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Biomedical subjects

M Breckwoldt

Publications and source records attributed to M Breckwoldt.

At least 109 records · Page 6Linked to original sources

[Effects of sex steroids on the lipoprotein profile].

Plasma testosterone levels were measured pre- and postoperatively as well as during estrogen substitution in a 47-year-old woman with excessive hyperandrogenaemia due to a Leydig-cell tumour of the left ovary. In addition, the lipoprotein profile was determined before and 14 days after removal of the tumour and four weeks later during estrogen substitution. The preoperative plasma testosterone level was between 6.25 and 8.50 ng/ml; at the same time there was a hypercholesterolaemia with increased beta-lipoprotein and decreased alpha-lipoprotein fractions: the ratio of beta- to alpha-lipoprotein cholesterol was 3.0, a type IIa hyperlipoproteinaemia. After the testosterone concentration had returned to normal both the beta- and pre-beta cholesterol fell significantly, while the alpha-lipoprotein fraction remained unaltered. The alpha-cholesterol fraction increased significantly after estrogen substitution, the beta- to alpha-lipoprotein ratio being 1.20. It is concluded from these results that hyperandrogenaemia goes together with raised peripheral beta and pre-beta-cholesterol concentration, while estrogens cause a rise in the alpha-fraction.

Cholesterol↗

Diurnal variations in unconjugated oestriol levels during early pregnancy and their relation to maternal cortisol levels.

We studied maternal plasma levels of oestriol (measured by radioimmunoassay) and total cortisol (measured by a protein binding method) in 11 women from 8 to 22 weeks gestation. Blood specimens (5 ml) were drawn over a 24-h period at 60 and 30 min intervals. The diurnal rhythm of cortisol with higher values in the morning than in the afternoon and evening was present at all gestational ages studied. Unconjugated plasma oestriol showed a similar circadian rhythm to maternal cortisol (r = 0.576, P less than 0.01) in the 8th week. From the 9th to the 11th week oestriol values rose and there was no evidence of a circadian rhythm. In the 12th week plasma oestriol again showed a circadian rhythm, with higher values at night (117.3 +/- 9.5 pg/ml) than during day-time (104 +/- 7.5 pg/ml, P less than 0.001). This pattern remained until the 22nd week, when plasma oestriol levels at night (3.78 +/- 0.49 ng/ml) were markedly higher than in the day-time (3.16 +/- 0.3 ng/ml, P less than 0.001). An inverse relation between oestriol and cortisol levels as shown in late human pregnancy could not be demonstrated for the early stages we studied. The interval between rising cortisol and falling oestriol levels decreased from 6 h in the 12th week to 3.5 h in the 22nd week of gestation. This suggests an increasing sensitivity of the fetal hypothalamus to the feedback effect of maternal cortisol.

Circadian Rhythm↗

Effects of estradiol-17 beta and progesterone on the synthesis of prostaglandin F2 alpha, prostaglandin E2 and prostaglandin I2 by fibroblasts from human endometrium in vitro.

Estradiol-17 beta increases the production of prostaglandin F2 alpha (PGF2 alpha) in long term monolayer cell cultures of the human endometrium in a dose dependent manner. Progesterone in pharmacological dosage stimulates the syntheses of PGF2 alpha and of prostaglandin E2 (PGE2). The synthesis of prostaglandin I2 (PGI2) is not influenced by sex steroids in long term monolayer cell cultures of the human endometrium.

Dinoprost↗

Management of multiple conceptions after gonadotropin-releasing hormone analog/human menopausal gonadotropin/human chorionic gonadotropin therapy.

The treatment course of a 31-year-old infertility patient due to PCO disease is presented. Because the patient failed to conceive after various treatment cycles with CC, she was subjected to a combined GnRHa/hMG/hCG therapy. After plasma E2 levels had reached 2400 pg/ml, three leading follicles, with diameters of 20 to 24 mm, were detected. Induction of ovulation was achieved by 10,000 IU hCG. The patient conceived and developed ovarian hyperstimulation. At 8 weeks of gestation, seven cystic structures were detected within the uterine cavity, five containing single embryos, and two with twin embryos. All nine embryos were vital, as evidenced by their heart beats. Embryo reduction was achieved by transabdominal puncture on three occasions. The three surviving fetuses were carried to the 34th week of gestation. After delivery by cesarean section, three healthy babies developed normally. This communication illustrates the complications that can be associated with ovulation induction in PCO disease: ovarian hyperstimulation, polyovulation, multiple conceptions, and their clinical management.

