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.     

Case study of a failed merger of hospital systems

The failed merger between Geisinger Health System and Hershey Medical Center is an instructive case study. The advantages of merging include: 1) support of financially threatened academic health centers, 2) access to greater capital, and 3) integration of managed care principles in the delivery system. Nevertheless, if the leadership of the new organization fails to deal effectively with the inevitable winners and losers, underestimates the role of cultural differences, does not have the management skills necessary to achieve cost savings and address the operational inefficiencies resulting from a larger clinical enterprise, does not anticipate the distrust of other local health care providers, and fails to anticipate the market forces that determine the success or failure of a managed health care system, mergers can fail. Lessons to be learned include: mergers involving health care systems with competing programs need to plan aggressively and execute carefully their clinical consolidation; cultural differences and the impediments they cause can be easily underestimated; health system mergers do not automatically result in economies of scale; and not all stakeholders in the surrounding community necessarily will welcome a merger.