Expression pattern of osteogenic protein-1 (bone morphogenetic protein-7) in human and mouse development.

Osteogenic protein-1 (OP-1; BMP-7) is a member of the bone morphogenetic protein subfamily. Because members of the TGF-beta superfamily have a role in tissue development, the distribution of OP-1 expression in developing human embryos (5-8 gestational weeks) and fetuses (8-14 gestational weeks) and mouse (9.5-17.5 gestational days) fetuses was examined. Northern hybridization with specific OP-1 probes revealed two mRNA species of 4 and 2.2 KB. Highest levels of OP-1 mRNA were found in human fetal kidney and heart between 12-14 weeks of gestation. By in situ hybridization, the OP-1 transcripts were found in various tissues, i.e., the ectodermal epithelium of the mouse fore- and hindlimbs, heart, teeth, intestinal epithelium, perichondrium, hypertrophic chondrocytes, and periosteum/osteoblast layer of developing human bones. In kidneys, transcripts were first detected in the epithelium of the branching uretheric buds, whereas at later stages glomeruli were the major site of OP-1 mRNA accumulation. These data suggest that, although OP-1 has been isolated from bone matrix, it may have additional regulatory roles in the morphogenesis and/or function of the kidney, limb bud, tooth, heart, and intestine.

Biometric and dynamic ultrasound assessment of small-for-dates infants: report of 260 cases.

The accuracy of 4 ultrasonic parameters and their combined use of detecting fetal growth retardation in a group of 260 small-for-dates infants are analyzed. Abdominal circumference measurement was the most accurate single ultrasonic technique. By combining this measurement with fetal cephalometry, it was possible to diagnose antenatally 96.8% of the small-for-dates infants. Fetal urinary production was below the normal mean in 94.3% of these infants. All except 1 asymmetric growth-retarded fetus had a fetal breathing movement rate lower than that of a normal fetus. The perinatal mortality was significantly decreased in a group of ultrasonically detected growth-retarded fetuses, as compared with the group of unrecognized small-for-dates fetuses.

Ultrasound diagnosis and perinatal management of surgically correctable fetal malformations.

Among 276 fetal malformations detected during the nine year period there were 97 potentially correctable anomalies which are described in detail as are the antenatal and postnatal corrective procedures undertaken. On 35 hydrocephalic fetuses 9 were operated upon postnatally in the last 2 yr. Three months after the operation four of the babies were found to be developing normally, three moderately well while two were severely retarded. Two out six babies with cystic hygroma were successfully operated after birth and their development is now normal. Of 23 malformations of the gastro-intestinal tract (two diaphragmatic hernias, three esophageal, four duodenal and four jejunal atresias, seven omphalocele, three gastroschisis) 13 babies were successfully operated and are developing normally. In 8 out of 10 antenatally detected cases of obstructive uropathy antenatal intervention was undertaken. In one case a shunt catheter was inserted for the last three weeks before delivery. Puncture and urine evacuation was performed in seven of the babies. Five were live born and surgical correction was successfully undertaken after birth, while two died (one multiple malformations and the other respiratory distress syndrome). After excluding multiple and chromosomal anomalies the best results are obtained in the correction of gastro-intestinal tract atresia (9 of 11) and obstructive uropathy (5 of 7), where once a passage has been established the baby develops normally. Interventions such as shunts in hydrocephalic babies are always a matter for discussion in relation to the final outcome, but when there is no other choice, this too is a way of endeavouring to help such a baby. Early antenatal diagnosis is therefore extremely important when interruption of pregnancy is still feasible. In cases of malformations detected at a later gestational age early diagnosis facilitates the assessment of the development of the affected organ, possible timely antenatal correction, team consultation regarding the time and mode of delivery and preparations for postnatal correction. Such an antenatal approach makes it possible to significantly influence the perinatal outcome.

Glycoprotein and ganglioside changes in human trophoblasts after exposure to pulsed Doppler ultrasound.

