[Plasma concentrations of non-esterified fatty acids and lipids in high-dose medroxyprogesterone therapy of metastatic breast cancer]. / Plasmakonzentrationen der unveresterten Fettsäuren und der Lipide unter einer hochdosierten Medroxyprogesteron-Therapie beim metastasierten Mammakarzinom.

The objective of this study was to investigate the influence of high dose MPA on serum cholesterol, triglyceride, phospholipids as well as free fatty acids given to 17 patients with metastatic breast cancer. Before the therapy, the patients with cancer revealed higher level in serum cholesterol, triglyceride, phospholipids and C 12:0, C 18:0 as we found it in the control (13 patients without cancer). There was no significant change in lipid parameters by treatment with MPA whereas cortisol decreases and insulin increases under therapy. The results are discussed under biochemical aspects.

[Maternal and fetal metabolic parameters in acute and chronic fetal malnutrition]. / Mütterliche und fetale Stoffwechsel-Parameter bei akuter und chronischer Versorgungsstörung des Feten.

The respiratory pathophysiology of placental insufficiency is well understood, whereas the metabolic effects of chronical or acute malnutrition still need further evaluation. In a comprehensive study of 20 deliveries respiratory parameters and substrates of carbohydrate- and lipid-metabolism were analysed simultaneously from maternal blood at 4 cm dilatation, at cord clamping immediately delivery and 2 hours post partum as well as from arterial and venous umbical blood samples. Normal deliveries were compared with cases of fetal retardation and moderate acute fetal acidosis. For glucose, insulin, c-peptide and pyruvate a strong rise in maternal blood during labour was observed as well as for the non-esterified fatty acids (NEFA), which have a high materno-fetal gradient. Arterio-venous differences of concentrations were found in the umbilical cord blood for glucose, pyruvate and NEFA. In cases of chronical insufficiency of the placenta especially elevated lactate levels were measured, whereas a moderate fetal acidosis obviously leads to an additional feto-maternal pyruvate transfer. The results lead to the conclusion that the fetal metabolism has considerable means of adaptation during delivery even under chronical or moderate acute stress conditions.

[Plasma lipoprotein fractions in high-dose medroxyprogesterone acetate therapy in metastatic breast cancer]. / Plasma-Lipoproteinfraktionen unter hochdosierter MPA-Therapie beim metastasierenden Mammakarzinom.

Metabolic disorders induced by synthetic gestagens have been discussed under the aspect of single endocrine parameters or the carbohydrate or lipid metabolism. In order to obtain more complex information a prospective study of 26 patients was performed, who were treated with 1,000 mg medroxyprogesterone acetate (MPA) per day over a period of 5 weeks as a second-line therapy of breast cancer. Before treatment and afterwards once a week the serum concentrations of MPA, androstenedione, DHEA-S, cortisol, prolactin, insulin, c-peptide, glucose, cholesterol, triglycerides, phospholipids and the lipoprotein fractions (VLDL, IDL, LDL, HDL) were analyzed. Besides the reduction of the androgens and changes in the glucose regulation significant effects on the lipoprotein metabolism were observed, leading to the conclusion that under high-dose gestagen therapy very complex interactions of the endocrine and metabolic system occur.

[Long-chain non-esterified fatty acids in pregnancy, labor and post partum]. / Langkettige unveresterte Fettsäuren in der Schwangerschaft, unter der Geburt und post partum.

Serum concentrations of non-esterified fatty acids (NEFA) remain unchanged up to the 21th week of gestation in comparison to non-pregnant women; also after the 37th gestational week only slightly increased concentrations are observed in women without labour. Under delivery, however, NEFA in maternal serum are approximately three times higher than those of non-pregnant women. This increase occurs only in NEFA with a chain-length of C12 to C18. Post partum values reach those of non-pregnant women within a few days. The concentrations of NEFA with a chain-length of C12 to C18 in umbilical artery and vein are significantly lower than in maternal serum.

