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Wang Y.-L.,Taoyuan Chang Gung Memorial Hospital | Wang Y.-L.,Chang Gung University | Liou J.-D.,Taipei Chang Gung Memorial Hospital | Liou J.-D.,Chang Gung University | And 2 more authors.
Taiwanese Journal of Obstetrics and Gynecology | Year: 2013

Objective: It has been suggested that periodontal disease is an important risk factor for preterm low birth weight (PLBW). The purpose of this study was to determine the association of maternal periodontitis with low birth weight (LBW) and preterm birth (PB). Materials and Methods: Pregnant women (n = 211) aged 22-40 years were enrolled while receiving prenatal care. Dental plaque, probing depth, bleeding on probing, and clinical attachment level were used as criteria to classify three groups: a healthy group (HG; n = 82), a gingivitis group (GG; n = 67), and a periodontitis group (PG; n = 62). At delivery, birth weight was recorded. Results: Mean infant weight at delivery was 3084.9 g. The total incidence of preterm birth and LBW infants was 10.4% and 8.1%, respectively. The incidence of LBW infants was 4.2% for term and 40.9% for preterm gestations. Maternal height was not correlated with infant birth weight (p = 0.245). Significant differences in mean infant birth weight were observed among the HG, GG, and PG groups (p = 0.030). No significant relationship was found between periodontal disease and PB, but the association between periodontal disease and LBW was significant. Conclusion: After appropriately controlling for confounding variables, our results do not support the hypothesis of an association that was observed in previous studies of maternal periodontal disease and infant PB, but the association between periodontal disease and LBW is significant. © 2013.


PubMed | Chang Gung University, Taipei Chang Gung Memorial Hospital, Taipei Veterans General Hospital and National Taiwan University Hospital
Type: Journal Article | Journal: Hematological oncology | Year: 2016

Prior studies found bendamustine is efficacious in patients with indolent B-cell non-Hodgkin lymphoma (NHL). To date, no studies have reported the efficacy of bendamustine in a Chinese population. This multicentre phase II trial evaluated the pharmacokinetics (PK), safety and efficacy of bendamustine monotherapy in Chinese patients in Taiwan with pretreated indolent B-cell NHL or mantle cell lymphoma (MCL). For PK assessments, patients were randomized (n=16; 11 with indolent B-cell NHL and five with MCL) to 90 or 120mg/m(2) of bendamustine for the first cycle. Plasma levels of bendamustine and its two metabolites were analyzed. For efficacy and safety evaluations, bendamustine 120mg/m(2) was given to all patients every 3weeks starting at cycle 2 for a minimum of a total of six cycles. The median age of patients was 61.7years, and the majority were men (75%). The median number of prior treatments was 4 (range, 1-9 regimens), and all patients were previously treated with rituximab. Bendamustine plasma concentration peaked near the end of infusion and was rapidly eliminated with a mean elimination half-life (t(1/2)) of 0.67-0.8h. Of the evaluable patients (n=14), the overall response rate was 78.6%, including 7.2% of patients having a complete response. Mean progression-free survival was 27.5weeks. The most common grade 3-4 adverse events were leucopenia (56.3%), neutropenia (56.3%) and thrombocytopenia (25%). In conclusion, bendamustine was efficacious and well tolerated in Taiwanese patients with indolent NHL and MCL with a similar PK profile to that of other populations.


PubMed | Chang Gung Memorial Hospital and Taipei Chang Gung Memorial Hospital
Type: Journal Article | Journal: Journal of natural products | Year: 2016

The overexpression of ATP-binding cassette (ABC) drug transporter ABCB1 (P-glycoprotein, MDR1) is the most studied mechanism of multidrug resistance (MDR), which remains a major obstacle in clinical cancer chemotherapy. Consequently, resensitizing MDR cancer cells by inhibiting the efflux function of ABCB1 has been considered as a potential strategy to overcome ABCB1-mediated MDR in cancer patients. However, the task of developing a suitable modulator of ABCB1 has been hindered mostly by the lack of selectivity and high intrinsic toxicity of candidate compounds. Considering the wide range of diversity and relatively nontoxic nature of natural products, developing a potential modulator of ABCB1 from natural sources is particularly valuable. Through screening of a large collection of purified bioactive natural products, hernandezine was identified as a potent and selective reversing agent for ABCB1-mediated MDR in cancer cells. Experimental data demonstrated that the bisbenzylisoquinoline alkaloid hernandezine is selective for ABCB1, effectively inhibits the transport function of ABCB1, and enhances drug-induced apoptosis in cancer cells. More importantly, hernandezine significantly resensitizes ABCB1-overexpressing cancer cells to multiple chemotherapeutic drugs at nontoxic, nanomolar concentrations. Collectively, these findings reveal that hernandezine has great potential to be further developed into a novel reversal agent for combination therapy in MDR cancer patients.