Adult↗

[Use of gonadotropin releasing hormone analogs in Marcumar-treated patients for contraception and prevention of life-threatening ovulation hemorrhages].

Five severe cases of intra-abdominal gynaecological haemorrhage (four haemorrhages from corpora lutea haemorrhagica and one haemorrhage of the endometritis genitalis externa) are described in relation to prolonged marcumar therapy. The problem of contraception in patients under marcumar therapy is highlighted and the possibility is discussed of prevention of ovulation and cardio-vascularly neutral treatment, to achieve contraception as well as avoidance of haemorrhage at ovulation with the Gn-RH analogue Buserelin.

4-Hydroxycoumarins↗

[Effect of sex steroids on the lipoprotein profile].

Hyperandrogenemia is associated with relatively high LDL- and low HDL-cholesterol levels, increasing the risk of the development of arteriosclerotic disease. In three women suffering from androgen producing ovarian tumors, this observation could be confirmed. After surgical removal of the ovaries, lipoprotein profiles returned to normal. In contrast, androgens did not affect lipoproteins in two testicular feminized individuals. Despite elevated testosterone levels, the lipoprotein profiles were absolutely normal. This observation indicates that the affects on the lipoprotein profile is receptor mediated.

Adolescent↗

[Regulation of the fetoplacental unit. 1. Comparison of the suppressive effect of cortisol and cortisone on estradiol synthesis].

The present study compares the negative feed back action of cortisol and cortison on oestriol production in late human pregnancy. 10 women from the 38th to 40th week of gestation volunteered in this study. All had uncomplicated courses of pregnancy and delivered healthy babies at term. 5 patients received a continuous infusion of 100 mg Cortisol from 10 a.m. to 12 a.m. To the other 5 patients 100 mg Cortison were infused during the same period. Blood specimens (5 ml) were drawn in 60 and 30 minutes intervals from 8 a.m. to 5 p.m. Plasma levels of unconjugated oestriol were measured by radioimmunoassay. The suppression of oestriol levels was nearly identical in both groups: After Cortisol oestriol concentrations decreased from 17.1 +/- 9.1 ng/ml to 6.0 +/- 1.2 ng/ml (p less than 0.001) and after Cortison from 15.5 +/- 5.8 ng/ml to 5.9 +/- 1.8 ng/ml (p less than 0.001), respectively. According to these results the placental metabolism of maternal cortisol to cortison does not impair the negative feed back action of this hormone on the foetal hypothalamus-hypophysis-system.

Estradiol↗

[Regulation of the fetoplacental unit. 2. Circadian changes in the sensitivity of the fetal hypothalamo-hypophyseal system for the feedback effect of cortisol].

The present study investigates the significance of a circadian changing sensitivity on the feed back action of cortisol for the foetal hypothalamic hypophyseal system. 9 patients with uncomplicated courses of pregnancy in the 37th to 40th week volunteered in this study. All of them delivered healthy babies at term. 5 patients received a continuous infusion of 0.25 mg ACTH1-24 (Synacthen) in the morning from 10 a.m. to 4 p.m. (group I). To 4 patients an analogous ACTH infusion was applied in the evening from 8 p.m. to 2 a.m. (group II). Blood specimens (5 ml) were drawn from 8 a.m. to 5 p.m. in group I and from 5 p.m. to 3 a.m. in group II in 60 and 30 minutes intervals, respectively. Free plasma oestriol was measured by radioimmunoassay, total plasma cortisol by the protein binding method. In group I cortisol increased from 294.3 +/- 52.9 ng/ml to 774.5 +/- 170 ng/ml, whereas oestriol decreased from 13.1 +/- 6.1 ng/ml to 6.8 +/- 2.1 ng/ml (p less than 0.001). In group II cortisol rose from 267.5 +/- 76.2 ng/ml to 1010 +/- 284 ng/ml, whereas oestriol levels were suppressed from 21.7 +/- 10.5 ng/ml to 10.8 +/- 3.2 ng/ml (p less than 0.001). Two hours after starting ACTH infusion rising cortisol and falling oestriol concentrations were negatively correlated (r = -0.9657, p less than 0.001 in the morning; r = -0.9119, p less than 0.001 in the evening). Plasma oestriol levels were in the evening suppressed on an average of 10.9 ng/ml and exceeded the oestriol decrease in the morning (6.3 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

[Gonadotropin resistance in Rothmund-Thomson syndrome].

