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Biomedical subjects

H Sarles

Publications and source records attributed to H Sarles.

At least 253 records · Page 14Linked to original sources

Controlled trial of chenodeoxycholic therapy for radiolucent gallstones. A multicenter study.

134 patients with radiolucent gallstones were randomly allocated to receive either placebo or 1 of 3 different doses of chenodeoxycholic acid (CDCA); 750, 1,500, or 3,000 mg). The initial dose was lowered if not well tolerated. 107 patients were treated for more than 3 months. Among them, stones dissolved in 21 and were smaller in 25 patients. Partial or complete dissolution occurred in 4 of the 13 receiving 375 mg/day, 14 of 37 receiving 750 mg, 24 of the 38 receiving 1,500 mg and 4 of 8 receiving 3,000 mg/day. The number of responders to the therapy was significantly greater in the groups of patients receiving 1,500 mg/day or 17-24 mg/kg body weight than in any other group. However, side effects, i.e., diarrhea and transaminase increase, are also dose related. It appears from this study that the optimal dose of CDCA may be between 17 and 20 mg/kg body weight.

Adult↗

Chronic alcoholism and canine exocrine pancreas secretion. A long term follow-up study.

Sequential changes in pancreatic secretion were evaluated during a 2- to 3-year follow-up study in 8 dogs provided with Thomas gastric and duodenal fistulas. Four animals were given intragastric ethanol (2 g kg-1) daily for 3 years; 4 others served as controls. In alcohol-fed animals: (1) Flow rate and bicarbonate output in response to 1 clinical unit kg-1 hr-1 of secretin were increased at the end of 2 years but not after 1 year of alcohol feeding. (2) At the end of 2 years, the dose-response curve of pancreatic secretion to cholecystokinin was unchanged but the maximal bicarbonate and water secretion in response to high doses of secretin were increased. Modifications (1) and (2) are explained by reduplication of pancreatic ducts secondary to the development of chronic pancreatitis, verified by biopsy. (3) The previous report by our group of an increased cholecystokinin release in the course of chronic alcohol consumption in dogs seems to be attributable to an artefact. This work shows that the pancreatic response to intraduodenal oleic acid is not significantly modifed by 3 years of alcohol feeding.

Alcoholism↗

Histochemical study of cholinergic activities in exocrine pancreas of dogs. Modifications related to chronic alcoholism.

An histochemical study has been made of pancreatic biopsies from 5 dogs with gastric and pancreatic Thomas cannulae. 3 dogs received 2 g kg-1 day-1 ethanol for 3, 4 and 48 months; 2 dogs which did not received alcohol served as controls. Acetylcholinesterase has been studied by the histochemical method of Koelle. Choline acetyl transferase by the method of Burt. Our results suggest that there is less acetylcholinesterase activity in the pancreas of alcoholic dogs than in control dogs. This is as more pronounced when the alcohol consumption is prolonged. On the contrary, the intensity of the histochemical reaction for choline acetyl transferase is greater in alcoholic dogs than in controls. Although histochemical methods are only semi-quantitative, these results suggest that the cholinergic tone of the exocrine pancreas is increased in chronic alcoholic dogs. This has already been suggested by previous physiological experiments performed on the same animals.

Acetylcholinesterase↗

Nonparallel secretion of enzymes in human duodenal juice and pure pancreatic juice collected by endoscopic retrograde catheterization of the papilla.

Duodenal juice was collected from 50 healthy patients in the basal state, and after intravenous injection of 1 clinical unit of secretin kg-1 + 3 Crick-Harper-Raper units of cholecystokinin-pancreozymin (CCK-PZ) kg-1. Amylase to chymotrypsin and amylase to lipase ratios were significantly decreased by stimulation. Pure pancreatic juice was collected from 7 healthy subjects by endoscopic retrograde catheterization of the papilla. Secretin (1 clinical unit kg-1 hr-1) was infused intravenously during 30 min, and a single intravenous injection of CCK-PZ (3 Crick-Harper-Raper units kg-1) was done at the 15th min of the secretin infusion. Chymotrypsinogen and lipase secretions did not parallel that of amylase during CCK-PZ stimulation. As in the first set of experiments, amylase secretion was proportionally less stimulated by CCK-PZ injection than were chymotrypsinogen and lipase secretions. However, in approximately 20% of subjects the secretion of the enzymes was parallel in both duodenal and pancreatic juice.