PubMed | Far Eastern Memorial Hospital, National Taiwan University Hospital, Buddhist Tzu Chi General Hospital, Linkou Chang Gung Memorial Hospital and 4 more.
Type: Controlled Clinical Trial | Journal: Hepatology (Baltimore, Md.) | Year: 2015

The efficacy and safety of maternal tenofovir disoproxil fumarate (TDF) in reducing mother-to-infant hepatitis B virus (HBV) transmissions is not clearly understood. We conducted a prospective, multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)- and hepatitis B e antigen-positive pregnant women with HBV DNA 7.5 log10 IU/mL. The mothers received no medication (control group, n=56, HBV DNA 8.220.39 log10 IU/mL) or TDF 300 mg daily (TDF group, n=62, HBV DNA 8.180.47 log10 IU/mL) from 30-32 weeks of gestation until 1 month postpartum. Primary outcome was infant HBsAg at 6 months old. At delivery, the TDF group had lower maternal HBV DNA levels (4.290.93 versus 8.100.56 log10 IU/mL, P<0.0001). Of the 121/123 newborns, the TDF group had lower rates of HBV DNA positivity at birth (6.15% versus 31.48%, P = 0.0003) and HBsAg positivity at 6 months old (1.54% versus 10.71%, P = 0.0481). Multivariate analysis revealed that the TDF group had lower risk (odds ratio=0.10, P = 0.0434) and amniocentesis was associated with higher risk (odds ratio 6.82, P = 0.0220) of infant HBsAg positivity. The TDF group had less incidence of maternal alanine aminotransferase (ALT) levels above two times the upper limit of normal for 3 months (3.23% versus 14.29%, P = 0.0455), a lesser extent of postpartum elevations of ALT (P = 0.007), and a lower rate of ALT over five times the upper limit of normal (1.64% versus 14.29%, P = 0.0135) at 2 months postpartum. Maternal creatinine and creatinine kinase levels, rates of congenital anomaly, premature birth, and growth parameters in infants were comparable in both groups. At 12 months, one TDF-group child newly developed HBsAg positivity, presumably due to postnatal infection and inefficient humoral responses to vaccines.Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations. (Hepatology 2015;62:375-386.


Chang F.-Y.,Taipei City Hospital | Cheng S.-W.,Taipei Chang Gung Memorial Hospital | Wu T.-Z.,Taipei City Hospital | Fang L.-J.,Taipei City Hospital
Pediatrics and Neonatology | Year: 2013

Background: The benefits of feeding human milk to infants, even in prematurity, have been well documented. Well-organized donor milk processing has made the milk bank a good source of nutrition for premature or sick infants if their own mother's milk is not sufficient or suitable. The Taipei City Hospital Milk Bank was established in 2005 and is the first nonprofit human milk bank to operate in Taiwan. Methods: The milk bank has adopted standards of practice laid down by the Human Milk Banking Association of North America and United Kingdom Association for Milk Banking. The clinical characteristics of the eligible milk donors, the recipients, and the donor milk were reviewed retrospectively. Results: In the past 6 years, 816 eligible donors donated a total or 13,900 L (mean 17.03 L/donor) of breast milk. The mean age of these donors was 31.3 years, and 79.7% of them had college education. Most had term delivery (91.2%), with mean birth weight of their babies being 3120 g; 68.9% of the donors were primiparas. A total of 551 infants had received bank milk, with these indications: prematurity (65.4%), malabsorption (7.6%), feeding intolerance (7.2%), maternal illness (5.1%) and post-surgery (4.6%). The pass rate of raw donor milk was around 72.1%. The most common reasons to discard raw milk were Gram-negative rods contamination (72.8%) and ≥104 colony-forming units/mL of coagulase-negative Staphylococcus (62.3%). Only 0.63% of donor milk post pasteurization showed bacterial growth. Conclusion: Proper management and operation of a human milk bank can support breastfeeding, and provide a safe alternative to artificial formula for feeding preterm or ill infants in Taiwan. Sustainability of the milk bank needs more propagation and financial support by health authorities. Copyright © 2012, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rights reserved.


