Localization and distribution of vasoactive neuropeptides in the human placenta.

Neuropeptides play an important role in the regional regulation of blood flow and hormone secretion. Few studies report the presence of peptides in the human placenta. Our experiment evaluates neuropeptides in the human placenta using immunocytochemical techniques. Representative tissue sections from full-term placentae were fixed immediately after delivery and processed into paraffin sections or frozen. They were treated with multiple immunofluorescence, streptavidin-biotin-peroxidase complex and immunogold-silver staining techniques in combination with well-established monoclonal and polyclonal antibodies, using appropriate absorption controls to ensure the validity of the staining. Vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), neuropeptide tyrosine (NPY), galanin, somatostatin, met-enkephaline, helodermin and substance P-like immunoreactivities were demonstrated within decidual cells. Endothelin-1 was found in both trophoblasts and endothelial cells. Peptide immunoreactivities in the human placenta especially at the decidual interface between mother and fetus supports a role for the diffuse neuroendocrine system (DNES) in the regulation of placental blood flow critical for fetal growth and development.

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.

[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.

[Five-year evaluation of implants in the resorbed maxilla]. / Vijfjaarsoverleving van implantaten in de geresorbeerde bovenkaak.

The survival of implants placed in the resorbed maxillae was investigated. Both edentulous and partially edentulous patients were evaluated including those who underwent 'sinus lift' procedures. The group of patients with a sinus floor augmentation showed a five-year cumulative survival rate varying between 100% for fixed bridges on implants in the partially edentulous maxillae and 75.6% for implants under overdentures placed in severely resorbed edentulous maxillae. It is concluded that placement of implants in the augmented sinus-floor is justified, if the patient is well informed. The procedure can provide a good solution for the prosthetic problems of patients with a resorbed maxilla.

Reference values for resistance index and pulsatility index of uteroplacental Doppler flow velocity waveforms based on 612 uneventful pregnancies.

Using a 4-MHz continuous-wave Doppler device, standard rates were established for resistance index (RI) and pulsatility index (PI) of uterine and arcuate arteries of 612 patients with uneventful pregnancies and deliveries. From 18 to 41 weeks of gestation, neither RI nor PI of uterine or arcuate arteries proved to vary with gestational age, maternal heart rate, or maternal age. By contrast, a significant effect of placental location on the measurement results was found in both uterine and arcuate arteries. The differences between measurements on the placental or opposite site are more distinct in arcuate than in uterine arteries. Taking the 90th percentile as a localization gauge, cutoff levels of 0.52 (RI) and 0.98 (PI) were found in uterine arteries. In arcuate arteries, cutoff levels of 0.45 (RI) and 0.82 (PI) were found on the placental site or with a placenta without lateralization. On the nonplacental site of a lateralized placenta, the cutoff levels were 0.51 (RI) and 0.92 (PI).

[Pharmacological influences on fetal lung maturity, part V: Influencing the pulmonary DPL (dipalmitoyl lecithin) level with L-thyroxin (T4)]. / Pharmakologische Beeinflussung der fetalen Lungenreife Teil V.: Beeinflussung des pulmonalen DPL-(Dipalmitoyllezithin)-Spiegels durch L-Thyroxin (T4).

Dipalmitoyl lecithin (DPL = DPPC, dipalmitoyl phosphatidyl choline) is both quantitatively and functionally the most important constituent of the surfactant complex. The effect of thyroxin (T4) on fetal lung maturity was investigated by means of selective DPL determination. Following administration of thyroxin to the mother animal an increase in the DPPC content was demonstrated in rat fetuses. This increase was greater than that of the total phospholipids. This effect of thyroxin could be due to the following causes: 1, Earlier and accelerated differentiation of lung cells: more Type II cells are formed earlier and these synthesize DPPC more effectively than other lung cells (approx. 40-50% of the phosphocoline in Type II cells in DPPC). 2. Stimulation of the deacylation-reacylation cycle. 3. A combination of these mechanisms.

[The acridine orange test. A new parameter in assessing the fertilizing capacity of spermatozoa]. / Der Acridin-Orange-Test. Ein neuer Parameter zur Beurteilung der Befruchtungsfähigkeit von Spermatozoen.

Simultaneously with in vitro fertilization (IVF), the acridine orange (AO) test was performed on 51 patients according to the method of Tejada et al. This test allows a differentiation of spermatozoa with intact (double-stranded) and denatured (single-sanded) DNA. A significant relationship was demonstrated between the percentage of green-fluorescing (intact) sperm and the results of IVF. For both, the groups with (n = 40) and without (n = 11) fertilization of human eggs, a positive correlation was found between AO-test and sperm motility, and AO-test and normal sperm morphology.

[Ultrasonic monitoring of intravascular transfusion in severe Rhesus incompatibility. Diagnostic and therapeutic aspects after fetal relaxation]. / Die intravasale Transfusion unter Ultraschallkontrolle bei schwerer Rhesus Inkompatibilität. Diagnostische und therapeutische Aspekte unter Einfluss der intrauterinen Retardierung.

