Family medicine physician identification of obstetric lacerations: a US national survey.

INTRODUCTION AND HYPOTHESIS: We evaluated family medicine obstetric providers' identification and categorization of vaginal delivery lacerations in the USA. We hypothesized that there would be inaccuracy in family medicine physicians' identification of vaginal delivery injuries, similar to our previous studies of midwives and obstetricians (OBs). METHODS: We included clinically active physicians who attended deliveries within 2 years and evaluated their identification and categorization of delivery lacerations using descriptive text and visual images. We asked about their education on this topic and how they document lacerations in the labor and delivery record. RESULTS: We analyzed 250 completed responses (70% of opened surveys). Fifty-five percent of respondents characterized their obstetric laceration training as "good" or "excellent" and half previously had education on obstetric lacerations. The median accuracy overall for the classification and identification of perineal lacerations was 78% (IQR 56-91%). Respondents frequently mischaracterized nonperineal lacerations. Few respondents (36%) reported using the third-degree injury subclassification system. In adjusted analysis, the highest scoring respondents were board certified in family medicine, with fewer years in practice, and a higher obstetric volume. CONCLUSIONS: Obstetric laceration diagnoses may be inaccurate, which could influence perinatal quality and patient outcomes. We found gaps in knowledge similar to previous reports on midwives and obstetricians in the USA. These data suggest a need for increased education and training on obstetric injuries, perhaps especially for physicians with less obstetric activity. Improved categorization and identification of vaginal delivery trauma can impact management and improve women's postpartum care and long-term pelvic floor outcomes.

Diagnosis, management and training in perineal trauma: a UK national survey of obstetricians.

INTRODUCTION AND HYPOTHESIS: Perineal trauma during vaginal delivery is very common. Training in diagnosis and repair of trauma, including obstetric anal sphincter injuries, varies in the UK. We aimed to investigate the current knowledge and training received by obstetric physicians. METHODS: A national, validated survey was conducted online, using Qualtrics. The National Trainees Committee distributed the survey. It was also sent directly to consultants via email. RESULTS: A total of 302 physicians completed the survey and were included in the analysis. 3.9% of participants described their training in obstetric perineal trauma as "very poor" or "poor". 20.5% said they have not received training. 8.6% of physicians practising for more than 10 years had not had training for over 10 years. 70.5% responded "somewhat agree" or "strongly agree" when asked if they would like more training. Identification of first, second, third-, and fourth-degree tears from images and descriptions was very good (more than 80% correct for all categories). Classification of other perineal trauma was less consistent, with many incorrectly using the Sultan Classification. "Manual perineal support" and "Controlled or guided delivery" were the most frequently selected methods for the prevention of obstetric anal sphincter injury (OASI). CONCLUSIONS: Training experience for physicians in obstetric perineal trauma varies. Further improvement in training and education in perineal trauma, particularly in OASI, is needed for physicians. Perineal trauma that is not included in the Sultan Classification is often misclassified.

Obstetric anal sphincter injuries and other delivery trauma: a US national survey of obstetrician-gynecologists.

INTRODUCTION AND HYPOTHESIS: Obstetric lacerations complicate the majority of deliveries. The application of standardized guidelines for assessing delivery trauma has not been assessed thoroughly in the United States. We recently identified gaps in US midwives' clinical assessment of delivery trauma. We conducted a cross-sectional national survey of practicing obstetricians in the USA to characterize their classification of obstetric lacerations. We hypothesized that attending obstetricians' identification and diagnosis of delivery trauma would be similar to our findings for midwives with frequent inaccuracy. METHODS: We recruited clinically active obstetricians through the Pregnancy-Related Care Research Network. We asked participants to classify (from written definitions) and diagnose (from standard illustrations) common forms of vaginal delivery trauma using the widely employed perineal laceration degree system. We performed bivariate analysis of high- and low-scoring respondents and logistic regression to model characteristics associated with higher diagnostic accuracy. RESULTS: Of the 162 respondents who started the survey, 76% (123) were included for analysis (22% of solicited emails). Overall, we found wide variation in response accuracy with as few as 62% of respondents correctly classifying certain types of lacerations. Only 49 out of 123 (40%) use the Sultan third-degree subclassification system and 67 out of 123 (52%) continue to use the midline/median approach for episiotomies. Providers reporting fewer deliveries per month and fewer publicly insured patients earned higher scores. CONCLUSIONS: Obstetricians in a nationally representative US perinatal provider network inconsistently identify perineal and nonperineal lacerations. We found important clinical knowledge gaps, suggesting that vaginal delivery diagnoses in obstetric quality studies and pelvic floor research might be inaccurate.

