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This retrospective study investigated the nature and severity of venom-induced consumption coagulopathy (VICC) and determined the clotting factors involved in VICC in patients after envenomation by South Korea's snakes. Additionally, we studied the effectiveness of antivenom for the treatment of VICC after envenomation. Included patients were divided into three groups according to the severity of VICC (no VICC, partial VICC, and complete VICC). Data, including changes in coagulation parameters during hospitalization and clotting factors at presentation, were collected and analyzed. One hundred nineteen patients who presented at our emergency department within 3 h after snake envenomation were included. VICC developed in 34 patients (27 patients with partial VICC and 7 patients with complete VICC). Two of 34 patients with VICC required blood transfusions. Five patients with complete VICC had an undetectable fibrinogen concentration at presentation. Three patients with complete VICC had an unmeasurable INR and aPTT within 24 h. The median times of the most extreme values were 10 h for INR, 12 h for aPTT, and 16 h for fibrinogen after presentation in the VICC group. The D-dimer concentration peaked at a median of 63.5 h after presentation. The activities of factors II and X were significantly reduced in the complete VICC group (factor II: 88 (84-99.3)% in the non-VICC group vs. 69 (49.5–83.5)% in the complete VICC group; factor X:94 (83–102) in the non-VICC group vs. 70 (66.5–79.8)% in the complete VICC group), while there was no difference in factor V activity at presentation. The time from bite to first antivenom administration did not correlate with the time course and most extreme concentrations for fibrinogen and D-dimer within the VICC groups. VICC occurs in approximately one-quarter of snakebite patients in South Korea; however, VICC itself does not appear to lead to clinical deterioration. Fibrinogen is an early diagnostic maker for complete VICC. Clotting factors II and X are involved in VICC. Future investigations should explore the mechanism of VICC from Korean snakebites and the effect of antivenom on VICC. [ABSTRACT FROM AUTHOR]

This paper presents micro-particle tracking velocimetry measurements over cultured bovine aortic endothelial cell monolayers in microchannels. The objective was to quantify fluid forces and cell morphology at the sub-cellular scale for monolayers subjected to steady shear rates of 5, 10, and 20 dyn/cm2. The ultimate goal of this study was to develop an experimental methodology for in vitro detailed study of physiologically realistic healthy and diseased conditions. Cell topography, shear stress, and pressure distributions were calculated from sets of velocity fields made in planes parallel to the microchannel wall. For each experiment, measurements were made in 3 h intervals for 18 h. It was found that there is a three-dimensional change in cell morphology as a result of applied shear stress. That is, cells flatten and become more wedge shaped in the stream direction while conserving volume by spreading laterally, i.e., in the cross-stream direction. These changes in cell morphology are directly related to local variations in fluid loading, i.e., shear stress and pressure. This paper describes the first flow measurements over a confluent layer of endothelial cells that are spatially resolved at the sub-cellular scale with a simultaneous temporal resolution to quantify the response of cells to fluid loading. [ABSTRACT FROM AUTHOR]

Background and purpose: Fabry disease is an X‐linked disease, and enzyme‐based screening methods are not suitable for female patients. Methods: In total, 1000 young stroke patients (18–55 years, 661 with ischaemic stroke and 339 with hypertensive intracerebral hemorrhage) were recruited. The Sequenom iPLEX assay was used to detect 26 Fabry related mutation genes. The frequency of Fabry disease in young stroke was reviewed and compared between Asian and non‐Asian countries. Results: Two male patients with ischaemic stroke were found to have a genetic mutation of IVS4+919G>A. There was no α‐galactosidase A (GLA) gene mutation in female patients. The frequency in Asian stroke patients was 0.62% (male vs. female 0.63% vs. 0.58%) with 0.72% for ischaemic stroke and none for hemorrhagic stroke, compared to 0.88% (0.77% vs. 1.08%) with 0.83% for ischaemic stroke and 1.40% for hemorrhagic stroke reported in western countries. Conclusion: IVS4+919G>A is the GLA mutation in Taiwanese young ischaemic stroke patients. Fabry disease is more frequent among non‐Asian patients compared to Asian patients. [ABSTRACT FROM AUTHOR]

