Thrombolysis and thrombectomy for acute ischaemic stroke

The likelihood of disability-free recovery after acute ischemic stroke is significantly improved by reperfusion either by intravenous thrombolytic drug treatment or with endovascular mechanical thrombectomy in selected cases. The use of intravenous thrombolysis is limited by the short treatment window and you need to assess individual balance of benefit and risk of symptomatic intracranial haemorrhage. Benefit is greater for shorter onset-to-reperfusion time intervals, requiring optimisation of pre-hospital and in-hospital pathways. Symptomatic haemorrhage is more likely with more severe strokes, but a greater proportion of patients are left free of disability than suffer a treatment-related haemorrhage at all levels of severity. Extracranial haemorrhage and orolingual angioedema are less common complications. Endovascular mechanical thrombectomy can be used in selected patients with imaging-proven large artery occlusion. Successful therapy depends on well-organised services that can deliver treatment within a short time window at centres with adequate expertise to perform the procedure

Neuroimaging as a selection tool and endpoint in preclinical and clinical trials

Standard imaging in acute stroke enables the exclusion of non-stroke structural CNS lesions and cerebral haemorrhage from clinical and pre-clinical ischaemic stroke trials. In this review, the potential benefit of imaging (e.g., angiography and penumbral imaging) as a translational tool for trial recruitment and the use of imaging endpoints are discussed for both clinical and pre-clinical stroke research. The addition of advanced imaging to identify a “responder” population leads to reduced sample size for any given effect size in phase 2 trials and is a potentially cost-efficient means of testing interventions. In pre-clinical studies, technical failures (failed or incomplete vessel occlusion, cerebral haemorrhage) can be excluded early and continuous multimodal imaging of the animal from stroke onset is feasible. Pre- and post-intervention repeat scans provide real time assessment of the intervention over the first 4–6 h. Negative aspects of advanced imaging in animal studies include increased time under general anaesthesia, and, as in clinical studies, a delay in starting the intervention. In clinical phase 3 trial designs, the negative aspects of advanced imaging in patient selection include higher exclusion rates, slower recruitment, overestimated effect size and longer acquisition times. Imaging may identify biological effects with smaller sample size and at earlier time points, compared to standard clinical assessments, and can be adjusted for baseline parameters. Mechanistic insights can be obtained. Pre-clinically, multimodal imaging can non-invasively generate data on a range of parameters, allowing the animal to be recovered for subsequent behavioural testing and/or the brain taken for further molecular or histological analysis

Cracking the role of cocaine in stroke

No abstract available

Scarlet Phosphorus: A New Chemically Active Variety of Red Phosphorus, and Its Use in the Manufacture of Matches

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Crystal Structure Analyses of Organic and Organometallic Compounds

The thesis is divided into three parts: the first part is a brief review of the theory and methods of x-ray crystallography, the second part describes a number of computer programmes devised either wholly or partly by the author, and in the third part accounts of three structure analyses are presented. The computer programmes described in Part II are written in ALGOL for the English Electric KDP9 Computer. The molecular functions system is a group of six programmes for interpreting the results of a structure analysis: bond lengths and interbond angles with their standard deviations, intermolecular contacts, and mean plane equations may be calculated and rigid-body vibrational analysis can be carried out. The automatic structure solution (ASS) system allows semi-automatic Fourier refinement to be performed. The minimum residual programme permits crystal structures to be refined in projection by direct calculation of the minimum R-factor. The structure analyses presented in Part III are applications of the x-ray method to organic and organo-metallic structural problems. It has been known for more than twenty years that indene can form a 1:2 adduct with dimethylacetylene-dicarboxylate. Earlier chemical and spectroscopic studies on the adduct did not lead to a successful structure determination. The molecular structure of the adduct has now been definitely established by x-ray analysis of its dibromo-derivative. The structure analyses of phenanthrenechromium tricarbonyl, C14H10Cr(CO)3, and of 9,10-dihydrophenanthrenechromium tricarbonyl, C14H12Cr(CO)3, were undertaken to obtain accurate dimensions for aromatic rings bonded to chromium. In both analyses the standard deviations of the C-C bonds range from 0.006 to 0.010 A. The results suggest that the chromium atom causes a slight increase in the mean bond length of the bonded ring without alteration of the ring symmetry. Structural studies on related arenechromium complexes are discussed

Stroke in the acute setting

Acute stroke and transient ischaemic attack (TIA) are focal neurological syndromes of vascular origin and should be treated as medical emergencies. Brain imaging with computed tomography or magnetic resonance imaging is required to distinguish ischaemic stroke from intracerebral haemorrhage, recognize non-stroke pathologies that mimic stroke and guide investigation into the underlying mechanism. Acute interventions of benefit in ischaemic stroke include intravenous thrombolysis with alteplase given within 4.5 hours of onset, endovascular thrombectomy within 6 hours of onset in selected patients, stroke unit care and aspirin. Decompressive hemicraniectomy reduces mortality in ischaemic stroke complicated by severe brain swelling. Intracerebral haemorrhage accounts for 10–15% of strokes, and while specific treatments are lacking at present, patients benefit from general measures, notably stroke unit care. TIA carries a high short-term risk of stroke, and immediate investigation and institution of secondary preventive treatment prevents a high proportion of this. Secondary prevention for ischaemic stroke and TIA should be tailored according to mechanism in individual patients

Clinical trial design for stem cell therapies in stroke: What have we learned?

Stem cells of various sources have been investigated in a series of small, safety and feasibility-focused studies over the past 15 years. Understanding of mechanisms of action has evolved and the trial paradigms have become focused on two different approaches – one being an early subacute delivery of cells to reduce acute tissue injury and modify the tissue environment in a direction favourable to reparative processes (for example by being anti-inflammatory, anti-apoptotic, and encouraging endogenous stem cell mobilisation); the other exploring later delivery of cells during the recovery phase after stroke to modulate the local environment in favour of angiogenesis and neurogenesis. The former approach has generally investigated intravenous or intra-arterial delivery of cells with an expected paracrine mode of action and no expected engraftment within the brain. The latter has explored direct intracerebral implantation adjacent to the infarct. Several relevant trials have been conducted, including two controlled trials of intravenously delivered bone marrow-derived cells in the early subacute stage, and two small single-arm phase 1 trials of intracerebrally implanted cells. The findings of these studies and their implications for future trial design are considered

Respiratory challenge MRI: practical aspects

Respiratory challenge MRI is the modification of arterial oxygen (PaO2) and/or carbon dioxide (PaCO2) concentration to induce a change in cerebral function or metabolism which is then measured by MRI. Alterations in arterial gas concentrations can lead to profound changes in cerebral haemodynamics which can be studied using a variety of MRI sequences. Whilst such experiments may provide a wealth of information, conducting them can be complex and challenging. In this paper we review the rationale for respiratory challenge MRI including the effects of oxygen and carbon dioxide on the cerebral circulation. We also discuss the planning, equipment, monitoring and techniques that have been used to undertake these experiments. We finally propose some recommendations in this evolving area for conducting these experiments to enhance data quality and comparison between techniques