Een patient met gecompliceerd verlopende shigellose

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Treatment of invasive aspergillosis with itraconazole in a patient with chronic granulomatous disease

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Protection of neutropenic mice from lethal Candida albicans infection by recombinant interleukin-1

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Biological and biochemical characterization of clinical isolates of herpes simplex virus type 2 resistant to acyclovir

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Титульні сторінки та зміст

The pharmaceutical industry is increasingly focusing on the development of biological therapeutics. These molecules generally cause no off-target toxicity and are highly species specific. Therefore, non-human primates (NHPs) are often the only relevant species in which to conduct regulatory safety testing to support clinical trials. However, species specificity and immunogenicity may negatively impact the predictive value of these ethically contentious animals and thus limits their value as a test species for drug development. To study what the value has been of 30 years of NHP testing in drug development, we investigated the drug registration files of all therapeutic monoclonal antibodies (mAbs) which were approved in the European Union to date. We analysed 30 mAbs of which 5 were diagnostic agents. As the industry moved towards the development of more human proteins, we observed that the average use of NHPs also increased. 16 registration files described studies in which anti-drug-antibodies caused increased clearance of the therapeutic and potentially confounded the study. Post mortem analysis in repeated-dose toxicity studies rarely revealed new or unexpected findings nor did embryofetal and peri-postnatal developmental toxicity studies. These issues limited the value of NHPs in the safety assessment of new monoclonal antibodies. To reduce the use of less relevant NHP studies in the development of new biological drugs, regulatory demands might be decreased, and manufacturers should be given incentives for successfully evaluating the safety of biological therapeutics using alternative technologies

The efficacy of itraconazole against systemic fungal infections in neutropenic patients : a randomised comparative study with amphotericin B

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Visie op toekomstig onderzoek naar gasvormige emissies uit de Nederlandse veehouderij

De Nederlandse veehouderij bevindt zich op een belangrijk kruispunt: de veehouderij kan niet aan consumenten- en milieuwensen voldoen en tegelijkertijd voortgaan op de huidige weg. Een belangrijke vraag is hoe milieubelasting door gasvormige emissies (ammoniak, geur, broeikasgassen (lachgas, methaan en kooldioxide) en fijn stof) uit de veehouderij kan worden teruggedrongen in een nieuw vormgegeven veehouderij, die bijdraagt aan de ontwikkeling van een duurzame Nederlandse landbouw. Om inzicht te krijgen in de vraag welk onderzoek hiervoor noodzakelijk is een onderzoek uitgevoerd met als doel een visie te ontwikkelen op toekomstig onderzoek naar gasvormige emissies uit de Nederlandse Veehouderij. Belangrijke informatie voor de vorming van deze visie is verzameld uit interviews met verschillende maatschappelijke groeperingen

Dynamics of vibrofluidized granular gases in periodic structures

The behavior of a driven granular gas in a container consisting of $M$ connected compartments is studied employing a microscopic kinetic model. After obtaining the governing equations for the occupation numbers and the granular temperatures of each compartment we consider the various dynamical regimes. The system displays interesting analogies with the ordering processes of phase separating mixtures quenched below the their critical point. In particular, we show that below a certain value of the driving intensity the populations of the various compartments become unequal and the system clusterizes. Such a phenomenon is not instantaneous, but is characterized by a time scale, $\tau$, which follows a Vogel-Vulcher exponential behavior. On the other hand, the reverse phenomenon which involves the ``evaporation'' of a cluster due to the driving force is also characterized by a second time scale which diverges at the limit of stability of the cluster.Comment: 11 pages, 17 figure

Immune reactivity in relationto cytomegalovirusinfection after allogeneic bone marrow transplantation

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