Serum concentrations of dimeric inhibin during the spontaneous human menstrual cycle and after treatment with exogenous gonadotrophin.

A recently described two-site enzyme immunoassay incorporating a pre-assay oxidation step was validated and used to measure serum concentrations of dimeric inhibin in five normally cycling women and in 13 women undergoing gonadotrophin therapy. Recombinant human inhibin A (standard) gave an assay response curve which was parallel to those for human serum samples and recovery of exogenous inhibin added to serum samples before assay was quantitative (109 +/- 8%, n = 11). During the normal menstrual cycle dimeric inhibin concentration increased from 9.0 +/- 2.0 pg/ml during the early follicular phase to reach a mid-cycle peak of 55.3 +/- 11.1 pg/ml coincident with the pre-ovulatory gonadotrophin surge. After falling to 27.9 +/- 5.7 pg/ml 1 day after the luteinizing hormone surge, inhibin then rose in parallel with serum progesterone to reach a peak value of 115.6 +/- 19.3 pg/ml during the mid-luteal phase, before falling to 14.1 +/- 4.9 pg/ml by the onset of next menses. During the follicular phase, dimeric inhibin concentrations were closely correlated with those of serum oestradiol (r = 0.69; P < 0.001), whereas during the luteal phase they were most closely correlated with serum progesterone concentrations (r = 0.73; P < 0.001). Daily treatment with human menopausal gonadotrophin promoted a progressive increase in serum dimeric inhibin concentration which increased approximately 20-fold in 6 days. In the same period total alpha-inhibin (measured by radioimmunoassay) increased approximately 5-fold, while serum oestradiol increased approximately 30-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Accumulation of human chorionic gonadotrophin in the serum of patients during in-vitro fertilization treatment cycles with Pergonal.

We examined the possible contribution of human chorionic gonadotrophin (HCG) in Pergonal to the serum luteinizing hormone (LH)-like bioactivity in 10 patients (median age 32 years, range 28-38) with tubal infertility who were undergoing in-vitro fertilization (IVF), together with 19 controls (median age 30 years, range 21-43). IVF patients were treated with clomiphene (50 mg twice daily) over days 2-6 and Pergonal (150 IU i.m.) daily from day 5 until at least day 10. Serum LH was measured by fluoro-immunometric assay (I-LH) and in-vitro Leydig cell bioassay (B-LH). Serum HCG was measured by fluoro-immunometric assay. The data were analysed by paired two-tailed t-test, following logarithmic transformation. From days 1-5, there was an increase in serum B-LH (mean, 95% confidence intervals given in parentheses) from 8.3 (6.8, 10.2) IU/l to 11.7 (9.8, 13.9) IU/l [P = 0.004], and in serum I-LH from 4.5 (3.7, 5.4) IU/l to 5.4 (4.6, 6.3) IU/l [P = 0.002]. From days 5-8, there was a rise in B-LH to 16.6 (12.6, 21.9) IU/l [P = 0.023]. The rise in I-LH to 6.3 (5.1, 7.8) IU/l [P = 0.081] failed to reach significance. Furthermore, serum HCG was < 0.75 IU/l until after Pergonal was administered on day 5, then rose to a plateau on day 8 at 1.2 (0.8, 1.6) IU/l. Serum HCG in the controls remained < 0.75 IU/l throughout.(ABSTRACT TRUNCATED AT 250 WORDS)

Exogenous steroids and the control of oestradiol secretion by human granulosa-lutein cells by follicle stimulating hormone and insulin-like growth factor-I.

This study first examined the relative activities of 17 alpha-hydroxylase, 17,20-lyase and aromatase in human granulosa-lutein cells by challenging the cells with steroid precursors in the oestradiol biosynthetic pathway. When cells from four patients were challenged with precursor steroids on the pathway to oestrogen synthesis (pregnenolone, 17 alpha-hydroxypregnenolone, progesterone, 17 alpha-hydroxyprogesterone and androstenedione at 5 x 10(-6) M), oestradiol (nmol/l) outputs after 1 day of culture were (median, interquartile range) as follows: 4.1 (2.1-8.8; pregnenolone), 3.1 (1.7-6.0; progesterone), 12.5 (6.9-18.1; 17 alpha-hydroxypregnenolone), 8.2 (4.1-16.7; 17 alpha-hydroxyprogesterone) and 251 (140-819; androstenedione). No further increases were seen when the steroid concentration was increased to 1 x 10(-5) M. Basal oestradiol secretion was 3.5 (1.6-8.2) nmol/l. We conclude that the conversion of pregnenolone/progesterone to oestradiol by granulosa-lutein cells is rate limited by 17 alpha-hydroxylase activity but that these cells are capable of oestradiol secretion (in the nmol/l range) in the absence of androstenedione. In the second part of this study we examined the control of granulosa-lutein oestradiol secretion by follicle stimulating hormone (FSH) and insulin-like growth factor-I (IGF-I) in the presence and absence of exogenous androstenedione (10(-6) M). Cells were cultured for up to 6 days and basal oestradiol (nmol/l) fell dramatically over this period both in the presence and absence of androtenedione, e.g. from 339 (223-419) (median and interquartile range, cells from five patients cultured in the presence of androstenedion) after 2 days to 14 (7-59) after 6 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin-like growth factor-I stimulated growth and progesterone production by granulosa-lutein cells. Lack of interaction with physiological concentrations of luteinizing hormone and follicle stimulating hormone.

