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Biomedical subjects

R McKay

Publications and source records attributed to R McKay.

At least 91 records · Page 5Linked to original sources

Comparison of the aortic homograft and the pulmonary autograft for aortic valve or root replacement in children.

To assess late results of aortic homograft and pulmonary autograft valves implanted into the left ventricular outflow tract of children, we reviewed the case histories of 146 patients 18 years of age or younger who underwent aortic valve or root replacement between November 1964 and April 1990. One hundred three patients (mean, 12 +/- 3.9 years) received an aortic homograft and 43 (mean, 14 +/- 4.1 years) had their own pulmonary valve transferred to the aortic position. There were 54 valve and 49 root replacements with homografts and 36 valve and seven root replacements with autografts. Hospital mortality rate was 15.5% (16 patients) in the homograft group and 11.6% (five patients) in the autograft group. Survivors were followed up for a total of 867 (homograft) and 297 (autograft) patient-years. The late mortality rate was 16.7% (1.9% per patient-year) for patients with homografts and 13.2% (4.4% per patient-year) for patients with autografts, whereas the incidence for reoperation per patient-year was 2.9% and 2.0%, respectively. At 15 years actuarial rates for homografts and autografts for freedom from reoperation were 54% +/- 8.1% and 68% +/- 11.1%; freedom from endocarditis, 97% +/- 2.4% and 75% +/- 10.2%; and freedom from any complication, 41% +/- 6.5% and 50% +/- 10.3%. Valve degeneration occurred in 19 homografts (2.2% per patient-year), whereas there was no definite instance of primary tissue failure among the pulmonary autografts. This experience would indicate that either the homograft or the autograft valve can be used with acceptable results in children. However, the pulmonary autograft gives better long-term performance and, if growth potential is realized, may be the ideal valve substitute in children.

Adolescent↗

Proliferation and differentiation of neuronal stem cells regulated by nerve growth factor.

Nerve growth factor plays an important part in neuron-target interactions in the late embryonic and adult brain. We now report that this growth factor controls the proliferation of neuronal precursors in a defined culture system of cells derived from the early embryonic brain. Neuronal precursor cells were identified by expression of the intermediate filament protein nestin. These cells proliferate in response to nerve growth factor but only after they have been exposed to basic fibroblast growth factor. On withdrawal of nerve growth factor, the proliferative cells differentiate into neurons. Thus, in combination with other growth factors, nerve growth factor regulates the proliferation and terminal differentiation of neuroepithelial stem cells.

Animals↗

Determinants of survival following repair of interrupted aortic arch in infancy.

Between January 1971 and March 1987, surgery was performed in 26 infants with interrupted aortic arch. At operation the 14 boys and 12 girls weighted between 1.71 and 4.23 kg (mean +/- SD = 3.1 +/- 0.63 kg) and ranged in age from 2 to 90 days (13 +/- 18 days). The interruption was distal to the left subclavian artery in 4 (15%), between the left carotid and subclavian arteries in 20 (77%) and between the brachiocephalic (innominate) and left carotid arteries in 2 (8%). Associated complex cardiac lesions in 8 patients included complete transposition (2), common arterial trunk (2), aortopulmonary window (2), double inlet left ventricle (1) and tricuspid atresia (1). The remaining patients had an isolated ventricular septal defect. The arch was reconstructed with a prosthetic conduit in 14 patients; by a direct anastomosis in 6; using the subclavian artery in 3; and with the pulmonary trunk and the arterial duct in 2. Twenty patients (77%) underwent palliative surgery as the first stage of management, and banding of the pulmonary trunk was also performed in 16 of these. Five patients (19%) underwent primary complete repair of the interruption and intracardiac anomalies. One patient (4%) died soon after thoracotomy for palliative surgery. Of the 15 (57%, 70% confidence limits CL = 46-69%) early deaths, 7 occurred in patients with complex associated defects and 4 occurred when single stage repair was attempted. Survival following first-stage palliative surgery for arch interruption with isolated ventricular septal defect was 64% (9/14) [70% CL = 47-79%]. All of these patients subsequently underwent complete repair. Chi-squared and t-tests showed the year of operation and the type of operation (two-stage repair) to be associated with improved survival. It is concluded that a two-stage repair of interrupted aortic arch offers a reasonable alternative to primary complete correction and will lead to satisfactory subsequent repair in most cases.

Anastomosis, Surgical↗

Mechanisms regulating cell number and type in the mammalian central nervous system.

In the developing brain, neurons are derived from multipotential precursor cells in a precise sequence, where the time when a neuron becomes postmitotic is closely linked to the differentiated function of the neuron. Work from our group (1) identifies the Nes+ neuronal precursor state, (2) defines growth factors that regulate the proliferation of Nes+ precursor cells and their differentiation into neurons, and (3) establishes immortal cell lines that may be useful models for the terminal differentiation of Nes+ cells into neurons and astrocytes. These results suggest that the basic technical requirements are now in place to define the signals that control the transition from a precursor cell to a postmitotic neuron in the mammalian CNS. Control of this terminal differentiation is a key step in generating the large numbers and types of cells in the CNS.

