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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 42 (1992), S. 389-393 
    ISSN: 1432-1041
    Keywords: Adverse events ; Phase I studies ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary All the clinical, laboratory and electrocardiographic adverse events detected during 24 Phase I studies in the same unit over a 5 y period are reported here. 430 healthy male volunteers were involved, corresponding to 5488 days of follow-up. The overall incidence of adverse events was 13.5%, with a significant difference between active drug (15.3%) and placebo (7.4%) treatments. There were 69 distinct types of adverse events. Headache was the most frequent symptom (2%). There were severe adverse events in 20 cases (0.36%), with an incidence of 20/430 per subject (4.6%). There were no deaths or life-threatening events. Although the main objective of Phase I studies is to determine the maximum dose tolerated, cause-effect relationships with adverse events are hard to establish, because of the frequency of adverse events with placebo, and because of the limited number of subjects included such studies.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Clinical and experimental medicine 154 (1971), S. 87-100 
    ISSN: 1591-9528
    Keywords: Portacaval shunting ; Liver and glucose tolerance ; Liver and insulin ; Intestinal hormones and insulin release ; Porta cava-Anastomose ; Leber- und Glucose-Toleranz ; Leber und Insulin ; Intestinale Hormone und Insulinsekretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die vorliegende Arbeit schafft die Grundlagen für eine systematische Untersuchung der physiologischen Bedeutung der Gegebenheit, daß aus dem gastrointestinalen Trakt stammendes Blut die meisten Gewebeindirekt, erst nach Filtrierung in der Leber erreicht. Hierzu wurden Ratten mit Porta cava-Anastomosen benutzt, wobei vorerst über 140 Tiere dazu dienten, die technische Durchführbarkeit der Operation sowie den allgemeinen Gesundheitszustand der über viele Monate beobachteten operierten Tiere zu beurteilen. Vorausgesetzt, daß wirklich alle Tiere, bei denen während der Operation Zweifel an der Funktionstüchtigkeit der Anastomose entstehen, sofort verworfen werden, erwies sich das Vorgehen als befriedigend. Insbesondere konnte die gute Funktion der Anastomose über viele Monate dargestellt werden, während keine Hinweise auf portale Hypertonie, auf das Entstehen einer collateralen Zirkulation oder irgendwelche morphologisch erfaßbare Leberpathologie erkannt werden konnten. Das Lebergewicht war, wie zu erwarten, um etwa ein Dritte] vermindert. Während der ersten 2 Wochen nach der Operation nahm das Körpergewicht um 5–10% ab, Gewichtszunahme stellte sich hiernach wieder ein, und zwar etwa parallel der Gewichtszunahme von leer-operierten oder Kontrolltieren. Die anfängliche Gewichtsabnahme ließ sich auf verminderte Nahrungszufuhr, ohne verminderte Resorption zurückführen. Genau kontrollierte Bedingungen der Haltung der operierten Tiere sind notwendig, um eine so bescheidene und nur vorübergehende Gewichtsabnahme sowie einen allgemein guten Gesundheitszustand zu erreichen. Die gewählte Operationstechnik und die für die Haltung der operierten Tiere gewählten Bedingungen scheinen sich somit für systematische Untersuchung der Stoffwechselfolgen von Porta cava-Anastomosen gut zu eignen.
    Notes: Summary In order to study systematically the physiologic significance of blood from the gastrointestinal tract reaching most tissuesindirectly, after prior exposure to the liver, end-to-side portacaval shunting was carried out in rats. A technique derived from that described by Lee and Fisher was evaluated in more than 140 animals, first as to general applicability and its effects on overall health, body weight, food intake, intestinal absorption and hepatic morphology. In the hands of the authors, and provided that all animals where any doubt as to the patency of the shunt arises during operation are immediately discarded, the procedure used proved reproducible and satisfactory. Specifically, there was good evidence for continued shunt patency for many months postoperatively, while there was no evidence for portal hypertension, for significant collateral circulatory bypass of the shunt, or for hepatic pathology, although liver weight was diminished by about one third, as expected. After an initial loss of 5 to 10% in body weight during the first 2 weeks postoperatively, weight gain resumed and paralleled that in the sham-operated and control animals. The initial weight loss resulted from decreased food intake, not from decreased absorption of one or several components of the diet. The importance of precisely controlled environmental conditions for achieving such limited initial weight loss with prompt resumption of weight gain and good general health has been stressed. The operative procedure used and the conditions selected for the subsequent maintenance of the portacaval shunted animals would thus appear well-suited to the systematic and more detailed analysis of the metabolic and endocrine consequences of portacaval shunting in the rat.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0584
    Keywords: Amyloidosis ; Monoclonal protein ; Immunoglobulins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Among 55 amyloidoses, the detection of a monoclonal protein (MP) led to the selection of 15 primary and 3 myeloma-associated types of amyloidosis. Therefore the presence of a MP gives evidence for an immunocytic amyloidosis. The λ-light-chain nature of MP and the abundant production of free light-chains are two of the factors predisposing to the production of amyloid deposits (AL) in the course of immunocyte dyscrasias.
    Type of Medium: Electronic Resource
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