Preeclampsia -- a state of prostaglandin deficiency? Urinary prostaglandin excretion, the renin-aldosterone system, and circulating catecholamines in preeclampsia.

Urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), plasma concentrations of renin, aldosterone, norepinephrine (NE) and epinephrine (E) were determined during pregnancy, 5 days, 3, and 6 months after delivery in preeclampsia, normotensive pregnant, and nonpregnant control subjects. The PGE2 was higher in normotensive pregnant control subjects than in nonpregnant subjects. In preeclampsia, PGE2 was reduced to nonpregnant level. PGF2 alpha was the same in preeclampsia and in normotensive pregnancy, but elevated when compared to the normotensive nonpregnant control group. Plasma concentrations of renin and aldosterone were increased during pregnancy, but considerably less in preeclampsia than during normotensive pregnancy. NE and E were the same as in nonpregnant subjects during both hypertensive and normotensive pregnancy. All parameters were normal 3 months after delivery. There were no correlations between PGE2, PGF2 alpha, plasma concentrations of renin, aldosterone, NE, or E and blood pressure level in third trimester either in preeclampsia or in normotensive pregnancy. PGE2 was positively correlated to plasma concentrations of renin. It is suggested that the lack of renal PGE2 in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion. It is hypothesized that preeclampsia is a state of prostaglandin deficiency. The changes in the renin-aldosterone system may be secondary to changes in prostaglandin concentration both in preeclampsia and normotensive pregnancy.

Amelioration of some pregnancy-associated variations in thyroid function by iodine supplementation.

Knowledge of the effect of differences in iodine intake levels on public health in areas with no endemic goiter is limited. Groups at risk when iodine intake is relatively low are pregnant and lactating women and their newborns. A prospective randomized study was performed to evaluate the effect of iodine supplementation in an area where the median daily iodine excretion in urine is around 50 micrograms. Fifty-four normal pregnant women were randomized to be controls or to receive 200 micrograms iodine/day from weeks 17-18 of pregnancy until 12 months after delivery. In the control group, serum TSH, serum thyroglobulin (Tg), and thyroid size showed significant increases during pregnancy. These variations were ameliorated by iodine supplementation. Iodine did not induce significant variations in serum T4, T3, or free T4. Cord blood Tg was much lower when the mother had received iodine, whereas TSH, T4, T3, and free T4 levels were unaltered. The results suggest that a relatively low iodine intake during pregnancy leads to thyroidal stress, with increases in Tg release and thyroid size. However, the thyroid gland is able to adapt and keep thyroid hormones in the mother and the child normal, at least under normal circumstances, as evaluated in the present study. It is not known whether this stress is sufficient to be of importance for late development of autonomous thyroid growth and function.

Treatment of dysplasia of the cervical epithelium with an interferon gel.

Human leukocyte interferon was incorporated into a hydrophilic gel and applied to the cervix of six patients suffering from moderate to severe dysplasia or carcinoma in situ of the cervix. Only patients showing no spontaneous regression during at least 27 consecutive weeks were admitted to the trial. The diagnoses were established by Papanicolaou smears and biopsy specimens of the cervix. The gel was applied directly on the cervix twice weekly for six weeks, and only minor clinical improvements were seen. However, after an additional six weeks, six of six patients responded positively; three of them regressed completely. No side effects were noted.

[Chorionic villi biopsy as an alternative to amniocentesis]. / Chorion villus biopsi som alternativ til amniocentese.

The results of a retrospective assessment of the first 112 chorion villus biopsies carried out in the Department of Obstetrics and Gynaecology in the Central Hospital in Randers are presented. Karyotype determination was obtained in 98.2% and in 83.9% already by means of direct microscopic examination after incubation for 24 hours. No complications which could be attributed to the biopsies were registered. The present authors consider that the method should be employed more extensively for prenatal cytogenetic diagnosis.

[Amniocentesis and chorionic villi biopsy. A 10-year material]. / Amniocentese og chorion villus biopsi. Et 10-års materiale.

