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Biomedical subjects

M O Pulkkinen

Publications and source records attributed to M O Pulkkinen.

At least 19 recordsLinked to original sources
PubMed1991

Distribution of oral nimesulide in female genital tissues.

Nimesulide is a non-steroidal anti-inflammatory agent which has proved to be effective in reducing menstrual discomfort in dysmenorrhoeaic women. To determine the concentrations of this drug in the uterus (fundus, cervix), oviduct, and ovaries and to correlate these findings with plasma concentrations, a single oral dose of 100 mg nimesulide was administered 1 to 6 h before surgery to 12 women undergoing hysterectomy and salpingo-oophorectomy, mainly for fibroids. Tissue samples were taken, concentration of nimesulide measured by HPLC, and findings compared with plasma concentrations. One patient not undergoing treatment served as control. Nimesulide concentration in the tissues studied was highest 3 h after administration, as expected from the drug's pharmacokinetic profile. The highest tissue/plasma ratio (0.5) was also found at that time. Average tissue concentrations at 1, 2, 3, and 6 h after drug intake ranged from 0.3 to 1.8 micrograms g-1, and plasma concentrations from 2.6 to 4.1 micrograms ml-1. Nimesulide was evenly distributed in the tissues studied.

Administration, Oral↗
PubMed1991

Androgen synthesis in human fetal testis exposed in utero to a combination of norethindrone acetate and ethinyl estradiol.

The effect of norethindrone acetate (NET-Ac) and ethinyl estradiol (EE2) on the 3 beta-hydroxysteroid dehydrogenase (HSD)-delta5-isomerase complex of the human fetal testis was studied by administration of 20 mg NET-Ac and 0.04 mg EE2 p.o on a single day to 4 women, pregnant 10-16 weeks, before abortion was induced, the other 4 patients serving as controls. Testosterone and androstenedione formation from radioactive dehydroepiandrosterone was measured in 8 fetuses by incubation of testicular tissue in vitro. The presence of normal feta Leydig cells was confirmed by electron microscopy. There was no difference between the enzyme activities of testicles in the experimental and control groups. The findins give values of 3 beta-HSD-isomerase activity in human fetal testis and suggest that the steroidogenic function of the fetal testis exposed for a short time to normally used contraceptive steroids remains at the same magnitude.

Androgens↗
PubMed1990

Pancreatic and catalytic phospholipase A2 in relation to pregnancy, labor and fetal outcome.

The serum pancreatic and catalytic phospholipase A2 level (PLA2) in human pregnancy is normal, and the increase of pancreatic enzyme before delivery is small. In patients with pruritus associated with obstetric hepatosis maternal serum had a slightly lower pancreatic PLA2 level if the cholic acid level was higher. Umbilical cord blood has twice as much pancreatic PLA2 as maternal blood. If the enzyme concentration was very high, pregnancies were postterm and the newborns had low Apgar scores. Amniotic fluid contains these enzymes, but there is no change in the enzymes during the course of pregnancy. The amount of pancreatic enzyme was not reflected in catalytic activity. A very high PLA2 activity was observed in 1 patient with suspected amniotic fluid embolism and in the meconium, but low in the first urine of neonates.

Amniotic Fluid↗
PubMed1989

A study of the effect of mifepristone (antiprogesterone) followed by prostaglandin on uterine activity and fetal heart rate in patients having a termination of pregnancy.

In the 72 h after a single oral dose of 400 mg of the antiprogesterone mifepristone, 12 out of 14 first and one second trimester fetuses had a slight increase in heart rate; 2 fetuses died and one aborted. During the same 72 h, uterine activity increased moderately, and was physiological with no increase in resting pressure. The treatment sensitized the uterus to prostaglandin (PG) about ten-fold. A low, 0.05 mg IM, dose of sulprostone caused the demise of 5 more fetuses and caused the onset of clinical abortion in less than 2 h. After a relatively short hypertonic phase uterine resting pressure fell to normal levels and active contractions occurred leading to expulsion of uterine contents. The plasma level of progesterone (P) remained unaltered after mifepristone treatment, but the levels of estradiol 17b (E2) and cortisol increased. The plasma level of mifepristone was 1640 +/- 424 ng. ml -1 at 72 h, and the substance was still detectable after one week.

