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Hepatic esterase and nonhepatic cytochrome P-450 play minor roles in cocaine metabolism. Increased or decreased central nervous system outflow determines how much neurotransmitter is actively released from distal nerve terminals, and thus influences cocaine's effect. Perfused hearts from both groups showed similar responses to cocaine, and there were no differences in resting autonomic tone or cocaine metabolism between the two groups. While the central nervous system may mediate some of cocaine's effects, its precise role remains unclear. Cocaine's effect on placental and endothelialprostaglandin production could explain the inability of alpha receptor antagonists to completely block cocaine's vasoconstrictive effect. In rat liver cell cultures, hepatic demethylation accounts for approximately 20% of cocaine's metabolism. The myometrium is sensitive to adrenergic stimulation, and because cocaine prolongs the stimulatory effect of catecholamines on adrenergic receptors, cocaine's relation to uterine contractility has been studied.

Although there are many synthetic methods to produce fluorinated and trifluoromethylated organic structures, the construction of difluoromethylated compounds remains a synthetic challenge. We have discovered that using magnesium salts and organic bases, unactivated imines will react with difluoroenolates, generated under exceedingly mild conditions. We have applied this approach to the iminoaldol reaction to produce difluoromethylene groups as α,α-difluoro-β-amino-carbonyl groups. This method provides synthetically useful quantities of difficult to access α,α-difluoro-β-aminoketones without the need of protecting groups or the use of activated imines. Moreover, we have applied this strategy to create analogues of the dual orexin receptor antagonist, almorexant, in only two synthetic steps.

Recent studies suggest that leukemia stem cells (LSCs) play a critical role in the initiation, propagation, and relapse of leukemia. Herein we show that (-)-15-methylene-eburnamonine, a derivative of the alkaloid (-)-eburnamonine, is cytotoxic against acute and chronic lymphocytic leukemias (ALL and CLL) and acute myelogenous leukemia (AML). The agent also decreases primary LSC frequency in vitro. The cytotoxic effects appear to be mediated via the oxidative stress pathways. Furthermore, we show that the compound kills AML, ALL, and CLL stem cells. By the use of a novel humanized bone marrow murine model of leukemia (huBM/NSG), it was found to decrease progenitor cell engraftment.

β-Hydroxy difluoromethyl ketones represent the newest class of agonists of the GABA-B receptor, and they are structurally distinct from all other known agonists at this receptor because they do not display the carboxylic acid or amino group of γ-aminobutyric acid (GABA). In this report, the design, synthesis, and biological evaluation of additional analogues of β-hydroxy difluoromethyl ketones characterized the critical nature of the substituted aromatic group on the lead compound. The importance of these new data is interpreted by docking studies using the X-ray structure of the GABA-B receptor. Moreover, we also report that the synthesis and biological evaluation of β-amino difluoromethyl ketones provided the most potent compound across these two series.

Pregnancy is a dynamic process, and maternal as well as fetal risks from cocaine use in pregnancy may differ as pregnancy progresses. Three areas of biology offer opportunities for reevaluating cocaine's effects in pregnancy: (1) Maternal cardiovascular and neurologic responses to cocaine hydrochloride are enhanced when compared with responses in nonpregnant subjects to the same dose per kilogram or to metabolites of crack cocaine. (2) During first trimester placental implantation, oxygen availability to the fetus may normally be limited. Cocaine-induced uterine artery vasoconstriction may lead to reperfusion and oxygen toxicity to the fetus from released reactive oxygen species. (3) Cocaine transport in the first and early second trimester may, in part, be across the placental chorion-amnion. Lacking a skin barrier, the fetus at mid-pregnancy may come in direct contact with high concentrations of cocaine in amniotic fluid, a reservoir that clears cocaine slowly, thereby prolonging exposure during critical periods of fetal neurotransmitter formation. Exploring these three areas of biology may offer new approaches to understanding the ultimate impact of prenatal cocaine exposure on maternal and fetal biology.

The sesquiterpene lactone class of natural products displays a diverse array of biological activities due to the presence of the α-methylene-γ-lactone motif. However, clinical translation of this class has been hampered by poor aqueous solubility and non-selective binding as a Michael acceptor at undesired targets. A prodrug approach has been developed to overcome these problems in which an amine is added into the α-methylene-γ-lactone to mask this group from nucleophiles and increase solubility. The medicinal chemistry of amino-derivatives of the sesquiterpene lactones is described, beginning with synthetic development, moving into pharmacological applications, and finishing with clinical translation.

