Search PubMed⌕ Search

Biomedical subjects

D Engelhardt

Publications and source records attributed to D Engelhardt.

At least 73 records · Page 4Linked to original sources
PubMed1988

[Results of radioiodine treatment of patients with immunogenic and non-immunogenic hyperthyroidism using different focal doses].

The aim of this study was to check the efficacy of radioiodine (131I) therapy (RIT) in a large number of patients (n = 506) suffering from immunogenic or non-immunogenic hyperthyroidism (Graves' disease, Plummer's disease). Since there is no causal cure for immunogenic hyperthyroidism RIT provides, like all other modalities, only a moderate rate of success which is clearly dose-related. Applying 60 Gy, normal thyroid function can be achieved in only 54% of the cases. A dose of 150 Gy succeeds in 86% of the cases. The solitary decompensated autonomous adenoma (DAA) can be eliminated surgically as well as by RIT with a high degree of success (95%). Contrary to surgery, RIT does not have any noticeable early or late morbidity. The high rate of success of RIT in patients with DAA could be confirmed in two groups with different follow-up periods (16 and 65 months). As expected, the rate of hypothyroidism increased from 11% in the early group to 23% in the late group. Multinodular autonomous adenomas can be eliminated successfully using RIT as well. The concept to apply a dose of 400 Gy to the total functional autonomous tissue as determined by ultrasound yields better results (95%) than 150 Gy to the whole thyroid gland as measured by ultrasound (88%). The rate of hypothyroidism as shown by these results (up to a maximum of 62% after RIT of Graves' disease using 150 Gy) is the lesser evil compared to remaining or recurrent hyperthyroidism since these patients can be treated with thyroid hormones without problems.

Adenoma↗
PubMed1985

Ketoconazole blocks cortisol secretion in man by inhibition of adrenal 11 beta-hydroxylase.

We investigated basal and ACTH stimulated levels of cortisol, corticosterone, 17 alpha-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 of 3H-17 alpha-hydroxyprogesterone to 3H-11-deoxycortisol and 3H-cortisol and of 3H-11-deoxycortisol to 3H-cortisol as well as of 3H-11-deoxycorticosterone to 3H-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 inconsistently 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 with 3H-17 alpha-hydroxyprogesterone showed that ketoconazole inhibited the transformation of 3H-17 alpha-hydroxyprogesterone to 3H-cortisol but not to 3H-11-deoxycortisol so that the ratio 3H-11-deoxycortisol/3H-cortisol increased 15-80 fold. After incubation of adrenal slices with 3H-11-deoxycortisol or 3H-11-deoxycorticosterone and ketoconazole, a 2-260 fold increase of the ratios 3H-11-deoxycortisol/3H-cortisol and 3H-11-deoxycorticosterone/3H-corticosterone were also found.

17-alpha-Hydroxyprogesterone↗
PubMed1985

[Comparison between cimetidine-pirenzepine and antacids for the prevention of stress hemorrhage in intensive care patients. A controlled clinical study on 125 patients].

In a controlled clinical trial, the efficacy of an intravenous combination of cimetidine and pirenzepine (group A: 62 patients) was compared with that of an intragastric administration of a magnesium-aluminium-hydroxide concentrate (group B: 58 patients) in preventing visible and occult upper gastrointestinal tract bleeding in intensive-care patients. It was found that both forms of therapy had the same favourable effect on the extent and incidence rate of visible and occult gastric bleeding. The antacid was more effective than the cimetidine-pirenzepine combination in raising the pH level to 4 or higher (P less than 0.05). Intensive-care patients should, therefore, be treated with the antacid whenever possible, since it is equally effective as the cimetidine-pirenzepine combination in preventing bleeding from the upper gastrointestinal tract, whereas it is superior in elevating the gastric pH. Besides, the use of the antacid is also less costly.

Adult↗
PubMed1985

Effect of a single bolus of etomidate upon eight major corticosteroid hormones and plasma ACTH.

