Valve surgery for infective endocarditis complicated by stroke: surgical timing and perioperative neurological complications.

BACKGROUND AND PURPOSE: Ischaemic and hemorrhagic strokes are dreaded complications of infective endocarditis (IE). The timing of valve surgery for IE patients with stroke remains uncertain. The aim was to study perioperative neurological complications in relation to surgical timing. METHODS: The study cohort consisted of patients diagnosed with acute IE from January 2010 to December 2016. Early surgery was defined as valve surgery within 14 days of IE diagnosis, and late surgery as after 14 days. Neurological complications that occurred within 14 days post-surgery were considered perioperative and classified as new ischaemic stroke or hemorrhagic stroke, expansion of an existing intracranial hemorrhage and new-onset seizures. Perioperative neurological complications were compared by surgical timing and other variables, including pre-surgical imaging. RESULTS: Overall, 183 patients underwent valve surgery: 92 had early surgery at a median of 8 days (interquartile range 6-11); 91 had late surgery at a median of 28 days (interquartile range 19-50). Twenty patients (10.9%) had 24 complications: 11 ischaemic, six intraparenchymal hemorrhages, three subarachnoid hemorrhages (SAHs) and four new-onset seizures. Rates of neurological complications were similar for early and late surgery groups (10.9% vs. 11%). Enterococcal IE was more common amongst patients with perioperative neurological complications (35% vs. 12.3%, P < 0.01). An acute infarct was present on pre-surgical magnetic resonance imaging of 134 patients (74%) and was not associated with perioperative neurological complications. Thirty-five patients (19.3%) had intracranial hemorrhage on pre-surgical imaging. SAH on pre-surgical imaging was associated with developing SAH perioperatively (66.7% vs. 13.5%, P < 0.01). CONCLUSION: Early valve surgery for patients with IE complicated by stroke was not associated with perioperative neurological complications.

Modular cis-regulatory logic of yellow gene expression in silkmoth larvae.

Colour patterns in butterflies and moths are crucial traits for adaptation. Previous investigations have highlighted genes responsible for pigmentation (ie yellow and ebony). However, the mechanisms by which these genes are regulated in lepidopteran insects remain poorly understood. To elucidate this, molecular studies involving dipterans have largely analysed the cis-regulatory regions of pigmentation genes and have revealed cis-regulatory modularity. Here, we used well-developed transgenic techniques in Bombyx mori and demonstrated that cis-regulatory modularity controls tissue-specific expression of the yellow gene. We first identified which body parts are regulated by the yellow gene via black pigmentation. We then isolated three discrete regulatory elements driving tissue-specific gene expression in three regions of B. mori larvae. Finally, we found that there is no apparent sequence conservation of cis-regulatory regions between B. mori and Drosophila melanogaster, and no expression driven by the regulatory regions of one species when introduced into the other species. Therefore, the trans-regulatory landscapes of the yellow gene differ significantly between the two taxa. The results of this study confirm that lepidopteran species use cis-regulatory modules to control gene expression related to pigmentation, and represent a powerful cadre of transgenic tools for studying evolutionary developmental mechanisms.

Cerebral microbleeds predict infectious intracranial aneurysm in infective endocarditis.

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) features such as cerebral microbleeds and sulcal susceptibility-weighted imaging (SWI) or gradient-echo T2* lesions in infective endocarditis (IE) have been associated with the presence of infectious intracranial aneurysm (IIA). Our aim was to validate these MRI predictors for IIA in order to better assist in assessing the appropriate indications for digital subtraction angiography (DSA). METHODS: The derivation cohort comprised IE patients with neurological evaluation, MRI and DSA at a single tertiary referral center from January 2015 to July 2016. Validation was performed in a cohort of IE patients who underwent MRI and DSA at the same center from 2010 to 2014. RESULTS: Of 62 patients in the derivation cohort, 10 (16%) had IIAs. Of 129 in the validation cohort, 19 (15%) IIAs were identified. The MRI predictors for IIA consist of (i) contrast enhancement with microbleeds, (ii) cerebral microbleeds >5 mm or sulcal SWI lesions and (iii) any MRI hemorrhages. The sensitivity for the presence of IIA in each group of the derivation cohort was 90%, 80% and 100%, respectively. The sensitivity in the validation cohort was 47%, 68% and 94% respectively. The specificity in the derivation cohort was 87%, 85% and 18%. In the validation cohort, the specificity was similar at 87%, 75% and 27%. CONCLUSIONS: The absence of MRI hemorrhages may not necessitate the need for DSA.

