Nitric oxide synthase activities in human myometrium and villous trophoblast throughout pregnancy

OBJECTIVE: To study the changes in nitric oxide synthase activities in human myometrium and trophoblast throughout pregnancy and around delivery. METHODS: Samples of villous trophoblast were collected from women undergoing elective cesarean delivery at term (n = 12) or voluntary termination of pregnancy in the first (n = 27) or second (n = 11) trimesters of pregnancy. Myometrial samples were obtained from nonpregnant women undergoing hysterectomy (n = 5) and pregnant women both before (n = 7) and after (n = 7) the onset of spontaneous labor at term. Nitric oxide synthase activity was quantified for homogenized samples using the L-citrulline assay in the presence and absence of calcium. RESULTS: The highest levels of nitric oxide synthase activity were found in first-trimester villi (range 2-29 nmol L-citrulline/minute/g protein), with a significant fall in activity in the third trimester (range 2-10 nmol L-citrulline/minute/g protein; P < .001 for both calcium-dependent and calcium-independent activity). Myometrial activities were relatively low compared with those in the trophoblast (0-2 nmol L-citrulline/minute/g protein), with no significant differences in calcium-dependent activities between subgroups. Myometrial calcium-independent activities were lower in pregnant than in nonpregnant women (P = .007), with those in labor having levels higher than those not in labor (P = .048). CONCLUSION: Levels of nitric oxide synthase activity are relatively high in villous trophoblast, particularly during the first trimester. Although the contribution to total nitric oxide production in the uterus by myometrial nitric oxide synthase appears to be relatively small, nitric oxide produced by the trophoblast may play a role in maintaining uterine quiescence by a paracrine effect. Further work is needed to test this hypothesis and explore other possible roles for trophoblast-derived nitric oxide in early pregnancy.     

Age-related increase in auditory impairment in monkeys exposed in utero plus postnatally to methylmercury

During the first trimester, chorionicity can be assessed as early as five weeks post-conception, but a reliable detection of amnionicity cannot be performed before the 8th week when the amnion can be clearly imaged. The late second and third trimesters twin pregnancies are a true challenge to the imaging specialist because the detection of chorionicity and amnionicity has to rely upon sonographic clues, such as placenta location, fetal gender, membrane origin, thickness, and layer. Sonographic methods used to determine chorionicity and amnionicity in twins can be extrapolated to any multifetal pregnancy, regardless of the number of fetuses present.     

Maternal thyroid function in multiple pregnancy: the variable thyrotropic activity of human chorionic gonadotropin

The present study was undertaken to evaluate thyroid function and thyrotropic action of hCG in multiple pregnancy. We examined serum samples from 9 multiple pregnant women (3 triplets and 6 twins) and 27 singleton pregnant women as control subjects. Serum hCG levels in multiple pregnancy were higher than those in singleton pregnancy in the second and third trimesters (P < 0.01). The mean free T3 and T4 concentrations in multiple pregnancy did not differ from those in singleton pregnancy in each trimester. Serum hCG levels showed a statistically significant positive correlation with free T3 and T4 levels in singleton pregnancy (P < 0.001). However, these correlations were not observed in multiple pregnancy. Thyroid stimulation activity (TSA) determined by cAMP accumulation in FRTL-5 cells in multiple pregnancy sera was significantly higher than that in singleton pregnancy in the first trimester (P < 0.05), but did not differ in the second and third trimesters. Moreover, TSA did not show any correlation with serum hCG levels in multiple pregnancy in contrast with the results in normal pregnancy. A bioactivity/immunoreactivity ratio of hCG in multiple pregnancy was lower than in singleton pregnancy in the second and third trimesters. The discrepancy between immunoreactivity and thyrotropic activity of hCG may be caused by the variable thyrotropic potency of heterogeneous hCG molecules in multiple pregnancy.     

