uPA and PAI-1 are becoming established as amongst the most effective markers of poor prognosis for patients with node-negative breast cancer; tPA is an index of longer survival. This paper describes a sensitive ELISA for the measurement of uPA, tPA and PAI-1 in breast cancer cytosols. The structure of the assay involves coating Ab (sheep alpha-Chicken IgY), catching Ab (chicken alpha-analyte), tagging Ab (rabbit alpha-analyte) and detecting Ab (goat alpha-rabbit IgG) labelled with HRP. The assay has a high degree of accuracy and specificity. Comparison with the American Diagnostic kits shows the results' equivalence for PAI-1 and tPA. For uPA the results of the assay were twice as high. The assay is sensitive and relatively inexpensive. It is the first published assay to yield strictly comparative values for uPA, tPA and PAI-1 in tissue extracts and is readily subject to external quality control.

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A series of 258 breast cancer patients with known estrogen receptor (ER) status of the primary tumour who subsequently developed metastases were reviewed for site of first metastasis. In 188 cases progesterone receptor (PgR) data were also available. Univariate analysis showed metastatic patterns to differ statistically significantly related to ER status and (less pronounced) PgR status of the primary tumour. Patients with ER-positive tumours had bone metastases three times more often than patients with ER-negative tumours. With respect to PgR-positive and PgR-negative tumours this frequency differed by a factor of two. With regard to visceral metastases ER and PgR status were equally potent prognosticators, patients with receptor negative tumours having a 50% higher frequency of visceral metastasis than patients with receptor positive tumours. Assessment of metastatic patterns in relation to combined receptor status did not substantially enhance the discriminatory value of ER and PgR when assessed separately. Multivariate analysis showed that the observed differences in metastatic patterns were all attributable to differences in the ER status of the primary tumour, and were not influenced by age, menopausal status, axillary lymph node involvement, duration of disease-free interval (DFI), mode of postoperative treatment, or the PgR status of the primary tumour.

Androstenedione (A-dione) and 17-hydroxyprogesterone (17-OHP) levels were measured in matched samples of saliva and of plasma collected from patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (eight patients) and 11-hydroxylase deficiency (one patient). Positive correlations were found between salivary and plasma values of either steroid with correlation coefficients of 0.968 for A-dione and 0.935 for 17-OHP. All five inadequately treated patients with 21-hydroxylase deficiency had greatly elevated plasma and salivary 17-OHP concentrations compared to values in age matched controls. In two of three well controlled patients plasma 17-OHP levels were less than 40 nmol/liter and salivary levels were less than 1.5 nmol/liter, the upper limits which have been formulated as a guideline for monitoring control in treated CAH patients. Patients in good control had A-dione levels in plasma (0.6-2.2 nmol/liter) and saliva (0.04-0.15 nmol/liter) which were both within the normal range for prepubertal children (0.14-2.40 nmol/liter and 0.02-0.25 nmol/liter respectively). Patients in poor control had A-dione levels in plasma of 5.2-25.4 nmol and in saliva of 0.50-2.21 nmol/liter. These values exceeded without exception the normal ranges for their respective ages. Salivary A-dione and 17-OHP determinations are a useful adjunct in the diagnosis and the monitoring of CAH patients since they can be obtained easily and nonstressfully.

Two hundred micrograms of corticotropin-releasing factor (CRF) were administered as an iv bolus injection to 10 normal subjects (5 men and 5 women). Mean plasma ACTH levels rose significantly (P less than 0.0005, by Friedman's nonparametric analysis of variance) from a basal value of 27 +/- 5 pg/ml (mean +/- SEM) to a peak value of 63 +/- 8 pg/ml 30 min after CRF administration. This ACTH response was followed by a rise in plasma mean cortisol levels (P less than 0.0005, by Friedman's test) from a baseline value of 12.3 +/- 1.4 micrograms/100 ml to a peak value of 21.0 +/- 0.7 micrograms/100 ml 60 min after CRF and a rise in mean plasma aldosterone levels from a basal value of 13 +/- 2 ng/100 ml to a peak value of 23 +/- 2 ng/100 ml. There was no significant difference between men and women in the responsiveness of ACTH, cortisol, and aldosterone to CRF administration. The individual basal cortisol levels were highly significantly and negatively correlated with the areas under the individual ACTH curves (r = -0.76; P less than 0.005, by Pearson's correlation test) and cortisol curves (r = -0.91; P less than 0.001, by Pearson's test). These data suggest a modulatory effect of physiological cortisol levels on the response of the pituitary-adrenal axis to CRF.