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Biomedical subjects

G R Sutherland

Publications and source records attributed to G R Sutherland.

At least 433 records · Page 24Linked to original sources

Assignment of anonymous DNA probes to specific intervals of human chromosomes 16 and X.

Anonymous DNA probes mapping to human chromosome 16 and the distal region of the human X chromosome were isolated from a genomic library constructed using lambda EMBL3 and DNA from a mouse/human hybrid. The hybrid cell contained a der(16)t(X;16)(q26;q24) as the only human chromosome. Fifty clones were isolated using total human DNA as a hybridisation probe. Forty six clones contained single copy DNA in addition to the repetitive DNA. Pre-reassociation with sonicated human DNA was used to map these clones by a combination of Southern blot analysis of a hybrid cell panel containing fragments of chromosomes 16 and X and in situ hybridisation. One clone mapped to 16pter----16p13.11, one clone to 16p13.3----16p13.11, four clones to 16p13.3----16p13.13, two clones to 16p13.13----16p13.11, one clone to 16p13.11, seven clones to 16p13.11----16q12 or 16q13, four clones to 16q12 or 16q13, three clones to 16q13----16q22.1, four clones to 16q22.105----16q24, and nineteen clones to Xq26----Xqter. Two clones mapping to 16p13 detected RFLPs. VK5 (D16S94) detected an MspI RFLP, PIC 0.37. VK20 (D16S96) detected a TaqI RFLP, PIC 0.37 and two MspI RFLPs, PIC 0.30 and 0.50. The adult polycystic kidney disease locus (PKD1) has also been assigned to 16p13. The RFLPs described will be of use for genetic counselling and in the isolation of the PKD1 gene. Similarly, the X clones may be used to isolate RFLPs for genetic counselling and the isolation of genes for the many diseases that map to Xq26----qter.

Animals↗

A linkage group with FRA16B (the fragile site at 16q22.1).

Polymorphic DNA markers located in bands 16q13, 16q21 and 16q22 were examined for recombination with FRA16B, the fragile site at 16q22.100. A tight linkage cluster D16S10-FRA16B-D16S4-HP was established. There were no recombinants (theta = 0.0, z = 8.3) between D16S10 and D16S4, which flank FRA16B. The markers D16S10 and D16S4 are in close proximity on the genetic map and delineate a small chromosomal segment, which contains the distamycin A-inducible fragile site.

Chromosome Fragile Sites↗

Biological and methodological implications of prostaglandin involvement in mouse brain lipid peroxidation measurements.

Enhanced cyclooxygenase-mediated prostaglandin (PG) turnover occurring during sacrifice and biochemical processing of tissues also generates malondialdehyde (MDA), a product of lipid peroxidation (LPO). Studies reporting on LPO estimated by thiobarbituric acid reactive substances (TBARS) have failed to consider such artefactual increases. This study reports the relative proportion of PG metabolism-derived MDA (PG-MDA) in mouse brain regions during the TBARS assay. The cyclooxygenase inhibitor indomethacin significantly lowered MDA in fronto-parietal cortex and corpus striatum. Indomethacin (50-800 micrograms/ml, in vitro) increased estimated TBARS in whole brain. Such enhancement was absent when indomethacin (20-80 micrograms/sample) was added to the MDA standard curve, reflecting its interaction with TBARS other than MDA. PG-MDA contributes as much as 15% to the total estimated value of MDA in fronto-parietal cortex and corpus striatum and must be corrected for in LPO studies.

Animals↗

The surgical complications of acute myocardial infarction: color Doppler evaluation.

Two-dimensional echocardiography in combination with Doppler and color Doppler flow mapping is now considered the technique of choice for the early diagnosis and assessment of the 'surgical' complications of acute myocardial infarction. It has the advantage of being a rapid, safe technique with ease of portability and repeatability, at relatively low cost. Transesophageal echocardiography may provide an alternative 'window' for imaging cardiac structure and function, but as yet its value in the diagnosis of the complications of myocardial function is not proven. In the acute phase, color Doppler flow mapping can diagnose the cause of hemodynamic deterioration by distinguishing primary pump failure from the mechanical complications such as ventricular septal rupture or papillary muscle rupture. In the subacute phase, complications including left ventricular true and false aneurysms may be detected and this information allows optimal management decisions to be made. Thus, color Doppler flow mapping has become an indispensable technique in the coronary care unit. It provides a complete picture of cardiac structure and function making it superior to other methods in the clinical situation of an acute myocardial infarction which has such a volatile and unpredictable course.

Blood Flow Velocity↗

Open heart surgery in the first 24 hours of life.

The results of open heart surgery in infants have steadily improved. The performance of corrective surgery very early in life has thereby been encouraged. We report four patients who underwent successful surgical correction within 24 h of birth. Two patients with total anomalous pulmonary venous drainage and one patient with pulmonary atresia and intact septum were corrected with the aid of profound hypothermia by the combined surface and bypass cooling technique. Cardiopulmonary bypass alone was used for the fourth patient with aortic stenosis. The usual surgical techniques can be applied successfully to infants even within 24 h of life.

