Showing papers by "Guy's and St Thomas' NHS Foundation Trust published in 1990"

Prenatal measurement of cardiothoracic ratio in evaluation of heart disease.

Abstract: The cardiothoracic ratio was measured in 410 normal fetuses and in a group of 73 fetuses with functional or structural heart disease. In normal fetuses it was fairly constant throughout pregnancy, but of those with congenital heart disease it was raised in cases of Ebstein's anomaly, tricuspid dysplasia, atrioventricular septal defect, and complete heart block. In some forms of congenital heart disease, however, it was within the normal range. There was a significant positive correlation between the cardiothoracic ratio and fetal hydrops in the group of 15 fetuses with supraventricular tachycardias. In these fetuses the cardiac size decreased significantly once the fetus reverted to sinus rhythm after the mother had been treated. Measurement of the cardiothoracic ratio is essential in the evaluation of fetal hydrops, as an increased value may point to the diagnosis of an intermittent fetal tachycardia if the fetus is assessed during a period of sinus rhythm. The measurement of this index forms a part of the complete prenatal evaluation of structural heart disease. The degree of cardiomegaly may provide useful information about secondary lung compression or cardiac failure and therefore assist in giving an accurate prognosis for postnatal survival.

Expression of glutathione S-transferases and cytochrome P450 in normal and tumor breast tissue.

Abstract: The level of expression of glutathione S-transferases (GSTs) and cytochrome P450s in breast tissue are potentially important determinants in both the susceptibility of this tissue to the mutagenic effects of chemical carcinogens and in the response of breast tumors to chemotherapy. In this study we have investigated the expression of these proteins in 41 tumor and surrounding normal breast tissue samples by measurement of substrate metabolism. Western blot analysis and immunohistochemistry. In addition, we have quantitated the concentration of alpha, mu and pi class GST subunits using radioimmunoassay. All three classes of GST were expressed in breast tissue. The pi and mu class enzymes preponderate. Both the polymorphic mu class GST as well as a further form, present in all individuals, were found in high concentration. The polymorphic mu class GST was expressed in approximately 50% of the samples, which is consistent with the frequency of this polymorphism in the population and therefore does not appear to be a factor in susceptibility to this disease. Interestingly, although levels of the alpha class GST were very low, in two tumor samples extremely high levels of the B1B1 subunit were detected. Immunohistochemical studies showed significant variability in the localization of the pi class of GST between normal epithelial cells, infiltrating plasma cells and tumor cells, and in some samples GST pi appeared to be almost absent from the tumor tissue. No direct, or inverse correlation was found between GST pi concentration determined by radioimmunoassay and estrogen receptor levels. However, when studied by immunohistochemistry estrogen receptor negative tumors did tend to have higher GST pi content. The only cytochrome P450 detectable by Western blot analysis was a member of the P450IIC gene family. This was apparently distinct from the P450IIC proteins expressed in the liver and was detected in normal and tumor tissues to a similar extent.

Isoproterenol and the genesis of reperfusion-induced arrhythmias in isolated rat heart: adrenoceptor or free radical-mediated mechanisms?

Abstract: In the isolated rat heart, reperfusion-induced arrhythmias were exacerbated by isoproterenol (0.01-1.0 microM). The proarrhythmic action of isoproterenol was primarily the result of a beta 1-receptor-mediated tachycardia rather than via a free radical-mediated process, since it was prevented competitively by the beta 1-receptor antagonist metoprolol, but not by the free radical scavengers mannitol, superoxide dismutase, and catalase. If heart rate was maintained by electrical pacing, the protective action of metoprolol against the isoproterenol-induced arrhythmias was lost. At high concentrations (5 and 50 microM), metoprolol alone produced a bradycardia that was probably not related to beta 1 blockade, and this resulted in some nonspecific antiarrhythmic activity. The data provide evidence that, in this model, heart rate during ischaemia is an important determinant of reperfusion-induced arrhythmias, and that free radical formation from the oxidation of high levels of exogenous isoproterenol present at the time of reperfusion does not contribute in a major way to the detrimental action of isoproterenol.