Elevated placental cytokine release, a process associated with preterm labor in the absence of intrauterine infection.

OBJECTIVE: To investigate the role of cytokines in normal term and preterm labor in the absence of intrauterine infection. METHODS: Cytokine (interleukin [IL]-1 beta, IL-6 and tumor necrosis factor-alpha [TNF-alpha]) release was estimated from placental and decidual cell cultures from 22 nonlaboring women at term with cesarean deliveries, 18 women with spontaneous labor at term, and 21 women with preterm labor (19-36 weeks gestation) who delivered vaginally or by cesarean, according to gestational age. Eight of 21 women delivering preterm had clinical evidence of intrauterine infection, and 13 were not infected. RESULTS: Placental cell cultures obtained from women with spontaneous term labor released significantly larger amounts of cytokines (median: IL-1 beta 6450 pg/mL, IL-6 1821 ng/mL, and TNF-alpha 13,506 pg/mL) compared with placental cell cultures from nonlaboring women at term (median: IL-1 beta 2602 pg/mL, IL-6 993 ng/mL, TNF-alpha 3475 pg/mL; P < .02). Placental cells from women delivering preterm with intrauterine infection did not produce significantly different amounts of cytokines (median: IL-1 beta 3929 pg/mL, IL-6 1084 ng/mL, TNF-alpha 2847 pg/mL) when compared with those of nonlaboring women at term, whereas placental cells from uninfected women delivering preterm produced significantly larger amounts of cytokines (median: IL-1 beta 22,903 pg/mL, IL-6 1899 ng/mL, TNF-alpha 15,005 pg/mL; P < .01) than cells from nonlaboring women at term. Cytokine release from decidual cell cultures was similar in all groups tested. CONCLUSION: In the absence of intrauterine infection, preterm labor was associated with elevated placental cytokine release.

Changes in lymphocyte subsets during normal pregnancy.

Peripheral blood lymphocytes from healthy women were studied during pregnancy and postnatally, and were compared with lymphocytes from an age-matched non-pregnant control group. Compared with non-pregnant women, the total white cell count was significantly increased at all pregnancies and also post-partum. In pregnancy the absolute number and percentage of T lymphocytes was slightly elevated while almost no changes in B cells were found. No significant changes were found in the percentage of suppressor/cytotoxic (CD8+), of helper/inducer (CD4+) T lymphocytes, nor of CD4+/CD8+ ratio at any stage of pregnancy and puerperium. The most remarkable changes of the immune system occurred in the group of HLA-DR+ and CD56+ activated T cells. The cell numbers showed a significant increase in the first trimester (< 14 weeks) and decreased slightly from stage to stage. Lower values in NK (natural killer) cells and higher levels of IL-2 receptor positive T lymphocytes did not reach significant levels of change.

[Secretion of inflammatory cytokines and prostaglandins by fetal trophoblast cells induces uterine contraction and labor onset]. / Die Sekretion inflammatorischer Zytokine bzw. Prostaglandine durch fetale Trophoblastzellen induziert Wehentätigkeit und Geburtsbeginn.

OBJECTIVE: Induce infection-associated cytokines intrauterine secretion of prostaglandins and term labor? METHODS: Concentrations of Il-6, Il-1 beta, TNF-alpha, PGF2 and PGF2 alpha were determined in cervical secretions and amniotic fluid during spontaneous term labor. The supernatant of amnion-, chorion-, decidua- and trophoblast cells, cultured after elective cesarean section or spontaneous delivery, was analysed for cytokine- and prostaglandin activity. RESULTS: Term labor always is associated with intrauterine cytokine- and prostaglandin release. Increased production of cytokines and prostaglandins in case of normal term labor only was found by fetal trophoblast cells. CONCLUSIONS: Signal for parturition is of trophoblast and therefore of fetal origin.

[Drug abuse, pregnancy and HIV infection]. / Drogenabusus, Schwangerschaft und HIV-infektion.

