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Background/aims: Our investigation aimed to evaluate the impact of endoscopic transpapillary forceps biopsies (ETP) in bile duct strictures of unknown etiology based on the largest European patient cohort at a tertiary referral center. To date only studies with limited patient numbers exist., Methodology: Three-hundred-and-twelve patients (162 males, 150 females, mean age 62±12.7 years) with bile duct strictures of unknown etiology were examined with ETP. Sensitivity, specificity and accuracy of ETP were compared to the definite diagnosis proved by histopathology of surgical resection specimens or long-term follow-up of those patients not undergoing surgery., Results: Using ETP a correct pe-interventional diagnosis was achieved in 211 out of 312 patients resulting in an accuracy rate of 67.6%. Eighty-six out of 187 malignant stenoses were correctly diagnosed by ETP, giving rise to sensitivity and specificity rates of 46 and 100%, respectively. Sensitivity of ETP in cholangiocellular carcinoma was significantly superior to that in pancreatic carcinoma (52.5% vs. 35.6%, p = 0.026). Sensitivity and accuracy rates of ETP did not depend on the localization of the stenosis in the common bile duct., Conclusions: ETP alone is not reliable enough in diagnosing bile duct malignancies as shown by low sensitivity and accuracy rates (false-negative rate of 32%).

Background/aims: Ampulla of Vater tumors represent a rare tumor entity and bear a malignant potential. This study at our tertiary referral center aimed at evaluating the feasibility of endoscopic snare papillectomy and long-term endoscopic surveillance in comparison to results of a meta-analysis of comparative trials., Methodology: Retrospective study in comparison to results of a meta-analysis. Twenty-one patients (mean age 60.2±12.8 years) with ampullary adenoma were included. All patients had undergone ERCP with endoscopic forceps biopsies prior to endoscopic snare papillectomy. Statistical analysis was applied including descriptive analysis of symptoms, therapy and complications., Results: ESP was technically successful in all 21 patients. Histopathology showed 18 adenomas and 3 focal adenocarcinomas which were referred to surgery for modified Whipple's procedure. Follow-up was available in all patients with a mean follow-up of 64 months. Adenoma recurrence occurred in three patients with a mean recurrence time of 25 months (range, 4-66 months). One patient had residual adenoma growth., Conclusions: In the majority of cases ampullary adenomas can be treated endoscopically. Forceps biopsies alone are not reliable enough in detecting malignancy. All patients with ampullary tumor should therefore undergo ESP. Due to the recurrence rate of 16% patients should have close follow-up.

Conventional medical curricula present information pertinent to chronic inflammatory diseases, infectious diseases and transplantation, via systematic lectures and courses in medical specialties without any integrated approach. The authors report on a 3-week model course that attempts to provide students with an overview of clinical presentation, diagnostics, and therapy of representative disease entities with particular emphasis on the interdisciplinary approach to these problems in hospital practice. In addition to problem-based learning in small groups, the model course comprises interdisciplinary concept lectures, practical demonstrations of specific diagnostic procedures, and bedside teaching. In the meantime, the course "Problem-Based Learning--Inflammation and Transplantation" has been held twice successfully as a mandatory course in the clinical part of the curriculum at the Muenster Medical School.

In conscious fasted dogs, with chronically-implanted electrodes in stomach and small intestine, typical aborally-propagated interdigestive myoelectric complexes were induced by the infusion of 13-nor-leucine motilin (13-Nle-M); whereas when the normal interdigestive activity was abolished by the infusion of pentagastrin, the resulting 'postprandial' pattern of activity was not significantly modified by the administration of 13-Nle-M. Results from this study provide further evidence that Motilin as well as Gastrin may be involved in the control of gastrointestinal motility in dogs.

Using vitamin B12 labelled with Co58 as an exogenous marker, and bilirubin as an endogenous marker, the duodeno-gastric reflux was determined quantitatively in 13 gastric ulcer patients under basal conditions and under stimulation (1 CU secretin/kg body weight + 1 CU pancreozymin/kg body weight) of the exocrine pancreas; in addition, a histological examination of the gastric mucosa was carried out by taking multiple biopsies from along the greater and lesser curvatures of the stomach. Altogether, a more marked mean duodeno-gastric reflux was found in the ulcer patients than in the 14 control subjects. If, however, the ulcer patients are differentiated in accordance with the results of the histological findings in the biopsy material, it is seen that an increased reflux is found only in those ulcer patients presenting with an intestinal metaplasia in the antrum. Statistically, no increase in the duodeno-gastric reflux can be verified under secretin/pancreozymin stimulation of the pancreas.

