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Adhesions frequently occur postoperatively, causing morbidity. In this noninterventional observational cohort study, we enrolled patients who presented for repeat abdominal surgery, after a history of previous abdominal myomectomy, from March 1998 to June 20210 at St. Vincent’s Catholic Medical Centers. The primary outcome of this pilot study was to compare adhesion rates, extent, and severity in patients who were treated with intraperitoneal triamcinolone acetonide during the initial abdominal myomectomy (n = 31) with those who did not receive any antiadhesion interventions (n = 21), as documented on retrospective chart review. Adhesions were blindly scored using a standard scoring system. About 32% of patients were found to have adhesions in the triamcinolone group compared to 71% in the untreated group (p < 0.01). Compared to controls, adhesions were significantly less in number (0.71 vs. 2.09, p < 0.005), severity (0.54 vs. 1.38, p < 0.004), and extent (0.45 vs. 1.28, p < 0.003). To understand the molecular mechanisms, human fibroblasts were incubated in hypoxic conditions and treated with triamcinolone or vehicle. In vitro studies showed that triamcinolone directly prevents the surge of reactive oxygen species triggered by 2% hypoxia and prevents the increase in TGF-β1 that leads to the irreversible conversion of fibroblasts to an adhesion phenotype. Triamcinolone prevents the increase in reactive oxygen species through alterations in mitochondrial function that are HIF-1α-independent. Controlling mitochondrial function may thus allow for adhesion-free surgery and reduced postoperative complications.

OBJECTIVES To compare a traditional ultrasound (US) method for estimated fetal weight (EFW) calculation and fetal growth restriction diagnosis with 2 newer methods for the prediction of small for gestational age (SGA) at birth. METHODS We reviewed deliveries at our institution from January 1, 2013, to March 31, 2017. Singleton, nonanomalous, well-dated fetuses with a US examination within 2 weeks of delivery were included. Estimated fetal weights and percentiles were calculated by a traditional method (Hadlock et al; Radiology 1991; 181:129-133) and 2 newer methods: Intergrowth-21st (INTG; Ultrasound Obstet Gynecol 2017; 49:478-486) and Salomon et al (Ultrasound Obstet Gynecol 2007; 29:550-555). We calculated each method's test characteristics to predict SGA (birth weight

Condyloma Acuminatum is a sexually transmitted viral disease caused by the human papilloma virus (HPV). It is the most common viral sexually transmitted disease. In this randomized controlled trial, cantharidin was found to be more effective and better tolerated than trichloroacetic acid for the treatment of these lesions. Patients treated with cantharidin healed with less scarring than those treated with TCA (P

Background The fetal growth standard in widest use was published by Hadlock >25 years ago and was derived from a small, homogeneous cohort. In 2015, The Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Study published updated standards that are specific to race/ethnicity. These do not allow for precise estimated fetal weight percentile calculation, however, and their effectiveness to predict neonatal morbidity and small for gestational age has not yet been compared to the long-standing Hadlock standard. Objective We compared the ability of the Hadlock standard to predict neonatal morbidity and small for gestational age at birth with that of The Eunice Kennedy Shriver National Institute of Child Health and Human Development race-/ethnicity-specific standard. Our secondary objective was to compare their performance among our Native American population, which is not accounted for in the Eunice Kennedy Shriver National Institute of Child Health and Human Development standard. Study Design For this retrospective study of diagnostic accuracy, we reviewed deliveries at the University of New Mexico Hospital from Jan. 1, 2013, through March 31, 2017. We included mothers with singleton, well-dated pregnancies and nonanomalous fetuses with an estimated fetal weight within 30 days of delivery. Cubic spline interpolation was performed on the Eunice Kennedy Shriver National Institute of Child Health and Human Development estimated fetal weight-percentile tables to calculate percentiles specific to the gestational day. Estimated fetal weight percentiles were then calculated using both the Hadlock and Eunice Kennedy Shriver National Institute of Child Health and Human Development race-/ethnicity-specific standards according to maternal self-identified race/ethnicity. We calculated the receiver operator area under the curve of each method to predict composite and severe composite neonatal morbidity and small for gestational age at birth (birthweight Results We included 1514 women, with a mean ultrasonography-to-delivery interval of 14.4 days (±8.8) and a small for gestational age rate of 13.6% (n = 206). For the prediction of both composite and severe composite neonatal morbidity, the Hadlock method had superior performance, with higher areas under the curve than the Eunice Kennedy Shriver National Institute of Child Health and Human Development method (P Conclusion Despite its publication >25 years ago, the Hadlock standard is superior to the Eunice Kennedy Shriver National Institute of Child Health and Human Development race-/ethnicity-specific standard for the prediction of both neonatal morbidity and small for gestational age.

Background: Multiple tools including Accreditation Council for Graduate Medical Education (ACGME) standardized milestones can be utilized to assess trainee and residency program performance. However, little is known regarding the objective validation of these tools in predicting written board passage. Methods: In this retrospective study, data was gathered on n = 45 Wayne State University Obstetrics and Gynecology program graduates over the five-year period ending July 2018. United States Medical Licensing Examination (USMLE) scores, Council on Resident Education in Obstetrics and Gynecology (CREOG) in-training scores and ACGME milestones were used to predict American Board of Obstetrics and Gynecology (ABOG) board passage success on first attempt. Significance was set at p < 0.05. Results: Written board passage was associated with average CREOGs (p = 0.01) and milestones (p = 0.008) while USMLE1 was not significantly associated (p = 0.055). USMLE1

