The Hayek oscillator: a new method of ventilation in microlaryngeal surgery.

The Hayek oscillator is an externally (body) mounted cuirass ventilator used in the intensive care unit. We have used it to ventilate patients undergoing microlaryngeal surgery. It was found to be a relatively safe method of ventilation in these cases, with the advantage of dispensing with any form of endolaryngeal or endotracheal intubation.

Aromatase activity in normal breast and breast tumor tissues: in vivo and in vitro studies.

Infusions of isotopically labeled [3H] androstenedione with measurement of [3H] estrone in normal breast and breast tumor tissue have been carried out in an attempt to determine the contribution that aromatization makes to the estrogen content of breast tissues. After infusion of [3H] androstenedione for 12h there was significant uptake of this steroid by normal breast and breast tumors. [3H] Estrone was detected in all samples of normal breast tissue examined so far but not in all tumors. Aromatase activity when measured in vitro was found to be higher in breast tumors than in fat next to the tumor or normal breast fat. Studies in which we have examined the effect of epidermal growth factor on aromatase activity in cultured breast adipose tissue suggests that the response may be influenced by a subject's menopausal status. Results from these preliminary studies suggest that the aromatization of androgens may make a significant contribution towards the estrogen content of some breast tumors and that growth factors may also be involved in regulating aromatase activity.

Peripheral oestrogen metabolism in postmenopausal women with or without breast cancer: the role of dietary lipids and growth factors.

Studies we have carried out have revealed significant differences in oestrogen production and metabolism between normal women and postmenopausal women with breast cancer. The free, biologically available fraction of oestradiol is elevated in plasma from women with breast cancer and we have found that metabolic clearance rates and production rates of oestradiol are also increased. In vitro studies have suggested that lipids can influence the distribution of sex steroids in plasma and we have therefore examined the effect of dietary lipids on the distribution of sex steroids in plasma in vivo. Consumption of a meal with a high saturated fat content or the oral or i.v. administration of "Intralipid", a stabilised emulsion of soya bean oil that is high in unsaturated free fatty acids, had little effect on the available fractions of oestradiol in plasma. However, results from a preliminary study suggest that long-term changes in dietary fat intake can alter the distribution of steroids in plasma. It is concluded that dietary lipids may influence the availability of sex steroids to tissues. Such a mechanism could account for the significant correlation that has been found between dietary fat consumption and the incidence of breast cancer on a world-wide basis.

The role of tissue steroids in regulating aromatase and oestradiol 17 beta-hydroxysteroid dehydrogenase activities in breast and endometrial cancer.

We have observed that oestradiol concentrations in breast and endometrial tumours are relatively higher than oestrone, in contrast to peripheral tissues. Infusion of radiolabelled oestrogen also suggested there was a difference in metabolism between normal and tumour tissue. We have therefore looked for factors which could modulate tissue steroid metabolism and conclude that progesterone may influence aromatase, and that the adrenal androgens can inhibit oestradiol dehydrogenase activity. The latter mechanism, in particular, may be important in increasing tissue exposure to oestradiol.

A comparison of the in vivo uptake and metabolism of 3H-oestrone and 3H-oestradiol by normal breast and breast tumour tissues in post-menopausal women.

After infusion of 3H-oestradiol or 3H-oestrone into post-menopausal women with breast cancer, there was a significant uptake of both steroids by breast tumour and normal tissue. The proportion of oestrogen present in tumour tissue as 3H-oestradiol after infusion of 3H-oestradiol (89.4 +/- 3.5%, mean +/- SD, n = 4) was significantly higher (p less than 0.001) than in normal breast tissue (72.8 +/- 3.3%) obtained from the same women. Similarly, after infusion of 3H-oestrone, the proportion of oestrogen present as 3H-oestradiol (48.4 +/- 14.4%) was significantly higher than in normal breast tissue (19.1 +/- 6.4%). These results suggest that conversion of oestrone to oestradiol is enhanced in breast tumour tissue with little metabolism of oestradiol. This would account for the higher concentrations of oestradiol reported in breast tumour tissue in the presence of increased oestradiol 17 beta-hydroxysteroid dehydrogenase activity.

The effect of epidermal growth factor, transforming growth factor and breast tumour homogenates on the activity of oestradiol 17 beta hydroxysteroid dehydrogenase in cultured adipose tissue.

The effect of epidermal growth factor (EGF), transforming growth factor (TGF alpha) and breast tumour homogenates on oestradiol 17 beta hydroxysteroid dehydrogenase (E2DH) activity has been examined using cultured human breast adipose tissue. EGF (100-1000 ng/ml) inhibited E2DH activity (E1----E2) in a dose dependent manner. TGF alpha (250 and 500 ng/ml) stimulated E2DH activity, with conversion of E1----E2 increasing to a greater degree than E2----E1 activity. Breast tumour homogenates (2-10% w/v) also influenced E2DH activity. It is concluded that growth factors, produced by breast tumours, may modulate E2DH activity in tissues surrounding the tumour and thereby influence tumour growth.

The formation of mutagenic derivatives of benzo[a]pyrene by peroxidising fatty acids.

Benzo[a]pyrene (B[a]P) when incubated in the presence of peroxidising polyunsaturated fatty acids such as linoleic acid (C18:2), arachidonic acid (C20:4), eicosapentaenoic acid (C20:5) or docosahexaenoic acid (C22:6) was converted to oxidised products. Between 7% and 9% of the B[a]P was oxidised in one hour when incubated with arachidonic acid and docosahexaenoic acid. 1,6- 3,6- and 6,12-Quinone derivatives of B[a]P were identified by HPLC. The products of B[a]P oxidation were shown to be mutagenic when tested using Sister chromatid exchange (SCE) technique and the occurrence of SCEs in CHV79 cells was increased significantly. Lipid peroxides also induced SCEs in the absence of B[a]P and there was a positive correlation between the frequency of SCEs and the extent of lipid peroxidation. The results indicate that the oxidation of B[a]P mediated by the non-enzymic peroxidation of polyunsaturated fatty acids is likely to play a role in mutagenesis and, possibly, also in carcinogenesis.