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Background/purpose Malignant hyperthermia (MH) is a life-threatening pharmacogenetic disease with only two known causative genes, RYR1 and CACNA1S. Both are huge genes containing numerous exons, and they reportedly only account for 50–70% of known MH patients. Next-generation sequencing (NGS) technology and bioinformatics could help delineate the genetic diagnosis of MH and several MH-like clinical presentations. Methods We established a capture-based targeted NGS sequencing framework to examine the whole genomic regions of RYR1, CACNA1S and the 16.6 Kb mitochondrial genome, as well as 12 other genes related to excitation-contraction coupling and/or skeletal muscle calcium homeostasis. We applied bioinformatics analyses to the variants identified in this study and also to the 48 documented RYR1 pathogenic variants. Results The causative variants were identified in seven of the eight (87.5%) MH families, but in none of the 10 individuals classified as either normal controls (N = 2) or patients displaying MH-like clinical features later found to be caused by other etiologies (N = 8). We showed that RYR1 c.1565A>G (p.Tyr522Cys)(rs118192162) could be a genetic hot spot in the Taiwanese population. Bioinformatics analyses demonstrated low population frequencies and predicted damaging effects from all known pathogenic RYR1 variants. We estimated that more than one in 1149 individuals worldwide carry MH pathogenic variants at RYR1. Conclusion NGS and bioinformatics are sensitive and specific tools to examine RYR1 and CACNA1S for the genetic diagnosis of MH. Pathogenic variants in RYR1 can be found in the majority of MH patients in Taiwan.

Background Great efforts were made to collect information and identify risk factors in predicting post-anesthetic mortality. In this study, we use national health insurance data base, including medications, underlying comorbidities and surgical factors to assess the relationship between these factors and mortality after surgery. Methods This is a retrospective, population based study. The study population who underwent general anesthesia (GA) were retrieved from the National Health Insurance Research Database in Taiwan between January 1, 2005 and December 31, 2013. We classified the study patients into 4 major comparison groups by surgical procedures, including major organ transplantation (heart, liver, lung, kidney, or pancreas), CV surgery, major neurosurgery, and others according to the diagnostic codes of the international classification of diseases, ninth revision, clinical modification (ICD-9-CM) codes. We proposed a logistic regression model with valuable variables which can significantly predicts the post-anesthesia mortality. We also designed different models for 4 subgroups according the results. Results A total of 833,685 subjects were included in this study, and the most common comorbidity was hypertension. Age was an important determinant associated with post-operation mortality among different surgical types. Perioperative prescription could reduce risks of operation. The prediction model based on the preliminary training group also performed well in the validation group (AUROC=0.8753 for in-hospital mortality; AUROC= 0.8767 for 30-days mortality). A reliable predicting model can help anesthesiologists to decide the anesthesia method or monitors, as well as helping physicians to take care of their patients after operation. Conclusions While GA is commonly used for the majority of the patients undergoing operations, the prediction model that we proposed from this nationwide study could identify the predictors for post-operation mortality. The potentially protective effects of anti-lipid, hypoglycemic, and anti-hypertensive agents were encouraging in geriatric preoperative group. It is expected that applying this prediction model and prescription into clinical practice could improve surgical risk stratification and further improve patient outcomes. Trial registration The protocol of this study was approved by the National Taiwan University Hospital Research Ethics Committee (Trial Registration 201411078RINC). Informed consent was waived by the National Taiwan University Hospital Research Ethics Committee due to the retrospective and anonymous nature of the claims data.

Temporal cardiac properties provide alternative information in analyzing heart rate variability (HRV), which may be disregarded by the standard HRV analyses. Patients with congestive heart failure (CHF) are known to have distinct temporal features from the healthy individuals. However, the underlying mechanism leading to the variation remains unclear. Whether or not these parameters can finely classify the severity for CHF patients is uncertain as well. In this work, an electrocardiogram was monitored in advanced CHF patients using 24-h Holter in four conditions, including baseline, one and three months after atenolol therapy, and healthy individuals. Slope and area under the curve (AUC) of multiscale entropy (MSE) curve over short (scales 1–5) and long (scales 6–20) scales, and detrended fluctuation analysis (DFA) scaling exponents at short (4–11 beats) and intermediate (>11 beats) window sizes were calculated. The results show that short-time scale MSE-derived parameters (slope: −0.08 ± 0.10, −0.03 ± 0.10, 0.02 ± 0.06, 0.08 ± 0.06; AUC: 4.03 ± 2.11, 4.69 ± 1.28, 4.73 ± 0.94, and 6.17 ± 1.23) and short-time scale DFA exponent (0.79 ± 0.16, 0.95 ± 0.22, 1.11 ± 0.19, and 1.35 ± 0.20) can hierarchically classify all four conditions. More importantly, simulated R-R intervals with different fractions and amplitude of respiratory sinus arrhythmia (RSA) components were examined to validate our hypothesis regarding the essentiality of RSA in the improvement of cardiovascular function, and its tight association with unpredictability and fractal property of HRV, which is in line with our hypothesis that RSA contributes significantly to the generation of the unpredictability and fractal behavior of HR dynamics. NEW & NOTEWORTHY Temporal cardiac properties provide useful diagnostic parameters for patients with congestive heart failure (CHF). Our study hierarchically classified CHF patients with β-blocker treatment by using multiscale entropy and detrended fluctuation analysis. Also, we provided the evidence to validate the critical role of respiratory sinus arrhythmia in the fractal properties of heart rate variability.

