Perinatal outcome after recent cocaine usage.

Eighty-eight neonates born to mothers with a history of cocaine use during pregnancy were divided into two groups based upon the detection of cocaine metabolites in the first neonatal urine. Forty neonatal urine samples were positive for cocaine and 46 were negative. Preterm labor, premature rupture of membranes, and meconium-stained amniotic fluid were significantly more frequent in those mothers whose neonates tested positive for cocaine metabolites than in those whose infants were negative (P less than .05). Neonates testing positive were more likely to exhibit signs and symptoms of acute cocaine intoxication. Low birth weight, growth retardation, and abruptio placentae were also more frequent than would be expected in the general population, but were not statistically different between the groups. These findings suggest that the differences noted in the cocaine-positive group may represent acute and chronic exposure, whereas the negative group reflects the problems associated with chronic usage alone.

Sequential outpatient application of intravaginal prostaglandin E2 gel in the management of postdates pregnancies.

A randomized blinded investigation was undertaken to determine the efficacy and safety of sequentially applied intravaginal prostaglandin E2 (PGE2) gel for accelerating cervical ripening in an outpatient setting in low-risk prolonged pregnancies. Fifty women with uncomplicated pregnancies at or beyond 41 weeks' gestation and Bishop scores below 9 received twice-weekly outpatient administration of gel containing 2.0 mg of PGE2 or placebo. Thirty nulliparas and 20 multiparas were enrolled. The PGE2 gel failed to improve cervical ripening over placebo, as judged by Bishop scores. There was no difference between the groups in gestational age on admission to the labor and delivery suite, number of gel applications, requirement for oxytocin, incidence of cesarean delivery, or neonatal outcome. Only two patients (4%) experienced regular uterine contractions after gel insertion; these subsided spontaneously in both. None of the subjects experienced labor, tetanic contractions, evidence of fetal distress, or any other side effects related to gel insertion. We conclude that PGE2 gel in this dosage may be used safely in an outpatient setting, but more frequent application or earlier initiation may be required to produce a clinical effect.

Patient-administered outpatient intravaginal prostaglandin E2 suppositories in post-date pregnancies: a double-blind, randomized, placebo-controlled study.

OBJECTIVE: To shorten post-date pregnancies in a safe, effective manner by outpatient acceleration of cervical ripening. METHODS: Eighty patients with uncomplicated pregnancies at or beyond 41 weeks' gestation and a cervical Bishop score less than 9 were randomized to daily self-administered, 2-mg intravaginal prostaglandin E2 (PGE2) or placebo suppositories. Each followed a standard post-date antepartum surveillance protocol. Patients were admitted for spontaneous labor or for induction if the Bishop score reached 9, antepartum testing was nonreassuring, exclusion criteria were fulfilled, or if the gestational age reached 44 weeks. RESULTS: Fewer suppositories were used in the PGE2 group (four versus seven; P = .006), resulting in earlier gestational age on admission (295 versus 297 days; P = .021) and lower antepartum testing charges ($476.97 versus $647.29; P = .001). Labor and delivery time was significantly decreased in nulliparas (10.7 +/- 5.1 versus 15.3 +/- 7.6 hours; P = .035). CONCLUSIONS: Daily low-dose, patient-administered PGE2 vaginal suppositories can decrease the gestational length and cost of uncomplicated post-date pregnancies by reducing the time to achieve a favorable cervix, the need for antepartum testing, and, potentially, post-date-related complications.

Fetal head molding. Diagnosis by ultrasound and a review of the literature.

Head molding refers to changes in cranial bone relationships that occur in response to external compression force. In the normal term labor with vertex presentation, the suboccipito-bregmatic diameter shortens and the mentovertical diameter lengthens. This is accomplished partially through the unbending or straightening of the parietal bones rather than the frequently taught mechanism of overlapping sutures. The occipital and frontal bones may also contribute by an inward movement of their apex, using their basal portions as a hinge. A locking mechanism may occur in protracted labors as the free edges of the cranial bones are forced into one another, preventing further molding and providing more protection for the fetal brain. The preterm skull has weaker material properties and wider sutures. Thus, more molding at lower pressures is possible and the protective effect of "locking" may not be operational. A case of extreme antenatal preterm fetal head molding discovered at ultrasound is presented as an introduction to review the literature regarding molding.

Critical management of the very low birth weight infant and macrosomic fetus.

