[Ambroxol versus betamethasone for the promotion of antepartum lung maturity in pathological pregnancies]. / Ambroxol versus Betamethason zur Förderung der antepartalen Lungenreife bei pathologischen Schwangerschaften.

Although glucocorticoids have been universally implemented to stimulate fetal lung maturity, their effectiveness and side effects are still widely contested. In search of alternative drugs a double-blind study was conducted between June 1981 and June 1984 comparing betamethasone, a conventional corticoid, and ambroxol, a bromhexine metabolite for efficacy and tolerance in prenatal prevention of the respiratory distress syndrome (RDS) in premature infants and full-term neonates. The therapeutic efficacies of betamethasone and ambroxol for this indication proved to be comparable. Since the possible risks of corticoid therapy in abnormal pregnancies are repeatedly discussed in the literature and in daily clinical practice. 137 patients with EPH gestosis, placental insufficiency, diabetes mellitus, and premature rupture of the membranes were selected from the original group of 308 patients. Only minor side effects (e.g. nausea) were present in a few of the 137 cases undergoing treatment with the 2 test substances. No side effects were observed in the neonates. The incidence of fetal RDS was comparable in both groups (2.9% with ambroxol, 2.2% with betamethasone). Transient and mild RDS cases were slightly more frequent in the ambroxol group than in the betamethasone group. To date, contraindications to ambroxol treatment in abnormal pregnancies are unknown and since generally the rate of potential side effects is considered to be lower in comparison with corticoid treatment, the use of ambroxol especially in abnormal pregnancies corresponding indication can be recommended.

[Successful further prolongation of immature twin pregnancy by tocolysis and re-cerclage following unavoidable delivery of the first foetus after emergency cerclage (author's transl)]. / Erfolgreiche weitere Prolongation unreifer Zwillingsschwangerschaft durch Tokolyse und Re-Cerclage nach unaufhaltsamer Geburt des ersten Feten nach Notfall-Cerclage.

The article reports on a twin pregnancy with EPH gestosis in a 20-year old primipara which could be prolonged by tocolysis and emergency cerclage after signs of premature delivery and prolapse of the amniotic sac in the 28th/29th pregnancy week. At the beginning of the 30th gestation week there was an unavoidable delivery of the first twin (920 g) who survived for 5 days only due to immaturity and hypotrophy. Directly after delivery of the first twin the pregnancy for the second twin was prolonged by renewed tocolysis and renewed circular suture of the cervix. This enabled the second child, whose growth had been retarded like that of the first one, to continue to grow for some time. Unavoidable delivery of the second twin (1,650 g) eventually occurred at the beginning of the 32nd week of pregnancy. The eutrophic child survived without the slightest complication. This case is presented in detail and discussed, including the histology of the placenta. The most important points for enabling the survival of a twin foetus are sufficient tocolysis, a satisfactory technique for occlusion of the os uteri, as well as exclusion and prevention of chorioamnionitis.

[Reduced frequency of gestoses in beta-mimetic treated risk pregnancies with added magnesium therapy]. / Reduzierte Frequenz von Gestosen bei Betamimetika-behandelten Risikoschwangerschaften mit Magnesium-Zusatztherapie.

Retrospectively the 4,905 single pregnancies of the four years 1979-1982 are divided into 882 (18.0%) patients treated by tocolysis and 4,023 (82.0%) patients treated without tocolysis (R). The patients with tocolysis (BMG) received in addition to the Betamimectic agents since 1979 a low dose of magnesium (feto- longoral ) to protect the heart (3-6 mval Mg ++) daily and since early in 1981 to assist in the tocolysis 30 to 40 mval Mg ++ daily in the oral from of magnesium aspartate (Mg 5- Longoral ). The incidence of pre-eclampsia (G) in the groups BMG and R is recorded. The R group constitutes the normal group (N) by substracting the group G. Compared were in the groups NG and BMG the mean age and parity, the incidence of adjuvant magnesium medication, the duration of pregnancy and the incidence of intra-uterine growth retardation ( IUR ). The incidence of pre-eclampsia (G) in the 882 patients treated with Betamimetics and magnesium was 0. In the other 4,093 patients the incidence was 97 (2%). The rate of intra-uterine growth (lower than the 10% BPE ) was 9.4% in the 3,093 normal patients, 45.4% in the 97 patients with pre-eclampsia and in the 398 BMG patients of the years 1979 and 1980 with the small addition of magnesium (BMG 1) the incidence was 17.8%. In the 484 patients of the years 1981 and 1982, with large additional doses of magnesium (BMG 2) the incidence was 10.1%. The correlation of the intra-uterine growth retardation degrees (lower than 25% Hohenauer , 10% BPE ) was highest in the group G (1.3:1).(ABSTRACT TRUNCATED AT 250 WORDS)

Magnesium therapy decreased the rate of intrauterine fetal retardation, premature rupture of membranes and premature delivery in risk pregnancies treated with betamimetics.

