[Epilepsy and pregnancy].
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Biomedical subjects
Publications and source records attributed to M J Keirse.
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The effects of treatment with the synthetic long-acting somatostatin analogue SMS-201-995 were studied in a patient with a fluid and electrolyte secreting villous adenoma of the rectum. The effects of SMS-201-995 on rectal fluid volume and electrolyte loss, and local and general prostanoid production were compared with those of treatment with indomethacin. During treatment with the somatostatin analogue iso-osmolar rectal fluid production increased about 25%; the quantity of prostaglandin E2 in the rectal fluid rose almost 20-fold. Prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha and 13,14-dihydro-15-keto-prostaglandin F2 alpha output showed similar, though less impressive increments during somatostatin treatment. The somatostatin analogue did not affect urinary prostanoid excretion except for levels of 2,3-dinor-thromboxane B2, which doubled. With indomethacin treatment diurnal rectal fluid production dropped by about 50% and all prostanoids measured in urine and rectal fluid decreased below control values. It appears that the somatostatin analogue SMS-201-995 has a marked stimulatory effect on the in vivo prostanoid production by the villous adenoma. Perhaps this stimulation is not confined to the tumor only, but also affects thromboxane synthesis.
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We have recently demonstrated that corticotropin releasing hormone (CRH) potentiates the contractile response to oxytocin of human gestational myometrium, using a high flow microsuperfusion system and electrical field stimulation. We now report this potentiation to be equivalent to that of 1 nM prostaglandin F2 alpha (PGF2 alpha), while 10 nM PGF2 alpha did not potentiate the response to oxytocin. Prostaglandin E2 (PGE2) also showed no augmentation of the contraction force of the myometrium in response to oxytocin. The CRH potentiated response was inhibited by the lipoxygenase and cyclooxygenase inhibitor BW755C (1 microM) and by indomethacin (0.1 microM), but not by the lipoxygenase inhibitor BW4C (1 microM). Measurements of prostaglandins in the superfusate showed no significant trends. It is concluded that the potentiation of contraction force to oxytocin by CRH is dependent on prostaglandins, probably PGF2 alpha and that leukotrienes, generated via the lipoxygenase pathway are not involved.
We measured circulating angiotension II by radioimmunoassay in women with pregnancy-induced hypertension (n = 54), and compared these values with those obtained in women with normal pregnancy (n = 18) and in non pregnant women (n = 20). Pregnant women had statistically significantly higher plasma angiotensin II [mean (SD): 41.3 (12.6) pg/ml] than non-pregnant women [29.2 (11.3) pg/ml; P less than 0.004]. Angiotensin II concentrations in women with pregnancy-induced hypertension [mean (SD): 31.7 (16.2) pg/ml] were, on average, 25% lower than in normal pregnancy (P less than 0.003) and resembled those obtained in non-pregnant women. The lowest angiotensin II levels were found in women with more severe forms of pregnancy-induced hypertension, such as proteinuric or superimposed pregnancy-induced hypertension. Review of the published studies on angiotensin II and our data suggest that the conflict among studies on angiotensin II levels in pregnancy-induced hypertension is largely due to the heterogeneity of the study populations in the various reports.
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Individual angiotensin peptides were measured by a high pressure liquid chromatography-RIA (HPLC-RIA) technique in the plasma of 20 nonpregnant women, 17 women with normal pregnancy, and 49 with pregnancy-induced hypertension. Immunoreactive angiotensin-II (ANG-II) consisted mainly of ANG-(1-8) octapeptide (greater than 65%), variable proportions (15-25%) of ANG-(4-8) pentapeptide, and small to negligible proportions of ANG-(2-8) heptapeptide and ANG-(3-8) hexapeptide. Levels of ANG-(1-8) were significantly higher in women with normal pregnancy than in both nonpregnant women (P less than 0.0006) and women with pregnancy-induced hypertension (P less than 0.008); in the latter, levels were lower with increasing severity of disease. Levels of ANG-(4-8) were higher in women with normal pregnancy than in women with pregnancy-induced hypertension or nonpregnant women. When expressed as a proportion of ANG-(1-8) levels, however, ANG-(4-8) levels were not higher in normal pregnancy than in women with pregnancy-induced hypertension or nonpregnant women. It is concluded that the well known increase in ANG-II levels in normal pregnancy relates predominantly to the active ANG-(1-8) octapeptide and to a far lesser extent to the smaller ANG peptides. Similarly, lower ANG-II levels in pregnancy-induced hypertension relate predominantly to lower ANG-(1-8) levels.
Several studies indicate that prostaglandins and platelet activating factor (PAF) affect implantation of the embryo. Most studies relate to animal data on prostaglandin synthesis at the site of implantation and on prostaglandin production by blastocysts. The few experimental data available on human implantation suggest that prostaglandins and PAF behave similarly in man. A review of the literature on this subject suggests possible mechanisms for prostaglandin and PAF participation in the process of human implantation.
