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Biomedical subjects

H Goebell

Publications and source records attributed to H Goebell.

At least 199 records · Page 11Linked to original sources

Fecal bile acid excretion pattern in cholecystectomized patients.

The fecal bile acid excretion pattern was investigated in 25 cholecystectomized and 26 noncholecystectomized patients as a measure for the exposure of the colonic mucosa to bile acids. Separation of free, conjugated, and sulfated bile acids was achieved by liquid-gel chromatography using DEAP Sephadex LH-20 and quantification of individual bile acids by gas-liquid chromatography. Total bile acid concentration was higher in cholecystectomized (5.33 +/- 0.71 mg/g) than in noncholecystectomized patients (3.69 +/- 0.65 mg/g). Deoxycholic acid excretion was elevated in cholecystectomized patients in three aspects: the concentration of deoxycholic acid was higher (2.92 +/- 0.39 mg/g and 1.71 +/- 0.35 mg/g, respectively), its percentage proportion of total bile acids was increased (53.9 +/- 2.8% and 41.4 +/- 3.1%, respectively), and its daily output was twice as large as that in patients without previous cholecystectomy (63.2 +/- 11.5 and 32.9 +/- 5.9 mg/day, respectively).

Adult↗

Enhanced formation of sulfidopeptide-leukotrienes in ulcerative colitis and Crohn's disease: inhibition by sulfasalazine and 5-aminosalicylic acid.

Release of sulfidopeptide (SP)-leukotrienes (LT) in vitro from normal human colonic mucosa and from mucosal tissue obtained from patients with Crohn's disease (CD) and ulcerative colitis (UC) was investigated. It was found that inflamed mucosal tissue released significantly more SP-LT than normal colonic mucosa both under control conditions and after addition of calcium ionophore A23187. These results indicate the presence of endogenous stimuli as well as an increased responsiveness to an exogenous stimulus of LT formation in the inflamed mucosa. Sulfasalazine (SASP), a drug used in inflammatory bowel diseases, and its active metabolite 5-aminosalicylic acid (5-ASA) were found to inhibit colonic mucosal SP-LT formation, while only 5-ASA inhibited simultaneously synthesis of another arachidonic acid-derived inflammatory mediator, prostaglandin (PG) E2. The results suggest that SP-LT might be important mediators of inflammation in CD and UC.

Aminosalicylic Acids↗

Action of atropine on the pancreatic secretory response to secretin before and after cutting the extrinsic nerves of the pancreas in dogs.

In two sets of dogs with gastric and pancreatic fistulas, we studied the effect of atropine on the pancreatic secretory response to intravenous secretin before and after cutting the extrinsic nerves of the pancreas, i.e., celiac and superior mesenteric ganglionectomy alone or truncal vagotomy plus celiac and superior mesenteric ganglionectomy. Neither truncal vagotomy alone nor ganglionectomy alone, nor the two together, altered the incremental bicarbonate response to secretin. Irrespective of the degree of integrity of the extrinsic vagal and splanchnic innervation of the pancreas, intravenous atropine (14 nmol/kg X h) significantly (p less than 0.05) depressed the incremental bicarbonate responses to the two lowest (5.2 and 10.3 pmol/kg X h) doses of secretin by 85% and 61%, respectively, but had no significant effect on responses to high doses. We conclude that the pancreatic bicarbonate response to secretin, and the action of atropine on that response, are independent of an intact extrinsic innervation of the gland. The observation of the persistent inhibitory action of atropine after extrinsic denervation of the pancreas is compatible with the hypothesis that endogenous cholinergic activity augments the pancreatic bicarbonate response to secretin.

Animals↗

Effect of GIP on insulin release to intravenous glucose infusion in hyperthyroid rats.

Triiodothyronine induced hyperthyroidism caused significantly elevated basal and stimulated glucose and insulin levels in rats. The release of Gastric Inhibitory Polypeptide (GIP) following an oral glucose load was not significantly different between euthyroid and hyperthyroid rats. The insulin response, however, was significantly higher in hyperthyroid rats. Following intravenous glucose hyperthyroid rats showed a diminished insulin response when compared with euthyroid rats but intravenous infusion of glucose together with GIP caused a significantly higher insulin response in hyperthyroid rats. It is hypothesized that in hyperthyroidism there is an increased sensitivity to the insulinotropic action of GIP and that this mechanism could emphasize the importance of the enteroinsular axis in pathophysiological states.

Administration, Oral↗

Increased release of gastrin in hyperthyroid rats in vitro.

