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Biomedical subjects

M Breckwoldt

Publications and source records attributed to M Breckwoldt.

At least 91 records · Page 5Linked to original sources

Hypertensive disorders in pregnancy. The role of eicosanoids.

Pregnancies complicated by hypertensive disorders are always extremely hazardous for mother and child. In up to 30% of pregnant women this disease is characterized by feto-maternal dysfunction, looking like a kind of "chronic anaphylactoid reaction". As a result of defective genetic control, immunologic events seem to be the central etiologic aspect. Arteriolar vasospasm, pathology of platelets, disseminated intravascular coagulation and finally, elevation of maternal blood pressure, all these symptoms can be regarded as a reaction to immunologic processes. The central role of eicosanoids in the pathogenesis of pregnancy induced hypertension/preeclampsia-eclampsia is generally accepted. We can explain almost all known pathophysiologic abnormalities to be the consequence of disturbed eicosanoid production in a multitude of organs or organ systems. Defective placentation provokes poorly perfused placental tissue. This is correlated with endothelial cell disorder, endothelial damage and denudation. The resulting platelet activation, dysfunction of coagulation and vasoconstriction are due to an increased ratio between vasoconstricting and vasodilating eicosanoids. The suppression of prostacyclin (and PGE) formation in the fetal-placental-maternal unit even before the clinical manifestation of the disease seems to be the conditio sine qua non. So, the homeostatic response to the effects of vasoconstrictors (such as angiotensin, serotonin etc.) in the general and in the placental circulation is impaired. The depressed prostacyclin (and PGE) biosynthesis can be measured in urine. Altered urinary metabolite excretion appears to be a very early index for patients at risk to develop pregnancy-induced hypertension.

Eicosanoids↗

Oral contraception in disease states.

Oral contraceptives are clearly contraindicated in patients with a history of thromboembolic disease, ischemic heart attack, or cerebral stroke. Patients requiring long-term anticoagulant treatment can be treated with gonadotropin-releasing hormone analogs to prevent ovulation, because ruptured follicles can cause massive intraperitoneal bleeding. Patients with essential hypertension and severe liver diseases should also discontinue treatment 4 weeks before major elective surgery. Migraine and diabetes mellitus are regarded as relative contraindications, depending on the individual situation. Long-term diseases, such as Crohn's disease, epilepsy, and sickle cell anemia, also require individualized consultation.

Cerebrovascular Disorders↗

[Oral contraceptive-induced liver tumors and pregnancy].

This paper reports on four pregnancies with maternal liver tumors induced by oral contraceptives. No increase in size and no rupture of these liver lesions were observed during the gestational and postpartum period. The toxic potentials of orally active sex steroids and the role of natural sex steroids are discussed. Criteria for differential diagnosis and practical suggestions are presented.

Adenoma↗

[GnRH-analogs in the therapy of uterine myomatosis].

Uterine fibroids are the commonest tumors of the female genital tract. Hysterectomy is the typical therapy in patients whose families are complete. In women desirous of children GnRH-analogues can effect a shrinkage of leiomyomata before a myomectomy. Furthermore, GnRH-A treatment can be an alternative to hysterectomy in inoperable patients or in premenopausal women with symptoms of uterine fibroids. In this study eleven patients were treated with 3.2 mg triptorelin monthly and ten patients with 900 micrograms buserelin daily for 6 months. With triptorelin, a 50% reduction of the uterus volume can be observed after 3 months. A further treatment has no benefit. With buserelin, a regression in the same range as with triptorelin can be reached only after 6 months. In contrast, fibroid volumes revealed a regression of 28% with triptorelin and 21% with buserelin in the same time. In this period all fibroid-associated symptoms disappeared. Less bleeding resulted in an increase of hemoglobin. Therefore, treatment with GnRH analogues can be an important factor in the management of uterine fibroids patients in at-risk.

Adult↗

[Endocrinology and therapy of breast diseases].

In 193 patients with fibrocystic breast diseases in 46% basal prolactin levels were elevated and many women had an increased reaction to TRH test with increased TSH and PRL serum levels. The author recommend for treatment progestogens dopamine antagonists and danazol.

Animals↗

[Pregnancy in Addison's disease].

A 29-year-old woman with Addison's disease was hospitalized in the eighth week of pregnancy because of an Addisonian crisis. The crisis was successfully treated with physiological saline infusions, as well as hydrocortisone (25 mg/d) and fludrocortisone (0.05 mg/d). The dose of fludrocortisone had to be increased to 0.1 mg/d from the 21st week of pregnancy onwards, because hyponatraemia and hypotension had once again developed. The hydrocortisone dose was raised to 37 mg/d from the 32nd week of pregnancy onwards because of a latent hypoglycaemia and raised further to 50 mg/d from the 35th week onwards because the retardation in fetal growth had become more marked. A mature infant was delivered spontaneously on the 282d day of pregnancy. At the start of labour the patient had been given 100 mg hydrocortisone intravenously and then 50 mg at the moment of delivery. The substitution treatment was gradually reduced to the original (pre-pregnancy) dosage during the first three post-partum days.

