Jens Lyndrup

Inhibition of uterine contractions of premature labour with an oxytocin analogue. Results from a pilot study

Summary. A competitive inhibitor of the action of oxytocin on the uterus, l‐deamino‐2‐D‐Tyr‐(OEt)‐4‐Thr‐8‐Orn‐oxytocin, was studied for the first time in 13 patients with established, uncomplicated premature labour. Intravenous infusion of 10–100 μg/min of the analogue was given for 1–10 h and the effect was monitored by external cardiotoco‐graphy. In all women an inhibition of uterine activity was observed, and in the majority of patients infused with 25 μg/min and a total dose of about 5 mg or more of the drug total inhibition of uterine contractions was achieved. There were no effects on the maternal and fetal pulse rates, nor were there any other side‐effects. The results of this preliminary study support the concept of an increased concentration of uterine oxytocin receptors being aetiologically important in uncomplicated premature labour. They also suggest that the present oxytocin antagonist could be an interesting therapeutic alternative in the condition, primarily because of the marked selectivity of its effect.

Plasma oestrogens in postmenopausal women with endometrial cancer

Objective To study plasma levels of oestrogens and androgens, sex hormone‐binding globulin (SHBG) and follicle stimulating hormone (FSH) in postmenopausal patients with endometrial cancer.

Biochemical and immunohistochemical estrogen and progesterone receptors in adenomatous hyperplasia and endometrial carcinoma: Correlations with stage and other clinicopathologic features

Abstract OBJECTIVE: This study investigates clinicopathologic associations of estrogen and progesterone receptor content in endometrial carcinoma. STUDY DESIGN: One hundred fifty-two patients with endometrial cancer and 12 with adenomatous hyperplasia were included. Dextran-coated charcoal receptor assay and immunohistochemical analysis were used. The immunohistochemical analysis receptor content was estimated semiquantitatively by a total and a cancer immunohistochemical histologic score. Multiple regression analysis was used in testing independence of established correlations. RESULTS: Estrogen and progesterone receptor dextran-coated charcoal values and immunohistochemical histologic scores correlated inversely ( p p CONCLUSION: The inverse correlation between clinical stage of endometrial carcinoma and content of estrogen and progesterone receptors may reflect tumor biologic behavior.

The choice of a tocolytic for the treatment of preterm labor: a critical evaluation of nifedipine versus atosiban

Preterm birth is the major cause of neonatal mortality and morbidity in the developed world. The perfect tocolytic that is uniformly effective with complete fetomaternal safety does not exist. Tocolytic agents differ in cost, utero-specificity, safety, efficacy and whether they are licensed for use. The main three agents that are used worldwide are β-agonists, Ca2+ channel blockers and vasopressin/oxytocin receptor antagonists. β-Agonists are gradually being phased out of use and are being replaced by either nifedipine or atosiban. The evidence base for atosiban is strong but the evidence is of poor quality for nifedipine. The balance of evidence indicates that atosiban is as effective as nifedipine and more effective than β-agonists and is significantly safer than both. Atosiban was developed specifically to treat preterm labor, so the cost is higher than nifedipine or ritodrine. However, the cost of a course of atosiban (∼ £200) should not only be considered in comparison with other tocolytic agents but to other medical budgets (e.g., oncology, fertility, cardiology and psychiatry) and to the huge healthcare costs associated with the morbidity and mortality caused by preterm birth. Atosiban is a new advance in the management of spontaneous preterm labor.

Estrogen and progesterone receptors in endometrial carcinoma: comparison of immunohistochemical and biochemical analysis.

