SUMMARY Six subjects with a normal endoscopic pancreatogram were investigated after an overnight fast by means of a side-viewing duodenoscope. After cannulation of the main pancreatic duct, juice was collected in five-minute samples for 20 minutes. An iso-osmolar solution of 6 g cattle bile was then infused into the duodenum through a separate catheter attached to the outside of the duodenoscope, and pancreatic juice collected in five-minute samples for another 20 minutes. Blood was frequently drawn from an arm vein through an indwelling catheter for estimation of immunoreactive secretin (IRS) by radioimmunassay. The flow rate of pancreatic juice and outputs of bicarbonate, amylase, and protein increased significantly after intraduodenal infusion of bile. A significant rise in plasma IRS was also found after instillation of bile in the duodenum.The effect of bile on the exocrine pancreatic secretion is not well understood. Previously, it has been shown that bile in the duodenum augments the stimulating /l effect of exogenous secretin on pancreatic enzyme secretion (Wormsley, 1970;Forell et al., 1971). The effect of bile on the endogenously stimulated enzyme secretion (Malagelada et al., 1976) and the effect on 1 the exogenously stimulated bicarbonate secretion (Wormsley, 1970;Forell et al., 1971) is uncertain.\ ! The purpose of the present investigation was to study the effect of intraduodenal instillation of bile _ on the basal pancreatic secretion obtained from the main pancreatic duct after endoscopic cannulation (Osnes et al., 1976), and its effect on immunoreactive -, secretin (IRS) release in man. MethodsSix patients, three men and three women, aged 27-73 years (mean 54 years) were selected for the study. After an overnight fast they were examined by means of a side-viewing duodenoscope (Olympus JF B2). After visualisation of the papilla of Vater, [15][16][17][18][19][20] ,

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The exocrine pancreatic secretion of water, bicarbonate, amylase, trypsin, chymotrypsin, and lipase and the plasma concentration of immunoreactive secretin (IRS) were studied before and after repeated intraduodenal infusions of cattle bile in man. After endoscopic cannulation of the main pancreatic duct, juice was collected in 5-min samples for 20 min. A solution of 6 g dried cattle bile in 60 ml water was then infused into the duodenum through a separate catheter attached to the outside of the duodenoscope. Juice was collected for another 20 min. After this period a solution of 6 g dried cattle bile in 40 ml water was infused into the duodenum, and juice again collected for 20 min. Blood was frequently drawn from an arm vein for estimation of plasma concentration of secretin by radioimmunoassay. Both bile infusions caused significant rises in flow rate, bicarbonate concentration and output, and IRS (p less than 0.05). Enzyme concentrations decreased significantly after intraduodenal bile infusions (p less than 0.05). Outputs of enzymes rose significantly after the first bile infusion; however, a rise after the second bile infusion was found only for amylase. Further, a significant decrease in amylase and lipase concentration was found after the second bile infusion. The findings indicate that the increase in proteolytic enzyme and lipase secretion was due to a washout phenomenon. The increase in the plasma concentration of secretin after repeated bile infusions, with a corresponding effect on flow rate and bicarbonate secretion, indicates that secretin may be the main factor responsible for the exocrine pancreatic secretion caused by intraduodenal bile infusions.

The strength and the validity of the multi-crossover model (MCO model) were investigated to optimalize the procedure for correctly classifying individual responders to a given therapy. One hundred and fifteen patients with non-ulcer dyspepsia from seven Norwegian hospitals were included in a 6-week double-blind MCO-designed trial with alternating weekly treatments with ranitidine and placebo. An individual effect score (X score) was calculated on the basis of the number of times the active drug was associated with less symptoms than the preceding or following placebo period. Patients categorized as responders (X score greater than or equal to 4) or unclassifiables (X scores = 2 or 3) after the MCO period continued single-blind active treatment for 4 weeks and were then reclassified by means of cross-tabulation of efficacy and adverse effects. Eighty-five per cent of the MCO responders and 62% of the 42 MCO unclassifiables were reclassified as responders. The reclassified responders were then included in a single-blind follow-up placebo period until relapse or for a maximum of 8 weeks. The relapse rate was significantly greater (p less than 0.01) and the time to relapse significantly shorter (p less than 0.01) in the group of MCO responders than in the MCO unclassifiables. The large response and relapse rates in the group of MCO responders verify that the MCO model is a reliable method for correctly classifying responders to treatment. Our results indicate that by including patients with an X score of 3 in the definition of 'responder', the MCO model could be modified to optimalize the procedure for correct classification.