We undertook a multicenter double-blind study comparing ranitidine to placebo in 73 patients with symptomatic gastroesophageal reflux ranging in age from 22 to 80 years (mean 49). Initially, all patients had moderate to severe symptoms associated with abnormal endoscopic and/or microscopic appearance of the mucosa. After six weeks, 46% of ranitidine-treated patients had a one-grade improvement in their symptom of regurgitation, as compared with 19% treated with placebo (p less than 0.01); ranitidine was no better than placebo in the improvement of pain or dysphagia. Endoscopic improvement occurred in 61% of ranitidine- and 48% of placebo-treated patients (p less than 0.05). Histological improvement occurred in a similar and small portion of patients treated with ranitidine and placebo; there was no correlation between clinical, endoscopic, and histological improvement. Antacid consumption was only half as great in the ranitidine as in the placebo group. Therapy with ranitidine was maintained for up to 12 months. The patients remained free of regurgitation or pain and there was a trend towards further improvement in the endoscopic or histopathologic appearance of the esophagus. Ranitidine 150 mg b.i.d. is recommended for the relief of symptoms and improvement in the endoscopic appearance of the esophagus. Treatment should be for a minimum of 6 weeks, but may be continued for up to a year if the patient's symptoms persist or return.

Adult↗

PubMed1978

Effect of glucagon on canine exocrine pancreatic secretion stimulated by a test meal.

The effect of glucagon on exocrine pancreatic secretion stimulated by a test meal was studied in three dogs with a chronic gastric fistula and a modified Thomas duodenal fistula which allows easier collection of pure pancreatic juice after a meal. Glucagon was given by continuous intravenous infusion in doses of 5, 10, 15, or 30 microgram/kg per hour, before and during a test meal. At each dose level glucagon significantly reduced the water and electrolyte secretion of the pancreas. At 15 and 30 microgram/kg per hour glucagon inhibited protein output; this effect was absent at lower doses. These findings demonstrate a dose-dependent inhibition by glucagon of the pancreatic bicarbonate and protein response to a meal. Inhibition of bicarbonate output was more sensitive to glucagon than that of protein output.

Animals↗

PubMed1978

Impaired secretin release in chronic alcoholic dogs.

Plasma immunoreactive secretin has been compared before and after stimulation by intraduodenal infusion of HCl in 3 dogs who had received 2 g-kg-1-day-1 alcohol for 3 years and 4 non-alcoholic control dogs. After HCl infusion, blood secretin was lower in chronic alcoholic animals than in controls. This decreased post-stimulation concentration of secretin in chronic alcoholic dogs was in contrast to the increased release of gastrin after a meal which has been previously described.

Alcoholism↗

PubMed1977

Canine exocrine pancreatic secretory changes induced by an intragastric ethanol test meal.

In five dogs with chronic gastric fistulas (Thomas cannula) and a new type of chronic pancreatic fistula which permits collection of pure nonactivated pancreatic juice after ingestion of a test meal, the following series of experiments were performed: In the first series, a test meal (400 gm. canned dog meat) was given with 200 ml. saline simultaneously infused through the gastric cannula. In response to this stimulus, the 20-minute peak pancreatic flow rate and bicarbonate output were respectively 33% and 34%, of the maximal secretion of the pancreatic gland obtained with secretin in six control dogs provided with gastric and the classical Thomas duodenal fistula. The 20-minute peak protein output represented 84% of the maximal secretory capacity attained with dose-response curves to CCK in the same group of control animals. In the second series either 1.5 or 2.0 gm./kg. ethanol were given instead of saline. Intragastric ethanol induced a dissociation of pancreatic secretion: a significant inhibition of flow rate, of bicarbonate concentration and output and a significant rise of protein concentration; protein output remaining unchanged. It is postulated that ethanol, acting on the stomach and duodenojejunum, evokes, independently of its gastrin-releasing capacity, and unknown humoral or nervous mechanism that counteracts the ethanol-elicited cholinergic-mediated inhibition of pancreatic protein secretion which has been previously described.

