Identification by flow cytometry of the prostaglandin-producing cell populations of term human decidua.

Human term decidua produces prostaglandins (PGs) which have been implicated in the initiation of human parturition. Using flow cytometry to isolate pure cell populations, we have investigated the cell types responsible for decidual PG production. Cell dispersions were prepared enzymatically from decidua vera isolated from term placentae, and were incubated in Dulbecco's Modified Eagle's Medium containing 0.25% bovine serum albumin at 37 degrees C. PGF2 alpha and PGE2 output were measured by radioimmunoassay of the conditioned medium. Production of PGF2 alpha (fmol/10(6) cells per 3 h) exceeded that of PGE2 at 273 (108-322) versus 97 (38-127) respectively (median (range]. The decidual cell dispersions were then incubated with monoclonal antibodies (anti-CD45 which labels the leukocyte common antigen or anti-human leukocyte antigen class II (HLA-DR) which is specific for macrophages in this tissue) and sorted by flow cytometry. The resultant antibody-positive and -negative cell populations were incubated and PG production was measured. Controls showed that antibody labelling and sorting did not alter PG production. PGF2 alpha and PGE2 output by bone marrow-derived (CD45-positive) cell populations exceeded that of non-bone marrow-derived (CD45-negative) cells. Furthermore, we were able to demonstrate that the HLA-DR-positive macrophage population had the highest PGF2 alpha and PGE2 production rates in human term decidua in vitro.

Experience with the first 250 endometrial resections for menorrhagia.

234 patients with menorrhagia were treated hysteroscopically by transcervical resection of the endometrium (TCRE) instead of hysterectomy. 250 procedures were performed under general anaesthesia (63%) or under sedation plus local anaesthesia (38%). The endometrium was excised either totally (91%) or partially (9%) in all but one case, and 56 (22%) of the patients underwent simultaneous resection of submucous fibroids. Surgical time (range 10-100 min) varied with the gynaecologist's experience. 479 ml was the average volume of uterine irrigant absorbed by the patient. Blood loss was usually slight. Operative complications were uncommon, but 4 (2%) women sustained a uterine perforation (without serious sequelae), 7 (3%) absorbed more than 2 litres of fluid, and 1 required tamponade to control postoperative bleeding. Hospital stay was short and full recovery usual by 1-2 weeks. Menstrual symptoms improved in over 90% of the patients throughout the follow-up of up to 2 1/2 years; 27-42% of the women became amenorrhoeic at some time after total TCRE. Results were best in women greater than 35 years of age, but was not influenced by the presence of fibroids or pretreatment dysmenorrhoea. 10 (4%) women later underwent hysterectomy. Hysteroscopy 3 and 12 months after surgery revealed a small, fibrotic uterine cavity in the majority.

The redistribution of the blood flow under nifedipine treatment in the sheep foetuses.

The Ca(++)-antagonist nifedipine has been successfully employed in the treatment of non-gravid hypertension, and was found to inhibit uterine contractions in the perimenstrual period, as well as during premature labour in animal models. The use of antihypertensive drugs in pregnancy introduces the possibility of iatrogenic foetal distress. It has been established that nifedipine crosses the placental barrier in the sheep and causes a fall in mean arterial pressure and tachycardia in both the ewe and the foetus. This paper examines the effects of nifedipine on the foetus when administered to the pregnant ewe. Catheters and electrodes were implanted by surgical procedures in 15 ewes and foetal lambs between days 118 and 122 of gestation. The redistribution of foetal blood flow was measured by the radioactive microsphere injection technique. The infusion of nifedipine caused a 9% increase in the combined ventricular output (CVO) from 446 to 509 ml/min/kg in the foetus. Foetal lung blood flow increased from 29 +/- 6 to 69 +/- 14 ml/min/kg while figures for the skeletal muscle flow were 109 +/- 34 and 141 +/- 41.6 ml/min/kg. Heart and brain blood flow, expressed as percentages of CVO showed variations of 4.3 and 5.6 percent, respectively. Blood flow in the gut, placental membranes, skin, kidney and spleen was reduced. The present results show that nifedipine, in addition to its known effects causes a redistribution of the foetal circulation.

Effects of prostaglandin E2 on the newborn respiratory system.

