Hans Rudolf Koelz

Evolution of gastro-oesophageal reflux disease over 5 years under routine medical care - the ProGERD study

Aliment Pharmacol Ther 2012; 35: 154–164

A summary of Food and Drug Administration-reported adverse events and drug interactions occurring during therapy with omeprazole, lansoprazole and pantoprazole

Background : Pantoprazole is claimed to have a lower potential for drug interaction than other proton pump inhibitors.

When is esophagitis healed? esophageal endoscopy, histology and function before and after cimetidine treatment.

In order to asses whether in reflux esophagitis morphological and functional disorders persist after macroscopic healing, cimetidine was given for 6–12 weeks at a dose of 1.6 g/day to 30 patients with acid gastroesophageal reflux and esophagitis. The mucosal defects healed in 6 patients, improved in 14 patients, and remained unchanged in 10 patients. Lower esophageal sphincter pressure, acid clearance, acid perfusion test, and histological signs of mucosal inflammation were assessed before and after treatment. The histological and functional findings did not improve after healing of the mucosal defects. Therefore, endoscopic normalization in patients with reflux esophagitis is not associated with the disappearance of inflammation and abnormal motor function. The persistence of these abnormalities might explain the tendency of esophagitis to recur after symptomatic and endoscopic “healing.”

Inhibition of hepatic demethylation of aminopyrine by oral contraceptive steroids in humans.

Abstract. The effect of oral contraceptive steroids (OCS) on the rate of hepatic demethylation of 14C‐dimethyl‐aminoantipyrine (DAP) was studied directly in healthy young volunteers using a newly developed noninvasive breath analysis technique. After oral administration of a trace dose of DAP the specific activity of 14CO2 in breath was determined during 6 h and expressed as half life. The half life of eighteen female and twelve male control subjects was 2.4 ± 1.2h (2 SD) and 2.2 ± 0.6h (2 SD), respectively. In seven women starting OCS a progressive prolongation of DAP half life during a single menstrual period was observed. In seventeen women who had taken OCS in 21 clay cycles, for more than 3 months, the half life was significantly (P< 0.001) prolonged (4.4 ± 2.1 h) when measured after 21 consecutive days of OCS intake. On average, stopping OCS for 7 days or giving phenobarbital in addition to OCS shortened DAP half life significantly (from 4.4 ± 2.1 h to 3.2 ± 1.1h, n= 17, P 0.005; and from 4.6 ± 2.0 h to 3.2 v 1.0h, n= 12, P<0.01, respectively). Eight of twelve women on OCS responded to OCS intake and to OCS cessation and phenobarbital, whereas four women did not respond to any of these measures. These data suggest that inhibition of hepatic demethylation of DAP by OCS is time dependent and reversible. The extent of inhibition appears to be an individual characteristic of a given person.

Sucralfate and ranitidine in the treatment of acute duodenal ulcer: Healing and relapse

Healing and relapse of acute duodenal ulcer were investigated in an endoscopically controlled multicenter study using a double-blind design. Patients with acute uncomplicated duodenal ulcer were randomly assigned to treatment with sucralfate (1 g four times per day) or ranitidine (150 mg twice per day) for four to eight weeks. After healing, all anti-ulcer treatment was discontinued except for low-dose antacids needed for occasional upper abdominal pain, and the patients were observed for up to one year. Endoscopy was repeated after one year or at any time earlier if symptoms suggested ulcer relapse. Of the 83 patients who entered the study, 75 (sucralfate 40, ranitidine 35) underwent endoscopy after four weeks and could be fully evaluated. Healing rates after four and eight weeks were similar in the two groups (four- and eight-week healing rates after sucralfate and ranitidine: 78 and 74 percent, and 95 and 94 percent, respectively). Fifty-three patients with healed ulcers (sucralfate 29, ranitidine 24) were observed for up to one year. Duodenal ulcers occurred somewhat later after sucralfate than after ranitidine treatment, but life table analysis showed no significant difference. Thus, this study confirms a similar efficacy of sucralfate and ranitidine in healing of duodenal ulcer. A tendency to delayed relapse early after discontinuation of sucralfate failed to reach statistical significance.

