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  • 1
    ISSN: 1619-7089
    Keywords: Alphafetoprotein ; Cirrhosis ; Hepatocellular carcinoma ; Immunoscintigraphy ; Monoclonal antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The actual interest of immunoscintigraphy for the detection of liver tumours was investigated by both visual examination and quantitative analysis in 41 patients with hepatoma (HCC, 21 cases, 13 AFP-secreting), other primary or secondary liver cancer (9 cases), testicular cancer (2 cases) and cancer free cirrhosis (9 cases). All patients were injected with 123I-anti-alphafetoprotein (AFP) monoclonal antibodies (MAbs) and scans were performed after 28±2 h. In the hepatoma-bearing patients, 11 positive anti AFP scans were found; 9 of them had an enhanced serum; besides, 3 non HCC tumours were also detected. With respect to hepatoma diagnosis, sensitivity was 52.5% and specificity 66.5%. For all hepatomas, it was striking that the positivity rate was 2/10 and 9/11, respectively, when HCC was and was not associated with cirrhosis. Among 6 patients with a positive anti AFP scan who were also injected with control anti hCG 123I-MAb, 5 positive anti hCG scans were surprisingly found, with specificity indices ranging between 1.00 and 1.75. The quantitative study also highlighted the importance for hepatoma detection of specific and non specific factors such as serum AFP, tumoural vascularization, non tumoural liver uptake and intrahepatic distribution of HCC. Anti AFP immunoscintigraphy appears as a poorly sensitive and moderately specific method for hepatoma diagnosis. In contrast, non tumoural liver uptake level could be more useful for discriminating HCC from liver metastases and perhaps to detect the early extension of HCC.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-904X
    Keywords: allometric scaling ; interspecies scaling ; pharmacokinetics ; clearance ; in vitro models ; bosentan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The goal of this study was to find a rational and reliable method of using animal data to predict the clearance of metabolised drugs in humans. Methods. One such approach is to use in vitro liver models (e.g. hepatocytes and microsomes) to determine the relative capacities of the various animal species and humans to metabolise the test compound. These data can then be combined with the in vivo clearances in animals, to calculate the in vivo clearance in humans using allometric scaling techniques. In this study, this approach was evaluated with a new endothelin receptor antagonist, bosentan, which is eliminated mainly through metabolism and is characterized by very large interspecies differences in clearance. Therefore, this compound provided a stringent test of our new extrapolation method for allometric scaling. Results. The results obtained with bosentan showed that adjusting the in vivo clearance in the different animal species for the relative rates of metabolism in vitro gave a far better prediction of human clearance than an empirical correcting factor (brain weight). Conclusions. This approach provided a more rational basis for predicting the clearance of metabolised compounds in humans.
    Type of Medium: Electronic Resource
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