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Biomedical subjects

C G Hatjis

Publications and source records attributed to C G Hatjis.

At least 19 recordsLinked to original sources

Uteroplacental Doppler flow velocity waveform indices in normal pregnancy: a statistical exercise and the development of appropriate reference values.

In a prospective cross-sectional study, we examined 154 normal pregnant women and measured the systolic to diastolic (S/D) ratio and resistance index (RI) in the umbilical artery and both uterine arteries. Placental location with respect to laterality was determined by real-time ultrasound. In patients with unilateral placental location, each uterine artery was evaluated according to its relationship with the placenta. Doppler flow velocity waveforms were obtained by a continuous wave Doppler device. Kolmogorov D tests revealed that RI values follow gaussian distribution, but that S/D values were markedly skewed to the right. There was a significant negative linear relationship between gestational age and umbilical artery RI and a significant negative curvilinear relationship between gestational age and umbilical artery (S/D (r = 0.83, p less than 0.001; and r = -0.79, p less than 0.001, respectively). Confidence bands for umbilical artery RI were developed based on the linear model with gestational age (fitted umbilical artery RI = 0.97199 - 0.01045*gestational age). Confidence bands for umbilical artery S/D were derived from the corresponding RI values by means of the functional relationship S/D = 1/(1 - RI). The RI and S/D values of the uterine arteries declined until 24 to 25 weeks' gestation and remained unchanged thereafter. This relationship, however, was not statistically significant (r = -0.10, p = 0.22). The placental uterine artery is different from the nonplacental quantitatively and qualitatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Cross-Sectional Studies

Atrial natriuretic factor concentrations during pregnancy and in the postpartum period.

Atrial natriuretic factor (ANF) is a hormone that regulates fluid and electrolyte homeostasis. Increased intra-atrial pressure or atrial distention, which might occur secondary to intravascular volume expansion, stimulate the secretion of ANF by human atrial myocytes. During normal human pregnancy, there is a progressive increase in total intravascular fluid volume. Thus, we asked the following question: Does this physiologic adaptation to pregnancy result in an increase in ANF concentrations? Concentrations of alpha-human ANF (alpha-hANF) were measured by a specific radioimmunoassay in venous blood samples obtained longitudinally in the first, second, and third trimesters of pregnancy, during the intrapartum period, in the early postpartum period, and 6 to 8 weeks postpartum from 11 normal women who had no antepartum, intrapartum, or postpartum complications. Maternal circulating alpha-hANF levels were not different from those seen in the nonpregnant state. However, higher alpha-hANF concentrations were noted in the early postpartum period. Although the hypervolemia of normal pregnancy is not associated with higher alpha-hANF concentrations, other possibilities (such as increased ANF clearance, dilutional effects) need to be investigated. Finally, the etiology for the transient increase in alpha-hANF levels in the early postpartum period remains to be elucidated.

Adult

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.

Adult

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.

Accidents, Traffic

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.

Adult

Interrelationship between atrial natriuretic factor concentrations and acute volume expansion in pregnant and nonpregnant women.

The secretion of atrial natriuretic factor by human atrial myocytes is stimulated by increased intraatrial pressure or atrial distention. To determine whether acute intravascular volume expansion affects atrial natriuretic factor concentrations during pregnancy, circulating atrial natriuretic factor levels were measured in pregnant women at term (before elective cesarean section) and nonpregnant control subjects before and during intravenous infusion of lactated Ringer's solution (approximately 30 ml/kg). Venous plasma concentrations of alpha-human atrial natriuretic factor were determined by a specific radioimmunoassay. A significant increase in alpha-human atrial natriuretic factor levels in nonpregnant subjects was seen. Pregnant women did not show a significant response to a similar stimulus. Finally, basal alpha-human atrial natriuretic factor levels in pregnant and nonpregnant women were not different. Volume expansion (long-term or short-term) in normal human pregnancy may not be sensed by atrial volume sensors, possibly because it is accommodated by an enlarged maternal vascular compartment.

Atrial Natriuretic Factor

Atrial natriuretic peptide receptors in guinea pig placentas.