Akt phosphorylation of neuronal nitric oxide synthase regulates gastrointestinal motility in mouse ileum.

Nitric oxide (NO) is a major inhibitory neurotransmitter that mediates nonadrenergic noncholinergic (NANC) signaling. Neuronal NO synthase (nNOS) is activated by Ca2+/calmodulin to produce NO, which causes smooth muscle relaxation to regulate physiologic tone. nNOS serine1412 (S1412) phosphorylation may reduce the activating Ca2+ requirement and sustain NO production. We developed and characterized a nonphosphorylatable nNOSS1412A knock-in mouse and evaluated its enteric neurotransmission and gastrointestinal (GI) motility to understand the physiologic significance of nNOS S1412 phosphorylation. Electrical field stimulation (EFS) of wild-type (WT) mouse ileum induced nNOS S1412 phosphorylation that was blocked by tetrodotoxin and by inhibitors of the protein kinase Akt but not by PKA inhibitors. Low-frequency depolarization increased nNOS S1412 phosphorylation and relaxed WT ileum but only partially relaxed nNOSS1412A ileum. At higher frequencies, nNOS S1412 had no effect. nNOSS1412A ileum expressed less phosphodiesterase-5 and was more sensitive to relaxation by exogenous NO. Under non-NANC conditions, peristalsis and segmentation were faster in the nNOSS1412A ileum. Together these findings show that neuronal depolarization stimulates enteric nNOS phosphorylation by Akt to promote normal GI motility. Thus, phosphorylation of nNOS S1412 is a significant regulatory mechanism for nitrergic neurotransmission in the gut.

Identification of obstetric anal sphincter injuries (OASIs) and other lacerations: a national survey of nurse-midwives.

INTRODUCTION AND HYPOTHESIS: Clinical quality improvement relies on accurate understanding of current practice. We performed a cross-sectional national survey of certified nurse-midwives (CNMs) assessing classification and identification of obstetric anal sphincter injury (OASI) and other delivery lacerations. We hypothesized laceration diagnoses are frequently inaccurate, and delivery records for obstetric lacerations may be of questionable quality. METHODS: We emailed 6909 American College of Nurse Midwives members an internet-based survey link. Of respondents, we included clinically active CNMs who perform at least one delivery per month. We evaluated laceration knowledge and application using standard descriptive text and images and asked about processes for recording lacerations in the delivery record. RESULTS: We received 1070 (15.5%) completed surveys and 832 (77.8%) met inclusion criteria. Over 50% characterized their OASI training and ability to identify OASI as good/excellent. Most (79%) had never attended education review on OASI. The overall accuracy for classification and identification of perineal lacerations ranged from 49 to 99%. Non-perineal lacerations were frequently categorized using the perineal/OASI system. Half of respondents (51%) document their deliveries in an electronic medical record but a quarter (28%) are not personally responsible for approving delivery data. Younger participants without a doctoral degree, with self-assessed good/excellent laceration training, and caring for < 50% publicly insured patients had higher accuracy for laceration identification and diagnosis. CONCLUSIONS: We found high rates of inaccurate laceration diagnosis and inappropriate application of the perineal OASI degree system, suggesting education and training are needed. Clinical studies that rely on delivery diagnosis of OASI may not be reliable.

Accuracy of obstetric laceration diagnoses in the electronic medical record.

INTRODUCTION AND HYPOTHESIS: Patient safety data including rates of obstetric anal sphincter injury (OASI) are often derived from hospital discharge codes. With the transition to electronic medical records (EMRs), we hypothesized that electronic provider-entered delivery data would more accurately document obstetric perineal injury than traditional billing/diagnostic codes. METHODS: We evaluated the accuracy of perineal laceration diagnoses after singleton vaginal deliveries during one calendar year at an American tertiary academic medical center. We reviewed the entire hospital chart to determine the most likely laceration diagnosis and compared that expert review diagnosis (ExpRD) with documentation in the EMR delivery summary (EDS) and ICD-9 diagnostic codes (IDCs). RESULTS: We retrospectively selected 354 total delivery records. OASI complicated 56 of those. 303 records (86%) were coded identically by the EDS and IDCs. Diagnoses from the IDCs and the EDS were mostly correct compared with ExpRD (sensitivity = 96%, specificity = 100%). There was no systematic over- or under-diagnosis of OASI for either the EDS (p = 0.070) or the IDCs (p = 0.447). When considering all laceration types the EDS was correct for 21 (5.9%) lacerations that were incorrect according to the IDCs. Overall, the EDS was more accurate (p < 0.05) owing to errors in IDC minor laceration diagnoses. CONCLUSIONS: Electronic medical record delivery summary data and EMR-derived diagnostic codes similarly characterize OASI. The EDS does not improve OASI reporting, but may be more accurate when considering all perineal lacerations. This assumes that providers have correctly identified and categorized the lacerations that they record in the EMR.