Addison Disease↗

[Hormone antagonists in gynecology].

The therapeutic use of antihormones plays a significant and increasing role in gynecological practice. Antihormones in their true sense such as antiestrogens, antiandrogens, and antigestagens are defined as compounds competing with a given hormone at the receptor level of the target organ. Antihormones in a broader sense are compounds such as Gn-RH agonists, Gn-RH antagonists, and dopaminagonists. The mode of action of these compounds and the indication for their clinical application are outlined.

Androgen Antagonists↗

The effect of cortisol on the synthesis of prostaglandins (PGF2 alpha, PGE2) by human endometrial fibroblasts in vitro with and without addition of estradiol-17 beta or progesterone.

Cortisol is known as a potent inhibitor of phospholipase A2 activity in several tissues. In fibroblast monolayer cell cultures from proliferative human endometrium cortisol alone does not affect the basal PGF2 alpha or PGE2 synthesis. After stimulation of PGF2 alpha production by 10(-7) mol/l estradiol-17 beta increasing concentrations of cortisol up to 10(-5) mol/l dosedependently reduce the PGF2 alpha production. Also the progesterone (10(-4) mol/l) stimulated increase of PGF2 alpha and PGE2 synthesis is inhibited by cortisol (10(-7) mol/l).

Cells, Cultured↗

The effect of clomiphene on the synthesis of prostaglandins (PGF2 alpha, PGE2, PGI2) in human endometrial cells in vitro with and without addition of estradiol-17 beta or progesterone.

The production of prostaglandin F2 alpha in monolayer stromal cell cultures of proliferative human endometrium is enhanced by 10(-7) mol/l estradiol-17 beta or 10(-4) mol/l progesterone. Progesterone in high concentration (10(-4) mol/l) also enhanced the synthesis of prostaglandin E2. Clomiphene citrate reduced this increased prostaglandin production dose dependently. The synthesis of prostaglandin I2 was not influenced either by sex steroids or by clomiphene citrate.

Cells, Cultured↗

Effects of progesterone and oestradiol-17 beta on 17 beta-ol-dehydrogenase activity in stromal cells of human endometrium under in-vitro conditions.

A 17 beta-ol-dehydrogenase activity could be demonstrated in fibroblast monolayer cell cultures of proliferative human endometrium. After 24 h incubation 100 nCi [6,7-3H]oestradiol-17 beta was completely oxidized to oestrone. Progesterone was not able to enhance the metabolizing velocity. In contrast, progesterone incubation revealed a decreasing oxidation rate with increasing molarity. Histological changes after transformation of the endometrium are discussed to explain in-vivo results showing an increased 17 beta-ol-dehydrogenase activity in the secretory phase of the cycle.

17-Hydroxysteroid Dehydrogenases↗

Hirsutism, its pathogenesis.

Hirsutism can be regarded as a virilizing symptom and may be defined as a male type of body hair distribution in the female. The pathogenesis of hirsutism may be due to an increased androgen production or to an enhanced sensitivity of the hair follicles in sexual areas. The androgen production in the female depends upon direct secretion by the ovaries and the adrenals and upon peripheral conversion of androgen precursors and finally on the metabolic clearance rate which may be regarded as a function of androgen production. More than 98% of the androgens circulating in the blood are bound to specific plasma proteins such as steroid hormone binding globulin (SHBG), cortisol binding globulin (CBG) and albumin. The synthesis of SHBG is controlled by the ratio of oestradiol to testosterone (T). Elevation of oestrogens results in an increase of SHBG. In hirsutism the plasma concentrations are decreased, resulting in elevated levels of free androgens. The intracellular reduction of T to 5 alpha-DHT (dihydrotestosterone) has to be considered as a basic requirement for the androgen-mediated growth of the hair follicle in sexual skin areas. The sensitivity of these areas for androgen depends upon the activity of the local 5 alpha-reductase. In patients suffering from hirsutism, the conversion rate of T to 5 alpha-DHT is significantly increased, almost reaching male levels. DHT is further metabolized by the target cells to 3 alpha- and 3 beta-androstanediol and the corresponding glucuronides. The elucidation of its complex pathogenesis is still incomplete; however,the information available so far provides a reasonable basis for further diagnostic and therapeutic approaches.

Female↗