Selective induction of labour following administration of an oral prostaglandin E2 0.5 mg tablet hourly

Induction of labour was performed on 20 patients with favourable induction features by amniotomy and administration of a fixed dose of 0.5 mg of prostaglandin E₂ (PGE₂) hourly. Effective uterine action resulted in a mean time to delivery of 6 hrs 57 mins in primagravid patients and 4 hrs 40 mins in multigravid subjects. In two patients an intravenous oxytocin infusion was used to assist labour. There were no significant maternal or fetal side effects.     

Experience with prostaglandin F2α (free acid) for the induction of labour

Labour was induced or augmented in 115 patients by amniotomy followed by intravenously administered prostaglandin F_2α (PGF_2α). The results were compared to those obtained retrospectively from a similar number of patients, matched for age, parity, induced and augmented labour, epidural anaesthesia and induction score; in whom labour had been induced by amniotomy followed by intravenous oxytocin titration. Both regimes were very effective, but there was a higher incidence of side effects in the patients receiving oxytocin. There was one maternal death associated with Prostaglandin infusion. Labour was also induced in a further group of 50 patients by amniotomy followed by oral PGF_2α (free acid). 42 patients (84%) were successfully induced. Vomiting and diarrhoea occurred in 22 patients (45%).     

Induction of Labour by Simultaneous Intravenous Administration of Prostaglandin E2 and Oxytocin

In a group of 20 matched primigravid patients labour was induced by forewater amniotomy followed by intravenous oxytocin (Syntocinon) administered in escalating doses. Ten of these patients, in a double-blind trial, also received prostaglandin E₂ infused simultaneously with the oxytocin. In the combined prostaglandin-oxytocin group there was a noticeable reduction in the dosage of oxytocin required to produce effective uterine action, and the duration of labour was also reduced. No side effects were observed.     

Amniotomy and Oral Prostaglandin E2 Titration for Induction of Labour

The efficacy of oral prostaglandin E₂ used on a titration basis in association with amniotomy for the induction of labour was investigated in a series of 50 patients. Induction was successful in 29 out of 32 primigravid and 17 out of 18 multigravid patients. The mean induction-delivery intervals in successful cases were 10½ and 6 hours respectively. There were no significant effects on the fetuses.     

The PGE2 vaginal film: An alternative to conventional induction in multiparae with poor cervical scores

In a study involving 50 multiparous subjects with poor cervical scores (⪕3), induction of labour by conventional amniotomy and oxytocin was compared with preinduction cervical ripening using a single administration of prostaglandin E₂ (850ug) in a new vaginal film formulation. Indications for elective delivery, maternal characteristics and distribution of cervical scores in the two groups were similar. Significant changes in mean cervical score were achieved within 12 hours of film insertion. In this group, 11 subjects (45.8%) established labour within 12 hours and a further 8(33.3%) did so before 24 hours so that only 5 cases required amniotomy and oxytocin. Instrumental delivery was less in this group and none of these subjects required Caesarean section for a failure of induction. No adverse maternal or fetal side effects were observed. Convenience, ease of administration and stability of this new prostaglandin formulation make it a useful alternative to conventional induction of labour in the multiparous patient with a poor cervical score.     

Uterine Hypertonus during Labour Induced by Prostaglandins

Labour was induced successfully at or near term in 34 out of 35 cases by combined amniotomy and intravenous infusion of either prostaglandins F₂α, E₂, or E₁. Of particular importance is the finding of hypertonus in 4 of the 18 cases induced with prostaglandin E₂.     

Single shot prostaglandin gel for labor induction

A viscous suspension of prostaglandin E₂ was introduced endocervically to induce labor in patients with favourable induction features. The method was found to be effective and compared favourably with the conventional practices of amniotomy and intravenous oxytocin infusion or oral prostaglandin therapy. Several advantages were found including a high degree of patient acceptability.     

