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1.
Rev Sci Instrum ; 92(11): 115102, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-34852535

ABSTRACT

The Comet Physics Laboratory (CoPhyLab) is an international research program to study the physical properties of cometary analog materials under simulated space conditions. The project is dedicated to studying, with the help of multiple instruments and the different expertise and background from the different partners, the physics of comets, including the processes inside cometary nuclei, the activity leading to the ejection of dust and gas, and the sub-surface and surface evolution of cometary nuclei when exposed to solar illumination. CoPhyLab will provide essential information on the formation and evolution of comets and insights into the origins of primitive Solar System bodies. To this end, we constructed a new laboratory that hosts several small-scale experiments and a large-scale comet-simulation chamber (L-Chamber). This chamber has been designed and constructed to host ice-dust samples with a diameter of up to 250 mm and a variable height between 100 and 300 mm. The cometary-analog samples will be kept at temperatures below 120 K and pressures around 10-6 mbar to ensure cometary-like conditions. In total, 14 different scientific instruments are attached to the L-Chamber to study the temporal evolution of the physical properties of the sample under different insolation conditions. Due to the implementation of a scale inside the L-Chamber that can measure weight changes of the samples with high precision, the cooling system is mechanically decoupled from the sample holder and cooling of the samples occurs by radiation only. The constructed chamber allows us to conduct uninterrupted experiments at low temperatures and pressures up to several weeks.

2.
Z Kinder Jugendpsychiatr Psychother ; 31(1): 7-15, 2003 Feb.
Article in German | MEDLINE | ID: mdl-12616745

ABSTRACT

OBJECTIVE: While an association between androgens and different types of aggression has been well documented in male offenders, the influence of androgens on externalizing behavior in adolescents at risk for antisocial behavior has not been investigated so far. METHODS: Plasma levels of the main androgen metabolites testosterone (T) and 5a-dihydrotestosterone (DHT) were measured in N = 119 14-year-olds (51 boys, 68 girls) from a prospective longitudinal study of children at risk. The Achenbach Child Behavior Checklist (CBCL) and the Youth Self Report Form (YSR) were used to assess externalizing behavior at age 14. RESULTS: The CBCL revealed significant positive correlations between DHT levels and the subscales "externalizing problems" and the problem scales "aggressive behavior" and "delinquent behavior" in male adolescents. Only the YSR subscale "delinquent behavior" exhibited a marginally significant association with DHT. Neither scale showed any significant correlations between androgen levels and externalizing behavior in female adolescents. CONCLUSIONS: Earlier findings of androgen effects on aggressive and antisocial behavior in male offenders were confirmed for male adolescents from a general population sample. The results stress the importance of the androgen metabolite DHT.


Subject(s)
Aggression/physiology , Antisocial Personality Disorder/physiopathology , Dihydrotestosterone/blood , Internal-External Control , Testosterone/blood , Adolescent , Aggression/psychology , Antisocial Personality Disorder/diagnosis , Antisocial Personality Disorder/psychology , Female , Humans , Longitudinal Studies , Male , Personality Assessment , Prospective Studies , Sex Factors
3.
Int J Surg Investig ; 2(5): 369-75, 2001.
Article in English | MEDLINE | ID: mdl-12678541

ABSTRACT

BACKGROUND: The Ileo-Pouch-Anal-Anastomosis (IPAA) is the standard restorative procedure for Ulcerative Colitis and Familial Adenomatous Polyposis (FAP). IPAA may lead to considerable losses of fluids, especially in association with a protective loop ileostomy. AIM: The aim of this study was to investigate adrenal mechanisms in the regulation of volume homeostasis immediately after IPAA and protective ileostomy. METHODS: For that purpose, 20 patients out of our patient population with elective IPAA with ileostomy participated in this study between 1993 and 1997. In all patients, routine laboratory tests and gluco- and minealocorticoid hormone measurements were performed preoperatively and 10 days after operation. RESULTS: These blood analyses indicated functional hyperaldosteronism immediately after IPAA. Significantly elevated levels of Aldosterone (36.4 +/- 25.1 ng/dl) and 18-OH-Corticosterone ( 173 +/- 11.3 ng/dl) were found. Among hormones with glucocorticoid effects, blood levels of Cortisol (10.4 +/- 4.8 microg/dl) were significantly elevated, while 11-Desoxycortiosterone (13.9 +/- 8.4 ng/dl) and Corticosterone (0.8 +/- 0.6 microg/dl) were not significantly elevated. Serum electrolytes remained unchanged. CONCLUSIONS: Our results indicate that hormones with mineralocorticoid effects play a predominant role in the compensation of ileostomy losses after IPAA.


