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Biomedical subjects

M Bygdeman

Publications and source records attributed to M Bygdeman.

At least 109 records · Page 6Linked to original sources
PubMed1989

Somatic complications and contraceptive techniques following legal abortion.

The purpose of this study was to establish the frequency of complications following legal abortion at our hospital, and also to examine the use of contraceptives among these patients. All women who requested abortion in the first or second trimester up to week 15 during an 8-month period (n = 1000) were included in the study. The patients were characterized with regard to age, parity, previous abortion, contraceptive technique before and after the abortion, presence of endocervical/urethral Chlamydia trachomatis and frequency and type of somatic complications following the abortion. The overall frequency of complications (infection, bleeding, recurettage) was 5.4%, and 2.7% were readmitted to the hospital. No certain relation between complication rate and gestational length, age or parity was seen, possibly related to selective prostaglandin pretreatment of the cervix and doxycycline treatment of patients with positive cultures for Chlamydia trachomatis. In contrast to previous Scandinavian studies, we found a smaller proportion of young patients, a low percentage of Chlamydial infections, and an unchanged high rate of failure to use contraceptives.

Abortion, Legal↗
PubMed1989

Human fetal mesencephalic tissue grafted to dopamine-denervated striatum of athymic rats: light- and electron-microscopical histochemistry and in vivo chronoamperometric studies.

Human fetal mesencephalic tissue obtained from elective first-trimester abortions was grafted to 6-hydroxydopamine-denervated striatum of athymic (nude) rats. After 3-6 months, the transplants were evaluated by light and electron microscopy using antibodies against tryosine hydroxylase (TH), human specific Thy-1 (Thy-1), 5-hydroxytryptamine (5-HT), and laminin. In vivo chronoamperometric studies of K+-induced release of electroactive species were done prior to the histochemical evaluations. At the light microscopical level, Thy-1-immunoreactivity was evenly distributed throughout the entire transplants. Thy-1-immunoreactive nerve fibers were observed radiating from the graft into the host striatum. In sections that were double-stained with antibodies against Thy-1 and TH, such nerve fibers contained both markers. Also 5-HT-immunoreactive cells were found in the grafts with processes both in the grafts and radiating into host neuropil. Laminin immunohistochemistry showed an even distribution of capillaries in the graft with less density than in host brain, suggesting immaturity of graft tissue. At the ultrastructural level, TH-immunoreactive axons made symmetric contacts with unlabeled dendritic shafts and dendritic spines within the host brain. A few asymmetric contacts with TH-immunoreactive axons were seen. 5-HT-immunoreactive terminals made both symmetric and asymmetric contacts with unlabeled dendritic shafts and spines. In vivo chronoamperometry using local application of K+ revealed average signals that were lower on the transplanted side than in control striatum. However, close to the grafts significant amounts of the K+-evoked signal amplitudes were as large as 1.3 microM, and the ratio of the reduction to oxidation currents suggested release of a mixture of dopamine and 5-HT. Taken together, this study shows that human fetal mesencephalic tissue pieces survive grafting into nude rats, develop normal vascularization, and express coexistence of TH- and Thy-1-immunoreactivity. Human TH- and 5-HT-immunoreactive nerve fibers form synapses in host striatum and release monoamine neurotransmitters.

Animals↗
PubMed1989

Medical approaches to termination of early pregnancy.

Termination of early pregnancy by vacuum aspiration is a well-established technique. The procedure is highly effective and has a low complication rate, particularly when performed during the first few weeks after missed menses. However, this parasurgical method requires skilled health care personnel, and attempts have therefore been made to find medical alternatives. Prostaglandins were the first agents to be used successfully for this purpose, but the high incidence of mainly gastrointestinal side-effects has limited their widespread use. More recently, attention has focused on antiprogestational steroids, i.e., compounds that prevent the action of progesterone either by inhibiting its biosynthesis or by preventing it from binding to the cellular receptors in target organs. Current experience indicates that these compounds, particularly when used in combination with a low dose of a synthetic prostaglandin analogue, have the potential to become a safe, effective, and acceptable medical method for the termination of early pregnancy.

Abortifacient Agents↗
PubMed1988

Development of a vaginal gel containing 9-deoxo-16,16-dimethyl-9-methylene PGE2 for cervical dilatation and pregnancy termination.