PURPOSE: The aim of the study was to evaluate the prenatal diagnosis at a secondary referral hospital. METHOD: A retrospective study was carried out on 1752 women examined by amniocentesis (AC) (n = 1037) or chorion villus sampling (CVS) (n = 715) at Randers Centralsygehus from 1 April 1987 to 31 December 1996. RESULTS: A cytogenetic diagnosis was made in 99.8% of the AC group and 99.4% of the CVS group. Complications, recorded as either spontaneous abortion, bleeding/threatening abortion, pain/contractions or amniotic fluid leakage, were seen in 1.9%, 3.3%, 2.9%, and 2.3% after AC and 1.8%, 7.3%, 3.4%, and 0% after CVS. There were significantly more re-examinations after CVS when the procedure was carried out by less experienced operators (p < 0.003), whereas experience did not influence the number of re-examinations after AC (p = 0.8). CONCLUSION: The frequency of complications during prenatal procedures performed over a period of ten years was comparable with that reported in other studies. It is expedient and safe to perform prenatal examinations at a secondary referral hospital where currently 200 procedures are performed each year.

Characteristics of resistance vessels in pre-eclampsia and normotensive pregnancy.

Isolated omental resistance vessels from women with pre-eclampsia had an increased media thickness/lumen diameter ratio compared to similar vessels from normotensive pregnant women. The active and passive tension length curves for the two groups of vessels were similar and like the classical tension length curve for skeletal muscles. The maximal media stress (force per media cross-section) was also similar; however, calculating in terms of equivalent pressure (on basis of Laplaces law) indicated that the vessels in vivo would have been able to contract against an increased blood pressure. The results indicate that pre-eclampsia is associated with structural alterations of the resistance vessels which might be of importance for the haemodynamics of pre-eclampsia.

Cysteine is essential for transcriptional regulation of the sulfur assimilation genes in Saccharomyces cerevisiae.

Transcription of the genes for sulfur assimilation and methionine biosynthesis in Saccharomyces cerevisiae is regulated by the size of the intracellular pool of an organic sulfur compound. The identity of this compound is not clear, but suggestions include S-adenosylmethionine (SAM) and cysteine. By studying the repression of selected sulfur assimilation (MET) genes, we found that the ability to form cysteine from homocysteine is crucial for methionine-mediated repression to take place. The transcription of MET14 and MET25 could not be repressed by methionine in strains in which either STR4 (which encodes cystathionine beta-synthase) or STR1 (cystathionine gamma-lyase) was disrupted, whereas the repression was independent of GSH1 (which encodes the enzyme responsible for the first step in glutathione biosynthesis from cysteine). In contrast, cysteine could repress the MET genes in all of these strains. Two genes that presumably encode cystathionine gamma-synthase and cystathionine beta-lyase were identified by genetic disruption (ORFs YJR130c and YGL184c), yielding yeast strains that cannot convert cysteine into homocysteine. Repression by cysteine was possible in either disruptant, suggesting a role in repression for cysteine alone. While some repression of MET genes could be accomplished by homocysteine in a strain that cannot form SAM from methionine, a low intracellular level of SAM seems to be necessary for full cysteine-mediated repression to take place.

Arginine vasopressin in amniotic fluid, arterial and venous cord plasma and maternal venous plasma.

High concentrations of arginine vasopressin (AVP) in arterial umbilical cord blood at the time of delivery have been attributed to either a generalized increase in the activity of the fetal endocrine system at the onset of labor or to fetal asphyxia. We measured AVP in amniotic fluid, arterial and venous cord blood and in maternal venous blood from 13 patients at 38-40 weeks of gestation at the time of elective cesarean section with a nonasphyxic fetus (group I), in amniotic fluid from 19 patients at 15-17 weeks of gestation (group II) and in venous blood from 13 nonpregnant control subjects (group III). Our results showed a high concentration of AVP in the amniotic fluid both in the middle and at the end of normal pregnancy and at the same level as in arterial cord blood, whereas AVP in the venous cord blood was significantly lower and at the same level as in the maternal venous blood and in the control group. It is concluded that the fetus produces AVP and this is at least not solely caused by fetal asphyxia or related to parturition.