Since October 1985 47 ultrasound-guided intrauterine intravascular transfusions were performed in 14 patients at the Department of Obstetrics and Gynecology of the University of Ulm. All newborns were delivered in good condition. The successful diagnostic and therapeutic management of severe erythroblastosis in a twin pregnancy is described. The twin with severe signs of erythroblastosis had an initial hematocrit of 12% at 26 weeks of gestation. Intravascular transfusion of 60 ml packed red cells raised the hematocrit to 41%. The ascites disappeared completely ten days after the first transfusion. Two further transfusions were performed at 29 and 33 weeks of gestation. The intrauterine intravascular relaxation with Norcuron (Vecuroniumbromid) has proved advantageous in preventing interfering fetal movement. Both newborns were delivered in good condition at 36 weeks of gestation.

[The value of Doppler ultrasound studies of insulin-dependent diabetic patients]. / Die Wertigkeit dopplersonographischer Untersuchungen bei insulinpflichtigen Diabetikerinnen.

Measurement of umbilical, uterine and arcuate velocity waveforms was used to study 40 pregnancies complicated by insulin dependent diabetes. Continuous wave doppler velocimetry was used to identify flow velocity profiles during the second and third trimester of pregnancy. Resistance index (RI) was calculated to evaluate waveforms. In most of the patients with fetal growth retardation and/or pregnancy induced hypertension an increase in vessel resistance was found in uterine and arcuate arteries as well as diastolic notching. In comparison to that fact White's classification showed no significant correlation to vascular resistance determined by doppler flow measurement. This study indicates that doppler ultrasound examination may have an adjunctive role in the surveillance of pregnancies complicated by diabetes.

Polynomial analysis of placental flow patterns in growth-retarded fetuses.

Correct interpretation of conspicuous blood flow velocity waveforms cannot rely solely on the evaluation of uteroplacental vascular Doppler flow patterns by means of angle-independent indices such as the resistance or pulsatility index. In addition to the degree of pulsatility, the waveform shape between the systolic and diastolic peak values is of considerable consequence. A subdivision of the total flow waveform into orthogonal polynomial components allows both pulsatility evaluation and notching to be registered, providing a higher sensitivity in identification of pathological vascular resistance. Accurate recording and assessment of the flow waveform is therefore an important qualitative criterion for the classification of Doppler flow patterns in pregnancies with reduced uteroplacental perfusion.

[The value of continuous wave Doppler ultrasound in risk pregnancy-intrauterine growth retardation and pregnancy-induced hypertension]. / Wertigkeit der Continuous-wave-Dopplersonografie bei Risikoschwangerschaft-intrauteriner Wachstumsretardierung und schwangerschaftsinduzierter Hypertonie.

To evaluate the frequency of abnormal doppler results in pregnancies complicated by placental insufficiency, flow waveforms of 100 patients with documented intrauterine growth retardation--birthweight below the 10th percentile--were analysed. Uterine, arcuate and umbilical artery velocimetry were performed by means of a continuous wave Doppler ultrasound. Neither the range of serial examination nor the interval between last prepartal doppler test und delivery showed influence on the doppler results. Compared to normal pregnancy, a significant increase of diastolic notching and incomplete registration of maternal vessels were found. Using 90th percentile as cut-off limit last doppler examination before delivery showed pathological results in 76% of all cases with growth retardation and 90% of pregnancies with an additional risk of pregnancy induced hypertension. As pathological waveforms in the maternal compartment contribute a major part to abnormal velocity waveforms, doppler study of utero-placental vessels plays an important role in the diagnose of impaired persuasion of the placenta.

[Diagnostic value of continuous wave (cw) Doppler sonography in maternal diabetes mellitus]. / Der diagnostische Stellenwert der Continuous-wave-(cw) Dopplersonographie bei mütterlichem Diabetes mellitus.

Doppler studies of umbilical, uterine and arcuate artery velocity wave forms were performed in 40 insulin-dependent diabetic women in the first and second half of pregnancy. Using a continuous-wave Doppler device, the resistance index (RI) was calculated to determine the degree of vascular resistance in utero-placental and foeto-placental compartment. The 90th percentile was used to classify flow velocity profiles. In addition, diastolic notching and incomplete registration of uterine and arcuate arteries were considered as an abnormal result in utero-placental perfusion. The prevalence of abnormal velocity wave forms in this risk group was higher than in a non-diabetic population. No significant correlation was found between abnormal Doppler studies and White's classification. Patients with vasculopathy represent a high-risk group for foetal growth retardation, which may be detected early by umbilical and especially uterine artery Doppler studies. Abnormal uterine and arcuate artery wave forms allowed identification of patients who developed pregnancy-induced hypertension/preeclampsia.

Continuous-wave Doppler investigation of uteroplacental vessels in high-risk pregnancies as predictor of fetal growth retardation and pregnancy-induced hypertension.

