Dating Ultrasounds are Fundamental to Modern Obstetric Care.

Aims Dating ultrasounds for all women remains a goal of the National Maternity Strategy. We sought to examine the utility of guideline based first trimester scanning when performed in a tertiary maternity unit. Methods A retrospective review of all public dating ultrasound scans was preformed over a one year period. Results 6,077 scans were reviewed. Viability was confirmed in 97.9% (n=5953), 1.5% (n=94) were deemed non-viable, and 0.48% (n=29) required follow up for uncertain viability. There were 97.9% (n=5,951) singleton pregnancies, 1.8% (n=112) multiple pregnancies, and 0.2% (n=14) with an absent fetal pole. Of those attending for a first dating ultrasound, 81.7% (n=4,966) were between 10 and 13+6 weeks. 16% (n=977) of women relied on dating scans rather than last menstrual period (LMP) to estimate gestational age. Overall, the mean difference between ultrasound scan and recalled menstrual dates was 3.9 gestational days. Other findings of significance included 0.4% (n=25) pregnancies with fetal anomalies diagnosed and 1.2% (n=78) of women were reported as having uterine anomalies. Conclusion Dating ultrasound confirms viability, pregnancy number and due date. These factors are the basis of antenatal care. This study reinforces the need for routine scanning of all pregnancies in the first trimester.

Routine screening for hepatitis C in pregnancy is cost-effective in a large urban population in Ireland: a retrospective study.

OBJECTIVE: To investigate whether risk factor-based screening in pregnancy is failing to identify women with hepatitis C virus (HCV) infection and to assess the cost-effectiveness of universal screening. DESIGN: Retrospective study and model-based economic evaluation. SETTING: Two urban tertiary referral maternity units, currently using risk factor-based screening for HCV infection. POPULATION: Pregnant women who had been tested for hepatitis B, HIV but not HCV. METHODS: Anonymised sera were tested for HCV antibody. Positive sera were tested for HCV antigen. A cost-effectiveness analysis of a change to universal screening was performed using a Markov model to simulate disease progression and Monte Carlo simulations for probabilistic sensitivity analysis. MAIN OUTCOME MEASURES: Presence of HCV antigen and cost per quality-adjusted life year (QALY). RESULTS: In all, 4655 samples were analysed. Twenty had HCV antibodies and five HCV antigen. This gives an active infection rate of 5/4655, or 0.11%, compared with a rate of 0.15% in the risk-factor group. This prevalence is 65% lower than a previous study in the same hospitals from 2001 to 2005. The calculated incremental cost-effectiveness ratio (ICER) for universal screening was €3,315 per QALY gained. CONCLUSION: This study showed that the prevalence of HCV infection in pregnant women in the Dublin region has declined by 65% over the past two decades. Risk factor-based screening misses a significant proportion of infections. A change to universal maternal screening for hepatitis C would be cost-effective in our population. TWEETABLE ABSTRACT: Universal maternal screening for hepatitis C is cost-effective in this urban Irish population.

Hepatic infarction, hematoma, and rupture in HELLP syndrome: support for a vasospastic hypothesis.

Purpose: HELLP syndrome is a relatively uncommon pregnancy-related condition characterized by hemolysis, elevated liver function tests, and low platelets. It can be accompanied by life-threatening hepatic complications including hepatic infarction, hematoma formation, and hepatic rupture. HELLP syndrome occurs in approximately 0.2% of pregnancies. Major hepatic complications occur in less than 1% of HELLP patients suggesting an incidence of 1/50,000. The pathogenesis is incompletely understood and in particular, it is difficult to understand a disorder with both major thrombotic and bleeding manifestations.Methods: Literature review.Results: On the basis of reports in the published literature, and our own clinical experience, we suggest that vasospasm is one of the principal drivers with hepatic ischemia, infarction, and hemorrhage as secondary events. It is known that vasoactive substances are released by the failing placenta. We suggest these cause severe vasospasm, most likely affecting the small post-sinusoidal hepatic venules. This leads to patchy or confluent hepatic ischemia and/or necrosis with a resultant increase in circulating liver enzymes. Reperfusion is associated with a fall in platelet count and microvascular hemorrhage if the microvasculature is infarcted. Blood tracks to the subcapsular space causing hematoma formation. If the hematoma ruptures the patient presents with severe abdominal pain, intra-abdominal hemorrhage, and shock.Conclusions: We suggest that hepatic and other complications associated with HELLP syndrome including placental abruption, acute renal failure, and posterior reversible encephalopathy syndrome (PRES) may also be due to regional vasospasm.

