The impact of route of delivery and presentation on twin neonatal and infant mortality: a population-based study in the USA, 1995–97

Objective: We examined whether the route of delivery for near-term (???34 weeks' gestation) twins, as candidates for vaginal delivery, affected neonatal and infant mortality rates. We further evaluated whether these mortality rates were modified by fetal presentation.

Methods: A population-based retrospective cohort study based on the matched multiple births data in the USA (1995–97) was performed. Analyses were restricted to non-malformed liveborn twins delivered at ??34 weeks' gestation. Twins with breech–breech and breech–vertex presentations were excluded, since they are not candidates for vaginal delivery. Neonatal mortality rates (death within the first 27 days) and post-neonatal mortality rates (death between 28 and 365 days) per 1000 twin live births, by route of delivery and fetal presentation, were derived. The associations between neonatal mortality, post-neonatal mortality and the route of delivery for vertex–breech versus vertex–vertex presentations were expressed based on relative risks (RR) and 95% confidence intervals (CI) derived from logistic regression models based on the method of generalized estimating equations.

Results: Of the 177?622 twins analyzed, 87% (n?=?154?531) presented as vertex-vertex. Fifty-five per cent (n?=?97?692) of twins were both delivered vaginally, 41% (n?=?72?825) were both delivered by Cesarean section and, of the remaining 4% (n?=?7105), the first twin was delivered vaginally and the second by Cesarean section. Twins with vertex–breech presentations delivered by Cesarean–cesarean sections, as well as those with vertex–vertex presentations delivered vaginally, had the lowest neonatal mortality rate (1.6 per 1000 live births). The highest neonatal mortality rate in the vertex–breech pairs occurred with vaginal–Cesarean deliveries (2.7 per 1000 live births). Among twins with vertex–vertex presentations, twins delivered via the vaginal–Cesarean route experienced the highest neonatal mortality (3.8 per 1000 live births). The RR for neonatal mortality in this group was 2.24 (95% CI 1.35, 3.72) compared with twins both delivered vaginally.

Conclusion: Route of delivery and fetal presentation both confer an impact on twin infant mortality rates. Strategies to reduce discordant routes in complicated vaginal deliveries may lead to improved neonatal survival.     

Isolation of a new homeobox gene belonging to the Pitx/Rieg family: expression during lens development and mapping to the aphakia region on mouse chromosome 19

We recently reported the positional cloning of a homeobox gene involved in the pathogenesis of Rieger syndrome, RIEG1 , and its mouse homolog, Rieg1 . Rieg1 (also independently described as Pitx2) is highly homologous to the Ptx1/Potx gene product, suggesting that there may be additional members of this novel Pitx family. The Pitx genes play an important role in eye, tooth, pituitary and umbilical region development as evidenced by Rieger syndrome and iris hypoplasia phenotypes, resulting from mutations in the RIEG1 gene and by expression studies. In order to characterize further the Pitx gene family we searched mouse cDNA libraries to identify additional members. A new gene was isolated which encodes a homeoprotein with strong homology to the other Pitx proteins and 97-100% identity in the homeodomain itself, suggesting that this is a third member of the family, Pitx3 . In whole mount in situ hybridization on mouse embryos ranging from 8.5 to 11.5 days post-coitum (d.p.c.), Pitx3 mRNA was seen only in the developing lens starting at day 11. Hybridization on cross- sections revealed strong signals in the lens vesicle in 11 d.p.c. embryos and throughout the lens, particularly in the anterior epithelium and equator region in 15 d.p.c. embryos. Pitx3 was mapped close to aphakia on mouse chromosome 19. The aphakia homozygous mouse is characterized by small eyes lacking a lens, which fail to develop beyond 11 d.p.c. These data make Pitx3 a strong candidate gene for the aphakia phenotype in the mouse and suggest a role for the human homolog in congenital lens malformations.      

Supine versus upright anterior images: comparison in T1-201 myocardial scintigraphy

In patients undergoing exercise thallium-201 myocardial scintigraphy, activity in the inferior wall on anterior images may appear diminished when the standard supine view is used, but normal when the view is acquired with the patient upright. To determine the clinical significance of this observation, the distribution of thallium-201 activity was semiquantitatively assessed in supine and upright anterior images obtained immediately after exercise in 93 patients (65 men, 28 women). The presence of inferior wall and coronary artery disease was established with coronary angiography or from documentation of previous myocardial infarction. Supine and upright images were compared with use of receiver operating characteristic curves. In male patients diagnostic accuracy for identification of both inferior wall and coronary artery disease was improved through the use of the upright anterior image. In women, there was no significant difference in reader performance with upright and supine images. Upright anterior images should be routinely obtained in men in order to reduce the frequency of false-positive identification of inferior wall defects.     

Cyclic AMP-dependent anion secretion in human small and large intestine

Cyclic AMP-dependent Cl secretion is the major secretion pathway in human intestine. The aim of the present study was to examine mechanisms involved in cAMP-dependent anion secretion in human small and large intestine. Surgical resection specimens from both jejunum and distal colon were studied under short circuited conditions. Addition of the phosphodiesterase inhibitor IBMX induced an increase in the short-circuit current (Isc) equivalent to the net increase in Cl secretion. The Isc was inhibited by diphenylamine decarboxylate (DPC; Cl channel blocker), bumetanide (basolateral Na⁺/K⁺/2Cl cotransporter), BaCl₂ (basolateral K⁺ channel) and Cl free buffer in both segments and indomethacin (cyclo-oxygenase inhibitor) in colon alone. Diphenylamine decarboxylate appears to directly inhibit secretion in jejunum, although its inhibitory effect is possibly mediated by inhibition of cyclo-oxygenase in the colon. A small component of IBMX-stimulated Isc was inhibited by acetazolamide. Cyclic AMP-dependent secretion is largely apical Cl secretion, although a small component appears to be HCO₃. Secretion is dependent on basolateral K⁺ channels and Na⁺/K⁺/2Cl cotransporters and, in the colon, is inhibited by indomethacin, implying a role for cyclo-oxygenase metabolites. The chloride channel blocker DPC inhibits secretion in both areas. This class of compounds may have potential for treatment of secretory diarrhoea.     

Posttranslational processing and targeting of transgenic human defensin in murine granulocyte, macrophage, fibroblast, and pituitary adenoma cell lines

Human defensins are 29 to 30 amino acid (aa) antimicrobial peptides that are among the principal constituents of the neutrophil's azurophil granules. To determine the tissue specificity of posttranslational processing and subcellular targeting of defensins, the cDNA for a 94 aa human preprodefensin was transduced into murine cell lines (NIH 3T3 embryonic fibroblasts, AtT-20 pituitary adenoma, J774.1 and RAW 264.7 macrophages, and 32D and 32D cl3 granulocytes) using retroviral vectors. All transduced cell types expressed and to a variable extent constitutively secreted a 75 aa prodefensin formed by the removal of the amino terminal signal sequence. In AtT-20 cells, the 75 aa form accumulated intracellularly in granules and was releasable by secretagogues. Proteolytic processing to mature defensins was seen only in myeloid cells (J774.1, RAW 264.7, 32D, and 32D cl3). Newly formed mature defensin was rapidly degraded in J774.1 and RAW 264.7 macrophages, but accumulated stably in multivesicular bodies in 32D cells and in cytoplasmic granules of 32D cl3 cells. Our data suggest that the enzymatic and transport machinery required to process preprodefensin to mature defensin and to store it in cytoplasmic granules is a specialized feature of cells of granulocytic lineage.