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Biomedical subjects

H Goebell

Publications and source records attributed to H Goebell.

At least 73 records · Page 4Linked to original sources
PubMed1996

Inhibition of canine exocrine pancreatic secretion by peptide YY is mediated by PYY-preferring Y2 receptors.

It is still unclear, which receptor subtype, Y1 and/or Y2, mediates the inhibitory action of PYY on exocrine pancreatic secretion. The present study was undertaken to characterize functionally the Y receptor subtype that mediates the inhibition of exocrine pancreatic secretion by peptide YY (PYY). In eight conscious dogs with chronic gastric and pancreatic fistulas, we compared the action of intravenous infusion of 200 and 400 pmol/kg/h of the Y receptor agonists PYY 1-36, PYY 3-36, PYY 13-36, Pro34PYY 1-36, and NPY 1-36 on the pancreatic secretory response to secretin (20.5 pmol/kg/h) and cerulein (29.6 pmol/kg/h). PYY 13-36, Pro34PYY 1-36, and NPY 1-36 were also studied by giving a fivefold dose (1,000 and 2,000 pmol/kg/h). PYY 1-36 and the Y2 receptor agonist PYY 3-36 significantly inhibited pancreatic secretory responses to secretin and cerulein, whereas inhibition by NPY 1-36 and the Y2 receptor agonist PYY 13-36 was attainable only at doses of 1,000 and 2,000 pmol/kg/h. The Y1 receptor agonist Pro34PYY 1-36 was without effect on pancreatic secretion. We conclude that in dogs the inhibition of exocrine pancreatic secretion by PYY is mediated via Y2 receptors of a PYY-preferring subtype.

Animals↗
PubMed1996

Effect of cigarette smoking on the course of Crohn's disease.

OBJECTIVE: It has been shown that smokers are more likely than non-smokers to develop Crohn's disease. In order to examine the influence of smoking on the course of Crohn's disease, as measured by the risk of surgery, the need for surgery was assessed in patients with Crohn's disease. DESIGN: The course of Crohn's disease was evaluated as to smoking status by life table analysis. SETTING: A tertiary hospital in Essen, Germany. PATIENTS: The study involved 346 patients with Crohn's disease admitted to hospital between 1989 and 1992. Only patients residing in the City of Essen were included. RESULTS: Of the 346 patients, 144 smokers and 143 non-smokers were included in the analysis. Overall, 73% of smokers and 39% of non-smokers required one or more operations. The corresponding relative risks (RR) and 95% confidence intervals were for one operation and more than one operation or no operation at all (RR 1.0) 3.9 (2.2-6.9) and 10.8 (5.3-22.1), respectively. There were significant differences as to recurrence rates (defined as further surgery after first surgery for control of disease) between smokers and non-smokers. For smokers the 5- and 10-year recurrence rates were 43% and 64%. For non-smokers corresponding recurrence rates were 26% and 33%. For 5- and 10-year recurrence rates the RR estimates for smokers versus non-smokers were 3.1 (1.7-5.8) and 6.7 (2.7-6.8). When stratified by gender, the increased risk for recurrence was obvious in both sexes. For the number of cigarettes smoked a dose-response effect was obvious in women. CONCLUSION: These data suggest that the course of Crohn's disease is less favourable in smokers than in non-smokers.

Abscess↗
PubMed1996

Physical activity at work and the risk of chronic pancreatitis.

OBJECTIVE: To examine the hypothesis that low social status in chronic pancreatitis is accounted for by high physical activity at work. DESIGN: A case-control study comparing 50 patients with an established diagnosis of chronic pancreatitis with 100 age- and sex-matched community controls. RESULTS: There was a significant association between a high level of physical activity and chronic pancreatitis risk, the relative risk being 3.9 (1.3-11.7). After controlling for age, sex, smoking and alcohol intake, a high amount of calorie expenditure during work was still significantly associated with chronic pancreatitis risk, the relative risk being 4.5 (1.2-17.7). When social class was controlled for physical activity the increased risk for low social class status disappeared. CONCLUSION: This study suggests that the social class gradient may be explained by the amount of manual labour.

Adult↗
PubMed1996

Budesonide prolongs time to relapse in ileal and ileocaecal Crohn's disease. A placebo controlled one year study.

