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Aim: Although a lower level of non-high-density lipoprotein cholesterol (HDL-C) was reported to be inversely associated with spontaneous intracranial hemorrhage (ICH), no enough evidence has verified whether lipid profiles modify hemorrhagic transformation and functional outcomes in patients with acute ischemic treated with thrombolysis. Methods: This multicenter cohort study included 2373 patients with acute ischemic stroke treated with intravenous thrombolysis between December 2004 and December 2016. Of these, 1845 patients were categorized into either the hyperlipidemia or non-hyperlipidemia group. Symptomatic ICH (SICH) rates within 24–36 h of thrombolytic onset and functional outcomes at 30 and 90 days were longitudinally surveyed. Models of predicting hemorrhagic transformation were used to validate our findings. Results: For enrolled 1845 patients, SICH rates were ≥ 2-fold reduced for the hyperlipidemia group by the NINDS (adjusted RR: 0.488 [0.281–0.846], p = 0.0106), the ECASS II (adjusted RR: 0.318 [0.130–0.776], p = 0.0119), and SITS-MOST standards (adjusted RR: 0.214 [0.048–0.957], p = 0.0437). The favorable functional rates between the two groups were not significantly different. Lower levels of LDL-C were showed in robust association with SICH. With a cut-off LDL-C value of < 130 mg/dL, new models are more robust and significant in predicting hemorrhagic transformation within 24–36 h. Conclusions: This study supports the strong association between reduced LDL-C and increased SICH, but not for functional outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis. LDL-C level of < 130 mg/dL is supposed to a candidate marker for predicting SICH within 24–36 h.

OBJECTIVES Dabigatran etexilate is a direct thrombin inhibitor that clinicians increasingly prescribe to prevent stroke in patients with non-valvular atrial fibrillation (NVAF). Clinicians also commonly prescribe statins for primary and secondary prevention of cardiovascular diseases. Little is known about the bleeding risk in patients taking a statin and dabigatran together. The aim of this study was to evaluate the safety and persistence of dabigatran after co-medication with statins. MATERIALS AND METHODS We performed a prospective, multicenter registry study of stroke patients with NVAF who initiated dabigatran therapy within 3 months after a clinically evident ischemic cerebrovascular event between 2013 and 2017. The main outcome measure was symptomatic bleeding after 90, 180, and 360 days. RESULTS In total, 652 patients (336 statin users, 316 non-users) were followed for 1 year after dabigatran therapy. Cox multivariate analysis demonstrated that male sex, prior use of aspirin, and concurrent use of an antiarrhythmic drug were associated with a higher risk of bleeding at 360 days. After adjusting time-dependent covariates, statin users had a significantly lower bleeding risk (adjusted hazard ratio: 0.11, P

Human norovirus (NoV) is the leading cause of acute gastroenteritis and the rapid transmission of NoV renders infection control problematic. Our study aimed to investigate viral shedding in gastroenteritis in children caused by variants of emerging norovirus strains infections.We used RNA-dependent RNA polymerase (RdRp) sequencing to measure NoV genome copies in stool to understand the relationship between the clinical manifestations and viral shedding in hospitalized patients. The near full-length NoV genome sequence was amplified via reverse transcription-polymerase chain reaction (RT-PCR) and NoV recombination was analyzed using the Recombination Analysis Tool (RAT).From January 2015 to March 2018, 77 fecal specimens were collected from hospitalized pediatric patients with confirmed NoV gastroenteritis. The NoV genotypes were GII.4 (n = 22), non-GII.4 (n = 14), GII.4 Sydney (n = 21), and GII.P16-GII.2 (n = 20). Viral load increased from days 2 to 9 from the illness onset, resulting in an irregular plateau without peaks. After day 9, the viral load declined gradually and most viral shedding in feces ceased by day 15. The average viral load was highest in GII.4 Sydney followed by GII.P16-GII.2 infections and lowest in non-GII.4 infections. GII.4 unclassified infections showed the longest viral shedding time, followed by GII.4 Sydney infections, GII.P16-GII.2 recombinant infection resulted in the shortest duration. NoVs evolved to form a group of GII.P16-GII.2 variants during the 2017 to 2018 period.The viral load and shedding period and was different in variants of NoV infections in children. High mutation rate of emerging and re-emerging variants was observed to an enhanced epidemic risk rendering continuous surveillance.

Background/Purpose: Rotavirus vaccines were launched in Taiwan since early 2006. Our study was aimed to figure out long-term extended molecular epidemiology in acute gastroenteritis (AGE) in hospitalized young children after rotavirus vaccination in Taiwan. Methods: During the 10-year period from January 2007 to December 2016, fecal samples from children under 5 years old with AGE hospitalized in Chang Gung Children's Hospital (CGCH) were examined for enteric pathogens and they were divided into two time intervals: early post-vaccine (Jan. 2007 to Dec. 2011; EPV) and late post-vaccine (Jan. 2012 to Dec. 2016; LPV). Results: In total, 837 patients with AGE were enrolled with complete study. In the EPV period, 106 (26.7%) rotavirus and 65 (16.4%) norovirus infections were identified as major pathogens. In the LPV period, 79 (17.9%) rotavirus and 98 (22.2%) norovirus infections were diagnosed. Statistical analyses showed a significantly decreased prevalence of rotavirus infection (P = 0.002) and a significantly increased prevalence of norovirus (P = 0.034) and enteric bacterial infections (P

Background and aims Renal dysfunction is a potent risk factor for cardiovascular diseases, including stroke. This study aimed to evaluate the impact of admission estimated glomerular filtration rate (eGFR) levels on short-term (1-month) and long-term (1-year) mortality in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we classified ischemic stroke patients, identified from April 2006 to December 2015, into 5 groups by eGFR at admission: ≥ 90, 60–89, 30–59, 15–29, and Results Among 52,732 ischemic stroke patients, 1480 died within one month. The 1-month mortality rate was over 5-fold greater in patients with eGFR Conclusions After acute ischemic stroke, patients with reduced eGFR are at elevated risks of short-term and long-term deaths in a graded relationship.

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients.From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013.Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of 120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of 120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively.Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or 120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

Despite the development of vaccines in 2006, rotavirus is still a major cause of acute gastroenteritis worldwide. This study was performed to analyze the presence of circulating rotaviruses before and after the introduction of rotavirus vaccines to allow phylogenetic comparisons of vaccine strains in northern Taiwan. Rotavirus genotyping and sequencing of rotavirus VP7 and VP4 PCR products were performed by Reverse Transcriptase Polymerase Chain Reaction and DNA autosequencing. Phylogenies were constructed by the neighbor-joining and maximum-likelihood methods using CLUSTAL W software included in the MEGA software package (version 6.0). Between April 2004 and December 2012, a total of 101 rotavirus specimens from pediatric patients with acute gastroenteritis hospitalized in Chang Gung Children's Hospital were amplified, and their VP4 and VP7 sequences were determined. These 101 specimens consisted of 55 pre-vaccine strains (G1 [13, 23.6%], G2 [12, 21.8%], G3 [16, 29.1%], and G9 [14, 25.5%]) and 46 post-vaccine strains (G1 [25, 54.3%], G2 [12, 26.1%], G3 [5, 10.9%], and G9 [4, 8.7%]). The most common combination of the G and P types was G2P[4], accounting for 36% cases, followed by G9P[8] (25%), G1P[8] (20%), G3P[4] (15%), G3P[8] (10%), G1P[4] (5%), and G2P[8] (5%). Phylogenetic analysis showed that only the G1 and P[8] genotypes clustered in the same lineages with the rotavirus vaccine strains. Based on our results, the inclusion of G9, modified G2 and G3 with target lineages, and the combination G2P[4] and G9P[8] in the rotavirus vaccines in Taiwan is warranted as a vaccination strategy.

