Inconsistent classification of pusher behaviour in stroke patients: a direct comparison of the Scale for Contraversive Pushing and the Burke Lateropulsion Scale.

OBJECTIVE: To compare the classification of two clinical scales for assessing pusher behaviour in a cohort of stroke patients. DESIGN: Observational case-control study. SETTING: Inpatient stroke rehabilitation unit. SUBJECTS: A sample of 23 patients with hemiparesis due to a unilateral stroke (1.6 ± 0.7 months post stroke). METHODS: Immediately before and after three different interventions, the Scale for Contraversive Pushing and the Burke Lateropulsion Scale were applied in a standardized procedure. RESULTS: The diagnosis of pusher behaviour on the basis of the Scale for Contraversive Pushing and the Burke Lateropulsion Scale differed significantly (χ2 = 54.260, p < 0.001) resulting in inconsistent classifications in 31 of 138 cases. Changes immediately after the interventions were more often detected by the Burke Lateropulsion Scales than by the Scale for Contraversive Pushing (χ2 = 19.148, p < 0.001). All cases with inconsistent classifications showed no pusher behaviour on the Scale for Contraversive Pushing, but pusher behaviour on the Burke Lateropulsion Scale. 64.5% (20 of 31) of them scored on the Burke Lateropulsion Scale on the standing and walking items only. CONCLUSIONS: The Burke Lateropulsion Scale is an appropriate alternative to the widely used Scale for Contraversive Pushing to follow-up patients with pusher behaviour (PB); it might be more sensitive to detect mild pusher behaviour in standing and walking.

Immediate effectiveness of single-session therapeutic interventions in pusher behaviour.

Some stroke patients with hemiparesis exhibit a so-called pusher behaviour, i.e., they actively push away from the unaffected side and lean towards the hemiparetic side. This impairs their postural balance to such a degree that they are often unable to sit or stand. Pusher behaviour thus substantially hampers the rehabilitation of these patients. So far only a few case studies on treatment strategies have been performed. This study investigated the immediate after-effects of galvanic vestibular stimulation (GVS), machine-supported gait training with the Lokomat, and physiotherapy with visual feedback components (PT-vf). Fifteen pusher and 10 non-pusher patients participated in an observer-blinded cross-over pilot study. Patients were measured on the scale for contraversive pushing (SCP) and on the Burke lateropulsion scale (BLS) immediately before and after a single-session of the specific intervention. Compared to PT-vf, Lokomat therapy had a significant effect on the BLS of pusher patients but no significant effect on the SCP values. GVS had no significant effect on these values on either scale. BLS is more useful than SCP to detect small changes for clinical trials and routine treatment. Forced control of the upright position during locomotion seems to be an effective method for immediately reducing the pushing behaviour of stroke patients, probably because it recalibrates a biased sense of verticality, via the somatic graviception. This finding, however, does not allow prediction of its long-term effects. Furthermore, it would be interesting to evaluate repetitive, multi-session DGO therapy and the amount of therapy needed to effectively reduce the pusher behaviour.

The human immunodeficiency virus (HIV)-1 protease inhibitor saquinavir inhibits proteasome function and causes apoptosis and radiosensitization in non-HIV-associated human cancer cells.

Cancer cells frequently show high constitutive activity of the antiapoptotic transcription factor nuclear factor kappaB (NF-kappaB), which results in their enhanced survival. Activation of NF-kappaB classically depends on degradation of its inhibitor IkappaBalpha by the 26s proteasome. Specific proteasome inhibitors induce apoptosis in cancer cells and, at nonlethal concentrations, sensitize cells to the cytotoxic effects of ionizing radiation and chemotherapeutic drugs. Recently, the protease coded by the HIV-I virus has been shown to share cleavage activities with the proteasome. For this reason, we investigated whether the HIV-I protease inhibitor saquinavir can inhibit NF-kappaB activation, block 26s proteasome activity in prostate cancer cells, and promote their apoptosis. The effect of saquinavir on LPS/IFN-gamma-induced activation of NF-kappaB was assessed by gel-shift assays and by Western analysis of corresponding IkappaBalpha-levels. Its effect on 20s and 26s proteasome activity was analyzed with a fluorogenic peptide assay using whole cell lysates from LnCaP, DU-145, and PC-3 prostate cancer cells pretreated with saquinavir for 9 h. Proteasome inhibition in living cells was assessed using ECV 304 cells stably transfected with an expression plasmid for an ubiquitin/green fluorescence protein fusion protein (ECV 304/10). Apoptosis was monitored morphologically and by flow cytometry. Saquinavir treatment prevented LPS/IFN-gamma-induced activation of NF-kappaB in RAW cells and stabilized expression of IkappaBalpha. It inhibited 20s and 26s proteasome activity in lysates from LnCaP, DU-145, and PC-3 prostate cancer cells with an IC(50) of 10 micro M and caused the accumulation of an ubiquitin/green fluorescence protein fusion protein in living ECV 304/10 cells. Incubation of PC-3 and DU-145 prostate cancer, U373 glioblastoma, and K562 and Jurkat leukemia cells with saquinavir caused a concentration-dependent induction of apoptosis. In the case of PC-3 and DU-145, saquinavir sensitized the surviving cells to ionizing radiation. We conclude that saquinavir inhibits proteasome activity in mammalian cells as well as acting on the HIV-I protease. Because saquinavir induced apoptosis in human cancer cells, HIV-I protease inhibitors might become a new class of cytotoxic drugs, alone or in combination with radiation or chemotherapy.

N-acetyl-L-cysteine inhibits 26S proteasome function: implications for effects on NF-kappaB activation.

Ionizing radiation shares with cytokines, such as TNF-alpha, an ability to generate free radicals in cells and activate downstream proinflammatory responses through NF-kappaB-dependent signal transduction pathways. Support for the role of free radicals in triggering such responses comes from the use of free radical scavengers like N-acetyl-L-cysteine (NAC). The nature of the link between free radical generation and NF-kappaB activation is, however, unclear. In this study, we explore the possibility that scavenging of free radicals by NAC might not be the mechanism by which it inhibits NF-kappaB activation, but rather that NAC acts through inhibition of proteasome function. The effect of NAC on the chymotryptic function of the 26s and 20s proteasome complex was measured in extracts from EVC 304 bladder carcinoma cells by assessing degradation of fluorogenic substrates. NAC inhibited 26s but not 20s proteasome activity, suggesting that it interferes with 19s regulatory subunit function. NAC blocked radiation-induced NF-kappaB activity in ECV 304 cells and RAW 264.7 macrophages, as measured by a gel shift assay, at doses that inhibited proteasome activity. This provides a possible mechanism whereby NAC could block NF-kappaB activation and affect the expression of other molecules that are dependent on the ubiquitin/proteasome system for their degradation, other than by scavenging free radicals.