Quality control of centrifugal elutriation for studies of cell cycle regulations.
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Animals↗
Biomedical subjects
G Bernaschek
Publications and source records attributed to G Bernaschek.
Fetal bradycardia following cordocentesis.
Several clinical investigations on the course and outcome of pregnancies following cordocentesis have mentioned the occurrence of fetal bradycardia at the time of umbilical cord puncture. The prognostic impact of this common complication has remained controversial. Our purpose was to investigate the prevalence and the short-term and long-term consequences of fetal bradycardia associated with cordocentesis. This study included all 339 cordocenteses performed in 290 fetuses at the Division of Prenatal Diagnosis and Therapy, University of Vienna, between 1991 and 1994. Clinically significant bradycardia was defined as a drop in the heart rate to less than 100 beats/min for a period of > or = 60 s. Bradycardia during or immediately after cordocentesis was observed in 13 cases (3.8 per cent). The fetal/neonatal loss rate per procedure was 61.5 per cent (8/13) in cases with bradycardia and 3.1 per cent (10/326) in those without bradycardia (P < 0.001). Early gestational age and hydrops fetalis correlated significantly with the development of bradycardia at cordocentesis. The other risk groups, including fetuses with intrauterine growth retardation, the puncture site, and the number of puncture attempts did not correlate with fetal bradycardia. Our results indicate that prolonged fetal bradycardia during or after cordocentesis is characteristic of a group of fetuses with an especially unfavourable prognosis.
Bradycardia↗
Effect of detailed fetal echocardiography as part of routine prenatal ultrasonographic screening on detection of congenital heart disease.
BACKGROUND: Cardiac abnormalities are frequently not detected by routine ultrasound screening examinations. Although detailed fetal echocardiography is more sensitive in detection of congenital heart disease, it is used only for high-risk cases. The main aim of this study was to assess the prenatal detection of congenital heart disease by detailed fetal echocardiography in an unselected, consecutive group of pregnant women. METHODS: Between Jan 1, 1993, and Sept 30, 1994, all women who attended our antenatal-care unit were routinely offered a detailed fetal echocardiography examination at 18-28 weeks' gestation. 3085 consecutive women were screened: 2181 were screening cases with no known risk factor for congenital heart disease; 540 had maternal risk factors for congenital heart disease, such as a family history or coexisting maternal disease; 364 had sonographically detected abnormalities. The examination included the four-chamber view, outflow-tract scan, and colour-flow mapping; doppler and M-mode investigations were also done when appropriate. FINDINGS: 46 cases of congenital heart disease were detected prenatally by echocardiography-15 in the group with no risk factors, three in the group with maternal risk factors, and 28 in the group with sonographic abnormalities. Postnatal assessments found six further cases of congenital heart disease that had not been detected prenatally, but these were all minor cases. There were no false-positive diagnoses (sensitivity 85.5%, specificity 100%). The incidence of congenital heart disease in screening cases with no risk factors and in those with maternal risk factors was low (6.9% per 1000, 5.6 per 1000) and similar to the expected overall incidence of 8.0 per 1000 livebirths in the general population. In the group with sonographic abnormalities congenital heart disease was found significantly more often (79.9 per 1000). INTERPRETATION: Inclusion of detailed fetal echocardiography as a screening examination has a substantial effect on detection of congenital heart disease since a major proportion of prenatally detectable cases occur in a low-risk population.
Adult↗
Specific transformation abolishes cyclin D1 fluctuation throughout the cell cycle.
We analysed cyclin D1 mRNA and protein expression in several different cell types after separating these cells according to their different cell cycle phases by centrifugal elutriation. In normal human and rat fibroblasts cyclin D1 expression is high in early to mid G1 and decreases about 6-7 fold before onset of replication. It has been demonstrated that specific transforming events, such as loss of functional retinoblastoma protein, overexpression of c-myc, and transfection with the human papillomavirus oncoproteins E6 and E7 cause transcriptional downregulation of cyclin D1 expression in logarithmically growing cells. We found that such transformed cells exhibit loss of the cell cycle-dependent cyclin D1 fluctuation accompanied with reduced upregulation of cyclin D1 in G1 phase. The data presented here provide the experimental support for a recently suggested model involving the function of the retinoblastoma protein in cyclin D1 cell cycle regulation.
Animals↗
The influence of the experience of the investigator on the rate of sonographic diagnosis of fetal malformations in Vienna.