A higher percentage of intrauterine growth retarded (IUR) infants was found in patients treated with tocolytic drugs, indicating that placental insufficiency could be the cause of both premature labor and IUR. In order to evaluate the results of oral treatment with betamimetics and magnesium at different dosages, 534 (10.9%) pregnancies treated with tocolysis + cerclage (TC) of 4,905 single pregnancies managed in our hospital between 1979 and 1982 wee studied retrospectively. Addition of magnesium to betamimetics: since 1979/1980 3-6 mEq Mg2+ daily per os aimed towards 'cardioprotection', and since 1981, to 'support tocolyis' 30-40 mEq Mg2+ daily per os in the form of Mg aspartate. We compared: mean age, parity, percentage supplemented with Mg and outcome of pregnancy for each year; these parameters were also compared with those of normal pregnancies. The frequency of (completed) gestational periods less than or equal to 36 weeks was about 11% in the TC groups (only 2% in normal pregnancies). However, this was reduced annually from 11.0% in 1979 to 4.9% in 1982. The frequency of premature ruptured membranes (PROM) in premature infants was about 6% in the TC groups from 1979 to 1980. It was reduced to 2.2% in 1981 and to 1.6% in 1982 (normal pregnancies, about 1%). In the TC group the frequency of IUR (less than 10th percentile; Bavarian Perinatal Evaluation; BPE) amounted to 20.5% in 1979, and to 17.5% in 1980. It was reduced to 8.8% in 1981 and to 10.6% in 1982 (normal groups, between 8.3 and 11.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

[The use of partusisten in the delivery of triplets with an incarcerated fetus (author's transl)]. / Einsatz von Partusisten bei einer Drillingsgeburt mit inkarzeriertem Feten.

A triplet delivery is reported. The multiple pregnancy was undiagnosed prior to labor. Twins were diagnosed on admission for delivery. The ultrasonic and abdominal EKG findings at term are discussed. The hitherto undiagnosed third triplet became incarcerated following the administration of two units of syntocinon after the delivery of the second triplet. The intrapartum tocolysis with partusisten became life saving for the third triplet on three counts. 1. The progressive acidosis was stopped. 2. Time was gained to prepared for delivery of the last triplet. 3. Internal podalic version and extraction was much easier.

[A test for early detection of hypertonias conditioned by pregnancy (gestosis selection test - GST) (author's transl)]. / Ein Test zur Früherkennung schwangerschaftsbedingter Hypertonien (Gestose-Selektions-Test = GST).

72 patients were subjected to the gestosis selection test (= GST) during the 28th (+/- 3 weeks) week of pregnancy in the sense of a "screening" with regard to potential risk of gestosis. A detailed description of GST, which consists of the injection of a bolus of fenoterol is given. Depending upon the possibility of reducing the diastolic blood pressure, 2 groups of pregnant women can be distinguished with regard to the prospective assessment of the course of pregnancy: GST Group I: The diastolic blood pressure can be reduced by 30 mmHg and more - Development of gestosis is hardly probable. GST Group II: The diastolic blood pressure can be reduced by less than 30 mmHg - Development of gestosis probable. Of the prospectively examined 72 patients, 40 have meanwhile delivered. There was no gestosis in group I, whereas in group II there were 8 gestoses. The GST is compared with other screening methods based on blood pressure which were also carried out at the same time: the "roll over test" (ROT) as well as calculation of the mean arterial blood pressure during the second trimenon (MAP-2).

[The significance of betamimetics and magnesium for the outcome of pregnancy: II. The role of magnesium in the development of gestosis and fetal hypotrophy]. / Die Bedeutung von Betamimetika und Magnesium für den Schwangerschaftsausgang: II. Zur Rolle des Magnesiums bei der Entstehung der Gestose und fetalen Hypotrophie.

