Angle of progression measured using transperineal ultrasound for prediction of uncomplicated operative vaginal delivery: systematic review and meta-analysis.

OBJECTIVE: To determine whether intrapartum transperineal ultrasound measurement of the angle of progression (AoP) during the second stage of labor can predict uncomplicated operative vaginal delivery (OVD) using vacuum or forceps extraction. METHODS: A systematic search in PubMed, EMBASE, Scopus, Web of Science and Google Scholar was performed from inception to February 2021. Studies assessing the predictive accuracy of AoP, measured using intrapartum transperineal ultrasound, for uncomplicated OVD, defined as successful vaginal delivery within three pulls using forceps or no more than two detachments of the vacuum extractor cup, were included. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Summary receiver-operating-characteristics (ROC) curves, pooled sensitivity and specificity, area under the ROC curve (AUC) and summary likelihood ratios (LRs) were calculated. RESULTS: Seven studies reporting on a total of 782 patients undergoing OVD were included in this systematic review and meta-analysis. Second-stage AoP measured during maternal rest had a pooled sensitivity of 80% (95% CI, 59-92%) and specificity of 89% (95% CI, 76-95%), with a LR+ of 7.3 (95% CI, 3.1-15.8) for uncomplicated OVD. AoP measured during active pushing had a sensitivity of 91% (95% CI, 85-94%) and specificity of 83% (95% CI, 69-92%), with a LR+ of 5.4 (95% CI, 2.7-10.6) for uncomplicated OVD. The performance of AoP measured at rest was particularly high in nulliparous women, with a sensitivity of 87% (95% CI, 75-94%) and specificity of 90% (95% CI, 82-94%) for uncomplicated OVD. CONCLUSION: AoP may be a reliable predictor for uncomplicated OVD when measured during the second stage of labor, especially in nulliparous women. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Pharmacogenomic study of side-effects for antidepressant treatment options in STAR*D.

BACKGROUND: Understanding individual differences in susceptibility to antidepressant therapy side-effects is essential to optimize the treatment of depression. METHOD: We performed genome-wide association studies (GWAS) to search for genetic variation affecting the susceptibility to side-effects. The analysis sample consisted of 1439 depression patients, successfully genotyped for 421K single nucleotide polymorphisms (SNPs), from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Outcomes included four indicators of side-effects: general side-effect burden, sexual side-effects, dizziness and vision/hearing-related side-effects. Our criterion for genome-wide significance was a prespecified threshold ensuring that, on average, only 10% of the significant findings are false discoveries. RESULTS: Thirty-four SNPs satisfied this criterion. The top finding indicated that 10 SNPs in SACM1L mediated the effects of bupropion on sexual side-effects (p = 4.98 × 10(-7), q = 0.023). Suggestive findings were also found for SNPs in MAGI2, DTWD1, WDFY4 and CHL1. CONCLUSIONS: Although our findings require replication and functional validation, this study demonstrates the potential of GWAS to discover genes and pathways that could mediate adverse effects of antidepressant medication.

Fetal heart rate mirrors maternal temperature during posterior fossa craniotomy: a case report.

While it is well known that maternal temperature affects fetal heart rate, the exact relationship is not well described. The circumstances accompanying most cases of maternal hypothermia and rewarming (e.g. a drowning event) have precluded a precise quantitative description of this relationship. We describe hypothermia and controlled rewarming during resection of a maternal brain stem tumor in the early third trimester. Continuous electronic fetal heart rate and core temperature monitoring demonstrated a near linear relationship during the development of hypothermia and rewarming. Recognition of the close relationship between maternal temperature and fetal heart rate can help safeguard maternal and fetal health, and prevent unnecessary delivery during non-obstetric surgery in pregnancy.

Incorporation of sulfate by the mouse thymus: its relation to secretion by medullary epithelial cells and to thymic lymphopoiesis.