BACKGROUND AND AIMS: To evaluate the efficacy and safety of the topical corticosteroid budesonide, given in an oral controlled release formulation for maintenance of remission in patients with ileal and ileocaecal Crohn's disease (CD). PATIENTS AND METHODS: Out of 176 patients with active CD who had achieved remission (CD activity index score < or = 150) after 10 weeks' treatment with either budesonide or prednisolone, 90 were randomised to continue with once daily treatment of 6 mg budesonide, or 3 mg budesonide or placebo for up to 12 months in a double blind, multicentre trial. Time to symptomatic relapse was calculated using Kaplan-Meier estimates. Morning plasma cortisol was measured at clinic visits and a corticotropin stimulation test was performed after three months of treatment. RESULTS: Thirty two patients were allocated to the 6 mg budesonide group, 31 to the 3 mg group, and 27 to the placebo group. After three months, 19 per cent of the patients in the 6 mg group had relapsed, compared with 45 per cent in the 3 mg group and 44 per cent in the placebo group (p = 0.047). The corresponding results after 12 months was 59 per cent in the 6 mg budesonide group, 74 per cent in the 3 mg group, and 63 per cent in the placebo group (p = 0.44). The median time to relapse or discontinuation was 258 days in the 6 mg group, 139 days in the 3 mg group, and 92 days in the placebo group (p = 0.021). Mean morning plasma cortisol values increased from entry in all three groups with no statistically significant differences at 12 months. All 13 patients remaining in the placebo group after three months had a normal corticotropin stimulation response, compared with 18 of 23 patients in the 6 mg, and 19 of 21 in the 3 mg budesonide groups (p = 0.14). Acne and moon face were slightly more common in the budesonide groups. CONCLUSION: 6 mg budesonide once daily is significantly more efficacious than placebo in prolonging time to relapse in CD, and causes only minor systemic side effects.

Administration, Oral↗
PubMed1996

Liver function in patients with pulmonary emphysema due to severe alpha-1-antitrypsin deficiency (Pi ZZ).

Alpha 1-Antitrypsin deficiency predisposes to pulmonary emphysema, liver cirrhosis and hepatocellular carcinoma. Anecdotal evidence and a large autopsy study suggest that severe lung and liver disease rarely coexist in the same subject, but this has not been studied in patients. Therefore we investigated 27 patients with severe alpha 1-deficiency (Pi ZZ) and pulmonary emphysema for signs of liver disease and impaired hepatic function. A subgroup of 7 patients underwent quantitative liver function tests. On physical examination or ultrasonography, cirrhosis or tumor was not suspected in any patient. Conventional liver function tests were completely normal in 17 patients. Elevated serum activities of gamma-glutamyltranspeptidase and/or aminotransferases were seen in 10 patients. In some, the elevation was only marginal and in none more than twice normal. The serum bilirubin concentration and activity of alkaline phosphatase were increased in 1 patient. Serum protein, albumin, fibrinogen, antithrombin III, alpha 1-fetoprotein concentrations, serum activities of cholinesterase and glutamate dehydrogenase, activated partial thromboplastin time and prothrombin time were normal in all patients. The indocyanine green half-life was abnormal only in 1 of 6 patients, suggesting that hepatic blood flow was not impaired in the study group. However, the lidocaine half-life and galactose elimination capacity, parameters of hepatic metabolization, were impaired in 4 and 6 of 7 patients, respectively. We conclude that liver disease or impaired liver function is not a clinically relevant problem in most patients with pulmonary emphysema due to alpha 1-antitrypsin deficiency. But results of quantitative liver function tests, although performed in only a small group of patients, suggest that hepatic metabolization might be impaired even in those patients who present with pulmonary disease.

Adult↗
PubMed1996

Impaired small intestinal peristaltic reflexes and sensory thresholds are independent functional disturbances in patients with chronic unexplained dyspepsia.