Brief communication: effects of diagnostic irradiation during pregnancy on head circumference at birth

A historical cohort study was carried out to evaluate the effects in utero medical ionizing radiation on head circumference at birth. The nature of medical practice in Rochester, Minnesota, and the Mayo Clinic medical records linkage system enabled us to provide accurate estimates of medical radiation absorbed dose in 9,793 pregnancies of 2,980 women pregnant in Rochester between 1917 through 1973. Data were controlled for sex of the fetus, duration of pregnancy and congenital head abnormalities. It was found that medical ionizing radiation in the second and third trimesters of more than 300 mrad were related to significantly decreased head circumference. There was no significant effect of radiation exposure in the first trimester or periconceptional period. Medical ionizing radiation in the second and third trimesters of more than 300 mrad is related to a significant yet minimal, decreasing head circumference at birth. Maximum effects were seen during the midgestational and second trimester periods.     

Changes in steroid hormones in plasma and myometrium and uterine activity in ewes during late pregnancy and parturition

In 7 ewes during late pregnancy, peripheral plasma concentrations of oestrogens were correlated with uterine activity (P less than 0-01; r=+0-47). In myometrial tissue, the concentration of progesterone was similar to that in plasma; it rose to a plateau from Days 115 to 130 of pregnancy and then fell, but was still detectable during parturition. Myometrial oestrogen concentration was much higher than in plasma; from a peak at Days 100-115 it decreased, but rose sharply just before parturition.     

Hydrosonography as an alternative or supplement to endosonography in stomach carcinoma

This study examined the effect of mothers' exposure to the 1957 A2/Singapore influenza virus in the first, second, and third trimesters of pregnancy on the electrodermal activity of their 15-year-old offspring. The epidemic occurred during cold months of the year. The results show that maternal viral (and cold) exposure during all trimesters of pregnancy produced a lower frequency of nonspecific electrodermal responses and diminished responsivity to 75-db and 90-db tones as compared with the offspring of mothers who were not exposed. However, there was a critical effect of second trimester exposure as indicated by an increase in frequency of nonresponses to orienting tones. The findings are compared with those from an earlier study from Mauritius involving 3-year-old children in which the effects of exposure to the 1968 A2/Hong Kong virus were examined and in which the effect of could exposure could be examined separately because viral exposure occurred during the hot months.     

Corticotropin-releasing hormone receptor subtype 1 is significantly up-regulated at the time of labor in the human myometrium

Circulating concentrations of CRH rise late in human pregnancy, reaching a peak at labor. The presence of functional CRH receptors, CRH-R1 and CRH-R2, in the human myometrium suggests that CRH may modulate uterine activity. We hypothesized that the number of CRH receptors would be higher in myometrium than fetal membranes (FM) and would change during labor. Myometrial samples were collected from the lower segment (LS) in nonpregnant, preterm (32 +/- 2 weeks), and term (39 +/- 1.6 weeks) pregnant patients before and at labor. Fundus and LS samples were also collected from nonpregnant, pregnant, laboring, and postpartum women. FM were collected at term and at labor. We identified CRH receptors in myometrium and FM by semiquantitative RT-PCR and immunohistochemistry. CRH-R1 messenger ribonucleic acid (mRNA) in the LS was decreased in pregnancy and increased significantly in both preterm and term labor (P < 0.05), but remained unchanged in the fundus. CRH-R2 mRNA was present in 28% of LS myometrium with no change at labor. CRH-R1 and CRH-R2 protein was localized to myometrial smooth muscle in nonpregnant and laboring patients, with lower levels at term. CRH-R1 mRNA was present in chorion and decidua, but CRH-R2 was undetectable in these tissues. We conclude that CRH-R1 is expressed preferentially in myometrium and FM. Changes in CRH receptors during labor are consistent with CRH mediating effects on myometrial activity.     