The total synthesis of the rare but extremely potent antitumor agent shishijimicin A has been achieved via a convergent strategy involving carboline disaccharide 3 and hydroxy enediyne thioacetate 4.

Our understanding of the pathophysiologic processes leading to preterm premature rupture of membranes (PPROM) has grown tremendously in recent years. Evidence suggests that there may be a genetic susceptibility to PPROM and that genetic and environmental elements are important cofactors in its development. A number of risk-based protocols have been proposed in an attempt to identify those women at highest risk for PPROM. While we have made advances in the area of predicting PPROM, treatments based on current risk-based systems have failed to distinguish a specific, effective preventive therapy for PPROM. The concept that genetic factors increase susceptibility or decrease resistance to disease has stimulated new work in the field of PPROM. Several maternal and fetal gene polymorphisms have been identified that are associated with an increased risk for PPROM. Patients with 'susceptible' genotypes may also have clinical risk factors for PPROM resulting in a synergistic increase in the risk for PPROM, a so-called gene-environment interaction. The concept that these gene-environment interactions represent new targets for our efforts to prevent PPROM is explored.

Objective We sought to determine whether vitamins C and E could be delivered to the fetal-placental unit through maternal oral supplementation. Study design In a randomized, double-blind study, 20 women received a daily prenatal vitamin with or without 400 IU of vitamin E and 500 mg of vitamin C, starting at 35 weeks' gestation. At randomization, a nutritional questionnaire, plasma vitamin C and E and red blood cell (RBC) vitamin E levels were determined. At delivery, concentrations of maternal and fetal plasma vitamin C and E, maternal and fetal RBC vitamin E, amniotic fluid vitamin C, and chorioamnion vitamin E and tensile strength were determined. Results Maternal plasma vitamin E levels increased in the supplemented women but not in the control subjects. No changes in maternal vitamin C levels were noted. Maternal plasma vitamin C concentrations at delivery correlated closely with amniotic fluid vitamin C levels. Similarly, maternal plasma vitamin E levels at delivery correlated with the chorioamnion concentration of vitamin E. Conclusions Maternal plasma vitamin E levels are increased by oral supplementation. Maternal plasma vitamin C and E concentrations correlate with the concentration of vitamin C in the amniotic fluid and vitamin E in the chorioamnion, respectively.

This study was conducted to compare maternal and fetal plasma, amniotic fluid, and chorioamnion levels of vitamins C and E in term (38 weeks' gestation) subjects undergoing elective repeat cesarean section (CS) without labor with values of subjects of similar gestational age and dietary intake undergoing labor and vaginal delivery (VD).Healthy women undergoing elective repeat CS (n = 5) or uncomplicated VD (n = 5) at term (38 weeks' gestation) were studied. For CS patients, maternal and fetal (cord) blood, amniotic fluid, and chorioamnion samples were collected at time of surgery. For VD patients, maternal blood and amniotic fluid were obtained at 5 cm cervical dilation and fetal cord blood and chorioamnion were collected at delivery. Each patient completed a nutritional questionnaire. Plasma and membrane vitamin E concentrations were determined by reversed-phase high-performance liquid chromatography and standardized to cholesterol or membrane protein, respectively. Vitamin C was determined with the use of the 2,4-DNPH method.Dietary intakes for vitamins C and E as well as maternal and fetal vitamin E plasma concentrations were similar for CS and VD patients. In both groups, maternal levels were higher than fetal levels(P.05). Chorioamnion membrane vitamin E measurements in both groups were similar. Vitamin C concentrations in CS and VD patients were highest in amniotic fluid, lower in fetal plasma, and lowest in maternal plasma. However, mean vitamin C concentrations in maternal plasma, amniotic fluid, and fetal plasma of VD patients were significantly lower, being only 20% +/- 6%, 29% +/- 11%, and 22% +/- 2% of values obtained from CS patients.During labor in healthy women at term, uterine contractile activity may generate reactive oxygen species (ROS) through the process of repetitive ischemia and reperfusion. With the significant depletion of vitamin C during labor, we speculate that water-soluble vitamin C scavenges ROS in the aqueous phase and recycles lipid-soluble vitamin E to combat ROS-induced tissue damage.

