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Biomedical subjects

F Fuchs

Publications and source records attributed to F Fuchs.

At least 91 records · Page 5Linked to original sources

Effect of beta-mimetic tocolysis on cervical ripening and plasma prostaglandin F2 alpha metabolite after endocervical application of prostaglandin E2.

To suppress uterine contractions during cervical ripening induced by prostaglandin E2 (PGE2) gel, beta-mimetic drugs were given orally 30 minutes before PGE2 application to 17 patients with unripe cervix. This prevented the increase in contraction frequency observed during the first four hours after PGE2 application in 17 controls. Nevertheless, cervical ripening proceeded at a similar rate and the clinical outcome was comparable in both groups. Prostaglandin E2 application caused a transient rise in plasma levels of the PGE2 alpha metabolite (13,14-dihydro-15-keto), which was not prevented by pretreatment with beta-mimetics. Patients with premature rupture of the membranes had higher initial plasma PGF2 alpha metabolite levels than those with intact membranes but cervical ripening proceeded with the same rate, and the effect of beta-mimetics was the same in both groups. Thus, cervical ripening induced by PGE2 does not depend on uterine contractions, and increased production of PGF2 alpha is unrelated to the ripening process. There was no difference between the three beta-mimetic agents in the present study.

Adrenergic beta-Agonists↗

Oxytocin receptors in the human uterus during pregnancy and parturition.

We have determined the concentration and distribution of oxytocin receptors in myometrial and decidual tissues obtained at cesarean section or hysterectomy during pregnancy. Myometrial receptor concentration was low at 13 to 17 weeks but had risen about twelvefold by 37 to 41 weeks. After the onset of labor, either preterm or term, the receptor levels were maximal and significantly higher than before the onset of labor. In cases of failed induction of labor with oxytocin and in postterm pregnancies (43 to 46 weeks), the receptor concentration was significantly lower than in spontaneous labor. Myometrial receptor concentrations in the fundus and the corpus were similar and significantly higher than in the lower part of the uterine segment, and the cervix had the lowest concentration. The parietal decidua had oxytocin receptor concentrations of the same magnitude as the myometrium. These results are consistent with a functional role of endogenous oxytocin in the activation of the human uterus during pregnancy and parturition.

Binding, Competitive↗

[Influence of fenoterol, ritodrine and clenbuterol on maternal oxytocin and PGFM levels].

In this investigation, the Oxytocin (OT) and 13, 14-Dihydro-15 Keto PGF 2-alpha (PGFM) levels were investigated in patients who required ripening of the cervix prior to induction of labour. Under randomized conditions four PGE2-Gel-groups and 1 Placebo group was formed. The patients who received PGE2-Gel were treated either with .4 mg PGE2-Gel intercervically without prior treatment with Betamimetica (n = 6) or 30 minutes prior to the application of .4 mg PGE2-Gel intercervically with 5 mb Fenoterol (n = 6) or 10 mg Ritadrine (n = 6) or 20 micrograms Clenbuterol (n = 6). These drugs were given by mouth. A control group of 6 patients received Gel without PGE2 Placebo. In previous investigations, it was shown that the Oxytocin level rises following the intercervical administration of PGE2-Gel to an unripe cervix whereas the PGFM level remains unchanged. Oral administration of Fenoterol inhibited the PG induced rise of the Oxytocin level and kept the Oxytocin level in the same range as following the administration of a Placebo. The present investigation served to check whether Ritadrine and Clenbuterol had an Oxytocin inhibiting effect as well as Fenoterol. It was found that administration of Betamimetica did not inhibit the ripening effect of PGE2-Gel on the cervix. Although labour did not start in 12 of 18 women treated with Betamimetica during four hours, the cervix ripened in the same manner as in women with labour. The administration of Placebo instead of PGE2-Gel showed no ripening effect (P less than 00001). Following the administration of Fenoterol the maternal heart rate increases significantly compared to Placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Clenbuterol↗

[Premature membrane rupture: effect of intracervical PGE2 gel administration on plasma oxytocin, PGFM and PGEM levels in mother and child].