Usefulness of color kinesis imaging for evaluation of regional right ventricular wall motion in patients with surgically repaired tetralogy of Fallot

We evaluated regional right ventricular wall motion during systole in patients with surgically repaired tetralogy of Fallot (TOF) using color kinesis imaging. Color kinesis images were obtained in a subcostal sagittal view from 19 patients with repaired TOF (TOF group), aged 3 to 5 years, and 20 age-matched normal subjects (control group). For regional wall motion analysis, the endocardial motion distance and the fractional area change (FAC) were calculated for 6 segments obtained from color kinesis images. The endocardial inward excursion distances and the FACs in the upper, middle, and lower posterior segments of the TOF group were significantly greater than those of the control group (p <0.01 for each segment). The upper anterior segment showed significantly reduced inward excursion distance and FAC in the TOF group than in the control group (p <0.01, both). The dyskinetic outward excursion distances of the middle and lower posterior segments were significantly lower in the TOF group than in the control group (p <0.01, both). In the upper and middle anterior segments, the endocardial outward excursion distances were significantly higher in the TOF group than in the control group (p <0.01 and 0.05). Correlation between right ventriculographic and color kinesis measurements was excellent (y = 1.14x - 1.30, r = 0.87 for the endocardial inward excursion, and y = 1.03x +/- 0.56, r = 0.91 for the FAC). In conclusion, color kinesis is a useful method for assessing regional right ventricular wall motion. Segmental analysis of color kinesis images provides accurate, automated, and quantitative diagnosis of regional right ventricular wall motion abnormalities in patients with surgically repaired TOF.     

Interaction of dexamethasone and Salmonella enteritidis immune lymphokines on Salmonella enteritidis organ invasion and in vitro polymorphonuclear leukocyte function

OBJECTIVE: To evaluate the effects of gemeprost on utero-placental and luteal circulation and on the embryo/fetus in normal first trimester pregnancies. STUDY DESIGN: Sixty-seven women with a normal first trimester pregnancy requesting termination of pregnancy for psychosocial reasons were randomly allocated to pre-operative treatment with vaginal suppositories containing placebo or gemeprost. The women underwent transvaginal color and spectral Doppler ultrasound examination before the application of the suppository, 4 h after the application of the suppository but before the abortion, and on the seventh post-operative day. Blood flow velocities in the uterine and subchorionic arteries, the intrachorionic area and arteries in the wall of the corpus luteum and the embryonic/fetal heart rate were measured. RESULTS: The median value for pulsatility index (PI) in the dominant uterine artery was 2.4 before treatment with gemeprost and 8.5 4 h after treatment (P = 0.0006); the corresponding values for time-averaged maximum velocity (TAMXV) being 27 cm/s and 10 cm/s (P = 0.0006). Four (14%) of 28 embryos/fetuses in the gemeprost group were dead 4 h after treatment with gemeprost and the median heart rate of those still alive was significantly lower than before treatment (130 vs. 163 bpm; P = 0.003). In the placebo group, the results for the uterine arteries and the embryonic/fetal heart rate did not differ significantly between the first and second ultrasound examinations. The median values for PI and TAMXV in the arteries of the corpus luteum wall at the first ultrasound examination were 0.71 and 18 cm/s, respectively, in the placebo group and 0.71 and 20 cm/s, respectively, in the gemeprost group. These values remained almost unchanged at the second and third ultrasound examinations in both groups. CONCLUSION: Gemeprost has profound effects on utero-placental circulation in the first trimester and can induce embryonic/fetal bradycardia and sometimes embryonic/fetal demise. It has no unequivocal effect on luteal circulation.     

Decreased interleukin-2 production by rat uterine artery, aorta and uterine tissues during pregnancy

Changes in size and function during pregnancy are unique to the uterine artery. The aim of this study was to determine the interleukin (IL)-6 activity of the uterine artery wall tissue in pregnant rats. A total of 18 Charles River white rats (nine virgin and nine in midpregnancy) were used for the study. Bilateral uterine arteries were obtained, together with reference tissues from aorta and uterus. IL-6 production was measured as optical density (OD)/mg protein, in control culture media, and in the presence of stimulants including IL-1, tumour necrosis factor alpha and lipopolysaccharide. Polyclonal rabbit anti-human IL-6 antibodies were used to assess IL-6 activity. In control culture medium, uterine artery tissue samples from virgin rats produced significantly higher concentrations of IL-6 than samples obtained from pregnancy animals (1.8 +/- 0.3 versus 0.9 +/- 0.25 OD/mg protein respectively (mean +/- SE, P = 0.001). Stimulation by lipopolysaccharide increased IL-6 activity of the uterine artery wall. In comparison with the uterine artery, the aorta produced higher activities of IL-6, and its production in virgin animal samples was higher than during pregnancy. Stimulants increased IL-6 production by both aorta and uterus tissues. Neutralization of IL-6 activity was obtained in a range of 77-93% in all samples. The lower level of IL-6 activity during pregnancy in the uterine artery and in reference tissues including aorta and uterus, may be related to acceptance of pregnancy by maternal tissues.     