Objective: Our purpose was to assess the tensile strength of the chorioamnion at various gestational ages. Study Design: Segments of chorioamnion were obtained from 35 patients delivered at gestational ages ranging from 17 to 41 weeks. Clinical information including gestational age, chorioamnionitis, premature rupture of membranes, and onset of labor was recorded. Tensile strength (grams to burst and deflection at rupture) was measured on 2 to 16 specimens per patient. Tensile strength of several commercial products was used for comparison. Results: Tensile strength increases up to 20 weeks of gestation and then plateaus until 39 weeks of gestation, when it falls dramatically. Clinical chorioamnionitis alone did not affect tensile strength, but gross membrane inflammation resulted in reduced tensile strength. Conclusions: Tensile strength of the chorioamnion varies with gestational age. This baseline information will be useful in assessing the effects of various conditions and therapies on membrane strength and may provide insight into spontaneous rupture of membranes. (Am J Obstet Gynecol 2002;187:672-5.)

As obstetrics and gynecology (ob/gyn) practices move toward becoming patient-centered medical homes for their patients, the need for providing integrated behavioral health care has increased. Themes common in ob/gyn settings-such as menstruation concerns, initiation of contraception, pregnancy, childbirth, and menopause-serve as occasions for health promotion and as life transitions where behavioral health concerns may arise. When these transitions are complicated by issues such as trauma, infertility, and pregnancy loss, the need for sensitive, collaborative care between psychology and obstetrics/gynecology becomes particularly critical. Women's health psychologists can serve a key role for ob/gyn practices by co-managing patients' care, offering consultation to providers, providing brief behavioral health consultations to patients, facilitating psychotherapy engagement, and providing treatment for women and their families.

Our objective was to assess the perinatal management and neonatal outcomes of premature, severely intrauterine growth-restricted (IUGR) neonates. A cohort of neonates1000 grams,or = first percentile for weight, and37 weeks' gestation was identified and matched 2:1 to two control sets of premature, appropriate-for-gestational age (AGA) infants-one with similar gestational age (AGA-GA group) and the other with similar birth weight (AGA-BW group) to determine the effect of IUGR on the outcome of the premature infant. The IUGR group was then examined in detail for descriptive statistics. Data were analyzed by t-tests and Chi-square analyses where appropriate. The IUGR infants had worse outcomes than AGA-GA controls but had somewhat better results than the AGA-BW controls. In the IUGR group, a birth weight less than 550 grams was significantly associated with neonatal death (p0.001). However, increasing gestational age was not associated with neonatal survival (p = 0.661) if birthweight remained below 550 grams. Classical cesarean delivery was associated with neonatal death (p = 0.003). Neonatal variables associated with poor outcome included patent ductus arteriosus (p = 0.034), feeding intolerance (p = 0.046), and failure to thrive (p = 0.05). Overall, neonatal survival was 73%. Of the surviving neonates, 69% had evidence of neurodevelopmental delay when tested at 6 and 12 months. Premature, growth-restricted neonates with birth weights of550 grams versus those of550 grams have dismal outcomes despite a gestational age that is compatible with survival.

We propose that generation of reactive oxygen species may be a potentially reversible pathophysiologic pathway leading to preterm premature rupture of the membranes. Reactive oxygen species generated by the body's response to diverse insults such as infection, cigarette smoking, bleeding, or cocaine use can activate collagenolytic enzymes and impair fetal membrane integrity. Vitamin E, a lipid-soluble antioxidant, inhibits membrane-damaging effects of reactive oxygen species-induced lipid peroxidation. Vitamin C, a water-soluble antioxidant in plasma, stimulates and protects collagen synthesis while recycling vitamin E. Prior evidence shows that (1) damage by reactive oxygen species can impair fetal membrane integrity, (2) reduced midgestation levels of vitamin C are associated with preterm premature rupture of membranes, and (3) these vitamins can be safely and effectively absorbed and delivered to gestational tissues. Current prenatal vitamin preparations contain vitamins C and E in concentrations that are less than 1/3 and 1/10, respectively; these levels have been suggested for effective antioxidant protection. We hypothesize that increased dietary consumption or supplementation of vitamins C and E during pregnancy may reduce physiologically the risks of that portion of preterm premature rupture of membranes that is mediated by excessive or undamped peroxidation of fetal membranes. This hypothesis, if confirmed, should stimulate initiation of therapeutic trials to test the efficacy of enhanced supplementation with vitamins C and E during pregnancy to prevent preterm premature rupture of membranes.