Abortifacient Agents↗
PubMed1989

Low serum progesterone levels and tubal dysfunction--a possible cause of ectopic pregnancy.

We analyzed 22 human oviducts by the suction electrode method for electrical activity (preceding and reflecting the mechanical activity), as related to serum progesterone levels. Eleven patients had high progesterone levels (greater than or equal to 20 nmol/L), but the other 11 patients had low levels. When the serum progesterone level was low, the oviductal electrophysiologic characteristics were those associated with poor ovum transfer: low probability of prouterine propagation of the activity at the fimbrial end of the tube: high-frequency but low number of electrical bursts, reflecting possible weak propulsive force; and a high occurrence rate of sine-wave-like activity and inactive areas where ovum retention can occur. These phenomena could be related to the higher incidence of ectopic pregnancies in patients with luteal phase defect.

Adult↗
PubMed1989

Acute and chronic effects of oral enprostil, a synthetic dehydroprostaglandin E2, on uterine contractility.

In acute experiments eleven nonpregnant women received a single oral dose of enprostil (prostaglandin E2 analogue) 35-140 mcg. Uterine activity was measured by a microtransducer-tipped Millar catheter. A single, oral dose of enprostil caused a long-lasting contracture response of the uterus. 3 h after enprostil, uterine resting pressure (RP) was still high. In chronic experiments, eleven women with regular menstrual cycles received 35 mcg or 70 mcg BID enprostil and placebo in a crossover, double-blind fashion from cycle day 10 +/- 3 for four weeks, then had a washout period of four weeks followed by another four-week treatment period. An increase of uterine RP after enprostil was dose-dependent. After two weeks of twice-daily administration of enprostil, the baseline RP was lower than after placebo (p less than 0.01) and the increase in RP after the morning enprostil less than that seen on the first day. In eight patients studied, the mean values of plasma progesterone were normal, both during placebo--and enprostil--treated cycles.

Administration, Oral↗
PubMed1989

Oral administration of the prostaglandin enisoprost induces uterine activity and softens the cervix during first trimester pregnancy.

48 patients in the first trimester of pregnancy received a single oral dose of placebo or enisoprost (prostaglandin E1 analogue): 10, 25, 50, 100, 200 or 400 micrograms. Uterine activity was recorded for 1 h before and for 4 h after administration of the study drug with a Millar microtransducer. There was a dose-related increase in mean resting and active pressure, but not in frequency of pressure cycles. At the highest dose used, namely 400 micrograms, all 6 subjects bled. Enisoprost dilated the cervix and any further dilatation required was easy to accomplish.

Abortion, Induced↗
PubMed1987

Alterations in intrauterine pressure, menstrual fluid prostaglandin F levels, and pain in dysmenorrheic women treated with nimesulide.

A double-blind crossover study was carried out to evaluate the therapeutic efficacy of nimesulide and its effects on uterine activity, menstrual fluid prostaglandin F, and pain in women suffering from primary dysmenorrhea. Twenty-three women entered the clinical pharmacologic study. Intrauterine pressure was monitored with a microballoon-tipped catheter on the first day of menstruation. During the maximal pain period (based on monitoring in six patients), nimesulide significantly decreased intrauterine pressure; the measure of pain relief was consistent with decrease of uterine activity. In another six patients, the registration of intrauterine pressure during the submaximal pain period demonstrated that both in the nimesulide- and placebo-treated cycles, the uterine activity was at a lower mean level than that registered during maximal pain. Furthermore, when two 100-mg oral doses of nimesulide were administered to 11 dysmenorrheic women, in double-blind, crossover conditions with placebo as a blank reference, it brought about a reduction of menstrual fluid prostaglandin F2 levels from 382 to 94 ng/mL, (P less than .001). Fourteen women entered a four-cycle, double-blind, crossover therapeutic trial. Each patient was randomly assigned to one of two treatment sequences with nimesulide 200 mg/d PO or placebo. The therapy was judged very effective or good in 22 of 28 cycles treated with nimesulide compared with nine of 27 cycles treated with placebo (P less than .01). The amount of bleeding during the treated cycles did not change, and there were no complaints of untoward signs or symptoms related to the therapies.