Diagnosing gestational hypertension and preeclampsia with the 24-hour mean of blood pressure

The use of ambulatory blood pressure monitoring has provided a method of blood pressure assessment that may compensate for some of the limitations of isolated measurements. Here we aim to examine prospectively the effectiveness of the commonly used 24-hour mean as a potential screening test for the identification of gestational hypertension and preeclampsia. We analyzed 503 blood pressure series from 71 healthy pregnant women and 256 series from 42 women who developed gestational hypertension or preeclampsia. Forty-eight-hour blood pressure monitoring was done once every 4 weeks after the first obstetric consultation. Sensitivity and specificity of the 24-hour mean of blood pressure were computed for each trimester of pregnancy by comparing distributions of values obtained for healthy and complicated pregnancies, without assuming an a priori threshold for diagnosing gestational hypertension on the basis of mean blood pressure. Sensitivity ranges from 31.8% for diastolic blood pressure in the second trimester to 84.1% for systolic blood pressure in the third trimester. However, specificity is as low as 6.9% for diastolic blood pressure in the first trimester. The positive predictive value does not reach 55% for any variable in any trimester. The higher relative risk was consistently obtained for systolic blood pressure (4.9 in the third trimester). Despite the highly statistically significant differences in blood pressure found between healthy and complicated pregnancies in all trimesters, the daily mean of blood pressure does not provide a proper and stable individualized test for diagnosing hypertensive complications in pregnancy. Other indexes obtained from the blood pressure series have been shown, however, to identify early in pregnancy those women who subsequently will develop gestational hypertension or preeclampsia, rendering ambulatory blood pressure monitoring a useful, but still costly, technique in pregnancy.     

Introduction to microscopic research of silver halides and related dispersed systems

> Objective: To establish whether uterine artery flow velocity waveforms in the second trimester are associated with adverse pregnancy outcome in women with a poor obstetric history. Methods: We reviewed the obstetric case notes of 50 women with a poor obstetric history in previous pregnancies in whom uterine artery flow velocity waveforms had been obtained at 18 weeks gestation. Results: In this population 40% had an adverse pregnancy outcome (preeclampsia, pregnancy-induced hypertension, preterm delivery, birthweight <10th percentile or perinatal death). Preeclampsia, perinatal death, and preterm delivery were all significantly associated with abnormal uterine artery waveforms at 18 weeks. Conclusions: Assessment of uterine artery flow velocity waveforms at 18 weeks gestation shows promise as a screening test in the high risk obstetric population. The technique requires formal evaluation in a prospective, double blinded study.     

Ultrasonographic and hormonal monitoring of pregnancy in the saddle back tamarin, Saguinus fuscicollis

Ultrasonography was used in six saddle back tamarin females (Saguinus fuscicollis) to diagnose pregnancy, monitor the patterns of uterine growth and embryonic/foetal development and examine the incidence loss of single embryos/foetuses. Pregnancy was reliably diagnosed 17 days after conception, 10 days earlier than by plasma progesterone measurement. The patterns of uterine and embryonic/foetal growth paralleled those reported for the common marmoset, including a delay in embryonic development. The results support the hypothesis of retardation of organogenesis in most callitrichid species. Individual embryos could be reliably identified from day 50 of pregnancy; a loss of single embryos/foetuses after this stage did not occur. All pregnancies were carried to term, resulting in five times twins and one singleton. The smaller litter size compared to the common marmoset may be due to loss of single embryos at earlier stages of pregnancy or to a lower ovulation rate.     

