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12 Gutsche BB. Lumbar epidural analgesia in obstetrics: taps and patches. In: Reynolds F, ed.Epiduralandspinalblockadein obstetrics. London: Bailliere Tindall, 1990:95-106.13 WoolfCJ. Recentadvancesin thepathophysiologyofpain. Br7Anaesth 1989;63:139-46.14 Edelman JD, Wingard DW. Subdural hematomas after lumbar dural puncture. Anesthesiology

The development of the antiprogestin RU-486, and its current use in France and the UK, potential other application, politics in the US, and future are presented. Ru-486, as commonly known by its company code name, rather than its generic name mifepristone, is an analogue of a progestin used in oral contraceptives, with an added chemical group that allows it to link up with the progesterone receptor, but prevents progesterone's effects. It was approved in France in 1988, and has been used for early abortion up to 7 weeks LMP on 80,000 women. French women, after an initial diagnostic appointment, take 3 200 mg tablets of RU-486, then 36-48 hr later return for a Sulprostone (prostaglandin) injection, and are checked up 4-6 weeks later. About 96% abort completely. Some have nausea, vomiting, or pain. Bleeding averages 9 days, and 1% require treatment for bleeding. 2 cardiovascular events and 1 heart attack have been associated with the prostaglandin, now contraindicated in smokers or women 35. In England, RU-486 abortions began in late 1991, for pregnancies up to 9 weeks, using a gentler prostaglandin, Gemeprost, in a vaginal suppository. Only company-trained doctors may order the drug. Research continues on lower doses of RU-486, other prostaglandins, and effects on the fetus if abortion fails. While there is no known basis for a teratogenic effect of the antiprogestin, strong uterine contractions brought on by prostaglandins, such as misoprostol, as abused for illegal abortion in Latin America, may cause birth defects. RU-486 is expected to be useful for inducing labor, dilating the cervix, emergency contraception, pre-surgical management of Cushing's syndrome, brain cancers with profesterone receptors, among other conditions. Several of the 400 or so antiprogestins known are being tested clinically, notably HRP 2000 by WHO. Political controversy is so intense in the US that Roussel, the maker of RU-486, has no intention of marketing it, and even research supplies are unreliable. Meanwhile, pro-choice groups are innovating ways to test and market antiprogestins legally, perhaps inside state lines. It is expected that a suitable prostaglandin, misoprostol, licensed for peptic ulcer, will be available soon, and even RU-486 will become generic by 1998 when its patent expires.

PIP: This is a general coverage of the entire topic of PGs (prostaglandins). It includes an extensive literature review. The history, nomenclature, biosynthesis, analytical methods of detection, stability, metabolism, pharmacodynamic effects, and clinical uses of PGs are discussed. The discussion of PG biosynthesis is illustrated with chemical structure diagrams showing the progression from prostanoic acid, the parent 20-carbon acid, to various PG analogs. Since natural PGs under both basic and acidic conditions are generally unstable, chemists encounter problems in synthesizing them and physical pharmacists in developing chemically stable dosage forms. The main clinical use for PGs is to induce abortions and labor. PGs also have powerful gastrointestinal, bronchoconstrictive, and antihypertensive properties.

Available published material of adverse reactions to prostaglandins (PGs) at various dosages routes and levels is reviewed. Animal studies are of 2 kinds: studies of pharmacological effects and studies of toxicological reactions (i.e., acute dose levels). The pharmacology of PGs show the drugs have 3 areas of action: 1) smooth muscle effects, either contraction or relaxation (cardiovascular effects and reproductive tract; relaxation of vascular smooth muscles by some PGs and contraction by others); 2) nervous system effects; and 3) lipid and carbohydrate metabolism. In humans, PGE1 was administered intravenously and it was found that adverse effects were related to rate of administration rather than to total dose; side effects included flushing, headache, visual disturbances, and restlessness, factors which might suggest a correlation with central nervous system effects (as found in animal studies). PGE1 administered at acute doses orally, by inhalation, and intradermally show effects attributable to gastrointestinal disturbances, respiratory problems, and erythematous responses. In general, studies in humans of other PGs have found similar adverse reactions, all of which are explained by known mechanisms of action of PGs. Dose levels constituting acutity are dependent on route (i.e., oral doses are much higher than intravenous doses), with rapid intravenous infusion causing the most adverse reactions.