BackgroundCompassion fatigue, unprofessional behavior, and burnout are prompting educators to examine medical students’ affective reactions to workplace experiences. Attributes of both students and learning environments are influenced by their socio-cultural backgrounds. To prevent ‘educational cultural hegemony’, opinion leaders have advocated research in under-represented cultural contexts, of which Asia is a prime example. This study aimed to broaden the discourse of medical education by answering the question: how do students react affectively to workplace experiences in a Chinese cultural context?MethodsIn 2014, the authors recruited five female and seven male Taiwanese clerkship students to make 1–2 audio-diary recordings per week for 12 weeks describing affective experiences, to which they had consciously reacted. The authors analyzed transcripts of these recordings thematically in the original Mandarin and prepared a thick description of their findings, including illustrative extracts. An English-speaking education researcher helped them translate this into English, constantly comparing the interpretation with the original, untranslated data.Results(Mis) matches between their visions of future professional life and clerkship experiences influenced participants’ affective reactions, thoughts, and behaviors. Participants managed these reactions by drawing on a range of personal and social resources, which influenced the valence, strength, and nature of their reactions. This complex set of interrelationships was influenced by culturally determined values and norms, of which this report provides a thick description.ConclusionTo avoid educational cultural hegemony, educators need to understand professional behavior in terms of complex interactions between culturally-specific attributes of individual students and learning environments.Trial registrationThe ethics committee of the National Taiwan University (NTU) Hospital gave research ethics approval (20130864RINB).

This study aimed to investigate the risks of thromboembolic vascular disease following androgen deprivation therapy (ADT) administered to prostate cancer (PCa) patients. A total of 24,464 men with newly diagnosed PCa during 2000–2008 were recruited through a longitudinal health insurance database in Taiwan. All PCa patients were stratified into two: ADT and non-ADT groups. Patients with ADT treatment were grouped into three: surgical castration, chemical castration, and anti-androgen alone. The risks of pulmonary embolism (PE), peripheral arterial occlusion disease (PAOD), and deep vein thrombosis (DVT) were assessed in multiple Cox proportional-hazards regression with time-dependent covariates. During the 12-year follow-up period, incidence rates per 1000 person-years in ADT and non-ADT groups were 2.87 and 1.62 for DVT, 1.00 and 0.52 for PE, and 1.03 and 0.70 for PAOD, respectively. The DVT and PE risks were significantly increased in patients receiving combined androgen blockade (CAB) compared with the counterpart ADT non-recipients. After adjusting for potential risk factors, PCa patients receiving CAB had the highest PE risk (HR = 3.11), followed by DVT risk (HR = 2.53). The DVT risk remained elevated throughout the entire duration of chemical castration. However, high PE risk was observed in patients with ≤720-day treatment duration. No association was found between ADT and PAOD risks. Overall, the risks of PE and DVT were considerably heightened in Asian men subjected to CAB for PCa, whereas PAOD risk was unrelated to such treatments.

Becoming a doctor is fundamentally about developing a new, professional identity as a physician, which in and of itself may evoke many emotions. Additionally, medical trainees are increasingly moving from one cultural context to another and are challenged with navigating the resulting shifts in their professional identify. In this Article, the authors aim to address medical professional identity formation from a polyvocal, multidisciplinary, cross-cultural perspective. They delineate the cultural approaches to medical professionalism, reflect on professional identity formation in different cultures and on different theories of identity development, and advocate for a context-specific approach to professional identity formation. In doing so, the authors aim to broaden the developing professional identity formation discourse to include non-Western approaches and notions.

A 65-year-old man, with suspected right adrenal metastasis from hepatic carcinoma, was scheduled to undergo a laparoscopic right adrenalectomy.

Background/Purpose Brugada syndrome (BrS) is a hereditable sudden cardiac death (SCD). Mutations in the SCN5A gene (the most common BrS-causing gene) are responsible for 20–25% of this disease in Caucasian populations. However, the prevalence of SCN5A mutations in patients with BrS in the Chinese Han population in Taiwan remains unknown. Therefore, in this study, we investigated the prevalence of the SCN5A mutation in the largest BrS cohort in Taiwan. Methods We consecutively enrolled 47 unrelated patients with BrS from medical centers and hospitals in Taiwan between 2000 and 2010. Mutations within all the 27 translated exons, and exon–intron boundaries of the SCN5A -encoded cardiac sodium channel were screened in all patients with BrS using direct sequencing. A total of 500 unrelated healthy volunteers with a normal electrocardiogram were genotyped as a control group. Results SCN5A genetic variants were identified in 14 of the 47 patients with BrS and four of the 14 patients with BrS had missense mutations (1651 G>A, 1776 C>G, 3578 G>A). The prevalence rate of SCN5A mutations was approximately 8% (4/47), which was significantly lower than that reported in Caucasian populations (20–25%; p = 0.0007). The average age of these 14 BrS patients with SCN5A variants at diagnosis (12 men and 2 women) was 40 ± 13 years. Four patients experienced SCD, and six presented with seizure or syncope. Only three patients (3/14, 21.4%) had a family history of SCD. Conclusion The prevalence of SCN5A mutations in the Chinese Han population in Taiwan may be lower than that reported in the Caucasian populations. In addition, most patients with BrS did not have a family history of SCD.