Duodenal acidification is known to inhibit gastric H+ secretion while stimulating pancreatic HCO-3 secretion, but the mechanisms of these effects have not been fully explained. This study was designed to determine the role of endogenous and exogenous secretin in gastric inhibition and pancreatic stimulation by an acidified liver extract (LE) meal in conscious dogs prepared with chronic gastric and pancreatic fistulas pretreated with normal serum (control) or anti-secretin serum. In control tests, plasma gastrin and gastric H+ secretion showed a marked rise with LE meals at pH ranging from 7.0 to 4.0, but significantly declined at pH 3.0 and 2.0. Plasma secretin and pancreatic secretion started to rise with LE meals at pHs below 4.5, and both reached peaks at pH 2.0. Exogenous secretin infused at graded doses suppressed plasma gastrin and gastric H+ responses to LE meals at doses of 1.0 and 2.0 U/kg-h, but increased, dose-dependently, plasma secretin and pancreatic HCO-3 starting with a dose of 0.03 U/kg-h. Following the administration of anti-secretin serum, the effects of exogenous secretin on plasma gastrin and secretin levels as well as on gastric and pancreatic secretion were almost completely abolished. The increase in plasma secretin and pancreatic HCO-3 responses to LE meals at pH below 4.5 were also abolished by anti-secretin serum, but the suppression of plasma gastrin level and the inhibition of gastric H+ responses to LE meals at lower pH (3.0 and 2.0) remained virtually unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

The enzymatic-isotopic method for determination of histamine has been reevaluated. Modifications, permitting routine analysis of the amine in blood, plasma and biopsy tissues of various origin have been described; this permits convenient application of the technique in various fields of clinical pharmacology, gastroenterology and immunology.

Dermatitis herpetiformis (DH) has been reported to be associated with various degrees of intestinal villous atrophy in 19 to 68 percent of the cases studied. This was true particularly in British and American populations. The present investigation deals with morphological and functional characteristics of small intestinal mucosa in a group of German DH patients (n=16): No case of villous atrophy could be detected, whereas interepithelial lymphocytes were shown to be slightly but significantly elevated. Intestinal disaccharidase activities were not statistically different from those of healthy control subjects, and oral lactose tolerance tests were normal in each of 8 patients tested. Genetical and immunological differences between our DH patients and those studied by British and American authors may be responsible for the basically different results as to "dermatogenic enteropathy".

In three male duodenal ulcer patients, the effects of a 4-week treatment with a long-acting synthetic secretin -- daily s.c. administrations of 10 clinical units secretin/kg b.w. -- were assessed symptomatically, endoscopically, immunologically, and by means of gastric and pancreatic secretory analyses. Improvement in epigastric pain was noted within a few days following the onset of secretin therapy. In all cases, duodenoscopy revealed complete healing of ulcers after a 2- to 3-week treatment period. Before therapy, cutaneous anaphylactoid reactions due to intradermal injections of secretin could be elicited in each subject; skin reactions were found mitigated after 4 weeks of therapeutic secretin administration thus suggesting some desensitisation. Neither gastric acid secretion nor pancreatic bicarbonate production were substantially influenced by the 4-week course of secretin therapy; consequently, prevention of ulcer relapse is rather unlikely to be achievable with the conditions employed in this study. However, it seems therapeutically promising that the duodenal ulcers under study showed complete healing already after 2-3 weeks of secretin administration.

A secretin analogue in which the normal amino acid sequence had been elongated by a (Des-Tyr-betaAla)-residue was studied as tracer for secretin radioimmunoassay. 125I-(DATA)-secretin exhibited superior immunoreactivity with several rabbit anti-secretin sera compared to 125I-6-Tyr-secretin and also to secretin iodinated at its N-terminal histidyl residue. This may be due, at least in part, to higher conformational integrity of the secretin moiety in the 125I-(DATA)-secretin molecule. Thus, at present, 125I-(DATA)-secretin appears to be most suitable as tracer for sensitive secretin radioimmunoassay.