A stable hydrophilic gel for vaginal administration containing 9-deoxo-16,16-dimethyl-9-methylene PGE2 (9-methylene PGE2) was developed and its clinical usefulness for preoperative cervical dilatation and for termination of first and second trimester pregnancy evaluated in 521 pregnant patients admitted to the hospital for therapeutic abortion. Following vaginal administration of 3 mg of 9-methylene PGE2 gel a peak plasma level of between 3.5 and 10 ng/ml was found 3 to 6 hours following treatment. The "bioavailability" of the drug was in the order of 25-30%. 9-methylene PGE2 was found to be equally effective as 1 mg Cervagem for preoperative cervical dilatation. With a pretreatment period of 3 hours side effects were rare with both compounds. If the pretreatment period was extended to 12 hours the degree of cervical dilatation, but also the frequency of side effects increased significantly. Repeated administration of 9-methylene PGE2 was found to be effective (96% complete abortion) in terminating very early pregnancy provided the total dose was 10 mg or more. During second trimester the minimum effective dose was 4.5 mg of the compound repeated every fourth hour. The results of the present study have shown that with the new gel formulation the amount of 9-methylene PGE2 needed to terminate first and second trimester pregnancy was approximately ten times less in comparison with the previously used lipid base suppositories. The treatment was also associated with a low frequency of side effects.

16,16-Dimethylprostaglandin E2↗
PubMed1988

Effect of prostaglandins on human sperm function in vitro and seminal adenosine triphosphate content.

The aim of the present study was to evaluate the effect of addition of physiologic amounts of different prostaglandins normally present in semen, on sperm motility, on sperm penetration capacity in cervical mucus in vitro, and on the adenosine triphosphate (ATP) concentration in semen. Semen samples were obtained from volunteers who were attending the fertility outpatient clinic. Sperm motility was measured on a video recorder with a built-in timer, sperm penetration by the Kremer test, and ATP by bioluminescence assay. The addition of 19-hydroxy prostaglandin (PG) E to ejaculates positively stimulated sperm motility and sperm penetration capacity. The opposite effect was observed with 19-hydroxy PGF. PGE1, PGE2, and PGF2 alpha had no effect on either parameter, while PGF1 alpha reduced the sperm motility. The addition of 19-hydroxy PGE to ejaculates increased and the addition of 19-hydroxy PGF reduced semen concentrations of ATP. However, only the last-mentioned effect was statistically significant (P less than 0.05). It is suggested that, in particular, 19-hydroxy PGE and 19-hydroxy PGF are important regulators of sperm motility and that the effect may be mediated via effects on the ATP content in the spermatozoa.

Adenosine Triphosphate↗
PubMed1988

The effects of oral administration of prostaglandin E2 on the human ejaculate.

A single 1 mg dose of prostaglandin (PG) E2 was given orally to 19 men. Ejaculates were obtained 90 minutes and 24 and 48 hours thereafter. Before treatment, each man delivered another three semen samples with the same time intervals as during the study period. PGE2 was also administered to seven men during naproxen treatment and ejaculates were sampled as above. PGE2 did not influence the 90 minutes' posttreatment ejaculates, but after 24 hours there was a significant (P less than 0.05) decrease in sperm counts as compared to the control samples. The change in sperm count was suggested to be due to an effect of PG on the contractile elements in the deferent duct. Sperm motility, viability, and morphology as well as semen volume and adenosine triphosphate (ATP) content remained unchanged. The total semen PGE content was increased 24 hours after treatment from 169 micrograms/ejaculate to 213 micrograms/ejaculate (P = 0.02). In the combined PGE2/naproxen treatment the PGE levels were significantly (P less than 0.05) elevated in the ejaculate 48 hours after treatment. The increase may indicate an increased de novo synthesis of prostaglandins. Based on the results from the analysis of the composition of the 19-hydroxy PGF-isomers with and without naproxen treatment, it is speculated that oral PGE2 influences the cyclo-oxygenase activity.

Administration, Oral↗
PubMed1988

Anti-progesterones for the interruption of pregnancy.

Therapeutic abortion can be performed effectively and safely by vacuum aspiration of the uterus up to 12 weeks of amenorrhoea. Although the operative procedure could be regarded as simple, complications do occur and attempts have been made to develop non-surgical means of terminating pregnancy in the first 3-4 weeks following the first missed menstrual period. A variety of PG analogues have been developed which induce abortion in over 90% of women when given by vaginal pessary or intramuscular injections (see Bygdeman, 1984). In a large multicentre study (WHO, 1987) 0.5 mg sulprostone, administered three times with 3 h intervals, was recently found to be equally as effective as vacuum aspiration for termination of early pregnancy. The frequencies of complete abortion were 91 and 94%, respectively. However, the widespread acceptance of PG treatment is limited by a relatively high incidence of gastrointestinal side-effects and uterine pain. Treatment with antiprogesterones, both mifepristone and epostane, effectively induces abortion during early pregnancy, but the frequency of complete abortion is too low to be clinically acceptable. It remains to be demonstrated if other antiprogesterones such as ZK 98.734 and ZK 98.299, currently under development, may change this conclusion. Administration of mifepristone induces uterine contractions and increases the sensitivity of the myometrium to prostaglandins. These effects allowed the development of sequential treatment with a low dose of mifepristone and PG analogues administered vaginally or intramuscularly. The combined therapy has been shown to be highly effective (frequency of complete abortion between 95 and 100%) and is seemingly associated with a lower frequency of side-effects than if PG analogues are used alone. Whether this medical abortion method will be a realistic alternative to vacuum aspiration during the first 8 weeks of pregnancy depends on the outcome of further clinical trials, including randomized studies comparing the two procedures. It has been shown that mifepristone crosses the placenta (Frydman et al, 1985). An important factor which needs to be verified in future studies is therefore the possible embryotoxicity of this type of compound. The risk that pregnancy continues in spite of treatment can never be excluded.(ABSTRACT TRUNCATED AT 400 WORDS)