The multiple physiologic effects of atrial natriuretic peptide are mediated through specific atrial natriuretic peptide plasma membrane receptors. We have attempted to determine whether atrial natriuretic peptide receptors are present in guinea pig placentas and subplacentas at approximately 45 and 65 days' gestation. A microsomal plasma fraction was prepared from each component. Atrial natriuretic peptide receptors were detected by in vitro radioligand techniques with alpha-human atrial natriuretic peptide labeled with iodine 125. In placentas we identified one set of specific binding sites for atrial natriuretic peptide at both gestational ages. Although the maximal concentration of the receptors did not change with advancing gestation, the dissociation constant was higher at 65 than at 45 days' gestation. In subplacentas two sets of binding sites were identified, one of low capacity-high affinity and the other of low affinity-high capacity. The maximal concentration of the atrial natriuretic peptide receptors did not change as a function of gestation. However, the dissociation constant, for both the high- and low-affinity sites, significantly decreased with advancing gestation.

Animals

Atrial natriuretic factor maternal and fetal concentrations in severe preeclampsia.

There is a reduction in intravascular volume in patients with preeclampsia. Since the secretion of atrial natriuretic factor by human atrial myocytes is stimulated by increased intraatrial pressure or atrial distention, we sought to determine whether circulating maternal plasma atrial natriuretic factor concentrations were lower in patients with preeclampsia compared to normal pregnant women. The level of alpha-human atrial natriuretic factor was measured by a specific radioimmunoassay. Maternal venous concentrations of a alpha-human atrial natriuretic factor were higher in patients with severe preeclampsia (116.12 +/- 13.37 pg/ml) than in normal pregnant women (80.30 +/- 4.02 pg/ml). Umbilical artery alpha-human atrial natriuretic factor concentrations were higher in fetuses born to patients with severe preeclampsia (197.68 +/- 29.10 pg/ml) than normal control subjects (118.00 +/- 12.52 pg/ml). Umbilical artery alpha-human atrial natriuretic factor concentrations were higher than umbilical or maternal venous concentrations. In cases of severe preeclampsia, despite the presumed volume changes, maternal atrial natriuretic factor concentrations are higher than in normal pregnant women. The fetus appears to produce its own atrial natriuretic factor. Umbilical artery atrial natriuretic factor concentrations in fetuses born to preeclamptic mothers are higher than those seen in normal control subjects.

Adolescent

Up-regulation of guinea pig myometrial adenylate cyclase activity by intrauterine estradiol and progesterone pellets.

The effects of intrauterine implantation of 17 beta-estradiol and progesterone on basal and stimulated adenylate cyclase activity in guinea pig myometria were studied in nonpregnant, previously oophorectomized guinea pigs receiving intrauterine implants of either estradiol, progesterone, a combination of the two hormones, or placebo for 7 days. Guanine nucleotides resulted in a significant increase in basal enzymatic activity. The extent of enzymatic stimulation in estradiol-treated animals was significantly higher than that observed in either controls, animals receiving progesterone, or a combination of estradiol and progesterone. Sodium fluoride stimulation occurred in all treatment groups to a similar degree. However, guanine nucleotides resulted in a significant decrease in percent stimulation of maximal sodium fluoride-stimulated enzymatic activity. Finally, beta-adrenergic receptor-mediated enzymatic activity, as assayed by isoproterenol stimulation, was higher in those animals that received estradiol implants than in controls or the other two hormonally treated groups. Intrauterine administration of these sex steroid hormones, directly or indirectly, modulates myometrial adenylate cyclase activity.

Adenylyl Cyclases

Effect of placental laterality on uterine artery resistance and development of preeclampsia and intrauterine growth retardation.