Managing vasomotor symptoms effectively without hormones.

Vasomotor symptoms (hot flushes and/or night sweats) affect approximately 80% of women over the menopause transition and can affect quality of life, productivity, and relationships. Vasomotor symptoms are the main reason for seeking treatment during the menopausal transition. Although menopausal hormone therapy (MHT) is effective for symptom management, the majority of symptomatic women do not take MHT. In this article, we review the evidence for non-hormonal treatments for vasomotor symptoms, including pharmacological and non-pharmacological approaches, and provide a clinical algorithm for managing symptomatic women.

Brainstem acoustic areas in the marine catfish, Arius felis.

The marine catfish Arius felis produces low frequency sounds for communication and obstacle detection. It was hypothesized that the utriculus of the inner ear might play an important role in these behaviors. In the current study, brainstem acoustic areas were studied to reveal possible neuroanatomical specializations in utricular processing areas. The first-order octaval nuclei in Arius were identical in number, anatomical characteristics, and organization of saccular, lagenar, and utricular inputs to previous reports of these features in Ictalurus, a closely related species of catfish that does not exhibit the specialized acoustic behaviors present in Arius. Similarly, injections of neural tracer in the acoustic midbrain (nucleus centralis) of Arius revealed afferent and retrograde pathways almost identical to those previously reported in Ictalurus. It is suggested that areas within the primary and higher-order octaval nuclei that utilize utricular input in acoustic processing are likely identical in Arius and Ictalurus. Two sets of higher-order connections in Arius differ from those in Ictalurus. First, Arius apparently lacks the direct input from the anterior octaval nucleus to nucleus centralis reported in Ictalurus. Second, in Arius nucleus centralis projects bilaterally to a strip of neurons positioned ventral to the ventral boundary of the torus semicircularis. This projection is apparently absent in Ictalurus and in the related species Carassius (goldfish), but has been previously reported in Porichthyes, a sound-producing species belonging to a different teleost taxon.

Organization and connections of the dorsal descending nucleus and other presumed acoustic areas in the brainstem of the teleost fish, Astronotus ocellatus.

This study provides new information on brainstem areas, assumed to be auditory based on observations in other species, in the oscar, Astronotus ocellatus. The primary goal of the study was to explore the morphology of the dorsal descending octaval nucleus, which contains a population of neurons that receives acoustic afferents from the inner ear. Using cytoarchitectonic and connectional criteria, we revised the previously defined dorsal boundary of the descending octaval nucleus, such that the most dorsomedial neurons in this nucleus are positioned ventral to the cerebellar crest and medial to nucleus medialis. At some levels, these dorsomedial cells are continuous with another part of the dorsal descending nucleus that underlies nucleus medialis. The terminal fields of the saccule and lagena are located within this latter, more ventral part of the dorsal descending nucleus. However, the dorsomedial cells that are proximate to the cerebellar crest have long ventral dendrites that extend into these terminal fields, and therefore likely receive saccular and lagenar input. In contrast to a previous report, saccular afferents terminate more medially within the dorsal descending nucleus than do lagenar inputs. Injections of horseradish peroxidase in nucleus centralis of the torus semicircularis revealed that many descending nucleus neurons that lie within the saccular and lagenar terminal fields, including the dorsomedial neurons proximate to the cerebellar crest, project to this acoustic midbrain area. These injections also revealed a secondary octaval population like that described in otophysan fishes.

