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With the increasing incidence of breast cancer in patients over 70 years, there is interest in the best therapeutic approach.To review the management of breast cancer in elderly women and to identify the factors involved in the decision to treat patients with tamoxifen as first line therapy.Between 1986 and 1999, 302 female patients agedor = 70 years presented with primary breast cancer, of whom 219 underwent surgery, 79 received tamoxifen as first line treatment and four received primary radiotherapy. A retrospective review was performed on these 79 patients and the outcome recorded.Of these 79 patients, data was available on 68. Follow-up ranged from one to 63 months (median 17 months). Co-morbidity was the principal reason for choosing first line tamoxifen therapy in 61% and patient preference in 11%. Tumour size was less than 5cm in 51%. In 25% tumour size decreased, in 24% it remained stable and in 27% it increased in size following tamoxifen therapy. Additional treatment was prescribed for 33% of patients.In the authors' experience, for those elderly patients suffering considerable co-morbidity or who refuse surgical intervention, tamoxifen is an acceptable alternative.

Our aim was to determine the role of fetal breathing movements (FBM) in the maintenance of fetal lung liquid volume. Experiments were performed in 14 chronically catheterized fetal sheep. FBM were selectively abolished for 48 h by the infusion of tetrodotoxin (TTX) onto the phrenic nerves of five fetuses. Lung liquid volumes and secretion rates were measured before each treatment, 46–48 h after the start of the TTX infusion, and 22–24 h after the end of the infusion. Blockade of the phrenic nerves reduced fetal lung liquid volumes from 27.6 +/- 1.9 to 21.8 +/- 2.6 ml/kg and increased lung liquid secretion rates from 3.8 +/- 0.6 to 6.2 +/- 1.1 ml.h-1.kg-1. Control experiments confirmed the lack of effect of TTX infused intravenously and saline infused intrapleurally on changes in fetal lung liquid volume and secretion rate. To measure the static relaxation volume of the fetal lung, in six fetuses we combined skeletal muscle paralysis with bypass of the upper airway for 48 h. This reduced fetal lung liquid volume from 39.1 +/- 3.1 to 23.0 +/- 2.5 ml/kg and increased lung liquid secretion rates from 4.1 +/- 0.7 to 5.8 +/- 0.9 ml.h-1.kg-1. This experiment demonstrates that the fetal lung is normally maintained at a level of expansion that is much greater than its static relaxation volume. We conclude that the volume of luminal liquid in the fetal lungs is dependent on the diaphragmatic contractions associated with FBM. Their effect is to resist the elastic recoil of the fetal lungs, thereby reducing the loss of liquid from the lungs via the trachea.

We have examined the effects of reduced uterine blood flow and prolonged fetal hypoxemia on the temporal relationship between changes in hormones associated with the activity of the pituitary–adrenal axis (corticotrophin-releasing hormone (CRH), adrenocorticotrophin (ACTH), cortisol, and prostaglandin E2 (PGE2)) in the ovine fetus at 120–125 days of pregnancy, and we sought evidence for placental secretion of CRH and ACTH during prolonged hypoxemia. Uterine blood flow was reduced by placing an adjustable Teflon clamp around the maternal common internal iliac artery to decrease fetal arterial oxygen saturation from mean values of 59.1 ± 3.3 to 25.7 ± 4.6% (±SEM, n = 10). There was a transient peak in immunoreactive (IR-) CRH at 1–2 h after reducing uterine blood flow. IR-ACTH rose to peak values at +2 h, then gradually decreased to control level by +12 h. Fetal plasma cortisol and PGE2 concentrations were elevated significantly by +2 and +4 h, respectively, and at 20–24 h. The identity of IR-CRH in fetal plasma and in ovine placental extracts was confirmed by HPLC, but there was no consistent umbilical vein – femoral arterial concentration difference for either IR-CRH or IR-ACTH during normoxemia or hypoxemia. We conclude that a sequence of endocrine changes involving CRH, ACTH, PGE2, and cortisol occurs in the fetus during a prolonged reduction in uterine blood flow. However, we did not obtain evidence, for placental secretion of either CRH or ACTH in response to this manipulation.Key words: fetus, adrenocorticotrophin, corticotrophin-releasing hormone, prostaglandin E2, placenta.

