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Factors affecting neonatal jaundice.

Plasma bilirubin was estimated on 690 term infants on about the 6th day of life. Perinatal factors were recorded and the results analysed. Hyperbilirubinaemia was defined as a level greater than 205 micromol/1 (12 mg/100 ml) and this was present in 20% of cases. Three factors--epidural analgesia, breast feeding, and poor weight recovery--showed highly significant associations with jaundice. The relative importance of these is discussed and compared with recent reports. Induction of labour, for reasons other than postmaturity, and a gestational age less than 39 weeks showed a slightly increased incidence of jaundice. There was no correlation with other factors tested including oxytocic drug administration. Despite the high incidence (20%) of hyperbilirubinaemia, only 2.5% infants needed treatment and none required exchange transfusion. Radical changes in obstetric management or infant feeding are not indicated.

Anesthesia, Epidural↗

Oxytocin release by infused prostaglandin.

Plasma oxytocin levels were measured serially in 22 women receiving prostaglandin E(2) or F(2alpha) intravenously for the induction of labour. Oxytocin was detected in the plasma of 19 of the 22 women; positive levels were found in 60 (43%) of 139 plasma samples, an incidence similar to that in the late first stage of spontaneous labour. Oxytocin was found in the maternal plasma even when the fetus was dead, and in the plasma of two men receiving prostaglandin infusions. This indicates that prostaglandins stimulate the pituitary directly and suggests that this mechanism may play a part in the oxytocic action of infused prostaglandins.

Female↗

Ambulation in labour.

In a randomised prospective study of 68 women in spontaneous labour half were allocated to an ambulant group and half to a recumbent group. The duration of labour was significantly shorter, the need for analgesia significantly less, and the incidence of fetal heart abnormalities significantly smaller in the ambulant group than in the recumbent group. Apgar scores at one and five minutes were also significantly greater in the ambulant group. More patients in the recumbent group required augmentations with oxytocic drugs. There was no statistically significant difference in the third stage loss in the two groups. Ambulation in labour should be encouraged: it may bring human benefits while allowing the advantages of hospital supervision.

Adolescent↗

Treatment of acute massive pulmonary embolism by streptokinase during labour and delivery.

A 29-year-old woman sustained an acute massive pulmonary embolism in the 32nd week of pregnancy. Rapid clinical improvement followed the use of streptokinase. Treatment was continued for 41 hours, including labour and the first three hours after delivery. There was slow but severe postpartum haemorrhage. Partial uterine atony occurred, and may have been due, at least in part, to fibrin degradation products arising from thrombolysis. No adverse effects were noted in the baby.Our experience suggests that streptokinase may be given during labour but that an oxytocic agent may be needed; and that reversal of fibrinolysis before delivery is best achieved by the use of aprotinin (Trasylol) rather than aminocaproic acid.

Acute Disease↗

[3H]-[Thr4,Gly7]OT: a highly selective ligand for central and peripheral OT receptors.

Oxytocin receptors in rat hippocampal synaptic plasma membranes were compared with mammary gland and uterine oxytocin receptors. For this purpose, a highly specific oxytocic agonist [Thr4,Gly7]oxytocin was tritiated. We demonstrated that this ligand labels oxytocin receptors selectively. Scatchard analyses revealed a high affinity for all the oxytocin receptors investigated, with equilibrium dissociation constants between 1.0 and 2.0 nM. Binding appeared to take place at a single population of receptor sites. Competition experiments confirmed the high affinity of arginine vasopressin for hippocampal oxytocin receptors but also revealed that mammary gland and uterine oxytocin receptors do not discriminate more efficiently between oxytocin and arginine vasopressin. This lack in specificity is not affected by applying different concentrations of Mg ions.

Animals↗

Hemodynamic effects of neurohypophyseal peptides with antidiuretic activity in dogs.