AIM The study aims to determine resident applicant metrics most predictive of academic and clinical performance as measured by the Council of Resident Education in Obstetrics and Gynecology (CREOG) examination scores and Accreditation Council for Graduate Medical Education (ACGME) clinical performance (Milestones) in the aftermath of United States Medical Licensing Examination Scores (USMLE) Step 1 becoming a pass/fail examination. METHODS In this retrospective study, electronic and paper documents for Wayne State University Obstetrics and Gynecology residents matriculated over a 5-year period ending July 2018 were collected. USMLE scores, clerkship grade, and wording on the letters of recommendation as well as Medical Student Performance Evaluation (MSPE) were extracted from the Electronic Residency Application Service (ERAS) and scored numerically. Semiannual Milestone evaluations and yearly CREOG scores were used as a marker of resident performance. Statistical analysis on residents (n = 75) was performed using R and SPSS and significance was set at P RESULTS Mean USMLE score correlated with CREOG performance and, of all 3 Steps, Step 1 had the tightest association. MSPE and class percentile also correlated with CREOGs. Clerkship grade and recommendation letters had no correlation with resident performance. Of all metrics provided by ERAS, none taken alone, were as useful as Step 1 scores at predicting performance in residency. Regression modeling demonstrated that the combination of Step 2 scores with MSPE wording restored the predictive ability lost by Step 1. CONCLUSIONS The change of USMLE Step 1 to pass/fail may alter resident selection strategies. Other objective markers are needed in order to evaluate an applicant’s future performance in residency.

The Royal College of Obstetricians and Gynaecologists (RCOG) defines fetal growth restriction as ultrasound-estimated fetal weight less than the 10th percentile or abdominal circumference less than the 10th percentile; the American College of Obstetricians and Gynecologists (ACOG) defines fetal growth restriction as estimated fetal weight less than the 10th percentile alone. We compared each method's ability to predict small for gestational age (SGA) at birth.For this retrospective study of diagnostic accuracy, we reviewed deliveries at the University of New Mexico Hospital from January 1, 2013, to March 31, 2017. We included mothers with singleton, well-dated pregnancies and nonanomalous fetuses undergoing indicated fetal growth restriction surveillance with an ultrasound-estimated fetal weight within 30 days of delivery. Estimated fetal weights and percentiles were calculated using the Hadlock intrauterine growth curve. Small for gestational age was defined as birth weight less than the 10th percentile based on a recent, sex-specific curve. We calculated the area under the curve, sensitivity, specificity, and positive and negative likelihood ratios for various approaches using abdominal circumference and estimated fetal weight to diagnose fetal growth restriction, including the definitions endorsed by ACOG and RCOG.We included 1,704 pregnancies with a mean ultrasonography-to-delivery interval of 14.0 days (±8.6). There were 235 SGA neonates (13.8%). The rate of fetal growth restriction was 13.6% when using ACOG's criteria and 16.9% according to RCOG's criteria (P=.007). The area under the curve of RCOG's diagnostic approach was 0.78 (95% CI 0.76-0.80), which was higher than ACOG's (0.76, 95% CI 0.74-0.78, P=.01). Sensitivities and specificities of the various methods were similar. Adopting estimated fetal weight or abdominal circumference less than the 10th percentile instead of estimated fetal weight alone to predict SGA at birth would correctly identify one additional case of SGA for each 14 patients assessed.The diagnostic approach endorsed by RCOG is a marginally better predictor of SGA at birth compared with the method endorsed by ACOG. Future research should consider the potential benefits and harms of the different methods in different populations.

To compare a traditional ultrasound (US) method for estimated fetal weight (EFW) calculation and fetal growth restriction diagnosis with 2 newer methods for the prediction of small for gestational age (SGA) at birth.We reviewed deliveries at our institution from January 1, 2013, to March 31, 2017. Singleton, nonanomalous, well-dated fetuses with a US examination within 2 weeks of delivery were included. Estimated fetal weights and percentiles were calculated by a traditional method (Hadlock et al; Radiology 1991; 181:129-133) and 2 newer methods: Intergrowth-21st (INTG; Ultrasound Obstet Gynecol 2017; 49:478-486) and Salomon et al (Ultrasound Obstet Gynecol 2007; 29:550-555). We calculated each method's test characteristics to predict SGA (birth weight 10th percentile) using both traditional (EFW 10th percentile) and receiver operating characteristic (ROC)-derived fetal growth restriction cutoffs. Mean percentile discrepancies between EFW and birth weight measurements were calculated to compare method accuracy. We hypothesized that the INTG and Salomon methods would have superior SGA prediction compared with the Hadlock method.Of 831 pregnancies with a US examination within 2 weeks of delivery, 138 (16.7%) were SGA at birth. Hadlock had the smallest US-birth weight percentile discrepancy (P .001 versus both INTG and Salomon). When comparing ROC curves, the Hadlock and INTG methods performed comparably, with areas under the curve of 0.91 and 0.90 (P = .08) and optimal EFW cutoffs of the 15th and 22nd percentiles, respectively. The Salomon method performed less well, with an area under the curve of 0.82 (P .001 versus both Hadlock and INTG methods).In our study cohort, the Hadlock method predicted the birth weight percentile more accurately than the INTG or Salomon methods and performed comparably with INTG to predict SGA when ROC-derived cutoffs were used.

