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Biomedical subjects

H Koop

Publications and source records attributed to H Koop.

At least 19 recordsLinked to original sources
PubMed1998

[Prevention of gastric cancer: Helicobacter--eradication and immunization].

Adenocarcinoma of the stomach (excluding carcinoma of the cardia) has been established as a consequence of gastric infection with Helicobacter pylori (H.p.). The specific role of H.p. in the pathogenesis is unknown so far; yet, several other factors are involved in the development of the neoplasia. Since-in contrast to the wide prevalence of the infection-only very few persons will develop gastric carcinomas, prophylaxis by H.p. eradication is not advisable. This may change after a vaccination has become available; however, studies on the characterization of efficient vaccines are still under investigation. Thus, H.p. eradication treatment may, if at all, be used as prophylaxis for gastric carcinoma only in clinical studies and in subjects at a high risk for this tumour.

Adenocarcinoma↗
PubMed1997

Impairment of hepatic transport processes in perfused rat liver by the specific CCK receptor antagonist loxiglumide.

The specific cholecystokinin (CCK) receptor antagonist loxiglumide has been used in several human and animal studies to investigate the role of CCK in gastrointestinal physiology. In the present study, the interference of this CCK receptor antagonist with hepatic transport processes was characterized in the perfused rat liver. Indocyanine green, an organic dye which is secreted into bile without being metabolized, was taken up in control experiments at a rate of 68.1 +/- 7.7%. The CCK receptor antagonist lowered the extraction to 0.5 +/- 2.6% (P < 0.001). The compound diminished the hepatic extraction of CCK-8 from 90.95 +/- 2.60% to 4.90 +/- 1.95% (P < 0.001) and of gastrin from 22.2 +/- 1.1% to 8.2 +/- 1.9% (P < 0.001). The hepatic extraction of lidocaine, which is metabolized by the cytochrome P450 system, was only slightly altered. For leukotrienes and taurocholate, the rate-limiting step for transport into bile is secretion across the canalicular membrane; the hepatic extraction of leukotriene D4 was markedly diminished by loxiglumide whereas the transport of taurocholate was only slightly inhibited. The present study demonstrates that the specific CCK receptor antagonist loxiglumide diminished the hepatic extraction of various substances, including peptides and organic anions. It did not interfere with the cytochrome P450 system. The pronounced reduction of hepatic uptake of indocyanine green and leukotriene may be due to an interference with the transport system of these substances in the liver.

Animals↗
PubMed1997

One-year prophylactic efficacy and safety of pantoprazole in controlling gastro-oesophageal reflux symptoms in patients with healed reflux oesophagitis.

BACKGROUND: Pantoprazole is a benzimidazole derivative which selectively inhibits the proton pump H+. K+-ATPase necessary for the final step in gastric acid secretion. AIM: To investigate the tolerability and the prophylactic effect of pantoprazole 40 mg once daily on relapse in patients whose reflux oesophagitis had been healed. METHODS: The safety of pantoprazole 40 mg once daily was assessed in an open 1-year trial on 222 patients whose reflux oesophagitis had been healed with omeprazole or pantoprazole. Relapse was defined as endoscopically-confirmed reflux oesophagitis (at least Grade I), with endoscopies being performed for patients experiencing 3 consecutive days of disease-specific symptoms. RESULTS: Kaplan-Meier survival analysis at 6 and 12 months gave estimated treatment failure rates of 2% and 6% from confirmed relapses (per-protocol), and of 9% and 30% for a worst-case group (all withdrawals counted as failures). The only population shift in laboratory variables was a doubling of the median serum gastrin level over the first 6 months; thereafter it stabilized. Fifty-four (24%) patients experienced adverse events; 15 of these withdrew. Serious adverse events were reported for 12 patients. CONCLUSIONS: Pantoprazole appears to be highly effective and to have a good safety profile for long-term prophylaxis of reflux oesophagitis.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Gastro-oesophageal reflux disease: medical or surgical treatment? Report of an interactive workshop.