Arginine vasopressin (AVP) is known to produce increases in total peripheral resistance (TPR) and mean arterial pressure (MAP) and decreases in heart rate (HR), cardiac output (CO), and plasma renin activity (PRA). Some recent observations with AVP and synthetic analogues have suggested that under certain conditions, AVP can induce cardiovascular and reninsecretory responses in the opposite directions. To characterize the receptors mediating these responses, the effects of AVP, oxytocin, and synthetic neurohypophyseal analogues with specific antidiuretic, vasoconstrictor, or oxytocic activities were studied in conscious dogs. AVP and 2-phenylalanine-8-ornithine-oxytocin (Phe2Orn8OT, a selective vasoconstrictor agonist) produced similar responses when infused at 10 ng X kg-1 X min-1. That is, TPR and MAP increased, and CO, HR, and PRA decreased. Pretreatment with a selective vasoconstrictor antagonist, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid) 2-(O-methyl)tyrosine]AVP, abbreviated d(CH2)5Tyr(Me)-AVP (10 micrograms/kg), blocked the actions of Phe2Orn8OT. However, in the presence of d(CH2)5Tyr(Me)AVP, AVP actually decreased TPR and increased CO, HR, and PRA. An analogue with selective antidiuretic activity, 4-valine-8-D-AVP (VDAVP, 10 ng X kg-1 X min-1), produced the same effects as the combination of vasopressin plus d(CH2)5Tyr(Me)AVP. Neither the effects of VDAVP nor of AVP plus antagonist were blocked by propranolol (1 mg/kg). These data indicate that vasopressin, by its antidiuretic activity, produces cardiovascular effects that are opposite to many of those produced by its vasoconstrictor action and that these effects are not dependent on mediation by beta-adrenoceptors.

Animals↗

Antidiuretic peptide in mammalian choroid plexus.

Lyophilized bovine, porcine, and human choroid plexuses contain .02-.09 U of antidiuretic activity per milligram. The antidiuretic factor in bovine choroid plexus was concentrated 100 times by extraction with acetic acid, fractional precipitation with acetone and ethyl ether, gel filtration, and paper chromatography. Resulting choroid plexus fraction IIgammaB2 was eluted from Sephadex G-25 in position corresponding to molecular weight between 750 and 3,500; its antidiuretic activity was destroyed by trypsin, performic acid, and thioglycollic acid, but was not affected by leucine aminopeptidase, carboxypeptidase A or B, or cyanogen bromide. HgammaB2 possesses antidiuretic, pressor, and oxytocic potencies (measured in anesthetized-hydrated rat, anesthetized rat, and isolated rat uterus, respectively) of 1.9, 0.5, and 0.1 U/mg, respectively.

Aminopeptidases↗

Avian postovulatory follicle homogenate effect on the genital tract motility.

The recently ruptured follicles of the avian ovaries were found to contain an oxytocic substance. The substance was found to be heat-labile, nondialyzable and not extractable by lipid solvents. The crude homogenate stimulated the frequency and amplitude of the chicken infundibulum, uterus and uterovaginal junction, if they were taken from hens 2 h before predicted oviposition. The homogenate was found to induce premature oviposition and to stimulate the uterine contractions of rats treated with progesterone. Uterine tissues taken from estrogen-treated rats either did not respond to the homogenate or were inhibited. Addition of phenoxybenzamine or propanolol did not inhibit the stimulatory effect of the homogenate. It is possible that this factor might be involved in regulating oviposition in the hen.

Animals↗

Contractile effects of endothelin 1 and endothelin 3 on myometrium and small intramyometrial arteries of pregnant women at term.

