[A case of metastatic malignant melanoma of the stomach diagnosed by endoscopy].
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Biomedical subjects
Publications and source records attributed to J Pokora.
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In the experiments performed on Wistar rats it was found that histamine (0.05 and 0.5 mg/kg i.p.) caused an acceleration of the turnover of serotonin (5-HT) in the stomach. After the lowest dose of ranitidine (3 mg/kg i.p.) a decrease in the rate of 5-HT turnover in the stomach was observed, whereas the higher doses (15.0 and 30 mg/kg i.p.) accelerated the turnover of this amine. In the duodenum, both doses of histamine accelerated the turnover of 5-HT, however, ranitidine in all doses induced a reduction in the rate of 5-HT turnover in this part of the alimentary tract. In the intestine, both doses of histamine enhanced the turnover of 5-HT but after all doses of ranitidine a decrease of the turnover was observed. The blockade of histamine H2 receptors with ranitidine did not completely abolish the effects of histamine on the 5-HT system, in the parts of the rat digestive system studied which suggests also an indirect activity of other receptors in presented observations. In the rat brain, an acceleration of the turnover of 5-HT after both doses of histamine was found. However, ranitidine only reduced the rate of 5-HT turnover at the lowest dose. In animals treated with ranitidine (15 mg/kg i.p.) for three days, histamine did not produce any change in the turnover of 5-HT in rat brain. These experiments show, that in the alimentary tract a relationship exists between histaminergic and serotoninergic systems.
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Our first stage 3-week trial (6) and second stage up to 6 weeks (7) showed that ranitidine provides the highest healing rate of 97% for duodenal and 95% for gastric ulcer. The study has been now prolonged for one year to assess the efficacy of maintenance therapy. Out of 258 patients who completed the second stage 232 voluntarily entered the open stage 3 in which they were given a single dose R 150 mg nocte, and were endoscopied after 4, 8 and 12 months. There were 153 duodenal and 79 gastric ulcers. 191 patients completed the study; no undesired effects were found and there was no medical reason to withdraw the drug from the long term use. Recurrent ulcer was found in 33.3% out of 126 duodenal ulcer cases, and in 29.2% out of 65 gastric ulcer patients who completed stage three. Sixteen percent of recurrent gastric ulcers and 26% of duodenal ulcers were asymptomatic. Recurrence rate was about twice as high in smokers as in non-smokers. These findings were compared with our long-term endoscopic survey of the natural history of peptic ulcer disease (8) in which yearly recurrence rate of duodenal ulcer was 68.4% and of gastric ulcers 73.5%, 14% of them being painless. This indicates that R is fairly well tolerated in long term use and may be useful to curb the ulcer recurrence rate.
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One hundred and seventy seven duodenal ulcer and eighty-one gastric ulcer patients were treated with either ranitidine or placebo in a prospective double-blind study. Groups treated with active drug and placebo were comparable and ulcer healing was assessed by weekly endoscopic examinations. Ranitidine was shown to accelerate the rate of spontaneous ulcer healing in both duodenal and gastric ulcer. This acceleration is significant after one week of treatment in duodenal ulcer and from three weeks onwards in gastric ulcer. The ulcer healing rate after three weeks treatment with ranitidine was 85.5% in duodenal ulcer, and 72.5% in gastric ulcer which was significantly higher than in the placebo group where it was 51.7% and 41.5% respectively (P less than 0.005 and P less than 0.01). Treatment with ranitidine for a maximum of six weeks healed 97.1% of duodenal ulcer patients (172 out of 177) and 96.5% of gastric ulcer patients (77 out of 81). Out of total of 258 patients only 9 failed to heal. No adverse events were seen with ranitidine and it would appear free of the side effects that have been seen with cimetidine. In addition there were no significant changes in blood haematology or clinical chemistry parameters. Ranitidine is also given in a more convenient regimen, 150 mg daily as compared to 200 mg three times daily and 400 mg nocte with cimetidine.
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The study was carried out in 168 patients treated in 5 Departments of Gastroenterology according to a standardized design. All were diagnosed and followed-up by panendoscopy: they were give similar diet and antacids ad libitum, and were urged not to smoke. Such basic therapy in our studies resulted in 30-40% of gastric, and about 50% of duodenal ulcers coded packages of the tested drug. Tablets contained wither 150 mg of Ranitidine or placebo They were taken twice a day. Spontaneous healing under such conditions occurred in the present study in 37% of gastric, and 45% of duodenal, ulcers, while in patients taking Ranitidine 62% of gastric (P less than 0.05) and 82% of duodenal ulcers (p less than 0.01) were cicatrized after 3 weeks. There were no drop-outs, and no undesired effects were observed.
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