We conducted a systematic search of the world literature up to January 1, 1990 on the use of angiotensin-converting enzyme inhibitors for treatment of hypertension during pregnancy. A total of 25 publications reported 85 pregnancies in 81 women, including three twin pregnancies. Captopril had been used in 49, enalapril in 35, and both drugs in one of these pregnancies. The number of unbiased data are too limited to permit firm conclusions on teratogenicity, if any, of these agents. Contrary to earlier suggestions, we found no evidence that the use of these agents increases the likelihood of low weight for gestational age, respiratory distress syndrome, and/or persistent ductus arteriosus. Use of these agents in pregnancy can cause severe disturbance of fetal and neonatal renal function, such as oligohydramnios, pulmonary hypoplasia, and long-lasting neonatal anuria. Although the true incidence of these perinatal problems cannot be derived from the type of data hitherto available, there are strong suggestions that renal dysfunction is more common with the use of enalapril than with captopril. The frequency of serious perinatal complications is high enough to warrant extreme reluctance in prescribing angiotensin-converting enzyme inhibitors during pregnancy.
Semi-structured interviews were conducted with 49 women who had experienced stillbirth in 1987-1989. Only 55% were satisfied with the manner in which the first suspicion had been communicated to them, while 85% were satisfied with the communication at the time of the diagnosis. Opinions about care in the labour ward, while largely positive, indicate that lack of tact from an individual may cloud the entire perception of care. Although only 40% had expressed a desire to see the baby, the others were happy to have been persuaded to do so and all were positive about the contact with the dead baby. Of 42 women (86%) who gave consent for autopsy, only one regretted this decision. Support received post partum was considered to be inadequate or insufficient by 10%. Despite the short hospital stay (average 1 day), most women afterwards felt that they would have preferred to return home earlier; only 9% felt that they would have preferred to stay longer.
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We report a randomised controlled trial of external version in 52 women with breech presentation after 36 weeks' gestation; 83% gave informed consent to undergo the management to which they had been randomized. Only 5% of initial attempts without tocolysis succeeded, but 31% of the failures subsequently had a successful version under tocolysis. External version resulted in a small decrease in the frequency of breech presentation at birth (64% vs. 74%), and in an unexpected increase in the caesarean section rate (28% vs. 11%). The increase in caesarean section rate could be attributed to failed versions, which apparently greatly influenced the choice between abdominal and vaginal delivery. Our findings and data from similar research suggest that benefits of external version at term may not apply to populations with a low caesarean rate, unless versions are carried out with maximal efficiency (which, on the basis of available data, would imply tocolysis) or so indifferently that failed attempts do not influence the choice between abdominal and vaginal delivery.
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Plasma renin activity, active renin concentrations, and total renin concentrations were measured serially in 15 women in preterm labor treated with ritodrine. All three parameters showed rapid increases during treatment that depended on ritodrine doses and paralleled changes in maternal pulse rate. The slope of the correlation between plasma renin activity and active renin concentrations suggested an increase in both active renin and renin substrate during ritodrine treatment. In contrast, levels of inactive renin remained unchanged for several hours during ritodrine infusion, showing only a late and much smaller response than that of either total or active renin concentrations. Thus ritodrine treatment results in further activation of an already activated renin-angiotensin system in pregnancy. This activation relates to an increase in both renin enzyme and its substrate. It may be responsible for the disturbance in water balance and the risk of pulmonary edema associated with beta-sympathomimetic drug treatment in preterm labor.
Urinary TXB2 and 6-keto-PGF1 alpha were measured by high pressure liquid chromatography combined with radioimmunoassay, in order to determine whether or not urinary excretion of 6-keto-PGF1 alpha and TXB2 followed a same pattern in pregnancy and labor. The excretion of 6-keto-PGF1 alpha was higher than that of TXB2 in both non-pregnant and pregnant women, but the ratio between them increased in pregnancy. The urinary excretion of both 6-keto-PGF1 alpha and TXB2 excretion was significantly increased (p less than 0.001) in pregnancy. Labor was associated with a much wider inter-individual variation in the excretion of 6-keto-PGF1 alpha and TXB2 than observed in pregnancy and in non-pregnant women. Also, the ratio between the two compounds varied more in labor than in pregnancy. The data indicate that the urinary levels of these two compounds do not follow a single well-determined pattern in pregnancy and labor.
Solvent extraction of 6-keto-PGF1 alpha from aqueous solutions with ethyl acetate was found to result in variable and irreproducible elution patterns, when the extracts were subjected to high pressure liquid chromatography. These problems could not be resolved satisfactorily by using ethyl acetate from different suppliers, nor by changing acids or pH for acidification. After a number of unsuccessful attempts to resolve this problem, we found that variable and irreproducible elution patterns could be avoided by using methyl t-butyl ether as extraction solvent.