Oral Prostaglandins in the Induction of Labour

Prostaglandins E₂ and F₂α were administered by mouth to induce labour in 24 patients at or past term. The drugs were administered at two-hourly intervals in doses ranging from 0·5 to 1·5 mg for prostaglandin E₂ and from 5 to 15 mg for prostaglandin F₂α. Of the 10 cases in which prostaglandin E₂ was used, labour was successfully induced in eight and there were no side effects. With prostaglandin F₂α labour was induced in 12 of 14 patients nine of whom had gastrointestinal disturbance, mostly of mild degree. With both drugs the infant was apparently unaffected and Apgar scores were satisfactory. Uterine hypertonus was not observed and the postpartum blood loss was within normal limits.     

Oral Administration of Prostaglandins for the Induction of Labour

Prostaglandins E₂ and F₂α administered by mouth were used to induce labour in 100 patients between 35 and 44 weeks of gestation. The usual effective dose of prostaglandin E₂ was 0·5 and of F₂α 5 mg. These were repeated every two hours until labour was established. Induction was successful in 79 out of 80 women treated with oral prostaglandin E₂ and in 16 out of 20 women treated with F₂α     

Prospective study of different methods and routes of administration of prostaglandin E2 to improve the unripe cervix

Methods of vaginal and extra-amniotic prostaglandin administration to achieve ripening of the cervix as a preliminary to induction of labour are described. Three groups of twenty patients with unfavourable induction features were studied, each receiving prostaglandin E₂ the evening prior to planned induction. One group received PGE₂ 500 μg suspended in a viscous medium extra-amniotically. One group received PGE₂ 3 mg suspended in a viscous medium into the vaginal vault. A third group received a 3 mg PGE₂ vaginal pessary to the posterior fornix. Improvement in cervical status at time of induction occurred in all groups but no single group had a significant advantage when regarding mean improvement, the induction-delivery interval or the number of patients in whom labour began before formal induction. However, with regard to relative cost, ease of preparation and storage, as well as patient and medical staff convenience, Prostaglandin E₂ in pessary form is a superior form of administration.     

Radioimmunoassay of 15-keto-prostaglandin E2 in peripheral plasma after oral administration of prostaglandin E2 tablets used for induction of labour

A radioimmunoassay of the 15-keto-metabolite of prostaglandin E₂ has been developed. The details of the assay are described. Using unextracted plama, serial measurements of 15-keto-PGE₂ have been carried out every 15 minutes for 3 hours in 9 women ingesting 0.5 mg PGE₂ oral tablets used for the induction of labour.     

Inhibitory effect of prostaglandin E2 on noradrenaline secretion from sympathetic nerves as a function of external calcium

The calcium dependence of the inhibitory effect of prostaglandin E₂ on sympathetic neurotransmitter secretion was studied in isolated superfused field stimulated guinea-pig vas deferens, by determination of the nerve stimulation induced rise in efflux of total tritium after preincubation of the tissue with tritium-labelled 1-noradrenaline. Reuptake of noradrenaline was blocked by desipramine and normetanephrine, added to the medium. Reduction of the calcium in the superfusion medium strongly depressed the nerve stimulation induced rise in efflux of tritium. Addition of the alpha-adrenoceptor blocking drug phentolamine markedly raised the efflux of tritium on nerve stimulation, even at low calcium. The inhibitory effect of prostaglandin E₂ on nerve stimulation induced rise in efflux of tritium was inversely related to the calcium concentration. The results are consistent with the possibility that prostaglandin E₂ depresses neural secretion by facilitating efflux of intraaxonal calcium.     

The mechanisms of preterm labour; the interaction between amnion cells and leukocytes in the metabolism of arachidonic acid

Chorioamnionitis is frequently associated with preterm labour. We have used a cell culture model system to examine the effects of leukocytes upon the metabolism of endogenous arachidonic acid from within amnion cells. We have demonstrated that activated leukocytes release substances which increase the overall release and metabolism of endogenous arachidonic acid within amnion cells causing an increase in prostaglandin E₂ production as well as a smaller increase in non-cyclooxygenase metabolism. When amnion cells and leukocytes are cultured together, in addition to prostaglandin E₂ production by amnion cells, arachidonic acid released by the amnion cells appears to be metabolised by leucocytes to prostaglandin F_2α, prostacyclin and thromboxane A₂. Prostaglandins E₂ and F_2α are the principal cyclo-oxygenase products of this interaction.We postulate that chorioamnionitis stimulates preterm labour not only by causing an increase in prostaglandin E2 synthesis by amnion cells but by metabolism of amnion derived arachidonic acid to the powerfully oxytocic prostaglandin F_2α by leukocytes.     