PubMed | Chang Gung University and Taipei Chang Gung Memorial Hospital
Type: Journal Article | Journal: Taiwanese journal of obstetrics & gynecology | Year: 2016

To investigate the associations between maternal pregestational body mass index (BMI), gestational weight gain (GWG), and adverse pregnancy outcomes among Taiwanese women.A retrospective cohort study was conducted among all singletons without fetal anomalies delivered to women at Taipei Chang Gung Memorial Hospital between 2009 and 2015. Two study cohorts were selected for analysis: all deliveries after 24 0/7weeks of gestation (Cohort 1, n=12,064) and all live births after 37 0/7weeks of gestation excluding maternal overt diabetes mellitus and chronic hypertension (Cohort 2, n=10,973). The associations between pregestational BMI, GWG outside the 2009 Institute of Medicine (IOM) guidelines, and adverse pregnancy outcomes were assessed using multivariable logistic regression analysis.In Cohort 1, the prevalence of pregestational underweight, normal weight, overweight, and obesity was 14.0%, 74.8%, 9.0%, and 2.2%, respectively. Compared with the women with normal weight, maternal underweight was associated with increased risk for placental abruption, small-for-gestational age, and low birth weight (<2500g). In contrast, overweight and obese women were at risk for gestational diabetes mellitus, preeclampsia, dysfunctional labor, cephalopelvic disproportion, large-for-gestational age, and macrosomia (>4000g). In Cohort 2, GWG below the IOM guidelines were associated with higher rates of gestational diabetes mellitus, small-for-gestational age, and low birth weight, while GWG above the IOM guidelines were with higher rates of primary cesarean delivery, large-for-gestational age, and macrosomia in women with pregestational underweight or normal weight. Normal weight women were more likely to have placental abruption with GWG below the guidelines and to have preeclampsia with GWG above the guidelines. For overweight and obese women, GWG below the guidelines was associated with a higher rate of gestational diabetes mellitus, but GWG above the guidelines was associated with a higher rate of macrosomia.Women with abnormal pregestational BMI are at risk for adverse maternal and neonatal outcomes. Moreover, GWG has a differential effect on the rates of adverse pregnancy outcomes between women of different pregestational BMI categories.


PubMed | Chang Gung University, Cheng Hsin Rehabilitation Medical Center and Taipei Chang Gung Memorial Hospital
Type: Comparative Study | Journal: Taiwanese journal of obstetrics & gynecology | Year: 2015

To compare the duration of second stage labor among modern Taiwanese women who achieved vaginal delivery without adverse neonatal outcomes and women who delivered during the early 1990 s.Data were collected from women who underwent spontaneous labor and vaginally delivered cephalic singleton fetuses with normal neonatal outcomes at the Taipei Chang Gung Memorial Hospital, Taipei, Taiwan from 1991-1995 (Cohort 1, n = 10,721) and 2010-2014 (Cohort 2, n = 3734). We calculated the median duration and 95th percentiles of second stage labor. The women were stratified according to analgesia and parity. Multiple linear regression analysis was used to determine the association between the maternal/pregnancy characteristics and second stage labor duration.The median second stage labor duration was significantly longer for Cohort 2 than for Cohort 1. For nulliparous women, the 95th percentile second stage labor thresholds were 255 minutes and 152 minutes (Cohort 2) and 165 minutes and 107 minutes (Cohort 1) for women with and without epidural analgesia, respectively. For multiparous women, the 95th percentile second stage labor thresholds were 136 minutes and 43 minutes (Cohort 2) and 125 minutes and 39 minutes (Cohort 1) for women with and without epidural analgesia, respectively. Birth weight, maternal age at delivery, and time period (2010-2014 vs. 1991-1995) were significant factors associated with the duration of second stage labor.Modern Taiwanese women who achieved vaginal delivery without adverse neonatal outcomes experienced longer second stage labors than women 25 years ago. The 95th percentile thresholds differed between nulliparous and multiparous women with and without epidural analgesia.


PubMed | Chang Gung University, Cheng Hsin Rehabilitation Medical Center and Taipei Chang Gung Memorial Hospital
Type: Comparative Study | Journal: Taiwanese journal of obstetrics & gynecology | Year: 2015

To investigate perinatal outcomes according to the 2009 Institute of Medicine (IOM) gestational weight gain (GWG) guidelines.A retrospective cohort study was conducted among all term, singleton, live births to women who delivered at the Taipei Chang Gung Memorial Hospital, Taipei, Taiwan between 2009 and 2014. Women were categorized into three groups based on prepregnancy body mass index and GWG relative to the IOM guidelines. Multivariable logistic regression analysis was used to assess the associations between GWG outside the IOM guidelines and adverse perinatal outcomes. Women with GWG within the guidelines served as the reference group.Of 9301 pregnancies, 2574 (27.7%), 4189 (45.0%), and 2538 (27.3%) women had GWG below, within, and above the IOM guidelines. Women with GWG above the IOM guidelines were at risk for preeclampsia [adjusted odds ratio (OR) 3.0, 95% confidence interval (CI) 1.9-4.7], primary cesarean delivery (adjusted OR 1.4, 95% CI 1.2-1.6) due to dysfunctional labor and cephalopelvic disproportion, large-for-gestational age (adjusted OR 1.8, 95% CI 1.5-2.1), and macrosomic neonates (adjusted OR 2.2, 95% CI 1.6-3.1). Women with GWG below the IOM guidelines were more likely to be diagnosed with gestational diabetes mellitus (adjusted OR 1.5, 95% CI 1.3-1.8) and were at higher risk for placental abruption (adjusted OR 1.7, 95% CI 1.1-2.5), small-for-gestational age (adjusted OR 1.6, 95% CI 1.4-1.9), and low birth weight neonates (adjusted OR 1.9, 95% CI 1.4-2.4).Women with GWG outside the 2009 IOM guidelines were at risk for adverse maternal and neonatal outcomes.


