In a prospective study, 215 pregnancies of known gestational age were investigated using Doppler sonography. Multiple pregnancies and pregnancies complicated by fetal malformations were excluded. A pulsed Doppler machine was used to record the flow velocity waveforms in the umbilical artery (UA) and middle cerebral artery (MCA). The pulsatility index (PI) of both vessels and the ratio of PI UA to PI MCA were calculated. A total of 127 pregnancies ended in the birth of appropriate-for-gestational age babies with no perinatal problems; these formed the normal group (Group A). Of the 88 pregnancies which made up the risk group, 17 were appropriate-for-gestational age babies with perinatal problems (Group B), 55 were small-for-gestational-age babies with no perinatal problems (Group C), and 16 were small-for-gestational age babies with perinatal problems (Group D). Normal ranges were calculated based on the results for Group A; the measured values for the risk groups were then compared to these. There were highly significant differences between values obtained from the risk groups and those of Group A with the exception of the umbilical artery in Group B and the middle cerebral artery in Group C. The best results came from the values for MCA in Group B (sensitivity = 71%), UA in Group D (sensitivity = 75%), and the PI ratio UA : MCA in Group D (sensitivity = 81%). The sensitivity for the ratio in Group D increased to 93% if only the last measurement for each patient taken within 14 days of delivery was analyzed. A drop in the MCA PI in appropriate-for-gestational-age fetuses was the best indicator of imminent risk of hypoxemia. The PI ratio of UA : MCA is valuable in monitoring small-for-gestational-age fetuses, particularly those with high UA PI levels, as a rise in the ratio provides an early indication of fetal risk.
Objective To investigate the effect of cordocentesis on the umbilical and fetal cerebral circulation. Design Cross sectional study. Setting Department of Obstetrics and Gynaecology, Regional Referral Centre for Fetal Medicine, Klagenfurt Hospital, Austria. Subjects Thirty pregnant women undergoing diagnostic cordocentesis at 18 to 38 weeks' gestation. Interventions The pulsatility index (PI) in the umbilical artery and fetal middle cerebral artery was measured by pulsed Doppler ultrasound before and immediately after cordocentesis. Main outcome measures Change in umbilical artery PI and middle cerebral artery PI. Results Cordocentesis was associated with a significant decrease in both umbilical artery PI (median −0.18, range −2.21 to 1.5, P<0.004) and middle cerebral artery PI (mean ‐0.15, SD 0.32, P<0.03) and the decrease in umbilical artery PI was most marked when cordocentesis was performed transplacentally. In four cases, there were absent or reversed frequencies at the end of diastole (EDF) in the umbilical artery before cordocentesis, and in all cases there were positive EDF after the procedure. In contrast, one of the 26 cases with positive EDF developed reversed EDF following the procedure. Conclusions Acute alterations in the waveforms from both the umbilical and fetal cerebral circulation can be induced by cordocentesis. The decrease in resistance in the fetoplacental circulation could be attributed to the release of vasodilators, and the increase in resistance observed in some cases could be secondary to arterial vasospasm. Better understanding of the underlying mechanisms might help in making cordocentesis a safer procedure.
In 19 out of 20 human fetuses we recorded blood velocity waveforms in the renal artery by means of a duplex Doppler sector scanner. One fetus was at 22 weeks gestation, 7 fetuses were between 32 and 35 weeks, and 12 fetuses between 36 and 40 weeks. There was no evidence of intrauterine growth retardation and there was a normal quantity of amniotic fluid in all pregnancies. We also recorded waveforms in the umbilical artery, the descending aorta, and the internal carotid artery. The RI in these vessels showed normal values in all cases. There was no end-diastolic flow in four of the seven fetuses studied at 32 to 35 weeks gestation. The mean RI of fetuses with end-diastolic flow was 0.86 (SD 0.03). The interpretations of these results, and ideas for future studies are discussed.
!Purpose: To evaluate whether ultrasound accuracy of estimated fetal weight (EFW) differs in women with diet controlled gestational diabetes mellitus (GDM) compared to nondiabetic pregnant women. Material and Methods: We included 363 patients, 121 patients with diet controlled GDM and 242 patients with a normal oral glucose tolerance test (oGTT). Each case of diet controlled GDM was matched with 2 unaffected controls. All patients were screened/diagnosed for GDM by means of an oGTT. Both groups received ultrasound examination including fetal biometry, using Hadlockʼs Formula, within 7 days to delivery. After birth, gestational age, birthweight and Apgar scores were collected from each newborn. Results: There was a good correlation between EFW and birth weight (coefficient = 0.747, p < 0.001 by Pearson correlation, even after adjustment for glucose status). Regression analyses, including noGDM/GDM, maternal age, maternal body mass index, birth weight and time interval between ultrasound and delivery revealed that only fetal birth weight significantly influences weight difference between ultrasound EFW and actual birth weight at term. Conclusion: Our data suggests that ultrasound accuracy of EFW using Hadlockʼs Formula at term does not differ in women with diet controlled GDM compared to women with normal glucose tolerance.
The IMP dehydrogenase inhibitor, tiazofurin (TR)-2-beta-D-ribofuranosylthiazole-4-carboxamide, which exhibited oncolytic activity in patients with chronic myelogenous leukaemia (CML) in blast crisis was found to inhibit the growth of human neuroblastoma SK-N-SH cells with an IC50 of 4.2 microM. TR treatment of cells perturbed nucleic acid and catecholamine pathways. As biochemical markers of TR action decreased cellular GTP pools, increased inosine and hypoxanthine concentrations and depleted dopamine content were found. Incubation of tumour specimens obtained from paediatric patients with grade-IV neuroblastoma with TR resulted in the formation of the active metabolite, thiazole-4-carboxamide adenine dinucleotide, in concentrations sufficient to inhibit tumour growth. Cytotoxic and biochemical effects of TR were enhanced by combining it with allopurinol (an inhibitor of xanthine dehydrogenase), and hypoxanthine (an alternate substrate for hypoxanthine-guanine phosphoribosyltransferase). Induction of transdifferentiation of SK-N-SH cells from a neuroblast to an epitheloid, substrate-adherent phenotype was more pronounced with TR than with all-trans-retinoic acid. Transdifferentiating treatment with TR resulted in a 2-fold-enhanced sensitivity towards adriamycin. However, differentiation with all-trans-retinoic acid rendered the cells more resistant to adriamycin. Our results suggest that TR might be a promising agent for the treatment of children suffering from neuroblastoma.
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