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Biomedical subjects

R McKay

Publications and source records attributed to R McKay.

At least 19 recordsLinked to original sources
PubMed1992

An oligodendrocyte precursor cell line from rat optic nerve.

We have established permanent cell lines from the optic nerve of the rat with a temperature sensitive immortalizing oncogene (Simian Virus 40 large T-antigen carrying both the tsA58 and U19 mutations). The oncogene was transduced into primary cultures via a replication deficient retrovirus, and infected cells were selected with the antibiotic G418. A clonal cell line (tsU19-5) displayed some properties of oligodendrocyte precursors: it proliferated, bound the monoclonal antibody A2B5 (which recognizes minor ganglioside species), and expressed the intermediate filament vimentin and the enzyme 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP) at 33 degrees C (the permissive temperature for the oncogene). At 39 degrees C (the non-permissive temperature), some cells had the potential to differentiate further, and expressed several oligodendrocyte specific components: galactocerebroside, myelin basic protein, proteolipid protein and CNP. These results suggest that conditional oncogenes can establish neural precursor cell lines which are still capable of differentiation in vitro.

Animals↗
PubMed1992

Thrombolysis with tissue-type plasminogen activator following cardiac surgery in children.

Three children with major intracardiac or vascular thrombosis following cardiac operations were treated with intravenous recombinant tissue-type plasminogen activator. The first patient, aged 10 yr, developed a left atrial thrombus following replacement of the mitral valve with a Björk-Shiley prosthesis. The second patient, aged 16 months, had a right atrial thrombus following a modified Fontan procedure for tricuspid atresia. Both were successfully treated with a short course of intravenous tissue plasminogen activator. The third patient, aged 19 months, developed the Budd-Chiari syndrome with occlusion of the inferior caval vein following a modified Fontan operation for double inlet left ventricle. Even though near-complete thrombolysis and recanalization of the inferior caval vein was achieved with three courses of tissue plasminogen activator on successive days, she died with failure of multiple organs. In all cases, the diagnosis was established by cross-sectional and Doppler echocardiography, and the response to therapy was monitored using the same technique. Thrombolytic therapy with systemic tissue-type plasminogen activator was safe and effective in the postoperative period, with no major haemorrhagic complications.

Cardiac Surgical Procedures↗
PubMed1992

Reconstituting animals from immortal precursors.

Several recent experiments have shown that immortal neural and muscle cells retain the specific temporal and spatial properties of their precursor cells in the animal. In addition, the immortal cells retain the ability to differentiate in vitro and, after transplantation, in vivo. The results of these experiments suggest that the use of precursor cell lines may lead to powerful approaches for understanding the mechanisms that generate the ordered distribution of cell types in mammals.

Animals↗
PubMed1992

Multipotential stem cells in the vertebrate CNS.

The functional differences between the many mature neuronal types make the origins of cellular diversity in the nervous system one of the most intriguing problems in biology. This paper discusses recent experiments which explore the mechanisms generating cell diversity in the vertebrate central nervous system, focusing particularly on the immediate precursor to neurons and on neuronal differentiation. Transplantation experiments have been used to explore regional and temporal differences in the cells of the neuroepithelium. The effects of specific genes on neuronal development have been examined by mutational analysis in transgenic mice and in established neuronal stem cell lines. The combination of methods now available allow increasingly powerful dissection of the molecular and cellular mechanisms that generate the large number of different neurons in the vertebrate brain.

Animals↗
PubMed1992

Morphology of the ventriculoaortic junction in critical aortic stenosis. Implications for hemodynamic function and clinical management.

The clinical presentation of infants with critical aortic stenosis, as well as the results of surgical treatment, differs from obstruction of the left ventricular outflow tract in older children. To investigate a possible anatomic basis for this situation, we performed a detailed morphometric study of 21 hearts from infants who had critical aortic stenosis and 11 normal hearts from infants less than 3 months of age. In each of the hearts with critical aortic stenosis, only one commissure extended to the sinutubular ridge. The other two commissures were represented by folds in the aortic wall that suspended the leaflet below the level of the sinutubular junction. The leaflet thus had a free edge shorter than the circumference of the sinus, in contrast with the normal valve, in which leaflets always were longer than the circumference of their supporting sinus. Analysis of the fibrous triangles on the ventricular aspect of abnormal valves showed a symmetric three-sinus arrangement. In all but one specimen, however, only the triangle related to the mitral valve was fully developed. Although incision of both rudimentary commissures to the aortic wall should achieve some relief of obstruction, these morphologic features strongly mitigate against surgical restoration of normal function or growth in aortic valves having the morphology observed in this series of hearts.

Aortic Valve↗
PubMed1991

The myth of the aortic annulus: the anatomy of the subaortic outflow tract.

Surgical repair of the small aortic root is limited in part by the very structure of the outflow tract from the left ventricle. The root is not constructed on the basis of a ringlike annulus supporting the leaflets of the aortic valve. The only truly circular structure within the outflow tract is the junction of the aortic wall with the underlying ventricular structures, themselves partly muscular and partly fibrous. This circular ventriculoarterial junction is crossed by the semilunar attachments of the leaflets of the aortic valve, producing an interlinking arrangement between the expanded aortic sinuses and three triangles of fibrous tissue placed beneath the apexes of the commissures between the valve leaflets. The triangles form extensions of the left ventricle that are related, in part, to the pericardial cavity surrounding the heart. The arrangements of the attachment of the leaflets in malformed valves with two (or only one) effective leaflets are highly abnormal, although these valves are usually produced on the template of three aortic sinuses. The valve with two leaflets rarely gives problems during childhood. In valves producing "critical stenosis", there is usually only one effective leaflet, a condition due to incomplete liberation of two of the anticipated three commissures. Detailed study shows that, in these malformed hearts, the attachment of the leaflets is much more annular than in normal valves, with inadequate formation of the fibrous triangles.

