Biomedical subjects
Publications and source records attributed to R Stockbrügger.
As sulphonylurea derivatives are used ubiquitously, the possibility that they may cause liver disease deserves attention. In contrast to the known pattern of reversible parenchymal liver disease due to sulphonylurea derivatives, we describe a fatal case of glyburide-induced cholestatic hepatitis with liver failure.
Multiple biopsies from the lower duodenum were obtained during endoscopy of 171 patients with dyspepsia, diarrhoea and/or suspected malabsorption. Histological evidence of lambliasis was obtained in six (3.5%). Antibiotic treatment with metronidazole, 250 mg two or three times daily for seven to 11 days (which had to be repeated in two cases), improved symptoms in four. In most of the patients "functional upper-abdominal symptoms" had been diagnosed after extensive examinations. In case of unclear upper-abdominal symptoms, chronic or chronic-recurrent diarrhoea and/or malabsorption lambliasis should be considered and histological examination of the duodenal mucosa undertaken.
In order to elucidate whether or not the increased stool frequency that occurs during cisapride treatment is a result of malabsorption of water, fat, and bile acids, 12 healthy volunteers were dosed with either tablets of placebo q.d.s. or tablets of 10 mg cisapride q.d.s. during two periods of 5 days in a double-blind, crossover study. Stool frequency, stool consistency, and side-effects were recorded each day. Total faecal mass, faecal water content, and faecal excretion of fat and bile acids were determined during the last 72 h of each study period. Mean daily stool frequency was 18.8% higher during cisapride [1.68 +/- 0.12 (S.E.M.)] administration than during placebo (1.42 +/- 0.12); P = 0.038. The stool consistency score increased by 11.8% towards softer stools during cisapride dosing (N.S.). There were no significant differences in total faecal mass (placebo 399.4 g/72 h; cisapride; 414.5 g/72 h), faecal water content (placebo; 75.6%: cisapride 76.2%), or faecal excretion of fat (placebo; 12.7 g/72 h: cisapride; 11.6 g/72 h) and total bile acids (placebo; 2212 mumol/72 h: cisapride; 2261 mumol/72 h). The side-effects reported during placebo were constipation (n = 3), and during cisapride meteorism (n = 4) and increased appetite (n = 2). The increased stool frequency during cisapride treatment is not caused by malabsorption of water, fat, or bile acids, but seems to be the consequence of a direct motor effect.
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Serum vitamin B12 concentrations were determined in 129 patients and a pentagastrin test performed in 116 patients with dermatitis herpetiformis (DH). Low serum vitamin B12 levels were found in 27 patients (21%) and achlorhydria in 30. Forty-two patients with achlorhydria and/or vitamin B12 deficiency were subjected to further haematological and gastrointestinal investigations. Functional or morphological involvement of the small intestine was seen in almost all patients with vitamin B12 deficiency but, in addition, atrophic gastritis resulting in defective secretion of intrinsic factor (pernicious anaemia) was found in 8 cases (7% of all DH patients). Thus, a low vitamin B12 level in DH patients should result in a careful gastrointestinal examination as both an atrophic gastritis and a coeliac-like enteropathy have further clinical implications.
There is a recognised association between pernicious anaemia and the development of gastric carcinoma, endocrine cell hyperplasia, and carcinoid tumour. Multiple endoscopic biopsies from the body mucosa of seven patients with pernicious anaemia showed small intestinal metaplasia with varying degrees of inflammation, fibrosis, and expansion of the lamina propria. Using conventional silver and lead stains, endocrine cells were inconspicuous. Staining for the general neural and neuroendocrine markers NSE and PGP 9.5 revealed a proliferation of endocrine cells in the epithelium and isolated clumps of endocrine cells in the lamina propria. The clumps were composed of two cell types, either small or large. Some of these endocrine cells showed gastrin, 5HT, VIP and substance P immunoreactivity of varying intensity. Ultrastructurally nine morphologically distinct types of granules were found some of which correlated with the immunohistochemistry. Some separate islands were composed solely of endocrine cells while others had a definite neural component, suggesting that the former arise from 'budding off' of enteroendocrine cells and the latter originate from the neuroendocrine cells of the lamina propria plexus. Thus there may be a dual origin of carcinoid tumours. Carcinoid tumours associated with pernicious anaemia tend to be multifocal and are infrequent. Less than 50 such cases have hitherto been reported. Our findings of endocrine cells proliferations in seven cases of pernicious anaemia indicate that this may be an adaptive change that occurs frequently and provides the basis on which carcinoids, less frequently, develop.
