The total peroxyl radical-trapping ability of plasma and cerebrospinal fluid in normal and preeclamptic parturients.

Plasma and cerebrospinal fluid total peroxyl radical-trapping antioxidative parameter (TRAP) and the main antioxidant components of TRAP (vitamin E, ascorbic acid, uric acid, protein sulfhydryl groups, and the unidentified antioxidant proportion) were analyzed in 11 preeclamptic parturients, 9 healthy parturients with an uncomplicated pregnancy, and 10 healthy nonpregnant women. In addition, the possible effects of ongoing labor were studied in 10 healthy parturients. The samples of plasma and cerebrospinal fluid (CSF) were collected at cesarean section (pregnant women) or minor surgical procedure (nonpregnant women). Normal pregnancy or ongoing labor induced no significant changes in total TRAP, as compared with nonpregnant women, but significant changes in the percentage contributions of individual antioxidants were noted in plasma and CSF. In preeclampsia, a significant increase in TRAP was noted in both plasma and CSF. This increase was mainly due to an increased proportion of uric acid and unidentified antioxidants in plasma samples, and an increased proportion of unidentified antioxidants in CSF. The concentration of CSF ascorbic acid was decreased in preeclampsia, and a negative correlation between CSF ascorbic acid and blood pressure was observed.

A relationship between cord blood and maternal blood lymphocytes and term placenta in the induction of aryl hydrocarbon hydroxylase activity.

Correlations between lymphocyte aryl hydrocarbon hydroxylase (AHH) inducibility in cord blood and maternal lymphocytes and placental AHH activity were studied in 15 smokers and 11 non-smokers. Placental AHH activity was extremely low in the non-smokers regardless of the lymphocyte AHH induction ratio, but was elevated to a variable extent in the smokers, in whom it showed a statistically significant correlation (r = 0.75, P less than 0.01) with cord blood lymphocyte AHH inducibility. The correlation between maternal lymphocyte AHH inducibility and placental AHH activity was poor (r = 0.04, not significant). These findings suggest that AHH induction in man may be 'systematically' regulated and that the genetic background will determine the extent of induction at a given level of exposure to polycyclic aromatic hydrocarbons.

Effect of fenoterol and isoxsuprine on myometrial and intervillous blood flow during late pregnancy.

The use of beta-adrenergic agonists in high-risk pregnancies has shown evidence of favorable effects on the fetus. Intravenous injections of 133Xe were given to evaluate the effects of short-term administration of fenoterol (3 microgram/min) and isoxsuprine (150 migrogram/min) on the intervillous and myometrial blood flow in a series of 48 women during the last trimester of pregnancy. Both fenoterol and isoxsuprine treatment increased the maternal heart rate significantly. There was a significant rise in myometrial blood flow when fenoterol was given, but the intervillous blood flow did not change significantly during the administration of either isoxsuprine or fenoterol. Previous oral isoxsuprine treatment did not diminish the cardiac effect of intravenous fenoterol, but the improvement in myometrial blood flow was eliminated. This result indicates that beta-adrenergic agonists may have a specific dilatational effect on the myometrial blood vessels. From the hemodynamic point of view, the beta-adrenergic agonists have a limited value in the treatment of chronic fetal asphyxia or intrauterine fetal growth retardation.

Inefficacy of 17 alpha-hydroxyprogesterone caproate in the prevention of prematurity in twin pregnancy.

There are indications that prophylactic administration of 17 alpha-hydroxyprogesterone caproate (17 alpha-OHP-C) could be beneficial in the treatment of women at risk for preterm delivery. Since twin pregnancy is commonly associated with prematurity, 77 women with twin pregnancy were treated during the last trimester until the 37th gestational week with weekly injections of either 17 alpha-OHP-C or a placebo, following double-blind principles. The gestational length and birth weight and the outcome of the neonates were similar in both groups. The administration of 17 alpha-OHP-C thus seems ineffective in the prevention of prematurity risks associated with twin pregnancy.

Umbilical cord and neonatal cortisol levels. Effect of gestational and neonatal factors.

