[Expert physicians in the Swiss mountain rescue service].
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Biomedical subjects
Publications and source records attributed to L Helleberg.
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Sixty-seven patients with rheumatic disease, treated with non-steroidal anti-inflammatory drugs (NSAIDs), entered a controlled trial with a diagnosis of duodenal (n = 51), gastric (n = 14), or gastric and duodenal (n = 2) ulcers. The main objectives of the study were a comparison of ranitidine and sucralfate in ulcer treatment, and to observe the influence of continued NSAID administration during peptic ulcer therapy. Ulcers healed within nine weeks in 52 patients. The mean healing time was similar in 27 patients given ranitidine 150 mg bd (4.9 weeks) and 25 patients given sucralfate 1 g qid (4.6 weeks). In patients with unhealed ulcers after nine weeks of treatment, healing was obtained in seven after further therapy for 3-9 weeks. Of the 30 patients who continued NSAIDs during treatment with either ranitidine or sucralfate, 23 ulcers healed (mean healing time: 5.0 weeks). Of 32 patients in whom NSAIDs were stopped, ulcer healing was documented in 29 (mean healing time: 4.6 weeks). The difference in healing rates was not statistically significant (p greater than 0.10). The outcome of ulcer treatment did not differ in patients with rheumatoid arthritis and patients suffering from osteoarthritis. During a 12 month follow up 14 symptomatic ulcer recurrences were recorded.
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Indomethacin (1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid) is an anit-in-flammatory antipyretic drug commonly used for symptomatic relief of pain and stiffness in rheumatic diseases. Following oral administration the absorption of the drug is rapid and complete, but with important inter-and intraindividual variations. In general, peak plasma concentrations of 2 to 3 microgram/ml are achieved with 1 to 2 hours, but concomitant ingestion of food reduces and delays the peak concentrations without reducing the amount absorbed. Rectal administration is associated with earlier but lower peak plasma concentrations, incomplete absorption form suppositories, and offers no clinical advantages when compared with equivalent oral dosage. In plasma at 90% of indomethacin is bound to albumin at therapeutic plasma concentrations. Indomethacin is distributed into the synovial fluid, is excreted in human breast milk and crosses the placenta in significant amounts. It is metabolised to O-desmethylindomethacin, N-deschlorobenzoylindomethacin and O-desmethy-N-deschlorobenzoylindomethacin, which are devoid of anti-inflammatory activity and are present in significant amount in the plasma. About 60% of an oral dose is excreted in the urine predominantly in glucuronidated form, while about 40% is excreted in the faeces after biliary secretion. A large amount of the dose undergoes biliary recycling. The biotransformation is independent of the route of administration. A 2-compartment open model with correction for biliary recycling can be used to describe the disposition of indomethacin. The drug has a biological half-life of about 5 to 10 hours and a plasma clearance of 1 to 2.5ml/kg/min. In premature infants the half-life of indomethacin is inversely correlated with gestational age and is significantly prolonged as compared with adults. Renal failure does not affect the serum concentrations of indomethacin. Probenecid results in increased plasma concentrations of indomethacin with enhanced pain relief without increasing the incidence of side effects. There seem to be no significant pharmacokinetic interactions between indomethacin and aspirin or warfarin. To date it has not been possible to identify a relationship between the clinical effects and plasma concentration of indomethacin.