[Maternal lipoproteins post partum. Qualitative and quantitative studies of the effect of lactation]. / Mütterliche Lipoproteine post partum. Qualitative und quantitative Untersuchungen über den Einfluss der Laktation.

Quantitative and qualitative examinations of serum lipoproteins separated by use of discontinuous ultracentrifugation were performed in 17 lactating and 13 non-lactating healthy women 5 days and 5 weeks after delivery. In general a normalisation of the lipid parameters, which are increased during gestation, was observed during this period. Within 5 weeks after delivery all single parameters were in levels of normal non-pregnant women. A significant effect of lactation on the decrease of pregnancy-induced hyperlipoproteinemia after delivery could not be detected.

[Medicamentous obstetric analgesia with pentazocine in comparison with an untreated control group]. / Medikamentöse geburtshilfliche Analgesie durch Pentazocin im Vergleich mit einer unbehandelten Kontrollgruppe.

In order to establish whether a powerful analgesic such as pentazocine administered during birth may damage the child or have negative influence on the course of birth, the course of delivery was studied in 40 patients, 20 of whom were given a single dose of 30 mg pentazocine administered intramuscularly. There were no differences in duration of birth, CTG, blood gases post partum, or Apgar scores as compared to the untreated control group. As regards the pharmacokinetics, the serum pentazocine levels of the gravidae corresponded to those found in non-pregnant subjects; the levels found in blood from umbilical cords and new-borns were at the lower limit of detectability. Almost all of the gravidae described the obstetric analgesia as good or adequate. The principal side effect, mentioned by one-third of the pentazocine group, was slight fatigue. As regards the newborns, the fetal outcome in the two groups was the same.

[Pattern of distribution of apolipoproteins A and B in the lipoprotein fractions of serum in pregnant patients and post partum]. / Verteilungsmuster von Apolipoprotein A und B in den Lipoproteinfraktionen des Serums bei Schwangeren und post partum.

Investigating the for gestationally caused changes and their restitution p. partum we determined in 104 women without metabolic disorders the apolipoproteins A and B respectively in serum, in the main lipoprotein fractions VLDL, IDL, LDL, HDL and in the "rest protein" remaining after separation of the lipoproteins from the serum. In gestation there is an increase in the serum level of apo A of about 30% (p less than 0.001) reaching its maximum in the middle period of pregnancy. The post partal restitution of these changes takes more than 5 weeks happening faster at primarily delactated women. Gestational changes concerning apo A are only caused by a 30% higher concentration of apo A in HDL (p less than 0.001). The serum level of apo B seems to increase continuously meanwhile gestation reaching its maximum from about 60% (p less than 0.001) at the term. The restitution of the gestational changes concerning apo B also requires more than 5 weeks showing no dependence from lactation. The changes of serum apo B are quantitatively most influenced by the 45% higher concentration of apo B in LDL (p less than 0.001), despite the marked changes of apo B in relation to the nonpregnant comparative group found in VLDL and IDL respectively with either 270% (each p less than 0.001). Hyperbetalipoproteinemia in pregnancy was proved in 32%, but in no case the ratio apo B/apo A showed pathological values, because of also raised levels of apo A in these women. By this astonishing phenomenon the gestational hyperlipoproteinemia is characterized as an autonomic metabolic situation, which represents no earlier described type according to the Fredrickson classification.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of long-chain nonesterified fatty acids in sera of young women in different phases of the menstrual cycle. Application of a new gas chromatographic microliter method.

Nonesterified fatty acids (NEFA) from C12 to C24 have been determined in sera of 13 young women at menstruation, and in the follicular and luteal phase of the menstrual cycle applying a new gas chromatographic microliter method. Neither the total NEFA content nor the concentrations of individual fatty acids showed significant differences in the three phases of the menstrual cycle. With the exception of stearic acid we found almost constant relative concentration values for the individual fatty acids within the medium range of the long-chain NEFA spectrum. Intraindividual and interindividual dispersion was hardly greater than the variation caused by the method of determination itself, whereas the intra- and interindividual scattering of the rim fractions of the NEFA spectrum was much more distinct. The coefficients of variation for the as well as individual NEFA content related to all examined women at any phase of the menstrual cycle were lower than 40% with the exception of the rare erucic acid, behenic acid and lignoceric acid.

