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.     

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.