Effect of neuronal nitric oxide synthase serine-1412 phosphorylation on hypothalamic-pituitary-ovarian function and leptin response.

Hypothalamic neuronal nitric oxide synthase (nNOS) potentiates adult female fertility in rodents by stimulating gonadotropin releasing hormone (GnRH) secretion, which in turn promotes luteinizing hormone (LH) release and ovulation. The mechanism of hypothalamic nNOS activation is not clear but could be via nNOS serine1412 (S1412) phosphorylation, which increases nNOS activity and physiologic NO effects in other organ systems. In female rodents, hypothalamic nNOS S1412 phosphorylation reportedly increases during proestrus or upon acute leptin exposure during diestrus. To determine if nNOS S1412 regulates female reproduction in mice, we compared the reproductive anatomy, estrous cycle duration and phase proportion, and fecundity of wild-type and nNOS serine1412➔alanine (nNOSS1412A) knock-in female mice. We also measured hypothalamic GnRH and serum LH, follicle stimulating hormone (FSH), estradiol, and progesterone in diestrus mice after intraperitoneal leptin injection. Organ weights and histology were not different by genotype. Ovarian primordial follicles, antral follicles, and corpora lutea were similar for wild-type and nNOSS1412A mice. Likewise, estrous cycle duration and phase length were not different, and fecundity was unremarkable. There were no differences among genotypes for LH, FSH, estradiol, or progesterone. In contrast to prior studies, our work suggests that nNOS S1412 phosphorylation is dispensable for normal hypothalamic-pituitary-ovarian function and regular estrous cycling. These findings have important implications for current models of fertility regulation by nNOS phosphorylation.

Adiponectin links maternal metabolism to uterine contractility.

Adiponectin is secreted by adipose tissue and promotes insulin sensitivity. Low circulating adiponectin is associated with increased risk for preterm labor, but the influence of adiponectin on uterine myometrial physiology is unknown. We hypothesized that adiponectin receptors (AdipoRs) decrease myometrial contractility via AMPK to promote uterine quiescence in pregnancy. Using quantitative RT-PCR, we found that nonpregnant or pregnant human and mouse myometrium express AdipoR1 and AdipoR2 mRNAs. We confirmed AdipoR2 protein expression in human and mouse myometrium, with increased abundance in late mouse pregnancy. Both recombinant adiponectin and a pharmacologic AdipoR agonist, AdipoRon, potently inhibited uterine myometrial strip contractions in physiologic organ bath. The relaxation was independent of contractile stimulus (oxytocin, KCl, U46619). AdipoR agonists increased AMPK phosphorylation in pregnant mouse myometrium, and the direct AMPK activator A769662 also relaxed myometrial strips. However, the AMPK inhibitor dorsomorphin (compound C) blocked AMPK phosphorylation but did not abolish relaxation with either AdipoRon or A769662. In summary, adiponectin inhibits myometrial contractility consistent with the possibility that it is a previously unrecognized link between maternal metabolism and pregnancy maintenance. We also identify a separate role for AMPK regulating myometrial contractions that may influence labor onset.-Vyas, V., Guerra, D. D., Bok, R., Powell, T., Jansson, T., Hurt, K. J. Adiponectin links maternal metabolism to uterine contractility.

Taurine alleviates repression of betaine-homocysteine S-methyltransferase and significantly improves the efficacy of long-term betaine treatment in a mouse model of cystathionine ß-synthase-deficient homocystinuria.