The extrinsically denervated and vascularly perfused stomach of the hyperthyroid rat exhibits an increased basal gastrin release and an exaggerated response to stimulation with the b-agonist isoproterenol. The b-blocker propranolol does not inhibit the increased basal release of gastrin, but completely blocks the effect of isoproterenol. Vagal stimulation is not different between hyperthyroid and euthyroid rats. We conclude, that there are two mechanisms which are responsible for the increased release of gastrin in hyperthyroidism: firstly a direct effect of thyroid hormones on gastrin cells, and secondly an increase in sensitivity of gastrin cells towards b-adrenergic stimulation.

Animals↗

Action of intravenous ethanol and atropine on the secretion of gastric acid, pancreatic enzymes, and bile acids and the motility of the upper gastrointestinal tract in nonalcoholic humans.

To investigate the influence of the cholinergic nerves on the action of i.v. ethanol on interdigestive gastric acid, pancreatic enzyme, and bile acid output, seven healthy volunteers were studied. On each of 4 different days, they swallowed a multilumen intestinal tube system that allowed the measurement of intraluminal pressures and the collection of gastric and duodenal juice. The subjects received an i.v. infusion of either ethanol (600 mg/kg for 30 min followed by 3 mg/kg/min), atropine (5 mu/kg/h), a combination of both drugs, or NaCl. Whereas ethanol did not significantly influence motility, atropine induced motoric quiescence. Ethanol significantly (p less than 0.05) stimulated gastric acid output, by 55%, whereas atropine inhibited it by 91%. When ethanol and atropine were given together, gastric acid output was significantly higher than during atropine use alone. Both ethanol and atropine inhibited pancreatic amylase output--by 47% and by 82%, respectively. The degree of inhibition was 80% when ethanol and atropine were given simultaneously. Atropine but not ethanol significantly reduced bile acid output. The finding that atropine did not completely reverse the stimulating effect of i.v. ethanol on gastric acid secretion suggests that ethanol stimulates gastric acid secretion not only by a cholinergic but also by a noncholinergic mechanism. The observation that atropine did not reverse the inhibiting effect of ethanol suggests, but does not prove, that the effect of ethanol on the pancreas is predominantly mediated by cholinergic nerves.

Adult↗

Stimulatory effect of hypercalcemia on pancreatic secretion is prevented by pretreatment with cholecystokinin and cholinergic agonists.

Recently, we demonstrated that hypercalcemia causes marked stimulation of feline exocrine pancreatic secretion, and that this effect is absent when a large dose of cholecystokinin (CCK) is infused prior to induction of hypercalcemia. To investigate this effect in more detail, anesthetized cats were given calcium i.v. after preadministration of CCK or urecholine (a cholinergic agonist) at specific doses, or of saline as a control. We found that the hypercalcemia-induced stimulation of pancreatic protein secretion was abolished after preadministration of CCK at large doses. After the prestimulus dose was decreased or the calcium dose was increased, however, the pancreatic secretory response to hypercalcemia was preserved. In contrast, the response to a submaximal dose of CCK was unchanged after prestimulation with a large dose of CCK. Similar results were obtained when urecholine instead of CCK was used as prestimulus. These findings indicate that loss of pancreatic responsiveness to hypercalcemia following prestimulation with CCK is dependent on doses of both prestimulus and calcium used, and that it is not specific for prestimulation with CCK but also inducible by cholinergic agonists. They further suggest that this phenomenon is not due to exhaustion of pancreatic secretory capacity, but may reflect decreased sensitivity to the hypercalcemic stimulus instead.

Animals↗

Interaction of acetylcholine and gastric inhibitory polypeptide on endocrine and exocrine rat pancreatic secretion: augmentation of acetylcholine-induced amylase and volume secretion by the insulinotropic action of gastric inhibitory polypeptide.

Exocrine pancreatic secretion is under partial control of endocrine pancreatic hormones. We studied the interaction of three doses of acetylcholine (Ach), a stimulator of exocrine and endocrine pancreatic secretion, with one dose of gastric inhibitory polypeptide (GIP) which is strongly insulinotropic, but has no effect on exocrine pancreatic secretion. The effects of Ach and GIP on insulin secretion from the rat pancreas were additive at 0.05 X 10(-6) M Ach and slightly, but not significantly less than additive at 0.25 or 2.5 X 10(-6) M Ach. GIP had an augmenting effect on amylase and volume secretion from the pancreas, when pancreatic secretion was stimulated by 2.5 X 10(-6) M Ach, but not by 0.05 or 0.25 X 10(-6) M. Exogenous rat insulin could exert an effect similar to that of GIP, although a higher dose was required. Atropine inhibited the effect of Ach on exocrine and endocrine pancreatic secretion, but not the insulinotropic action of GIP. It is hypothesized that GIP could play a role in regulating exocrine pancreatic secretion by its insulinotropic action.

Acetylcholine↗

Epidemiology of gallstones in a German industrial town (Essen) from 1940-1975.