The two extremes of birth weight ( < 1500 g and > 4000 g) require antepartum surveillance and anticipation of complications during labor and delivery. Prognosis for the very low birth weight carries with it inherent neurologic impairment even when cared for under the best of conditions. In contrast, the macrosomic fetus enjoys a generally excellent outcome regardless of management. The current concern is too much intervention to avoid a low probability of complications.

Cocaine affects prostaglandin production in human umbilical cord cell cultures.

OBJECTIVE: To investigate the possible effects of cocaine on prostacyclin and prostaglandin (PG) E2 production from endothelial cells derived from human umbilical cord. STUDY DESIGN: First-passaged endothelial cells derived from the umbilical vein were incubated with various doses of cocaine, procaine and lidocaine and 24 h later the supematants were assayed for prostacyclin metabolites 6-keto-PGF1alpha and PGE2. Cocaine concentrations tested were 0, 10, 100, 500 and 1000 microg/ml. RESULTS: Cocaine produced a dose-dependent reduction in prostacyclin and PGE2 production from endothelial cells (p) < 0.05). Acetylcholinesterase (a possible detoxifier of cocaine) abolished the effect of cocaine on prostacyclin production. Procaine, an esterol-type anesthetic, produced a similar effect on prostacyclin production, an effect not observed with lidocaine. CONCLUSION: It is speculated that, when present in high concentrations, cocaine may affect vascular tone by inhibition of endothelial cell prostacyclin and PGE2 release.

Cocaine decreases urinary prostacyclin release in pregnancy: correlation with uterine and umbilical Doppler velocimetry.

OBJECTIVE: The purpose of this study was to determine maternal urinary prostacyclin and thromboxane excretion in patients with recent cocaine use, compared to cocaine-free controls, and correlate the findings with Doppler velocimetry. STUDY DESIGN: Seventeen patients admitted with premature rupture of membranes between the gestational ages of 24 and 34 weeks were tested for urinary cocaine metabolites. Eleven patients had positive screening and six patients were negative and served as controls. After initial stabilization, 24-h urine collections were obtained and were assayed for the prostacyclin metabolite 2,3-dinor-6-keto-PGF(1alpha), and the thromboxane metabolite 2,3-dinor TXB2. These patients underwent uterine and umbilical arterial Doppler velocimetry expressed as the pulsatility index. Statistical analysis was performed by the SPSS statistical package using the non-paired Student t test, and Spearman correlation coefficient with p < 0.05 being considered significant. RESULTS: Compared with controls, urinary excretion of prostacyclin in pregnant women with recent cocaine use was significantly lower. The pulsatility index of the uterine arteries of the cocaine-positive individuals was higher than in controls and had a significant inverse correlation with prostacyclin metabolite excretion. Umbilical arterial velocimetry was similar in the two groups. CONCLUSION: Recent cocaine ingestion in pregnant women decreases production of prostacyclin and negatively affects the pulsatility index of the uterine artery.

The "Allis" test for easy cesarean delivery.

Cesarean delivery may be complicated by dystocia if the incision size is inadequate. A test is described that may be easily applied at cesarean section, creating greater objectivity in the determination of surgical incision size. One hundred patients were studied prospectively. Patients with incisions that passed the test had a shorter mean time of delivery and less difficult deliveries than those of patients with incisions that failed the test. We conclude that the "Allis" test is a simple way to reduce the incidence of dystocia at cesarean delivery.

Potential role of endothelin-1 in normal and hypertensive pregnancies.

Endothelins are the most potent naturally occurring vasoconstrictors yet discovered. Both normal and abnormal pregnancies are associated with significant changes in vascular smooth muscle; therefore the potential role of endothelin in pregnancy was investigated. Plasma immunoreactive endothelin-1 concentration was measured by radioimmunoassay in blood from women with normal pregnancy and preeclampsia and in cord blood from normal pregnancies. Endothelin-1 levels were elevated in pregnant women during labor when compared with levels in nonpregnant women and patients with normal pregnancies before labor. Preeclampsia in nonlaboring women before treatment was associated with higher endothelin values when compared with values in normal nonlaboring patients and women with preeclampsia after magnesium sulfate infusion. The umbilical venous concentration of endothelin was 10 times higher than normal pregnant levels and four times higher than levels in laboring patients.

The effect of acetaminophen on prostacyclin production in pregnant women.

