Plasmin generation potential and recanalization in acute ischaemic stroke; an observational cohort study of stroke biobank samples

Rationale: More than half of patients who receive thrombolysis for acute ischaemic stroke fail to recanalize. Elucidating biological factors which predict recanalization could identify therapeutic targets for increasing thrombolysis success. Hypothesis: We hypothesize that individual patient plasmin potential, as measured by in vitro response to recombinant tissue-type plasminogen activator (rt-PA), is a biomarker of rt-PA response, and that patients with greater plasmin response are more likely to recanalize early. Methods: This study will use historical samples from the Barcelona Stroke Thrombolysis Biobank, comprised of 350 pre-thrombolysis plasma samples from ischaemic stroke patients who received serial transcranial-Doppler (TCD) measurements before and after thrombolysis. The plasmin potential of each patient will be measured using the level of plasmin-antiplasmin complex (PAP) generated after in-vitro addition of rt-PA. Levels of antiplasmin, plasminogen, t-PA activity, and PAI-1 activity will also be determined. Association between plasmin potential variables and time to recanalization [assessed on serial TCD using the thrombolysis in brain ischemia (TIBI) score] will be assessed using Cox proportional hazards models, adjusted for potential confounders. Outcomes: The primary outcome will be time to recanalization detected by TCD (defined as TIBI ≥4). Secondary outcomes will be recanalization within 6-h and recanalization and/or haemorrhagic transformation at 24-h. This analysis will utilize an expanded cohort including ~120 patients from the Targeting Optimal Thrombolysis Outcomes (TOTO) study. Discussion: If association between proteolytic response to rt-PA and recanalization is confirmed, future clinical treatment may customize thrombolytic therapy to maximize outcomes and minimize adverse effects for individual patients.Thomas Lillicrap … Timothy Kleinig … Simon Koblar, Monica Anne Hamilton-Bruce … et al

Study of hard scattering processes in multi - hadron production from gamma gamma collisions at LEP

The production of multihadronic states in γγ collisions at LEP has been studied with the DELPHI detector. The analyzed data correspond to an integrated luminosity of about 32pb−1, collected in the LEP runs of 1990–1992. Minimum bias data and a sample of events with jets at highp T have been selected under the requirement that no scattered electron or positron is observed. The two data sets have been compared to Monte Carlo predictions. The non-perturbative contribution described by the vector meson dominance Model and direct qqˉ production from pointlike photons described by the quark parton model were found to be insufficient to reproduce the data. It has been necessary to include a third interaction component, which is due to perburbative hard scattering of the partonic constituents of the photon. Several parametrisations of the quark and gluon densities of the photon have been tested. The interplay with the cut in jet transverse momentum, which is necessary for the separation of the perturbative and non-perturbative regions, is discussed. The data favour parametrisations with rather soft partonic content of the photon