Search

Aims: Prostanoids are indicated in the treatment of peripheral arterial disease (PAD). Available trials suggest that these compounds could reduce the symptoms of intermittent claudication, even though the quality of studies is poor. The present meta-analysis is aimed at verifying the effects of prostanoids on amputation rate and ulcer healing in patients with lower limb PAD., Materials and Methods: The review protocol was published on http://www.crd.york.ac.uk/prospero (CRD42015020258). A comprehensive search for published and unpublished trials comparing iloprost, alprostadil, prostaglandin-E1, epoprostenol, or taprostene with placebo/no therapy on amputation rate in patients with PAD and ulcer healing rate in patients with concomitant foot ulcers. Mantel-Haenzel odds ratio (MH-OR) was calculated with random effect models for the chosen endpoints., Results: A total of 18 trials, enrolling 3,077 and 2,763 patients in the prostanoid and comparator groups, respectively were included in the analysis. Only 11 and 10 of those trials reported data on total and major amputations, respectively. Prostanoids were associated with a significantly lower risk of major (MH-OR [95% confidence interval] was 0.77 [0.63; 0.93], p=0.007), but not total, amputations. Healing rate (available only in 7 trials) was not significantly augmented by prostanoid treatment., Conclusions: Available data are not sufficient to support an extensive use of prostanoids in patients with critical limb ischemia, as an adjunct to revascularization or as an alternative to major amputation in cases which cannot undergo revascularization., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cervical priming with misoprostol has shown to facilitate transcervical procedures and to reduce side-effects. Cervical priming is recommended by several evidence-based guidelines prior to surgical abortion, dilatation and curettage, hysteroscopy and intrauterine device insertion. It is effective in pregnant as well as in non-pregnant women while the results in post-menopausal women are conflicting. Misoprostol is the best suited prostaglandin for a number of reasons: it has a short half-life, few side effects, it is stable at room temperature, it is relatively cheap and the dosage can easily be adjusted according to the clinical need. Various doses, routes, and time intervals between misoprostol application and the intervention have been evaluated. A single dose of 400 microg given sublingually or vaginally 3h before the intervention has given the best efficacy with the least side effects. Higher doses or longer intervals do not improve the effect on the cervix. Pain is a frequent side effect, but usually responds well to NSAIDs. Other side effects are rare.

A case of vasospastic angina pectoris with loss of consciousness, bradycardia and seizures induced by medical abortion following administration of mifepristone and gemeprost is reported. The patient had a history of smoking and migraine, and former treatment with ergot alkaloids or serotonin agonists had also resulted in chest pain and lipothymia. The case underlines the importance of obtaining a detailed history of vasospastic disorders in women referred for medical abortion.

Medical termination of early pregnancy with mifepristone (RU 486) followed by a prostaglandin analogue (Cervagem) is a fairly new abortion method in surgical and gynaecological departments in Denmark. Sixty-two patients were evaluated during the period December 1, 1997 to the June 10, 1998 at Kalundborg hospital. The success rate was 97%. Side effects were rare. The study illustrates the need for strong analgesics in half of the patients. In conclusion RU 486 followed by a prostaglandin analogue provides an efficient and attractive alternative to surgical abortion methods.

The use of gemeprost vaginal pessaries is generally thought to be a method with little complications used for cervical softening within the first two trimesters of pregnancy. Though in our hospital two cases presented with severe cardiovascular reactions, to be attributed to the effect of prostaglandins. The first patient experienced a severe cardiogenic shock due to vasospasm several hours after primary administration of gemeprost vaginal pessaries and a cerebral stroke some hours later. The second patient suffered of a myocardial infarction ensuing from coronary spasm.

The aim of the retrospective analysis is to estimate the results of PGE treatment/or cervical ripening with Bishop score < or = 4--effectiveness and safety. The research includes 60 patients with different induction indications. The comparative analysis has been carried out between 2 groups of patients with premature ruptiere of the ammotic membranes. The first group includes 22 patients treated only with Pg; and the second one includes 18 patients treated only with....

