Significant variation in mortality and functional outcome after acute ischaemic stroke between Western countries: data from the tinzaparin in acute ischaemic stroke trial (TAIST).

BACKGROUND: The medical care of patients with acute stroke varies considerably between countries. This could lead to measurable differences in mortality and functional outcome. OBJECTIVE: To compare case mix, clinical management, and functional outcome in stroke between 11 countries. METHODS: All 1484 patients from 11 countries who were enrolled into the tinzaparin in acute ischaemic stroke trial (TAIST) were included in this substudy. Information collected prospectively on demographics, risk factors, clinical features, measures of service quality (for example, admission to a stroke unit), and outcome were assessed. Outcomes were adjusted for treatment assignment, case mix, and service relative to the British Isles. RESULTS: Differences in case mix (mostly minor) and clinical service (many of prognostic relevance) were present between the countries. Significant differences in outcome were present between the countries. When assessed by geographical region, death or dependency were lower in North America (odds ratio (OR) adjusted for treatment group only = 0.52 (95% confidence interval, 0.39 to 0.71) and north west Europe (OR = 0.54 (0.37 to 0.78)) relative to the British Isles; similar reductions were found when adjustments were made for 11 case mix variables and five service quality measures. Similarly, case fatality rates were lower in North America (OR = 0.44 (0.30 to 0.66)) and Scandinavia (OR = 0.50 (0.33 to 0.74)) relative to the British Isles, whether crude or adjusted for case mix and service quality. CONCLUSIONS: Both functional outcome and case fatality vary considerably between countries, even when adjusted for prognostic case mix variables and measures of good stroke care. Differing health care systems and the management of patients with acute stroke may contribute to these findings.

Presentation and mechanisms of concussion in professional Rugby League Football.

The present study prospectively recorded the circumstances, incidence, mechanisms, injury detection and presentation of concussion in Rugby League. Forty-three consecutive concussions were recorded over three competitive seasons in 175 professional Rugby League players. Data showed (i) the incidence of concussion ranged from 5.9 to 9.8 injuries/1000 player hours across grades - except when age-group players were mismatched (18.4): (ii) 'head-high tackles' accounted for a significant number of concussions; (iii) concussion rarely involved a loss of consciousness with the most common indicators of concussion being amnesia, headache and unsteadiness, with the mechanism of injury often missed: and (iv) concussion often occurs concurrently with other injuries. Concussion (including repeated episodes) is a common injury in Rugby League. Systematic mental status questioning is warranted whenever concussion is suspected. Coaches, trainers and players need more education in the recognition and management of concussion. Stricter penalties for illegal 'head-high' tackling are strongly recommended.

Integrating advanced functionality in a microfabricated high-throughput fluorescent-activated cell sorter.

The integration of complete analyses systems "on chip" is one of the great potentials of microfabricated devices. In this study we present a new pressure-driven microfabricated fluorescent-activated cell sorter chip with advanced functional integration. Using this sorter, fluorescent latex beads are sorted from chicken red blood cells, achieving substantial enrichments at a sample throughput of 12000 cells s(-1). As a part of the sorter chip, we have developed a monolithically integrated single step coaxial flow compound for hydrodynamic focusing of samples in flow cytometry and cell sorting. The structure is simple, and can easily be microfabricated and integrated with other microfluidic components. We have designed an integrated chamber on the chip for holding and culturing of the sorted cells. By integrating this chamber, the risk of losing cells during cell handling processes is eliminated. Furthermore, we have also developed integrated optics for cell detection. Our new design contributes to the ongoing efforts for building a fully integrated micro cell sorting and analysing system.

[Thrombotic or embolic stroke?]. / Trombotisk eller embolisk hjerneslag?

BACKGROUND: Transoesophageal echocardiography reveals a possible source of embolism in many patients who present with acute brain ischaemia. The aim of this study was to observe the prevalence of possible sources of embolism in a representative Norwegian stroke population in a county hospital with a defined reference population. METHODS: All 103 patients with ischaemic stroke or transient ischaemic attack admitted to our hospital during a five-month period were enrolled. We performed transthoracic echocardiography in 98 patients, transoesophageal echocardiography in 83, and Doppler examination of the precerebral arteries in 92. RESULTS: Mean patient age was 72 years; 19 patients had atrial fibrillation. Examinations revealed 70 potential sources of embolism in 55 patients. Twenty-eight findings were in the heart. Five patients had thrombi in left-sided heart chambers. Ten patients had patent foramen ovale; 11 had atrial septal aneurysm; four had both. Thirty-three had atheromas of the aorta with a protrusion of more than 4 mm, ten of them with mobile elements. Nine patients had carotid stenosis of high grade or carotid occlusion ipsilateral to a hemispheric stroke. INTERPRETATION: Potential precerebral sources of embolism are common in a representative population of patients with ischaemic stroke. Atheromas of the aorta may be an important contributor to brain ischaemia.

