Up-regulation of guinea pig myometrial beta-adrenoreceptors by systemic estradiol and progesterone.

The effects of systemic administration of 17 beta-estradiol (E2) and progesterone (P) on the concentration and affinity of myometrial beta-adrenoreceptors were studied in non-pregnant, previously oophorectomized guinea pigs receiving a continuous infusion of E2, P, a combination of the two hormones, or placebo for 7 days. Myometrial beta-adrenoreceptors were characterized by using (-)-[125I-cyanopindolol as the specific beta-adrenoreceptor ligand. Compared to that in the control group, E2 administration resulted in a 7-fold increase in the density of myometrial beta-adrenoreceptors. Administration of P alone resulted in a significant increase in both beta-adrenergic receptor concentration and the receptor dissociation constant (Kd). Finally, a combination of E2 and P treatment did not result in any synergistic or additive effect for the beta-adrenergic receptors, while the Kd was twice that of the control or E2-treated animals. We conclude that systemic administration of these sex steroid hormones, directly or indirectly, modulates myometrial beta-adrenergic receptor concentrations and their ligand affinity.

Changes in placental atrial natriuretic peptide receptors associated with severe toxemia of pregnancy.

We have previously demonstrated the presence of atrial natriuretic peptide (ANP) specific receptors in normal human placentas. Since toxemia of pregnancy may affect important metabolic, transport and hemodynamic functions of placentas, we have asked the question whether binding properties of human placental ANP receptors are changed in patients with severe toxemia of pregnancy when compared to normal patients. ANP receptors in plasma membranes from normal and severely toxemic patients were characterized by in vitro radioligand assays utilizing [125I]-alpha-hANP. In all cases, we identified specific, high affinity, low capacity ANP binding sites in a microsomal fraction of human placentas. Although the total concentration of receptors did not differ between the two groups, the dissociation constant, KD, was significantly higher in placentas from severely toxemic patients than from normal controls. From the above we conclude that placental ANP receptors are dynamically modulated and their characteristics may be altered in severe toxemia of pregnancy.

Diagnosis and successful treatment of fetal goitrous hyperthyroidism caused by maternal Graves disease.

BACKGROUND: Intrauterine diagnosis and treatment of fetal goitrous hyperthyroidism due to maternal Graves disease has not been reported. CASE: A case of fetal goitrous hyperthyroidism caused by maternal Graves disease was diagnosed and treated in the second trimester. High concentrations of both thyroid-stimulatory immunoglobulins (Igs) and thyrotropin-binding inhibitory Igs were detected in both maternal and fetal umbilical venous blood. Maternal propylthiouracil (PTU) treatment resulted in normalization of fetal thyroid function and a decrease in the size of the fetal thyroid goiter. Although euthyroid immediately after birth, the infant later became hyperthyroid and required treatment with PTU. CONCLUSION: The relatively high frequency of fetal thyroid disorders in maternal Graves disease warrants complete maternal and fetal evaluation. Fetal diagnosis and treatment of either hyperthyroidism or hypothyroidism are feasible and necessary to prevent fetal morbidity and mortality.

Nonimmunologic fetal hydrops associated with hyperreactio luteinalis.

A case of nonimmunologic fetal hydrops associated with maternal bilateral theca lutein cysts (hyperreactio luteinalis) is presented. It is proposed that the theca lutein cysts were caused by elevated human chorionic gonadotropin (hCG) production from the hydropic placenta. These cysts appeared to regress after the patient's delivery, while beta-hCG levels declined.

Total parenteral nutrition in pregnancy.

Total parenteral nutrition has been used infrequently during pregnancy. Because of the special nutritional needs and hormonal environment of the maternal-fetal unit, there is uncertainty as to the optimal composition and quantity of total parenteral nutrition therapy. In this report two important questions are examined: whether or not a protein replacement commonly used in total parenteral nutrition provides adequate levels of essential amino acids to fetus and mother, and whether or not the daily use of fat emulsion as part of total parenteral nutrition is associated with unwanted side effects. The authors' data suggest that certain adjustments have to be made in the quantity and composition of total parenteral nutrition constituents to provide the necessary nutritional requirements for metabolic and anabolic needs without increasing the overall risk for complications.

Sinusoidal fetal heart rate pattern associated with butorphanol administration.