This paper reports the conformation energy (CE) calculations on three forms of prostaglandins (PGs) PGA1, PGB1 and PGE1 on the basis of the empirical potential energy functions, for the simultaneous rotations around C7–C8 (θ), C12–C13 (β) and C14–C15 (β) bonds [Fig. 1(a)]. The isoenergy contours plotted for θβ rotations for the different β values show the existence of two low energy regions for thg equal to about 90° and 240° in all the three cases. The absolute minimum was obtained for thg = 240° and almost coincided with the crystallographic conformation for PGE1 and PGA1. In the case of PGB1 series of low energy conformations were obtained with the thg values equal to about 90° and 270°, but none of them coincided with the observed crystallographic conformation. The paper discusses the comparison of the different low energy conformations in these three molecules, their biological relevance and the cause of disagreement in the case of PGB1 with the crystallographic data.

Geschlechtsreife weibliche Cynomolgus-Affen (Macaca fascicularis) wurden aktiv gegen das schwangerschaftsspezifischeβ 1-Glykoprotein (SP1) des Menschen immunisiert. Als Antigene sind natives SP1 und chemisch modifizierte Derivate dieses Proteins verwendet worden. Anschliesend ist die Wirkung dieser Immunisierung auf die Fortpflanzungsfahigkeit der Tiere untersucht worden. Bei den immunisierten Affen wurde eine signifikante Reduktion der Fertilitat festgestellt. Die Konzeptionsrate war im Vergleich zu den Kontrollen nur wenig verringert; aber ein groser Teil der Schwangerschaften bei den immunisierten Tieren endete mit einem Abort. Eine Immunisierung des Menschen gegen das schwangerschafts-spezifischeβ 1-Glykoprotein konnte moglicherweise fur eine immunologische Kontrazeption von Bedeutung werden.

A series of 3,5-diaryl-s-triazoles were synthesized and evaluated as postimplantation contragestational agents. The introduction of various substituents (e.g., an o-alkyl chain on one phenyl and a m-alkoxy group on the other) was found to increase the potency. Several compounds with very high pregnancy-terminating activity in both hamsters and rats were obtained. One of these, 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-s-triazole, DL 111 (36), was selected for detailed evaluation in various animal species. A synthetic scheme for the preparation of these compounds and preliminary structure-activity relationships are presented.

Extra-amniotic ethacridine lactate plus intramuscular prostaglandin has become a popular method for terminating second trimester pregnancies. In this study, intrauterine pressure was continuously monitored in order to objectively compare the efficacy of 3 different times of administration of Carboprost (15-methyl PGF2 alpha) - at 2 hours, 4 hours and 8 hours after the instillation of ethacridine lactate. The best results were obtained with the administration of Carboprost 8 hours after the instillation of the extra-amniotic ethacridine lactate. The synergistic effect of ethacridine lactate and Carboprost is optimal after this time. This is probably because the ethacridine lactate will have produced sufficient cervical ripening to ensure optimal efficacy of the prostaglandin-induced uterine contractions in expelling the products of conception.

Plasma levels of 15(S)15-methyl PGF2alpha were measured by gas chromatography - mass spectrometry following intravenous, intramuscular and subcutaneous administration. During intravenous infusion of 1.0 and 2.5 microgram/min of the drug for six hours the plasma levels were relatively constant around 600 and 1200 picog/ml, respectively. At an infusion rate of 5 microgram/min the plasma level continuously increased during the administration. Intramuscular injections of 100-400 microgram of 15(S)15-methyl PGF2alpha gave maximum levels in plasma (700-1700 picog/ml) after 15-20 minutes followed by a gradual decrease during more than three hours. This rapid resorption of drug into plasma could be delayed by addition of 5 microgram epinephrine to the injected solution. Analyses during a series of intramuscular injections demonstrated that a therapeutical plasma level could be maintained by injections at two to three hour intervals.Plasma levels of 15-methyl-prostaglandin F2 alpha (PGF2a) were measured by gas chromatography-mass spectrometry after iv, im, and sc administration in 22 pregnant women. During 6-hour iv infusions plasma PG analog levels were constant at about 600 pg/ml in 2 women receiving 1.0 mcg 15-methyl-PGF2a than salt/minute, 1200 pg/ml in 3 women receiving 2.5 mcg/minute, and levels rose to a peak of about 3000 pg/ml in 1 woman given 5 mcg/minute. In 8 subjects given im injections of 100, 200, 300, or 400 mcg, the PG levels peaked 15-20 minutes after 300 mcg. This spiking pattern of PG levels was apparent with both the therapeutic dose schedule of serial im injections and with serial sc injections. Adding 5 mcg epinephrine to the PG immediately before im injection lowered absorption to a broad peak of 1000 pg/ml over 1-2 hours in 3 subjects. Unlike the parent PGF2a, this analog resulted in very similar levels between individuals.