Premature rupture (= PR) of the amnion is a serious complication even for the mature child if it occurs earlier than 24 hours before birth. To keep the interval as short as possible, the authors induce labour from week 35/0 in case of PR, provided the Bishop score is greater than 7. If the bishop score is lower, they conduct intracervical priming of the cervix with 0.4 mg PGE2 gel before induction of labour. This has proved clinically superior to intravenous procedures. In the study presented here, the authors attempted to find out whether intracervical administration of PGE2 gel would result in changes in the maternal and foetal plasma concentrations of oxytocin, PGFM, or PGEM when comparing conditions in case of ruptured amnion with those if the amnion remained intact. If the amnion is intact and the cervix immature (less than 2 cm), intracervical administration of 0.4 mg PGE2 gel produces a significant OT increase within 30 minutes. From a cervical width of 2 cm onwards, the OT levels are already primarily enhanced and will hardly change even after PGE2 gel administration. Similar conditions obtain in PR. PGFM plasma levels will rise only slightly within an hour after intracervical PGE2 gel administration, independent of whether there has been a rupture or not, or whether the cervix is dilated less than 2 cm or 2 cm and more.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Endocrinology of human parturition: a review.

The existing data on the hormonal factors involved in human parturition indicate that the steroid hormones, progesterone and the oestrogens, play only a facilitatory role in the initiation of labour. A definite role for fetal adrenal steroids in this process has yet to be established, and they too may serve only a facilitating function. The stimulation of the uterine muscle during labour results from an interaction of oxytocin and prostaglandin (PG) F2 alpha. Recent evidence suggests that oxytocin is most important for the initial phase of labour, whereas increased synthesis of PGF2 alpha is essential for the progression of labour. The role of PGE2 remains unclear, but this PG may play an important role in the ripening of the cervix which in turn is essential for successful parturition. The finding of maximal oxytocin receptor concentrations in the myometrium in labour adds strong support to the notion that oxytocin is the trigger for uterine contractions. The factors which control oxytocin receptor formation are therefore important; this may be one of the processes where the steroids play a crucial role. Oxytocin is also one of the stimuli that increase uterine PG synthesis; the coupling of oxytocin receptor occupancy and PG synthetase activity in uterine tissues may be another crucial factor in the mechanism of labour. The formation of gap junctions between the myometrial cells also seems essential for the synchronization and progression of myometrial activity. We propose, therefore, that the co-ordinating of oxytocin receptor formation, PG synthesis and gap junction formation is a key to the initiation and maintenance of human labour. The fetus may fulfil such a co-ordinating role through its influence on placental oestrogen production, through mechanical distention of the uterus, and through its secretion of neuro-hypophysial hormones and other stimulators of PG synthesis.

Adrenal Cortex Hormones↗

Oxytocin and initiation of human parturition. III. Plasma concentrations of oxytocin and 13,14-dihydro-15-keto-prostaglandin F2 alpha in spontaneous and oxytocin-induced labor at term.

The plasma concentrations of oxytocin and 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) were measured in serial samples collected during the first stage of spontaneous and oxytocin-induced labor in 17 and 15 women, respectively. Four women in late pregnancy served as control subjects, with serial samples collected at similar intervals as during labor. During spontaneous labor, mean plasma oxytocin levels were consistently raised over the levels observed 1 to 2 weeks before the onset of labor and were higher than the levels in the control patients (mean, 19.9 +/- 3.1 pg/ml) and the initial levels in the oxytocin-induced group of women (mean, 17.4 +/- 4.8 pg/ml). The mean plasma oxytocin levels during spontaneous labor (45 +/- 3.9 pg/ml) were similar to those observed during infusion of 4 to 6 mU/min of synthetic oxytocin (49.1 +/- 10.9 pg/ml). Plasma oxytocin levels increased progressively with stepwise increments of the infusion. Plasma PGFM levels also rose during labor, but, in contrast to the oxytocin levels which increased in early labor, plasma PGFM levels did not increase significantly until relatively late in labor, provided the membranes were intact. The state of the membranes had a marked influence on plasma PGFM; patients with spontaneous rupture of membranes had significantly increased PGFM levels when admitted early in labor or when membranes ruptured during labor. This increase in prostaglandin F2 alpha (PGF2 alpha) production does not by itself suffice to initiate labor, as evidenced by the failure of premature rupture of the membranes to initiate labor in a number of patients with elevated PGFM levels in whom labor was then induced with oxytocin. Conversely, oxytocin induction was successful only when PGFM levels increased during the infusion of oxytocin; in the absence of a rise in plasma PGFM, oxytocin induction failed. These data add support to the view that both oxytocin and PGF2 alpha are required for adequate stimulation of the human uterus during labor. In addition, the data suggest that oxytocin rather than PGF2 alpha may be the major stimulus that initiates labor, whereas PGF2 alpha appears responsible for the progress of labor.

Cervix Uteri↗

Oxytocin and the initiation of human parturition. IV. Plasma concentrations of oxytocin and 13,14-dihydro-15-keto-prostaglandin F2 alpha during induction of labor by artificial rupture of the membranes.

