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Biomedical subjects

J M van Vugt

Publications and source records attributed to J M van Vugt.

At least 19 recordsLinked to original sources

Identification of triploid trophoblast cells in peripheral blood of a woman with a partial hydatidiform molar pregnancy.

In a woman with a partial hydatidiform molar pregnancy with 69,XXY karyotype, the presence of male fetal cells of trophoblastic origin was demonstrated in maternal blood by X/Y-chromosome specific PCR and by immunostaining combined with FISH on two cell populations isolated from maternal blood. Blood was obtained three weeks prior to the detection of fetal demise, at 13 weeks' gestation. Results were confirmed on formalin-fixed paraffin-embedded molar tissue, removed at 16 weeks' gestational age for therapeutic reasons. The results indicate that both plasma and cells from maternal peripheral blood might be useful for non-invasive prenatal diagnosis of fetal aneuploidies, as described in the current case with a partial molar pregnancy.

Dilatation and Curettage↗

Plasma placenta growth factor levels in midtrimester pregnancies.

OBJECTIVE: Previous studies have shown decreased levels of placenta growth factor in serum of pregnant women with preeclampsia. The aim of this study was to investigate whether levels of placenta growth factor are decreased before the clinical onset of preeclampsia, and whether placenta growth factor levels are decreased in pregnancies complicated by intrauterine growth restriction. METHODS: From an ongoing longitudinal study, 101 plasma samples were collected from 72 pregnant women at weeks 11-21 of gestation. Placenta growth factor levels were determined retrospectively in plasma using an enzyme-linked immunosorbent assay. Correlations between plasma concentrations of placenta growth factor and pregnancy outcome were evaluated. RESULTS: Plasma samples of 72 patients were analyzed. Forty-four patients had no pregnancy complications, 18 developed preeclampsia, and 10 women had pregnancies complicated by intrauterine growth restriction. Between week 17 and week 21 of pregnancy, a significantly lower level of placenta growth factor was found in plasma of patients who later developed preeclampsia (n = 10), compared with control pregnancies (n = 25, P = .004). In women with a growth-restricted baby at birth (n = 5), levels of placenta growth factor were also low. CONCLUSIONS: Our results show that plasma placenta growth factor levels are decreased before preeclampsia is clinically evident. The data suggest that placenta growth factor may be useful to determine the relative risk of developing preeclampsia and intrauterine growth restriction.

Adult↗

The role of magnetic resonance imaging in prenatal diagnosis of fetal anomalies.

Magnetic resonance imaging (MR) has become a useful adjuvant in evaluating fetal structural anomalies when ultrasound (US) is equivocal. It has a significant promise in confirming a US suspected abnormality and providing new information that was previously not available. The first studies on prenatal MR were hindered by fetal motion and long acquisition times. This degraded imaging and, therefore, maternal or fetal sedation was needed. Since fast and ultrafast MR with scan times of <1 s have become available, the amount of motion artifacts is decreased and sedation is no longer needed.MR has proved to be especially beneficial in detecting CNS anomalies. Agenesis of the corpus callosum, migration abnormalities and abnormalities of the posterior fossa are better seen on MR. Masses in the fetal neck and thorax can be identified on MR, as some abdominal anomalies. However, the fetal skeletal is difficult to visualize with MR. In the future, it is most likely that real time MR will become clinically available which would improve MR imaging even more.

Abdomen↗

HLA-G expression in trophoblast cells circulating in maternal peripheral blood during early pregnancy.

OBJECTIVE: The aim of this study was to assess the use of circulating trophoblast cells in maternal peripheral blood for noninvasive prenatal diagnosis of numeric chromosomal aberrations. STUDY DESIGN: A combined procedure for immunocytochemical identification and deoxyribonucleic acid fluorescence in situ hybridization was used after a single enrichment step consisting of density gradient centrifugation. A specific HLA-G monoclonal antibody was used in combination with X and Y chromosome specific probes in deoxyribonucleic acid fluorescence in situ hybridization to confirm fetal identity of cells bearing HLA-G in the case of a male fetus. RESULTS: We detected fetal trophoblast cells expressing HLA-G in maternal blood starting at 9 weeks' gestation. In addition to fetal sex prediction with X and Y chromosome-specific probes, fetal aneuploidy was confirmed in peripheral blood from a pregnancy complicated by trisomy 21. CONCLUSION: Although the numbers of fetal cells were extremely low, the proof of concept was demonstrated. Early noninvasive prenatal screening for numeric chromosomal abnormalities with fetal trophoblast cells is feasible.