Abortifacient Agents↗
PubMed1988

Intracerebral xenografts of human mesencephalic tissue into athymic rats: immunochemical and in vivo electrochemical studies.

Intracerebral allografts of fetal neurons have been studied in both rodents and nonhuman primates. Such research has been directed towards problems in developmental neurobiology and in animal models of neurological diseases. Whether intracerebrally transplanted human fetal neurons are capable of forming synapses and releasing neurotransmitters are key questions in any application of this approach to human brain development and dysfunction. We studied these questions by examining the immunocytochemical and in vivo electrochemical properties of xenografts of human mesencephalic dopaminergic neurons placed into athymic "nude" rats. The transplanted neurons survive, continue to express human-specific Thy-1 immunoreactivity, and extend neuronal processes into the host brain where morphologically identifiable synapses form. Potassium-evoked release of monoamines occurs in the vicinity of the graft but is absent in more remote areas of the host neuropil. These results indicate that human fetal tissue fragments can provide a source of viable neuroblasts for transplantation. Further, synapses form between pre- and postsynaptic elements expressing different species-specific cell surface markers; thus, these markers do not play a determining role in synaptogenesis.

Animals↗
PubMed1988

The effect of RU486 administered during the proliferative and secretory phase of the cycle on the bleeding pattern, hormonal parameters and the endometrium.

Seventeen healthy women aged 24-45 years with regular menstrual periods, proven fertility and not using steroidal contraceptives or IUD were recruited for the study. The volunteers were followed during one control, one treatment and one follow-up cycle. Daily morning urine samples were obtained during the control and the treatment cycle. The samples were analysed with regard to pregnanediol glucuronide (P2-G), oestrone glucuronide (E1-G), oestradiol (E2), progesterone (P4), LH and creatinine. During the entire 3-month study the subjects kept a record of uterine bleeding and side effects. The subjects received 50 mg RU486 daily either on cycle days 7-10 (n = 7) or on cycle days 20-23 (n = 10). An endometrial biopsy was taken on cycle day 10 in the first group and on cycle days 21-28 in the second group of patients. Treatment during the proliferative phase caused significant prolongation of the cycle length due to a delay of the oestrogen and LH surge. However, once the oestrogen concentration started to increase, the remaining part of the cycle was normal. The length of the follow-up cycle was similar to that of the control cycle. The morphology of the endometrium did not differ from control samples taken from untreated women at the same time of the cycle. All ovulating women (n = 9) treated in the mid-luteal phase started to bleed on the 3rd to 4th day of the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Endocrine, seminal and peripheral effects of depot medroxyprogesterone acetate and testosterone enanthate in men.

Depot medroxyprogesterone acetate (D-MPA, 250 mg) and testosterone enanthate (TE, 200 mg) were administered twice with a 4-week interval to nine healthy men, and the levels in blood of steroids, gonadotrophins, lipoproteins, sex hormone binding globulin (SHBG) and prostaglandins (PGs) were measured, as well as steroid levels in semen and the sperm count and motility. The hormones analysed were: MPA, testosterone, androstenedione (A), dihydrotestosterone (DHT), oestradiol (E2), cortisol (C), luteinizing hormone (LH), follicle stimulating hormone (FSH) and the sulphoconjugated forms (-S) of testosterone, DHT, pregnenolone (5-P) and dehydroepiandrosterone (DHEA). Peak values of MPA (10.2 +/- 4.6 nmol/l) and testosterone (28.0 +/- 10.0) were found in the first blood samples 2 days after each injection. Thereafter the levels of MPA decreased gradually and reached the limit of detection 18-20 weeks after the second injection. Blood levels of testosterone fell sharply from the peak values and were grossly subnormal 2 weeks after each injection; levels did not return to pretreatment values during 24 weeks of follow-up. The pattern of change of DHT, A, E2 and sulphonated androgens was similar to that of testosterone. These data suggest that D-MPA and TE are absorbed at similar rates, and that the TE is metabolized rapidly. The subsequent reduction in the levels of A, testosterone-S and DHT-S was less marked and reached pretreatment values earlier than did the testosterone levels. No obvious changes were found in the levels of C, 5-P-S and DHEA-S or in the seminal plasma levels of the various steroids studied. The blood levels of LH and FSH fell precipitously 2 days after the first injection, then started to increase 4 weeks after the second injection to reach pretreatment values 12 weeks later. Of the lipoproteins studied only the levels of HDL-cholesterol and SHBG were found suppressed after treatment. Severe oligozoospermia and the complete absence of progressively motile sperm, in at least one semen sample, was observed in all subjects at 3-7 and at 5-16 weeks, respectively, after the last injection, suggesting that the men were infertile for at least 1 month after treatment. A spurious increase in the PG content of semen was also observed. In spite of the low blood testosterone levels, no subject reported changes in sexual behaviour or other signs of anabolic imbalance during or after the study. However, the increase in levels of E2 in some individuals should be kept in mind as a possible cause of side-effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