The influence of artificial rupture of the membranes on plasma levels of 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) and oxytocin was examined in 23 pregnant women at term. Serial blood samples were collected before and 15 minutes, 2 hours, 5 hours, and 8 hours after artificial rupture of the membranes. A significant rise in the concentration of plasma PGFM was observed at 15 minutes in the majority of women (20 of 23), but the magnitude of this early rise or the lack thereof was not related to the subsequent course of labor. The concentration of plasma PGFM at 2 hours was, on the other hand, significantly correlated with the induction-delivery interval. Amniotomy, by itself, induced labor and delivery when the increased PGFM levels were maintained from 2 to 5 hours after the procedure (n = 16). In those cases where Pitocin stimulation was required for adequate uterine contractions, it was found that plasma PGFM levels had declined to initial values at 2 hours. Pitocin infusions then partially reversed this decline. In one patient, the cervix failed to dilate in spite of prolonged Pitocin infusion which did not induce significant uterine contractions, and the infusion did not reverse the marked fall in plasma PGFM after the early but transient rise. Mean plasma oxytocin levels did not rise significantly during labor induced by artificial rupture of the membranes and were, on the average, similar to the levels observed during the first stage of spontaneous or oxytocin-induced labor. Considering the previously demonstrated maximal levels of uterine oxytocin receptors in early labor, the absence of a rise in the plasma oxytocin levels does not negate a role for oxytocin in working synergistically with prostaglandins in the mechanism of labor.

Amnion↗

[Effect of ritodrine on prostaglandin production in vivo and in vitro].

In 11 women between the 26th and 36th week of gestation the concentration of 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) was measured serially in the peripheral maternal plasma before and during treatment with ritodrine at a concentration of up to 350 mcg/min. On admission the mean plasma PGFM concentration was 268.0 +/- 43.3 pg/ml, which was significantly higher than the mean PGFM plasma level of the control group (156.0 +/- 21.8; n = 10). Treatment with ritodrine was successful in 7 women and led to a small, but statistically significant decrease in maternal plasma PGFM levels. In unsuccessful treated cases plasma PGFM levels also dropped initially, but increased again at 12 and 24 hours after initiation of therapy. The addition of ritodrine in concentrations of 10(-8) to 10(-6)M to the incubation medium led to a decrease in prostaglandin-(PG-)synthesis in vitro in the decidua and amnion. These changes were, however, only significant for PGE at a concentration of 10(-6)M in decidua and for PGE and PGF in a concentration of 10(-7)M in amnion. In the myometrium no effect of ritodrine on prostaglandin production could be observed. The measurement of PGFM production in the incubation vials indicated that ritodrine has no influence on the conversion of PGF2 alpha to its metabolite in any of these tissues. The results of the present study allow the following conclusions. 1. PGF2 alpha seems to play a role in the mechanism of premature labor. 2. In premature labor patients successful treated with ritodrine a significant decrease in circulating plasma PGFM levels is observed. In vitro ritodrine led to a small, but significant decrease in PGE and PGF synthesis in decidua and amnion which may add to the uterus-relaxing effect of ritodrine.

Amnion↗

[Oxytocin- and prostaglandin plasma concentrations before and after spontaneous labor: evidence of involvement of prostaglandins in the mechanism of placental separation].

The concentrations of oxytocin and PGE, PGF, and 13,14-dihydro-15-keto-PGF2 alpha (PGFM) in maternal peripheral plasma were measured in serial samples taken at full cervical dilatation and 5, 30 and 120 minutes postpartum. The prostanoid levels were also measured in serial samples of umbilical cord blood taken from the placental end in 4 instances. At full dilatation, plasma PGFM, but not PGE and PGF, was significantly raised over control (no labor) values. Just before or at the time of placental separation (5 minutes postpartum), the concentrations of PGF and PGFM were maximal, about twice the level at full dilatation. The level then decreased but at a slower rate than the metabolic clearance rates, indicating that considerable PGF production occurs in decidua and myometrium in the early postpartum period, after fetus, placenta, and the membranes are expelled. The rapid increase in the prostanoid concentrations in the umbilical cord blood draining the placenta after delivery of the infant suggests that the surge of prostaglandins 5 minutes postpartum originates in the placenta, and probably contributes to uterine contraction and placental separation and expulsion. Plasma OT was significantly raised over prelabor values at full cervical dilatation, and during the third stage, but dropped to control levels 30 minutes postpartum. Exogenous oxytocin infusions begun at delivery of the infant caused a marked increase in plasma OT and maintained the PGFM concentrations at a higher level than in the parturients not receiving oxytocin 2 hours postpartum.