Objective: Preterm premature rupture of fetal membranes has been associated with infection, cigarette smoking, and bleeding. Hypochlorous acid (a reactive oxygen species) is central to the body’s response to infection, yet it may damage surrounding tissue while destroying pathogens. We examined in vitro the tissue-damaging actions of hypochlorous acid on the amnion-chorion and the protective role provided by pretreatment with vitamins C and E. Study Design: Amnion-chorion samples were obtained from 4 term pregnancies, cut into segments, and divided into 6 exposure groups. Half were treated in advance with vitamins C and E (Trolox C) and half were treated with buffer solution alone. After rinsing, amnion-chorion samples were exposed to hypochlorous acid at 1 or 10 mmol/L for 4 hours. Histologic and immunocytochemical evaluations were conducted with antibodies for collagen I and IV. Results: Extensive damage to amniotic epithelium and collagen I but not collagen IV resulted from hypochlorous acid exposure and was dose related. Pretreatment with vitamins C and E prevented this damage in all cases. Conclusion: Hypochlorous acid damages the amniotic epithelium and collagen I in the amnion-chorion. The protection against hypochlorous acid–induced damage provided by antioxidant therapy (vitamins C and E) is of therapeutic significance. (Am J Obstet Gynecol 2000;183:979-85.)

Cocaine continues to be abused during pregnancy, creating increased demands on the health care system. Epidemiology and basic science research have identified and confirmed risks of adverse maternal and fetal effects when cocaine is used during pregnancy. These effects of cocaine in pregnant women often are influenced by a number of confounding variables. This article reviews those cocaine effects as well as recent data, which examine in greater detail the risks of adverse outcomes of prenatal cocaine exposure during pregnancy.

There is a growing body of information relating diverse diseases and the consequences of injury to generation and toxicity of reactive oxygen species (ROS). Recently, it has been shown that the fetus and its membranes are also vulnerable to this toxicity, suggesting that a number of obstetric diseases may result from exposure to ROS, which are ubiquitous in aerobic organisms. Endogenous antioxidants, including superoxide dismutase, catalase, and glutathione peroxidase are essential for defense against ROS. It is significant that all antioxidants appear to be down-regulated in the fetus and membranes, suggesting the possibility that any process that further depresses their activities or increases the burden of ROS may compromise fetal development or maternal health. When permitted to accumulate, ROS can damage all classes of macromolecules, including lipids, proteins, and nucleic acids. Toxicity includes mutation, protein degradation, and lipid peroxidation, which can severely disturb membrane permeability and alter intracellular calcium and pH. An understanding of the generation and toxicity of ROS should help to define their potential roles in obstetric disease and lead to innovative preventive and therapeutic approaches.

The biological role of installing a critical exocyclic enone into the structure of the alkaloid, (−)-eburnamonine, and characterization of the new chemical reactivity by quantitative NMR without using deuterated solvents are described. This selective modification to a natural product imparts potent anticancer activity as well as bestows chemical reactivity toward nucleophilic thiols, which was measured by quantitative NMR. The synthetic strategy provides an overall conversion of 40%. In the key synthetic step, a modified Peterson olefination was accomplished through the facile release of trifluoroacetate to create the requisite enone in the presence of substantial steric hindrance.

Our appreciation of the impact on health of illicit drug use is growing. Once considered a maternal risk, prenatal drug exposure may target fetal neurobehavior, affecting attention and learning as the child grows into adulthood. Cocaine, opiates, marijuana, and amphetamines have each been scrutinized for adverse actions on placental transport, fetal behavior states, newborn withdrawal, and childhood learning and attentive skills. Neurotransmitter analysis in the animal model after prenatal drug exposure now provides biological support for these clinical findings. The increasing prevalence of drug use by pregnant women, the effect of illicit drug use on transmission of the human immunodeficiency virus, and the maternal and fetal consequences of illicit drug exposure make illicit drug use in pregnancy a central challenge in maternal-fetal medicine and a need-to-know field in general obstetrics.

