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Kuo H.-C.,Chang Gung University | Chang J.-C.,Chang Gung University | Yu H.-R.,Chang Gung University | Wang C.-L.,Pojen Hospital | And 3 more authors.
Arthritis and Rheumatology | Year: 2015

Objective Kawasaki disease (KD) is characterized by systemic vasculitis, and it is the most common acquired heart disease in children. However, the etiology and immunopathogenesis of KD are still unclear. A genome-wide association study (GWAS) identified polymorphisms in CD40, BLK, and FCGR2A as the susceptibility genes for KD. No epigenetic array studies of KD have previously been published. This study was undertaken to investigate differences in DNA methylation in patients with KD as compared to controls. Methods The HumanMethylation27 BeadChip (Illumina) was used to survey the differences in DNA methylation between KD patients and controls. DNA methylation array validation was performed in a separate cohort by pyrosequencing assay and reporter gene assays. Messenger RNA (mRNA) expression was determined, and the association of methylation with response to intravenous immunoglobulin (IVIG) treatment was analyzed. Results HumanMethylation27 BeadChip assay showed a 15% difference in methylation of 10 genes between KD patients and controls. The FCGR2A cg24422489 group, which was recently reported to be associated with KD susceptibility in a GWAS, had significant hypomethylation of 15.54% less in the KD group than in the control group. Validation of FCGR2A methylation in another cohort also showed significant hypomethylation in the KD group (5 of 5 CpG sites [P < 0.01]; n = 43 in the KD group and n = 55 in the control group). KD patients with IVIG resistance showed hypomethylation of 5 CpG sites (P < 0.05). FCGR2A mRNA expression was significantly increased in patients in the acute stage of KD compared to controls. Reporter gene assays indicated that the CpG sites of the FCGR2A promoter region were sufficient to modulate gene expression. Conclusion This is the first study to examine the DNA methylation array in KD and identify a role of hypomethylation of FCGR2A in susceptibility to KD and IVIG resistance. Copyright © 2015 by the American College of Rheumatology.


Tu C.-C.,Chang Bing Show Chwan Memorial Hospital | Hsu P.-K.,Taipei Veterans General Hospital | Hsu P.-K.,National Yang Ming University
Journal of Thoracic Disease | Year: 2016

In the era of video-assisted thoracoscopic surgery (VATS), uniportal and single incision thoracoscopic surgeries are gaining popularity. The spectrum of uniportal VATS indications is now almost equal to that of conventional VATS. For example, successful uniportal sleeve lobectomy, rib segmental resection, and management of intraoperative bleeding have all been reported. According to published data in the English-language literature, more than 9,545 uniportal VATS have been performed to date, including 1,293 lobectomies, 1,024 procedures for pneumothorax, and 6,845 sympathectomies. Of the 192 articles discussing this topic, 35 were conducted in Spain, and there were an increasing number of publications from China, Korea, and other Asian countries. There were 41 technical and review articles, all of which provided an excellent foundation of surgical concept and skill learning. The benefits of uniportal VATS include better surgical geometry and cosmetics. Regarding postoperative outcomes, thirteen out of the 15 articles reviewed showed that uniportal VATS has similar or superior outcomes to conventional VATS. Most studies demonstrated that uniportal VATS produced less postoperative pain and paresthesia. In conclusion, uniportal VATS can produce excellent operative outcome, which is becoming a mature surgical approach in thoracic disease, supported by fast-accumulating and abundant experience. © Journal of Thoracic Disease. All rights reserved.


Klein R.,University of Ottawa | Hung G.-U.,Chang Bing Show Chwan Memorial Hospital | Wu T.-C.,Taipei Veterans General Hospital | Huang W.-S.,Changhua Christian Hospital | And 3 more authors.
Journal of Nuclear Cardiology | Year: 2014

Methods: Twenty-eight patients underwent dipyridamole-stress and rest imaging with dynamic SPECT/CT acquisition. Quantitative images were iteratively reconstructed with all physical corrections and then myocardial and arterial blood regions of interest (ROI) were defined semi-automatically. A compartmental model was fitted to these ROI-sampled time-activity-curves, and flow-dependent MIBI extraction correction was applied to derive regional MBF values. Myocardial flow reserve (MFR) was estimated as stress/rest MBF ratio. MBF and MFR in low and high risk populations were evaluated for ability to detect disease. Images were each processed twice (≥7 days apart) by one expert and one novice operator to evaluate intra- and inter-operator variability of MBF and MFR measurement in the three coronary artery vascular territories.Purpose: Myocardial blood flow (MBF) quantification with dynamic SPECT could lead to widespread utilization of MBF imaging in clinical practice with little cost increase over current standard SPECT myocardial perfusion imaging. This work evaluates the feasibility and operator-dependent variability of MBF and flow reserve measurements with 99mTc-sestamibi (MIBI) dynamic SPECT imaging using a standard dual-head SPECT camera.Results: Mean rest flow, stress flow, and MFR values were 0.83, 1.82 mL·minute−1·g−1, and 2.45, respectively. For stress/rest MFR, the inter-operator reproducibility was r2 = 0.86 with RPC = 1.1. Stress MBF and MFR were significantly reduced (P < .05) in high risk (n = 9) vs low risk populations (n = 19), indicating ability to detect disease. For expert and novice operators very good intra-operator correlations of r2 = 0.98 and 0.95 (n = 168, P < .001) were observed for combined rest and stress regional flow values. Bland-Altman reproducibility coefficients (RPC) were 0.25 and 0.47 mL·minute−1·g−1 for the expert and novice operators, respectively (P < .001). Inter-operator correlation was r2 = 0.91 and Bland-Altman RPC = 0.58 mL·minute−1·g−1 (n = 336).Conclusions: MBF and reserve measurements using 99mTc-sestamibi on a traditional, two-headed camera with fast rotation and with quantitative dynamic SPECT appears to be feasible, warranting further investigation. © 2014, American Society of Nuclear Cardiology.


