Methods and findings in experimental and clinical pharmacology
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Two key factors are of main importance for the development of a common GCP legislation in the Member States of the European Community: 1) July 1991, Enforcement of the EEC Note for Guidance: "Good Clinical Practice for Trials on Medicinal Products in the European Community". This enforcement was setting into operation GCP guidelines which were, however, not yet legally binding at that time. 2) January 1992, Enforcement of EEC Commission, Directive 91/507/EEC: Analytical, pharmacotoxicological and clinical standards and protocols in respect of the testing of medicinal products. By this enforcement the EEC Member States were obliged to bring into force the laws, regulations and administrative provisions necessary to comply with the Directive which requests--besides others--all clinical trials to be designed, implemented and recorded in accordance with GCP. ⋯ Country by country this has to be regulated soon by appropriate measures of the legislators in order to establish a uniform standard which will assure clinical trials to be internationally acceptable. Only recently the CPMP introduced the requirement for a "Compliance with GCP" Statement as an indispensable part of the Clinical Expert Reports in registration documentations. Even more than in legislation, there is a lack of inspections in clinical trials by health authorities in most European countries.(ABSTRACT TRUNCATED AT 250 WORDS)
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Methods Find Exp Clin Pharmacol · Apr 1993
Case ReportsProconvulsant effect of ketotifen, a histamine H1 antagonist, confirmed by the use of d-chlorpheniramine with monitoring electroencephalography.
Ketotifen produced seizures in a 5-year-old boy with secondary generalized epilepsy (SGE) and allergic rhinitis. To confirm that the seizures were due to histamine H1 receptors blockade, d-chlorpheniramine was administered with monitoring electroencephalography (EEG). Administration of d-chlorpheniramine significantly increased the number of epileptic discharges in the patient, compared with those before administration. ⋯ Recently, several experimental reports have shown that histamine has an inhibitory role on convulsions through histamine H1 receptors. Experimental findings and present results show that histamine H1 antagonists have proconvulsant effects, especially in the developmental period. Thus, it is recommended that centrally-acting histamine H1 antagonists should be avoided in epileptic patients, especially in children of pre-school age.
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Methods Find Exp Clin Pharmacol · May 1992
Water: mechanism of oral rehydration, water deficiency = deficiency in salt.
UNICEF, the United Nations International Children Emergency Funds, has staged an enormous program to improve children's health conditions in the developing countries. One extremely fruitful field of engagement was, and still is, the treatment of dehydration. Oral rehydration therapy (ORT) has reluctantly been accepted in the industrialized countries. ⋯ We discuss additional causes of dehydration and its immediate and secondary consequences. We demonstrate not only that, but why and how, a very simple, inexpensive regimen is beneficial and effective in the treatment of dehydration. Without consideration of sodium deficit, understanding will fail, and treatment will remain ineffective.
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Methods Find Exp Clin Pharmacol · Nov 1990
A pharmacological model of cerebral ischemia. The effects of indomethacin on cerebral blood flow velocity, quantitative EEG and cognitive functions.
Indomethacin decreases cerebral blood flow. Such an effect in humans might offer the possibility to establish a human model of cerebral ischemia. In the present study the effects of a single oral dose of 100 mg indomethacin were studied in male subjects with quantitative electroencephalography, cerebral blood flow velocity and the memory comparison task as parameters. ⋯ Ninety minutes after indomethacin ingestion recordings of quantitative electroencephalography and blood flow velocity were repeated and a parallel version of the memory comparison task was performed. The blood flow velocity decreased to 60% of the initial value; quantitative electroencephalography showed a -0.3 Hz slowing of the alpha peak frequency (p less than 0.01) and a decrease in the relative power of the alpha band (p less than 0.10) without any change in the delta or theta band. The memory comparison task showed an increase of the slope index (p less than 0.05), indicating a deterioration of cognitive functioning.
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Methods Find Exp Clin Pharmacol · Feb 1989
Comparative StudyAcceptability of visual analogue scales in the clinical setting: a comparison with verbal rating scales in postoperative pain.
Pain is the clinical symptom most difficult to evaluate. Although clinical trials methodology have permitted assessment of pain objectively through rating scales, these strategies have not been used in clinical setting. The present study was undertaken to determine if visual analogue scales could be useful in the measurement of postoperative pain in usual medical practice. ⋯ The VAS of patients and researchers were also found to be highly correlated (p less than 0.001). When values of each group were compared by pain intensity a total agreement of VAS scores at low pain level could be established, but differences were found at high pain intensity levels, suggesting that physicians scored lower than patients when pain was severe to unbearable. It is concluded that VAS could be a reliable method to assess pain in clinical setting.