We report a case of acute myocardial infarction which occurred after administration of a synthetic analog of prostaglandin E2 (PGE2) for the voluntary interruption of pregnancy in a 31-year-old woman who had previously been asymptomatic, with myocardial bridging of the left anterior descending artery. The pathogenesis of the severe ischemia causing myocardial infarction and left ventricle aneurysm is quite unclear. The temporal connection is highly indicative of a causal relationship between the pharmacological effects of a synthetic PGE2 analog and coronary spasm responsible for severe ischemia. The hypothesis of endothelial dysfunction proximal to the intramyocardial artery tract and paradoxical vasoconstriction with platelet activation should be taken into consideration. A possible additional effect seems to be a horizontal coronary steal produced by the administration of PGE2 in the myocardium below the intramyocardial artery tract. It cannot be excluded that pharmacological doses of a synthetic analog of PGE2 may have inverted the vasoactive effects of the substance due to direct stimulation on the delivery of constrictive agonist factors.

The authors have examined 48 patients aged 17-70 years with erectile disorders. In 15 cases sexual adaptation was achieved after teaching them autoinjections. Pharmacological aid with PGE1 (Edex, Caverject) proved effective for sexual adaptation of patients with erectile disorders. In case of well adjusted dose and strict compliance of the autoinjection regimen the number of complications was minimal. In 50-70-year-olds PGE1 do not cause systemic complications due to pharmacokinetics and endogenic nature of PGE1. This prostaglandin is highly effective in some forms of psychogenic erectile dysfunction especially in expecting failure. For such patients 1 or 2 autoinjections of minimal dose are enough to correct erection.

The results of a study of 101 consecutive second trimester terminations by Dilatation and Evacuation (D & E) under ultrasound control is presented. All had a Cervagem pessary inserted into the vagina prior to the procedure. The PGE1 analogue was assessed as 'effective' in 97% of patients. Concomitant ultrasound resulted in no patient leaving the operating table with retained products. The high efficacy of the single pessary associated with a low incidence of side-effects makes this combination the method of choice for nearly all second trimester terminations.

In a double-blind, multicentre study 77 patients with benign gastric ulcer were randomly allocated to treatment with either enprostil 35 micrograms bd or pirenzepine 50 mg bd. After four weeks of treatment 13/26 (50 per cent) of evaluable enprostil-treated patients and 9/30 (30 per cent) of evaluable pirenzepine-treated patients were healed. Corresponding healing figures after eight weeks were 20/25 (80 per cent) and 25/31 (81 per cent). Both drugs rapidly reduced the severity of ulcer pain and the need for antacid use. No statistically significant differences were detected between the treatments with respect to healing rate or symptom control. Adverse events were reported by eight patients taking enprostil and by 17 patients taking pirenzepine. Two patients withdrew from each treatment group because of adverse events. None of these was serious. In conclusion, enprostil and pirenzepine were equally effective in healing gastric ulcers and no statistically significant differences in safety and efficacy were detected. There was a tendency for earlier healing and fewer side effects in the enprostil-treated patients.

Motor changes could be involved in the pathogenesis of diarrhoea that complicates the treatment of ulcer disease by prostaglandins. Our aim was to assess the effect of enprostil, a synthetic analogue of PGE2, on duodeno-jejunal motility. During this randomized double-blind crossover study, two manometric recordings, each lasting 20 h (12.00-08.00 hours), were carried out during dosing with 35 micrograms enprostil b.d. or placebo (eight volunteers: part 1), or during dosing with 35 or 70 micrograms enprostil b.d. (nine volunteers: part 2). Subjects were only allowed a standard dinner at 18.00 hours. During fasting, in part 1, the number of phase 3 activity patterns (PIIIs) was higher with enprostil than with placebo (P less than 0.01), without any difference in their characteristics; the overall duration of phase 1 activity was longer with enprostil than with placebo (P less than 0.01). In part 2, during fasting the number and characteristics of the PIIIs were not different, but there was a dose-related increase in PI, and decrease in PII activity. Fed motor patterns did not differ between the two doses of enprostil.