Aortic Valve Stenosis↗

Intraoperative ultrasound monitoring of banding of the pulmonary trunk: a new technique?

We report an intraoperative real-time echo/Doppler study of the hemodynamic effects of banding of the pulmonary trunk in complete transposition seven years after a neonatal Mustard procedure. The patient had developed severe right ventricular failure. To prepare the left ventricle for an arterial switch procedure, banding of the pulmonary trunk was performed. While tightening the band, we monitored the pressure drop produced by using real time continuous wave Doppler interrogation. After banding, we used combined M-mode and cross-sectional echocardiography to image the left changes induced in left and right ventricular dimensions, shape and function by the acute change in hemodynamics.

Child↗

Limitations of Doppler ultrasound in the diagnosis of neonatal coarctation of the aorta.

Blood flow velocities were recorded using Doppler ultrasound in 40 babies aged between 1 day and 4 weeks who had coarctation of the aorta or interruption of the aortic arch. High velocity jets of 3 m/sec or more in the descending aorta were detected in only 3 patients, two of whom had interruption of the aortic arch. There was very poor agreement between upper and lower limb blood pressure difference and Doppler derived peak pressure drop. Doppler ultrasound may provide useful information on coexisting intracardiac abnormalities, but in the presence of ductal patency is of little value in the diagnosis of coarctation itself.

Aortic Coarctation↗

The value of Doppler color flow mapping in determining pulmonary blood supply in infants with pulmonary atresia with ventricular septal defect.

Thirty-two neonates and infants with pulmonary atresia with ventricular septal defect were initially investigated with cross-sectional and spectral Doppler echocardiography and Doppler color flow mapping. All 32 had subsequent correlative angiography. This demonstrated that 24 infants had adequate-sized right and left pulmonary arteries (19 confluent, 5 nonconfluent). Of the five infants with nonconfluent pulmonary arteries, four had bilateral ductus arteriosus and one had a single left-sided ductus with anomalous origin of the right pulmonary artery from the ascending aorta. Nineteen infants had confluent pulmonary arteries, all of which were supplied by a single ductus. Eight infants had complete absence of or inadequate pulmonary arteries; all had multiple aortopulmonary collateral vessels arising from the descending aorta. The presence of adequate-sized right and left pulmonary arteries was correctly predicted in 21 of 24 infants by cross-sectional echocardiography alone and in all 24 by Doppler color flow mapping. Confluence of the right and left pulmonary arteries was predicted by cross-sectional imaging in 14 of the 19 infants in whom it occurred, and by Doppler color flow mapping in all 19 infants. The precise definition of the pulmonary blood supply was correctly predicted by Doppler color flow mapping in 16 of the 19 infants with confluent pulmonary arteries and a single ductus. However, in three infants in this group, Doppler color flow mapping made a false diagnosis of multiple aortopulmonary collateral vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiography↗

Mapping the short arm of human chromosome 16.

Physical mapping of 13 different breakpoints on the short arm of chromosome 16 using previously mapped probes and the subsequent mapping of additional probes enabled the division of this portion of the chromosome into six different intervals. D16S94 was mapped between HBA and D16S80 and is closer to PKD1 than either HBA or D16S80. A tight linkage group which includes FRA16A, D16S8, and D16S79 was identified. Seven breakpoints, including FRA16A, could not be separated by probe localizations. This study provides the basis for the development of detailed maps of the short arm of chromosome 16.

Animals↗

A study of monoamine metabolism in human epilepsy.

Fourteen patients with intractable epilepsy underwent surgical resection of their epileptogenic focus. Hippocampal and temporal cortical samples were obtained, and subjected to high performance liquid chromatography with electrochemical detection. Levels of 5-hydroxyindoleacetic acid (5-HIAA) in actively spiking temporal cortex were 0.454 +/- 0.012 ng/mg (mean +/- SEM), contrasting with less actively spiking cortex values of 0.248 +/- 0.042 ng/mg and normal literature values, obtained from post-mortem material, of 0.140 +/- 0.050 ng/mg. Similarly, homovanillic acid (NVA) levels were significantly increased in epileptic tissue compared to normal literature values. Actively spiking cortex values were 0.172 +/- 0.001 pg/mg, less active cortex values were 0.058 +/- 0.012 pg/mg, and literature values were 0.011 +/- 0.002 pg/mg. Although a direct statistical comparison between the data reported here and literature values may not be valid, the findings show a continuum from normal through increasingly active electrode sites, likely reflecting a true biologic phenomena. Similarly, statistically significant increases in 5-HIAA and HVA levels were found in hippocampal tissue, which also showed significantly lower dihydroxyphenylacetic acid levels. We conclude that raised levels of serotonin and dopamine metabolites in actively spiking cortex likely reflect an increase in their turnover, and are an epileptic epiphenomenon. Exaggeration of turnover may represent the "metabolic noise" of epilepsy, rather than a concerted strategy of local or distal neurons to contain an epileptogenic focus.

