Bo Lindberg

Radioimmunological Methods for the Estimation of Oestrone, Oestradiol 17β and Oestriol in Pregnancy Plasma

SummaryAntibodies to oestradiol-17β and oestriol have been produced by immunization of sheep with oestradiol-6-oxime and oestriol-6-oxime attached to bovine serum albumin (BSA). The antibodies were used in radioimmunoassays.In the oestradiol-17β assay the free and bound steroids were separated by means of dextran-coated charcoal. This technique caused a heavy stripping when tried in the oestriol assay. A new assay for oestriol in plasma was thus devised. In this assay, oestriol and antibody were incubated at 40d`C for 30 minutes. Free and bound steroids were separated with saturated ammonium sulphate. The specificity of the antibody raised after immunization with oestradiol-17β-6-oxime BSA was compared with a previously used antibody obtained after conjugation in the 17th position of oestradiol-17β to BSA. The former antibody had a higher specificity and crossreacted only 11 per cent with oestrone compared to 50 per cent for the latter. The oestriol antibody was highly specific, crossreacting only 13 per ...

Pregnancy‐induced increase in metoprolol metabolism

Five women who developed hypertension during pregnancy received metoprolol, 10 mg iv; 3 days later they received metoprolol, 100 mg by mouth. Blood and urine samples were collected after each dose. The same procedure was repeated 3 to 6 months after delivery. The apparent oral clearance of metoprolol during pregnancy exceeded that after pregnancy by a factor of 2 to 13. As a result, after oral dosing the peak plasma concentrations during pregnancy were only 12% to 55% those after delivery, and the plasma AUCs were reduced to the same extent. Oral bioavailability increased by a factor of 1.3 to 3.7 after pregnancy. Systemic clearance after pregnancy was 26% to 97% that during pregnancy, but this difference was not significant. Metoprolol plasma protein binding was the same on both study occasions. Our data cannot be explained by a change in gastrointestinal absorption, because the urinary recovery of metoprolol and its metabolites was slightly higher during pregnancy. It is concluded that the greater metoprolol clearance during pregnancy results from increased hepatic metabolism of the drug.

Plasma Levels of Nonconjugated Oestrone, Oestradiol‐17β and Oestriol During Uncomplicated Pregnancy

SummaryPlasma levels of unconjugated oestrone,1 oestradiol-17β and oestriol from the 22nd week of uncomplicated human pregnancy until delivery have been estimated by means of radioim-munoassays. In some cases, the oestrogens were separated by Sephadex LH-20 chromatography before the radioimmunoassays. Plasma levels of unconjugated oestrone increased from a mean of 3 ng/ml in the 22nd week to 9.9 ng/ml in week 41. Oestradiol-17β concentrations in plasma were estimated by two different radioimmunoassays. With the most specific method, plasma mean concentrations were found to rise from 7.5 ng/ml in the 22nd week to 23.6 ng/ml in the 38th week. A somewhat less specific assay with a cross-reaction of 50 per cent for oestrone gave a mean level of 8.3 ng/ml in week 22 increasing to 26.2 ng/ml in week 41. When unconjugated oestradiol-17β in plasma was estimated after Sephadex LH-20 chromatography somewhat lower concentrations were found.The results for the estimation of unconjugated oestriol in plasma were simila...

Potentially avoidable perinatal deaths in Denmark and Sweden 1991

Background. Since 1950 the perinatal mortality has been significantly higher in Denmark than in Sweden. In 1991 the rate in Denmark was 8.0/1000 deliveries compared to 6.5/1000 in Sweden. An international audit was designed to investigate whether the perinatal death rates in the two countries to some extent could reflect differences in the quality of care, indicated by the numbers of perinatal deaths in categories of potentially avoidable deaths.

Maternal kinetics of morphine during labour

The disposition of parenterally administered morphine was investigated in 13 nulliparous parturients in comparison with six healthy non-pregnant women of child-bearing age. Morphine was administered intravenously or intramuscularly and repeated venous blood samples were taken up to 360 minutes after the dose, or until delivery. At delivery samples were taken from the umbilical artery and vein. The plasma concentrations of morphine and M3G (morphine-3-glucuronide) were determined. The elimination half-life of morphine was shorter (43 +/- 19 versus 84 +/- 40 min) and the plasma clearance larger (3.4 +/- 1.4 versus 2.0 +/- 0.5 l/min) in the parturients than in the non-pregnant women. There was no difference in the apparent volume of distribution of morphine between those two groups. The time to peak plasma concentration of M3G was shorter (11 +/- 3 versus 21 +/- 6 min) and the M3G/morphine concentration ratio at 10 minutes higher (6.4 +/- 1.0 versus 3.4 +/- 0.6) in parturients than in non-pregnant women. In all but one infant, three of whom were born within three hours after the dose, no morphine was detectable. The rapid elimination of morphine by the parturients, resulting in only a short period of intrauterine exposure of the fetus to this drug, may be of clinical importance in the choice of obstetric analgesic agent.

Transplacental transfer of morphine in man.

