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The clinical value of lymph node immunohistochemistry was assessed in 343 consecutive patients with apparently node-negative breast cancer using antimucin monoclonal antibodies BC2, BC3 and 3E1.2. Occult metastases were detected in 41 patients (12 per cent). Although most of these were micrometastatic (< 2 mm in diameter), larger or diffuse deposits were found in ten patients. Blind assessment of repeat haematoxylin and eosin stained sections detected metastases in ten of the 41 patients with occult metastases. After a median follow-up of 79 months, patients with occult metastases had a shorter time to disease recurrence (P < 0.05) but not to death. After adjustment for other prognostic factors, the presence of occult metastases in two or more nodes was the most significant predictor of both disease recurrence (P < 0.01) and death (P < 0.01). When the ten patients with positive haematoxylin and eosin sections were excluded from the analysis, the presence of occult metastases in two or more nodes was still associated with a reduced disease-free interval (P < 0.05) and survival (P < 0.05). Lymph node immunohistochemistry is a simple technique affording more accurate definition of nodal involvement than conventional methods.

The clinical features and hormonal abnormalities were surveyed in 117 men with cirrhosis of the liver. Compared with healthy men of similar ages, the patients had significantly lower metabolic clearance rates, plasma production rates and total and free levels of testosterone, reduced testosterone responses to human chorionic gonadotrophin stimulation, higher oestradiol, luteinizing hormone and follicle stimulating hormone levels and higher binding capacities of sex steroid binding globulin. The peripheral conversion of testosterone to oestradiol was also found to be significantly increased. However, the metabolic clearance and plasma production rates of oestradiol were not significantly different from those of healthy men. Patients who were severely ill with liver failure and one with haemochromatosis had low levels of luteinizing hormone and follicle stimulating hormone and sub-normal responses to clomiphene and luteinizing hormone-releasing hormone. Higher plasma oestradiol levels were found in patients with gynaecomastia and spider naevi than in those without these signs. However, the clinical features of androgen deficiency--that is, testicular atrophy, impotence and loss of secondary sex hair--were only poorly related to the low testosterone levels, and production rates and longtitudinal studies indicated that the hormonal levels, endocrine features and severity of the liver disease could change independently. It is concluded that the clearance of oestradiol from plasma is not limited by liver disease in all patients, and that reduced degradation of oestrogens is not the initial event in the sequence leading to the hormonal abnormalities of cirrhosis. While gonadotrophin deficiency occurs with liver failure and in some patients with haemochromatosis, the more usual findings are of elevated gonadotrophin levels and a poor Leydig cell response to chorionic gonadotrophin. These suggest that the hypogonadism is primary in most patients with cirrhosis. The causes of the high oestradiol levels were not discovered. Increased peripheral conversion of precursors to oestradiol or increased testicular secretion of oestradiol are possibilities. The high binding capacities of sex steroid binding globulin were not significantly correlated with either the low testosterone or high oestradiol level and the cause of this abnormality remains uncertain. The low metabolic clearance rates of testosterone appeared to result from the increased plasma protein binding of testosterone. The discrepancies in the expected relationships between the hormone and clinical changes suggest that factors other than those studied are also involved in the genesis of the endocrine features of hepatic cirrhosis.

A practical bioassay for the acid-ethanol soluble non-suppressible insulin-like activity (NSILA-S) of individual serum samples has been developed utilizing the incorporation of 14C-glucose into the lipid faction of isolated adipocytes. NSILA-S activity was correlated with somatotropin status. Thus, the mean potencies (+/-SD) relative to an extract of pooled normal human serum were: normal samples 1.11 +/- 0.14, acromegalic 2.91 +/- 0.72, and somatotropin deficient 0.13 +/- 0.06. This variation in NSILA-S was not due to variability in extraction recoveries. The within assay precision was 9% (coefficient of variation) and the between assay 23%. This method allows the simultaneous extraction and processing of relatively large numbers of samples, and compares favorably with other more complex methods. Because of the evidence that NSILA-S may be related to the somatomedins, the present method should provide a simpler and more reliable alternative to the cartilage bioassays used to measure somatomedin activity.

The effects on the serum levels of NSILA-S of the administration of human GH (hGH) or of hypophysectomy have been studied. hGH given im (5 mg daily for 3 days) raised the NSILA-S levels of three GH-deficient subjects into the normal range. Significant elevations of NSILA-S were also seen in three normal subjects given im GH. In the same groups of three normal and three GH-deficient subjects, 5 mg hGH administered iv induced an elevation of NSILA-S within 15-60 min. Hypophysectomy in three acromegalics and one subject with a chromophobe adenoma was followed by significant falls of serum NSILA-S. These studies provide further evidence of the dependence of NSILA-S levels on GH.

A longitudinal study of serum NSILA-S during normal human pregnancy and the puerperium has demonstrated that levels rose progressively during pregnancy and returned to nonpregnant values about 48 h after delivery. Low concentrations were defined within the feto-placental circulation at term. Cord arterial and venous levels were equivalent, but there was no significant correlation between these and matched maternal values.

Studies were undertaken to determine the effects of intravenous infusions of bovine testicular extracts on plasma levels of FSH and LH in castrate male sheep. Decapsulated bovine testes were homogenized with phosphate buffer, the homogenates centrifuged at 30,000 X g for 30 min, and the supernatants extracted with diethyl ether. The aqueous extracts were filtered using Diaflo XM-100 membranes and the ultra-filtrates lyophilized. The extracts were infused over 24 hours, and plasma FSH and LH were measured prior to, during, and after the infusion. Control studies using infusions of saline and liver extracts demonstrated no decrease in FSH levels in 6 out of 7 controls, while LH levels tended to rise. Following infusions with the testicular extracts, the levels of FSH were selectively decreased to between 42% and 85% of baseline levels, and they subsequently remained suppressed for at least 24 hours. These results suggest that the testis is the site of production of a water-soluble, non-steroidal substance which exerts an inhibitory effect on the production and/or release of FSH.

A number of different factors are known to be correlated with survival of patients with breast cancer. Among these are lymph node status, tumour size, oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) status. The purpose of this study was to investigate the relative significance of these factors and use this information to construct a prognostic index capable of predicting survival. These factors together with age and menopausal status were studied and correlated with prognosis in 796 women with primary breast cancer. The data were analysed in a stepwise manner by the Cox proportional hazards regression technique. Statistically, greater than 3 nodes involved gave the worst prognosis (P less than 0.001). This was followed by ER if less than 10 fmol/mg cytosol protein (P less than 0.001), PR if less than 10 fmol (P less than 0.01), greater than 0 lymph nodes involved (P less than 0.01) and the number of years over age 65 (P less than 0.01). When these factors were accounted for, tumour size, menopausal status and AR did not significantly improve prediction of survival. The significant factors were incorporated into a prognostic index: I = N + E + P + A, where N = 0 if no nodes involved, 13 (if 1-3 nodes involved and 31 if greater than 3 nodes involved, E = 15 if ER less than 10 fmol, P = 12.5 if PR less than 10 fmol and A = number of years over 65. Using this index five year survival curves were constructed corresponding to groups of patients with widely differing prognoses. Predicted five year survival ranged from 96 to 12 per cent.