Aortic Valve↗
PubMed1991

Identifying and manipulating neuronal stem cells.

Fetal brain tissue has been shown to have clear behavioral effects when transplanted into adult lesioned brains. These results have focused attention on the cell types of the embryonic brain. Transplantation experiments using primary cells are beginning to define the plasticity of these cells and the times when they become committed to specific neuronal fates. Growth factors have been defined that regulate the proliferation of these cells in culture. Cell lines have been established that express stem cell properties and that are capable of differentiation when implanted into the developing brain. In this article we review this work on mammalian neuroepithelial stem cells and discuss how these studies might contribute to the therapeutic use of brain transplants.

Animals↗
PubMed1991

Traumatic ventricular septal defect: serial follow-up with Doppler ultrasound.

A three-year-old girl presented with a gunshot wound of the chest. Cross-sectional and Doppler echocardiography enabled precise location of the bullet, and assessment of the haemodynamic effects of the traumatic ventricular septal defect. Serial ultrasound examination in the acute stage confirmed that the bullet was well embedded in the left ventricular myocardium, and the ventricular septal defect was restrictive, enabling conservative management.

Cardiac Catheterization↗
PubMed1991

Results of balloon pulmonary valvuloplasty as a palliative procedure in tetralogy of Fallot.

Balloon pulmonary valvuloplasty was attempted in 67 patients with tetralogy of Fallot at a median age of 5 months (range 0.03 to 52 months) for relief of cyanosis. In three patients, the valve could not be crossed and an aortopulmonary shunt was performed. In 35 patients, follow-up angiography was performed 3 to 30 months (average 12) after valvuloplasty. In 24 of these 35 patients (group A), the stenosis had been adequately palliated by valvuloplasty; the other 11 patients (group B) had required an aortopulmonary shunt 1 month (range 0 to 3 months) after valvuloplasty. The two groups were similar (p greater than 0.1) with respect to age at valvuloplasty, pulmonary anulus diameter, ratio of pulmonary artery to descending aorta diameter before valvuloplasty and interval to follow-up angiography. In contrast to patients in group B, patients in group A had a significant immediate improvement in systemic arterial oxygen saturation (p less than 0.01) and a significant increase in pulmonary anulus diameter at follow-up angiography (p less than 0.001). The growth of the branch pulmonary arteries was similar (p greater than 0.1) in the two groups. Among 42 patients who have had surgical correction, a transannular patch for right ventricular outflow tract reconstruction was used in 27 (64%); there was no difference between groups A and B with respect to its use. Eight patients died (three after repair) and death could not be directly attributed to valvuloplasty in any. Balloon valvuloplasty promotes growth of the pulmonary valve anulus and pulmonary arteries and is a useful alternative to an aortopulmonary shunt in patients with small pulmonary arteries or associated complex intracardiac defects.

Angiocardiography↗
PubMed1991

Renal function after cardiopulmonary bypass in children: comparison of dopamine with dobutamine.

We have compared low dose dopamine with dobutamine in conserving renal function in 142 children younger than 10 yr undergoing cardiopulmonary bypass (CPB). Patients were allocated randomly to receive a continuous infusion of either dopamine 2.5 micrograms kg-1 min-1 (group 1) or dobutamine 2.5 micrograms kg-1 min-1 (group 2) from the time of induction of anaesthesia. Administration of inotropes and diuretics was controlled strictly to agreed regimens. There was no clinical or statistically significant difference between the two groups in postoperative urine output, serum concentration of creatinine, fractional sodium excretion or need for diuretic therapy. This was true also of the subgroup of patients who received no other inotropic support. However, the subgroup of patients in group 1 who underwent periods of CPB in excess of 2 h (n = 17) had persistently greater postoperative serum concentrations of creatinine. Low dose dopamine did not appear to be superior to dobutamine for protection of renal function in these patients.

Acute Kidney Injury↗
PubMed1990

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↗
PubMed1978

Malignant hyperthermia and central core disease in a child with congenital dislocating hips.

We describe a development of a malignant hyperthermia (MH) syndrome, partially aborted by therapy, in a child with central core disease and congenital dislocating hips. Patients with central core disease appear to be more susceptible to MH; possibly those with elevated serum creatine phosphokinase levels, as in our patient, are especially susceptible. We review the clinical and pathologic aspects, possible pathogenesis, and treatment of the MH syndrome. An increased calcium level within the muscle fiber is suggested as the major cytodestructive factor, and that increase could be consequent to a plasmalemmal susceptibility to the provoking drugs hypothesized to be the basic defect in MH. Prevention of the full manifestations of MH is predicated on (1) a high index of suspicion in the search for history of anesthetic complications in the patient and his family, with or without evident neuromuscular disease, (2) recognition that there is a somewhat greater risk of MH developing in a patient who has certain "musculoskeletal" abnormalities or muscle weakness but that is not-except for central core disease-a classic clinicopathologically defined disease, (3) close monitoring of patients during anesthesia, and (4) if the syndrome develops, prompt therapeutic measures, including cessation of anesthesia.

Adult↗
PubMed1976

Acute aortic dissection and medial degeneration in patients with 'floppy' mitral valves.

Mitral regurgitation due to 'floppy' valves is frequently associated with areas of medical necrosis in the ascending aorta. Application of the aortic clamp to such an area during valve replacement may produce an intimal tear followed by acute dissection. This complication occurred in three patients and was treated successfully by repair of the tear in the two cases where the dissection was observed at the time of operation. Is is suggested that infrequent clamping of the aorta and careful control of the pefusion pressure may decrease the risk of intimal trauma and acute dissection.

Aged↗