Biomedical subjects

W B Warren

Publications and source records attributed to W B Warren.

15 recordsLinked to original sources

PubMed1995

Corticotropin-releasing hormone and pituitary-adrenal hormones in pregnancies complicated by chronic hypertension.

OBJECTIVE: We hypothesized that maternal plasma corticotropin-releasing hormone levels are elevated in chronic hypertension and that elevations modulate maternal and fetal pituitary-adrenal function. STUDY DESIGN: Venous blood samples and 24-hour urine specimens were obtained in normal and hypertensive pregnancies at 21 to 40 weeks of gestation. Corticotropin-releasing hormone, corticotropin, cortisol, dehydroepiandrosterone sulfate, and total estriol levels were measured by radioimmunoassay. Mean hormone levels were compared by unpaired t test or two-way analysis of variance. RESULTS: Plasma corticotropin-releasing hormone levels were elevated early in hypertensive pregnancies but did not increase after 36 weeks. Levels of pituitary and adrenal hormones were not different in normal and hypertensive women. However, maternal plasma estriol levels were lower in hypertensive pregnancies compared with normal pregnancies. CONCLUSIONS: Fetal 16-hydroxy dehydroepiandrosterone sulfate, the major precursor to placental estriol production, has been reported to be lower than normal in hypertensive pregnancies, possibly explaining the decreased plasma estriol levels reported here. Early stimulation of placental corticotropin-releasing hormone production or secretion may be related to accelerated maturation of placental endocrine function in pregnancies complicated by chronic hypertension.

Adrenocorticotropic Hormone↗

PubMed1995

Cellular localization of corticotrophin releasing hormone in the human placenta, fetal membranes and decidua.

Corticotrophin releasing hormone (CRH), is produced by the human placenta, fetal membranes and decidua and has been detected in maternal and fetal plasma and amniotic fluid during human pregnancy. Previous studies of the cellular localization of CRH in the placenta and fetal membranes have yielded conflicting results. In this study, placentae were obtained from uncomplicated pregnancies immediately after elective termination or after normal delivery at term. Zamboni's fixed sections of villi and membrane-decidua, were cut at 10 microns by cryostat and immunocytochemistry was performed using an anti-rat/human CRH antiserum. In first and second trimester placentae, the amount of CRH reaction product present was variable. CRH was localized in both the syncytiotrophoblast and cytotrophoblast in first and second trimester tissue. In term placentae, CRH was identified consistently in the syncytiotrophoblast. In addition, strong CRH reaction was localized to the amnion epithelium of the fetal membranes. Positive immunoreactivity was also detected in the chorion and decidua although at a lower level of intensity. In trophoblast cells and in the amnion epithelium, CRH reaction product was contained in distinct granules. The regulation of CRH and its physiological role may differ in these diverse cell types. Possible effects of CRH include autocrine or paracrine actions within the amnion, chorion and decidua while CRH derived from syncytiotrophoblast may have endocrine effects through access to the maternal and fetal circulations.

Antibody Specificity↗

PubMed1995

Concentrations of corticotrophin-releasing hormone in the umbilical-cord blood of pregnancies complicated by pre-eclampsia.

The effect of pre-eclampsia on concentrations of corticotrophin releasing hormone (CRH) in umbilical-cord blood of fetuses at delivery was studied in order to determine if fetal CRH is elevated in this disorder when compared with uncomplicated pregnancy. Placental CRH may be a regulator of fetal pituitary-adrenal function and we therefore also measured ACTH, cortisol and dehydroepiandrosterone sulfate (DHEAS) in the umbilical-cord blood. The mean umbilical-cord plasma CRH in the fetuses from pregnancies complicated by pre-eclampsia, 667 +/- 153 pg mL-1, was significantly higher than the plasma CRH in the fetuses from normotensive pregnancies, 185 +/- 22 pg mL-1 (P < 0.001). The mean fetal cortisol concentration was significantly higher in pre-eclampsia, than in the normotensive, pregnancies (pre-eclampsia, 13.5 +/- 1.8; normotensive, 7.6 +/- 1.3 micrograms dL-1; P < 0.001). Plasma DHEAS was 217 +/- 23 micrograms dL-1 in the umbilical-cord blood of the fetuses from pregnancies complicated by pre-eclampsia and 281 +/- 35 micrograms dL-1 in the normotensive pregnancies (P < 0.01). Placental CRH synthesis and release, in contrast to hypothalamic CRH, appears to be stimulated by glucocorticoids. In pregnancies complicated by uteroplacental insufficiency, as may occur in pre-eclampsia, placental CRH production may be enhanced by increased fetal glucocorticoids. In turn, placental CRH may modulate fetal pituitary-adrenal steroidogenesis to favour increased cortisol secretion. Thus, placental CRH may play an important role in the fetal response to a compromised intrauterine environment.

