Nuclear and chromosomal replication patterns in chorionic villi cells by bromodeoxyuridine labelling and DNA flow cytometry.

Cell kinetics of chorionic villi (CV) were studied by BrdUrd-incorporation detected by fluorescence-plus-Giemsa and BrdUrd-antibody techniques, and by DNA flow cytometry. Growth characteristics of long-term cultures of CV resembled fibroblasts with a total cell cycle time of 26 h, final S phase of 9 h, penultimate S phase of 16 h and G2/M phase of 3-4 h. Especially useful for a quick routine diagnostic approach, Ultroser RG, a commercially available serum supplement, significantly increased cell proliferation and stabilized cell cycle lengths to a total cell cycle time of 14 h, final S phase of 7 h, penultimate S phase of 6 h and G2/M phase of 4 h. Moreover, mitotic activity steadily increased in cultured CV, when studying six successive subculturings. This reflects adaptation to the culture conditions rather than an inherent response of cultured CV cells of increasing passage numbers. Native villi exposed to BrdUrd immediately after biopsy show lower rates of uptake than do aliquots after overnight incubation. As shown by BrdUrd-pulse labelling studies, more than 7 h are required to overcome the proposed 'biopsy stress'. This correlates with routine diagnostic techniques, in which many more metaphase cells are observed in short-term cultures than in direct preparations.

In vitro studies on clonal growth of chondrocytes in thanatophoric dysplasia.

Thanatophoric dysplasia (TD) is characterized by a disorganized growth plate with markedly reduced proliferative and hypertrophic cartilage zones. Therefore, we studied in vitro the proliferation rates of articular chondrocytes from five TD patients and age-matched controls in response to bFGF, IGF-I, IGF-II, and TGF-beta 1. In human fetal controls bFGF was the most potent growth factor. Clonal growth the articular chondrocytes in response to bFGF was reduced in two of five TD patients and slightly below the range of controls in a third case. Stimulation of chondrocyte proliferation by IGF I and II was reduced in the patient whose response to bFGF was most markedly impaired. The effect of TGF-beta 1 ranged from normal to slightly elevated values in TD fetuses. These results indicate heterogeneity of the underlying defects in TD. Low proliferative responses of chondrocytes to bFGF and IGF-I/II are likely to play a key role in the pathogenesis of some cases. In two of five patients studied, the mechanisms of bFGF and IGF-signal transduction are candidates for the primary molecular defect.

Proliferation and collagen biosynthesis of osteoblasts and chondrocytes in short rib syndrome type beemer.

We report on a case of lethal short-limbed skeletal dysplasia with extremely short ribs, median cleft upper lip and palate, malrotation of intestine, lung hypoplasia with bilateral segmentation defect, atrial septum defect, union of distal urethra and vagina, and complex brain malformations. Based on radiological criteria and the pattern of associated abnormalities a short rib syndrome without polydactyly (Type Beemer) was diagnosed. Morphologically, the growth plate showed a reduced proliferation zone and an enlarged zone of hypertrophic cartilage. In addition, islands of persistent hypertrophic cartilage were present even in the metaphysis. In monolayer cell cultures supplemented with 10% fetal calf serum proliferation was normal in articular chondrocytes, reduced in costal chondrocytes, and elevated in osteoblasts from the patient. Clonal growth of costal and articular chondrocytes in methylcellulose could be stimulated normally by insulin-like growth factor-I (IGF-I), IGF-II, and human growth hormone (hGH). However, the response to transforming growth factor beta 1 (TGF-beta 1) was markedly elevated in articular chondrocytes of the patient compared to those of 3 fetal controls. Quantitative collagen synthesis in both osteoblasts and chondrocytes from the patient did not differ significantly from that of controls. Osteoblasts synthesized predominantly collagen I and minor amounts of collagen III, chondrocytes synthesized primarily collagen II. All collagen chains including CNBr-peptides of collagen II showed normal migration in PAA gel electrophoresis.

Treatment of fetal erythroblastosis by intravascular transfusions: outcome at 6 years.