The fetal growth standard in widest use was published by Hadlock25 years ago and was derived from a small, homogeneous cohort. In 2015, The Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Study published updated standards that are specific to race/ethnicity. These do not allow for precise estimated fetal weight percentile calculation, however, and their effectiveness to predict neonatal morbidity and small for gestational age has not yet been compared to the long-standing Hadlock standard.We compared the ability of the Hadlock standard to predict neonatal morbidity and small for gestational age at birth with that of The Eunice Kennedy Shriver National Institute of Child Health and Human Development race-/ethnicity-specific standard. Our secondary objective was to compare their performance among our Native American population, which is not accounted for in the Eunice Kennedy Shriver National Institute of Child Health and Human Development standard.For this retrospective study of diagnostic accuracy, we reviewed deliveries at the University of New Mexico Hospital from Jan. 1, 2013, through March 31, 2017. We included mothers with singleton, well-dated pregnancies and nonanomalous fetuses with an estimated fetal weight within 30 days of delivery. Cubic spline interpolation was performed on the Eunice Kennedy Shriver National Institute of Child Health and Human Development estimated fetal weight-percentile tables to calculate percentiles specific to the gestational day. Estimated fetal weight percentiles were then calculated using both the Hadlock and Eunice Kennedy Shriver National Institute of Child Health and Human Development race-/ethnicity-specific standards according to maternal self-identified race/ethnicity. We calculated the receiver operator area under the curve of each method to predict composite and severe composite neonatal morbidity and small for gestational age at birth (birthweight10th percentile). As an additional measure of method accuracy, we calculated the mean ultrasound-birthweight percentile discrepancy. For Native Americans, percentiles were calculated using the Hadlock and Eunice Kennedy Shriver National Institute of Child Health and Human Development race/ethnicity standards (white, black, Hispanic, Asian), and test characteristics were calculated for each to predict neonatal morbidity and small for gestational age.We included 1514 women, with a mean ultrasonography-to-delivery interval of 14.4 days (±8.8) and a small for gestational age rate of 13.6% (n = 206). For the prediction of both composite and severe composite neonatal morbidity, the Hadlock method had superior performance, with higher areas under the curve than the Eunice Kennedy Shriver National Institute of Child Health and Human Development method (P.001 for both), though neither had good discriminatory value (all areas under the curve0.8). For the prediction of small for gestational age at birth, the Hadlock standard had higher sensitivity (61.1%) than the Eunice Kennedy Shriver National Institute of Child Health and Human Development standard, both when using the interpolated Eunice Kennedy Shriver National Institute of Child Health and Human Development method (36.2%, P.01) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development whole-week 10th percentile cutoff (46.7%, P.01). The Hadlock method also had a higher area under the curve than the Eunice Kennedy Shriver National Institute of Child Health and Human Development interpolated method to predict small for gestational age (0.89 vs 0.88, P .01). The Hadlock method had a lower ultrasound-birthweight percentile discrepancy than the Eunice Kennedy Shriver National Institute of Child Health and Human Development method (6.1 vs 16.5 percentile points, P.01). Fetuses classified as growth restricted by Hadlock but not Eunice Kennedy Shriver National Institute of Child Health and Human Development had significantly higher composite morbidity than normally grown fetuses. Among Native American women, the Hadlock method had the highest area under the curve to predict composite and severe composite morbidity, while the Hadlock and all Eunice Kennedy Shriver National Institute of Child Health and Human Development race-/ethnicity-specific methods performed comparably to predict small for gestational age.Despite its publication25 years ago, the Hadlock standard is superior to the Eunice Kennedy Shriver National Institute of Child Health and Human Development race-/ethnicity-specific standard for the prediction of both neonatal morbidity and small for gestational age.

Spontaneous fetal swallowing occurs at a markedly higher rate compared with spontaneous adult drinking activity. This high rate of fetal swallowing is critical for amniotic fluid volume regulation. Central NO is critical for maintaining the normal rate of fetal swallowing, as nonselective inhibition of NO (with central N G -nitro-l-arginine methyl ester) suppresses spontaneous and angiotensin II (ANG II)-stimulated swallowing. We sought to differentiate the contributions of central endothelial vs. neuronal NO in the regulation of spontaneous and stimulated fetal swallowing, using a selective neuronal NO synthase (nNOS) inhibitor. Six time-dated pregnant ewes and fetuses were chronically prepared with fetal vascular and intracerebroventricular (icv) catheters and electrocorticogram (ECoG) and esophageal electromyogram electrodes and studied at 130 ± 1 days of gestation. After an initial 2-h baseline period (0–2 h), the selective nNOS inhibitor N-propyl-l-arginine (NPLA) was injected icv (2–4 h). At 4 h, the dose of NPLA was repeated, together with ANG II, and fetal swallowing was monitored for a final 2 h. Four fetuses also received an identical control study (on an alternate day) in which NPLA was replaced with artificial cerebrospinal fluid (aCSF). Suppression of nNOS by icv NPLA significantly reduced mean (± SE) spontaneous fetal swallowing (1.35 ± 0.12 to 0.50 ± 0.07 swallows/min; P< 0.001). Injection of ANG II in the presence of NPLA had no dipsogenic effect on fetal swallowing (0.68 ± 0.09 swallows/min). In the aCSF study, icv aCSF did not change fetal swallowing (0.93 ± 0.10 vs. 0.95 ± 0.09 swallows/min), whereas icv ANG II resulted in a significant increase in the rate of fetal swallowing (2.0 ± 0.04 swallows/min; P = 0.001). We speculate that the suppressive dipsogenic effects of central NPLA indicate that spontaneous and ANG II- stimulated fetal swallowing is dependent on central nNOS activity.