The definition of the orocoecal transit time by means of the hydrogen (H2) breath test is not unequivocal. In this study the orocoecal transit time as measured with an H2 breath test was compared with that obtained with a radiologic method. Two definitions of orocoecal transit time by the H2 breath test were evaluated: the time from eating to the first of three consecutively rising H2 values, and the interval to H2 values 50% above 'small-bowel level'. Transit times measured in accordance with both definitions were closely correlated to that obtained with the radiologic method (A, r = 0.84; B, r = 0.90; for both, p less than 0.001), but transit time measured by definition A gave shorter values than the radiologic method (p less than 0.05). The mean transit time in patients with constipation was significantly longer than that in normal subjects and patients with functional diarrhoea (p less than 0.05). There was a significant correlation between the difference in transit time measured with the H2 breath test and the radiologic method and the transit time measured by the control method. This may indicate that rapid transit is associated with a delayed 'colonic' rise in H2 levels and slow transit with an early H2 rise.
Out of 98 patients with dermatitis herpetiformis (DH) living in Gothenburg, 14 were in spontaneous remission (29% of the patients without gluten free diet). Eight of these volunteered for dietary interviews and further studies. They do not seem to differ from symptomatic DH patients in the frequency of HLA-B8, achlorhydria or small-bowel enteropathy. Their estimated mean daily intake of gluten was below 12 g in six. The mean gluten intake of the eight patients in remission is significantly less than in a group of 34 patients with dapsone-requiring DH on non-restricted diet. Urinary iodine excretion was low in five, all previously instructed to restrict their iodine intake. Dietary factors could thus be suspected to be responsible for some spontaneous remissions in DH.
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Achlorhydric atrophic gastritis occurs in approximately 25% of patients with dermatitis herpetiformis (DH). The effect of gluten withdrawal on the gastric condition was studied in 35 patients, with a control group of 20 patients continuing their habitual diet. Gastrointestinal examinations were performed initially and repeated after about 1 3/4 years. Adherence to the diet was confirmed by dietary interviews, improvement of malabsorption test results and intestinal villous structure, and decreased dapsone requirement. Neither the non-restricted diet nor the gluten-free diet had any effect on gastric morphology, the ability to secrete gastric acid, serum gastrin levels, or the frequency or titres of circulating parietal cell antibodies. The findings indicate that gluten is not responsible for the perpetuation of the gastric affection in DH, in contrast to the enteropathy.
Gastric acid secretory capacity was evaluated in 116 patients with dermatitis herpetiformis by means of the pentagastrin test. Endoscopic gastric mucosal biopsy specimens were obtained from both the body and the antrum in 90 of them. Forty-eight patients (41%) had a maximal acid output less than 10 mmol/h, and 30 of them (26%) were achlorhydric. The frequency of achlorhydria increased with age, and 27 out of 58 patients (47%) more than 50 years old were achlorhydric. Antrum-sparing chronic atrophic gastritis was present in 92% of the achlorhydric patients, and hypergastrinaemia and serum parietal cell antibodies were found in most of them. The prevalence of chronic gastritis of the body and of the antrum increased with age. There was no correlation between atrophic gastritis or achlorhydria and small-intestinal villous atrophy, the results of the D-xylose test, and blood folate and serum zinc determinations. The transferrin saturation index was lower in patients with achlorhydria. The frequency of achlorhydria was significantly higher in patients with dermatitis herpetiformis than in 69 patients with coeliac disease.
Pirenzepine is a new tricyclic drug used in the treatment of peptic ulcer disease. The effect of two doses of pirenzepine (25 mg twice daily and 50 mg thrice daily) was examined in ten healthy volunteers during basal acid secretion and under stimulation with two doses of pentagastrin (0.166 microgram/kg . h and 1 microgram/kg.h given as continuous intravenous infusion). Serum drug concentrations were determined by radioimmunoassay, and parallel studies of the salivary function were performed. Pirenzepine, 25 mg twice daily, reduced basal acid output by 50% and 55%, respectively, and inhibited stimulated acid output by 31% and 26%, respectively. The higher dose of pirenzepine, 50 mg thrice daily, augmented the effect insignificantly despite markedly increased serum drug levels. The recommended therapeutic dose of 25 mg twice daily gave no salivary inhibition. Pirenzepine may have an anticholinergic effect on the parietal cell, although systemic side effects were not seen. Pirenzepine does not competitively inhibit pentagastrin-stimulated acid secretion.
The effect of pirenzepine on basal and stimulated acid secretion was tested in five patients with peptic ulcer disease and gastric hypersecretion. Two types of stimulation were compared, namely pentagastrin by intravenous infusion (1 microgram/kg/h) and hypoglycaemia induced by insulin given subcutaneously (0.125 IU/kg). Basal acid output/30 min was reduced by 44% and 69%, respectively. Pentagastrin-stimulated acid output was reduced by 30%/120 min, and insulin-stimulated acid output by 47%. The reduction was similar during the first and second hour of stimulation in both series. These results strengthen our previous impression that pirenzepine may interfere with cholinergic receptors at the parietal cell level. As the inhibition of gastric acid secretion by pirenzepine is similar to that produced by oral doses of cimetidine, pirenzepine may be useful in the treatment of peptic ulcer disease.