Membrane-tethered Drosophila Armadillo cannot transduce Wingless signal on its own.

Drosophila Armadillo and its vertebrate homolog beta-catenin are key effectors of Wingless/Wnt signaling. In the current model, Wingless/Wnt signal stabilizes Armadillo/beta-catenin, which then accumulates in nuclei and binds TCF/LEF family proteins, forming bipartite transcription factors which activate transcription of Wingless/Wnt responsive genes. This model was recently challenged. Overexpression in Xenopus of membrane-tethered beta-catenin or its paralog plakoglobin activates Wnt signaling, suggesting that nuclear localization of Armadillo/beta-catenin is not essential for signaling. Tethered plakoglobin or beta-catenin might signal on their own or might act indirectly by elevating levels of endogenous beta-catenin. We tested these hypotheses in Drosophila by removing endogenous Armadillo. We generated a series of mutant Armadillo proteins with altered intracellular localizations, and expressed these in wild-type and armadillo mutant backgrounds. We found that membrane-tethered Armadillo cannot signal on its own; however it can function in adherens junctions. We also created mutant forms of Armadillo carrying heterologous nuclear localization or nuclear export signals. Although these signals alter the subcellular localization of Arm when overexpressed in Xenopus, in Drosophila they have little effect on localization and only subtle effects on signaling. This supports a model in which Armadillo's nuclear localization is key for signaling, but in which Armadillo intracellular localization is controlled by the availability and affinity of its binding partners.

Organization and connections of octaval and lateral line centers in the medulla of a clupeid, Dorosoma cepedianum.

In the clupeid fishes, the functionally specialized utricle and cephalic lateral line respond to sound pressure by virtue of their mechanical coupling to the auditory bullae. The cytoarchitecture of, and primary inputs to, the octavolateralis area were studied in the gizzard shad, Dorosoma cepedianum, in order to determine whether first-order acoustic and lateral line areas of the medulla are likewise specialized. The octavolateralis area of Dorosoma is composed of the nuclei that have been observed in other teleosts: nucleus medialis, the descending and anterior octaval nuclei, nucleus magnocellularis, nucleus tangentialis, and a caudal granular-cell region that likely represents nucleus caudalis and the posterior octaval nucleus. The descending octaval nucleus can be divided into dorsomedial, intermediate, and ventral zones using cytoarchitectonic criteria, whereas the anterior octaval nucleus can be divided into caudal, rostral, and medial portions. Primary inputs to the octavolateralis area were determined by means of in vitro application of horseradish peroxidase to nerves from the otolithic endorgans of the inner ear and the lateral line neuromasts. These primary inputs are generally organized like those of other teleosts: the otolithic endorgans supply the posterior, descending, magnocellular, and anterior nuclei, whereas the majority of lateral line fibers project to nucleus medialis, nucleus caudalis, and to the magnocellular nucleus. However, other characteristics of these projections may be unique to clupeids. The medial subdivision of the dorsomedial zone of the descending nucleus is dominated by a bilateral projection from at least a portion of the utricle, while the lateral subdivison of the dorsomedial zone is supplied by the saccule and lagena. This pattern is not present in non-clupeid fishes; in many species, the saccule has the most dorsomedial projection zone within the descending nucleus. In Dorosoma, both lateral line nerves contribute a light, bilateral projection to the medial and lateral subdivisions of the dorsomedial zone. The apparently specialized, bilateral utricular and lateral line inputs to the dorsomedial zone of the descending nucleus may be related to the specialized sensitivity of the utricle and the cephalic lateral line to sound pressure. A prominent group of neurons, tentatively identified as a secondary octaval population, is also described. Like the secondary octaval population of otophysans, the presumed secondary octaval population of Dorosoma is composed of a dorsal, fusiform region, an intermediate spherical cell region, and a ventral fusiform cell region.

Cytoarchitecture of the medial octavolateralis nucleus in the goldfish, Carassius auratus.