The quality of prenatal ultrasound may be influenced by different factors. In this study, the influence of the experience of the investigator on the quality of routine ultrasound screening during pregnancy was evaluated. We related the detection rate of fetal malformations in routine ultrasound screening in the region of Vienna to the experience level of the examiner. All 323 cases of fetal malformations registered by the obstetrical departments of Vienna or registered by the Vienna perinatal mortality statistics of 1990 and 1991 were evaluated. For analysis we used the medical charts or the patient-held antenatal records ("Mutter-Kind-Pass'). Obstetricians in private offices (level I) detected 22 per cent, the examiner in the hospital (level I-II) 40 per cent, and the examiner in the centre for prenatal diagnosis and therapy (level III) 90 per cent of all fetal malformations. The detection rate before the 24th week of gestation was significantly different (25 per cent vs. 34 per cent vs. 58 per cent). Our results suggest that an important factor for the quality of prenatal ultrasound investigation is the education of the sonographers. Furthermore, each pregnant woman should undergo ultrasound screening once in a level II or III centre before 24 weeks or before fetal viability.
Austria↗
Fetal lung volume determination by three-dimensional ultrasonography.
OBJECTIVE: Pulmonary hypoplasia is common in compromised pregnancies. However, prenatal diagnosis by volume measurement has not become routine until now. The performance of three-dimensional ultrasonography in fetal lung volume determination was evaluated in this study. STUDY DESIGN: In a total of 78 singleton pregnancies 108 measurements were performed. Lung volume was calculated by subtraction of the fetal heart volume from the volume of the fetal thorax. RESULTS: Linear regression of transformed fetal lung volume growth gave best results (R2 = 0.77, p < 0.001), ranging from 2.8 ml at 14 weeks' gestation to 148 ml at term. CONCLUSION: Three-dimensional ultrasonography provides not only access to surface rendered images but it also enables more sophisticated volume measurements. In this study three-dimensional ultrasonography provided fast, easy access for volume estimation of the fetal lung. This technique can be used to reasonably predict fetal lung volume.
Female↗
Antenatal depiction of fetal digits with three-dimensional ultrasonography.
OBJECTIVE: The effectiveness of three-dimensional ultrasonography in visualizing fetal digits was examined. STUDY DESIGN: The digits of 72 fetuses, including 2 with skeletal dysplasia, were examined prospectively with both conventional and three-dimensional ultrasonography. RESULTS: Complete visualization of all fetal digits was obtained more often with three-dimensional ultrasonography than with two-dimensional ultrasonography. CONCLUSION: Three-dimensional ultrasonography has the potential to facilitate depiction of fetal digits, which may enhance prenatal identification of fetal malformations and chromosomal abnormalities in high-risk pregnancies.
Female↗
[Doppler ultrasound in cases of Rhesus incompatibility. Effect of intravascular punctures with or without transfusion on feto-placental Doppler blood flow velocity curves].
OBJECTIVE: To investigate the influence of cordocentesis with or without blood transfusion on umbilical and fetal blood flow characteristics. METHODS: Of 42 pregnant women suffering from Rh. incompatibility 15 had a puncture of the umbilical cord for diagnostic reasons only. In 27 cases a total of 86 punctures was done for blood transfusion. Fetal heart rate, umbilical artery A/B Ratio and Pulsatility Index (PI) in the fetal aorta were measured before and after cordocentesis in all cases having or having not a transfusion. RESULTS: Diagnostic and therapeutic cordocentesis resulted in a slight decrease of peripheral resistance. Significant differences were only observed in cases with a haematocrit < 20% compared to cases with values > 40% or if the final haematocrit after transfusion resulted in a value of < 30%. CONCLUSION: The decrease peripheral resistance in cases of therapeutic cordocentesis can be attributed to the increase in blood volume and sufficient oxygenation of blood improving fetal perfusion. Doppler sonography is not helpful in the clinical management of red blood cell immunisation.
Adult↗
[Does the risk of complications after amniocentesis depend on the indications for intervention? An evaluation of 2,066 punctures].
Data from 2066 amniocenteses were analysed retrospectively to test the hypothesis whether the indications for amniocentesis influence the risk of post-procedural complications. Compared to the reference group of 35-39 year-old gravidae, the complication rates were similar in women with a previous child with chromosomal abnormality, in cases with maternal disease, abnormal biochemical markers, maternal anxiety, and translocation carriers. If the maternal age was 40 years and over, only the percentage of pregnancy terminations for fetal abnormalities was higher than in the reference group; high parental age was associated with a significantly decreased fetal loss rate. In the group of amniocenteses performed for sonographic evidence of fetal malformation, the highest total complication rates and the highest fetal loss rates were observed.
Adult↗
[Modular education in diabetes and pregnancy: analysis of results of 58 pregnancies in diabetic patients with functional insulin treatment].