Changes in glycoprotein and ganglioside composition in human trophoblasts (eighth week of gestation) after in vitro exposure to pulsed Doppler ultrasound (pulse duration 1.22 microseconds; repetition frequency 11.1 kHz; center frequency 4 MHz; ISPPA = 175.5 W/cm2; ISPTA = 0.59 W/cm2) were investigated. Evacuated trophoblasts were divided in two halves and insonated for 10 min on top of a 6-cm layer of 5% gelatin in 50-mL tubes (Falcon) at 37 degrees C. One half of each trophoblast was sham insonated and served as an internal control. After insonation trophoblasts were maintained at 37 degrees C for 24 h. Glycoproteins were detected using alpha-D-mannose specific lectins from Galanthus nivalis and Narcissus pseudonarcissus. A decrease in the expression of mannose containing glycoprotein mgp47 and an increase in expression of mgp54 were observed. Ganglioside composition was also significantly altered. Concentrations of two gangliosides migrating similarly to GM2, and one similarly to GQ1, decreased by more than 75%. At the same time, concentrations of one ganglioside migrating similarly to GM3, and two other unidentified gangliosides increased two- to fourfold.

Ultrasonic markers of fetal chromosomal abnormalities.

OBJECTIVE: The aim of this brief investigation was to correlate the most common sonographically detectable markers with certain type of chromosomal disorder diagnosed by available karyotyping procedures. STUDY DESIGN: During the 3 year study period fetal karyotyping was performed in 1055 patients for a variety of clinical indication. Twenty one percent (21%; 222/1055) of procedures were done because of sonographically detectable structural disorders related to phenotype expression of chromosomopathies. Sonographic examinations and karyotyping procedures were performed between the 10th and 36th week. The average maternal age was 27 years, unselected. RESULTS: The fetal karyotype was abnormal in 13.5% of cases (30/222). Within the group of single marker, 11.6% (7/60) of karyotypes were abnormal. Multiple markers of chromosomal abnormalities resulted in 14.2% (23/162) of abnormal karyotypes. The most frequent chromosomal disorder detected in sonographic screening is trisomy 18 (50%; 15/30). The data on the frequency of different types of chromosomal abnormalities are given. CONCLUSIONS: The incidence of chromosomal abnormalities for ultrasonographically detectable malformations is much higher than the incidence reported in screening studies based on maternal age or biochemical screening. Trisomy 21 showed the relative lack of variety in phenotypic expression, and nuchal translucency screening has to be accepted rationally. Associated numerous major and minor malformations were the most prominent factors leading to the diagnosis of chromosomopathies, particularly trisomy 18.

Effect of pulse Doppler ultrasound on placental hormone excretion in vitro.

There is no literature data on the effects of ultrasound on the metabolism of placental tissue. In the present study, the authors have investigated the possible influence of pulsed field Doppler ultrasound on hormonal excretion of human placental trophoblasts in vitro. For the detection of placental hormones, specific immunoassays for chorionic gonadotropin (hCG), human placental lactogen (hPL), estrogen and progesterone were used. Compared to control trophoblast hormone excretion, pulsed field ultrasound exposure induced no changes in the excretion of the hormones in vitro. The authors were unable to demonstrate any alterations caused by pulsed field Doppler ultrasound in this in vitro model. Additional studies are required to deepen our understanding of the effect of pulsed Doppler ultrasound on other biomolecules and their metabolism.

Histopathologic findings of placenta and arcuate artery Doppler velociometry in preeclampsia and intrauterine growth retardation.

The aim was to analyze the histopathologic changes of placentas and to compare them to the results of arcuate artery color Doppler velocimetry. Fifty four placentas were from pregnancies complicated with pre-eclampsia that ranged from mild forms to convulsions (group 1), 42 from pregnancies complicated with intrauterine growth retardation (IUGR) (group 2) and 40 from uncomplicated pregnancies (group 3). The arcuate artery resistance index (AARI) was increased in 66.66% in group 1 and 59.52% in group 2 (NS). In all uncomplicated pregnancies (group 3) AARI was normal. In group 2, increased AARI was significantly more frequently associated with minimal hypoxic damage (MHD) of placental tissue than in group 1 (p < 0.005), whereas multiple infarcts were more common in group 1 than in group 2 (p < 0.005). At normal AARI multiple infarcts were significantly more frequently found in group 1 than in groups 2 and 3 (p < 0.005), whereas normal placental findings were significantly more common in group 3 than in groups 1 and 2 (p < 0.001). Hypoxic lesions were significantly more often associated with increased AARI (p < 0.01). The positive predictive value of arcuate artery color Doppler velocimetry for hypoxic placental lesions was 93%, and negative predictive value was 10%. Sensitivity and specificity of the method in the prediction of hypoxic placental lesions was 62% and 91%, respectively.