In a double-blind cross-over randomized study adjunct therapy with ranitidine (2 x 150 mg) was compared with enprostil (2 x 35 micrograms) in eight adult cystic fibrosis (CF) patients receiving a fixed dose of enteric-coated microsphere capsules of pancreatin (Pancrease). The study consisted of two consecutive 14-day treatment periods. All patients kept a fixed daily fat intake during the last 5 days of each treatment period and performed 72-h faecal collections during the last 3 days of each treatment period. Gastrointestinal complaints were scored at the end of each treatment period. During treatment with ranitidine there was less faecal fat excretion (18.9% versus 25.1%; NS), less faecal weight (263 versus 303 g/day; NS), and a lower gastrointestinal complaints score (5.3 versus 3.1; P less than 0.05) compared with the treatment with enprostil. One patient dropped out during the treatment period with enprostil because of very severe diarrhoea and abdominal discomfort. We conclude from this study that adjunct therapy with ranitidine has significantly less side effects and may give a better reduction of faecal fat excretion and daily faecal weight in CF.

Enprostil, a synthetic PGE2, has been shown to have an inhibitory effect on gastric acid secretion, a mucoprotective effect and a postprandial lowering effect on gastrin. A double blind randomized study was performed in 80 patients, in order to evaluate the efficacy and safety enprostil (35 mu b.i.d) as compared to cimetidine (400 mg b.i.d) in duodenal ulcer. Healing rates after two, four and six weeks of treatment, as based on endoscopic evaluation, were 35, 72 and 83 p. 100 for enprostil and 45, 73 and 83 p. 100 for cimetidine, respectively. There were no significant differences between treatment groups. The time to relief of nighttime and daytime ulcer pain and antacid consumption were similar in the two groups. The patient's overall subjective assessment was better in the cimetidine group, but this was not confirmed by physicians' opinions. Diarrhea was observed in 7 p. 100 of patients treated by enprostil compared with 5 p. 100 for patients treated by cimetidine. One enprostil treated patient withdrew from the trial prematurely because of abdominal pain. This study demonstrates the efficacy and safety of enprostil in the treatment of active duodenal ulcer at the dosage of 35 micrograms twice daily.

A double-blind, randomized, placebo-controlled study was undertaken to evaluate the efficacy of a single-dose, shelf-stable preparation of prostaglandin E2 gel (PGE2) when used intracervically in patients with low Bishop scores. Two different preparations (0.5 and 0.25 mg) of PGE2 were used and a total of 45 patients were studied. Both preparations of PGE2 demonstrated a statistically significant increase in the spontaneous labor rate as compared with the placebo gel. Bishop scores were altered in all patients not proceeding to labor spontaneously, but the changes were most significant in the low- and high-dose groups. No significant deleterious affects were noted. The efficacy and safety of this new, sterile, and stable preparation makes it suitable for clinical use.

The efficacy of intravenously administered prostaglandin E2 (PGE2) compared to that of intravenously administered 16-phenoxy-17,18,19,20 tetranor prostaglandin E2 methyl sulfonylamide (SHB 286) for termination of fetal death in utero was evaluated in 20 pregnant women from 14 to 38 weeks' gestation. Ten subjects received 1 microgram of PGE2 per minute intravenously. This rate of infusion was doubled at hourly intervals up to 8 microgram per minute. Ten subjects received 0.25 microgram of SHB 286 per minute. This rate of infusion was doubled at hourly intervals up to 2 microgram per minute. It appears that the dosage schedules of PGE2 and SHB 286 were equally effective in inducing labor. Cumulative expulsion rates and mean induction times were similar in both groups. Rates of emesis were low in both groups. Either fever greater than 38.0 degrees C, or shivering, or phlebitis at the site of infusion was observed in three patients treated with PGE2 but in no patient receiving SHB 286.