Intravenous magnesium sulfate is widely used in obstetrics for the treatment of both preterm labor and preeclampsia. Although therapeutic levels of total magnesium have been proposed, the levels remain controversial. Because the active form of magnesium is the free or ionized form, it is essential to determine whether ionized magnesium and total magnesium levels are highly correlated in vivo. We sought to examine the correlation between ionized magnesium and total magnesium under basal and therapeutic conditions and to define the initiation and elimination pharmacokinetics of both forms during intravenous magnesium sulfate infusion.Twenty-four singleton pregnant patients who were candidates for magnesium sulfate were studied (preterm labor, 15; preeclampsia, 9). Serial blood samples were taken before the magnesium sulfate infusion, during the first 4 hours after the initiation of magnesium sulfate infusion and for 4 hours after the discontinuation of the infusion.Baseline levels of total magnesium and ionized magnesium were not different between patients with preterm labor and with preeclampsia. Among patients with preeclampsia, although not patients with preterm labor, the initial apparent volume of distribution was significantly smaller for total magnesium than for ionized magnesium (16,397 +/- 1441 vs 23,856 +/- 2745 mL, respectively; P =.03), and the elimination half-life was greater for total magnesium as compared to ionized magnesium (707 +/- 160 vs 313 +/- 29 minutes;P.05). Linear regression analysis demonstrated a lack of correlation between ionized magnesium and total magnesium during the pretreatment period and during the steady state infusion for both preterm labor and preeclampsia.The measurement of total magnesium may not be adequate for the titration of therapeutic magnesium infusions in patients with preeclampsia or preterm labor because of the lack of correlation between total magnesium and the physiologically active ionized magnesium. Further studies may determine whether the measurement of ionized magnesium is a superior method for following the adequacy and safety of the treatment of preeclampsia and preterm labor.

Objective: Fetal plasma angiotensin II levels are 10 times the levels found in adults. Despite these high levels, central injection of angiotensin II may stimulate fetal swallowing and increase fetal arterial blood pressure. We postulated that the high rate of spontaneous fetal swallowing and normal fetal pressor regulation may be dependent, in part, on central angiotensin II. In view of the potential dipsogenic role of both type 1 and type 2 angiotensin II receptors, we examined the central effect of the nonselective angiotensin II receptor antagonist saralasin on fetal swallowing and cardiovascular responses. Study Design: Six time-dated pregnant ewes and fetuses were chronically prepared with fetal vascular and intracerebroventricular catheters, electrocorticograms, and esophageal electromyogram electrodes and studied at 130 ± 1 days' gestation. After an initial 2-hour baseline period (0 to 2 hours), saralasin (1 mL, 64 μg) was injected intracerebroventricularly (2 to 4 hours). After 4 hours the dose of saralasin was repeated together with angiotensin II (1 mL, 6.4 μg), and the fetuses were monitored for a final 2 hours. Four fetuses also underwent an identical control study (on an alternate day) in which saralasin was replaced with artificial cerebrospinal fluid. Results: Blockade of central angiotensin II receptors by intracerebroventricular saralasin significantly reduced mean (± SEM) spontaneous fetal swallowing (1.3 ± 0.1 to 0.4 ± 0.1 swallows per minute; P

Objective: Human and ovine fetuses demonstrate an enhanced rate of spontaneous and angiotensin II–stimulated swallowing. Angiotensin II and nitric oxide synthase have been localized to thirst centers in the brain. This study was performed to determine whether central nitric oxide contributes to the regulation of angiotensin II–induced fetal swallowing. Study Design: Six pregnant ewes with near-term singleton fetuses were chronically prepared with fetal vascular and lateral ventricle catheters and electrocorticogram and esophageal electromyogram electrodes. After a 2-hour control period, fetuses were administered serial lateral ventricle injections (1 mL) of angiotensin II (3.2 μg; time, 2 hours) and N ω-nitro-L -arginine methyl ester (3 mg; time, 3 hours) and a repeat angiotensin II injection (3.2 μg; time, 5 hours). All fetuses received an additional control study of lateral ventricle injections of artificial cerebrospinal fluid on a previous day. Results: Angiotensin II injection significantly increased mean ± SEM fetal swallowing (0.9 ± 0.1 to 2.7 ± 0.4 swallows/min). N ω-nitro-L -arginine methyl ester significantly decreased fetal swallowing to below the basal rate (0.4 ± 0.1 swallows/min), and swallowing did not increase with the second angiotensin II dose (in the presence of nitric oxide blockade). Conclusions: These results demonstrate that inhibition of central nitric oxide suppresses fetal swallowing behavior in response to central angiotensin II. We speculate that tonic nitric oxide facilitates angiotensin II swallowing stimulation by maintenance of glutamate activation of hypothalamic N -methyl-D -aspartate receptors. (Am J Obstet Gynecol 2000;182:713-9.)

Human and ovine fetuses demonstrate an enhanced rate of swallowing, an activity critical for amniotic fluid regulation. Fetal swallowing may be modulated by both systemic and central factors. Nitric oxide (NO) is a central neuromodulator that has been localized to brain regions regulating thirst and swallowing. We sought to determine if NO contributes to the regulation of spontaneous ovine fetal swallowing. Six time-dated pregnant ewes with singleton fetuses (129 ± 1 day) were chronically prepared with fetal vascular and lateral ventricle catheters and electrocorticogram (ECoG) and esophageal electromyogram electrodes. After a 2-h control period, fetuses were given lateral ventricle injection of NO synthase inhibitor nitro-l-arginine methyl ester (l-NAME) and monitored for 2 h. NO precursor l-arginine was then injected into the lateral ventricle, and fetuses were monitored for a final 2 h. All fetuses received an additional control study of fetal swallowing before and after lateral ventricle injection of artificial cerebrospinal fluid (aCSF). Data were analyzed with repeated-measures ANOVA and paired t-test ( P < 0.05). Suppression of a central NO with central l-NAME significantly reduced mean (±SE) spontaneous fetal swallowing (1.2 ± 0.1–0.6 ± 0.1 swallows/min low-voltage ECoG; P < 0.01). Restoration of central NO by l-arginine significantly increased fetal swallowing to pre-l-NAME levels (1.2 ± 0.1 swallows/min low voltage). There were no changes in fetal swallowing during the control study of aCSF. Fetal ECoG activity and blood pressure did not change during the study or control aCSF injection. We conclude that NO is an important neuromodulator of fetal swallowing activity. Central NO synthase activity may contribute to the heightened level of spontaneous fetal swallowing and thus amniotic fluid regulation.