OBJECTIVE: To assess 6 years' neurologic outcome of a complete cohort of survivors of intrauterine intravascular transfusions. METHODS: From January 1986 to December 1991, 136 intravascular transfusions were performed in 43 fetuses presenting with signs of severe erythroblastosis. Before the initial transfusion, 11 of 43 fetuses had some degree of hydrops fetalis, and hemoglobin values ranged between 1.5 and 10.7 g/dL. Neurologic outcome of a complete cohort of 35 long-time survivors was assessed for up to 6 years by reviewing the hospital charts and questionnaires sent to the family physicians or pediatricians. RESULTS: Long-time follow-up was available in all survivors with hydrops at initial transfusion (seven of seven) and in 23 of 28 survivors without hydrops. Only one of 35 survivors had mild psychomotoric disabilities up to 1 year of age, but was free of sensorineural problems on further examination. In a second case, delayed speech development was observed. Fetuses presenting with hydrops fetalis before initial transfusion tended to have a higher perinatal mortality and had a significantly higher rate of preterm delivery (P = .03). However, moderate or severe neurologic impairment was never observed, even when severe cases with hydrops fetalis or extremely low hemoglobin levels were included. CONCLUSION: Treatment of severe fetal erythroblastosis by intrauterine intravascular transfusions is associated with a favorable neurologic long-time outcome.

Doppler sonographic findings and their correlation with implantation in an in vitro fertilization program.

In 45 women from an in vitro fertilization (IVF) program, the uterine and ovarian blood flows were investigated by vaginal Doppler sonography. The resistance index was used to evaluate the blood pattern. When comparing the patients who became pregnant after embryo transfer (ET [group I, n = 12]) with those who did not conceive (group II, n = 33), it is evident that in group I the vascular resistance of the uterine arteries is significantly lower on the day of follicular aspiration. No differences could be detected in the ovarian vessels. The data obtained so far suggest that the receptivity of the endometrium is a crucial factor for successful implantation. In the final analysis, this can be appraised not only on the basis of morphological but also of hemodynamic parameters.

Coping styles of pregnant women after prenatal ultrasound screening for fetal malformation.

OBJECTIVE: Ultrasound is a widespread noninvasive method of prenatal diagnosis. The detection of fetal abnormalities can provoke anxiety, which needs coping. The coping process of pregnant women with different risk conditions for fetal abnormality were studied in a longitudinal design and compared with a nonrisk control group of women with healthy uncomplicated pregnancies. METHODS: The coping strategies of women (n=664) during the second trimester were assessed with a questionnaire [Heim E, Augustiny KF, Blaser A, Schaffner L. Berner Bewältigungsformen (BEFO) Handbuch. Bern: Huber, 1991]. Data were collected at three points in time: immediately before the ultrasound scanning for fetal malformation, at 5-6 and 10-12 weeks after the prenatal ultrasound examination. Questionnaires were also used to collect information about sociodemographic data, anxiety, pregnancy data and personality. RESULTS: The analysis of the coping strategies of women with high-risk pregnancies (n=497) and as well of these with no-risk conditions in the control group (n=167) revealed three different factors of coping: Factor I: positive emotional attitude/distance, Factor II: negative emotional attitude/disapproval and Factor III: active coping. At all three points in time, Factor I correlated significantly with anxiety decrease, Factor II with increase and Factor III did not correlate with anxiety at all. CONCLUSIONS: Women with risk-pregnancies used coping strategies similar to those women in the control-group. Different spectrums of coping strategies corresponded significantly to increasing or decreasing anxiety. These women with high levels of anxiety, especially, should be offered sensitive care or psychotherapeutic counseling, as their coping processes did not lead to successful coping in the form of a reduction in anxiety.

[Uteroplacental circulation in growth retardation--experiences with the clinical use of continuous-wave Doppler]. / Uteroplazentare Durchblutung bei Wachstumsretardierung--Erfahrungen mit der klinischen Anwendung des Continuous-wave-Dopplers.

Doppler ultrasound measurement of blood flow velocity represents a non-invasive method of studying uteroplacental and feto-placental haemodynamics. Using a continuous-wave Doppler device, the blood flow velocity was examined in the uterine and arcuate arteries, as well as in the umbilical artery in 81 patients demonstrating fetal growth retardation. An increase in vessel resistance was found in the uterine and arcuate arteries in most of the patients. In addition, patients with fetal retardation showed a significantly higher rate of diastolic notching and incomplete registration of uterine and arcuate wave forms, especially in pregnancies complicated by hypertension. The implementation of the continuous-wave technique as a simple Doppler system allows differential evaluation of placental function and provides information on the nutritional supply to the fetus.

[Early diastolic incisures in uteroplacental blood vessels. Experiences in patients with uneventful pregnancy and labor]. / Frühdiastolische Inzisuren in uteroplazentaren Gefässen. Erfahrungen bei Patientinnen mit unauffälligem Schwangerschafts- und Geburtsverlauf.

