Use of cytokeratin fragments 19.1 and 19.21 (Cyfra 21-1) in the differentiation of malignant and benign pleural effusions.

BACKGROUND: Differentiation between malignant and benign pleural effusions is often difficult. Serum level of Cyfra 21-1, a marker of cytokeratin 19 fragments, has been used in the diagnosis and monitoring of epithelial tumours, especially bronchogenic carcinomas. AIM: This study is designed to establish the usefulness of effusion Cyfra 21-1 level in differentiating malignant from benign effusions. METHODS: Forty-eight malignant effusion aspirates (proven by cytology or pleural biopsy) and 34 benign samples were compared. Cyfra 21-1 concentration was measured by a solid phase sandwich radioimmunoassay (Centocur, USA). RESULTS: Cyfra 21-1 level was significantly higher in malignant effusions (geometric mean 123.6 ng/mL, 95% confidence interval [CI] 76.6-199.4) than in benign ones (geometric mean 14.3 ng/mL, 95% CI 8.5-23.9), p<0.00005. By Receiver Operating Characteristics curve analysis, the sensitivity is 77% for a specificity of 79% if the cut-off is set at 32 ng/mL. No significant difference was observed (p=0.1) in Cyfra 21-1 concentration between adenocarcinoma and mesothelioma effusions. Cyfra 21-1 level was not influenced by the effusion protein concentration (r=0.29), or by renal function as measured by serum creatinine (r=0.1). There was no significant difference between Cyfra 21-1 levels in benign exudate and transudate effusions, p=0.28. CONCLUSIONS: Cyfra 21-1 is a useful adjunct in the workup of effusions but should not replace conventional investigations as there is considerable overlap in levels between benign and malignant groups. It is unable to differentiate between subgroups of malignancies.

Characteristics of the menstrual cycle at the time of surgery for breast cancer.

Hormone measurements during the menstrual cycle were assessed in six premenopausal women undergoing breast cancer surgery and ten controls to determine whether the stress of diagnosis and surgery influenced cycle characteristics. There was hormonal evidence for normal ovulation in all cancer and control women, although the length of the luteal phase of the cycle was prolonged because of a delay in menstruation in two cancer patients. The timing of surgery in the cycle did not influence the hormonal data. The hormonal characteristics of the menstrual cycle thus appear to be normally preserved in women during the month in which breast cancer surgery is performed.

Sex differences in umbilical cord serum levels of inhibin, testosterone, oestradiol, dehydroepiandrosterone sulphate, and sex hormone-binding globulin in human term neonates.

The contribution of the fetus to inhibin production in human pregnancy is unclear. Previous studies have reported inhibin concentrations in cord blood but on limited sample numbers. The present study is a more extensive examination of sex differences in immunoreactive inhibin and steroidal hormones in term umbilical cord blood. Venous serum concentrations of inhibin were found to be significantly higher in males (mean +/- SD 2,168 +/- 914 pg/ml, n = 62) than in females (1,761 +/- 951 pg/ml, n = 63) (p < 0.01). Male concentrations of total testosterone (p < 0.005), free testosterone (p < 0.005), and estradiol (p < 0.05) were also significantly higher. The concentration of dehydroepiandrosterone sulphate (DHEAS) and the sex hormone-binding globulin (SHBG) capacity were similar in males and females. Multivariate regression analysis showed that the inhibin concentration in males correlated with the testosterone concentration and in females it correlated not only with testosterone concentration but also with gestational age at delivery and SHBG capacity (all p < 0.001). Inhibin concentrations in cord arterial serum in a subgroup of 24 males and 31 females were higher than in the venous serum in both sexes but the differences were not statistically significant. Concentrations of DHEAS determined in 22 female cord arterial blood samples (6.0 +/- 2.5 mumol/l) were significantly higher than the venous concentrations (5.2 +/- 1.8 mumol/l) (p < 0.05). Inhibin did not correlate with DHEAS either in their arterial serum concentrations or in the arteriovenous concentration differences. The findings of this study are consistent with the placenta being the principal source of inhibin circulating in the human fetus in late pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Concentrations, metabolic clearance rates, production rates and plasma binding of cortisol in Antarctic phocid seals.