The antihypertensive action of arachidonic acid in the spontaneous hypertensive rat and its antagonism by anti-inflammatory agents

Changes in arterial blood pressure and heart rate were observed in the spontaneous hypertensive (SH) rat following the intravenous administration of arachidonic acid, the precursor of prostaglandin E₂ (PGE₂). The pronounced fall in blood pressure and the increase in heart rate induced by arachidonic acid were also observed in SH rats receiving either prostaglandin E₁ (PGE₁) or PGE₂. In SH rats receiving various anti-inflammatory agents the cardiovascular responses to arachidonic acid were inhibited, but the blood pressure responses to the E-type prostaglandins were not altered. The data are interpreted to suggest that cardiovascular changes induced by arachidonic acid are mediated via its conversion to PGE₂.     

Beneficial effects of prostaglandin E2 in endotoxic shock are unrelated to effects on PAF-acether synthesis

The effects of endotoxic shock on the synthesis of PAF-acether by the stomach, duodenum and lung were examined in the rat. Furthermore, the effect of pretreatment with prostaglandin E₂ on endotoxin induced PAF-acether synthesis and changes in vascular permeability were examined. Administration of endotoxin resulted in significant increases in PAF-acether synthesis in all tissues studied. Such increases were apparent within 5–15 minutes of the administration of endotoxin, corresponding to the time when significant hypotension, hemoconcentration and increases in gastrointestinal vascular permeability were first observed. Pretreatment with prostaglandin E₂ resulted in a significant reduction of endotoxin-induced hypotension, hemoconcentration and changes in vascular permeability in the gastrointestinal tract. However, prostaglandin pretreatment did not significantly alter endotoxin-induced PAF-acether release from the gastrointestinal tissues studied. These results demonstrate that prostaglandin E₂ can significantly attenuate several of the systemic and gastrointestinal manifestations of endotoxic shock. The mechanism responsible for these beneficial actions appears to be unrelated to effects of prostaglandin E₂ on PAF-acether synthesis.     

Absorption of prostaglandin E2 and uterine sensitivity of the non-pregnant and pregnant monkey in vivo

Radioactive (11-³H) prostaglandin E₂(PGE₂) levels in plasma of non-pregnant Rhesus and Japanese monkeys were determined by radioimmunoassay. The amounts of PGE₂ in plasma increased gradually and reached a peak 90 minutes after oral administration. Comparatively low levels were detected 24 hours after oral administration. Plasma PGE₂ levels increased rapidly and disappeared within 5 minutes when 5 μg/kg of PGE₂ was administered intravenously.Uterine contractile sensitivity to PGE₂ and F_2α was measured by the threshold of a venous dosage required to evoke an elevation of uterine contractility in non-pregnant and pre- and post-labor Japanese monkeys. Uterine sensitivity to PGE₂ in the non-pregnant monkey appear to vary in accordance with the sexual life span. At term of pregnancy, PGE₂ was much more potent in causing uterine contraction than PGF_2α. During labor and at postpartum period with lactation, effectiveness of PGE₂ appear to be less than that of PGF_2α. The non-pregnant and pregnant uterus of the third trimester are more sensitive to PGE₂ than the laboring and postpartum uterus.The long latency of the elevation of uterine contractility induced by the intravenous administration of PG suggests that the PG compounds have potent actions on the central nervous system.     

Mechanism of increased renal prostaglandin E2 in uranyl nitrate-induced acute renal failure

