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Biomedical subjects

D Haack

Publications and source records attributed to D Haack.

At least 19 recordsLinked to original sources
PubMed1995

A new subset of mineralocorticoid hypertension with excess of 21-deoxyaldosterone and Kelly's-M1 steroid: clinical and morphological findings.

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.

Adenoma↗
PubMed1994

Role of 21-deoxyaldosterone in human hypertension.

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.

Adenoma↗
PubMed1993

[Unilateral autonomous aldosterone production in hyperaldosteronism suppressible by dexamethasone].

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.

Adrenal Cortex Hormones↗
PubMed1993

Late-onset 3 beta-hydroxysteroid dehydrogenase deficiency with virilization induced by a large ovarian cyst.

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.

3-Hydroxysteroid Dehydrogenases↗
PubMed1992

The MEE/PEE ratio as a predictor of excess weight loss for up to 1 year after vertical banded gastroplasty.

Thirteen morbidly obese individuals were studied prospectively for 1 year after vertical banded gastroplasty (VBG) to determine the relationships between energy balance equation parameters and excess weight loss. The measured energy expenditure (MEE), as determined by indirect calorimetry, was not correlated with weight loss. However, when this parameter was expressed as a ratio to the predicted energy expenditure (PEE), the ratio was significantly correlated with the postoperative excess weight loss at 2, 6, and 12 months. The mean daily energy intake after the VBG was 2715 +/- 865 kJ. The postoperative energy intake was not correlated with the excess weight loss. Diet-induced thermogenesis was studied in eight patients. The mean diet-induced thermogenesis was 10.31% +/- 13.92%. The diet-induced thermogenesis was not correlated with the postoperative excess weight loss. The preliminary findings of this trial suggest that the MEE/PEE ratio is useful in predicting excess weight loss after VBG.

Adult↗
PubMed1991

Disturbed glucocorticoid receptor autoregulation and corticotropin response to dexamethasone in depressives pretreated with metyrapone.

We studied glucocorticoid receptor autoregulation and corticotropin response to dexamethasone in depressed patients and controls, attempting to control for the confounding effect of endogenous glucocorticoids. After depletion of endogenous cortisol, depressed patients showed an attenuated suppressibility of corticotropin by dexamethasone in the face of unchanged dexamethasone plasma levels. Beta-endorphin levels were strongly correlated with adrenocorticotropic hormone (ACTH) concentrations. Although metyrapone administration resulted in a marked rise of glucocorticoid receptor sites per cell in controls, this effect was not present in depressives. These data support the hypothesis of a decreased glucocorticoid receptor plasticity and a partial steroid resistance in depression.

Adolescent↗
PubMed1991

Multihormonal response to dexamethasone. A study in atopic dermatitis and normal controls.

Although minor disturbances of the circadian serum cortisol rhythm and diminished excretion of steroid metabolites have been reported in patients with atopic dermatitis, test assays regarding subtle neuroendocrine alterations have not been employed so far. We therefore studied the serum concentrations of cortisol, prolactin and adrenocorticotropin under baseline conditions, after 1 mg dexamethasone and after a defined methylprednisolone treatment in 15 patients with atopic dermatitis, in comparison with 10 healthy controls. The assessment of the hormones revealed no remarkable differences between either group at any of the blood sampling time points. However, in 3 patients and 2 control subjects, though exhibiting no concomitant disease, we could find no suppression of endogenous cortisol to below 5 micrograms/dl after oral intake of 1 mg dexamethasone. These cortisol non-suppressors showed lower dexamethasone serum concentrations in the morning after its administration, as compared with the suppressors. Acute (1 mg dexamethasone) or prolonged (40 mg methylprednisolone over 6 days) intake of glucocorticoids suppressed prolactin levels in both groups, demonstrating that the effect of glucocorticoids on the hormone system is not restricted to the hypothalamic-pituitary-adrenal axis. Our results indicate an intact feedback response of this hormonal axis to 1 mg dexamethasone and the ability of long-term as well as acute glucocorticoid administration to influence the prolactin secretion in patients with atopic dermatitis.

Adolescent↗
PubMed1990

[Experiences with a combination therapy of methylprednisolone and troleandomycin in severe bronchial asthma requiring high-dose corticoids].

Although treatment comprising a combination of methylprednisolone (MP) and troleandomycin (TAO) has been employed to treat cases of severe bronchial asthma requiring high doses of corticosteroids, for about 20 years, now, it has always been associated with major adverse reactions (1). A new protocol avoids these adverse effects by a rapid reduction in the dose of MP to alternating administrations and low TAO dosage (250 mg). Nineteen patients were treated using this protocol, 16 of whom for more than two months (maximum 21, minimum 4 months). Three patients were taken out of the study as early non-responders in the initial phase. Five patients must be considered to be late non-responders, or were discharged from the study on account of pathological liver parameters. In 8 patients who showed good tolerance, an appreciable reduction in the dose of steroids, with stabilisation of the asthma, was observed.