Background The ingestion of multiple magnets may lead to severe complications including bowel obstruction, perforation, fistula, peritonitis, short bowel syndrome, life-threatening injuries, and even death. The annual case number of high-powered neodymium magnets ingestion has been increasing in the western world and the dearth of available data demonstrates that this issue has been neglected in Taiwan. Methods We searched the electronic medical records of our institution for patients younger than 18 years old who were diagnosed with, who had ever visited our emergency department, or been hospitalized for magnetic foreign body ingestion between January 2009 and March 2018. Demographic data including the number, shape, and size of magnets ingested, the clinical presentation, type of intervention, and complications were reviewed. Results Thirteen patients who met the enrollment criteria were analyzed. One patient was documented between 2009 and 2013, and twelve were documented between January 2014 and March 2018. Five of the cases documented between 2014 and 2018 had ingested Buckyballs. The median age of the patients was 5 years. All of the patients with clinical symptoms had ingested more than one magnet and required endoscopic or surgical intervention. Bowel perforation or deep ulcer with impending perforation was found in three patients during surgery. Conclusion The number of children who visited our emergency department or were hospitalized due to the ingestion of magnets has increased recently. The presence of high power of neodymium magnets in many products increases the risk of ingesting multiple magnets resulting in serious complications. Therefore, stricter policies are needed to prevent children from obtaining products that contain magnets.

Prediabetes increased risk of diabetes and diabetes‐related macrovascular and microvascular complication. Glycohemoglobin (HbA1c) is clinically used as the gold standard for glycemic control of diabetes. Glycated albumin (GA) is an early Amadori‐type glycation protein between glucose and serum albumin, which changes in a shorter period of time than HbA1c and is superior to HbA1c in reflecting fluctuations in blood glucose. In this study, we aim to assess the predictive value of GA and glycohemoglobin (HbA1c) on a progression of diabetic retinopathy (DR) in prediabetic patients in Taiwan. This study was conducted at the outpatient department of a regional hospital in Southern Taiwan, and recruited 291 patients with prediabetes from January 2016 to February 2017. Blood and urine samples were obtained from all patients after fasting for 12 hours within 1 month of enrollment. The mean age is 62.5 ± 13.0 years and there are 161 males and 130 females. A total of 24.1% of patients have DR. The average value of GA and HbA1c are 14.6% ± 2.8% and 6.0% ± 0.4%, respectively. Old age, male, high systolic blood pressure, high HbA1C, and low total cholesterol are significantly associated with DR in patients with pre‐DM. Therefore, in the prediabetic populations, high HbA1C, but not GA nor GA/HbA1C ratio, is significantly associated with DR.

Background and purpose The optimal dose of alteplase for acute ischemic stroke among geriatric patients is unclear. We aimed to assess the efficacy and safety of a low-dose (0.6 mg/kg) and standard-dose (0.9 mg/kg) alteplase for varying severity of Asian geriatric stroke patients. Methods The favorable functional outcome on day 90 after stroke onset, and the symptomatic intracranial hemorrhage (SICH) rate following 24–36 h of intravenous alteplase were measured. The baseline NIHSS of 4–8, 9–13, ≥14 were defined as mild, moderate, and high severity, respectively. Results Totally, 249 geriatric patients treated with low-dose (n = 108) and standard-dose (n = 141) alteplase. Compared to standard-dose alteplase, low-dose alteplase had decrease in favorable functional outcome (22.2% versus 34.8%), and no difference in SICH rates was observed. For mild severity patients, the mortality was significantly increased with standard-dose alteplase (the NNT/NNH = 22.9/8.0 for mild severity, the NNT/ NNH = 15.0/14.7 for moderate severity, and the NNT/NNH = 13.5/19.6 for high severity). Conclusions Standard-dose and low-dose alteplase were comparable in reducing major disability, but low-dose alteplase for mild stroke showed much reduced mortality on day 90 for octogenarians.

Red blood cell (RBC) aggregation and iron status are interrelated and strongly influenced by dietary factors, and their alterations pose a great risk of dyslipidemia and metabolic syndrome (MetS). Currently, RBC aggregation-related dietary patterns remain unclear. This study investigated the dietary patterns that were associated with RBC aggregation and their predictive effects on hyperlipidemia and MetS. Anthropometric and blood biochemical data and food frequency questionnaires were collected from 212 adults. Dietary patterns were derived using reduced rank regression from 32 food groups. Adjusted linear regression showed that hepcidin, soluble CD163, and serum transferrin saturation (%TS) independently predicted RBC aggregation (all p &lt, 0.01). Age-, sex-, and log-transformed body mass index (BMI)-adjusted prevalence rate ratio (PRR) showed a significant positive correlation between RBC aggregation and hyperlipidemia (p-trend &lt, 0.05). RBC aggregation and iron-related dietary pattern scores (high consumption of noodles and deep-fried foods and low intake of steamed, boiled, and raw food, dairy products, orange, red, and purple vegetables, white and light-green vegetables, seafood, and rice) were also significantly associated with hyperlipidemia (p-trend &lt, 0.05) and MetS (p-trend = 0.01) after adjusting for age, sex, and log-transformed BMI. Our results may help dieticians develop dietary strategies for preventing dyslipidemia and MetS.

Contrast transcranial Doppler (c-TCD) is sensitive in detecting right-to-left shunt (RLS). However, the methodology and ideal posture are controversial. Consecutive migraine patients were prospectively examined for RLS using c-TCD. Each patient was examined while at rest and subsequently with the Valsalva maneuver (VM) in three positions: supine, left lateral decubitus and right lateral decubitus. RLS was diagnosed with at least one microbubble detected at any position. RLS was highest in the left lateral decubitus position, both during rest and with VM. The left lateral decubitus position was associated with the highest total number of microbubbles and greater shunt grades. Patients who tested positive in the other two positions had the lowest index position failure rate during rest in the left lateral decubitus position. In some patients in whom RLS is detected at rest, it may not be detected (false negative) under VM. To ensure c-TCD's the sensitivity to RLS, testing in the left lateral decubitus position at rest and under VM is suggested; testing in other positions is necessary to avoid false negatives.

Poorly controlled blood glucose was reported to cause deterioration of acute ischemic stroke. In this study, we investigated whether an elevated admission serum glucose level in the 3-h time window of intravenous thrombolysis for acute ischemic stroke determined poor functional outcomes among Chinese population.This was a prospective cohort study. From December 1, 2004 to December 31, 2016, a total of 2370 patients were enrolled and categorized into two cohorts by blood glucose levels of ≥200 and200 mg/dl in the 3 h after stroke onset. The primary objective was to determine whether admission hyperglycemia increased major disability and death at 30 and 90 days, which was defined by a modified Rankin Scale of 3-6. The secondary objective was to determine whether admission hyperglycemia increased the symptomatic intracranial hemorrhage (SICH) at 90 days. The number needed to harm (NNH) and patient expected event rate (PEER) were evaluated for both the primary and secondary objectives.The primary outcome occurred in 216 of 305 patients (70.8%) in the blood glucose ≥200 mg/dl cohort and in 951 of 1587 patients (59.9%) in the blood glucose200 mg/dl cohort at 30 days, and in 191 of 287 patients (66.6%) in the blood glucose ≥200 mg/dl cohort and in 827 of 1517 patients (54.5%) in the blood glucose200 mg/dl cohort at 90 days. Patients with admission hyperglycemia had significantly increased major disability and death at 30 (adjusted relative risk (RR): 1.194 [1.073-1.329], p = 0.0012) and 90 days (adjusted RR: 1.203 [1.079-1.340], p = 0.0008). Admission hyperglycemia increased the risk of the occurrence of SICH by nearly 2-fold (adjusted RR: 1.891 [0.977-3.657], p = 0.0585 with the SITS-MOST criteria and adjusted RR: 1.884 [1.138-3.121], p = 0.0139 with the NINDS criteria). NNH values of admission hyperglycemia in major disability and death at 30 and 90 days were 9 and 10, and NNH values of SICH by the SITS-MOST NINDS criteria were 44 and 34, respectively.The study evidenced the association and temporal relationship of admission hyperglycemia causing deterioration of functional outcomes and increased SICH among Chinese population with acute ischemic stroke treated with intravenous thrombolysis.