[Hormone therapy of spontaneous abortion. Our experience with treatment with Gravibinan]. / Hormonska terapija spontanih pobacaja. Nasa iskustva u lijecenju Gravibinanom.

The results of the treatment of 151 pregnancies with threatened and/or habitual abortions by using high hormonal dosages (Gravibinan "Alkaloid") are presented. Eight pregnancies were in primigravidas, the remaining 143 patients having previously had 47 interruptions of pregnancy, 66 deliveries, and 313 spontaneous abortions. Disregarding artificial abortions in 379 previous pregnancies there were 313 or 82.5 per cent spontaneous abortions. The treatment was performed by i. m. applications of Gravibinan, during the first week every two days, during the following two weeks every three days, and until the accomplished 16 weeks of pregnancy every five days. Besides hormonal therapy, all patients were on bed rest; in the following course of pregnancy tocolysis and in the case of opened cervix the cerclage cervicis were performed. The vitality of the ovum and the fetus, as well as the efficacy of the treatment were evaluated by clinical findings, HCG and estriol urinary eliminations, and by ultrasonography. Out of 151 treated pregnancies, 21 (13.91%) resulted in early abotion, 17 (11.26%) in mid-trimester abortion, 6 (3.97%) in pre-term, and 107 (70.86%) in term deliveries. There were two (1.77%) perinatally dead premature infants. HCG urinary eliminations were significantly lower in pregnancies resulting is missed abortion or first-trimenon miscarriage, whereas no difference was established between pregnancies resulting in delivery or mid-trimester abortion. The authors recommend hormonal treatment in early threatening and/or habitual abortions by administering high dosages of estrogens and gestagens. Such a treatment stimulates secretory transformation of the endometrium at the beginning of pregnancy, and this allows early placentation and the uterine growth with a simultaneous quiescence of the myometrium, which, in turn, makes the growth of the ovum possible. The authors stress the importance of a complex procedure in the establishment of the etiology and in the treatment of spontaneous and/or habiutal abortion.

Ultrasound diagnosis of fetal abnormalities in multiple pregnancy.

Over a period of four years, 41 cases of abnormal multiple pregnancies were diagnosed successfully by ultrasound. These include several rare combinations of abnormalities. The most frequent was a normal pregnancy and a synchronous blighted ovum. Others were twin blighted ova, blighted ovum and missed abortion, missed abortion in both gestational sacs, two embryonic echoes with the development of only one baby, normal fetus and an anencephalic twin, normal fetus and fetus papyraceous, and triplets with two fetuses papyraceous. The results suggest that one or more gestational sacs may be resorbed during pregnancy without any adverse effect on the coexisting normal fetus. From a practical point of view, it is important to be aware of these possibilities before giving the final diagnosis of multiple pregnancy to the patient. The more diagnostic ultrasound is used in obstetrics, the more rare abnormalities associated with multiple pregnancies will be revealed.

[Atypical adenomatous hyperplasia of the endometrium]. / Hyperplasia adenomatosa atypica endometrii.

By women in climacterium and postmenopause the authors found 30 adenomatous atypical hyperplasias out of a total of 909 active hyperplasias. They also detected 68 endometrial carcinomas and 65 other changes. Out of 30 patients with adenomatous atypical hyperplasia, 23 had been subjected to curettage earlier but at that time had revealed only milder forms of hyperplasia. Surgery was performed in 21 patients: in 15 patients the diagnosis based on the operative preparation agreed with that based on curettage findings, in 2 patients endometrial carcinoma and in 2 patients glandular hyperplasia were detected, while in 2 patients there was no functional endometrium. Out of 9 patients who for various reasons were not surgically treated and represented an unintentional prospective study, 5 subsequently developed endometrial carcinoma, 3 mild forms of hyperplasia, and 1 atrophia cystica. In the authors' opinion, the histogenesis of endometrial carcinoma in late postmenopause is still an open question.