Prostaglandin E2 tablets were administered intravaginally 505 patients for the induction of labour, without amniotomy, using doses ranging from 1 to 5 mg as a single insertion. The advantages and limitations of this method of induction of labour are discussed.Prostaglandin E2 (PGE2) tablets were administered intravaginally to 505 patients for labor induction, without amniotomy, in doses ranging from 1-5 mg as a single insertion in this randomized, double-blind study conducted at 2 hospitals. Patient mean age, pregnancy duration, and pretreatment Bishop score did not differ significantly among the groups of patients receiving various doses of PGE2. The preinduction Bishop score and percentage of patients successfully induced with 3-mg intravaginal PGE2 tablets were significantly greater, whereas the induction-delivery time was significantly shorter, in patients delivered at Whipps Cross Hospita vs. Charing Cross Hospital (P .05). Plasma levels of 15-keto-PGE2 after the 3-mg dose of PGE2 in 4 selected patients showed wide variation. Labor was not induced in 1 patient with intermittent low plasma 15-keto-PGE2 levels, but it was successfully induced in the other 3, although the patient with the highest plasma level did not become established in labor until the end of the sampling period. Other unpublished studies showed no detectable levels of endogenous 15-keto-PGE2 in patients in spontaneous labor, and so these measurements illustrated the wide variation in plasma levels of 14-keto-PGE2 after a single intravaginal cose. No instances of gastrointestinal side effects or uterine hypertonus were recorded. An increase by 1-mg increments up to 5 mg did not increase the success rate. The effectiveness of this method of labor induction was greater than that of oxytocin without amniotomy and comparable with that achieved using extra-amniotic PGE2, and it is simpler than these 2 methods.

9-Deoxo-16,16-dimethyl 9-methylene PGE2 was given as a vaginal suppository at 0 and 8 hours to 37 patients. Two different doses were given, a 75-mg and 60-mg dose. The larger dose achieved an 86% abortion rate at 24 hours and for the smaller dose it was 53%. When an intramuscular injection of 15-methyl PGF2 alpha Tham was added at 24 hours, the success rate was 91% and 80% at 36 hours. The incidence of gastrointestinal side effects were significantly reduced when compared to vaginal administration of either PGE2 or 15-methyl PGF2 alpha methyl ester. The incidence of temperature elevation was similar to that achieved with the use of vaginal PGE2 but higher than with the use of vaginal 15-methyl PGF2 alpha methyl ester.A comparative study was conducted to assess the relative efficacy and side effects of 2 dosage schedules using 9-deoxo-16,16-dimethyl-9-methylene PGE2alpha (prostaglandin) for 2nd-trimester abortion. 37 healthy women received the PGE2alpha analog. 22 received an initial 75-mg dose in a vaginal suppository repeated at 8 hours; 15 recived a 60-mg dose which was repeated at 8 hours. If abortion had not occurred at 24 hours, an intramuscular injection of 250 mcg 15-methyl PGF2alpha was administered and repeated at 2-hour intervals for at least 6 injections. The success rate with the 75-mg dose was 86% at 24 and 91% at 36 hours. The mean time for abortion was 14.7 hours with a range of 5.5 to 36 hours. 6 of the women aborted completely and 14 required curettage to complete the procedure. The success rate for the 60-mg dose was 53% at 24 and 80% at 36 hours. The mean time was 21.9 hours with a range of 5.8 to 36 hours. 8 aborted completely and 5 required curettage. The lower dosage required a longer abortion time and produced slightly more side effects. The incidence of gastrointestinal side effects with this method of administration was significantly reduced when compared to vaginal administration of either PGF2 or 15-methyl PGF2alpha methyl ester. All of these PG abortifacients are preferable to saline solution.