The thymus was examined in suckling mice during normal development and the involution and regeneration produced by injection of cortisol, in experiments designed to test the hypothesis that medullary epithelial cells secrete a ymphopoietic hormone responsible for controlling the magnitude of thymic lymphopoiesis. Cellular events were observed by light and electron microscopy. Lymphopoiesis was assessed, after injection of thymidine-(3)H, by counting the proportion of lymphocytes labeled in radioautographs of thymus. Cortical lymphopoiesis was distributed heterogeneously, being concentrated in the subcapsular region, but medullary lymphopoiesis was statistically homogeneous in distribution and similar in magnitude to the average level of cortical lymphopoiesis in suckling mice. Therefore counts of the labeling index in the medulla were used to estimate the size of the proliferating population of lymphocytes. Epithelial secretory activity was estimated by measuring the incorporation of (36)sulfate by the thymus, using gel filtration chromatography to isolate soluble macromolecular (35)sulfate-presumed on radioautographic evidence to represent the mucoid epithelial secretory product. Incorporated (35)sulfate accumulated rapidly for 4 hr, reached a peak at 12 hr, and had fallen to half that level by 24 hr after a single injection-as would be expected of a secretory product. During normal postnatal development the size of the proliferating population of lymphocytes and the magnitude of (35)sulfate incorporation increased in parallel. During acute involution induced by cortisol both parameters diminished greatly but rose to high levels during subsequent regeneration. Accordingly, lymphopoiesis and sulfate incorporation -as defined and measured in these experiments-correlated linearly over a wide range of variation, providing circumstantial evidence to support the hypothesis that medullary epithelial cells secrete a sulfated mucoid lymphopoietic hormone. This conclusion is discussed in terms of the roles of thymus and adrenal cortex in development of the lymphoid system and maturation of immunological competence.

Regulation of G-protein alpha i2 subunit expression by oxidized low-density lipoprotein.

Oxidized low-density lipoprotein (LDL) inhibits signalling pathways mediated by pertussis toxin-sensitive guanine nucleotide-binding proteins (Gi proteins). To determine whether this inhibition is due to altered G protein alpha i subunit expression, mRNA and protein levels of alpha i isoforms were assessed in bovine aortic endothelial cells treated with oxidized LDL (0-100 micrograms/ml, 0-72 h). Oxidized LDL did not affect the expression of alpha i3, but did cause time- and concentration-dependent decrease in alpha i2 mRNA and protein resulting in a 3.2- and 3.5-fold reduction, respectively, after 72 h. This decrease in alpha i2 coincided with a 86% decrease in alpha i2 GTPase activity. Nuclear run-off studies did not show any significant effect of oxidized LDL on alpha i2 or alpha i3 transcription. In the presence of actinomycin D, oxidized LDL shortened the t1/2 of alpha i2 mRNA from 16 h to 8 h which was attenuated by cycloheximide. In addition, pulse-chase labelling with [35S]methionine revealed that oxidized LDL reduced the t1/2 of alpha i2 protein from 27 to 14 h. Our results indicate that oxidized LDL can modulate receptor-Gi coupling by downregulating the expression of alpha i2, but not alpha i3. The mechanism involves both mRNA destabilization and protein degradation.

Airway management for cesarean delivery performed under general anesthesia.

BACKGROUND: With the increasing popularity of neuraxial anesthesia, there has been a decline in the use of general anesthesia for cesarean delivery. We sought to examine the incidence, outcome and characteristics associated with a failed airway in patients undergoing cesarean delivery under general anesthesia. METHODS: A retrospective review of airway management in women undergoing cesarean delivery under general anesthesia over an eight-year period from 2006-2013 at an academic medical center was conducted. RESULTS: During the study period, 10 077 cesarean deliveries were performed. Neuraxial anesthesia was used in 9382 (93%) women while general anesthesia was used in 695 (7%). Emergent cesarean delivery was the most common indication for general anesthesia. Failed intubation was encountered in only three (0.4%) women, who were successfully managed with a laryngeal mask airway. The overall incidence of failed intubation was 1 in 232 (95% CI 1:83 to 1:666) and general anesthesia was continued in all cases. There were no adverse maternal or fetal outcomes directly related to failed intubation. CONCLUSION: Advances in adjunct airway equipment, availability of an experienced anesthesiologist and simulation-based teaching of failed airway management in obstetrics may have contributed to our improved maternal outcomes in patients undergoing cesarean delivery under general anesthesia.

The antinociceptive action of etorphine in the dorsal horn is due to a direct spinal action and not to activation of descending inhibition.

