium. A similar density of PGP 9.5-immunoreactive innervation was observed between the sinus node, the transitional region of the atrioventricular node, and the penetrating atrioventricular bundle. A differential pattern of PGP 9.5-immunoreactive innervation was present within the atrioventricular node and between the components of the ventricular conduction tissues, the latter being formed by an intricate network of Purkinje fibres. Numerous ganglion cell bodies were present in the peripheral regions of the sinus node, in the tissues of the atrioventricular groove, and even in the interstices of the compact atrioventricular node. Acetylcholinesterase (AChE)-containing nerves were the dominant subpopulation observed, representing 60-70% of the total pattern of innervation in the nodal tissues and penetrating atrioventricular bundle. Tyrosine hydroxylase (TH)-immunoreactive nerves were the next most abundant neural subpopulation, representing 37% of the total pattern of innervation in the compact atrioventricular node compared with 25% in the transitional nodal region. A minor population of ganglion cell bodies within the atrioventricular nodal region displayed TH immunoreactivity. The dominant peptidergic nerve supply possessed immunoreactivity for neuropeptide Y (NPY), which displayed a similar pattern of distribution to that of TH-immunoreactive nerve fibres. Calcitonin gene-related peptide (CGRP)-immunoreactive nerves represented 8-9% of the total innervation of the nodal tissues and penetrating atrioventricular bundle, increasing to 14-19% in the bundle branches. Somatostatin-immunoreactive nerve fibres were relatively sparse (4-13% of total innervation) and were most abundant in the nodes, especially the compact atrioventricular node. The total pattern of innervation of the porcine conduction system was relatively homogeneous. A substantial proportion of nerve fibres innervating the nodal tissues could be traced to intracardiac ganglia indicative of an extensive intrinsic supply. The innervation of the atrioventricular node and ventricular conduction tissues was similar to that observed in the bovine heart, but markedly different to that of the human heart. It is important that we are aware of these findings in view of the future use of transgenic pig hearts in human xenotransplantation.

Acetylcholinesterase↗

Localisation and quantitation of autonomic innervation in the porcine heart II: endocardium, myocardium and epicardium.

The immunological problems of pig hearts supporting life in human recipients have potentially been solved by transgenic technology. Nevertheless, other problems still remain. Autonomic innervation is important for the control of cardiac dynamics and there is evidence suggesting that some neurons remain intact after transplantation. Previous studies in the human heart have established regional differences in both general autonomic innervation and in its component neural subpopulations. Such studies are lacking in the pig heart. Quantitative immunohistochemical and histochemical techniques were used to demonstrate the pattern of innervation in pig hearts (Sus scrofa). Gradients of immunoreactivity for the general neural marker protein gene product 9.5 were observed both within and between the endocardial, myocardial and epicardial plexuses throughout the 4 cardiac chambers. An extensive ganglionated plexus was observed in the epicardial tissues and, to a lesser extent, in the myocardial tissues. The predominant neural subpopulation displayed acetylcholinesterase activity, throughout the endocardium, myocardium and epicardium. These nerves showed a right to left gradient in density in the endocardial plexus, which was not observed in either the myocardial or epicardial plexuses. A large proportion of nerves in the ganglionated plexus of the atrial epicardial tissues displayed AChE activity, together with their cell bodies. Tyrosine hydroxylase (TH)-immunoreactive nerves were the next most prominent subpopulation throughout the heart. TH-immunoreactive cell bodies were observed in the atrial ganglionated plexuses. Endocardial TH- and NPY-immunoreactive nerves also displayed a right to left gradient in density, whereas in the epicardial tissues they showed a ventricular to atrial gradient. Calcitonin gene-related peptide (CGRP)-immunoreactive nerves were the most abundant peptide-containing subpopulation after those possessing NPY immunoreactivity. They were most abundant in the epicardial tissues of the ventricles. Several important differences were observed between the innervation of the pig heart compared with the human heart. These differences may have implications for the function of donor transgenic pig hearts within human recipients.

Acetylcholinesterase↗

Echocardiographic and morphological correlations in tetralogy of Fallot.