Metabolic changes in the rat liver during pregnancy. II. Tricarboxylic acid cycle.

During pregnancy the rat liver shows alterations in metabolism which apparently do not to occur in the non-pregnant animal. In our study, the following metabolite concentrations and enzyme activities in the liver of pregnant and non-pregnant rats were measured after fasting periods of 6 and 12 h: malate, fumarate, isocitrate, alpha-keto-glutarate, glutamate, malate-dehydrogenase, fumarate-hydratase, glutamate-dehydrogenase, isocitrate-dehydrogenase, aspartate-aminotransferase and after 12 h fast, the concentrations of acetyl coenzyme A and citrate. These results are discussed with regard to their possible importance for the maternal and fetal energy supply.

The influence of oral contraceptives on the composition of bile.

The increased risk of cholelithiasis during intake of oral contraceptives may be due to estrogen-induced saturation of the bile with cholesterol. In a randomized, prospective, crossed-over double-blind study 20 healthy women after roentgenological exclusion of gall-stones received either 1.0 mg of norethindrone acetate and 50 microgram ethinyl estradiol daily - as usual in oral contraception - for 21 days with 7 days of placebo treatment in each cycle or one fifth of this hormone dose in form of a continuous daily medication. After a 4 month's treatment the medication form was crossed-over. At the beginning of the study, before the cross-over and after the study bile was collected by duodenal intubation after a 12-h fast and the lithogenic index as a measure for cholesterol saturation of the bile was determined. No correlation between the dose and the lithogenic index was demonstrated, neither in 15 women, who had used oral contraceptives before the study nor in five women without any previous hormonal contraceptives.

PIP: The increased risk of cholelithiasis during oral contraceptive (OC) intake may be due to the estrogen-induced saturation of the bile with cholesterol. In a randomized, prospective, crossover double-blind study, 20 healthy women after roentgenological exclusion of gallstones received either 1.0 mg of norethindrone acetate and 50 mcg of ethinyl estradiol daily for 21 days with 7 days of placebo treatment in each cycle or 1/5 of this hormone dose in the form of continuous daily medication. After 4 months of treatment, the medication form was crossed over. At the beginning of the study, before the crossover and after the study, bile was collected by duodenal intubation after a 12 hour fast and the lithogenic index as a measure for cholesterol saturation of the bile was determined. No correlation between the dose and the lithogenic index was demonstrated, neither in 15 women who had used OCs prior to the study nor in 5 women without any previous OC taking history. (author's)

A microliter method for the gas chromatographic determination of long-chain non-esterified fatty acids in human serum or plasma.

Non-esterified fatty acids (NEFA) from C12 to C24 are assayed in human serum or plasma in a four-step procedure: extraction, volume reduction, methylation and gas chromatography. NEFA are extracted with chloroform--heptane--methanol from 50--100 microliter of serum or plasma buffered with phosphate. After adding ethyl acetate the volume of the extract is reduced under partial reflux to 5--7 microliter. Potassium carbonate, methyl iodide and a crown ether are added to the dry concentrate and the NEFA are selectively methylated with a yield of 100% by heating in a microrefluxer for 10 min. Gas chromatography is carried out with 1 microliter of the reaction mixture on a packed column by temperature-programmed operation. Thirteen individual fatty acids are determined in sera of normal adults. The coefficients of variation for 24 determinations of a pooled serum were 2.7% for the total NEFA content and 3--10% for most of the individual NEFA.

Serum prolactin and tumors of the prostate: unchanged basal levels and lack of correlation to serum testosterone.

