Biomedical subjects
Publications and source records attributed to M O Pulkkinen.
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).
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.
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.
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.
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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.
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.
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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.
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The administration of ampicillin to three women in the last trimester of pregnancy caused a transient reduction in the plasma concentration of total conjugated estriol and of estriol-16alpha-glucuronide, as measured by a specific radioimmunoassay. Similar changes were seen in plasma conjugated estrone and estradiol levels, but the effect seemed to be more prolonged. In most cases, the reduction in plasma conjugated estrogens was greatest on the second and third day of ampicillin administration, the pattern being similar to that described previously for urinary estriol and other estrogens. There were no obvious differences in the ampicillin effect between the morning and afternoon plasma levels. Ampicillin caused no consistent change in the plasma levels of unconjugated estrone, estradiol, and estriol or in plasma progesterone. These results are discussed with consideration of our present understanding of the effect of ampicillin on the intestinal metabolism and enterohepatic circulation of steroids.
The Prostaglandin-synthesis inhibitor: Naproxen-Sodium (NS) (an analgesic agent) very significantly (P less than 0.001) reduced the "resting" and "active" pressures and the frequency of cyclic uterine activity of 10 dysmenorrheic patients. It also highly significantly reduced (P less than 0.001) menstrual pain. Since these effects were observed after a single oral dose of 1100 mg NS, without side effects or complications, extensive field trials are recommended for assessing therapeutic benefits of this treatment.
On the 30th day of pregnancy, the experimental fetuses in 19 rabbits were injected intraperitoneally with 0.1-1.0 mg progesterone (P). The control fetuses in the contralateral uterine horn were treated with the solvent, sesame oil. Both the experimental and control fetuses were delivered 10 min after treatment by hysterotomy to measure the P concentration of their lung tissue and observe their respiration during the initial 2 h of postnatal life. In comparison with the controls, the experimental newborns had greatly elevated P levels and showed typical respiratory distress syndrome, confirmed by histology.
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Pregnancy had been terminated in 6 normal midtrimester pregnant patients by the extraovular injection of 10 mg prostaglandin F2alpha (PGF2alpha). In these 6 Experimental and 3 Control patients utero-placental blood flow had been measured, by changes in the density of radioactive Indium, distributed over the uterine area, as a function of time. In comparison with Controls utero-placental blood flow decreased in the Experimental patients already at 5 minutes after PG-treatment, long before advanced cyclic IUP evolved. This finding substantiates the conclusion (1-3), based on experiments in animal "models', that decrease in utero-placental blood flow is an early step in the mechanism of PG action.
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