Plasma VIP, secretin and motilin were measured in 9 volunteers following intraduodenal instillation of 50 ml of 0.1 mol/1 HCl over 3 minutes. VIP rose from 1.7 +/- 0.7 pmol/1 to a peak at 6 minutes of 6.6 +/- 0.9 pmol/1 and was still significantly elevated at 30 minutes. By comparison the elevation of secretin was more transitory rising from a basal value of 2.5 +/- 0.4 pmol/1 to a peak of 10 +/- 1.5 pmol/1 at 3 minutes and returning to baseline by 10 minutes. The rise of motilin, from a higher baseline, was intermediate in pattern, from 23 +/- 7 pmol/1 basally to a 4 minute peak of 40 +/- 10 pmol/1. Thus the elevation of VIP was the most longlasting, and while probably not of sufficient magnitude to stimulate pancreatic bicarbonate secretion via the circulation, could reflect a significant local role in regulating the response of the intestinal mucosa to acid.

In six healthy volunteers the interdigestive motor activity and the secretory pattern were recorded in the duodenum by open tip catheters and intraluminal titration, respectively. The duodenal part of the interdigestive myoelectric complex (IDMEC) was regularly associated with a significantly increased alkali load to the duodenum amounting to 2.4 +/- 0.4 mmol per IDMEC. Thus, the intestinal "housekeeper" function of the IDMEC may be brought about by a coupled action of propagated motility and flushing secretion.

In two double-blind, randomized German multicentre trials the effects of omeprazole 20 mg mane and ranitidine 150 mg b.i.d. were compared for the first time in 334 outpatients with duodenal ulcer and 184 outpatients with gastric ulcer. In patients with duodenal ulcer endoscopically controlled healing rates after two weeks were 72% with omeprazole and 59% with ranitidine (p = 0.012); after 4 weeks 96 and 92%, resp. were healed (n.s.). In patients with gastric ulcer the healing rates after two, four, and eight weeks were 43, 81, and 95%, respectively, with omeprazole and 45, 80, and 90%, respectively, with ranitidine (n.s.). Smoking impaired healing in duodenal, but not in gastric ulcer. Symptom relief was comparable with both drugs. Serious side effects or clinically relevant changes in laboratory screening results were not detected. - Our results demonstrate for the first time that omeprazole 20 mg mane is superior to ranitidine 150 mg b.i.d. in the short-term treatment of duodenal, but not gastric ulcer.

The effect on serum gastrin levels of lysin-acetylsalicylate (LAS), water soluble derivative of acetylsalicylic acid, was investigated in mice. Intragastrically administered LAS did not at all alter serum gastrin values while--when given via the intravenous route--LAS not earlier than at the very high dose of 450 mug/g caused a short-lived significant increase in serum gastrin. These results are in keeping with the view that salicylates do not owe their potential ulcerogenic properties to stimulation the gastrin-gastric secrection mechanism.

Gastric epithelial cell loss was studied in healthy volunteers before and after intragastric instillation of four aspirin (ASA) formulations and three strengths of alcohol. Each test solution was administered three times over a period of three hours during one of the experiments. Three of the four aspirin formulations significantly increased gastric epithelial cell loss. Microencapsulated aspirin increased gastric epithelial cell loss significantly, but only after the third dose. Alcohol, 10% (wine), increased cell loss to a similar extent as did microencapsulated aspirin. Alcohol, 20% (campari), and 40% (whisky), significantly enhanced cell loss to such a degree as was elicited by the two strengths of soluble aspirin. Thus, gastric cell loss increased dose-dependently after both aspirin and alcohol. The data suggest that, in man, gastric epithelial cell damage caused by different aspirin formulations and alcohol concentrations is reproducible and dose-dependent.

In 6 healthy volunteers, following intragastric instillation of a prostaglandin analogue pentagastrinstimulated gastric secretion of acid, pepsin, and glycoprotein N-acetylneuraminic acid (NANA) was assessed. There was only a slight and statistically insignificant inhibition of acid output while pepsin secretion remained entirely unaffected. On the other hand, gastric mucus (NANA) secretion was significantly increased dependent on the prostaglandin dose administered. It is concluded that prostaglandins in addition to their well-known gastric acid inhibitory action may exert mucus stimulating properties and thus may have a direct protective effect on the gastric mucosa.