Subject(s)
Glucocorticoids/metabolism , Ileostomy/adverse effects , Mineralocorticoids/metabolism , Proctocolectomy, Restorative/adverse effects , Water-Electrolyte Imbalance/etiology , Adaptation, Physiological , Adenomatous Polyposis Coli/surgery , Adult , Colitis, Ulcerative/surgery , Female , Glucocorticoids/analysis , Homeostasis/physiology , Humans , Ileostomy/methods , Male , Middle Aged , Mineralocorticoids/blood , Probability , Proctocolectomy, Restorative/methods , Prognosis , Sampling Studies , Sensitivity and Specificity , Water-Electrolyte Imbalance/physiopathology
4.
Chirurg ; 72(12): 1446-52, 2001 Dec.
Article in German | MEDLINE | ID: mdl-11824030

ABSTRACT

UNLABELLED: The two-phase restorative proctocolectomy is the treatment of choice for surgical therapy of the familial adenomatous polyposis (FAP) and also for the ulcerative colitis (UC). Besides the well-known complications the entire removal of the colorectum leads to an impairment of fluid and electrolyte resorption. PATIENTS AND METHODS: Over a time period of two years we observed 320 proctocolectomized patients with ileal pouch-anal anastomosis (IPAA). All patients with high pouch output but without organic malfunction were identified. The organic reasons were excluded with the help of pouchoscopy, radiography or MR imaging. We evaluated routine parameters, the kidney function, the electrolyte changes, the acid-base balance and the urine pH, as well as the hormonal changes of the suprarenal glands. We identified seven patients with 'high pouch output' out of 320 patients observed. The control group consisted of 14 proctocolectomized patients without hints of complications in the endoscopic, radiographic and routine laboratory diagnostics. RESULTS: Neither group showed any significant differences in the analysis of the routine parameters. A significant drop of the urine sodium concentration of 40.5 +/- 18.7 mmol/l (control group 98 +/- 43.4 mmol/l) was observed in the group with 'high pouch output'. In this group the plasma aldosterone values were strongly increased with an average of 42.6 +/- 28.9 ng/dl (control group 13.2 +/- 6.8 ng/dl) as well as the plasma 18-hydroxycorticosterone with an average of 153.7 +/- 121.1 ng/dl (control group 153.7 +/- 121.1 ng/dl). Neither group of patients showed increased activity of free corticosterone and free cortisol. Only free 11-desoxycorticosterone was elevated in the group with 'high pouch output'. CONCLUSION: Our results prove that the mineralocorticoid adrenal activity plays a central role in order to preserve the volume and electrolyte homeostasis. The low frequency of 'high-pouch-output'-complications in realms of the restorative proctocolectomy proves the excellent compensation of the removal of the colon mucosa. Plasma aldosterone seems to be a diagnostic marker encapsulating the reabsorption problems of intestinal salt and volume losses after proctocolectomy.


Subject(s)
Adenomatous Polyposis Coli/surgery , Colitis, Ulcerative/surgery , Mineralocorticoids/blood , Postoperative Complications/physiopathology , Proctocolectomy, Restorative , Water-Electrolyte Balance/physiology , 18-Hydroxycorticosterone/blood , Adrenal Glands/physiopathology , Adult , Aldosterone/blood , Female , Homeostasis , Humans , Ileostomy , Male , Postoperative Complications/diagnosis , Reoperation , Risk Factors
5.
Acta Paediatr ; 89(9): 1098-103, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11071092

ABSTRACT

Adrenal insufficiency is suspected in some ill preterm infants. The aim of this prospective study was to compare serum cortisol concentrations during the first 2 wk of life of well preterm infants (group A) less than 30 wk of gestational age with the cortisol concentrations of ill preterm infants whose arterial hypotension-a potential sign of adrenal insufficiency-had been treated with catecholamine (group B), and the cortisol concentrations of ill preterm infants who had not been so treated (group C). Cortisol concentrations did not differ significantly between group A (240 nmol/l, 58-659; n = 46) (median, minimum-maximum) and group C (268 nmol/l, 58-1007; n = 25). Group B had a double-peaked distribution of cortisol. Two subgroups were formed by taking the highest cortisol level of group A as a threshold: group B1 (110 nmol/l, 41-378; n = 20) and group B2 (1200nmol/l, 764-1482; n = 8). The cortisol concentrations of group B1 were significantly lower (p = 0.00097) compared to the cortisol concentrations of the well preterm infants (group A). The severity of illness, which was quantified by two scoring systems, differed significantly among the groups (p < 0.003 for all comparisons) with the following sequence: A < C < B, but not between B1 and B2, as clinical variables were not different between the subgroups.