We have reported previously that plasma of the Weddell seal, a member of the phocid family, contains a very high concentration of cortisol. The present study was undertaken to determine whether high cortisol levels were common to seals in the Antarctic environment, or to other phocidae, and to determine the mechanism of the hypercortisolaemia. High levels of cortisol (0.82-2.38 mumol/l) were found in 4 phocidae (Weddell, crabeater, leopard and Southern elephant seals), whereas levels in a member of the otariid family (Antarctic fur seal) were similar to human values. Metabolic clearance rates (MCR) and production rates (PR) of cortisol were determined in the field in Weddell (N = 1), crabeater (N = 3) and leopard (N = 3) seals following bolus injections of [3H] cortisol. The MCR and PR did not differ between the three phocids, but whereas the MCR of 410-590 1/day was twice that of human values, the PR of 460-1180 mumol.m-2 x d-1 was up to 40-fold greater. The binding capacity of corticosteroid-binding globulin (CBG) was equal to or greater than the plasma concentrations of cortisol, resulting in relatively low concentrations of free cortisol. We conclude that hypercortisolaemia is maintained in phocid seals mainly by a high production rate--the highest (corrected for surface area) reported in any species. The relatively low cortisol levels in otariid seals studied in the same environment suggest that the high PR in phocidae is unrelated to the harsh climatic conditions, but may be part of their adaptation for diving to extreme depths.(ABSTRACT TRUNCATED AT 250 WORDS)

Characteristics of natural conceptual cycles occurring in a prospective study of sex preselection: fertility awareness symptoms, hormone levels, sperm survival, and pregnancy outcome.

A prospective study of sex preselection provided the opportunity to characterize the fertile menstrual cycle. We describe from 91 natural conceptual cycles, or sub-groups thereof, cervical mucus symptoms, basal body temperature (BBT) changes, hormonal characteristics, and the outcome of pregnancy. The cervical mucus symptoms defined a potential fertile period of 10 days' average length, with the "peak" mucus symptom occurring at a mean of day 15.5 of the cycle. A fertile period of 9 to 10 days was also indicated by pregnancies resulting from single acts of intercourse between -6 and +3 days from ovulation. The BBT chart was biphasic in 73 of 76 cycles. The duration of the LH surge as observed in early morning urine samples averaged five days, with the peak occurring 1.4 days after the onset. Considerable inter-subject variability was seen in the LH excretion levels. Hormone measurements of peripheral plasma during the luteal phase showed the first detectable presence of hCG between day 7 and day 13 after conception. Progesterone concentrations in the midluteal phase exceeded 20 nmol/L and tended to be higher than in a comparison group of nonfertile cycles, whereas the estradiol concentrations were similar in fertile and nonfertile cycles. The birth sex ratio favored males when intercourse preceded ovulation/fertilization by two days or longer. While this association was statistically significant, the number of pregnancies involved is too small to conclude that the relationship is real.

Zoladex treatment of symptomatic prostatic carcinoma.

The depot LH-RH agonist Zoladex was used to treat 38 patients with previously untreated symptomatic stage D2 prostate carcinoma. Side effects were minimal and patient acceptability excellent, although temporary tumor flare occurred in 11% of patients. Eighty-four percent experienced subjective improvement and 87% had objective evidence of initial disease stabilization or remission lasting 3 months. Serum levels of gonadotrophin and free testosterone as well as androgens of adrenal origin fell significantly with treatment. Long-term survival to date appears at least as good as that described for conventional endocrine therapy.

Treatment of metastatic prostate carcinoma with the depot LRH analog Zoladex.

A long-acting LRH agonist (ICI 118630, Zoladex) was given by monthly subcutaneous injection to 25 patients with previously untreated symptomatic advanced prostatic carcinoma. The medication was well tolerated with the only side effect being hot flushes in 15 patients. Subjective improvement occurred in 22 patients, and disease remission or stabilization judged by objective criteria was seen in 21 and 18 patients from the total group at 3 and 6 months of treatment, respectively. Twelve of 18 patients followed for 1 year were still in objective remission/stabilization. Prostate volume measured by ultrasound decreased by a mean value of 75% and urine flow increased significantly. There were significant falls in serum testosterone and gonadotrophin levels and significant although lesser reductions in serum androstenedione and dehydroepiandrosterone. These changes were accompanied by significant reductions in serum acid and alkaline phosphatase and a rise in serum osteocalcin. Four patients (16%) experienced an initial tumor flare. Although only a small number of patients were studied, Zoladex appeared to be a well-tolerated agent for treatment of prostatic carcinoma, with an initial clinical response similar to that seen with standard endocrine therapy.

Clinical and biochemical evaluation of patients with hirsutism.