Instrumentation for transient evoked otoacoustic emissions elicited by maximum length sequences.

A system for recording Transient Evoked Otoacoustic Emissions (TEOAE) for neonatal screening, utilizing Maximum Length Sequences (MLS) for the generation of stimulus signals, is described. The main advantage of the system is its ability to obtain responses within a very short period of time, compared to conventional OAE systems. The actual recording time for the MLS system is reduced by a factor of between 10 and 20 for comparable signal-to-noise ratios. Stimulus levels range from 50 to 90 dB peak equivalent SPL and available stimulus rates are 31, 62, 125, 250, 500, 1000 and 2000/sec. A dynamic noise rejection algorithm is performed during data collection, and, moreover, all sweeps (both accepted and rejected) are stored in memory so that the signal-to-noise ratio can be optimized by post-processing immediately after data collection. As a result, robust response can be achieved even if the subject is noisy during the test. A new semi-non-linear recording technique is described, combining the benefits from the conventional linear and non-linear recording methods. Examples of adult and neonatal responses under different conditions are provided to demonstrate the value of the recording principle.

The osmoregulatory system and the renin-angiotensin-aldosterone system in pre-eclampsia and normotensive pregnancy.

Plasma concentrations of arginine vasopressin (AVP), angiotensin II (A II), aldosterone (Aldo), serum osmolality (Sosm), urine volume (V), and free water clearance (CH2O) were determined in the third trimester of pregnancy, and 5 days and 3 months after delivery in pre-eclampsia (group I), in normotensive pregnancy (group II), and in non-pregnant control subjects (group III). The AVP was the same in the third trimester of pregnancy in groups I and II and did not deviate significantly from the level in group III. However, 5 days after delivery, AVP was lower and V and CH2O higher in group I than in group II. There was no correlation between AVP and Sosm in the third trimester in either group I or II, but 5 days after delivery a significant positive correlation was found between these parameters in both groups I and II as well as in group III. The A II and Aldo changed qualitatively in the same way in groups I and II, that is, considerable elevation in the third trimester and normalization after delivery. Also, A II and Aldo were lower in group I than in II. The AVP and A II were not correlated and there was no significant relationship between systolic or diastolic blood pressure on the one hand and AVP, A II or Aldo on the other in either group I or II. Thus the osmoregulatory system appears to be altered in both pre-eclampsia and normotensive pregnancy, but becomes normal again 5 days after delivery. In pre-eclampsia a suppression of AVP seems to be responsible for the elimination of excess water in pre-eclampsia 5 days after delivery. There was no evidence for a causal relationship between blood pressure and the osmoregulatory system or the renin-angiotensin-aldosterone system in any of the pregnant groups.

Abnormal vascular function and morphology in pre-eclampsia: a study of isolated resistance vessels.

In order to obtain direct information about vascular changes associated with pre-eclampsia, the morphological and functional characteristics of isolated omental resistance vessels from 11 women with pre-eclampsia, 10 normotensive pregnant women and eight normotensive non-pregnant women were determined. In vessels from the women with pre-eclampsia, the ratio of media thickness to lumen diameter was increased, compared with that in vessels from the other two groups. The vessels from the women with pre-eclampsia had an increased responsiveness to angiotensin II and a decreased rate of relaxation, but only when compared with the vessels from the normotensive pregnant women. However, no difference in responsiveness to noradrenaline was found between any of the groups. The angiotensin II responsiveness of the vessels from the women with pre-eclampsia and from the non-pregnant women were similar, suggesting that pre-eclampsia is associated with an absence of the change in vascular function which normally occurs during pregnancy. The study provides direct evidence for an involvement of vascular abnormalities in the pathogenesis of pre-eclampsia.

