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Biomedical subjects

S C Robson

Publications and source records attributed to S C Robson.

233 records · Page 13Linked to original sources

Reproducibility of cardiac output measurement by cross sectional and Doppler echocardiography.

The variability of Doppler echocardiographic estimation of cardiac output at the aortic orifice was investigated in eight healthy subjects. Cross sectional echocardiograms of the aortic orifice and aortic Doppler velocities were recorded and measured by four echocardiographers. Between subject variability was significantly larger than within subject variability for all variables. Variability owing to different echocardiographers and different measurement times was small compared with total variability. Coefficients of variation for aortic annular diameter, aortic velocity integral, and heart rate were 4.1%, 6.4%, and 5.0% respectively. The coefficient of variation for cardiac output was 8.8% and the 95% confidence interval for measurement of cardiac output by the Doppler method was 4.45 to 6.35 l/min. One echocardiographer reanalysed all the recordings and the results showed that recording the echocardiograms introduces a significantly larger source of error than measuring them. Thus serial measurements of cardiac output by the Doppler method can be performed with acceptable reproducibility; this indicates that the technique can be accurately applied in clinical practice.

Adult↗

Cardiac output during labour.

Serial measurements of cardiac output and mean arterial pressure were performed in 15 women during the first stage of labour and at one and 24 hours after delivery. Cardiac output was measured by Doppler and cross sectional echocardiography at the pulmonary valve. Basal cardiac output (between uterine contractions) increased from a prelabour mean of 6.99 l/min to 7.88 l/min at greater than or equal to 8 cm of cervical dilatation as a result of an increase in stroke volume. Over the same period basal mean arterial pressure also increased. During uterine contractions there was a further increase in cardiac output as a result of increases in both stroke volume and heart rate. The increment in cardiac output during contractions became progressively greater as labour advanced. At greater than or equal to 8 cm of dilatation cardiac output increased from a basal mean of 7.88 l/min to 10.57 l/min during contractions. There were also further increases in mean blood pressure during contractions. One hour after delivery heart rate and cardiac output had returned to prelabour values, though mean arterial pressure and stroke volume remained raised. By 24 hours after delivery all haemodynamic variables had returned to prelabour values. Haemodynamic changes of the magnitude found in this series are of considerable clinical relevance in managing mothers with complicated cardiovascular function.

Adult↗

Combined Doppler and echocardiographic measurement of cardiac output: theory and application in pregnancy.

A non-invasive technique for the measurement of cardiac output in pregnancy by combined cross-sectional and Doppler echocardiography at three intracardiac sites is described. The validity of the technique for use during pregnancy is reviewed. Comparison with cardiac output determined simultaneously by the direct Fick technique in 15 non-pregnant subjects showed close agreement for all three measurement sites. Acceptable measurements were obtained from the aortic and pulmonary valves in all pregnant subjects and from the mitral valve in 84% of pregnant subjects. The within-patient intra-observer and hour-to-hour variabilities of cardiac output in pregnant and non-pregnant subjects were less than 5% of the mean for all three valves studied. Flow measurements at each of the three intracardiac sites correlated closely. The advantages and limitations of the technique for use during pregnancy are discussed.

Adolescent↗

Haemodynamic changes during the puerperium: a Doppler and M-mode echocardiographic study.

Serial haemodynamic investigations were performed in 15 women at 38 weeks gestation and then 2, 6, 12 and 24 weeks after delivery. Cardiac output was measured by Doppler and cross-sectional echocardiography at the aortic, pulmonary and mitral valves. Cardiac chamber size and ventricular function were investigated by M-mode echocardiography. Flow measurements at the three intracardiac sites correlated closely. Cardiac output fell from a mean of 7.42 l/min at 38 weeks to 4.96 l/min at 24 weeks after delivery, a fall of 33%. Most of this decrease (28%) had occurred by 2 weeks. This was associated with a 20% reduction in heart rate and an 18% reduction in stroke volume. By 2 weeks after delivery there was a significant decrease in left atrial dimension and left ventricular end-diastolic dimension. Left ventricular wall thickness and mass declined throughout the period of study as did aortic, pulmonary and mitral valve areas. M-mode derived indices of myocardial contractility were all significantly reduced by 2 weeks and thereafter showed no further change. No haemodynamic differences were found between lactating and non-lactating mothers.