Functional insulin treatment based on the patient's education for selective use of insulin for fasting, eating or correction of hyperglycaemia was used between 1985 and 1994 prospectively in 58 pregnancies (in 18 cases after conception) in 47 pregnant diabetic patients. We hypothesised that near-normalisation of glycaemia is possible throughout pregnancy by modular outpatient group education, individual counselling and functional insulin treatment. We wanted to investigate to which degree it might eliminate classical diabetes-associated neonatal complications. To avoid hospitalisation if possible and premature induction of labour, patients were taught both the primary adjustment (immediate correction of hyperglycaemia) and the secondary adjustment of the insulin dosages: correction of individual algorithms for insulin use according to daily insulin consumption and mean blood glucose MBG. A target metabolic control (HbA1c levels in the normal range, MBG < 100 and < 90 mg/dl after the 28th week of gestation respectively) was achieved in the majority of the 58 pregnancies. Severe hypoglycaemia occurred in 12 patients (21%). The gestational age at delivery was 39.0 +/- 1.6 (34-41; in 3 cases only [5%] < 37) weeks with an average birth weight of 3335 +/- 521 (1950-4450) g. The birth weight of only 5 newborn (9%) was above the 90th percentile and no one below the 10th percentile for weight of a comparable population. No cases of respiratory distress were observed. Hypoglycaemia was recorded in only 4 newborn (7%) and was comparable also to that of offsprings in non-diabetic women. Malformations were found in two offsprings whose mothers had presented first for diabetes education after conception, pregnancy being terminated in one case of meningomyelocele. Caesarean section (n = 15; 26%) was primarily due to maternal reasons. Functional insulin treatment prior to conception, modular diabetes group education, specific patient motivation for a near-normal glycaemia throughout pregnancy as well as interdisciplinary care allow pregnancy outcome in diabetic patients similar to that in non-diabetic women and thus the realisation of the 5-year targets of the WHO Declaration of St. Vincent 1989.
Adolescent↗
Chromosomal abnormalities: how much can we predict by ultrasound examination in low-risk pregnancies?
We examined the rates of chromosomal anomalies detected by ultrasound investigations for the whole region of Vienna. We evaluated the data of 250 private offices, 10 clinics for Obstetrics and Gynecology, and one university Department of Prenatal Diagnosis and Therapy during the period from January, 1990, to July, 1991. The study group consisted of low-risk patients, since cases where prenatal karyotyping has been performed for other reasons than sonographic findings (for example, maternal age) were excluded from the study. An overall detection rate of 53.7% was found for the region. Structural malformations of fetuses (41.5%) were the most prominent factors leading to the diagnosis of chromosomal abnormalities. In addition, detection rate of trisomy 21 (17.6%) by prenatal ultrasonography was found to be significantly lower compared to all other chromosomal abnormalities in our study (50 to 100%).
Austria↗
Loss of the p16/MTS1 tumor suppressor gene causes E2F-mediated deregulation of essential enzymes of the DNA precursor metabolism.
Homozygous deletions of the tumor suppressor gene p16/MTS1 were reported in a wide variety of tumors and tumor cell lines. Its product inhibits the phosphorylation of the retinoblastoma protein (pRb) by CDK4 and CDK6. Because phosphorylation of pRb is a major regulatory event in the activation of the transcription factor E2F, a role for p16 in the regulation of E2F-dependent transcription was presumed. We investigated the effect of the loss of p16 on E2F-mediated transcription in a tumor progression model consisting of three cell lines originating from a common precursor cell--one p16-positive cell line established from the primary biopsy and two lines derived from more advanced stages of the tumor representing the same cell clone after loss of p16. We observed up- and deregulation of E2F-dependent transcription during the cell cycle of the p16-negative cell clones, which returned to normal after transient expression of p16. This p16-dependent regulation affects a set of enzymes necessary for the activation of all four DNA precursors; it is paralleled by the interconversion of transcriptionally active free E2F and transcriptionally inactive higher molecular complexes of E2F and is dependent on the existence of endogenous pRb. Furthermore, we show that p16-negative cell clones exhibit a growth advantage compared to their p16-positive counterparts. One might speculate that one feature of tumor progression could be deregulation of E2F-dependent transcription caused by loss of p16.
Carrier Proteins↗
Expression of the cyclin-dependent kinase inhibitor p16 during the ongoing cell cycle.
It has been demonstrated that protein expression of p16, the inhibitor of cyclin-dependent kinase 4 and 6, increases 4 fold at the G1/S transition when serum-arrested cells are restimulated to logarithmic growth. We examined the cell cycle regulation of this cyclin-dependent kinase inhibitor in cells separated according to their cell cycle phases by centrifugal elutriation. Neither p16 mRNA nor its protein expression are regulated during the cell cycle of normal phytohemagglutinin-stimulated lymphocytes, retinoblastoma protein-negative cells, papilloma virus-transformed cells, and acute promyelocytic leukemia cells. p16 mRNA is constitutively expressed in cells in which we detected the normal E2F-dependent S-phase specific expression of thymidine kinase mRNA. We further observed a G1-phase specific expression of cyclin D1 mRNA in the same cells separated by centrifugal elutriation.