The pYC plasmids, a series of cassette-based yeast plasmid vectors providing means of counter-selection.

A series of 24 general-purpose yeast plasmid vectors has been constructed. The plasmid series is composed of inter-replaceable cassettes, allowing for easy interconversion of plasmid types. In addition to the usual replication origins, selectable markers and multiple cloning sites (MCS), cassettes dedicated to counter-selection have been constructed. A pair of unique 8 bp restriction enzyme recognition sites flank each type of cassette, FseI in the case of yeast replication origins, AscI in the case of selectable markers, PacI in the case of counter-selectable markers and NotI in the case of the MCS. Thus, any given cassette can be replaced by another cassette of the same type, facilitating interconversion of any given plasmid from one type to another, even after the insertion of DNA into the MCS. Hence, the plasmids have been named pYC for 'yeast cassettes'. The cassettes consist of either NONE, CEN4/ARS or 2micro as replication origin, either URA3, MET2-CA (Lg-MET2) or the G418 resistance gene (the apt1 gene from bacterial transposon Tn903, encoding aminoglycoside phosphotransferase) as selectable markers, either NONE, PMET25-PKA3 or PCHA1-PKA3 as counter-selectable marker, and the MCS, containing recognition sites for AflII, AvrII, BspEI, PmeI, SacII, SalI, SunI, BamHI, EcoRI, HindIII, KpnI, MluI, NarI and SacI (of which the seven first are unique in all plasmids). The counter-selectable markers consist of the PKA3 gene under control of the conditional MET25 or CHA1 promoters. At activating conditions these promoters express the PKA3 gene at toxic levels, facilitating easy selection for loss of plasmid or 'loop-out' of plasmid DNA sequence after genomic integration.

Plasma prostaglandin F2 alpha and plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha levels in women during induction of labor with i.v. infusion of prostaglandin F2 alpha in relation to uterine contractions.

The concentrations of plasma PGF2 alpha and its main metabolite, 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were measured in serial samples of blood collected in 10 pregnant women at term who were given iv infusions of low doses of PGF2 alpha for induction of labor. Six other women served as controls and were given saline infusions. Uterine contractions began with a mean latency of 62 min in the PGF2 alpha infused women, in controls uterine activity remained unchanged. Plasma PGFM levels had increased significantly 30 min after PGF2 alpha infusion began, rising thereafter in a dose dependent manner. Plasma PGF2 alpha also rose reaching a steady state at 2 hours. No significant changes were observed in the controls. The 6-h infusion resulted in delivery in 5 of the 10 women, in the 5 others the cervical scores increased only by 1.25 points on the average and further treatment was needed to achieve delivery, although prostanoid levels rose to similar levels in all. The data show that when uterine contractions are induced by systemic PGF2 alpha, the levels of PGFM are significantly raised. In spontaneous labor uterine contractions begin long before plasma PGFM rises. Thus, if endogenous PGF2 alpha generation is involved in the initiation of uterine contractions during spontaneous labor, it must be synthetized in the myometrium at quantities too low to raise the levels of circulating PGFM.

Neonatal hearing screening using otoacoustic emissions elicited by maximum length sequences.