The medial octavolateralis nucleus (MON) is the principal first-order medullary lateral line sensory nucleus found in the majority of anamniotic vertebrates. Although its presence has been confirmed in numerous taxa, the cytoarchitecture of this region has not been extensively studied in any species. The purpose of this study was to examine in detail the cytoarchitecture of the MON in the goldfish using Golgi staining and HRP histochemical techniques. The results of this study demonstrated the presence of a number of cell types with distinct cellular morphologies, several of which strongly resemble those described in octavolateralis nuclei dedicated to audition and electroreception. The most prominent of these MON neurons included crest cells of two varieties, either possessing or lacking basilar dendrites. Additionally, we described stellate and cristal interneurons and granule-like cells in the molecular layer, and lateral interneurons and granule-like neurons in deeper MON layers. These morphological similarities together with similarities in functional organization, and the probable close phyletic relationships of this "family" of hair cell sensory systems, argue for parallels in mechanisms of sensory processing and analysis in strongly divergent sensory modalities.

Connections of octaval and lateral line nuclei of the medulla in the goldfish, including the cytoarchitecture of the secondary octaval population in goldfish and catfish.

Cytoarchitectural analyses combined with injections of the tracer horseradish peroxidase in various structures in the brain of the goldfish, Carassius auratus, have defined some of the major components of acoustic and lateral line mechanosensory circuits between the medulla and midbrain. The main acoustic receptor in Carassius, the saccule, is known to provide a major input to the dorsomedial zone of the descending octaval nucleus. The dorsomedial zone in turn projects bilaterally to the secondary octaval population (SO) and to nucleus centralis of the torus semicircularis. The SO is composed of three major subdivisions which are also present in a related otophysan, the catfish Ictalurus punctatus. The SO in Carassius projects bilaterally to nucleus centralis and to the saccular recipient zones of the ipsilateral descending octaval nucleus. By contrast, the mechanosensory lateral line receptors are known to direct most of their input to nucleus medialis. Nucleus medialis in turn projects bilaterally to nucleus praeeminentialis, nucleus ventrolateralis of the torus semicircularis, and the optic tectum, and to the contralateral nucleus medialis. We also provide evidence for a bilateral projection of nucleus medialis to the sensory trigeminal nucleus, and for a reciprocal input from the sensory trigeminal nucleus to the ipsilateral nucleus medialis.

Similarities between trunk and spätzle, putative extracellular ligands specifying body pattern in Drosophila.

The basic body plan of Drosophila is specified by four determinant systems that organize pattern along the anteroposterior and dorsoventral axes. Two of these systems (anterior and posterior) depend on localized mRNAs. In contrast, the other two (ventral and terminal) require locally generated extracellular ligands that are transduced, respectively, by the transmembrane receptors Toll and torso (tor). The ligand for the Toll receptor is thought to be spätzle (spz), a secreted protein that is activated by proteolytic cleavage. Here we report that trunk (trk), a gene required for activity of the tor receptor, encodes a protein that resembles spz in several respects. In particular, the sequence suggests that trk is a secreted protein and that it contains an internal site for proteolytic cleavage. Furthermore, the carboxy-terminal domain of trk has a similar arrangement of cysteines to that of spz. We propose that trk encodes an extracellular ligand involved in specifying terminal body pattern and suggest by analogy with spz that a cleaved form of trk constitutes the ligand for the tor receptor.

Organization of inner ear endorgan projections in the goldfish, Carassius auratus.

