Potential for improvement of docetaxel-based chemotherapy: a pharmacological review

Since the introduction of docetaxel, research has focused on various approaches to overcome treatment limitations and improve outcome. This review discusses the pharmacological attempts at treatment optimisation, which include reducing interindividual pharmacokinetic and pharmacodynamic variability, optimising schedule, route of administration, reversing drug resistance and the development of structurally related second-generation taxanes

Total Sulphur Content and N:S Ratio as Indicators for S Deficiency in Grasses

Recently, sulphur (S) deficiencies have been observed throughout Europe (Zaoh et al., 2002). Grassland covers about 50 % of the agricultural area in the European Union. In cutting regimes exports are ca 30 kg S/ha per year. Atmospheric depositions provide, at the present, ca15 kg S/ha per year and S is not considered in fertiliser programmes. Without fertilisation, the S balance at the field scale is negative and therefore some cut swards could be S deficient. Tools for determining whether the grassland is deficient are required. The utilisation of indicators based on S content and N:S ratio was investigated by using S deficient grasses produced in a controlled environment

Study of Soil Characteristics to Estimate Sulphur Supply for Plant Growth

During the last decades, sulphur (S) deficiencies have been observed throughout Europe (Zaoh et al., 2002). Accurate estimation of S supply by the soil-atmosphere system is required to give advice for S fertilisers. Soil is an important S source for plants and it is therefore important to evaluate supply by the soil to avoid deficiencies or excessive S fertilisation. The purpose of this preliminary study was to estimate which soil characteristics could be useful for predicting S supply by soil. Lolium multiflorum was grown on different soils in a growth chamber and S supply was correlated with soil characteristics

Design of the LHC Beam Dump Entrance Window

7 TeV proton beams from the LHC are ejected through a 600 m long beam dump transfer line vacuum chamber to a beam dump block. The dump block is contained within an inert gas-filled vessel to prevent a possible fire risk. The dump vessel and transfer line are separated by a 600 mm diameter window, which must withstand both the static pressure load and thermal shock from the passage of the LHC beam. In a previous paper [1] the functional requirements and conceptual design of this window were outlined. This paper describes the analysis leading to the final design of the window. The choice of materials is explained and tests performed on the prototype window are summarized

Tomographic imaging and scanning thermal microscopy: thermal impedance tomography

The application of tomographic imaging techniques developed for medical applications to the data provided by the scanning thermal microscope will give access to true three-dimensional information on the thermal properties of materials on a mm length scale. In principle, the technique involves calculating and inverting a sensitivity matrix for a uniform isotropic material, collecting ordered data at several modulation frequencies, and multiplying the inverse of the matrix with the data vector. In practice, inversion of the matrix in impractical, and a novel iterative technique is used. Examples from both simulated and real data are given

Effect of Short-Term Fasting on Systemic Cytochrome P450-Mediated Drug Metabolism in Healthy Subjects: A Randomized, Controlled, Crossover Study Using a Cocktail Approach

Background and Objective: Short-term fasting can alter drug exposure but it is unknown whether this is an effect of altered oral bioavailability and/or systemic clearance. Therefore, the aim of our study was to assess the effect of short-term fasting on oral bioavailability and systemic clearance of different drugs. Methods: In a randomized, controlled, crossover trial, 12 healthy subjects received a single administration of a cytochrome P450 (CYP) probe cocktail, consisting of caffeine (CYP1A2), metoprolol (CYP2D6), midazo

Feasibility of sedation and analgesia interruption following cannulation in neonates on extracorporeal membrane oxygenation

Purpose: In most extracorporeal membrane oxygenation (ECMO) centers patients are heavily sedated to prevent accidental decannulation and bleeding complications. In ventilated adults not on ECMO, daily sedation interruption protocols improve short- and long-term outcome. This study aims to evaluate safety and feasibility of sedation interruption following cannulation in neonates on ECMO. Methods: Prospective observational study in 20 neonates (0.17-5.8 days of age) admitted for ECMO treatment. Midazolam (n = 20) and morphine (n = 18) infusions were discontinued within 30 min after cannulation. Pain and sedation were regularly assessed using COMFORT-B and visual analog scale (VAS) scores. Midazolam and/or morphine were restarted and titrated according to protocolized treatment algorithms. Results: Median (interquartile range, IQR) time without any sedatives was 10.3 h (5.0-24.1 h). Median interruption duration for midazolam was 16.5 h (6.6-29.6 h), and for morphine was 11.2 h (6.7-39.4 h). During this period no accidental extubations, decannulations or bleeding complications occurred. Conclusions: This is the first study to show that interruption of sedatives and analgesics following cannulation in neonates on ECMO is safe and feasible. Interruption times are 2-3 times longer than reported for adult ICU patients not on ECMO. Further trials are needed to substantiate these findings and evaluate short- and long-term outcomes

In silico evaluation of limited sampling strategies for individualized dosing of extended half-life factor IX concentrates in hemophilia B patients

PURPOSE: Hemophilia B is a bleeding disorder, caused by a factor IX (FIX) deficiency. Recently, FIX concentrates with extended half-life (EHL) have become available. Prophylactic dosing of EHL-FIX concentrates can be optimized by assessment of individual pharmacokinetic (PK) parameters. To determine these parameters, limited sampling strategies (LSSs) may be applied. The study aims to establish adequate LSSs for estimating individual PK parameters of EHL-FIX concentrates using in silico evaluation. METHODS: Monte Carlo simulations were performed to obtain FIX activity versus time profiles using published population PK models for N9-GP (Refixia), rFIXFc (Alprolix), and rIX-FP (Idelvion). Fourteen LSSs, containing three or four samples taken within 8 days after administration, were formulated. Bayesian analysis was applied to obtain estimates for clearance (CL), half-life (t(1/2)), time to 1% (Time(1%)), and calculated weekly dose (Dose(1%)). Bias and precision of these estimates were assessed to determine which LSS was adequate. RESULTS: For all PK parameters of N9-GP, rFIXFc and rIX-FP bias was generally acceptable (range: −5% to 5%). For N9-GP, precision of all parameters for all LSSs was acceptable (< 25%). For rFIXFc, precision was acceptable for CL and Time(1%), except for t(1/2) (range: 27.1% to 44.7%) and Dose(1%) (range: 12% to 29.4%). For rIX-FP, all LSSs showed acceptable bias and precision, except for Dose(1%) using LSS with the last sample taken on day 3 (LSS 6 and 10). CONCLUSION: Best performing LSSs were LSS with samples taken at days 1, 5, 7, and 8 (N9-GP and rFIXFc) and at days 1, 4, 6, and 8 (rIX-FP), respectively

Transitions/relaxations in polyester adhesive/PET system

The correlations between the transitions and the dielectric relaxation processes of the oriented poly(ethylene terephthalate) (PET) pre-impregnated of the polyester thermoplastic adhesive have been investigated by differential scanning calorimetry (DSC) and dynamic dielectric spectroscopy (DDS). The thermoplastic polyester adhesive and the oriented PET films have been studied as reference samples. This study evidences that the adhesive chain segments is responsible for the physical structure evolution in the PET-oriented film. The transitions and dielectric relaxation modes’ evolutions in the glass transition region appear characteristic of the interphase between adhesive and PET film, which is discussed in terms of molecular mobility. The storage at room temperature of the adhesive tape involves the heterogeneity of the physical structure, characterized by glass transition dissociation. Thus, the correlation between the transitions and the dielectric relaxation processes evidences a segregation of the amorphous phases. Therefore, the physical structure and the properties of the material have been linked to the chemical characteristics