[What's wrong with asthma clinics?].
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Biomedical subjects
Publications and source records attributed to O Flaten.
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Pain ratings from 268 migraine patients have been used to compare the visual analogue scale (VAS) and a four-point verbal rating scale. All patients completed pain ratings on both scales at the beginning of a migraine attack and 4 h after starting treatment with sumatriptan or placebo. The VAS scores showed large variability within each category on the verbal rating scale. A common way of analysing pain in migraine studies is to classify patient response as a success or failure based on the score on the four-point verbal rating scale. In this study, the statistical power of analysing response either as "success or failure" or by means of the VAS score has been investigated by stochastic simulation. The simulations showed that the two response measures resulted in approximately equal power.
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The strength and the validity of the multi-crossover model (MCO model) were investigated to optimalize the procedure for correctly classifying individual responders to a given therapy. One hundred and fifteen patients with non-ulcer dyspepsia from seven Norwegian hospitals were included in a 6-week double-blind MCO-designed trial with alternating weekly treatments with ranitidine and placebo. An individual effect score (X score) was calculated on the basis of the number of times the active drug was associated with less symptoms than the preceding or following placebo period. Patients categorized as responders (X score greater than or equal to 4) or unclassifiables (X scores = 2 or 3) after the MCO period continued single-blind active treatment for 4 weeks and were then reclassified by means of cross-tabulation of efficacy and adverse effects. Eighty-five per cent of the MCO responders and 62% of the 42 MCO unclassifiables were reclassified as responders. The reclassified responders were then included in a single-blind follow-up placebo period until relapse or for a maximum of 8 weeks. The relapse rate was significantly greater (p less than 0.01) and the time to relapse significantly shorter (p less than 0.01) in the group of MCO responders than in the MCO unclassifiables. The large response and relapse rates in the group of MCO responders verify that the MCO model is a reliable method for correctly classifying responders to treatment. Our results indicate that by including patients with an X score of 3 in the definition of 'responder', the MCO model could be modified to optimalize the procedure for correct classification.
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Elevated serum levels of gastrin, pancreatic polypeptide, and glucagon were found in 10 uraemic patients, whereas gastric inhibitory polypeptide and somatostatin levels were normal. After renal transplantation there was a significant reduction in serum gastrin (median, 5 pmol/l; p = 0.05, n = 9), pancreatic polypeptide (145 pmol/l; p less than 0.01, n = 9), GIP (9.5 pmol/l; p = 0.02, n = 7), and glucagon (92 pg/l; p less than 0.02, n = 9), whereas no alteration was seen in the somatostatin level. Meal stimulation produced consistent increases in serum levels of all hormones, and the response appeared to be unchanged after renal transplantation.
The present study in the rat demonstrates an inhibitory mechanism of gastric emptying, sensitive to the osmolality of a liquid meal. Gastric emptying and intestinal transit were studied in groups that differed with regard to the osmolality of the gastric or duodenal instillation, experimental time, and indomethacin treatment. By intragastric instillation animals were fed an aqueous solution containing the nonabsorbable marker 51CrO2-4. After certain fixed time intervals the rats were killed and the stomach and small intestine were dissected out en bloc. The distribution of the isotope along the gastrointestinal canal was then determined. Intestinal transit was evaluated in a similar manner. The marker solution was introduced into the duodenum. A hyperosmolar solution, 1200 mOsm kg-1, was emptied from the stomach significantly more slowly than was an iso-osmolar solution, 300 mOsm kg-1. Of the iso- and hyper-osmolar solutions 87% and 74%, respectively, were emptied in 1 h. The isotope distribution along the intestinal canal after intraduodenal instillation was not affected by the osmolality of the installation. The osmotic inhibition of gastric emptying was not affected by indomethacin treatment (4 mg kg-1) or related to elevated plasma levels of gastrin, neurotensin, somatostatin, or gastric inhibitory polypeptide.