Administration, Oral↗
PubMed1989

Primary glucocorticoid receptor defect with likely familial involvement.

A 29-year-old woman with moderately elevated blood pressure and signs of hyperandrogenism (hirsutism and acne) but without typical Cushing's syndrome symptoms has been followed for almost 6 years. Steroid and glucocorticoid receptor studies indicated a primary glucocorticoid receptor defect. Elevated androgen values were of special interest. Clinical manifestation of hyperandrogenism seemed not to be proportional to the biochemical findings. Therefore, the possibility of a partial androgen receptor defect should also be considered.

Acne Vulgaris↗
PubMed1989

Lymphocyte beta-adrenoreceptor density in patients with unipolar depression and normal controls.

Values of binding maximum (Bmax) and dissociation constant (Kd) of (-)3-[125I]iodocyanopindolol (ICYP) were determined in beta-adrenergic receptors of membranes of peripheral lymphocytes in 32 patients with unipolar depression (DSM-III-R) and 31 normal controls. Results were analyzed by a two-way Analysis of Covariance method. A significant difference was noted for group assignment (patient versus control, p less than 0.05). Mean Bmax (fmol ICYP bound/mg lymphocyte membrane fraction total protein) of patients was 31.9 +/- 3.84 (SE) and controls 46.3 +/- 3.92 (SE). A significant interaction was found between group membership and gender (p less than 0.05). In the female patient group (n = 14), mean Bmax was 30.5 +/- 5.79 (SE); in female controls, mean Bmax was 56.0 +/- 5.15 (SE). Differences between male patients and male controls were not significant. Mean values of Kd (pmol/liter) showed a trend for patient values to be lower than control values [69.0 +/- 13.66 (SE) versus 108.5 +/- 14.42 (SE), respectively]. A significant inverse relationship was noted between lymphocyte beta-receptor Bmax and frequency of panic attacks during the depressive episode in 18 patients (p = 0.05). No relationship was found between values of Kd and frequency of panic attacks in these patients. Thus, preliminary evidence is provided for relationships among altered beta-adrenergic receptor binding, gender, and indices of panic-anxiety in unipolar depressed patients.

Adult↗
PubMed1989

Relationship between admission hyperglycemia and neurologic outcome of severely brain-injured patients.

Severe head injury is associated with a stress response that includes hyperglycemia, which has been shown to worsen outcome before or during cerebral ischemia. To better define the relationship between human head injury and hyperglycemia, glucose levels were followed in 59 consecutive brain-injured patients from hospital admission up to 18 days after injury. The patients who had the highest peak admission 24-hour serum glucose levels had the worse 18-day neurologic outcome (p = 0.01). Patients with peak 24-hour admission glucose levels greater than 200 mg/dL had a two-unit increase in Glasgow Coma Scale score while patients with admission peak 24-hour serum glucose levels less than or equal to 200 mg/dL had a four-unit increase in Glasgow Coma Scale score during the 18-day study period (p = 0.04). There was a significant relationship between 3-month and 1-year outcome and peak admission 24-hour serum glucose level (p = 0.02 and p = 0.02, respectively). Those patients with admission peak 24-hour serum glucose levels less than or equal to 200 mg/dL had a greater percentage of favorable outcome at 18 days, 3 months, and 1 year than those with admission peak 24-hour glucose levels greater than 200 mg/dL (p = 0.0007, p = 0.03, and p = 0.005, respectively). A significant relationship between admission peak 24-hour Glasgow Coma Scale score and 18-day, 3-month, and 1-year outcomes was found (p = 0.0001, p = 0.0002, and p = 0.0002, respectively). Patients with mean admission peak 24-hour Glasgow Coma Scale scores of 3.5, 6, and 10 had mean admission 24-hour peak serum glucose levels of 252 +/- 23.5, 219.1 +/- 19, and 185.8 +/- 21, respectively (p = 0.05). These relationships were not significantly altered when confounding variables such as the amount of glucose given over the initial 24-hour postinjury period, the presence of diabetes or multiple injuries, and whether patients were given steroids, dilantin, or insulin were statistically incorporated. These data suggest that admission hyperglycemia is a frequent component of the stress response to head injury, a significant indicator of severity of injury, and a significant predictor of outcome from head injury.

Analysis of Variance↗
PubMed1989

[Morphology and endocrinology of a fatal course of Addison crisis].

A 36 year-old man fell ill with violent dorsalgia seemingly related to spondylosis. The diagnosis of tuberculous spondylitis was made as late as 18 months after the onset of symptoms. The disease rapidly progressed to death in spite of adequate tuberculostatic and surgical therapy. The post-mortem examination revealed a massively caseating tuberculosis of both adrenal glands suggestive of Addison's disease. Severe adrenocortical insufficiency was confirmed by low steroid hormone levels in the post-mortem blood; the validity of these results is indicated by comparative hormone level determinations in a series of recent and stored post-mortem blood specimens.