Adrenocorticotropic Hormone↗

PubMed1995

Effects of parturition on corticotropin releasing hormone and products of the pituitary and adrenal in term fetuses at delivery.

Corticotropin releasing hormone (CRH), a hypothalamic hormone which regulates pituitary-adrenal function, is also produced by the human placenta. We studied umbilical cord concentrations of CRH to determine whether placental secretion of this hormone into the fetal compartment is altered during parturition. We also measured adrenocorticotropic hormone (ACTH), cortisol and dehydroepiandro-sterone sulfate (DHEAS) to determine whether levels of these pituitary and adrenal hormones were correlated to CRH in the fetal plasma. Blood was obtained from umbilical cords of 111 healthy term fetuses at delivery. Concentrations of CRH, ACTH, cortisol and DHEAS were measured by radio-immunoassay. Hormone levels were analyzed according to the presence of labor and delivery mode. In addition correlations between different hormones were determined. Fetal plasma CRH levels were similar for all conditions of labor and delivery as were levels of DHEAS. Fetal plasma ACTH and cortisol were increased after vaginal delivery. There were no significant correlations between placental CRH, ACTH and cortisol levels. However, an inverse correlation between fetal plasma CRH and DHEAS levels was found (r = -0.41, p < 0.001). Increases in ACTH during parturition are likely due to stimulated release by the fetal pituitary. Our data suggest that placental CRH does not mediate this acute response to the stress of parturition. We hypothesize that continuous stimulation of the pituitary and adrenal by circulating CRH during development may occur and the inverse correlation between fetal plasma CRH and DHEAS may be due to this chronic regulatory effect.

Adrenocorticotropic Hormone↗

PubMed1993

Elevated levels of umbilical cord plasma corticotropin-releasing hormone in growth-retarded fetuses.

CRH is synthesized in the hypothalamus and released in response to stress into the portal hypophyseal blood; an additional site of synthesis, the placenta, is present only during pregnancy. Placental CRH is released into the maternal and fetal circulation during human pregnancy, and we hypothesized that the chronic fetal stress associated with fetal growth retardation may stimulate placental CRH release. We measured plasma CRH concentrations in the umbilical cord blood of 28 growth-retarded fetuses and 28 normally grown fetuses matched for gestational age and mode of delivery. Plasma ACTH, dehydroepiandrosterone sulfate (DHEAS), and cortisol were also measured in the umbilical cord samples to determine if CRH levels were correlated with levels of pituitary and adrenal hormones. The mean umbilical cord plasma CRH level in the growth-retarded fetuses was 206 +/- 25.8 pmol/L, which was significantly higher than that in the normally grown fetuses matched for gestational age, presence or absence of labor, and mode of delivery (49.4 +/- 16.7 pmol/L; P < 0.01). The mean plasma ACTH level in the growth-retarded fetuses (5.7 +/- 1.2 pmol/L) was significantly higher than that in the normally grown fetuses (3.3 +/- 0.7 pmol/L; P < 0.05). The mean cortisol concentration in the growth-retarded fetuses was 260 +/- 32.5 nmol/L, and that in the normally grown fetuses was 220 +/- 40 nmol/L. The mean DHEAS level was significantly lower in the growth-retarded fetuses (4.8 +/- 0.6 mumol/L) than that in the normally grown fetuses (7.7 +/- 0.6 mumol/L; P < 0.001). There was a significant correlation between umbilical cord plasma CRH and both ACTH and cortisol concentrations as well as a significant negative correlation between CRH and DHEAS levels in the growth-retarded fetuses. The umbilical cord plasma CRH level is extremely elevated in growth-retarded fetuses compared to that in normal fetuses. Placental CRH, like hypothalamic CRH, may be stimulated in conditions of chronic stress and may modulate fetal pituitary-adrenal function in high risk pregnancies.

Adrenocorticotropic Hormone↗

PubMed1992

Elevated maternal plasma corticotropin-releasing hormone levels in pregnancies complicated by preterm labor.

