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Biomedical subjects

D Haack

Publications and source records attributed to D Haack.

At least 55 records · Page 3Linked to original sources

The influence of dimetindene maleate on the endogenous hydrocortisone synthesis suppressing potency of betamethasone.

Plasma hydrocortisone (cortisol) levels in 7 healthy volunteers were measured following administration of 0.25 mg betamethasone or 0.25 mg betamethasone and 1 mg dimetindene maleate. The H1-receptor antagonist dimetindene maleate did not influence the hydrocortisone suppressing activity of betamethasone, which was proved by comparison with the published plasma hydrocortisone levels of 162 young healthy untreated volunteers.

Adult↗

Development of plasma 21-deoxycortisol radioimmunoassay and application to the diagnosis of patients with 21-hydroxylase deficiency.

Specific 21-deoxycortisol (21-DF) antiserum was raised in New Zealand white rabbits using a 21-DF-3,20-oxime-bovine serum albumin complex. Plasma radioimmunoassay of 21-DF was developed and used together with a radioimmunoassay of 17-hydroxyprogesterone (17-OH-P) for diagnosis of patients with 21-hydroxylase deficiency of congenital and postpubertal forms. The assays were performed in plasma extracts after isolation by paper chromatography. The response of plasma 21-DF and 17-OH-P to i.v. ACTH (25 IU) was studied in 15 adult controls and compared to 8 women with the late onset form of 21-hydroxylase deficiency and 23 women with idiopathic hirsutism. Normal 21-DF values for women were 6.9 +/- 3.6 ng/dl and for men 9.71 +/- 2.73 ng/dl. Newborn children (age: 3-10 days) had a value of 8.3 +/- 4.8 ng/dl. These values are definitely lower than the lowest value ever published. This is possibly due to the specificity of the antibody. During the menstrual cycle the 21-DF values did not change. The baseline and post-stimulated concentrations of hormone were similar in controls and women with hirsutism but were significantly higher in women with the late onset form of 21-hydroxylase deficiency. In the congenital form of 21-hydroxylase deficiency the 21-DF values (baseline) were high. In general, the 21-DF and 17-OH-P values have shown parallel changes. However, one case of 21-hydroxylase deficiency with elevated 21-DF but normal 17-OH-P was observed. The use of 21-DF for the diagnosis of 21-hydroxylase deficiency is suggested.

17-Hydroxycorticosteroids↗

Comparative accuracy of five intravenous-fluid controllers.

The accuracy of five gravity-feed infusion-control devices was compared using a gravimetric method. Two nonvolumetric drop-counting devices (IVAC 230 and, IMED 350) and three volumetric devices (Quest/Cutter Infusor, Anatros Rateminder, and IVAC 260) were compared at four different flow rates (10, 40, 125, 250 ml/hr) using four different solutions and two head heights (30 and 100 cm). The mean error rates for the IVAC 230 and the IVAC 260 devices were consistently high and negative (-6.32 and -12.60%, respectively). The mean error rates for the IMED, Anatros, and Quest/Cutter devices were 2.2, 1.8, and 0.7%, respectively. Conversion charts must be used to account for variation in drop size when different solutions and flow rates are used in the IVAC 230 and IMED 350 devices. At the low flow rates, the 60-drop/ml sets were more accurate than the 20-drop/ml sets. Of the volumetric devices, the Quest/Cutter Infusor and the Anatros Rateminder were more accurate than the IVAC 260. The Quest/Cutter Infusor was the most accurate of all controllers tested. For volumetric devices that use drop-counting technology, selecting an internal fluid code on the basis of solution ingredients is still necessary. For the new volumetric devices, conversion charts and fluid code selection are not necessary to achieve a high level of accuracy.

Evaluation Studies as Topic↗

The pharmacokinetics of fluocortolone and prednisolone after intravenous and oral administration.

The pharmacokinetics of fluocortolone and of prednisolone were examined following a single intravenous injection of 5 mg and oral administrations of 10 and 20 mg to five healthy male volunteers. After intravenous injection the plasma levels of fluocortolone decreased biexponentially with half-lives of 9 +/- 5 min and 1.3 +/- 0.3 h. Total plasma clearance of fluocortolone was calculated to be 7.0 +/- 1.5 ml/min/kg. Oral administrations of fluocortolone revealed maximum plasma levels of 86 +/- 12 ng/ml (10-mg dose) and 174 +/- 34 ng/ml (20-mg dose) after 1.4 +/- 0.2 h. Intravenously administered prednisolone was rapidly distributed (t 1/2 alpha = 5 +/- 3 min) but more slowly eliminated from plasma than fluocortolone (t1/2 beta = 3.1 +/- 0.8 h). Correspondingly a total plasma clearance of 2.2 +/- 0.2 ml/min/kg was calculated. Oral administrations revealed maximum prednisolone plasma levels of 172 +/- 25 ng/ml (10-mg dose) and 278 ng/ml (20-mg dose) after 1.6 +/- 0.7 h. The absolute bioavailability of both corticosteroids was higher than 80% and independent of both dose levels investigated.