Cocaine's cardiotoxicity was reported in our laboratory to be augmented by progesterone. This study was designed to replicate these findings and determine the mechanism. Rats were pretreated with progesterone (study) or vehicle (control). Papillary muscles were attached to transducers in Krebs' baths. Paced contractility parameters were measured while increasing concentrations of cocaine, norepinephrine, or tetrodotoxin were added. In nine baths, yohimbine was added before the cocaine. Twelve rats were pretreated with reserpine, and cocaine added to the baths. In muscles from nonreserpinized control rats, there was a small positive inotropic effect (8.6% above baseline) at 10(-6) M cocaine, not seen in study muscles. There were no differences between study and control muscles in cocaine concentrations at which muscles became acontractile, nor in responses to norepinephrine, tetrodotoxin, or to cocaine after the addition of yohimbine or following reserpine pretreatment. We could not replicate cocaine's previously reported increased negative inotropic effect in progesterone-treated rats, nor was there evidence supporting possible mechanisms for this reported effect.

Progesterone increases cocaine's cardiovascular toxicity in sheep and rats. To determine whether progesterone enhances the lethality of cocaine, nonpregnant female rats were treated with either IM progesterone (P4) or vehicle, and pregnant rats (Preg) were untreated. The rats received one IP injection of cocaine at a dose between 25-75 mg/kg and were observed for seizures and/or death. All 62 rats that died did so within 17 min, preceded by seizures in 90.3%. Mean times-to-seizure and times-to-death, and mean lethal serum cocaine concentrations did not differ among groups. Serum progesterone levels (ng/ml +/- SEM) at the time of death were different among groups: 24 +/- 1.7 (C), 102 +/- 6.4 (P4), and 139 +/- 5.2 (Preg). Logistic regression dose/fatality curves, LD50s, and LD10s for the pregnant, progesterone, and control groups were not significantly different from one another. Though progesterone has enhanced cocaine's cardiac toxicity in some studies, it does not increase the risk of death from acute cocaine exposure in rats.

The design, synthesis, and biological activity of fluorinated amino-derivatives of the sesquiterpene lactone, parthenolide, are described. A fluorinated aminoparthenolide analogue with biological activity similar to the parent natural product was discovered, and its X-ray structure was obtained. This lead compound was then studied using (19)F NMR in the presence and absence of glutathione to obtain additional mechanism of action data, and it was found that the aminoparthenolide eliminates amine faster in the presence of glutathione than in the absence of glutathione. The exact changes in concentrations of fluorinated compound and amine were quantified by a concentration-reference method using (19)F NMR; a major benefit of applying this strategy is that no deuterated solvents or internal standards are required to obtain accurate concentrations. These mechanistic data with glutathione may contribute to the conversion of the amino-derivative to parthenolide, the active pharmacological agent, in glutathione-rich cancer cells.

Although malignant transformation of fetal cervical teratoma is extremely rare, perinatal morbidity is high and usually related to the size of the tumour, which may compromise fetal swallowing and subsequently lead to upper airway obstruction. We present a case in which mid-trimester serial sonography demonstrated markedly rapid early growth of a lesion of this type between 17 and 19 weeks' gestation indicating the aggressive nature of this tumour, assisting parental decision to terminate the pregnancy. Histopathology confirmed grade 3 immaturity of the lesion.

Objective To evaluate in vivo the anatomy and physiology of the normal early uteroplacental circulation. Design Forty-six women were included, all of whom continued their pregnancy into the second trimester. Color Doppler was used to identify peritrophoblastic flow, and spectral Doppler was used to analyze waveforms obtained from the different segments of the uteroplacental circulation. Results Flow was detected in the spiral arteries of the peritrophoblastic region in all patients. Flow was detected within the intervillous space in only one case. Conclusions This study demonstrated that color Doppler imaging can be employed as an in vivo means of studying the uteroplacental circulation. The study confirmed the in vitro findings that trophoblastic invasion of the decidual spiral arteries occurs at 5 to 6 weeks' gestation. The study also confirmed the fact that there is no noticeable blood flow within the intervillous space during most of the first trimester of a normal pregnancy. Both of these findings may serve to protect the early gestation from the forces of arterial blood flow.