Subject(s)
Hydrocortisone/blood , Infant, Premature, Diseases/blood , Female , Gestational Age , Humans , Infant, Newborn , Male , Prospective Studies
6.
Pharmacotherapy ; 20(6): 644-52, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10853619

ABSTRACT

STUDY OBJECTIVE: To evaluate the efficacy and safety of caffeine citrate for treatment of apnea of prematurity. DESIGN: Multicenter, parallel, randomized, double-blind, placebo-controlled trial with open-label rescue. SETTING: Nine neonatal intensive care units. PATIENTS: Eighty-five infants, 28-32 weeks postconception and 24 hours or more after birth who had six or more apnea episodes within 24 hours. INTERVENTION: Caffeine citrate 10 mg/kg (as caffeine base) administered intravenously, followed by 2.5 mg/kg/day orally or intravenously, or placebo, for up to 10 days. Infants failing double-blind therapy could receive open-label rescue. MEASUREMENTS AND MAIN RESULTS: Success was defined as 50% or greater reduction in apnea episodes and elimination of apnea. Caffeine citrate was significantly more effective than placebo in reducing apnea episodes by at least 50% in 6 days (p<0.05), and approached statistical significance (p<0.10) in 3 days. It was significantly better than placebo in eliminating apnea in 5 days (p<0.05), and approached significance (p<0.10) in 2 days. The number of infants with an aggregate of 7-10 days of at least a 50% reduction in apnea events or elimination of apnea was significantly higher in the caffeine citrate than in the placebo group. Adverse events did not differ significantly between groups. No correlations were found between success and mean daily plasma concentrations or baseline characteristics. Volume of distribution and clearance increased with weight, supporting weight-adjusted dosing of caffeine citrate. CONCLUSION: Caffeine citrate 10 mg/kg caffeine base (equivalent to 20 mg/kg caffeine citrate) intravenously followed by 2.5 mg/kg/day caffeine base (equivalent to 5 mg/kg/day caffeine citrate) either intravenously or orally for 10 days is safe and effective for treating apnea of prematurity in infants 28-32 weeks postconception.


Subject(s)
Apnea/drug therapy , Caffeine/therapeutic use , Citrates/therapeutic use , Caffeine/adverse effects , Caffeine/pharmacokinetics , Citrates/adverse effects , Citrates/pharmacokinetics , Double-Blind Method , Drug Combinations , Female , Humans , Infant , Infant, Newborn , Male
7.
Arch Dis Child Fetal Neonatal Ed ; 81(3): F171-4, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10525017

ABSTRACT

AIM: To establish a reference range for serum cortisol concentrations in preterm infants with a gestational age of less than 30 weeks during the first two weeks of life. METHODS: Infants were prospectively classified by the following exclusion criteria: surfactant administration, arterial hypotension, acute or uncontrolled infection, ventricular haemorrhage II degrees or above, serum glucose < 2.2 mmol/l, exchange transfusion, stress as a result of any kind of examination or nursing for at least 4 hours before blood sampling. The cortisol value was measured once using radioimmunoassay in each infant. RESULTS: In appropriate for gestational age (AGA) infants (n = 37, median gestational age 27.7 weeks, median birthweight 1030 g) the distribution of the cortisol concentrations was non-Gaussian. These had a nearly normal distribution, when log(10) values of the data were used. The points determined by mean (2 SD) on the logarithmic scale were transformed back to the original units to provide a reference range: 73-562 nmol/l. Gestational age was significantly (p = 0.033) associated with cortisol values (log(10)) with a regression coefficient (standard error) of -0.045 (0.020). Small for gestational age (SGA) infants (n = 8) had significantly higher cortisol values (median 357 nmol/l) than AGA infants (median 199 nmol/l) (p=0.028). CONCLUSIONS: There is a strictly defined reference range of serum cortisol concentrations in AGA preterm infants.