Antibodies, Monoclonal↗

Are elevated FSH concentrations in the pre-conceptional period a risk factor for Down's syndrome pregnancies?

Recent publications have reported a relation between a decreased ovarian reserve and Down's syndrome pregnancies. Using the data of a case-control study into risk factors for a Down's syndrome pregnancy, we estimated the usefulness of pre-conceptional basal follicle stimulating hormone (FSH) screening (detection rate, false positive rate, positive and negative likelihood ratio, as well as the loss rate of unaffected pregnancies) to identify Down's syndrome pregnancies. The optimal detection rate of pre-conceptional basal FSH screening for Down's syndrome pregnancies was 14%, corresponding to a false positive rate of 5% and a positive likelihood ratio of 2.8. Incorporation of basal FSH screening into the regimen of first trimester serum screening followed by nuchal translucency measurement would increase the detection rate from 85 to 87%. However, basal FSH screening alone or in combination with other screening methods would cause an unacceptably high loss rate of unaffected pregnancies compared with current screening protocols, indicating that routine pre-conception basal FSH screening would not be useful to identify women at risk for a Down's syndrome pregnancy. However, when elevated basal FSH concentrations are diagnosed during subfertility evaluation, an elevated risk for a Down's syndrome pregnancy could be discussed with women who become pregnant.

Down Syndrome↗

Sequentially combined hormone replacement therapy reduces impedance to flow within the uterine and central retinal arteries in healthy postmenopausal women.

OBJECTIVE: The purpose of this study was to investigate the long-term effects of combined hormone replacement therapy on the impedances of the uterine, central retinal, and ophthalmic arteries in healthy postmenopausal women. STUDY DESIGN: In a prospective controlled study we randomly assigned 30 healthy postmenopausal women (mean age, 52 +/- 3 years) to 2 groups. Women in the hormone replacement therapy group (n = 15) received 1 mg micronized 17beta-estradiol daily sequentially combined with 5 or 10 mg dydrogesterone for 14 days of each 28-day cycle during 12 months and 2 mg 17beta-estradiol combined with 10 mg dydrogesterone thereafter for a period of 3 months. The control group (n = 15) received no treatment. Color Doppler ultrasonography was used to measure the impedance to flow (pulsatility index) within the uterine, central retinal, and ophthalmic arteries in the 17beta-estradiol phase at baseline and after 3, 12, and 15 months. RESULTS: With respect to values in the control group, 12 months of hormone replacement therapy was associated with a significantly lower (by 39%) mean pulsatility index of the uterine artery (decrease from baseline of 25% in hormone replacement therapy group and increase of 14% in control group) and a significantly lower (by 29%) mean pulsatility index of the central retinal artery (decrease of 9% in hormone replacement therapy group and increase of 20% in control group). After 3 months this effect was already evident. During hormone replacement therapy the reductions in mean pulsatility index values of the uterine and central retinal arteries with respect to baseline were larger (both P =.002) in the women with high pretreatment pulsatility index values than in those with low pretreatment values. The baseline pulsatility index of the uterine artery correlated positively with age and with duration of amenorrhea (r = 0.42, P =. 01; r = 0.48, P =.008; respectively). CONCLUSION: These results suggest that 12 months of sequentially combined hormone replacement therapy with a low dose of estradiol (1 mg) lowers arterial impedance in specific vascular territories. These data may help in understanding the effects of hormone replacement therapy on the cerebral circulation.

Drug Administration Schedule↗

Topical timolol therapy in pregnancy: is it safe for the fetus?

At 21 weeks of gestation, a 37-year-old woman was referred to our hospital. The fetus showed bradycardia and arrhythmia. Because of glaucoma the woman had previously been treated with timolol eye drops. In this paper a possible association between the timolol eye drops and the fetal cardiac arrhythmia is discussed.