[The effect of segmental epidural analgesia on the duration of labor in spastic dystocia]. / Utjecaj segmentalne epiduralne analgezije na trajanje porodaja sa spasticnom distocijom.

In 77 parturients, owing to spastic distotia, the labour was conducted in continuous epidural analgesia, while in the control group of parturients with the same diagnosis (N = 32), the intramuscular use of pethidine and diazepam was repeatedly applied. The epidural catheter was placed at the 2-3 cm dilated cervix. Carticain with or without fentanyl was used as a local anaesthetic. The average duration of labour from the beginning to the 2-3 cm cervical opening was 9.3 hours in the group of epidural analgesia applied parturients and 4.3 hours in the control group. The continuation of labor in the examined group lasted 3.7 hours and in the control group 12 hours. The difference is significant (p less than 0.01). A spontaneous vaginal delivery in the examined group was recorded in 77.9% women. There were 14.3% cesarean sections in the examined and 46.8% in the control group. A protracted labour was a significantly more frequent indication (p less than 0.01) for such a termination of labour in the control group.

Diagnosis and assessment of fetal malformation and abnormalities by ultrasound.

With remarkable improvements in antenatal, intrapartum and the newborn care, the proportion of perinatal problems attributable to congenital abnormalities has significantly increased. The number of deaths due to fetal malformations in some countries now approaches the number due to prematurity and it is justifiable to believe that abnormalities will soon be heading the league of causes of perinatal death. Even with the most advanced treatment teams and resources, many seriously malformed children cannot be habilitated to any reasonable degree. It is therefore obvious that the future of these types of disorders lies ultimately in their prevention. This has long been the hope of obstetricians and in certain abnormalities this can become a reality. With the advent of ultrasound, many structural anomalies cannot be evaluated by direct visualization of the placenta and fetal anatomy. The number of pregnancies monitored available and as public education about genetics increases. Diagnostic ultrasound has proved to be a powerful means of preventing the birth of babies with significant defects. If this has not been achieved in early pregnancy, the knowledge that the fetus is or may be abnormal at the end of pregnancy can still be valuable, since the management of patients before and during labour could be radically altered. Therefore, ultrasound examination should be preferred as the initial test because it is without risk and produces no side effects.

[Correlation between levels of prolactin in maternal serum, fetal serum and amniotic fluid in childbirth at term]. / Korelacija vrednosti nivoa prolaktina u serumu majke, serumu ploda i plodovoj vodi kod porodaja trudnice u terminu.

In 117 parturients with 38-41 gestation weeks, prolactin was analysed by the radioimmunologic method in the mother serum, the umbilical cord serum and vein, and in the amnionic fluid. Three groups of parturients and their newborns were examined: the group (n = 44) with the birth having started spontaneously with the appearance of labour pains 1/10 minutes, the group (n = 38) with a programmed birth induced by the infusion of oxytocin, and the group (n = 35) with the birth comprising elective cesarean section. The concentration of prolactin in the examined sera is characterized by considerable individual oscillations. The highest prolactin level was in the amnionic fluid (395.6 +/- 130.1 mu/L) and the lowest in the mother serum (174.6 +/- 84.1 mu/L) which shows a statistically significant difference (p less than 0.01). Prolactin values in the umbilical artery (244.6 +/- 98.3 mu/L) and vein (230.4 +/- 91.7 mu/L) are significantly (p less than 0.001) higher than the value in the mother sera and significantly lower (p less than 0.001) than the prolactin concentration in the amnionic fluid. The difference of the prolactin values in the sera of the umbilical cord blood vessels has no statistical significance (p greater than 0.05). Nor is there any statistically significant difference between prolactin concentrations in spontaneous and induced deliveries versus those in deliveries terminated with elective cesarean section (p greater than 0.05). A correlation analysis of the functional connection of prolactin in the sera of the mother, fetus, and amnionic fluid gives the correlation coefficient values of high statistical significance (0.482 less than r less than 0.906; p less than 0.001).

Ultrasonic assessment of fetal kidney function in normal and complicated pregnancies.

