Treatment of premature labor with indomethacin.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
D A Blake
Publications and source records attributed to D A Blake.
Hybrid glycosaminoglycans synthesized by monolayers of chick embryo arterial fibroblasts.
Monolayer cultures of arterial fibroblasts from 13-day chick embryonic aorta incorporated 35SO42- into glycosaminoglycans containing both glucuronic and iduronic acids. Bacterial chondroitinase ABC converted more than 98% of the 35SO4-labeled polymer to mono- or disaccharides, including (1) N-acetyl-D-galactosamine 4-sulfate, (2) delta 4,5-glucuronic acid 2- or 3-sulfate leads to N-acetylgalactosamine 6-sulfate, and (3) the unsaturated disaccharides normally obtained from chondroitin 4-sulfate and chondroitin 6-sulfate sequences. Chondroitinase AC converted only 77% of the 35SO4-labeled polymer to the same mono- and disaccharides and yielded, in addition, the following oligosaccharide products: (1) delta 4,5-glucuronic acid leads to N-acetylgalactosamine 4- or 6-sulfate leads to iduronic acid leads to N-acetylgalactosamine 6- or 4-sulfate; (2) N-acetylgalactosamine 4-sulfate leads to iduronic acid 2- or 3-sulfate leads to N-acetylgalactosamine 6-sulfate; (3) delta 4,5-glucuronic acid leads to N-acetylgalactosamine 4-sulfate leads to (iduronic acid leads to N-acetylgalactosamine 4-sulfate)2; (4) delta 4,5-glucuronic acid leads to N-acetylgalactosamine 4- or 6-sulfate leads to (iduronic acid leads to N-acetylgalactosamine 6- or 4-sulfate)2; (5) higher oligosaccharides containing iduronic acid and N-acetylgalactosamine 4-sulfate.
Animals↗
The effect of chlorotrianisene as postpartum lactation suppression on blood coagulation factors.
Coagulation changes and increased risk of thromboembolic disease may occur in association with estrogen administration. The puerperium is also a high-risk period for thromboembolism, and estrogen administration at this time may increase this risk. Patients with congenital deficiency of antithrombin III have recurrent venous thromboembolic disease, suggesting that low levels of this factor may be associated with "hypercoagulability" states. We studied 50 postpartum patients who received chlorotrianisene (Tace) or placebo for lactation suppression in a prospective, double-blind, randomized fashion. Antithrombin III values were significantly lower on the third day post partum in the treated group compared to the placebo group (p less than 0.05). In addition, our clinical data from a total of 99 patients support the previous evidence that estrogens delay rather than prevent breast engorgement. Thus, with questionable benefit and a possible increased thromboembolic risk, it would appear prudent to discontinue the practice of estrogen administration for lactation suppression.
Adult↗
13, 14-dihydro-15-keto-prostaglandin F2alpha concentrations in human plasma and amniotic fluid.
An antiserum to 13,14-dihydro-15-keto-prostaglandin F2alpha (PGF2alphaM) was prepared and a radioimmunoassay evaluated in various reproductive states. PGF2alphaM plasma concentration was 63.6 +/- 10.3 pg/ml (mean +/- SEM) in cycling women. The concentration fluctuated throughout the menstrual cycle and pregnancy, but no discernible patterns were noted. PGF2alphaM concentrations were elevated at the time of urea + oxytocin induced abortion (238 +/- 54 pg/ml) and during late stages of normal labor (352 +/- 107 pg/ml) but were not elevated during labor prior to 7 cm dilatation. Following intra-amniotic instillation of 5 mg of PGF2alpha tromethamine into the amniotic sac, PGF2alphaM concentration increased in the amniotic fluid. In the plasma of these patients there was an eighteenfold rise in plasma PGF2alphaM concentration compared to a 3.5-fold rise in PGF2alpha at 1 hour, suggesting changes in PGF2alphaM may be more easily detected than the parent compound. While PGF2alphaM may be a useful index of PGF2alpha production, it appears that PGF2alphaM is of little value in predicting the occurrence of uterine contraction.