One hundred nineteen fetal heart rate monitor tracings from term-pregnant patients in labor were reviewed by two independent observers to test the hypothesis that Stadol administration to mothers does not result in sinusoidal fetal heart rate pattern. There was agreement with regard to the interpretation of the tracings in 106 instances. Fifty-one patients received intravenous Stadol for narcotic analgesia. Seventy-five percent of these patients demonstrated a transient sinusoidal fetal heart rate pattern after Stadol administration. In a small number of patients, this pattern recurred either with or without additional Stadol treatment. In contrast, patients who did not receive Stadol therapy (N = 55) demonstrated a significantly lower incidence of sinusoidal fetal heart rate pattern (13%), the duration of which was significantly shorter than that seen in the former group. From these we conclude that Stadol therapy during labor is strongly associated with the appearance of sinusoidal fetal heart rate pattern. There were no short-term maternal or neonatal adverse sequelae. In the absence of other fetal heart rate signs suggestive of fetal distress, the presence of sinusoidal fetal heart rate pattern after Stadol administration does not indicate fetal hypoxia.

Efficacy of combined administration of magnesium sulfate and ritodrine in the treatment of premature labor.

Seventy-four patients in preterm labor at 20-35 weeks' gestation were randomly assigned to receive ritodrine (N = 36) or ritodrine plus magnesium sulfate treatment (N = 38) for tocolysis. Ten did not complete therapy and were excluded from analysis. Nineteen of 32 patients (59%) in the ritodrine plus magnesium sulfate group were successfully treated, compared with only 11 of 32 patients (34%) in the ritodrine-only group (P less than .05). Of the 21 patients who failed to respond to the initial ritodrine treatment, 16 received intravenous magnesium sulfate supplemental therapy; 75% of this group were treated successfully. The frequency of adverse maternal and fetal side effects did not differ between the treatment groups. In the combined group compared with the ritodrine group, the dose requirements for ritodrine therapy as well as the total duration of treatment for both ritodrine and magnesium sulfate were reduced significantly. We conclude that concurrent administration of ritodrine and magnesium sulfate is more efficacious than ritodrine alone and does not appear to increase the frequency of adverse side effects.

Anterior sacral meningocele in pregnancy.

Anterior sacral meningocele is a rare abnormality. Only 14 cases of it have been reported in association with pregnancy. Of those 14 patients, three died as a result of rupture of the meningocele during labor and postpartum. A new case is presented; the clinical presentation, the diagnosis, and treatment are discussed. The obstetric management of the case is discussed and a plan for management is suggested.

Premature rupture of membranes: a prospective, randomized evaluation of steroids, latent phase, and expectant management.

A prospective, randomized study was conducted comparing the use of betamethasone and early delivery, early delivery alone, and expectant management in patients in the 28th to 34th week of pregnancy with premature rupture of the membranes (PROM). Tocolytic drugs were used to delay delivery until 24 hours had elapsed after the first dose of steroid or 24 to 48 hours of latent period had elapsed in the second group. There were no significant differences in maternal age, gestation at PROM, maximum maternal temperature, birth weights, maternal hospital days, respiratory distress, maternal sepsis, or delivery routes in the three groups. Comparisons with one other similar prospective, randomized study support the concept that expectant management offers less risk from tocolytic side effects.

Heparin-induced thrombocytopenia in pregnancy. A case report.

A patient developed heparin-associated thrombocytopenia during pregnancy. Pregnant patients with pulmonary embolisms can be treated with long-term anticoagulation, but platelet counts must be done periodically.

An unusual cause of postoperative fever: a case report.

A typical gynecologic approach to postoperative fever and its theoretical as well as practical shortcomings is discussed. Difficulties in establishing a specific diagnosis in the gynecologic patient with postoperative fever are explored. A case of exacerbation of dermatomyositis in the immediate postoperative period illustrates the failings of our current approach to postoperative fever.

Type II congenital cystic adenomatoid malformation of the lung with a mediastinal shift. A case report.

We report a case of an early (22-week) prenatal diagnosis of type II congenital cystic adenomatoid malformation of the lung complicated by a mediastinal shift. Detailed ultrasound examination of the fetus, including fetal Doppler velocimetry and echocardiography, and diagnostic amniocentesis were normal. There was a gradual, spontaneous resolution of the mediastinal shift and improvement in the lung lesions. The intrapartum and early neonatal clinical courses were uneventful.

