Preparation and evaluation of paclitaxel-containing liposomes.

Paclitaxel, an antitumoral drug, is poorly soluble in aqueous media. Therefore, in a commercialised formulation (Taxol), paclitaxel (30 mg active compound) is dissolved in polyethoxylated castor oil (Cremophor EL) and ethanol. After dilution of Taxol in aqueous media paclitaxel tends to precipitate. Several side effects, attributed to the surfactant Cremophor EL, occur, e.g. bronchospasm, hypotension, neuro- and nephrotoxicity, and anaphylactic reactions. To eliminate these side effects, the solubility of paclitaxel was enhanced using liposomes instead of Cremophor EL. The amount of entrapped paclitaxel in crystal-free liposomes was 0.5 mg/ml liposome suspension, i.e. almost 85 times the native solubility. Thus, 30 mg paclitaxel had to be dissolved in 60 ml liposome suspension, of either multi-lamellar vesicles (MLV's) or of small unilamellar vesicles (SUV's) with 5% sucrose as cryoprotector. No precipitation was observed after dilution of the MLV-formulation with (physiological) water or with 5% aqueous dextrose solution, which proves their suitability for administration with perfusions. The chemical stability of paclitaxel in the prepared MLV's stored at 4 degrees C was demonstrated during a period of 5 months. The chemical degradation to conjugated dienes and hydroperoxides, two oxidative degradation products of EPC, was negligible (less than 1%).

Text cohesion and metacomprehension: immediate and delayed judgments.

In three experiments, we examined comprehension judgments made after a piece of text had been read. We propose that such metacognitive judgments are based on the content of working memory at the exact moment of assessment. Generally speaking, this working metacognition hypothesis is in agreement with Koriat's cue utilization approach, which implies that different elements of information will be available (and used) depending on the moment at which a judgment is made. More specifically, our hypothesis focuses on the management of working memory during reading as a cause for cue (un)availability. In support of these views, the results of Experiment 1 showed that a cohesion manipulation affecting the comprehension of specific paragraphs influences judgments only on these paragraphs, and not on judgments on the whole text. In Experiment 2, we showed that an interfering task that takes place just before this paragraph judgment is made wipes out this cohesion effect. Experiment 3 showed, on the other hand, that the whole-text judgment may, nevertheless, be affected by text cohesion, provided that the readers keep an access to the text when the judgment is made. These results support the idea that working memory management makes different cues available for metacognitive ratings at different delays.

The abstraction of a central tendency in amnesic patients.

Amnesic patients and control subjects were asked to reproduce arm movements of a given amplitude and to average amplitudes on series of three such movements. The error in averaging was found to be equal in patients and control subjects while reproduction performance was clearly affected by amnesia. The implications of these data for a theory of amnesia are briefly discussed.