A 65-year-old man, with suspected right adrenal metastasis from hepatic carcinoma, was scheduled to undergo a laparoscopic right adrenalectomy. About 75 minutes into the operation, when attempting to remove the adrenal gland that was tightly adhesive to the inferior vena cava (IVC), the surgeon accidently nicked the inferior vena cava which resulted in a large tear of about 2 x 2 cm. Considering the difficulty of performing exploratory laparotomy due to previous hepatic tumor excision related intra-abdominal adhesion, the surgeon tried to sow the torn IVC through the use of the laparoscope and to control the bleeding via carbon dioxide (CO2) insufflation pressure. This resulted in a massive amount of gas entering the vessel via the IVC broken hole. When we performed a transesophageal chocardiography (TEE), it was revealed that the right atrium and right ventricle were totally white out because they were full of air. About 20 minutes after the IVC tear, the TEE image also revealed that the left heart also contained scattered air embolisms. The surgeon spent about 60 minutes on repairing the IVC tear. Blood pressure was stable during the IVC tear insult but dropped slightly after the IVC tear repaired. Low dose norepinephrine and dopamine continuous infusion were administered to stabilize the patient’s blood pressure. After the operation, the patient presented mild weakness in his left limbs. Fortunately, the symptoms dissipated two days after the surgery. 12 days later, the patient was discharged without any neurologic sequelae.

Background Elderly patients with aged physical status and increased underlying disease suffered from more postoperative complication and mortality. We design this retrospective cohort study to investigate the relationship between existing comorbidity of elder patients and 30 day post-anesthetic mortality by using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) from Health Insurance Database. Methods Patients aged above 65 years old who received anesthesia between 2000 and 2010 were included from 1 million Longitudinal Health Insurance Database in (LHID) 2005 in Taiwan. We use age, sex, type of surgery to calculate propensity score and match death group and survival one with 1:4 ratio (death: survival = 1401: 5823). Multivariate logistic model with stepwise variable selection was employed to investigate the factors affecting death 30 days after anesthesia. Results Thirty seven comorbidities can independently predict the post-anesthetic mortality. In our study, the leading comorbidities predict post-anesthetic mortality is chronic renal disease (OR = 2.806), acute myocardial infarction (OR = 4.58), and intracranial hemorrhage (OR = 3.758). Conclusions In this study, we present the leading comorbidity contributing to the postoperative mortality in elderly patients in Taiwan from National Health Insurance Database. Chronic renal failure is the leading contributing comorbidity of 30 days mortality after anesthesia in Taiwan which can be explained by the great number of hemodialysis and prolong life span under National Taiwan Health Insurance. Large scale database can offer enormous information which can help to improve quality of medical care. Electronic supplementary material The online version of this article (10.1186/s12877-017-0629-7) contains supplementary material, which is available to authorized users.

PurposeCurrent knowledge about the interplay between emotions and professional identity formation is limited and largely based on research in Western settings. This study aimed to broaden understandings of professional identity formation cross-culturally.MethodIn fall 2014, the authors purposively sampled 22 clinical students from Taiwan and the Netherlands and asked them to keep audio diaries, narrating emotional experiences during clerkships using three prompts: What happened? What did you feel/think/do? How does this interplay with your development as a doctor? Dutch audio diaries were supplemented with follow-up interviews. The authors analyzed participants’ narratives using a critical discourse analysis informed by Figured Worlds theory and Bakhtin’sconcept of dialogism, according to which people’s spoken words create identitiesin imagined future worlds.ResultsParticipants talked vividly, but differently, about their experiences. Dutch participants’ emotions related to individual achievement and competence. Taiwanese participants’ rich, emotional language reflected on becoming both a good person and a good doctor. These discourses constructed doctors’ and patients’ autonomy in culturallyspecific ways. The Dutch construct centered on “hands-on” participation, which developed the identity of a technically skilled doctor, but did not address patients’ self-determination. The Taiwanese construct located physicians’ autonomy within moral values more than practical proficiency, and gave patients agency to influence doctor–patient relationships.ConclusionsParticipants’ cultural constructs of physician and patient autonomy led them to construct different professional identities within different imagined worlds. The contrasting discourses show how medical students learn about different meanings of becoming doctors in culturally specific contexts.

The emergent crisis of global warming calls for energy education for people of all ages and social groups. The Taiwanese government has publicized 10 declarations on energy conservation and carbon reduction as public behavior guidelines to mitigate global warming. This study uses interviews with quantitative assessment to explore the values and behaviors of 91 Taiwanese people in implementing the declarations. The results of factor analysis reveal that the 10 declarations include 3 value constructs (nature, domestic technology, and transportation technology) and 3 behavior constructs (ease, driving consideration, and vehicle consideration). Correlation and regression analyses show that nature and domestic technology values can predict easy behavior (EB) but cannot predict either consideration behavior. Females have more positive energy values, but not energy behaviors, than males. Age is positively related to EB, and income does not play a significant role in determining either values or behaviors. These ...