Unusual sonographic visualization of the interlobar fissure of the herniated fetal liver in a case of right congenital diaphragmatic hernia was misinterpreted as the right diaphragm leading to misdiagnosis of this fetal anomaly.

We describe a case in which twin-twin transfusion with fetal death of the donor at 23 weeks was complicated by suspected intracranial embolic insult of the surviving recipient twin. Dynamic transient intracranial ultrasonographic findings were noted with complete resolution by 28 weeks. Subsequent severe microcephaly of the survivor with no further growth of any of the cranial parameters beyond 25 weeks was thought to be a result of this very unusual pathophysiologic mechanism.

Pulmonary hypoplasia is often associated with sonographically detectable conditions: oligohydramnios, prolonged premature rupture of membranes, and, not infrequently, fetal anomalies. In their efforts to improve prenatal sonographic diagnosis of this condition, investigators have used an array of different sonographic biometric measurements and fetal behavioral patterns. Definitions of these measurements and their respective successes in predicting pulmonary hypoplasia are presented. The sonographic parameters that have been of most value in the prediction of pulmonary hypoplasia are chest circumference, direct measurements of the lung, lung length, lung span to hemithorax diameter, and more complex formulas, such as lung area/heart area x 100/chest area. Although fetal measurements may help predict pulmonary hypoplasia, no single sonographic finding consistently leads to a prediction of the presence of pulmonary hypoplasia. Therefore, obstetric management (i.e., nonintervention) cannot currently be altered with the finding of abnormal biometric parameters unless a known lethal anomaly is observed.

Our purpose was to establish a nomogram of fetal sacral length throughout gestation and to assess its value in cases of abnormal fetal growth.A prospective cross-sectional study of 506 singleton fetuses with normal growth between 15 and 41 weeks' gestation was performed. Regression analyses were performed on sacral length, gestational age, biparietal diameter, head circumference, and femur length. The sacral length in 80 singleton gestations with abnormal growth (4090th percentile and 4010th percentile for gestational age) were compared with the nomogram.Linear relationships between gestational age and sacral length, biparietal diameter, head circumference, and femur length were demonstrated. Sacral length (centimeters) as a function of gestational age (weeks) was expressed by the regression equation: Sacral length = -0.108 + 0.102 Gestational age, with a Pearson correlation coefficient of R2 = 0.959. The sacral length of all 80 fetuses with abnormal growth demonstrated the same relationship to gestational age as did the 506 normal controls.This study defines the normal limits of sacral length; demonstrates a high correlation between sacral length, gestational age, and other standard measurements of fetal growth; and indicates that sacral length can predict gestational age, irrespective of fetal nutritional status.

The incidence of velamentous insertion of the umbilical cord is increased in multiple gestations. In singleton and twin gestations, this condition has been associated with lower mean birth-weight. We present three sets of twins (two monozygotic and one dizygotic) in which marked growth discordancy, ranging between 25 and 50%, was associated with velamentous insertion of the umbilical cord of the smaller twin in the absence of any other obvious pathology. In cases of marked growth discordancy in twins, velamentous insertion should be considered a possible etiology, and sonographic inspection of the placental insertion of the umbilical cord, particularly of the smaller twin, performed.

Objective Elevated interleukin-6 (IL-6) level in midtrimester amniotic fluid is associated with preterm delivery. We hypothesized that, in patients with elevated IL-6, vitamin C and alpha-fetoprotein may provide protection from spontaneous preterm delivery through antioxidant functions. Study Design Antioxidant potential of alpha-fetoprotein was assessed in vitro. Amniotic fluid was collected from a prospective cohort of patients who underwent midtrimester amniocentesis. In patients with IL-6 >600 pg/mL, alpha-fetoprotein, vitamin C, tumor necrosis factor–alpha, tumor necrosis factor receptors, and antioxidant capacity were compared between subjects with spontaneous preterm and term deliveries. Results Alpha-fetoprotein demonstrated 75% the antioxidant capacity of albumin in vitro. Of 388 subjects, 73 women had elevated IL-6 levels. Among these subjects, alpha-fetoprotein, but not vitamin C, was significantly lower in 9 women with preterm birth. Antioxidant capacity correlated with vitamin C and tumor necrosis factor receptors, but not with alpha-fetoprotein or pregnancy outcome. Conclusion Amniotic fluid alpha-fetoprotein, but not vitamin C, may protect against preterm birth in patients with elevated midtrimester IL-6 levels.