RU 38-486 (17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)-17 alpha-(1-propynyl)estra-4,9-dien-3-one), an antiprogestational compound, was given to 33 women seeking termination of pregnancy. The patients were divided into two groups, 24 patients in group I with amenorrhoea up to 7 6/7 wk = 55 days, and 9 patients in group II with 8-10 wk amenorrhoea. The patients received 200 mg orally per day for 4 days. The start, duration and amount of bleeding were determined for 14 days. beta-HCG, plasma progesterone, estradiol and cortisol were determined at day 0 and day 7. All patients started to bleed during treatment. The frequency of complete abortion was 79% (19 out of 24 patients) in group I. In group II 33% (3 out of 9 patients) had a complete abortion. Most of the patients experienced only minor side-effects in terms of mild uterine pain and bleeding as in a spontaneous abortion. However, 2 patients in group II with 8 and 9 2/7 wk amenorrhoea suffered from heavy bleeding, requiring blood transfusion and curettage. In the patients with complete abortion, beta-HCG, estradiol and progesterone decreased significantly within 1 week. Cortisol concentrations remained within the normal range at day 0 and day 7. Treatment with RU 486 provides an acceptable method of early abortion, especially in women who refuse operative treatment and prefer a 'spontaneous abortion'. In 22 women RU 486 was administered from day 24 to day 27 of the menstrual cycle as a late 'morning-after pill' in the same dosage. All women except one started to bleed before day 28 and observed a normal menstrual period. One woman stayed amenorrhoeic for 2 months; she was not pregnant but apparently had an anovulatory cycle with a low progesterone level.

Two different vaginal suppositories have been developed suitable for one single treatment for preoperative dilatation of the cervix prior to vacuum aspiration in late first trimester abortion. The study included 60 patients equally distributed in one control group (Group I) where vacuum aspiration was performed without pretreatment; one group (Group II) where the patients obtained 2.0 mg 15-methyl-PGF2alpha-methyl ester in a rapid releasing base six hours prior to operation and one group (Group III) where the prostaglandin dose was increased to 2.5 mg 15-methyl-PGF2alpha-methyl ester and a more slow releasing base was used and the operation performed after 12 hours. The mean cervical dilatation at operation was in Group II 9 mm and in Group III 11 mm in comparison with 4.8 mm in the control group. The bleeding at the operation was also significantly reduced.Cervical dilatation was compared in 20 women 10-20 weeks pregnant 6 hours after placement of a vaginal suppository containing 2.0 mg 15-methyl-prostaglandin F2 alpha (PGF2a) methyl ester in a rapidly releasing base, in 20 women 12 hours after 2.5 mg PG in a slower releasing base, and in 20 controls before vacuum aspiration. Mean cervical dilatations measured were 4.8 mm in controls, 9 mm in the 2.0 mg group, and 11 mg in the 2.5 mg group. Thus further mechanical dilatation was required in all controls, 65% of the low-dose group, and 25% of the high-dose group. All treated women began to bleed before aspiration. Mean blood loss at operation was 90 ml in controls, 62 ml in the low, and 50 ml in the high-PG dose group. Occasional vomiting, diarrhea, and moderate uterine pain were reported.

A sesquiterpene lactone given the trivial name leucanthanolide, from the Mexican zoapatle plant (Montanoa leucantha), long used as an herbal remedy, was isolated and was found to have cytotoxicity but no uterine activity. The compound was isolated from the fraction containing zoapatanol, a substance being investigated for its ability to induce menses, abortion and labor. The compound has a molecular formula of C19H2606, a 5-membered lactone ring, an ester group, and a germacradienolide skeleton. It was evaluated for abortifacient activity in pregnant guinea pigs by intraperitoneal injection on day 22 of gestation. 3 of 5 animals had abnormal fetuses, but there was no evidence of early uterine activity. Cytotoxic testing in vitro was done on KB and P-388 test systems in cell culture. The ED50 of leucanthanolide was 0.57 mcg/ml (KB) and 0.93 (P-388). In comparison, the ethyl acetate fraction had an ED50 of 1.35 mcg/ml and 5.2 mcg/ml respectively.