Patients with moderate to severe hirsutism presenting over an 18-month period to an endocrine clinic were assessed by clinical evaluation and hormone measurements. Hair growth rate was estimated by a photographic technique and the severity of hirsutism graded using an objective scale. Of 43 patients, 9 had polycystic ovaries and the remainder were considered to have idiopathic hirsutism. The most severely affected group had significantly increased hair growth rates compared with less clinically affected subjects, and 47% of this group showed objective features of virilization. However, apart from a significantly higher 24-hr urine 17-ketosteroid excretion all other hormonal patterns were not significantly different between severely and mildly affected patients. Serum levels of testosterone (T), sex hormone-binding globulin (SHBG), free T (calculated from T and SHBG values), and androstenedione (A) were abnormal in 44%, 51%, 60% and 60% of patients respectively, whereas plasma levels of the specific adrenal androgen DHAS were increased in 40% of patients. There was an overlap between patients with elevated hormone levels, although isolated elevation of T, A or DHAS were seen in 9%, 19% and 3% of patients respectively. In 19% of patients all serum androgen measurements were normal. Gonadotrophin levels were significantly lower in the more severely affected group. Thus androgen levels in patients with idiopathic hirsutism or polycystic ovaries, show considerable overlap with measurements in normal subjects, and elevated plasma androgens may be of adrenal (DHAS) or combined adrenal/ovarian (T, A) origin.

Evaluation of a new commercial solid-phase direct radioimmunoassay for unconjugated estriol in pregnancy plasma.

We evaluated a new radioimmunoassay kit for unconjugated estriol in pregnancy plasma. The overall mean intra-assay precision (CV), as determined from replicate analyses of three plasma pools with different estriol concentrations, was 5%; the overall mean inter-assay precision was 7.7%. The assay system had acceptable linearity, with a correlation coefficient of 0.97 between results for 24 plasma samples assayed at 10 and 20 microL. Analytical recovery of estriol added to plasma to give three concentrations averaged 98.6%. Estriol values were generally higher with the kit than with our conventional charcoal-separation RIA method. The regression line equation was y = 1.11x + 1.0, the correlation coefficient 0.97. In plasma from 28 normal pregnant women, sampled serially during the last trimester, the mean unconjugated estriol concentration in plasma increased steadily from 29 nmol/L at 28 weeks of gestation to 42 nmol/L at 34 weeks, and then more rapidly to 93 nmol/L at term. This kit provides a rapid, technically simple, and reliable assay method, offering advantages to clinical laboratories with a high estriol workload.

Determination of beta-choriogonadotropin in human plasma; evaluation and comparison of five "kit" methods.

We evaluated five quantitative, commercially available radioimmunoassay methods (Beta-Tec, BIO-RIA, Cambridge Nuclear, Mallinckrodt, and Serono) for rapid determination of the beta-subunit of human choriogonadotropin in serum or plasma. Only three of the kits (Beta-Tec, Mallinckrodt, and Serono) were found suitable for reliable determination of low concentrations of this analyte, which is of importance in the early diagnosis of trophoblastic disease in men and monitoring effectiveness of chemotherapy of trophoblastic tumors in men and women.

High corticosteroid levels in plasma of adult and foetal Weddell seals (Leptonychotes weddelli).

Pregnant and non-pregnant Weddell seals and foetuses were found to have very high plasma concentrations of corticosteroids (1--7 mumol/l) that were unaffected by stress. Cortisol comprised most of the corticosteroid in the adult but only 50% of that in the foetus. The affinity constant (4.30-5.53 x 10(7) l/mol) and specificity of CBG and the MCR (4.5 l/d/kg lean body mass) in adult seals were similar to those of Man. The binding capacity of CBG (1.48--1.86 mumol/l) which is approximately three times that of Man contributed to the high plasma corticosteroid concentrations but the main factor was the cortisol turnover rate of 3670 mumol/d (1.3 g/d) which is the highest value reported in any species.

Parturition in the sheep.

Parturition in sheep is initiated by a sharp rise in the rate of secretion of cortisol by the fetal adrenal. Increased secretion is due partly to enhanced responsiveness to corticotropin (ACTH) and partly to increased fetal concentrations of corticotropin. Cortisol acts on placental enzymes active in the biosynthesis of oestrogens from progesterone. Thus placental secretion of oestrogen increases and that of progesterone decreases. This change in the ratio of oestrogen: progesterone, particularly the rise in oestrogen, stimulates release of prostaglandin F2alpha (PGF2alpha) from the maternal placenta and to a lesser extent from the myometrium. PGF2alpha enhances the myometrial response to oxytocin and, after a latent period, stimulates contractions. The onset of parturition is normally associated with softening of the cervix, the mechanism of which is uncertain. Uterine contractions in the presence of a distensible cervix lead to parturition.