PIP: It is estimated that there are between 50,000 and 90,000 drug abusers in the former West Germany. IV drug users are the second largest group of AIDS victims after homosexual and bisexual men. From 1989 to 1990, IV drug users up 16.1% of 1425 reported AIDS cases. 52% of 124 female AIDS cases were drug abusers. 4-12 weeks pass from the time of HIV infections to the appearance of HIV antibodies, thus testing is not foolproof. Heroin abuse often leads to oligo- or amenorrhea. yet 593 female IV drug users in New York City had 2289 pregnancies (often detecting their pregnancy too late for abortion), averaging 2.5 live births and 1.3 abortions. Fetal HIV transmission occurs in 20-40% of cases. The effectiveness of azidothymidine (AZT) prophylaxis is not clear. Only 29% of 50 HIV-infected women had complication-free pregnancies: 34% had premature pain and contractions, and 11 of 49 children were born prematurely before the 35th week. Drugs used include opiates, barbiturates, cocaine, cannabis, amphetamine, LSD, and mescaline. The daily cost of addiction leads to illegal activities. 80% of addicted women turn to prostitution. Methadone has been used for substitution in the US. In Germany, levomethadone (L-Polamidon) is approved and has a half time of 29 hours which is much longer than that of heroin. The heroin substitution regime consists of 4-5 ml of levomethadone and later 1-3 drops/day. Asphyxia of the fetus could occur in unmedicated withdrawal, necessitating the use of levomethadone even during pregnancy. The reduction of .2 ml of this drug every 2 days was well tolerated. Outpatient drug treatment is risky, it should be carried out only in maternal-child care facilities.^ieng

[Biochemical maturation of organs in the foetus and its induction (author's transl)]. / Die biochemische Organreifung des Feten und ihre Induktion.

Several biophysical and biochemical changes are prerequisites for the adaptation of the newborn to extrauterine life. Enzyme induction is the mechanism on which this adaptation of metabolism is based. The theoretical fundamentals of enzyme induction are presented, and the perinatal origin of enzymes explained by means of the example of PEP carboxykinase. Among the mose frequent disturbances of the maturing of organs are hyperbilirubinaemias and the respiratory distress syndrome of newborn. The biochemical and physical concepts underlying these disease pattens are explained, and possibilities of enzyme induction and hence acceleration of maturity are shown. On the grounds of clinical experience, enzyme induction appears to be safely established as a membrane prophylaxis.

[Determination of the protein binding capacity of corticosteroids from the serum (author's transl)]. / Zur Bestimmung der Proteinbindungskapazität von Corticosteroiden aus dem Serum.

This article describes a method which enables determination of the binding capacity of the corticosteroids from untreated serum with relatively little effort. The method is based on the principle of competitive protein binding. The binding capacity is given for cortisol and DOC and it is shown that progesterone enters into a bond with CBG.

[The behaviour of endocrinal parameters under prophylaxis of hyaline membrane disease with glucocorticoids (author's transl)]. / Das Verhalten endocriner Parameter unter der Membranprophylaxe mit Glucocorticoiden.

Prevention of hyaline membrane disease with glucocorticoids produces suppression of the hypopituitary-adrenocortical axis of the mother as well as of the foetus. The extent of the suppression is significantly higher under medication with the 9 alpha-fluorinated preparations, betamethasone and dexamethasone, than under medication with 16-methyleneprednisolone. Increases in the concentration levels of the mineralocorticoid DOC are to be expected in 37% to 50% of the patients, depending on the administered corticoid. The percentage of increase is 150% under 16-methyleneprednisolone and 220% under betamethasone and dexamethasone.

[Studies on placental transfer of 16-methylene prednisolone (decortilen) (author's transl)]. / Untersuchungen zum plazentaren Ubertritt von 16-Methylenprednisolon (Decortilen).

The placental transfer of 16-methylene prednisolone is demonstrated via thin layer chromatography. Concentrations of 100-500 ng/ml plasma result in the umbilical cord blood on intravenous application of 60 mg methylene prednisolone administered to the mother 5-30 minutes ante partum.

[11-Desoxycorticosterone * (DOC) during pregnancy and labor]. / 11-Desoxycorticosteron (DOC) während der Schwangerschaft und unter der Geburt.

In this paper investigations into the increase in the concentration of DOC during the 8th and 40th week of pregnancy are described. It was found that the DOC values sub partu in the umbilical cord are higher than in the maternal blood and that a rapid decrease in the corticoid level occurs post partum both in the mother and in the infant. The fetoplacental unit is discussed as the possible site of synthesis of the steroid.

[Experimental investigations in regard to the optimal stimulation of lecithin synthesis in the fetal lung via glucocorticoids (author's transl)]. / Tierexperimentelle Untersuchungen zur Frage der optimalen Synthesestimulierung des Lezithins in der fetalen Lunge durch Glukokortikoide

On the basis of curves illustrating the effects of dosage on experimental animals, it was shown that glucocorticoids inhibit as well as stimulate lecithin synthesis in the fetal lung. Equivalent doses of corticoids produce comparable results. It was established that the concentration necessary to produce an optimal stimulation of lecithin synthesis was 0.5 to 2.0 mg/kg body weight.

[Regarding the effect of bromhexine metabolite VII on lecithin synthesis in fetal lungs (author's transl)]. / Zur Wirkung von Bromhexine Metabolit VIII auf die Lezithinsynthese in der fetalen Lunge.

