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  • 1
    Electronic Resource
    Electronic Resource
    Uptake of Adriamycin in tumour and surrounding brain tissue in patients with malignant gliomas (1990)
    Springer
    Acta neurochirurgica 104 (1990), S. 13-16 
    Details
    ISSN: 0942-0940
    Keywords: Adriamycin ; malignant gliomas ; glioblastoma ; chemotherapy ; tissue concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Eight patients with malignant gliomas verified on CT scan, received an intravenous injection of 50 mg of Adriamycin R, 24 hours prior to surgical removal of the tumour. Peroperatively, both tumour and surrounding tissue specimens were obtained for determination of the tissue concentrations of Adriamycin and its reduced metabolite Adriamycinol. It was found that Adriamycin could be detected in tumour tissue from all patients. The concentration varied between 0,9 and 4,6 nmol/g tissue. In contrast, Adriamycin could only be detected in surrounding brain tissue from one patient. In anin vitro study a human malignant glioma cell line (U-251 MG) was exposed to various concentrations of Adriamycin for 24 hours. It was found that an intracellular drug concentration above 30 nmol/g cells caused a concentration dependent inhibition of cell growth. Thus, it is likely that the poor effect of Adriamycin on patients with malignant gliomas is due to an ineffective drug accumulation in the tumour tissue.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01842886
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  • 2
    Electronic Resource
    Electronic Resource
    Spontaneous reporting of suspected adverse reactions to antihistamines: a national and international perspective (1999)
    Oxford BSL : Blackwell Science Ltd
    Clinical & experimental allergy 29 (1999), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Twenty-one sedative and five non-sedating antihistamines are presently available on the UK market. Analysis of spontaneous reports of suspected adverse drug reactions was performed for those drugs with more than 90 reported reactions on the UK ADROIT database to the period ending 31 December 1997. Thus nine antihistamines, (four sedative antihistamines and five non-sedating antihistamines) were included. For each of the four sedative agents (azatidine, chlorpheniramine, diphenhydramine and trimeprazine), reactions associated with the cardiovascular, gastrointestinal, central nervous systems, the skin, general and psychiatric reactions made up more than 70% of total reported reactions. For all four agents, fatal reactions constituted less than 2.5% of total reactions. For each of the five non-sedating agents (acrivastine, astemizole, cetirizine, loratidine and terfenadine), reactions associated with the cardiovascular, gastrointestinal central nervous systems, the skin, general and psychiatric disorders together made up more than 75% of total reported reactions. For all five non-sedating agents, fatal reactions constituted less than 1% of total reactions. However, there were 21 reports of fatality in association with terfenadine, 11 (52%) of which were either sudden deaths or those associated with a cardiac rate of rhythm reaction. Analysis of the WHO database for non-sedating drugs showed a similar pattern, with terfenadine being associated with the highest frequency of reports of potentially serious arrhythmias and of sudden death and death related to disturbances of cardiac rate and rhythm combined. Despite the limitations of spontaneous reporting systems, comparison of the benefit–risk profiles of drugs using this data within a class of drugs can provide valuable information, and pharmacovigilance of antihistamines (and all other agents) using this and other means should continue for the lifetime of their use in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.1999.0290s3240.x
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  • 3
    Electronic Resource
    Electronic Resource
    The effect of non-contingent amphetamine injections on the extinction of food- and drug-reinforced lever pressing in rats
    Amsterdam : Elsevier
    Addictive Behaviors 2 (1977), S. 167-179 
    Details
    ISSN: 0306-4603
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine , Psychology
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0306-4603(77)90014-4
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  • 4
    Electronic Resource
    Electronic Resource
    Withdrawal reactions with selective serotonin re-uptake inhibitors as reported to the WHO system (1997)
    Springer
    European journal of clinical pharmacology 53 (1997), S. 163-169 
    Details
    ISSN: 1432-1041
    Keywords: Key words Selective serotonin re-uptake inhibitors ; Adverse drug reactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The present study was performed both to investigate whether there might be a difference between the selective serotonin re-uptake inhibitors, (SSRIs) with regard to the incidence of withdrawal reactions, and to describe the associated symptoms. From the WHO database, therefore, all case reports from the year of introduction for each of the SSRIs, fluoxetine, paroxetine and sertraline, were retrieved. Sales figures were obtained from Intercontinental Medical Statistics International. The reporting rates were calculated as the number of reports per million defined daily doses (DDDs) sold per year. Results: The reporting rate of withdrawal reactions for paroxetine was found to be higher than that for sertraline and fluoxetine in each of the countries selected for detailed analyses (US, UK and Australia), as well as for all 16 countries combined. Moreover, using the WHO system of organ classification, the ratio of central nervous system to psychiatric withdrawal symptoms was 1.9 and 2.1 for paroxetine and sertraline, respectively, whereas that for fluoxetine was 0.48, indicating a possible qualitative difference between the SSRIs with respect to the nature of the withdrawal syndrome.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050357
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  • 5
    Electronic Resource
    Electronic Resource
    A Bayesian neural network method for adverse drug reaction signal generation (1998)
    Springer
    European journal of clinical pharmacology 54 (1998), S. 315-321 
    Details
    ISSN: 1432-1041
    Keywords: Key words Adverse drug reactions ; Database
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The database of adverse drug reactions (ADRs) held by the Uppsala Monitoring Centre on behalf of the 47 countries of the World Health Organization (WHO) Collaborating Programme for International Drug Monitoring contains nearly two million reports. It is the largest database of this sort in the world, and about 35 000 new reports are added quarterly. The task of trying to find new drug–ADR signals has been carried out by an expert panel, but with such a large volume of material the task is daunting. We have developed a flexible, automated procedure to find new signals with known probability difference from the background data. Method: Data mining, using various computational approaches, has been applied in a variety of disciplines. A Bayesian confidence propagation neural network (BCPNN) has been developed which can manage large data sets, is robust in handling incomplete data, and may be used with complex variables. Using information theory, such a tool is ideal for finding drug–ADR combinations with other variables, which are highly associated compared to the generality of the stored data, or a section of the stored data. The method is transparent for easy checking and flexible for different kinds of search. Results: Using the BCPNN, some time scan examples are given which show the power of the technique to find signals early (captopril–coughing) and to avoid false positives where a common drug and ADRs occur in the database (digoxin–acne; digoxin–rash). A routine application of the BCPNN to a quarterly update is also tested, showing that 1004 suspected drug–ADR combinations reached the 97.5% confidence level of difference from the generality. Of these, 307 were potentially serious ADRs, and of these 53 related to new drugs. Twelve of the latter were not recorded in the CD editions of The physician's Desk Reference or Martindale's Extra Pharmacopoea and did not appear in Reactions Weekly online. Conclusion: The results indicate that the BCPNN can be used in the detection of significant signals from the data set of the WHO Programme on International Drug Monitoring. The BCPNN will be an extremely useful adjunct to the expert assessment of very large numbers of spontaneously reported ADRs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050466
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