A double-blind, placebo-controlled, dose-ranging study was undertaken to evaluate the efficacy of two doses of intracervical prostaglandin E2 gel in patients with unfavorable Bishop scores. Mean change in Bishop score, success of softening, time to labor, and time to delivery were all significantly different in the two treatment groups as compared with the placebo group. Twenty-three of 30 treated patients had uterine contractions lasting greater than four hours and eight patients delivered during the observation period. Moreover, one case of uterine hyperactivity and five cases of severe fetal heart rate decelerations were noted in the treatment groups. Although efficacious for cervical ripening, caution is warranted when using this technique in patients at risk for placental insufficiency.

Abortifacient effects of 16,16-dimethyl-trans delta 2-PGE1 methyl ester (ONO-802) were studied clinically. The uterine contractile effect of the agent was compared with those of PGF2 alpha and oxytocin (OXY) in the unanesthetized rabbit. 1. Intermittent intravaginal administration of ONO-802 was applied to 32 cases of legal abortion, 15 of missed abortion and 17 of hydatid mole. Eighty eight, 100 and 81 per cent of these patients resulted in abortion, respectively, with fewer side effects than those of natural PGs. 2. In the five groups of non- or pseudo-pregnant rabbits and those in their 7-9, 14-16 and 19-28 days in pregnancy, uterine contractile effects of these agents were assessed by both the contractile patterns and area of contractile curves of initial 5 minutes. The results are as follows: 1) In the non-pregnant rabbits, all of these agents revealed marked uterine contractile effect. 2) ONO-802 induced uterine contraction characterized by its wedge-shaped curves continued considerably longer than that induced by others. 3) ONO-802 revealed much stronger effect on uterine contraction in 7-9 day-of-pregnant rabbits. 4) Fourteen-16-day-of-pregnant rabbits were least influenced by the three agents as regards their uterine contraction in accordance with the highest progesterone levels in their sera among the three groups of pregnant rabbits.

Report on 114 terminations of pregnancy during the second and third trimester of pregnancy with a new prostaglandin E2 derivative "Sulprostone". In 84 cases legal therapeutic abortions were induced. In 30 women an abnormal pregnancy was terminated. "Sulprostone: is a prostaglandin with selective activity in the uterus. It can be administered parenterally or locally. 48 women received intravenous sulprostone, 35 patients had extraamniotic injections and 31 patients had extra-amniotic injections following an intramuscular injection for priming of the cervix the night before. In 103 women the pregnancy was terminated within the first 24 hours after the administration of sulprostone (90.3%). 8 patients (7.0 %) had a cervical dilatation over 2 cm. In 3 women no effect was noted. In 1 patient the prostaglandin application was stopped because of severe vomiting. The mean administration abortion interval was 12 hours and 54 minutes following extra amniotic application and 10 hours and 30 minutes with extra amniotic application and following intramuscular priming. In 5 patients the abortion was completed after the priming administration. More than 90% of the patient's required analgesia. There were 32.4% side effects of mild character. The results and the methods are described and compared to other methods.

A basic understanding of the physiologic effects of the prostaglandins on the human reproductive system has been one of the diverse scientific interests of Professor Axel Ingelman-Sundberg (19). Although the obvious clinical ultility of these ubiqitous compounds directed early attention to their therapeutic aspects, more recently there has been renewed interest in the basic physiologic mechanisms of the prostaglandins in reproductive medicine. Undoubtedly, the work of Dr Ingelman-Sundberg has stimulated many of his colleagues, students, and fellow scientists to pursue such basic studies in greater details.