A case of Rothmund-Thomson syndrome of a 24-year old woman with primary amenorrhoea is presented. This autosomal recessive disorder is characterised by atrophy, hyperpigmentation and teleangiectasiae of the skin, furthermore by juvenile cataracts and congenital bone defects as saddle nose. Endocrinologic and morphologic parameters suggest a resistant ovary syndrome as cause of this hypergonadotropic hypogonadism.

Adult↗

Linkage analysis with RFLPs in families with androgen resistance syndromes: evidence for close linkage between the androgen receptor locus and the DXS1 segment.

Three families with androgen resistance syndromes--two with testicular feminization and one with Reifenstein syndrome--have been studied for linkage analysis. Using three cloned DNA sequences from the centromere region and the proximal long arm of the X chromosome (p8, pDP34, and S9, which define respectively the chromosomal segments DXS1, DXYS1, and DXS17), we found no recombination between the DXS1 locus and the mutant genes in the three families. Assuming that these disorders are the result of allelic mutations at the same locus for the androgen receptor, we can conclude that there is a close linkage between DXS1 and the androgen receptor locus, with a maximum lod score zeta = 3.5 at a recombination fraction theta = 0.0 using the LIPED program (Ott 1974).

Androgen-Insensitivity Syndrome↗

Effect of progestins, androgens, estrogens and antiestrogens on 3H-thymidine uptake by human endometrial and endosalpinx cells in vitro.

The present study describes the effects of 11 steroid hormones and 3 non-steroidal antiestrogens on the 3H-thymidine uptake by human endometrial and endosalpinx cells in long-term cultures. The compounds were added in various concentrations ranging from 10(-9) to 10(-4) M. Progesterone and 19-nortestosterone caused a dose-dependent reduction of the 3H-thymidine incorporation resulting in a 94-98% inhibition at a concentration of 10(-4) M, gestonoroncaproate and d,1-norgestrel were less effective causing a 49% and 40% decrease. Antiproliferative effects were also noted after the addition of androgens (testosterone, 5 alpha-dihydrotestosterone, 5 beta-dihydrotestosterone and danazol). The inhibitory effect of testosterone was equivalent to progesterone at concentrations of 10(-4) M. The addition of estrogens (estrone, estradiol-17 beta and estriol) and antiestrogens (tamoxifen, N-desmethyl- and 4-OH-tamoxifen) produced a dual response in monolayer cultures as low concentrations (10(-9)-10(-6) M) were associated with a slightly increased 3H-thymidine incorporation while pharmacological concentrations (10(-5)-10(-4) M) were followed by a significant decrease. Cells originating from the endosalpinx did not respond to either estradiol-17 beta or progesterone. These results suggest that in contrast to endometrium, the proliferation of endosalpinx cells is independent of sex steroids.

Androgens↗

Cyclic administration of an LHRH analogue and of progesterone in risk patients to oral contraceptives.

Fifty-five cycles of 9 patients with normogonadotropic ovarian function having risks against oral contraceptives (OCs) and intrauterine devices (IUDs) were treated for contraception with buserelin in a dosage of 300 to 450 micrograms per day i.n. from day 5 to day 26 of the cycles. Additionally, progesterone (P) in a dosage of 75 mg per day was given by intravaginal suppositories from day 20 to day 26 of the cycle followed by a 7-day drug-free interval. Serum levels of LH, FSH and estradiol-17 beta (E2) showed a wide variability. However, most E2 levels were in the early or middle follicular phase range. Mean serum P levels monitored during P replacement were found to be in the secretory phase range. Pattern of menstrual cycles was regular in all patients except one whose menstrual bleedings were already disturbed prior to treatment. This mode of contraception was well accepted, no side effects were observed, no pregnancy occurred. In conclusion, contraception by low-dose intranasal application of buserelin combined with transvaginal P replacement seems to be a useful approach for contraception in patients at risk for both OCs and IUDs.