OBJECTIVE: The purpose of this study was to determine if acetaminophen decreased prostacyclin production by endothelial cells in culture and by pregnant women. STUDY DESIGN: The effect of acetaminophen on endothelial cells in culture was determined by the addition of acetaminophen in concentrations of 10 and 100 micrograms/ml with comparison to control and indomethacin at 10 micrograms/ml. Prostacyclin production was estimated in 24 and thromboxane A2 production in six third-trimester pregnant women by measurement of excretion of urinary metabolites before and after ingestion of either 1000 mg of acetaminophen or placebo. RESULTS: Compared with control (549 +/- 61 pg/well, mean +/- SD), production of prostacyclin in vitro was significantly inhibited by acetaminophen at 10 micrograms/ml (321 +/- 25) and 100 micrograms/ml (257 +/- 14). This inhibition is similar to inhibition by 10 micrograms/ml of indomethacin (228 +/- 11). Excretion of prostacyclin metabolite was significantly lower after ingestion of acetaminophen (2233 +/- 446 vs 1246 +/- 199 pg/mg creatinine, mean +/- SEM) but unchanged after ingestion of placebo (1745 +/- 304 vs 1712 +/- 211). There was no difference in response between normal and hypertensive women, and there was no effect of acetaminophen on thromboxane metabolite excretion. CONCLUSION: Acetaminophen in typical oral doses results in reduced production of prostacyclin by endothelial cells in culture and in a reduction in prostacyclin, but not thromboxane, production in pregnant women.

Macrophages specifically regulate the concentration of their own growth factor in the circulation.

The physiological mechanism of clearance of the mononuclear phagocyte growth factor, colony-stimulating factor 1 (CSF-1), from the circulation of normal mice was investigated by following the fate of a trace amount of i.v. injected 125I-labeled CSF-1. Macrophages selectively cleared CSF-1 by CSF-1 receptor-mediated endocytosis and degraded the growth factor intracellularly. This manner of clearance provides a feedback control mechanism whereby the rate of macrophage production is determined by the number of mature macrophages.

Effect of magnesium sulfate on plasma endothelin-1 levels in normal and preeclamptic pregnancies.

OBJECTIVE: We attempted to determine the effects of magnesium sulfate on: (1) endothelin-1 concentration in preeclampsia, preterm labor, and term pregnancy and (2) endothelin-1 release from human umbilical cord endothelial cells. STUDY DESIGN: Plasma samples were prospectively collected from eight women with preeclampsia, six preterm labor patients, and eight term patients undergoing external cephalic version before and 2 hours after magnesium sulfate infusion. Supernatants were collected from human umbilical cord endothelial cells exposed to magnesium sulfate and controls. All samples were assayed with a specific radioimmunoassay for endothelin-1. Paired Student t test and analysis of variance were used for statistical analysis. RESULTS: Magnesium sulfate infusion in preeclampsia lowered endothelin-1 levels compared with preinfusion values (6.6 +/- 3.81 before and 4.75 +/- 2.28 after infusion, p < 0.02). Magnesium sulfate did not have an effect on endothelin-1 concentration in preterm and term pregnancies. Magnesium sulfate did not alter the endothelin-1 release from human umbilical cord endothelial cells. CONCLUSION: A significant reduction of endothelin-1 plasma levels after magnesium sulfate therapy is limited to preeclampsia. In contrast, this lowering effect was not exhibited in women without preeclampsia or in normal endothelial cells.

Enzyme activities and maturation in unstimulated and exogenous gonadotropin-stimulated human oocytes.

With the advent of new techniques of human in vitro fertilization (IVF), identifying parameters of oocyte quality to allow selection of those most likely to fertilize becomes crucial. Morphology of oocytes, which correlates positively with biological performance, is the currently utilized classification criterion. However, biological links between form and function are tenuous, and underlying mechanisms remain elusive. We investigated whether biochemical activation is quantitatively associated with the stages of maturation in ova obtained from patients undergoing gynecologic surgery during unstimulated cycles and women undergoing IVF after exogenous gonadotropin stimulation. Changes in selected enzymes from protein, lipid, and carbohydrate metabolism (hexokinase, phosphoglucomutase, glycogen synthetase, uridine diphosphoglucose pyrophosphorylase, glucose-6-phosphate dehydrogenase, cytosolic thiolase, beta-hydroxyacyl-CoA dehydrogenase, alanine aminotransferase, and aspartate aminotransferase) were determined simultaneously, in individual oocytes, utilizing a highly sensitive biochemical methodology. Several enzyme activities paralleled maturation grade and were higher in stimulated oocytes after correction for grade. These biochemical findings quantify metabolic and functional changes that increase as ova mature, possibly contributing to their reproductive performance.