Classical cystathionine ß-synthase-deficient homocystinuria (HCU) is a life-threatening inborn error of sulfur metabolism. Treatment for pyridoxine-nonresponsive HCU involves lowering homocysteine (Hcy) with a methionine (Met)-restricted diet and betaine supplementation. Betaine treatment efficacy diminishes significantly over time due to impairment of betaine-Hcy S-methyltransferase (BHMT) function. Little is known regarding the regulation of BHMT in HCU. Using a betaine-responsive preclinical mouse model of HCU, we observed that this condition induces a 75% repression of BHMT mRNA, protein and enzyme activity, and significant depletion of hepatic betaine levels. BHMT repression was proportional to plasma Hcy levels but was not observed in mouse models of homocystinuria due to either methylenetetrahydrofolate reductase or Met synthase deficiency. Both Met supplementation and chemically induced glutathione depletion exacerbated hepatic BHMT repression in HCU mice but not wild-type (WT) controls. Conversely, cysteine treatment normalized hepatic BHMT expression in HCU mice but had no effect in WT control animals. Taurine treatment induced BHMT expression in HCU mice by 5-fold and restored maximal lowering of Hcy levels during long-term betaine treatment with a concomitant normalization of inflammatory cytokine expression and a significantly improved coagulative phenotype. Collectively, our findings indicate that adjuvantial taurine treatment has the potential to significantly improve clinical outcomes in HCU.-Maclean, K. N., Jiang, H, Phinney, W. N., Keating, A. K., Hurt, K. J., Stabler, S. P. Taurine alleviates repression of betaine-homocysteine S-methyltransferase and significantly improves the efficacy of long-term betaine treatment in a mouse model of cystathionine ß-synthase-deficient homocystinuria.

Prevention and Management of Severe Obstetric Anal Sphincter Injuries (OASIs): a National Survey of Nurse- Midwives.

INTRODUCTION AND HYPOTHESIS: There are no data on midwives' knowledge and management of obstetric anal sphincter injuries (OASIs) in the USA. We performed a cross-sectional national survey characterizing OASI practice by certified nurse midwives (CNMs), hypothesizing that few midwives personally repair OASIs and that there are gaps in CNM OASI training/education. METHODS: We emailed a REDCap internet-based survey to 6909 American College of Nurse Midwives members (ACNM). We analyzed responses from active clinicians performing at least one delivery per month, asking about OASI risks, prevention, repair, and management. We summarized descriptive data then evaluated OASI knowledge by patient and provider characteristics. RESULTS: We received 1070 (15.5%) completed surveys, and 832 (77.8%) met the inclusion/exclusion criteria. Participants were similar to ACNM membership. Respondents most frequently identified prior OASI (87%) and nutrition (71%) as antepartum OASI risk factors and, less frequently, nulliparity (36%) and race (22%). Identified intrapartum risks included forceps delivery (94%) and midline episiotomy (88%). When obstetric laceration is suspected, 13.6% of respondents perform a rectal examination routinely. Only 15% of participants personally perform OASI repair. Overall, participants matched 64% of evidence-based answers. OASI education/training courses were attended by 30% of respondents, and 44% knew of OASI protocols within their group/institution. Of all factors evaluated, the percent of evidence-based responses was only different for respondent education/CME and protocols. CONCLUSIONS: Quality initiatives regarding OASI prevention and management may improve care. Our data suggest OASI training for midwives may improve delivery care in the US. Further studies of other obstetric providers are needed.

Outcomes of trial of labor after cesarean birth by provider type in low-risk women.

BACKGROUND: One approach to decreasing the cesarean birth rate in the United States is to increase the availability of birth attendants, including certified nurse-midwives (CNMs), who offer trial of labor after cesarean (TOLAC). We examined associations between provider type and mode of birth for women attempting vaginal birth after cesarean (VBAC). METHODS: We performed a retrospective cohort study at a United States academic medical center using prospectively-collected data (2005-2012). We included healthy women with term singleton vertex pregnancies after one or two prior cesareans who were managed by obstetricians or CNMs. We assessed unplanned cesarean birth by provider type using univariate and logistic regression and examined labor interventions and predicted VBAC success. RESULTS: Overall VBAC success was 88% for 502 included patients. Unplanned cesarean rates were similar by provider type. Black race, no prior VBAC, recurring clinical indication for cesarean, labor augmentation/induction, and any Pitocin use were associated with increased unplanned cesarean. Higher parity and early-term gestational age at delivery were associated with decreased unplanned cesarean. Postpartum hemorrhage and composite maternal morbidity were increased with unplanned cesarean, but there was no difference in neonatal outcome by mode of delivery or provider type. Obstetricians had slightly higher composite adverse maternal outcomes. Nomogram-predicted VBAC success but not provider type was associated with unplanned cesarean. CONCLUSIONS: Unplanned cesarean was similar for patients attempting labor after cesarean managed by midwives or obstetricians. Increasing the number of CNMs who manage TOLAC may help decrease the high rate of cesareans.

