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排序方式: 共有1314条查询结果,搜索用时 15 毫秒
101.
Nicolaides E Galia E Efthymiopoulos C Dressman JB Reppas C 《Pharmaceutical research》1999,16(12):1876-1882
Purpose. To assess the usefulness of biorelevant dissolution tests in predicting food and formulation effects on the absorption of four poorly soluble, lipophilic drugs.
Methods. Dissolution was studied with USP Apparatus II in water, milk, SIFsp, FaSSIF, and FeSSIF. The in vitro dissolution data were compared on a rank order basis with existing in vivo data for the tested products under fasted and fed state conditions.
Results. All drugs/formulations showed more complete dissolution in bile salt/lecithin containing media and in milk than in water and SIFsp (USP 23). Comparisons of the in vitro dissolution data in biorelevant media with in vivo data showed that in all cases it was possible to forecast food effects and differences in absorption between products of the same drug with the physiologically relevant media (FaSSIF, FeSSIF and milk). Differences between products (both in vitro or in vivo) were less pronounced than differences due to media composition (in vitro) or dosing conditions (in vivo).
Conclusions. Although biorelevant dissolution tests still have issues which will require further refinement, they offer a promisingin vitro tool for forecasting the in vivo performance of poorly soluble drugs. 相似文献
102.
Smith GC Yu CK Papageorghiou AT Cacho AM Nicolaides KH;Fetal Medicine Foundation Second Trimester Screening Group 《Obstetrics and gynecology》2007,109(1):144-151
OBJECTIVE: We sought to relate the risk of antepartum stillbirth to uterine artery Doppler flow velocimetry at 22-24 weeks. METHODS: Data were available from 30,519 unselected women from seven units in the UK who had uterine artery Doppler performed between 22 and 24 weeks of gestation. The risk of stillbirth (n=109) was assessed using time to event and logistic regression analysis. Stillbirths were subdivided into placental (due to abruption, preeclampsia, or growth restriction) or unexplained. RESULTS: The risk of placental stillbirth was increased among women with a mean pulsatility index in the top decile (adjusted hazard ratio [HR] 5.5, 95% confidence interval [CI] 2.8-10.6) and those with a bilateral notch (adjusted HR 3.9, 95% CI 2.0-7.8). The relationship between a mean pulsatility index in the top decile and the risk of unexplained stillbirth was weaker (adjusted HR 2.5, 95% CI 1.1-5.6) and there was no association with a bilateral notch. Placental stillbirths occurred at earlier gestations than unexplained stillbirths (median [interquartile range] 30 [26-36] compared with 38 [36-40], P<.001). Consequently, being in the top 5% of predicted risk of stillbirth on the basis of the combination of mean pulsatility index and notching was a good predictor (sensitivity, specificity, and positive likelihood ratio) of all cause stillbirth up to 32 weeks (58%, 95%, and 12.1, respectively) but a poor predictor of stillbirth at later gestations (7%, 95%, and 1.3, respectively). CONCLUSION: Abnormal uterine artery Doppler was a better predictor of the risk of stillbirth due to placental causes than unexplained stillbirth. Consequently, abnormal uterine artery Doppler was a good predictor of stillbirth at extreme preterm gestations but a poor predictor of stillbirth at term. LEVEL OF EVIDENCE: II. 相似文献
103.