Adult↗

Erythrocyte membrane ATP binding cassette (ABC) proteins: MRP1 and CFTR as well as CD39 (ecto-apyrase) involved in RBC ATP transport and elevated blood plasma ATP of cystic fibrosis.

In addition to the better-known roles of the erythrocyte in the transport of oxygen and carbon dioxide, the concept that the red blood cell is involved in the transport and release of ATP has been evolving (J. Luthje, Blut 59, 367, 1989; G. R. Bergfeld and T. Forrester, Cardiovasc. Res. 26, 40, 1992; M. L. Ellsworth et al., Am. J. Physiol. 269, H2155, 1995; R. S. Sprague et al., Am. J. Physiol. 275, H1726, 1998). Membrane proteins involved in the release of ATP from erythrocytes now appear to include members of the ATP binding cassette (ABC) family (C. F. Higgins, Annu. Rev. Cell Biol. 8, 67, 1992; C. F. Higgins, Cell 82, 693, 1995). In addition to defining physiologically the presence of ABC proteins in RBCs, accumulating gel electrophoretic evidence suggests that the cystic fibrosis transmembrane conductance regulator (CFTR) and the multidrug resistance-associated protein (MRP1), respectively, constitute significant proteins in the red blood cell membrane. As such, this finding makes the mature erythrocyte compartment a major mammalian repository of these important ABC proteins. Because of its relative structural simplicity and ready accessibility, the erythrocyte offers an ideal system to explore details of the physiological functions of ABC proteins. Moreover, the presence of different ABC proteins in a single membrane implies that interaction among these proteins and with other membrane proteins may be the norm and not the exception in terms of modulation of their functions.

ATP-Binding Cassette Transporters↗

Composition of the pulmonary interstitium during normal development of the human fetus.

Normal lung development is dependent on epithelial-mesenchymal interactions. This study was undertaken to examine the structure of the interstitium of the developing human fetal lung, concentrating particularly on the first and second trimesters. Lung tissue was obtained at autopsy from nonmalformed, nonmacerated cases of spontaneous abortion (n = 15), stillbirth (n = 9), and very early neonatal death (n = 5) (range of gestations, 10-42 weeks). Paraffin-embedded tissue sections were examined using immunohistochemical methods to determine expression of collagens I, III, IV, V, and VI; the glycoproteins fibronectin and laminin; and the intermediate filaments vimentin, alpha-smooth muscle actin (alphaSMA), and desmin. Collagens III and VI and cells expressing alphaSMA were present consistently at points of airway branching and secondary crest formation, indicating a role for these components in the initiation and stabilization of airway branches in the developing lung. Desmin expression by stromal cells succeeded alphaSMA temporally, and may represent a marker of terminal smooth muscle differentiation within the airway; it was not detected in the vascular tree. Other components were widely expressed throughout the extracellular matrix, including basement membranes, at all gestations. The spatial and temporal patterns of expression of components of the lung interstitium provide clues to the mechanisms underlying normal human lung development and possible insights into the pathogenesis of fetal and neonatal lung disease.

Collagen↗

Potential of aspirin to inhibit thrombotic microangiopathy in alpha1,3-galactosyltransferase gene-knockout pig hearts after transplantation in baboons.