Adult↗

Maternal and fetal plasma concentrations of endothelin, lipidhydroperoxides, glutathione peroxidase and fibronectin in relation to abnormal umbilical artery velocimetry.

OBJECTIVE: To study plasma concentrations of endothelin (ET), lipidhydroperoxides (LOOH), glutathione peroxidase (GSHpx) and fibronectin in relation to abnormal umbilical artery velocimetry. STUDY DESIGN: Plasma concentrations of ET, LOOH, GSHpx and fibronectin were measured in fetal and maternal venous blood in: (i) a control group (n=10); (ii) in pregnancies complicated by intrauterine growth retardation (IUGR) (n=6) or preeclampsia (n=5) with positive end diastolic flow; and in (iii) pregnancies complicated by absent or reversed end diastolic (ARED) flow in the umbilical artery (n=18). All children were delivered by primary caesarean section. RESULTS: The significantly highest maternal and fetal ET concentrations were found in plasma collected in pregnancies complicated by ARED flow in the umbilical artery. Maternal fibronectin levels were significantly raised in the ARED flow group. Maternal plasma ET levels were lowest in pregnancies complicated by IUGR. The maternal and fetal plasma concentrations of LOOH and GSHpx did not differ significantly between the groups. CONCLUSION: Abnormal Doppler velocimetry, especially ARED flow is associated with elevated maternal and fetal plasma levels of ET. The exact mechanism causing the placental vasoconstriction is unknown yet, but oxidative stress seems not to be involved.

Endothelins↗

Ultrasonographic and radiologic visualization of the developing embryonic skeleton.

We investigated the development of the skeleton in the embryonic and early fetal period both with ultrasonography and radiology. Eight normal embryos/fetuses were studied weekly with real-time transvaginal sonography between 8 and 16 weeks of gestation to establish the ultrasonographic characteristics of normal ossification. Additionally, ossification was studied in radiographs obtained from five embryos/fetuses between 9 and 14 weeks of gestation. Ossification centers, visualized as increased echogenicity of the bone, were recognized with ultrasonography from 9 weeks onwards. The appearance of primary ossification centers as observed by transvaginal ultrasonography was at the same gestational age or at most 1 week later than when obtained with radiography or whole-specimen staining techniques. Transvaginal ultrasonography enables early visualization of ossification centers in the embryo and fetus. Detailed knowledge of the development of ossification of the skeleton may contribute to early prenatal diagnosis of skeletal dysplasias.

Bone Development↗

First-trimester sonographic detection of neurodevelopmental abnormalities in some single-gene disorders.

A number of single-gene disorders are detectable early in pregnancy through DNA analysis on chorionic villi. In some genetic disorders that are not yet amenable with this technique, prenatal diagnosis is based on the sonographic detection of neurodevelopmental abnormalities. In nine fetuses at risk for the Meckel-Gruber, Walker-Warburg, and Joubert syndromes, sonographic scanning was accomplished in the first and early second trimesters of pregnancy. In five out of nine fetuses, structural anomalies were detected. In two out of five affected fetuses, sonographic detection of a cephalocele was predated by the visualization of an enlarged rhombencephalon cavity diameter.

Abnormalities, Multiple↗

Enrichment of fetal trophoblast cells from the maternal peripheral blood followed by detection of fetal deoxyribonucleic acid with a nested X/Y polymerase chain reaction.

OBJECTIVE: Fetal cells circulate in the maternal blood during early pregnancy. Because these cells are rare, noninvasive prenatal diagnosis from fetal cells can be achieved only after efficient enrichment procedures. Our aim was to develop a two-step enrichment procedure to isolate trophoblast cells from 20 ml of peripheral blood. STUDY DESIGN: Blood was obtained from pregnant women between 6 and 15 weeks of gestation, before invasive procedures were performed. After enrichment, the success of isolating fetal cells was determined by amplification of Y chromosome sequences. RESULTS: A highly specific X/Y polymerase chain reaction was established, sensitive enough to detect X and Y chromosome-specific sequences in one single cell and in one male among 100,000 female cells. Sex determination by polymerase chain reaction was compared with results from conventional karyotyping. The success rate was 91.7%. CONCLUSION: Enrichment of trophoblast cells from maternal blood as described here might be useful for early noninvasive prenatal diagnosis.