Background The CHA 2 DS 2 -VASC scoring scheme may not be better than the CHADS 2 scoring scheme in predicting thromboembolic risk for patients with atrial fibrillation (AF) in Asians. Metabolic syndrome is associated with an increased risk of thrombosis. Objective To evaluate whether metabolic syndrome offers incremental information over the CHADS 2 scheme in predicting thromboembolic risk for patients with AF in the Taiwanese population. Methods The study population consisted of 721 consecutive patients with AF who had been followed up for a median of 10.8 years. Thromboembolic end points were defined as ischemic stroke/transient ischemic accident and peripheral embolisms. Clinical factors associated with thromboembolic end points were identified by Cox regression analysis. Different scoring systems were compared by receiver operating characteristic (ROC) analysis. Results We found that components in the CHADS 2 scheme were associated with an increased risk of thromboembolism. The CHA 2 DS 2 -VASC scheme did not provide information additional to that provided by the CHADS 2 scheme on thromboembolism risk (ROC area: 0.670 vs 0.665; P > .05). Metabolic syndrome components were also associated with increased risk of thromboembolism. The incident thromboembolic rate increased incrementally when metabolic syndrome score increased. Additional metabolic syndrome components provide additional information to the CHADS 2 scheme on thromboembolism risk (ROC area: 0.670 vs 0.729; P = .034). We therefore proposed a new scoring scheme called CHADS 2 -MS scoring scheme. In patients with low to intermediate CHADS 2 scores (0–1), the use of the CHADS 2 -MS score may additionally identify patients with high-risk AF for future thromboembolism. Conclusions We, for the first time, demonstrated that metabolic syndrome components were associated with thromboembolic risk in Taiwanese patients with AF. In addition to the conventional CHADS 2 scheme, the calculation of the CHADS 2 -MS score provides additional information on stroke risk assessment.

Aims Connective tissue growth factor (CTGF) is an emerging marker for tissue fibrosis. We investigated the association between CTGF and cardiac diastolic function using cellular and animal models and clinical human data. Methods and results A total of 125 patients with a diagnosis of diastolic heart failure (DHF) were recruited from 1283 patients of the Taiwan Diastolic Heart Failure Registry. The severity of DHF was determined by tissue Doppler imaging (E/e'). Cardiac magnetic resonance imaging (CMRI) was used to evaluate myocardial fibrosis in some of the patients (n = 25). Stretch of cardiomyocytes on a flexible membrane base serves as a cellular phenotype of cardiac diastolic dysfunction (DD). A canine model of DD was induced by aortic banding. A significant correlation was found between plasma CTGF and E/e' in DHF patients. The severity of cardiac fibrosis evaluated by CMRI also correlated with CTGF. In the cell model, stretch increased secretion of CTGF from cardiomyocytes. In the canine model, myocardial tissue CTGF expression and fibrosis significantly increased after 2 weeks of aortic banding. Notably, the expression of CTGF paralleled the severity of LV DD (r = 0.40, P Conclusion Plasma CTGF level correlated with the severity of DD and tissue fibrosis in DHF patients. The mechanism may be through myocardial stretch. Our study indicated that CTGF may serve as an early marker for DHF.

Original and operating code. We aggregated original codes into disease group to resemble clinical pre-anesthetic usage, and called it operating code. This process was conducted independently by three anesthesiologists. (DOCX 78 kb)

Background/PurposeSex differences in response to noxious stimuli or analgesia have been demonstrated. We investigated sex differences in conscious sedation during upper gastrointestinal panendoscopic examination with regard to drug dose and entropy scores.MethodsWe investigated sex differences in 30 men and 30 women who were undergoing conscious sedation during upper gastrointestinal panendoscopic examination. The drug mixture was prepared as 5 mg midazolam plus 1 mg alfentanil diluted with normal saline to a volume of 10 mL. An initial injection of 4 mL was followed by an additional 1 mL every 1 minute, until the modified Observer Assessment of Alertness and Sedation (OAAS) rating scale was ≤ 3 when the panendoscope was inserted. Further injection was allowed thereafter. Entropy values, including state entropy (SE) and response entropy (RE), were monitored from baseline to full recovery.ResultsThe volume of mixture needed to achieve an OAAS score of ≤ 3 was significantly lower in men than in women (4.4 ± 0.7 mL vs. 4.8 ± 0.8 mL, p = 0.034). The initial drug demand was not significantly influenced by age, body weight, or body height. The RE and SE values at the time of panendoscope insertion were not significantly different between men and women. The total volume for men was also significantly lower than that for women (5.7 ± 1.1 mL vs. 6.5 ± 1.4 mL, p < 0.01). The lowest RE and SE values during the procedure were not significantly different between men and women.ConclusionWomen need more analgesic agents than men during panendoscopic examination. There was no significant difference between men and women with regard to anesthetic depth and response to noxious stimuli, as revealed by similar SE and RE values.

