Pharmacokinetics of repeated doses of misoprostol

BACKGROUNDMisoprostol is widely used in obstetrics and gynaecology for medical abortion, cervical priming and induction of labour. To aid the design of effective and safe regimens, we have investigated the pharmacokinetic parameters after the vaginal or sublingual administration of repeated doses of 400 g of misoprostol.METHODSWomen undergoing termination of pregnancy by suction evacuation were randomized to receive 400 g of sublingual or vaginal misoprostol every 3 h for five doses. Venous blood was taken at 180, 200, 240, 360, 380, 420, 540, 560, 600, 720, 740, 780 and 900 min after the first dose of misoprostol for determination of the plasma level of misoprostol acid (MPA).RESULTSThe peak plasma levels of MPA decreased with successive doses of vaginal misoprostol, whereas the peak plasma levels were similar with successive doses of sublingual misoprostol. After the third dose, the peak plasma levels of MPA after sublingual misoprostol were significantly higher than those after vaginal administration. After the final dose, the area under the MPA concentration-time curve after sublingual administration was significantly higher than that after vaginal misoprostol (P < 0.031). However, subgroup analysis in the vaginal administration group showed that the progressive decline in the peak plasma levels of MPA occurred only in women with significant vaginal bleeding.CONCLUSIONSThe peak plasma level of MPA after each dose of misoprostol is higher and the bioavailability is also greater after sublingual administration, compared with that after vaginal administration, of repeated doses of misoprostol. The difference was probably due to the reduction in absorption of vaginal misoprostol in the presence of significant vaginal bleeding.postprin

A pilot study on the use of letrozole with either misoprostol or mifepristone for termination of pregnancy up to 63 days

Background: Letrozole is a third-generation selective aromatase inhibitor. Animal data suggested that it might be useful in medical abortion. We performed two pilot studies to assess the feasibility of using letrozole in combination with either mifepristone or misoprostol for termination of pregnancy up to 63 days. Study Design: We recruited 40 subjects who requested legal termination of pregnancies up to 63 days. Medical abortion was performed with letrozole 7.5 mg daily for 2 days followed by 800 mcg vaginal misoprostol in 20 subjects and letrozole 7.5 mg combined with 200 mg mifepristone in another 20 subjects. Results: The mean induction-to-abortion interval of the regimen of letrozole and misoprostol was 9.1 h (median 7.9 h, range 2.7-23.6 h). The complete abortion rate was 80% (95% CI: 56.3-94.3%). For those with gestation of ≤49 days, the complete abortion rate was 87.5% (14/16; 95% CI: 61.7-98.5%). The mean induction-to-abortion interval of letrozole combined with mifepristone was 90.1 h (median 93.4 h, range 66.0-121.2 h). The complete abortion rate was 71.4% (95% CI: 47.8-88.7%). Conclusion: These preliminary results suggest that a regimen of letrozole and misoprostol may be useful in medical abortion, but the combination with mifepristone is less effective and takes longer. Randomized studies comparing letrozole and misoprostol to misoprostol alone are warranted. © 2011 Elsevier Inc. All rights reserved.postprin

Replication study of genetic loci influencing age at menopause in Southern Chinese women

Session - Ovarian AgeingThis journal issue contain Abstracts: 10th EMAS Congress 2015INTRODUCTION: Age at menopause is a highly heritable trait. Previous genome-wide meta-analysis in European and Northern Chinese identified 26 loci underlying age at menopause. OBJECTIVES: To validate these 26 genetic loci in Southern Chinese women. AIMS: To study genetic factors which may influence age at menopause in Southern Chinese. METHODS: This study was performed on 653 women who participated in the Hong Kong Osteoporosis Study, whose age at menopause was available. These women consented to have blood taken and archived for genotyping. DNA was extracted from the buffy coat, and genotyping was performed using Sequenom iPLEX. Age at menopause ...postprin

Differential neutrophil activation in viral infections: Enhanced TLR-7/8-mediated CXCL8 release in asthma

© 2015 The Authors. Respirology published by Wiley Publishing Asia Pty Ltd on behalf of Asian Pacific Society of Respirology. Background and objective Respiratory viral infections are a major cause of asthma exacerbations. Neutrophils accumulate in the airways and the mechanisms that link neutrophilic inflammation, viral infections and exacerbations are unclear. This study aims to investigate anti-viral responses in neutrophils from patients with and without asthma and to investigate if neutrophils can be directly activated by respiratory viruses. Methods Neutrophils from peripheral blood from asthmatic and non-asthmatic individuals were isolated and stimulated with lipopolysaccharide (LPS) (1 μg/mL), f-met-leu-phe (fMLP) (100 nM), imiquimod (3 μg/mL), R848 (1.5 μg/mL), poly I:C (10 μg/mL), RV16 (multiplicity of infection (MOI)1), respiratory syncytial virus (RSV) (MOI1) or influenza virus (MOI1). Cell-free supernatants were collected after 1 h of neutrophil elastase (NE) and matrix metalloproteinase (MMP)-9 release, or after 24 h for CXCL8 release. Results LPS, fMLP, imiquimod and R848 stimulated the release of CXCL8, NE and MMP-9 whereas poly I:C selectively induced CXCL8 release only. R848-induced CXCL8 release was enhanced in neutrophils from asthmatics compared with non-asthmatic cells (P < 0.01). RSV triggered the release of CXCL8 and NE from neutrophils, whereas RV16 or influenza had no effect. Conclusion Neutrophils release CXCL8, NE and MMP-9 in response to viral surrogates with R848-induced CXCL8 release being specifically enhanced in asthmatic neutrophils. Toll-like receptor (TLR7/8) dysregulation may play a role in neutrophilic inflammation in viral-induced exacerbations. We aimed to investigate and compare neutrophil responses to bacterial compounds and viral mimetics as well as compare responses between people with and without asthma. We also investigated neutrophil responses to live respiratory viruses. Here we provide a novel comprehensive comparison showing differential and specific activation in innate immune cells. See Editorial, page 1

