[Allopurinol hypersensitivity syndrome: Liver transplantation after treatment of asymptomatic hyperuricaemia]. / Allopurinol-Hypersensitivitätssyndrom: Lebertransplantation nach Behandlung einer asymptomatischen Hyperurikämie.

ADMISSION FINDINGS: A 41 year old patient started treatment with 300 mg/d allopurinol for asymptomatic hyperuricaemia (9,2 mg/dl). COURSE: 4 weeks later he developed exfoliative skin lesions with haemorrhage, fever, eosinophilia and acute liver and renal failure, typical for an allopurinol hypersensitivity syndrome (AHS).An orthotopic liver-transplantation was performed. CONCLUSION: The AHS is a serious iatrogenic disease. 2 % of the treated patients develop a skin rash. 0,4 % of these patients experience suddenly and unforeseen a severe hypersensitivity with a mortality of 14-30 %. An early diagnosis is often very difficult. In the pathogenesis different causes are discussed. A hereditary component is involved. Of essential importance is the amount of the starting dose, the kidney function and concomitant drugs. In an asymptomatic hyperuricaemia the application of allopurinol is not indicated. If strong indications are present, the allopurinol therapy has to start with the lowest dose (100 mg/d). If required this dose should be increased under consequent supervision only.

Magaldrate stimulates endogenous prostaglandin E2 synthesis in human gastric mucosa in vitro and in vivo.

BACKGROUND/AIMS: Prostaglandin E2 (PGE2) plays an important role in the inhibition of gastric acid production and exerts cytoprotective action. The in vitro and in vivo effect of magaldrate, an aluminum containing antacid, on PGE2 synthesis in the gastric mucosa was investigated. METHODOLOGY: In the first part of the study, magaldrate was added to a suspension of isolated gastric mucosal cells. In the second part, the antacid gel was applied to the gastric mucosa during gastroscopy and biopsies were taken from the same site 5 and 10 min later. RESULTS: The antacid significantly stimulated PGE2 release from the suspension of isolated gastric cells in vitro. The biopsies obtained after the application of magaldrate showed an increased PGE2 production compared to specimens obtained before. CONCLUSIONS: The data suggest that in addition to its neutralizing capacity as an antacid, magaldrate contributes to the cytoprotective activity of the mucosa by stimulating endogenous PGE2 synthesis.

Profound increase of Helicobacter pylori urease activity in gastric antral mucosa at low pH.

The effect of pH on H. pylori urease activity in its ecological niche was studied in gastric antral biopsy specimens. Specimens were incubated in 10 mmol/liter urea solutions at pH range 3.3-8.2. Activity of urease was studied by measuring production of ammonia and change in pH of the solutions. Urease activity was reduced at pH 8.2 (1424 +/- 218 mumol/liter) but decreasing initial pH to neutral and acidic values resulted in significant maximal 6.5-fold increase in ammonia production (9491 +/- 1073 mumol/liter, P < 0.0005), which considerably raised the pH of the test solutions. Peak urease activity was between pH 5.0 and 7.0. In contrast to specimens incubated initially at pH 8.0, reincubation of washed specimens from solutions with initial pH 7.0 showed eightfold decreased urease activity. It is concluded that urease activity is markedly pH dependent with pH optima below the physiological mucosal surface pH. Furthermore, availability of urease is limited. Thus, an impaired gastric mucosal integrity allowing back diffusion of hydrogen ions may release urease activity, which might further weaken the mucus barrier and damage the gastric epithelium.

[Ranitidine and clarithromycin for eradication of Helicobacter pylori in patients with duodenal ulcer]. / Ranitidin und Clarithromycin zur Eradikation von Helicobacter pylori bei Patienten mit Ulcus duodeni.

To compare the efficacy of ranitidine (CAS66357-35-5, Sostril) in combination with clarithromycin (CAS 81103-11-9, Cyllind) against H. pylori, a controlled randomized double-blind study was carried out. Fourty duodenal ulcer patients were treated either with ranitidine 150 mg b.i.d. and clarithromycin 500 mg q.i.d. (20 patients, group 1) or ranitidine 300 mg q.i.d. and clarithromycin 500 mg q.i.d. (20 patients, group 2) for 14 days. Both treatment groups received an additional treatment with ranitidine 300 mg daily for another 14 days. Endoscopy 6 weeks after the beginning of the trial showed complete ulcer healing in all patients. The control of H. pylori status done by CLO (Campylobacter-like organism) test and histology yielded an eradication rate of 84% (group 2) and 61% (group 1) in patients with duodenal ulcer disease treated with ranitidine and clarithromycin. Whether higher suppression of gastric acidity with a higher dose of ranitidine in combination with the antibiotic clarithromycin presents clear advantages in eradication of H. pylori should be investigated in further studies.

