[How Reliable are Meta-Analyses? An Appraisal Using the Example of Magnesium Tocolysis]. / Wie verlässlich sind Metaanalysen? Eine Überprüfung am Beispiel der Magnesiumtokolyse.

INTRODUCTION: Crowther et al. 3 analysed the effectivity of magnesium tocolysis in preventing preterm birth. They conclude that there is no evidence for protection. In its latest guidelines, based on this Cochrane analysis, the German Association of Gynaecology and Obstetrics (DGGG) does not recommend any more the use of magnesium for tocolysis. Magnesium tocolysis is said neither to delay nor to prevent preterm birth. Moreover, magnesium could be responsible for increased mortality in infants. These conclusions are mostly based on the research of Mittendorf et al. 4. In a Cochrane study from 2014, which in principal was identical to the study mentioned above 3, Crowther et al. 6 confirm the previous findings and conclusions. METHOD: Having successfully applied magnesium tocolysis for many years, these surprising conclusions led us to review the soundness of the publications mentioned above. Combining the practical experience of many years with the results of a comprehensive literature retrieval, we finally contrasted this knowledge with the findings of the aforementioned publications that caused the DGGG to withdraw the recommendation for magnesium. RESULTS: To draw binding consequences from a meta-analysis is possible only when stringent quality guidelines are observed. The studies that were included in the Cochrane review of Crowther et al. 3 are very heterogeneous and are not suitable for concluding on poor or even lacking effectiveness of magnesium tocolysis. Furthermore, the cases of infant deaths, as stated by Mittendorf et al. 4, are very unlikely caused by magnesium. CONCLUSION: When including studies in a meta-analysis special attention has to be given to the relevance and unbiased selection of studies. To prevent any misjudgment, a thorough knowledge of the included studies seems essentiell. There is not sufficient evidence to withdraw the recommendation for applying magnesium tocolysis as a preventive measure to prevent preterm birth. In the sense of evidence-based medicine, long-standing, scientifically proven therapeutic success should be incorporated into the meta-analysis as well.

Rupture of an aneurysm of the splenic artery and pregnancy: a case report.

The mortality risk in rupture of an aneurysm of the splenic artery is 69.4% for pregnant women and 90.8% for the foetus. 95% of all patients are asymptomatic up to this stage. If the aneurysm is diagnosed earlier, the maternal mortality rate can be reduced to 0.5% by prophylactic surgery. 25% of patients with symptoms display prodromes which, with accurate knowledge of the syndrome, make it possible to make an early diagnosis. Characteristics of the disorder, its risk factors, signs for early diagnosis and therapeutic measures, as well as an up-to-date review of the literature are presented here, illustrated by one of our own case studies.

Apolipoprotein A-I-containing lipoproteins in human umbilical cord blood. Relation to proapolipoprotein A-I and lecithin:cholesterol acyltransferase.

Lipids, apolipoproteins, lipoproteins, as well as lipoproteins containing both apo A-I and apo A-II (Lp A-I:A-II) or apo A-I but no apo A-II (Lp A-I), proapolipoprotein (proapo) A-I and the activity of lecithin:cholesterol acyltransferase (LCAT), were investigated in umbilical cord sera of 67 term human neonates (30 females and 37 males). Lp A-I and Lp A-I:A-II were present in umbilical cord sera with levels of 0.26 +/- 0.1 and 0.33 +/- 0.15 g/l, respectively. Furthermore, the absolute amount of proapo A-I was lower in cord blood than in adult plasma, but in view of the lower apo A-I levels in umbilical cord sera it comprised 10.48 +/- 3.86% of total apo A-I and was thus significantly higher than in adult plasma (7.1 +/- 0.9%). Proapo A-I was highly correlated with HDL cholesterol and apo A-I. Total serum LCAT activity was about 50% of adult plasma and was highly correlated with Lp A-I, but not with Lp A-I:A-II. We conclude that human umbilical cord serum contains both Lp A-I and Lp A-I:A-II particles and that the LCAT activity is predominantly related with the Lp A-I subfraction. The higher percentage in umbilical cord sera of proapo A-I may indicate a higher turnover of apo A-I or a lower activity of the proapo A-I cleaving enzyme which is still not identified.

Polymorphism of apolipoprotein E influences levels of serum apolipoproteins E and B in the human neonate.

To gain more insight into the genetic vs. environmental influence of the apoE phenotypes on plasma lipoprotein variation we studied human umbilical cord sera at birth. Apolipoprotein E genetic phenotypes were determined in 110 individuals by immunoblotting and shown to be identical to the adult human isoforms with six phenotypes present and occurring at a similar frequency as reported previously for the adult population in the same area. Total serum cholesterol and triglyceride levels were low in the neonates and did not differ significantly between apoE phenotypes. On the other hand as in the adult, levels of apoE and B differed significantly between the phenotypes. ApoE was highest in individuals with the epsilon 2 allele and lowest in individuals expressing apoE4, and vice versa for apoB. We conclude that apoE phenotypes in human umbilical cord blood serum are already associated with pronounced differences in apoE and B levels in the newborn. The study demonstrates that the association of apoE and apoB levels with the apoE polymorphism occurs independently of significant enteral nutrition in the relatively constant in utero environment.