Background: We sought to investigate the utility of arterial pressure, end-tidal carbon dioxide (ETCO2 ), and central venous oxygen saturation (SCVO2 ) to guide compression depth adjustment. Thus, in a pig model of cardiac arrest, we observed these parameters during cardiopulmonary resuscitation (CPR) with optimal and suboptimal compression depths.Methods: Sixteen pigs underwent three experimental sessions after induction of ventricular fibrillation. First, the animals received two 4-min CPR trials with either optimal (20% of the anteroposterior diameter) or suboptimal (70% of the optimal depth) compression depth. Second, the animals received two 5-min CPR trials with optimal compression depth, in which adrenaline (0.02 mg/kg) or saline placebo was administered. Third, the animals randomly received compression with either optimal or suboptimal depth during advanced cardiovascular life support.Results: The systolic arterial pressure reflected compression depth most accurately and immediately (area under the curve [AUC], 0.895-0.939 without adrenaline and 0.928-1.000 with adrenaline). Although the response of ETCO2 to the change in compression depth was 0.5 min slower than that of the systolic arterial pressure, the performance of ETCO2 was comparable with that of systolic arterial pressure. SCVO2 did not reflect compression depth. Adrenaline administration remarkably increased systolic arterial pressure, diastolic arterial pressure, and coronary perfusion pressure but did not affect the ETCO2 readings.Conclusion: In a pig model of cardiac arrest, systolic arterial pressure reflected compression depth immediately and accurately. The performance of ETCO2 was comparable with that of systolic arterial pressure. SCVO2 did not reflect compression depth. [ABSTRACT FROM AUTHOR]

Background and purpose Our aim was to investigate the influence of admission dehydration on the discharge outcome in acute ischaemic and hemorrhagic stroke. Methods Between January 2009 and December 2011, 4311 ischaemic and 1371 hemorrhagic stroke patients from the stroke registry of Chang Gung healthcare system were analyzed. The eligible patients were identified according to inclusion/exclusion criteria. In total, 2570 acute ischaemic and 573 acute hemorrhagic stroke patients were finally recruited. According to the blood urea nitrogen ( BUN) to creatinine (Cr) ratio ( BUN/Cr), these patients were divided into dehydrated ( BUN/Cr ≥ 15) and non-dehydrated ( BUN/Cr < 15) groups. Demographics, admission costs and discharge outcomes including modified Rankin scale (m RS) and Barthel index ( BI) were examined. Data were analyzed using multivariate analysis of two-stage least squares including logistic and linear regression. Results Acute ischaemic stroke with admission dehydration had higher infection rates ( P = 0.006), worse discharge BI (62.8 ± 37.4 vs. 73.4 ± 32.4, P < 0.001, adjusted P < 0.001), worse m RS (2.7 ± 1.6 vs. 2.3 ± 1.5, P < 0.001, adjusted P = 0.009) and higher admission costs (2470.8 ± 3160.8 vs. 1901.2 ± 2046.8 US dollars, P < 0.001, adjusted P = 0.013) than those without dehydration. However, acute hemorrhagic stroke with or without admission dehydration showd no difference in admission costs ( P = 0.618) and discharge outcomes ( BI, P = 0.058; m RS, P = 0.058). Conclusion Admission dehydration is associated with worse discharge outcomes and higher admission costs in acute ischaemic stroke but not in hemorrhagic stroke. [ABSTRACT FROM AUTHOR]

Major vault protein (MVP), the main component of vault complex, is overexpressed in many multidrug-resistant cancer cell lines, suggesting a possible role for MVP in cell signaling and survival. In this study, we have found that MVP is markedly increased in senescent human diploid fibroblasts (HDFs) as well as in aged organs. We examined whether MVP expression might be affected by apoptotic stress in an aging-dependent manner. We treated young and senescent HDFs with apoptosis-inducing agents such as H2O2, staurosporine and thapsigargin, and monitored MVP expression. We found that MVP expression is markedly reduced in young HDFs but not in senescent HDFs, in response to apoptotic stresses. Downregulation of MVP increased the sensitivity of senescent HDFs to apoptosis. Also, the level of antiapoptotic B-cell lymphoma protein-2 (Bcl-2) was significantly reduced and the accumulation of c-Jun increased in MVP knocked-down senescent HDFs. Moreover, treatment of MVP knocked-down senescent HDFs with SP600125, a specific c-Jun NH(2)-terminal kinase (JNK) inhibitor, restored the level of Bcl-2 protein. Taken together, these results suggest that MVP is important in the resistance of senescent HDFs to apoptosis by modulation of Bcl-2 expression by JNK pathway.Cell Death and Differentiation (2008) 15, 1673–1680; doi:10.1038/cdd.2008.96; published online 4 July 2008 [ABSTRACT FROM AUTHOR]