The effects of 24 h of reduced maternal uterine blood flow (RUBF) on relative DNA synthesis rates in different tissues and on blood glucose and lactate concentrations were studied in fetal sheep. In six sheep, RUBF was induced for 24 h, whereas in another six sheep (controls), uterine blood flow was not reduced. To estimate DNA synthesis rate, [3H]thymidine (1 mCi/kg) was injected intravenously into each fetus 8 h before the end of the 24-h experimental period. Fetal arterial oxygen saturation decreased from 59.1 +/- 3.3 to 25.7 +/- 5.6% after 1 h of RUBF and remained significantly reduced for the duration of the experiment. Fetal blood lactate concentrations were significantly increased by RUBF from 14.3 +/- 6.5 to 57.8 +/- 12.4 mg/dl at 1 h and remained elevated, whereas fetal blood glucose concentrations were not affected. A 24-h period of RUBF did not significantly alter fetal body weights, tissue weights, tissue-to-body weight ratios, or tissue DNA content. Over the last 8 h of the 24-h experimental period, RUBF was found to significantly reduce the relative rate of DNA synthesis (as assessed by [3H]thymidine incorporation into DNA) in the lung (104.7 +/- 26.6 vs. 17.1 +/- 3.1 dpm/micrograms DNA), quadriceps muscle (92.8 +/- 20.7 vs. 14.4 +/- 5.3 dpm/micrograms DNA), and thymus gland (87.5 +/- 7.1 vs. 32.9 +/- 12.2 dpm/micrograms DNA). Relative DNA synthesis rates in the fetal liver, kidney, small intestine, cerebral cortex, cerebellum, placenta, thyroid gland, and adrenal gland were not significantly affected by RUBF. In this study, we have shown that DNA synthesis was greatly reduced in selected fetal tissues (lung, quadriceps muscle, and thymus gland) by a 24-h period of RUBF, although it is not known why a reduction was only observed in these tissues.

Oxytocin (OT), progesterone and prostaglandin F2α (PGF2α) concentrations were measured in the utero-ovarian vein (UOV) of ewes which displayed persistence of the corpus luteum (CL). During the period of expected luteolysis, the frequency of OT and PGF2α pulses in the UOV was significantly (P < 0.005 for both) lower in ewes with persistent CLs, compared with ewes that underwent normal luteal regression. In contrast, the amplitude of both OT and PGF2α pulses was similar in both groups of animals. It is suggested that persistence of the CL resulted from a decreased PGF2α pulse frequency, which may have arisen from a decreased frequency of stimulation by OT. In two persistent CL ewes, however, it appeared that a failure at the level of the uterus may have contributed to the observed decrease in PGF2α release. Although a PGF2α analogue (Lutalyse) infusion into the uterine vein of two ewes with persistent CLs failed to induced luteolysis, it did stimulate a large release of OT into the UOV. This suggests that persistent CLs maybe more resistant to PGF2α and, that at day 22 post-oestrus, these CLs are capable of releasing large quantities of OT into the UOV.

A technique for implanting and maintaining catheters in both utero-ovarian veins (UOV) of intact, conscious sheep has been developed. Both UOV catheters remained patent for more than 2 weeks in 72.7% of animals. In non-pregnant ewes, large pulses of PGF2α were observed in UOV plasma collected on days 13 to 16 of the cycle (frequency 1.3 ± 0.2/12 h; pulse height range 1.0–26.9 ng/ml). In contrast, on days 13 to 16 of gestation, significantly (P < 0.001) fewer pulses of PGF2α (frequency 0.42 ± 0.2/12 h) were observed in both UOVs of pregnant ewes, which were significantly (P < 0.001) smaller in amplitude (pulse height range 1.4–4.9 ng/ml). The maintenance of the corpus luteum (CL) during early pregnancy may therefore directly result from a decreased uterine PGF2α release. During the luteal phase (day 4–12), the PO2 of UOV blood draining an ovary containing a CL (UOV/CL) was significantly higher than blood in the contralateral UOV (P 2 of UOV/CL blood had decreased and was not significantly different to that observed in the contralateral UOV (P >0.1). On day 17, the PO2 of blood in both UOVs was elevated significantly compared to levels observed on the two preceding and the two following days (P < 0.001). We consider that the higher PO2 in UOV/CL blood resulted from a very high luteal blood flow, and that the decrease on days 15 and 16 of the cycle resulted from a decline in luteal blood flow during luteolysis. The subsequent increase in PO2 of blood from both UOVs on day 17 was considered to result from an increased uterine blood flow.