3,4-Dihydroxyphenylacetic Acid↗

Colour flow mapping in cardiology: indications and limitations.

Colour flow mapping (CFM) produces a two-dimensional representation of blood flow within the heart and great vessels by analysing data acquired from multiple pulsed Doppler sample volumes, and displaying mean velocity and turbulence of flow at each site. Constraints imposed by the time required to process these data mean that CFM cannot be used for precise velocity measurements. Instead it depicts flow patterns in healthy and abnormal hearts and the precise location and direction of turbulent jets. CFM is an integral part of the standard echocardiographic examination; it is especially useful in neonates and children with congenital heart disease, and in adults for the semi-quantitative assessment of valve regurgitation, and the description of flow patterns in complex acquired disease. Transoesophageal echocardiography with CFM is invaluable for the diagnosis of mitral prosthetic valve dysfunction, aortic dissection, and complications of infective endocarditis. Intraoperative epicardial CFM provides the equivalent of intraoperative angiography.

Blood Flow Velocity↗

What is the ideal orientation of a mitral disc prosthesis? An in vivo haemodynamic study based on colour flow imaging and continuous wave Doppler.

Doppler colour flow imaging demonstrates normal laminar flow to enter the left ventricle in diastole through the mitral inflow tract located posteriorly in the left ventricle. Laminar flow then passes around the left ventricular apex to the anteriorly located outflow tract. As this is the normal physiologic flow pattern, it would seem appropriate that in the surgical implantation of a mitral tilting disc prosthesis the greater orifice should be directed posteriorly to mimic the normal native valve flow pattern. To determine whether variable positioning of the greater orifice had any significant haemodynamic consequences, intracavitary blood flow patterns were studied in 30 patients with mitral Björk-Shiley prostheses variously orientated in the mitral orifice. The orientation of the greater orifice (OGO) of the prosthesis was determined by fluoroscopy and the pattern of the left ventricular inflow from Doppler colour flow imaging. Twelve patients had their OGO and inflow directed towards the inflow tract (orientation I): nine patients had their OGO and inflow directed anteriorly towards the outflow tract (orientation II) and nine patients had their prosthesis with OGO and inflow in an intermediate position (orientation III). The mean prosthetic diastolic gradient, calculated using continuous wave Doppler, averaged 2.8 mmHg (+/- 0.5 mmHg) for the 25-mm prosthesis in orientation I, but 6.0 mmHg (+/- 0.7 mmHg) for the same size prosthesis in orientation II and 5.8 mmHg (+/- 0.9 mmHg) with a 25-mm prosthesis in orientation III. Similarly, for prostheses of 27 mm and 29-31 mm the lowest mean diastolic gradient was found in orientation I (2.7 mmHg +/- 0.8 and 2.8 mmHg +/- 0.5, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Advantages of colour flow imaging in the diagnosis of left ventricular pseudoaneurysm.

Eleven cases of left ventricular pseudoaneurysm in nine patients were studied by cross sectional echocardiography, conventional Doppler echocardiography, and colour flow imaging. In two patients recurrent pseudoaneurysms developed after cardiac surgery, three had acute rupture after myocardial infarction, two were the result of stab wounds, one was a late rupture of a true left ventricular aneurysm, one developed after surgical resection of a true left ventricular aneurysm, and two as a consequence of left ventricular venting. In all 11 cases the diagnosis was confirmed by angiographic or surgical information or both. The diagnosis was suspected clinically in only four cases. Cross sectional echocardiography alone confirmed the diagnosis in five cases. Neither pulsed wave Doppler nor continuous wave Doppler established the diagnosis when they were used without colour flow imaging in five and three cases respectively. In all 11 cases colour flow imaging showed flow in and out of the pericardial cavity at the defect site as well as the abnormal flow within the pseudoaneurysm. Subsequent use of pulsed Doppler showed a consistent "to and fro" flow pattern across the myocardial defect with characteristic respiratory variation of the peak systolic velocity. This unique intrapericardial flow pattern is diagnostic of a pseudoaneurysm. Colour flow imaging is a valuable addition to cross sectional and Doppler echocardiography, and is the best technique for detecting left ventricular pseudoaneurysms.

Color↗

Aortic valvotomy for critical aortic stenosis in neonates and infants aged less than one year.

Between April 1974 and December 1987, 20 infants (six under one month of age) (mean weight 4.9 kg) underwent surgical valvotomy for critical aortic stenosis. Three of the four patients treated before 1976 died. Since 1979, 16 infants (four neonates) have undergone valvotomy with no deaths. Mortality for the whole group was 15%; in the neonates it was 33%. There were no late deaths. The survivors were followed up for a mean of 3 years 9 months and two required re-operations. The considerable improvement in surgical results in the past decade should be taken into account when newer techniques such as balloon dilatation are evaluated.

Aortic Valve↗