Prostaglandin E2 (Sulproston, S) can induce parturition and luteolysis during late pregnancy in the pig. We now tested whether Sulproston is able to interfere with the duration of the pig's estrous cycle. Sulproston was given i.m. in two injections (0.008 mg/kg each) at 12-hour-intervals to ten gilts day 10, to five gilts day 14 and to five gilts day 16 of the estrous cycle. Blood was collected shortly before and up to 48 hrs after the onset of treatment; further daily blood samples were taken from day 0 (1st day of standing heat) to the end of the cycle. Sulproston-administration did not shorten or lengthen the duration of the estrous cycle, nor were plasma-progesterone levels altered when compared to controls. In a second study five gilts received the tenfold amount of S on day 10 of the cycle. A significant decrease in plasma-progesterone (8.52 +/- 2.8 SEM ng, treatment vs. 32.95 +/- 1.86 SEM ng/ml, control) occurred on day 11, which had returned by day 16 to the level of controls (19.22 +/- 6.28 ng/ml vs. 26.75 +/- 2.10 SEM ng/ml, respectively). No alteration in cycle length occurred. Therefore the PGE2-analogue Sulproston - though luteolytic in late pregnancy - is neither luteolytic nor luteotrophic during the estrous cycle of the pig.

Enprostil is a new synthetic prostaglandin E2 with antisecretory and mucosal-protective effects. We compared it with ranitidine in the healing of duodenal ulcer and also examined the subsequent relapse rate. Three hundred thirteen patients were recruited in 15 centers in Europe, of whom 158 were treated with enprostil (E) 35 micrograms twice daily and 155 with ranitidine (R) 150 mg twice daily for up to 6 weeks, using a double-blind method. Patients in both groups were of comparable demography. Healing was significantly quicker with ranitidine. Of patients randomized to treatment, healing (intention-to-treat analysis) at 4 weeks was E 47% and R 69%, and at 6 weeks it was E 66% and R 88%. In patients who met all protocol criteria and completed treatment, healing at 4 weeks was E 58% and R 80%, and at 6 weeks it was E 81% and R 92%. Early relief of pain, both during the day and at night, was significantly quicker with ranitidine. Nausea, diarrhea, vomiting, and abdominal pain occurred more often with enprostil. There were no clinically important abnormalities in hematology or biochemistry. Relapse rates were similar. In conclusion, enprostil is not as effective as ranitidine in healing duodenal ulcers.

The prostaglandin E2 derivative, Sulproston, was administered extra-amniotically for the induction of abortion in an average dosage of 200 microgram, in ten patients. With a success rate of 50%, the subjective side effects were very slight. Temperature, pulse rate, blood pressure and frequently of breathing did not change markedly. The ADP- and collagen-induced platelet aggregation showed a tendency to increase but disaggregation remained the same. Spontaneous platelet aggregation according to Breddin did not change. The parameters examined of the coagulation and fibrinolytic system showed only a slight increase in fibrinolytic activity during and after induction of abortion. The remaining hematological parameters showed no changes.

The cervix-ripening effect of the prostaglandin E analogue 16-phenoxy-tetranor PGE2 methyl- and sulfonylamide, Sulprostone, was examined in 25 primigravidae and 19 women who had earlier been pregnant. Three hours before vacuum aspiration of a 1st trimester conceptus the patients received an i.m. injection of 0.5 mg Sulprostone and the cervical dilatation was assessed under general anesthesia by means of Hegar dilatators immediately prior to vacuum aspiration. In the primigravida group an average cervical dilatation to 7 mm was obtained, compared with 5 mm in a control group. Further dilatation occurred easily in 74% of the patients, compared with 14% in the control group. In the group of previously pregnant women an average cervical dilatation to 8 mm was obtained, compared with 6 mm in the control group. Further dilatation occurred easily in 86% of the patients, compared with 67% in the controls. Routine use of Sulprostone before vacuum aspiration of a 1st trimester conceptus is not recommended because of the rather high frequency of side effects.