OBJECTIVE: To study disturbances of gastrointestinal motility and afferent (sensory) dysfunction in functional (unexplained) dyspepsia, and the interrelationships between motility and sensory dysfunction. METHODS: Twelve patients with functional dyspepsia and 12 controls matched for age and gender were studied. Intestinal perception thresholds were tested by a standardized stepwise distension procedure in the third portion of the duodenum with a barostat device. Small intestinal motility was measured with a low compliance perfusion system proximal and distal to the distending balloon. RESULTS: First perception of duodenal balloon distension occurred at significantly (p <0.01) lower pressures in patients (23 +/- 3 mm Hg, mean +/- SEM) than in healthy controls (31 +/- 3 mm Hg). Patients had a lower maximal intestinal pain tolerance than controls (31 +/- 2 mm Hg vs. 39 +/- 1 mm Hg, p <0.05). Duodenal distension inhibited intestinal motility distal to the distending balloon (peristaltic reflex) more often in health controls (11/12) than in patients with functional dyspepsia (5/12, p <0.05). These alterations of small intestinal motility occurred at pressure values below the perception thresholds, and disturbed motility responses were not associated with perception thresholds. CONCLUSION: Disturbed peristaltic reflexes and decreased sensory thresholds for perception of intestinal sensations are prevalent but may be independent abnormalities in patients with unexplained dyspepsia.

Adult↗
PubMed1996

[Primary sclerosing cholangitis: conventional and quantitative liver function tests during long-term therapy with ursodeoxycholic acid].

Primary sclerosing cholangitis, a chronic cholestatic liver disease, frequently leads to an impairment of liver function. In nine men and two women, aged 23 to 57 years, we prospectively studied for three to six years the effect of treatment with ursodeoxycholic acid (UDCA) on liver function. 10 mg UDCA/kg bw significantly reduced serum activities of AP, gamma GT, AST and ALT for several years. After three years of treatment, however, serum concentration of bilirubin was higher than before therapy in eight out of eleven patients (1.8 +/- 0.8 versus 0.9 +/- 0.1 mg/dl; p = 0.01). Likewise, serum concentration of bilirubin was higher in eight out of nine patients after four years of treatment (1.3 +/- 0.3 versus 0.9 +/- 0.1 mg/dl; p = 0.03). In most cases, however, the increase was discrete. Parameters of synthetic liver function (coagulation, serum protein concentration, serum activity of cholinesterase) remained constant in the observation time. Quantitative liver function tests (galactose elimination capacity and indocyanine green half-life) also showed little variation in the observation time. We conclude that UDCA treatment significantly improves serum activities of liver enzymes for several years. Nevertheless, serum bilirubin concentration, believed to be of prognostic value in patients with PSC, seems to rise slowly over time. Serial determinations of galactose elimination capacity and indocyanine green halflife are not superior to conventional liver function tests in the timing of liver transplantation in the individual patient.

Adult↗
PubMed1996

[Are proton pump inhibitors superior to H2 receptor antagonists within the scope of H. pylori eradication therapy? Meta analysis of current parallel group comparisons].

The combined treatment with acid lowering drugs and antibiotics is widely accepted for H. pylori-eradication therapy. There are, however, controversies regarding the influence of the acid lowering drug on H. pylori-eradication rates. Therefore, this meta-analysis aimed to assess the available parallel-group eradication studies with proton pump inhibitors and H2-receptor antagonists and to compare H. pylori-eradication rates for both classes of acid lowering drugs. METHODS. We performed a broad based medline search to retrieve all published treatment trails for H. pylori-infection. In addition, a manual search of the abstracts of major national and international meetings was conducted. In total seven publications of eight comparisons with a parallel group design comparing H2-receptor antagonists and proton pump inhibitors plus antibiotics with a total of 538 patients were identified. Non parametric tests were utilized to assess the influence of the acid lowering drug on eradication rates. Furthermore, logistic regression adjusting for duration of antibiotic treatment and the number of antibiotics was used to compare the different acid lowering drugs. RESULTS. All studies utilized omeprazole as the proton pump inhibitor with doses ranging from 20 mg/die to 2 x 20 mg/die. Ranitidine (with doses ranging from 2 x 150 mg/die to 2 x 300 mg/die) was used in six trials and nizatidine (2 x 300 mg/die) in one trial. H. pylori was successfully eradicated in 78.6% (95% 73.6-83.5) with the proton pump inhibitor and in 76.5% (95% Cl 71.4-81.5) in patients treated with the H2-receptor antagonists. Utilizing two antibiotics instead of one antibiotic significantly increased eradication rates by 16.1% (95% Cl 9.3-22.8, p < 0.001). However, neither in protocols with one nor in protocols with two antibiotics the eradication rates significantly differed for regimens using H2-receptor antagonists or proton pump inhibitors. CONCLUSION. H. pylori-eradication rates for treatment protocols with one or two antibiotics in combination with an acid lowering drug are not different for the proton pump inhibitors or h2-receptor antagonists. Therefore, the question whether H2-receptor antagonists or proton pump inhibitors should be used in combination with antibiotics for H. pylori eradication therapy is without clinical relevance.