Establishment of a specific cell death induction system in Bombyx mori by a transgene with the conserved apoptotic regulator, mouse Bcl-2-associated X protein (mouse Bax).

The induction of apoptosis in vivo is a useful tool for investigating the functions and importance of particular tissues. B-cell leukaemia/lymphoma 2-associated X protein (Bax) functions as a pro-apoptotic factor and induces apoptosis in several organisms. The Bax-mediated apoptotic system is widely conserved from Caenorhabditis elegans to humans. In order to establish a tissue-specific cell death system in the domestic silkworm, Bombyx mori, we constructed a transgenic silkworm that overexpressed mouse Bax (mBax) in particular tissues by the Gal4-upstream activation sequence system. We found that the expression of mBax induced specific cell death in the silk gland, fat body and sensory cells. Fragmentation of genomic DNA was observed in the fat body, which expressed mBax, thereby supporting apoptotic cell death in this tissue. Using this system, we also demonstrated that specific cell death in sensory cells attenuated the response to the sex pheromone bombykol. These results show that we successfully established a tissue-specific cell death system in vivo that enabled specific deficiencies in particular tissues. The inducible cell death system may provide useful means for industrial applications of the silkworm and possible utilization for other species.

A retrospective analysis of the risk factors for allergic reactions induced by the administration of oxaliplatin.

This study retrospectively investigated the clinical features and risk factors of allergic reactions induced by oxaliplatin administration. This study investigated the incidence of allergic reactions and analysed the background and laboratory data in patients with colorectal cancer treated with oxaliplatin-based chemotherapy at Kyushu Medical Center between April 2012 and September 2012. A total of 62 patients were included in this study. The number of patients in the allergic and non-allergic groups was 7 and 55 respectively. The incidence of allergic reactions was 11.3%. We compared the patients' characteristics and laboratory data between the two groups and found that the average dose of dexamethasone in the allergic group was significantly lower than that observed in the non-allergic group (P = 0.0111). Furthermore, the incidence of allergic reactions in the group that received prophylaxis of less than 12 mg of dexamethasone was significantly higher than that observed in the group that received more than 12 mg of dexamethasone (P = 0.0103). In conclusion, a lower dexamethasone dose is a possible risk factor for allergic reactions induced by the administration of oxaliplatin; however, given the retrospective design used in this study, further validation of this finding is warranted.

Establishment of transgenic silkworms expressing GAL4 specifically in the haemocyte oenocytoid cells.

Insect haemocytes play significant roles in innate immunity. The silkworm, a lepidopteran species, is often selected as the model for studies into the functions of haemocytes in immunity; however, our understanding of the role of haemocytes remains limited because the lack of haemocyte promoters for transgene expression makes genetic manipulations difficult. In the present study, we aimed to establish transgenic silkworm strains expressing GAL4 in their haemocytes. First, we identified three genes with strong expression in haemocytes, namely, lp44, Haemocyte Protease 1 (HP1) and hemocytin. Transgenic silkworms expressing GAL4 under the control of the putative promoters of these genes were then established and expression was examined. Although GAL4 expression was not detected in haemocytes of HP1-GAL4 or hemocytin-GAL4 strains, lp44-GAL4 exhibited a high level of GAL4 expression, particularly in oenocytoids. GAL4 expression was also detected in the midgut but in no other tissues, indicating that GAL4 expression in this strain is mostly oenocytoid-specific. Thus, we have identified a promoter that enables oenocytoid expression of genes of interest. Additionally, the lp44-GAL4 strain could also be used for other types of research, such as the functional analysis of genes in oenocytoids, which would facilitate advances in our understanding of insect immunity.