Sulprostone, a new synthetic prostaglandin E2 derivative, was used for interruption of pregnancy in 479 patients with different lengths of pregnancy. Systemic forms of administration (i.v. and i.m.) were superior to non-systemic ones (intraamnial, extraamnial). In comparison with prostaglandins used up to now this substance is characterised by a higher rate of success and clearly reduced systemic side effects. As a consequence of these results a new clinical concept of artificial abortion with prostaglandins using sulprostone is presented: 1. i.m. application for induction of early abortion before the 6th week of pregnancy and for softening of the cervix up to the 12th week of pregnancy. 2. i.v. drip of termination of intact and disturbed pregnancies beyond the first trimenon.

In 64 patients with pathological pregnancies (missed abortion, molar pregnancy, intrauterine fetal death, fetal malformation, maternal disease) termination of pregnancy was induced by local application of PGE2 by means of a portio cap and subsequent intramuscular application of Sulproston. In 21 women 1,5 mg and in 43 2,25 mg PGE2 or more were used for cervical priming. In 21 cases expulsion of the fetus could be obtained during or shortly after the priming procedure. In the remaining 43 women Sulproston was administered on the following day with a starting dose of 200 mcg and 100 mcg subsequently at two hours intervals up to a total dose of 500 mcg. With the exception of 3 cases this led to the expulsion of the products of conception. In the remaining 3 patients abortion was obtained on the third day by additional Sulproston-application. The mean expulsion time was 6,3 +/- 2,1 hours, being significantly lower when the fetus was not alive compared to viable pregnancies. Side effects during the priming procedure were only observed in 3 cases; the total rate of side effects was 57,8% and the incidence of use of analgetics 51,5%. The softening effect of locally applied prostaglandins apparently adds in an advantageous manner to the strong contractile effects of Sulproston resulting in shorter expulsion intervals, lower total dosage of prostaglandins and a reduction of the incidence of side effects and the use of analgetics.

A multicentre trial was conducted to compare the efficacy and side-effects of an intramuscularly administered PGE2 analogue and vacuum aspiration in women with a delay of up to 21 days in the expected onset of menses. A total of 473 such women were randomly allocated to treatment with either 16-phenoxy-W-17, 18, 19, 20-tetranor PGE2 methyl sulfonylamide (three intramuscular injections of 0.5 mg at 3-h intervals) or vacuum aspiration, and the outcome of therapy assessed 1, 2 and 6-8 weeks later. Retrospective analysis of hCG levels indicated that 419 (88.6%) women had been pregnant at the time of treatment. With few exceptions, administration of the PGE2 analogue induced vaginal bleeding in both pregnant and non-pregnant women but the duration and subjectively perceived amount of bleeding were greater than after vacuum aspiration. Both treatments were equally effective. In pregnant women the overall frequency of complete abortion was 91% for prostaglandin treatment and 94% for vacuum aspirations. If non-pregnant women were included, the respective success rates (i.e. percentages of women not pregnant 2 weeks after treatment) were 92% and 95%. Gastrointestinal side-effects and lower abdominal pain requiring intramuscular analgesia were more common after prostaglandin therapy than following vacuum aspiration in both pregnant and non-pregnant women.