OBJECTIVES: We investigated whether maternal plasma levels of the placental hormone corticotropin-releasing hormone are elevated in pregnancies complicated by preterm labor. STUDY DESIGN: Mean maternal corticotropin-releasing hormone levels were studied in women who met specific criteria for preterm labor and in women with normal pregnancies. Levels were also compared in the latent and active phases during term labor. RESULTS: In pregnancies complicated by preterm labor, maternal corticotropin-releasing hormone levels were higher than in normal pregnancies; this elevation occurred before labor was diagnosed clinically (p less than 0.05). When preterm labor was associated with infection, the mean levels were not elevated. Mean plasma levels were similar in latent and active phases during labor at term. CONCLUSION: Maternal plasma corticotropin-releasing hormone levels are elevated in association with preterm labor. This elevation does not appear to be due to labor itself and may reflect an early activation of the placenta before the onset of preterm labor.

Corticotropin-Releasing Hormone↗

PubMed1992

Placental corticotropin-releasing hormone and pituitary-adrenal function during pregnancy.

The placenta secretes large amounts of the hypothalamic releasing hormone, corticotropin-releasing hormone (CRH), into both the maternal and fetal circulation during pregnancy. We characterized the relationship between maternal plasma CRH and products of the pituitary and adrenal in order to investigate the physiologic role of placental CRH in modulating maternal pituitary-adrenal function. Plasma was obtained from 8 women at biweekly intervals between 21 and 40 weeks of full-term pregnancy for CRH, adrenocorticotropin (ACTH), alpha-melanocyte-stimulating hormone (alpha MSH), cortisol, and dehydroepiandrosterone sulfate (DHEAS) measurements by radioimmunoassay. Eighteen women were also studied once at 22-34 weeks of pregnancy with plasma CRH and 24-hour urinary free cortisol measurement. Eight nonpregnant women served as control subjects. Plasma CRH was undetectable in the nonpregnant subjects and rose over the time period studied in the pregnant women. Concentrations of afternoon ACTH and cortisol also rose during pregnancy while DHEAS levels declined in the pregnant women. The alpha-MSH levels were beneath the level of detection (< 20 pg/ml) in both the pregnant and nonpregnant subjects. The overall mean afternoon ACTH concentration was higher in the pregnant than in the nonpregnant women (11.4 +/- 1.8 vs. 5.9 +/- 1.8 pg/ml; p < 0.05), although the ACTH levels in both groups remained within the normal range. The mean plasma cortisol concentrations were higher in the pregnant women, while the mean DHEAS levels were lower in the pregnant women when compared to the nonpregnant subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMed1992

Corticotropin releasing hormone concentrations in umbilical cord blood of preterm fetuses.

Corticotrophin releasing hormone (CRH), dehydroepiandrosterone sulfate (DHEAS) and cortisol were measured in umbilical cord plasma obtained from 90 preterm and 98 term fetuses. Maternal plasma was obtained from 23 women who delivered preterm and from 23 women matched for gestational age who ultimately delivered term infants. Mean umbilical cord plasma CRH concentration was significantly higher in the preterm fetuses (n = 69, 538 +/- 63 pg/ml) compared to the term fetuses (n = 98, 280 +/- 22 pg/ml, P < 0.01). Mean DHEAS level in the preterm fetuses was 208 +/- 22 mg/dl (n = 56), cortisol level was 7 +/- 1 mg/dl (n = 58). Umbilical plasma CRH concentrations (808 +/- 170 pg/ml) were significantly higher at 24-27 weeks than at 28-31 or 31-34 weeks gestation. Cortisol levels (12 +/- 3 micrograms/dl) were highest at 24-27 weeks. Mode of delivery and the presence of labor did not affect fetal CRH levels. The highest fetal CRH levels were measured in the pregnancies complicated by hypertension as well as prematurity; however, fetal CRH levels remained higher in the preterm group compared to the term group when hypertensive pregnancies were excluded. Maternal plasma CRH levels were significantly higher in the group that delivered preterm compared to women who delivered at term matched for gestational age (1058 +/- 184 pg/ml compared to 456 +/- 71 pg/ml, P < 0.00).(ABSTRACT TRUNCATED AT 250 WORDS)

Corticotropin-Releasing Hormone↗

PubMed1991

Transvaginal ultrasonographic definition of the central nervous system in the first and early second trimesters.