Anti-Ulcer Agents↗
PubMed1996

Ileal inhibition and modulation of carbachol-stimulated proximal small intestinal motor functions in humans.

Carbohydrates within the distal small intestine inhibit endogenously stimulated proximal gastrointestinal motor activity and induced an interdigestive-like pattern in humans. In order to further investigate the intermediary mechanisms of the ileal inhibitory effects, we intubated eight healthy volunteers with an oroileal multilumen tube and stimulated small intestinal motility exogenously with a continuous intravenous infusion of the cholinergic agonist carbachol. Additionally, the ileum was perfused for 15-min intervals with either carbohydrates (total load: 18 g) or normal saline as volume control. Ileal carbohydrate perfusion inhibited the carbachol-stimulated motility pattern significantly (p < 0.001) and induced phase-III-like motor activity; ileal saline had no effect. These data suggest that a direct inhibition of cholinergic systems may be involved in the ileal inhibitory effects on proximal small intestinal motility.

Adult↗
PubMed1995

Endocrine and exocrine pancreatic function after camostate-induced growth of the organ.

It is well known that oral administration of camostate induces hyperplasia and hypertrophy of the rat pancreas. It is not clear, however, whether pancreatic hormone and enzyme secretion are affected by camostate treatment. In rats, daily administration of 200 mg camostate/kg b. wt for 14 days significantly increased pancreatic weight and pancreatic content of DNA, protein, amylase, lipase, trypsin and chymotrypsin, as well as the amount of insulin, glucagon and somatostatin. In the intact animal, blood glucose levels and serum concentrations of insulin and glucagon in response to an oral glucose load were not impaired after camostate treatment. In the isolated perfused pancreas, however, insulin and glucagon secretions were reduced, whereas somatostatin release was not affected. The volume of pancreatic juice produced by the unstimulated isolated perfused organ, as well as protein and enzyme secretion, were increased after camostate treatment. Likewise, the isolated perfused pancreas from camostate-treated rats secreted a larger volume of pancreatic juice and more protein in response to cholecystokinin (CCK), while enzyme secretion was affected in a non-parallel manner: amylase release was markedly reduced, lipase release was unchanged, and release of trypsin and chymotrypsin was increased.

Animals↗
PubMed1995

[Results of the 75selenium homotaurocholic acid retention test (SeHCAT test) in diagnosis of diarrhea].

PATIENTS AND METHOD: For that reason absorption of bile acids was investigated using the 75Se-homotaurocholate (SeHCAT) in 239 patients with diarrhoea. SeHCAT retention time was measured as 7 day retention time in a whole body counter. An intact bile acid absorption (negative SeHCAT test) was confirmed in 23 healthy volunteers within the range of 11 to 50% (mean +/- double standard deviation). RESULTS: In 135 patients with a possible type I bile salt malabsorption the SeHCAT test was positive in 78%, thus indicating bile salt malabsorption. The test is very sensitive detecting bile salt malabsorption in Crohn's disease, identifying ileal disease more precisely than radiology. The SeHCAT test ascertained type II primary bile salt malabsorption in 7 patients, as well as type III bile salt malabsorption in patients (9 out of 28) with cholecystectomy, vagotomy, partial gastrectomy and chronic pancreatitis. In addition, a positive SeHCAT test indicating bile acid malabsorption was found in 5 out of 11 patients with irritable syndrome, diarrhoeic form, and in 4 out of 12 patients with lactose intolerance. CONCLUSION: SeHCAT retention should be measured routinely in patients with chronic diarrhoea for which the cause is not obvious.