Fetal renal function was evaluated in 255 normal singleton pregnancies between 22 and 41 weeks of gestation and in 133 complicated pregnancies. Hourly fetal urinary production rate (HFUPR), fetal glomerular filtration rate (GFR), fetal tubular water reabsorption (TWR), and the effect of furosemide on fetal micturition was evaluated by ultrasound and a combination of ultrasound and biochemical tests. In normal pregnancies, the HFUPR increased from 2.2 ml/hr at 22 weeks of gestation to 26.3 ml/hr at 40 weeks of gestation. The fetal GFR was 2.66 ml/min at term, and the percentage of TWR was 78%. In complicated pregnancies, the HFUPR was above normal in 5.7% of the growth-retarded fetuses and below the tenth percentile in 58.6%. The GFR was below normal in 68.2% of the group of complicated pregnancies, but TWR did not significantly differ from that in the normal pregnancies. The effect of furosemide was the same in both growth-retarded and normal fetuses. In diabetic pregnancies, HFUPR values varied considerably and correlated with the fetal size. The HFUPR was normal in anencephalic fetuses and in 90.0% of the pregnancies with hydramnios.

Corpus luteum blood flow in normal and abnormal early pregnancy: evaluation with transvaginal color and pulsed Doppler sonography.

One hundred and thirteen (66.5%) women in this study had a normal intrauterine pregnancy with ages ranging 6 to 12 weeks of gestation. Fifty-seven (33.5%) patients were admitted to the hospital owing to clinically suspected abnormal early pregnancy. Dilatation and curettage were done on all women and tissue sample sent to the pathologist for a final diagnostic. Diagnosis of ectopic pregnancy was made on laparoscopy. Both ovaries were examined carefully by color Doppler in sonography in all patients. Color flow was used as a guide for pulsed Doppler exploration. Corpus luteum blood flow was defined as random, usually semilunar in appearance, dispersed vessels with very low impedance to blood flow. The resistive index and pulsatility index were calculated. Overall detection rate of corpus luteum blood flow in normal pregnancies was higher for the left ovary (62.6%) than for the right ovary (37.4%) (P < 0.01). The mean resistive and pulsatility indices from corpus luteum blood flow were not influenced by gestational age in normal pregnancy. The overall mean value for for resistive index was 0.452 +/- 0.04 and for pulsatility index 0.636 +/- 0.09. The overall detection rate of corpus luteum in abnormal pregnancies also was higher for the left ovary (56.7%) than for the right ovary (43.4%) (P < 0.01). The mean resistive indices from corpus luteum blood flow in patients with missed abortion was higher than in women with normal pregnancy (P < 0.01). Both resistive and pulsatility indices were higher in patients with incomplete or threatened abortion in comparison with normal pregnancy (P < 0.01). No statistically significant difference was seen in the case of anembryonic, molar, or ectopic pregnancy.

Correlation of confined placental mosaicism with fetal intrauterine growth retardation. A case control study of placentas at delivery.

OBJECTIVE: Our purpose was to determine if the frequency of confined placental mosaicism in newborns with unexplained intrauterine growth retardation (IUGR) was higher compared with infants with appropriate growth in utero and the outcome of these pregnancies. STUDY DESIGN: A total of 20 cases with unexplained IUGR and 20 cases with appropriate growth for gestational age has been studied. Amnion, chorion and villi biopsy specimens were obtained from growth-retarded cases and controls at delivery. Cord blood specimens for 48-hour lymphocyte cultures were obtained from all infants with IUGR. RESULTS: Karyotype analysis revealed confined placental mosaicism in two of 20 (10%) cases with IUGR. In one growth retarded case and one appropriate growth for gestational age case, mosaicism was also confirmed in the amnion. Cytogenetic analysis from peripheral blood of newborns showed normal karyotype in all cases. Three pregnancies in the group of fetuses with IUGR (15%) ended with fetal death compared with normal fetal surveillance of all cases from the control group. CONCLUSION: Confined placental mosaicism was detected two times more frequently from placentas of growth- retarded infants compared with those of newborns with appropriate growth. The fetal loss was significantly higher in the group of cases with IUGR compared with the control group.