Blotting, Western↗
Sonographic depiction of fetal tooth germs.
Recently, sonography of the fetal face has gained increasing importance in prenatal diagnosis. It is not yet clear whether sonographic depiction of fetal tooth germs would have an influence on the prenatal diagnosis of ectodermal dysplasia syndromes. During routine malformation screening, horizontal sections of fetal jaws were visualized and examined for tooth germs in 124 pregnant women following sonographic 'facing'. Histological jaw sections of fetuses that had died in utero at various gestational ages were produced in order to examine the degree of correspondence between the sonographic and histological findings. At least four tooth germs were found in the jaws of all fetuses between 19 and 34 gestational weeks (n = 104). Although jaw visualization was possible between 14 and 18 gestational weeks (n = 20), the exact number and location of the tooth germs could not be determined. Assessment of tooth germs may become increasingly important, as aplasia of the tooth germs is one of the principal signs of various hereditary ectodermal diseases.
Anodontia↗
Complications of cordocentesis in high-risk pregnancies: effects on fetal loss or preterm delivery.
Between 1990 and 1993, 166 cases underwent cordocentesis and were followed for at least the following 4 weeks in the Prenatal Diagnosis and Therapy Centre of Vienna University. The indications for the procedure were structural malformations in 46.4 per cent of the cases, other high-risk diagnosis in 48.8 per cent, and maternal age over 35 years in only 4.8 per cent. We investigated retrospectively all cases of complications resulting in fetal loss or preterm labour. Abortion, intrauterine fetal death, chorioamnionitis, and preterm delivery occurred in 0.6, 5.4, 0.6 and 9.0 per cent of these cases, respectively, adding up to a total of 26 cases (15.7 per cent). Although this rate looks relatively high, 20 of the 26 cases had already displayed signs implying a complicated prognosis. Neither maternal age, gestational age, number of attempts, nor placental location correlated with fetal loss or preterm delivery. Significantly higher rates of fetal loss or preterm delivery were observed when cordocentesis was performed in cases diagnosed as duodenal/intestinal stenosis or hydrops-ascites-hydrothorax/hygroma colli (P = 0.0488 and P = 0.0005). The frequency of complications did not decrease as the experience of the operators increased.
Abortion, Spontaneous↗
Three-dimensional ultrasound in diagnosing phocomelia.
Deformations of the extremities with limb reduction are rare congenital defects which affect one in 1692 live babies. Three-dimensional ultrasound can be of value in the prenatal diagnosis of such deformities. We present a case of upper phocomelia and congenital thrombocytopenia (TAR syndrome). Visualization of the upper extremities was achieved by three-dimensional ultrasound after surface and volume rendering. This new technique allows imaging not only of surfaces like the fetal skin, but also of internal structures like the fetal skeleton.
Adult↗
[Prenatal management of fetofetal transfusion syndrome].
The twin-twin transfusion syndrome is a rare but severe complication in monozygotic twins. A total of 172 twin pregnancies were investigated in our hospital between January 1990 and August 1993. The patients were divided into 4 groups: Group I: Normal twin pregnancy, treatment only in our hospital. Group II: Twin-twin transfusion syndrome, treatment only in our hospital. Group III: Normal twin pregnancy, delivery in another hospital. Group IV: Twin-twin transfusion syndrome, after treatment and therapy delivery in another hospital. These cases were analysed concerning prenatal management and perinatal outcome. The perinatal mortality rate in group I-IV was 17%, 58%, 18% and 60%, respectively. A benefit of aggressive amniocentesis in case of polyhydramnios, administration of digoxin and timing of labour could be demonstrated.
Adult↗
Three dimensional ultrasound: abnormalities of the fetal face in surface and volume rendering mode.
OBJECTIVE: To evaluate three dimensional ultrasound in surface and volume rendering mode in fetal malformations of the face. SETTING: Day assessment unit in a university hospital. SUBJECTS: Four cases have been examined: two cases represented cleft lip, one case was a male with trisomy 13 (Patau syndrome) with proboscis, and one case represented a male fetus with unilateral anophthalmia. CONCLUSION: A new technique of three dimensional ultrasound visualisation in fetal malformation using surface and volume rendering is presented. The equipment consisted of a commercially available ultrasound machine, a built-in graphic workstation, and three dimensional software. Post-processing of data required approximately 10 minutes of calculation. The application of three dimensional ultrasound in complex malformations of the face appears to provide reasonable value for prenatal diagnosis and may become clinically useful in the near future.
Adult↗