Abortion, Induced↗
South American plants II: taspine isolation and anti-inflammatory activity.
Croton lechleri L. (Euphorbiaceae), a plant from the Upper Amazon Valley of Peru, yielded the alkaloid taspine. The anti-inflammatory activity of taspine hydrochloride was studied using the carrageenan-induced pedal edema method, the cotton pellet-induced granuloma method, and the adjuvant polyarthritis model.
Alkaloids↗
Fetal tissues from various strains of induced mice metabolize benzo(a)pyrene to mutagenic metabolites.
Explore the source record for details and available documents.
Animals↗
Interaction of wild-type and variant mouse 3T3 cells with lectins from Bandeiraea simplicifolia seeds.
An isolectin (BS I-B4) derived from Bandeiraea simplicifolia seeds and specific for terminal alpha-D-galactopyranosyl groups was found to be cytotoxic to Swiss 3T3 mouse cells. After mutagenesis and selection with BS I-B4, a variant clonal cell line resistant to both this isolectin and the alpha-D- and beta-D-galactose-binding lectin abrin was isolated. The parental cell line showed homogeneous and noninteracting binding sites for BS I-B4, whereas the variant cells exhibited a curved plot with a reduced number of binding regions. Another lectin, BS II, which is derived from the same seeds by specific for terminal N-acetyl-D-glucosaminyl groups, was cytotoxic to the variant but not the parental cells. These results suggest a possible lesion in the biosynthesis of cell surface structures resulting in the exposure of subterminal N-acetyl-D-glucosaminyl moieties in the variant line.
Acetylglucosamine↗
Carbamazepine levels in pregnancy and lactation.
An epileptic patient whose seizures were controlled with carbamazepine and primidone was followed throughout pregnancy and lactation. Blood levels of primidone decreased during pregnancy and rose postpartum requiring dosage adjustments. Pharmacologically insignificant amounts of the drug were detected in breast milk. A review of the literature revealed 94 infants exposed to carbamazepine in utero and no evidence to date that this drug carries a teratogenic risk.
Adult↗
Intrauterine ethanol-induced termination of pregnancy in cynomolgus monkeys (Macaca fascicularis).
The effectiveness of locally applied ethanol in terminating early pregnancy in cynomolgus monkeys was studied. In a randomized trial ethanol (70 per cent, 1 ml.) or saline (0.9 per cent, 1 ml.) was injected extra-amniotically through a sterile blunt-end needdle inserted through the cervix into the uterine cavity. Six of seven monkeys receiving ethanol showed vaginal bleeding beginning one or two days after treatment. With the one failure, alcohol leakage occurred from the Luer-lock needle joint at the time of injection and the amount entering the uterus was unknown. No animal receiving saline showed any vaginal bleeding. The six monkeys showing vaginal bleeding were found to have nonenlarged or subnormally enlarged uteri one month after treatment. All monkeys subsequently resumed menstrual cycles within one year. Three monkeys became pregnant and were delivered at term of healthy offspring. Histologic evaluation of uteri from ethanol-treated monkeys revealed necrosis of decidua and, to a lesser degree, of the placenta one day after injection. The high efficacy of 70 per cent ethanol in inducing endometrial sloughing and the documentation of normal subsequent pregnancies in 50 per cent of treated monkeys make this technique worthy of consideration as a menstrual induction agent in women.
Abortion, Induced↗
The pharmacologic inhibition of premature labor.
Oxytocin, elevated estrogen-progesterone ratio, fetal corticosteroids, prostaglandins, catecholamines, and changes in uterine blood flow have all been implicated as triggers of labor. In approximately one-third of cases of threatened premature labor contractions stop spontaneously. Thus placebo-controlled randomized trials of any new drug for inhibition of premature labor are necessary, as the spontaneous cessation of contractions always favors the claimed therapeutic efficacy. Alcohol inhibits the release of endogenous oxytocin and has an additional direct effect on the myometrium. In one study alcohol was more effective than placebo in the postponement of delivery. Isoxsuprine, ritodrine, and terbutaline have also been shown to be better than placebo in the inhibition of premature labor, and the beta adrenergic agents appear to be more effective than alcohol. Prostaglandin inhibitors such as indomethacin are currently under investigation. Success is correlated with early administration of the therapy, which requires treating some patients whose contractions might have stopped spontaneoulsy. As different factors may be involved in triggering premature labor, if one therapeutic approach fails another should be initiated promptly.