In 5 duodenal-ulcer patients with anaphylactic skin reaction to intradermal secretin and in 4 healthy controls, biopsy samples from the fundic region of the stomach were superfused with phosphate buffer alone and with phosphate buffer containing 20 C.U./ml synthetic secretin. In response to secretin, the mucosa from duodenal-ulcer patients released significantly increasing amounts of histamine (P is less than 0.05) whereas control tissue did not respond. Additionally, in duodenal-ulcer patients the histamine content of untreated gastric mucosa was about twice as high as in controls (P is less than 0.02). It is suggested that the elevated mucosal histamine could account for the basal and stimulated gastric hypersecretion of duodenal-ulcer patients. In addition, the results are compatible with the concept that in a certain type of duodenal ulceration, secretin does drive rather than inhibit gastric secretion.

The release of histamine from isolated gastric mucosa of the rat was studied by a superfusion model. Pentagastrin increased the basal efflux of histamine in a dose dependent manner. Secretin failed to influence the release of histamine under similar conditions. The results are compatible with the view that in gastric mucosa pentagastrin releases histamine which then may react with the receptors of the parietal cell thus serving as mediator in the acid secretory process.

The therapeutic effectiveness of a conventional (Pankreon-Granulat) and an acid-protected (Kreon) porcine pancreatic enzyme preparation, and an acid-stable fungal enzyme preparation (Nortase) in the treatment of severe pancreatogenic steatorrhoea was investigated. The study comprised 17 patients with chronic pancreatitis and exocrine pancreatic insufficiency with (A) or without (B) a previous Whipple's procedure (B II resection + partial duodenopancreatectomy). With all three enzyme preparations, a significant (p less than 0.05) reduction in the total faecal fat excretion/day was achieved. In therapy group A, this reduction was, on average, 58% for Kreon (100,000 U lipase/day), 67% for Pankreon-Granulat (360,000 U lipase/day) and 54% for Nortase (75,000 U lipase/day), the respective figures for therapy group B being 58%, 52% and 46% at identical dosages. Thus, in both groups, the effect produced by the conventional porcine pancreatic enzyme preparation and the acid-protected porcine or the acid-stable fungal enzyme preparation was largely equivalent, although the latter two preparations were administered at only 1/4 of the dosages of the former preparation. On the basis of the respective average reduction in total faecal fat excretion and average number of stools/day, it would appear that in patients with chronic pancreatitis and prior Whipple's procedure, Pankreon-Granulat should be administered for enzyme replacement while in patients with an intact upper gastrointestinal tract, Kreon should be administered, in the treatment of steatorrhoea in chronic pancreatitis.

Prostaglandin E2 (PGE2) prevented hemorrhagic ulceration of rat stomach mucosa induced by various procedures when given orally at a non-antisecretory dose. This effect of PGE2 is called gastric cytoprotection. We used absolute ethanol, 0.6 N hydrochloric acid and 0.2 N sodium hydroxide as damaging agents. Ranitidine at an antisecretory dose did not exhibit any cytoprotective effect. However, the poorly absorbable antacids, magnesium hydroxide plus aluminium hydroxide and aluminium phosphate inhibited the development of hemorrhagic lesions significantly. A similar protective effect was seen after intragastric administration of papaverine, which is known to stimulate endogenous prostaglandin synthesis. However, the question as to whether or not stimulation of endogenous prostaglandin synthesis is the mode of action of the cytoprotective effect of papaverine and poorly absorbable antacids, cannot yet be answered.

The degree of correlation between exocrine pancreatic function and endocrine secretory capacity was examined in 13 chronic pancreatitis patients with secondary diabetes mellitus, 8 chronic pancreatitis patients without diabetes, and 11 healthy subjects. The two parameters were studied under maximal stimulation (volume-corrected secretin-pancreozym test and glucose-tolbutamide-glucagon provocation, respectively). A close, linear correlation was found between all endocrine variables and pancreatic acinar function (e.g. rs = 0.77 for chymotrypsin output and C-peptide release; p less than 0.0001). The correlation was less strong with pancreatic bicarbonate output (e.g. rs = 0.49 for C-peptide release; p less than 0.05). In our patients, secondary overt diabetes occurred in chronic pancreatitis when protease outputs were, on an average, reduced to about 10% of the mean maximal protease output of normal subjects.

