Incident at Shaifa Hospital.
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Biomedical subjects
Publications and source records attributed to S Yagel.
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First-trimester normal human trophoblast cells show some phenotypic similarities to malignant cells, e.g., rapid proliferation and ability to invade neighboring tissue, including basement membrane in situ, but do not have the ability for unlimited growth or metastasis. The present study examined whether the invasive ability of normal trophoblast cells is an intrinsic property of these cells, independent of the microenvironment provided by the pregnant uterus, and if so, whether they share some of the molecular mechanisms of invasion exercized by metastatic malignant cells. The ability of in vitro grown human trophoblast lines to invade an epithelium-free human amniotic membrane was measured from the temporal kinetics of retention of radioactivity within this membrane resulting from a penetration by 125I-iododeoxyuridine-labeled trophoblast cells. The magnitude of this invasion was compared to that of the highly metastatic human JAR-choriocarcinoma cell line and murine B16F10 melanoma line. Trophoblasts were found to share some of the same molecular mechanisms of invasion with the metastatic cell lines. Inhibitors of collagenase, plasmin, plasminogen, and plasminogen activators completely prevented invasion of the amnion by the trophoblast lines as well as by the metastatic JAR and B16F10 lines. Mersalyl, a compound known to activate collagenase, stimulated invasion by all cell lines tested, including under conditions in which plasmin activity was inhibited. In addition, trophoblasts produced significant levels of type IV collagenase and laminin, both of which appear to be important products of metastatic tumor cells required for basement membrane invasion. It may be concluded from these findings that the invasive property of first trimester human trophoblasts is genetically determined; that the magnitude of amnion invasion cannot differentiate between metastatic cell lines and invasive but nonmetastatic cell lines; and that invasiveness is not a sufficient prerequisite for metastatic ability.
Pulsed Doppler echocardiography is an excellent technique for cardiac diagnosis and assessment of cardiac performance in combination with M-mode and two-dimensional echocardiography. Its exact role in fetal cardiac diagnosis has not been established. We examined 67 high-risk fetuses for cardiac malformations and found cardiac abnormalities or malfunction in 15. In four fetuses pulsed Doppler echocardiography played a primary or a definitive diagnostic role: One fetus had a complete atrioventricular canal, another lacked the pulmonary valve, the third had transposition of the great vessels without ventricular septal defect, and the fourth had high cardiac output failure caused by placental chorioangioma. Pulsed Doppler echocardiography is an integral part of the ultrasonic cardiac examination in high-risk fetuses and should be used in combination with two-dimensional and M-mode echocardiography. It has an important place in the diagnosis of high-risk fetuses and may have a primary role in the diagnosis of fetuses when ultrasound resolution is poor, where cardiac circulatory hemodynamics are essential for diagnosis, and in complicated cardiac malformations in which a comprehensive and accurate diagnosis can be achieved only with pulsed Doppler echocardiography.
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Seven cases of fetal duodenal obstruction were diagnosed during an ultrasound examination. In 5 out of the 7, Down's syndrome was later diagnosed. The finding of duodenal obstruction in a fetus is a high risk indicator for Down's syndrome. We therefore recommend prenatal cytogenetic examination to be performed in such cases.
We examined the immunosuppressor role of the first-trimester human placental macrophages on maternal lymphocyte alloreactivity in vitro to determine whether these macrophages and their secreted mediator(s) participate in the local immunoregulation at the fetomaternal interface. These cells were tested for their effects on maternal lymphocyte proliferation when added alone (as stimulator cells) or as regulator cells in 1) a one-way mixed lymphocyte reaction for six days and 2) lymphocyte cultures in the presence of phytohemagglutinin for three days. We detected a dose-dependent inhibition of phytohemagglutinin-induced proliferation with 48-hour macrophage culture supernatants. Placental macrophages, when used alone as stimulator cells in the mixed lymphocyte reaction, were stimulatory only at a concentration of 1-2%; the stimulation was abolished at a concentration of 10%. When used as regulator cells, they showed a strong inhibition of mixed lymphocyte reaction and phytohemagglutinin-induced proliferation at a concentration of 10%; no effect was observed at a concentration of 1-2%. The major class of the molecules mediating the suppression was identified as prostaglandins, primarily prostaglandin E2 (PGE2), based on the findings that the presence of indomethacin (10(-5) M) or various dilutions of an anti-PGE2 antibody abrogated suppression substantially or completely. Prostaglandin E2 levels measured in the mixed leukocyte culture wells containing placental macrophages as regulator cells correlated positively with the macrophage dose and its suppressive effect.
Between December 1981 and June 1986, 52 women examined by ultrasonography were found to have clear pelvic cysts more than 5 cm in average diameter, without septa or solid areas. The cysts were persistent and did not respond to contraceptive pills for four to eight weeks. In all cases, there were histologic or cytologic results from surgical specimens or fluid aspirated from the cysts. In 15 women, the cysts were aspirated and revealed no malignant cells. Thirty-seven women underwent laparotomy, of whom 11 (29%) were found to have benign ovarian neoplasms (nine cystadenomas and two dermoid cysts). Because benign ovarian neoplasms are potentially malignant, and because a large number was found in our study, we recommend removal of the cysts by excision rather than aspiration.