With the help of incorporated amounts of radioactively labeled choline, it was shown that bromhexine metabolite VIII in vivo (10 mg, 5 mg, 1 mg/kg body weight) and in vitro (100 microgram to 0,01 microgram/g fetal lung tissue) does not stimulate lecithin synthesis in fetal lungs of rats.

Immunmodulating cytokines induce term and preterm parturition.

The aim of our study was to investigate if cytokines, which are able to cause preterm delivery is case of intraamniotic infection, also participate in the mechanisms of normal term labor. Therefore we estimated cytokine concentrations in cercicovaginal secretions of 96 patients, divided into four different collectives. In collective A (women with spontaneous term labor) cytokine concentrations raised from a median level of 278 pg/ml for Il-1 beta and 263 pg/ml for Il-6 in early term labor to a median level of 3351 pg/ml for Il-1 beta and 39,442 pg/ml for Il-6 at complete cervical dilatation. TNF-alpha-exclusively appeared after spontaneous rupture of fetal membranes. In collective B and C (women with preterm rupture of fetal membranes) cytokine concentrations declined from a maximum level of 1425 pg/ml for TNF-alpha, 12,982 pg/ml for Il-1 beta and 29,727 pg/ml for Il-6 soon after preterm rupture of membranes to a minimum level of 93 pg/ml for TNF-alpha, 851 pg/ml for Il-1 beta and 780 pg/ml for Il-6 with remission of labor in case of successful tocolytic treatment. High concentrations reappeared with the onset of labor, unresponsive to tocolysis. In collective D (women with intact membranes) TNF-alpha was not detectable and Il-1 beta and II-6 appeared exclusively in the presence of labor. Our results suggest, that normal term labor may be controlled by biochemical processes, similar to infection-associated signal transduction, which is commonly accepted to induce preterm labor.

Signal for term parturition is of trophoblast and therefore of fetal origin.

Up to now we know, that cytokines are key intermediates in the mechanisms, responsible for intrauterine activation in case of intra amniotic infection. The aim of our study was to investigate the role of cytokine- and prostaglandin production in normal term labor. Release of Il-6, Il-1 beta, TNF-alpha, PGE2, PGF2 alpha, was monitored in vaginal secretions originating from uterine cavity, cervix and vagina during normal course of labor. Cells from fetal membranes, decidua and villous trophoblast, obtained from placentas of patients after spontaneous delivery (n = 12), or without labor, after elective cesarean section (n = 12), were cultured, in order to identify cytokine and prostaglandin producing cells. In all cases, term labor and parturition was associated with strongly elevated cytokine- and prostaglandin concentrations in cervical secretions. Cell culture experiments clearly demonstrated, that cells from villous trophoblast, cultured after spontaneous delivery produced significantly more cytokines and prostaglandins than cells form villous trophoblast, cultured after elective cesarean section. Cells from fetal membranes also produced more Il-6 and PGE2 after labor. In contrast to that, cells from decidua produced similar amounts of cytokines and prostaglandins before and after spontaneous term labor. Therefore we conclude, that the signal for term labor and delivery is of trophoblast and so of fetal origin.

[Diagnosis of fetal ovarian cysts. Follow-up or differential diagnosis?]. / Diagnostik fetaler Ovarialzysten. Kontrolle oder differenzierte Abklärung?

AIM: To find better diagnostic and prognostic criteria for the prenatal evaluation of suspected fetal ovarian cysts. METHOD: 13 abdominal tumors were diagnosed sonographically and evaluated. The ultrasound equipment was an Acuson Computer Sonograph XP 128 with 3.5 MHz sector transducer (Acuson) and a realtime-ultrasound machine Sonoline SL 1 with 3 MHz linear transducer (Siemens). Picture documentation was made by Agfa Scopix camera, Sony printer documentation UPS or Panasonic video documentation VHS. If a cyst was aspirated, hormonal concentrations were measured by RIA (Radioimmunoassay). Protein levels electrolytes were also analysed and cytology performed. RESULTS: Fetal ovarian cysts are rare connatal abdominal tumours of unknown pathogenesis. Typical sonographic findings are cystic structures, partially septated with homogenous inner structures and sharp outer contours. Their ovarian origin is documented by demonstrating high hormonal activity (estrogen, progestin, testosterone). Sonographic structural variations may hint at tissue trauma or a rare fetal teratoma. CONCLUSIONS: Ultrasound guided cyst puncture with fluid analysis is helpful in the differential diagnose of suspected fetal ovarian cysts. This approach will also help avoid obstetric procedures with possible prematurity complications and post-delivery abdominal surgery. Ultrasound can be used for monitor clinically asymptomatic, uncomplicated cysts, both pre- and postnatally to avoid removal of normal ovarian tissue.