OBJECTIVE: To examine whether in smokers there is a significant dose dependency between the number of cigarettes per day and levels of free ss-hCG and pregnancy-associated plasma protein A (PAPP-A) at 11-13(+6) weeks of gestation. METHODS: This was a retrospective analysis of the maternal serum free ss-hCG and PAPP-A levels in relation to the maternal smoking status in 109 263 chromosomally normal singleton pregnancies that had undergone first-trimester screening for Down syndrome by a combination of fetal nuchal translucency thickness and maternal serum biochemistry. RESULTS: There were 95 287 nonsmokers and 13 976 cigarette smokers. The overall median PAPP-A MoM among cigarette smokers was 0.827, which was 19.6% lower than the value of 1.029 in nonsmokers (p < 0.0001 for log(10) MoM). The respective values for beta-hCG MoM were 1.003 for smokers and 1.035 for nonsmokers (p < 0.0001 for log(10) MoM) which corresponds to a reduction of 3.1%. There was a significant inverse relationship between the number of cigarettes per day and the level of PAPP-A MoM (r = 0.989, p < 0.0001) but not the level of free beta-hCG MoM (r = 0.733; p = 0.098). Using a statistical modeling approach we found that the screen-positive rate when correcting the PAPP-A MoM by an all or nil smoking factor was reduced by only 0.1% (3.75 vs 3.85%) when compared to correcting with a factor related to the smoking dose per day. CONCLUSION: In first-trimester screening for Down syndrome by maternal serum PAPP-A and free beta-hCG the impact of correcting for the dose dependant rather than the all or nil effect of smoking is marginal. However, a dose dependent correction improves the accuracy of the individual patient-specific risk. 相似文献
104.
An unexpected case of trisomy 18 was diagnosed after a chorionic villous biopsy at 9 weeks gestation, obtained to exclude a probable case of sickle cell disease. Difficulties in confirming the original diagnosis after fetal tissue culture are examined. The value of pathological examination of the termination specimen is emphasized. 相似文献
105.
Choroid plexus cysts and chromosomal defects 总被引:1,自引:0,他引:1
During a 4-year period, 83 pregnant women with fetal choroid plexus cysts were investigated in our unit. Abnormal karyotypes were found in 20 fetuses, including trisomy 18 (n = 16), trisomy 13 (n = 1), triploidy (n = 1) and translocation Down's syndrome (n = 2). All fetuses with chromosomal defects had structural malformations in addition to the choroid plexus cysts. 相似文献
106.
Makrina D Savvidou Lut Geerts Kypros H Nicolaides 《American journal of obstetrics and gynecology》2002,186(1):84-88
OBJECTIVE: The purpose of this study was to investigate the vascular function of pregnant women with insulin-dependent diabetes mellitus, using a noninvasive method. STUDY DESIGN: This was a cross-sectional study that examined vascular function, which was assessed by flow-mediated dilatation of the brachial artery, in 37 pregnant women with insulin-dependent diabetes mellitus and in 37 healthy pregnant women at 20 weeks of gestation. The control of diabetes was also assessed by the measurement of glycosylated hemoglobin. Data were analyzed by 2-sided unpaired t test and multivariate regression analysis. RESULTS: In the pregnant women with insulin-dependent diabetes mellitus, flow-mediated dilatation of the brachial artery was significantly lower than in healthy pregnant women (6.43% +/- 3.66% vs 9.43% +/- 3.69%, respectively; P =.0008). This difference was apparent even after an adjustment was made for blood vessel diameter, which was different between the 2 populations (P =.01). Flow-mediated dilatation in diabetic women was significantly correlated with the duration of diabetes (P =.01) but not with the levels of glycosylated hemoglobin. CONCLUSION: Maternal insulin-dependent diabetes mellitus is associated with an impaired vasodilatory response to a blood flow stimulus. This vascular dysfunction is associated with the duration of the diabetes. 相似文献
107.
R Bindra P Curcio S Cicero A Martin K H Nicolaides 《Ultrasound in obstetrics & gynecology》2001,18(6):587-589
OBJECTIVE: To determine whether the major chromosomal abnormalities are associated with impaired placentation in the first trimester of pregnancy. METHODS: This was a prospective study of 692 singleton pregnancies undergoing fetal karyotyping at 11-14 weeks of gestation. Uterine artery Doppler was carried out and the mean pulsatility index was calculated just before chorionic villus sampling. RESULTS: The fetal karyotype was normal in 613 pregnancies and abnormal in 79, including 39 cases of trisomy 21, 11 of trisomy 18, 11 of trisomy 13, eight of Turner syndrome and 10 with other defects. There were no significant differences in the median value of uterine artery mean PI between any of the individual groups. Although in the combined group of trisomy 18, trisomy 13 and Turner syndrome fetuses, the median pulsatility index (1.60) was significantly higher than in the chromosomally normal group (median pulsatility index, 1.51; P = 0.021), in the majority of abnormal fetuses (24 of 30) mean pulsatility index was below the 95th centile of the normal group (mean pulsatility index, 2.34). There was no significant association between uterine artery mean pulsatility index and fetal nuchal translucency thickness or fetal growth deficit. CONCLUSIONS: The high intrauterine lethality and fetal growth restriction associated with the major chromosomal abnormalities are unlikely to be the consequence of impaired placentation in the first trimester of pregnancy. 相似文献
108.
