Abstract Objective Pregnancies complicated by intrauterine growth restriction (IUGR) are at increased risk for neonatal morbidity and mortality. The Dutch nationwide disproportionate intrauterine ...growth intervention trial at term (DIGITAT trial) showed that induction of labour and expectant monitoring were comparable with respect to composite adverse neonatal outcome and operative delivery. In this study we compare the costs of both strategies. Study design A cost analysis was performed alongside the DIGITAT trial, which was a randomized controlled trial in which 650 women with a singleton pregnancy with suspected IUGR beyond 36 weeks of pregnancy were allocated to induction or expectant management. Resource utilization was documented by specific items in the case report forms. Unit costs for clinical resources were calculated from the financial reports of participating hospitals. For primary care costs Dutch standardized prices were used. All costs are presented in Euros converted to the year 2009. Results Antepartum expectant monitoring generated more costs, mainly due to longer antepartum maternal stays in hospital. During delivery and the postpartum stage, induction generated more direct medical costs, due to longer stay in the labour room and longer duration of neonatal high care/medium care admissions. From a health care perspective, both strategies generated comparable costs: on average €7106 per patient for the induction group ( N = 321) and €6995 for the expectant management group ( N = 329) with a cost difference of €111 (95%CI: €−1296 to 1641). Conclusion Induction of labour and expectant monitoring in IUGR at term have comparable outcomes immediately after birth in terms of obstetrical outcomes, maternal quality of life and costs. Costs are lower, however, in the expectant monitoring group before 38 weeks of gestation and costs are lower in the induction of labour group after 38 weeks of gestation. So if induction of labour is considered to pre-empt possible stillbirth in suspected IUGR, it is reasonable to delay until 38 weeks, with watchful monitoring.
Castor oil for induction of labour: Not harmful, not helpful BOEL, Machteld Elisabeth; LEE, Sue Jean; RIJKEN, Marcus Johannes ...
Australian & New Zealand journal of obstetrics & gynaecology,
10/2009, Letnik:
49, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Background: Castor oil is one of the most popular drugs for induction of labour in a non‐medical setting; however, published data on safety and effectiveness of this compound to induce labour remain ...sparse.
Aim: To assess the safety and effectiveness of castor oil for induction of labour in pregnancies with an ultrasound estimated gestational at birth of more than 40 weeks.
Methods: Data were extracted from hospital‐based records of all pregnant women who attended antenatal clinics on the Thai–Burmese border and who were more than 40 weeks pregnant. The effectiveness of castor oil to induce labour was expressed as time to birth and analysed with a Cox proportional hazards regression model. Measures associated with safety were fetal distress, meconium‐stained amniotic fluid, tachysystole of the uterus, uterine rupture, abnormal maternal blood pressure during labour, Apgar scores, neonatal resuscitation, stillbirth, post‐partum haemorrhage, severe diarrhoea and maternal death. Proportions were compared using Fisher's exact test.
Results: Of 612 women with a gestation of more than 40 weeks, 205 received castor oil for induction and 407 did not. The time to birth was not significantly different between the two groups (hazard ratio 0.99 (95% confidence interval: 0.81 to 1.20; n = 509)). Castor oil use was not associated with any harmful effects on the mother or fetus.
Conclusions: Castor oil for induction of labour had no effect on time to birth nor were there any harmful effects observed in this large series. Our findings leave no justification for recommending castor oil for this purpose.