Administration, Intranasal↗

[Stimulation of ovarian function with gonadotropins following suppression of endogenous gonadotropin secretion by long-term infusion of the LHRH analog buserelin].

The treatment of infertile women by gonadotropins is more effective in hypogonadotropic than in normogonadotropic ovarian insufficiency. In order to induce a hypogonadotropic state the luteinizing hormone-releasing hormone analog (LHRHA) buserelin was administered in eight cycles of four infertile patients suffering from luteal phase defect. Buserelin was infused subcutaneously in a dosage of 400 micrograms/d for 26-44 days using a portable external osmotic minipump system. Following suppression of estradiol-17 beta below 35 pg/ml within 11 +/- 5 days, gonadotropins were injected intramuscularly to stimulate ovarian function. In all cycles treated, ovulation and formation of a functional corpus luteum were observed without signs of premature luteinization. Whereas constant administration of LHRHA by a slow release system seems very useful for long-term reversible suppression of follicular maturation, further studies should evaluate the clinical usefulness of combined LHRHA/gonadotropin treatment in cases of infertility.

Adult↗

[Modification of lipid metabolism by hPL in late pregnancy].

In the clinical study reported here, the relationship between the behavior of the serum lipids and the concentration of placental lactogen (HPL) was investigated in 107 gravidae in the last trimester. Among the patients examined there were 99 single pregnancies and eight multiple pregnancies--2x twins, 3x triplets, and 3x quadruplets. In these examinations, a significant positive correlation (p less than 0.01) was found between the HPL concentrations and the triglyceride values. Increases in HPL concentrations were associated with increasing total cholesterol and LDL cholesterol values. There was no relation to HPL values in the HDL and VLDL fraction of the cholesterol. Nor was there any relation between estrogen secretion in urine, which was measured in 42 patients, and plasma lipid concentrations. Extreme HPL values in multiple pregnancies, of more than 9 micrograms/ml, were associated with triglyceride concentrations of 383 +/- 37 mg/dl. Total cholesterol in these patients reached values of 294 +/- 19 mg/dl. These values returned to normal on the third day post partum. The mean HDL: total cholesterol ratio was 0.245 +/- 0.065 and was thus clearly above the pathognomonic limit of 0.150. The findings obtained in this study are indicative of the pronounced lipolytic potency of HPL.

Cholesterol↗

[Significance of the estriol profile as an endogenous function test of the fetoplacental unit].

Oestriol profile represents a functional parameter of the foetal placental unit. Basing on the fact that maternal cortisol regulates oestriol production via a negative feedback action on foetal hypothalamus, relative low serum oestriol concentrations in the morning are compared with increasing oestriol concentrations in the evening, spaced out at short-time intervals, pointing to a dynamic oestriol production of the foetal placental unit. The mean oestriol concentration in the morning and maximum peak values in the evening were determined as criteria of the oestriol profile. In normal pregnancies (n = 74) the oestriol concentration in the morning increases from an average value of 8.0 ng/ml in the 32nd/33rd week to 11.6 ng/ml in the 40th/41st week of gestation. During the same period the peak values in the evening rise from 8.8 to 15.9 ng/ml. The mean cortisol concentrations in normal pregnancies (n = 49) from 32nd to 41st week are in the range of 333 +/- 88 ng/ml in the morning and 205 +/- 66 ng/ml in the evening. There is no significant difference between individual weeks. The predictive value of the oestriol profile was assessed regarding the foetal outcome of 55 high-risk pregnancies. 32 newborn infants exhibited intrauterine growth retardation with birth weights below the 10th and 5th percentile, respectively. In this group 6 patients exhibited low oestriol values in the morning, whereas 12 demonstrated a pathological profile in the evening. In 11 of 12 high-risk pregnancies exhibiting pathological oestriol profile growth, retardation of the newborn was found to be below the 5th percentile. Cortisol concentrations do not significantly differ between normal and high-risk pregnancies.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian Rhythm↗