Background/Purpose: The diagnostic and therapeutic benefits of double-balloon enteroscopy (DBE) in adults are established, but few data are available on pediatric patients. The aim of this study was to evaluate the clinical efficacy and safety of DBE in pediatric patients in Taiwan. Methods: From April 2005 to September 2015, DBE procedures performed for diagnosis or therapy of small-bowel disease in children less than 18 years of age at Linkou Chang Gung Memorial Hospital, Taiwan were evaluated. The clinical decision to perform DBE via the oral or anal approach was based on the patient's primary clinical presentation. Data on indications, endoscopic findings, treatment outcome, and complications associated with the procedure were collected and reviewed retrospectively. Result: In total, 20 pediatric patients underwent a total of 29 DBEs due to suspicion of small-bowel disease. Among them, nine patients were evaluated for suspected small-bowel bleeding, six for Peutz-Jeghers syndrome, two for chronic abdominal pain, two for chronic diarrhea, and one for suspected protein-losing enteropathy. After excluding the six Peutz-Jeghers syndrome patients, 9 of the 14 patients (64%) got a positive endoscopic finding and diagnosis in 8 of the 14 patients (57%). DBE resulted in a further therapeutic intervention (endoscopic or surgical) in 50% of the patients (10/20) without serious complications. Conclusion: DBE has a high diagnostic yield and leads to therapeutic interventions in pediatric patients and shows promise for assessment and treating small-intestinal diseases in children in Taiwan. Keywords: Double-balloon enteroscopy, Pediatric, Taiwan, Suspected small-bowel bleeding

Delayed detection of atrial fibrillation (AF) is common in patients with stroke. However, it is not well known whether delayed identification of AF in patients with stroke affects the prognosis of patients.To evaluate the association between the timing of AF diagnosis after stroke and clinical outcomes.We identified a cohort of all patients admitted with a primary diagnosis of first-ever ischaemic stroke, which was categorised into three groups, namely, non-AF, AF presenting with stroke and delayed AF diagnosis groups. The study patients were individually followed for 5 years to evaluate the occurrence of recurrent stroke and death.In total, 17 399 patients were hospitalised with first-ever ischemic stroke, of whom 16 261 constituted the non-AF group, 907 the AF presenting with stroke group and 231 the delayed AF diagnosis group. During the 5-year follow up, 2773 (17.1%), 175 (19.3%) and 68 (29.4%) patients in the non-AF, AF presenting with stroke and delayed AF diagnosis groups, respectively, were hospitalised for recurrent stroke. The delayed AF diagnosis group exhibited a 1.57-times higher risk of recurrent stroke than the AF presenting with stroke group, after adjustment for the CHA2DS2-VASc scores (adjusted hazard ratio (HR): 1.57; 95% confidence interval (CI) = 1.19-2.08; P = 0.002). In addition, delayed diagnosis of AF significantly increased the risk of recurrent stroke in men, but not in women, after adjustment for the CHA2DS2-VASc scores.Delayed diagnosis of AF after stroke increased the risk of recurrent stroke, particularly in men.

The early identification of patients with large hemisphere infarctions (LHIs) at risk of fatal brain edema may result in better outcomes. A quantitative model using parameters obtained at admission may be a predictor of in-hospital mortality from LHI. This prospective study enrolled all patients with LHI involving >50% of the middle cerebral artery (MCA) admitted to our neurological intensive care unit within 48 hours of symptom onset. Early clinical and radiographic parameters and the baseline CHADS2 score (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke [double weight]) were analyzed regarding their ability to predict patient outcomes. Seventy-seven patients with LHIs were identified, 33 (42.9%) with complete MCA infarction (CMCA), and 44 (57.1%) with incomplete MCA infarction (IMCA). The predictors of CMCA score included: >1/3 early hypodensity in computed tomography findings, hyperdense MCA sign, brain edema, initial National Institutes of Health Stroke Scale (NIHSS) score ≥17, and stroke in progression during the 1st 5 days of admission. The cutoff CMCA score was 2, with a sensitivity of 81.8% and specificity of 70.5%. Mortality score 1, used for predicting in-hospital mortality from LHI, included CMCA and CHADS2 scores ≥4 (sensitivity 100.0%, specificity 57.4%), and mortality score 2 included CMCA and CHADS2 scores ≥4, and NIHSS score ≥26, during the 1st 5 days (sensitivity 100.0%, specificity 91.7%). Patients qualifying for a mortality score of 2 were at high-risk of in-hospital mortality from LHI. These findings may aid in identifying patients who may benefit from invasive therapeutic strategies, and in better describing the characteristics of those at risk of mortality.

This study evaluated the prevalence of clinical multidrug-resistant organisms (MDROs) and analyzed correlations between MDROs and patient characteristics in a regional teaching hospital of Taiwan. A retrospective comparative case-control study was conducted from January 2016 to August 2018 by collecting data from 486 hospitalized and non-hospitalized patients (M = 286, F = 200), including patient gender and age, microbial species, and antibiotic susceptibility. The results indicated that at least one MDRO was isolated from 5.3&ndash, 6.3% of patients (p &lt, 0.05), with an average age of 61.08 years. Of the MDROs strains, vancomycin-resistant enterococcus and carbapenem-resistant acinetobacter baumannii increased annually (p &lt, 0.002 and p &lt, 0.012, respectively). Three factors of age (over 60 years), treatment in an intensive care unit (ICU), and specimen category were statistically significant (p &lt, 0.039, p &lt, 0.001 and p &lt, 0.001, respectively) and indicated that elderly patients in an ICU have a higher risk of being infected by MDROs. The outpatients infected by methicillin-resistant staphylococcus aureus (MRSA) were more frequent than inpatients, implying the existence of community-acquired MRSA strains. The results of this study could provide valuable information for the detection and colonization of multidrug-resistant organisms in hospital infection control systems.

Background Interleukin 10 (IL-10) has multifaceted anti-inflammatory properties that are known to regulateinsulin sensitivity and atherosclerotic development. However, studies in children are limited and have yieldedconflicting results. The aim of this study was to evaluate whether changes in this circulating anti-inflammatorycytokine is a marker for metabolic syndrome.Materials and methods This cross-sectional study involved children and young adolescents from eight ele-mentary schools and two junior high schools located in Taipei and New Taipei City. A total of 553 children ages8, 11 and 13 years old were included in the analysis. Parameters for obesity, anti- and pro-inflammatorycytokines, and metabolic risk profiles were evaluated.Results Overweight/obese children had lower serum IL-10 concentrations compared with normal weight chil-dren in the same age group (all P < 0 001). IL-10 quartiles were negatively associated with body mass index(BMI) and percentage (%) body fat (all P < 0 05). Multivariate regression analysis showed significant inverserelationship between IL-10 concentrations and % body fat (b = 0 009, P < 0 0001), and total cholesterol(b = 0 726, P = 0 003), and a small positive correlation between IL-10 and systolic blood pressure (b = 0 980,P = 0 027). In normal weight children, IL-10 concentrations were independently associated with fasting plasmainsulin (b = 0 2912, P = 0 001) and waist circumference (b = 0 0069, P = 0 022). By contrast, % body fat(b = 0 016, P = 0 0009) was independently associated with IL-10 concentrations in overweight and obesechildren. Association between IL-10 and fasting plasma insulin concentrations was weaker in overweight/obesechildren compared with normal weight (b = 0 283, P = 0 011 vs. b = 0 2912, P = 0 001).Conclusion Our data indicate that changes in circulating IL-10 concentrations are marker of metabolic risk inchildren.Keywords Fasting plasma insulin, interleukin 10, metabolic syndrome, obese children, percentage body fat,total cholesterol.Eur J Clin Invest 2014; 44 (4): 384–394

Accurate diagnosis of subtypes of transverse sinus (TS) hypoplasia requires more expensive methods like magnetic resonance (MR) imaging. We hypothesized ultrasound findings of the internal jugular vein (IJV) can be surrogate indicators for diagnosis of TS hypoplasia. MR images were reviewed in 131 subjects to evaluate TS diameter and the location and degree of venous flow stenosis and obstruction. Ultrasound parameters including the cross-sectional lumen area (CSA), time-average-mean velocity (TAMV), and flow volume (FV) at each IJV segment were also evaluated. Sixty-nine subjects had TS hypoplasia based on MRV criteria, of which 39 TS hypoplasia were considered a subtype of TS hypoplasia, which is secondary to the downstream venous compression/stenosis or left brachiocephalic vein. In the ultrasound study, the CSA of the IJV ipsilateral to TS hypoplasia was significantly smaller. Further, a contralateral/ipsilateral IJV CSA ratio >1.55 provided good sensitivity, specificity, and positive predictive value for discriminating TS hypoplasia.

