SCH 66336 can be administered safely using a continuous oral bid dosing regimen. The recommended dose for phase II studies using this regimen is 200 mg bid.

Myelosuppression is the predominant toxicity of E7070. Clinical efficacy with E7070 was observed. The recommended dose for further studies at this daily times five schedule is 130 mg/m2/day.

No abstract

Anticipatory control of motor output enables fast and fluent execution of movement. This applies also to motor tasks in which the performance of movement brings about a disturbance to balance that is not completely predictable. For example, in bi-manual lifting the pick-up of a load causes a forward shift of the centre of mass with consequent disturbance of posture. Anticipatory postural adjustments are scaled to the expected magnitude of the perturbation and are initiated well before the availability of sensory information characterising the full nature of the postural disturbance. However, when the postural disturbance unexpectedly changes, the anticipatory adjustment of joint torques is not equilibrated and may result in a disturbance to balance. In a previous study, it was demonstrated that apart from anticipatory postural adjustments, corrective responses after load pick-up are used to further compensate the postural disturbance. In this study it was examined whether the central nervous system (CNS) assembles a strategy that incorporates both anticipatory control and corrective responses, in which the magnitude of the anticipatory postural adjustments depends on the perceived level of predictability of the postural disturbance. Subjects performed series of lifts in which the magnitude of the load was never revealed to the subject. Two boxes equal in size and colour, but different in mass (6 and 16 kg), were used. Differences in expectation were created by several lifts with the 16-kg load before the 6-kg box was presented. It was observed that the number of strong corrective responses (stepping) varied with the number of 16-kg trials that formed the prior experience when the final 6-kg trial was presented. The follow-up question was whether control relied more on anticipation in the stepping trials, compared with trials in which such gross signs of imbalance were absent. In this study it was shown that subjects when stepping (i) exhibited differential anticipatory postural adjustments in comparison with 6-kg trials in which expectation was not shaped by preceding 16-kg trials, and (ii) scaled the anticipatory postural adjustments similar to those preceding lift-off of the 16-kg trial preceding it. These findings emphasise the programmed nature of the anticipatory postural adjustments and the ability of the CNS to selectively tune the anticipatory postural adjustments to stored information gained during the previous lift(s).

No abstract