Introduction of a new model for time-continuous and non-contact investigations of in-vitro thrombolysis under physiological flow conditions

<p>Abstract</p> <p>Background</p> <p>Thrombolysis is a dynamic and time-dependent process influenced by the haemodynamic conditions. Currently there is no model that allows for time-continuous, non-contact measurements under physiological flow conditions. The aim of this work was to introduce such a model.</p> <p>Methods</p> <p>The model is based on a computer-controlled pump providing variable constant or pulsatile flows in a tube system filled with blood substitute. Clots can be fixed in a custom-built clot carrier within the tube system. The pressure decline at the clot carrier is measured as a novel way to measure lysis of the clot. With different experiments the hydrodynamic properties and reliability of the model were analyzed. Finally, the lysis rate of clots generated from human platelet rich plasma (PRP) was measured during a one hour combined application of diagnostic ultrasound (2 MHz, 0.179 W/cm²) and a thrombolytic agent (rt-PA) as it is commonly used for clinical sonothrombolysis treatments.</p> <p>Results</p> <p>All hydrodynamic parameters can be adjusted and measured with high accuracy. First experiments with sonothrombolysis demonstrated the feasibility of the model despite low lysis rates.</p> <p>Conclusions</p> <p>The model allows to adjust accurately all hydrodynamic parameters affecting thrombolysis under physiological flow conditions and for non-contact, time-continuous measurements. Low lysis rates of first sonothrombolysis experiments are primarily attributable to the high stability of the used PRP-clots.</p

Multicentre comparison of a diagnostic assay: Aquaporin-4 antibodies in neuromyelitis optica

Objective Antibodies to cell surface central nervous system proteins help to diagnose conditions which often respond to immunotherapies. The assessment of antibody assays needs to reflect their clinical utility. We report the results of a multicentre study of aquaporin (AQP) 4 antibody (AQP4-Ab) assays in neuromyelitis optica spectrum disorders (NMOSD). Methods Coded samples from patients with neuromyelitis optica (NMO) or NMOSD (101) and controls (92) were tested at 15 European diagnostic centres using 21 assays including live (n=3) or fixed cell-based assays (n=10), flow cytometry (n=4), immunohistochemistry (n=3) and ELISA (n=1). Results Results of tests on 92 controls identified 12assays as highly specific (0-1 false-positive results). 32 samples from 50 (64%) NMO sera and 34 from 51 (67%) NMOSD sera were positive on at least two of the 12 highly specific assays, leaving 35 patients with seronegative NMO/spectrum disorder (SD). On the basis of a combination of clinical phenotype and the highly specific assays, 66 AQP4-Ab seropositive samples were used to establish the sensitivities (51.5-100%) of all 21 assays. The specificities (85.8-100%) were based on 92 control samples and 35 seronegative NMO/SD patient samples. Conclusions The cell-based assays were most sensitive and specific overall, but immunohistochemistry or flow cytometry could be equally accurate in specialist centres. Since patients with AQP4-Ab negative NMO/SD require different management, the use of both appropriate control samples and defined seronegative NMOSD samples is essential to evaluate these assays in a clinically meaningful way. The process described here can be applied to the evaluation of other antibody assays in the newly evolving field of autoimmune neurology

Determination of nutrient salts by automatic methods both in seawater and brackish water: the phosphate blank

9 páginas, 2 tablas, 2 figurasThe main inconvenience in determining nutrients in seawater by automatic methods is simply solved: the preparation of a suitable blank which corrects the effect of the refractive index change on the recorded signal. Two procedures are proposed, one physical (a simple equation to estimate the effect) and the other chemical (removal of the dissolved phosphorus with ferric hydroxide).Support for this work came from CICYT (MAR88-0245 project) and Conselleria de Pesca de la Xunta de GaliciaPeer reviewe

Optimal coil orientation for transcranial magnetic stimulation.

We study the impact of coil orientation on the motor threshold (MT) and present an optimal coil orientation for stimulation of the foot. The result can be compared to results of models that predict this orientation from electrodynamic properties of the media in the skull and from orientations of cells, respectively. We used a robotized TMS system for precise coil placement and recorded motor-evoked potentials with surface electrodes on the abductor hallucis muscle of the right foot in 8 healthy control subjects. First, we performed a hot-spot search in standard (lateral) orientation and then rotated the coil in steps of 10° or 20°. At each step we estimated the MT. For navigated stimulation and for correlation with the underlying anatomy a structural MRI scan was obtained. Optimal coil orientation was 33.1 ± 18.3° anteriorly in relation to the standard lateral orientation. In this orientation the threshold was 54 ± 18% in units of maximum stimulator output. There was a significant difference of 8.0 ± 5.9% between the MTs at optimal and at standard orientation. The optimal coil orientations were significantly correlated with the direction perpendicular to the postcentral gyrus ([Formula: see text]). Robotized TMS facilitates sufficiently precise coil positioning and orientation to study even small variations of the MT with coil orientation. The deviations from standard orientation are more closely matched by models based on field propagation in media than by models based on orientations of pyramidal cells

Risk of acute brain lesions in dizzy patients presenting to the emergency room: who needs imaging and who does not?

