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Biomedical subjects

S Yagel

Publications and source records attributed to S Yagel.

At least 19 recordsLinked to original sources

Poor prenatal detection rate of cardiac anomalies in Noonan syndrome.

BACKGROUND: The wide variation and nonspecific nature of many of the associated ultrasonographic findings complicate prenatal diagnosis of Noonan syndrome. The aim of the present study was to define the rate of prenatal diagnosis of heart malformations in cases diagnosed postnatally with Noonan syndrome. METHODS: English-language literature review of 29 cases of Noonan syndrome examined prenatally with confirmed postnatal diagnosis and four case reports from our center. RESULTS: Cases were evaluated for cervical spine pathologies, cardiac anomalies and other pathological findings, including hydrops fetalis and polyhydramnios. Cardiac anomalies were suspected in only nine of 33 cases; three of these were associated with cystic hygroma. Cardiac anomalies were eventually diagnosed in 31/33 cases postnatally. Polyhydramnios was diagnosed in 19/33 cases in the third trimester, and hydrops fetalis was detected in eight of 33. Cystic hygroma was present in a total of nine cases at mid-trimester. CONCLUSIONS: Noonan syndrome is characterized by late-onset and progressive pathologies, particularly the associated cardiac anomalies, which develop through the course of gestation and postnatal life. This complicates or precludes prenatal diagnosis at mid-trimester or at any time in the prenatal period, and partly explains the low rate of detection of fetal cardiac lesions in this syndrome.

Female↗

Conservative management of two ectopic pregnancies implanted in previous uterine scars.

Cesarean section scar pregnancy is rare. A variety of interventions have been implemented to terminate the pregnancy and preserve the uterus; however, the optimal treatment is unknown. We describe two cases of this rare condition diagnosed by transvaginal ultrasound. In the first case the diagnosis of an 8-week non-viable gestation in a uterine scar was made sonographically in a 40-year-old woman. The patient was treated with intramuscular methotrexate. Myometrial integrity was suggested both by ultrasound findings and laparoscopic findings. In the second case, an early cervicoisthmic pregnancy in a uterine scar was diagnosed by sonography in a 39-year-old woman. This patient was treated successfully with a full course of intramuscular methotrexate. Complete disappearance of the gestational sac took place 4 months following beta-human chorionic gonadotrophin normalization. Intramuscular methotrexate may be a treatment alternative for Cesarean section scar pregnancies.

Abortifacient Agents, Nonsteroidal↗

Monopaternal superfecundation of quintuplets after transfer of two embryos in an in vitro fertilization cycle.

OBJECTIVE: To present the first genetically proven identity of quintuplets in an IVF treatment cycle after transferring only two embryos. DESIGN: Case report. SETTING: IVF unit and obstetrics department of university-affiliated general hospital. PATIENT(S): Twenty-five-year-old patient undergoing IVF treatment for unexplained infertility. INTERVENTION(S): In vitro fertilization with intracytoplasmic sperm injection performed on 50% of oocytes, resulting in successful production of nine early-cleavage embryos. Transfer of two embryos on day 3 and freezing of the remaining embryos. MAIN OUTCOME MEASURE(S): Development of five separate embryonic sacs. Fetal reduction of three embryos at 12 weeks of gestation. RESULT(S): Successful completion of the twin pregnancy and full genetic analysis of the three embryos and the twins that were born at term. CONCLUSION(S): Despite transferring only two embryos, superfecundation occurred, resulting in five embryos. Genetic analysis can be used to determine paternity and identity of all the embryos.

Adult↗

Risk of fetal loss in twin pregnancies undergoing second trimester amniocentesis(1).

OBJECTIVE: To assess the rate of fetal loss among bichorionic twin gestations undergoing genetic amniocentesis compared with singletons undergoing the procedure and untested twins. METHODS: In a retrospective cohort study, three groups were compared: 476 women with twins undergoing amniocentesis, 489 women with singleton gestations undergoing amniocentesis, and 477 women with twins presenting at a similar gestational age for ultrasound studies only. All subjects were scanned at 17-18 weeks' gestation and again approximately 4 weeks after the procedure or first ultrasound scan. Excluded were twin pregnancies after fetal reduction or chorionic villus sampling, fetuses with structural anomalies, and cases in which one fetus had died at the time of examination or after fetal reduction. RESULTS: Thirteen twin gestations in the tested group (2.73%) aborted spontaneously up to 4 weeks after the procedure compared with three twin controls (0.63%, P =.01) and three post-procedure singleton controls (0.6%, P =.01). An abnormal karyotype was discovered in 15 tested twin pregnancies (3%) and in six tested singletons (1.23%). All affected twin pairs were discordant for the chromosomal anomaly. CONCLUSION: The risk of early fetal loss in twins undergoing amniocentesis appears to be higher than that of exposed singletons or unexposed twins.