As well as being an efficacious abortifacient agent, PGF2alpha is known to be an endogenous mediator of parturition. It is the hypothesis of this paper that PGF2 alpha may also be an effective macrophage tumouricidal activator; if correct, PGF2alpha may be said to 'abort' tumour cell mass. Indirect evidence for such a mechanism of action, as well as a theory as to the mode of action itself, is presented.

Clinical research has shown that prostaglandins (PGs) play an important role in every phase of human reproduction. The logical consequence of early basic biological research into PGs is the current interest in clinical evaluation of PGs as agents to induce labor and abortion and to stimulate menstruation. This is a review of the current literature dealing with PG research. Both PGF2alpha and PGE2 are known to induce labor at term when administered by intravenous infusion. Their relative effectiveness as compared to oxytocin has yet to be assessed. Intravenous infusion of PGE1, PGE2, and PGF2alpha will also induce abortion. Current research is being directed toward finding more practical methods of administration than continuous intravenous infusion. There is hope that PGs will be able to be used as a once a month contraceptive administered at the time of expected menstruation following exposure and a possible unwanted pregnancy. The exact mechanism of action of PGs on smooth muscle is still largely unknown. The differences in response of a specific muscle to different PGs have also not received much research attention. Little is known, for example, regarding the action of PGs on the cervix as opposed to the rest of the uterus. Particularly unknown is the mechanism of action of PGs at the molecular level. In most of the situations studied, PGs seem to stimulate adenyl cyclase activity and cyclic adenosine monophosphate formation or accumulation.

Prostaglandin, a smooth muscle-stimulating depressor acidic lipid discovered int he human seminal plasma in 1935, is now used as a generic term for a family of closely related derivatives of prostanoic acid which are widely distributed in animal tissues. Prostaglandins are biosynthesized from arachidonic acid and dihomo-gamma-linolenic acid, both of which are derived from dietary linoleic acid. This finding provided a link to the observation that linoleic acid is an essential constituent of the diet. It is possible that prostaglandin compounds play a biochemical role fundamental to many, or all, animal cells. They have been implicated in sperm transport, menstruation, parturition, and control of placental blood flow. They may also play a role in the central nervous system, although this role may well be other than that of synaptic transmitter. Release of prostaglandin from various tissues is brought about by nerve stimulation. In adipose tissues, the amounts released may be sufficient to inhibit formation of cyclic AMP by the released noradrenaline, thus providing a local negative feedback mechanism. Prostaglandins also possibly play a role in muscular contractility, essential fatty acid deficiency, inhibition of lipid mobilization, atherosclerosis, and thrombosis.

The effect of prostaglandin E2 (PGE2) release rate from an intravaginal suppository on induced abortion was investigated in a randomized, double-blind study of 71 women who were 7-22 weeks pregnant. 2 dosage forms were compared. Base A was selected to provide a more hydrophilic character than base B. 6 vaginal suppositories, inserted at 4-8 hour intervals as deemed necessary for the clinical progress of abortion, were available for each patient. If abortion did not occur within 48 hours, the trial was discontinued. When time for 50% dissolution of PGE2 (t50%) was plotted as a function of pH for the 2 suppository formulations, the curve for base A was sigmoidal in shape, showing a more rapid release of PGE2 and pH increase. In contrast, base B demonstrated a t50% value of 30 hours which was independent of pH. This independence suggested the hypothesis that the clinical performance of base B would be more uniform than a base A formulation and would exhibit a longer duration of biologic action. Use of base A was found to produce a slight increase in the frequency of successful abortions (79% with base A versus 70.3% with base B). There were no significant differences in the mean times from treatment initiation to complete abortion, the number of incomplete abortions, or failure to abort between the 2 study groups. There was a nonsignificant trend toward reduced total drug use in the base A group. Examination of side effects indicated that women receiving PGE2 in base B had a greater but nonsignificant tendency to experience nausea (62.2% in group B, 58.8% in group A) and vomiting (83.8% group B, 76.5% group A); however, there was a significantly greater amount of diarrhea in the base B group (70.3%) than in the base A group (41.2%). It was concluded that there are no major differences in abortifacient efficiency or the general incidence of side effects when PGE2 therapy in 2 dosage forms is compared. However, a more hydrophilic base, which exhibits a more rapid release of PGE2, appears to slightly reduce side effects and efficacy.