Background Norovirus (NoV) GII.4 is the most common genotype for norovirus gastroenteritis worldwide. New variants or subgenotypes are continuously emerging, thus posing a serious threat to child health. Methods We compared retrospectively the clinical manifestations and complications of norovirus gastroenteritis in children from April, 2004 through December, 2012. NoV variants were analyzed to investigate the association of circulating viral strains with the complications. A modified disease severity score system based on Vesikari score system was devised and to evaluate disease severity. Results Compared to the outbreak in 2004/2005 winter, significant higher incidence of complications in the later periods are: convulsive disorder (p 39 °C, p = 0.001) in 2011/2012 winter. GII.4 Den_Haag_2006b, GII.4 2010, GII.4 Sydney 2012, and GII.4 2012b were the predominant strains in the outbreaks after 2006. By the modified severity score system, severe norovirus disease occurred in 28.5 %, 32 %, 33.3 %, and 30.2 % of the patients in the four periods. A longer duration of hospitalization (p = 0.02) were found in those with high score irrespective of the year of admission. Conclusions Our study demonstrated NoV outbreaks in northern Taiwan caused by different GII.4 variants that were associated with specific complications and uncommon clinical presentations. A modified severity score system first proposed in this study was able to identify severe cases with a longer hospital stay in NoV-infected children.

cope Diabetes is associated with increased risks of anemia and activation of advanced glycation end products (AGEs) and the receptor for AGEs (RAGE). However, the effects of pharmacological doses of iron supplementation on AGE metabolism are less clear. The aim was to investigate the effect of ferric citrate supplementation on AGE metabolism. Methods and results Diabetes was induced in overnight starved rats by intraperitoneal injections of 40 mg/kg streptozotocin and 120 mg/kg nicotinamide. Diabetic rats were fed a standard diet or pharmacological doses of ferric citrate (0.5, 1, 2, and 3 g of ferric iron/kg diet) for 10 weeks. Ferric citrate supplementation showed a dose-related effect on the hepatic steatosis score, malondialdehyde, cathepsin D, and glyoxalase I. A Western blot analysis revealed that >1 g of ferric iron suppressed hepatic AGE receptor 1 and high-mobility group-box 1 expressions but increased heme oxygenase-1 and RAGE expressions. Further analysis showed that high doses of ferric iron triggered sterol regulatory element-binding protein 1c, p38-mitogen-activated protein kinase, and nuclear factor-κB protein expressions. Conclusions Overall, the present results suggest a dose-related effect of ferric citrate supplementation on AGE metabolism, and this effect was more evident at high iron doses (>1 g of ferric iron/kg diet). This article is protected by copyright. All rights reserved

Background Few data are available on the tolerance of reirradiation in patients with hepatocellular carcinoma (HCC). This study determined the clinical parameters contributing to the development of radiation-induced liver disease (RILD). Methods We included 36 patients with HCC who received 2 courses of radiotherapy (RT) to the liver. Using α/β = 15 for tumor and α/β =8 for normal liver tissue for biologically equivalent doses in 2 Gy fractions, mean cumulative to the hepatic tumor and normal liver were 87.7 Gy15 and 31.1 Gy8, respectively. Hepatic toxicities were classified according to the Common Terminology Criteria for Adverse Events, Version 4.0. Clinical data, including liver function test results, radiological study findings, and RT parameters before and after both courses of RT were retrieved for analysis. Using multivariate analysis, logistic regression was used to identify the predictors of RILD, and Cox regression was performed to explore the prognostic factors for overall survival (OS). Results Thirteen patients (36 %) developed RILD after reirradiation. Nine of them died because of progressive liver failure without evidence of tumor progression and were categorized to have lethal RILD. A pretreatment Child–Turcotte–Pugh (CTP) score ≥6 was the only predictor of RILD [odds ratio (OR): 15.83, p = 0.001] and lethal RILD [OR: 72.56, p = 0.005]. In addition, a CTP score ≥6 and the presence of portal vein tumor thrombosis before reirradiation were 2 prognostic factors for OS. Conclusion Despite a limited sample size, residual liver function using a preirradiation CTP score ≥6 is a clinical parameter associated with an increased risk of RILD in patients requiring hepatic reirradiation.

Introduction Early diagnosis and treatment of central nervous system (CNS) tuberculosis (TB) are very important because of its high morbidity and mortality characteristics. However, the clinical symptoms, laboratory and neuroimaging findings of CNS TB are nonspecific, no matter whether they are the common form, tuberculous meningitis (TBM), or the rare form, intracranial tuberculomas. We report a case of TBM with miliary pattern of intracranial tuberculomas, although the initial diagnosis was masked by an atypical neuropsychiatric presentation, cerebrospinal fluid (CSF) finding, and other medical comorbidity. Case report A 51-year-old man was brought to the emergency room due to a traffic accident. The initial impression was Wernicke encephalopathy due to his alcohol use history and the clinical triad. After admission, fever and mental confusion lead to the suspicion of CNS infection. Although the initial CSF analysis was inconclusive, the miliary pattern of intracranial tuberculomas was highly suspected by brain magnetic resonance imaging finding. The diagnosis of TBM and miliary TB was finally confirmed by positive CSF and sputum culture of Mycobacterium tuberculosis. The patient had a good response to standard antituberculous therapy, although paradoxical expansion of cerebral tuberculomas occurred during treatment. Conclusions TB is still a major public health problem in the world, and there is a rising tendency of extrapulmonary TB incidences in the developed countries. Because of the high mortality and treatable characteristics of CNS TB, physicians should be familiar with it and keep the diagnosis in mind.

Aims. The purpose of this study was to explore the relationships between specific nurse care-giving behaviours and preterm infant behavioural responses during bathing and to identify nurse behaviours associated with infant ‘stress’. Background. Although recent advances in medical technology have improved neonatal intensive care, the high mortality and morbidity rates in preterm infants have not decreased proportionally. As caregivers strive to reduce infant mortality and morbidity, a factor for consideration is which caregiver behaviours are associated with preterm infant well-being. Design. A descriptive correlational design. Method. Convenience samples of 24 preterm infants and 12 nurses were recruited. A total of 120 baths were videotaped. Infant and nurse behaviours were measured using the coding schemes developed by the researchers. Pearson coefficient correlation, non-parametric Kruskal–Wallis test, t-test and generalised linear models were methods for data analysis. Results. As nurses provided more support, stress was reduced in the infants, and their self-regulation during the bath was enhanced especially by the use of ‘containment’ and ‘positional support’. Conversely, non-therapeutic caregiver behaviours including ‘rapid and rough handling’ of the baby, ‘chatting with other people’ and ‘inappropriate handling’ increased infant ‘stress’ during the bath. Conclusion. The findings provide new information about the link between care-giving and infant responses and how caregivers can better interact with preterm infants during a very sensitive period of brain development. Relevance to clinical practice. How nurses take care of the preterm infants influences their responses to care-giving stimuli. To interact better with the infant during care-giving procedures, nurses need to provide more supportive care-giving behaviours especially ‘position support’ and ‘containment’ based on the infant’s needs, and avoid care-giving that may be too rough and occur too quickly without attending the baby’s stressful signals, positioning the baby in hyperextension posture, or chatting with other people during procedures.

The definition and clinical significance of vertebral artery hypoplasia (VAH) remain inconclusive. VAH has been proposed as a predisposing factor of posterior circulation ischemic stroke. The aim of this study was to determine a best cut-off diameter of vertebral artery (VA) for VAH and to investigate if unilateral VAH is associated with a decrease in net vertebral flow volume. Retrospective data of 1000 presumably healthy subjects free of cerebrovascular disease or apparent carotid atherosclerosis were analysed. We found that a VA diameter

Background We performed endoscope-assisted MVD or fully endoscopic MVD for minimizing the risks of brain retraction and extensive dissection and got good results. In addition, we highlighted the value of endoscopy in the diagnosis and therapy for cranial nerve pathologic condition in the posterior fossa. Methods Among 300 consecutive patients with microsurgically treated HFS, 32 patients underwent endoscope-assisted MVD or fully endoscopic MVD through the retromastoid approach between July 1998 and December 2002, at the Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan, ROC. The use of endoscopes is indicated for patients who had difficulty in identifying the nerve-vessel conflicts. Results The procedure was successful in 96.9% of patients and improved in 3.1%. No failure or recurrence was noted. The postoperative complications were found in 2 patients who were treated by endoscope-assisted MVD. One patient (3.1%) showed delayed facial palsy on the seventh day but was fully recovered 2 months later. Hearing impairment was noticed in one patient (3.1%). There was no perioperative mortality. Conclusion From our experience, we conclude that the endoscope's superior visualization more accurately identifies neurovascular conflicts and provides a comprehensive evaluation of the completeness of the decompression. In addition, this method minimizes the risks of brain retraction and extensive dissection often required for microscopic exposure. Endoscopes are good as an adjunctive imaging modality to confirm nerve-vessel conflicts identified by the microscope and to reveal others that escaped from microscopic survey.

