[Is digestive intolerance of corticotherapy a myth?].
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Biomedical subjects
Publications and source records attributed to J F Bergmann.
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Ethanol undergoes gastric first pass metabolism by alcohol dehydrogenase (ADH). We have shown that cimetidine and famotidine both cause competitive inhibition of human gastric ADH in vitro. However, in a randomized 4-way cross-over study in 12 healthy subjects a 7-day course of treatment with cimetidine (800 mg day-1), ranitidine (300 mg day-1) or famotidine (40 mg day-1), did not modify the pharmacokinetics of ethanol given as a post-prandial 0.3 g kg-1 dose. We conclude that gastric mucosal concentrations of histamine H2-receptor blockers achieved after oral dosing are probably too low to cause significant inhibition of gastric ADH in vivo.
To determine whether informed consent in a therapeutic trial modifies the analgesic effect of naproxen and placebo, we conducted a prospective, randomised, single dose, placebo-controlled trial. Patients were randomly selected to receive or not information concerning the study. All patients included were then given a single dose of naproxen and placebo according to a crossover, double-blind design. Forty-nine patients with mild or moderate cancer pain which did not need narcotic analgesics entered the study. Twenty-five received both treatments without any information and constituted the uninformed group. Twenty-four had a complete information about the trial; six refused to participate. The 18 others constituted the informed-consent group. Visual analogue scales of pain before and 30, 60, 120 and 180 min after the intake of naproxen and placebo were recorded. As an analgesic, naproxen was more effective than placebo in both groups of patients (p = 0.001). For naproxen as well as for placebo, the analgesic effect was better in the informed-consent group compared to the uninformed group (p = 0.012). The difference in therapeutic activity between naproxen and placebo was moderately higher in the uninformed patients (p = 0.08). We concluded that, in contrast with parallel studies, giving information in a crossover, placebo-controlled trial may increase the apparent efficacy of both the tested agent and the placebo, and decrease the perceived difference the two.
Tuberculosis choroidal granulomas ("tubercules de Bouchut") are rare, even in patients with AIDS and active tuberculosis. The authors report the clinical and angiographical findings of three cases. Choroidal involvement was bilateral, with multiple lesions, mostly located at the posterior pole. The size of the granuloma ranged from 1/8 to 1/2 of a disc diameter. Fluorescein angiography showed early prolonged hypofluorescence and late moderate hyperfluorescence. The lesions remained stable for months despite treatment of tuberculosis, and then gradually subsided. In two cases, the choroidal granulomas were discovered before the diagnosis of disseminated tuberculosis and guided the investigations, which allowed the identification of Mycobacterium Tuberculosis bacillus in the body. In the third case, pulmonary tuberculosis had already been diagnosed. The number of tuberculosis cases is increasing together with the number of AIDS cases. This should make the observation of tuberculosis choroidal granulomas more frequent. The discovery of the typical aspects of granulomas described above during fundus examination of AIDS patients can help in diagnosing tuberculosis.
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Gaucher's disease is characterized by accumulation of glucocerebroside (caused by an autosomally inherited deficiency of glucocerebrosidase) in the cells of the reticuloendothelial system. We report the clinical, laboratory, radiologic features of 17 patients with type 1 Gaucher's disease.
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In order to obtain information on prescribing habits concerning the prevention of gastroduodenal lesions induced by non-steroidal anti-inflammatory agents (NSAI), 356 physicians practicing in 2 French departments were asked to fill a posted questionnaire. Fifty-one percent of these doctors gave an assessable answer. Among these, 84 percent occasionally prescribe "gastric protectors" associated with NSAI's in 32 percent of the prescriptions. They use antacids (48 percent), anti-H2 products (27 percent), sucralfate (11 percent) or prostaglandins (13 percent). This represents a daily cost of additional treatment ranging from 0.87 to 2.49 francs. If fibroscopies and further consultations necessitated by the prescription of NSAI's are taken into account, then 86 to 140 percent must be added to the cost of NSAI's. The profitability of these preventive measures in terms of public health will be really estimated only when the number of severe gastroduodenal lesions effectively prevented by taking topical gastric protectors or anti-secretory agents will be known.
