Enhancement of duodenal and jejunal ulceration by histamine-induced gastric hypersecretion in dogs with diversion of duodenal contents.

In a previous investigation deviation of duodenal contents protected rats significantly from the development of peptic ulceration under maximal acid secretion. We have now assessed the effect of diversion of duodenal contents in dogs submitted to the same operative procedure under histamine-induced hypersecretion. Six mongrel dogs underwent the following procedure: A two cm duodenal segment was left adjacent to the intact pylorus, proximal jejunum anastomosed to this segment and a Roux-en-Y duodeno-jejunostomy performed. The dogs were given 30 mg histamine in beeswax daily i.m. Unexpectedly their physical condition deteriorated rapidly by the second day and they were sacrificed on the 4th day. Necropsy revealed multiple and severe peptic ulceration. There was a total of 9 duodenal ulcers with no perforations. 5 anastomotic and 24 jejunal ulcers with 1 and 3 perforations respectively. It was concluded that the diversion of duodenal contents enhanced ulcer formation in dogs and that the model mimicked a Zollinger-Ellison Syndrome. Ulceration occurred in transitional or jejunal type of duodenal mucosa. No gastric lesions were found and this suggests that the diversionary procedure was an effective means of preventing bile from reaching the gastric mucosa.

Diversion of bile and pancreatic secretion in the rat and its effect on cysteamine-induced duodenal and peptic ulcer development under maximal acid secretion.

In this investigation we assess whether diversion of bile and pancreatic secretion protects rats from ulceration under maximal acid secretion as it does in cysteamine-induced ulcers. The rats were divided into a cysteamine-group (Cy) comprising 16 rats and a secretagogue group (PC) with 18 white male rats. Half of the animals of each group were submitted to the diversion-operation (division of the duodenum distally from the pylorus, jejuno-duodenostomy and entero-y-anastomosis), Cy2 and PC2 respectively. The other animals were not operated (Cy1 and PC1). In the cysteamine group the rats were given twice cysteamine-HC1 injections subcutaneously and the PC group were given a 24 h infusion with pentagastrin and carbachol. All animals of the Cy1 group had duodenal ulcers, 3 perforated. However, only 2 rats had one ulcer each in the Cy2 group (p less than 0.01). The PC1 group totalled 30 duodenal ulcers in the 9 animals with 10 perforations, 13 ulcers in 6 animals with 3 perforations in PC2. Furthermore in PC1 group 34 gastric ulcers were found in 7 rats and only 4 ulcers in the PC2 group. It is therefore concluded, that the diversion operation provided protection against cysteamine-induced duodenal ulcers (p less than 0.01) and ulcer formation under maximal acid stimulation in the duodenum (p less than 0.02) as well as in the rat stomachs (p less than 0.05). In the PC group the restraint haltering of the animals promoted presumably a stress situation with bile reflux in the non-operated whereas in the operated animals (PC2) reflux did not occur.

The role of bile salts in cysteamine-induced duodenal ulcer in the rat and the ulceroprotective property of lysolecithin.

UNLABELLED: Cysteamine induces duodenal ulcers in rats, but bile diversion inhibits ulcer formation. Since lysolecithin inhibits stress ulceration in rats, it is assessed now whether lysolecithin inhibits cysteamine-induced ulcers, too. Male rats were operated: division of the duodenum distally to the pylorus, duodenojejunostomy. Roux-en-Y duodenojejunostomy. 4 groups comprising 10 animals. Drinking solution for group 1, 3 and 4: Na taurocholate and glycocholic acid (5 mmol/l). For group 2 addition of 0.2 mmol/l lysolecithin. Cysteamine-HCl (10%) twice subcutaneously on the 19th day in group 1, 3 and 4, isotonic NaCl in group 2. In group four 1 ml lysolecithin per gastric tube 1 h before cysteamine. RESULTS: Group 1: 8 animals with 16 ulcers, group 2: 7 with 10 ulcers, group 3: no ulcers, group 4: 3 with 5 ulcers (p less than 0.05/p less than 0.02). CONCLUSION: Lysolecithin, a substance produced during fat digestion, exerted an ulceroprotective property (lyso-protection) under experimental conditions, as shown here for the first time, to the author's knowledge. The enhancement of cysteamine-induced duodenal ulcer development by bile salts is again documented.

The role of taurocholic acid, glycocholic acid and lysolecithin in experimental stress ulcer in the rat.

The stress ulcer formation is enhanced significantly in rats operated with pyloro-jejunostomy and Roux-en-Y anastomosis by taurocholic acid or a mixture of taurocholic and glycocholic acid. However, the incidence of stress ulcers is significantly reduced by adding lysolecithin to the drinking solution containing these bile acids in the same concentration, though lysolecithin alone induces significantly more stress ulcers than tap water in rats with the same operation submitted to immobilisation stress.

Inhibition of experimental stress ulcer formation in rats.

We present an operation model in rats, which according to our opinion prevents duodenogastric reflux effectively. The duodenum is divided distally from the pylorus and a pyloro-jejunostomy performed combined with a Roux-en-Y anastomosis. Rats operated this way and submitted to restraint stress developed significantly less stress lesions than operated control under same conditions. However, operated rats submitted to the operation and offered a 5 mMol/l drinking solution of crude taurocholic acid during 20 days before submitted to stress had significantly more stress lesions than operated animals with tap water before restraint stress.