In 93 patients with known exocrine pancreatic function (secretin-pancreozymin test), NMR spectrometry and chloroform-methanol extraction of quantitatively collected, homogenized and lyophilized stools provided significantly correlated results with respect to stool fat concentration (r = 0.872) and total stool fat excretion/day (r = 0.983). In 83% of 24 patients with total stool fat excretion/day of more than 15 g (chloroform-methanol extraction), the indication for enzyme replacement was also established by stool fat concentrations of more than 35% determined by NMR spectrometry, irrespective of whether stool fat was measured in total stools or in 3 consecutive unhomogenized samples. In the remaining (17%) patients total stool fat excretion/day was only slightly elevated (16-21 g). Interestingly, in only 58% of patients actually needing enzyme replacement, did the secretin-pancreozymin test reveal a reduction of stimulated enzyme secretion to below 15% of the lower normal limit. The results indicate that NMR spectrometry of lyophilized samples of 3 consecutive unhomogenized stools is suitable for stool fat quantitation and for establishing the indication for enzyme replacement in chronic pancreatitis.

To further elucidate the pathophysiological role of peptide hormones in duodenal ulcer (DU) disease, several endocrine, paracrine and neurocrine peptides were determined radioimmunologically in biopsies of gastroduodenal mucosa obtained endoscopically in 8 subjects without upper gastrointestinal disease, and in 8 duodenal ulcer patients. The DU patients had a BAO of 6.6 +/- 1.9 and a PAO of 41.8 +/- 6.1 mEq/h. In DU patients, a lack of the acid and gastrin-release inhibiting agent somatostatin was found neither in antral nor in fundic mucosa (185 +/- 60 vs 83 +/- 19 pmol/g tissue wet weight in controls). Basal and peak acid outputs of DU patients were positively correlated with fundic somatostatin concentrations (p less than 0.01). While gastrin levels were not significantly elevated in the antrum of DU patients, the mucosal content of potentially releasable gastrin of the duodenal bulb and the descending duodenum was higher than in controls (p less than 0.01). In the whole duodenum, CCK-like immunoreactivity was also more abundant in DU patients than in controls, whereas GIP and motilin did not exhibit characteristic profiles. Presumably as a reactive phenomenon, the mucosal levels of the peptidergic neurotransmitters VIP and substance P were markedly increased in the proximal duodenum of DU patients.

In man (n = 5), after intraduodenal instillation of 50 ml of 0.1 N hydrochloric acid the lower esophageal sphincter pressure (LESP) and plasma motilin concentrations rise concomitantly exceeding basal by about 80% (p less than 0.025) and 90% (p less than 0.05), respectively, at 3 to 4 minutes. These results suggest that the increase in LESP after duodenal acidification may be brought about by endogenously released motilin.

A disturbed intraduodenal milieu and pancreatic scarring in advanced chronic pancreatitis (CP) may lead to changes of gut and pancreatic hormones. In the present study, the gastroduodenal mucosal content of several regulatory peptides was determined in 8 patients with severe calcific CP and 8 healthy volunteers. In addition, hormone release into the bloodstream was estimated after intraduodenal acid/glucose stimulation in the control subjects and 8 CP patients each with or without secondary diabetes mellitus (DM), and in 8 patients with juvenile DM, so that disturbed gut hormone release could be attributed either to CP or DM. While VIP release into the circulation was similar in all participants, mucosal levels of VIP and substance P were significantly elevated in the duodenal bulb and descending duodenum of CP patients. The somatostatin content of gastroduodenal mucosa in CP was at least as high as in normals. Gastrin was significantly more abundant only in the duodenal bulb of CP patients, while plasma gastrin was normal. Duodenal CCK concentrations tended to be elevated in the duodenal bulb, but not significantly. The release of secretin seemed to be higher in type-1 diabetics than in CP patients. The mucosal pattern of GIP was nearly identical in CP patients and controls. Compatible with this finding, the GIP release did not show any peculiarities in CP with or without DM or in DM. Basal and stimulated plasma levels of motilin were abnormally high in CP. Pancreatic polypeptide plasma levels were normal in DM, but significantly reduced in CP, especially in CP with DM. Fasting PP and stimulated pancreatic enzyme outputs were linearly related.(ABSTRACT TRUNCATED AT 250 WORDS)