Administration, Oral↗

Plasma dexamethasone concentrations and differential suppression response of cortisol and corticosterone in depressives and controls.

After a dexamethasone suppression test (DST), cortisol, corticosterone, and the test substance were determined by a direct radioimmunoassay in 42 samples obtained from 22 depressed patients and 8 controls. The DST results of both glucocorticoids agreed in most of the tests. In all seven cases with elevated but not definitely abnormal post-DST (1600 hr) cortisol levels (transitional range 30-50 ng/ml) the concurrent determination of corticosterone indicated that this corticosteroid may serve as a potent additional discriminator. Dexamethasone plasma concentrations at 1600 hr after a 1-mg test dose of dexamethasone at 2300 hr were significantly (p less than 0.01) lower in cortisol and corticosterone nonsuppressors than in suppressors. Since these data were obtained 17 hr after ingestion of dexamethasone (half-life 3.5-5 hr) any conclusions about an inverse correlation between dexamethasone and corticosteroid plasma concentrations would be speculative. However, the dexamethasone pharmacokinetics might be an important variable and may contribute to some of the recent uncertainty about the DST.

Adult↗

Failure of prophylactically administered phenytoin to prevent post-traumatic seizures in children.

We report the results of a randomized, double-blind, placebo-controlled study to determine whether phenytoin administered soon after a head injury lessens the incidence of late post-traumatic epilepsy in children. 41 patients were randomized into either a phenytoin or placebo group and followed for 18 months. The patients were administered phenytoin or placebo intravenously or intramuscularly within 24 h of hospital admission. The patients were parenterally administered phenytoin or placebo until oral doses could be tolerated. There was no significant difference in the percentage of children having seizures in the treated and placebo groups (p = 0.25).

Brain Injuries↗

Failure of prophylactically administered phenytoin to prevent early posttraumatic seizures.

A randomized double-blind placebo-controlled study was carried out to determine whether phenytoin administered soon after injury lessens the incidence of epilepsy in the 1st week after severe head trauma. In this study, 244 patients were randomized into either a phenytoin or placebo group. The patients in the phenytoin group were administered phenytoin intravenously or intramuscularly within 24 hours of hospital admission. Patients in the placebo group received intravenous or intramuscular diluent. The patients were switched from parenterally administered phenytoin or placebo as soon as oral doses could be tolerated. Over 78% of the phenytoin patients had plasma concentrations of at least 10 micrograms/ml at 1, 3, and 7 days after injury. There was no significant difference in the percentage of patients having early seizures in the treated and placebo groups (p = 0.99). There was no significant difference in the interval from injury to first seizure between the treated and placebo groups (p = 0.41). The early administration of phenytoin did not lessen the occurrence of seizures in the 1st week after head injury. Since the effectiveness of seizure prophylaxis has not been established, the authors suggest that anticonvulsant drugs be administered only after an early seizure has occurred.

Brain Injuries↗

Failure of prophylactically administered phenytoin to prevent late posttraumatic seizures.

This randomized double-blind placebo-controlled study was undertaken in a series of 179 patients to determine whether phenytoin administered soon after head injury lessens the incidence of late posttraumatic epilepsy. When delayed hypersensitivity to phenytoin developed, the patient was switched to phenobarbital. The patients were followed for 18 months to detect the occurrence of seizures and to serially measure plasma phenytoin concentrations. There was no significant difference in the percentage of patients having late seizures in the treated and placebo groups (p = 0.75). The time between injury and seizures did not significantly differ between the two groups. The results provide no support for the continued use of phenytoin in the low therapeutic range for prophylaxis against late posttraumatic seizures. It cannot be concluded that higher phenytoin plasma concentrations and higher compliance rates than obtained in this study would not have significantly decreased the occurrence of late posttraumatic epilepsy. The finding that no patient with a phenytoin plasma concentration of 12 microgram/ml or higher had a seizure raises the question of whether phenytoin in blood concentrations in higher therapeutic ranges might lessen the occurrence of posttraumatic epilepsy, and should be studied further. Posttraumatic epilepsy is a major public health problem deserving a large cooperative trial to determine if phenytoin at higher blood levels than obtained in this study, or other currently available or newly developed drugs, can prevent the occurrence of posttraumatic epilepsy.