Subject(s)
Hydrocortisone/blood , Infant, Premature/blood , Gestational Age , Humans , Infant, Newborn , Radioimmunoassay , Reference Values
8.
Dis Colon Rectum ; 42(10): 1318-24, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10528771

ABSTRACT

PURPOSE: Restorative proctocolectomy is a standard procedure in the surgical treatment of ulcerative colitis and familial adenomatous polyposis. The radical removal of the colorectum with construction of an ileostomy often results in high stoma losses. These may lead to changes in the electrolyte and acid-base balance and to alterations in renal and suprarenal gland function. METHODS: In this study 33 patients who received an ileoanal pouch before and after proctocolectomy were investigated at different time intervals for electrolyte changes, alteration of the acid-base balance, kidney function, and hormonal changes of the suprarenal glands. Measurements were performed before proctocolectomy, ten days after proctocolectomy with ileal pouch-anal anastomosis under protective loop ileostomy, before ileostomy closure, and 6 to 12 months after ileostomy closure. Neither acute renal failure nor other vital complications were observed. RESULTS: Statistical analysis showed a significant decrease of urine pH to 5.4 +/- 0.22 (before ileostomy closure) and metabolic acidosis (pH 7.32 +/- 0.04; base excess -1.3 +/- 5.6 (before ileostomy closure)). Likewise, we found a decrease in renal clearance to 86 ml/minute (before ileostomy closure) without signs of tubular damage. The most important change during the phase with ileostomy was a functional secondary hyperaldosteronism with aldosterone levels of 63.2 +/- 70.8 ng/dl (before ileostomy closure). In comparison with preoperative levels, there was a ten-fold increase in mineralocorticoid adrenal activity. Additionally, during the period with protective ileostomy, the hepatic synthesis of aldosterone-18-glucuronide was only slightly increased, and the cortisol/cortisone ratio was extremely decreased. CONCLUSIONS: These results show that restorative proctocolectomy with ileal pouch-anal anastomosis and protective loop ileostomy significantly influences fluid, electrolyte, and acid-base balance. Functional secondary hyperaldosteronism is of central importance for subsequent renal recompensation. Approximately one-half year after ileostomy closure, the endogenous hormones with mineralocorticoid effects returned to normal levels.


Subject(s)
Adrenal Glands/physiopathology , Kidney/physiopathology , Proctocolectomy, Restorative , Acid-Base Equilibrium/physiology , Adenomatous Polyposis Coli/surgery , Adrenal Cortex Hormones/analysis , Colitis, Ulcerative/surgery , Follow-Up Studies , Humans , Hyperaldosteronism/etiology , Hyperaldosteronism/physiopathology , Ileostomy , Prospective Studies , Time Factors , Urinalysis , Urine , Water-Electrolyte Balance/physiology
9.
Pediatr Nephrol ; 13(8): 653-6, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10502121

ABSTRACT

The variable response of patients with idiopathic nephrotic syndrome (NS) to glucocorticoid (GC) treatment has not been explained. Earlier studies indicated that the response is limited by cellular GC receptors. We investigated these receptors in mononuclear leukocytes of 28 pediatric patients with NS divided into three groups: steroid-sensitive in relapse, steroid-sensitive in remission, and steroid-resistant. Density and binding affinity of GC receptors were determined by a dexamethasone binding assay; no significant differences were found between the three patient groups and between these and healthy controls, although a few patient values fell outside the range of controls. Total and free plasma concentrations of cortisol were low in all three patient groups. A weak positive correlation was found between the number of GC receptors and total plasma cortisol (r=0.36, P=0.03). The results suggest that factors other than GC receptors that mediate the cellular effects of GC are involved in the variable response of NS patients to GC.


Subject(s)
Nephrotic Syndrome/metabolism , Receptors, Glucocorticoid/analysis , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Hydrocortisone/blood , Male , Nephrotic Syndrome/blood
10.
J Clin Endocrinol Metab ; 81(7): 2534-40, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8675573

ABSTRACT

There is a large body of evidence that points to a systemic link between the somatotropic axis and sex hormones, but epidemiologic data on the interactions between the two hormonal systems are still missing. We examined here the associations between the plasma levels of insulin-like growth factor (IGF) I, IGF-II, IGF-binding protein 3 (IGFBP-3), and sex hormones in a population-based sample of 486 men and women, aged 50-80 yr. The strongest association was an age-independent inverse correlation between all three circulating IGF components and sex hormone-binding globulin (SHBG), the major testosterone-binding protein in plasma. Consistent with this, bio-available (non-SHBG-bound) but not total testosterone levels were positively associated with the IGF system in men, and 3 alpha-androstanediol glucuronide was positively correlated with circulating IGFs in women. Moreover, part of the correlation between the circulating IGF system and bone mineral density at the femur and the calcaneus could be accounted for by SHBG. Our data suggest that sex hormones and the GH/IGF system are significantly interrelated in the elderly population. These hormonal interactions may play an important role in human aging and the pathogenesis of age-related diseases.