This in vitro study was undertaken to investigate the effects of endothelin 1 (ET-1) and endothelin 3 (ET-3) on intramyometrial arteries and myometrial tissue of the uterus from pregnant women at term. Segments of small myometrial arteries (outer diameter 100-500 microns) obtained at cesarean section were isolated and mounted in tissue chambers. The effect of ET-1 and ET-3 on isometric tension was compared with the action of noradrenaline. In similar experiments on myometrial strips, the effect of ET-1 and ET-3 was studied in comparison with oxytocin. ET-1 and ET-3 both produced contractions of arteries and myometrial strips, ET-1 being the most potent. The response of ET-1 was more powerful than the effect of the reference compounds, i.e. noradrenaline with regard to myometrial arteries and oxytocin with regard to the myometrium. It is concluded that endothelins are powerful constrictors of myometrial arteries from pregnant women and possess strong oxytocic effects. In particular, ET-1 could be involved in the regulation of myometrial contractility and/or uteroplacental blood flow.

Adult↗

Comparison between the influence of methylergometrine and oxytocin on the incidence of retained placenta in the third stage of labour.

Twenty randomly selected birth centres were questioned about their oxytocic use in the third stage of labour and incidence of retained placenta in relation to the number of vaginal deliveries during 1987. Ten centres used either methylergometrine or oxytocin routinely. Of 6,906 vaginal deliveries treated with 0.2 mg methylergometrine immediately after birth, 187 (2.7%) were complicated by retained placenta. Significantly fewer (p less than 0.001) of the 10,680 vaginal deliveries treated with 5-10 IU oxytocin were complicated by retained placenta (n = 192; 1.8%).

Cesarean Section↗

A randomised controlled trial of an oral solution of prostaglandin E2 and oral oxytocin used immediately after low amniotomy for induction of labour in the presence of a favourable cervix.

A randomised controlled trial was carried out in 50 primigravidae and 50 multigravidae to compare the effectiveness in induction of labour after low amniotomy of prostaglandin E2, given as an oral solution, and oxytocin, given as buccal tablets. The results showed that in dosages recommended by the manufacturers, both oxytocic preparations were almost equally effective. With oral oxytocin, once labour had been established and dosage was left to the discretion of the staff, there appeared to be a potentially dangerous tendency to continue giving large doses despite adequate uterine contractions. The authors comment that this was probably the reason why oxytocin-treated multigravidae having normal deliveries within 24 hours had labours significantly shorter on average than those of other successfully induced patients.

Administration, Oral↗

Misoprostol for treating postpartum haemorrhage: a randomized controlled trial [ISRCTN72263357].

BACKGROUND: Postpartum haemorrhage remains an important cause of maternal death despite treatment with conventional therapy. Uncontrolled studies and one randomised comparison with conventional oxytocics have reported dramatic effects with high-dose misoprostol, usually given rectally, for treatment of postpartum haemorrhage, but this has not been evaluated in a placebo-controlled trial. METHODS: The study was conducted at East London Hospital Complex, Tembisa and Chris Hani Baragwanath Hospitals, South Africa. Routine active management of the third stage of labour was practised. Women with more than usual postpartum bleeding thought to be related to inadequate uterine contraction were invited to participate, and to sign informed consent. All routine treatment was given from a special 'Postpartum Haemorrhage Trolley'. In addition, participants who consented were enrolled by drawing the next in a series of randomised treatment packs containing either misoprostol 5 x 200 microg or similar placebo, which were given 1 orally, 2 sublingually and 2 rectally. RESULTS: With misoprostol there was a trend to reduced blood loss >/=500 ml in 1 hour after enrolment measured in a flat plastic 'fracture bedpan', the primary outcome (6/117 vs 11/120, relative risk 0.56; 95% confidence interval 0.21 to 1.46). There was no difference in mean blood loss or haemoglobin level on day 1 after birth < 6 g/dl or blood transfusion. Side-effects were increased, namely shivering (63/116 vs 30/118; 2.14, 1.50 to 3.04) and pyrexia > 38.5 degrees C (11/114 vs 2/118; 5.69, 1.29 to 25). In the misoprostol group 3 women underwent hysterectomy of whom 1 died, and there were 2 further maternal deaths. CONCLUSIONS: Because of a lower than expected incidence of the primary outcome in the placebo group, the study was underpowered. We could not confirm the dramatic effect of misoprostol reported in several unblinded studies, but the results do not exclude a clinically important effect. Larger studies are needed to assess substantive outcomes and risks before misoprostol enters routine use.