To test the hypothesis that prostaglandin (PG) E2 is a respiratory depressant in the newborn lamb, 12 chronically catheterized, unanesthetized lambs (age 2 to 6 days) were infused with progressively increasing doses of PGE2 (0.1, 0.5, 1.0 and 5.0 ug/kg/min: 30 min for each dose) into the ascending aorta. PGE2 caused significant, progressive decrease in ventilation (due to decreased tidal volume and breathing rate) heart rate, blood pressure and percent of the time spent in low voltage electrocortical activity (LVA). PGE2 also caused respiratory acidosis, hypoxemia and increased frequency and duration of apneic events (greater than 3 sec). During the infusion, there was a dose related increase in plasma concentration of PGE2. At 30 min post-infusion, all measured variables showed recovery, although arterial pH carbon dioxide tension and plasma PGE2 remained significantly different from control values and the percent time in LVA was even higher than during control. Infusion of the vehicle alone (n = 5) caused no significant changes in any of the measured variables. The results, taken in combination with previous fetal studies, indicate that PGE2 has marked inhibitory effects on breathing movements both before and after birth.

Gestrinone in the treatment of menorrhagia.

The role of gestrinone, 2.5 mg twice weekly, in treating proven menorrhagia (greater than 80 ml) was examined in 19 women. They were treated for five cycles (2 placebo, 3 active), taking one capsule twice weekly. Placebo had no effect on menstrual blood loss (MBL). On gestrinone 10 women became amenorrhoeic, in five MBL was markedly reduced (5-74 ml) and four did not respond. In three of the non-responders submucous leiomyomas were found at subsequent hysterectomy. Follow-up periods showed a persistent reduction in MBL for nine women in the first post-treatment menstruation.

Placental leukotriene B4 release in early pregnancy and in term and preterm labour.

The production of leukotriene B4 (LTB4) by the human placenta in vitro was measured by radioimmunoassay. In early pregnancy (7-12 weeks gestation) LTB4 production rate (pmol/mg dry weight/2 h) was 3.7 (2.6-4.7) (median and range; n = 9) and at term it was 0.7 (0.4-2.3; n = 10) in placental tissue obtained at elective caesarean section, and 2.7 (1.3-3.6; n = 10) in samples following labour of spontaneous onset and vaginal delivery. In spontaneous preterm labour (26-36 weeks gestation) with normal placental histology LTB4 production was 0.7 (0.3-1.7; n = 14), but it was significantly higher in preterm placentas with inflammatory infiltration: 3.1 (0.8-4.8; n = 6). These data show that the production of LTB4 by human placenta is high in early pregnancy, but remains low during the third trimester, with a significant increase in spontaneous labour at term. LTB4 output is low in uncomplicated preterm labour but markedly increased in chorioamnionitis-associated preterm labour.

Prostaglandin E production by the fetal membranes in unexplained preterm labour and preterm labour associated with chorioamnionitis.

The production of prostaglandin E (PGE) by amnion, choriodecidua and placenta was measured in 45 women delivered after spontaneous preterm labour, in 10 women delivered electively preterm, in 30 women at elective caesarean section at term, and in 28 women after spontaneous labour at term. In the preterm labour group 24 women had normal placental histology, and gestational age was 34 (31-36) weeks (median and range); 18 women had evidence of chorioamnionitis and gestational age was significantly shorter, 30 (24-36) weeks; three other patients had placental abruption. In the absence of inflammatory infiltration of these tissues the highest PGE output (fmol/mg dry weight/2 h) was found after labour at term and the lowest after uncomplicated preterm labour: 2640 (360-15,580) (median and range) compared with 1414 (164-11,045) in amnion, 677 (100-3245) compared with 308 (39-1086) in choriodecidua, and 1200 (520-3022) compared with 578 (150-1859) in placenta, respectively. Tissues showing chorioamnionitis produced much higher outputs of PGE from amnion (12,278, 1799-82,617) and from choriodecidua (1018, 216-11,768), but not from placenta (616, 89-4131). Chorioamnionitis seems to cause very early preterm labour by increasing PG production in the amnion and choriodecidua.

The early diagnosis of impending premature labour.

Early diagnosis of impending premature labour offers the possibility of early and effective tocolysis. This paper reviews recent work which has suggested that excessive uterine contractility or early cervical dilatation during pregnancy would provide this early diagnosis. Since marked uterine contractility and cervical dilatation can occur in pregnancy which proceeds to term, however, these features may not be specific enough predictors of preterm labour for clinical use. The evidence is also reviewed that the presence or absence of fetal breathing movements (FBM) predicts the outcome of preterm labour. This finding has now been confirmed in four centres outside Oxford. For women admitted in preterm labour, an expertly performed real-time ultrasound scan has now become an essential investigation. Since more than 50% of preterm 'labours' appear to subside spontaneously without tocolysis, a knowledge of the presence or absence of FBM should avoid unnecessary treatment and ensure that clinical efforts are concentrated on patients most in need.

Managing gynaecological emergencies with laparoscopy.