Double immunofluorescence microscopy reveals that epidermal growth factor (EGF) treatment of A431 cells results in more apparent co-localization of EGF receptor (EGFR) and actin filaments, as ...compared to control cells. This indicates that EGF induces actin polymerization as well as additional association of the EGFR with similar sites on the membrane-skeleton. We show that immunoprecipitation of the cytoskeleton-linked EGFR after fragmentation of the cytoskeleton results in specific co-precipitation of F-actin and a limited set of other unidentified proteins. Interestingly, EGF treatment of intact cells results in increased immunoprecipitation of cytoskeleton-associated EGFR as well as of F-actin, while actin does not co-precipitate with the non-ionic detergent-solubilized EGFR. These results demonstrate that the cytoskeleton-linked EGFR is associated with the actin microfilament system. EGF induces additional formation of protein complexes, containing the EGFR and F-actin and a limited set of other unidentified proteins. The increased co-precipitation of F-actin is most likely related to EGF-induced actin polymerization, which is specifically associated with the apical cortical microfilament system, as demonstrated by confocal laser scanning microscopy and a phallicidin-binding assay.
Several studies have shown that altered gravity conditions influence mammalian cell growth and differentiation. The molecular mechanisms underlying these effects, however, remain relatively obscure. ...In this paper we show that microgravity reached in a sounding rocket strongly decreases epidermal growth factor (EGF)-induced expression of the proto-oncogenes c-fos and c-jun, which are both implicated in the regulation of proliferation and differentiation. Decreased activity of the serum response element (SRE), present in the c-fos promoter-enhancer region, is probably responsible for the decrease in EGF-induced c-fos expression. In addition, we show that gravity alterations differentially modulate distinctive signal transduction pathways, indicating that gravity-dependent modulations of mammalian cell proliferation are unlikely to be caused by a nonspecific stress response of the cell.
The purpose of this study was to examine the delayed effects of antivascular endothelial growth factor treatment on tumor growth and vascularity in a subcutaneous mouse tumor model of human ...glioblastoma.
Antivascular endothelial growth factor antibody treatment was administered for a period of 6 weeks, to suppress tumor growth. To detect late vascular effects, tumor vascular parameters for treated tumors and control tumors were analyzed 4 weeks thereafter. By that time, tumors had grown to adequate sizes (diameter, 8-10 mm) for comparison with untreated control tumors. Vascular parameters were quantified by using an image-analysis system.
Vascular density was significantly lower in antivascular endothelial growth factor antibody-treated tumors, compared with control tumors of similar size. The vascular architecture of treated tumors was also distinctly different, compared with control tumors, showing larger but sparser vessel structures.
These findings suggest that antiangiogenic therapy may have a prolonged effect on the vascular architecture of certain tumors, resulting in enduring changes in the tumor vessels. Because tumor vasculature plays an important role in the sensitivity to various treatment modalities, these changes are likely to influence the responses of these tumors to further therapy.
A number of studies have suggested that gravity changes may influence mammalian cell growth and differentiation. To obtain insight in the molecular mechanisms underlying these effects, we have ...studied immediate early gene expression in response to activation of cytoplasmic signal transduction under microgravity conditions. In this paper we show that epidermal growth factor (EGF)- and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced expression of the c-fos and c-jun protooncogenes is decreased in microgravity, while no effect of gravity changes was observed on A23187- and forskolin-induced expression of these genes. These decrease in c-fos expression was not due to delayed kinetics under microgravity. These results demonstrate that gravity differentially modulates distinctive signal transduction pathways.
Epidermal growth factor (EGF)-induced c-fos and c-jun expression is strongly suppressed in microgravity. We investigate here whether this is due to inhibition of processes occurring during the ...initiation of EGF-induced signal transduction. For this purpose, EGF-induced receptor clustering is used as a marker. The lateral distribution of EGF receptors is directly visualized at an ultrastructural level by the label-fracture method. Quantification of the receptor distributions shows that EGF-induced receptor redistribution is similar under normal and microgravity conditions. This suggests that microgravity influences EGF-induced signal transduction downstream of EGF binding and EGF receptor redistribution, but upstream of early gene expression in human A431 cells.
