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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Der Anaesthesist 46 (1997), S. 783-786 
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Phäochromozytom ; Phenoxybenzamin ; Prazosin ; Natriumnitroprussid ; Key words Pheochromocytoma ; Phenoxybenzamine ; Prazosin ; Sodium nitroprusside
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Pheochromocytomas are functionally active, catecholamine-secreting tumours of chromaffin tissue. The mainstay of pharmacological therapy is preoperative treatment with oral phenoxybenzamine. This drug irreversibly alkylates alpha-1-adrenergic receptors on vascular smooth muscle and renders them nonfunctional, thereby causing vasodilatation. The duration of action of a single dose is approximately 24 h. Therefore, postoperative hypotension is a hazard of therapy with phenoxybenzamine if adequate plasma volume repletion is not provided. Prazosin, a short-acting, competitive alpha-1 blocker, has been used preoperatively, but has been criticized for its failure to adequately prevent perioperative hypertensive episodes. We report the case of a 73-year-old woman who was admitted for elective pheochromocytoma resection. Preoperative therapy with phenoxybenzamine was impossible because of the patient’s refusal to take the drug. Preoperative antihypertensive preparation was therefore performed with prazosin 30 mg/24 h and metoprolol 100 mg/24 h. During the surgical preparation of the tumor, sodium nitroprusside was started at an average infusion rate of 4.1 μg/kg/min. After resection of the primary tumor, when the sodium nitroprusside infusion was stopped the patient exhibited an increase in systolic blood pressure (BP) up to 210 mg Hg. This hypertensive crisis was managed with sodium nitroprusside, nitroglycerin, and esmolol. A multilocular pheochromocytoma was diagnosed. Further stimuli due to tumour palpation resulted in repeated increases in BP. In this manner, two additional areas of tumour could be diagnosed by BP peaks after reduction of the sodium nitroprusside infusion. After complete resection of a total of three tumours, no further hypertensive crises occurred. The patient’s postoperative course was uneventful. We conclude that in this patient presenting with an unsuspected multilocular pheochromocytoma, the lack of permanent alpha-blockade was probably helpful in allowing complete resection of all the tumours.
    Notes: Zusammenfassung Wir berichten über den Fall einer 73jährigen Patientin, die elektiv an einem Phäochromozytom operiert wurde. Eine präoperative alpha-Rezeptoren-Blockade mit Phenoxybenzamin konnte nicht durchgeführt werden, da sie von der Patientin abgelehnt wurde. Die präoperative antihypertensive Therapie erfolgte daher mit dem kompetitiven alpha-Rezeptor-Antagonisten Prazosin und dem beta-Rezeptoren-Blocker Metoprolol. Intraoperativ wurde zur Blutdruckkontrolle Natriumnitroprussid eingesetzt. Nach Entfernung des Primärtumors und Absetzen des Natriumnitroprussids kam es noch intraoperativ zu rezidivierenden Blutdruckspitzen, woraus sich die Verdachtsdiagnose eines multilokulären Phäochromozytoms ergab. Ein im makroskopisch unauffälligen Pankreasschwanz liegender Tumor konnte lediglich durch Blutdruckanstieg bei Palpation lokalisiert werden. Nach vollständiger Resektion aller Tumorherde traten keine weiteren hypertensiven Phasen mehr auf. Der postoperative Verlauf war unauffällig. Schlußfolgerung: In diesem Fall erleichterte vermutlich die alpha-Rezeptoren-Blockade mit Prazosin anstelle des längerwirksamen Phenoxybenzamin die intraoperative Tumorlokalisation sowie die Kontrolle über die vollständige Resektion aller Tumoranteile.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Pseudohermaphroditism ; Gynecomastia ; Androstenedione ; 17β-Hydroxysteroid-oxydoreductase deficiency ; Testosterone inborn error ; Pseudohermaphroditismus masculinus ; Gynäkomastie ; Androstendion ; 17β-Hydroxysteroid-oxydoreductase Defekt ; Testosteron-Synthesestörung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Beschreibung eines Jungen mit Pseudohermaphroditismus maskulinus, mit normalem männlichen Karyotyp, welcher bei der Geburt als Mädchen angesehen worden war. Mit 12 Jahren Auftreten einer hochgradigen Gynäkomastie. Steroiduntersuchungen wurden mit Radiogaschromatographie und mit radioimmunologischen Methoden durchgeführt. Die Steroidbestimmungen ergaben im Plasma bei altersnormalen Testosteronspiegeln Androstendionwerte, welche die Norm um den Faktor 9–23 überstiegen. Die Plasmaoestrogene wurden insgesamt erhöht gefunden, Oestron weit mehr als Oestradiol. In Inkubationsversuchen vom bioptisch gewonnenen Hodengewebe des Jungen konnte gezeigt werden, daß zugesetztes markiertes Androstendion nur in geringem Maß zu Testosteron metabolisiert wurde, während normales Hodengewebe rund 60% zu Testosteron metabolisierte. Auf Grund dieser biochemischen Befunde wird eine Testosteron-Synthesestörung mit Defekt einer 17β-Hydroxy-steroid-Oxydoreduktase als Ursache des Pseudohermaphroditismus und der Gynäkomastie angenommen. Der Enzymdefekt ist bisher zweimal beschrieben, scheint aber nach entsprechender Untersuchung häufiger zu sein.