PubMed | Chang Gung University, Changhua Christian Hospital, Puli Christian Hospital and Taipei Chang Gung Memorial Hospital
Type: | Journal: Thrombosis journal | Year: 2016

Heritable thrombophilias are assumed important etiologies for recurrent pregnancy loss. Unlike in the Caucasian populations, protein S and protein C deficiencies, instead of Factor V Lieden and Prothrombin mutations, are relatively common in the Han Chinese population. In this study we aimed to investigate the therapeutic effect of low molecular weight heparin upon women with recurrent pregnancy loss and documented protein S deficiency.During 2011-2016, 68 women with recurrent pregnancy loss (RPL) and protein S deficiency (both the free antigen and function of protein S were reduced) were initially enrolled. All the women must have experienced at least three recurrent miscarriages. After excluding those carrying balanced translocation, medical condition such as diabetes mellitus, chronic hypertension, and autoimmune disorders (including systemic lupus erythematosus and anti-phospholipid syndrome), coexisting thrombophilias other than persistent protein S deficiency (including transient low protein S level, protein C deficiency, and antithrombin III), only 51 women with RPL and sole protein S deficiency were enrolled. Initially they were prescribed low dose Aspirin (ASA: 100mg/day) and unfortunately there were still 39 women ended up again with early pregnancy loss (12 livebirths were achieved though). Low-molecular-weight-heparin (LMWH) was given for the 39 women in a dose of 1mg/Kg every 12h from the day when the next clinical pregnancy was confirmed to the timing at least 24h before delivery. The perinatal outcomes were assessed.Of 50 treatment subjects performed for the 39 women (i.e. 11 women enrolled twice for two pregnancies), 46 singletons and one twin achieved livebirths. The successful live-birth rate in the whole series was 94% (47/50). Nineteen livebirths delivered vaginally whereas 28 delivered by cesarean section. The cesarean delivery rate is thus 59.57%. Emergent deliveries occurred in 3 but no postpartum hemorrhage had been noted.Our pilot study in Taiwan, an East Asian population, indicated anti-coagulation therapy is of benefit to women with recurrent pregnancy loss who had documented sole protein S deficiency.ISRCTN64574169. Retrospectively registered 29 Jun 2016.


PubMed | Chang Bing Show Chwan Memorial Hospital, Chang Gung University and Taipei Chang Gung Memorial Hospital
Type: Journal Article | Journal: Taiwanese journal of obstetrics & gynecology | Year: 2015

Preeclampsia is a major cause of mortality in pregnant women but the underlying mechanism remains unclear to date. In this study, we attempted to identify candidate proteins that might be associated with preeclampsia in pregnant women by means of proteomics tools.Differentially expressed proteins in serum samples obtained from pregnant women with severe preeclampsia (n = 8) and control participants (n = 8) were identified using two-dimensional gel electrophoresis (2-DE) followed by peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Additional serum samples from 50 normal and 41 pregnant women with severe preeclampsia were analyzed by immunoassay for validation.Ten protein spots were found to be upregulated significantly in women with severe preeclampsia. These protein spots had the peptide mass fingerprints matched to 1-antitrypsin, 1-microglobulin, clusterin, and haptoglobin. Immunoassays in an independent series of serum samples showed that serum 1-antitrypsin, 1-microglobulin, and clusterin levels of severe preeclampsia patients (n = 41) were significantly higher than those in the normal participants (n = 50; 1-antitrypsin 295.95 50.94 mg/dL vs. 259.31 33.90 mg/dL, p = 0.02; 1-microglobulin 0.029 0.004 mg/mL vs. 0.020 0.004 mg/mL, p < 0.0001; clusterin 77.6 16.15 g/dL vs. 67.6 15.87 g/dL, p < 0.05).Identification of these proteins by proteomics analysis enables further understanding of the pathophysiology of preeclampsia. Further studies are warranted to investigate the role of these biomarkers in prediction of this disease.

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