Of 4905 single pregnancies between 1979 and 1982 the 882 (18.0%) risk pregnancies managed tocolytically with Betamimetics and Magnesium were retrospectively compared with the remaining collective (R) of 4023 (82.0%) patients without management. The tocolysed patients (B/Mg) received Magnesium in addition to Betamimetics: since 1979/1980 a low dose Mg containing drug (Feto-Longoral) aimed at "cardioprotection" (3-6 mval Mg++ daily), and since 1981 to "support tocolysis" 30-40 mval Mg++ daily per os in the form of Mg-aspartate (Mg 5-Longoral). All cases of gestosis (G) in both collectives B/Mg and R were investigated. A normal collective (N) is obtained by subtracting G from R. For all collectives N, G, and B/Mg the following data were compared: mean age, parity, percentage with supplement Mg medication (only the B/Mg collective), the pregnancy outcome with respect to pregnancy duration and the number of intrauterine retarded infants (IUR: less than 10th percentile of the Bavarian Perinatal Evaluation (BPE), less than 25th percentile according to Hohenauer). The number of gestosis in the 882 B/Mg cases is zero. It is 97 (2.0%) in the remaining 4023 patients. The IUR rate (less than 10th perc. BPE) is 9.4% in the 3926 N patients, and is 45.4% in the 97 gestosis patients. The IUR rate is 17.8% in the 398 B/Mg patients of 1979 and 1980 who had received less adjuvant Mg (B/Mg [1]), and it is 10.1% in the 484 B/Mg patients of 1981 and 1982 who had received much higher Magnesium (B/Mg [2]).(ABSTRACT TRUNCATED AT 250 WORDS)

[The importance of betamimetics and magnesium for the outcome of pregnancy: I. Reduction of intrauterine growth retardation, premature rupture of membranes and premature birth after supplemental magnesium therapy]. / Die Bedeutung von Betamimetika und Magnesium für den Schwangerschaftsausgang: I. Reduzierung der Mangelgeburt, sowie der vorzeitigen Amnionruptur und Frühgeburt nach Magnesium-Zusatztherapie.

Of 4 905 single pregnancies recorded within a 4 year period (1979-1982) 882 (18%) were risk pregnancies managed with Betamimetics (B); of these 348 (7,1%) had tocolysis (T) and 534 (10,9%) tocolysis and cerclage (T/C). Since the end of 1979 the patients received in addition to the Betamimetic a K-Mg-Vitamin drug (Feto-Longoral) aimed at "Cardioprotection", and since the beginning of 1981 30-40 mval oral Mg daily in the form of Magnesium aspartate (Mg 5-Longoral) to "support tocolysis". The mean age, parity, percentage with Magnesium therapy, the pregnancy outcome using a gestational age limit less than or equal to 36 weeks, the frequency of premature ruptured membranes (PROM) in premature and mature infants as well as the number of intrauterine growth retarded infants (IUR) (less than 10th percentile BPE) were yearly evaluated and compared for both risk collectives T and T/C as well as for the normal collectives (N). While only 2% of the normal collectives had a pregnancy duration of less than or equal to 36 weeks (completed) the figure was five fold in both T and T/C groups, and however was yearly reduced in the T/C group from 11,0% (1979) to 4,9% (1982). The frequency of PROM with premature infants in the T and T/C groups is about 6% (N-collectives about 1%). It is however reduced in the T/C group in 1981 to 2,2% and in 1982 to 1,6%. For mature infants it is N: 17-12% (fluctuating) and B (T + T/C): 22-11% (yearly decreasing). The rate of IUR (less than 10th percentile BPE) in the T and T/C groups in 1979 was 22,2 and 20,5% respectively and in 1980 12,6 and 17,5% respectively. It is further reduced in 1981 to 11,6 and 8,8% respectively and in 1982 to 9,7 and 10,6% respectively (N-collectives between 8,3 and 11,5%). The "weight gain" exceeds the 25th percentile (Hohenauer): 1979 and 1980 for B: 33,1 and 30,2% respectively, and 1981 and 1982 for B: 25,4 and 24,2% respectively (N between 26,5 and 19,5%). The results show that patients with tocolysis--with or without cerclage--have more premature and growth-retarded infants than normal collectives (a sign of more placenta insufficiencies). In the two years where Magnesium was supplemented at 30-40 mval daily, short term pregnancies, the PROM frequency and the IUR rate decreased (statistically evaluated). It could thus be concluded that a relative Magnesium deficiency might have been responsible for a certain percentage of premature births and hypotrophic infants and that better results were obtained after Magnesium substitution.

[Induction of osmiophilic lamellar bodies by corticosteroids, Fenoterol and Ambroxol in lung tissue cultures from human fetuses]. / Induktion von osmiophilen Lamellenkörperchen durch Kortikosteroide, Fenoterol und Ambroxol in Lungengewebskulturen von menschlichen Feten.

