The renin-angiotensin-aldosterone system, antidiuretic hormone levels and water balance under tocolytic therapy with Fenoterol and Verapamil.

The effects of long-term infusion of fenoterol (a beta 2-sympathomimetic drug) in combination with the calcium antagonist verapamil on water balance, the renin-angiotensin-aldosterone system and antidiuretic hormone during pregnancy were studied. Within two hours of the start of infusion, plasma renin and antidiuretic hormone levels were significantly increased, but plasma aldosterone was strongly decreased. There was a concomitant marked reduction of urinary, sodium, and potassium excretion and a decreased creatinine clearance. The long-lasting reduction of urinary excretion which resulted in an elevated water retention is apparently due to other unknown factors. Results are discussed with special regard to the relationship between water balance disturbances and pulmonary edema.

[Risks of pharmacotherapy in heart diseases in pregnancy]. / Risiken einer Pharmakotherapie bei kardialen Erkrankungen in der Schwangerschaft.

Normal physiological changes in the cardiovascular system in pregnancy such as increase in cardiac output, vasodilatation and hypervolemia are of clinical relevance as they are able to aggravate, mask or even imitate cardiovascular diseases. There is an increase of cardiac size and volume during pregnancy; furthermore hormonal changes lead to diaphragmatic elevation and barrel-shaped thorax followed by a rotation of the cardiac axis to the left (15 degrees-30 degrees). Cardiac topography and size, changes in cardiac functioning and physiology as well as hemodynamic changes lead to auscultatory and ECG changes (i.e. S1-Q3-type, ST-depression, T wave flattening). In addition there is a high incidence of functional systolic and diastolic sounds during pregnancy, which are also able to imitate cardiovascular diseases. The physiological changes in pregnancy are similar to those under heavy exercise. This results in continuous cardiac stress during the whole pregnancy. This stress is specifically high from the 28th to the 34th week of pregnancy and in the post-partum period; the maximum of cardiac stress is reached during labor. Important for the specific cardiac risk during pregnancy is not the type of heart disease but cardiac functioning and the severity of complaints before pregnancy. Principally it has to be expected that preexisting heart diseases will experience an aggravation of one grade according to NYHA during pregnancy. In cases of heart diseases with shunt defects, with shunt defect and injured myocardium, with continuous arrhythmia or atrial fibrillation, patients are at extremely high risk of cardiac death. A termination of pregnancy should be considered in all patients with heart diseases grade III or IV according to NYHA, severe pulmonary hypertension, Eisenmenger's syndrome, severe aortic or pulmonary stenosis, Marfan's syndrome, and severe continuous cardiac insufficiency. The drug therapy of cardiac diseases during pregnancy depends on the specific type of heart disease. Prescription of most drugs is principally possible during pregnancy and breast feeding. However, for most drugs there is only very limited therapeutic experience during this period. Definitively contraindicated during pregnancy and breast feeding are ACE inhibitors, angiotensin I and II blocking agents, vasopeptidase inhibitors and molsidomin, a NO-prodrug. In life-threatening conditions, however, sometimes it will be necessary to administer drugs with only poor experiences in pregnancy.

[Constriction ring dystocia: a special form of uterine dystocia (author's transl)]. / Constriktion Ring Dystokie. Eine Sonderform der uterinen Dystokie

Constriction Ring Dystocia means a rare form of uterine dystocia (0.1%--1.7%). Pathophysiologically it means a hypertonic incoordinate anomaly of labor. The paper reports two cases of constriction ring, which had been recognized first during sectio cesarean. As the measure of choose is suggested to use tocolytica, although there do not exist any experiences and there was yet no chance to utilise these medicines because of lack of early recognition.

[Genital malformations in thalidomide-damaged girls (author's transl)]. / Genitalmissbildungen bei thalidomidgeschädigten Mädchen

Due to the close morphological relationships and the dependence of the genital system on inductive impulses from the uropoietic system, the possibility of an increased incidence of malformations in the area of the female genitals for thalidomide-damaged children is to be expected. This suspicion is supported by the accumulation of reports of genital malformations in deceased children from mothers who took thalidomide-containing medicaments during the early weeks of pregnancy. - A 14-year-old patient with malformations of both upper extremities whose mother had taken thalidomide during the 6th to the 9th week of pregnancy presented at our hospital with complaints of cyclic pain in the lower abdomen. Although the ovaries and fallopian tubes were normally developed, the uterus and the vagina were absent in this patient. After this manuscript had been completed, we heard of 3 additional cases of genital malformation with a known thalidomide anamnesis.