A prospective study of 98 pairs of nonstress tests (NSTs) was obtained simultaneously from members of 30 twin gestations. Fifty-five percent of the total fetal heart rate (FHR) accelerations of both twins were associated with each other and occurred within 15 seconds of each other. There were 8.46% synchronous FHR accelerations of both twins, possibly reflecting evoked fetal movements. Statistical analysis failed to reveal evidence of a dominant twin in utero, with one twin initiating the majority of coinciding fetal movements with statistical significance in only three gestations. Examination of combinations of the 30 separate individual significance tests using techniques of meta-analysis demonstrated a p value of 0.81, indicating lack of dominance in any of the 30 pairs of twins. The probability plot, consistent with the large p value for the combination test statistic, suggested that fetal movements in two gestations are related, strengthening the hypothesis of in utero tactile communication between twins. We conclude that the existence of a "dominant twin" in utero cannot be detected by electronic FHR monitoring methods.

Contraction dynamics of isolated papillary heart muscles from nonpregnant, pregnant, and progesterone-treated nonpregnant Long Evans rats were studied during exposure to cocaine. With increasing cocaine concentrations from 10−16 to 10−4 m , papillary muscles from nonpregnant rats demonstrated a biphasic pattern of positive, then negative, inotropy. Only negative inotropy with increasing cocaine concentrations was observed in papillary muscles from pregnant and progesterone-treated nonpregnant rats. Papillary muscles from pregnant and progesterone-treated nonpregnant rats became nonfunctional at cocaine concentrations 1–4 orders of magnitude lower than those for nonpregnant rats. These findings demonstrate that pregnancy and progesterone treatment alter cocaine effects upon cardiac papillary muscle function and response patterns and shift the cocaine dose-function curve to the left when compared to the nonpregnant group. We conclude that pregnancy increases the direct cardiotoxicity to cocaine, and progesterone may be responsible for this enhanced cocaine toxicity.

We present a case that describes a partial fetal response to external vibratory acoustic stimulation in that, although no fetal movements were elicited, a blunted, brief positive cardioacceleratory response was noted. This fetus exhibited features of the Pena-Shokeir syndrome, characterized by skeletal neurogenic atrophy, yet with a normal auditory system at autopsy. This observation may suggest that the prolonged increase in the basal fetal heart noted after fetal vibratory acoustic stimulation is sustained by active fetal movements, absent in this fetus due to joint contractures.

Pulmonary hypoplasia has been associated with persistent severe oligohydramnios. We present a twin gestation in which one twin had agenesis of the cloacal membrane and absent amniotic fluid with normal neonatal pulmonary structure and function prior to neonatal death. This case adds further knowledge to one of the suggested pathophysiologic mechanisms underlying pulmonary hypoplasia.

The Roberts-SC phocomelia syndrome (pseudothalidomide syndrome) is a rare, usually lethal condition involving short limbs and occasional hydrocephalus. Presented is a case in which prenatal sonographic findings were highly suggestive of this syndrome, although not definite. In this fetus, findings of hydrocephalus, short limbs, and probable pulmonary hypoplasia changed the intrapartum management. The findings, correlated with the postmortem radiography, led to diagnosis of probable Roberts-SC syndrome.

Cocaine produces a greater hypertensive response in pregnant ewes than in nonpregnant ewes. To determine whether pregnancy-related progesterone levels augmented this cocaine response, six nonpregnant ewes were surgically oophorectomized, implanted with femoral artery and vein catheters, and later administered progesterone 10 mg/kg intramuscularly for 3 days. Consistent responses in blood pressure and heart rate to intravenous norepinephrine 0.4 and 0.6 wg/kg, before and during progesterone treatment, indicated that progesterone did not increase a-adrenergic receptor sensitivity to exogenous norepinephrine. In contrast, intravenous cocaine at either 1.0 or 2.0 mg/kg produced approximately twofold greater increases in blood pressure and threefold greater increases in heart rate during each day of progesterone treatment when compared with responses to the same dose of cocaine before progesterone treatment. These results indicate that progesterone enhances the cardiovascular response to cocaine and does not involve an increase in «-adrenergic receptor sensitivity. (AM J OBsTET GVNECOL 1990;163:1659-64.)