The efficacy of intravaginal administration of prostaglandin F2 alpha (PGF2alpha) in induction of abortion was determined in a clinical trial of 16 gravidas aged 21-38, parity 0-4, between the 6th-11th weeks of pregnancy. PGF2alpha tablet (50 mg) was inserted into the posterior fornix of the vagina and repeated at 1-2 hour intervals; dose range varied from 50-250 mg. Slight to severe labor-like pain was felt by all patients in the lower abdominal region 20 minutes-4 hours after PGF2alpha administration. Vaginal bleeding occurred within 30 minutes-8 hours. In all but 1 case, the fetus and the villi were expelled broken into small pieces. All 16 patients aborted, 7 completely and 9 incompletely. This form of administration is deemed efficacious as 3 patients aborted completely within 5 hours and 4 aborted completely between 15-18 hours. Bleeding in most cases occurred following the onset of abdominal pain, 30 minutes-8 hours after treatment. In another clinical trial, the efficacy of intravaginal administration of PGF2alpha in inducing menstruation was tested in 10 volunteers aged 31-40. Either 50 or 25 mg PGF2alpha tablets were used. The patients recorded their basal body temperature (BBT) every morning. Menstruation was successfully induced in 6 of 10 patients. 6 patients treated 2-3 days before the expected date of menstruation had menstrual-like bleeding 1-9 hours after PGF2alpha administration. 3 patients treated 5, 7, and 13 days (a day before BBT shift) before the expected date of menstruation did not have vaginal bleeding. 1 patient, with monophasic BBT who was treated 3 days before the expected menstruation, did not have menstrual bleeding. Amount of induced flow was more or less the same in most patients; duration of flow was normal in all cases. The mechanism of action of PG in menstruation induction is not known. The authors speculate that PGF2alpha mechanically stimulates separation of the superficial endometrium from the remainder of the uterine wall when the endometrium is in the premenstrual state. Side effects noted were nausea, diarrhea, pyrexia, slight flushing of the face, and headache.

This brief historical survey documenting the use of ergot alkaloids throughout Ancient times for obstetrical purposes (labor induction and control of uterine hemmorrhage) takes its data from works of Theophrastus (who wrote Enquiry into Plants around 300 B.C.), Pliny, Dioscorides, and others. What this history documents is another source for the ergot besides the fungus Clavicips purpurea; notations from Greek, Mexican, and English catalogers show that the family Convolvulaceae is a constant source of ergot alkaloids; this family is the home of Rivea corymbosa, the morning glory seed used by Mexican Indians for both medicinal and religious purposes. In addition, an argument made from salient quotations from historical texts indicates that Scammony may also contain ergot alkaloids, although such compounds have yet to be chemically isolated. Only 1 extant study intimates the possible existence of ergot-like activity in Scammony, a study which showed that small doses of an ether extract of Scammony resin stimulated an isolated guinea pig uterus. If Scammony does contain ergot alkaloids, it is suggested that it will be an excellent source for this material, since the plants cultivation is inexpensive and easy.

Various extracts of HIBISCUS ROSA-SINENSIS flowers have been studied for their antifertility activity on female albino rats. Benzene extract was found to be the most effective. For isolation of active constituents, the benzene extract was separated chemically into a number of fractions and their antifertility activities were studied systematically. The ether soluble portion of the water insoluble fraction of a benzene extract showed significant anti-implantation and abortifacient activities.