Continuous-wave Doppler sonography of uteroplacental vessels and the umbilical artery was used as an additive method in the management of risk pregnancies. Its major advantage lies in permitting noninvasive access to placental perfusion. In a sample of 650 singleton pregnancies considered at risk, flow patterns of the right and left uterine and arcuate arteries and of the umbilical artery were obtained. Increased resistance in uteroplacental circulation alone (90th percentile of resistance index and/or notching) was seen in 62 of 100 patients with confirmed growth retardation, proving the key role played by uteroplacental perfusion disorders. Early diastolic notching as well as incomplete vascular flow patterns were also found significantly more often in the growth-retarded group compared to the controls, especially in pregnancies additionally beset by hypertensive disorders. Doppler study of both utero- and fetoplacental circulation increased the sensitivity to 76% in pregnancies with intrauterine growth retardation, and to 90% in those cases with an additional risk of pregnancy-induced hypertension, while the false-positive rate (100-specificity) remained acceptable (17%).

Umbilical cord haematoma as a complication of intrauterine intravascular blood transfusion.

Between October 1985 and February 1989, 49 ultrasound-guided intravascular fetal blood transfusions were performed in 16 patients (14 with rhesus (Rh) isoimmunization, 2 with non-immunologic hydrops fetalis (NIHF)). As an intra-operative complication, perivascular haematoma of the cord occurred in three patients (7 per cent). In two cases, fetal bradycardia necessitated delivery by Caesarean section at 30 and 32 weeks' gestation, respectively. In the third case, fetal bradycardia developed during transfusion, at 31 weeks' gestation, but normalized within 3 min. The baby was delivered as planned at 36 weeks of gestation, after another transfusion at 34 weeks. Dislodgement of the needle tip into perivascular tissue, caused by sudden fetal or maternal movements, is the reason for this complication. The haematoma develops as a result of delayed recognition and continuous transfusion into Wharton's jelly. Cord haematoma may be diagnosed in time by continuous ultrasound imaging, as illustrated in case 3. To minimize the risk of needle dislodgement during transfusion, sedation of the mother and complete immobilization of the fetus by injecting a short-acting muscle relaxant into the umbilical vessel are recommended.

[Continuous-wave Doppler ultrasound in the 2d and 3d trimester of pregnancy--normal values]. / CW-Dopplersonographie im 2. und 3. Schwangerschaftstrimenon--normalwerte.

Based on 427 patients with uneventful pregnancies and deliveries standard rates were established for the resistance index (RI) and the pulsatility index (PI) of the uterine, arcuate, and umbilical arteries. Percentiles, above all the 90th percentile, are more suitable localisation gauge than are standard deviations. In the observation period, i.e. from 18th to 42nd week of gestation, neither resistance nor pulsatility Index in the utero-placental compartment proved to be dependent on gestational age to any significant degree. By contrast, the umbilical artery showed a definite linear relation between the indices measured and gestational age. If the heart rates are in physiological ranges no clinically relevant effects of the heart rate on the measurement results were observed in either the maternal or the foetal compartment.

[Reproducibility of continuous wave Doppler studies in pregnancy]. / Reproduzierbarkeit von continuous-wave Doppleruntersuchungen in der Schwangerschaft.

The inter- and intraobserver variability of Doppler flow velocimetries of uterine, arcuate and umbilical arteries was studied using a 4 MHz continuous wave system in the second and third trimester of pregnancy. There was no significant variation in indices used to characterize the maximum frequency outline of waveforms of uteroplacental and umbilical arteries neither when two observers examined the same patient nor the examination was performed several times on the same day or over a 24 hour period by the same observer. In uteroplacental and umbilical arteries continuous wave measurements are highly accurate and are not inferior to the more expensive pulsed Duplex systems.

Uteroplacental diastolic notching in 510 uneventful pregnancies.

In a collective of 510 patients with uneventful pregnancies and deliveries the rate of waveform notching in the uteroplacental flow velocity pattern was examined. Notching appeared to be significantly more frequent in the uterine than arcuate artery. It was unilateral and mainly affected placenta-contralateral sites. Bilateral notching or notching on placental site were the exception. In both flow patterns notching was seen to increase as pregnancy progressed and was slightly higher in the third compared to the second trimester.

[Comparison of different blood flow parameters for evaluating blood flow spectra in fetal growth retardation]. / Vergleich unterschiedlicher Blutflussparameter zur Beurteilung von Blutflussspektren bei fetaler Wachstumsretardierung.

Uteroplacental and foetoplacental vascular resistance is generally high in pregnancies complicated by intrauterine growth retardation. Assessment of flow velocity curves using angle-independent indices as A/B ratio, resistance index (RI) or pulsatility index (PI) cannot classify all cases with pathological flow velocity profiles. Beneath the pulsatility the maximum frequency outline of the flow velocity waveform offers additional clinical information. The evaluation of flow velocity curves using polynome analysis (including III degrees) provides additional data including occurrence of diastolic notching and can be used as a more sensitive indicator of impaired uteroplacental blood flow. In such pregnancies accurate evaluation of the maximum flow velocity outline with polynome analysis has been shown to be an important qualitative criterion in the assessment of blood flow velocity waveforms.