Placental implantation at 18 weeks and migration throughout pregnancy

BACKGROUND: We wanted to find the most frequent site of placental implantation at 18 weeks' gestation and placental migration during gestation. METHODS: Placental location was identified in 2,526 singleton pregnancies at 18 weeks' gestation and characterized into nine groups. Placental migration in 1,336 of these pregnancies was assessed by serial ultrasonography. RESULTS: At 18 weeks' gestation, posterior, high placental implantation was more common (45.1%) than anterior, high implantation (42.1%). Relocation of posterior, high placentas farther fundally (16.9%) was three times more likely than farther fundal migration of anterior, high placentas (4%). CONCLUSIONS: Posterior fundal placental implantation is more common at 18 weeks' gestation than anterior implantation. Posteriorly implanted placentas are more likely than anterior placentas to migrate farther fundally during gestation. The greater relocation of posterior placentas farther fundally suggests a greater growth of posterior versus anterior uterine wall smooth muscle.     

Angiotensin II has depressor effects in pregnant and nonpregnant women

Studies in anesthetized animals suggest that angiotensin II evokes a depressor as well as a pressor effect, which becomes evident on cessation of infusion. We have studied 18 nonpregnant and 8, 23, and 22 women in the first, second, and third trimesters of pregnancy to determine whether such an effect is present in conscious women, whether it is dose dependent, and whether it is influenced by pregnancy. Angiotensin II was infused intravenously in doubling concentrations at 10-minute intervals until a pressor effect of approximately 20 mm Hg was observed. The infusion was stopped, and blood pressure was monitored at 2-minute intervals for 30 minutes. There was a significant diastolic depressor effect after stopping angiotensin II in the nonpregnant women and those in the second and third trimesters of pregnancy. Individual women required differing doses of angiotensin II to evoke the standardized pressor response. It was thus possible to examine the depressor response in each group in relation to infused doses of angiotensin II. In nonpregnant women and in those in the second and third trimesters of pregnancy, the depressor response was dose dependent (P<.001). At any given dose, the depressor response deepened as pregnancy progressed (P<.001). Basal plasma prostacyclin concentrations rise in pregnancy, and angiotensin II can stimulate prostacyclin synthesis. This might mediate the depressor effect. In conclusion, the diminished pressor response to angiotensin II in normal pregnancy may be partly due to an increasing depressor effect of the hormone.     

Spontaneous carotid-cavernous fistula: correlations between clinical findings and venous drainage

OBJECTIVE: The purpose of this study was to compare the routine pre-natal surveillance carried out in nine European Gyneco-Obstetric units. MATERIAL AND METHOD: A survey was carried out between October 1992 and November 1993 with the aid of a questionnaire. The questionnaire contained 118 questions covering clinical examinations and explorations undertaken systematically during the first, second and third trimesters and at the end of pregnancy before delivery. To ensure that the replies were accurate, the survey was carried out on the spot in the units concerned with the head of the unit. RESULTS: The survey revealed a certain number of differences in the surveillance carried out in the various units. The units did not all carry out systematic blood tests for toxoplasmosis, AIDS and hepatitis B at the first examination. The same applied to fasting blood glucose and the bacterial culture of the urine. Nor did all the units automatically undertake vaginal examination during the second and third trimesters and the English departments were not all convinced of the need for systematic ultrasound tests. Only five of the nine units undertook routinely cardiotocographic recordings of the fetal heart rate at the end of the pregnancy. CONCLUSION: The differences observed in the various surveillance procedures simply reflect our uncertainty regarding the different tests we use to monitor pregnancies. At a time when financial constraints are forcing us to make choices, there is an urgent need to assess the effectiveness and the cost of the various elements of our prenatal monitoring.     