Objective Transient monocular blindness (TMB) attacks may occur during straining activities that impede cerebral venous return. Disturbance of cerebral and orbital venous circulation may be involved in TMB. Methods Duplex ultrasonography and Doppler-flow measurement of jugular and retrobulbar veins were performed in 134 consecutive patients with TMB and 134 age- and sex-matched control subjects. All recruited patients received thorough examinations to screen for possible underlying causes. Results Of the 134 patients with TMB, 48 patients had ipsilateral carotid arterial lesion and 7 patients had TMB attack(s) caused by cardiac embolism. Of the remaining 79 patients with undetermined cause, 46 had 3 or more TMB attacks (undetermined-frequent group) and 33 had fewer than 3 attacks. In comparison with the control subjects, the TMB patients had greater frequencies of jugular venous reflux (57 vs 30%; p < 0.0001; odds ratio [OR]: 3.079, 95% confidence intervals [CI]: 1.861–5.096) and flow reversal in the superior ophthalmic vein (RSOV; 37 vs 9%; p < 0.0001; OR: 6.052, CI: 3.040–12.048). The undetermined-frequent group had the greatest frequencies of jugular venous reflux (74%, 34 patients; OR: 6.66, CI: 3.13–14.17) and RSOV (59%, 27 patients; OR: 6.51, CI: 3.12–13.58). Of the 50 patients with RSOV, 47 (94%) had RSOV on the side of the TMB attacks. Interpretation The increased incidences of jugular and orbital venous reflux in TMB patients suggest that disturbance of cerebral and orbital venous circulation is involved in the pathogenesis of TMB, especially among patients with frequent attacks of undetermined cause. Ann Neurol 2008

Venous reflux in the internal jugular vein branches (JB) was found frequently in patients of certain neurologic disorders. We hypothesized that the retrograde-flow in JB is associated with retrograde hypertension transmitted from the internal jugular vein (IJV), which presumably underlies those neurologic disorders. In this study, we used color-Doppler imaging to evaluate the dynamic venous flow patterns in the IJV and its branches in 50 normal individuals (21 men, 29 women; mean age: 40.9 +/- 14.9 y, range: 22 to 70 y). The flow-direction of all detected JB (n = 100) was flowing into the IJV at baseline. During the Valsalva maneuver (VM), 38 JB (38%) had a retrograde-flow. Retrograde-flow in JB was significantly associated with IJV valve incompetence (OR = 7.6; 95% CI = 2.6 to 21.8; p = 0.0002) and greater IJV blood flow volume (blood flow volume >670 mL/min) (OR = 6.6; 95% CI = 1.8 to 24.5; p = 0.0052), both of which may reflect higher IJV pressure transmission during VM. The sonographic findings can be used in the future studies of diseases that are suspected to be related with retrograde cerebral venous hypertension due to an elevated IJV venous pressure.

ObjectiveFe is an essential element for erythropoiesis and Hb synthesis. High Hb levels affect the blood’s viscosity and are associated with cardiovascular dysfunction. The aim of the present study was to examine relationships of Hb and cardiometabolic abnormalities with the risk of alanine aminotransferase (ALT) elevation in adolescents.DesignA population-based, cross-sectional study.SettingNational Nutrition and Health Survey in Taiwan (2010–2011, adolescents).SubjectsHealthy adolescents aged 13–18 years.ResultsIn total, 1941 adolescents (963 boys and 978 girls) were entered in the study. The mean age was 15·3 (sd0·1) years (boys, 15·3 (sd0·1) years; girls, 15·2 (sd0·1) years). ALT tertile cut-off points for boys were 11 and 16 U/l, and for girls were 9 and 12 U/l. Girls without dyslipidaemia and presenting in the highest quartile (Q1) of Hb (>13·6 g/dl) were 1·89 and 3·76 times more likely to have raised serum ALT (9 and >12 U/l, respectively) than the reference (lowest quartile of Hb (Q1), 12 U/l) than the reference (Q1 of Hb, 15·4 g/dl), who were 7·40 times more likely to have elevated serum ALT of >16 U/l than the reference (Q1 of Hb, ConclusionsOur findings suggest that an increased Hb level is a predictor of elevated serum ALT in adolescent girls with dyslipidaemia. Our study also highlights the importance of further research to establish cut-off points for Hb and its utility in diagnosing and preventing the onset of dyslipidaemia in adolescents.

Objective The transition from childhood to teenaged years is associated with increased testosterone and a decreased iron status. It is not clear whether higher testosterone levels cause the decreased iron status, and to what extent, obesity-related inflammation influences the iron-testosterone relationship. The aim of the present study was to examine relationships of testosterone, iron status, and anti-/proinflammatory cytokines in relation to nutritional status in boys and young adolescent Taiwanese males. Methods In total, 137 boys aged 7~13 yr were included. Parameters for obesity, the iron status, testosterone, and inflammatory markers were evaluated. Results Overweight and obese (ow/obese) boys had higher mean serum testosterone, interleukin (IL)-1β, and nitric oxide (NO) levels compared to their normal-weight counterparts (all p

Baroreflex sensitivity (BRS) and heart rate variability (HRV) are potential therapeutic targets. The present study was conducted to assess changes in BRS and HRV after monotherapy with losartan versus that of atenolol in uncomplicated essential hypertension. Thirty subjects with uncomplicated essential hypertension were randomized to receive atenolol 50 mg to 100 mg (n = 15) or losartan 50 mg to 100 mg (N = 15) daily for 6 months. Instantaneous systolic blood pressure (SBP) and heart rate were assessed using servo-controlled infrared finger plethysmography before treatment and at the end of 3 months and 6 months after treatment. The fluctuation in SBP and interpulse interval (IPI) was divided into three specific frequency ranges by fast Fourier transform as high frequency (HF; 0.15 Hz-0.4 Hz), low frequency (LF; 0.04 Hz-0.15 Hz), and very low frequency (VLF; 0.004 Hz-0.04 Hz). The BRS was expressed as (1) SBP-IPI transfer function with its magnitude in the HF and LF ranges and (2) BRS index alpha. The HRV was expressed as total power and power in the LF and HF ranges of interpulse interval. Blood pressure was reduced to a similar extent in both groups. Compared with the baseline, BRS did not improve in both groups at month 3. However, BRS was significantly improved in the losartan group (P0.05) but not in the atenolol group at month 6. In addition, BRS was significantly higher in the losartan group than the atenolol group at month 3 and month 6 (P0.05). Moreover, heart rate variability was significantly reduced in the atenolol group at month 6 (P0.05), but not in the losartan group. The HRV in the losartan group was significantly higher than that in the atenolol group at month 6 (P0.05). These findings suggest superior effects of losartan on BRS and HRV than atenolol in uncomplicated essential hypertension, which may be beyond blood pressure reduction/resetting.

Background It remains unclear whether interleukin (IL) 6 plays a role in initiating either the inflammatory or antiapoptotic responses in severe acute pancreatitis. This study examined the effect of neutralizing antibody against IL-6 on the induction of pancreatic acinar cell apoptosis and attenuation of the severity of severe acute pancreatitis. Methods Experiments were conducted on laboratory mice with severe acute pancreatitis induced by lipopolysaccharide injection following six injections of caerulein at intervals of 6 h. Neutralizing monoclonal anti-IL-6 antibody was administered either 5 min or 2 h after the first caerulein injection. Apoptosis in pancreatic sections was determined by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labelling method. Results Administration of caerulein and LPS induced an increase in serum amylase and IL-6 levels, severe acute pancreatitis, pancreatitis-associated lung injury, and phosphorylation of signal transducer and activator of transcription (STAT) 3 in the pancreas. A neutralizing antibody against IL-6 effectively suppressed these responses. Application of IL-6 neutralizing antibody caused the induction of apoptosis in the pancreatic acinar cells of mice with acute pancreatitis. Conclusion Blocking IL-6 suppresses STAT-3 activation in the pancreas and consequently attenuates the severity of severe acute pancreatitis by promotion of pancreatic acinar cell apoptosis.