[Occurrence of pulmonary oedemas without myocardial necroses under beta 2-sympathomimetic therapy with fenoterol (experimental investigations in the rabbit (author's transl)]. / Auftreten von Lungenödemen ohne Herzmuskelnekrosen unter beta 2-sympathomimetischer Therapie mit Fenoterol (Tierexp. Untersuchungen am Kaninchen.

Experimental investigations in the rabbit were aimed at solving the question whether the development of a pulmonary oedema during tocolytic therapy with beta 2-sympathomimetics can be explained by hyperhydration, since myocardial necroses are not likely to be the cause of a pulmonary-oedema at the standard clinical dosage level. Fenoterol is infused over a period of 24 hours in combination with low (2.5 mgl/h) and high (30 ml/h) supply of liquid (isotonic solution, Sterofundin). Essential changes in the measured parameters occur only if the quantity infused is high. The following findings were established: 1. an increase in the liquid content of the lung and heart from 80 to 90%. 2. blood gas analysis revealed marked signs of a ventilatory disturbance, 3. histologically, the lungs showed partly massive changes pointing to the presence of an interstitial and intraalveolar oedema. Since no myocardial necroses can be histologically identified, the pulmonary insufficiency cannot be due to cardiac decompensation as a result of myocardial necroses.

Plasma glucocorticosteroid and aldosterone levels during physiological and stress conditions in rabbits. II. adult animals.

The pattern of adrenal steroid secretion under basal and stress conditions and the response to tetracosactid (20.0 micrograms/kg body weight) were studied in adult male rabbits. In animals repeatedly stressed by artery puncture, plasma glucocorticosteroid levels were slightly higher than those found in unstressed control animals. The combined stress of repeated exposure to ether vapor for 60 sec, followed by artery puncture, significantly stimulated glucocorticosteroid release, concentrations progressively increasing with the number of ether exposures applied. A much faster and more pronounced stimulation of glucocorticosteroid release was seen in animals treated with 20.0 micrograms/kg body weight tetracosactid. Plasma aldosterone levels in animals stressed by artery puncture were higher, although not significantly, than those of unstressed control animals. Repeated exposure to ether vapor for 60 sec, followed by artery puncture, on the other hand slightly decreased plasma aldosterone concentrations. A strong stimulation of aldosterone release at 20--60 min after injection could be elicited only by intravenous administration of 20.0 micrograms/kg body weight tetracosactid. Because of the insensitivity of the zona glomerulosa cells to increased ACTH levels under stress conditions, it is concluded that ACTH is only of minor importance both under basal and stress conditions in the regulation of aldosterone secretion in the rabbit.

Basal plasma aldosterone levels and tetracosactid-induced increase of aldosterone secretion in conscious male rabbits: lack of correlation with glucocorticosteroid levels.

The adrenocortical secretory activity under basal conditions and after treatment with tetracosactid (1-24ACTH) has been investigated in chronically cannulated male rabbits. Basal plasma concentrations of glucocorticosteroids (0.74 micrograms/100 ml) and aldosterone (78 pg/ml) have been determined in a greater number of animals. No significant positive correlation between basal glucocorticosteroid and aldosterone plasma levels could be found. After intravenous injection of 2.5, 5.0, 10.0 and 20.0 micrograms/kg body weight tetracosactid glucocorticosteroid concentrations were significantly elevated between 40--100 min after administration; aldosterone release, on the other hand, was significantly increased only after injection of 10.0 or 20.0 micrograms/kg body weight tetracosactid between 20--60 min after injection. After administration of high tetracosactid doses glucocorticosteroid and aldosterone plasma concentrations were significantly correlated (10.0 micrograms/kg: r = 0.62; 20.0 micrograms/kg: r = 0.26). Because of the relative insensitivity of the zona glomerulosa cells to tetracosactid administered intravenously, it is concluded that ACTH is only of minor importance in the regulation of aldosterone secretion in the rabbit.