SummaryIn 159 endometrial carcinomas, estrogen (ER) and progesterone receptors (PR) were determined biochemically by dextran-coatcd charcoal (DCC) assay and immunohistochemically (ICA) on frozen sections. ICA receptor content was estimated by a total histologie score (HSCORE), including all tissue components, and by a cancer HSCORE, including malignant cells only. These scores were closely correlated. A single biopsy was found to be representative for each tumor. ER-DCC status was positive in 90.3% and PRDCC status in 92.2% of the tumors. ER total HSCORE was positive in 47% and PR total HSCORE in 89% of tumors. ER and PR correlated inversely with tumor grade (p < 0.001). Correlations were found between ER and PR content determined by either method (DCC: r = 0.77; ICA: r = O.SO), as well as between DCC and ICA content (ER: r = 0.52; PR: r = 0.76). The association between DCC and ICA was affected by the tumor grade: the DCC values decreased relatively more than total HSCOREs with increasing grade. The sensitivity of ICA against DCC assay was 56% for ER and 86% for PR. Maximal agreement between receptor status as determined by ICA and by DCC would result from a DCC cutoff level of 130 fmol/mg for ER and 114 fmol/mg for PR.

Predictive value of pelvic scores for induction of labor by local PGE2

The predictive value of pelvic scores, parity, age and gestational age for induction of labor by local prostaglandin-E2 (PGE2) was examined in 336 women attempting induction of labor by intracervical or vaginal PGE2. The patient characteristics were correlated to: (1) vaginal delivery within 48 h, (2) the period from induction to onset of labor (latency period), and (3) the duration of labor. The Bishop score (P < 0.01) and even more the Lange score (P < 0.0001) were significantly inversely correlated to both latency period and induction-delivery period. This was caused by cervical dilatation (P < 0.001), fetal station (P < 0.05) and cervical length (P < 0.05), whereas position and consistency of the cervix were of no importance. All three periods studied were significantly (P < 0.0001) shorter in parous women. In primiparous women, gestational age was of no importance for the latency period; however, higher gestational age was associated with longer labor (P < 0.001). We conclude that the predictive value of pelvic scores on induction hardly differs using local PGE2 compared to conventional methods; furthermore, the Bishop score should be substituted, disregarding position and consistency of the cervix, but putting more weight to cervical dilatation. A new pelvic score is proposed.

Cord entanglement in monoamniotic twin pregnancies.

Monoamniotic twin pregnancy involves a heavy risk of fatal umbilical cord entanglement. Two cases are reported. In the first case, both twins were found dead in the 36th week, and the monoamnionicity was recognized at birth. In the second case, the monoamnionicity was discovered during an ultrasound examination, and cord entanglement was suspected in the 35th week on the basis of a non-stress test (NST) with variable decelerations. Cesarean section was performed and two healthy children were delivered.

Progesterone receptor content in endometrial carcinoma correlates with serum levels of free estradiol.

Objective. To study a possible relationship between serum levels of estrogens and androgens and the tumor content of estrogen receptors and progesterone receptors in endometrial cancer.

Induction of labor by PGE2 and other local methods. Physiology, methods and guidelines for patient selection.

Local prostaglandin prostaglandin E2 (PGE,) i.e. applied transvaginally to cervix, ripens the cervix and induces myornetrial contractions (which also dissolves the cervix). Therefore, in this thesis, cervical ripening and myornetrial contractions are considered integrated parts of induction of labor aiming at a vaginal delivery. Furthermore, in comparison with induction by oxytocin, induction by local PGE? differs by exerting a direct ripening effect on the cervical connective tissue. Accordingly, the well-known impact of cervical conditions on inducibility might be different when using local PGE, rather than conventional methods.

Inhibition of Uterine Contractions of Premature Labour with an Oxytocin Analogue: Results from a Pilot Study

A competitive inhibitor of the action of oxytocin on the uterus, 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin, was studied for the first time in 13 patients with established, uncomplicated premature labour. Intravenous infusion of 10-100 micrograms/min of the analogue was given for 1-10 h and the effect was monitored by external cardiotocography. In all women an inhibition of uterine activity was observed, and in the majority of patients infused with 25 micrograms/min and a total dose of about 5 mg or more of the drug total inhibition of uterine contractions was achieved. There were no effects on the maternal and fetal pulse rates, nor were there any other side-effects. The results of this preliminary study support the concept of an increased concentration of uterine oxytocin receptors being aetiologically important in uncomplicated premature labour. They also suggest that the present oxytocin antagonist could be an interesting therapeutic alternative in the condition, primarily because of the marked selectivity of its effect.