Subject(s)
Gonadal Steroid Hormones/blood , Insulin-Like Growth Factor Binding Protein 3/blood , Insulin-Like Growth Factor II/metabolism , Insulin-Like Growth Factor I/metabolism , Aged , Aged, 80 and over , Androstane-3,17-diol/analogs & derivatives , Androstane-3,17-diol/blood , Bone Density , Female , Humans , Male , Middle Aged , Sex Hormone-Binding Globulin/metabolism , Testosterone/blood
11.
J Pediatr Endocrinol Metab ; 8(4): 281-6, 1995.
Article in English | MEDLINE | ID: mdl-8821906

ABSTRACT

In order to assess hypothalamic-pituitary-adrenocortical axis function, we conducted low and single oral dose metyrapone tests (35 mg/kg) in dexamethasone treated very low birth weight infants with bronchopulmonary dysplasia (n = 12). The responses to metyrapone of tetrahydro-11-deoxycortisol (THS) and cortisol metabolites were analyzed by gas chromatography and mass spectrometry in 24-h urinary specimens. For comparative reasons, morning plasma 11-deoxy-cortisol and cortisol were measured by radioimmunoassay before and after metyrapone. No side effects of metyrapone were observed in our patients. In 5 of 12 patients, no urinary THS could be stimulated after metyrapone and most of the other patients had small increases in urinary THS. These findings suggest suppressed or strongly impaired hypothalamic-pituitary-adrenocortical axis function in most patients. While the concentrations of plasma 11-deoxycortisol showed little variation, those of plasma cortisol were grossly different from the respective urinary values. We recommend steroid analysis in 24-h urinary specimens by gas chromatography and mass spectrometry, because urinary steroids provide more information and the highly specific analytical technique is independent of phenomena such as cross reactivity or matrix effects. The low and single oral dose metyrapone test in combination with urinary steroid analysis by gas chromatography and mass spectrometry therefore provides a noninvasive, convenient and safe means of evaluating the integrity of the hypothalamic-pituitary-adrenocortical axis in very low birth weight infants.


Subject(s)
Adrenal Cortex/physiology , Dexamethasone/therapeutic use , Hypothalamus/physiology , Infant, Very Low Birth Weight , Metyrapone , Pituitary Gland/physiology , Bronchopulmonary Dysplasia/drug therapy , Cortodoxone/analogs & derivatives , Cortodoxone/urine , Gas Chromatography-Mass Spectrometry , Humans , Hydrocortisone/urine , Infant, Newborn
12.
J Clin Endocrinol Metab ; 80(3): 737-44, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7883826

ABSTRACT

Ten cases of adrenal adenomas, one case with unilateral adrenal hyperplasia, and another case with apparent bilateral are reported, in whom an alternative pathway of aldosterone via 21-deoxyaldosterone is operative. They all manifested hypertension, low renin activity, low normal potassium values, as well as high urinary excretion rates of 21-deoxyaldosterone and its related metabolite Kelly's-M1 steroid. In all cases, urinary aldosterone metabolites (aldosterone-18-glucuronide and tetrahydroaldosterone) and aldosterone precursor 18-hydroxycorticosterone levels were normal. Hence, the adrenal lesions give rise to hyper-21-deoxyaldosteronism. 21-Deoxyaldosterone is a weak mineralocorticoid, and its elevated production in the presence of normal aldosterone can induce a pathological state of hypermineralocorticoidism. Adrenalectomy resulted in normalization of hypertension in six of eight and amelioration in two of eight cases. Six of seven adenoma cases examined as well as the case of unilateral adrenal hyperplasia were sensitive to ACTH. One of the seven adenomas and, as expected, the case with apparent bilateral hyperplasia were angiotensin responsive. Histologically and electron microscopically, the operated adenomas consisted predominantly of clear cells, characterized by mitochondria with tubulo-vesicular internal structure similar to those of the zona fasciculata (in contrast, our classical Conn's adenoma with normal 21-deoxyaldosterone excretion exhibited a more heterogenous histological appearance and were, in terms of ultrastructure, more similar to cells of the zona glomerulosa). Ultrastructurally and immunocytochemically, the clear cells of 21-deoxyaldosterone adenomas showed features of both the zona glomerulosa and the zona fasciculata and are, hence, considered to be hybrid cells. We conclude that the determination of 21-deoxyaldosterone and Kelly's-M1 should be considered in the diagnosis of mineralocorticoid-induced forms of hypertension, especially when an adrenal adenoma has been detected with an imaging procedure.