We have previously demonstrated that decreased cortical prostaglandin metabolism can contribute significantly to an increase in renal tissue levels and activity of prostaglandin E₂ in bilateral ureteral obstruction, a model of acute renal failure. In the present study, we have further investigated whether alterations in prostaglandin metabolism can occur in a nephrotoxic model of acute renal failure. Prostaglandin synthesis, prostaglandin E₂ metabolism (measured as both prostaglandin E₂-9-ketoreductase and prostaglandin E₂-15-hydroxydehydrogenase activity), and tissue concentration of prostaglandin E₂ were determined in rabbit kidneys following an intravenous administration of uranyl nitrate (5 mg/kg). No changes in the rates of cortical microsomal prostaglandin E₂ and prostaglandin F_2α synthesis were noted at the end of 1 and 3 days, while medullary synthesis of prostaglandin E₂ fell by 47% after 1 day and 43% after 3 days. Cortical cytosolic prostaglandin E₂-9-ketoreductase activity was found to be decreased by 36% and 76% after 1 and 3 days respectively. No significant changes were noted in cortical cytosolic prostaglandin E₂-15-hydroxydehydrogenase activity after 3 days. Cortical tissue levels of prostaglandin E₂ increased by 500% at the end of 3 days. These data demonstrate that in nephrotoxic acute renal failure, decreased prostaglandin metabolism (i.e., prostaglandin E₂-9-ketoreductase activity) can result in increased tissue levels of prostaglandin E₂ in the absence of increased prostaglandin synthesis and suggest that alterations in prostaglandin metabolism may be an important regulator of prostaglandin activity in acute renal failure.     

Prostaglandin E2 Compared with Oxytocin for the Induction of Labour

A comparison has been made between the effectiveness of infusing prostaglandin E₂ with Syntocinon for the induction of labour in the presence of intact membranes. Rapid titration schedules were used to induce an early uterine response. All 15 subjects receiving prostaglandin E₂ achieved cervical dilatation, whereas this occurred in only 9 out of 15 patients receiving Syntocinon.     

Light activation of fructose bisphosphatase in photosynthetically competent pea chloroplasts.

The ipsilateral kidney was removed from a rabbit 48h after unilateral partial renal-vein-constriction and was perfused with Krebs–Henseleit media at 37°C. Hourly administration of a fixed dose of bradykinin to the renal-vein-constricted kidney demonstrated a marked time-dependent increase in the release of bioassayable prostaglandin E₂ and thromboxane A₂ into the venous effluent as compared with the response of the contralateral control kidney. The renal-vein-constricted kidney produced up to 60 times more prostaglandin E₂ in response to bradykinin after 6h of perfusion as compared with the contralateral kidney; thromboxane A₂ was not demonstratable in the contralateral kidney. Inhibition of protein synthesis de novo in the perfused renal-vein-constricted kidney with cycloheximide lessened the hormone-stimulated increase in prostaglandin E₂ by 94% and in thromboxane A₂ by 90% at 6h of perfusion. Covalent acetylation of the renal cyclo-oxygenase by prior oral administration of aspirin to the rabbit inhibited initial bradykinin-stimulated prostaglandin E₂ biosynthesis 71% at 1h of perfusion. However, there was total recovery from aspirin in the renal-vein-constricted kidney by 2h of perfusion after bradykinin stimulation. Total cyclo-oxygenase activity as measured by [¹⁴C]arachidonate metabolism to labelled prostaglandins by renal cortical and renal medullary microsomal fractions prepared from 6h-perfused kidneys demonstrated that renal-vein-constricted kidney-cortical cyclo-oxygenase activity was significantly greater than the contralateral-kidney-cortical conversion, whereas medullary arachidonate metabolism was comparable in both the renal-vein-constricted kidney and contralateral kidney. These data suggest that perfusion of a renal-vein-constricted kidney initiates a time-dependent induction of synthesis of prostaglandin-producing enzymes, which appear to be primarily localized in the renal cortex. The presence of the synthetic capacity to generate very potent vasodilator and vasoconstrictor prostaglandins in the renal cortex suggests that these substances could mediate or modulate changes in renal vascular resistance in pathological states.     

The use of oral prostaglandin E2 in the management of intrauterine fetal death

12 otherwise healthy patients with intrauterine fetal death 1 to 6 weeks earlier were treated with oral prostaglandin E₂. 9 of the 12 patients delivered within 48 hours after treatment began. 2 others delivered within 48 hours after unsuccessful treatment ceased. In a third patient the cervix relaxed after treatment, and the uterine contents were removed by curettage. No serious complications, such as hemorrhage occurred. The uterus seemed surprisingly responsive to oral prostaglandin E₂ in cases of intrauterine fetal death.