Field investigations of lateral gas transport and subsequent emissions in soil adjacent to an old landfill in Denmark have been conducted during a one-year period. A significant seasonal variation in the emissions with high carbon dioxide and low methane fluxes in the summer (May to October) was observed. This was attributed to methane oxidation. Diumal measurements during a drop in barometric pressure showed that the fluxes of landfill gas changed dramatically within a very short time. The concentrations and the soil moisture content in the upper part of the soil profile had significant influence on the fluxes, as did the distance from the landfill border, temperature, barometric pressure and the pressure gradient. Statistical analyses proved that soil moisture described the largest part of the variation. No methane at all emitted during the summer. Calculations and isotope analyses showed that very high fractions of the laterally migrating methane were oxidised.
Field investigations of lateral gas transport and subsequent emissions in soil adjacent to an old landfill in Denmark were conducted during a 1-year period. A significant seasonal variation in the emissions with high carbon dioxide and low methane fluxes in the summer (May to October) was observed. This was attributed to methane oxidation. Diurnal measurements during a drop in barometric pressure showed that the fluxes of landfill gas changed dramatically within a very short time. The concentrations and the soil moisture content in the upper part of the soil profile had significant influence on the fluxes, as did the distance from the landfill border, temperature, barometric pressure and the pressure gradient. Statistical analyses proved that soil moisture described the largest part of the variation. No methane is emitted during the summer. Calculations and isotope analyses showed that very high fractions of the laterally migrating methane were oxidised.
To attain effective and safe pharmacotherapy, formulations in (pre)term neonates should enable extensive dose flexibility. During product development and subsequent authorization and clinical use of such formulations, there is also a need for informed decisions on excipient exposure: in addition to the need to improve the knowledge on active compounds, there is a similar need to improve the knowledge on excipients in neonates. Excipients are added to formulations as co-solvent, surfactant, preservative, colorant and/or sweetener as vehicle(s) to result in a suitable (e.g. taste, shelf life, stability) product. Progress has been made in the awareness, knowledge and access to this knowledge on the clinical pharmacology of excipients in neonates. This is thanks to different initiatives focussing on epidemiological data, excipient pharmacokinetics, or building datasets to create this knowledge. We highlight the Safe Excipient Exposure in Neonates and Small Children (SEEN) and propylene glycol project to illustrate the feasibility to build knowledge, and discuss the methods applied and problems observed during these studies. The information generated in these and other studies (European Study on Neonatal Exposure to Excipients, ESNEE) should be integrated in repositories like the Safety and Toxicity of Excipients for Paediatrics (STEP) to facilitate access to all stakeholders. This merged knowledge should have impact and assist in improving the quality of risk assessment and decision making during drug development, applying a risk-benefit framework (explicit justification of excipients, plan product development early and engage all stakeholders, data sharing and modeling, challenges related to new excipients, context sensitive risk-benefit analysis).
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 an in 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.
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