Journal Article↗

Steroid sulfatase deficiency.

Placental steroid sulfatase deficiency is a genetic disorder only recently reported in the medical literature. Most documented cases of placental sulfatase deficiency have been marked by delay in onset of labor, lack of cervical dilatation, and relative refractoriness of oxytocic agents and amniotomy. We have studied the placenta, cultured fibroblasts, and amniotic fluid cells from an affected patient. The activities of estrone sulfatase, pregnenolone sulfatase, dehydroepiandrosterone sulfatase, and arylsulfatase C in the placenta from the patient were severely deficient. Arylsulfatases A and B were present at levels within the normal range for this tissue. Fibroblast dehydroepiandrosterone sulfatase activity was virtually absent in the patient's cells and present at normal levels in individuals with a variety of lysosomal disorders. It would thus appear that the mutation responsible for steroid sulfatase deficiency is genetically and biochemically distinct from those involved in the lysosomal sulfatase deficiency states. The cell culture studies further suggest that the defect is a generalized one which should be detectable in midtrimester of pregnancy and may have phenotypic consequences in later postnatal life.

Estriol↗

In vivo adrenocorticotropin-releasing activity of neurohypophyseal hormones and their analogs.

The ability of 21 neurohypophyseal hormones and related synthetic peptides to raise plasma ACTH or corticosterone concentrations was studied in female rats anesthetized with chlorpromazine, morphine, and pentobarbital. Corticotropin-releasing factor (CRF) activity was significantly correlated with pressor but not with antidiuretic or oxytocic activity. However, peptides with little or no pressor but very potent antidiuretic activity had weak CRF activity if given in a dose greater than 4 antidiuretic units/100 g BW; the dose-response slopes of these analogs were significantly flatter than that of arginine vasopressin. Pretreatment with antagonists with antipressor but not antiantidiuretic activity consistently reduced the CRF activity of the analogs with potent pressor activity. We conclude that the CRF activity of the neurohypophyseal hormones is primarily related to pressor activity.

Adrenocorticotropic Hormone↗

Identification and characterization of arginine vasopressin receptors in the rat testis.

We have previously shown that arginine vasopressin (AVP) directly inhibits testicular steroidogenesis in vitro. In the present study, binding of neurohypophysial peptides to interstitial cells of the rat testis was studied using [3H]AVP as the ligand. Interstitial cells were obtained from adult rat testis after collagenase dispersion and were incubated with [3H]AVP in the presence or absence of unlabeled AVP. Binding equilibrium was reached by 60 min at 4 C, while incubation at higher temperatures (23 and 37 C) resulted in an apparent decrease in binding. Scatchard plot analysis of equilibrium binding data revealed the existence of one class of high affinity, low capacity binding sites (Kd = 1.0 +/- 0.3 nM; maximal binding = 8.5 fmol/10(6) cells). In addition, the rate constants of association and dissociation were calculated to be 0.024 nM-1 min-1 and 0.009 min-1, respectively. Addition of naturally occurring neurohypophysial hormones as well as their synthetic analogs inhibited [3H]AVP binding to testis cells, resulting in parallel displacement curves. The order of potencies for the native peptides was: AVP = lysine vasopressin = arginine vasotocin (IC50, 5 X 10(-10) M) greater than oxytocin = mesotocin (IC50, 4 X 10(-7) M) greater than isotocin = glumitocin (IC50 greater than 10(-6) M). Furthermore, two potent vasopressor antagonists, d(CH2)5Tyr(Me)AVP ([1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine]AVP) and dPTyr(Me)AVP ([1-deaminopenicillamine-2-(O-methyl)tyrosine]AVP) competed for [3H]AVP binding with a higher affinity (IC50, approximately 10(-11) M) than native AVP. In contrast, a selective antidiuretic agonist, dDAVP (1-deamino-8-D-AVP), only competed weakly for receptor binding, while a specific oxytocic agonist, (Thr4,Gly7)oxytocin, did not affect AVP binding. These results suggested that the testis may contain the V1 receptor subtype. Studies on the intratesticular distribution of AVP receptors indicated minimal binding to cells derived from the seminiferous tubule, while most of the AVP-binding sites sediment with enriched fractions of Leydig cells after Metrizamide density gradient centrifugation. AVP-binding sites were also found in rat liver, kidney, and anterior pituitary (10.7, 2.6, and 1.7 fmol/mg protein), whereas adrenal, cerebellum, prostate, and hypothalamus were devoid of AVP-binding sites. Thus, we have demonstrated the presence of high affinity, stereospecific receptors for AVP in the interstitial cell compartment of the rat testis. These V1 receptors may mediate the direct inhibitory action of neurohypophysial hormones on testicular Leydig cell steroidogenesis.