Adrenal Cortex Hormones↗
Intra-amniotic urea and prostaglandin F2alpha for midtrimester abortion: clinical and laboratory evaluation.
The clinical management of the elective midtrimester abortion continues to be unsatisfactory as judged by either national mortality or morbidity rates. This report documents the results of a randomized series of 19 midtrimester abortions induced by either intra-amniotic hyperosmolar urea and 5 mg. of prostaglandin F2alpha (PGF2alpha) or intra-amniotic hyperosmolar urea alone. Pertinent clinical characteristics and biochemical determinations were compared between these two groups. A series of 150 patients were then treated with urea and 5 mg. of PGF2alpha. The clinical results of this series of patients are presented and compared with a previous group who had urea and 10 mg. of PGF2alpha. These studies demonstrate that 5 mg. of PGF2alpha with 80 Gm. of urea achieves injection-abortion intervals that are less than 24 hours.
Abortion, Induced↗
Uterine activity and prostaglandin production following intraamniotic hyperosmolar urea.
The relationship between endogenous prostaglandin (PG) production and uterine activity was studied in hyperosmolar urea induced abortion patients. Polygraphic recordings of intraamniotic pressure were obtained at periodic intervals following intraamniotic injection of 80 gm urea. At 0, 0.25, 1, 4 and 8 hours amniotic fluid and blood samples were obtained for PGE, PGF and 13,14-dihydro-15-keto-prostaglandin of abortion. In eight patients studied, uterine tone was elevated by 0.25 hour although no rhythmic contractions were observed by 1 hour. At 4 hours, amniotic fluid PGF concentration increased significantly (P less than .01) over the pre-injection value and continued to increase at 8 hours. Amniotic fluid PGE, PGFM and all plasma PG's showed no change during the 8 hour period following urea administration. At time of abortion the plasma PGFM concentration was significantly. At time of abortion the injection (238 +/- 54.4 vs. 86.7 +/- 7.3 pg/ml). There was no significant concentrations. In the present study, there is no evidence that increased prostaglandin production precedes urea induced contractions. The possible role of PG's in uterine contractions is discussed.
Abortion, Induced↗
Hyperosmolar urea-induced uterine contractions following prostaglandin inhibition.
Explore the source record for details and available documents.
Animals↗
Experience with an adolescent pregnancy program. A preliminary report.
A program has been designed to give comprehensive health care services to pregnant adolescents. The program components include community liason, patient education, counseling and social services, a nurse "on call" program for labor and delivery, and pediatric nurse-practitioner followup. In addition, a drug use identification component screens the patients by interview and urinalysis. Hypertensive disorders of pregnancy occurred in 10% of the first 202 patients. Forty-three percent had anemia (hematocrit less than 35%), and screening cervical cultures for gonorrhea were positive in 3.5%. Cigarettes, alcohol, and marijuana constituted the most common nonmedical drugs used, and aspirin the most common medical drug. Eighty-one percent of the patients attended 7 or more antenatal visits, one-half did not miss a single clinic appointment, and 95% completed a post-partum visit, indicating that the program was well accepted by the adolescents.
Adolescent↗
Phenytoin teratogenesis: correlation between embryopathic effect and covalent binding of putative arene oxide metabolite in gestational tissue.