The objective of this study was to determine the variation in first-trimester fetal size and fetal heart rates in multifetal pregnancies, and to study the effect of fetal reduction on the surviving fetal heart rate. Fetal crown-rump length and fetal heart rates were measured in 44 patients with multifetal pregnancies who underwent fetal reduction. The heart rates of the surviving fetuses were also measured immediately after, and 1 h following the procedure. A total of 143 fetuses were evaluated prior to reduction and 75 fetuses following the procedure. There was no significant difference in crown-rump length between fetuses of the same gestation. The interfetal fetal heart rate variation between fetuses of the same gestation, expressed as a standard deviation, was 4.78 ± 0.51 beats/min (mean standard deviation ± standard error of the mean) before reduction; this was a significantly greater variation than could be attributed to error in the measurement of heart rate. In the surviving fetuses, the mean heart rate did not change. However, immediately after the reduction, interfetal heart rate variation was abolished, but was observed again 1 h after the reduction. We conclude that in first-trimester multifetal pregnancies (1) there is no significant difference in fetal crown-rump length; (2) there is interfetal variation in heart rates; and (3) fetal reduction has only a limited effect on the heart rates of surviving fetuses. Copyright © 1997 International Society of Ultrasound in Obstetrics and Gynecology

Background: We compared outcomes between neonates receiving either single course, multiple courses, or no antenatal glucocorticoid exposure.Methods: We retrospectively identified neonates whose mothers received a single course (SIN) of dexamethasone, multiple (2-3) weekly courses (MULT), or no (NO) glucocorticoids. Multiple gestations and infants with chromosomal abnormalities or not receiving a full course of antenatal dexamethasone were excluded from the study. The incidences of the following outcomes were examined: respiratory distress syndrome (RDS), Grades III or IV intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), sepsis, and in-hospital death. Means were compared with analysis of variance and outcome variable frequencies with chi-square test.Results: A total of 147 infants were included in the analysis. There were no differences in the gestational age or growth parameters among the groups. As anticipated, infants ...

The early time period following ischemia may be of pathogenetic importance in hypoxic-ischemic brain injury. Global cerebral oligemia was induced in ten late gestation fetal sheep by inflation of a balloon occluder around the brachiocephalic artery. Cerebral blood flow, oxygen, glucose, and lactate net flux, and oxygen delivery were measured by the Fick principle following 1 h of oligemia and at 5, 30, and 60 min of postoligemic reperfusion. During oligemia, cerebral blood flow decreased by 74 ± 10% (mean ± SD) and oxygen consumption decreased by 34 ± 24%. The glucose:oxygen quotient was elevated throughout the oligemic period. In the early (5 min) reperfusion period, blood flow and oxygen delivery were not different from control but oxygen consumption was persistently depressed by 27 ± 32%; fractional extraction of oxygen was 0.38 ± 0.10 during control and 0.24 ± 0.09 during early reperfusion. The venous oxygen tension increased modestly from 15.2 ± 2.4 to 18.0 ± 1.7 mm Hg; the postoligemic venous pO2 was limited by the lack of reactive hyperemia combined with the low arterial pO2 of the intrauterine environment. Postoligemic carbohydrate fluxes could not be differentiated from control, possibly due to blood–brain barrier limitations. These factors may be related to the relative resistance of the fetal brain to hypoxic–ischemic injury.

Massive hemoptysis is a life-threatening situation that rarely complicates pregnancy. Presented is a case of massive hemoptysis during pregnancy, which was successfully diagnosed and treated with bronchial artery angiogram and embolization. A 26-year-old multigravida at 19 weeks' gestational age with a history of intravenous substance abuse and infective endocarditis presented with hemoptysis. Extensive workup, including bronchoscopy, echocardiography, and magnetic resonance pulmonary angiography were negative. The patient left the hospital against medical advice to return 4 weeks later with massive hemoptysis. Bronchial arteriography revealed multiple areas of potential bleeding in the right and left lower lobes. Bilateral bronchial artery embolization was performed. The patient carried the pregnancy to term with no further episodes of hemoptysis. Hemoptysis during pregnancy requires a thorough workup and prompt treatment if the etiology is diagnosed. When faced with massive hemoptysis, the obstetrician should strongly consider bronchial artery angiography and embolization.

In adult rats, N-methyl-D-aspartate (NMDA) receptors have been implicated in the central control of body fluid homeostasis, as intracerebroventricular (ICV) injection of NMDA receptor antagonists suppresses stimulated drinking behavior. Fetal swallowing occurs at a significantly higher rate as compared to adult drinking, contributing to amniotic fluid volume regulation and fetal gastrointestinal development. The aim of present study was to determine the role of central NMDA receptors in the modulation of fetal swallowing activity.Eight time-dated pregnant ewes and fetuses were chronically prepared with fetal vascular and ICV catheters, electrocorticogram (ECoG), and esophageal electromyogram electrodes and studied at 130 +/- 1 days' gestation. Following an initial 2-hour baseline period (time 2 h), the NMDA receptor antagonist, dizocipline (1 mg), was injected ICV. At time 4 h, the dose of dizocipline was repeated, together with angiotensin II (AngII, 6.4 microg). Fetal swallowing was monitored for 2 hours after each injection. Four of these fetuses also received an identical control study (on an alternate day) in which dizocipline was replaced with artificial cerebrospinal fluid (aCSF).ICV dizocipline injection nearly abolished spontaneous fetal swallowing activities (0.6 +/- 0.1 to 0.2 +/- 0.1 swallows/min; P.001). ICV AngII in the presence of dizocipline did not demonstrate a dipsogenic effect on fetal swallowing (0.1 +/- 0.1; P.001). In the control study, ICV injection of aCSF did not change fetal swallowing activity (1.0 +/- 0.1 swallows/min), while ICV AngII resulted in a significant increase in fetal swallowing (2.0 +/- 0.1 swallows/min; P.001).This study demonstrates that central NMDA-glutamate receptor-mediated activity contributes to the high rate of spontaneous and AngII-stimulated fetal swallowing. We speculate that reduced NMDA receptor expression within the forebrain dipsogenic neurons may account for observed differences in drinking activities between the fetus/neonate and the adult.