Apolipoproteins in human amniotic fluid: concentrations, isoforms and polymorphism.

Apolipoproteins were determined in 50 human amniotic fluids obtained by amniocentesis during weeks 16 and 22 (n = 26) or 33 and 41 (n = 24) of gestation. Whereas apo A-I, A-II, A-IV, and E were identified at levels of 1, 0.7, 0.8 and 1% of normal human adult plasma, respectively, apo B levels were only 0.04% of plasma concentration and apo C-III levels were below the detection limits of the assay. Amniotic fluid levels of apo A-II, A-IV and E did not differ between early and late stages of pregnancy, but levels of apo B decreased and apo A-I increased significantly in late pregnancy. Isofocusing showed apo A-I, A-II and A-IV in identical positions as compared to human adult plasma. Furthermore the known genetic polymorphism of apo A-IV was detectable. Individuals heterozygous, for the variant form apo A-IV-2, showing the phenotype apo A-IV (2-1), had significantly higher levels of apo A-I and A-II as compared to the common phenotype apo A-IV (1-1). We conclude that human amniotic fluid contains the major plasma apolipoproteins at about 1% of plasma levels with the exception of apo B which shows a level at an order of magnitude less than high-density lipoprotein apoproteins in comparison to their plasma counterparts.

Changes of apolipoprotein A-IV in the human neonate: evidence for different inductions of apolipoproteins A-IV and A-I in the postpartum period.

The levels, isoforms and distribution of apolipoprotein A-IV (apo A-IV) were investigated in 127 term human umbilical cord sera. In addition, apo A-IV levels and isoforms were determined on the 3rd (n = 82) and 6th (n = 68) day following parturition and compared to apo A-I concentrations. Levels of apo A-IV were low in umbilical cord serum (5.7 +/- 1.9 mg/dl) as compared to adult serum (17.6 +/- 4.8 mg/dl). No difference was found between male and female neonates. The serum distribution of apo A-IV closely resembled that seen in the adult human. Apo A-IV concentrations dramatically increased during the first week of life reaching levels of 13.4 +/- 4.1 mg/dl on day 3 and 16.7 +/- 3.4 mg/dl on day 6 post-partum. During this time apo A-I levels did not change significantly (81.0 +/- 16.5 mg/dl in cord serum, 75.3 +/- 10.6 mg/dl and 84.2 +/- 14.5 mg/dl on day 3 and 6, respectively). Cord serum already exhibited the major serum apo A-IV isoforms seen in the adult. Isofocusing of apo A-IV also identified the known genetic polymorphism of apo A-IV. Among 127 cord sera studied we identified 109 homozygote normal patterns, apo A-IV (1-1), 16 heterozygotes, apo A-IV (1-2) and 2 individuals homozygote for the variant peptide, apo A-IV (2-2). We provide evidence that apo A-IV and apo A-I are differently induced in the human neonate during the beginning of the feeding period.(ABSTRACT TRUNCATED AT 250 WORDS)

[Rapidly progressing thrombocytopenia as a threatening form of pre-eclampsia]. / Die rasch progrediente Thrombozytopenie als bedrohliche Form der Präeklampsie.

Atypical courses of pregnancy-induced hypertension (PIH) have been reported quite frequently during the last time. They include prepartal coagulation disorders with slight or missing typical symptoms of PIH. In cases of quickly increasing thrombocytopenia during the last trimenon, in company with elevated liver enzymes, PIH must always be taken into account. We give a case report about a nearly asymptomatic secundigravid woman who developed low platelet counts (8,000 platelets/microliter) within a few hours, which later was confirmed to be severe preeclampsia. Transient and moderate thrombocytopenia down to 50,000 platelets/microliter caused by PIH may first be treated conservatively. Progredient symptoms should lead to an early delivery, as neonatal mortality in such cases is high. We give a review about current literature which reflects on differential diagnosis, pathogenesis and therapy of this disease.

Biochemical balance in the energy metabolism of fetal organs after perfusing the amniotic cavity with oxygenated fluorocarbon.

In order to determine the oxygen-dependent energy balance after perfusing the amniotic cavity with oxygenated fluorocarbon, hearts and livers of 30 rabbits [correction of rat] fetuses were investigated on the 28th day of gestation in a double-blind study 20 min after complete interruption of the uterine blood supply. ATP, creatine phosphate, glucose, lactate and glycerine were quantitatively measured by direct spectrofluorometry. The results show a tendency towards higher energy reserves after fluorocarbon treatment. However, under the described experimental conditions the oxygen supply seems yet too small for clinical purposes.

[Is the determination of glycosylated hemoglobins in neonatal macrosomia useful?]. / 1st die Bestimmung glykosylierter Hämoglobine bei Neugeborenenmakrosomie sinnvoll?