[Pulmonary edema during tocolytic treatment (author's transl)]. / Zur Frage des Lungenödems bei der tokolytischen Therapie.

During tocolytic treatment with Beta 2-Sympathomimetic drugs pulmonary edema is occasionally observed. The cause remains uncertain. Within 48 hours after the onset of treatment marked water retention is observed. The weight increases, the hemoglobin decreases the hematocrit decreases, the albumin concentration decreases, the water and sodium excretion decreases. The pathogenesis is discussed and recommendations for the management are proposed. Water retention due to tocolytic treatment in addition to the physiologic water retention of pregnancy or in addition to pre-eclampsia cortisone treatment, renal insufficiency, or treatment with intravenous infusions may lead to a hypervolemia which can no longer be compensated by diuresis and therefore can lead to pulmonary edema. A list of 10 groups of patient with a high risk is described. These require thorough observation following tocolytic treatment.

[SUSILAP-G: a surgical simulator for training minimal invasive interventions in gynecology]. / SUSILAP-G: Ein Operationssimulator zum Training minimal-invasiver Eingriffe in der Gynäkologie.

After a brief introduction about virtual reality and model-building this paper describes the special technical and theoretical requirements of dynamic surgical simulation in contrast to traditional static systems. This is done by means of the simulator SUSILAP-G. With SUSILAP-G an example of an application in telemedicine is given.

Urinary protein electrophoresis profile in normal and hypertensive pregnancies.

By using of modified urine preparation and a highly sensitive SDS-polyacrylamide gel electrophoresis (SDS-PAGE) we determined the urinary protein profile in 21 healthy males, 25 healthy females, 64 patients with uncomplicated pregnancy and 110 hypertensive pregnant women. The urinary protein patterns were similar in controls and in women with a normal pregnancy. There were no increase in the number of protein bands from the 1st trimester to term, and the electrophoresis pattern did not change in the postpartum period. In both groups, an intensively stained protein band with an apparent molecular weight of 105 kD was detected. The 105 kD band was significantly reduced or completely absent in 91 (83%) out of 110 hypertensive pregnant women. The urinary protein electrophoresis profile correlated significantly with the severity of the disease. The 105 kD band disappeared just before or simultaneously with the onset of clinical symptoms in 18 out of 32 hypertensive pregnant women followed throughout pregnancy. Postpartum the 105 kD in urine reappeared at 2 to 14 days after delivery in 49 of the 53 patients. Using a silver staining and Western blot, the 105 kD band was identified as Tamm-Horsfall protein, which is identical to the immunosuppressive glycoprotein uromodulin. The findings in the SDS-PAGE may reflect a transitory tubular dysfunction in cases of pre-eclampsia, which is usually reversible after delivery. The results of our study support the hypothesis of an immunological basis for this disorder.

Urinary excretion, osmolarity and electrolytes after bolus-injection of fenoterol in female rabbits.

The effects of bolus injections of 1.0-80.0 micrograms/kg body weight fenoterol on urinary excretion, osmolarity and electrolytes were studied in unanesthetized, water-loaded rabbits. In animals infused initially with isotonic solution over 2 h with 60 ml/h and thereafter over 10 h with 45 ml/h, urine excretion was 538 ml/12 h, sodium excretion was 65.4 mmol/12 h, and potassium excretion was 4.8 mmol/12 h. In animals injected with 5.0-80.0 micrograms/kg body weight fenoterol, a strong antidiuresis occurred, lasting for 2 (10.0 micrograms/kg) to 4 h (80.0 micrograms/kg). Due to the strong antidiuresis, urinary osmolarity was significantly elevated for 2 (10.0 micrograms/kg) to 3 h (80.0 micrograms/kg). The changes of sodium excretion after fenoterol injection were very similar to those of urine excretion. Maximum reduction of sodium excretion was found after injection of 10.0-80.0 micrograms/kg body weight fenoterol, the effect lasting for 1 h (10.0 micrograms/kg) to 4 h (80.0 micrograms/kg). Potassium excretion was significantly reduced after injection of 5.0-80.0 micrograms/kg body weight fenoterol. In contrast to all the other parameters measured, potassium excretion remained significantly reduced until the end of the infusion period in animals treated with 10.0-80.0 micrograms/kg body weight fenoterol and was not dose dependent. Our data presented in this work extend earlier findings in the rabbit in that bolus injection of fenoterol also results in a drastic decrease of urine and electrolyte excretion. The results are discussed with special reference for the management of acute fetal distress with betamimetics and to the development of pulmonary edema that has been shown to occur under therapy with betamimetics on both female rabbits and humans.