Adult↗
PubMed1987

Pancreatic phospholipase A2 (PPLA2) during human pregnancy.

Pancreatic phospholipase A2 in human serum during pregnancy is within the normal range. In the amniotic fluid, the amount of immunoreactive pancreatic phospholipase A2 increases from 1.3 microgram/l at 16 weeks to 2.9 micrograms/l near term, but does not correlate with PLA2-activity. Meconium-stained amniotic fluid had highly elevated pancreatic, but not kinetic, PLA2. The fetal pancreas and its high PLA2-content may contribute to the progressive increase in uterine activity during human pregnancy.

Amniotic Fluid↗
PubMed1986

Constriction of the fetal ductus arteriosus by progesterone.

Progesterone substitution in the rat during pregnancy days 17-21 or administration 6 h before spontaneous delivery constricted the fetal ductus arteriosus. The rapid whole-body freezing technique was used. Indomethacin-induced constriction of the fetal ductus arteriosus was not affected by progesterone treatment.

Animals↗
PubMed1985

Acute urinary bladder tamponade with hypovolemic shock due to placenta percreta with bladder invasion. Case report.

A rare case with residual tissue of placenta previa invading posterior parts of the bladder as placenta percreta complicated by massive late hematuria with hypovolemic shock two months after gynecologic-obstetric operation is presented. The patient was finally treated by emergency bladder resection. If a grand multipara with a history of hysterotomies, such as cesarean sections, presents lower abdominal pain involving hematuria during pregnancy, placental invasion of the bladder may be suspected. The primary treatment by hysterectomy should be complemented by bladder resection. This placental type may have high steroidogenesis.

Acute Disease↗
PubMed1985

Induction of human labor at term: uterine activity, inducibility, duration and neonatal jaundice.

A total of 821 patients, 39-40 weeks pregnant, was obstetrically normal at admission. In 212 of them intra-uterine pressure (IUP) was monitored before and during inducing labor by oxytocin, in 212 patients delivery was also induced by oxytocin but not monitored, in 197 by combining oxytocin and amniotomy, and 200 had spontaneous delivery. Inducibility could be predicted by uterine baseline activity and a 50 mu i.v. shot of oxytocin, together with determination of cervical status and placental location. The duration of labour induction was affected by parity, placental location and cervical status, but was predicted only to a minor degree by baseline activity and uterine oxytocin sensitivity. Amniotomy did not affect caesarean, section rate. The newborn child benefited from IUP monitoring: fewer transfers to pediatrics were necessary, there was less neonatal jaundice and fewer blood exchanges. It is assumed that if labor is not monitored through IUP, oxytocin may cause neonatal hyperbilirubinaemia through episodes of increased uterine resting pressure.

Female↗
PubMed1984

Collagen types and fibronectin in the uterine muscle of normal and hypertensive pregnant patients.

Specimens from the uterine wall were obtained from 16 patients at 31 to 40 weeks of pregnancy: 10 underwent surgical procedures for a hypertensive disorder and six for abnormality of the birth canal or faulty presentation. Collagen types I, III, and V and fibronectin antibodies were used for immunohistologic studies. Collagen types I and V were located mainly around single cells, but type III and fibronectin were found mainly around cell bundles. Collagenous structures in the uterine muscle of patients with hypertensive disorder in pregnancy were torn. Abundant fibronectin fluorescence was detected in the lobuli within the disrupted tissue. Disruption of the uterine structure correlated with the amount of urinary protein excreted.

Adult↗
PubMed1984

Myoelectrical activity in the human oviduct with tubal pregnancy.

Myoelectrical activity and progesterone (P) and 17 beta-estradiol (E2) concentrations were measured in 12 human oviducts with tubal pregnancy. Spikes were frequently superimposed on a single, smooth, slow wave. The region above a large conceptus (P dominance) was inactive in eight of 10 oviducts. The myoelectrical activity spread toward these conceptuses from both sides, apparently holding the conceptus in place. In three cases with small placentas, the spread of weak activity tended to push the conceptus out of the oviduct. A steep decline of P and E2 levels distally in both directions from the conceptus was coincident with frequency of peaks.

Adult↗
PubMed1984

Norethisterone acetate and ethinylestradiol in early human pregnancy.