Termination of pregnancy with prostaglandin E analogues is in general associated with a lower frequency of gastrointestinal side effects than if corresponding F analogues are used. Their clinical use has, however, been limited by stability problems. In the present study the efficacy of different dose schedules of two new stable E analogues for termination of early pregnancy and for preoperative dilatation of the cervical canal was evaluated in 389 women. In early pregnant patients, vaginal administration of 75 mg of 9-deoxo-16, 16-dimethyl-9-methylene PGE2 repeated after six hours or three intramuscular injections of 0.5 mg 16-phenoxy-omega-17, 18, 19, 20-tetranor PGE2 methyl sulfonylamide administered in three-hour intervals resulted in a complete abortion in 94 to 100 per cent of the patients. Both treatments were associated with a low frequency of side effects. The 9-methylene analogue had the advantage of causing less uterine pain than 16-phenoxy-omega-17, 18, 19, 20-tetranor PGE2 methyl sulfonylamide with the dose schedules used. Single vaginal administration of 30 mg of 9-deoxo-16, 16-dimethyl-9-methylene PGE2 and one intramuscular injection of 0.5 mg of the methyl sulfonylamide analogue 12 hours prior to vacuum aspiration were equally effective in dilating the cervix in late first trimester pregnant patients. For both compounds, the frequency of side effects were lower than that previously reported for different PGF analogues administered by non-invasive routes.

In the article are presented the results of a randomized study comparing the efficiency and tolerance of 250 micrograms or 500 micrograms of 16-phenoxy-omega-17, 18,19,20-tetranor-PGE2 methyl sulfonylamide (Sulprostone) as a pretreatment to vacuum aspiration for termination of pregnancy in the 8th to 12th week of gestation. Two-hundred patients, mainly nulliparous, received either 250 micrograms or 500 micrograms Sulprostone intramuscularly three hours prior to vacuum aspiration. The patients were continuously supervised during treatment and during at least three hours after the operation. Side-effects and analgesic injections administered were recorded. At operation the degree of cervical dilatation, amount of blood loss and other operative complications were registered. Both doses of Sulprostone administered three hours prior to vacuum aspiration were equally effective in dilating the cervix and controlling the peroperative blood loss in late first trimester abortion patients. When the dose was doubled from 250 to 500 micrograms, no significant further dilatation of the cervix was achieved. Instead, there was an increase in the frequency of gastro-intestinal side-effects and the need for analgesic injection for relief of painful uterine contractions.

Labor was induced via intravenous infusion of 16-phenoxy-prostaglandin-E2-methylsulphonylamide in 13 cases of missed abortion and 19 cases of intrauterine fetal death. In all cases Bishop score was less than 4. Delivery occurred within 24 hours in all cases, with a minimal frequency of side effects (six cases of erythema above the incannulated vein and 1 case of diarrhea). The interval between the beginning of the infusion and delivery was 9.42 minutes. Uterine curettage was performed in 9 cases.

Sulprostone, a new synthetic prostaglandin E2-derivate has been tested for artificial abortion in 628 women with intact or disturbed pregnancies in all stages of gestation. Compared with other prostaglandins used for this purpose systemic side-effects were low and success-rate was high. Systemic routes of application (constant intravenous drop infusion, intramuscular injection) were evaluted to be more successful and conventient than the local ones (extra- and intraamniotic). Suppositories showed no clinical success. Based on our expereince recommendations for the treatment with sulprostone are given: Intramuscular injections for inducing early abortion or menstrual regulation (less than 6th week of pregnancy) without necessity of curettage and for cervical rpiening (less than 12th week of pregnancy) prior to curettage, constant intravenous drop infusion for induction of abortion in second and third trimester pregnancy.

Forty-eight patients affected with missed abortion, intrauterine fetal death and hydatiform mole were treated with vaginal suppositories containing 1 mg of 16,16-dimethyl-trans-delta 2-PGE1 methyl ester (ONO-802). The patients were divided into two treatment groups. The first, Group A, was given one vaginal suppository every 3 h to a maximum of five suppositories. The product of conception was expelled in 95.8% of patients. In Group B the maximum number of suppositories was reduced to three. The product of conception was expelled in 100% of cases and the average duration of treatment was similar to that for the first group. Although side-effects were mild in both groups, they were reduced in the patients of Group B.