A 6.5 MHz transvaginal sector scanner was used to describe the fetal central nervous system anatomy from 6 to 14 weeks. One hundred thirty-three pregnant patients were scanned after the crown-rump measurements were found to be within a range of less than or equal to 4 days from menstrual age. The number of possible ultrasonographic sections ("slices"), as well as the number of successful views in the axial, coronal, and sagittal sections, was tabulated. A detailed list of central nervous system structures that are seen at each gestational age is presented. The results showed that a significant number of brain structures could be imaged. The number and the clarity of the structures and the number of successful views in the three scanning planes increased with gestational age. We concluded that transvaginal scanning for central nervous system maldevelopment can be started in the late first and early second trimesters.

Central Nervous System↗

PubMed1991

Adrenocorticotropin and cortisol responses to vasopressin during pregnancy.

CRH is secreted by the placenta into the maternal and fetal circulation during pregnancy in humans and non-human primates. ACTH and cortisol responses to exogenous CRH are blunted during pregnancy. In the present study we examined the pituitary-adrenal response to another corticotropin releasing factor, vasopressin. Studies were performed in chronically catheterized female baboons moving freely in their home cages; 13 studies were performed in 4 pregnant animals, and 8 studies were performed in 6 nonpregnant animals. Vasopressin was administered iv in 2 doses (0.3 and 3.0 U), and plasma samples were obtained for CRH, ACTH, and cortisol measurements. Results are expressed as the mean +/- SEM. Baseline plasma CRH was 240 +/- 20 pmol/L in the pregnant animals and unmeasurable (less than 20) in the nonpregnant animals. In the pregnant animals, ACTH concentrations rose from a baseline of 6.4 +/- 1.3 pmol/L to 10.1 +/- 0.4 after 0.3 U vasopressin and to 24.9 +/- 5.2 after 3.0 U vasopressin. In the nonpregnant animals, ACTH levels were 5.8 +/- 1.3 at baseline, 6.7 +/- 1.3 after the 0.3-U dose, and 14.6 +/- 2.4 after the 3.0-U dose. The peak ACTH response after each dose of vasopressin was higher in the pregnant animals than in the nonpregnant animals (P less than 0.05). The baseline cortisol level in the pregnant animals was 960 +/- 80 nmol/L and rose to 1370 +/- 110 and 1535 +/- 165 after the 2 doses of vasopressin, respectively. The baseline cortisol concentration in the nonpregnant animals was 910 +/- 86 nmol/L. The cortisol level was 990 +/- 75 after the 0.3-U vasopressin dose and 1380 +/- 140 after the 3.0-U dose. The peak cortisol response after the 0.3-U dose was significantly higher in the pregnant animals (P less than 0.02), while the peak cortisol responses after the 3.0-U dose were similar in the 2 groups of animals. In a single animal, vasopressin was administered sequentially at 4 gestational ages during pregnancy and then 2 times in the postpartum period. The ACTH response to vasopressin increased as pregnancy progressed and then decreased in the postpartum period. In summary, the ACTH and cortisol responses to 0.3 and 3.0 U vasopressin, iv, are enhanced during pregnancy in the baboon, although the responses to exogenous CRH are blunted during gestation. We conclude that the chronic placental CRH stimulation of the pituitary-adrenal axis during pregnancy leads to an enhanced response to vasopressin and a down-regulation of the response to exogenous CRH.

Adrenocorticotropic Hormone↗

PubMed1991

Transvaginal sonographic characterization of ovarian disease: evaluation of a new scoring system to predict ovarian malignancy.

With the advent of high-frequency transvaginal ultrasonography, new opportunities are presented to better define ovarian lesions. The goal of this study was to develop a scoring system using transvaginal sonographic characterization of pelvic/ovarian lesions. Our purpose was to maximize the discrimination between benign and malignant entities. Transvaginal sonographic pelvic images of 143 patients were correlated with surgical findings or histopathology. Of 281 ovaries, 108 had benign lesions (30 endometriomas, 24 teratomas, 21 simple cysts, and 33 other abnormalities) and 20 had malignancies. The scoring system devised was useful in distinguishing benign from malignant masses, with a specificity of 83%, sensitivity of 100%, and positive and negative predictive values of 37 and 100%, respectively. Further experience and refinements of this method of scoring should maximize the benefit of high-resolution transvaginal sonography of ovarian lesions.

Adult↗

PubMed1990

Prevalence of use of cocaine and other substances in an obstetric population.