A consecutive series of 49 women (50 procedures), whose conditions were haemodynamically stable, presenting with acute lower abdominal pain, pelvic tenderness, and either a urine concentration of greater than 50 U/l beta human chorionic gonadotrophin or a pelvic mass shown by ultrasonography were treated with operative laparoscopy under video monitoring (videopelviscopy) as an alternative to laparotomy. Ectopic pregnancy, ovarian and non-ovarian cysts, pelvic adhesions, endometriosis, and fibroids were found, for which salpingotomy, salpingectomy and salpingo-oophorectomy, cystectomy, adhesiolysis, thermocoagulation, and myomectomy were carried out by laparoscopy. In one patient pelviscopy was repeated because of persistent tubal pregnancy after the fimbria was expressed. Laparotomies were carried out on three patients because treatment was not possible by laparoscopy and on a further patient two days after adhesiolysis had been attempted. These were the only serious complications. For the 46 cases (45 patients) in which operative laparoscopy was successful the mean stay in hospital was 1.9 days after operation, and this group of patients returned to normal activities and to work after an average of 2.3 and 2.6 weeks respectively. Most gynaecological emergencies that are managed by laparotomy can be treated by laparoscopy and benefit both patients and the health service.

Transcervical resection of endometrium in women with menorrhagia.

As an alternative to hysterectomy 16 women with menorrhagia were treated with hysteroscopic transcervical resection of the endometrium with an unmodified urological resectoscope. Twelve patients requested total resection of the endometrial lining with the intention of producing amenorrhoea, and four chose partial resection and hypomenorrhoea. Surgery was completed successfully in 15; the remaining woman, who had an acutely retroflexed uterus, sustained a uterine perforation during insertion of the rigid hysteroscope. There were no important postoperative complications, and 13 patients were discharged from hospital the day after operation. Follow up for up to six months showed beneficial effects on the duration of menses and the subjective assessment of menstrual blood loss and pain in the treated women, six of them becoming amenorrhoeic after total resection. Hysteroscopy at three months in 13 patients showed fibrosis confined to the upper half of the uterine cavity. Endouterine biopsy specimens showed the presence of microscopic deposits of normal endometrium in 10 women. Although these results are preliminary, transcervical resection of the endometrium may have an important role in managing this common complaint.

Are leukotrienes involved in human uterine contractility?

The effects of leukotrienes (LT) on the contractility of human and rat myometrial strips in vitro were compared with the effects of prostaglandins (PGs) and oxytocin. Preparations of human myometrial membranes were investigated for the presence and characteristics of LTC4 receptors. Neither the peptido-leukotrienes (LTC4, LTD4, LTE4) nor LTB4 had any consistent effect, stimulatory or inhibitory, on human pregnant or non-pregnant myometrium, at doses up to 1.25 microM; nor did they have any effect in rat non-pregnant myometrium. As expected, PGE2, PGF2 alpha (0.3 microM) and oxytocin (5 nM) stimulated human pregnant myometrium. PGF2 alpha stimulated and PGE2 inhibited human non-pregnant myometrium but oxytocin had no effect; all three compounds stimulated rat non-pregnant myometrium. The binding of 3H-LTC4 to human myometrium was specific (LTC4 greater than LTD4 much greater than LTE4, LTB4, PGE2, PGF2 alpha, arachidonic acid) but of low affinity compared with the binding of 3H-PGE2 to the same membrane preparations. These data support the view that leukotrienes have little direct influence on myometrial contractility.

Effect of lipid and protein fractions from fetal pulmonary surfactant on prostaglandin E production by a human amnion cell line.

Discs of amnion and choriodecidua prepared from women delivered at term were incubated with and without surfactant prepared from human amniotic fluid and the output of prostaglandin E (PGE) was estimated by radioimmunoassay. Surfactant stimulated the release of PGE in both tissues. The stimulatory effect was characterized further using cultured human amnion cells. The effect was dose- and time-dependent and required for full expression both protein and lipid components of surfactant. Arachidonate constituted about 3.5% of the fatty acids of fetal surfactant phospholipids. These findings suggest that surfactant is an important source of arachidonate for intrauterine PG synthesis.

Surfactant stimulates prostaglandin E production in human amnion.

Discs of human amnion prepared from nine women delivered by elective caesarean section at term were incubated with and without purified human amniotic fluid surfactant (9 micrograms lipid P/ml), and the output of prostaglandin E (PGE) was estimated by radioimmunoassay. Surfactant stimulated the release of PGE from 3.8 (SD 2.9) to 5.4 (SD 2.5) pmol/mg dry weight/3 h (P less than 0.01). Arachidonic acid accounted for 2% of the fatty acids of surfactant lecithin. These results show that surfactant has a stimulatory effect on amniotic PGE production and that it is an important source of arachidonic acid in amniotic fluid.