Adolescent↗

The favorable effect of early parenteral feeding on survival in head-injured patients.

This prospective randomized controlled clinical trial compares the effects of early parenteral nutrition and traditional delayed enteral nutrition upon the outcome of head-injured patients. Thirty-eight head-injured patients were randomly assigned to receive total parenteral nutrition (TPN) or standard enteral nutrition (SEN). Clinical and nutritional data were collected on all patients until death or for 18 days of hospitalization. Survival and functional recovery were monitored in survivors for 1 year. Of the 38 patients, 18 were randomized to the SEN group and 20 to the TPN group. Demographically, the two groups of patients were similar on admission. There was no significant difference in the severity of head injury between the two groups as measured by the Glasgow Coma Scale (p = 0.52). The outcome for the two groups was quite different, with eight of the 18 SEN patients dying within 18 days of injury, whereas no patient in the TPN group died within this period (p less than 0.0001). The basis for the improved survival in the TPN patients appears to be improved nutrition. The TPN patients had a more positive nitrogen balance (p less than 0.06), and a higher serum albumin level and total lymphocyte count. More adequate nutritional status may have improved the patients' immunocompetence, resulting in decreased susceptibility to sepsis. The data from this study strongly support the favorable effect of early TPN on survival from head injury.

Adult↗

[Problems of differentiating sacral fractures and fissure formations in the sacrum].

It is shown on the basis of two observations that computed tomography represents a valuable additional means to clarify the diagnosis of congenital and traumatic changes in the pelvis, especially the sacrum and vertebral column. The article explains the differential diagnosis between congenital fissures of the pelvic arch and fractures by means of computed tomography. This is illustrated with the help of x-ray morphologic criteria.

Adult↗

Aldosterone metabolites and possible aldosterone precursors in hypertension.

The value of the urine tests: free aldosterone, aldosterone-18-glucuronide, tetrahydroaldosterone 18-hydroxycorticosterone and 18-hydroxydeoxycorticosterone in distinguishing primary aldosteronism from essential hypertension was studied in patients with typical and atypical primary aldosteronism and in patients with essential hypertension. The discriminating function of the tetrahydroaldosterone determination was the best, followed by 18-hydroxycorticosterone, free aldosterone and aldosterone-18-glucuronide. The measurement of 18-hydroxydeoxycorticosterone was without distinguishing value. Three cases with hypertension, adrenal adenoma, elevated 18-hydroxycorticosterone but normal aldosterone values were observed. In longitudinal studies the excretions of aldosterone, aldosterone metabolites and possible precursors periodically varied independently of each other. Determinations of urine aldosterone, aldosterone metabolites, 18-hydroxycorticosterone and 18-hydroxydeoxycorticosterone were not applicable for differential diagnosis of the adenoma and hyperplasia forms of primary aldosteronism.

Adenoma↗

Characterisation of aldosterone metabolites cross reacting with aldosterone and tetrahydroaldosterone antibodies.

Metabolites of aldosterone were extracted from human urine collected over three days following the intravenous injection of a tracer dose of tritium labelled hormone. After enzymic hydrolysis, steroids were separated by column, paper and thin-layer chromatography and the polarities of the labelled metabolites were compared with the chromatographic properties of known aldosterone products. The pattern of metabolites changed over the three days, from that associated with typical aldosterone metabolites, to less polar metabolites. Materials in the organic extract from a pH-1 hydrolysate of pooled pregnancy urine, were located by their ability to bind with aldosterone and tetrahydroaldosterone antisera and exhibited similar chromatographic properties to the radioactive metabolites. Using GC-MS, the identity of this immunoactive material could not be established in extracts after purification from 200 ml pregnancy urine but some synthetic derivatives of aldosterone as candidate compounds, were excluded.

Adrenal Cortex Neoplasms↗

Increased excretion of 18-hydroxycorticosterone in patients with adrenal adenomas and hypertension.

Two female patients, 54 and 34 years old, each presented with an adrenal adenoma and hypertension. Blood pressure fell after removal of the tumors. The first patient had high urinary 18-hydroxycorticosterone and periodically elevated 18-hydroxy-deoxycorticosterone excretions. The second patient had elevated 18-hydroxycorticosterone and free cortisol excretions. Urinary aldosterone, aldosterone metabolites and plasma aldosterone were not increased. Plasma renin activity was suppressed and serum potassium levels were normal. After surgery, no elevated steroid values were found. Elevated 18-hydroxycorticosterone excretion may be an indicator of yet unknown hypertensinogenic mechanisms. The role of 18-hydroxycorticosterone in the etiology of hypertension is still unknown.