This study examined the effect of physiological concentrations of insulin-like growth factor-I (IGF-I), follicle stimulating hormone (FSH) and luteinizing hormone (LH) alone and in combination on growth and progesterone production by human granulosa-lutein cells. Granulosa-lutein cells were obtained from patients (n > 5) undergoing in-vitro fertilization (IVF) or gamete intra-Fallopian transfer (GIFT) treatment. Cells were cultured for 2 and 4 days in the presence of physiological concentrations of human LH (code 68/40, 5 IU/l), FSH (code 83/575, 20 IU/l), or IGF-I (30 ng/ml) alone and in combination. Medium was changed every 2 days. No change in cell number (relative to each patient's own control) was observed after treatment with FSH or LH alone or in combination at any time. IGF-I alone produced a 117 +/- 8% and 176 +/- 15% (mean +/- SEM, n = 5) increase in cell number after 2 and 4 days respectively. This increase was unaffected by the addition of LH or FSH at any time. Basal progesterone secretion was variable (1633, 975-2409 nmol/l, median and interquartile range, day 2) and decreased with time in culture (564, 375-1089 nmol/l, day 4). After 2 days culture progesterone output increased by 116 +/- 5% of control in response to LH and 153 +/- 13% (mean +/- SEM, n = 5) of control in response to IGF-I. After 4 days, LH and IGF-I stimulated progesterone levels by 279 +/- 52% and 264 +/- 37% (mean +/- SEM, n = 5) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The Salford Third Stage Trial. Oxytocin plus ergometrine versus oxytocin alone in the active management of the third stage of labor.

OBJECTIVES: To compare oxytocin plus ergometrine against oxytocin alone, when administered as part of the active management of the 3rd stage of labor, in terms of postpartum hemorrhage and manual removal of the placenta. DESIGN: A double-blind, randomized controlled trial. SETTING: A university teaching hospital: Hope Hospital, Salford. PATIENTS: All women delivering in the hospital over the period of the trial, except those for whom a cesarean section was planned, or who had significant hypertension or cardiac disease. INTERVENTIONS: Syntometrine (5 units of oxytocin with 0.5 mg of ergometrine) versus 5 units of Syntocinon (oxytocin), both given by intramuscular injection with delivery of the anterior shoulder. MAIN OUTCOME MEASURES: Postpartum blood loss, the length of the 3rd stage of labor, and the need for manual removal of the placenta. RESULTS: Four hundred sixty-one women were recruited, 230 allocated to ergometrine plus oxytocin and 231 to oxytocin alone. The duration of the 3rd stage of labor in each group was similar (difference in means 0.2 mins; 95% confidence interval [CI], -1.0 to 1.5) and the need for manual removal of the placenta (odds ratio [OR] 1.21; 95% CI, 0.37 to 4.00). There was less postpartum blood loss in the oxytocin plus ergometrine group, reflected in the lower incidence of primary postpartum hemorrhage (> 500 mL) (OR 0.37; 95% CI, 0.16 to 0.85). CONCLUSIONS: Judged on the basis of this trial alone, oxytocin plus ergometrine is more effective than oxytocin alone in the prevention of postpartum hemorrhage. However, evidence from other trials shows that the ergometrine component not uncommonly has side effects of nausea, vomiting, and raised blood pressure. The implications for practice therefore depend on the relative weights placed on these competing risks by women and clinicians. Further research is needed to quantify these along with research into possible differential effects on longer-term outcomes and into the implications of a higher dose of oxytocin.

Atherosclerosis impairs endothelium-dependent vascular relaxation to acetylcholine and thrombin in primates.