    Notes: Summary A boy with male pseuodhermaphroditism described here with normal male caryotype was at first raised as a girl. The error was detected within the first year of life. At the age of 12 years the boy developed a severe gynecomastia. At this time determinations of plasma and urinary steroids were undertaken. 17-ketosteroids and total 17-OHCS were determined by colorimetry. Plasma testosterone, androstenedione, 17α OH-progesterone, urinary pregnantriol and pregnantriolone were measured by GLC. Plasma estrone and estradiol were determined by radioimmunoassay (RIA). Investigations at 12 years of age and later revealed plasma testosterone in the lower normal range and androstenedione 9–23 times higher compared to normal boys. Plasma estrogens were found to be elevated, estrone much more than estradiol. Incubation studies with testicular tissue showed very little conversion of3H-androstenedione (15%) whereas normal testicular tissue converted up to 60% to3H-testosterone. On the basis of these data 17β-hydroxysteroid-oxydoreductase deficiency is suggested as the underlying cause of pseudohermaphroditism and gynecomastia in this boy. Up to the present this enzyme deficiency is described only two times but it would seem to be more frequent if one looked at the elevated androstenedione plasma level.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 61 (1983), S. 373-375 
    ISSN: 1432-1440
    Keywords: Cortisol secretion ; Adrenal adenoma ; Ketoconazole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ketoconazole (Nizoral), an oral broad spectrum antifungal agent, inhibits ergosterol synthesis in fungi and cholesterol synthesis in mammalian cells by inhibition of the 14-demethylation of lanosterol. After a blunted cortisol response to ACTH in normal men after ketoconazole has been shown by others we studied the influence of the antifungal agent on the cortisol secretion in a patient with a cortisol producing adrenal adenoma in vivo and in vitro. Repeated oral doses of ketoconazole (200 mg every 5 h over a period of 48 h) induced a reproducible clear cutt fall of serum cortisol levels under 2.5 µg/dl. The inhibitory effect on the cortisol secretion could be detected first 5 h after the first dose, 9 h after the last dose cortisol levels recovered. In addition the inhibitory effect of ketoconazole on cortisol secretion could be reproduced in vitro by incubating tissue slices of the excised adrenal tumor together with the antifungal agent in concentrations equivalent to therapeutic serum levels. These findings emphasize that patients with an autonomous cortisol production caused by an adrenal tumor are proned to dangerous hypoadrenalism if treated with ketoconazole.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 63 (1985), S. 607-612 
    ISSN: 1432-1440
    Keywords: Cortisol secretion ; 11β-hydroxylation ; Ketoconazole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We investigated basal and ACTH stimulated levels of cortisol, corticosterone, 17α-hydroxyprogesterone, 11-deoxycortisol and 11-deoxycorticosterone as well as plasma levels of ACTH before and during the oral administration of ketoconazole in five patients with Cushing's syndrome (3 with bilateral adrenal hyperplasia, 1 with adrenal adenoma and 1 with adrenal carcinoma) and in three controls. The influence of ketoconazole on the transformation of3H-17α-hydroxyprogesterone to3H-11-deoxycortisol and3H-cortisol and of3H-11-deoxycortisol to3H-cortisol as well as of3H-11-deoxycorticosterone to3H-corticosterone was also examined in slices or homogenates of normal and hyperplastic adrenal tissue from four patients. Ketoconazole induced a rise of 11-deoxycortisol and 11-deoxycorticosterone, but not of cortisol and inconsistantly of corticosterone which were increased by ACTH. Thus the ratio 11-deoxycortisol/cortisol rose more after ketoconazole than after ACTH and the ratio 11-deoxycorticosterone/corticosterone rose after ketoconazole but fell after ACTH. Plasma ACTH levels were stimulated 2–50 fold by ketoconazole. Incubation studies of adrenal tissue slices with3H-17α-hydroxyprogesterone showed that ketoconazole inhibited the transformation of3H-17α-hydroxyprogesterone to3H-cortisol but not to3H-11-deoxycortisol so that the ratio3H-11-deoxycortisol/3H-cortisol increased 15–80 fold. After incubation of adrenal slices with3H-11-deoxycortisol or3H-11-deoxycorticosterone and ketoconazole, a 2–260 fold increase of the ratios3H-11-deoxycortisol/3H-cortisol and3H-11-deoxycorticosterone/3H-corticosterone were also found. In conclusion, the in vivo data indicate and the in vitro data confirm that ketoconazole inhibits cortisol and corticosterone secretion by blocking adrenal 11β-hydroxylase activity in normal subjects as well as in patients with Cushing's syndrome, an effect which is compensated in vivo by high ACTH levels.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Leberstanzcylinder, gewonnen durch Blindpunktion, wurden mit (4-14C)-Testosteron und (1,2-3H)-Δ4-Androstendion inkubiert und die Interkonversion sowie der Katabolismus dieser Androgene in vitro mit Hilfe einer radiogaschromatographischen Methode untersucht. Es zeigte sich, daß Testosteron durch histologisch normales und cirrhotisches Lebergewebe in der gleichen Größenordnung abgebaut wurde, durch Fettlebergewebe dagegen in geringerem Ausmaß. Der Abbau von Δ4-Androstendion durch normales Lebergewebe von Frauen war etwa 3mal größer als von Männern; auch die cirrhotische Leber von Männern baute mehr Δ4-Androstendion ab als die normale. Die Interkonversion von Testosteron in Δ4-Androstendion war durch normales Lebergewebe von Männern wesentlich höher als von Frauen. Abgebaut wurde Testosteron und Δ4-Androstendion mehr zu 5β-hydrierten Metaboliten als zu 5α-hydrierten Verbindungen.