Animals↗

Doppler echocardiographic evaluation of pulmonary artery flow after modified Fontan operation: importance of atrial contraction.

Doppler echocardiography was used to evaluate blood flow in the pulmonary artery in 14 patients 2 to 42 months (mean (SD) 17 (12) months) after a modified Fontan operation incorporating a direct atriopulmonary anastomosis. Preoperatively six patients had tricuspid atresia, six had a double inlet left ventricle, and two had pulmonary atresia with an intact ventricular septum. The postoperative rhythm was sinus in 11 patients, junctional in one, ventricular pacing in one, and atrioventricular sequential pacing in one. In one patient the Doppler trace was unsatisfactory for analysis. In all patients forward flow in the pulmonary artery had biphasic peaks related to both atrial and ventricular contraction. The mean (SD) peak flow velocity that was synchronous with atrial contraction was 80 (30) cm/s and that synchronous with ventricular contraction was 74 (23) cm/s. The atrial contribution to total pulmonary artery flow, assessed by velocity-time integrals, varied between 22% and 73% (mean (SD) 45 (14)%). In patients with tricuspid atresia the mean (SD) peak flow velocity with atrial contraction was 90 (27) cm/s and that with ventricular contraction was mean (SD) 68 (24) cm/s. In patients with double inlet left ventricle the mean (SD) peak flow velocity was 67 (36) cm/s with atrial contraction and 80 (25) cm/s with ventricular contraction. The atrial contribution to total pulmonary blood flow in patients with tricuspid atresia was significantly higher (53 (11)%) than in those with double inlet left ventricle (37 (14)%). Pulmonary artery flow after modified Fontan operation was biphasic and was related to both atrial and ventricular contraction. The atrial contribution to pulmonary blood flow is greater in patients with tricuspid atresia than in those with a double inlet left ventricle. The mechanism of the second peak related to ventricular contraction is unknown.

Adolescent↗

Operative findings after percutaneous pulmonary balloon dilatation of the right ventricular outflow tract in tetralogy of Fallot.

Since 1983 percutaneous balloon dilatation of the right ventricular outflow tract has been performed as an alternative to surgical palliation in selected cases of tetralogy of Fallot at the Royal Liverpool Children's Hospital. From 31 December 1984 to 31 December 1988, 27 of these patients underwent subsequent surgical correction. Age at operation ranged from 7 to 58 months (median 2.7 years). The mean interval between balloon dilatation and correction was 15.6 months (range 3-39 months). Two patients had a systemic pulmonary shunt operation performed before dilatation and a further five required one afterwards. Overall 20 (74%) patients had some anatomical alteration as the result of balloon dilatation, while in seven (26%) there was no discernible change in the right ventricular outflow tract. There was no consistent relation between the ratio of balloon size to pulmonary annulus diameter and the morphological findings. Balloon dilatation may obviate the need for systemic-pulmonary shunt at the expense of some structural damage, particularly to the posterior cusp. The present data suggest that dilatation does not bring about growth of the annulus to such an extent that transannular patch is no longer needed at intracardiac repair.

Catheterization↗

Right-sided intrathoracic bypass graft for complex or recurrent coarctation of the aorta.

A simple technique is described for the interposition of a tube graft between the ascending and descending aorta in the right chest. Directing the graft posteriorly preserves the integrity of the pericardium and avoids potential damage to the prosthesis at a subsequent sternotomy for open heart surgery. This procedure was used successfully and without complication in an 18-month-old boy who had undergone two previous operations for coarctation of the aorta, and in a 20-year-old girl with William's syndrome and diffuse hypoplasia of the distal aortic arch.

Adult↗

Truncus arteriosus with interrupted aortic arch: successful correction in a neonate.

Truncus arteriosus (type II) with interrupted aortic arch (type B) was successfully repaired at 11 days of age using anterior translocation of the pulmonary arteries, resection of the ductus arteriosus, and direct anastomosis between the descending aorta and truncus. This technique permitted wide reconstruction of the aortic arch and minimized the number of suture lines. It also positioned the right ventricle-pulmonary artery conduit anteriorly, which may simplify its subsequent replacement.

Abnormalities, Multiple↗

Anomalous origin of the left coronary artery from the pulmonary trunk. Anatomic findings in relation to pathophysiology and surgical repair.

Anomalous origin of the left coronary artery from the pulmonary trunk, though a discrete anatomic malformation, manifests a spectrum of clinical and pathologic consequences. The objectives of this study were to characterize the primary anatomic findings in a group of specimens with anomalous left coronary artery and the extent of secondary morphologic and pathologic changes. Although the cases studied probably represent the least favorable end of the spectrum, the observed pathogenesis and evolution of secondary changes suggest that reconstruction of a two-coronary arterial system supplied through two coronary arteries would be advantageous to most patients. A high origin of the right coronary artery or location of the left coronary artery adjacent to a pulmonary cusp or branch may complicate the tunnel-type repair. In these cases, transfer of the left coronary artery to the aorta may be preferable.