Compliance-weight deficit index. Combining umbilical artery resistance and growth deficit for predicting intrauterine growth retardation and poor perinatal outcome.

One hundred sixty-six patients underwent examination of the umbilical artery (UA) by continuous wave Doppler ultrasound one week prior to delivery. The UA compliance deficit (CD) and weight deficit (WD) were combined into an index (CWDI) by a formula based on the Pythagorean Theorem. CWDI represents the hypotenuse, and CD and WD represent the two perpendicular lines of a triangle: (CWDI = square root of CD2 + WD2). Perinatal outcomes were evaluated by the number of perinatal deaths, delivery for fetal indications prior to 37 weeks' gestation, five-minute Apgar score < 7, neonatal intensive care unit (NICU) admission and the presence of intrauterine growth retardation (IUGR). A CWDI value of > or = 20 was the most discriminatory in identifying fetuses with poor outcomes. Fetuses with CWDI > or = 20 were more likely to be premature (P < .001) or growth retarded (P < .001) or have lower Apgar scores (P < .005) and longer NICU stays (P < .001). Seven of the eight perinatal deaths occurred in patients with abnormal CWDI (P < .001). The sensitivity of an abnormal CWDI was 95% for IUGR, 60% for preterm delivery, 82% for NICU admission, 90% for Apgar score < 7 at five minutes, 87% for perinatal mortality and 68% for overall poor perinatal outcomes. CWDI is a sensitive index for the identification of fetuses with IUGR and poor perinatal outcome.

Umbilical vessel flow velocity waveforms in cord entanglement in a monoamnionic multiple gestation. A case report.

An unusual flow velocity waveform pattern was seen in a case of cord entanglement in a monoamnionic multiple pregnancy. The umbilical artery systolic:diastolic ratio was abnormally high (greater than 95th percentile for gestation), and diastolic notching was present. The umbilical vein flow velocity waveform was pulsatile, with flow absent during the diastolic phase of the cardiac cycle. The presence of that pattern strongly suggested a severe cord accident and mandated an immediate evaluation of fetal well-being.

Vasopressin-resistant diabetes insipidus, liver dysfunction, hyperuricemia and decreased renal function. A case report.

A case of transient nephrogenic diabetes insipidus occurred in late pregnancy, the first associated with biopsy-proven hepatitis. Five previously reported cases occurred in pregnancy. All six patients demonstrated similar but transient signs, symptoms and laboratory abnormalities suggesting a syndrome peculiar to pregnancy. The characteristics of this syndrome are elevated liver function studies, decreased renal function, hyperuricemia and transient vasopressin-resistant diabetes insipidus.

Conservative management of splenic subcapsular hematoma in the third trimester of pregnancy. A case report.

A delayed splenic hemorrhage from a subcapsular hematoma occurred in association with pregnancy. That rare complication carries a high mortality rate, is rarely diagnosed preoperatively and is correctly diagnosed only 20% of the time. The clinical setting and a high index of suspicion led us to investigate for the presence of a splenic hematoma. A computed tomographic scan was invaluable in establishing the diagnosis. We adopted a conservative approach and followed the patient's clinical course from 28 to 40 weeks' gestation, until she delivered vaginally. In general, patient management (conservative vs. splenectomy) and mode of delivery will depend on how close one is to the initial event, on the patient's and fetus's clinical condition and on the gestational age.

Forskolin: unique diterpene activator of adenylate cyclase in pregnant and nonpregnant guinea pig myometrial membranes.

