[Prevention of stress ulcers with acid decreasing drugs: an effective and sensible therapeutic approach? Arguments contra].
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Biomedical subjects
Publications and source records attributed to W P Fritsch.
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By means of a case-report of a 33 years old pat., having colitis ulcerosa for 16 years with serious epitheldysplasia and developing primary sclerosing cholangitis, the typical progress of the disease with manifestation of a secondary biliary cirrhosis is shown. The course was complicated by the development of a bile-duct carcinoma. Present possibilities of diagnosis and therapy are discussed.
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Mucus protects the gastric mucous membrane from aggressive substances in the gastric juice. It consists of glycoproteins, the composition of which determines its ability of viscosity, adhesiveness, and cohesiveness. There is a special interest in sialic acids, which are found mostly in humans as N-acetylneuraminic acid (NANA). NANA is estimated by the thiobarbituric acid method. A special feature of this method is that only free sialic acids are estimated. A mild acid hydrolysis is necessary in order to measure the total NANA-content. Some conditions of the hydrolysis are investigated with respect to the special properties of the gastric juice. Hydrolysis sulfuric acid 0.01 mol/l results in an about 10% higher yield than hydrolysis with hydrochloric acid 0.01 mol/l. A maximal yield of hydrolysates is found when the gastric juice pH is adjusted to 2.0. After 45 minutes hydrolysis at 80 degrees C in a water bath there is for at least 60 minutes a constant NANA-concentration in the gastric juice samples. Human bile has no influence on the estimation with the thiobarbituric acid method. In regard to these conditions of hydrolysis pentagastrin (6 micrograms/kg KG s. c.) does not change the NANA-secretion over 60 minutes in patients with duodenal ulcer. During an intragastric bile salt infusion the NANA-output remains unchanged over 45 minutes.
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Inhibition of acid secretion was investigated in 5 patients with Zollinger-Ellison syndrome and 12 patients with duodenal ulcer after administration of 200 mg cimetidine alone and combined with 50 mg methanthelinebromide. A preinvestigation of 5 patients had not shown any significant decrease of acid secretion after 50 mg methanthelinebromide alone. Compared with a single dose of 200 mg cimetidine, combined drugs' use (200 mg cimetidine and 50 mg methanthelinebromide) led to significant increase of inhibition of secretion both as regards degree and duration. In 6 patients with duodenal ulcer basal secretion of more than 2.0 mmol H+/h 200 mg cimetidine led to inhibition of secretion by 91.4% over 120 min compared to 96.4% over 225 min after combined administration. Similar results were obtained in 6 patients with a basal secretion of less than 2.0 mmol H+/h.
Using Gastrin 14-17 as immunogen it was possible to raise an antiserum, which showed a high sensitivity for the C-terminal octapeptide of CCK in a radioimmunoassay with 125J-gastrin as tracerhormon. High immuno-reactivity could be demonstrated in the grey and white matter of the human cortex as well as in the putamen and nucleus caudatus using this assay. By comparing the unknown brain substance with different peptides in different physico-chemical systems, the brain substance was shown to be homogenous and being similar to CCK-8.
Following selective proximal vagotomy (SPV) in duodenal ulcer patients basal acid output (BAO) and peak acid output (PAO) decrease by 79,3% and 41,8% respectively. Serum gastrin levels increase by 83% within the first five days after operation. Patients having had a SPV release evidently more gastrin after test meals as compared with the results before vagotomy. In consideration of the elevated praeoperative values insulin hypoglycaemia does not cause an augmented secretion of gastrin. There is no correlation between the fall in acid secretion and the increase in gastrin levels. Acidification of the gastric antrum (pH 2,0) did not influence the raised serum gastrin levels at the 10. day and one year after operation. There is a close correlation (r=0,94) between the percental increase in the basal gastrin concentration and the percental change of the vagal influence on the secretion of the parietal cell. It is postulated that together with the dissection of stimulating vagal fibres reaching the parietal cells other fibres are cut which cause an inhibition of gastrin release from the antral G-cells. Thus, the disinhibition of an oxyntopyloric reflex may account for the increase in serum gastrin levels after SPV.
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Gastrin antisera were raised by immunization of rabbits or guinea pigs with synthetic human gastrin I conjugated to bovine serum albumin by carbodiimide. Radioiodination of SHG: 2-17 was performed by the chloramine T-method and by an enzymatic procedure. AE-cellulose was used to get a monoiodinated tracer hormone. Antibody reactions with the different forms of gastrin and with CCK-PZ was characterized. Precision (VK = 6-8%) and reproducibility (VK less than 15%) of the gastrin values were comparable to the insulin assay. Gastrin stimulates the parietal cell and has trophic effects on gastric mucosa. Hypergastrinaemia in combination with hypersecretion exhibits clinical significance in patients suffering from Zollinger-Ellison-syndrome or excluded antrum-syndrome which are due to autonomous gastrin release. Some findings suggest a pathogenetic role of gastrin in duodenal ulcer disease. Those disease in which gastrin determinations are of clinical value are discussed.