Abortion, Spontaneous↗

The great tocolytic debate: some pitfalls in the study of safety.

The controversy surrounding the use of tocolytic agents has been raging for decades. Tocolytic drugs play a pivotal role in the prevention of preterm birth, which is the major cause of neonatal morbidity and mortality. Studies on the efficacy and safety of these drugs are of the utmost importance to many disciplines within the medical community. Unfortunately, many clinical decisions regarding tocolytic agents are based on incorrect information resulting from flawed studies. In this article we discuss the major design flaws common to many studies of tocolytic safety and in so doing explain some of the conflicting evidence regarding safety. Each of the two major types of study designs, preterm birth retrospective studies and prospective randomized trials, is associated with a serious flaw. Retrospective preterm birth studies give misleading and inconclusive results to the question of safety because of the use of incomplete cohorts. The inadequately sized prospective studies in the current literature lack the power to detect important clinical differences.

Cerebral Hemorrhage↗

A study of human leukocyte antigen G expression in hydatidiform moles.

OBJECTIVE: Human leukocyte antigen G (HLA-G) is a nonclassic major histocompatibility gene normally expressed only in extravillous trophoblasts throughout pregnancy. It may be responsible in part for the successful evasion of the hemiallogenic trophoblasts from maternal immune surveillance. We investigated whether HLA-G is expressed in molar pregnancies. STUDY DESIGN: We examined 5 complete hydatidiform mole specimens and 5 partial hydatidiform mole specimens to determine whether HLA-G is expressed by immunohistochemistry and by RNA in situ hybridization analysis. RESULTS: We found that both the protein and RNA of HLA-G is expressed in complete and partial hydatidiform moles. CONCLUSION: HLA-G RNA and protein are expressed in molar pregnancies. HLA-G expression is independent of embryonic development and may therefore be an integral part of placental development. Furthermore, expression of HLA-G in the complete hydatidiform mole, a naturally occurring androgenote, confirms expression of the paternal allele of HLA-G. Imprinting of HLA-G is therefore unlikely to play a role in protecting fetal trophoblasts from maternal immune rejection.

Female↗

Noonan syndrome: a cryptic condition in early gestation.

Noonan syndrome is one of the most common of genetic syndromes and manifests at birth, yet it is usually diagnosed during childhood. Although prenatal diagnosis of Noonan syndrome is usually not possible, in a few cases the ultrasonographic findings suggested the diagnosis in utero. Reported sonographic clues include septated cystic hygroma, hydrothorax, polyhydramnios, and cardiac defects, such as pulmonic stenosis and hypertrophic cardiomyopathy. During a 6-year period, 46,224 live-born infants were delivered at the Chaim Sheba Medical Center. Seven newborn infants and four fetuses were found to have Noonan syndrome. One fetus showed transient nuchal translucency of 4 mm and bilateral neck cysts at the 13th gestational week. Both findings resolved spontaneously by the 18th gestational week, but during the third trimester this fetus developed hydrothorax, skin edema, and polyhydramnios. In the three other fetuses, first- and second-trimester ultrasonographic findings were normal, and the diagnosis of Noonan syndrome was suggested only during the third trimester. All three fetuses had polyhydramnios and skin edema. A cardiac malformation, hydrothorax, and a large head were present in one fetus. Sonographic facial findings were investigated. In all four fetuses posteriorly angulated, apparently low-set ears and depressed nasal bridge were identified. Wide nasal base was seen in two fetuses. In two fetuses, persistent opening of the fetal mouth was interpreted as fetal hypotonia. One fetus developed progressive postnatal hypertrophic cardiomyopathy and in one case, pulmonic stenosis became apparent at age 6 months. This small series suggests that Noonan syndrome has an evolving phenotype during in utero and postnatal life. Amelioration of early nuchal region findings and late onset of the more "typical" ultrasonographic changes may limit early prenatal detectability.