Background: The reliability of critical closing pressure (CrCP) estimates derived from peripheral blood pressure (BP) measurements is unclear. We attempted to evaluate the influences of peripheral circulation on determining CrCP. Methods: Twenty-five young healthy volunteers were studied. BP waves were obtained with plethysmography (Portapres) and carotid applanatory tonometry, respectively, for analysis. Transcranial Doppler was used to monitor cerebral flow velocity. Using linear regression analysis, beat-to-beat CrCP was calculated at rest, during voluntary hyperventilation and during 5% CO2 inhalation. Results: Twenty of 25 participants demonstrating satisfactory tonometric tracings for both tests were included in the analysis. The systolic BP measured using plethysmography was higher than that derived from tonometry (139.4 ± 24.7 vs. 105.5 ± 29.6, p < 0.001). CrCP values derived from tonometry were all positive and higher than CrCP values derived from plethysmography (62.9 ± 19.9 vs. 11.1 ± 17.8, p < 0.001). The changes in CrCP induced by 5% CO2 inhalation and hyperventilation had a correlation between two BP monitoring methods (r = 0.52, p = 0.001). Conclusions: Pressure waveform is an important determinant in calculating CrCP by linear regression analysis. The relative changes in CrCP induced by hemodynamic challenges remained a relevant indicator of cerebrovascular regulation regardless of the methods used for non-invasive BP recording.

A vertebral artery (VA) terminating in a posterior inferior cerebellar artery (PICA) is often considered to be a normal variation associated with VA hypoplasia. We aimed to investigate the clinical significance of this cerebrovascular variant. A total of 80 patients with clinically evident cerebrovascular events in posterior circulation were examined by duplex sonography and magnetic resonance angiography (MRA). Eighty healthy subjects who had MRA check-up were recruited as controls. PICA termination of the VA (PICA-VA) was identified as the VA not communicating with the basilar artery (BA) but ending into a PICA. We compared the prevalence of PICA-VA and associated hemodynamic parameters between the patients with and without PICA-VA, and investigated their relationships with VA hypoplasia. The prevalence of PICA-VA was higher in the patient group than in the controls (18.7% vs. 6.3%, p = 0.015). Most measurements (73.3%) of PICA-VA did not fit the criteria of VA hypoplasia. In comparison with the non-PICA-terminating group, the PICA-VA has a smaller diameter (3.7 ± 0.7 mm vs. 3.0 ± 0.5 mm, p < 0.001), lower mean velocity (241 ± 100 mm/sec vs. 164 ± 88 mm/sec, p < 0.01), and higher pulsatility index (1.3 ± 0.5 vs. 1.9 ± 0.6, p < 0.001). Moreover, a smaller diameter of the BA (3.2 ± 0.5 mm vs. 2.5 ± 0.9 mm, p = 0.004) and the posterior cerebral artery (PCA) (2.0 ± 0.1 mm vs. 1.6 ± 0.1 mm, p = 0.006) were also noted in the PICA-VA group. The higher prevalence of PICA-VA in the patient group with smaller diameter of VA, BA and PCA reflected its clinical significance, suggesting that PICA-VA may have a detrimental impact on cerebral hemodynamics. However, the sample is small, and further studies are needed with larger sample size for confirmation.

Background Discharge disposition planning is vital for poststroke patients. We investigated clinical factors associated with discharging patients to nursing homes, using the Taiwan Stroke Registry data collected from 39 major hospitals. Methods We randomly assigned 21,575 stroke inpatients registered from 2006 to 2008 into derivation and validation groups at a 3-to-1 ratio. We used the derivation group to develop a prediction model by measuring cumulative risk scores associated with potential predictors: age, sex, hypertension, diabetes mellitus, heart diseases, stroke history, snoring, main caregivers, stroke types, and National Institutes of Health Stroke Scale (NIHSS). Probability of nursing home care and odds ratio (OR) of nursing home care relative to home care by cumulative risk scores were measured for the prediction. The area under the receiver operating characteristic curve (AUROC) was used to assess the model discrimination against the validation group. Results Except for hypertension, all remaining potential predictors were significant independent predictors associated with stroke patient disposition to nursing home care after discharge from hospitals. The risk sharply increased with age and NIHSS. Patients with a cumulative risk score of 15 or more had an OR of 86.4 for the nursing home disposition. The AUROC plots showed similar areas under curves for the derivation group (.86, 95% confidence interval [CI], .85-.87) and for the validation group (.84, 95% CI, .83-.86). Conclusions The cumulative risk score is an easy-to-estimate tool for preparing stroke patients and their family for disposition on discharge.

We read with great interest the results of Liao et al reporting that standard-dose intravenous tissue-type plasminogen activator (tPA) for stroke had more favorable outcome than low-dose tPA without increasing the risk of symptomatic intracranial hemorrhage (SICH).1 They concluded that 0.9 mg/kg should be the optimal dose of tPA for Asians to treat acute ischemic stroke. The authors in the study reported there was no significant difference in the rate of SICH between 0.5 to 0.7 and 0.85 to 0.95 groups; and SICH in 0.7 to 0.85 group was even greater than in 0.85 to 0.95 group. For functional independence (mRS, 0–2) at 3 month, 0.7 to 0.85 mg/kg group did also significantly worse than 0.85 to 0.95 mg/kg group. However, they evaluated and compared the safety and efficacy only with analysis adjusted …

Aim This study examined the effect of underlying contextual factors on the intention to stay in nurses. Background Workplace promotion, social support, work stress, job satisfaction and organisation-based self-esteem (OBSE) are psychosocial factors influencing the intention to stay in nurses. However, few studies have analysed the relationships among these factors. Method A cross-sectional survey was conducted and a sample was recruited in convenience sampling method from a medical centre in Taiwan. A total of 791 nurses completed a self-report questionnaire over a 3-month period in 2013. Results Social support, work stress, job satisfaction and OBSE significantly affected the intention to stay in nurses. Furthermore, social support and job satisfaction showed a positive direct effect on the intention to stay and an indirect effect on the intention to stay; the indirect effect was mediated by OBSE. Conclusion Organisation-based self-esteem mediates the effects of social support and job satisfaction on the intention to stay in nurses. Implications for Nursing Management The results showing the influence of OBSE on the intention to stay in nurses can serve as insight for hospital managers to make decisions when encouraging and managing employees.

Panic disorder (PD) is characterized by panic attacks accompanied with respiratory symptoms. Internal jugular vein (IJV) alters its hemodynamics in response to respiration and which might cause cerebral blood flow (CBF) changes. In the present study, we compared (1) respiratory-related IJV hemodynamics and (2) CBF changes during Valsalva maneuver (VM) between PD and normal subjects.42 PD patients and age/gender-matched controls (14 men; 52.3 ± 11.4 years) were recruited. Duplex ultrasonography measured time-averaged mean velocity (TAMV) and lumen in IJV at baseline and deep inspiration. Lumen area0.10 cm(2) at deep inspiration was defined as IJV collapse. CBF changes during VM were recorded by transcranial Doppler (TCD).Compared with normal group, PD patients had significantly higher frequency of IJV collapse at deep inspiration (Left: 40.0% vs. 7.0%, p = 0.0003, Right: 17.0% vs. 0%, p = 0.0119). IJV collapse was associated with symptoms of respiratory subtype in our PD patients. PD group also had smaller lumen (Left: 0.53 ± 0.29 vs. 0.55 ± 0.26 cm(2), p = 0.8296, Right: 0.63 ± 0.36 vs. 0.93 ± 0.45 cm(2), p = 0.0014) and slower TAMV of IJV at baseline (Left: 11.8 ± 8.43 vs. 20.6 ± 16.5 cm/s, p = 0.0003, Right: 15.9 ± 9.19 vs. 24.1 ± 15.7 cm/s, p = 0.0062). PD patients with inspiration-induced IJV collapse had more decreased CBF during VM compared with the other PD patients and normal individuals respectively.We are the first to show that PD have less IJV flow at baseline and more frequent collapse at deep inspiration. Inspiration-induced IJV collapsed was associated with CBF decrement during VM in PD patients. These results suggest that venous drainage impairment might play a role in the pathophysiology of PD by influencing CBF.