Organ cultures were set up from human fetal lung originating from the first trimester of gestation (8-12 weeks) and followed their morphological differentiation in the absence and in the presence of Dexamethasone, Betamethasone, Ambroxol and Dexamethasone + Fenoterol. We were especially interested in studying whether multilamellar bodies and tubular myelin structures which are characteristic of the human surfactant, could be demonstrated in the cells after different treatment. Dexamethasone and Betamethasone promoted directly the development of the multilamellar bodies and the tubular myelin structures in the type II cells. - Furthermore, Ambroxol (Bromhexin-metabolite VIII) produced a prominent stimulatory effect in the synthesis of the surfactant in a concentration of 12 ng/ml. Fenoterol has probably no stimulatory effect on the surfactant production. In cultures treated with 10 ng/ml Fenoterol + 10 ng/ml Dexamethasone the benefit effect of Dexamethasone in stimulation of the multilamellar bodies was impaired. Our investigation shows that the human fetal lung is able to respond to the action of glucocorticoids and Ambroxol as early as in the first trimester of gestation by accumulating phospholipids.

[Intra-abdominal bleeding following subcutaneous heparin application in septic abortion (author's transl)]. / Intraabdominale Blutung nach subkutaner Heparinapplikation bei einem infizierten Abort

Report on intra-abdominal hemorrhage following inexpert injection into the abdominal wall of calcium-heparin concentrate (Calciparin, Nattermann, Cologne) in a patient with septic abortion. A hematoma developed in the abdominal muscles which perforated via the parietal peritoneum into the abdominal cavity.

[Ambroxol versus betamethasone for stimulating antepartal lung maturity--a multicenter study]. / Ambroxol versus Betamethason zur Förderung der antepartalen Lungenreife--eine multizentrische Studie.

In a multicenter, randomized double-blind study, the effect of Betamethasone and Ambroxol, both used for prenatal prevention of RDS in premature and newborn infants, is compared in a total of 185 patients with premature labour or an induced termination of pregnancy between the 28 and 36th week of gestation. The Ambroxol group of 93 patients is reduced to 77 due to a break up of therapy in 16 patients. The Betamethasone group is likewise reduced from 92 to 85 due to a break up of therapy in 7 patients. The main reason for breaking up therapy in these patients is the impossibility of stopping labour and delivery within 72 hours after admission to the hospital. Both treatment groups show no significant differences with regard to age, weight, history, rate of premature rupture of membranes, gestational age at beginning of therapy and at time of delivery, mode of delivery, rate of tocolytic therapy and prematurity. RDS morbidity, established by a standardized evaluation of the infants considering X-ray, clinical and blood-gas analyses findings, is 9% (7 out of 79 infants) in the Ambroxol group, and 6% (5 out of 86 infants) in the Betamethasone group. Statistically seen, the difference between the two groups is insignificant. Amniotic fluid analyses carried out in a total of 46 patients of both groups show increased surfactant parameters after therapy as compared to initial values before therapy. A significant difference between the two groups is not manifest. The objections against corticosteroids regarding there indications and side effects are generally known. The results of this study indicate that Ambroxol compared to Betamethasone can be considered as an effective drug for prevention of neonatal respiratory distress syndrome.

[The advantage of preventive vaginal antisepsis with hexetidine in obstetrics and gynecology]. / Nutzen der prophylaktischen Vaginalantiseptik mit Hexetidin in Geburtshilfe und Gynäkologie.

In five studies, the advantage of repeated vaginal prophylaxis by a new preparation of hexetidine vaginal suppositories (10 mg) was investigated prospectively, randomised and method-controlled (n = 2 x 50). After a five-day application, the hexetidine group achieved bacterial reductions of five log CFU/ml in the vagina and nearly three log CFU/ml in the cervix uteri, whilst no reduction was found in the controls at any time (p less than 0.01). The reduction of individual bacterial species was investigated in 224 pregnant and also gynaecological patients. In cases of impending preterm childbirth, a five-day application of 20 mg hexetidine/day could reduce all bacteria sufficiently with the exception of lactobacilli; especially beta Streptococci were reduced. The same was achieved by a three-day application of 10 mg hexetidine/day pre-operatively. A long-term study in 11,724 deliveries showed, that neonatal infectious mortality and morbidity after 36 gestational weeks could be reduced significantly by hexetidine. The new hexetidine preparation appeared to be efficient in vaginal antisepsis, especially in pregnancy. A favourable lactobacilli-selective effect was demonstrated. Since the importance of lactobacilli in vaginal ecology is known, hexetidine prophylaxis must be considered as advantageous in Obstetrics and Gynecology. From a practical and economic point of view, the application of hexetidine as vaginal suppositories appears favourable compared to antiseptic solutions.