Hearts from alpha1,3-Galactosyltransferase gene-knockout (GaIT-KO) pigs were transplanted heterotopically into 8 baboons that received an anti-CD154 monoclonal antibody (mAb)-based immunosuppressive regimen and heparin. Three baboons died or were euthanized with beating grafts on 16, 23, and 56 days, respectively, and the remaining 5 grafts functioned for 59-179 days. Hyperacute rejection did not occur, and classical features of acute humoral xenograft or acute cellular rejection were rare. However, thrombotic microangiopathy (TM) developed in all cases; its onset was delayed in 2 baboons that received aspirin. Function of a pig organ in a baboon for a period approaching 6 months has not been reported previously and lends encouragement that the barriers to xenotransplantation will be overcome, but TM requires investigation.

Animals↗

Co-localization of P2Y1 receptor and NTPDase1/CD39 within caveolae in human placenta.

Nucleoside triphosphate diphosphohydrolase-1 (NTPDase1/CD39) is the dominant ecto-nucleotidase of vascular and placental trophoblastic tissues and appears to modulate the functional expression of type-2 purinergic (P2) G-protein coupled receptors (GPCRs). Hence, this ectoenzyme could regulate nucleotide-mediated signalling events in placental tissue. This immunohistochemical and immuno-electron microscopic study demonstrates the expression of NTPDase1/CD39, P2Y1 and P2Y2 receptors in different cell types of human placenta. Specifically P2Y1 has an exclusive vascular distribution whereas P2Y2 is localized on trophoblastic villi. Co-localization of P2Y1 and NTPDase1/CD39 are observed in caveolae, membrane microdomains of endothelial cells. The differential localization of these P2 receptors might indicate their unique roles in the regulation of extracellular nucleotide concentrations in human placental tissues and consequent effects on vascular tone and blood fluidity.

Adenosine Triphosphatases↗

Differential expression of extracellular matrix proteins and integrins in hepatocellular carcinoma and chronic liver disease.

UNLABELLED: Extracellular matrix (ECM) molecules play an important role in the orderly development, differentiation and function of tissues. The interaction of ECM with heterodimeric transmembrane glycoproteins called integrins is thought to be an important factor in cell-cell and cell-substrate adhesions in tumours, tumour invasion and metastases. PURPOSE: To investigate ECM and adhesion molecules in hepatocellular and breast carcinomas, chronic hepatitis and hepatic cirrhosis. MATERIALS AND METHODS: Frozen in liquid nitrogen and also paraffin-embedded biopsies from hepatocellular adenomas (3), well-differentiated (53) and poorly differentiated (19) hepatocellular carcinomas, lobular (3) and poorly differentiated (7) breast carcinomas, chronic hepatitis (10) and hepatic cirrhosis (10) were collected and investigated. Immunohistochemical techniques were applied for the detection of ECM molecules fibronectin, laminin, tenascin, vitronectin and integrins alpha 5 and beta 4. RESULTS: Poorer differentiation of the tumours was characterised by up-regulation of fibronectin, tenascin and vitronectin and downregulation of laminin and both integrins. These changes were observed in the interface between tumour and invaded tissues and within cancerous sinusoids. CONCLUSION: Increased expression of some ECM glycoproteins around tumour foci suggests a role in stimulating cancer cells or a host defence mechanism accompanied by desmoplastic response to them. Downregulation of laminin in poorly differentiated tumours identifying loss of basement membrane components and parallels quantitative changes in the expression of adhesion molecules in both hepatic and breast carcinomas. This may be an important step in enhancing local invasiveness of tumour cells, facilitating tumour spreading and biological malignancy.

Antibodies, Monoclonal↗

Hepatic vascular lesions associated with malignant lymphomas.

Veno-occlusive disease is a serious complication of malignant conditions and often follows irradiation or is drug-induced. We report on the liver histology of a consecutive series of 32 cases of Hodgkin's and non-Hodgkin's lymphomas. Veno-occlusive lesions were noted in 27 biopsies prior to treatment. These patients had no apparent malignant infiltrate to the liver. The pathogenesis of these lesions is unclear.

Adult↗