Lin W.-L.,Chung Shan Medical University |
Kuo W.-H.,Armed Force Hualien General Hospital |
Kuo W.-H.,Central Taiwan University of Science and Technology |
Chen F.-L.,Chung Shan Medical University |
And 6 more authors.
Annals of Surgical Oncology | Year: 2011
Background: Although overexpression, amplification, and somatic mutation of the HER2 gene have been noted in various types of human cancers, we report here for the first time that novel mutations and amplification of the HER2 gene occurred concomitantly in mucinous epithelial ovarian cancer (EOC). Methods: Twenty-seven tissue microarray samples from EOC patients were analyzed by immunohistochemistry (IHC) with Dako c-erb-B2 antibody and subsequently were examined by fluorescence in situ hybridization (FISH) with the Abbott PathVysion HER2 DNA Probe Kit. HER2 gene, exon 18-24, encoding a tyrosine kinase domain, was analyzed by polymerase chain reaction (PCR) and direct sequencing. Results: The FISH-IHC paired results confirmed 19 concordant negative results and 3 concordant positive results. Moreover, all 4 HER2-amplified cases were of the mucinous type, whereas the remaining 23 HER2-nonamplified cases were of the nonmucinous type. The 4 mucinous EOC cases with HER2 gene amplification were selected and further analyzed for HER2 gene mutations. Data revealed that somatic mutations were present in 2 cases (R970W and E971G), but absent in the other 2 cases. Conclusions: HER2 protein overexpression correlated significantly with HER2 gene amplification in EOC (P = 0.027). It is surprising that all 4 cases of mucinous EOC showed HER2 gene amplification confirmed by FISH testing. However, we suppose that increasing the number of cases would possibly modify the results. This study also showed that both HER2 gene amplification and somatic mutations are not mutually exclusive in mucinous EOC. Further studies are warranted to investigate the potential role of anti-HER2 therapy. © 2011 Society of Surgical Oncology.
Yang C.-F.,Taipei Veterans General Hospital |
Liu H.-C.,Taipei Veterans General Hospital |
Hsu T.-R.,Taipei Veterans General Hospital |
Hsu T.-R.,National Yang Ming University |
And 10 more authors.
American Journal of Medical Genetics, Part A | Year: 2014
The aim of this study was to: (a) analyze the results of a large-scale newborn screening program for Pompe disease, and (b) establish an effective diagnostic protocol to obtain immediate, valid diagnosis of infantile-onset Pompe disease (IOPD) to promote earlier treatment and better outcomes. In this study, 402,281 newborns were screened for Pompe disease from January 1, 2008 to May 1, 2012. Infants with low acid α-glucosidase (GAA) activity were referred to Taipei Veterans General Hospital for diagnostic confirmation. Physical examination, biochemical parameter (creatine kinase [CK], alanine transaminase, aspartate aminotransferase, and lactate dehydrogenase), and echocardiogram assessments were performed immediately to effectively differentiate IOPD from suspected late-onset Pompe disease (LOPD) or false-positive cases with pseudodeficiency mutation. Six infants with IOPD all presented with hypotonia, extremely low GAA enzyme activity (≤0.5μmol/L/hr) in initial dried blood spot analysis, high CK (≥250U/L), and high left ventricular mass index (LVMI, ≥80g/m2). By analyzing these parameters, IOPD was distinguished effectively and immediately from suspected LOPD and false-positive cases. Except for the first referred case, five of the infants with IOPD received first-time enzyme replacement therapy (ERT) within 4hr of admission and exhibited marked improvement. Our findings indicate that certain clinical manifestations (hypotonia, high CK, enlarged LVMI, and extremely low GAA enzyme activity in initial dried blood spot analysis) can help in the rapid and effective differentiation of patients with IOPD from other patient with low GAA activity. Such differentiation allows for the early application of first-time ERT and leads to better outcomes. © 2013 Wiley Periodicals, Inc.
Wang L.-Y.,National Taiwan University |
Wang L.-Y.,Taipei Institute of Pathology |
Chen N.-I.,National Taiwan University |
Chen N.-I.,Taipei Institute of Pathology |
And 5 more authors.