Maternal Amino Acid Profiles to Distinguish Constitutionally Small versus Growth-Restricted Fetuses Defined by Doppler Ultrasound: A Pilot Study.

OBJECTIVE: Fetuses measuring below the 10th percentile for gestational age may be either constitutionally small for gestational age (SGA) or have pathologic fetal growth restriction (FGR). FGR is associated with adverse outcomes; however, identification of low-risk SGA cases is difficult. We performed a pilot study evaluating maternal markers of pathologic FGR, hypothesizing there are distinct amino acid signatures that might be used for diagnosis and development of new interventions. STUDY DESIGN: This was a cohort study of healthy women with sonographic fetal estimated fetal weight <5th percentile divided into two groups based upon umbilical artery (UmA) Doppler studies or uterine artery (UtA) Doppler studies. We collected maternal blood samples prior to delivery and used ion pair reverse phase liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry to assess 44 amino acids. RESULTS: Among 14 women included, five had abnormal UmA, and three had abnormal UtA Doppler results. Those with abnormal UmA showed elevated ornithine. Those with abnormal UtA had lower dimethylglycine, isoleucine, methionine, phenylalanine, and 1-methylhistidine. CONCLUSION: We found several amino acids that might identify pregnancies affected by pathologic FGR. These findings support the feasibility of future larger studies to identify maternal metabolic approaches to accurately stratify risk for small fetuses.

Gasotransmitters in pregnancy: from conception to uterine involution.

Gasotransmitters are endogenous small gaseous messengers exemplified by nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S or sulfide). Gasotransmitters are implicated in myriad physiologic functions including many aspects of reproduction. Our objective was to comprehensively review basic mechanisms and functions of gasotransmitters during pregnancy from conception to uterine involution and highlight future research opportunities. We searched PubMed and Web of Science databases using combinations of keywords nitric oxide, carbon monoxide, sulfide, placenta, uterus, labor, and pregnancy. We included English language publications on human and animal studies from any date through August 2018 and retained basic and translational articles with relevant original findings. All gasotransmitters activate cGMP signaling. NO and sulfide also covalently modify target protein cysteines. Protein kinases and ion channels transduce gasotransmitter signals, and co-expressed gasotransmitters can be synergistic or antagonistic depending on cell type. Gasotransmitters influence tubal transit, placentation, cervical remodeling, and myometrial contractility. NO, CO, and sulfide dilate resistance vessels, suppress inflammation, and relax myometrium to promote uterine quiescence and normal placentation. Cervical remodeling and rupture of fetal membranes coincide with enhanced oxidation and altered gasotransmitter metabolism. Mechanisms mediating cellular and organismal changes in pregnancy due to gasotransmitters are largely unknown. Altered gasotransmitter signaling has been reported for preeclampsia, intrauterine growth restriction, premature rupture of membranes, and preterm labor. However, in most cases specific molecular changes are not yet characterized. Nonclassical signaling pathways and the crosstalk among gasotransmitters are emerging investigation topics.

Na+-Leak Channel, Non-Selective (NALCN) Regulates Myometrial Excitability and Facilitates Successful Parturition.