The possibility that phenytoin (DPH) teratogenesis is due to an arene oxide (epoxide) metabolite was examined. On gestational day 11, Swiss mice were given teratogenic doses of DPH (50, 75 and 100 mg/kg) with and without a nonteratogenic dose of 1,2-epoxy-3,3,3-trichloropropane (TCPO; 100 mg/kg), an epoxide hydratase inhibitor. TCPO significantly increased the incidence of DPH-induced cleft lip and palate and enhanced the embryolethality 2-fold over DPH alone. Four hours after treatment with 14C-DPH (75 mg/kg, 80-90 muCi) the covalent binding of DPH radioactivity in fetuses and placentae was enhanced 2-fold in groups cotreated with TCPO (100 mg/kg). Enhancement was still evident in placentae 24 hours after treatment. There was no effect of TCPO on maternal plasma DPH level, which was comparable to that found in clinical therapeutics (20-30 microgram/ml). Likewise, fetal and placental DPH uptake was not increased by TCPO. DPH teratogenesis is postulated to result from DPH-epoxide formation and covalent binding of epoxide, the ultimate teratogen, to constituents of gestational tissue.
Animals↗
The influence of aspirin on the course of induced midtrimester abortion.
Prostaglandins appear to mediate the uterine contractions of abortion and labor, and aspirin has been shown to be an inhibitor of prostaglandin synthesis. In this double-blind, placebo-controlled, prospective, and randomized study, aspirin was administered orally in doses of 600 mg. every 6 hours to patients undergoing induced midtrimester abortions with hyperosmolar urea and oxytocin augmentation. The mean injection-abortion interval was significantly prolonged by aspirin in nulliparous patients (aspirin 32.3 +/- 3.3 hr. vs. placebo 21.5 +/- 3.5 hr.) and no aspirin-treated nullipara aborted in less than 18 hours. There was no significant difference between treatment groups in the mean injection-abortion interval in the multiparous patients at the dose of aspirin used. The effectiveness of aspirin in the prolongation of the injection-abortion interval has potential therapeutic implications for the treatment of premature labor.
Abortion, Induced↗
Comparative effects of hyperosmolar urea administered by intra-amniotic, intravenous, and intraperitoneal routes in rhesus monkeys.
Hypertonic urea solutions (58 per cent weight/volume) were injected rapidly into ten anesthetized rhesus monkeys at a dose of approximately 2 Gm. per kilogram by the intravenous, intraperitoneal, or intra-amniotic routes. An additional monkey received an intra-amniotic dose of 12.5 Gm. per kilogram. A tracer dose 14C-urea was included for measuring absorption and elimination. The following parameters were monitored before and for four hours after urea injection: arterial and cerebrospinal fluid pressures, heart and respiration rates, urine flow, and urea clearance. Serum electolytes, hematocrit and white count, and cumulative urea excretion were measured for one week. Monkeys were observed for three to six months after injection. At doses up to approximately twice the human dose (on a body weight basis) there were no urea-related deaths and no serious side effects noted in any of the experiments. These results support the suggestion that urea is a relatively safe hyperosmolar agent for inducing midtrimester abortions, especially with regard to inadvertent systemic injection.
Abortifacient Agents↗
Pharmacokinetics of intra-amniotically administered hyperosmolar urea in rhesus monkeys.
Three rhesus monkeys in midgestation were injected intra-amniotically with hyperosmolar 14C-urea (58 per cent weight/volume, 2.3 Gm. per kilogram, 25 muc) and the concentration of 14C-urea measured serially for 24 hours in amniotic fluid, maternal serum, and maternal urine. The volume of the amniotic space was measured by isotope dilution of 99mTc-albumin. The experimental values were fitted to a three-compartment mathematical model with the aid of a digital computer program for nonlinear data. The computer-derived concentration versus time curves were in close agreement with the measured values when the flux of urea was primarily from amniotic fluid to fetal water to maternal water with insignificant direct transport between the amniotic fluid and maternal serum. The half-times for distribution of urea into fetus and mother were approximately 30 minutes and 7 hours, respectively. Thus, although the uptake of urea by the fetus from surrounding amniotic fluid is rapid, the further movement of urea from fetus to mother is relatively slow.
Abortifacient Agents↗