The purpose of this study was to examine cardiovascular responses to fourth cerebral ventricle (4V) administration of nitroglycerin (NTG) or an inhibitor of nitric oxide (NO) synthase (NOS) in the near-term ovine and to determine whether, during birth, neuronal NOS (nNOS) is induced in noradrenergic A1 neurons in the medial nucleus tractus solitarius (mNTS). In chronically instrumented fetal sheep, 4V injection of NTG (1.2 nmol), an NO donor, produced an arterial blood depressor and a moderate decrease in heart rate. Arterial blood pressure is increased by 4V administration of NG-nitro-l-arginine methyl ester (10 nmnol), an inhibitor of NOS, in fetuses. Sections of the medulla from fetuses and newborn lambs were examined by using immunolabeling with tyrosine hydroxylase (TH) antibody combined with NADPH diaphorase (NADPHd) histochemistry, a marker of nNOS activity. The NADPHd-positive cells and TH-positive cells containing NADPHd reactivity were significantly increased in the mNTS of newborns compared with the fetuses. The results suggest that during birth, there is upregulation of NADPHd/nNOS in the noradrenergic neurons of mNTS resulting in a centrally mediated reduction of fetal arterial blood pressure.

Transition from fetal to newborn life is accompanied by a marked rise in circulating norepinephrine (NE) concentrations though arterial blood pressure does not substantively change. Nitric oxide (NO) plays an important role in the central regulation of sympathetic tone in the nucleus tractus solitarius (NTS) and neuronal NO synthase (nNOS) expression is functionally regulated in the brain. The purpose of these studies was to determine the influence of transition at birth on nNOS expression in the brainstem nuclei, particularly in the NTS, associated with changes in arterial pressure and plasma NE concentration. Experiments were performed using time-dated gestational ewes with twin fetuses. Arterial blood pressure was recorded and arterial blood NE concentrations were measured in the term fetus (gestational 147–148 days) and newborn lambs (4 h of postnatal age). The fetal and newborn animals were then perfused with 4% paraformaldehyde. Sections of the medulla were examined by using both immunolabeling with a polyclonal antibody directed against nNOS and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry, a marker for expression of nNOS. Micrographs were quantified using a microscope with reticule grid to measure the number of positive cells containing color staining in the brainstem nuclei. Plasma NE concentration in the newborn was more than two-fold greater compared to fetal values but mean arterial blood pressure was similar between fetus and newborn. The nNOS positive cells and NADPHd positive cells were significantly increased in the medial NTS (mNTS) of the newborn compared to fetus. nNOS immunoreactivity and NADPHd reactivity tended to increase in the rostral ventral medulla (RVM) in newborn, but were not altered in other brainstem nuclei during the transition from fetal to newborn life. The results suggest that nNOS expression in the mNTS is predominately enhanced at 4 h of neonatal age vs. the term fetus. We conclude that elevated circulating NE is associated with up-regulation of nNOS in the mNTS which may serve a protective role in central regulation of neonatal arterial blood pressure.

OBJECTIVE: Our purpose was to test whether cocaine stimulates uterine activity in nonpregnant and pregnant rats. STUDY DESIGN: The carotid artery and jugular vein were chronically catheterized, and a microballoon probe was inserted into the uterine cavity of 15 pregnant and 14 nonpregnant female rats. Conscious animals received a bolus dose of either cocaine or saline solution intravenously. Cardiovascular and uterine contractile responses were studied. RESULTS: Cocaine (2.5 mg/kg) induced a marked increase in uterine activity and arterial blood pressure in both pregnant and nonpregnant animals without producing systemic toxicity. The maximum change in uterine contractions was greater in the pregnant group than in the nonpregnant group, and blood pressure responses were transient in both. CONCLUSION: This study is the first demonstration that cocaine stimulates the rat uterus in vivo, with a greater increase in contractions in pregnant compared with nonpregnant animals. These differences are not related to the hemodynamic response or pharmacokinetic profile of cocaine. (Am J Obstet Gynecol 1996;175:188-93.)

Cocaine administration during pregnancy results in major maternal cardiovascular effects that in some cases exceed those observed in the nonpregnant state. Animal studies have shown increases in heart rate and blood pressure and decreases in regional organ blood flow. Fetal effects include arterial hypoxemia, increases in blood pressure and heart rate, and increases in cerebral blood flow that may be related not only to hypertension and hypoxemia, but also to direct effects on cerebral blood vessels. Fetal intestinal blood flow is decreased. These effects may be related to the clinical consequences of cocaine use during pregnancy.