Effect of pentobarbital anesthesia and bile acids on cysteamine-induced duodenal and gastric ulcers in rats.

Cysteamine given three times within 8 h produced severe duodenal and gastric ulcers in female SIV rats. A pentobarbital anesthesia during the first 10 h prevented gastric ulcer formation without affecting duodenal ulcer. An additional 10 h lasting intragastric infusion with 0.6 ml/h Ringer containing 5 mmol/l of a mixture 3: 1 pure taurocholic and glycocholic acid or 20 and 50 mmol/l pure taurocholic acid in 0.2 N HCl did not reverse the protective effect of pentobarbital, e.g. incidence and intensity of gastric ulcer did not change. Treatment with somatostatin significantly reduced the intensity of duodenal ulcer. The inhibition of cysteamine-induced gastric ulcer formation by pentobarbital does not seem to be due to a possible inhibition of duodenogastric reflux but more likely to an inhibition of central nervous stress reactions by anesthesia.

[Conservative therapy of peptic ulcer]. / Die konservative Therapie des peptischen Ulkus.

Ulcer disease is the product of different pathogenetic mechanisms which destroy the balance between protection and aggregation in the human organism. Investigation of such errors of physiologic balance in the human organism is in full swing, and has provided the theoretical elements for appropriate therapy. Therapy for ulcer disease must take into consideration the patient's personality as well as the surrounding conditions. Though duodenal and gastric ulcer show many different characteristics, therapy does not greatly differ. Food and antacids neutralize hydrochloric acid already produced and bind bile acids and other substances which have been regurgitated from the duodenum into the stomach. Furthermore, very potent inhibitors of acid secretion are available, such as the H2-receptor-antagonist cimetidine, and pirenzepine. Antacids, inhibitors of acid secretion and placebo may lead to disappearance of symptoms, but it should be borne in mind that abut one third of patients with an ulcer recurrence remain asymptomatic. Pain and other symptoms of active ulcer disease usually disappear as early as a few days after initiating therapy. On average the healing ratio of ulcers is higher with pharmacologically active substances than with placebo. In the present state of knowledge, endoscopic follow-up of ulcer disease is to be recommended not only because active ulcer disease and ulcer recurrences may be asymptomatic, but, above all, because of the risk of malignancy in gastric ulcer.

[Hemolysis-inducing substances in gastric secretion, incidence-rate of lysolecithin]. / Hämolysierende Substanzen im Magensekret, Häufigkeit des Lysolecithin-Nachweises.

Samples of gastric contents from 152 patients with pyloric reflex were taken during gastroscopy after an overnight fast and examined for hemolytic activity. Hemolysis was induced by 97 specimens (64%). The hemolysis test was positive in 45% of patients with a histologically normal gastric mucosa, in 76% of patients suffering from chronic atrophic gastritis with intestinal metaplasia, in 83% with gastric erosions and in 67% with gastric ulcer. No lysolecithin was found in 9 of the 97 positive specimens. The other aspirates contained widely differing values up to 320 mg/100 ml. The average quantities of lysolecithin in gastric contents varied in the different patient groups from 20 to 60 mg/100 ml. These values are much higher than the mean value of 0.9 mg/100 ml quantified in patients without pyloric reflex during an earlier investigation. It is now widely accepted that pyloric reflex promotes gastritis. Furthermore, it has been shown on several occasions that bile constituents exert a damaging effect on the gastric mucosa barrier. The same is true of lysolecithin, which promotes (for example) acute cholecystitis under experimental conditions. These findings, together with the results of our investigation, seem to afford evidence that lysolecithins may exert a pathogenic influence in the development of different gastric lesions.

[Endoscopic and histological changes at the Z-line (author's transl)]. / Endoskopische und histologische Befunde an der Z-Linie. Ihre Bedeutung für die Frühdiagnose der Reflux-Osophagitis

The Z-line, the transitional zone from oesophageal to gastric mucosa, is a clearly defined point of reference. Selective forceps biopsies were obtained from the Z-line, just below it from the cardia and 1-3 cm above it from the oesophagus, in 79 patients with an age average of 47 1/2 years. A comparison was made between endoscopic and histological findings, on the one hand, and symptoms on the other. Moderately severe inflammatory changes correlated positively with only minor endoscopic changes of the Z-line: patients of this group had significantly more symptoms of reflux than those with a normal line. Exact endoscopy, complemented by histological examination, can discover reflux oesphagitis in its early stages, although endoscopically and histologically the delineation from normal is difficult.

[Lysolecithin and stress ulcers in rats]. / Lysolecithin und Stressulkuks bei der Ratte.

The effect of lysolecithin on gastric mucosa in rats has been investigated using a new operative model. Ten rats underwent sham-laparotomy. In 4 other groups, each of 10 animals, the rats underwent pyloro-jejunostomy and Roux-en-Y anastomosis. 9 of 10 rats operated upon in this way, and given a solution of lysolecithin to drink before administration of restraint stress, produced stress ulcers. However, only 3 of 10 animals given Ringer-solution produced minor mucosal defects. Lysolecithin not combined with stress had no noteworthy deleterious effect on gastric mucosa either in sham-operated rats or in those with our operation model. Thus, lysolecithin combined with stress in our model performed an important function in the pathogenesis of stress lesions. Lysolecithin is produced in considerable quantities during fat metabolism in the intestine, and may be regurgitated together with duodenal contents into the stomach.