The prevalence of gallstones was studied in 11,840 consecutive autopsies from 1940 to 1975 in the University hospitals of Essen. The total prevalence was 20.7%: 13.1% for men and 33.7% for women. The male to female sex ratio is 1:2.6. The crude prevalence for three 12-year periods showed a significant increase from 8.2 to 15% in men and from 25.7 to 36.3% in women (p less than 0.001). A detailed analysis showed that this increase occurred only in the age groups over 60 and was the consequence of the fact that a greater proportion of women over 60 came to autopsy. The age- and sex-specific morbidity ratio was calculated to standardize the data. This demonstrated considerable fluctuations in 3-year periods since 1940. It can be concluded that no real increase in the prevalence of gallstones occurred in the last 30 years.

Adult↗

Duodenal calcium in chronic pancreatitis: is it of diagnostic value?

Chronic pancreatitis has been reported to be associated with an increased secretion of calcium in pancreatic juice. To determine whether estimation of duodenal calcium may be useful for diagnosing chronic pancreatitis, we compared duodenal calcium output in patients with chronic pancreatitis and in subjects without pancreatic disease, during intravenous infusion of secretion alone, with calcium, or with cholecystokinin-pancreozymin (CCK-PZ). Duodenal calcium output increased during infusion of both calcium and CCK-PZ to a similar extent in chronic pancreatitis and controls. Overall, duodenal output of chymotrypsin was markedly lower in chronic pancreatitis; however, chymotrypsin output increased in response to both intravenous calcium and CCK-PZ in both groups. Bilirubin output increased in both groups during calcium infusion, but this increase was significantly reduced in chronic pancreatitis; in contrast, CCK-PZ caused a similar increase in both groups. The high calcium output observed in hypercalcemia in the presence of low enzyme output suggests increased pancreatic secretion of enzyme-independent calcium in chronic pancreatitis. However, the difference is obscured by biliary calcium, which is secreted in much higher concentrations. Thus, duodenal calcium determination does not appear to be a useful diagnostic test in chronic pancreatitis.

Bilirubin↗

Pancreatic exocrine secretion in response to intraduodenal infusion of different detergent agents in anesthetized cats.

Bile salts, when instilled into the intestine at pH 6, stimulate pancreatic exocrine secretion in man and cat. We investigated if the surface tension as a major physicochemical property of bile acids might be responsible for this effect. In anesthetized cats, either conjugated taurocholate (TC) or unconjugated ursodesoxycholate (UDC) as steroidal detergents or oleate as nonsteroidal detergent were perfused into the duodenum. The critical micellar concentration (CMC) and the surface tension (gamma) were as follows: for oleate 18.6 mmol/l and 27.7 dyn . cm-1, for UDC 10.75 mmol/l and 46.5 dyn . cm-1, for TC 14.5 mmol/l and 58.6 dyn . cm-1. The intraduodenal perfusion of the three solutions at 30 mmol/l and pH 8 evoked an equal pancreatic flow (about 300 mg/15 min) and bicarbonate secretion. It is suggested that the free ionized form of TC perfused intraduodenally is responsible for stimulation of the pancreatic exocrine secretion. We show that the stimulatory effect seems to be independent of the detergency of these molecules.

Animals↗

Fecal bile acids in patients with adenomatous polyps of the colon. Case-control study.

Populations with a high colonic cancer incidence excrete larger amounts of bile acids in their feces. Patients with adenomatous polyps of the colon are at a greater risk of developing colonic cancer. Therefore, we studied the fecal bile acid excretion pattern in 12 patients with adenomatous polyps in comparison to 12 control subjects matched for age and sex. Analysis of bile acids was performed using liquid-gel chromatography for the separation of free, conjugated and sulfated bile acids and gas liquid chromatography for quantitation. This case-control study did not confirm the previous finding of an increased fecal bile acid excretion in patients with adenomatous polyps. Total bile acid excretion, the pattern of the primary and major secondary bile acids and their mode of conjugation were essentially the same for both groups. This negative result may be explained by similar dietary habits of both groups.

Adenoma↗

Bile-stimulated secretin release in cats.

Duodenal perfusion with sodium taurocholate (TC), pH 10.5 (60 mM, made isotonic with NaCl, 30 ml/h for 90 min), increased the plasma immunoreactive secretin level (IRS) from 2.1 +/- 1.0 to 19.1 +/- 6.0 pM (p less than 0.025; n = 6) in anaesthetized cats. Dose-response studies with TC, pH 7.2 (0-60 mM, made isotonic with NaCl, 45 ml/h for 20 min), demonstrated a threshold concentration of TC for IRS release between 10 and 15 mM (p = 0.05; n = 6). Instillation of gallbladder bile from the same animal (1.5 +/- 0.1 ml, pH 7.0 +/- 0.1, over 12 min) increased the IRS concentration from 1.5 +/- 0.4 to 8.1 +/- 3.4 pM (p less than 0.025; n = 6). IRS concentrations also increased when gallbladder bile was mixed with either saline (from 3.4 +/- 1.7 to 11.6 +/- 2.5 pM; p less than 0.05; n = 5) or feline pure pancreatic juice (PPJ) (from 3.1 +/- 0.7 to 5.7 +/- 1.1 pM; p less than 0.025; n = 6). The peak value was significantly lower when bile was mixed with PPJ than with saline (p less than 0.05). We conclude that TC, the dominating bile salt in feline bile, can release IRS also above pH 7, that physiological concentrations of TC can elicit this response, that the response is also produced by gallbladder bile from the same animal, and that PPJ inhibits the bile-induced IRS release. Thus secretin release by bile is likely to be a physiological principle in the regulation of the pancreatic secretion.