Outcomes of intravenous tissue plasminogen activator for acute ischaemic stroke in HIV-infected adults.

BACKGROUND AND PURPOSE: To our knowledge there are no studies reporting the use and short-term outcomes of intravenous tissue plasminogen activator (IV-TPA) for the treatment of acute ischaemic stroke (AIS) in people living with HIV. METHODS: The US Nationwide Inpatient Sample (NIS) (2006-2010) was searched for HIV-infected AIS patients treated with IV-TPA. RESULTS: In the NIS, 2.2% (62/2877) of HIV-infected AIS cases were thrombolyzed with IV-TPA (median age 52 years, range 27-78, 32% female, 22% Caucasian) vs. 2.1% (19 335/937 896) of HIV-uninfected cases (median age 72 years, range 17-102 years, 50% female, 74% Caucasian; P = 0.77). There were more deaths in HIV-infected versus uninfected patients with stroke (220/2877, 7.6% vs. 49 089/937 547, 5.2%, P < 0.001) but no difference in the proportion of deaths amongst IV-TPA-treated patients. The age- and sex-adjusted odds ratio for death following IV-TPA administration in HIV-infected versus uninfected patients was 2.26 (95% CI 1.12, 4.58), but the interaction on mortality between HIV and IV-TPA use was not statistically significant, indicating no difference in risk of in-hospital death by HIV serostatus with IV-TPA use. A higher number of HIV-infected patients remained in hospital versus died or were discharged at both 10 and 30 days (P < 0.01 at 10 and 30 days). No difference in the proportion of intracerebral hemorrhage in the two groups was found (P = 0.362). CONCLUSIONS: The in-hospital mortality is higher amongst HIV-infected AIS patients than HIV-uninfected patients. However, the risk of death amongst HIV-infected patients treated with IV-TPA is similar to HIV-uninfected groups.

PhiC31 integrase-mediated cassette exchange in silkworm embryos.

To construct an effective site-specific integration system in the silkworm, we examined if phiC31 integrase works in silkworm embryos. As an assay system, we constructed an extrachromosomal cassette exchange reaction system between two attP sites of an acceptor plasmid and two attB sites of a donor plasmid. To evaluate the activity, integrase mRNAs synthesized from three different plasmids were used. We injected a mixture of the acceptor and donor plasmids with the mRNA synthesized in vitro from one of the three plasmids into silkworm embryos at 4-6 h after oviposition and recovered plasmid DNAs from the embryos 3 days after injection. The resultant plasmids were transformed into Escherichia coli and spread on selection medium plates containing the appropriate antibiotics. A colony-forming assay and restriction enzyme digestion of the plasmids purified from the colonies showed that the phiC31 integrase worked very efficiently in the silkworm embryos. Notably, a phiC31 integrase mRNA synthesized from two of the plasmids produced cassette exchange plasmids at a high frequency, suggesting that the mRNA can be used to construct a targeted integration system in silkworms.

Transgenic analysis of the BmBLOS2 gene that governs the translucency of the larval integument of the silkworm, Bombyx mori.