7 Helicobacter pylori and functional dyspepsia: a real causal link?

This chapter reviews the evidence for a link between functional dyspepsia and Helicobacter pylori infection from three angles. In the section on pathophysiology, we evaluate how H. pylori could theoretically produce dyspeptic symptoms: many mechanisms can be proposed. In the discussion on epidemiology, we evaluate possible associations between the occurrence of symptoms and infection. Here, many studies claiming a coincidence or chronological sequence of infection and symptoms are criticized because of their poor design. In the section on the improvement of functional dyspepsia by the treatment of H. pylori infection, the conclusion is reached that if such an effect occurs at all--which is unlikely--it is very weak. The controversy on the link between H. pylori infection and functional dyspepsia is presently ongoing. Some authors are still trying to save an elegant concept that once looked so plausible but now has the facts against it.

Prevention of Ulcer Recurrence

Peptic ulcer disease is a recurrent illness. Within the first year after healing of an acute ulceration, at least one further ulcer attack will occur in approximately 70% of patients with duodenal and in approximately 50% of those with gastric ulcers. Every recurrent ulceration bears the risk of medical and economic complications.

Diagnose des Ulkus-Typs

Herr Grimmer leidet seit 2 Monaten an ulkusartigen Beschwerden. Ein epigastrischer Schmerz tritt 2–3 Stunden nach dem Essen auf. Die Nahrungsaufnahme lindert den Schmerz. Die Schmerzschube dauern mehrere Stunden bis Tage. Vier Grunde sprechen fur die Durchfuhrung einer Endoskopie des oberen Gastrointestinaltraktes: 1. Die Anamnese ist fur die Entscheidung ausschlaggebend. Die Symptome von Herrn Grimmer sind mit einer Ulkuskrankheit vereinbar. Die Differenzierung einer organischen von einer funktionellen Dyspepsie aufgrund der Beschwerden ist nicht moglich (1). Gewisse anamnestische Hinweise wie eine positive Familienanamnese und der fruhere endoskopische oder radiologische Nachweis eines Ulkus sprechen bei Patienten mit ulkusartigen Symptomen fur das Vorliegen einer Ulkuskrankheit. Das Fehlen solcher Hinweise wie im Falle von Herrn Grimmer kann jedoch nicht gegen eine solche Annahme verwendet werden. 2. Durch die Anamnese werden exogene gastrotoxische Faktoren erfast. Von Bedeutung sind die nichtsteroidalen Antirheumatika und der Zigarettenkonsum. Herr Grimmer ist Raucher und hat in den letzten Wochen Aspirin-Tabletten eingenommen. Diese zwei Noxen konnen zur Entstehung von Ulzera beitragen und sprechen fur eine endoskopische Untersuchung (2, 3). 3. Die Durchfuhrung der Endoskopie ist auch wegen des grosen Leidensdrucks und der Angst des Patienten vor einer schweren Krankheit angebracht (4). Ein positiver Befund ist die Basis fur eine kausale Therapie. Ein negativer endoskopischer Befund kann zur besseren Akzeptanz der Beschwerden beitragen. 4. Bei der korperlichen Untersuchung von Herrn Grimmer wird ein Druckschmerz im Epigastrium ausgelost. Ein solcher Befund findet sich sowohl bei organischen als auch bei funktionellen Erkrankungen. Nur die Endoskopie erlaubt eine Differenzierung.

Pathophysiologie des Ulkus-Typs

Herr Grimmer leidet an dyspeptischen Beschwerden, die eine Ulkuskrankheit vermuten lassen. Bei der Endoskopie ist jedoch kein Ulkus gesehen worden. Differentialdiagnostisch ist zu bedenken, das epigastrische Schmerzen auch in den Nachbarorganen des Magens ihren Ursprung haben konnen, beispielsweise im Kolon. Unter experimentellen Bedingungen kann die Dehnung des Querkolons mit einem Ballon epigastrische Schmerzen verursachen (1). Die Art der Schmerzen von Herrn Grimmer, ihre Nahrungsabhangigkeit und das Fehlen von Stuhlunregelmasigkeiten sprechen jedoch fur eine Ursache im oberen Gastrointestinaltrakt.

Diagnose des Magenstase-Typs

Fraulein Eisenstein leidet an vorzeitigem Sattigungsgefuhl, das manchmal mit Ubelkeit assoziiert ist, sowie an postprandialem Vollegefuhl und Blahungen. Die Beschwerden lassen eine verzogerte Magenentleerung vermuten (1, 2). Die in Kap. 6, S. 61 besprochenen bekannten Ursachen von Motilitatstorungen sind aus der Anamnese nicht ersichtlich (3). Bei den durchgefuhrten Laboruntersuchungen ergeben sich keine Hinweise auf eine Anamie oder eine hepatologische Erkrankung.