Animals↗

PubMed1976

Atropine-induced inhibition of the enhanced CCK release observed in alcoholic dogs.

As it has been previously shown, the pancreatic secretory response to an intraduodenal infusion of oleic acid is increased in animals accustomed to daily ethanol consumption compared to matched controls. This action has been verified in dogs provided with a Thomas cannula and consuming 2 g kg-1 ethanol or not, daily since 3 years. An intravenous infusion of 0.75 mg kg-1 h-1 of atropine suppresses the difference between alcoholic and non-alcoholic animals. Therefore, the increased release of CCK-PZ in response to meal, which is characteristic of chronic alcoholic animals, is under cholinergic control.

Alcoholism↗

PubMed1976

Canine exocrine pancreatic secretory changes induced by calcium or ethanol plus calcium intraduodenal infusion.

In dogs provided with chronic gastric and pancreatic fistulas (Thomas cannula), an 80-minute intraduodenal CaCl2 (0.6 mM/kg.) infusion against a background of secretin perfusion (GIH, 1.0 CU/kg./hr.) elicits a complex "pancreon" response consisting of both excitatory and inhibitory effects on the protein and alkaline components, respectively, of pancreatic secretion. It is postulated that these pancreatic secretion changes are the result of the interplay of released CCK and calcitonin. The lack of pancreatic secretion modifications when ethanol (0.7 mg./kg.) was added to the intraduodenal CaCl2 infusion suggests that the former counteracts the effects of the latter on the nerves and/or the endocrine cells of the gut. Ca++ concentration and output in pancreatic secretion did not change significantly either with the intraduodenal CaCl2 alone or associated with ethanol. Fasting blood Ca++ levels were not modified either by the secretin perfusion or by the intraduodenal CaCl2 infusion, either given alone or associated with ethanol.

Alkalies↗

PubMed1976

Evidences for duodenopancreatic reflexes and an anti-CCK factor with lidocaine infused intravenously and sprayed topically on pancreatic papilla in nonalcoholic and alcohol-fed dogs.

In 14 duodenal Thomas fistula dogs, four of them alcohol-fed for two years, lidocaine, applied topically to the duodenal pancreatic papilla, inhibited secretin-induced pancreatic secretion probably by interrupting duodenopancreatic reflexes that contribute to the "pancreon's" cholinergic tone. Opposite effects were observed with lidocaine administered against a CCK plus secretin background stimulation of the pancreas. The significant rising of volume and protein output above plateau levels were enhanced by chronic alcohol feeding. Lidocaine infused intravenously did not change secretin-induced pancreatic secretion but raised CCK and secretin evoked plateau secretion levels. Chronic alcoholism enhanced these latter effects. Atropine perfusion superimposed on CCK and secretin stimulation did not prevent but raised the intravenous lidocaine-induced pancreatic secretion changes. It is postulated that the modifications elicited by lidocaine sprayed topically and infused intravenously on CCK plus secretin evoked pancreatic secretion plateau levels are due to depression of an anti-CCK factor secreted by the small intestine mucosa.

Administration, Topical↗

PubMed1976

Reserpine-induced dissociation of canine pancreatic secretion.

In five dogs, provided with chronic pancreatic and gastric fistulas (Thomas' cannula), the effects on exocrine pancreatic secretion of an intravenous continuous perfusion of gastrin (Eurorga, hog gastrin I-II, 6 mug./kg./hr.) and secretin (GIH, 0.5 C.U./kg.hr.) was studied before and after 48 hours of reserpine treatment (0.1 mg./kg./24 hr.). When compared with the pretreated plateau levels, reserpine induced a significant pancreatic secretion dissociation, a depressive of the alkaline and a rising of the protein component. The former phenomenon suggests a participation of a catecholamines in the secretin-elicited pancreatic electrolyte secretion. The latter, an enhanced sensitivity of intranpancreatic and/or acinar cells of the "pancreon" to gastrin stimulation.

Animals↗