We studied 153 pregnant women with normal pregnancies and 147 women with complicated pregnancies (diabetes, hypertensive disorders, and intrauterine growth retardation) to evaluate the association of placental location and the development of preeclampsia, intrauterine growth retardation, and uterine artery resistance. The placental location was determined by real-time ultrasonography, and the uterine artery resistance was determined by continuous-wave Doppler flow velocity waveform analysis. In the presence of preeclampsia or intrauterine growth retardation, up to 75% of the patients had unilaterally located placentas and 25% central placentas, whereas in the absence of these two conditions only 51% of the patients had unilateral and 49% central placentas (p less than 0.02). In patients with unilateral placentas, the incidence of preeclampsia and intrauterine growth retardation was 2.8-fold and 2.7-fold greater than in patients with central placentas (p less than 0.03 and p less than 0.01). Among all patients unilateral placental location was more likely to be associated with abnormal artery flow velocity waveforms than central placental location (p less than 0.001). We conclude that unilateral placental location may predispose to the development of preeclampsia and intrauterine growth retardation by its effect on uterine artery resistance.

Adolescent

Treatment of oophorectomized guinea pigs with intrauterine 17 beta-estradiol pellets may modulate myometrial beta-adrenergic receptor binding properties.

Intrauterine 17 beta-estradiol pellets can induce an up-regulation of guinea pig myometrial beta-adrenergic receptor density and l-isoproterenol-dependent adenylate cyclase activity. Does 17 beta-estradiol influence the ability of beta-adrenergic receptors to form a "high affinity" state with l-isoproterenol, which is a necessary step for adenylate cyclase activation? Nonpregnant, oophorectomized guinea pigs received intrauterine pellets of either placebo, 17 beta-estradiol, progesterone, or 17 beta-estradiol plus progesterone for 1 week. 17 beta-Estradiol resulted in pharmacologic, whereas progesterone resulted in physiologic plasma 17 beta-estradiol and progesterone concentrations, respectively. The affinity of myometrial beta-adrenergic receptors for l-isoproterenol was measured by percentage of inhibition of -[125I]cyanopindolol binding. In all groups, the competition curves in the presence of magnesium chloride could be resolved into two affinity states of the beta-adrenergic receptor, "high" and "low," respectively. The ratio of their dissociation constants was not influenced by hormonal treatment. However, the relative concentration of beta-adrenergic receptors in the high affinity state was significantly higher in the 17 beta-estradiol-treated group than that in the control group. This correlates with the up-regulation in myometrial adenylate cyclase activity and suggests that myometrial beta-adrenergic receptor-adenylate cyclase function may be modulated by 17 beta-estradiol.

Adrenergic beta-Antagonists

Pregnancy-induced changes in the interaction of guinea pig myometrial beta-adrenergic receptors with l-isoproterenol.

The ability of myometrial beta-adrenergic receptors to form a "'high-affinity state" with beta-adrenergic receptor agonists might be greater in pregnant guinea pigs at greater than or equal to 0.9 of gestation than in nonpregnant animals. To determine whether this difference is due to pregnancy in general or is associated only with late pregnancy and to determine whether it persists in the postpartum period, we studied the interaction of l-isoproterenol with beta-adrenergic receptors in myometrial membranes obtained from nonpregnant (nulligravid) animals, pregnant (primigravid) animals at 0.3, 0.7, and 0.9 to 1.0 of gestation (term 65 days), and postpartum guinea pigs (2 to 3 days). The affinity of myometrial beta-adrenergic receptors for l-isoproterenol was measured by percent inhibition of -[125I]cyanopindolol binding. In the presence of magnesium chloride, the competition curves could be resolved into two affinity state of the beta-adrenergic receptor, "high" and "low," respectively, in all groups. The ratio of the dissociation constant of the "low"-affinity state to that of the "high"-affinity state was significantly higher in pregnant guinea pigs at greater than or equal to 0.9 of gestation than in nonpregnant or postpartum animals and in pregnant animals of earlier gestations. In the presence of guanosine triphosphate only one (low-affinity) state of the receptor was detectable. Thus it is only in pregnant guinea pigs at greater than or equal to 0.9 of gestation that the ability of myometrial beta-adrenergic receptors to form a high-affinity state is enhanced.

Adrenergic beta-Antagonists

Up-regulation of guinea pig myometrial beta-adrenergic receptors by intrauterine estradiol and progesterone pellets.