[Optimal or maximum acid inhibition in ulcer therapy? A decision guide for routine general practice based on personal studies]. / Optimale oder maximale Säurehemmung in der Ulkustherapie? Eine Entscheidungshilfe für die tägliche Praxis anhand eigener Untersuchungen.

The mucosal barrier in the stomach is complete only when the mucous layer has become saturated with bicarbonate. The latter arises as a waste product, as it were, of acid production in the parietal cell, but is then actively secreted via the surface epithelial cells and tight junctions. If the acid secretion is inhibited by means of drugs, the bicarbonate concentration also decreases. This situation probably occurs only when the bicarbonate batteries in the mucous layer and the surface epithelial cells have become "discharged" after a period of about 24 hours, which indicates an intermittent, non-maximum block. In the region between the surface epithelial cells and the mucous layer, Helicobacter pylori has its ecological niche. As studies with, for example, ranitidine nocte, amoxycillin and metronidazole have shown, a 12 hour alternation between acid secretion inhibition and the physiological buildup of the gastric mucosal barrier appears to promote the eradication of Helicobacter pylori. Hypotheses about the role of sudden ammonia production on the part of the pathogen and on the regulation of bicarbonate and acid production in humans underscore these findings.

[Prostaglandins and the prevention of non-steroidal antirheumatic drug-induced gastric lesions]. / Prostaglandine und die Prävention NSAR-induzierter gastraler Läsionen.

By the mechanism of the inhibition of the endogenous prostaglandin synthesis by NSAIDs, and thus the attenuation of the protective factors in the gastrointestinal mucosa, gastric lesions frequently develop, and the healing of existing peptic ulcers is appreciably slowed. The combination of several risk factors increases the probability of peptic ulcers or ulcer complications developing under NSAID treatment. In such at-risk patients, treatment with NSAIDs should be accompanied by prophylactic measures. The use of various anti-ulcer drugs has shown that for the treatment of NSAID-induced gastropathies the prostaglandin analog, misoprostol is equally as good as the other anti-ulcer drugs, for the prevention of NSAID-induced lesions however it is superior to H2-receptor antagonists (cimetidine, ranitidine), antacids and sucralfate.

[Lattice structure antacids and antacid mixtures]. / Gitterförmige Antazida und Antazidagemische.

In the last years the importance of the evaluation of antacid compounds according to their neutralizing capacity decreased. Clinical investigations have shown that antacid mixtures of aluminum-magnesium hydroxide healed gastric an duodenal ulcers (neutralizing capacity 100-150 mmol/day) as well as H2 receptor antagonists and better than a placebo. By this the necessary daily dosage could be reduced essentially. This paper presents studies showing that lattice like structured antacids (e.g. Magaldrate) healed gastric and duodenal ulcers (neutralizing capacity 100-350 mmol/day) as well as Ranitidine (150 mg b.d.). Maintenance therapy should be evaluated critically because sufficient data are not available and mineral metabolism is changed significantly by extremely small dosages of aluminium-magnesium hydroxide antacids even in patients with normal kidney function.

Effect of glucagon on adenylate cyclase activity and acid production of isolated human parietal cells.

The direct effect of glucagon on human parietal cell function in vitro was tested by measuring adenylate cyclase (AC) activity and H+ production in homogenates of human gastric mucosa obtained during surgery or at biopsy. Cells isolated from mucosa obtained during surgery showed an increase in AC with histamine and glucagon. In parietal cell enriched fractions (75%) glucagon and histamine stimulated AC much more effectively than in parietal cell depleted fractions (15% and 7%). In contrast, glucagon did not affect basal or histamine stimulated 14C amino pyrine uptake. In homogenates of mucosal biopsy specimens 2 X 10(-7) mol/l glucagon enhanced AC activity by 76% (corpus) and 20% (antrum). In the same homogenates 10(-4) mol/l histamine caused a stimulation by 161% (corpus) and 38% (antrum). In fundic biopsy specimens glucagon displayed a biphasic concentration response curve with an increase at 10(-10) mol/l (46% above basal AC activity) and a maximum at 2 X 10(-7) mol/l (97%). Histamine elicited the maximal response (192%) at 10(-3) mol/l. Increasing histamine and glucagon concentrations caused additive stimulation of AC. Ranitidine did not change AC in response to glucagon but abolished the effect of histamine. Data suggest that the glucagon action is mediated by separate (glucagon?) receptors. As H+ production was not affected by glucagon, the coexistence of two AC systems in the human parietal cell is postulated: One that is activated via histamine H2-receptors and which stimulated H+ production; another that is activated by glucagon and is directed towards other, possibly metabolic effects.