Base Sequence↗

Placenta morphology and absent or reversed end diastolic flow velocities in the umbilical artery: a clinical and morphometrical study.

The aim of the study was to investigate if a relation exists between absent or reversed end diastolic (ARED) flow in the umbilical artery and morphometric characteristics of the placenta. Geometric parameters were measured in the terminal villi of nine placentae, collected after a pregnancy complicated by ARED flow. Placentae from pregnancies with normal Doppler velocimetry in the umbilical artery were matched for gestational age and formed the control group. Mean placental weight in the ARED group was significantly lower than in the control group. Morphometric characteristics of the terminal placental villi did not differ substantially between the two groups before 30 weeks gestation. After 30 weeks mean villous profile cross sectional area and diameter were significantly smaller in the ARED group than in the control group. The mean profile cross sectional villous diameter in the ARED group did not differ substantially before and after 30 weeks of gestation (2287 microns2 and 2303 microns2, respectively). Accelerated maturation of terminal villi occurs in placentae delivered after a pregnancy with ARED flow in the umbilical artery. Morphometric characteristics are significantly different between placentae expelled after ARED velocities or after normal Doppler recordings in the umbilical artery. In ARED placentae, a significantly more uniform pattern of small villi is found compared with control placentae.

Blood Flow Velocity↗

First-trimester nuchal translucency: a risk analysis on fetal chromosome abnormality.

PURPOSE: To investigate the importance of nuchal translucencies in the first trimester of pregnancy as an ultrasonographic marker for fetal chromosome abnormalities. MATERIALS AND METHODS: One hundred two first-trimester fetuses with a nuchal translucency of 3 mm or more were karyotyped. Multiple logistic regression analysis was performed to estimate the risk of fetal chromosomal abnormalities related to nuchal translucencies. RESULTS: Fifty-five (54%) of the fetuses had a normal karyotype. Forty-seven (46%) had an abnormal karyotype. The risk of chromosome abnormality was strongly increased in fetuses with a septated nuchal translucency compared with fetuses with a nonseptated nuchal translucency. CONCLUSION: First-trimester nuchal translucency is an important ultrasonographic marker for chromosomal abnormalities in the fetus. The presence of a normal karyotype in a fetus is a strong indication that detailed ultrasonographic examination for associated anomalies should be undertaken.

Adult↗

Early second-trimester diagnosis of sirenomelia.

Two cases of sirenomelia are described, detected in the 14th and 16th weeks of gestation by transvaginal ultrasonography. A hypothesis for the aetiology of sirenomelia and its associated anomalies is discussed.

Adult↗

Recurrent uterine rupture diagnosed by ultrasound.

A case of recurrent rupture of the uterus is presented. The patient had a history of left cornual uterine rupture, which was repaired, and she was considered to be suitable for a subsequent pregnancy. During the subsequent pregnancy, attempts were made to evaluate the condition of the uterine scar by ultrasound in order to anticipate threatening rupture of the scar. No signs of dehiscence could be detected until the patient presented with clinical signs. Ultrasound examination revealed protrusion of the membranes at the fundus uteri. Uterine rupture is a rare, but hazardous, obstetric complication that can affect both mother and child. The possible role of ultrasound in cases of elevated risk for uterine rupture is discussed.

Adult↗

First and early second trimester diagnosis of anomalies of the central nervous system.

To study central nervous system development, 18 normally developing embryos or fetuses were examined sonographically between 6 and 16 weeks of pregnancy. Furthermore, in a 5 year period, 693 fetuses with an elevated risk for congenital defects were examined before 16 weeks of gestation. Abnormal development of the central nervous system was found in 28 fetuses. Early in pregnancy, normal central nervous system formation can be recognized, and pathologic cerebral development can be diagnosed already in the first trimester of pregnancy. We recommend routine use of safe and noninvasive transvaginal ultrasonography early in pregnancy for patients at risk.

Case-Control Studies↗