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  • Pharmacology  (2)
  • Liver tumours  (1)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric surgery international 3 (1988), S. 382-395 
    ISSN: 1437-9813
    Keywords: Liver tumours ; Children ; Incidence ; Pathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This paper reviews the incidence and pathology of liver tumours in children in the State of Victoria from 1955 to 1987. Seventy-four cases were found and are believed to represent all liver tumours in the State during that time. There were 29 benign and 45 malignant tumours. The benign tumours comprised 13 haemangiomas, 12 mesenchymal hamartomas, and 4 epithelial lesions. The malignant tumours were 30 hepatoblastomas, 8 embryonal sarcomas, 4 hepatocellular carcinomas, and 3 miscellaneous tumours. The haemangiomas were more commonly cavernous. Four were associated with skin lesions and 3 of these were capillary in type. Mesenchymal hamartomas varied from predominantly solid to predominantly cystic. All, however, contained hamartomatous collections of ducts and liver cells irregularly arranged in dense fibrous tissue. The commonest malignant tumour was hepatoblastoma, and there were 15 of predominantly epithelial type and 15 of mixed epithelial and mesenchymal type. The 8 undifferentiated sarcomas of embryonal pattern were characterised by pleomorphism of cells, bizarre giant cells, and extensive mucoid stromal change. Four examples of hepatocellular carcinoma were seen. All were multifocal and no further case has been seen for the last 15 years. The 3 miscellaneous tumours were gastrinoma, rhabdoid tumour, and myofibroblastic tumour of uncertain histogenesis. Incidence was calculated for the period of review. The rate for benign tumours was 0.81 per million children per year and for malignant tumours 1.33 per million children per year. Surgery for hepatobalstoma was shown to be the most important factor in improving survival.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0843
    Keywords: Etoposide ; Pharmacology ; Breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pharmacokinetics and pharmacodynamics of prolonged oral etoposide chemotherapy were investigated in 15 women with metastatic breast cancer who received oral etoposide 100 mg as a single daily dose for up to 15 days. There was considerable interpatient variability in the day 1 pharmacokinetic parameters: area under the plasma concentration time curve (AUC) (0–24 h) 1.95±0.87 mg/ml per min (mean ± SD), apparent oral clearance 60.9±21.7 ml/min per 1.73 m2, peak plasma concentration 5.6±2.5 μg/ml, time to peak concentration 73±35 min and half-life 220±83 min. However, intrapatient variability in systemic exposure to etoposide was much less with repeated doses. The intrapatient coefficient of variation (CV) of AUC for day 8 relative to day 1 was 20% and for day 15 relative to day 1 was 15%, compared to the day 1 interpatient CV of 45%. Neutropenia was the principal toxicity. Day 1 pharmacokinetic parameters were related to the percentage decrease in absolute neutrophil count using the sigmoidal Emax equation. A good fit was found between day 1 AUC and neutrophil toxicity (R 2=0.77). All patients who had a day 1 AUC〉2.0 mg/ml per min had WHO grade III or IV neutropenia. The predictive performance of the models for neutrophil toxicity was better for AUC (percentage mean predictive error 5%, percentage root mean square error 18.1%) than apparent oral clearance, peak plasma concentration, or daily dose (mg/m2). A limited sampling strategy was developed to predict AUC using a linear regression model incorporating a patient effect. Data sets were divided into training and test sets. The AUC could be estimated using a model utilizing plasma etoposide concentration at only two time points, 4 h and 6 h after oral dosing (R 2=98.9%). The equation AUCpr=−0.376+0.631×C4h+0.336×C6h was validated on the test set with a relative mean predictive error of −0.88% and relative root mean square error of 6.4%. These results suggest monitoring of AUC to predict subsequent myelosuppression as a strategy for future trials with oral etoposide.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0843
    Keywords: Key words Etoposide ; Pharmacology ; Breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The pharmacokinetics and pharmacodynamics of prolonged oral etoposide chemotherapy were investigated in 15 women with metastatic breast cancer who received oral etoposide 100 mg as a single daily dose for up to 15 days. There was considerable interpatient variability in the day 1 pharmacokinetic parameters: area under the plasma concentration time curve (AUC) (0–24 h) 1.95±0.87 mg/ml per min (mean±SD), apparent oral clearance 60.9±21.7 ml/min per 1.73 m2, peak plasma concentration 5.6± 2.5 μg/ml, time to peak concentration 73±35 min and half-life 220±83 min. However, intrapatient variability in systemic exposure to etoposide was much less with repeated doses. The intrapatient coefficient of variation (CV) of AUC for day 8 relative to day 1 was 20% and for day 15 relative to day 1 was 15%, compared to the day 1 interpatient CV of 45%. Neutropenia was the principal toxicity. Day 1 pharmacokinetic parameters were related to the percentage decrease in absolute neutrophil count using the sigmoidal Emax equation. A good fit was found between day 1 AUC and neutrophil toxicity (R 2=0.77). All patients who had a day 1 AUC 〉2.0 mg/ml per min had WHO grade III or IV neutropenia. The predictive performance of the models for neutrophil toxicity was better for AUC (percentage mean predictive error 5%, percentage root mean square error 18.1%) than apparent oral clearance, peak plasma concentration, or daily dose (mg/m2). A limited sampling strategy was developed to predict AUC using a linear regression model incorporating a patient effect. Data sets were divided into training and test sets. The AUC could be estimated using a model utilizing plasma etoposide concentration at only two time points, 4 h and 6 h after oral dosing (R 2=98.9%). The equation AUCpr=−0.376+ 0.631×C4h+0.336×C6h was validated on the test set with a relative mean predictive error of −0.88% and relative root mean square error of 6.4%. These results suggest monitoring of AUC to predict subsequent myelosuppression as a strategy for future trials with oral etoposide.
    Type of Medium: Electronic Resource
    Location Call Number Limitation Availability
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