Animals↗

Differential regulation of contractility and nitric oxide sensitivity in gravid and nongravid myometrium during late pregnancy in a marsupial.

Marsupials have two anatomically separate uteri; and in macropodids (kangaroos and wallabies), there is a single ovulation from alternate ovaries in each cycle. During late pregnancy, the two uteri are differentially regulated by local hormonal influences from the corpus luteum, the fetus, and placenta on one side and by the developing Graafian follicle on the other. In this study, we report striking differences in contractile behavior of nongravid and gravid myometrium from the tammar wallaby (Macropus eugenii) in late pregnancy and immediately post partum. Nongravid myometrium, from the uterus ipsilateral to a Graafian follicle, was spontaneously active but unresponsive to the oxytocic peptide mesotocin and the smooth muscle relaxant nitric oxide. Myometrium from the contralateral, gravid uterus, which contained a conceptus and was associated with an active corpus luteum, was not spontaneously active. Gravid myometrium became increasingly sensitive to mesotocin stimulation as pregnancy progressed, and nitric oxide induced marked relaxation at all stages examined, by a guanylyl-cyclase mediated pathway. These results provide further evidence that the two uteri of marsupials are under differential control, suggesting that local endocrine and paracrine influences, derived from the ovaries, the fetus, and placenta, can regulate concurrent but distinct physiological responses in the reproductive tracts of these mammals.

Animals↗

Management of a parturient with cardiac valve prosthesis.

The parturient with a cardiac valve prosthesis presents a twofold problem of management: (1) that of a rising cardiac workload in the presence of serious heart disease, and (2) that of chronic anticoagulant therapy. Pain relief, a shortened 2nd stage of labor, and avoidance of bearing-down efforts reduce stress. Vaginal delivery is preferred to cesarean section, and segmental lumbar extradural block is the optimal anesthetic method. Oxytocics must be used with caution and heparin is preferred to longacting oral anticoagulants.

Adult↗

Characterization of renin-like activity in human plasma protein IV-4 fraction.

Cohn's fraction IV-4 of human plasma protein generates by itself a substance with slight pressor activity when incubted without any additives. This renin-like activity was readily inactivated by alkaline treatment. Furthermore, the generated pressor substance, when purified, was found very similar to [Aspl]-[Ile5]-angiotensin-I in the following characteristics; 1) heat-stability, 2) dializability, 3) inactivation by trypsin, 4) Rf value and 5) electrophoretic mobility at various pHs, 6) marked enhancement in pressor and oxytocic activities after incubation with normal human plasma or rabbit's lung extract, and 7) cross reactivity with [AspI]-[Ile5]-angiotensin-I in radioimmunoassay. It is concluded that renin-like activity in the preparation of fraction IV-4 of human plasma protein must be renin or an extremely similar enzyme.

Blood Proteins↗