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Endoscopic lesions of the gastric mucosa were evaluated in 12 healthy volunteers after administration of single doses of ketoprofen (25 mg), ibuprofen (200 mg) and aspirin (500 mg) in a randomized, double-blind, cross-over study. The grades of the lesions (according to Lanza's scale) were lower after the administration of ketoprofen than aspirin and were comparable to ibuprofen. An endoscopic score greater than 1 was observed in 3 cases after ibuprofen or ketoprofen, and in 8 cases after aspirin. At a time when low, single doses of NSAIDs are widely used as analgesics, gastroscopy makes it possible directly to assess the local aggressivity of these molecules. In this way it was possible to demonstrate that the local toxicity of NSAIDs was lower than that of aspirin.
The aim of the study was to use a novel combination of two methods for the simultaneous evaluation of two effects of oral cisapride in 10 diabetic patients with autonomic neuropathy; gastric empyting time was measured by following radio-opaque markers and orocaecal transit time by the sulphasalazine-sulphapridine method. The study was of double-blind, randomized, placebo-controlled, cross-over design. It was possible to evaluate the effect of a prokinetic drug on gastric emptying and orocaecal transit times using these two noninvasive techniques at the same time. Cisapride significantly reduced both the gastric empyting (1.2 h versus 2.1 h) and orocaecal tansit (5.9 h versus 7.7 h) times.
The protective effect of lansoprazole, a new proton pump inhibitor, against aspirin-induced gastric lesions was studied in a double-blind crossover trial with a simultaneous measure of the functional capacities of the mucosal barrier (by a recording of the gastric potential difference) and of the morphologic changes in the mucosa (by gastric endoscopy). After 1 week of treatment with lansoprazole (30 mg per day) or placebo, each healthy volunteer received 1 gm aspirin by mouth. Recording of the gastric potential difference lasted for 3 hours and was followed by gastric endoscopy. Morphologic lesions induced by aspirin were effectively prevented by lansoprazole: Lanza score was 0.67 +/- 0.98 (mean +/- SD) versus 2.25 +/- 1.1 with placebo (p < 0.005, ANOVA). Conversely, the decrease in the gastric potential difference was similar. The inhibition of acid secretion induced by lansoprazole was therefore sufficient to prevent aspirin-induced mucosal lesions without reinforcing the defense capacities of the mucosa. This simple pharmacologic model makes it possible to simultaneously evaluate the functional and morphologic effects of aspirin intake on the gastric mucosa.
Acetorphan is a potent enkephalinase inhibitor displaying antidiarrhoeal activity attributable to its intestinal antisecretory action mediated by endogenous enkephalins. The effect of acetorphan on digestive motility was studied in 12 healthy volunteers. Oro-caecal transit time was evaluated using the sulphasalazine/sulphapyridine method and colonic transit times using radiopaque markers. These measurements were successively performed after one week treatment with an antidiarrhoeal dose of acetorphan (100 mg t.d.s.) or placebo. There was no significant modification in transit time linked to acetorphan treatment: total oro-caecal times were 303 +/- 32 min vs. 287 +/- 27 min and colonic transit times 25.8 +/- 5.8 h vs. 31.3 +/- 5.5 h after acetorphan and placebo, respectively (means +/- S.E.M.). There was no significant modification either in right colonic, left colonic or rectosigmoid segmental transit times, or in the mean number of stools. These results, consistent with those from animal studies, confirm that, unlike classical antidiarrhoeal mu opiate receptor agonists, which act by delaying intestinal transit, acetorphan does not affect the transit. Antidiarrhoeal activity not accompanied by a delayed intestinal transit could have beneficial therapeutic consequences in the management of infectious diarrhoea. In addition, we show that the sulphasalazine and radiopaque markers methods can be simultaneously applied in the same study.
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The correlation between ultrasonographic gastric emptying and appetite was studied. Echographic evaluation of gastric emptying by measurement of the antral vertical diameter and assessment of sensations of hunger and satiety using analogue visual scales were performed simultaneously in 12 healthy volunteers. Measurements were carried out after the intake of 10.8 g psyllium or placebo in a randomised, crossover, double blind trial. The correlation between echographic gastric emptying and sensations of hunger and satiety was excellent (p < 0.001) after the intake of either psyllium or placebo. Psyllium significantly delayed gastric emptying from the third hour after a meal. It increased the sensation of satiety and decreased hunger at the sixth hour after the meal. The association between echographic measurement and visual scales is a simple method of evaluating the relationship between the stomach and appetite. The pharmacodynamic effect of psyllium should be confirmed by longterm therapeutic trials.