To test the hypothesis that atherosclerosis impairs endothelium-dependent vascular relaxation, we examined the effect of the endothelium-dependent vasodilators acetylcholine and thrombin and the endothelium-independent vasodilator nitroglycerin on iliac arteries from normal cynomolgus monkeys and cynomolgus monkeys with diet-induced atherosclerosis. Rings of iliac artery were suspended in organ chambers at their optimal length for generating tension. After preconstriction with prostaglandin F2 alpha, cumulative concentration-response curves to acetylcholine, thrombin, and nitroglycerin were examined. The presence of endothelium was confirmed in each vessel by scanning electron microscopy. Atherosclerotic vessels showed morphologic evidence of moderate to severe atherosclerosis. Acetylcholine produced a maximal relaxation of 65 +/- 10% in the normal group and 27 +/- 10% in atherosclerotic vessels (P less than 0.05). Thrombin (10.0 U/ml) produced relaxation of 39 +/- 9% in the normal group and 13 +/- 7% in atherosclerotic iliac arteries (P less than 0.05). Nitroglycerin relaxed both normal and atherosclerotic blood vessels to an equal extent; maximal relaxation was 92 +/- 4% in normal vessels and 98 +/- 2% in atherosclerotic vessels. To determine if hypercholesterolemia alone produces an abnormality in endothelium-dependent relaxation, we performed two additional studies. First, because veins are exposed to hypercholesterolemia, but do not develop atherosclerosis, we studied relaxation responses to acetylcholine and thrombin in veins from normal monkeys and monkeys with diet-induced atherosclerosis. Veins from normal and atherosclerotic monkeys relaxed to a similar extent upon exposure to the endothelium-dependent vasodilators acetylcholine and thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

Cimetidine-induced cutaneous vasculitis.

A rash developed in a man consistent with urticarial vasculitis as demonstrated by biopsy on each of two occasions that he was exposed to cimetidine. The vasculitis resolved on discontinuation of the drug. This is the first report demonstrating by biopsy and rechallenge that oral cimetidine therapy may cause type III hypersensitivity.

Effect of administering two prostaglandin synthetase inhibitors (indomethacin and aspirin) on egg production in the domestic fowl (Gallus domesticus).

The injection of 50 mg/kg bodyweight of a prostaglandin synthetase inhibitor (indomethacin) brought about a delayed oviposition time in birds of three breeds of layers, whereas the injection of 5 mg indomethacin had no effect. The daily ingestion of up to 400 mg aspirin or up to 10 mg indomethacin for three weeks, or 750 mg aspirin or 200 mg indomethacin for two weeks had no effect on egg production, oviposition time, egg-shell water conductance, oviducal prostaglandin synthetase activity or bird behaviour. Prostaglandin synthetase activity was demonstrable in both control and treated birds only in the tubular glands of the shell gland. These observations suggest that prostaglandins play a minor role in normal reproductive activity in the female domestic fowl.

Lactate dehydrogenase isozymes in the spermatozoa of the domestic fowl, Gallus domesticus and turkey, Meleagris gallopavo.

1. Electrophoresis of extracts of turkey spermatozoa for lactate dehydrogenase activity revealed the usual five tissue LDHs (LDH-1 to LDH-5). 2. The presence of LDH-X (the spermatozoan-specific isozyme) was not obvious. 3. Only one band was present on electrophoresis of fowl spermatozoan extracts and it coincided with LDH-1 (heart type). 4. Kinetic investigations, the use of inhibitors and the heat-stability test confirmed that the fowl spermatozoan LDH was probably LDH-1 and not LDH-X.

Haematological indices of the mother and baby during labour.

Haematological indices were obtained by Coulter Counter analysis from 325 women in the first stage of labour, and from the cord blood of their newborn babies. The mean maternal haemoglobin concentration was 12.49 g/dl and the mean cord haemoglobin 16.18 g/dl. The mean corpuscular volume measured directly was 89.00 fl from maternal blood and 106.73 fl from the cord blood; the two ranges barely overlapped and it should be possible by automated analysis to differentiate between fetal and maternal blood obtained at amniocentesis or artificial rupture of the membranes at term.

Pregnancy following bilateral uterine artery ligation.

A successful pregnancy following bilateral uterine artery ligation performed in an attempt to relieve dysfunctional menorrhagia is reported. Serial biparietal diameters showed a normal growth curve and the newborn infant weighed 2640 g. The patient was normotensive throughtout the pregnancy. Prior to uterine artery ligation, she had had four pregnancies but there were no surviving children. It is suggested that uterine artery ligation may have a limited place in the management of patients with dysfunctional menorrhagia.