Cytoarchitectural analysis of the octavolateralis area of the goldfish, Carassius auratus, reveals that as in other teleosts, five first-order octaval nuclei are present: the anterior octaval, magnocellular, descending, tangential, and posterior octaval nuclei. The descending nucleus appears to be anatomically specialized relative to that of the halecomorph Amia calva and many teleosts in that a large dorsomedial subpopulation of the nucleus lies medial to nucleus medialis, a first-order lateral line nucleus. In addition to this dorsomedial zone, the descending nucleus is made up of an intermediate and a ventral zone. Application of horseradish peroxidase (HRP) to individual inner ear endorgans reveals that the distribution of these afferents to the octaval nuclei is generally similar to that in another otophysan, Ictalurus punctatus [McCormick and Braford, 1993]. Nucleus magnocellularis receives a diffuse projection from all of the endorgans. The semicircular canals project heavily to the nucleus tangentialis, the entire ventral zone and portions of the intermediate zone of the descending nucleus, the ventral portion of the caudal anterior nucleus, and the bulk of the rostral anterior nucleus. The macula neglecta projects to the intermediate zone of the descending nucleus and to ventral locations within the dorsal half of the caudal anterior nucleus. The otolithic endorgans--the saccule, lagena, and utricle--project, in an overlapping manner, to the dorsal half of the caudal anterior nucleus and minimally to the rostral anterior nucleus. The inputs of the otolithic endorgans to the intermediate zone of the descending nucleus are more segregated, though a given region is sometimes supplied by more than one endorgan. The projections of the saccule tend to be concentrated more medially than those of the other two endorgans. The dorsomedial zone of the descending nucleus receives the majority of its primary input from the saccule, and a much smaller input from the lagena, over most of its rostrocaudal extent. At caudal-most levels of the dorsomedial zone, afferents from the three otolithic endorgans overlap.

The primary octaval nuclei and inner ear afferent projections in the otophysan Ictalurus punctatus.

Physical coupling between the swimbladder and the inner ear is believed to contribute to the enhanced hearing abilities of otophysans relative to those of teleosts lacking comparable otic specializations. We hypothesized that the auditory circuitry of otophysans might also exhibit derived features [McCormick and Braford, 1988]. As a first test of this hypothesis, we examined the normal anatomy and inner ear inputs of the primary octaval nuclei in the catfish Ictalurus punctatus. From Nissl-stained sections we conclude that Ictalurus, like other teleosts, has five first-order octaval nuclei: the anterior, magnocellular, tangential, descending, and posterior octaval nuclei. The overall projection pattern of the seven inner ear endorgans, determined using the exsanguinated horseradish peroxidase procedure [McCormick and Braford, 1984], is very similar to that hypothesized as primitive for gnathostome fishes. The otolithic endorgans project to dorsal areas of the descending and anterior nuclei, whereas the macula neglecta and cristae of the semicircular canals project more ventrally. Three zones are recognized within the descending nucleus-the dorsomedial, intermediate, and ventral zones. The dorsomedial zone, which is the main terminus of saccular fibers, has specialized morphological features: it extends far dorsally and contacts the medial portion of the cerebellar crest, and it is partitioned into lateral and medial portions by entering facial nerve fibers. The caudal anterior nucleus is likewise partitioned into lateral and medial portions by the facial nerve. Hypotheses addressing these derived features are presented.

A low cost microprocessor-controlled electrofusion and electroporation system.

An important recent development in the field of biotechnology has been the use of high electric fields to render cell membranes temporarily permeable (electroporation). Cells in this state are receptive to gene transfer or can be induced to fuse with each other (electrofusion) to form hybrid cells containing the combined characteristics of the parent cells. A major reason for fusing cells is to form hybridoma cells which secrete monoclonal antibodies. A problem for research workers has been the high price of some of the electrofusion equipment. This problem has been addressed by designing a device that is inexpensive (less than $800 Canadian) and can be assembled by an electronics technician. The system uses a Radio Shack CoCo III microcomputer which is programmed in BASIC and controls the electroporation voltage pulse amplitude (25-500 V) and duration (2-275 microseconds) to an electrofusion chamber; this yields electric field strengths of 0.25-5 kV cm-1 for a 0.1 cm electrode spacing. The system is capable of delivering pulse currents up to 3 A. This paper provides technical details on how to construct an instrument that has greater flexibility at less cost than comparable commercially available instruments.

A neuron-specific enhancer of the Drosophila dopa decarboxylase gene.