BMC Medical Genetics | Year: 2013
Background: Tandem mass spectrometry (MS/MS) analysis is a powerful tool for newborn screening, and many rare inborn errors of metabolism are currently screened using MS/MS. However, the sensitivity of MS/MS screening for several inborn errors, including citrin deficiency (screened by citrulline level) and carnitine uptake defect (CUD, screened by free carnitine level), is not satisfactory. This study was conducted to determine whether a second-tier molecular test could improve the sensitivity of citrin deficiency and CUD detection without increasing the false-positive rate.Methods: Three mutations in the SLC25A13 gene (for citrin deficiency) and one mutation in the SLC22A5 gene (for CUD) were analyzed in newborns who demonstrated an inconclusive primary screening result (with levels between the screening and diagnostic cutoffs).Results: The results revealed that 314 of 46 699 newborns received a second-tier test for citrin deficiency, and two patients were identified; 206 of 30 237 newborns received a second-tier testing for CUD, and one patient was identified. No patients were identified using the diagnostic cutoffs. Although the incidences for citrin deficiency (1:23 350) and CUD (1:30 000) detected by screening are still lower than the incidences calculated from the mutation carrier rates, the second-tier molecular test increases the sensitivity of newborn screening for citrin deficiency and CUD without increasing the false-positive rate.Conclusions: Utilizing a molecular second-tier test for citrin deficiency and carnitine transporter deficiency is feasible. © 2013 Wang et al.; licensee BioMed Central Ltd.
Tai C.-M.,I - Shou University |
Tai C.-M.,Kaohsiung Medical University |
Huang C.-K.,I - Shou University |
Hwang J.-C.,I - Shou University |
And 6 more authors.
Obesity Surgery | Year: 2012
Background: Obesity is a risk factor for nonalcoholic fatty liver disease (NAFLD), which appears to improve after weight loss induced by bariatric surgery in Western countries. The present study aims to determine the alterations of clinical measurements and liver histology of NAFLD after bariatric surgery in morbidly obese Chinese patients. Methods: Between November 2006 and December 2007, 21 morbidly obese patients receiving intra-operative liver biopsy and follow-up liver biopsy 1 year after laparoscopic Roux-en-Y gastric bypass were enrolled. NAFLD activity score (NAS) and fibrosis stage were histologically evaluated. Results: The mean body mass index fell from 43.8±7.5 to 28.3±4.6 kg/m2 (P<0.01). Biochemical improvement was found in serum levels of alanine aminotransferase (P<0.01) and γ- glutamyltransferase (P<0.01), but not aspartate aminotransferase (P=0.66). Histological improvement was noted in NAS (P<0.01) and individual components, including steatosis (P<0.01), ballooning degeneration (P<0.01), and lobular inflammation (P=0.02). Pre-operatively, 4 (19.0%), 11 (52.4%), and 6 (28.6%) patients were found to have NAS ≧5, 3 or 4, and ≦2, respectively. All patients had NAS ≦2 after surgery. Fibrosis stage also showed significant improvement (P<0.01). Conclusions: Bariatric surgery can achieve a dramatic improvement of NAFLD both biochemically and histologically in morbidly obese Chinese patients. © 2011 Springer Science + Business Media, LLC.
Liou J.-M.,National Taiwan University |
Chang C.-Y.,I - Shou University |
Sheng W.-H.,National Taiwan University |
Wang Y.-C.,I - Shou University |
And 9 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011
The accuracy of genotypic resistance to levofloxacin (gyrA mutations) and its agreement with treatment outcomes after levofloxacin-based therapy have not been reported. We aimed to assess the correlation. Helicobacter pylori strains isolated from patients who received levofloxacin-based and clarithromycin-based triple therapies in a previous randomized trial were analyzed for point mutations in gyrA and 23S rRNA. PCR followed by direct sequencing was used to assess the gyrA and 23S rRNA mutations. An agar dilution test was used to determine the MICs of clarithromycin and levofloxacin. We found that the agreement between genotypic and phenotypic resistance to levofloxacin was best when the MIC breakpoint was >1 μg/ml (kappa coefficient, 0.754). The eradication rates in patients with and without gyrA mutations were 41.7% and 82.7%, respectively (P = 0.003). The agreement between genotypic and phenotypic resistance to clarithromycin was best when the MIC breakpoint was >2 μg/ml (kappa, 0.694). The eradication rates in patients with and without 23S rRNA mutations were 7.7% and 93.5%, respectively (P < 0.001). The agreements (kappa coefficient) between therapeutic outcomes after clarithromycin-based triple therapy and genotypic and phenotypic resistance were 0.671 and 0.356, respectively. The agreements (kappa coefficient) between therapeutic outcomes after levofloxacin-based triple therapy and genotypic and phenotypic resistance were 0.244 and 0.190, respectively. In conclusion, gyrA and 23S rRNA mutations in H. pylori strains appeared to be better markers than phenotypic resistance in the prediction of treatment outcomes. The optimal breakpoints for levofloxacin and clarithromycin resistance appeared to be >1 μg/ml and >2 μg/ml, respectively. Copyright © 2011, American Society for Microbiology. All Rights Reserved.
