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Biomedical subjects

L Viinikka

Publications and source records attributed to L Viinikka.

At least 199 records · Page 11Linked to original sources

Metabolism of a new synthetic progestagen, Org 2969, in female volunteers. The distribution and excretion of radioactivity after an oral dose of the labelled drug.

The metabolism of a new synthetic progestagen, Org 2969 was studied in 4 healthy female volunteers. During the first part of the study (Phase I), the volunteers ingested 50 microgram (about 0.1 mCi) of [16-3H5Org 2969 together with 50 microgram of ethinyloestradiol as a single dose. During the second part of the study (Phase II), a 10-day pre-treatment with the same dosage of non-radioactive compound preceded the administration of the radioactive steroid. A peak level of total radioactivity, representing 3.16-5.02% of the dose given/l of serum, was achieved within 2-3 h in Phase I. During Phase II, the corresponding figures were 4.54-5.13% after 1.5-3 h. The difference was mainly due to an increase of freely-extractable steroids during Phase II. The difference can at least partly be explained by assuming a change in the kinetics of the metabolism of Org 2969 by pre-treatment with Org 2969 and ethinyloestradiol. The mean recovery of radio activity in urine and faeces was 83.0%/48.1%/34.9% (total/urine/faeces) of the total dose in Phase I and 76.1%/45.2%/30.9% during Phase II. The differences in the total excretion and in the radioactivity excreted in the faeces were significant.

Administration, Oral↗

Intraamniotic or intravenous injection of dehydroepiandrosterone sulfate in midgestation: effect on prolactin level in maternal serum and amniotic fluid.

The influence of dehydroepiandrosterone sulfate (DHEA-S) on PRL levels in maternal serum and amniotic fluid at midgestation was evaluated in a series of 32 women admitted for midtrimester abortion. Serum was collected hourly for 6 h in 13 women after intraamniotic (ia) instillation (100--200 mg) or in 10 women after iv injection (100 mg) of DHEA-S, and in 9 control women. Serum PRL levels rose significantly (P less than 0.05) 3--6 h after ia and 2--6 h after iv administration of DHEA-S but was unchanged in the control group. The elevation of serum PRL levels is most likely secondary to increased levels of serum estrogens which accompany ia or iv administration of DHEA-S. This suggests that maternal pituitary PRL secretion is responsive to additional stimulation by endogenous estrogens at midgestation. The amniotic fluid PRL level ranged from 1109-2473 ng/ml, with no consistent change after administration of ia DHEA-S, intimating that estrogens may not be implicated in the control of PRL in amniotic fluid.

Amnion↗

Pituitary and ovarian function in women with congenitally absent uterus.

Pituitary-ovarian function was studied in 2 women with congenital absence of the uterus and the vagina. Daily serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, estradiol-17beta, and progesterone were measured by radioimmunoassay for 1 month. Gonadotropins and ovarian steroids showed normal cyclic variations in both patients. Prolactin was persistently elevated in one of them, who also demonstrated 2 abnormally high testosterone values among 6 determinations. The pituitary gland was stimulated by intravenous leasing hormone (LRH-TRY). Gonadotropin and prolactin responses to LRH-TRH were normal. The lifelong absence of the uterus does not alter the function of the pituitary-ovarian axis. The relation of hyperprolactinemia to this syndrome must be ascertained in a greater number of patients.

Adolescent↗

Effects of intravenous isoxsuprine and ritodrine, with and without concomitant dexamethasone, on fetoplacental and pituitary hormones and cyclic adenosine monophosphate during late pregnancy.

Beta sympathomimetic drugs are used to inhibit preterm labor and glucocorticoids to accelerate fetal pulmonary maturation. A study was designed to investigate the hormonal effects of intravenous infusion of isoxsuprine 150 to 200 mcg. per minute or ritodrine 100 to 150 mcg. per minute in a series of 28 women at 28 to 40 weeks' gestation, with and without concomitant dexamethasone therapy. Serial serum samples taken before and during the six hours of infusion were assayed for cyclic adenosine-3,5-monophosphate (AMP), estradiol, estriol, progesterone, human placental lactogen (hPL), thyrotropin (TSH), follicle-stimulating hormone (FSH), and human growth hormone (gGH). Ritodrine was more potent than isoxsuprine in increasing the circulating levels of cyclic AMP. The levels of placental steroid hormones decreased slightly, as did the ratio of progesterone to estradiol. Human placental lactogen and pituitary hormones showed no consistent changes. Simultaneous administration of dexamethasone did not modify these results.

Adult↗

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.

Adolescent↗

Hormonal pattern of adolescent menstrual cycles.