A new prostaglandin analogue, 16,16-dimethyl=trans-delta 2-PGE1 methyl ester (16 me E1) was used for preoperative cervical dilatation in 23 pregnant women who had abortion induced for socio-economical reasons in the first trimester of pregnancy. A single vaginal pessary containing 1 mg 16 me E1 was inserted into the posterior fornix at 3-hour intervals. Thirteen (56.5 per cent) of the 23 patients had complete abortions and two patients (8.7 percent) had incomplete abortions. In six patients (26.1 per cent) the cervix was dilated to at least 10 mm and the remaining two patients (8.7 per cent) required mechanical dilatation at the time of vacuum evacuation. Apart from mild gastrointestinal symptoms, no serious side effects were noted. It is concluded that the new prostaglandin analogue, 16 me E1, could be used safely and effectively for preoperative dilatation of the cervix before surgical abortion in early pregnancy.

Prostaglandins protect against aspirin-induced damage to the gastrointestinal tract. This study tested the ability of enprostil, a synthetic analog of prostaglandin E2, given concurrently to prevent gastroduodenal injury. Twenty-four healthy subjects were randomly assigned to one of three groups. All received aspirin 650 mg q.i.d. for 5 days. One group received placebo and the other groups were given either 7 or 70 micrograms of enprostil b.i.d. for 5 days. Upper endoscopy was performed at entry and 2 h after the final dose of aspirin. Enprostil 70 micrograms b.i.d. afforded significant protection of both the antral and duodenal mucosa. The 7-micrograms dose protected only the antral mucosa. Side effects were not observed with the lower dose of enprostil. Serum salicylate levels did not differ significantly between the groups.

In a randomized, double-bind, parallel, multi-clinic study, the safety and efficacy of enprostil (35 micrograms twice daily) and ranitidine (150 mg twice daily) were compared in the treatment of active gastric ulcer in 93 outpatients (47 enprostil-treated patients and 46 ranitidine). The two treatment groups were well matched for demographic characteristics. The healing rates in the enprostil group were 22, 58, 80, and 86 percent at two, four, six, and eight weeks, respectively. The corresponding rates in the ranitidine group were 22, 66, 84, and 89 percent. None of these differences was statistically significant. The area of the ulcer at baseline and smoking status did not appear to influence healing rates. There were no significant differences between treatment groups in time to relief of ulcer symptoms, frequency of daytime or nighttime ulcer pain, or antacid use. Side effects attributable to enprostil treatment were diarrhea (10 percent versus 6 percent with ranitidine), gastrointestinal pain, and vomiting. These side effects, however, did not influence the patients' assessments of their overall response to enprostil and ranitidine therapy. Six enprostil-treated patients and one ranitidine-treated patient withdrew from the trial prematurely because of adverse experiences. Monitoring of clinical laboratory test results showed no significant changes in the two treatment groups. This study demonstrates that a prostaglandin E2 analogue, enprostil, in a dose of 35 micrograms twice daily, is similarly safe and effective as ranitidine in the treatment of active gastric ulcer.

A newly developed prostaglandin E2 derivative, enprostil (TA/RS-84135), was administered to five healthy volunteers in the stomach and duodenum through a teflon tube to examine its effect on amogastrin-stimulated gastric acid secretion. The acid output 1-3 h after administration of enprostil (35 micrograms) decreased remarkably as compared with that in the same period after placebo administration. However, no significant difference in antisecretory effect was observed between the two routes of administration. A decrease in pepsin output occurred in parallel with the decrease in acid output. These results suggest that the antisecretory effect of enprostil is at least partially due to systemic absorption and the predominantly topical action seen in animals does not seem to occur in man. No side-effects attributable to enprostil were observed during the test period. In conclusion, enprostil seems to be clinically useful as an antiulcer agent.

Rupture of the uterine body was found after induction of therapeutic abortion with vaginal suppositories containing 16, 16-dimethyl prostaglandin E 2 in a 20-year-old primigravida. A short discussion is given on the cervical complications that can occur after prostaglandin induction of abortion, stating that rupture of the uterine body also can be seen. So far, no prostaglandin compound seems to avoid such complications.