Management and outcome of antenatally diagnosed congenital cystic adenomatoid malformation of the lung

Objective: To review the management and outcome of babies with antenatally diagnosed congenital cystic adenomatoid malformation. Design: Retrospective cohort review. Setting: Tertiary neonatal care unit at Queen Mary Hospital and antenatal diagnostic centre at Tsan Yuk Hospital. Patients: Consecutive patients with antenatally suspected congenital cystic adenomatoid malformation in their concepti among antenatal patients attending Tsan Yuk Hospital from 1994 to 2002. Twenty-four of 33 cases were referred to Queen Mary Hospital for postnatal management and for whom comprehensive records were available for analysis in 23. Interventions: Postnatal interventions in their babies included investigational imaging for congenital cystic adenomatoid malformation and surgery. Main outcome measures: Antenatal and postnatal outcome, as well as pathology of the excised lesions. Results: Antenatal outcome: termination of pregnancy in two cases and spontaneous abortion in one; in-utero regression was documented in nine cases and in one hydropic change was apparent. Postnatal outcome: only eight of 20 babies born alive had symptoms in neonatal period. Two developed serious infective complications in infancy, one with documented in-utero regression. Pulmonary parenchymal abnormalities were detected on computed tomography of the thorax in six of seven cases with normal or non-specific chest radiograph findings. Among nine cases with in-utero regression, congenital cystic adenomatoid malformation was confirmed by operative histology in five and abnormal computed tomography findings in three. Fifteen babies underwent surgical excision, one of whom died because of severe pre-existing pulmonary hypoplasia and nine endured minor postoperative complications. A favourable outcome was documented at a mean follow-up of 22 months (range, 2 months-7 years). Conclusions: In-utero regression of congenital cystic adenomatoid malformation on antenatal ultrasound may not represent genuine resolution. Computed tomographic thorax should be considered in all newborns with antenatally diagnosed congenital cystic adenomatoid malformation, and if confirmed early operation before first hospital discharge is recommended.published_or_final_versio

Pre-implantation genetic diagnosis in Hong Kong

This paper presents the first two successful cases of pre-implantation genetic diagnosis in Hong Kong and discusses the indications and the advantages over prenatal diagnosis. Patients should be informed about the procedure and extensively counselled about the possibility of misdiagnosis and the need for conventional prenatal diagnosis during pregnancy.published_or_final_versio

Interface Engineering for Atomic Layer Deposited Alumina Gate Dielectric on SiGe Substrates.

Optimization of the interface between high-k dielectrics and SiGe substrates is a challenging topic due to the complexity arising from the coexistence of Si and Ge interfacial oxides. Defective high-k/SiGe interfaces limit future applications of SiGe as a channel material for electronic devices. In this paper, we identify the surface layer structure of as-received SiGe and Al2O3/SiGe structures based on soft and hard X-ray photoelectron spectroscopy. As-received SiGe substrates have native SiOx/GeOx surface layers, where the GeOx-rich layer is beneath a SiOx-rich surface. Silicon oxide regrows on the SiGe surface during Al2O3 atomic layer deposition, and both SiOx and GeOx regrow during forming gas anneal in the presence of a Pt gate metal. The resulting mixed SiOx-GeOx interface layer causes large interface trap densities (Dit) due to distorted Ge-O bonds across the interface. In contrast, we observe that oxygen-scavenging Al top gates decompose the underlying SiOx/GeOx, in a selective fashion, leaving an ultrathin SiOx interfacial layer that exhibits dramatically reduced Dit

Clinical management guidelines for osteoporosis in Hong Kong

The following guidelines provide a basis for the management of osteoporosis for the practising physician in Hong Kong. The guidelines have been complied by a working group that represents the specialties concerned with osteoporosis and summarise the current management of osteoporosis based on available published evidence and relevant local experience.published_or_final_versio

Interface Engineering for Atomic Layer Deposited Alumina Gate Dielectric on SiGe Substrates.

Optimization of the interface between high-k dielectrics and SiGe substrates is a challenging topic due to the complexity arising from the coexistence of Si and Ge interfacial oxides. Defective high-k/SiGe interfaces limit future applications of SiGe as a channel material for electronic devices. In this paper, we identify the surface layer structure of as-received SiGe and Al2O3/SiGe structures based on soft and hard X-ray photoelectron spectroscopy. As-received SiGe substrates have native SiOx/GeOx surface layers, where the GeOx-rich layer is beneath a SiOx-rich surface. Silicon oxide regrows on the SiGe surface during Al2O3 atomic layer deposition, and both SiOx and GeOx regrow during forming gas anneal in the presence of a Pt gate metal. The resulting mixed SiOx-GeOx interface layer causes large interface trap densities (Dit) due to distorted Ge-O bonds across the interface. In contrast, we observe that oxygen-scavenging Al top gates decompose the underlying SiOx/GeOx, in a selective fashion, leaving an ultrathin SiOx interfacial layer that exhibits dramatically reduced Dit

Genetic study of congenital bile-duct dilatation identifies de novo and inherited variants in functionally related genes

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