18-Hydroxycorticosterone↗

[Radioimmunologic detection of triamcinolone-acetonide and its application in a study on the hydrolysis of water soluble corticoid esters].

The rate of hydrolysis of different water soluble esters of corticoids was determined with newly developed specific radioimmunoassays in healthy subjects. It can be found, that triamcinoloneacetonide phosphate was significantly faster transformed into free form after i.v. application than the reference substances prednisolone- and methylprednisolone hemisuccinate. Moreover the plasma concentration of free triamcinolone-acetonide decreases much faster than that of free prednisolone and methylprednisolone. This shows, that triamcinoloneacetonide is distributed wider and very quickly, probably in the intracellular fluid volume. At this time it is not clear, whether only free steroids are biologically active or the water soluble derivatives as well. Our results can be of clinical importance because of the different rates of hydrolysis as well as of differences in the diffusion.

Adrenal Cortex Hormones↗

Direct radioimmunoassays for "aldosterone" and "18-hydroxycorticosterone" in unprocessed urine, and their use in screening to distinguish primary aldosteronism from hypertension.

For distinguishing primary aldosteronism from essential hypertension, we use simple direct radioimmunoassays for "aldosterone" (aldosterone and other materials that react with the antibody to aldosterone) and "18-hydroxycorticosterone" (similarly) in unprocessed urine. Patients with primary aldosteronism have high values for "aldosterone." This diagnosis can be validated by assays of further urine samples from the same person and by additional direct assays for "18-hydroxycorticosterone." In none of 65 urine samples from 26 patients with primary aldosteronism were both "aldosterone" and "18-hydroxycorticosterone" values within their reference intervals. However, a few "aldosterone" and "18-hydroxycorticosterone" values for patients with essential hypertension and normal aldosterone excretion were also (moderately) increased. Thus, when high values are found, true aldosterone values must be estimated by extraction and chromatography, to eliminate false positives. The "aldosterone" and "18-hydroxycorticosterone" values by our procedure are much higher than the corresponding values for urinary free aldosterone and 18-hydroxycorticosterone. Although not identified, the immunoactive materials are probably metabolites of aldosterone and 18-hydroxycorticosterone.

18-Hydroxycorticosterone↗

[Plasma concentration and systemic effect of betamethasone after intra-articular injection (author's transl)].

Plasma concentrations of betamethasone, cortisol and corticosterone were measured before and after intraarticular injection of a betamethasone-depot preparation (Celestan-Depot) by radioimmuno-assay in 31 patients. Plasma concentration of betamethasone reached its maximum of between of 10 and 17 microgram/dl 30 min after injection. It had fallen to half after 2 hours, and practically to nil from the eighth day onwards. Lowest plasma levels of cortisol and corticosterone occurred after 6--24 hours, returning to the normal range after four days. In nine patients with knee-joint effusion and synovitis the plasma concentration of betamethasone was significantly higher after 24 hours, and cortisol and corticosterone values after 48 hours significantly more suppressed, than in patients without joint effusions and signs of inflammation. The results indicate that plasma concentration of betamethasone and the suppressant effect on the adrenal cortex after intra-articular injection is similar to that after intramuscular applications. Correspondingly, systemic application of the cortisol derivatives can cause significant side effects and be contra-indicated also after intra-articular injection.

Adolescent↗

Early prediction of outcome in head-injured patients.

The relationship between Glasgow Coma Scale (GSC) scores obtained during the 1st week after head injury and outcome at 1 year was analyzed in 170 patients. Seventy-two of 76 patients with initial GCS scores of 3 or 4 lived, and only one had a favorable outcome. Favorable and unfavorable outcomes were almost equally divided when the initial GCS scores were in the intermediate range of 5, 6, or 7. No patients with an initial GCS score in this intermediate range that subsequently worsened had a favorable outcome, while over 80% of those improving to a score higher than 7 had a favorable outcome. Only 12% of those persisting with a score of 5, 6, or 7 for 1 week had favorable outcome. Outcome predictions using the multiple logistic model were made for this intermediate group of patients based on GCS scores and data on midline shift derived from computerized tomography (CT). The patients with initial scores of 5, 6, or 7 with midline shifts of less than 4.1 mm on initial CT scanning had a significantly higher favorable outcome rate compared with patients with a larger shift. However, outcome prediction made by combining shift data and initial GCS scores are not significantly more accurate than predictions based solely on initial GCS scores. Combining 48-hour GCS scores and shift data significantly improves predictive accuracy based only on coma scores. The data obtained by combining GCS scores at 72 hours and 1 week and shift data is marginally significant for improving accuracy of outcome predictions. It is concluded that GCS scores and shift data are highly accurate indicators of outcome in head-injured patients.

Adolescent↗