OBJECTIVE: To examine the association between increased nuchal translucency thickness and major cardiac defects in chromosomally normal fetuses. SETTING: Tertiary referral unit for fetal medicine and fetal cardiology. METHODS: During a 4-year period (January 1997 to January 2001), detailed echocardiography was performed in 1319 chromosomally normal fetuses with increased nuchal translucency thickness at 10-14 weeks of gestation. The incidence of major cardiac defects was examined in relation to the fetal NT at the 10-14-week scan. RESULTS: Major cardiac defects were diagnosed in 60 (4.5%) of the 1319 fetuses. In fetuses with a nuchal translucency thickness in the range of 2.5-3.4 mm, the incidence of major cardiac defects was 2.5% (18/722; 95% confidence interval, 1.5-3.9) and in those with a nuchal translucency thickness > or =3.5 mm, it was 7% (42/597; 95% confidence interval, 5.1-9.4). CONCLUSION: Specialist echocardiography is indicated in all fetuses with increased nuchal translucency thickness because, in such fetuses, the incidence of major cardiac defects is substantially higher than in pregnancies with maternal diabetes, family history and exposure to drugs, where fetal echocardiography is widely considered to be necessary. 相似文献
109.
A reference range of fetal noradrenaline levels related to gestational age was calculated from 27 normal pregnancies between 16 and 36 weeks of gestation. Growth retarded, hypoxic fetuses had significantly elevated noradrenaline levels (P less than 0.01). 相似文献
110.
M Borenstein P Cavoretto L Allan I Huggon K H Nicolaides 《Ultrasound in obstetrics & gynecology》2008,31(1):20-24
OBJECTIVES: To establish the feasibility of examining the subclavian artery at 11 + 0 to 13 + 6 weeks of gestation, and to determine the prevalence of aberrant right subclavian artery (ARSA) in chromosomally normal and chromosomally abnormal fetuses. METHODS: Fetal echocardiography was performed prospectively in 516 patients before chorionic villus sampling at 11 + 0 to 13 + 6 weeks of gestation. Transabdominal sonography was carried out, and color flow mapping was used to identify the right subclavian artery and determine whether this was normal or aberrant (ARSA). Second-trimester fetal echocardiography was also carried out in a subgroup of 183 fetuses. RESULTS: The median gestational age was 12 weeks and the median crown-rump length was 68 mm. Successful assessment of the right subclavian artery was achieved in 425/516 (82.4%) cases and the rate of failure to do so was significantly associated with decreasing fetal crown-rump length (r = 0.174, P < 0.001) and increasing maternal body mass index (r = 0.275, P < 0.001). An ARSA was observed in 2/353 (0.6%) fetuses with a normal karyotype, in 4/51 (7.8%) cases with trisomy 21 and in 2/20 (10.0%) with other chromosomal defects. In a subgroup of 183 fetuses examined in both the first and second trimester there were three cases of ARSA observed at both scans and an additional case in which ARSA was detected only at the second scan. CONCLUSIONS: Assessment of the position of the right subclavian artery is feasible at the 11 + 0 to 13 + 6-week scan and ARSA is more common in chromosomally abnormal than normal fetuses. However, ARSA in the first trimester is unlikely to be a useful marker of trisomy 21. 相似文献