James F. Smith

Fetal laceration injury at cesarean delivery

Objective To investigate the incidence of fetal laceration injury in cesarean delivery. Methods A retrospective review was conducted using a computer-based data coding system. All neonatal records were reviewed for infants delivered by cesarean during a 2-year period. Maternal records were reviewed in those cases of documented fetal laceration injury. The Fisher exact test was used when indicated. Results There were 904 cesarean deliveries performed during the study period; of these, 896 neonatal records (98.4%) were available for review. Seventeen laceration injuries were recorded (1.9%). The incidence of laceration appeared higher when the indication for cesarean was nonvertex (6.0% versus 1.4%, P = .02). One of 17 (5.9%) maternal records indicated the presence of the laceration of the fetus. Conclusion Fetal laceration injury at cesarean delivery is not rare, especially when it is performed for nonvertex presentation. The minority of obstetric records show documentation of such lacerations, suggesting that this complication often may not be recognized by obstetricians.

A simple model for learning stereotactic skills in ultrasound-guided amniocentesis

Background Amniocentesis is an important procedure for antenatal diagnosis but requires stereotactic skill acquisition that may be facilitated by the use of a model. Technique A model using a gelatin mold with “targets” within is created. The model is used to facilitate development of stereotactic skills and to demonstrate technique principles for ultrasound-guided amniocentesis. Experience The model has been incorporated into an educational program for antenatal diagnosis within a residency and provides a reasonable simulation of clinical features important in learning genetic amniocentesis. Conclusion The use of this model augments the learning of important skills needed for ultrasound-guided amniocentesis.

Umbilical artery regression: a rare complication of intravascular fetal transfusion.

BACKGROUND Intravascular fetal transfusion is an important therapeutic advance but is associated with several complications. Regression of an umbilical artery associated with transfusion is rare. CASE A case of red blood cell alloimmunization managed by serial transfusions was complicated by functional loss of an umbilical artery during pregnancy. Refractory fetal bradycardia occurred during the last transfusion procedure, requiring emergency preterm cesarean delivery. Coagulative necrosis, thrombosis, and focal calcification of one umbilical artery was confirmed after delivery. CONCLUSION Umbilical artery regression associated with transfusion therapy is rare and may complicate subsequent fetal transfusions.

Doppler evidence of improved fetoplacental hemodynamics following amnioreduction in the stuck twin phenomenon

Background Doppler utrasound of the umbilical cord has been used to assess stuck twin pregnancies, with variable results. We describe a case of immediate improvement in the umbilical artery velocimetry of a stuck twin following amnioreduction. Case Pregnancy complicated by the stuck twin phenomenon was managed by serial amnioreduction. Initial improvement was followed by progressive was followed by progressive evidence of hydrops in the smaller, stuck twin. Absent diastolic flow was corrected immediately by further amnioreduction; subsequently the evidence of hydrops resolved. Conclusion Amnioreduction may be associated with a measurable improvement in fetoplacental hemodynamics in the stuck twin phenomenon as assessed by Doppler ultrasound.

Monoamniotic twins discordant for anencephaly: diagnosis by CT amniography.

Prenatal diagnosis of monoamnionicity is necessary for optimal care of a twin gestation. When the fetuses are discordant for a lethal anomaly, unequivocal confirmation is imperative. Ultrasound evaluation of our patient revealed a twin gestation discordant for anencephaly and with possible monoamnionicity. When sonography was inconclusive, CT amniography confirmed a single amniotic cavity, permitting appropriate parental counseling and pregnancy management. CT amniography is a useful adjunct to ultrasound in evaluating twins discordant for a lethal anomaly when monoamnionicity is suspected.

Prenatal ultrasonographic findings associated with Jacobsen syndrome

Jacobsen syndrome results from deletion of the distal long arm of chromosome 11.1 Reported cases have been identified after chromosomal analysis of dysmorphic or mentally retarded persons.U We report the sonographic features of an affected fetus that led to prenatal cytogenetic diagnosis. One parent was newly identified as a carrier of a balanced translocation and the source of the aberrant chromosome.

Abstract 2228: Phosphatidylinositol-4-kinase - Potent and selective inhibitors of PI4Kα and PI4Kβ.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Phosphatidylinositol (PI) is a phospholipid that resides primarily on the cytosolic surface of cell membranes. PI can be phosphorylated to generate seven different phosphatidylinositol phosphates (PIPs), all of which have distinct biological activities.1 A major first step in the production of these PIPs is the conversion of PI into phosphatidylinositol-4-phosphate (PI4P) by PI4 kinase.2 Here we describe the identification of inhibitors of PI4 kinase via targeted screening of a kinase subset. This exercise has delivered inhibitors that are potent inhibitors of PI4 kinase (pIC50 >8), which are selective the α- or the β-subtypes and do not inhibit related enzymes on the PI pathway (PI3 kinase pIC50 <5 or PIP5 kinase pIC50 <4) and also exhibit good broader kinase selectivity. The effect of these useful probe compounds on cellular phosphatidylinositol-4,5-diphosphate and subsequent downstream markers will be described along with the comparison of these effects with the corresponding siRNA. 1. G. Di Paolo, P. De Camilli, Phosphoinositides in cell regulation and membrane dynamics. Nature 2006, 443, 651-657.2. T. Sasaki, S. Takasuga, J. Sasaki, S. Kofuji, S. Eguchi, M. Yamazaki, A. Suzuki, Mammalian phosphoinositide kinases and phosphatases. Progress in lipid research, 2009, 48, 307-343. Citation Format: Michael J. Waring, Darren Cross, David Andrews, Vikki Flemington, Carol Lenaghan, Jennifer McKelvie, Sarita Maman, Piotr Raubo, Graeme Robb, James Smith, Martin Swarbrick. Phosphatidylinositol-4-kinase - Potent and selective inhibitors of PI4Kα and PI4Kβ. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2228. doi:10.1158/1538-7445.AM2013-2228

Abstract 3324: The discovery and optimisation of small-molecule inhibitors of human 5’-tyrosyl DNA phosphodiesterase (Tdp2).

Topoisomerases (topo) regulate DNA topology by the transient cleavage and re-ligation of DNA during transcription and replication. Topo II poisons such as etoposide can induce abortive DNA strand breaks in which topo II remains covalently bound to a 5? DNA strand terminus via a phosphotyrosyl linker. Tyrosyl DNA phosphodiesterase 2 (Tdp2, TTRAP, EAPII) is a recently discovered human 5?-tyrosyl DNA phosphodiesterase which repairs this topo-mediated DNA damage, therefore playing a central role in maintaining normal DNA topology in cells. Cellular depletion of Tdp2 has been shown to result in an increased susceptibility and sensitivity to topo II-induced DNA double strand breaks. It has therefore been proposed that selective pharmacological inhibition of Tdp2 may be a novel approach to overcome intrinsic or acquired resistance to topo II targeted drug therapy. To date, no known drug-like inhibitors of Tdp2 have been identified. We have recently reported a robust ?mix and read? HTS compatible assay and this was used to screen a diverse chemical library of approximately 92,000 compounds. From this, 2 distinct hit series have been identified. Following further chemical exploration of the original hit compounds small molecule inhibitors of Tdp2 with sub-100nM potencies have been identified. This poster will describe our preliminary results in this area.