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Search Results: 1 - 10 of 18397 matches for " Stephen Tong "
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The Evolution of Methotrexate as a Treatment for Ectopic Pregnancy and Gestational Trophoblastic Neoplasia: A Review
Monika M. Skubisz,Stephen Tong
ISRN Obstetrics and Gynecology , 2012, DOI: 10.5402/2012/637094
Abstract:
The Evolution of Methotrexate as a Treatment for Ectopic Pregnancy and Gestational Trophoblastic Neoplasia: A Review
Monika M. Skubisz,Stephen Tong
ISRN Obstetrics and Gynecology , 2012, DOI: 10.5402/2012/637094
Abstract: Methotrexate was developed in 1949 as a synthetic folic acid analogue to compete with folic acid and thus interfere with cell replication. While initially developed as a potential treatment for acute lymphoblastic leukaemia, a serendipitous observation led to methotrexate's use to effect the dramatic cure of a case of advanced choriocarcinoma. This prompted the exploration for the potential of methotrexate to treat other conditions involving disordered trophoblastic tissue. Methotrexate has subsequently revolutionized the treatment of two pregnancy-related conditions—gestational trophoblastic neoplasia and ectopic pregnancy. This article reviews the development of modern treatment protocols that use methotrexate to medically treat these two important gynaecological conditions. 1. Introduction Methotrexate is an antifolate drug which inhibits cell division by interfering with DNA replication [1]. It is used clinically in medicine to treat a range of cancerous and noncancerous conditions. Methotrexate is currently used in gynaecology to treat disorders arising from trophoblastic tissue, namely, ectopic pregnancy and gestational trophoblastic disease. Whilst the incidences of these conditions in pregnancy are relatively rare (ranging from 0.7% for GTD [2] to 1-2% for ectopic pregnancy [3]), their impact on the lives of young women of reproductive age, both in terms of mortality and morbidity (especially loss of reproductive potential), are significant. Methotrexate has contributed to alleviating some of the disease burden of ectopic pregnancy, where it affords approximately 25% of women a nonsurgical and fertility-preserving treatment option [4]. Methotrexate has dramatically improved survival outcomes in gestational trophoblastic neoplasia, where surgery is now only occasionally used as an adjunct to treatment [5]. This article reviews methotrexate and its mechanism of action, gestational trophoblastic neoplasia and ectopic pregnancy, and how modern treatment protocols using methotrexate to medically treat these two conditions developed. 2. Methotrexate 2.1. History and Origins Methotrexate was one of the first drugs synthesized for a specific chemotherapeutic purpose—in situ folic acid inhibition for the treatment of acute lymphoblastic leukaemia (ALL) in children [1]. Its history is closely related to the discovery and characterisation of folic acid [6]. The “factor” later shown to be folic acid was discovered by missionary physician Lucy Wills in India in the 1930s, when she used Marmite to treat megaloblastic anaemia in impoverished, pregnant textile
Is Fetal Growth Restriction Associated with a More Severe Maternal Phenotype in the Setting of Early Onset Pre-Eclampsia? A Retrospective Study
Jane Weiler, Stephen Tong, Kirsten R. Palmer
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0026937
Abstract: Background Both pre-eclampsia and fetal growth restriction are thought to result from abnormal placental implantation in early pregnancy. Consistent with this shared pathophysiology, it is not uncommon to see growth restriction further confound the course of pre-eclampsia and vice versa. It has been previously suggested that superimposed growth restriction is associated with a more severe pre-eclamptic phenotype, however this has not been a consistent finding. Therefore, we set out to determine whether the presence of fetal growth restriction among women with severe early-onset pre-eclampsia was associated with more severe maternal disease compared to those without a growth-restricted fetus. Methods and Findings We undertook a retrospective cohort study of women presenting to a tertiary hospital with severe early-onset pre-eclampsia (<34 weeks' gestation) between 2005–2009. We collected clinical data, including severity of pre-eclampsia, maternal and neonatal outcomes. Of 176 cases of severe pre-eclampsia, 39% (n = 68) were further complicated by fetal growth restriction. However, no significant difference was seen in relation to the severity of pre-eclampsia between those with or without a growth-restricted baby. The presence of concomitant growth restriction was however associated with a significantly increased risk of stillbirth (p = 0.003) and total perinatal mortality (p = 0.02). Conclusions The presence of fetal growth restriction among women with severe early-onset pre-eclampsia is not associated with increased severity of maternal disease. However the incidence of stillbirth and perinatal death is significantly increased in this sub-population.
A Systematic Review of Proton Pump Inhibitors for the Prevention and Treatment of Preeclampsia and Gestational Hypertension  [PDF]
Manarangi De Silva, Fiona Brownfoot, Natalie J. Hannan, Susan P. Walker, Catherine A. Cluver, Anthea Lindquist, Stephen Tong, Roxanne Hastie
Open Journal of Obstetrics and Gynecology (OJOG) , 2019, DOI: 10.4236/ojog.2019.91003
Abstract: Background: Preeclampsia is a hypertensive disorder of pregnancy with a high rate of neonatal and maternal morbidity and mortality. The only definitive treatment is delivery. Through pre-clinical studies, proton pump inhibitors (PPIs), which are commonly and safely used in pregnancy, have been identified as potential therapeutic agents. Objective: To undertake a systematic review evaluating PPIs in the prevention and/or treatment of preeclampsia and gestational hypertension. Search strategy: Electronic databases were searched from inception to 2018. Search terms included preeclampsia, proton-pump inhibitors, pregnancy-induced hypertension, lansoprazole, rabeprazole, esomeprazole and omeprazole. Selection criteria: Studies were included if they were randomized control trials, case-control or cohort studies on human subjects. Case reports, review articles, opinion pieces and conference abstracts were excluded as well as studies with no or inappropriate control arms.