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper.

Barrett Esophagus↗
PubMed1996

[Therapy of Helicobacter infection].

Infection with Helicobacter pylori (H.p.) leads to mostly asymptomatic chronic gastritis. However, H.p. plays a role in peptic ulcer, giant fold gastritis (Menetrier's disease), and possibly in gastric carcinoma and low-grade MALT lymphoma. Whether functional dyspepsia also represents a Helicobacter-induced entity is questionable. H.p. should be eradicated in patients with peptic ulcer disease, Menetrier+s disease and - but in controlled studies only - in MALT lymphomas. Triple therapy with low-dose proton pump inhibitors and two antibiotics is the most favourable treatment compared to dual therapy with omeprazole and amoxicillin/clarithromycin despite the unresolved question of the development of drug resistance.

Anti-Bacterial Agents↗
PubMed1996

Physiological control of cholecystokinin release and pancreatic enzyme secretion by intraduodenal bile acids.

BACKGROUND: The physiological relevance of duodenal bile acids in the control of cholecystokinin release and pancreatic enzyme secretion is still unknown. AIMS: To provide a near physiological situation by perfusing a bile acid mixture mimicking the individual endogenous bile acid composition of the person under investigation. For maximal reduction of endogenous bile output the CCK-A receptor antagonist loxiglumide was infused intravenously. SUBJECTS AND METHODS: Seven healthy volunteers were studied on four different days by a duodenal marker perfusion technique. The individual bile acid composition in duodenal juice and test meal stimulated bile acid output was assessed on day 1. Bile acids were perfused at an amount of 30 or 100% as determined on day 1 in combination with the test meal in the presence or absence of loxiglumide. Pancreatic enzymes, bilirubin, and bile acid output were determined in duodenal juice. Plasma cholecystokinin (CCK) and plasma pancreatic polypeptide (PP) were measured radioimmunologically. RESULTS: Bile acid perfusion did not significantly alter stimulated pancreatic enzyme, bilirubin or bile acid output or plasma CCK. Loxiglumide did not alter basal CCK release but increased test meal stimulated CCK output fourfold (p < 0.05). The addition of bile acids to the test meal at a dose resembling 30% of bile acid output as determined on day 1 prevented this increase. Plasma PP concentration remained unchanged by bile acids and were mostly undetectable during loxiglumide infusion. CONCLUSIONS: The CCK producing cell is under constant suppression by intraduodenal bile acids which cannot be further enhanced by a physiological bile acid mixture. However, removal of duodenal bile acids by inhibition of gall bladder contraction unmasks this suppression leading to a dramatic increase in plasma CCK levels. As little as one third of postprandially released bile acids completely reverse this effect. Bile acids are the most important luminal regulator of CCK release in humans.

Adult↗
PubMed1996

[Can pharmaco-DSA of the kidney replace intraoperative rapid biopsy diagnosis?].

QUESTION: Can primary nephrectomy be performed without preliminary sample excision of the tumor if pharmaco-angiography of the kidney has demonstrated the typical tumor vascularization? MATERIAL AND METHOD: To clarify this question in 32 patients with "displacing mass" of the kidney, verified in sonography and computer-tomography, or hematuria of unknown origin, we prospectively performed and additional pharmaco-angiography of the respective kidney. RESULTS: In 18 patients with tumor vascularization in the pharmaco-angiography, intraoperatively we found 15 malignant renal cell carcinomas, 1 patient with transitional cell carcinoma of the renal pelvis, 1 leiomyosarcoma, and 1 high-differentiated tumor of only 2 cm in diameter with unclear dignity, which was treated by enucleation. CONCLUSION: In case of an intrarenal lesion of more than 3 cm in diameter and additional tumor vascularization seen in selective pharmaco-angiography, the kidney undoubtedly can be removed by primary nephrectomy without a preliminary sample excision to confirm the diagnosis. For tumors with a diameter of less than 3 cm and additional tumor-vascularization, the option should be enucleation. If there is a "tumor" without typical malignant vascularization, the exploration by sample excision should be performed. Depending on the histological result the tumor should be removed by enucleation or nephrectomy.