Adult↗

Abnormalities of the fetal central veins and umbilico-portal system: prenatal ultrasonographic diagnosis and proposed classification.

OBJECTIVES: Anomalies of the fetal venous system are poorly documented and their pathogenesis is not well understood. The present study was undertaken to review the spectrum of fetal central veins and umbilico-portal system anomalies, and to propose a classification system. METHODS: A 7-year restrospective survey was conducted. RESULTS: Nineteen fetuses showed abnormal connection between central veins and the fetal heart. Three fetuses showed abnormal connections of the cardinal veins, two of which had interruption of the inferior vena cava, and one had isolated persistent left superior vena cava. Anomalies of pulmonary veins were seen in four fetuses: in two with asplenia syndrome, a vertical confluent pulmonary artery was observed. In a further two cases total anomalous pulmonary venous connections were found. Abnormalities of the umbilical vein (UV) were seen in 10 cases; seven had persistent right UV, and three had a spectrum of anomalies: One had abnormal connections of the UV to the left iliac vein associated with agenesis of the ductus venosus (DV) and hydrops fetalis. One case showed in utero occlusion of the DV by echogenic foci that resulted in a persistent left proximal UV and porto-systemic shunt. One case had obliteration of the DV secondary to in utero fetal hepatic fibrosis. Abnormalities of the vitelline veins or portal system were demonstrated in two cases. One had a left porto-systemic shunt which resolved spontaneously at 3 months of age, and one had secondary partial occlusion of the left portal system with liver echogenicities and direct communication of the UV with the right atrium. None of the 19 cases had an abnormal karyotype or evidence of in utero infection. CONCLUSIONS: Detection of various fetal vein anomalies in utero is feasible. The anomalies vary according to embryologic precursors or etiology. Two major mechanisms seem to be involved in the genesis of fetal vein anomalies: in most cases primary maldevelopment of the venous system occurs, while in the minority secondary anomalies from possible thromboembolic events or systemic disease may play a role.

Abnormalities, Multiple↗

Tie-2 and angiopoietin-2 expression at the fetal-maternal interface: a receptor ligand model for vascular remodelling.

The blood vessels at the fetal-maternal interface widen dramatically during pregnancy in order to increase blood flow to nourish the developing fetus. This vessel remodelling destroys normal vessel integrity and encompasses the dissolution of vessel muscle and elastic tissue. It also includes the displacement of endothelial cells by fetal trophoblasts that invade the maternal arteries of the uterus. Interaction between the endothelial cell receptor, Tie-2, and its recently discovered antagonist ligand, angiopoietin-2 (Ang-2), has been implicated in the loosening of vessel structure. Using Northern blot hybridization and RNA in-situ hybridization analysis the expression pattern of Tie-2, and Ang-2 in the placenta throughout pregnancy, was investigated. We found Ang-2 expressed in the syncytiotrophoblast during the first trimester. In addition to the expected expression of the Tie-2 receptor in both fetal and maternal endothelial cells, we observed Tie-2 expression in endovascular invasive trophoblasts. These cells of epithelial origin invade the uterine spiral arteries and acquire endothelial cell properties. The temporal- and lineage-specific pattern of expression of Tie-2 and Ang-2 suggests that this receptor-ligand pair functions during the critical phase of development of the fetal vasculature and reworking of the maternal vessels during normal placentation.

Angiopoietin-2↗

Lack of human leukocyte antigen-G expression in extravillous trophoblasts is associated with pre-eclampsia.

Pre-eclampsia, a common complication of first pregnancies, is thought to result from a poorly perfused placenta and may reflect an abnormal maternal immune reaction to the hemiallogenic fetus. Human leukocyte antigen (HLA)-G, a major histocompatibility tissue-specific antigen expressed in extravillous trophoblast cells (fetal-derived), may protect trophoblasts from maternal-fetal immune intolerance and allow these cells to invade the uterus. Through RNA in-situ hybridization analysis, we studied the expression pattern of HLA-G in normal placentae and placentae from pregnancies complicated by severe pre-eclampsia. In normal placenta we found HLA-G expression in the anchoring extravillous trophoblasts with an increasing gradient of expression in the more invasive cells. However, in nine out of 10 pre-eclamptic placentae HLA-G expression was absent or reduced. We conclude that HLA-G is normally expressed in invasive trophoblasts and HLA-G expression is defective in most pre-eclamptic placentae. We propose that trophoblasts lacking HLA-G are vulnerable to attack by the maternal immune system. These defective trophoblasts will be unable to invade the maternal spiral arteries effectively, thereby developing vessels which cannot adequately nourish the developing placenta. This poorly perfused placenta may initiate the systemic cascade of events associated with pre-eclampsia.