BACKGROUND/AIMS: Uterine contractility is controlled by electrical signals generated by myometrial smooth muscle cells. Because aberrant electrical signaling may cause inefficient uterine contractions and poor reproductive outcomes, there is great interest in defining the ion channels that regulate uterine excitability. In human myometrium, the Na+ leak channel, non-selective (NALCN) contributes to a gadolinium-sensitive, Na+-dependent leak current. The aim of this study was to determine the role of NALCN in regulating uterine excitability and examine its involvement in parturition. METHODS: Wildtype C57BL/6J mice underwent timed-mating and NALCN uterine expression was measured at several time points across pregnancy including pregnancy days 7, 10, 14, 18 and 19. Sharp electrode current clamp was used to measure uterine excitability at these same time points. To determine NALCN's contribution to myometrial excitability and pregnancy outcomes, we created smooth-muscle-specific NALCN knockout mice by crossing NALCNfx/fx mice with myosin heavy chain Cre (MHCCreeGFP) mice. Parturition outcomes were assessed by observation via surveillance video recording cre control, flox control, smNALCN+/-, and smNALCN-/- mice. Myometrial excitability was compared between pregnancy day 19 flox controls and smNALCN-/- mice. RESULTS: We found that in the mouse uterus, NALCN protein levels were high early in pregnancy, decreased in mid and late pregnancy, and then increased in labor and postpartum. Sharp electrode current clamp recordings of mouse longitudinal myometrial samples from pregnancy days 7, 10, 14, 18, and 19 revealed day-dependent increases in burst duration and interval and decreases in spike density. NALCN smooth muscle knockout mice had reduced myometrial excitability exemplified by shortened action potential bursts, and an increased rate of abnormal labor, including prolonged and dysfunctional labor. CONCLUSIONS: Together, our findings demonstrate that the Na+ conducting channel NALCN contributes to the myometrial action potential waveform and is important for successful labor outcomes.

Association between provider type and cesarean birth in healthy nulliparous laboring women: A retrospective cohort study.

BACKGROUND: Term nulliparous women have the greatest variation across hospitals and providers in cesarean rates and therefore present an opportunity to improve quality through optimal care. We evaluated associations between provider type and mode of birth, including examination of intrapartum management in healthy, laboring nulliparous women. METHODS: Retrospective cohort study using prospectively collected perinatal data from a United States academic medical center (2005-2012). The sample included healthy nulliparous women with spontaneous labor onset and term, singleton, vertex fetus managed by either obstetricians or certified nurse-midwives. Univariate and multivariate logistic regression was used to compare labor interventions and mode of birth by provider type. RESULTS: A total of 1339 women received care by an obstetrician (n = 749) or nurse-midwife (n = 590). The cesarean rate was 13.4% (179/1339). Adjusting for maternal and pregnancy characteristics, care by obstetricians was associated with an increased risk of unplanned cesarean birth (adjusted odds ratio [aOR] 1.48 [95% confidence interval {CI} 1.04-2.12]) compared with care by midwives. Obstetricians more frequently used oxytocin augmentation (aOR 1.41 [95% CI 1.10-1.80]), neuraxial anesthesia (aOR 1.69 [95% CI 1.29-2.23]), and operative vaginal delivery with forceps or vacuum (aOR 2.79 [95% CI 1.75-4.44]). Adverse maternal or neonatal outcomes were not different by provider type across all modes of birth, but were more frequent in women with cesarean than vaginal births. DISCUSSION: In low-risk nulliparous laboring women, care by obstetricians compared with nurse-midwives was associated with increased risk of labor interventions and operative birth. Changes in labor management or increased use of nurse-midwives could decrease the rate of a first cesarean in low-risk laboring women.

Pancreatic Cancer in Pregnancy Presenting with Thromboembolic Events: Case Report and Review of the Literature.

Stroke and hepatic vein thrombosis are highly associated with neoplasia but are extremely rare events in young, pregnant women. Rare and recurrent thrombotic events in pregnancy increase the suspicion for occult malignancy. We describe the case of a healthy 31-year-old G2P1 who presented with visual changes and dysarthria during pregnancy. Imaging showed cerebral infarcts. Her thrombophilia evaluation was negative. During delivery, she was diagnosed with fulminant Budd-Chiari Syndrome. Hepatic ultrasound suggested malignancy or metastasis, and postpartum CT scan and biopsy confirmed the diagnosis of Stage IV pancreatic cancer. Although rare in pregnancy, a new diagnosis of malignancy should be considered in patients with recurrent unexplained hypercoagulable complications. We propose an evidence-based algorithm for evaluation of occult malignancy in pregnancy based upon this case and review of the literature.

Comparative histology of mouse, rat, and human pelvic ligaments.