To evaluate the effect of the type of delivery, gestational age, maternal dexamethasone treatment, and neonatal complications on the serum cortisol levels in early infancy, a total of 92 neonates were investigated with 611 cortisol determinations (specific radioimmunoassay after Lipidex chromatography). Umbilical cord blood samples were taken immediately after delivery and capillary blood samples from the infant's heel 30--60 minutes after delivery and at 8:00 AM and PM on the second, fourth, and sixth days of life. Umbilical cord cortisol concentration after elective cesarean section was lower than after emergency cesarean section or after normal vaginal delivery, while neonatal cortisol values did not show any correlation with the type of delivery. Prematurity did not affect neonatal cortisol levels. In postterm infants the activation of cortisol production was retarded to some degree. After maternal dexamethasone therapy, neonatal cortisol concentration decreased 30--60 minutes after delivery, but from the second day on it was at the same level as in infants without maternal therapy. Respiratory distress syndrome, especially in fatal cases, caused an elevation in neonatal cortisol levels, while hyperbilirubinemia did not have an effect on plasma cortisol concentrations of the neonates.

Response of pituitary-adrenal axis on partal stress.

The circulating level of ACTH (by radioimmunoassay) and cortisol (by competitive protein binding) were determined at 1- to 2-hour intervals during spontaneous labor (N=8) and induced labor (N=28) and after delivery. There were no differences in ACTH levels between primiparous and multiparous women. The primiparous women displayed a higher level of cortisol throughout labor than the multiparous women, but not after delivery. After spontaneous onset of labor, ACTH levels were always lower than after elective induction of labor, while there were no differences in the levels of cortisol. The hypertensive complications of pregnancy did not affect the secretion of ACTH. In normal pregnancy the rise of cortisol during labor and after delivery was significant, but it was not significant in the group of patients with hypertensive complications.

Fetal adrenocorticotropic hormone and prolactin at delivery.

The concentrations of adrenocorticotropic hormone (ACTH) and prolactin in fetal scalp and umbilical cord blood were measured in 49 full-term fetuses, 25 of whom were delivered spontaneously, 10 of whom underwent induced vaginal delivery, and 14 of whom underwent elective cesarean section. Serial fetal scalp blood samples taken during the 35 vaginal deliveries showed no change in concentration of these hormones. The mean (+/- SD) plasma level of ACTH in cord artery blood after vaginal delivery (315 +/- 249 ng/liter) was significantly higher (P less than .05) than after cesarean section (184 +/- 201 ng/liter), indicating that the fetal anterior pituitary is capable of responding to partal stress.

Placental steroid synthesis from DHEAS during dexamethasone therapy.

Maternal glucocorticoid treatment affects estrogen synthesis by decreasing estrogen precursors. Whether glucocorticoid has any effect on the placental conversion of estrogen precursors to estrogen is not known. A study was therefore undertaken to investigate the effect of 100 mg of intravenously administered dehydroepiandrosterone sulfate (DHEAS) on estradiol (E2), estriol (E3), and testosterone (T) serum levels. The test was conducted for 5 hours in 10 women treated with intramuscular dexamethasone and in 8 controls during the last trimester of pregnancy. The initial E2 and E3 serum concentrations were lower in women treated with dexamethasone than in controls, while T serum levels did not display any difference. Following the injection of DHEAS there was a significant increase in E2, with maximal levels reached between 1 and 3 hours after injection in both groups. Maximal levels of E2 were equal for both groups. There was no change in E3 levels after DHEAS administration in the nontreated group, while the increase in the dexamethasone group was significant. A significant rise in T, with maximal levels reached at 1 hour after infusion, was similar in both groups. It is concluded that maternal dexamethasone does not inhibit the conversion of DHEAS either to E2 in the placenta or to E3 and T.

Decreased intervillous and unchanged myometrial blood flow in supine recumbency.

The supine position in late pregnancy is associated with many hemodynamic changes caused by compression of the inferior vena cava and a resulting fall in cardiac output. To investigate the effect of this position on uteroplacental blood flow, 22 women with normal (N = 12) or hypertensive (N = 10) pregnancy were investigated using the intravenous 133Xe washout method, in both the supine and left-tilted (45-degree) lateral positions. The intervillous blood flow (113 +/- 48 ml/min/dl) was lower in the supine position than in the left-tilted position (141 +/- 48 ml/min/dl) (P less than 0.01), while the myometrial blood flow was similar in both (9.0 +/- 3.3 ml/min/100 g in supine and 8.7 +/- 2.7 ml/min/100 g in left-tilted position). The results suggest that the autoregulation system for uteroplacental circulation is operative only in the nonplacental component of the pregnant uterus.

