Feasibility of iterative learning control mediated by functional electrical stimulation for reaching after stroke.

BACKGROUND: An inability to perform tasks involving reaching is a common problem following stroke. Evidence supports the use of robotic therapy and functional electrical stimulation (FES) to reduce upper limb impairments, but current systems may not encourage maximal voluntary contribution from the participant because assistance is not responsive to performance. OBJECTIVE: This study aimed to investigate whether iterative learning control (ILC) mediated by FES is a feasible intervention in upper limb stroke rehabilitation. METHODS: Five hemiparetic participants with reduced upper limb function who were at least 6 months poststroke were recruited from the community. No participants withdrew. INTERVENTION: Participants undertook supported tracking tasks using 27 different trajectories augmented by responsive FES to their triceps brachii muscle, with their hand movement constrained in a 2-dimensional plane by a robot. Eighteen 1-hour treatment sessions were used with 2 participants receiving an additional 7 treatment sessions. OUTCOME MEASURES: The primary functional outcome measure was the Action Research Arm Test (ARAT). Impairment measures included the upper limb Fugl-Meyer Assessment (FMA), tests of motor control (tracking accuracy), and isometric force. RESULTS: Compliance was excellent and there were no adverse events. Statistically significant improvements were measured (P

A robotic workstation for stroke rehabilitation of the upper extremity using FES.

An experimental test facility is developed for use by stroke patients in order to improve sensory-motor function of their upper limb. Subjects are seated at the workstation and their task is to repeatedly follow reaching trajectories that are projected onto a target above their arm. To do this they use voluntary control with the addition of electrical stimulation mediated by advanced control schemes applied to muscles in their impaired shoulder and arm. Full details of the design of the workstation and its periphery systems are given, together with a description of its use during the treatment of stroke patients.

Specific inhibition of the endothelin A receptor with ZD4054: clinical and pre-clinical evidence.

Activation of the endothelin A receptor (ET(A)) by endothelin-1 (ET-1) mediates events that regulate mitogenesis, apoptosis, angiogenesis and metastasis in tumours. Specific blockade of ET(A) may have anticancer effects, while retaining beneficial endothelin B receptor (ET(B))-mediated effects such as apoptosis and clearance of ET-1. ZD4054 is an orally active, specific ET(A) antagonist in clinical development. In receptor-binding studies, ZD4054 specifically bound to ET(A) with high affinity; no binding was detected at ET(B). In a randomised placebo-controlled trial in eight healthy volunteers, a single oral dose of ZD4054 reduced forearm vasoconstriction in response to brachial artery infusion of ET-1, thus providing clinical evidence of ET(A) blockade. ET(B) blockade was assessed in an ascending, single-dose, placebo-controlled trial in 28 volunteers. For all doses of ZD4054, mean plasma ET-1 concentrations measured at 4 and 24 h were within the placebo reference range (a rise in ET-1 would indicate ET(B) blockade) and there was no evidence of dose-related changes. These data confirm the specificity of ZD4054 for ET(A), with no activity at ET(B) in a clinical or preclinical setting. As a result of this specificity, ZD4054 has the potential to block multiple ET(A)-induced pathological processes, while allowing beneficial ET(B)-mediated processes to continue, which may, in turn, lead to an effective cancer therapy.

Effects of zolmitriptan (Zomig) on central serotonergic neurotransmission as assessed by active oddball auditory event-related potentials in volunteers without migraine.

In this randomized, double-blind, three-period crossover trial, 24 healthy volunteers without migraine received zolmitriptan 5 mg, dexfenfluramine 15 mg or placebo orally. At 2, 6, and 24 h postdose, auditory stimuli of 1000 Hz (nontarget tone) and 2000 Hz (target tone) were randomly and binaurally presented in an active oddball paradigm (4:1 ratio). Cortical auditory evoked responses were recorded for 500 msec poststimulus. Plasma concentrations of zolmitriptan and a 17-lead quantitative EEG were assessed at the same timepoints. Relative to placebo, zolmitriptan reduced the maximum absolute amplitude, amplitude difference (from nontarget tone noise) and area under the curve of the cortical auditory target tone event-related potential (P300 ERP). The most dramatic effect of zolmitriptan was to diminish the point estimate of noise during the 200-400 msec poststimulus epoch. The effect of zolmitriptan appeared concentration dependent. The latency of the P300 ERP was unaffected by zolmitriptan and there was no clinically significant effect on the EEG. Modification by zolmitriptan of the cortical electrical activity evoked by auditory stimuli confirms a central action of this drug in humans, which appears to affect cortical information processing without global alteration of the quantitative EEG.