OBJECTIVE: Our purpose was to test the hypothesis that wedging of the cervical internal os determined by transvaginal ultrasonography is associated with premature labor and delivery. STUDY DESIGN: Seventy patients admitted to the hospital for threatened preterm labor were evaluated by transvaginal ultrasonography before institution of therapy. Bivariate and logistic regression analyses were performed to determine the variables that made a significant contribution to the prediction of preterm delivery. RESULTS: Preterm delivery was significantly associated with the presence of cervical wedging, as noted on cervical scan, and with short cervical length. A history of previous preterm delivery was of marginal significance as a predictor of preterm delivery ( p = 0.09). Preterm delivery was not significantly correlated with age, previous voluntary termination of pregnancy, gestational age at the time of study, previous normal spontaneous vaginal delivery, or tocolytic therapy. Use of wedging as a diagnostic test for the prediction of preterm delivery yielded a sensitivity of 100%, a specificity of 74.5%, a positive predictive value of 59.4%, and a negative predictive value of 100%. CONCLUSION: The presence of wedging and shorter cervical length was suggestive of true preterm labor requiring aggressive management. A transvaginal ultrasonographic "snapshot" view of the cervix seems to be a more reliable method to evaluate the cervix in patients with threatened premature labor than are uterine contractions alone. (AM J OBSTET GYNECOL 1996;174:990-5.)

Objective: Our purpose was to test the hypothesis that transvaginal ultrasonographically determined characteristics of the cervix are associated with duration of induced labor. Study Design: Fifty-three patients scheduled for induction of labor underwent transvaginal ultrasonography and digital cervical examinations before labor induction. Cox proportional-hazards multiple regression analysis was performed to determine the variables that made a significant contribution to the prediction of latent-phase and total labor duration. In the analysis the possible confounding effects of exogenous prostaglandin, previous vaginal delivery, and previous termination of pregnancy were controlled. Results: Latent-phase and total labor duration were significantly associated with the presence of cervical wedging noted on transvaginal ultrasonography and administration of prostaglandin but not with the result of digital examination of cervical effacement or dilatation. Latent-phase duration was also associated with cervical length measured by transvaginal ultrasonography. The presence of wedging was significantly associated with shorter latent (15.9 ± 1.7 vs 34.1 ± 3.8 hours, p = 0.0001) and total (22.0 ± 1.8 vs 38.3 ± 3.6 hours, p = 0.0001) labor length. Conclusion: The presence of wedging and decreased cervical length observed by transvaginal ultrasonography is associated with a shorter duration of induced labor and may be useful in the evaluation of induction candidates.

Objective: Our purpose was to determine characteristics of fetal breathing activity by recording fetal nasal fluid flow velocity in cases of congenital diaphragmatic hernia. Study Design: Fetal breathing-related nasal fluid flow was studied in 47 patients at 34 to 41 weeks of gestation, 16 cases of antenatally diagnosed congenital diaphragmatic hernia and 31 cases of uncomplicated pregnancy. The examination was performed by ultrasonography combined with color-flow and spectral Doppler analysis. An average of 25 breath cycles from each case was determined for each of the following timing parameters: breath-to-breath interval, time of inspiration, time of expiration, and ratio of time of inspiration and time of expiration. Results: In all cases with uncomplicated pregnancy fetal breathing-related nasal fluid flow was seen at the level of the nose, and the timing components of this flow were determined as control values. In two cases with diaphragmatic hernia no perinasal flow was demonstrated, although fetal breathing movements observed as chest wall movements were present. The other 14 cases with congenital diaphragmatic hernia who demonstrated perinasal flow had the following postnatal outcome: one stillbirth, five neonatal deaths (group I), and eight survived and were discharged (group II). The study revealed that the time of expiration (in milliseconds) in group II (493.2 ± 34.3 SEM) was significantly ( p = 0.0030) shorter than in group I (653.4 ± 38.4) and in cases of uncomplicated pregnancy (633.6 ± 18.5). The value of the time of inspiration/time of expiration ratio in group II was approximately 15% higher than in group I and approximately 30% higher than in cases of uncomplicated pregnancies. Conclusions: Observation of fetal breathing-related nasal fluid flow velocity in cases of antenatally diagnosed congenital diaphragmatic hernia provides a rationale for the hypothesis that time of expiration and the time of inspiration/time of expiration ratio may be useful in the prediction of postnatal outcome. We speculate that the changes in the group of survivors may represent a compensatory phenomenon by causing intermittent changes in the volume of fluid within the lungs.

An improved method for the simultaneous determination of cocaine and benzoylecgonine by means of gas chromatography with nitrogen—phosphorus detection is described. Following a solid-phase extraction and derivatization of benzoylecgonine to its butyl ester, chromatography was performed using a capillary column. The n-propylester of benzoylecgonine served as the internal standard. The assay was linear from 4 to 2000 ng/ml for both cocaine and benzoylecgonine, with a good precision over this concentration range. This method may be particularly useful for small volume samples since it requires only 250 μl of plasma for analysis of both cocaine and benzoylecgonine.

OBJECTIVE: Our purpose was to determine the Doppler ultrasonographic characteristics of fetal breathing—related nasal fluid flow velocity in uncomplicated pregnancies. STUDY DESIGN: Fetal nasal flow velocity was studied in 52 uncomplicated pregnancies at gestational ages ranging from 22 to 41 weeks. The evaluation of fetal breathing-related nasal fluid flow velocity was performed with ultrasonography combined with color flow and spectral Doppler analysis. RESULTS: The study revealed that the breath-to-breath interval and duration of the inspiratory phase of the fetal breathing-related nasal flow increased from 22 to 35 weeks and decreased thereafter. The breath-to-breath interval (milliseconds) at 33 to 35 weeks (1203.9 ± 295.7 SD) was approximately twice what it was in the earliest age group (22 to 25 weeks); subsequently it decreased by approximately 25% in the term group (38 to 41 weeks). A positive correlation existed between the mean breathing-related nasal peak inspiratory flow velocity and advancing gestational age ( r = 0.56, p = 0.0008), and between the inspiratory flow velocity acceleration and advancing gestational age ( r = 0.53, p = 0.0076). CONCLUSION: Changes in fetal breathing activity during uncomplicated pregnancies can be determined by measurement of fetal breathing-related nasal fluid flow velocity. Our observations in uncomplicated pregnancies may be useful in future studies of these parameters in complicated pregnancies such as those at risk for pulmonary hypoplasia.