Adult↗
PubMed1996

Intragastric pH and serum gastrin during administration of different doses of pantoprazole in healthy subjects.

OBJECTIVE AND DESIGN: The effect of increasing doses of pantoprazole, a newly developed proton pump inhibitor, given at once daily doses of 40, 80 and 120 mg, on intragastric pH and serum gastrin profiles was studied in 15 healthy subjects in a randomized, double-blind, crossover study and compared to recordings without therapy. Measurements of intragastric pH and serum gastrin were performed on the 7th day of treatment by continuous pH recording and radioimmunoassay in blood samples obtained in 1-h intervals, respectively. RESULTS: Pantoprazole significantly increased gastric pH above basal at all pantoprazole doses studied: median 24-h pH rose from 1.2 without therapy to 3.4, 3.3 and 3.6 at 40, 80 and 120 mg daily, respectively. The corresponding integrated 24-h gastrin output was 1632, 2338 and 2248 pg/ml x 24 h compared to 575 pg/ml x 24 h without pantoprazole. There was no interindividual correlation between values of 24-h median pH and 24-h gastrin output at any pantoprazole dose studied. However, fasting gastrin levels closely correlated with 24-h gastrin output (r = 0.789; P < 0.0001). The acid inhibitory effect was significantly (P < 0.01) augmented in Helicobacter pylori positive subjects. CONCLUSION: It is concluded that pantoprazole is an effective inhibitor of gastric acid secretion. Increasing a single pantoprazole dose above 40 mg does not lead to increased median pH elevation. The individual extent of acid inhibition does not predict the magnitude of gastrin elevation. Acid inhibition appears more efficient in Helicobacter pylori positive subjects.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Comparative trial of pantoprazole and ranitidine in the treatment of reflux esophagitis. Results of a German multicenter study.

In 249 patients with acute symptomatic reflux esophagitis grade II and III (Savary-Miller classification), we compared the efficacy and safety of pantoprazole, a newly developed proton pump inhibitor given at a once-daily dose of 40 mg, with a standard dose of the H2 receptor antagonist ranitidine (150 mg b.i.d.) in a randomized, double-blind, multicenter study. Complete healing was achieved after 4 and 8 weeks of therapy (protocol-correct) in 69 and 82% (pantoprazole) and 57 and 67% (ranitidine), respectively (p = 0.054 at 4 weeks and p < 0.01 at 8 weeks). The predominant symptoms of gastroesophageal reflux, i.e., heartburn and acid eructation, were more effectively reduced in pantoprazole- than in ranitidine-treated patients. The frequency of adverse events was low and did not differ between the two treatment groups. We conclude that pantoprazole is superior to ranitidine in the acute treatment of reflux esophagitis.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Autonomic dysfunction in patients with achalasia.

It has been previously shown that patients with achalasia may have motor abnormalities of the stomach, small bowel and biliary system. This study investigates whether a disturbance of extraintestinal autonomic function occurs. Autonomic function studies were performed in 15 patients with achalasia and 15 age- and sex-matched healthy controls. Pupillograms were obtained during darkness, light exposure and after pilocarpine administration. Cardiovascular function studies included determinations of heart rate variation during deep breathing and orthostasis. In addition, we determined blood pressure changes in response to sustained handgrip, cold exposure and orthostasis. Neurohormonal function was investigated by measuring serum pancreatic polypeptide (PP) levels prior to and following sham feeding. Pupillary function did not differ in patients as compared with controls. However, 9 of 15 patients (95% CI: 32-84%) and none of the controls showed at least one abnormal autonomic cardiovascular response. A significant difference between the two groups was observed in sympathetic function (P = 0.023). More patients than controls did not respond to sham feeding with a PP increase. It is concluded that some patients with achalasia exhibit an abnormality of the autonomic nervous system that extends beyond the gastrointestinal tract. These abnormalities mainly concern cardiovascular function but may also involve neurohormonal responses.