Abnormalities, Multiple↗

Homograft replacement of the pulmonary artery bifurcation.

Severe deformity or nonconfluence of the pulmonary arteries was repaired during correction of congenital heart defects by implantation of a complete, fresh, antibiotic-sterilized homograft pulmonary artery bifurcation in 17 patients, aged 15 months to 17 years. Six patients had Fallot's tetralogy; five, pulmonary atresia and ventricular septal defect; three, truncus arteriosus; two, ventricular septal defect; and one, pulmonary atresia with intact ventricular septum. All but one had previously undergone one or more palliative or corrective operations. Thirteen patients survived the operation (76%; 70% confidence interval = 61% to 88%) and were followed up from 2 to 56 months postoperatively (mean = 16 months). All had symmetrical pulmonary perfusion on chest x-ray films and satisfactory homograft function on Doppler echocardiograms. There were no late deaths or reoperations. Four patients (24%; 70% confidence interval = 12% to 39%) died in the hospital of pulmonary or cardiac dysfunction despite a technically satisfactory reconstruction. Comparison of predicted and observed ventricular pressure ratios in nine patients showed that the factor contributed by a right pulmonary artery branch stenois was cancelled in most. The use of a complete, adult-size homograft has thus facilitated reconstruction of the pulmonary artery bifurcation and given encouraging early results.

Adolescent↗

Immortalization of precursor cells from the mammalian CNS.

Recent studies show that the nervous system contains many molecularly distinct cell types. Clonal cell marking experiments demonstrate that different cell types in some areas of the CNS are products of a multipotential stem cell. The factors controlling the differentiation of vertebrate CNS precursor cells would be more accessible to molecular analysis if cell lines with precursor properties could be established. Here we show that cell lines expressing an antigenic marker specific for a major brain precursor cell population can be established from rat cerebellum. We demonstrate that cell lines express the precursor, neuronal or glial properties depending on the growth conditions. This work supports the view that brain precursor cells expressing the marker Rat 401 are multipotential and can differentiate into cells with either neuronal or glial properties. Cell lines capable of differentiation should be useful in defining the signaling systems generating the cell types of the brain.

Animals↗

Tricuspid valve replacement using an unstented pulmonary homograft.

In consideration of the limitations of mechanical and stent-mounted tissue valves, a technique was developed for tricuspid valve replacement using an inverted pulmonary homograft. It was used successfully in a 4-year-old patient operated on for pulmonary atresia with intact ventricular septum and in a 3 1/2-year-old girl with Ebstein's anomaly.

Arrhythmias, Cardiac↗

Where do different neurons come from? Identification and immortalization of CNS precursor cells.

The ability to make functionally competent brain precursor cell lines may have important consequences for a number of outstanding questions in mammalian CNS development. The diversity of neurons is one of the most striking conclusions of recent molecular studies of the nervous system. In our work we provided some of the earliest data to support this conclusion. Our preliminary data with precursor cell lines suggest that these cells give neurons with highly differentiated characteristics. If further work continues to support this conclusion, then immortal cell lines will be useful in analyzing the mechanisms that make neurons different. The methods that can be applied to these cell lines include manipulation in tissue culture, transplantation into the developing CNS, and application of the methods of mammalian cell genetics to link gene function to neuronal specificity.

Animals↗

Accessory mitral valve leaflet causing aortic regurgitation and left ventricular outflow tract obstruction. Case report and review of published reports.

Arrhythmias, aortic regurgitation, and symptoms of severe intermittent ventricular outflow obstruction developed in a 14 year old boy with a heart murmur who had been followed from infancy. These were caused by an accessory mitral leaflet, which was successfully removed at open heart operation. A review of 21 previously reported cases found a high incidence of associated cardiac malformations, appreciable subaortic obstruction in most patients, and a consistent attachment of the accessory tissue to the ventricular aspect of the anterior mitral leaflet. The characteristic echocardiographic appearance of a mobile mass arising from the area of aortic-mitral continuity is sufficient for the diagnosis of accessory mitral leaflet and echocardiographic examination will facilitate the surgical management of this condition.

Adolescent↗

Periarterial abscess: another cause of cyanosis after pulmonary artery banding.

Twenty seven months after pulmonary artery banding a boy aged two and a half developed rapidly progressive cyanosis. A periarterial abscess was found at the site of the band. Repair of the pulmonary artery and closure of the ventricular septal defect were complicated by profoundly low cardiac output and prolonged dependence on a ventilator. This near fatal complication would have been avoided by primary closure of the ventricular septal defect.

Abscess↗