The response of the premature fetus to speech stimuli was studied in 41 healthy pregnant patients at 26–34 weeks gestation. Speech stimuli consisted of repeated syllables (‘ee’ and ‘ah’) presented externally over the maternal abdomen at either 100, 105, or 110 decibels (dB). Sound stimuli were delivered during periods of both high and low fetal heart rate variability. During periods of low FHR variability, a decrease in fetal heart rate and an increase in the standard deviation of heart rate were found. During periods of high FHR variability, no significant change in either of these measures was observed. This is the first clear demonstration of heart rate responses to speech stimuli in the premature fetus. As is the case in the term fetus, this response is dependent on baseline heart rate variability which is the primary determinant of fetal state. The clinical usefulness of this finding may be limited by the magnitude of the response.

We hypothesized that because fetal stomach filling and emptying is a dynamic process, measurements of the stomach dimensions might not be reproducible. Serial measurements 20 minutes apart were made of the stomach in 146 fetuses at 14 to 41 weeks of gestation. In 88 of these fetuses, the biparietal diameter also was measured to provide a standard for comparison. The mean percentage change between each of the paired measurements was 16.6% to 43.1% for the different stomach dimensions, compared with only 2% for the biparietal diameter (P < 0.001). We suggest that caution be excised in the diagnostic use of stomach measurements owing to their dynamically changing nature.

The first-passage multiple-indicator dilution method was used to measure blood to brain transport of D- and L-glucose, D- and L-lactate and sucrose relative to 22Na, an impermeable reference tracer, in fetal sheep. Fractional extraction for D-glucose was 0.315 +/− 0.051 (S.E.M.) at normal glucose levels and fell to 0.198 +/− 0.041 at 5.2 +/− 0.4 mM-glucose. Fractional extractions for L-glucose, D- and L-lactate and sucrose were not different from zero. No specific blood-brain transport system was detected for L-lactate in fetal sheep in vivo (fractional extraction = -0.024 +/− 0.019). Uptake of L-lactate into isolated microvessels from fetal sheep cerebrum in vitro showed a slightly higher rate (32.2 +/− 8.9 pmol min-1 (mg protein)-1) than that for D-lactate (22.6 +/− 5.6). In fetal guinea-pigs, the carotid arterial injection method with tritiated water as the permeable reference was used to measure the brain uptake index (BUI). BUI was determined for D-glucose (0.304 +/− 0.065) sucrose (0.008 +/− 0.001), L-lactate (0.418 +/− 0.112) and D-lactate (0.071 +/- 0.024). Unidirectional influx calculated from these measurements and estimates of cerebral blood flow showed that transport would be rate-limiting for cerebral glucose utilization at arterial glucose levels below 0.5 mM in fetal sheep and 1.7 mM in fetal guinea-pig. In fetal sheep, but not in fetal guinea-pigs, lactate efflux may be limited by brain-blood transport.

The effect of hypoxemia and cephalic hypotension, alone and in combination, on hemispherical CBF and metabolism was examined in seven chronically catheterized fetal sheep. Hypoxemia was induced by lowering the maternal inspired oxygen fraction and cephalic hypotension was generated by partial occlusion of the fetal brachiocephalic artery. CBF was measured with radionuclide-labeled microspheres. During control, the arterial blood oxygen content (Cao2) was 3.2 ± 1.0 (SD) m M and CBF averaged 131 ± 21 (SD) ml min−1 100 g−1. The cephalic perfusion pressure (PP, mean cephalic arterial - sagittal venous) was 40 ± 4 mm Hg and cerebral vascular resistance (CVR, PP/CBF) was 0.31 ± 0.06 mm Hg ml−1 min 100 g. During induced hypoxemia, Cao2 was 1.4 ± 0.7 m M and CBF was elevated to 223 ± 60 ml min−1 100 g−1. PP was not different from control and CVR was lower at 0.19 ± 0.04 mm Hg ml−1 min 100 g, reflecting cerebral vasodilation. With cephalic hypotension alone (PP = 21 ± 4 mm Hg; Cao2 = 3.4 ± 0.9 m M), CBF fell to 83 ± 23 ml min−1 100 g−1 and there was no significant change in CVR (0.26 ± 0.05 mm Hg ml−1 min 100 g). During combined hypoxemia and hypotension (Cao2 = 1.5 ± 0.8 m M and PP = 18 ± 4 mm Hg), CBF was significantly greater than during hypotension alone (100 ± 6 ml min−1 100 g). CVR was 0.19 ± 0.05 mm Hg ml−1 min 100 g, identical to that measured in normotensive hypoxemia and significantly less than found during hypotension alone. Cerebral oxygen consumption was lower during combined hypoxemia and cephalic hypotension than during hypoxemia alone. Cerebral glucose uptake was significantly higher than control in both the hypoxemic and combined hypoxemic-hypotensive conditions. The glucose:oxygen quotient (6 × molar glucose uptake/molar oxygen consumption) was not different from unity during control or hypotension but was 2.31 ± 1.16 and 3.63 ± 1.99 during the hypoxemic and hypoxemic-hypotensive conditions, respectively, suggesting an anaerobic glucose utilization. No significant lactate efflux could be measured in any of these conditions.