Thomas Kerenyi

The Role of Progestationally Regulated Stromal Cell Tissue Factor and Type‐1 Plasminogen Activator Inhibitor (PAI‐1) in Endometrial Hemostasis and Menstruation

The physiologic mechanisms whereby the human endometrium maintains hemostasis during endovascular trophoblast invasion, yet permits menstrual hemorrhage, are unknown. This paradoxical relationship was investigated by evaluating endometrial expression of tissue factor (TF), the primary initiator of hemostasis, and plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor of fibrinolysis. We observed increased immunostaining for TF and PAI-1 in sections of decidualized stromal cells from luteal phase and gestational endometrium. To determine whether TF and PAI-1 expression are directly linked to decidualization, both endpoints were monitored in a well described in vitro model of decidualization. Thus, confluent stromal cell cultures were exposed to vehicle control, 10(-8) M estradiol (E2), 10(-8) to 10(-6) M medroxyprogesterone acetate (MPA) or both E2 + MPA for 2-24 days in serum-containing or defined media. The progestin enhanced the content of stromal cell-associated immunoreactive and functionally active TF and PAI-1 released into the medium and elevated levels of stromal cell TF and PAI-1 mRNA. While E2 alone was ineffective, it greatly augmented MPA-enhanced TF and PAI-1 protein and mRNA content. Dose-dependent effects on TF and PAI-1 content were observed between 10(-8) to 10(-6) M MPA +/- E2. Similar results were observed for decidual cells derived from first trimester endometrium and cultured in type 1 collagen gels. Following optimal induction of TF and PAI-1 expression by E2 + MPA in stromal cell cultures, removal of these steroids greatly reduced levels of both TF and PAI-1 protein and mRNA within 4 days. These studies suggest a mechanism whereby endometrial hemostasis is maintained during trophoblast invasion yet reduced at the end of nonfertile cycles to permit menses.

Results and Pitfalls in Prenatal Cytogenetic Diagnosis

Since 1969, we have cultured over 200 diagnostic amniotic fluids. Of these, 183 were for cytogenetic diagnosis. The chromosome analysis was successful in 168 cases. The indications and the results of the affected fetuses (followed by therapeutic abortion) are: (1) previous child with Downs syndrome: 62 cases (1:47,XX,+21); (2) advanced maternal age: 54 cases (1:47,XXY; 1:45,X/46,XY mosaicism; 1:47,+18); (3) previous child with multiple anomalies: 12 cases; (4) previous child with 47,XY,+18 or 47,+13: five cases; (5) translocation carrier: two cases; (6) parental mosaicism: three cases; (7) X-linked disorders: six cases (3:XY); (8) others: 24 cases. We have found firstly, that for prenatal sex determination, karyotype analysis of the cultured amniotic fluid cells is the only accurate means and that caution must be taken if sex chromatin and Y-fluorescent body determination from the uncultured amniotic fluid cells is used. Secondly, that diagnosis of chromosomal mosaicism can be problematic as exemplified by our case of 45,X/46,XY mosaicism, where only 45,X cells were recovered from the first culture. Thirdly, that in cases with enlarged satellites, cells of late prophase or early metaphase must be used to eliminate confusion with translocations. We encountered three cases of enlarged satellites—one in the D group and two in the G group—and all three resulted in normal infants. Fourthly, that the karyotype may be altered by contamination and/or treatment or other unknown factors. We have observed two such cases where each mother delivered a normal infant.

Volume and sodium concentration studies in 300 saline-induced abortions

In an attempt to clarify the role of volume changes and Na concentration in saline-induced midtrimester abortions, 800 amniotic fluid samples were studied in 300 cases. The immediate postinfusion values of Na ranged as high as 3,000 mEg. per liter and as low as 1,200 mEg. per liter, still resulting in abortion. In earlier gestation, higher Na concentration and greater volume increase was needed for successful induction of abortion. Volume increase, within limits, compensated for Na concentration decrease. Osmotically induced volume changes were proportionatenate to the advancing stage of gestation.

A suggested set of working definitions and criteria applicable to induction of labour.

A list of prerequisites, essential items of information and definitions applying to studies on induction of labour is presented. It is suggested that their use would permit proper analysis and comparison of results obtained by different investigators.

Rheumatic heart disease diagnosed during pregnancy: a 30-year follow-up.

One hundred one patients originally diagnosed as having rheumatic heart disease (RHD) during the years 1945–1948 were reevaluated in 1975 to determine the natural history of the disease. Twenty patients (19.8%) showed no sign of RHD. Of the patients with confirmed RHD, 56 (70.0%) had their original lesion confirmed, while 23 (28.8%) had developed additional valvular involvement. Pure mitral stenosis resulted in significantly lower mortality than all other valvular lesions, and congestive heart failure was the leading cause of death. Nineteen patients underwent cardiac surgery; the mortality in this group (52.6%) was not significantly higher than that in the overall RHD group (38.8%). False diagnosis of RHD during pregnancy is common. A more thorough evaluation of the “cardiac murmur of pregnancy” is advocated.

RESULTS AND PITFALLS IN PRENATAL CYTOGENETIC DIAGNOSIS

Since 1969, we have cultured over 200 diagnostic amniotic fluids. Of these, 183 were for cytogenetic diagnosis. The chromosome analysis was successful in 168 cases. The indications and the results ofthe affected fetuses (followed by therapeutic abortion) are: (1) previous child with Downs syndrome: 62 cases (1 :47,XX,+21); (2) advanced maternal age: 54 cases (1 :47,XXY; 1 :45,X/46,XY mosaicism; 1:47,+18); (3) previous child with multiple anomalies: 12 cases; (4) previous child with 47,XY, + 18 or 47,+ 13: five cases; (5) translocation carrier: two cases; (6) parental mosaicism: three cases; (7) X-linked disorders: six cases (3 :XY); (8) others: 24 cases. We have found firstly, that for prenatal sex determination, karyotype analysis of the cultured amniotic fluid cells is the only accurate means and that caution must be taken if sex chromatin and Y-fluorescent body determination from the uncultured amniotic fluid cells is used. Secondly, that diagnosis of chromosomal mosaicism can be problematic as exemplified by our case of 45,X/46,XY mosaicism, where only 45,X cells were recovered from the first culture. Thirdly, that in cases with enlarged satellites, cells of late prophase or early metaphase must be used to eliminate confusion with translocations. We encountered three cases of enlarged satellites-one in the D group and two in the G group -and all three resulted in normal infants. Fourthly, that the karyotype may be altered by contamination and/or treatment or other unknown factors. We have observed two such cases where each mother delivered a normal infant.