The usefulness of brain imaging studies in dizzy patients presenting to the emergency department (ED) is controversial. We aimed to assess the 'real-world' probability of ischemic stroke and other acute brain lesions (ABLs) in these patients to create an algorithm that helps decision-making on whether which and when brain imaging is needed. By reviewing medical records, we identified 610 patients presenting with dizziness, vertigo or imbalance to our university hospital's ED and receiving neurological workup. We collected timing/triggers of symptoms, ABC

What guides decision-making on intravenous thrombolysis in acute vestibular syndrome and suspected ischemic stroke in the posterior circulation?

Intravenous thrombolysis (IVT) is rarely performed in dizzy patients with acute vestibular syndrome (AVS) or acute imbalance (AIS) even if posterior circulation stroke (PCS) is suspected. Decision-making may be affected by uncertainties in discriminating central from peripheral vestibulopathy or concerns of IVT-related harm, particularly intracerebral hemorrhage (ICH), but related studies are missing. Using an in-house register of dizzy patients coming to the emergency room, we identified 29 AVS/AIS patients who presented within 4.5 h after onset, revealed clinical signs indicative of PCS (central oculomotor signs, mild focal abnormalities), and had non-contrast computed tomography (NCCT). Patients treated with IVT (n = 15) were compared to NoIVT patients (n = 14) with regard to clinical and imaging (including perfusion computed tomography, CTP) parameters, occurrence of ICH and short-term clinical outcome (NIHSS improvement; ability to walk independently). IVT and NoIVT patients did not differ in baseline characteristics, central oculomotor signs, or clinical outcome. IVT patients more often exhibited disabling vestibular symptoms (severe dizziness/vertigo, inability to stand unsupported) and focal abnormalities than NoIVT patients. There was no ICH in either group. CTP was performed in 0% of NoIVT versus 80% of IVT patients, seven of twelve revealing posterior circulation hypoperfusion. Comparison of initial hypoperfusion (CTP) and final stroke (NCCT) revealed IVT-related benefit (smaller lesion) in three of seven IVT patients. In AVS/AIS patients with suspected PCS, disabling vestibular symptoms, focal neurological deficits, and hypoperfusion on CTP seem to direct decision-making pro IVT. In our small cohort, there were no significant IVT-related clinical benefits, no IVT-related ICHs, and salvage of brain tissue in some patients

Posterior and anterior contribution of hand-movement preparation to late CNV

The late part of the Contingent Negative Variation (CNV) is assumed to be a composite potential, reflecting both movement preparation and several other processes. To assess the contribution of hand–motor preparation to overall CNV, 3 S1–S2 experiments were performed. Replicating earlier results that have been interpreted as demonstrating hand–motor preparation, Exp 1 showed that CNV gets larger centro–parietally under speed instruction. Exps 2 and 3 compared preparation for hand responses to preparation for ocular responses varying the effector system either between blocks (Exp 2) or between trials (Exp 3) and also comparing these preparation situations to no preparation (Exp 3). Ss consisted of 10 medical students aged 23–29 yrs in Exp 1, 12 Ss aged 23–31 yrs in Exp 2, and 11 Ss in Exp 3. Hand–motor preparation was reflected in CNV getting larger fronto–centrally, with this topography being different from the effect in Exp1. Thus, 2 different kinds of motor preparation appear to be reflected by CNV. One kind may consist of assembling and maintaining the stimulus–response links appropriate to the expected S2 patterns, the other is for activating the hand–motor area. These 2 motor contributions to CNV might reflect the 2 aspects of the parieto–frontal motor system

Deficits of smooth pursuit initiation in patients with degenerative cerebellar lesions.

It is well known that cerebellar dysfunction can lead to an impairment of eye velocity during sustained pursuit tracking of continuously moving visual target. We have now studied the initiation of smooth pursuit eye movements towards predictable and randomized visual step-ramp stimuli in six patients with degenerative cerebellar lesions and six age-matched healthy controls using the magnetic scleral search-coil technique. In comparison with the control subjects, the cerebellar patients showed a significant delay of pursuit onset, and their initial eye acceleration was significantly decreased. These cerebellar deficits of pursuit initiation were similarly found in response to both randomized and predictable step-ramps, suggesting that predictive input does not compensate for cerebellar deficits in the initiation period of smooth pursuit. When we compared initial saccades during smooth tracking of foveofugal and foveopetal step-ramps, the absolute position error of these saccades did not significantly differ between patients and controls. In fact, none of the patients showed any bias of the saccadic position error that was related to the direction or velocity of the ongoing target motion. This work presents further evidence that the effect of cerebellar degeneration is not limited to the impaired velocity gain of steady-state smooth pursuit. Instead, it prolongs the processing time required to initiate smooth pursuit and impairs the initial eye acceleration. These two deficits were not associated with an abnormal assessment of target velocity and they were not modified by predictive control mechanisms, suggesting that cerebellar deficits of smooth initiation are not primarily caused by abnormal information on target motion being relayed to the cerebellum