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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

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↗
PubMed1979

Plasma progesterone in the respiratory distress syndrome.

Seventeen newborns suffering from RDS (verified by X-ray and clinical parameters) had a mean plasma progesterone of 13.9 +/- 1.2 ng/ml (mean +/- S.E.) at 24h of age. This is only 62% of the normal level (22.6 +/- 1.5 ng/ml).

Humans↗
PubMed1979

The mechanism of prostaglandin action on the pregnant human uterus.

The concentrations of 15 methyl PGF2 alpha, progesterone and estradiol in the peripheral plasma were assayed sequentially and the resting and active pressures of the uterus were quantitated in 10 first trimester pregnant patients, treated with a vaginal suppository containing 3 mg U-36,384. The purpose of the study was to determine the sequence of the prostaglandin induced changes in regulatory profile and uterine function and thus expose further the mechanism of prostaglandin action. The temporal relationships of the changes revealed that the primary action of exogenous prostaglandin is the disruption of the normal endocrine function of the conceptus and that the delayed oxytocic effect of this compound is secondary, a consequence of the primary action. Apparently prostaglandins are only effective as postconceptional agents if they convert the refractory normal pregnant uterus into a reactive organ. The academic and therapeutic significance of this finding is discussed.

Abortifacient Agents↗
PubMed1979

Effect of ibuprofen on menstrual blood prostaglandin levels in dysmenorrheic women.

In a randomized crossover study 15 dysmenorrheic women were treated during two consecutive menstrual period, once with the potent prostaglandin-synthesis inhibitor: ibuprofen and once with an identical looking placebo. Each patient was medicated for 12 hours during the first day of her menstrual flow and was subsequently fitted with a cervical cup for the collection of menstrual blood during three hours. In these samples the concentrations of prostaglandin (PG)F and PGE were measured by radioimmunoassay. The patients receiving placebo had high PGF levels 135 +/- 27 ng/ml (Mean +/- S.E.) which were significnatly reduced by Ibuprofen to 24 +/- 5 ng/ml (P less than 0.001). The PGE concentrations decreased from 5 +/- 1 ng/ml to 2 +/- 1 ng/ml (P less than 0.05). Ibuprofen also reduced the menstrual pain significantly (P less than 0.001). These results substantiate the earlier conclusion that a causal relationship exists between effective treatment with PG-synthesis inhibitors and decrease in menstrual blood PG levels, intrauterine pressure and dysmenorrheic pain.

Adult↗
PubMed1979

The mechanism of prostaglandin action on the early pregnant human uterus.

To extend observations in 11 weeks pregnant patients the mechanism of prostaglandin (PG) action has been examined in 6 weeks pregnant women (LMP). In 10 gravidas menstrual induction was attempted with a single slow release vaginal suppository containing 3000 microgram (155)-methyl PGF2 alpha methyl ester (U-36,384). In 10 additional gravidas menstruation was provoked by the intramuscular injection of 500 microgram 16-phenoxy-omega-tetranor PGE2 methyl sulfonylamide (Sulproston) at 4 hour intervals, totalling 1250 +/- 154 microgram. The PGF2 alpha and PGE2-analogues provoked similar changes in hormone levels and uterine function, sequentially measured by radioimmunoassays and the recording of intrauterine pressure. However, the effects of the intramuscular regimen developed earlier. Both treatments successfully terminated early pregnancy with clinical symptoms of menstruation if they irreversible compromised the conceptus within 12 hours. However, while both formulations represent advances in postconceptional therapy, only further modifications may closely approximate the "ideal" method of non-surgical menstrual induction.

Abortion, Induced↗
PubMed1979

Suppression of uterine activity by prostaglandin synthetase inhibitors.

During hypertonic saline induction, the evolution of intrauterine pressure, the oxytocin response and abortion were delayed in naproxen-treated patients. The PG synthesis inhibitors naproxen, mefenamic acid and ibuprofen decreased the high uterine resting pressure ('tone'), the frequency of contractions but not always the active pressure ('amplitude') in dysmenorrheic patients, with a coincident decrease in pain. The naproxen-sodium treatment decreased prostaglandins F and E in menstrual blood and uterine jet washings by 60--80 per cent.

Abortion, Induced↗
PubMed1978

The effect of ibuprofen on the intrauterine pressure and menstrual pain of dysmenorrheic patients.

In 12 dysmenorrheic patients we examined the therapeutic action of the Prostaglandin-synthesis inhibitor: Ibuprofen, a non-steroidal analgesic agent. Ibuprofen highly significantly reduced the resting pressure (P less than 0.001), active pressure (P less than 0.001) and frequency (P less than 0.05) of cyclic activity of the uterus, as well as menstrual pain (P less than 0.001). Since these effects occurred after a single oral dose of 800 mg Ibuprofen, without side effects or complications, extensive field trials are recommended with this and other PG-synthesis inhibitors, to assess their therapeutic benefits.

Administration, Oral↗
PubMed1978

Pregnancy termination with the PGE2-analogue SHB 286.

A group of 94 volunteers were treated with PGE2-analogue SHB 286 at the 12+1 week of pregnancy. Of the 94 gravidas, 78 received a single extravular dose of 50-200 microgram (Mean +/- S.E. 76 +/- 7 microgram) while 16 a short intravenous infusion of 1000-2000 microgram SHB 286. Despite the single treatment and low dose, the success rate was 69% and the instillation abortion time only 15 +/- 1 hours. At 24 hours after treatment even those gravidas who failed to abort (31%) had sufficient cervical dilatation for curettage and thus could be spared from rapid surgical dilatation. Peripheral plasma progesterone and estradiol-17 beta decreased significantly at 4 hours after treatment in those gravidas who subsequently aborted. After an initial contracture response of the uterus to SHB 286, the cyclic intraterine pressure evolved gradually. In 4 hours it reached significantly higher levels in those gravidas who subsequently aborted than in those who did not.

Abortion, Induced↗