Adult↗
PubMed1995

Ileal release of glucagon-like peptide-1 (GLP-1). Association with inhibition of gastric acid secretion in humans.

There is evidence that the distal intestine participates in the regulation of gastric motor and secretory function. It was the aim of this study to examine in greater detail the effects of ileal nutrient exposure on human gastric acid secretion and to investigate potential intermediary mechanisms. Twelve normal subjects were intubated with an oroileal multilumen tube assembly for gastric, duodenal, and ileal perfusion of marker and test solutions, aspiration, and intestinal manometry. We studied ileal effects on gastric acid output in the unstimulated, interdigestive state (during early phase II, N = 6), and during endogenous stimulation by intraduodenal essential amino acid perfusion, N = 6) and on release of candidate humoral mediators, peptide YY (PYY) and glucagonlike peptide-1 (GLP-1), both known inhibitors of human gastric acid secretion. Compared with ileal saline perfusion, ileal carbohydrate (total caloric load: 60 kcal) decreased interdigestive gastric acid output by 64% (P < 0.01), and endogenously stimulated output by 68%, respectively (P < 0.005). Under all experimental conditions, ileal carbohydrate increased plasma GLP-1 by 80-100% (all P < 0.005). Ileal lipid perfusion had similar inhibitory effects on gastric acid output and stimulatory effects on GLP-1 release as had ileal carbohydrate. By contrast, ileal perfusion with peptone had no or only weak effects on either acid output or plasma GLP-1. Plasma PYY concentrations and suppression of gastric secretion in response to ileal perfusions were not correlated. In humans, both interdigestive and endogenously stimulated gastric acid output are inhibited in response to intraileal carbohydrate or lipids, but not protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Perception of gastric distension. Influence of mode of distension on perception thresholds and gastric compliance.

Gastric distension has been used to evaluate gastric sensory function in humans, but the methodology is poorly validated and studies in vivo comparing different distension protocols are lacking. We aimed to compare the influence of the mode of gastric distension on sensation and gastric compliance utilizing a barostat device. In seven healthy volunteers, we positioned a barostat bag in the proximal stomach and tested in random order (in triplicate) four different distension protocols: (1) standard ramp distension with 4 mm Hg pressure step increments of 20 sec duration; (2) slow ramp distension with 2 mm Hg pressure increments of 40 sec duration; (3) random distension using a pressure ramp consisting of 2 mm Hg increments of 40 sec duration with randomly interposed pressure steps 50% below the preceding pressure step; and (4) rapid random distension with 4 mm Hg pressure increments of 10 sec duration with randomly interposed pressure steps 50% below the preceding pressure step. The distension procedures yielded mean airflow rates during the different distension protocols between 2.4 ml/sec for standard ramp and 18.4 ml/sec for rapid random distension. First perception and maximal tolerable pressure were 10.9 +/- 1.1 mm Hg and 19.6 +/- 1.5 mm Hg, respectively. First perception and maximal tolerable pressures were significantly correlated (r = 0.93, P < 0.005). The gastric pressure at occurrence of perception and the maximal tolerated pressure were not significantly different for the different distension protocols but gastric compliance was significantly reduced during rapid ramp distension (P < 0.01 vs slow ramp and P < 0.05 vs random distension) but not during standard ramp distension. We conclude that gastric sensory pressure thresholds as assessed by isobaric distension are not influenced by the mode of distension. The high correlation of pressure thresholds at first perception and maximal tolerated distension suggest a single population of gastric mechanoreceptors that mediate first sensation at low intensity stimulation and pain at intense stimulation.

Adult↗
PubMed1995

Delivery and fate of oral mesalamine microgranules within the human small intestine.