In a double-blind randomized trial, 25 women (8-9 weeks pregnant) received 20 mg norethisterone acetate (NET-AC) and 0.04 mg ethinylestradiol (EE2), 25 women receiving placebo. The patients were followed by ultrasound and the products at curettage studied macroscopically and microscopically. In an open trial, ten patients (5-9 weeks pregnant) received NET-AC + EE2, 11 serving as controls. The concentrations of plasma progesterone, estradiol-17 beta, 17 alpha-hydroxyprogesterone, norethisterone, and FSH were followed. The frequency of intrauterine hemorrhage in early pregnancy was not affected by NET-AC + EE2. Ultrasound was not reliable when studying the occurrence of decidual hemorrhages during early pregnancy. The pharmacokinetics and bioavailability of NET remain unchanged during early pregnancy. The treatment with NET-AC + EE2 had no effect on the heights and the time courses of the mean plasma values of progesterone, estradiol-17 beta, 17 alpha-hydroxyprogesterone, and FSH. No differences were found between treated and nontreated patients in the pathology of the placenta or decidua as determined by both macroscopic and microscopic examinations. The hypothesis of Papp and Gardo, that decidual hemorrhages may be induced in early pregnancy as a consequence of a "withdrawal effect" of hormonal pregnancy tests, is not supported by the results of this investigation.

17-alpha-Hydroxyprogesterone↗
PubMed1984

Studies on the role of intestinal bacteria in metabolism of synthetic and natural steroid hormones.

Administration of antimicrobial agents to subjects taking oral contraceptives has been reported to lead to contraceptive failure and subsequent pregnancy. In women taking oral contraceptives antimicrobial agents could have an effect on both endogenous hormone levels and on the metabolism of the exogenously administered steroids. To investigate these possibilities, antimicrobial agents were administered for short periods to normal women taking various steroid drugs: Megestrol acetate (MA), medroxyprogesterone acetate (MPA), norethisterone (NET), a combination of NET and ethinylestradiol (EE) or a combination of lynestrenol and EE. During ampicillin administration the 24-h morning plasma concentrations of MA, MPA and NET were increased compared to the control values. In the MA and MPA experiments the afternoon values were determined and also found to be increased. In the subjects taking oral contraceptives plasma EE concentration showed a tendency to decrease during ampicillin administration on the third, fourth or fifth morning of ampicillin administration, but was never lower than the pretreatment values. In other experiments plasma estrone (E1) and estradiol (E2), urinary total E1, E2 and estriol (E3) and fecal unconjugated and conjugated E1, E2 or E3 were determined by RIA before, during and after administration of oxytetracycline (2 X 500 mg/day for 5 days) to 5 young male subjects. Furthermore urinary and fecal estrogens were determined in 1 male subject after administration of erythromycin for 6 days and in 2 normally menstruating women after tetracycline and trimethoprim administration, respectively. During treatment with antimicrobial drugs an increase in the excretion of fecal conjugated and, with the exception of the oxytetracycline experiments, also of unconjugated estrogens paralleled a decrease in urinary estrogen excretion, especially for E2 and E3. In both urine and feces the E1/E2 and E1 + E2/E3 ratios increased due to diminished reductive metabolism of estrogens in the gut. No significant effects on plasma unconjugated estrogen concentrations were observed. The results suggest that the intestinal bacterial flora plays a significant role in estrogen metabolism. However, further studies are necessary, because our results do not explain why administration of antibiotics may cause contraceptive failure.

Adult↗
PubMed1984

Electrical activity in the human oviduct after the menopause.

Electrical activity was recorded in 18 morphologically normal human oviducts excised from 17 women during hysterectomy. All women were in the first five years after menopause. The first part of the oviduct to become inactive after menopause was the isthmus near the uterus or the ampullary-isthmic junction. The region which exhibited electrical activity last was the ovarian end of the tube. The typical wave-form of electrical activity in post-menopausal oviducts resembled that recorded during the follicular phase in fertile women: a single smooth wave lasting 3-5s. In three cases, over a bulbous swelling of the ampulla, this typical activity was replaced in continuous, high frequency activity. A hypothesis is provided that the observed changes in electrical activity may be related to certain clinical phenomena such as the increased incidence of tubal pregnancy in the pre-menopause.

Electrodes↗