Animals↗

Action of intragastric ethanol on pancreatic exocrine secretion in relation to the interdigestive gastrointestinal motility in humans.

On different days, fasted volunteers were given either 100 ml of ethanol (40% v/v), glucose (isocaloric to ethanol) or distilled water intragastrically; the instillations always starting during the first observed duodenal phase I of the interdigestive migrating complex (IMC). Both ethanol and glucose produced a fed pattern of motility but only glucose significantly (P less than 0.05) delayed the reappearance of a new duodenal phase III of the IMC when compared to water. Ethanol and glucose significantly increased the 1-h duodenal bicarbonate output 7- and 16-fold, respectively. Glucose, but not ethanol, stimulated the duodenal amylase output when compared to water. Glucose, but not ethanol, caused a significant rise in plasma gastrin concentration; plasma secretin levels not being altered by both substances. We conclude that in non-alcoholic humans, an intragastric administration of ethanol in a concentration present in whisky and in an amount that is consumed in ordinary social drinking has a weak stimulatory action on pancreatic bicarbonate secretion and that this action is not mediated by release of secretin.

Adult↗

Effect of calcitonin on the interdigestive motility and on gastric and pancreatic secretion in humans.

Calcitonin given in doses (0.2 and 1 MRC U/kg-1h-1) reproducing the levels observed in medullary carcinoma of the thyroid, induced the appearance of phase III type activity and reduced the duration of the IMC in the small intestine from 123 to 87 min with 0.2 MRC U kg-1h-1 and from 123 to 43 min with 1 MRC U kg-1h-1 but not in the stomach of young volunteers. This increase in phase III-like activity occurred despite a sharp reduction in motilin levels. Only the highest dose of calcitonin reduced significantly acid secretion (by more than 90%) while both doses reduced amylase secretion by respectively 65 and 71% when compared to the control levels. These changes in motility and secretion could partly explain the diarrhea observed in patients with the medullary carcinoma of the thyroid.

Adolescent↗

[Methodological aspects of the use of the hydrogen (H2) breath test].

Normalization of the breath hydrogen (H2) concentration by simultaneous determination of breath carbon dioxide (CO2) and the addition of lactulose to a liquid meal have been recommended to improve the reproducibility of the hydrogen breath test. To assess the clinical relevance of these recommendations, we studied 64 children of 4 different age groups and 12 adults. Simultaneous determination of CO2 concentration and normalization of breath H2 resulted in a marked decrease of intestinal transit time and its variation in children; in adults, however, this correction was negligible. With lactulose alone, the mean coefficient of variation within individuals was only 11.7% and 13.2%, with and without H2 normalization, respectively. Therefore, the addition of a liquid meal does not seem to be necessary.

Adolescent↗

[Function tests of the lower small intestine with 75selenium-labeled homotaurocholic acid in Crohn disease and resections of the small intestine].

UNLABELLED: Faecal excretion of bile acids was investigated using 75Se-homotaurocholic acid (75SeHCAT) in a total of 75 patients: 9 with irritable colon, 58 with Crohn's disease and 8 with small-bowel resection due to various indications but without Crohn's disease. Bile acid malabsorption, taken as a pathological bile acid retention of less than 19%, was found present in 43 patients with diseased terminal ileum or with more than 20 cm resection of this organ, except in one case (12 cm). On the other hand a normal bile acid retention (21 to 27%) was found in 29 of 72 patients (including 9 patients with irritable colon) who showed either no radiologically detectable lesion of the ileum (n = 21) or changes involving an extension of up to 30 cm (inflammation or resection) in the terminal ileum (n = 8), with the exception of one case (50 cm). Three patients had a raised bile acid excretion contrary to clinical expectation: they had colitis Crohn without radiologically detectable involvement of the small intestine. Thus using the 75SeHCAT-retention test it seems possible to recognize functional disorders in diseased segments of the bowel before the appearance of radiologically detectable changes. CONCLUSION: 75SeHCAT is a suitable substance for investigations on the function of the lower small intestine.

Adolescent↗