Subject(s)
Adenoma/metabolism , Adrenal Gland Neoplasms/metabolism , Aldosterone/analogs & derivatives , Hypertension/etiology , Pregnanes/metabolism , Adenoma/pathology , Adrenal Gland Neoplasms/pathology , Adult , Aldosterone/analysis , Aldosterone/metabolism , Female , Humans , Hypertension/diagnosis , Hypertension/metabolism , Immunohistochemistry , Male , Middle Aged
13.
Endocr Res ; 21(1-2): 197-202, 1995.
Article in English | MEDLINE | ID: mdl-7588381

ABSTRACT

In the present study the aldosterone-18-glucuronide and tetrahydroaldosterone values in 24 hour urine collections of healthy nonpregnant women, women with normal pregnancies and women with pregnancy induced hypertension (PIH) were compared. In pregnancy an elevated excretion of both aldosterone metabolites was found. The Q-ratio (aldosterone-18-glucuronide/tetrahydro-aldosterone+aldosterone-18-glu cur onide) was also increased compared to healthy nonpregnant women. The elevated Q-ratios point out to increased formation of aldosterone-18-glucuronide. This predominantly renal metabolite may reflect greater availability of aldosterone molecules for interaction with mineralocorticoid receptor in the kidney.


Subject(s)
Aldosterone/analogs & derivatives , Hypertension/urine , Pregnancy Complications, Cardiovascular/urine , Pregnancy/urine , Aldosterone/urine , Case-Control Studies , Female , Humans , Hypertension/etiology , Reference Values
14.
J Steroid Biochem Mol Biol ; 50(5-6): 319-27, 1994 Sep.
Article in English | MEDLINE | ID: mdl-7918119

ABSTRACT

21-Deoxyaldosterone has been postulated to be a precursor of aldosterone in an alternative biosynthesis pathway and Kelly's-M1 is considered to be its metabolite. In healthy volunteers, the excretion rate of 21-deoxyaldosterone and of Kelly's-M1 are significantly lower than the aldosterone metabolites, aldosterone-18-glucuronide and tetrahydro-aldosterone and than the aldosterone precursor 18-OH-corticosterone. Essential hypertension patients (with low and normal renin) excrete comparable values of 21-deoxyaldosterone and Kelly's-M1 as normotensives. In 66% of aldosterone-producing adenoma cases (APA) and in 60% of idiopathic hyperaldosteronism (IHA) patients, significantly raised values of 21-deoxyaldosterone and Kelly's-M1 were found. The patients with the high excretion rates of both steroids showed only moderately increased values of the aldosterone metabolites, aldosterone-18-glucuronide and tetrahydro-aldosterone, as well as of the aldosterone precursor 18-OH-corticosterone. In contrast, the latter mentioned steroids were excreted in higher amounts in those patients with normal excretion of 21-deoxyaldosterone and Kelly's-M1. Hence, it is suggested that aldosterone is produced alternatively either via 18-OH-corticosterone alone or additionally via 21-deoxyaldosterone. Furthermore, in three cases of "incidentally" discovered adrenal adenomas, 21-deoxyaldosterone and Kelly's-M1 were the only elevated steroids. After adrenalectomy, excretion of 21-deoxyaldosterone and of Kelly's-M1 and blood pressure returned to normal, which proves that these steroids play a role in blood pressure regulation. In essential hypertension, ACTH infusion induced a significant increase of 21-deoxyaldosterone and Kelly's-M1. However, the increase after angiotensin II was 3- to 6-fold higher than after ACTH. IHA patients proved to be more responsive to angiotensin II; and, in contrast, APA cases proved to be more sensitive to ACTH. The data suggest that beside the main route of aldosterone biosynthesis via 11-deoxycorticosterone, corticosterone and 18-OH-corticosterone an alternative pathway exists via 21-deoxyaldosterone in healthy and in hypertensive patients. There are similarities between the regulation of 21-deoxyaldosterone and the regulation of aldosterone. The determination of 21-deoxyaldosterone and its possible metabolite Kelly's-M1 might be appropriate in the diagnosis of mineralocorticoid-induced forms of hypertension, especially when an adrenal adenoma is discovered.