Objectives We conducted a systematic review and meta-analysis to determine if pre-operative brain natriuretic peptide (BNP) (i.e., BNP or N-terminal pro–B-type natriuretic peptide [NT-proBNP]) is an independent predictor of 30-day adverse cardiovascular outcomes after noncardiac surgery. Background Pre-operative clinical cardiac risk indices have only modest predictive power. BNP predicts adverse cardiovascular outcomes in a variety of nonsurgical settings and may similarly predict these outcomes in the perioperative setting. Methods We employed 5 search strategies (e.g., searching bibliographic databases), and we included all studies that assessed the independent prognostic value of pre-operative BNP measurement as a predictor of cardiovascular complications after noncardiac surgery. We determined study eligibility and conducted data abstraction independently and in duplicate. We calculated a pooled odds ratio using a random effects model. Results Nine studies met eligibility criteria, and included a total of 3,281 patients, among whom 314 experienced 1 or more perioperative cardiovascular complications. The average proportion of patients with elevated BNP was 24.8% (95% confidence interval [CI]: 20.1 to 30.4%; I 2 = 89%). All studies showed a statistically significant association between an elevated pre-operative BNP level and various cardiovascular outcomes (e.g., a composite of cardiac death and nonfatal myocardial infarction; atrial fibrillation). Data pooled from 7 studies demonstrated an odds ratio (OR) of 19.3 (95% CI: 8.5 to 43.7; I 2 = 58%). The pre-operative BNP measurement was an independent predictor of perioperative cardiovascular events among studies that only considered the outcomes of death, cardiovascular death, or myocardial infarction (OR: 44.2, 95% CI: 7.6 to 257.0, I 2 = 51.6%), and those that included other outcomes (OR: 14.7, 95% CI: 5.7 to 38.2, I 2 = 62.2%); the p value for interaction was 0.28. Conclusions These results suggest that an elevated pre-operative BNP or NT-proBNP measurement is a powerful, independent predictor of cardiovascular events in the first 30 days after noncardiac surgery.

Malignant hyperthermia is a rare anesthetic-related disorder. We present a case with unusual presentation. A boy aged 3 years and 9 months who was scheduled for Hotz's operation presented normally before the operation. Anesthesia was induced by atropine, thiopental and sevoflurane. Trachea intubation was facilitated by succinylcholine. Jaw stiffness was first noted although trachea was intubated without difficulty. The following tachycardia, hypercapnia and hyperthermia led to the diagnosis of malignant hyperthermia. Symptoms were relieved dramatically after the discontinuation of sevoflurane. Molecular genetic testing identified a novel ryanodine receptor (RYR1) mutation in exon 39, which confirmed malignant hyperthermia susceptibility in this patient.

Background Plasma N-terminal pro-brain natriuretic peptide (NTproBNP) is a sensitive marker for heart failure. This study tested whether the preoperative plasma level of NTproBNP could predict cardiac complications in patients undergoing non-cardiac surgery. Methods A total of 190 consecutive patients who underwent elective non-cardiac surgery that required general anaesthesia were studied. In addition to routine preoperative evaluation, a blood sample was taken for estimation of plasma NTproBNP concentration. Postoperative cardiac complications were defined as cardiac death, acute coronary syndrome, heart failure and haemodynamic compromise from cardiac arrhythmias. Results Fifteen of the 190 patients had a cardiac complication: four had acute coronary syndrome and 13 had congestive heart failure. NTproBNP concentration was significantly higher in patients with a cardiac complication; a level greater than 450 ng/l was predictive of cardiac complications with a sensitivity of 100 per cent and a specificity of 82·9 per cent. Other factors associated with cardiac complications were a higher American Society of Anesthesiologists grade, age and clinical cardiac impairment, but in a multivariate analysis NTproBNP level was the only independent factor. Conclusion Preoperative plasma NTproBNP concentration may be an independent predictor of cardiac complications in patients undergoing non-cardiac surgery.

Up-Regulation of MLC-2V in Atrial Fibrillation. Introduction: Functional and structural changes of atrial tissue occur during the natural course of atrial fibrillation (AF), and these changes may contribute to further AF. We investigated the changes in AF tissue using cDNA microarray and two-dimensional protein electrophoresis techniques. Methods and Results: We established a porcine model of AF by rapid right atrial appendage pacing at a rate of 600/min. Atrial tissue was obtained after rapid atrial depolarization for 6 weeks. Microarrays containing 6,035 cDNA clones were used to evaluate the alterations of mRNA. Two-dimensional protein electrophoresis was performed to compare protein patterns. In cDNA microarray studies, we identified 387 genes with significant change in the left atrium and 81 genes in the right atrium. Among the genes, the ventricular isoform of the myosin regulatory light chain (MLC-2V) showed the greatest fold of change (9.4 and 7.3 in the left and right atrium, respectively). In protein electrophoresis, the expression levels of three protein spots spanning from 18 to 20 kDa in the acidic region (PI 4.5‐5.0) were specifically elevated in the AF group. Interestingly, through tandem mass spectrometric analysis, these three spots were identified as MLC-2V. Thus, MLC-2V expression at the mRNA and protein levels corresponded well, and both indicated a significant increase in AF. Conclusion: Both cDNA microarray and two-dimensional polyacrylamide protein electrophoresis studies revealed characteristic changes in AF tissue. We demonstrated the reprogramming of myosin regulatory light chain isoform composition, with a significant increase of its ventricular isoform (MLC-2V). (J Cardio

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson's correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis.