Increasing use of cocaine among pregnant women has been reported. This study was conducted to determine the prevalence of positive urine toxicologic screens for cocaine and other substances of patients admitted to the Sloane Hospital for Women. Urine samples were obtained from 509 women admitted to the delivery suite. The overall prevalence of cocaine was 10% (n = 51). Cocaine use was 10 times more prevalent in the clinic population (14%) than in the private population, (1.4%). In addition, women whose urine samples were positive for cocaine were more likely to have no prenatal care, previous induced abortions, to be human immunodeficiency virus-positive, and admitted previous use of cigarettes, alcohol, cocaine, and other drugs. Amphetamines were detected in 13% (n = 65) of patients. However, the screens did not distinguish between metabolites of amphetamines and other drugs such as cold medications. The medical history alone predicted only 37% (n = 19) of the cocaine-positive screens and none of the amphetamine-positive screens.

Adolescent↗

PubMed1990

Elevated maternal plasma corticotropin releasing hormone levels in twin gestation.

The placenta secretes large amounts of the hypothelamic hormone, corticotropin releasing hormone (CRH) into the maternal and fetal circulation during pregnancy. We and other investigators have shown that during normal pregnancy, maternal plasma CRH levels begin to rise in the second trimester with a dramatic increase in CRH levels during the 5-6 weeks preceding the onset of labor. This rise in maternal plasma CRH is parallel to the rise of placental CRH mRNA which has been reported to occur with gestational maturation. Mechanisms underlying the control of CRH secretion by the placenta have not yet been determined. In twin gestation, increased fetal-placental mass has been shown to be associated with elevated maternal levels of several placental hormones as compared to singleton gestation. We measured maternal plasma CRH in both twin and singleton gestation to investigate whether the larger size of the fetal-placental unit in twin gestation is associated with elevated maternal CRH levels. Seventy-six serial venous blood samples were collected from 20 women with twin gestation and 40 samples were obtained from 27 women with uncomplicated singleton gestation. Gestational age was determined by history of a known last menstrual period and first trimester clinical examination and confirmed by ultrasound examination. CRH was extracted from 1-2 ml plasma with SEP-Pak C18 cartridges and eluted with triethylamine-formic-acid propranolol. CRH was measured by radioimmunoassay (RIA) with human CRH standard and antiserum to human CRH raised in our laboratory. Mean CRH levels were calculated for four week intervals. In both singleton and twin gestation, the maternal plasma CRH levels increased with advancing gestational age. After 29 weeks of gestation, maternal plasma CRH levels in twin gestation were significantly higher than those in singleton gestation (p less than 0.01). At 37 to 40 weeks of gestation, mean maternal CRH was 1167 +/- 237 pg/ml in singleton gestation as compared to 6927 +/- 1725 pg/ml in twin gestation (p less than 0.05). In addition, the rapid rise in plasma CRH levels which occurs near term in singleton gestation, occurred earlier in twin gestation. This early rise in maternal CRH levels persisted when the data from twin pregnancies complicated by preterm labor were removed from the analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Corticotropin-Releasing Hormone↗

PubMed1989

Dating the early pregnancy by sequential appearance of embryonic structures.

A total of 97 transvaginal scans were performed from 4 to 12 weeks' gestation in normal and accurately dated gestations. The sequential appearance of six structures were examined: (1) the gestational sac only was present during week 4; (2) the yolk sac appeared in week 5; (3) the fetal pole with detectable heart motion was first seen in week 6; (4) the single unpartitioned ventricle in the brain marked week 7; (5) the falx cerebri appeared during week 9; and (6) the appearance and the disappearance of the physiologic midgut herniation were seen in week 8 and week 11, respectively. Inasmuch as the time in gestation at which these structures appear characterizes the gestational age more than any measurement at this age, we propose a practical method to determine the correct gestational age in early first-trimester pregnancy.

Brain↗

PubMed1989

First-trimester midgut herniation: a high-frequency transvaginal sonographic study.

The application of high-frequency transvaginal sonography offers new opportunities in scanning for malformations during the first trimester of pregnancy. Scanning of the anterior abdominal wall and the umbilical cord insertion at this gestational age is feasible. A cross-sectional study of 61 embryos-fetuses from 7 to 12 weeks of gestation was performed to observe the physiologic midgut hernia. This herniation was detected in 64% of the cases at 8 weeks, in 100% during weeks 9 and 10, and in 25% at 11 weeks' gestation. None of the fetuses studied at 12 weeks had a midgut herniation. Vaginal sonography of the well-dated fetus at 12 weeks can confirm the final development of the anterior abdominal wall.

Abdominal Muscles↗