The larval integument of the silkworm, Bombyx mori, is opaque because urate granules accumulate in the epidermis. Although the biosynthetic pathway of uric acid is well studied, little is known about how uric acid accumulates as urate granules in epidermal cells. In the distinct oily (od) mutant silkworm, the larval integument is translucent because of the inability to construct urate granules. Recently, we have found that the od mutant has a genomic deletion in the B. mori homologue of the human biogenesis of lysosome-related organelles complex1, subunit 2 (BLOS2) gene (BmBLOS2). Here, we performed a molecular and functional characterization of BmBLOS2. Northern blot analysis showed that BmBLOS2 was ubiquitously expressed in various tissues. We analysed the structure of a newly isolated mutant (od(B) ) allelic to od and found a premature stop codon in the coding sequence of BmBLOS2 in this new mutation. Moreover, the translucent phenotype was rescued by the germ-line transformation of the wild-type BmBLOS2 allele into the od mutant. Our results suggest that BmBLOS2 is responsible for the od mutant phenotype and plays a crucial role in biogenesis of urate granules in the larval epidermis of the silkworm. The relationships amongst Hermansky-Pudlak syndrome (HPS) genes in mammals, granule group genes in Drosophila and translucent mutant genes in B. mori are discussed.

Predicting ischaemic stroke subtype from presenting systolic blood pressure: the BASIC Project.

OBJECTIVE: We hypothesized that low presenting systolic blood pressure (SBP) predicted cardioembolic stroke aetiology. DESIGN: Active and passive surveillance were used to identify all ischaemic strokes as part of the Brain Attack Surveillance in Corpus Christi (BASIC) population-based study. Multinomial logistic regression was used to examine the association between stroke subtype and first documented SBP in the medical record. SETTING: Nueces County, TX, USA (313,645 residents in 2000). The community is urban with the majority of the population residing in the city of Corpus Christi. The area is served by seven adult acute care hospitals. PATIENTS: Three hundred and eight cases with completed ischaemic stroke and determined subtype aetiology between January 2000 and December 2002. RESULTS: Lower presenting SBP was associated with stroke subtype (P = 0.001). This association remained significant in the final model adjusted for age and history of coronary artery disease. The odds of cardioembolic versus small vessel occlusion increased by 20% (OR = 1.20, 95% CI: 1.07-1.35) for every 10 mmHg decrease in presenting SBP. Other covariates including race/ethnicity, gender, history of hypertension, and diabetes were neither significant predictors of stroke subtype, nor did they confound the association of SBP and stroke subtype. A 5 year increase in age increased the odds of cardioembolic subtype by 25% (OR = 1.25, 95% CI: 1.07-1.47). CONCLUSIONS: Lower initial SBP and older age at ischaemic stroke presentation were associated with cardioembolic stroke. Suspicion of cardioembolic stroke should be increased in those presenting with low SBP.

Compressive stress effect on the loss mechanism in a soft piezoelectric Pb(Zr,Ti)O3.

High power piezoelectric devices are often subjected to external mechanical biases, in applications such as underwater transducers. While the performance of these devices under external pressure has been rather extensively studied, there is a lack of study on the loss mechanism in terms of three dielectric, elastic, and piezoelectric losses. Thus, in this paper, we study the mechanical bias stress dependence of the loss mechanism in a soft piezoelectric Pb(Zr,Ti)O3 (PZT) from a scientific viewpoint, using an equivalent circuit methodology based on the fundamental longitudinal mode. In order to measure the loss behavior, a modified bolt-clamped Langevin transducer was designed and optimized using finite element analysis in order to facilitate the analysis easier. We present the preliminary experimental part of our project on the design of the proposed structure/methodology, material creep behavior, stress relaxation, and uniform stress distribution, in order to minimize the experimental errors. We also introduce a six terminal equivalent circuit analysis in order to determine three losses in the PZT specimen. The resonance/antiresonance frequencies and quality factors showed monotonous increase under compressive stress. Loss factors for one PZT composition are reported in this paper to show the feasibility of our methodology for measuring the uniaxial compressive stress dependence.

Factors predicting hemorrhagic complications after multimodal reperfusion therapy for acute ischemic stroke.