Tinzaparin in acute ischaemic stroke (TAIST): a randomised aspirin-controlled trial.

BACKGROUND: Low-molecular-weight heparins and heparinoids are superior to unfractionated heparin in the prevention and treatment of venous thromboembolism, but their safety and efficacy in acute ischaemic stroke are inadequately defined. METHODS: This randomised, double-blind, aspirin-controlled trial tested the safety and efficacy of treatment with high-dose tinzaparin (175 anti-Xa IU/kg daily; 487 patients), medium-dose tinzaparin (100 anti-Xa IU/kg daily; 508 patients), or aspirin (300 mg daily; 491 patients) started within 48 h of acute ischaemic stroke and given for up to 10 days. Primary intracerebral haemorrhage was excluded by computed tomography. Outcome was assessed, with treatment allocation concealed, by the modified Rankin scale at 6 months (independence [scores 0-2] vs dependence or death [scores 3-6]). FINDINGS: Of 1486 randomised patients, two did not receive treatment and 46 were lost to follow-up. The proportions independent at 6 months were similar in the groups assigned high-dose tinzaparin (194/468 [41.5%]), medium-dose tinzaparin (206/486 [42.4%]), or aspirin (205/482 [42.5%]). There was no difference in effect in any predefined subgroup, including patients with presumed cardioembolic stroke. Other outcome measures were similar between the treatment groups (disability, case-fatality, and neurological deterioration rates). During the in-hospital treatment period no patient assigned high-dose tinzaparin developed a symptomatic deep-vein thrombosis compared with nine assigned aspirin. Conversely, seven patients assigned high-dose tinzaparin developed symptomatic intracerebral haemorrhage compared with one in the aspirin group. INTERPRETATION: Treatment with tinzaparin, at high or medium dose, within 48 h of acute ischaemic stroke did not improve functional outcome compared with aspirin. Although high-dose tinzaparin was superior in preventing deep-vein thrombosis, it was associated with a higher rate of symptomatic intracranial haemorrhage.

Hemostatic activation in acute ischemic stroke.

BACKGROUND AND PURPOSE: The purpose of this study was to examine the association between hemostatic activation and stroke severity, and to provide data on hemostatic variables in acute ischemic stroke. METHODS: The patient material comprised 76 consecutive patients with acute ischemic stroke (median 16 h, interquartile range 3-48). Levels of hemostatic variables were determined in blood samples collected on the day of hospitalization. Stroke severity was assessed on admission by the Oxfordshire Community Stroke Project (OCSP) classification, and on discharge (median 9 days, interquartile range 6-14) by Barthel Index (BI, scores 0-50, 55-90, or 95-100) and modified Rankin Scale (mRS, scores 0-1 or 2-6). Associations were assessed by multiple linear regression analyses. RESULTS: Levels of the fibrin degradation product D-Dimer and the activation peptide prothrombin fragment 1 + 2 (F1 + 2) were linearly related to stroke severity, whether assessed on admission (P = .001 and.03, respectively, for the OCSP classification), or on discharge (P = .009 and.43, respectively, for BI; and.001 and.05, respectively, for mRS). High levels of D-Dimer and F(1 + 2), as well as low levels of antithrombin and protein C were also present in patients with a presumed embolic source, and low antithrombin or protein C was borderline significantly associated with atrial fibrillation (P = .072 and.058, respectively). Low levels of protein C or protein S, and the presence of antiphospholipid antibodies, including lupus anticoagulant (LA), was detected in 13/73 (18%) and 15/70 (21%) of the patients, respectively. CONCLUSION: Activation of the hemostatic system is independently related to acute stroke severity and short-term outcome. Low levels of coagulation inhibitors or presence of antiphospholipid antibodies is a relatively frequent finding in unselected patients with acute ischemic stroke, but a causative role cannot be inferred from our study.

Monolithic integration of microfluidic channels and optical waveguides in silica on silicon.