In 10 male subjects, the effects of oral S-(carboxy-methyl)-L-cysteine (SCMC) -- a mucolytic agent useful in the treatment of chronic obstructive bronchitis -- on gastric secretion of acid and N-acetylneuraminic acid (NANA) containing glycoproteins were investigated. Gastric acid outputs and mucus secretory rates remained unchanged during a 10-day period of daily administration of SCMC. Thus, the receptors of SCMC in the bronchial system appear to differ basically from those in the stomach.

In the present study, we investigated the question whether the zinc deficiency in Crohn's disease is, at least partly, related to defective zinc entry at the jejunal brush border membrane. Brush border membrane vesicles (BBMV) were prepared from surgically resected pieces of morphologically intact human jejunum by a Mg++ precipitation method. We studied zinc, D-glucose, sodium and D-mannitol uptake into BBMV in 27 patients: 1) 20 patients with Crohn's disease 2) 7 controls. In 8/20 patients with Crohn's disease we found a significant decrease in zinc uptake (-25% +/- 5%, p less than 0.05) into BBMV. This impairment of zinc uptake in 40% of our patients with Crohn's disease was not associated with changes in the transport rates for D-glucose, sodium or D-mannitol. In addition no differences in enzyme marker concentrations or electron microscopic appearance were found.

The effect of hydrochloric acid and sodium hydroxide on motilin release from human duodenal mucosa was studied in vitro. Tissue was incubated in 2 ml chambers continuously perfused with medium and was exposed repeatedly to the stimuli. Motilin released into the medium was determined by a specific radioimmunoassay. Whereas alkalinisation abolished basal motilin release, acidification resulted in a 14-fold increase of peptide secretion. The results indicate that motilin secretion can be stimulated in vitro and that the perfusion system described may be a useful tool in studying the mechanism of gastrointestinal hormone release.

In search of a physiological stimulus for secretin release, the effect of gastric acid secretion was investigated. In six healthy volunteers, pentagastrin (1.5 microgram/kg, hr i.v.) was administered without and with aspiration of gastric contents, and plasma secretin was estimated by radioimmunoassay. Administration of pentagastrin without aspiration of gastric juice resulted in steadily increasing plasma secretion which was significantly elevated at the end of 60 min of pentagastrin infusion and also in the post-infusion hour. These results are compatible with the concept that endogenous acid being delivered from the stomach to the duodenum does contribute to the release of secretin which in turn may serve as a physiological stimulus for pancreatic bicarbonate secretion.

Gastrointestinal myoelectric activity was studied in three conscious fasted dogs with electrodes surgically implanted in the stomach and small intestine, during separate and combined intravenous infusions of 13-norleucine motilin (13-nle-motilin) and pentagastrin (PG). Basal recordings confirmed the presence of regular interdigestive myoelectric complexes (MC's). 13-nle-motilin infusion below 50 ng/kg-h was without effect: higher doses up to 400 ng/kg-h resulted in the interpolation of one or more MC's in the spontaneous sequence. The rate of aboral transit of 13-nle-molitin-induced MC's did not differ significantly from that of spontaneous MC's. When MC's were abolished by feeding or PG infusion, simultaneous 13-nle-motilin administration was without effect on spike activity, but slightly attenuated the accelerating effect of gastrin on the gastric pacemaker frequency. The myoelectric events triggered by 13-nle-motilin suggest that in the conscious dog the polypeptide may not act directly on the smooth muscle cell, as it does in vitro, but through an extra-enteric neural control mechanism which is uncoupled by gastrin.

Lysine acetylsalicylate (LAS), a water soluble derivative of acetylsalicylic acid and parenterally administrable analgesic, locally inhibits the incorporation of 14C protein hydrolysate into proteins of the rat isolated gastric mucosa. A similar effect on protein synthesis was observed after s.c. administration of the drug, whereas DNA and RNA synthesis were not affected. Obviously, LAS inhibits the translation step during biosynthesis of proteins. It is conceivable that this effect contributes to the potential ulcerogenic action of acetylsalicylate and that parenteral administration is not a criteria to protect the stomach from salicylate-induced side effects.