1--Etorphine, microinjected into the brainstem or administered intravenously, inhibited the firing of dorsal horn neurones to noxious heat in spinal or non-spinal anaesthetized cats and in decerebrate, non-anaesthetized cats with intact spinal cords. 2--Small doses of etorphine sometimes caused facilitation, especially when the cord was intact, but this was invariably followed by inhibition at higher doses. 3--The ED50 for inhibition (mean 3.9 micrograms/kg) after microinjection into nucleus raphe magnus, nucleus reticularis magnocellularis or the lateral tegmental field was similar at all sites in anaesthetized, non-spinal cats. 4--The ED50 for microinjection was not increased by spinal transection in anaesthetized cats (mean ED50, 2.6 micrograms/kg) and was similar to the ED50 in decerebrate, non-anaesthetized cats. 5--Intravenous administration was 2 to 3 times more effective than microinjection and the time course of inhibition was faster after intravenous administration than after microinjection. 6--It is concluded that etorphine inhibits dorsal horn neurones after microinjection or intravenous administration by a direct action on the spinal cord and not by activating a descending inhibition. After microinjection it rapidly enters the general circulation and subsequently distributes into the spinal cord. 7--It is also concluded that naloxone readily gains entry to the circulation from the brain because microinjection antagonized the effects of systemic etorphine on dorsal horn neurones in spinal cats.

Inhibition by substance P of some peripheral actions of acetylcholine in the cat.

1 The effect of substance P on contractions of the nictitating membrane and pressor responses to acetylcholine (ACh) and dimethylphenyl-piperazinium (DMPP) which were mediated via nocotinic receptors was studied in cats anaesthetized with chloralose.2 Substance P (2-20 nmol) injected into the lingual artery giving estimated concentrations in arterial blood of 10(-6) to 10(-5) M, or intravenously giving estimated concentrations in blood of 10(-8) to 10(-7) M, reduced hexamethonium-sensitive but not atropine-sensitive responses.3 The pressor effects of ACh and DMPP injected intra-arterially in atropinized and non-atropinized cats respectively were consistently attenuated by substance P given intra-arterially or intravenously.4 The contractile effect of ACh in atropinized and of DMPP in non-atropinized cats was attenuated by substance P injected intra-arterially but only rarely when the polypeptide was injected intravenously.5 The depressor effects of substance P per se were variable in magnitude and duration as were the inhibitory effects upon nicotinic receptors. The depressor and inhibitory effects of substance P were unrelated.6 There was desensitization to all of these effects of substance P which probably contributed to the variation in the magnitude of the effects observed.7 Substance P had no effect on muscarinic actions of acetyl-beta-methylcholine on the nictitating membrane or blood pressure.8 The results are discussed in relation to the ubiquity of the modulatory actions of substance P on nicotinic receptors and in relation to the possible physiological significance of the action.

The relative significance of spinal and supraspinal actions in the antinociceptive effect of morphine in the dorsal horn: an evaluation of the microinjection technique.

Large quantities of morphine injected directly into the brainstem of spinal anaesthetized cats inhibited the noxious heat-evoked excitation of dorsal horn neurones. The amounts required were similar to those that were required intravenously in cats with the spinal cord intact or transected. When the spinal cord was intact the amount of morphine microinjected into the brainstem required to inhibit the excitation of dorsal horn neurones was about ten fold less than it was in spinal animals. It is concluded that large, but not small doses of morphine microinjected into the brainstem can exert effects on the spinal cord after first entering the circulation. The effects of small doses are attributed to a local action in the brainstem which causes inhibition of spinal neurones either by activating descending inhibitory neuronal systems or by liberating endogenous substances which reach the spinal cord via the cerebro-spinal fluid. The concentrations of morphine achieved at various distances from the site of injection by the microinjection of microgram quantities and the time courses of the concentration changes were calculated from diffusion equations, assuming diffusion coefficients of 3 or 5 X 10(6) cm2 s-1. The curves obtained closely approximated those obtained experimentally. The concentrations achieved at distances up to 2 mm from the site of injection of 10 micrograms of morphine were calculated to exceed 10(-4)M and the time-courses of these concentration changes were compatible with the time course of inhibition of spinal neurones, or the production of analgesia after microinjection. Such concentrations are vastly in excess of those achieved in the brain after the systemic administration of morphine in analgesic doses. It is concluded that the local effects in the brainstem produced by the microinjection of microgram quantities of morphine have no relevance to the mechanism of analgesia produced by systemic administration.

Asthma in pregnancy. National Asthma Education Program Working Group on Asthma and Pregnancy. National Institutes of Health, National Heart, Lung and Blood Institute.

This manuscript is a summary of a comprehensive report dealing with asthma and pregnancy issued by the working group on Asthma and Pregnancy, National Institutes of Health (NIH), National Heart, Lung, and Blood Institute. The report was developed by a panel of obstetricians, pharmacologists, internists, allergists, and pulmonologists, who met over an 18-month period under the auspices of the NIH. Undertreatment of pregnant asthmatics, partially because of unfounded fears of adverse pharmacologic effects on the developing fetus, remains the major problem in the management of asthma during pregnancy in the United States. The four key components of asthma management during pregnancy are: 1) objective assessment of maternal lung function and fetal well-being, 2) avoidance or control of environmental precipitating factors, 3) pharmacologic therapy, and 4) patient education.