In a prospective controlled trial we investigated the effect of an induction dose of etomidate (0.26 mg/kg i.v.) on plasma ACTH, progesterone, 17 alpha OH-progesterone, 11-deoxycortisol, cortisol, cortisone, corticosterone, 11-deoxycorticosterone, and aldosterone in seven males undergoing general anaesthesia. Seven other male patients receiving thiopentone at induction (5.0 mg/kg i.v.) served as controls. Plasma ACTH concentrations rose higher in the etomidate group (346 +/- 124 vs. 117 +/- 74 pg/ml, mean +/- SEM), but the difference was not significant. After etomidate we found a clear suppression of plasma cortisol (P less than 0.01), cortisone (P less than 0.01), corticosterone (P less than 0.01), and aldosterone (P less than 0.05) compared to corticosteroid levels after induction with thiopentone. Plasma 11-deoxycortisol and 11-deoxycorticosterone concentrations were grossly elevated 210 min after etomidate (91 +/- 28 nmol/l and 7.04 +/- 0.47 nmol/l, respectively, P less than 0.01) demonstrating inhibition of 11 beta-hydroxylation of both glucocorticoid and mineralocorticoid intermediates. In contrast, no significant difference in plasma progesterone and 17 alpha-OH-progesterone levels was found between the two groups indicating that the cholesterol-side-chain cleavage enzyme is less sensitive to etomidate than 11 beta-hydroxylase. Our results suggest that after induction of anaesthesia with a single bolus of etomidate, inhibition of other enzymes in the corticosteroid-synthetic pathway (e.g. cholesterol-side-chain cleavage enzyme) is of little clinical relevance.

17-alpha-Hydroxyprogesterone↗
PubMed1984

[Effect of etomidate and thiopental on ACTH and cortisol levels in serum. A prospective controlled comparative study in healthy probands].

A prospective controlled trial was carried out to determine the influence of etomidate and thiopentone on serum levels of cortisol and plasma levels of adrenocorticotrophic hormone (ACTH). There were two groups of nine healthy male volunteers: one group was given 0.3 mg/kg body wt. etomidate and the other 4 mg/kg body wt. thiopentone intravenously as a bolus. The hormone levels were measured before and every 30 min after injection of the anaesthetic over a period of 5 h. After thiopentone, cortisol levels dropped from a mean value of 13.2 micrograms/dl to a minimum of 9.0 micrograms/dl after 90 min and fluctuated between 9.2 and 10.9 micrograms/dl until the end of the experiment. Etomidate induced a more pronounced decrease in cortisol levels (from the 90th min the differences to the levels after thiopentone were statistically significant) from 13.9 micrograms/dl to a minimum of 5.0 micrograms/dl after 150 min. After 300 min cortisol levels had recovered only to 7.7 micrograms/dl. Plasma levels of ACTH were also different in the two groups. After thiopentone they decreased from 26.1 pg/ml to 18.2 pg/ml after 30 min, then increased to 30 pg/ml after 300 min. After etomidate, ACTH levels were as high at 30 min as before the injection and increased continuously to 67.1 pg/ml by the end of the experiment; from the 150th min on, the differences to the ACTH levels after thiopentone were statistically significant. We conclude from these hormone levels that a single intravenous bolus injection of thiopentone induces a slight but statistically significant and ACTH-independent decrease in adrenal cortisol secretion in healthy volunteers not stressed by an operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1983

Ketoconazole inhibits cortisol secretion of an adrenal adenoma in vivo and in vitro.

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-cut fall of serum cortisol levels under 2.5 micrograms/dl. The inhibitory effect of 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 prone to dangerous hypoadrenalism if treated with ketoconazole.

Adenoma↗
PubMed1980

17-ketosteroid reductase deficiency -- plasma steroids and incubation studies with testicular tissue.

The patient, diagnosed as a case of testicular feminisation in infancy, was examined at the age of 15 years because of severe symptoms of virilising puberty with poor breast development. Plasma steroid analyses revealed a 10-fold elevated androstenedione concentration (A: 1562 ng/100 ml). Testosterone (T: 266 ng/100 ml) was in the male pubertal range. Thus the A/T-ratio was far above normal. The oestrone/oestradiol ratio was also elevated (Oe1/Oe2: 10.2/2.2 ng/100 ml). A, T, Oe1 and Oe2 could not be suppressed by dexamethasone, but reacted promptly to fluoxymesterone (A: 781 ng/100 ml). hCG caused a further increase of the A/T-radio (2220/246 ng/100 ml); ACTH did not alter the A-concentration. These findings together with simular investigations after gonadectomy suggest that the failure to convert A to T and Oe1 to Oe2 is essentially located in the testes. In vitro incubations of testicular tissue showed reduced 17-ketosteroid reductase activity in tissue slices and in the subcellular fractions microsomes and cytosole. This form of male pseudohermaphroditism can easily be detected already in infancy, if steroid analyses and stimulation tests are performed. In case of female sex assignment patients should be submitted to early orchidectomy in order to avoid virilisation in puberty.

17-Hydroxysteroid Dehydrogenases↗