Niu D.-M.,National Yang Ming University |
Niu D.-M.,Taipei Veterans General Hospital |
Chien Y.-H.,National Taiwan University Hospital |
Chiang C.-C.,Chinese Foundation of Health |
And 9 more authors.
Journal of Inherited Metabolic Disease | Year: 2010
In Taiwan, during the period March 2000 to June 2009, 1,495,132 neonates were screened for phenylketonuria (PKU) and homocystinuria (HCU), and 1,321,123 neonates were screened for maple syrup urine disease (MSUD), methylmalonic academia (MMA), medium-chain acylcoenzyme A (CoA) dehydrogenase (MCAD) deficiency, isovaleric academia (IVA), and glutaric aciduria type 1 (GA-1) using tandem mass spectrometry (MS/MS). In a pilot study, 592,717 neonates were screened for citrullinemia, 3- methylcrotonyl-CoA carboxylase deficiency (3-MCC) and other fatty acid oxidation defects in the MS/MS newborn screening. A total of 170 newborns and four mothers were confirmed to have inborn errors of metabolism. The overall incidence was approximately 1/5,882 (1/6,219 without mothers). The most common inborn errors were defects of phenylalanine metabolism [five classic PKU, 20 mild PKU, 40 mild hyperphenylalaninemia (HPA), and 13 6-pyruvoyltetrahydropterin synthase (PTPS) deficiency]. MSUD was the second most common amino acidopathy and, significantly, most MSUD patients (10/13) belonged to the Austronesian aboriginal tribes of southern Taiwan. The most frequently detected among organic acid disorders was 3-MCC deficiency (14 newborns and four mothers). GA-1 and MMAwere the second most common organic acid disorders (13 and 13 newborns, respectively). In fatty acid disorders, five carnitine transport defect (CTD), five short-chain acyl-CoA dehydrogenase deficiency (SCAD), and two medium-chain acyl-CoA dehydrogenase (MCAD) deficiency were confirmed. This is the largest case of MS/MS newborn screening in an East-Asian population to date. We hereby report the incidences and outcomes of metabolic inborn error diseases found in our nationwide MS/MS newborn screening program. © 2010 SSIEM and Springer.
PubMed | Taipei City Hospital, Neonatal Screening Center, China Medical University at Taichung, Taipei Veterans General Hospital and 3 more.
Type: Journal Article | Journal: Journal of the American College of Cardiology | Year: 2016
Recently, several studies revealed a much higher prevalence of later onset Fabry disease (FD) than previously expected. It suggested that later onset FD might present as an important hidden health issue in certain ethnic or demographic populations in the world. However, the natural history of its phenotype has not been systemically investigated, especially the cardiac involvement.The study analyzed a large-scale newborn screening program for FD to understand the natural course of later onset FD.To date, 916,383 newborns have been screened for FD in Taiwan, including more than 1,200 individuals with the common, later onset IVS4+919G>A (IVS4) mutation. Echocardiography was performed in 620 adults with the IVS4 mutation to analyze the prevalence of left ventricular hypertrophy (LVH), and gadolinium-enhanced cardiac magnetic resonance imaging was performed in 129 patients with FD, including 100 IVS4 adults.LVH was observed in 67% of men and 32% of women older than 40 years. Imaging evidenced significant late gadolinium enhancement in 38.1% of IVS4 men and 16.7% of IVS4 women with the IVS4 mutation but without LVH. Seventeen patients underwent endomyocardial biopsies, which revealed significant globotriaosylceramide substrate accumulation in their cardiomyocytes.Significant cardiomyocyte substrate accumulation in IVS4 patients led to severe and irreversible cardiac fibrosis before development of LVH or other significant cardiac manifestations. Thus, it might be too late to start enzyme replacement therapy after the occurrence of LVH or other significant cardiac manifestations in patients with later onset FD. This study also indicated the importance of newborn screening for early detection of the insidious, ongoing, irreversible cardiac damage in patients with later onset FD.