Several observations have indicated that clustering of growth factor receptors plays an important role in the action of growth factors. In this investigation, we have used the label fracture method ...to study the effects of epidermal growth factor (EGF) on the lateral distribution of its receptors in A431 epidermoid carcinoma cells. This method allows a direct visualization of immunogold-labeled plasma membrane receptors on ultrastructural level and in addition permits an quantitative analysis of their lateral distribution. EGF receptors were immunogold-labeled according to standard procedures with the monoclonal anti-EGF receptor antibody 2E9 (IgG1), which binds to the EGF receptor in a 1:1 ratio. In the absence of EGF, EGF receptors located on the surface of A431 cells were found to be clustered, as deduced from Poisson variance analysis (p less than 0.001). Following treatment of A431 cells with EGF, receptor clustering increased rapidly, reaching the maximum within 10 min. Maximal clustering was maintained for 1 h, after which the lateral distribution of receptors returned to the control situation within another hour.
EGF and related polypeptides are involved in the regulation of cell growth and differentiation of continuously regenerating tissues, in tissue repair processes and in placental and fetal development. ...Their initial mode of action generally constitutes binding to specific plasma membrane localized receptors, transduction of the signal across the plasma membrane, subsequent activation of signalling pathways in the cell, and the induction of early nuclear gene expression. EGF-induced signal transmission from the plasma membrane to the nucleus has been studied in microgravity in order to gain insight in the molecular mechanisms that constitute the effects of gravity on cell growth. Exposure of human A431 cells to microgravity strongly suppresses EGF- and PMA-induced c-fos and c-jun expression. In contrast, forskolin- and A23187-induced c-fos expression and constitutive beta-2 microglobulin expression remain unaffected. This suggests that microgravity differentially modulates EGF-induced signal transduction pathways. Since both EGF and PMA are known to be activators of PKC, which is not the case for forskolin and A23187, PKC-mediated signal transduction may be a cellular target for microgravity. Inhibition of EGF-induced c-fos expression by microgravity occurs downstream of the initiation of EGF-induced signal transduction, i.e., EGF binding and EGFR redistribution. In addition to PKC signaling, actin microfilament organization appears to be sensitive to microgravity. Therefore, the inhibition of signal transduction by microgravity may be related to alterations in actin microfilament organization. The fact that early gene expression is affected by agents that alter the organization of the actin microfilament system supports this hypothesis. The decrease in c-fos and c-jun expression in microgravity may result in the decreased formation of the FOS and JUN proteins. Consequently, a short-term reduction in gene expression in microgravity may have a more dramatic effect over the long term, since both the JUN and FOS protein families are required for normal cell cycle progression. However, since more than 20 years of manned spaceflight have shown that humans can survive in microgravity for prolonged periods, it appears that cells in the human body can partly or completely overcome gravitational stress. Although some insight in the molecular basis on human cells has been obtained, future studies will be needed for a better understanding of the grounds for alterations in the cellular biochemistry due to altered gravity conditions.
Sulfhydryl (SH) reagents are known to influence the characteristics of many ligand-receptor systems. The SH reagent N-ethylmaleimide has been demonstrated to interact with EGF receptors, and to ...inhibit EGF receptor kinase activity. The data presented in this paper concern the effect of SH reagents on two intriguing features of the EGF receptor system, namely the presence of low and high affinity EGF binding sites, and the interaction of EGF receptors with the cytoskeleton. SH reagents were observed to induce a disappearance of high, but not low, affinity EGF receptors from the cell surface, and an increase in receptor-cytoskeleton interaction. Comparison of the effects of membrane-permeant and membrane-impermeant SH reagents on wild type and structurally modified EGF receptors suggested that sulfhydryl groups on the cytoplasmic, rather than the extracellular, receptor domain are involved. This indicates that the cytoplasmic domain of the EGF receptor plays a role in the high affinity binding of EGF, and in the interaction of EGF receptors with the cytoskeleton. Experiments with an anti-EGF receptor antibody that specifically blocks the binding of EGF to low affinity receptors indicated that EGF induces a shift in the EGF receptor from low to high affinity. SH reagents probably affect EGF binding by inhibiting this EGF-induced receptor conversion.
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