At least two cis-regulatory elements are necessary for correct neuron-specific expression of the Drosophila melanogaster dopa decarboxylase gene, Ddc. In addition to a previously described proximal element located approximately 60 bp upstream of the mRNA start site, we have now characterized a distal approximately 600-bp DNA fragment, extending from -1019 to -1623 bp, which possesses enhancer-like properties and is essential for normal neuron-specific expression. Immunofluorescent labeling of neurons expressing deleted Ddc genes indicates that this region contains both general neuronal regulatory elements and cell-specific elements that selectively affect Ddc expression in either dopaminergic or serotonergic neurons. These selective effects can be correlated with the removal of sequence elements that are protected from DNase digestion by factors present in embryonic nuclear extracts. Several of these elements are also homologous to sequences located upstream of the evolutionarily diverged Ddc gene of Drosophila virilis. These results suggest that the neuron-specific expression of Ddc results from the combined action of several factors binding within this distal enhancer region.

The three-dimensional localization of internal mammary lymph nodes by radionuclide lymphoscintigraphy.

In breast cancer patients, radiation therapy planning must account for individual anatomy to ensure optimal coverage of tumor and internal mammary nodes. To achieve this, three-dimensional radionuclide lymphoscintigraphy (RNLS) was performed in 167 patients by obtaining two images of the nodes using a 30-degree slant hole collimator rotated 180 degrees between images. Analysis of 768 nodes (mean 4.6/patient) visualized from the level of rib 1 through interspace 5 was performed. The number of nodes seen was not a function of patient age. Cross-communication to the contralateral node chain occurred in 13.8% of cases. Eighty-two percent of nodes were located near the first three ribs and interspaces; 23% were located beyond 3.0 cm from the mid-sternal line. At the level of the radiation beam match line (second rib or interspace), 4.5% of nodes were deeper than 3.0 cm. From rib 3 through interspace 5, 3.9% were deeper than 3.0 cm. Using an idealized tangential field, at least one node would have been missed in 16.2% of patients. Three-dimensional RNLS allows definition and localization of normal sized nodes and ensures that radiation therapy portals can be tailored for each individual under treatment.

CNS and hypoderm regulatory elements of the Drosophila melanogaster dopa decarboxylase gene.

Expression of the dopa decarboxylase gene (Ddc) is regulated in a tissue- and developmental stage-specific manner throughout the life cycle of the fruit fly, Drosophila melanogaster. Essential Ddc regulatory elements lie within 208 base pairs upstream from the RNA start point. Functional elements within this 5' flanking region were mapped by deletion analysis, which assayed expression in vivo after germline integration via P element vectors. One of the elements is essential for expression in both the larval and adult central nervous system, and at least two other elements are necessary for quantitatively normal expression in the hypoderm. Within each of the intervals that have regulatory effects are found sequence elements conserved between the Ddc genes of two distantly related species of flies. On the basis of this correlation, regulatory functions for these sequence elements can be postulated.

Clinical comparison of two radiocolloids for internal mammary lymphoscintigraphy.

Recent studies suggest that 99mTc-labeled radiocolloid (SC) compounded with hydrogen sulfide can be used to visualize lymph channels and nodes. Our study prospectively compared SC with 99mTc antimony sulfide (SbS) colloid, in 28 patients undergoing internal mammary lymphoscintigraphy. Images were recorded on a scintillation camera and computer at 0.5, 1.0, and 3.0 hr. Quantitative analysis included assessment of percent (%) injected dose in nodes, the percent remaining at the injection site, and the relative intensity of the most cephalad node compared to a 57Co standard. The mean (means) % injected dose of both radiocolloids within visualized nodes was less than 1% at each time interval, with no significant differences between means's. The means % injected dose remaining at the injection site at 3.0 hr was 83 for SbS and 76 for SC not statistically significant (N.S.). The means of the ratio of counts within the most cephalad node at 3.0 hr to counts within a 57Co standard was 0.98 for SbS and 1.03 for SC (N.S.). Clinical assessment of number of nodes visualized and extent of radiocolloid migration showed no difference between the two agents. The biological and clinical parameters for the two colloids appear similar when used for internal mammary lymphoscintigraphy.