Adult↗

Stimulation of myometrial and decidual prostaglandin production by amniotic fluid from term, but not midtrimester pregnancies.

The effect of amniotic fluid obtained from second trimester (16-20 wks) and term pregnancies (38-41 wks) on the production of PGE and F by human amnion, decidua and myometrium at term was determined using tissue slices incubated in vitro. Midpregnancy amniotic fluid neither inhibited nor stimulated the prostanoid production by any of the tissues. In contrast, term amniotic fluid obtained before as well as after the onset of labor markedly increased the production of both PGE and PGF in decidua and myometrium from levels in Krebs solution. The prostanoid production (PGE + PGF) in amnion was not significantly increased but the proportion of PGF was raised during incubations in term amniotic fluid. In decidua and myometrium the increase in PGE and PGF production in term amniotic fluid was approximately 200 and 400 percent respectively, from control values in Krebs solution. We propose that the stimulatory activity in term amniotic fluid is responsible for the accelerated synthesis of prostaglandins after rupture of membranes, which is reflected in raised PGF metabolite levels in maternal circulation. It may also be the reason for the rise in amniotic fluid prostaglandin levels around the 35th week of gestation, and perhaps for the onset of labor.

Amnion↗

Cervical ripening with intracervical prostaglandin-E2 gel. I. Clinical results and effect on plasma levels of oxytocin and 13,14-dihydro,15-ketoprostaglandin-F2 alpha.

Tylose gel containing 400 micrograms prostaglandin E2 in 3 ml gel was injected into the cervical canal of 20 patients with high-risk pregnancy and indication for induction of labor, but with unfavorable cervix. Ten were studied after the first gel application, five during repeat injection, and five after application of gel without PGE2. Blood samples were drawn serially during the first 8 hours for determination of oxytocin and 13,14-dihydro,15-ketoprostaglandin-F2 alpha (PGFM). The PGE2 gel increased the Bishop score within 8 hours in all patients; in half of them, artificial rupture of the membranes could be performed and labor induced without further gel application; in the others, it was repeated every 8 hours until a Bishop score of greater than or equal to 8 was achieved. Fourteen of the 15 PGE2-induced patients delivered vaginally. Mean PGFM levels did not increase significantly during the 8 hours of observation, but in patients who responded with rapid progression, an increase was seen after cervical dilation was 6 cm or more. The mean oxytocin levels increased within 60 minutes after PGE2 application and were increased for the remaining observation period. Application of inactive gel had no effect on cervical ripening nor on oxytocin or PGFM levels.

Adult↗

[Importance of oxytocin sensitivity for the spontaneous onset of human labor].

The significance of oxytocin for the onset of labour in humans is disputed, mainly because there is no increase in oxytocin concentration in the peripheral maternal blood before onset of labour. However, Fuchs et al. have recently shown that the concentration of oxytocin receptors in the myometrium is significantly higher directly before onset of labour than at the onset of spontaneous contractions. To establish a correlation with the clinical sensitivity to oxytocin, the authors determined the oxytocin sensitivity by means of intravenous administration of 3 X 10 m I.U. of oxytocin with continuous tocographic recording. Parallel to this determination, the cervical score was measured according to Bishop. The patients were 26 healthy pregnant women in whom both parameters were determined daily until onset of spontaneous labour pains. The sensitivity to oxytocin increased significantly during the last few days before spontaneous onset of labour. On the day before onset of pains, almost all of the pregnant women showed maximum sensitivity to oxytocin. Parallel to this, the cervical, scores also increased; on the day before onset of labour pains, almost all pregnant women had a cervical score of 5 or more than 5. On the basis of these results, which concur accurately with the results of measurement of oxytocin receptor concentrations, it is definitely possible to refute the arguments that oxytocin is irrelevant for the onset of labour because its concentration in the maternal plasma does not increase before the pains begin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Oxytocin (OT) and 13,14-dihydro-15-keto-PGF2 alpha (PGFM) levels after intracervical administration of PGE2 gel combined with administration of beta mimetics; biochemical changes and clinical consequences].