170 blood samples of mother and child of patients with and without risk of diabetes as well as of mothers with macrosomic newborns have been examined immediately after delivery. The procentual rate of glycosylated hemoglobin (GHb) was determined by an affinity chromatographic method. The mean of the GHb values of the children was 37% lower compared to the values of their mothers and in this showed a linear correlation. A dependence on the deviation of weight of the mothers from the Broca normal weight was found but not a dependence on the gain of weight during pregnancy, on height and age. In the GHb values of mothers and children a significant dependence on the weight of the mother before pregnancy was seen. There was no relation of the glycosylated hemoglobins to the birth weight of the newborn in regard to the age of pregnancy and the sex of the children. To our opinion the GHb measurement can therefore not be used for the diagnosis of latent diabetes in pregnancy in the case of newborn macrosomia.

[Submucous varicose veins of the lower uterine segment--a rare cause of pre- and postpartal hemorrhages]. / Submuköse Varikosis des unteren Uterinsegmentes--Seltene Ursache prä- und postpartaler Blutungen.

Report about one case of submucous varicosis of the lower uterine segment during pregnancy. Arrosion of these veins during labour was the reason of a severe postpartal bleeding. Recurrent haemorrhages ante partum presumably can be attributed to lesions of these veins, too.

[Tokolysis and dose-dependent effects of beta-blocking with atenolol in the rabbit]. / Tokolyse und dosisabhängige Effekte der Betablockade mit Atenolol beim Kaninchen.

In 11 pregnant rabbits we induced labor by parenteral infusion of Dinoprost (F2) (0.05 mg/min). By application of Fenoterol (0.01 mg/min) we had complete labor inhibition (P). Increasing dosages of Atenolol (T1 = 0.05 mg/min, T2 = 0.10 mg/min, T3 = 0.25 mg/min) followed. We registered systolic, diastolic and mean blood pressure directly after punction of a femoralis, cardiac frequency, and labor by integration of action potentials of uterus. Cardiac frequency decreased with increasing amounts of Atenolol. Mean blood pressure fell significantly under Fenoterol medication. There is no further decrement by additional application of high dosages of Atenolol. A certain dosage of Atenolol could be defined, that does not increase labor activity under Fenoterol medication but does decrease cardiac frequency without influence on mean blood pressure.

Electron microscopy findings in fetal organs after perfusion of the amniotic cavity with oxygenated fluorocarbon.

In 20 fetal rabbits a double-blind electron microscopy study of placenta, lung, heart, liver, and stomach was performed at 28 or 29 days of gestation. The amniotic cavity was continuously perfused with perfluorotetrahydrofuran (FC 77) before the fetuses were killed. Compared with control fetuses, no morphological changes of fetal lung and stomach nor of placenta related to FC were found. There were unexplained changes in liver parenchymal cells. However, a protective effect of FC on the myocardial tissue was observed.

[Is there a possibility of paraplacental oxygenation of fetal blood? First results of an investigation with fluorocarbon (author's transl)]. / Ist eine paraplazentare Oxygenierung fetalen Blutes möglich? Erste Ergebnisse einer Untersuchung mit Fluorocarbon.

By checking the cardiotropic effect on fetal rabbits we tried to find out weather there is a possibility of paraplacental oxygenation of fetal blood. Amniotic caves of nine fetal rabbits of 28th or 29th day of gestation are perfused with Perfluorobutyltetrahydrofuran (FX 80, 3 M Comp., St. Paul, Minn., USA) continuously. This was done by double blind investigation. The fetal heart rate is written by Hewlett-Packard-cardiotocograph. Therefore we use modificated EEG-electrodes. 48 h before we cut the spinal cord of the pregnant animals just for analgesie. So we exclude the influence of analgesics or narcotics. After complete interruption of uterine blood supply you can find an initial reduction of fetal heart rate. Using fluorocarbon we notice an increasing or stabilisation of fetal heart rate of all rabbit fetus. In comparison with control animals the difference is high significant. The cardial survival rate of four fetal rabbits treated with fluorocarbon is prolonged up to 50 min. During this time all "fluorocarbon fetus" never died earlier than the control animals. Lots of new questions are provoked by our results. One has to find an answer.

[Some experiences concerning the effect of fetal respiratory movement (author's transl)]. / Ein Beitrag zur Auswirkung fetaler Atembewegung.

The effect of negative pressure by intrauterine respiratory movements of 115 fetal rabbits is examined between the 25th and 28th day of gestation. An intraamnial injection of Burri-ink with particles of the size between 20 and 50 nm and of a suspension of polyamid (size between 25 and 40 micrometer) in physiological NaC1-solution was done. Both markers are not inspirated during the time of 24 h p.i. However you can find them after 19 min in the circulated fetal blood. There is the same effect if you block respiratory movements by drugs. There is a correlation to the concentration of the markers in the amniotic fluid, but no correlation to the size of the particles of those markers.