Some future contraceptives promise new reliability and convenience. The Silastic vaginal ring is expected to be available worldwide in the mid-1990s. The ring releases 250 to 280 mcg of levonorgestrel and 180 mcg of estradiol, a combination that virtually eliminates ovulation. A low-dose ring is also being investigated. Contraceptive implants of Silastic polymer-based rods or capsules are inserted under the skin; these slowly release progestogen that suppresses ovulation. These implants are currently available in Scandinavian countries, Indonesia, and South America. The cervical cap has recently returned to the US market. The woman applies a spermicidal cream or jelly in the cap and places it over her cervix. It can be left in place for up to 36 hours. At present, 80 countries use various injectable drugs that inhibit ovulation for 2-3 months, but they are not yet approved in the USA because of their potential side effects. Under investigation in the US and elsewhere are antispermatogenic agents that create temporary infertility by interfering either with spermatogenesis or with the sperm's ability to fertilize ova. The agents can be given by injection or taken orally. Developed in France and undergoing clinical trials in the US, RU-486 is a pill that disrupts gestation by interfering with progesterone receptors in the inner lining of the uterus. RU-486 can be used to induce early nonsurgical abortions or routinely each month just before menstruation is due.

Extraamniotic administration of prostaglandins (PGs) for labor induction was studied. 69 patients took part in this study, 43 of whom were primigravid and 26 of whom were parous. 65 of the cases had a normally developed child and 4 fetuses were known to be anencephalic. Pregnancy maturity ranged from 26-41 weeks. PGE2 was administered as for midtrimester abortion, except that a catheter with a balloon capacity of 30-50 ml was used. PGE2 concentration of 50, 75, or 100 mcg/ml was infused continuously by a Palmer pump at a rate of 1.8 ml per hour. Labor was successfully induced in all cases, judging by the establishment of regular uterine activity and softening, effacement, and dilatation of the cervix. Mean time of PG infusion was 6.5 hours. Mean dose was .9 mg. Oxytocin was used as a supplement if necessary, and 3 of 4 women with anencephalic fetuses needed oxytocin treatment. 39% of primigravida required oxytocin, and 17% of parous women did. Mean induction-delivery interval in the normal fetus group was 14 hours 48 minutes for primigravida, and was 9 hours 35 minutes in parous women. 12 patients were delivered by Caesarean section. 3 of the 65 normal fetuses died during labor. Uterine hypertonus occurred in 1 mother. PGE2 is indicated for labor induction when avoidance of artificial rupture of membranes is wanted.

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.Intensive observations of thermogenic parameters were made on 194 subjects (18-42 years old; 8-22 weeks gestation) aborted by prostaglandin (PG) analogs. Particular attention was paid to: 1) hourly temperature; 2) presence of visible shivering; 3) presence of endometritis or other infection; and 4) subjective feelings of hot and cold. Administration of F PGs elicited no significant thermogenic responses. However, administration of E PGs and their analogs by differing routes and dose schedules provoked thermal side effects such as temperature elevation (53%), rigors (93%), and subjective coldness (100%) in a high percentage of subjects. In 99 cases having abortion induced with intramuscular 15-methyl PGE2 analog, the concomitant administration of aspirin appeared to reduce the incidence and degree of these side effects (only 53% had fever above 38C). Severity of these side effects is dose-related. Although PGEs and their analogs appear to be thermogenic compounds, exerting their effects through a centrally mediated mechanism, there may also be peripheral vascular actions of these PGs which contribute to the appearance of thermal side effects.

A survey was conducted among medicinal plant sellers, healers, priests and local people in the rural population of Bhat, India. In this rural community medicinal plants are used for regulating fertility. Due to the fact that the majority of the Bhat community is illiterate, oral interviews were held in the villages. The information was then recorded. Plant samples were collected and preserved for future reference. Information on 28 plants and 11 recipes for doses from 2 or more vegetable species are presented, and popular names, empirical properties, and manner of using recipes are described. More than 90% of the information gathered was consistent among the informants, but some of the informants differed in their reports on the way to use the same plants. There is no certainty as to which of the plants are effective. Since the Bhat community has frequently observed the positive effects of their preparations, they have much faith in their recipes. The acceptability of these preparations is quite high among 95% of the Bhat population.

This paper reports the study of the long and short range interactions between the ring-chain and chain-chain portions for three different forms of prostaglandins (PGF2α, PGF1β and PGA1) for the possible rotations around C12-C13 (θ), C7-C8 (ψ) and C14-C15 (φ). The calculations were based on the long range interaction formalism of Claverie and Rein, using longitudinal and transverse polarizability data. Although the chain-chain interactions play predominant role in the stabilization of molecular geometry in the normal crystallographic forms, it is found that the ring-chain interactions and especially the interactions between the carboxylic chain and the ring vary in a specific way. They lead to the formation of several low lying conformations with the total interaction energy differing by few kcal/mole. The significant differences between the interaction energies of the active and inactive forms (in relation to their abortificient action) are noted and their relevance to the specificity of the molecular mechanism of the action discussed.