Intracervical application of 0.4 mg PGE2 gel for achieving maturity of the cervix before necessary inducement of labour results in 1-2% of the cases in permanent contractions in association with foetal bradycardias (Goeschen and Saling, 6). This Complication can be removed by the administration of the beta-mimetic Fenoterol given by the intravenous route. Basing on this fact we tried to find out whether it would be possible to prevent an increase in labour activity by administering Fenoterol before applying PGE2 without impairing the softening effect, and also how the OT and PGFM concentrations in the plasma are affected. To clarify this, we compared the clinical and biochemical results obtained in 5 patients who had been given 5 mg Fenoterol orally before receiving 0.4 mg PGE2 gel, with the results obtained in patients who had been treated without any previous Fenoterol administration with either 0.4 mg PGE2 (n = 10), 0.8 mg PGE2 (n = 6) or placebo gel (n = 5). In all groups treated with the preparation were obtained significant differences compared with the placebo group in respect of maturation of the cervix. Oral administration of Fenoterol did not produce any weaking of the softening effect; an increase of the dose to 0.8 mg did not result in an enhancement. After intracervical administration of 0.4 mg PGE2 gel the PGFM values remained unchanged with and without Fenoterol administration; the same was true also after 0.8 mg PGE2 and after placebo. As with spontaneous labour, a significant PGFM increase was seen only if the cervical diameter had attained 7 cm or more.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Effects of naproxen sodium on menstrual prostaglandins and primary dysmenorrhea.

Prostaglandins E2 and F2 alpha in the menstrual fluid from 12 patients with primary dysmenorrhea were measured by radioimmunoassay (RIA). Each patient was studied for 3 cycles, using vaginal tampons issued for this study. All tampons were collected individually for prostaglandin extraction and RIA. Severity of dysmenorrhea and clinical response to treatment were evaluated by a scoring method and by the patients' self-assessment. Each patient in this double-blind cross-over study had a control cycle and 2 treatment cycles with naproxen sodium tablets (275 mg) or placebo in random order. The treatment regimen was 2 tablets at the first sign of menses followed by one tablet 4 times daily for 3 days. Nine patients obtained good to excellent relief from naproxen sodium, but no relief from the placebo. Two patients had moderate to good response to both naproxen and placebo, and one patient showed no response. Naproxen therapy but not placebo therapy sharply reduced menstrual prostaglandin F2 alpha and prostaglandin E2 release. There was a positive correlation between menstrual prostaglandin levels and the severity of dysmenorrhea. Symptomatically, naproxen sodium was most effective in alleviating severe menstrual cramps but had little effect on mild cramps. It was also effective in ameliorating many but not all of the subjective symptoms such as dizziness, nausea, and vomiting. Relief of dysmenorrhea was apparent within one hour after the initial dose, attained maximum level in 2 hours, and was maintained throughout therapy.

Adult↗

Plasma levels of oxytocin and 13, 14-dihydro-15-keto prostaglandin F2 alpha in preterm labor and the effect of ethanol and ritodrine.

We have measured the concentrations of circulating oxytocin and the 13, 14-dihydro, 15-keto-metabolite of prostaglandin F2 alpha (PGFM) in women during preterm labor. Twelve women were given intravenous ethanol and 11 women received intravenous ritodrine for the prevention of preterm birth. Blood samples were obtained before and 1/2, 1, 2, 4, 12, and/or 24 hours after treatment began. On admission, the plasma concentrations of both oxytocin and PGFM were raised over levels observed in women with normal pregnancies of similar gestational age, 25 to 36 weeks. The initial oxytocin level was 58.5 +/- 8.2 pg/ml (mean +/- SE, n = 23) and the mean initial PGFM level was 264 +/ 33.1 pg/ml (n = 15); both values were significantly higher than in 10 control subjects (17.4 +/- 4.8 and 156 +/- 21.8 pg/ml, respectively). During infusion of ethanol, the plasma oxytocin level fell rapidly, the levels at 1/2 and 1 hour after infusion being significantly lower than before the infusion (29.0 +/- 5.5 and 27.8 +/- 3.5 pg/ml, respectively). The plasma oxytocin level remained low in women in whom the treatment arrested labor and prevented preterm birth (n = 8) but rose 2 to 4 hours after the infusion began in women in whom the treatment failed to arrest labor (n = 4). Ritodrine, on the other hand, had no significant effect on circulating oxytocin levels. The plasma PGFM level decreased significantly during ritodrine treatment only in the successfully treated patients. Ethanol had no consistent effect on plasma PGFM levels in the four patients in whom PGFM levels were measured. In the ritodrine-treated patients, the plasma PGFM level was positively correlated with the frequency of uterine contractions whereas in the ethanol-treated patients a correlation of plasma oxytocin to the frequency of contractions was observed. Thus, oxytocin secretion is increased during preterm labor, and the release of prostaglandin F is also increased. While it is not possible to determine whether any or both of these oxytocic agents actually trigger preterm labor, both seem to play a role in its mechanism.

Dinoprost↗