To investigate the possible role of circulatory levels of prolactin on the development of prostatic tumors, and to gain insight into the prolactin-androgen relationship, serum prolactin and testosterone were determined in 73 patients with newly diagnosed prostatic adenocarcinoma. Controls consisted of 32 patients with benign prostatic hyperplasia before treatment, 19 age-matched controls, and 21 young individuals. Hormones were measured under standardized conditions by highly specific and sensitive radioimmunoassays. There was no difference in prolactin in the elderly men regardless of prostate pathology, but a significant increment was found in young controls. Individual prolactin values did not correlate with serum testosterone, and there was no statistical regression in prolactin values of patients in the age range between 50 and 80 years. In a second study, serum testosterone and prolactin were measured in 7 patients with prostate cancer and in 6 individuals with benign prostatic hyperplasia before and 30 and 60 minutes after stimulation with an iv bolus of 200 microgram TRH. Both hormones were within the normal range at time T0, and a significant stimulation of prolactin was achieved (p less than 0.001). Prolactin values did not differ between patients with benign and malignant prostatic disease. Thus, when investigating the role of prolactin in neoplastic prostatic growth in the human, it seems necessary to investigate receptor-mediated prostatic tumor responsiveness, and interferences with androgen converting enzymes on a cellular level, rather than circulating prolactin concentrations.

[Hormonal contraception and lipid metabolism. Prospective and retrospective studies of lipid metabolic parameters during the use of contraceptives]. / Hormonale Kontrazeption und Fettstoffwechsel Prospektive und retrospektive Untersuchungen von Parametern des Fettstoffwechsels bei Einnahme von Kontrazeptiva.

Remarkable changes of several parameters of lipid metabolism were observed in a retrospective study of women, who had used different oral contraceptives for a longer time, in comparison with women without any hormonal contraception. In contrast, under the conditions of a prospective double-blind study no statistically significant alterations of the same parameters were seen under the use of two oral contraceptives different in dosage. Nevertheless, oral contraceptives should not be prescribed to patients with hyperlipidaemia.

PIP: 20 women, average age 24.4, participated in a double-blind prospective study to determine the effects of oral contraceptives (OCs) on lipid metabolism. A preparation containing 2 mg norethindrone acetate (NA) and 10 mcg ethinyl estradiol (EE) was used daily, while a preparation containing 1 mg NA and 50 mcg EE was used cyclically. 2 groups of 10 women each used 1 of the preparations for 16 weeks, then switched to the other for 16 weeks. Blood studies were taken after the 16th and 32nd weeks. No changes in lipid metabolism were observed upon comparison with a 20 member control group. A retrospective study was taken involving 30 women, average age 28.5, who had used a combination preparation containing 30-50 mcg EE for at least 1 year. In this group all serum lipid levels were significantly higher (p .01). The beta-lipoprotein level was found to be significantly lower, and the alpha and pre-beta lipoprotein levels were markedly higher (p .05). The difference in the results of the 2 studies could have to do with the difference in the types of preparations used or the length of preparation use. Hyperlipidemia should still be regarded as a relative contraindication for OC use.

Investigations of gestation-induced metabolic changes in the rat liver. I. Glycogen metabolism.

The activities of alpha-glucan-phosphorylase and phosphoglucomutase and the concentration of glycogen were measured in the liver of pregnant and non-pregnant rats. There were no significant differences between normal non-pregnant and pregnant animals nor was there any change of enzyme activities during pregnancy. Our results lend support to the idea that glycogen metabolism is not changed during normal pregnancy.

[The importance of ultra-sound cephalometry for the prediction of the date of delivery--a contribution to the assessment of duration of pregnancy (author's transl)]. / Zur Bedeutung der Ultraschall-Kephalometrie für die Voraussage des Entbindungstermins--Ein Beitrag zur Tragzeitbestimmung

On the basis of some statistical data ultrasound cephalometry for the prediction of term is discussed. These data should be considered when providing socalled test-graphs. The usefulness of the author's own standard graph is examined. Prediction with the biparietal diameter is not much less exact than after the rule of Naegele. Accuracy of prediction can be much improved by using both methods together, starting from the averages of both.