Amniotic fluid bile acids in normal and pathologic pregnancy.

Radioimmunologic techniques were used to determine 2 primary bile acids (cholic and chenodeoxycholic acid) and 1 secondary bile acid (deoxycholic acid) from human amniotic fluid of healthy pregnant women and from patients with diabetes, toxemia, or intrahepatic cholestasis during pregnancy. In general, the mean bile acid concentrations in the amniotic fluid were very similar to those in the serum, although in paired samples from individual patients these 2 values did not correlate significantly. Very high levels of the 2 primary bile acids were measured from the amniotic fluid of patients with intrahepatic cholestasis. The mean values were about 70 times higher than those in the controls. Amniotic fluid cholic acid content was slightly elevated in diabetic and toxemic patients, too. Deoxycholic acid was consistently found in the amniotic fluid specimens, but there was no change in its concentration among the various groups. In this limited series of patients, no significant correlation was found between the bile acid concentrations in the amniotic fluid and signs of fetal distress at the time of amniocentesis, although the lowest maternal serum estriol and human placental lactogen values were associated with the highest amniotic fluid bile acid concentrations. The condition of the newborn infants did not correlate with amniotic fluid bile acid concentrations in any of the patient groups studied. It thus appears that high amniotic fluid bile acid content present a threat to the fetus, but further studies are needed to clarify this point.

Endocrine and metabolic effects of low-dose estrogen-progestin treatment in climacteric women.

In a double-blind clinical trial with 31 premenopausal women suffering from climacteric symptoms, 16 (group A) were treated with an estrone (sodium estrone sulfate 1.5 mg)-norethisterone (5 mg) combination, and 15 (group B) were treated with an estrone-megestrol acetate (5 mg) combination. These treatments effectively alleviated climacteric symptoms without causing any bleeding disorders or pathological changes in the cytology of the uterine cervix or endometrium. In groups A and B, respectively, postovulatory progesterone concentrations above 5 nmoles/liter were found in six and five patients before, in five and seven patients during, and in two and four patients after the treatments. Serum levels of luteinizing and follicle-stimulating hormones decreased significantly and testosterone decreased slightly during both treatments. Serum cholesterol (P less than .01) and high-density lipoprotein cholesterol(P less than .001) in group A decreased during the treatment; only the high-density lipoprotein cholesterol values (P less than .05) decreased in group B. Because of the minor endocrine and metabolic changes without any significant difference between the progestins, both norethisterone acetate and megestrol acetate seem to be suitable for estrogen-progestin combinations aimed at alleviating climacteric symptoms.

The effect of parturition on umbilical blood plasma levels of norepinephrine.

The norepinephrine concentration in 77 umbilical, arterial, and venous plasma samples, and in 31 simultaneous maternal plasma samples, was measured. The mean (+/- SEM) of 8.7 +/- 1.9 ng/ml in the umbilical artery was higher (P less than .001) than that of 3.6 +/- 0.9 ng/ml in the umbilical vein. In paired fetal-maternal venous samples the norepinephrine concentration of 3.8 +/- 1.7 ng/ml in the fetus was higher (P less than .05) than that of 0.3 +/- 0.1 ng/ml in the mother. Among the different types of vaginal deliveries the umbilical arterial norepinephrine concentrations were: 5.8 +/- 2.1 ng/ml in uncomplicated vaginal deliveries; 16.4 +/- 2.1 ng/ml in breech deliveries (P less than .05 as compared with uncomplicated vaginal deliveries); 8.8 +/- 2.5 ng/ml in vacuum extraction deliveries; and 0.8 +/- 0.3 ng/ml and 11.3 +/- 7.7 ng/ml in twin A and twin B deliveries, respectively. All these values were higher (P less than .001) than those after elective cesarean section, except that for twin A, which was lower (P less than .01) than that for twin B, indicating that labor and vaginal delivery induced activation of the fetal sympathoadrenal system.

Fetal immunoglobulin production following prenatal glucocorticoid treatment.