[Current aspects of therapy of ovarian cancer. Surgical therapy of epithelial ovarian cancer at the Göttingen University Gynecologic Clinic. A retrospective analysis of 82 patients 1981-1984]. / Aktuelle Aspekte der Therapie des Ovarialkarzinoms. Die operative Therapie des epithelialen Ovarialkarzinoms an der Universitäts-Frauenklinik Göttingen. Eine retrospektive Analyse bei 82 Patientinnen der Jahre 1981-1984.

The most important step in the treatment of epithelial ovarian carcinoma is radical surgery which should be as radical as possible, since this can exercise a decisive influence on the effectiveness of subsequent chemotherapy or radiotherapy. During 1981-1984 98 patients with an ovarian carcinoma were operated upon. 82 of these patients had epithelial tumours that will be discussed in the article. The mean age was 59.9 years. 88% of the patients were additionally at risk by one or several risk factors. Surgical approach was standardised: longitudinal incision, hysterectomy, adenectomy, resection of omentum and, if necessary, maximum possible removal of the peritoneum of the pelvis. In 28 cases additional surgery became necessary at the intestine. 77% of the patients (n = 63) were in the advanced stages FIGO III and IV. In 50 patients the operation lasted for up to 4 hours, in 24 up to 6 hours and in 8 for more than 6 hours. Intraoperative complications occurred in 37% (twice lesion of the ureter, in 5 cases intestinal lesion, in 23 cases anaesthesiological problems due to preexisting risks). In stages I and II reduction of tumour size below 2 cm was achieved in 100% of the cases, in stage III in 87.5%, in stage IV in 45%. Two patients died postoperatively. The postoperative complication rate was 48%. Almost 30% of these were represented by cardiopulmonary disturbances. Although the percentage appears high, most of the problems were well manageable, so that the patients could be transferred to follow-up therapy within 2-3 weeks. For type of follow-up therapy, tumour response.(ABSTRACT TRUNCATED AT 250 WORDS)

[Postoperative therapy of epithelial ovarian cancer at the Göttingen University Gynecologic Clinic. A retrospective analysis of 82 patients 1981-1984]. / Die postoperative Therapie des epithelialen Ovarialkarzinoms an der Universitäts-Frauenklinik Göttingen. Eine retrospektive Analyse bei 82 Patientinnen der Jahre 1981-1984.

An epithelial ovarial carcinoma was diagnosed and treated during 1981 to 1984 in 82 patients of the Department of Gynaecology of the University of Göttingen. The diagnostic approach and therapy are described in the paper by Grospietsch et al. [Geburtsh. u. Frauenheilk. 46 (1986), 588]. The present paper deals with the results of postoperative treatment, with particular emphasis on those factors presently considered to be prognostically relevant, such as postoperative tumour residue, age of the patient and stage of tumour spread. The results are classified according to rate of response, progression-free interval and survival time or survival rate. Analysis of the results shows that on the one hand an improvement of long-term results (survival time) has been very unsatisfactory with present-day methods--and moreover, that partly such long-term results are obtained only on the basis of an accurate diagnosis--whereas on the other hand the short-term results (tumour-free interval) together with a clear improvement of the quantity and quality of life do justify the considerable effort required by the treatment concept. Improvement of the overall result is more likely to be achieved by clinical and preclinical research towards consolidation of the primary therapy effect than by employing "trial-and-error" methods within the framework of primary therapy.