Huang H.-C.,Chang Gung University | Yu H.-R.,Chang Gung University | Huang L.-T.,Chang Gung University | Chen R.-F.,Chang Bing Show Chwan Memorial Hospital | And 4 more authors.
Journal of Leukocyte Biology | Year: 2012

Neonates, although deficient in cell immunity, frequently reveal sepsis with augmented proinflammatory reactions. Here, we found that neonatal monocytes produced significantly higher TNF-α mRNA and protein than adult monocytes. Assessment of the transcriptional factor found no significant difference of NF-κB p65 level between neonatal and adult monocytes. Addition of Act D to access the half-life of TNF-α mRNA revealed no significant difference of the LPS-induced TNF-α mRNA half-life between them, whereas CHX increased neonatal TNF-α mRNA significantly. This suggests that a post-transcriptional mechanism involves the augmentation of TNF-α production by neonatal monocytes. To examine whether miRNA was involved in the post-transcriptional regulation, differential displays of miRNA array between neonatal and adult MNCs were performed, along with the discovery of hsa-miR-103, hsa-miR-125b, hsa-miR-130a, hsa-miR-454-3p, and hsa-miR-542-3p, which were greater than a twofold decrease or increase after LPS treatment for 4 h. The functional validation identified that miR-125b decreased significantly in association with higher TNF-α expression by neonatal monocytes after LPS stimulation. Transfection of the miR-125b precursor into neonatal monocytes significantly repressed the TNF-α mRNA and protein expression, suggesting that miR-125b negatively regulates TNF-α expression in neonatal monocytes. Modulation of miRNA expression may be used to regulate TNF-α production in newborns with altered proinflammatory reactions. © Society for Leukocyte Biology.


Chen C.-C.,Show Chwan Memorial Hospital | Shen T.-Y.,Show Chwan Memorial Hospital | Chang M.-C.,Changhua Christian Hospital | Hung G.-U.,Chang Bing Show Chwan Memorial Hospital | And 4 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2012

Purpose: In 201Tl SPECT myocardial perfusion imaging (MPI) data are acquired shortly after the stress injection to assess early post-stress left ventricle (LV) function. The purpose of this study was to use 201Tl SPECT MPI to investigate whether stress-induced myocardial ischemia is associated with LV mechanical dyssynchrony. Methods: Enrolled in the study were 75 patients who were referred for dipyridamole stress and rest 201Tl gated SPECT MPI. The early post-stress scan was started 5 min after injection, and followed by the rest scan 4 h later. The patients were divided into three groups: ischemia group (N025, summed stress score, SSS, ≥5, summed rest score, SRS,<5), infarct group (N016, SSS ≥5, SRS ≥5) and normal group (N034, SSS<5, SRS<5). LV dyssynchrony parameters were calculated by phase analysis, and compared between the stress and rest images. Results: In the ischemia group, LV dyssynchrony was significantly larger during stress than during rest. On the contrary, LV dyssynchrony during stress was significantly smaller than during rest in the normal and infarct groups. LV dyssynchrony during rest was significantly larger in the infarct group than in the normal and ischemia groups. There were no significant differences in LV dyssynchrony during rest between the normal and ischemia groups. Conclusion: Stress-induced myocardial ischemia caused dyssynchronous contraction in the ischemic region, leading to a deterioration in LV synchrony. Normal myocardium had more synchronous contraction during stress. The different dyssynchrony pattern between ischemic and normal myocardium early post-stress may aid the diagnosis of coronary artery disease using 201Tl gated SPECT MPI. © Springer-Verlag 2012.