The frequency of diastolic notching in uteroplacental arteries was examined in a collective of 510 patients with uneventful pregnancies and deliveries. Notching appeared to be more frequent in the uterine than arcuate artery. It was seen to increase as pregnancy progressed and was markedly higher in the third compared with the second trimester. Uteroplacental notching occurred more frequently unilaterally and mainly affected contralateral sites of the placenta. Bilateral and retroplacental notching was the exception in normal pregnancies.

[Clinical impact of fetal MRI in addition to ultrasonography in brain anomalies--three case reports]. / Klinische Bedeutung der MRT in Ergänzung zur Sonografie bei fetalen Hirnfehlbildungen--drei Fallberichte.

Fetal magnetic resonance imaging (MRI) is a reliable method to further evaluate brain anomalies detected on ultrasonography. MRI can reveal additional brain abnormalities which are consequential for counselling parents about the fetal prognosis and subsequently influence the decision about continuing the pregnancy. In case of fatal malformations, MRI can confirm a diagnosis established on ultrasonography, supplying more reliability.

Ultrasound-guided large-core needle biopsies of breast lesions: analysis of 962 cases to determine the number of samples for reliable tumour classification.

The objective of this one-institutional study was to determine the number of large-core needle biopsies (LCNB), under three-dimensional ultrasound (3D-US) validation, that are sufficient to obtain a reliable histological diagnosis of a sonographically detectable breast lesion. Over an 28-month period, 962 sonographically guided LCNB were performed under 3D-US validation to assess 962 breast lesions. All biopsies were carried out with an automated core biopsy device fitted with 14-gauge (22 mm excursion) needles. Data of 962 biopsied breast lesions were gathered. Surgical follow-up was available for 659 lesions. Breast malignancies were diagnosed by ultrasound-guided LCNB with a sensitivity of 98.2% by performing three cores per lesion. In few cases, the open surgical specimen revealed the presence of invasive carcinomas in contrast to initial LNCB-based classification as ductal carcinomas in situ (DCIS, 11 lesions), lobular carcinoma in situ (one lesion), and atypical ductal hyperpasia (one lesion). Owing to disagreement between classification based on breast-imaging and histological findings, eight of these tumours were subsequently excised. Of the lesions that were removed at the patients' requests despite benign LCNB diagnosis, two were infiltrating carcinoma and one a DCIS. We demonstrate that three 3D-US-guided percutaneous core specimens are sufficient to achieve tissue for a reliable histological assessment of sonographically detectable breast lesions and allow the detection of malignancies with high sensitivity and low rate of false-negative diagnoses.

Feto-amniotic shunting -- experience of six centres.

AIM: Foeto-amniotic shunting is an ultrasound-guided, therapeutic intervention for drainage of persistent intracavital fluid retention in severely affected foetuses with a high risk of mortality. In order to weigh up the comparatively high risk of intervention against the possible benefit, we evaluated the value of different indications, the complication rate and the time span of drains in situ. PATIENTS AND METHODS: We made a survey of all level III ultrasound centres of German-speaking countries from 1993 to 2001. Six level III centres returned the questionnaire: forty-seven foeto-amniotic shunting procedures were performed in 30 foetuses [megacystis in 18 foetuses (three of these with urinary ascites), hydrothorax in eight foetuses, hydronephrosis in two foetuses, cystic adenomatoid malformation of the lung in one foetus, ovarian cyst in one foetus]. RESULTS: The median gestational age at time of shunting was 23.5 (range 16 - 33) weeks, at time of delivery 35 (range 23 - 41) weeks. The median time span of drains in situ was 19 (range 0 - 170) days. Altogether 18 of 30 foetuses (60 %) had a benefit of foeto-amniotic shunting. CONCLUSION: The best possible selection of pregnancies which might profit from foeto-amniotic shunting is required. The decisive criteria are the underlying defect as well as the severity and progression of the disorder.

[Accident in the labor room. Monitoring responsibility of the midwife in relaxing baths before delivery]. / Ein Unglücksfall im Kreisssaal. Aufsichtspflicht der Hebamme bei Entspannungsbädern vor der Geburt.

During a relaxation bath, a 20-years old I-Para had an accident by submersion. In succession, both, mother and child, experienced irreparable cerebral injuries. While the counsel of prosecution pleads for manslaughter, forensic scientists and gynaecologists advise to discuss the inaccuracies in the law of midwife.