This study aims to understand students’ constructs regarding mathematical problems. Fifty-one Taiwanese primary students’ constructs are elicited using interviews with the repertory grid technique based on their responses to creative and non-creative problems. The results of qualitative data analysis show that students’ initial constructs can be categorized into three cognitive constructs (perception, strategy, and goal, each with deep and surface orientation constructs) and one affective construct. The results of correlation analysis reveal that deep strategy for both creative and non-creative problems and affect for creative problems are related to mathematics achievement. The results of multivariate analysis of variance reveal that students have fewer surface strategies and more surface goals for creative problems than those for non-creative problems. No significant gender differences or interaction effects between problem types and genders occur for either construct. The results reveal implications for teachers in the development of effective pedagogy for teaching different types of mathematical problems.

Congenital long QT syndrome (LQTS) is an ion channelopathy associated with genetic mutations. It is well known that most LQTS patients (91%) have a single mutation. The purpose of this study was to investigate the clinical characteristics of congenital LQTS patients with bigenic mutations in Taiwan, China.Congenital LQTS patients were recruited consecutively at Taiwan University Hospital in Taiwan from 2003 to 2009. The diagnosis of LQTS was defined by an LQTS Schwartz score greater than 4. Mutation screening in KCNQ1, KCNH2, KCNE1, and SCN5A was performed using direct sequencing.Three of 16 LQTS patients (18.7%) were identified with bigenic mutations. One patient had missense mutations in KCNQ1 and KCNH2, the second in KCNQ1 and KCNE1, and the third in KCNH2 and SCN5A. The mean age at onset of LQTS for patients with bigenic mutations was (17 ± 3) years, and all of these patients were female. Two of them experienced seizure and one presented with syncope, although one of them had a family history of syncope. The mean QTc interval was (515 ± 17) ms, similar to those with single mutation or SNPs ((536 ± 74) ms, P = 0.63). Compared to those LQTS patients with single mutation or SNPs, a significantly higher percentage of LQTS patients with bigenic mutations presented with seizure and were younger at onset of the first index event (P = 0.03 and 0.001, respectively), but lower percentage of them presented with sudden cardiac death (P = 0.03).Although the percentage of bigenic mutations in LQTS is less than 10% in Caucasian populations, we identified 3 of 16 LQTS patients (18.7%, 95% confidence interval: 0.04-0.46) with bigenic mutations in Taiwan. However, the severity of their clinical presentations was not higher than those patients with single mutation or SNPs.

We studied the hypothermic effect of adding 150 microg morphine during spinal anaesthesia in 60 parturients scheduled for elective caesarean section. All the parturients received intrathecal injection of a solution containing 150 mug morphine or normal saline in addition to 10-12 mg hyperbaric bupivacaine 0.5%. In both groups, a significant decrease in body temperature was noted. There was no difference in the area under the curve for temperature against time for the two groups; however, the maximum decrease in temperature from baseline was significantly larger after morphine than after saline injection (mean (SD) 1.11 (0.61) degrees C vs 0.76 (0.39) degrees C, respectively; p = 0.01) and the time to nadir temperature was significantly longer (59.5 (17.6) min vs 50.4 (15.9) min, respectively; p = 0.047). The lowest temperature observed in the morphine group was 34.3 degrees C. We conclude that intrathecal injection of 150 microg morphine intensified the intra-operative hypothermic effect of bupivacaine spinal anaesthesia for caesarean section.

Connective tissue growth factor (CTGF) is an emerging marker for tissue fibrosis. We investigated the association between CTGF and cardiac diastolic function using cellular and animal models and clinical human data.A total of 125 patients with a diagnosis of diastolic heart failure (DHF) were recruited from 1283 patients of the Taiwan Diastolic Heart Failure Registry. The severity of DHF was determined by tissue Doppler imaging (E/e'). Cardiac magnetic resonance imaging (CMRI) was used to evaluate myocardial fibrosis in some of the patients (n = 25). Stretch of cardiomyocytes on a flexible membrane base serves as a cellular phenotype of cardiac diastolic dysfunction (DD). A canine model of DD was induced by aortic banding. A significant correlation was found between plasma CTGF and E/e' in DHF patients. The severity of cardiac fibrosis evaluated by CMRI also correlated with CTGF. In the cell model, stretch increased secretion of CTGF from cardiomyocytes. In the canine model, myocardial tissue CTGF expression and fibrosis significantly increased after 2 weeks of aortic banding. Notably, the expression of CTGF paralleled the severity of LV DD (r = 0.40, P 0.001 for E/e') and haemodynamic changes (r = 0.80, P 0.001). After adjusting for confounding factors, CTGF levels still correlated with diastolic parameters in both human and canine models (human plasma CTGF, P 0.001; canine tissue CTGF, P = 0.04).Plasma CTGF level correlated with the severity of DD and tissue fibrosis in DHF patients. The mechanism may be through myocardial stretch. Our study indicated that CTGF may serve as an early marker for DHF.