INTRODUCTION AND HYPOTHESIS: The uterosacral (USL) and cardinal ligaments (CL) provide support to the uterus and pelvic organs, and the round ligaments (RL) maintain their position in the pelvis. In women with pelvic organ prolapse (POP), the connective tissue, smooth muscle, vasculature, and innervation of the pelvic support structures are altered. Rodents are commonly used animal models for POP research. However, the pelvic ligaments have not been defined in these animals. In this study, we hypothesized that the gross anatomy and histological composition of pelvic ligaments in rodents and humans are similar. METHODS: We performed an extensive literature search for anatomical and histological descriptions of the pelvic support ligaments in rodents. We also performed anatomical dissections of the pelvis to define anatomical landmarks in relation to the ligaments. In addition, we identified the histological components of the pelvic ligaments and performed quantitative analysis of the smooth muscle bundles and connective tissue of the USL and RL. RESULTS: The anatomy of the USL, CL, and RL and their anatomical landmarks are similar in mice, rats, and humans. All species contain the same cellular components and have similar histological architecture. However, the cervical portion of the mouse USL and RL contain more smooth muscle and less connective tissue compared with rat and human ligaments. CONCLUSION: The pelvic support structures of rats and mice are anatomically and histologically similar to those of humans. We propose that both mice and rats are appropriate, cost-effective models for directed studies in POP research.

Ultrasound-Guided Percutaneous Management of Splenic Ectopic Pregnancy.

Splenic ectopic pregnancies are a rare cause of abdominal pain in reproductive-age women. A 21-year-old woman with worsening abdominal pain and a positive pregnancy test presented with hemoperitoneum and no intrauterine pregnancy on transvaginal ultrasound. After 2 nondiagnostic laparoscopies, a splenic pregnancy was diagnosed by computed tomography scan and abdominal ultrasound. Currently, diagnosis and treatment of splenic pregnancies involve exploratory surgery and splenectomy. We report the successful treatment of this splenic ectopic pregnancy with combined intramuscular plus ultrasound-guided percutaneous methotrexate injection, with preservation of the patient's spleen. Abdominal implantation must be considered in patients with pregnancy of unknown location, and in carefully selected patients splenic ectopic pregnancy can be successfully managed by minimally invasive methods.

Parturition dysfunction in obesity: time to target the pathobiology.

Over a third of women of childbearing age in the United States are obese, and during pregnancy they are at increased risk for delayed labor onset and slow labor progress that often results in unplanned cesarean delivery. The biology behind this dysfunctional parturition is not well understood. Studies of obesity-induced changes in parturition physiology may facilitate approaches to optimize labor in obese women. In this review, we summarize known and proposed biologic effects of obesity on labor preparation, contraction/synchronization, and endurance, drawing on both clinical observation and experimental data. We present evidence from human and animal studies of interactions between obesity and parturition signaling in all elements of the birth process, including: delayed cervical ripening, prostaglandin insensitivity, amniotic membrane strengthening, decreased myometrial oxytocin receptor expression, decreased myocyte action potential initiation and contractility, decreased myocyte gap junction formation, and impaired myocyte neutralization of reactive oxygen species. We found convincing clinical data on the effect of obesity on labor initiation and successful delivery, but few studies on the underlying pathobiology. We suggest research opportunities and therapeutic interventions based on plausible biologic mechanisms.

Sustained nitric oxide (NO)-releasing compound reverses dysregulated NO signal transduction in priapism.

We evaluated the therapeutic potential of a sustained nitric oxide (NO)-releasing compound to correct the molecular hallmarks and pathophysiology of priapism, an important but poorly characterized erectile disorder. 1,5-Bis-(dihexyl-N-nitrosoamino)-2,4-dinitrobenzene (C6') and an inactive form of the compound [1,5-bis-(dihexylamino)-2,4-dinitrobenzene (C6)] were tested in neuronal cell cultures and penile lysates for NO release (Griess assay) and biological activity (cGMP production). The effect of local depot C6' or C6 was evaluated in mice with a priapic phenotype due to double neuronal and endothelial NO synthase deletion (dNOS(-/-)) or human sickle hemoglobin transgenic expression (Sickle). Changes in NO signaling molecules and reactive oxygen species (ROS) surrogates were assessed by Western blot. The physiological response after C6' treatment was assessed using an established model of electrically stimulated penile erection. C6' generated NO, increased cGMP, and dose dependently increased NO metabolites. C6' treatment reversed abnormalities in key penile erection signaling molecules, including phosphodiesterase type 5, phosphorylated endothelial nitric oxide synthase, and phosphorylated vasodilator-stimulated phosphoprotein. In Sickle mice, C6' also attenuated the increased ROS markers gp91(phox), 4-hydroxynonenal, and 3-nitrotyrosine. Finally, C6' corrected the excessive priapic erection response of dNOS(-/-) mice. Exogenous sustained NO release from C6' corrects pathological erectile signaling in mouse models of priapism and suggests novel approaches to human therapy.