Subject(s)
Aldosterone/analogs & derivatives , Hyperaldosteronism/metabolism , Hypertension/metabolism , Pregnanes/urine , Adenoma/metabolism , Adrenocorticotropic Hormone/pharmacology , Adult , Aldosterone/urine , Angiotensin II/pharmacology , Female , Humans , Male , Middle Aged
15.
J Clin Psychopharmacol ; 14(4): 255-63, 1994 Aug.
Article in English | MEDLINE | ID: mdl-7962681

ABSTRACT

Two hundred six outpatients with panic disorder and agoraphobia were randomly assigned to receive 4 weeks of treatment with placebo or sustained-release adinazolam under double-blind conditions. Eighty-eight percent of patients receiving drug and 85% of patients receiving placebo remained in the study at week 4. This report describes the "intent-to-treat" analysis of 202 patients who made at least one follow-up visit after randomization at baseline. On the basis of the Clinical Global Impressions-Improvement Scale, 69.7% of the adinazolam-treated patients were much or very much improved compared with 39.6% of the placebo-treated patients at week 4 or end-point (p = 0.0001). At week 4, panic attacks were completely blocked in 57.1% of adinazolam-treated patients and in 39.2% of the placebo-treated patients (p = 0.009). Adinazolam sustained-release treatment was statistically more effective than placebo treatment on measures of global improvement, number of panic attacks, SCL-90 phobia severity, main phobia severity, and anticipatory and general anxiety. No drug-placebo differences were found for overall self-rated phobia severity, unexpected or situational panic attacks, or for work, family, or social disability.


Subject(s)
Agoraphobia/drug therapy , Anti-Anxiety Agents , Antidepressive Agents/administration & dosage , Benzodiazepines/administration & dosage , Panic Disorder/drug therapy , Adult , Agoraphobia/psychology , Antidepressive Agents/adverse effects , Benzodiazepines/adverse effects , Delayed-Action Preparations , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Panic Disorder/psychology , Personality Assessment/statistics & numerical data , Personality Inventory/statistics & numerical data , Psychometrics , Treatment Outcome
16.
Dtsch Med Wochenschr ; 118(50): 1837-43, 1993 Dec 17.
Article in German | MEDLINE | ID: mdl-8269828

ABSTRACT

A 21-year-old woman with weight loss, palpitations and facial flush was found to have hypertension (up to 200/130 mm Hg) and mild hyperkalaemia (3.4 mmol/l). Extensive diagnostic tests revealed hyperaldosteronism with contrast storing in the right adrenal gland on scintigraphy after injection of dexamethasone (2 mg daily for one week). The hyperaldosteronism could not be suppressed by dexamethasone. Analysis of venous blood separately from each side pointed to aldosterone production in the right adrenal (right renal vein: 80 ng/dl, drainage area of the right adrenal vein: 114 ng/dl, left renal vein: too low to measure). The right adrenal gland was removed. No adenoma was found histologically. After the operation the aldosterone level was reduced and the blood pressure transiently fell. But both had risen again after 3 months. Renewed tests revealed dexamethasone-remediable hyperaldosteronism. On treatment with hydrocortisone (15-5-5 mg) and 50 mg metoprolol the patient became normotensive without any other medication.


Subject(s)
Aldosterone/metabolism , Dexamethasone , Hyperaldosteronism/blood , Adrenal Cortex Hormones/blood , Adult , Female , Humans , Hydrocortisone/therapeutic use , Hyperaldosteronism/complications , Hyperaldosteronism/drug therapy , Hypertension/etiology
17.
Klin Padiatr ; 205(3): 180-4, 1993.
Article in German | MEDLINE | ID: mdl-8350592

ABSTRACT

We report on three cases of Corticosterone Methyl Oxidase Typ II deficiency in two siblings and one boy. All three children were presented with typical symptoms of a saltlosing syndrome (vomiting, poor drinking, weight loss, hypotonia). Hyponatremia and hyperkalemia, low plasma aldosterone concentrations when related to high plasma-renin-activities suggested deficiency in the final steps of aldosterone biosynthesis. Variable degrees of enzyme deficiency and no relation of biochemical findings to the clinical symptoms were observed. Clinical symptoms became less severe with age. Diagnosis of CMO II-deficiency was established by an abnormal high ratio of 18-hydroxycorticosterone to aldosterone, by measurement of their precursors and metabolites in plasma and urine. In one sibling negative values may have been caused by suppression of the renin-angiotensin-system due to high sodium replacement therapy.