Chang Y.-C.,Chang Bing Show Chwan Memorial Hospital | Chang Y.-C.,Taichung Veterans General Hospital | Chen C.-H.,Taichung Veterans General Hospital | Lin M.-C.,Taichung Veterans General Hospital
Pediatrics and Neonatology | Year: 2012

Background: The concentrations of macronutrients in human milk can be influenced by various processes, such as storage, freezing, and thawing, that are performed by lactating working mothers and breast milk banks. We evaluated the impact of various containers on the nutrient concentrations in human milk. Methods: A total of 42 breast milk samples from 18 healthy lactating mothers were collected. A baseline macronutrient concentration was determined for each sample. Then, the breast milk samples were divided and stored in nine different commercial milk containers. After freezing at -20°C for 2 days, the milk samples were thawed and analyzed again. A midinfrared human milk analyzer (HMA) was used to measure the protein, fat, and carbohydrate contents. Results: There was a significant decrease in the fat content following the storage, freezing, and thawing processes, ranging from 0.27-0.30 g/dL (p = 0.02), but no significant decrease in energy content (p = 0.069) was noted in the nine different containers. There were statistically significant increases in protein and carbohydrate concentrations in all containers (p = 0.021 and 0.001, respectively), however there were no significant differences between the containers in terms of fat, protein, carbohydrate, or energy contents. Conclusion: Human milk, when subjected to storage, freezing, and thawing processes, demonstrated a significant decrease in fat content (up to 9% reduction) in various containers. It is better for infants to receive milk directly from the mother via breastfeeding. More studies are warranted to evaluate the effects of milk storage on infant growth and development.


Lin E.,Chang Bing Show Chwan Memorial Hospital
African journal of traditional, complementary, and alternative medicines : AJTCAM / African Networks on Ethnomedicines | Year: 2013

Wu-Ling-San (WLS) formula has been proved to prevent calcium oxalate nephrolithiasis both in vitro and in vivo. This is the first prospective, randomized and placebo-controlled clinical trial of WLS in calcium oxalate nephrolithiasis prevention. All patients who enrolled were asked to drink enough fluid to urinate at least 2 L daily during the study period. A 24-hour urine collection was performed to establish the baseline levels of multiple urinary parameters before taking the medicine. The patients were randomized and divided into two groups. The medication group took 2 gm WLS formula three times daily for 1 month. The control group took 2 gm placebo three times daily for 1 month. A 24-hour urine collection was performed to evaluate multiple urinary and serum parameters from all patients during the study period. A total of 39 patients were enrolled and 28 patients completed the study. Fourteen patients were allocated to WLS group and 14 patients to placebo group. After treatment, the mean urine output level increased to 2796.4 ± 525.7 ml/day (percentage of change, 13.9 %) in the WLS formula group. With placebo therapy, the mean decreased slightly to 2521.4 ± 762.7ml/day (percentage of change, -5.7 %). The percentage of change was significantly different between the two groups (independent t-test, P=0.02). No patient complained of side effects, such as fatigue, dizziness, musculoskeletal symptoms, or gastrointestinal disturbance. WLS formula is a promising adjunct to surgical and medical management of kidney stones. Active therapy with WLS formula has a positive effect on diuresis without leading to electrolyte imbalance.


Hung G.-U.,Chang Bing Show Chwan Memorial Hospital
Journal of Biomedical Research | Year: 2013

Over the past decades, stress/rest myocardial perfusion SPECT (MPS) has been utilized as a standard modality for the diagnosis, risk stratification and prognostic assessment of coronary artery disease (CAD). In addition to the perfusion information, MPS can also provide functional information of the left ventricle, including volume, ejection fraction, wall motion and dyssynchrony. This article introduces the incremental value of these non-perfusion parameters as markers and prognosticators of CAD. © 2013 by the Journal of Biomedical Research.


Chen R.-F.,Chang Bing Industrial Center | Lee C.-Y.,Chang Bing Show Chwan Memorial Hospital
International Reviews of Immunology | Year: 2014

Adenovirus is a common infectious pathogen in both children and adults. It is a significant cause of morbidity in immunocompetent people living in crowded living conditions and of mortality in immunocompromised hosts. It has more recently become a popular vehicle for gene therapy applications. The host response to wild-type infection and gene therapy vector exposure involves both virus entry receptor and the innate immune systems. Cell-mediated recognition of viruses via capsid components has received significant attention, principally thought to be regulated by the coxsackievirus-adenovirus receptor (CAR), CD46, integrins and heparin sulfate-containing proteoglycans. Antiviral innate immune responses are initiated by the infected cell, which activates the interferon response to block viral replication, while simultaneously releasing chemokines to attract neutrophils and NK cells. This review discusses the innate immune response primarily during wild-type adenovirus infection because this serves as the basis for understanding the response during both natural infection and exposure to adenovirus vectors. Copyright © Informa Healthcare USA, Inc.


Patent
Chang Bing Show Chwan Memorial Hospital | Date: 2013-08-09

A system for mosaicing endoscope images has an endoscope, a computer and a monitor. The endoscope has a relatively wide viewing angle such as 30 degrees to capture video images of a target area. The computer determines feature points on the captured video frames, aligns the video images in a common reference frame and displays them as one mosaiced image while dynamically extending the scene synchronous with the movement of the endoscope. The system creates a distortion free near real-time panorama of the endoscope scene using the wide angle view endoscope, and is useful for physicians while performing endoscopic procedures since the field of view can be extended to provide a better visual-spatial orientation.

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