    Notes: Summary Human liver tissue obtained by needle biopsy was incubated with (4-14C)-testosterone and (1,2-3H)-androst-4-enedione and the interconversion and catabolism of these androgenic hormones were investigated by a radio-gas chromatographic method. The rate of metabolism of testosterone in histologically normal hepatic tissue was as high as in cirrhotic tissue, while the rate of metabolism in fatty liver was lower. The catabolism of androst-4-enedione in normal liver tissue of women was three times higher than in that of men; metabolism of androst-4-enedione in cirrhotic tissue was also higher than in normal tissue. The interconversion of testosterone to androst-4-enedione by normal tissue of men was much higher than in women. Testosterone and androst-4-enedione catabolism to 5β-metabolites was greater than that to 5α-metabolites.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 72 (1994), S. 481-488 
    ISSN: 1432-1440
    Keywords: Steroid biosynthesis inhibitors ; Cushing's syndrome ; Aminoglutethimide ; Etomidate ; Ketoconazole ; Metyrapone ; Mitotane ; Trilostane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Conclusions About one-third of all patients with Cushing's syndrome cannot be cured by surgery (at the pituitary or adrenal level) or radiation therapy and are therefore candidates for medical treatment. As a conservative therapeutic approach to lower hypercortisolism, the use of steroid biosynthesis blocking substances has the greatest importance. Trilostane, an inhibitor of the adrenal 3β-hydroxysteroid dehydrogenase Δ5,4-isomerase system, has been studied in only a few patients with Cushing's syndrome and was not potent enough to normalize hypercortisolism, especially in patients with pituitary-dependent Cushing's disease. Aminoglutethimide, predominantly blocking side-chain cleavage, normalized elevated serum or urinary cortisol levels in only a minority of patients with Cushing's disease and showed adverse reactions in the majority. Metyrapone, a strong inhibitor of adrenal 11β-hydroxylase activity, has only an insufficient blocking effect on elevated cortisol levels in some patients with various forms of Cushing's syndrome and shows side effects in a significant number of patients. Ketoconazole in vitro blocks predominantly adrenal 17,20-desmolase activity and to a lesser extent 17α- and 11β-hydroxylase activity. Therefore the substance in vivo more markedly suppresses serum androgen levels (dehydroepiandrosterone sulfate, androstenedione, testosterone) than cortisol. However, clinical data from several groups show that the administration of ketoconazole normalizes the urinary excretion of cortisol in the mean in about 70% of patients with Cushing's disease. Furthermore, the antimycotic drug was effective in many patients with a benign primary adrenal form of Cushing's syndrome, in about 50% of patients with ectopic ACTH syndrome, but rarely in patients with adrenocortical carcinoma. The main side effect of ketoconazole is liver toxicity, in about 10% of all cases. Etomidate has strong inhibiting properties on adrenal 11β-hydroxylase activity and in vivo is the most potent substance to normalize hypercortisolism. However, its widespread use is prevented by the necessity of intravenous administration. Mitotane inhibits various pathways of adrenal steroid biosynthesis, but its main effect is a cytolytic effect especially on adrenocortical cells. It is therefore a special cytostatic drug for patients with adrenocortical carcinoma. High doses of the substance lower or normalize elevated cortisol parameters in the majority of these patients, but objective tumor regression has been documented in only in few cases.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0375-9474
    Keywords: Nuclear Reactions
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0370-2693
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    The @Journal of Steroid Biochemistry and Molecular Biology 49 (1994), S. 261-267 
    ISSN: 0960-0760
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0375-9474
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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