In order to accelerate fetal lung maturation 46 pregnant women were given either dexamethasone or betamethasone intramuscularly during 3 consecutive days during 29--36 weeks of gestation. At birth, the infants appeared to have intact humoral immune function in that they could produce normal amounts of immunoglobulins in utero, and 2 fetuses responded with increased synthesis of IgA or IgM following premature rupture of the membranes. The clinical course did not show any increased incidence of puerperal or neonatal illness attributable to intrauterine infection.

Effects of ritodrine and isoxsuprine with and without dexamethasone during late pregnancy.

beta-Adrenergic agents are used to inhibit preterm labor and glucocorticoids to accelerate fetal pulmonary maturation. A study was designed to investigate the metabolic effects of intravenous infusion of ritodrine (150 to 100 microgram/min) or isoxsuprine (200 to 150 microgram/min) in a series of 28 patients with gestations of 28 to 40 weeks, with and without concomitant dexamethasone therapy. Ritodrine was more potent than isoxsuprine in increasing the circulating levels of cyclic AMP, glucose, insulin, and triglycerides. The diabetogenic effect of both ritodrine and isoxsuprine was so slight that it did not have any clinical significance in women with normal glucose tolerance. The results were similar when these beta-adrenergic tocolytics were given to women concomitantly with intramuscular dexamethasone therapy, although dexamethasone appeared to minimally impair carbohydrate metabolism. Both ritodrine and isoxsuprine caused a significant fall in serum iron and potassium, and this effect was unaltered by dexamethasone. Serial serum potassium levels should be obtained during long-term infusion of beta-mimetics.

No effect of experimental noise exposure on human pregnancy.

The effect of experimental noise exposure (15 minutes of 90-dB white noise via headphones) was examined on systolic, diastolic, and mean arterial pressures; heart rate; and stress hormones (ACTH, cortisol, prolactin, epinephrine, and norepinephrine) in normotensive and hypertensive pregnant women. No significant effects induced by noise exposure could be registered in these variables. Fetal and uterine blood circulation was also examined with a duplex pulsed Doppler system. No changes were seen on the fetal side as measured from the descending aorta in blood flow velocity (cm/second) or pulsatility or resistance indexes in either normotensive or hypertensive pregnancy. The only change observed was an increase in fetal heart rate in normotensive pregnancy. However, this increase could not be confirmed by cardiotocographic registration and is not clinically important. Uterine blood circulation was recorded from the proximal uterine artery on the placental side, and no effect of exposure was seen on pulsatility or resistance indexes.

Subnormal postconceptional levels of prolactin do not interfere with the early events of human pregnancy.

To elucidate the role of bromocriptine treatment and serum prolactin levels in peri-implantational events, 30 healthy women asking for "morning after" type contraception were given bromocriptine. Treatment was started 30.6 +/- 18.4 (mean +/- SD) hours after unprotected intercourse and continued until the next menstruation. Blood samples were taken before and 1 and 2 weeks after initiation of treatment, and the samples were assayed for concentrations of prolactin, progesterone, human chorionic gonadotropin (hCG), and pregnancy-specific beta1-glycoprotein (PSBG) by radioimmunoassay. Prolactin concentrations fell significantly (P less than 0.001) from the pretreatment level of 11.4 +/- 7.9 ng/ml (mean +/- SD) to 2.8 +/- 2.3 ng/ml at 1 week and to 1.9 +/- 0.6 ng/ml after 2 weeks of treatment. Five women had demonstrable hCG in serum 8 to 15 days after unprotected intercourse, and one of them also had PSBG 14 days postcoitum. Pregnancy advanced normally until legal termination in three women, whereas menstruation-like bleeding ensued in two. Our results suggest that neither bromocriptine treatment nor a subnormal maternal serum prolactin level interferes with the early development of human pregnancy.

Comparison of the gonadotropin-releasing hormone agonist goserelin acetate alone versus goserelin combined with estrogen-progestogen add-back therapy in the treatment of endometriosis.