The aim of this study was to provide statistical information on otoacoustic emission (OAE) measurements in new-born infants, which could be useful in the interpretation of results and could add some clinical parameters that might be used for future objective and automatic response evaluations. Transient evoked OAEs (TEOAEs) using maximum length sequences (MLS) were recorded in 129 full-term new-born infants between 48 and 72 hours of age. The use of MLS enabled stimulus rates of up to 2000/sec to be utilized. The analysis comprised five main issues: (1) signal to noise ratio (S/N); (2) derived non-linear responses; (3) a combination of derived non-linear emissions called compound non-linear emissions; (4) time/frequency analysis and (5) signal power analysis. The result of the analysis were as follows. (1) The largest S/N ratio was obtained when more than 60% of the recordings were rejected. (2) The derived non-linear emissions comprised level non-linear and rate non-linear responses, the latter obtained by subtraction of recordings at fixed stimulus level, but at different stimulus rates. The rapid suppression of emission amplitude as the stimulus rate increases is the basis for this non-linear response which also features stimulus cancellation. (3) The compound non-linear emissions, consisting of a sum of derived non-linear responses may prove efficient by proper selection of stimulus parameters, but did not in the present form show the expected improvements of amplitude and stimulus cancellation. (4) The time/frequency analysis, however, based on calculations of the instantaneous frequency as a function time after stimulus onset, showed a consistent tendency of falling frequency versus time after stimulus onset as a basic characteristic feature of OAE. (5) The analysis of the emission power as a function of time after stimulus onset showed that linear recordings in new-born infants are reliable, with stimulus ringing fully decayed 3 ms after the stimulus onset. The findings may prove useful in future attempts to develop screening equipment with automatic response evaluation for new-born infants. From a clinical point of view the MLS technique was successful when measuring emissions in neonates, owing to the fast recording time and the utilization of an efficient noise rejection paradigm.

Urinary iodine excretion is low and serum thyroglobulin high in pregnant women in parts of Denmark.

In the Randers area of Denmark urinary iodine excretion (which reflects iodine intake) was found to be much lower than recommended intake levels, both in women in late pregnancy [52(23-118) micrograms iodine/g creatinine, median, range, n = 20] and in non-pregnant controls [42(23-71), n = 20]. Serum thyroglobulin which is high in iodine deficiency was 32.5 micrograms/l (median) (range 10.5-78.0) in the control women and considerably higher in the pregnant women [67.0 micrograms/l (9.0-385)]. This increase was probably due to the extra iodine requirement of pregnancy which was not satisfied with an adequate increase in iodine intake. The results may suggest that pregnant women in this area should receive iodine supplementation and that a general program of iodine supplementation should be considered.

The influence of normotensive pregnancy and pre-eclampsia on angiotensin-converting enzyme.

Serum angiotensin-converting enzyme (SACE) levels were determined in normotensive pregnant subjects and patients with pre-eclampsia in the third trimester of pregnancy and 5 days, 3 and 6 months after parturition, and also in the first and second trimester in the normotensive group. SACE levels were reduced during pregnancy and 5 days after delivery in the normotensive subjects compared with the levels 3 and 6 months after delivery and to the non-pregnant control subjects. After correction for plasma volume expansion, SACE was reduced in first and second trimester only. In pre-eclampsia both SACE and corrected SACE were significantly lower in third trimester and 5 days after parturition than 3 and 6 months after delivery and in non-pregnant control subjects. The reason for the reduced level of SACE in first and second trimester during normal pregnancy is not known. The low SACE levels in pre-eclampsia may be a secondary phenomenon due to a decreased placental synthesis without primary importance for the blood pressure regulation.

Plasma noradrenaline and adrenaline in pre-eclampsia, essential hypertension in pregnancy and normotensive pregnant control subjects.

Noradrenaline and adrenaline in plasma were determined in 15 patients with pre-eclampsia, 10 pregnant patients with essential hypertension, 2 patients with transient hypertension in pregnancy, 11 normotensive pregnant control subjects, and 16 non-pregnant normotensive control subjects. Measurements were performed in the second and third trimester, 5 days, and 3 months after delivery. Comparison within groups showed no significant differences in plasma noradrenaline or adrenaline between levels in pregnancy, 5 days after delivery, and 3 months after delivery in neither pre-eclampsia, essential hypertension nor normotensive pregnant control subjects. Comparison between groups showed no significant differences between the levels in pre-eclampsia, essential hypertension and normotensive pregnant control subjects, neither in pregnancy nor after delivery. Plasma noradrenaline and adrenaline in pregnancy were the same as in normotensive non-pregnant control subjects. Plasma noradrenaline and blood pressure were not correlated in any of the groups. It is concluded that the sympathetic adrenergic activity evaluated by plasma catecholamines is normal in patients with pre-eclampsia and pregnant patients with essential hypertension.