Maldigestion phenomena in patients subjected to a Billroth II (B II) operation are in part attributed to an atrophy of the pancreas due to inactivity. In order to investigate this, a Lagerlöf tube was introduced under endoscopic control into the afferent loop, and the function of the exocrine pancreas studied after endogenous and exogenous stimulation. During endogenous stimulation of the exocrine pancreas by means of a Lundh test meal, no significant differences in the secretory pattern of the Billroth II patients as compared with healthy test subjects were found. In contrast, during exogenous stimulation, the output of trypsin and chymotrypsin in healthy subjects was significantly greater than in the B II patients. Since, in comparison with maximal stimulation, the endogenous secretin released by the jejunal mucosa in response to the intake of food, effects only approximately 25% of the bicarbonate production and endogenous pancreozymin effects some 50% of the enzyme output, the maldigestion phenomena observed in B II patients are inpart understandable.

In the guinea pig isolated terminal ileum the opioid pentapeptides, methionine-enkephalin and leucine-enkephalin, dose-dependently inhibit contractile responses induced by electrical field stimulation releasing endogenous acetylcholine, and by specific noncholinergic compounds including histamine, barium chloride, and beta-acetyl-digoxin. Tissue levels of cAMP and cGMP remain unchanged. We conclude that enkephalins exert their effects by a direct action at or within the muscle cell and may play a physiological role in the local control of the gut smooth muscle motility.

In a double-blind trial, 12 in-patients with endoscopically proven duodenal ulceration were treated with cimetidine (0.8 g daily) or placebo. Ulcer sizes were assessed endoscopically before treatment and at weekly intervals during treatment. Duodenal-ulcer healing was significantly more rapid in patients on cimetidine than in those receiving the placebo (p less than 0.0005): half-times of ulcer healing were about 6 days (on cimetidine) as compared to about 20 days (on placebo). No untoward clinical or laboratory effects were observed.

In six healthy volunteers pure pancreatic juice was obtained by endoscopic cannulation of the main pancreatic duct. Following a 20-min basal period, secretin (0.03 CU/kg, h) was intravenously infused alone for 20 min and then with caerulein 15 ng/kg, h for further 20 min. From a basal level of 28 +/- 13 mu mol/5 min, secretin by itself significantly increased pancreatic bicarbonate to 182 +/- 24 mu mol/5 min. A further significant two-fold increase to 396 +/- 50 mu mol/5 min was observed during caerulein. The increment in plasma secretin of 2.1 +/- 0.3 pmol/l is comparable to the rise that may be observed post-prandially. It is concluded that secretin in combination with cholecystokinin may indeed play a physiological role in the regulation of duodenal pH.

This study in man (n = 35) deals with the effects of in vivo administration of pentagastrin, synthetic secretin, and 13-norleucine-motilin (13-nle-motillin), respectively, on the in vitro incorporation of 14C-leucine into gastric mucosal protein. From the results presented it may be concluded that pentagastrin has a trophic influence on gastric mucosa in man, too, while protein synthesis in human duodenal mucosa remains unaltered. As the incorporatin of 14C-leucine into gastric mucosal protein is inhibited both by secretion and 13-nle-motiln, it may be hypothesised that secretin and motilin act as functional antagonists of gastrin in the regulation of human gastric mucosal protein synthesis.

The effects of a 6-day course of treatment with a glucocorticoid (prednisolone, 1 g per day i.v.), a mineralocorticoid (9-alpha-fluorohydrocortisone, 0.3 mg per day orraly), or both the drugs on gastric secretion of acid, protein, pepsin, and N-acetylneuraminic acid (NANA) containing glycoproteins were investigated in 22 volunteers. None of the treatments produced any statistically significant changes in gastric secretion of aggressive factors, acid and pepsin. However, the output of protective NANA bound to glycoproteins was found to be decreased following prednisolone. The prednisolone effect was not prevented by 9-alpha-fluorhydrocortisone given concomitantly. Gastroduodenoscopy did not reveal any lesions attributable to drug adminstration.