Female↗

HLA-G expression in extravillous trophoblasts is an intrinsic property of cell differentiation: a lesson learned from ectopic pregnancies.

Human leukocyte antigen (HLA)-G is a major histocompatibility gene expressed almost exclusively in extravillous trophoblasts at the fetal-maternal interface. HLA-G may play a role in protecting the fetus from attack by the maternal natural killer cells. The extravillous trophoblasts invade the decidua and maternal spiral arteries. The factors which regulate the cell-specific expression of HLA-G are unknown. In this study we asked if HLA-G is expressed in extravillous trophoblasts that develop outside of their normal cellular environment, as in the case of ectopic pregnancies. Since all ectopic pregnancies implant in the absence of underlying decidua we also used a placenta accreta as an experimental control. We found that HLA-G mRNA and protein were expressed in the extravillous trophoblasts in the 13 ectopic specimens studied. In a case of placenta accreta (which develops without decidua basalis and is therefore adherent to the underlying myometrium), HLA-G mRNA and protein were also expressed. These results suggest that HLA-G expression is induced in a cell autonomous manner rather than determined by appropriate environmental cues.

Adult↗

Puerperal and intrapartum group A streptococcal infection.

OBJECTIVE: To determine the demographic and clinical variables characteristic of non-epidemic intrapartum or puerperal group A streptococcal (GAS) infection. METHODS: The records of 47 patients diagnosed with intrapartum or puerperal GAS infection over a 6 1/2 year period at Hadassah-University Hospital-Mt. Scopus, Jerusalem were reviewed. Data regarding 25,811 women, the general population of women that delivered during that period, were obtained from their computerized medical records. Frequency distributions, t-test, chi-square, and Spearman's Rank Correlation were used, as appropriate, to analyze and compare demographic and clinical variables associated with development of GAS infection, its clinical course and subsequent development of septic shock. RESULTS: Mean age of mothers with GAS infection was higher than that of our general pregnant population (30.4 versus 27.4 years, P = 0.0019), and a higher proportion of GAS infected patients (30% versus 12%, P < 0.005) experienced PROM. Thirty-one (66%) women had fever as their sole presenting symptom, eight (17%) had fever and abdominal pain, seven (15%) had fever and abnormal vaginal bleeding, and one patient (2%) presented with a rash. Three patients (6%) developed a septic shock. Two of these patients presented with symptoms more than 14 days after delivery. CONCLUSIONS: We describe the characteristics of non-epidemic intrapartum or puerperal GAS infection. Data from our study and review of the literature suggest that some patients who develop septic shock may present later in the puerperium than patients with an uncomplicated GAS infection.

Abdominal Pain↗

Simultaneous multigate spectral Doppler imaging of the umbilical artery and placental vessels: novel ultrasound technology.

OBJECTIVE: To establish gestational age-specific nomograms of pulsatility indices in the umbilical artery and chorionic and intraplacental vessels, using novel ultrasound technology. STUDY DESIGN: A prospective, cross-sectional study of 160 healthy singleton pregnancies between 18 and 33 weeks of gestation. MEASUREMENTS: Using simultaneous multigate spectral Doppler imaging specialized hardware and software, we measured the flow velocity waveforms of the umbilical artery, chorionic and intraplacental vessels. Computerized automatic mapping calculated the pulsatility indices in regions of interest. RESULTS: Data were adequately obtained for 160 fetuses. The pulsatility index values in the three sites measured decreased with advancing gestational age; the correlation coefficients r = -0.74, r = -0.67 and r = -0.68 for the umbilical artery, chorionic and intraplacental vessels, respectively, were found to be highly statistically significant (p < 0.0001). CONCLUSION: Simultaneous multigate spectral Doppler imaging provides simultaneous measurements of the velocity waveforms in the umbilical artery, chorionic and intraplacental vessels, and is a feasible and reproducible method of obtaining these data. The normal data presented may facilitate early detection of flow disturbances in the fetoplacental circulation.

Adult↗