The effect of intrauterine implantation of 17 beta-estradiol and progesterone on the concentration and affinity of myometrial beta-adrenergic receptor were studied in nonpregnant, previously oophorectomized guinea pigs receiving intrauterine implants of either 17 beta-estradiol, progesterone, a combination of the two hormones, or placebo for 7 days. Myometrial beta-adrenergic receptors were characterized by use of (-)-iodine 125-cyanopindolol as the specific beta-adrenergic receptor ligand. On comparison with the control group, administration of 17 beta-estradiol or progesterone resulted in a severalfold increase in the concentration (Bmax) of myometrial beta-adrenergic receptor and a lesser but significant increase in the dissociation constant, KD. Although a combination of 17 beta-estradiol and progesterone treatment increased the concentration and the dissociation constant of beta-adrenergic receptors, it did not result in any synergistic or additive effect. We conclude that intrauterine administration of these sex steroid hormones, directly or indirectly, modulates myometrial beta-adrenergic receptor concentrations and affinity.

Animals

Atrial natriuretic peptide and sodium azide dependent guanylate cyclase activities in placentas from normal and severely toxemic patients.

Particulate guanylate cyclase is stimulated by several hormones through receptor-dependent and by nitrosovasodilators through receptor-independent mechanisms. A subtype of atrial natriuretic peptide (ANP) receptors is coupled to guanylate cyclase. It has been shown that there is a down-regulation of the affinity of ANP receptors to alpha-hANP in placental plasma membranes obtained from severely toxemic patients. We have asked the question whether these changes are associated with a down-regulation of ANP-dependent guanylate cyclase activity. Guanylate cyclase was determined by in vitro experiments using a placental plasma membrane fraction obtained from normal and from severely toxemic patients. The presence of ANP-dependent placental guanylate cyclase activity was demonstrated both in normal and toxemic placentas. Although basal guanylate cyclase activity was not influenced by toxemia of pregnancy, there was a significant decrease in the maximum stimulation of this enzyme by alpha-hANP (104.81 +/- 12.02% (n = 4) vs 49.41 +/- 8.73% (n = 7) for normal and toxemics, respectively). Finally, stimulation by a nitrosovasodilator, sodium azide (NaN3), was also lower in toxemic placentas than in normal controls. These observations extend our previously reported results on placental ANP receptor function but also suggest the presence of a possibly receptor-independent decrease in guanylate cyclase activity in toxemic placentas.

Adult

Atrial natriuretic peptide receptors in sheep cotyledons.

Effects dependent on atrial natriuretic peptide are mediated through specific atrial natriuretic peptide plasma membrane receptors. We previously demonstrated the presence of specific atrial natriuretic peptide receptors in human placental membranes. We asked whether atrial natriuretic peptide specific receptors are present in sheep cotyledons. Sheep cotyledons were obtained from pregnant ewes at 125 to 142 days' gestation. Each cotyledon was separated into two components, the outer layer (maternal capsule) and the spongy inner layer (fetal component). A microsomal plasma membrane fraction was prepared from each layer. Atrial natriuretic peptide receptors were detected by in vitro radioligand techniques with 125I-alpha-human atrial natriuretic peptide. In sheep cotyledons there are two sets of atrial natriuretic peptide receptors that show either high-affinity/low-capacity or low-affinity/high-capacity binding characteristics. Moreover, membranes from the inner layer (fetal component) appear to have a lower concentration of high-affinity atrial natriuretic peptide binding sites than those from the maternal capsule.

Animals

Atrial natriuretic peptide receptors in normal human placentas.

We studied whether plasma membranes from normal human placentas contain receptors for atrial natriuretic peptide. We identified specific, high-affinity, low-capacity atrial natriuretic peptide binding sites in the nonbrush border, microsomal fraction presumed to originate from cellular membranes near the fetal circulation. In contrast, no atrial natriuretic peptide binding sites could be identified in the brush border; the latter is exposed to maternal blood in the intervillous space. The presence of atrial natriuretic peptide binding sites in human placentas suggests that atrial natriuretic peptide may be involved in fluid and electrolyte homeostasis in human gestation.

Alkaline Phosphatase