Addison Disease↗
PubMed1988

Judgement of the hypothalamic-pituitary-adrenocortical function in psychiatric patients by betamethasone-induced cortisol suppressibility.

Betamethasone induced cortisol suppressibility was examined in 62 drug free consecutively admitted psychiatric inpatients. Betamethasone was choosen instead of the commonly used dexamethasone, because its double half-life compared to dexamethasone and its higher tissue availability. After a base-line evaluation with blood samples drawn at 8 a.m., 4 p.m., and 11 p.m., 0.5 mg or 1.0 mg betamethasone was given orally at 11 p.m. Postbetamethasone cortisol as well as betamethasone blood levels were then measured at the same time points as on the baseline day. In the groups receiving 1.0 mg betamethasone non-depressed patients had significantly (p less than 0.05) lower postbetamethasone cortisol levels than depressed patients for each time point measured whereas 0.5 mg betamethasone did not differentiate depressed from non-depressed patients. Patients with other depressions like schizoaffective psychosis-depressive subtype- or organic brain syndrome with depressive symptomatology demonstrated similar postbetamethasone cortisol profiles as the group of patients with major depression. Betamethasone plasma concentrations differed significantly (p less than 0.001) with respect to the oral dosage with higher values for the 1.0 mg betamethasone groups.

Adolescent↗
PubMed1988

Intolerance to enteral feeding in the brain-injured patient.

Calorie and protein supplementation improves nutritional status. This support may improve outcome and decrease morbidity and mortality in acutely brain-injured patients. Investigators have observed a poor tolerance to enteral feedings after brain injury and have noted that this persists for approximately 14 days postinjury. This delay has been attributed to increased gastric residuals, prolonged paralytic ileus, abdominal distention, aspiration pneumonitis, and diarrhea. In the present investigation, 23 brain-injured patients with an admission 24-hour peak Glasgow Coma Scale (GCS) score between 4 and 10 were studied for 18 days from hospital admission. The mean duration from injury to initiation of full-strength, full-rate enteral feeding was 11.5 days. Seven of the 23 patients tolerated enteral feedings within the first 7 days following hospital admission (mean 4.3 days), four patients tolerated feedings between 7 and 10 days postadmission (mean 9 days), and 12 patients did not tolerate feedings until after 10 days postinjury (mean 15.9 days). There was a marginally significant relationship between low GCS scores on admission and length of days to enteral feeding tolerance (p = 0.07). A significant inverse relationship was observed between daily peak intracranial pressure (ICP) and time to tolerance of feedings (p = 0.02). There was no significant relationship between feeding tolerance and days to return of bowel sounds (p = 0.12). Serum albumin levels decreased during the investigation (mean +/- standard error to the mean: 3.2 +/- 0.12 gm/dl on Day 1; 2.7 +/- 0.23 gm/dl on Day 16; normal = 3.5 to 5.0 gm/dl), whereas the percentage of patients tolerating feedings increased over the course of the study. The authors conclude that patients with acute severe brain injury do not adequately tolerate feedings via the enteral route in the early postinjury period. Tolerance of enteral feeding is inversely related to increased ICP and severity of brain injury. It is suggested that parenteral nutritional support is required following brain injury until enteral nutrition can be tolerated.

Adult↗
PubMed1987

Effect of total parenteral nutrition upon intracranial pressure in severe head injury.

Animal investigations suggest that administration of hyperosmolar total parenteral nutrition (TPN) solutions may potentiate cerebral edema following head injury. Intravenous nutrition (TPN) is often required after head injury due to intolerance to enteral feeding (EN). This study evaluates the effect of TPN on intracranial pressure (ICP) measurements in severely brain-injured patients. Ninety-six severely brain-injured patients were randomly assigned to receive TPN or EN and were studied from hospital admission until 18 days postinjury. The TPN was started within 48 hours postinjury and the EN was started when tolerated. Peak daily ICP was not significantly different on admission and over time (overall mean +/- standard error of the mean 32.01 +/- 1.62 for TPN versus 32.5 +/- 1.25 for EN). Intracranial pressure was greater than 20 mm Hg in 75% of TPN patients and 73% of EN patients. Conventional therapy failed to control elevated ICP in 36% of TPN patients and 38% of EN patients. Of these patients, subsequent barbiturate therapy failed to control ICP in 56% of TPN patients and 64% of EN patients. Serum osmolality was not significantly different between groups at admission or over the course of the study. The TPN group tended to have higher mean serum glucose levels for the first 13 days postinjury, while the EN group had a higher mean serum glucose content thereafter, but these differences were not statistically significant. This study shows that TPN can be given safely to the severely brain-injured patient without causing serum hyperosmolality or affecting ICP levels or ICP therapy.

Brain Injuries↗