A case report of successful clinical use of prostaglandin-E2 vaginal suppositories to terminate a septic abortion is reported. A new indication for such therapy is suggested.Prostaglandin-E2 vaginal suppositories were used to terminate a septic abortion in a 23-year-old multiparous female. The patient, at 18 weeks gestation, complained of 36 hours of ruptured membranes. Past obstetrical history included a Cesarean section at term for cephalo-pelvic disproportion. In an effort to avoid a potentially morbid hysterectomy, a trial of vaginal Prostaglandin-E2 suppositores was undertaken. 70 minutes after insertion of the first 20 milligram suppository, regular uterine contractions were noted. The patient was closely monitored for signs of vascular collapse and uterine rupture. 6 hours later a macerated fetus was expelled. The placenta remained loosely attached to the anterior uterine wall and required uneventful curettage for removal. Broad spectrum antibiotic coverage and supportive measures continued. The patient began apyrexic 10 hours following prostaglandin administration. The rapid and efficient results produced in this case suggest a new indication for vaginal Prostaglandin-E2 therapy for termination of septic mid-trimester abortions as long as close patient monitoring with appropriate antibiotic and supportive therapy are instituted.

Second trimester abortion was induced in 92 women by extra-amniotic instillation of Rivanol and/or PGF2alpha followed by intravenous oxytocin after 24 hours. All instillations were made via a catheter with a balloon filled with 30 ml and left in place until abortion, but never for more than 24 hours. Induction was started by Rivanol alone (n = 23), PGF2alpha alone (n = 23), Rivanol combined with PGF2alpha (n = 23), or Rivanol combined with half dose PGF2alpha (n = 23) and the patients were allotted to the different groups in a random manner. The Rivanol solution was instilled as a single dose but PGF2alpha was instilled every 2nd hour for 24 hours. The mean induction-abortion time was similar in all 4 groups but a number of patients given PGF2alpha alone or in combination with Rivanol aborted earlier than patients induced by Rivanol alone, during the period before intravenous oxytocin was administered. Gastrointestinal side effects were equally common after Rivanol as after PGF2alpha. With the methods and doses used in the present investigation PGF2alpha alone or combined with Rivanol with subsequent oxytocin had no over-all advantage over Rivanol.Groups of 23 patients in second trimester pregnancy were given either Rivanol, prostaglandin F2a (PGF2a), Rivanol plus PGF2a, or Rivanol plus 1/2 the dose of PGF2a instilled in the previous group. Medication was instilled via catheter into the extraovular space of the internal cervical orifice. There were no significant differences between groups with respect to cumulative abortion rate, mean abortion time, or side effects. It is concluded that PGF2a does not have a significant advantage over Rivanol for induction of abortion.

During 1975-1977, 20 women undergoing mid-trimester (mean 16.1 weeks) abortions induced by Rivanol were treated with oral doses of 50 mg indomethacin every 6 hours starting immediately prior to the instillation of Rivanol. A group of 55 women undergoing Rivanol abortions (mean gestational age 15.6 weeks) during the same period acted as a control. It was found that administration of indomethacin, a strong inhibitor of prostaglandin synthesis, prolonged the induction-abortion interval significantly from a mean of 32.3 hours in the control group to a mean of 46.9 hours in the indomethacin group. This result adds support to the theory that the mechanism by which Rivanol induces abortion involves the stimulation of the endogenous production of prostaglandins.

The use of prostaglandin gel for therapeutic termination of second trimester pregnancy, the management of intrauterine fetal death, ripening of the cervix and induction of labour is reviewed. For these indications, prostaglandin gel is acceptable to patients, effective, and has a low incidence of side effects and complications.

In the present scenario of an ever-increasing global population the necessity of limiting births can not be denied. It seems that even nature is conscious of this fact since the number of pregnancies which are spontaneously interrupted has been found to be much higher than the number carried to term.