BACKGROUND AND PURPOSE: We sought to find predictors for hemorrhagic complications in patients with acute ischemic stroke treated with multimodal endovascular therapy. MATERIALS AND METHODS: We retrospectively reviewed patients with acute ischemic stroke treated with multimodal endovascular therapy from May 1999 to March 2006. We reviewed clinical and angiographic data, admission CT Alberta Stroke Programme Early CT Score (ASPECTS), and the therapeutic endovascular interventions used. Posttreatment CT scans were reviewed for the presence of a parenchymal hematoma or hemorrhagic infarction based on defined criteria. Predictors for these types of hemorrhages were determined by logistic regression analysis. RESULTS: We identified 185 patients with a mean age of 65+/-13 years and mean National Institutes of Health Stroke Scale score of 17+/-4. Sixty-nine patients (37%) developed postprocedural hemorrhages: 24 (13%) parenchymal hematomas and 45 (24%) hemorrhagic infarctions. Patients with tandem occlusions (odds ratio [OR] 4.6 [1.4-6.5], P<.016), hyperglycemia (OR 2.8 [1.1-7.7], P<.043), or treated concomitantly with intravenous (IV) tissue plasminogen activator (tPA) and intra-arterial (IA) urokinase (OR 5.1 [1.1-25.0], P<.041) were at a significant risk for a parenchymal hematoma. Hemorrhagic infarction occurred significantly more in patients presenting with an ASPECTS

Gastro-intestinal patch system for the delivery of erythropoietin.

The absorption of erythropoietin (EPO) from rat small intestine was studied using gastro-intestinal patches (GI-PS) in the presence of absorption enhancers. Surfactants such as a saturated polyglycolysed C8-C18 glyceride (Gelucire 44/14), PEG-8 capryl/caprylic acid glycerides (Labrasol), and polyoxyethylene hydrogenated castor oil derivative (HCO-60) were used as absorption enhancers at 143, 94 and 20 mg/kg, respectively. The absorption of EPO was studied by measuring serum EPO levels by an ELISA method after small intestinal administration of EPO-GI-PS preparation in rats at the EPO dose level of 100 IU/kg. Labrasol showed the highest absorption enhancing effect after intrajejunum administration with maximum serum EPO level of 84.1+/-11.4 mIU/ml while Gelucire 44/14 and HCO-60 showed 43.5+/-9.8 and 26.5+/-2.3 mIU/ml, respectively. The appropriate site for EPO absorption was also investigated. Jejunum was found to be the most efficient absorption site for the absorption of EPO from GI-PS. Using Labrasol as the absorption enhancer and jejunum as the absorption site, the effect of EPO dose on EPO absorption was studied by increasing the EPO dose from 50, to 100, 300 and 600 IU/kg. It was found that 100 IU/kg was the optimum dose with a serum EPO level of 84.1+/-11.4 mIU/ml while escalating doses showed decreases in serum EPO levels 48.3+/-5.6 for 300 IU/kg and 50.6+/-10.3 mIU/ml for 600 IU/kg. The percent bioavailability (BA) of EPO-GI-PS with Labrasol as absorption enhancer was 7.9 at 50 IU/kg, 12.1 at 100 IU/kg, 3.2 at 300 IU/kg and 1.2 at 600 IU/kg. Histological studies showed no adverse effect at the site of administration.

Jaw movement-related primary somatosensory cortical area in the rat.