Background and Purpose— This study was to evaluate the retrobulbar hemodynamics in patients who have transient monocular blindness (TMB) without carotid stenosis. Methods— Fifty-nine patients who have TMB without carotid stenosis were studied along with 59 age- and sex-matched controls. Color Doppler–imaging was used to study the retrobulbar hemodynamic by measuring the flow velocities (peak-systolic velocity, and end-diastolic velocity), vascular resistance indices (pulsatility index, and resistance index) in central retinal arteries, short posterior ciliary arteries, and ophthalmic arteries. The patients were divided into 2 groups according to the attack frequency: group 1 (occasional TMB, 2 or fewer attacks, 26 patients) and group 2 (frequent TMB, 3 or more attacks, 33 patients). Results— The risk factors for atherosclerosis were similar between the cases and controls. The means of end-diastolic velocity were significantly lower in central retinal arteries and ophthalmic arteries, and the pulsatility index and resistance index were significantly higher in all the 3 retrobulbar vessels in TMB patients than for the controls. The differences between patients and controls were greater for the group-2 patients. Conclusion— Patients who have TMB without carotid stenosis had altered retrobulbar hemodynamics with a generalized increase in vascular resistance in the retrobulbar arteries. The role of venous hypertension as an etiology needs further study.

The steady-state passive joint moment was considered as a nonlinear elasticity in the past. However, we found that it was path dependent and the estimation error could be large if the commonly used path-independent functions were adopted. The aim of this study was to develop a model to describe the movement history-dependent passive moment in the steady state. The steady-state passive ankle moments of the rabbit were measured by a series of ramp-and-hold angle changes (stairway angle trajectory). A customized discrete Preisach model was constructed and a commonly adopted double-exponential function was also implemented. Two sets of data with different angle paths (major loop and inward loop trajectories) were acquired for model validation. The performance of the two models was compared. The results showed that the proposed model could accurately estimate the steady-state passive moment for both sets of validation data. The estimated error of the proposed model was approximately 50% smaller than that of the double-exponential function approach. It is expected that this new approach, by reducing the error of estimating passive joint moment, may contribute to the active control of joint moments.

While there is evidence to suggest that endothelin-1 is involved in regulation of kidney function and blood pressure, the importance of endothelin ETA receptors in this area has not been clearly defined. The novel, non-peptide endothelin ETA receptor antagonist, BMS-182874, (5-(dimethylamino)-N-(3,4- dimethyl-5-isoxazolyl)-1-naphthalene sulfonamide) was used to examine effects of endothelin ETA receptor blockade on renal function in spontaneously hypertensive rats. Preliminary studies were conducted to determine an effective dose of BMS-182874. Infusion of BMS-182874 (10 mumol/kg/min, i.v.) inhibited effects of exogenous endothelin-1 on glomerular filtration rate, renal blood flow, and mean arterial pressure in Sprague-Dawley rats. Administration of BMS-182874 (10 mumol/kg/min, i.v.) to anesthetized, male, spontaneously hypertensive rats decreased renal blood flow by approximately 50% (1.2 +/- 0.11 ml/min/100 g body weight) compared to vehicle (2.7 +/- 0.23). There was no effect of BMS-182874 on glomerular filtration rate (0.5 +/- 0.05 ml/min/100 g body weight; vehicle: 0.7 +/- 0.06). Mean arterial pressure decreased significantly after BMS-182874 (123 +/- 3.8 mm Hg; vehicle: 162 +/- 4.8). Urine flow and renal vascular resistance were unchanged by BMS-182874. Endothelin ETA receptor density was increased approximately 50% in spontaneously hypertensive rat kidneys compared to normotensive kidneys, with no change in equilibrium dissociation constant. Endothelin ETB receptor density and equilibrium dissociation constant were similar in the two rat strains. Plasma immunoreactive endothelin was higher in hypertensive (5.9 +/- 0.31 fmol/ml) than normotensive rats (2.8 +/- 0.15). The results suggest endothelin ETA receptors may play a role in the regulation of renal function in this model of hypertension.

Patients with type 2 diabetes mellitus (DM) may experience chronic microvascular complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN) during their lifetime. In clinical studies, serum uric acid concentration has been found to be associated with DR and DN. The goal of this study was to evaluate the relationship between the increases in serum uric acid level and the severity of DR and albuminuria in Taiwanese patients with type 2 DM. We recorded serum uric acid concentration, the severity of DR, and the severity of albuminuria by calculating urinary albumin-to-creatinine ratio (UACR) in 385 patients with type 2 DM. In multivariate logistic regression analysis, a high uric acid concentration was a risk factor for albuminuria (odds ratio (OR), 1.227; 95% confidence interval (CI) = 1.015–1.482; p = 0.034) and DR (OR, 1.264; 95% CI = 1.084–1.473; p = 0.003). We also demonstrated that there was a higher concentration of serum uric acid in the patients with more severe albuminuria and DR. In conclusion, an increased serum uric acid level was significantly correlated with the severity of albuminuria and DR in Taiwanese patients with type 2 DM.

The main goal of this study was to study the performance of fuzzy logic controllers combined with simplified hybrid amplitude/pulse-width (AM/PW) modulation to regulate muscle force via nerve electrical stimulation. The recruitment curves with AM/PW and AM modulations were constructed for the calf muscles of rabbits. Integrated with the modulation methods, a proportional-integral-derivative (PID) and three fuzzy logic controllers were designed and applied for the electrical stimulation of tibial nerves to control the ankle torque under isometric conditions. The performance of the two modulation methods combined with the four controllers was compared when the ankle was fixed at three positions for both in vivo experiments and model simulations using a nonlinear muscle model. For the animal experiments, AM/PW modulation performed better than AM modulation alone. The fuzzy PI controller performed marginally better and was resistant to external noises, though it tended to have a larger overshoot. The performance of the controllers had a similar trend in the three different joint positions, and the simulation results with the nonlinear model matched the experimental results well. In conclusion, AM/PW modulation improved controller performance, while the contribution of fuzzy logic was only marginal.

Recent investigations have confirmed the presence of vasoconstrictory endothelinB (ETB) receptors in several tissues, including the rabbit saphenous vein (RSV). To determine the molecular nature of the ET receptor subtypes in RSV, radioligand-receptor binding with selective ligands was conducted. ET-1 inhibited 125I-ET-1 binding to RSV in a monophasic manner with an inhibition constant (Ki) of 0.08 +/- 0.03 nM. Inhibition of 125I-ET-1 binding by ET-3 or the ETA-selective peptide BQ-123 resulted in markedly biphasic inhibition curves with Ki values of 0.4 +/- 0.1 nM (36% of total sites)/37 +/- 10 nM (64% of total sites) for ET-3 and 10.4 +/- 1.9 nM (70%)/3.2 +/- 0.9 microM (30%) for BQ-123. The correspondence of high-affinity binding sites for BQ-123 with low-affinity binding sites for ET-3 agrees with the suggestion that 70% of the 125I-ET-1 binding sites in this tissue are ETA receptors. To further investigate the nature of the ET-B (non-ET-A) binding sites in RSV, 125I-ET-3 competition binding was conducted. ET-1 and BQ-123 inhibited 125I-ET-3 binding in RSV with Ki values of 40 +/- 7 pM and 7.2 microM, respectively, while ET-3 and the ETB receptor-selective agonist sarafotoxin S6c (S6c) inhibition curves were best fit to two-site models. Resultant Ki values for ET-3 and S6c were 50 pM (71%)/4 pM (29%) and 0.3 nM (76%)/115 nM (24%).(ABSTRACT TRUNCATED AT 250 WORDS)

Objective. The argument about why the head-up tilt table test (HUT) does not include the posterior cerebral circulation, which is mainly responsible for syncope, as a monitor target has not been resolved. It is also unclear whether there is a sex difference in cerebral blood flow (CBF) changes. We hypothesized that orthostatic CBF changes more in the posterior circulation than in the anterior circulation and is different between sexes. Methods. Thirty healthy volunteers (13 female and 17 male) were recruited for the HUT. The blood pressure (BP), middle cerebral artery flow velocity (MCAFV), and posterior cerebral artery flow velocity (PCAFV) were monitored simultaneously. Static cerebral autoregulation (CA) was calculated. Results. The female volunteers had a lower BP, but there was no difference in orthostatic BP changes (female versus male: 1.29% ± 5.26% versus 4.22% ± 12.65%; P = .65). The female volunteers had a significantly greater orthostatic drop in the PCAFV than in the MCAFV (23.8% ± 9.1% versus 18.2% ± 7.3%; P = .008). The static CA in the middle cerebral artery was better than in the posterior cerebral artery, although not significantly (13.6% ± 34.8% versus –2.8% ± 12.2%; P = .15). Conclusions. Our study showed the different cerebral hemodynamic responses between anterior and posterior circulations and between sexes during the HUT. We conclude that HUT studies for syncope should include the posterior cerebral circulation, especially for female patients. Key words: autoregulation; cerebral blood flow; head-up tilt table test; syncope; transcranial Doppler ultrasound.