The in utero ponderal index has become a method of estimating fetal growth. Several methods have been used in the formulation of the in utero ponderal index. In the present study, 1040 pregnant women underwent ultrasonic examination between 24 and 41 weeks of gestation, and the in utero ponderal index was determined by dividing the estimated fetal weight by the third power of the femur length, rendering a relatively constant value of 8.345 +/- 2.5 (2 SD). Fifty-one cases were defined as intrauterine growth retardation due to an estimated fetal weight lower than the tenth percentile for gestational age. The in utero ponderal index proved to be a valuable index in the prediction of fetal outcome in those cases of intrauterine growth retardation in which the in utero ponderal index was smaller than 1 SD from the average of 8.345. Fetal and neonatal well-being was clearly compromised when intrauterine growth retardation was associated with a low in utero ponderal index.
The role of progesterone in immunoregulation at the fetomaternal interface at physiological concentrations (2-6 micrograms/ml) is controversial. This study examines the effect of progesterone on maternal lymphocyte proliferation in a one-way mixed lymphocytic reaction (MLR) stimulated by allogenic lymphocytes as well as on prostaglandin production and secretion by fetal placental macrophages. No suppressive effect on maternal lymphocyte proliferation was found at progesterone levels of up to 20 micrograms/ml. However, physiological concentrations of progesterone were found to induce a significant increase in the fetal macrophage release of PGE2, which is well known as a strong immunosuppressant. PGI2 production and secretion by these cells, measured by the appearance of its 6-keto-PGF1 alpha product, was not affected by incubation with progesterone. Enhancement of PGE2 secretion by progesterone may partly explain the roles of progesterone and fetal placental macrophages in immunosuppression at the fetomaternal interface.
A case of prenatal diagnosis of hypoplastic left ventricle by means of echocardiography is presented. The method of detecting this syndrome is described and the importance of its prenatal diagnosis emphasized.
The use of femur length (FL) and biparietal diameter (BPD) for estimation of gestational age (GA) was investigated using 1123 ultrasound measurements between the 14th and 41st week of gestation. Femur length was found to provide a more accurate index than BPD for the entire range of gestational age considered. If an interval of approximately +/- 2.5 weeks is considered 'satisfactory', the accuracy of FL past the 31st week is not sufficient to justify its use. Combining the FL and BPD measurements via the formula: GA = 9.565 + (0.0414) FL + (0.0024573) FL2 + (0.15209) BPD - (0.00015827) BPD2 provides an index of gestational age accurate to approximately +/- 2.5 weeks up to the 32nd week of gestation and accurate to approximately +/- 2.75 weeks up to the 34th week of gestation. This is the first time that combining FL and BPD in a statistically rigorous manner has been proposed as an index of gestational age, and we suggest that this combination be used as a routine tool in its assessment.
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Cyclic changes were observed in the content of blood monocytes during the menstrual cycle of normal women. Elevated blood monocytes were found during the ovulation period as well as in other conditions which are associated with increased blood estradiol (E2). To understand the possible association between E2 and monocytosis, we analysed the in vitro effect of E2 on the development of myelomonocytic colonies in culture. E2 in physiological concentrations was found to increase the number of colonies developed from peripheral blood mononuclear cells (PBM) of both females and males. The optimal concentration for the augmenting effect on males' PBM was lower than that for females. Mononuclear cells derived from cord blood, which yielded much higher numbers of colonies than adult PBM, also responded to the stimulatory effect of E2. Estrone and estriol were less effective than E2 in adult PBM. In contrast, progesterone, diethylstilbestrol and testosterone did not affect the number of colonies at the range of physiological concentrations tested. The anti-estrogen Tamoxifen did not inhibit the stimulatory effect of E2. The augmenting effect of E2 on monomyelocytic colony formation may explain at least in part the increase in blood monocyte content of women with high E2 as well as other phenomena of macrophage and granulocyte changes associated with the menstrual cycle.
An investigation of real time sonographic features of the normal fetal brain at six levels in the axial plain was undertaken between the 26th and 40th week of gestation. Structures such as cerebrum, midbrain, basal ganglia, ventricular system, vascular system, and cerebellum can be routinely identified if ultrasound is performed systematically. The sonographic appearance of detailed brain anatomy at each level is presented with the hope that it may provide a systematic form of scanning the fetal brain. With such standardization of technique many erroneous interpretations may possibly be avoided.
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Eleven cases of nonimmunologic hydrops fetalis occurring during a six year period were reviewed. The etiology of hydrops fetalis was established only in four cases. It included one case of endocardial fibrosis, two cases of non-immunologic hemolysis and one case of tachycardia. The pregnancies were complicated by polyhydramnios in 9 cases, preterm delivery in 10 cases, twins in 3 cases and pre-eclampsia in one case. Four of 11 fetuses died in utero, on one of them, intrauterine blood transfusion and administration of digoxin and furosemide was carried out. Five fetuses died neonatally and two survived. In one of the later cases, intravenous administration of digoxin with quinidine to the mother was without effect, nor did such treatment cause any effect on the neonate after delivery. Electric cardioversion supplemented with digoxin slowed the neonatal cardiac rhythm to normal range with later successful outcome. Earlier diagnosis by ultrasonography especially in cases of hydramnios and appropriate treatment are likely to improve this outcome.