Endothelin receptor type A and B gene expression in human nonpregnant, term pregnant, and preeclamptic uterus

OBJECTIVE: The aim of this study was to quantify the gene expression of ETA and ETB receptors within the different uterine segments of nonpregnant, normal pregnant, and preeclamptic women. STUDY DESIGN: Biopsy samples from the cervix, isthmus, and corpus uteri were obtained from eight nonpregnant, nine term pregnant, and seven preeclamptic women. The concentration of ETA and ETB receptor messenger ribonucleic acid were determined by a solution hybridization technique with complementary ribonucleic acid probes. Results are presented in counts per minute per microgram of total nucleic acid as mean +/- SEM. RESULTS: The expression of messenger ribonucleic acid encoding the ETA receptor was generally higher in the upper than in the lower uterine segment in nonpregnant, normal pregnant, and preeclamptic myometrium, whereas the opposite pattern was seen with regard to ETB. During normal pregnancy the concentrations of ETA receptor messenger ribonucleic acid in the corpus and ETB receptor messenger ribonucleic acid in the isthmus were significantly elevated compared with those in nonpregnant women. This enhanced gene expression was, however, not observed in the preeclamptic group. CONCLUSION: Our finding of segmentally differentiated endothelin receptor gene expression is compatible with a role for endothelin-1 in stimulating uterine contractions through ETA receptors during spontaneous labor and suggests a relaxing effect of the ETB receptor on the myometrium.     

Ectopic pregnancy in the stump of the uterine tube after in vitro fertilization

A rare case of ectopic pregnancy in stump of uterine tube after IVF, which was done after bilateral removal of uterine tubes, caused by uterine tube pregnancies was described. Diagnostic difficulties were shown in that case.     

A congenital pulmonary anomaly (hamartoma) in a seven-month-old bovine fetus

A cage was developed which included a squeeze wall for easy handling of the gibbon (Hylobates lar) and which provided gibbon breeding pairs with privacy from others of the same species. Females living in this environment displayed menstrual and vaginal eversion cycles averaging 30 days (range 22-44). Twelve compatible pairs produced eight live infants from 15 conceptions in a 33-month period. Two full term stillbirths, two abortions, and three current pregnancies accounted for the other seven conceptions. Monthly uterine palpations were performed and pregnancy could be detected as early as 27 days after conception. The compatibility of the mating pairs was determined to be the major factor in the natural breeding of gibbons in captivity. This was demonstrated by obtaining only 12 compatible pairs from 22 attempted pairings.     

Maternal shunt dependency: implications for obstetric care, neurosurgical management, and pregnancy outcomes and a review of selected literature

OBJECTIVE: Because more women with cerebrospinal fluid shunts are surviving to child-bearing age, neurosurgeons, obstetricians, and other health care professionals require information about the care of these patients, especially during pregnancy and delivery. The purpose of this study was to gather comprehensive data from women with shunts regarding their clinical histories during and immediately after pregnancy. The following questions were addressed. 1) How does maternal shunt dependency influence the course of pregnancies and pregnancy outcomes? 2) What neurosurgical complications characterize this population of patients? 3) What complications of shunt dependency influence obstetric management, including prenatal testing and delivery? METHODS: A total of 37 respondents (age, 18-41 yr), accounting for 77 pregnancies, completed a questionnaire providing information on maternal background and medical history, shunt performance during pregnancy, management of delivery, pregnancy outcomes, and unusual complications. RESULTS: Fifty-six pregnancies resulted in live births; of these, 47 occurred in women with ventriculoperitoneal shunts. Three women underwent therapeutic abortions, 1 experienced preterm delivery, and 8 experienced 17 miscarriages. Four women experienced seizures during pregnancy, five reported third-trimester headaches, and eight described abdominal pains during the first and third trimesters. Four babies were diagnosed as having congenital defects. Shunt malfunctions and revisions occurred 10 times in 7 women, either during pregnancy or within 6 months after delivery. No acute malfunctions occurred during delivery. Forty-seven cases, representing 84% of all pregnancies, exhibited no shunt malfunctions or revisions. CONCLUSION: This study extends previous observations to a larger population of shunt-dependent mothers. The results suggest that maternal shunt dependency entails a relatively high incidence of complications but that proper care of these patients can lead to normal pregnancies and deliveries.