The effect of the antiprogestin RU 486 on uterine contractility and sensitivity to prostaglandin and oxytocin.

The effect of RU 486, a steroid acting as an antiprogestin at the receptor level, on uterine contractility and sensitivity to the prostaglandin analogue, 16-phenoxy-PGE2 methyl sulfonylamide (16-phenoxy-PGE2) and to oxytocin was studied in 29 women in early pregnancy. Seven untreated women at the same stage of pregnancy served as controls. In the untreated women no spontaneous uterine contractility was recorded and the response to 0.25 mg 16-phenoxy-PGE2 was characterized by an increase in uterine tonus with superimposed irregular contractions of low amplitude. Treatment with 25 mg RU 486 twice daily resulted in the appearance of regular uterine contractions at 24 h in two out of five patients and in all patients at 36, 48 and 72 h after the start of RU 486 treatment. The withdrawal of progesterone influence changed the inactive early pregnant uterus into an active organ. Administration of 16-phenoxy-PGE2 caused an obvious stimulation of both frequency and amplitude of the contractions. In addition, the significantly increased sensitivity to the prostaglandin analogue, but not to oxytocin, was already apparent 24 h after the start of RU 486 treatment. We have previously shown that the addition of one intramuscular injection of 16-phenoxy-PGE2 on the fourth day of treatment with RU 486 (25 mg twice daily) significantly increased the abortifacient effect of the antiprogestin during early pregnancy. The present study suggests that a shorter treatment may be possible.

Abortion, Therapeutic↗
PubMed1988

Obstetric pain medication and eventual adult amphetamine addiction in offspring.

Our purpose was to investigate whether obstetric analgesia, particularly by nitrous oxide, constitutes a risk that the infant might develop amphetamine addiction in later life. Of 200 current amphetamine addicts born between 1945 and 1966 in Stockholm, proportionately more were born at hospitals where pain medication had been administered in large doses (p less than 0.05). A blind matched comparison was made between 73 addicts and 109 non-addicted siblings by logistic regression, in which nitrous oxide administration was tested in competition with 12 other natal variables as possible confounders. The risk for amphetamine drug addiction in offspring was found to increase with duration of intermittent administration of pure nitrous oxide, i.e. it was estimated to be 5.6 times greater (95% confidence intervals 1.6-16.9, p = 0.005) when nitrous oxide had been given for greater than or equal to 4.5 h vis-à-vis less than or equal to 0.25 h. Calculated risks are probably underestimates. Results can be explained as an effect of imprinting. It is concluded that local or regional anesthesia are preferable to general anesthesia which allows substantial amounts of drugs to cross the placenta.

Adult↗
PubMed1988

Physiological and biochemical implications of prostaglandins from the perspective of developing safer first and second-trimester obstetrics.

Hungary has experienced one of the highest prematurity rate of the world due to the large number of induced abortions carried out by rapid mechanical dilation of the cervix during the last three decades. With the pioneering work of Professor Sune Bergström in the identification and isolation of the primary, naturally occurring prostaglandins and in elucidating their chemical structure, it became possible also in Hungary to start research with the help of the Swedish investigators and WHO assistance on the clinical application of PGs. Recently growing understanding of cervical physiology promotes their use for cervical dilatation and for pharmacological uterine stimulation which is especially important in Hungary from the perspective of changing the recent situation, i.e. preventing cervical incompetence and subsequent "short-gestations" in future pregnancies. The physiologic importance of the development of the PG-analogues with slowed-down metabolic degradation is outlined here. The implications of the PGs in cervical ripening is reviewed, and the role of the cervix,--as an endocrine gland, playing a biochemically preprogrammed role in controlling a wide array of physiological processes throughout human gestation--, is discussed.

Abortion, Induced↗