[Changes in maternal cardiovascular parameter during tocolysis and in the dorsal position shock syndrome (author's transl)]. / Anderungen der maternalen cardiovasculären Parameter während der Tokolyse und beim Rückenlageschocksyndrom

Maternal circulatory parameters and fetal heart rate were measured in 25 healthy pregnant women in the last trimenon during treatment with Fenoterol, Fenoterol in combination with Verapamil and Verapamil alone. Dosages were used in accordance with the tocolytic guidelines from Weidinger and Wiest. We were able to demonstrate that the betamimetic Fenoterol alone and in combination with the Ca++-antagonist Verapamil strongly increases the maternal heart rate an the maternal cardiac output whereas the peripheral resistance decreases accordingly. The average blood pressure stayed leveled, so that a decreased uterine blood flow cannot be assumed under betamimetics from the maternal cardiovascular point of view. However, there are indications for an increased placental blood flow during tocolysis. The betamimetic drug show no significant effect on the fetal heart rate. Additional application of the Ca++-antagonist Verapamil during tocolysis with Fenoterol (in dosages usually used for tocolysis) doesn't change cardiovascular reactions caused by Fenoterol. Change in position from supine to left lateral position caused a short term increase in the maternal cardiac output even noted in pregnant women without a clinically observed cavasyndrom. These changes of maternal cardiac output are comparable with those in orthostatic stress situations.

[Growth hormone in the newborn infant during the first 6 days of life]. / Das Wachstumshormon des Neugeborenen in den ersten 6 Lebenstagen

Human Growth Hormone (HGH) of the newborn during its first days of life is approximately 61 ng/ml, then it falls between the third and fourth day. This fall in serum concentration principally occurs when the infant stops losing weight and starts regaining it. Experiences show that HGH of newborn does not stem from the mother.

[Potassium substitutes during tocolysis]. / Kalium-Substitution bei Tokolyse

The level of serum potassium during tokolytic therapy with Partusisten and Isoptin decreases in the first 24 hours of therapy. This decrease is not due to an increase in renal potassium elimination. During tokolytic treatment the serum level of potassium returns to its normal value after 48 hours without potassium substitution. While there is a decrease in serum potassium noticeable changes in electrocardiogram which are typial for hypopotassemia are observed. These changes disappear afer 48 hours of tokolytic treatment but never the less the initial serum potassium drop should be balanced by potassium substitution within these 48 hours.

[Behaviour of serum concentrations of glucose, immunoreactive insulin and potassium ions in newborns after long term or crash treatments with Partusisten or Partusisten in combination with Isoptin (author's transl)]. / Zeitlicher Verlauf der Blutglukose, des immunoreaktiven Insulins und der Kaliumionen beim Neugeborenen nach Iangzeitiger und akuter Gabe von Partusisten mit und ohne Isoptin

The investigation was done on 50 infants born of metabolic healthy mothers. A group of 10 women received short term treatment with Partusisten and Isoptin. Another 10 were treated over the same period with Partusisten only. A further group of 15 received long term treatment (more than 7 days) with Partusisten and Isoptin and a final group of 15 mothers received placebos. Serum concentrations of glucose, immunoreactive insulin and potassium, together with acid-base-status and other important blood chemistry were determined in mothers and newborns directly postpartum. Blood sugar, immunoreactive insulin and potassium were further determined in the newborns 30 minutes, 60 minutes, 2 hours and 6 hours after birth. The results showed that a temporary relative hypoglycaemia occured in the newborns in short term as well as long term treatment with Partusisten or Partusisten in combination with Isoptin. Temporary derangements in insulin-glucose equilibrium were also seen in newborns from mothers receiving long term treatment. It was also demonstrated that approximately 1 hour post-partum, blood sugar and immunoreactive insulin of the newborn attained values compatible with normal carbohydrate metabolism. From these results it is indicated that infants born of mothers, who received tocolytic treatments with Partusisten or Partusisten in combination with Isoptin, should be given sodiumbicarbonate and glucose directly after birth.

The effects of betamimetic drugs used for tocolysis on the fetal myocardium.

During the last five years tocolysis with betamimetic drugs, e.g. Fenoterol has become a standard method for the treatment of impending premature births. We studied the effect of Fenoterol in vitro on organ cultures of human fetal hearts. At a concentration in the nutrient medium corresponding to the dose used in clinical application, light and electron microscopy demonstrated myocardia damage. In contrast the combined use of Fenoterol and the calcium antagonist Verapamil in a ratio of 1:40 showed no pathological findings either clinically or in vitro. The results are documented with light and electron photomicrographs.