Is Base of Support Greater in Unsteady Gait?

Abstract Background and Purpose. We investigated dynamic interfoot distance (IFD) throughout the gait cycle in people with unsteady gait caused by vestibulopathy and in people without known neuromuscular pathology. We expected that the subjects with unsteady gait would use a greater IFD than subjects without neuromuscular pathology and that this IFD would be correlated with other measures of locomotor stability. Subjects and Methods. Simultaneous whole-body (11-segment) dynamic kinematic data were collected from 22 subjects with vestibulopathy and 22 subjects without known neuromuscular pathology who were matched for age, height, weight, and body mass index. Two trials each of the participants' gait at preferred speed and paced gait at 120 steps/min were analyzed with a repeated-measures design with multiple dependent variables. Quantitative data were analyzed descriptively and with inferential statistics. Results. Interfoot distance at preferred gait speed did not differentiate unsteady subjects with vestibulopathy from the comparison subjects. Paced gait IFD total range and IFD in single-limb support differed between groups, but IFD at heel-strike did not. However, IFD at heel-strike, the traditional measure of “base-of-support width,” was correlated with measurements of whole-body center-of-gravity stability (r=.32–.55). Discussion and Conclusion. Gait at preferred speed permitted the unsteady subjects and the comparison subjects to select similar IFD values, but at the cost of slower gait in the unsteady subjects. When required to walk at a “normal” pace of 120 steps/min, subjects with vestibulopathy increased their IFD. These data suggest that wide-based gait alone cannot differentiate between subjects with and without balance impairments. Base of support and other whole-body kinematic variables are mechanical compensations of vestibulopathic instability. Further studies are needed to determine whether development of active control of these whole-body control variables can occur after vestibular rehabilitation.</jats:p

CD59 blocks not only the insertion of C9 into MAC but inhibits ion channel formation by homologous C5b-8 as well as C5b-9

Activation of the complement system on the cell surface results in the insertion of pore forming membrane attack complexes (MAC, C5b-9). In order to protect themselves from the complement attack, the cells express several regulatory molecules, including the terminal complex regulator CD59 that inhibits assembly of the large MACs by inhibiting the insertion of additional C9 molecules into the C5b-9 complex. Using the whole cell patch clamp method, we were able to measure accumulation of homologous MACs in the membrane of CD59− human B-cells, which formed non-selective ion channels with a total conductance of 360 ± 24 pS as measured at the beginning of the steady-state phase of the inward currents. C5b-8 and small-size MAC (MAC containing only a single C9) can also form ion channels. Nevertheless, in CD59+ human B-cells in spite of small-size MAC formation, an ion current could not be detected. In addition, restoring CD59 to the membrane of the CD59− cells inhibited the serum-evoked inward current. The ion channels formed by the small-size MAC were therefore sealed, indicating that CD59 directly interfered with the pore formation of C5b-8 as well as that of small-size C5b-9. These results offer an explanation as to why CD59-expressing cells are not leaky in spite of a buildup of homologous C5b-8 and small-size MAC. Our experiments also confirmed that ion channel inhibition by CD59 is subject to homologous restriction and that CD59 cannot block the conductivity of MAC when generated by xenogenic (rabbit) serum

Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: The ASSENT-3 randomised trial in acute myocardial infarction

Background: Current fibrinolytic therapies fail to achieve optimum reperfusion in many patients. Low-molecular-weight heparins and platelet glycoprotein IIb/IIIa inhibitors have shown the potential to improve pharmacological reperfusion therapy. We did a randomised, open-label trial to compare the efficacy and safety of tenecteplase plus enoxaparin or abciximab, with that of tenecteplase plus weight-adjusted unfractionated heparin in patients with acute myocardial infarction. Methods: 6095 patients with acute myocardial infarction of less than 6 h were randomly assigned one of three regimens: full-dose tenecteplase and enoxaparin for a maximum of 7 days (enoxaparin group; n=2040), half-dose tenecteplase with weight-adjusted low-dose unfractionated heparin and a 12-h infusion of abciximab (abciximab group; n=2017), or full-dose tenecteplase with weight-adjusted unfractionated heparin for 48 h (unfractionated heparin group; n=2038). The primary endpoints were the composites of 30-day mortality, in-hospital reinfarction, or in-hospital refractory ischaemia (efficacy endpoint), and the above endpoint plus in-hospital intracranial haemorrhage or in-hospital major bleeding complications (efficacy plus safety endpoint). Analysis was by intention to treat. Findings: There were significantly fewer efficacy endpoints in the enoxaparin and abciximab groups than in the unfractionated heparin group: 233/2037 (11.4%) versus 315/2038 (15.4%; relative risk 0.74 [95% CI 0.63-0.87], p=0.0002) for enoxaparin, and 223/2017 (11.1%) versus 315/2038 (15.4%; 0.72 [0.61-0.84], p&lt;0.0001) for abciximab. The same was true for the efficacy plus safety endpoint: 280/2037 (13.7%) versus 347/2036 (17.0%; 0.81 [0.70-0.93], p=0.0037) for enoxaparin, and 287/2016 (14.2%) versus 347/2036 (17.0%; 0.84 [0.72-0.96], p=0.01416) for abciximab. Interpretation: The tenecteplase plus enoxaparin or abciximab regimens studied here reduce the frequency of ischaemic complications of an acute myocardial infarction. In light of its ease of administration, tenecteplase plus enoxaparin seems to be an attractive alternative reperfusion regimen that warrants further study