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  • 1
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anaphylactoid reactions in man following administration of drugs solubilized with cremophor El® (polyethylenglycolglycerol riconoleate) are a considerable clinical problem. Since these reactions occur in dogs on first exposure and in pigs on second exposure, the ‘dog model’ was used in this communication to analyse components and chemical modifications of cremophor El and its components for their clinical effects, their hypotensive actions and their histamine-releasing capacity. Two series of experiments in 1978 and 1980 were performed in 144 adult mongrel dogs of both sexes. In these studies histamine release wasnot related to the effect of the solubilizing agents as tensides and was elicited by rather low doses (about 10–100 mg/kg i.v.). The effect of these substances on blood pressure and on blood histamine levels was connected with distinct chemical features: the most potent compounds were oxethylated and additionally esterified unsaturated or hydroxylated fatty acids. Several phases in hypotensive reactions were observed, including an immediate response, a delayed blood pressure response and a late response about 15–20 min after injection. Only the delayed response was associated with histamine release. The combination of cardiovascular effects and histamine release was fatal on some occasions indicating that histamine release can be dangerous. Compared to cremophor El, the tenside effect was equal, but the toxicity was reduced in oxethylated 12-hydroxystearic acid. It is recommended that this solubilizer should be used in further extended studies in animals and — if these are successful—in clinical trials.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-2451
    Keywords: Pancreatitis ; Pfeffer-model modification ; Pathogenesis ; Lethality ; Pankreatitis ; Pfeffermodell-Modifikation ; Pathogenese ; Letalität
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Modifikationen des Pfeffermodells mit 100 cm langen Duodenalloop und frühzeitiger Wiedereröffnung des 20cm langen Duodenalloop - Occlusion durch Boeremaknopf - führen zur hämorrhagisch nekrotisierenden Pankreatitis. Letalität des kurzen geschlossenen Loop: 100 %, überlebenszeit 27 h. Deutliche Senkung der Letalität und Verlängerung der überlebenszeit durch die Modekationen. Der schon nach 12 h nachweisbaren intracelluldren Bakterienbesiedlung im Pankreas kommt eine causalpathogenetische Bedeutung dieses Krankheitsablaufes zu. Das Modell ist für Studien plastischer geworden.
    Notes: Summary Modification of the Pfeffer model with a duodenal loop of 100cm - the occlusion made by the Boerema button - and the early reopening of the 20-cm-long duodenal loop result in hemorrhagic necrotic pancreatitis. There is 100 % lethality with the short closed loop, the survival time being only 27 h. Through modifications lethality is clearly reduced and the survival time extended. The endocellular bacterial flora in the pancreas - already identifiable after 12 h - is of causal pathogenetic importance. The model is clearly better for studies.
    Type of Medium: Electronic Resource
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