In guinea pig myometrium, beta-adrenergic receptors are functionally coupled to adenylate cyclase. beta-Adrenergic receptor agonists in the presence of guanosine triphosphate stimulate adenylate cyclase activity, thus increasing 3'5'-cyclic adenosine monophosphate synthesis and promoting myometrial relaxation. In pregnant animals close to term (65 days), beta-adrenergic receptor density as well as basal and (-)isoproterenol-dependent (in the presence of guanosine triphosphate) adenylate cyclase activity is significantly higher than that in nonpregnant animals or those in early pregnancy. Since this system appears to be made up of at least three components (beta-adrenergic receptor, guanosine triphosphate-binding protein, and a catalytic component), these observations on total adenylate cyclase activity may reflect alterations in one or more of these components. To answer the question whether the catalytic unit of this system can be directly assayed and whether its activity is influenced by pregnancy, we have performed in vitro experiments to measure the enzymatic activity of the catalytic component of the beta-adrenergic receptor-adenylate cyclase complex in guinea pig myometrial membranes. We have used two compounds that stimulate the catalytic component: forskolin and manganese chloride. Forskolin, regardless of the presence or absence of guanosine triphosphate, is the most potent stimulator of adenylate cyclase activity in myometrial membranes from nonpregnant and pregnant animals; manganese chloride is a less potent activator. The degree of adenylate cyclase stimulation by forskolin tends to be higher in uteri from pregnant (greater than or equal to 0.5 gestation) than from nonpregnant or postpartum animals. It was concluded: that adenylate cyclase stimulation by forskolin does not depend on the presence of beta-adrenergic receptor agonists or guanosine triphosphate and that with advancing gestation there might be a qualitative or quantitative change with regard to the interaction between forskolin and the presumed catalytic component of the beta-adrenergic receptor-adenylate cyclase complex.

Forskolin-stimulated adenylate cyclase activity in fetal and adult rabbit myocardial membranes.

It has previously been reported that there is an increase in the concentration of myocardial beta-adrenergic receptors as well as an increase in the sensitivity of adenylate cyclase stimulation by L-isoproterenol in fetal rabbit myocardial membranes from 21 to 31 days' gestation. To investigate whether a change in the catalytic component of the beta-adrenergic receptor-adenylate cyclase complex is responsible for the observed increase in adenylate cyclase activity, I have measured the latter in the presence of forskolin and manganese chloride, compounds that can directly stimulate the catalytic component. Myocardial membranes were obtained from fetal rabbits at 21, 28, and 31 days' gestation and from pregnant adult animals. There was an increase in basal adenylate cyclase activity from the fetal to the adult stage. The percent of maximal stimulation by L-isoproterenol in fetuses from 21 through 28 to 31 days' gestation and in the adult animal. However, although forskolin was the most potent stimulator of adenylate cyclase, the degree of stimulation was equivalent in all groups tested. Similar results were obtained with manganese chloride. We conclude that the catalytic component of the beta-adrenergic receptor-adenylate cyclase complex in myocardial membranes is stimulated to an equivalent degree at all gestational ages in fetal and adult rabbits and shows no maturational changes.

Adenylate cyclase activity in fetal rabbit myocardium.

Adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] was determined in vitro in fetal rabbit myocardial membranes from individual fetal pups at 21 to 31 days gestation (term, 31 days). Basal and NaF-stimulated adenylate cyclase activities did not change during 21-31 days gestation. Significant stimulation of the enzyme by l-isoproterenol was observed only in the presence of guanosine triphosphate (100 microM). Under these conditions, maximal adenylate cyclase stimulation by l-isoproterenol (100 microM) was significantly higher at 25-31 than at 21 days gestation. Moreover, EC50 (Kact) for l-isoproterenol at 25-31 days was significantly lower than at 21 days gestation. We conclude that, in fetal rabbit myocardial membranes, there is an increase in the sensitivity of adenylate cyclase stimulation by l-isoproterenol from 21 to 25-31 days gestation.

Beta-adrenergic receptor interaction with guanosine triphosphate in fetal rabbit myocardial membranes.

To investigate whether, in developing fetal rabbit myocardium, the affinity of beta-adrenoreceptors (beta-AR) for beta-AR agonists is regulated by guanosine triphosphate (GTP), we performed in vitro competition experiments utilizing 125I-hydroxybenzylpindolol (I-HYP), a beta-AR antagonist, as the radioligand, and l-isoproterenol (l-I) and l-propranolol (l-P), as beta-AR agonist and antagonist, respectively. At gestational ages from 21 to 31 days (term 31 days), in the presence of GTP, there was a 4-fold increase in the KI for the inhibition of specific I-HYP binding by l-I but not by l-P. Moreover, in the presence of GTP, there was a significant shift of the Hill coefficient to values closer to 1 only in the case of l-I. We conclude that: (1) beta-AR can form a 'high affinity' complex with l-I in the absence of GTP, detectable from days 21 to 31 of gestation; (2) the conversion of the former to a 'low affinity' state appears to be a GTP-dependent process.