Sealing of the flow channel is an important aspect during integration of microfluidic channels and optical waveguides. The uneven topography of many waveguide-fabrication techniques will lead to leakage of the fluid channels. Planarization methods such as chemical mechanical polishing or the etch-back technique are possible, but troublesome. We present a simple but efficient alternative: By means of changing the waveguide layout, bonding pads are formed along the microfluidic channels. With the same height as the waveguide, they effectively prevent leakage and hermetically seal the channels during bonding. Negligible influence on light propagation is found when 10-mum-wide bonding pads are used. Fabricated microsystems with application in absorbance measurements and flow cytometry are presented.

Ultraviolet transparent silicon oxynitride waveguides for biochemical microsystems.

The UV wavelength region is of great interest in absorption spectroscopy, which is employed for chemical analysis, since many organic compounds absorb in only this region. Germanium-doped silica, which is often preferred as the waveguide core material in optical devices for telecommunication, cannot accommodate guidance below 400 nm, owing to the presence of UV-absorbing centers. We show that silicon oxynitride (SiO(x) N(y)) waveguides exhibit very good UV performance. The propagation loss for 24-microm -wide SiO(x)N (y) waveguides was found to be ~1.0dB/cm in the wavelength range 220-550 nm. The applicability of these waveguides was demonstrated in a biochemical microsystem consisting of multimode buried-channel SiO(x)N (y) waveguides that were monolithically integrated with microfluidic channels. Absorption measurements of a beta -blocking agent, propranolol, at 212-215 nm were performed. The detection limit was reached at a concentration of 13microM , with an optical path length of 500microm (signal/noise ratio, 2).

Concussion in contact sports: reliable change indices of impairment and recovery.

This paper reports a follow-up study to an article on the sensitivity of three tests of speed of information processing to impairment after concussion (Hinton-Bayre, Geffen, & McFarland, 1997). Group analyses showed that practice effects can obscure the effects of concussion on information processing, thereby making the assessment of functional impairment and recovery after injury unreliable. A Reliable Change Index (RCI) was used to assess individual variations following concussion. It was found that 16 of the 20 concussed professional rugby league players were impaired 1-3 days following injury. It was also demonstrated that 7 players still displayed cognitive deficits at 1-2 weeks, before returning to preseason levels at 3-5 weeks. The RCI permits comparisons between different tests, players, and repeated assessments, thereby providing a quantitative basis for decisions regarding return to play.

Biochemical and ultrastructural studies of the C-type lectin bovine conglutinin.

The aim of this study was to correlate the supramolecular organization of conglutinin (BK) with its primary and tertiary structure and to gain more knowledge of functionally important regions of the molecule. BK analyzed by SDS-PAGE under standard reducing conditions (40 mM DTT) showed a major band at 43 kDa and weaker bands at 86 and 180 kDa. In contrast, reduction with 6-50 mM L-cysteine resulted in 37-kDa subunits indicating the presence of intrachain disulfide bonds within this subunit. Hydroxylamine treatment indicated presence of ester bonds in the 86- and 180-kDa subunits. Collagenase digestion and SDS-PAGE under reducing and nonreducing conditions resulted in bands of 20 and 15 kDa, respectively, indicating the presence of intrachain, rather than interchain, disulfide bonds in the carboxy terminus. Deglycosylation and glycan differentiation analysis of BK revealed the presence of O-linked glycans of GalNAc and alpha (2-3) linked sialic acid type, whereas no N-linked glycans were demonstrated. Binding experiments with GlcNAc-gold suggested that multivalency is required for carbohydrate binding to BK. Electron microscopy showed mostly tetramers, 96 nm in diameter, but also mono-, di-, and trimers were seen. The tetramers consisted of 40-nm strands, each with a peripheral globular head composed of subunits and connected to a common central lobe built from four ring-formed structures. The strands occasionally showed two bends, one close to the central lobe and another 25 nm from the lobe. These bends most likely correspond to the interrupted Gly-Xaa-Yaa repeats at residues 38 and 123.

Purification, subunit characterization and ultrastructure of three soluble bovine lectins: conglutinin, mannose-binding protein and the pentraxin serum amyloid P-component.