The pharmacological characteristics of muscarinic receptor (mAChR) subtypes in canine left ventricular membranes (LVM) were determined using [3H] quinuclidinyl benzilate ([3H]QNB) and [3H]N-methyl scopolamine ([3H]NMS) as ligands. Binding of [3H]QNB and [3H]NMS was saturable with respect to the radioligand concentrations. Analysis of binding isotherms by Scatchard plot showed that [3H]QNB and [3H]NMS bound to an apparently homogeneous population of mAChRs in LVM, with KD values of 390 +/- 100 and 285 +/- 34 pM and Bmax values of 240 +/- 20 and 133 +/- 9 fmol/mg protein, (n = 6), respectively. The Hill coefficients for [3H]QNB and [3H]NMS binding were 0.95 +/- 0.02 and 0.99 +/- 0.01, respectively. Based on the competitive inhibition of [3H]ligand binding, atropine and NMS as well as the selective M1 antagonist PZ revealed no selectivity for these mAChRs. PZ competed with [3H]QNB or [3H]NMS for a single binding site with a Ki value of 0.23 +/- 0.03 microM and 0.62 +/- 0.10 microM, (n = 6), respectively, which is close to the values of M2 or M3 receptors. The data indicate that the M1 receptor subtype did not exist in canine LVM. Competition of [3H]ligand binding with selective M2 antagonists, AF-DX 116 and methoctramine and the selective M3 antagonists, 4-DAMP and hexahydrosiladifenidol, gave a best fit for a two-binding site model. The inhibition of carbachol-mediated phosphoinositide hydrolysis by PZ, AF-DX 116 and 4-DAMP, generated an affinity profile for this response also dissimilar to that described for the classical cardiac M2 response. Although no other muscarinic receptor mRNA has been detected in this tissue, these data suggest the presence of a second population of muscarinic sites, which may signify an M2 receptor diversity.

We conducted a systematic review and meta-analysis to determine if pre-operative brain natriuretic peptide (BNP) (i.e., BNP or N-terminal pro-B-type natriuretic peptide [NT-proBNP]) is an independent predictor of 30-day adverse cardiovascular outcomes after noncardiac surgery.Pre-operative clinical cardiac risk indices have only modest predictive power. BNP predicts adverse cardiovascular outcomes in a variety of nonsurgical settings and may similarly predict these outcomes in the perioperative setting.We employed 5 search strategies (e.g., searching bibliographic databases), and we included all studies that assessed the independent prognostic value of pre-operative BNP measurement as a predictor of cardiovascular complications after noncardiac surgery. We determined study eligibility and conducted data abstraction independently and in duplicate. We calculated a pooled odds ratio using a random effects model.Nine studies met eligibility criteria, and included a total of 3,281 patients, among whom 314 experienced 1 or more perioperative cardiovascular complications. The average proportion of patients with elevated BNP was 24.8% (95% confidence interval [CI]: 20.1 to 30.4%; I(2) = 89%). All studies showed a statistically significant association between an elevated pre-operative BNP level and various cardiovascular outcomes (e.g., a composite of cardiac death and nonfatal myocardial infarction; atrial fibrillation). Data pooled from 7 studies demonstrated an odds ratio (OR) of 19.3 (95% CI: 8.5 to 43.7; I(2) = 58%). The pre-operative BNP measurement was an independent predictor of perioperative cardiovascular events among studies that only considered the outcomes of death, cardiovascular death, or myocardial infarction (OR: 44.2, 95% CI: 7.6 to 257.0, I(2) = 51.6%), and those that included other outcomes (OR: 14.7, 95% CI: 5.7 to 38.2, I(2) = 62.2%); the p value for interaction was 0.28.These results suggest that an elevated pre-operative BNP or NT-proBNP measurement is a powerful, independent predictor of cardiovascular events in the first 30 days after noncardiac surgery.

Uterine cramping pain is related to prostaglandins, which are mediated by cyclooxygenase. However, it is unknown whether the analgesic effects of the non-selective cyclooxygenase inhibitor tenoxicam are different between primiparous and multiparous women. This placebo-controlled, double-blind study compared the analgesic effect of tenoxicam on post-cesarean uterine cramping pain in primiparous and multiparous women.Forty primiparous women and 40 multiparous women who were scheduled for elective cesarean delivery were allocated into the following 4 groups: saline-primipara (SP) group, tenoxicam-primipara (TP) group, saline-multipara (SM) group, and tenoxicam-multipara (TM) group. Saline or 20 mg tenoxicam was intravenously injected immediately after clamping of the umbilical cord. All patients received patient-controlled analgesia for postoperative pain control. Resting wound pain, uterine cramping pain, morphine consumption, and morphine-related side effects were evaluated at 4 and 24 hours after surgery.At 24 hours after surgery, tenoxicam-related relief of uterine cramping pain was 2.1 in primiparous women (visual analog scale: SP 5.6 (4.4-6.8) minus TP 3.5 (2.2-4.9); p0.01). The tenoxicam-related morphine-sparing effect was 14 mg (45%) in primiparous women (SP 31.4 mg (23.9-38.8) minus TP 17.4 mg (11.6-23.2); p0.01). The tenoxicam-related relief of uterine cramping pain and tenoxicam-related morphine-sparing effect were not significant in multiparous women.This study revealed that the analgesic effect of tenoxicam on post-cesarean uterine cramping pain is greater in primiparous women than in multiparous women. Further studies are required to determine whether a higher dosage of tenoxicam is beneficial to reduce uterine cramping pain in multiparous women.