AIMS: Our aim was to clarify the location and structure of the outlet septum relative to the free-standing subpulmonary infundibulum in the setting of tetralogy of Fallot and to examine its relationship to the other components of the subpulmonary outflow tract, determining their potential influence on clinical outcome. METHODS AND RESULTS: We studied prospectively 41 patients with tetralogy of Fallot (mean age 14 +/- 10.9 months) prior to surgical repair, and compared them with 15 patients undergoing closure of a ventricular septal defect associated with malalignment of the outlet septum but no subpulmonary infundibular stenosis (Eisenmenger ventricular septal defect), and 20 healthy controls. We also examined available autopsied hearts from cases with uncorrected tetralogy of Fallot (8) and Eisenmenger ventricular septal defect (13). Data were indexed for body surface area, and diameter of the tricuspid valve, respectively. The overall length of the subpulmonary infundibulum, including the extent of the muscular outlet septum, was significantly greater for patients with tetralogy of Fallot compared to normals (2.34 +/- 0.6 vs 1.46 +/- 0.34 cm/BSA0.5, P<0.001), whereas the difference between those with tetralogy of Fallot and an Eisenmenger ventricular septal defect was confined to the degree of narrowing of the subpulmonary outlet (0.43 +/- 0.22 vs 2.17 +/- 0.64 cm/BSA0.5, P<0.001). Within the tetralogy of Fallot group, there were linear relationships between deviation of the outlet septum (r= -0.61, P<0.005) and the diameter of the pulmonary valvar orifice (r=0.75, P<0.001), suggesting that growth of the pulmonary arteries may be related to this feature. When patients requiring a transannular patch as part of their surgical repair were compared with those not needing this procedure, differences were found in the diameter of the pulmonary valvar orifice and the pulmonary trunk, but not in the dimensions of the outlet septum. CONCLUSION: The position of the outlet septum in relationship to the remainder of the muscular subpulmonary infundibulum represents a hallmark of tetralogy of Fallot, permitting its differentiation from Eisenmenger ventricular septal defects and normal hearts.

Cardiac Surgical Procedures↗

The affinity of lipid-coated microbubbles to maturing spinal cord injury sites.

OBJECTIVE: This laboratory has demonstrated that lipid-coated microbubbles (LCMs) effectively aggregate and deliver chemotherapeutic drugs into rat brain tumor cells and antigliosis agents into maturing rat brain injury sites. In this study, we report the affinity of tail vein-injected LCMs to the injured rat spinal cord by a compressive lesion to the upper thoracic region. METHODS: The accumulation of LCMs in the injured spinal cord was analyzed by labeling it with a lipid-soluble fluorescent dye, 3,3'-dioctadecyloxacarbocyanine perchlorate. Indices of glial fibrillary acidic protein were measured concomitantly with 3,3'-dioctadecyloxacarbocyanine perchlorate-labeled LCMs using confocal microscopy. RESULTS: There was no aggregation of LCMs accumulated 1 and 6 hours after injury; however, when given 2, 4, and 7 days after injury, LCMs showed a clear affinity for the injured region. LCM aggregation shifted from the central necrotic area of the injury on postinjury Day 2 and postinjury Day 4 to the white matter among glial fibrillary acidic protein-positive astrocytes by postinjury Day 7. CONCLUSION: Affinity of LCMs for spinal cord injury sites may be mediated in the early stages after injury by proliferating macrophages in the necrotic center, and then in later stages by glial fibrillary acidic protein-positive astrocytes in adjacent white matter. These findings suggest a potential for using LCMs as a delivery vehicle to concentrate lipid-soluble agents in spinal cord injury sites.

Animals↗

Anatomy of the left atrium: implications for radiofrequency ablation of atrial fibrillation.

INTRODUCTION: The feasibility of treating atrial fibrillation with radiofrequency ablation has revived interest in the structure of the left atrium, a chamber that has been neglected in many textbooks of anatomy. METHODS AND RESULTS: We reviewed the gross structure of the left atrium by examining the septum, the appendage, and insertions of the pulmonary veins in normal hearts. The limited extent of the true septal component is relevant to procedures using the transseptal approach. On gross examination, the musculature of the atrial wall is composed of overlapping bundles of aligned fibers that, in the majority of hearts, are arranged in characteristic patterns with only minor individual variations. Muscular sleeves extend into the walls of the pulmonary veins to varying distances. The longest sleeves are in the left upper veins. Bachmann's bundle anteriorly, and other smaller bundles superiorly and posteriorly, bridge the septal raphe to blend with musculature of the right atrium. Tongues of left atrial musculature from the posterior wall also extend into the wall of the coronary sinus. CONCLUSION: The left atrium is more complex than usually conceived. Understanding its structure, and the arrangement of its musculature, will help in improving strategies for linear lesions when attempting to compartmentalize the chamber, or when placing focal lesions for ablating ectopic sources.

Adult↗