Conglutinin and mannose-binding protein (MBP) are members of the C-type lectins which are widely present in mammalian plasma. Serum amyloid P-component (SAP) is a member of the pentraxin family with lectin properties. A scheme for the partial purification of all three lectins by carbohydrate affinity chromatography and selective elution was developed. The purification was monitored by SDS-PAGE, Western blotting and electron microscopy. Binding of the lectins to Sephadex-iC3b, their collagenase sensitivity, and the size and antibody reactivity of their subunits was investigated. The demonstration, by SDS-PAGE, of 25-kDa subunits, which were unaffected by collagenase treatment but bound to Sephadex-iC3b and antibodies to human SAP, indicated the existence of bovine SAP. Bovine conglutinin (BK) also showed calcium-dependent binding to Sephadex-iC3b, whereas bovine MBP did not. The binding of BK was inhibitable with GlcNAc. A 3000-fold increase in BK activity (ELISA) was obtained in eluates from Sephadex-iC3b. SDS-PAGE analyses of BK and MBP revealed subunits with an Mr of 43 kDa and 30 kDa, respectively. These subunits were sensitive to collagenase treatment which reduced the Mr to 20 kDa. Electron micrographs revealed a prominent flexible tetramer molecule (diameter 96 nm) in the BK preparations, a predominantly hexameric structure (diameter 30 nm) in the MBP preparations, and single annular pentameric disc-like molecules (diameter 11 nm) in the SAP preparations.

Conglutinin exhibits a complement-dependent enhancement of the respiratory burst of phagocytes stimulated by E. coli.

Conglutinin is a mammalian C-type lectin which shows anti-bacterial activity when tested in vivo and in vitro. This study concerns the effect of conglutinin on the respiratory burst of murine spleen cells, using a chemiluminescence assay for measurement of generated reactive oxygen metabolites. Conglutinin enhances, in a dose-dependent manner, the respiratory burst of spleen cells stimulated with serum-opsonized Escherichia coli. The enhancement was only demonstrable in the presence of a functional complement system. The conglutinin-mediated enhancement of the respiratory burst was inhibited in the presence of a N-acetyl-D-glucosamine, D-mannose and N-acetyl-D-mannosamine, monosaccharides reported to inhibit conglutinin-binding to zymosan and the complement factor iC3b. On the other hand, N-acetyl-D-galactosamine was non-inhibitory.

Toxin production in Pyrenophora teres, the ascomycete causing the net-spot blotch disease of barley (Hordeum vulgare L.).

Toxin production in a large number of Pyrenophora teres isolates have been investigated. During fungal growth, the pH of the medium decreases from 6.5 to about 3.0. Aspergillomarasmine A is the major toxin excreted into the culture medium. Nonenzymatic acid-catalyzed conversion of aspergillomarasmine A to anhydroaspergillomarasmine A proceeds at low pH and is prevented by repeated titration of the culture medium to pH 6.5. The four possible stereoisomers of N-(2-amino-2-carboxyethyl)aspartic acid have been chemically synthesized and their absolute configuration determined. From circular dichroism and NMR spectroscopy and by measurements of specific optical rotation, the LL-form is identified as the stereoisomer produced by P. teres. Biosynthetic experiments using radioisotopes demonstrate that the LL-isomer of N-(2-amino-2-carboxyethyl) aspartic acid is a direct precursor of aspergillomarasmine A. Consequently, L-configuration is assigned to the two corresponding asymmetric carbon atoms of aspergillomarasmine A. This is in contrast to earlier reports which had indicated D configuration. The phytotoxicity of anhydroaspergillomarasmine A is comparable with that of L-aspartic acid, whereas LL-N-(2-amino-2-carboxyethyl)aspartic acid exerts strong phytotoxicity in the bioassays as shown previously for aspergillomarasmine A. The amount of LL-N-(2-amino-2-carboxyethyl)aspartic acid which accumulates in the P. teres cultures is low, indicating that aspergillomarasmine A is the toxin which plays the major role in the pathological changes associated with the barley net-spot blotch disease.

The systemic availability of buprenorphine administered by nasal spray.

The kinetics and systemic bioavailability of intranasally administered buprenorphine have been investigated in 9 healthy volunteers in an intranasal/intravenous cross-over study. Each subject received a nominal 0.3 mg dose of buprenorphine intranasally followed one week later by a matched dose intravenously. For the intranasal administration mean tmax and mean Cmax were 30.6 min and 1.77 ng mL-1, respectively. Mean intranasal bioavailability was 48.2 +/- 8.35% (mean +/- s.e.m.) of the intravenous value. Intranasal administration may represent a valuable new delivery route for buprenorphine.