It has anatomically been revealed that the rostral part of the rat primary somatosensory cortex (S1) directly projects to the dorsal part of the trigeminal oral subnucleus (dorVo) and the dorsal part of juxtatrigeminal region (dorVjuxt), and that the dorVo and dorVjuxt contain premotoneurons projecting directly to the jaw-opening or jaw-closing motoneurons in the trigeminal motor nucleus (Vmo). However, little is known about how the rostral S1 regulates jaw movements in relation to its corticofugal projections. To address this issue, we performed intracortical microstimulation of the rat rostral S1 by monitoring jaw movements and electromyographic (EMG) activities. We for the first time found that low-frequency long-train stimulation of the rostral S1 induced single sustained opening of the jaw with elevated EMG activities of the anterior digastric muscles (jaw-opener). The effective sites for the low-frequency long-train stimulation overlapped the S1 sites where traditional high-frequency short-train stimulation was effective to induce single twitch-like jaw movement. We also found that the effective sites for the two kinds of train stimuli were included in the rostral S1 area, which has previously been identified to send direct projections to the dorVo or the dorVjuxt. Specifically, the most effective stimulation sites for the two kinds of train stimuli were located in the rostralmost part of S1 which has been reported to emanate strong direct projections to the dorVjuxt but less to the dorVo. Therefore, the present study suggests that the rat rostral S1, especially its rostralmost part, plays an important role in controlling jaw movements by activation of direct descending projections from the rostral S1 to the trigeminal premotoneuron pools, especially to the dorVjuxt.

Degree of Collaterals and Not Time Is the Determining Factor of Core Infarct Volume within 6 Hours of Stroke Onset.

BACKGROUND AND PURPOSE: Growth of the core infarct during the first hours of ischemia onset is not well-understood. We hypothesized that factors other than time from onset of ischemia contribute to core infarct volume as measured by MR imaging. MATERIALS AND METHODS: Prospectively collected clinical and imaging data of consecutive patients with stroke presenting between March 2008 and April 2013 with anterior circulation large-vessel occlusion and MR imaging performed within 6 hours from the time of onset were reviewed. The association of time from onset, clinical, and radiographic features with DWI volume was assessed by using χ(2) and Mann-Whitney U tests. RESULTS: Of 91 patients, 21 (23%) underwent MR imaging within 0-3 hours from onset, and 70 (76%), within 3-6 hours. Median MR imaging infarct volume was similar in both timeframes, (24.7 versus 29.4 mL, P = .906), and there was no difference in the proportion of patients with large infarct volumes (≥70 mL, 23.8% versus 22.8%, P = .928). Using receiver operating characteristic analysis, we detected no association between the time from onset and MR imaging infarct volume (area under the curve = 0.509). In multivariate analysis, CTA collaterals (>50% of the territory) (adjusted OR, 0.192; 95% CI, 0.04-0.9; P = .046), CTA ASPECTS (adjusted OR, 0.464; 95% CI, 0.3-0.8; P = .003), and a history of hyperlipidemia (adjusted OR, 11.0; 95% CI, 1.4-88.0; P = .023) (but not time from stroke onset to imaging) were independent predictors of MR imaging infarct volume. CONCLUSIONS: Collateral status but not time from stroke onset to imaging was a predictor of the size of core infarct in patients with anterior circulation large-vessel occlusion presenting within 6 hours from onset.

Construction of an overproduction vector containing the novel srp (sterically repressed) promoter.

We report the design, synthesis, and evaluation of a novel Escherichia coli promoter intended for use in overproduction of proteins that are deleterious to the host. In this sterically repressed promoter (srp), the lac operator site is positioned between the -10 and -35 elements, where it can interfere sterically with RNA polymerase and thereby prevent assembly of a poised transcriptional complex. An srp-containing phagemid, pKEN1, and a tac-containing phagemid, pHN1, which has been widely used in protein overproduction but is often unstable, are compared with respect to levels of uninduced and induced protein expression. The level of uninduced protein synthesis by the srp promoter in vivo is approximately 50% of that observed with tac, whereas the levels of induced protein synthesis with the 2 vectors are approximately equal. A remarkable increase in stability of overproduction and growth was observed when the toxic Ada protein was overproduced in pKEN1, demonstrating the potential utility of this vector in overproducing toxic proteins.

Mastoparan-stimulated prolactin secretion in rat pituitary GH3 cells involves activation of Gq/11 proteins.