Background and Purpose— The safety and efficacy of alteplase for ischemic stroke has not been examined in Chinese patients. We assessed the safety and efficacy of alteplase for acute ischemic stroke in daily clinical practice in Taiwan. Methods— A prospective, multicenter, observational study was conducted in Taiwan from December 2004 to July 2008. Eligible patients (241) receiving alteplase were recruited and divided into 2 groups: standard dose (0.90±0.02 mg/kg, n=125) and lower dose (0.72±0.07 mg/kg, n=116). Primary outcome measures were safety: symptomatic intracerebral hemorrhage and death within 3 months. The secondary outcome measure was efficacy a modified Rankin scale of 0 to 2 after 3 months. Results— The standard-dose group had higher rates of symptomatic intracerebral hemorrhage using National Institute of Neurological Diseases and Stroke, European Cooperative Acute Stroke Study, and Safe Implementation of Thrombolysis in Stroke-Monitoring Study definitions (10.4% versus 5.2%, 8.0% versus 2.6%, and 5.6% versus 1.7%, respectively) and mortality within 3 months (12.8% versus 6.9%), twice that of the lower-dose group. This pattern was more prominent in older patients. Significantly higher rates of symptomatic intracerebral hemorrhage per European Cooperative Acute Stroke Study (15.4% versus 3.3%, P =0.0257) and mortality (21.1% versus 5.0%, P =0.0099) and significantly lower independence rate (32.6% versus 53.6%, P =0.0311) were observed among patients ≥70 years old receiving the standard dose than those receiving the lower dose. Conclusions— This study suggests that the standard dose of 0.9 mg/kg alteplase may not be optimal for treating aged Chinese patients. However, the dose of recombinant tissue plasminogen activator for ischemic stroke in Chinese patients should be based on more broad and convincing evidences and randomized trials of lower versus higher doses are needed.

Cerebral venous outflow insufficiency via the internal jugular vein (IJV) is associated with several neurological disorders. However, a normal reference set of IJV hemodynamic parameters derived from a large, healthy population over a wide range of age has, until now, been lacking. Color-coded duplex sonography was performed on the IJVs of 349 subjects (55.60 ± 17.49,16 to 89 y; 167 M/182 F). With increasing age, increased lumen area and decreased time-averaged mean velocity of bilateral IJV and a decreased proportion of total flow volume, drainage in the left IJV were found. The frequency of left jugular venous reflux (JVR) also increased with aging. We report IJV hemodynamic parameters across a large population, which could be used as a normal reference for clinical and research purposes. Furthermore, we found a decreased proportion of venous drainage, increased JVR prevalence, dilated lumen and slowed flow velocity in the left IJV, all of which suggest increased left IJV outflow impedance with aging.

The authors assessed the effectiveness of percutaneous pulsed radiofrequency treatment for providing pain relief in patients with chronic low-back pain with or without lower-limb pain.Data were obtained in 127 patients who had chronic low-back pain with or without lower-limb pain due to a herniated intervertebral disc or previous failed back surgery and who underwent pulsed radiofrequency treatment. Their conditions were proven by clinical features, physical examination, and imaging studies. Low-back pain was treated with pulsed radiofrequency applied to the L-2 dorsal root ganglion (DRG) and lower-limb pain was treated with pulsed radiofrequency applied to the L3-S1 DRG. Patients underwent uni- or bilateral treatment depending on whether their low-back pain was unilateral or bilateral. A visual analog scale was used to assess pain. The patients were followed up for 3 years postoperatively.In patients without lower-limb pain (Group A), 27 (55.10%) of 49 patients had initial improvementor= 50% at 3-month follow-up. At 1-year follow-up, 20 (44.44%) of 45 patients in Group A had pain reliefor= 50%. An analysis of patients with pain reliefor= 50% for at least 1 month showed that the greatest effect was at 3 months after treatment. In patients with low-back pain and lower-limb pain (Group B), 37 (47.44%) of 78 patients had initial improvementor= 50% at 3-month follow-up. At 1-year follow-up, 34 (45.95%) of 74 patients had pain relief effector= 50%. An analysis of patients in Group B with pain reliefor= 50% for at least 1 month showed that the greatest effect was at 1 month after treatment.The results of this prospective analysis showed that treatment with pulsed radiofrequency applied at the L-2 DRG is safe and effective for treating for chronic low-back pain. Satisfactory pain relief was obtained in the majority of patients in Group A with the effect persisting for at least 3 months. The results indicate that pulsed radiofrequency provided intermediate-term relief of low-back pain. Further studies with long-term follow-up are necessary.

It has been demonstrated that internal jugular vein (IJV) compression aggravates headache intensity in patients of migraine. We hypothesized that patients with migraine may have veins that are less distensible; consequently, these veins are more likely to develop and transmit venous hypertension caused by the increased venous blood volume during IJV compression. We used ultrasonography to measure the extent of venodilatation and distensibility of IJV in response to increased transmural pressure, which was produced by a Valsalva maneuver. The extent of venodilatation were compared between 23 migraine patients (5 men, 18 women; mean age: 40.22+/-12.71 years, range: 27-7 years) and 23 age- and gender-matched normal individuals (5 men, 18 women; mean age: 40.23+/-12.04 years, range: 27-7 years). In the result, the venodilatation of IJV in response to each level of Valsalva pressure in patients with migraine was significantly less than that in normal individuals. Our results suggest that patients with migraine have less compliant IJVs, which makes them susceptible to cerebral venous hypertension. Further studies are needed to elucidate the clinical implications of decreased venous distensibility in migraine patients. (E-mail: hhhu@vghtpe.gov.tw).

Background: Adopting thrombolytic therapy with tissue plasminogen activator (tPA) in clinical practice presents many challenges. One major factor is the restrictive time window of 0–3 hours after symptom onset, for the commencement of treatment. Objective: To test the efficacy of a newly developed plasminogen activator (human tissue urokinase type plasminogen activator [HTUPA]) for the treatment of acute ischaemic stroke within 5 hours of symptom onset. Design: An open-label, dose escalation trial. The initial dose was 0.3 mg/kg and could be increased or decreased depending on tolerability. Setting: Three teaching hospitals in Taiwan. Participants: Thirty-three patients who presented with National Institute of Health Stroke Scale (NIHSS) scores of between 9 and 20, who had evidence of ischaemic stroke confirmed by CT. Main outcomes measures: Efficacy was assessed by the NIHSS, the Modified Rankin Scale (MRS), the Barthel Index and the Glasgow Outcome Scale. Preliminary efficacy endpoints included major neurological improvement at 24 hours and favourable outcome at 90 days after administration of HTUPA. Results: Of the 33 patients who received HTUPA, 29 received 0.3 mg/kg, 3 received 0.35 mg/kg and 1 received 0.4 mg/kg. Major neurological improvement, defined as improvement of ≥4 points on the NIHSS 24 hours after treatment, was observed in 45% of all patients treated (15/33) and in 48% (14/29) of those treated with 0.3 mg/kg. Ninety days after symptom onset, in those who received HTUPA 0.3 mg/kg, the proportion of patients with a favourable outcome was 34% on the NIHSS (≤1), 45% on the MRS (0 or 1), 41% on the Barthel Index (≥95) and 45% on the Glasgow Outcome Scale (1). Eighty six percent of the patients treated with 0.3 mg/kg within 0–3 hours of symptom onset reached scores of 0–1 on both the NIHSS and the MRS. Conclusions: Approximately 50% of patients treated with HTUPA 0.3 mg/kg within a 5-hour window after symptom onset experienced major neurological improvement within 24 hours of drug administration. Thrombolytic agents, in this case HTUPA, may be suitable for Taiwanese or Asian patients with acute ischaemic stroke who meet the inclusion criteria.