BACKGROUND/AIMS: Oral use of mesalamine in inflammatory bowel disease requires slow-release preparations to prevent premature absorption and inactivation. Resulting luminal concentrations within the human small intestine are unknown. The aim of this study was to determine human intestinal delivery patterns of mesalamine from a microgranule preparation (Pentasa; Ferring Arzeimittel, Kiel, Germany) effective in Crohn's disease with small bowel involvement. METHODS: A multilumen tube for duodenal, jejunal, and ileal aspiration and marker perfusion was placed in 6 normal subjects. Levels of luminal, plasma, and urinary mesalamine and its main metabolite, acetyl mesalamine, were measured for 7 hours after ingestion of mesalamine (500 mg) with a labeled meal. RESULTS: Gastric emptying of mesalamine paralleled the meal, and its release occurred throughout the small intestine (cumulative, 20% of dose). For 4 hours, mean luminal mesalamine and acetyl mesalamine concentrations were 52 and 38 micrograms/mL (duodenum), 59 and 82 micrograms/mL (jejunum), and 64 and 104 micrograms/mL (ileum). Cumulative colonic delivery was 82% (7% dissolved, 75% in microgranules), and urinary excretion was 3.5%. CONCLUSIONS: Although the major part of continuous-release mesalamine is delivered to the colon, large proportions are liberated and available at high concentrations within the small intestinal lumen, thus explaining its therapeutic efficacy in small intestinal Crohn's disease.

Administration, Oral↗
PubMed1995

Peptide YY inhibits exocrine pancreatic secretion in isolated perfused rat pancreas by Y1 receptors.

Peptide YY (PYY) inhibits exocrine pancreatic secretion in several species. Two receptors, Y1 and Y2, are known to mediate PYY actions. While PYY 1-36 binds equally to both receptor subtypes, a second endogenous form of PYY, PYY 3-36, selectively activates Y2 receptors. The importance of Y receptor subtypes for inhibition of exocrine pancreatic secretion by PYY is unknown. We studied the effects of PYY 1-36 on cholecystokinin octapeptide (CCK-8)-stimulated amylase secretion in an isolated perfused rat pancreas model. To characterize functionally the receptors involved we determined the effects of a Y1-selective agonist, [Pro34]PYY; a Y2 selective agonist, PYY 3-36; and neuropeptide Y (NPY) in this model. PYY 1-36 significantly inhibited stimulated amylase secretion in the denervated rat pancreas. [Pro34]PYY and NPY both inhibited exocrine pancreatic secretion as potently as PYY 1-36. Contrary to that, the Y2 selective agonist, PYY 3-36, was inactive. We conclude that PYY inhibits exocrine pancreatic secretion in this extrinsically denervated rat pancreas model by Y1 receptors.

Amylases↗
PubMed1995

Smoking as a risk factor for duodenal ulcer relapse. RUDER Study Group.

This study reports the influence of smoking on the two-year relapse rate of duodenal ulcers under treatment with ranitidine. 1899 patients with a healed duodenal ulcer received 150 mg ranitidine daily for one year, 1671 patients for two years. During this time period 23.4% of smokers relapsed compared with 26.3% of ex-smokers and 18.0% of non-smokers. The difference between smokers and ex-smokers versus non-smokers was statistically significant. There were significantly fewer relapses among smokers who stopped smoking (14.2%) compared with smokers who continued to smoke (25.2%) during maintenance treatment. These results show that continued and past smoking significantly increase the two-year relapse rate of duodenal ulcers during maintenance treatment with ranitidine.

Adult↗
PubMed1994

[Pro34]peptide YY is a Y1-selective agonist at peptide YY/neuropeptide Y receptors.

We have investigated binding and functional effects of a new peptide YY analogue, [Pro34]peptide YY, at Y1 and Y2-like subtypes of receptors for peptide YY and neuropeptide Y. In binding studies [Pro34]peptide YY had a similarly high affinity as peptide YY to human Y1-like receptors in SK-N-MC cells, a human neuroblastoma cell line of presumed neurogenic origin, and HEL cells, a human cell line derived from a patient with Hodgkin's disease. In functional studies [Pro34]peptide YY stimulated Ca2+ elevations in both Y1-like receptor cell lines with similar potency and efficacy as peptide YY. In contrast to peptide YY [Pro34]peptide YY was 1000-fold less potent in binding to Y2-like receptors in porcine splenic membranes and lacked agonistic effects in another Y2-like receptor-mediated model system, i.e. inhibition of [3H]serotonin release from rat cerebral cortical slices. Thus, [Pro34]peptide YY is a highly Y1-selective full agonist of peptide YY/neuropeptide Y receptors. [Pro34]peptide YY could be useful for studying the importance of Y receptor subtypes in mediating peptide YY physiological actions.

Amino Acid Sequence↗