Ampulla of Vater↗

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↗

Blocking of protein pancreatic secretion by maximal secretion infusion in the dog.

In conscious chronic gastric and pancreatic fistula dogs (Thomas cannula), secretin was perfused for three hours with a submaximal (GIH, 1.0 C.U./kg.) and a maximal dose (GIH, 8.0 c.u./kg.), according to the following schedule: 1. First hour submaximal stimulus; 2. second hour maximal stimulus; 3. third hour submaximal stimulus. The alkaline and protein components of pancreatic secretion were analyzed in 20-minute sample collections thoughout the three hours. The same protocol was followed in anesthetized dogs subjected to a mind line laparotomy. A biopsy of the pancreatic gland was taken before (control) and at the end of each perfused dose. The secretion showed a significant increase of protein concentration and output when passing from the maximal to the last submaximal secretin perfusion dose. These findings correlated well with the piling up of zymogen and prozymogen granules in the apical zone of the acinar cells during maximal secretin perfusion, with their subsequent discharge into the acinar lumen upon abrupt reversal to the initial secretin submaximal dose. The study confirms that secretin influences pancreatic protein secretion and indicates in addition, that pharmacologic doses of the hormone, have the capacity to block acinar cell zymogen granule release.

Animals↗

The effects of acute and chronic ethanol administration on canine bile secretion.

In 9 conscious dogs (4 of whom were alcohol-fed for 24 months with 50% intragastric ethanol), provided with gastric and duodenal fistulae (Thomas cannula), the effects were studied of an acute iv ethanol infusion (1.3 g/kg) on hepatic bile secretory plateau levels after emptying of the gallbladder was induced by a continuous perfusion of secretin (0.5 CU/kg/hr) plus CCK-PZ (8 Crick-Harper-Raper U/kg/hr) and sodium taurocholate (0.62 mumol/kg/min). Acute iv ethanol infusion in nonalcoholic dogs reduced hepatic bile flow rate (29%), bile salt concentration (55%) and output (67%). In alcohol-fed dogs, acute iv ethanol reduced only the rate of flow (25%). Hepatic bile salt concentration and output plateau values were significantly higher in the alcohol-fed than in the nonalcoholic dogs. There were no significant differences between the two groups of dogs in the rate of evacuation, bile salt output, or lipid composition of gall bladder bile following a single iv injection of CCK-PZ.

Animals↗

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↗

Lactoferrin in human pancreas. Immunohistological localization in normal and pathological pancreatic tissues.

The protein composition of normal human pancreatic juice and pancreatic juice of men with chronic calcifying pancreatitis (CCP) were compared using immuno-diffusion techniques. An additional protein was found in pathological pancreatic juice and this protein has been identified as lactoferrin. Its concentration has been determined. The indirect immunofluorescence method was used to detect and localize lactoferrin in 9 samples of human pancreas from 3 patients with CCP and 6 patients without CCP. The fluorescence was found in all samples. Lactoferrin staining was localized in lumen acinar and in the cytoplasm of the acinar cells. The fluorescence was stronger in the apical zone of acinar cells. When lactoferrin antiserum was incubated with lactoferrin insolubilized by glutaraldehyde, no fluorescence staining was detected. The differences between our results obtained by immunodiffusion and immunofluorescence techniques are explained by the different sensitivity of the two techniques and these results indicate that lactoferrin is a protein of pancreatic secretion.

Chronic Disease↗

[Medical and surgical management of chronic pancreatitis (author's transl)].

Chronic pancreatitis has to be treated in the first line by medical means. Dietary procedures, absolute abstinence from alcohol, compensation of malabsorption and treatment of diabetes will do in most cases. Surgery is indicated in cases resistent to this form of therapy of when complications arise (cysts, persistent jaundice, portal hypertension). The patient has to be given high caloric parenteral nutrition preoperatively. Pancreato-jejunostomy with an Y shaped loop and surgical removal of various amounts of pancreatic tissue are the only efficient surgical procedures. In cases of dilatation of the pancreatic duct drainage has to be performed. Results of surgery are satisfactory in 2/3 of cases.

Cholelithiasis↗

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↗