Mastoparan has been reported to induce a wide variety of cellular actions by activating GTP-binding proteins (G proteins) in various cells. Here, we demonstrate that mastoparan is able to stimulate the secretion of PRL from rat anterior pituitary tumor GH3 cells in dose- and time-dependent manners. Mastoparan had no effect on the accumulation of intracellular cAMP; however, it induced a rapid increase in the intracellular Ca2+ concentration in GH3 cells. Extracellular Ca2+ was required for mastoparan-induced PRL secretion, which was inhibited by nifedipine, an L-type Ca2+ channel blocker. Incubation of mastoparan with myo-[3H]inositol-labeled GH3 cells also resulted in the increased formation of inositol phosphates (InsPs) compared with control cells. Neomycin sulfate and U73122, both phospholipase C inhibitors, suppressed mastoparan-induced PRL secretion. Guanosine 5'-1beta-thioldiphosphate (GDPbetaS) encapsulated in GH3 cells by reversible electropermeabilization suppressed the response to mastoparan. However, pretreatment with pertussis toxin had no effect on the stimulation of PRL secretion by mastoparan, and both Mas7 (a highly active analogue of mastoparan) and Mas17 (an inactive analogue) enhanced the secretion of PRL to a similar level to that of mastoparan-induced GH3 cells. In contrast, the substance P-related peptide GPant-2A, a Gq antagonist, inhibited mastoparan-induced PRL release, whereas GPant-2, a G(i/o) antagonist, did not in electropermeabilized GH3 cells. Moreover, a specific G(q/11) antibody against the carboxyl terminus of the G(q/11) alpha-subunit blocked the stimulatory effect of mastoparan on secretion and mastoparan-stimulated InsPs production in digitonin-permeabilized GH3 cells. These results indicate that mastoparan induces the Ca2+-regulated secretion of PRL from GH3 cells by activating G(q/11) and the phospholipase C pathway.

Entry criteria and baseline characteristics predict outcome in acute stroke trials.

UNLABELLED: Background and Purpose-We sought to study the range of entry criteria and baseline characteristics in acute stroke trials and to understand their effects on patient outcomes. METHODS: -Randomized, placebo-controlled therapeutic trials in patients with acute ischemic stroke were identified. Entry criteria, baseline clinical characteristics, and outcome were extracted for the placebo group of each trial. The relationship between key variables was then determined. RESULTS: -Across 90 placebo groups identified, there was great variation in entry criteria and outcome measures. This was associated with divergent outcomes; for example, in some studies most placebo group patients died, while in other studies nearly all had no disability. Entry criteria were significantly correlated with outcome; for example, higher age cutoff for study entry correlated with 3-month mortality. Entry criteria also predicted baseline clinical characteristics; for example, wider time window for study entry correlated directly with time to treatment and inversely with stroke severity (initial National Institutes of Health Stroke Scale score). Baseline characteristics predicted outcome. Greater stroke severity predicted higher 3-month mortality rate; despite this, successful thrombolytic trials have enrolled more severe strokes than most trials. The mean age of enrollees also predicted 3-month mortality and was inversely related to percentage of patients with 3-month Barthel Index score >/=95. The strongest predictors of 3-month mortality were obtained with multivariate models. CONCLUSIONS: -Acute stroke studies vary widely in entry criteria and outcome measures. Across multiple studies, differences in entry criteria, and the baseline clinical characteristics they predict, influence patient outcomes along a continuum. In some studies, enrolling a specific subset of patients may have improved the chances of identifying a treatment-related effect, while in others, such chances may have been reduced. These findings may be useful in the design of future stroke therapeutic trials.

Diffusion abnormalities in patients with Wernicke encephalopathy.

Diffusion-weighted imaging (DWI) can help to diagnose acute ischemic stroke. Other nonischemic disorders may show abnormal signals with DWI. The authors report two cases of Wernicke encephalopathy with DWI signal changes in characteristic midline locations, one with reduction in apparent diffusion constant and one without. DWI abnormalities may suggest early thiamine deficiency and are useful in diagnosing Wernicke encephalopathy.