PubMed | The Chinese Foundation of Health Neonatal Screening Center, Taipei Institute of Pathology, Taipei City Hospital Heping Fuyou Branch, National Yang Ming University and Taipei Veterans General Hospital
Type: | Journal: The Journal of pediatrics | Year: 2016
To evaluate whether very early treatment in our patients would result in better clinical outcomes and to compare these data with other infantile-onset Pompe disease (IOPD) cohort studies.In this nationwide program, 669,797 newborns were screened for Pompe disease. We diagnosed IOPD in 14 of these newborns, and all were treated and followed in our hospital.After 2010, the mean age at first enzyme-replacement therapy (ERT) was 11.92 days. Our patients had better biological, physical, and developmental outcomes and lower anti-rh acid -glucosidase antibodies after 2 years of treatment, even compared with one group that began ERT just 10 days later than our cohort. No patient had a hearing disorder or abnormal vision. The mean age for independent walking was 11.6 1.3 months, the same age as normal children.ERT for patients with IOPD should be initiated as early as possible before irreversible damage occurs. Our results indicate that early identification of patients with IOPD allows for the very early initiation of ERT. Starting ERT even a few days earlier may lead to better patient outcomes.
PubMed | National Taiwan University Hospital, Taipei Veterans General Hospital, Meiho University, Taipei Medical University Hospital and 5 more.
Type: Journal Article | Journal: The American journal of gastroenterology | Year: 2016
The efficacy of levofloxacin triple therapy has fallen below 80% in the second-line treatment of Helicobacter pylori (H. pylori). We aimed to assess whether the levofloxacin sequential therapy is more effective than levofloxacin triple therapy in the second-line treatment.This open-label, randomized, multicenter trial was conducted between 2012 and 2015. H. pylori-infected subjects who failed from clarithromycin-based regimens (N=600) were randomized (1:1) to receive levofloxacin sequential therapy (LS: lansoprazole and amoxicillin for the first 5 days, followed by lansoprazole, levofloxacin, and metronidazole for another 5 days) or levofloxacin triple therapy (LT: lansoprazole, amoxicillin, and levofloxacin for 10 days). Successful eradication was defined as negative (13)C-urea breath test at least 6 weeks after treatment. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Antibiotic resistance was determined by agar dilution test.The prevalence of clarithromycin, levofloxacin, and metronidazole resistance was 60, 17.6, and 36.9%, respectively. The eradication rates of LS and LT were 84.3% (253/300) and 75.3% (226/300), respectively, in the ITT analysis (P=0.006) and 86.3% (253/293) and 78.8% (223/283), respectively, in the PP analysis (P=0.021). The efficacies of both LS and LT were affected by levofloxacin resistance. The secondary resistance of levofloxacin was 66.7 and 73.9% after LS and LT, respectively. The efficacies of LS and LT were not affected by the CYP2C19 polymorphism.Levofloxacin sequential therapy was more effective than levofloxacin triple therapy, and it is recommended in the second-line treatment for H. pylori (NCT01537055).
PubMed | Cheng Hsin General Hospital, Taipei Veterans General Hospital, MacKay Childrens Hospital, Foundation Medicine and 2 more.
Type: Journal Article | Journal: PloS one | Year: 2016
Early detection of critical congenital heart disease (CCHD) can significantly reduce morbidity and mortality among newborns. We investigate the feasibility of implementing a community-based newborn CCHD screening program in Taipei.Twelve birthing facilities in Taipei participated in a trial screening program between October 1, 2013, and March 31, 2014. Newborns underwent pulse oximetry at 24-36 h old, with probes attached to the right hand and one lower limb. Any screening saturation 95% in either extremity, with an absolute difference of 3% between the right hand and foot, was accepted as a screening pass. A screening result was considered as a fail if the oxygen saturation was <95% at either probe site, on 3 separate occasions, each separated by 30 min or the first result was <95% at either probe site, and any subsequent oxygen saturation measurement was <90%. Public health nurses would follow up all missed or refused cases.Of the 6,387 live births, 6,296 newborns (coverage rate: 6,296/6,387 = 98.6%) underwent appropriate pulse oximetry screening. Sixteen newborns (0.25%) were reported to have a failed screening result. Five of these screen positive newborns were confirmed with CCHD; two of them were diagnosed solely attributed to the failed screening results. The false-positive rate was 0.18%. Implementing a 6-month screening program for CCHD produced good case detection rate, while using efficient screening and referral systems.This program was successful in integrating screening, referral and public health tracking systems. The protocol outlined in this report could provide a community-based model for worldwide implementation.