We performed the present study to identify the mutation in patients in Taiwan with malignant hyperthermia (MH). We also test the hypothesis that a denaturing high-performance liquid chromatography (DHPLC) protocol can be used for mutation detection in these patients. We identified five Taiwanese patients with typical clinical presentations of MH after general anesthesia. We also enrolled 50 healthy volunteers. Polymerase chain reaction was used to amplify the ryanodine receptor (RYR1) gene mutation hot spots and DHPLC techniques were used to screen for mutations. Upon detection of a heterozygous elution pattern in DHPLC analysis, DNA sequencing reaction was performed to identify the nucleotide variations. We identified a RYR1 mutation in all 5 patients with MH. There were 4 different mutations in the 5 patients: Tyr522Cys, Arg552Trp, Val2168Met, and Thr2206Arg. Among the 5 patients, 2 unrelated patients had the same Thr2206Arg mutation. Three of the mutations had been reported before, but the Tyr522Cys mutation was novel. None of the MH-related mutations were found in the control group. In conclusion, we identified RYR1 mutations in 5 Taiwanese patients with MH using a DHPLC-based approach. A DHPLC-based genetic test may be developed as a noninvasive and convenient test for MH.

Port-A-Cath systems are widely used for long-term therapy in the treatment of malignancies and infection. Spontaneous migration of Port-A-Cath catheters after satisfactory initial placement is uncommon but is associated with a number of complications, including neck pain, shoulder pain, ear pain, infection, venous thrombosis, and neurological complications. We describe two cases of migration of the Port-A-Cath catheter into the ipsilateral internal jugular vein. Both received surgical reposition of the catheter with a longer one. We speculate that the migration is related to severe cough and vigorous changes of intrathoracic pressure. We also review the literature regarding such unusual complications of Port-A-Cath. Because catheter migration might be asymptomatic, monitoring the catheter position bimonthly when not used is recommended. Before a new course of chemotherapy or encountering symptoms of migration, obtaining a chest roentgenogram is essential to provide early detection and repositioning management of a migrated catheter.

The aim of this study is to investigate the optimal injection time of alfentanil during induction of anesthesia to blunt the circulatory responses induced by laryngoscopy and tracheal intubation.Seventy-five patients of ASA class I or II were randomly assigned to five groups. Group I was the placebo group in which the patients received normal saline 2 ml just before induction. Patients in groups II, III, IV and V received alfentanil 10 microg/kg at 5, 3, 1 and 0.5 min before intubation respectively. Anesthesia was maintained with 1.5% isoflurane and nitrous oxide in 50% oxygen (2:2 L/min). The patients' heart rate and blood pressure before and after intubation were documented and compared. The occurrence of adverse effects was also recorded.Patients' demographic data, baseline hemodynamic profile and the laryngoscopic time did not differ among the five groups. The patients in groups II, III and IV showed decreased heart rate compared with group I within 3 min after intubation. The patients in group V like those in group I did not show a reduction in heart rate 1 min after intubation. The patients in groups II, III, IV and V all showed reduced systolic blood pressure and rate-pressure product (RPP) 2 min after intubation. The occurrence of hypotension and bradycardia was not different among the five groups; hypertension and high RPP were less in groups II, III and IV as compared with group I. Ninety-three percent patients in group II and group III suffered from dizziness after alfentanil administration. One patient in group II had nausea and another one patient displayed hypoxemia after alfentanil administration.Considering equal effectiveness and fewer side effects, one minute before intubation is the optimal injection time of alfentanil to blunt the circulatory responses induced by laryngoscopy and tracheal intubation.

The aim of this study was to evaluate the effectiveness of lidocaine, propofol and ephedrine in suppressing fentanyl-induced cough.One hundred and eighteen patients were randomly assigned into four groups and the following medications were given intravenously: patients in Group I (n = 31) received normal saline 2 mL, Group II (n = 29) received lidocaine 2 mg.kg(-1), Group III (n = 30) received propofol 0.6 mg.kg(-1) and Group IV (n = 28) received ephedrine 5 mg. At one minute after the study medication, fentanyl 2.5 microg.kg(-1) was given intravenously within two seconds. The occurrence of cough and vital sign profiles were recorded within two minutes after fentanyl bolus by an anesthesiologist blinded to study design.Sixty-five percent of patients in the placebo group had cough, whereas the frequency was significantly decreased in Groups II (14%) and IV (21%). Although a numerically lower frequency of cough was noted in Group III (37%), it was not statistically different from that of the placebo group. SpO(2) decreased significantly in patients of Group III compared to placebo; one patient experienced hypoxemia necessitating mask ventilation. Patients in Group III showed a decrease in heart rate and systolic blood pressure (2 beats.min(-1) and 8 mmHg vs baseline). Patients in Group IV showed an increase in both measurements (5 beats.min(-1) and 8 mmHg vs baseline). No truncal rigidity was observed throughout the study.Intravenous lidocaine 2 mg.kg(-1) or ephedrine 5 mg, but not propofol 0.6 mg.kg(-1), was effective in preventing fentanyl-induced cough. The results provide a convenient method to decrease fentanyl-induced cough.