A Professional Learning Community Journey
Jenny Chiu,Mary Jane Huh,Diana Maliszewski,Stephen Tong
Partnership : the Canadian Journal of Library and Information Practice and Research , 2008,
Abstract:
A Professional Learning Community Journey
Diana Maliszewski,Stephen Tong,Jenny Chiu,Mary Jane Huh
Partnership : the Canadian Journal of Library and Information Practice and Research , 2008,
Abstract: Four teachers (three classroom teachers and a teacher-librarian) explain how their school applied a professional learning community framework to its operational practices. They discuss the process, the benefits, and the challenges of professional learning communities.
Exploration for matter stability & the material basis and mechanism for the interaction of light, electricity and magnetic  [PDF]
Zhengrong Tong
Natural Science (NS) , 2012, DOI: 10.4236/ns.2012.43028
Abstract: This paper is about the theory of “basic gravitinoes” (in early papers, it was referred to WG) in the material world, which make up the “dark matter” and the elementary particles as well. The strong interaction is generated by the Pressure Effect, which is resulted in the accumulation of the overall gravitation from all the galaxy gravitinoes. The Model for Stable-state Particle Basic Body indicates three stable states which correspond to protons, electrons and neutrons respectively and have been proven by all the particle collision experiments. It’s the root cause that only the short-lived particles resulted in the collisions. The study is supported by all experiments of light propagation, especially the wave-particle duality, and tries to make the theoretical interpretation for three laws of electromagnetic experiment so that the Maxwell’s field equations are derived ultimately and theoretically.
Valuation Adjustment Mechanism in M & A: Application, Analysis and Enlightenment  [PDF]
Tong Zhou
American Journal of Industrial and Business Management (AJIBM) , 2016, DOI: 10.4236/ajibm.2016.65051
Abstract: As a creative form of contract, the valuation adjustment mechanism is applied in M & A for many companies. Measures for Administration of Material Assets Reorganization of Listed Companies, which were adopted on November, 2014, required that listed companies must sign VAM with counterparty when pricing the assets. In M & A, the use of VAM can improve the efficiency and reduce the risk of failure. Based on the case of BlueFocus merged Accurate Sun, this paper thoroughly analyzes the structural design of VAM and its effects. Some suggestions are proposed in this paper in order to explain how to use VAM successfully.
Evaluation of ADAM-12 as a Diagnostic Biomarker of Ectopic Pregnancy in Women with a Pregnancy of Unknown Location
Andrew W. Horne, Jeremy K. Brown, Stephen Tong, Tu'uhevaha Kaitu'u-Lino
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0041442
Abstract: Background Ectopic pregnancy (EP) remains the most life-threatening acute condition in modern gynaecology. It remains difficult to diagnose early and accurately. Women often present at emergency departments in early pregnancy with a ‘pregnancy of unknown location’ (PUL) and diagnosis/exclusion of EP is challenging due to a lack of reliable biomarkers. Recent studies suggest that serum levels of a disintegrin and metalloprotease protein-12 (ADAM-12) can be used differentiate EP from viable intrauterine pregnancy (VIUP). Here we describe a prospective study evaluating the performance of ADAM-12 in differentiating EP from the full spectrum of alternative PUL outcomes in an independent patient cohort. Methodology/Principal Findings Sera were collected from 120 patients at their first clinical presentation with a PUL and assayed for ADAM-12 by ELISA. Patients were categorized according to final pregnancy outcomes. Serum ADAM-12 concentrations were increased in women with histologically-confirmed EP (median 442 pg/mL; 25%–75% percentile 232–783 pg/mL) compared to women with VIUP (256 pg/mL; 168–442 pg/mL) or miscarriage (192 pg/mL; 133–476 pg/mL). Serum ADAM-12 did not differentiate histologically-confirmed EP from spontaneously resolving PUL (srPUL) (416 pg/mL; 154–608 pg/mL). The diagnostic potential of ADAM-12 was only significant when ‘ambiguous’ PUL outcomes were excluded from the analysis (AROC = 0.6633; P = 0.03901). Conclusions/Significance When measured in isolation, ADAM-12 levels had limited value as a diagnostic biomarker for EP in our patient cohort. The development of a reliable serum biomarker-based test for EP remains an ongoing challenge.
β-Carboline Compounds, Including Harmine, Inhibit DYRK1A and Tau Phosphorylation at Multiple Alzheimer's Disease-Related Sites
Danielle Frost,Bessie Meechoovet,Tong Wang,Stephen Gately,Marco Giorgetti,Irina Shcherbakova,Travis Dunckley
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0019264
Abstract: Harmine, a β-carboline alkaloid, is a high affinity inhibitor of the dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) protein. The DYRK1A gene is located within the Down Syndrome Critical Region (DSCR) on chromosome 21. We and others have implicated DYRK1A in the phosphorylation of tau protein on multiple sites associated with tau pathology in Down Syndrome and in Alzheimer's disease (AD). Pharmacological inhibition of this kinase may provide an opportunity to intervene therapeutically to alter the onset or progression of tau pathology in AD. Here we test the ability of harmine, and numerous additional β-carboline compounds, to inhibit the DYRK1A dependent phosphorylation of tau protein on serine 396, serine 262/serine 356 (12E8 epitope), and threonine 231 in cell culture assays and in vitro phosphorylation assays. Results demonstrate that the β-carboline compounds (1) potently reduce the expression of all three phosphorylated forms of tau protein, and (2) inhibit the DYRK1A catalyzed direct phosphorylation of tau protein on serine 396. By assaying several β-carboline compounds, we define certain chemical groups that modulate the affinity of this class of compounds for inhibition of tau phosphorylation.
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