Adult↗
PubMed1994

A new CCK-B/gastrin receptor antagonist acts as an agonist on the rat pancreas.

The new CCK-B/gastrin receptor antagonist PD 136450 is of potential value in treating neurologic and psychiatric disorders. We investigated possible side effects on the rat pancreas using acute and chronic administration schedules. In chronic experiments, four groups of rats were given either PD 136450, the proton pump inhibitor BY 308 (in order to induce hypergastrinemia), a combination of both, or control solutions over 14 d. Pancreatic growth, DNA, and protein content were significantly increased in rats given PD 136450 irrespective of circulating gastrin levels. Furthermore, an anticoordinate shift in pancreatic enzyme content in favor of trypsin and chymotrypsin at the expense of amylase and lipase was observed. Plasma CCK levels remained unchanged in this group making a role of circulating hormone unlikely. In order to investigate a possible direct agonist effect of the CCK-B/gastrin receptor antagonist, we studied amylase release from isolated rat pancreatic acini in response to PD 136450 and sulfated CCK8 alone and in combination with the specific CCK-A receptor antagonist MK 329. Increasing concentrations of PD 136450 caused a monophasic dose-response curve in contrast to the well-known biphasic amylase release in response to CCK8. Addition of increasing doses of PD 136450 to a concentration of CCK causing maximal stimulation of amylase release (0.1 nM) further enhanced amylase release from pancreatic acini. The specific CCK-A receptor antagonist MK 329 dose-dependently inhibited CCK8- and PD 136450-induced amylase release. In conclusion, the new CCK-B/gastrin receptor antagonist PD 136450 exhibited profound agonist actions on the rat pancreas mediated via CCK-A receptors.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1994

Rat gastric somatostatin and gastrin release: interactions of exendin-4 and truncated glucagon-like peptide-1 (GLP-1) amide.

The effect of exendin-4, a peptide of the secretin-glucagon family with high homology of amino acid sequence with glucagon-like peptide-1 (GLP-1), on gastric hormone release was investigated in the isolated perfused rat stomach. Exendin-4 dose dependently stimulated somatostatin release up to 9-fold at a concentration of 10(-7) M whereas gastrin release was inversely inhibited by up to 63%. These effects could partially be reduced by concomitant perfusion of truncated exendin-4, exendin(9-39)amide. Similarly, stimulation of somatostatin secretion and inhibition of gastrin release induced by GLP-1(7-36)amide was partially reversed by exendin-4 (9-39)amide. These data are consistent with the assumption that exendin-4 and truncated GLP-1amide exert their effects on gastric D and G cell by interaction with the same receptor.

Animals↗
PubMed1994

Expression of the gastric H+/K(+)-ATPase and histidine decarboxylase during omeprazole treatment.

The gastric proton pump H+/K(+)-ATPase in the parietal cell is central to acid secretion into the stomach. We performed the following experiment to examine the pattern of expression of the alpha- and beta-subunits of the H+/K(+)-ATPase at the transcriptional level during 7 days' application of the proton pump inhibitor omeprazole, in relation to the expression of gastrin and histamine, two stimuli of gastric acid secretion. Serum gastrin concentrations and mRNA levels of antral gastrin, fundic histidine decarboxylase (HDC) and H+/K(+)-ATPase alpha- and beta-subunits were determined after 8 h, 1, 3 and 7 days. Omeprazole treatment rapidly caused an increase in the serum gastrin concentration and the antral gastrin mRNA level after 3 days. HDC mRNA expression showed a steady increase with a 5-fold induction after 1 week. However, mRNA levels of the alpha- and beta-subunits of the H+/K(+)-ATPase were unchanged during the course of omeprazole treatment. These results suggest that omeprazole inhibition of the gastric proton pump does not result in feedback activation of H+/K(+)-ATPase gene expression despite adaptive changes of the endocrine stomach.

Animals↗