Estimated fetal weights from 1684 cases with singleton, live infants born within 7 days of an ultrasonographic examinations were compared with their birth weights, which ranged from 520 to 5920 gm. Estimated weight calculated from Shepard's equation produced a linear relationship of birth weight against estimated weight with an intercept and slope of 209.5 gm and 0.929. Overall, 75% of the estimated weights were within 15% of the actual weight. A separate regression model that used the same variables from Shepard's equation failed to improve the comparison between estimated and actual weights. All cases were reevaluated with multiple regression modeling. Various examination-to-birth intervals were analyzed; intervals less than or equal to 3 days appeared optimal. The best equation increased the percent of cases that were within 15% of the actual birth weight to 80%. The plot of birth weight against estimated weight had an intercept and slope of 33.1 gm and 0.994. Unlike Shepard's equation, the best equation was not statistically different from the ideal one-to-one relationship between estimated and actual weight. When the new equation was applied to an additional 339 new cases, equally accurate results were obtained. Customizing a laboratory's ultrasonographic weight estimation equations may be necessary to obtain the best estimate of fetal weight.

The effects of intravenous cocaine on heart rate and blood pressure were studied in pregnant and oophorectomized nonpregnant ewes. In response to intravenous cocaine doses of 1.0 and 2.0 mg/kg, both pregnant and nonpregnant ewes demonstrated dose-dependent increases in systolic, diastolic, mean arterial, and pulse pressures with return to baseline by 30 to 60 minutes after cocaine administration. However, at both doses (1.0 and 2.0 mg/kg) pregnant ewes demonstrated greater increases in mean arterial pressure (+29.6%, +48.7%) than nonpregnant ewes (+15.6%, +27.7%) during the first 5 minutes after cocaine administration. Thereafter the responses were similar. Thus pregnancy increases the cardiovascular toxicity to cocaine.

Aim: To discuss the role of oxidant stress in preterm, premature rupture of the membranes (PPROM). Results: There is evidence to suggest that preterm, premature rupture of the membranes occurs secondary to focal collagen damage in the fetal membranes. Conclusion: Oxidant stress caused by increased ROS formation and/or antioxidant depletion may disrupt collagen and cause premature membrane rupture. We propose that supplementation with vitamins C and E may synergistically protect the fetal membranes, and decrease the risks of PPROM.

Congenital intracranial teratomas are rare and usually fatal. We present prenatal diagnosis of such a case associated with scalp, facial, and body skin edema, hepatomegaly, extramedullary hematopoiesis, polyhydramnios, and a hydropic placenta. These manifestations of high-output cardiac failure were thought to be the result of the large cardiac output required by massive intracranial tumor arteriovenous shunting.

Preterm premature rupture of membranes (PPROM) results initially from damage to collagen in the chorioamnion leading to a tear in the membrane. Tissue-damaging molecules called reactive oxygen species (ROS) are capable of damaging collagen in the chorioamnion that could lead to PPROM. This hypothesis is supported by epidemiological studies linking clinical conditions known to produce ROS or reduce antioxidant protection to PPROM, by in-vitro studies in which membrane segments exposed to ROS exhibited tissue alterations consistent with PPROM, and by clinical studies showing that chorioamnion and amniotic fluid samples obtained from PPROM patients exhibit excessive collagen degradation. The role of antioxidants to protect the chorioamnion from ROS damage has been demonstrated in one in-vitro study. A prospective, randomized blinded trial of antioxidant therapy during pregnancy is needed to evaluate this approach for the prevention of PPROM.

Infant survival with ever-decreasing birthweights is attainable with recent advances in maternal-fetal medicine and enhanced neonatal intensive care. We report a gestation complicated by severe chronic hypertension and fetal distress necessitating delivery at 26 1/7 weeks. The growth-retarded newborn weighed 345 g (12 oz) and survived with minimal sequelae despite a protracted and complicated neonatal course.