Subject(s)
Cytochrome P-450 CYP11B2 , Failure to Thrive/genetics , Hyperkalemia/genetics , Hyponatremia/genetics , Mixed Function Oxygenases/deficiency , Phenotype , Aldosterone/biosynthesis , Diagnosis, Differential , Failure to Thrive/enzymology , Female , Humans , Hyperkalemia/enzymology , Hyponatremia/enzymology , Infant, Newborn , Male , Mixed Function Oxygenases/genetics
18.
J Steroid Biochem Mol Biol ; 45(1-3): 65-8, 1993 Apr.
Article in English | MEDLINE | ID: mdl-8386933

ABSTRACT

Pregnancy-induced hypertension (PIH) is a frequent cause of maternal and neonatal morbidity and mortality. In the present study we focused on the pathophysiology of PIH, mainly on the role of mineralocorticoids, reversed blood pressure patterns, and the resulting necessity of continuous monitoring of the preeclamptic mother. Problems of antihypertensive therapy are discussed and the first results of a pilot study with Urapidil are presented. To examine the role of mineralocorticoids in the pathophysiology of PIH, we studied plasma aldosterone and 18-hydroxy-corticosterone (18-OH-B) levels in 25 women with PIH and in 25 healthy pregnant women. Furthermore, we evaluated the mineralocorticoid receptor (MR) count in mononuclear leukocytes in the 2 groups. The MR-count was significantly decreased in the PIH-group. The values of plasma aldosterone and 18-OH-B were also low. These results cannot be explained by receptor down-regulation due to higher level of mineralocorticoids of the zona glomerulosa. Perhaps deoxycorticosterone or a hitherto unknown mineralocorticoid is responsible for the hypertension and altered MR-status. The first results of continuous blood pressure measurements with a noninvasive, real-time blood pressure monitor (Finapres) are presented. The comparison of the obtained values with intraarterial measurements demonstrates a good correlation between the two methods. We also report on the first experiences with Urapidil in the treatment of hypertension in severe preeclampsia. The data show that hypertension in preeclamptic women can be treated by Urapidil without side effects or reflex-tachycardia. Further studies will have to prove if Urapidil is suited for prepartal treatment of PIH as well.


Subject(s)
Hypertension/physiopathology , Pre-Eclampsia/physiopathology , Pregnancy Complications, Cardiovascular/physiopathology , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/therapeutic use , Blood Pressure Determination/methods , Female , Humans , Hypertension/drug therapy , Hypertension/metabolism , Leukocytes, Mononuclear/metabolism , Mineralocorticoids/metabolism , Pilot Projects , Piperazines/administration & dosage , Piperazines/therapeutic use , Pre-Eclampsia/metabolism , Pregnancy , Pregnancy Complications, Cardiovascular/metabolism , Receptors, Mineralocorticoid , Receptors, Steroid/metabolism
19.
Horm Res ; 40(5-6): 227-30, 1993.
Article in English | MEDLINE | ID: mdl-8112725

ABSTRACT

A midpubertal girl presented with secondary amenorrhea and a rapidly progressive deepening of her voice as the only signs of virilization. Diagnostic work-up yielded an extremely elevated plasma testosterone (289 ng/dl), low estradiol (29 pg/ml) levels and a large solitary cyst of the right ovary, which was totally removed. Pathohistology was in keeping with a granulosa cyst with mild luteinization. Normalization of testosterone (to 27.3 ng/dl) and estradiol (to 62 pg/ml) and resumption of regular menses after 2 months clearly indicated an autonomous function of the cyst. A malignant tumor was unequivocally excluded. Basal and ACTH stimulated levels of adrenal androgens pointed to a late-onset 3 beta-hydroxysteroid dehydrogenase deficiency, which per se is known to induce polycystic ovarian changes, but to date has never been described to be accompanied with a large and autonomous follicular cyst.


Subject(s)
3-Hydroxysteroid Dehydrogenases/deficiency , Ovarian Cysts/enzymology , Virilism/etiology , Adolescent , Female , Humans , Ovarian Cysts/complications , Ovarian Cysts/surgery , Testosterone/blood , Virilism/enzymology
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