Reliability of intrapartum fetal heart rate monitoring in the postterm fetus with meconium passage.

Fifty-six postterm fetuses with intrapartum meconium passage underwent routine scalp stimulation and scalp blood sampling. Fetal heart rate (FHR) patterns were compared with blood pH. Nine fetuses (16%) had a scalp pH less than 7.20. Twenty-nine fetuses (54%) demonstrated spontaneous or induced FHR accelerations; none were acidemic. Acidemia with normal variability was found only in conjunction with severe variable decelerations, and may represent respiratory acidosis. In this group, two of nine acidemic fetuses demonstrated no decelerations (pH 7.04) or mild variable decelerations only (pH 7.19). The absence of late decelerations was not as reliable as the presence of accelerations in the prediction of fetal well-being. Thirty-three percent of the fetuses who failed to exhibit spontaneous or provoked FHR accelerations were acidemic. These findings suggest that in this high-risk group of fetuses, the absence of spontaneous FHR accelerations should be followed by an attempt to induce accelerations, scalp pH assessment, or cesarean section.

Prenatal diagnosis of cysts of the fetal choroid plexus.

Over a two-year period, cysts of the fetal choroid plexus were diagnosed prospectively by routine second-trimester ultrasonography in five patients, representing 0.18% of the population scanned for standard obstetric indications. Gestational age at the time of diagnosis ranged from 16-22 weeks. The cysts were located in the posterior portion of the choroid plexus within the lateral ventricle. The maximum diameter ranged from 3-14 mm. In two cases, the cyst was noted to be bilocular. No additional anomalies were detected in any fetus. Follow-up sonography two to five weeks after the initial scan documented disappearance of the cysts in all cases. The course of pregnancy in these patients was otherwise uneventful, and all infants were normal physically and neurologically both at the time of birth and between four and 24 months of follow-up.

A prospective evaluation of fetal pericardial fluid in 506 second-trimester low-risk pregnancies.

OBJECTIVE: To measure fetal pericardial fluid in low-risk second-trimester pregnancies and to evaluate outcome for those with measurements greater than 2 mm. METHODS: Five hundred and six women were referred for sonography between 16 and 25 weeks' gestation for common obstetric indications (dating, fetal survey, and placental location) unrelated to an increased risk of anomalies. All cases were evaluated with two-dimensional and M-mode real-time ultrasonography with the use of a mechanical sector transducer. The maximum distance of the fetal hypoechoic cardiac rim was recorded. We reviewed maternal and infant charts for those with measurements greater than 2 mm. RESULTS: Median (range) maternal age was 25 (15-42) years. Median gravidity and parity were two (1-14) and one (0-11), respectively. Median estimated gestational age was 20.4 (16.3-24.9) weeks. Fetal pericardial fluid was seen in 360 of 506 (71%) fetuses. Of these 360 fetuses, the mean distance (+/- 2 standard deviation) of the fetal hypoechoic cardiac rim was 1.20 mm +/- 0.91 mm (95% confidence interval 1.15, 1.25). Among the 506 cases, the maximum measurement was 3 mm. Ten of the 506 (2%) cases had measurements greater than 2 mm. None of these ten fetuses had a cardiac structural abnormality or arrhythmia, and perinatal outcome was unremarkable. CONCLUSION: During second-trimester fetal ultrasonographic examination, visualization of pericardial fluid up to 2 mm in the fetus with current high-resolution technology is common and should not be regarded as pathologic.

Placenta previa/accreta and prior cesarean section.

To assess the relationship between increasing numbers of previous cesarean sections and the subsequent development of placenta previa and placenta accreta, the records of all patients presenting to labor and delivery with the diagnosis of placenta previa between 1977 and 1983 were examined. Of a total of 97,799 patients, 292 (0.3%) had a placenta previa. The risk of placenta previa was 0.26% with an unscarred uterus and increased almost linearly with the number of prior cesarean sections to 10% in patients with four or more. The effect of advancing age and parity on the incidence of placenta previa was much less dramatic. Patients presenting with a placenta previa and an unscarred uterus had a 5% risk of clinical placenta accreta. With a placenta previa and one previous cesarean section, the risk of placenta accreta was 24%; this risk continued to increase to 67% (two of three) with a placenta previa and four or more cesarean sections. Possible mechanisms and clinical implications are discussed.