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A series of variables involved in glucose handling were monitored before and after gastric bypass operation for morbid obesity. Blood glucose, insulin, C-peptide, gastric inhibitory polypeptide (GIP), pancreatic polypeptide (PP), and gastrin were measured basally and after an oral glucose load. Blood glucose, insulin, C-peptide, and PP were also measured after an intravenous glucose load. Adrenocortical function was evaluated by measuring plasma cortisol and urinary excretion of 17-hydroxy-corticosteroids and 17-ketosteroids. Nine subjects were examined before and 3 and 12 months after operation. Glucose tolerance improved postoperatively concomitant with decreased basal levels of C-peptide and insulin, increased hepatic insulin extraction, and evidence of reduced adrenocortical function. Parallel with reduced insulin resistance, support for an increase in both insulin secretion and removal was obtained postoperatively. It is concluded that the considerable endocrine abnormalities seen in morbid obesity can be normalized after gastric bypass operation and weight reduction.
Twenty young men divided into two groups participated in a five day training course with prolonged and heavy physical exercise, calorie supply deficiency and severe sleep deprivation. Basal acid output (BAO) was measured immediately after the course in seven of ten subjects who were given placebo tablets (placebo group) and in four of ten subjects who had a daily intake of 1 g cimetidine (cimetidine-group) during the course. Median BAO increased 3-fold in the placebo subjects (from 2.7 mmol/h to 8.2 mmol/h) but showed no increase in the cimetidine treated subjects. The median fasting plasma concentrations of secretin increased 2-8-fold during the course. Gastric suction for 1 h or ingestion of cimetidine reduced the plasma concentration of secretin by approx. 50%. Vasoactive intestinal polypeptide (VIP) increased 2-fold and was not influenced by reduction of gastric acid. The placebo group showed a small increase (P less than 0.05) in plasma concentration of gastrin on day two during the course. The study shows a marked hyperchlorhydria which partly explains the fasting hypersecretinemia found during prolonged strain. This strain-induced hyperchlorhydria could be abolished by treatment with the selective H2-receptor antagonist cimetidine.
Thyrotrophin-releasing hormone (TRH) is present in the pancreas, mainly in the islets of Langerhans. We studied the effect of iv infused TRH on the plasma levels of pancreatic islet hormones in man, under different experimental conditions: 1) Arginine infusion. 2) Insulin induced hypoglycaemia. 3) Glucose clamp technique (maintainance of normoglycaemia by glucose infusion during insulin infusion). 4) TRH injection. Except for a minor inhibition of glucagon and pancreatic polypeptide following hypoglycaemic stimulation in one study, TRH had no significant effect on basal, stimulated or inhibited plasma glucagon, on insulin, somatostatin, pancreatic polypeptide or blood glucose. It is concluded that iv administration of TRH does not produce significant changes in peripheral plasma levels of pancreatic hormones. Application of techniques, which allow studies closer to the pancreatic islet, is probably necessary to assess the role of TRH in the regulation of endocrine pancreas.
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Jejunal biopsies and the postprandial response of pancreatic polypeptide (PP), gastrin, gastric inhibitory polypeptide (GIP), and somatostatin have been examined in nine patients with celiac disease before and 1 year after gluten withdrawal. All presented initially with total villous atrophy of the jejunal mucosa. After gluten withdrawal five showed marked mucosal regeneration on light microscopy examination (responders) and four only moderate or no regeneration (nonresponders). Before treatment the celiac patients had enhanced gastrin response and normal PP response compared with normal controls. After gluten withdrawal the integrated gastrin release was reduced to normal in the responders (275 versus 114; p less than 0.05) but remained elevated in the nonresponders (231 versus 204). Postprandial PP release was similar before and after treatment regardless of the degree of mucosal regeneration. In the responders the integrated release of GIP was increased (180 versus 241; p less than 0.05), and the somatostatin release was enhanced (-2.6 versus 8.4; p less than 0.05) after gluten withdrawal. We conclude that the postprandial release of GIP and somatostatin increases and that the release of gastrin decreases when the intestinal mucosa is regenerated in celiacs on a gluten-free diet. The release of PP after food is not influenced by mucosal regeneration.