The transplacental transfer of morphine and morphine-3-glucuronide (M3G) was studied in five cases of suspected Rh-isoimmunization. Ultrasound-guided fetal blood sampling from the umbilical vein was carried out as a diagnostic procedure before intrauterine blood transfusion. Morphine was given as a parenteral premedication to the mother at a dose of 0.13-0.20 mg/kg bw. Fetal blood was sampled 5-74 minutes after the morphine administration. These five women were investigated on 14 different occasions. The plasma concentrations of morphine and M3G were measured in blood samples collected simultaneously from mother and fetus. The feto-maternal ratio of morphine was 0.96 at five minutes and remained close to 1.0 in most samples taken later. At 12 minutes the ratio of M3G was less than 0.002 and between 0.2 and 0.6 in the later samples. The feto-maternal plasma ratios of morphine and M3G did not change over the studied period in one woman investigated five times between gestational weeks 26 and 32. This is the first time transplacental transfer of morphine has been quantified in man. Our results demonstrate a rapid transplacental passage and equilibration of morphine between mother and fetus.

Intravenous nitroglycerin for rapid uterine relaxation.

BACKGROUND To investigate the effect of nitroglycerin in vitro and in vivo on human uterine contractile activity. METHODS In vitro myometrial strips were obtained from six pregnant women at term who underwent elective cesarean section. The biopsies were mounted in tissue baths. After spontaneous or oxytocin-induced activity had been accomplished, nitroglycerin in various concentrations was added to the baths and the effects were continuously registered. In vivo, in an open study nitroglycerin was administered as a bolus injection of 100-200 micrograms intravenously to 32 women at cesarean section when uterine relaxation was urgently needed; to 22 other women after vaginal delivery for facilitation of manual removal of retained placentas, and to one patient at vaginal delivery of premature twins. RESULTS In vitro nitroglycerin induced a dose-dependent inhibition of spontaneous as well as oxytocin-induced myometrial contractile activity. Complete muscular relaxation was obtained at a concentration of 25-50 micrograms/ml. In vivo all patients had rapid effective uterine relaxation after intravenous injection of 100-200 micrograms nitroglycerin. CONCLUSION Nitroglycerin administered intravenously seems to be a rapid and effective uterine muscle relaxant agent without overt adverse effects on mother or fetus.

Plasma Progesterone Levels in Normal and Abnormal Pregnancies

Abstract. Plasma progesterone levels were estimated by competitive protein binding in 815 samples from healthy pregnant women with uncomplicated pregnancies. This series includes 32 patients who were followed serially throughout pregnancy. The mean level increased from 47 ng/ml in week 22 to 148 ng/ml in week 41. The spread was large. Individual patients showed very large variations between two consecutive weeks.

Urinary excretion of a glucose-containing tetrasaccharide. A parameter for increased degradation of glycogen

The urinary excretion of a glucose-containing oligosaccharide, Glc alpha[1-6Glc alpha[1-4Glc alpha[1-4Glc, (Glc4) has been measured in various physiological and pathological conditions. The Glc4 content of 24 h samples from the same individual was relatively constant, whereas 2 h samples showed up to 4-fold variations in Glc4 concentration. This variation is associated mainly with increased excretion of Glc4 after meals. A carbohydrate-rich diet, starvation or a protein-rich diet, and intense physical activity all affected the urinary excretion of Glc4. Both oral and intravenous administration of glycogen in a Rhesus monkey resulted in increased excretion of Glc4. When Glc4 itself was injected intravenously in small amounts renal clearance was rapid and complete. In contrast, injection of a larger amount resulted in incomplete (approximately 10%) renal clearance, probably due to uptake and metabolism of the oligosaccharide. In patients with glycogen storage diseases, certain malignancies, and pancreatitis, 24 h urinary Glc4 excretion exceeded the normal range. The diagnostic implications of these observations deserve evaluation. The results presented suggest a need for standardization of nutritional status and physical activity when monitoring urinary Glc4 excretion for diagnostic purposes.

Plasma Levels of Nonconjugated Oestradiol‐17β and Oestriol in High Risk Pregnancies

SummaryThe plasma concentrations of nonconjugated oestradiol-17β1 and oestriol were estimated by radioimmunoassay in pregnant women with pre-eclampsia, retarded fetal growth, diabetes mellitus and Rh-immunization.The plasma levels of nonconjugated oestradiol-17β showed a considerable spread in all groups of patients, and no significant difference between women with an uncomplicated pregnancy and those with high risk pregnancies could be found. No “fetal danger zone” with increased risk of fetal demise could be established. The prognostic value of measurement of nonconjugated oestradiol-17β thus seems to be limited.The plasma levels of nonconjugated oestriol displayed a similar spread as in uncomplicated pregnancy. Patients with pre-eclampsia or retarded fetal growth showing at least one plasma sample with an oestriol concentration of four ng/ml or less after the 35th week of pregnancy had, however, an increased risk of fetal death or neonatal asphyxia. At levels higher than this “fetal danger zone” no int...