OBJECTIVE: To investigate whether the addition of low-dose estrogen-P combination hormone replacement therapy (HRT) to GnRH agonist (GnRH-a) treatment for endometriosis reduces the pharmacologic side effects of such treatment without reducing efficacy and to determine the endocrinologic changes during treatment. DESIGN: Prospective, randomized, double-blind, placebo-controlled, comparative study of two drug regimens: 3.6 mg goserelin acetate in a 28-day SC depot formulation once monthly for 6 months plus either a combination of 2 mg 17 beta-E2 and 1 mg norethisterone acetate (NET) 1 mg or matching placebo tablets once daily for 6 months. SETTING: Multicenter study in three tertiary referral centers at university teaching hospitals and two central hospitals. PATIENTS: Women with laparoscopically confirmed symptomatic endometriosis were included in the study. RESULTS: Of the total of 109 patients screened, 93 were recruited and 88 patients were randomized to either the HRT or the placebo group. Four women were withdrawn because of various medical reasons, and 76 patients were followed-up for a total of 12 months. In terms of efficacy, there was no difference between the two drug regimens for objective or subjective response. There were significantly less postmenopausal symptoms in the patients treated with goserelin plus HRT compared with those treated with goserelin plus placebo. CONCLUSION: Goserelin diminished significantly the symptoms and laparoscopic scores of endometriosis. The addition of HRT did not reduce the efficacy of goserelin but diminished the postmenopausal symptoms during treatment.

Cytochrome P450IA1 activity in human myometrium and uterine leiomyoma: influence of smoking.

A xenobiotic-metabolizing enzyme, the P450IA1 (aryl hydrocarbon hydroxylase; AHH) was measured fluorometrically in myometrium and in uterine leiomyoma tissues. The material included both myometrium and leiomyoma tissue samples from 62 leiomyoma patients and 22 tissue samples of normal myometrium obtained from leiomyoma-free patients undergoing hysterectomy. Among 62 leiomyoma patients there were 14 cigarette-smokers and 48 non-smokers, and among 22 control patients 6 and 16, respectively. The P450IA1 activity of the leiomyomas was significantly (P < 0.0005) higher than that of the surrounding myometrium in both smoker and non-smoker groups. In smokers, myometrium an obvious induction of P450IA1 was seen. Smoking increased the P450IA1 activity also in the leiomyoma, but the increase was not statistically significant. Our study supports the idea that myometrial tissue can respond to xenobiotics from the environment.

Effect of selenium supplementation to fertilizers on the selenium status of the population in different parts of Finland.

Concentrations of selenium in the soil are very low in most regions in Finland, which explains the low selenium contents of agricultural plants and the low dietary intake of selenium. The poor selenium status of the population in Finland has been considered a possible risk to public health. In 1984, it was decided to increase the selenium intake by adding selenate to common agricultural fertilizers. In this study, the selenium concentrations of whole blood and plasma, as well as erythrocyte glutathione peroxidase activities, were measured in blood samples from four different localities in Finland, in 1984 and 1986, before and during the agricultural selenium supplementation. A low blood level of selenium in the inhabitants of central Finland was demonstrated in 1984. The selenium level of people from the south-west archipelago was a little higher, and that from the northern part of Finland considerably higher than the level in the rest of the country. By 1986, differences between these localities had almost disappeared, and most levels had increased. Plasma selenium concentrations were lower than those in whole blood samples; the concentrations showed a significant correlation. The glutathione peroxidase activities were at the same level in all four localities in 1984. By 1986, they had all increased to a slightly higher level. A weak correlation was found between erythrocyte glutathione peroxidase activity and blood selenium level.

Can climacteric women self-adjust therapeutic estrogen doses using symptoms as markers?

OBJECTIVES: To investigate if disappearance of climacteric symptoms during hormone replacement therapy (HRT) also means good therapeutic level of serum estradiol. The study group comprised of 32 postmenopausal women who had frequent climacteric symptoms. METHODS: The women increased the daily treatment doses of percutaneous estradiol every 2 weeks until they felt comfortable with it. Each woman continued at that treatment dose for up to 3 months. Blood samples for estradiol assay were drawn at baseline, every time before the estradiol dosage was increased and at the end of the study. Climacteric symptoms were scored according to the Kupperman menopausal index. RESULTS: Despite the relief of climacteric symptoms, serum estradiol concentration was at a menopausal level (< 50 pg/ml) in 22% of the women. In all, 45% of the subjects showed serum estradiol remaining under 60 pg/ml, 29% of the women showed levels of 60-100 pg/ml and 26% showed serum estradiol concentration more than 100 pg/ml. CONCLUSIONS: The disappearance of climacteric symptoms during HRT does not guarantee that estrogen levels are sufficiently high for obtaining long term benefits of HRT.