Serum FSH, LH, PRL, estradiol, pregnenolone, progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone, and androsterone were measured radioimmunologically in 20 normal girls aged 13-17 yr. Samples were taken every day or every second day during one menstrual cycle. The cycles recorded could be divided into three groups. The first and oldest group consisted of 10 girls with a mean gynecological age (years since menarche) of 2.9 yr. The luteal phase was at least 11 days and the progesterone concentration was at least 5 ng/ml. The testosterone rise (mean, 55%) on the day of LH surge correlated well with the simultaneous progesterone rise (mean, 270%) and the following luteal progesterone secretion. A negative correlation was seen between the FSH concentration on days 3-4 of the cycle and the length of the follicular phase. The second group consisted of 4 girls who had a mean gynecological age of 1.5 yr. The luteal phase was of 4- to 8-day duration and the progesterone secretion was lower than in group I. The follicular phase testosterone concentration was lower in group II as compared to group I. No "periovulatory" testosterone increases were seen, although every cycle displayed an LH and FSH peak. The third group consisted of 6 girls with a mean gynecological age of 1.1 yr. These cycles were anovulatory, as the serum progesterone concentration never exceeded 1.0 ng/ml. In two cycles, signs of follicular maturation were seen. In the four others, the androgen levels tended to be elevated. In two cases, the testosterone and androstenedione concentrations were 2-4 times elevated from the beginning of these two cycles. Thus, the hormonal pattern of adolescent menstrual cycles is far from uniform. It is very likely that in addition to gonadotropins, estradiol and progesterone, androgens may also have a role in the development and maintenance of normal menstrual function in the female.

Adolescent↗

Automation of radioimmunoassays for some sex steroids with use of both iodinated and tritiated ligands.

We describe an automated technique for estradiol, progesterone, and testosterone, in which System Olli 3000 pipetting and incubation units are used. After extraction or chromatography, steroids are redissolved in ethanol or buffer, and duplicate aliquots are arranged for radioimmunoassay in 24-tube blocks. Addition of antibodies, tracers (125I or 3H), dextran-coated charcoal for separating free and bound ligands, and removal of a portion of the supernate for counting are all performed by the pipetting instrument. Incubations are at 37 degrees C in the incubation unit, or at 4 degrees C. After counting, steroid concentrations are computed from punch tape records by a Nova 840 computer. The management of assays in 24-tube units, and accurate simultaneous pipetting has reduced experimental error, and because there is no carryover, many different assays can be performed concurrently or in rapid sequence. Various scintillation media are compared.

Antibody Specificity↗

Abortifacient efficiency of 15 (S) 15-methyl-prostaglandin F2alpha-methyl ester administered vaginally during early pregnancy.

Forty early pregnancies (menses delay 13 - 27 days) were terminated by administering four vaginal suppositoreis each containing 1.0 or 1.5 mg of 15 (S) 15-methyl-prostaglandin F2alpha-methyl ester, one every third hour. In 14 cases serial measurementsof serum estradiol and progesterone were performed during and after therapy. Uterine contractions and bleeding started 1 - 17 hours after administration of the first suppository. Abortion was complete after one week in five women (13%), and after two weeks in 30 (75%). A curettage was performed on eight women, residual placental fragments were found in seven and pregnancy continued in one woman. Mild diarrhoea (65%) and vomiting (40%) were the major side-effects, despite premedication. Estradiol and progesterone levels fell progressively during the therapy. Self-administration of 4 or 6 mg of the methyl ester caused too low a rate of complete abortion for use in practice, but it may be a valuable and practical agent for preoperative dilation of the cervix.

Abortion, Induced↗

Biological effects of a new and potent progestagen. A clinical study.

The biological effects of a new synthetic progestagen, Org 2969 (13-ethyl-11-methylene-18,19-dinor-17 alpha-pregn-4-en-20-yn-17-ol) were studied in healthy normally menstruating women. Two of them were given 0.125 mg, five 0.060 mg and two 0.030 mg of Org 2969 daily on days 1-20 during one menstrual cycle. Serum levels of follicle stimulating hormone, luteinizing hormone, progesterone and oestradiol were analyzed on days 8-23 in order to evaluate the function of the hypophyseal-ovarian axis. The serum concentrations of aspartate amino transferase, alanine amino transferase, alkaline phosphatase, gamma glutamyl transpeptidase and bilirubin were determined to evaluate possible side effects on live function on days 8, 15 and 23. Serum cortisol was measured on days 8 and 23. The basal body temperature was recorded daily during the whole cycle, and endometrium biopsies were taken on days 21 or 22 of the cycle. All samples were taken similaryl during the treatment cycle and the preceding control cycle. According to the hormone determinations, all the treatment cycles were anovulatory except in one woman receiving the lowest dose. The treatment led to decreased spinnbarkeit, arborization and sperum penetration in the cervical mucus. Liver function tests and serum cortisol remained unchanged during the treatment.

Administration, Oral↗