We previously reported that senescent human diploid fibroblasts (HDFs) are resistant to apoptosis induced by H2O2 and staurosporine. We report here that senescent HDFs are resistant to thapsigargin-induced apoptosis as well. These agonists caused the reductions in mitochondrial membrane potential (MMP) and in the apoptosis inhibitory protein (B-cell lymphoma) only in young HDFs but not in senescent HDFs. In addition, downregulation of Bcl-2 increased the sensitivity of senescent HDFs to apoptosis induction, suggesting the significant role of Bcl-2 in apoptosis resistance of the senescent HDFs. We further found that P-cAMP response element-binding protein (CREB), a positive regulator of Bcl-2, decreased in stress-induced apoptosis of young HDFs but not in senescent HDFs, and that Bcl-2 was markedly reduced in CREB small interfering RNA (siRNA), transfected senescent HDFs. In addition, activity of protein phosphatase 2A (PP2A), which dephosphorylates p-CREB, significantly increased in young HDFs but not in senescent HDFs treated with H2O2, staurosporine or thapsigargin. Taken together, these results suggest that failure of stress-induced downregulation of Bcl-2 underlies resistance of senescent HDFs to apoptosis.Cell Death and Differentiation (2007) 14, 1020–1028. doi:10.1038/sj.cdd.4402091; published online 9 February 2007 [ABSTRACT FROM AUTHOR]

A decreased apoptotic response toward noxious stress is an issuing characteristic of the aging phenotype. Hydrogen peroxide or staurosporine induced apoptosis readily in young cells but not in senescent cells. We showed that focal adhesion kinase (FAK) expression and its phosphorylation at Tyr397, autophosphorylation site for focal adhesion formation, and Tyr577, Src-dependent phosphorylation site, were both increased in senescent cells. Moreover, FAK was inactivated proteolytically by apoptotic stimuli in young cells, but not in senescent cells. In addition, senescent cells whose FAK expression was downregulated by siRNA showed the increased level of apoptosis by staurosporine treatment via caspase-3 activation but not by hydrogen peroxide treatment. Interestingly dephosphorylation at Tyr577 of FAK by PP2 treatment, Src-family kinase inhibitor, induced the apoptosis by staurosporine in senescent cells but dephosphorylation at Tyr397 by downregulation of caveolin-1 was not affected. These data suggest that FAK might differently regulate apoptosis and focal adhesion formation through site-specific tyrosine phosphorylation in senescent cells. [ABSTRACT FROM AUTHOR]

Four middle-aged male Chinese with polyneuropathy, skin hyperpigmentation, oedema, hepatosplenomegaly, ascites, gynaecomastia and white nails are described. In Japan and United States this syndrome has been associated with plasma cell dyscrasia. However, neither M-protein nor skeletal lesions were demonstrated in these four patients. [ABSTRACT FROM AUTHOR]

Background: This study examined how intracranial large artery stenosis (ILAS), symptomatic and asymptomatic ILAS, and risk factors affect unfavorable outcome events after medical treatment in routine clinical practice.Methods: This was a 24-month prospective observational study of consecutively recruited stroke patients. All participants underwent magnetic resonance angiography, and their clinical characteristics were assessed. Outcome events were vascular outcome, recurrent stroke, and death. Cox regression analyses were performed to identify potential factors associated with an unfavorable outcome, which included demographic and clinical characteristics, the risk factors, and stenosis status.Results: The analysis included 686 patients; among them, 371 were assessed as ILAS negative, 231 as symptomatic ILAS, and 84 as asymptomatic ILAS. Body mass index (p < .05), hypertension (p = .01), and old infarction (p = .047) were factors relating to vascular outcomes. Hypertension was the only factor for recurrent stroke (p = .035). Poor glomerular filtration rate (< 30 mL/min/1.73 m2) (p = .011) and baseline National Institutes of Health Stroke Scale scores (p < .001) were significant predictors of death.Conclusions: This study extended previous results from clinical trials to a community-based cohort study by concurrently looking at the presence/absence of stenosis and a symptomatic/asymptomatic stenotic artery. Substantiated risk factors rather than the stenosis status were predominant determinants of adverse outcome. Although the degree of stenosis is often an indicator for treatment, we suggest risk factors, such as hypertension and renal dysfunction, should be monitored and intensively treated. [ABSTRACT FROM AUTHOR]