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Biomedical subjects

P Heilmann

Publications and source records attributed to P Heilmann.

At least 37 records · Page 2Linked to original sources
PubMed1997

[The Wolfram syndrome: diabetes mellitus, hypacusis, optic atrophy and short stature in STH deficiency].

HISTORY AND CLINICAL FINDINGS: A 43-year-old man was known for 3 years to have diabetes mellitus. For 2 months before admission he had symptoms of hyperglycaemia with polyuria, polydipsia, weight loss, as well as impairment of vision and declining fitness. In addition to bilateral deafness he was clearly of normally proportioned short stature (150 cm). INVESTIGATIONS: The levels of blood sugar (221 mg/dl), HbA1c(10.2%), triglycerides (496 mg/dl) and cholesterol (323 mg/dl) were raised, while the concentration of somatotropic hormone was diminished, both before and after arginine administration. Fundoscopy revealed concentric diminution of the visual fields with left amblyopia. Visual evoked potentials and colour sense testing revealed bilateral optical atrophy, and the audiogram demonstrated deafness. These findings provided the diagnosis of Wolfram syndrome, namely insulin-dependent diabetes mellitus, deafness, optical atrophy and small stature with somatotropic hormone deficiency. TREATMENT AND COURSE: On insulin treatment the metabolic state became normal (HbA1c 7.5%, normal lipid profile). It was decided that the deficiency in somatotropic hormone regulation did not require treatment. CONCLUSION: Cardinal symptoms of the autosomally recessive Wolfram syndrome are insulin-dependent diabetes and optic nerve atrophy. Several types of hormonal abnormalities are associated with it, including a deficiency in the somatotropic axis. To obtain early and adequate hormonal substitution requires extensive endocrinological diagnosis of a disease which frequently becomes manifest in childhood or adolescence.

Adult↗
PubMed1997

Determination of 18 beta-glycyrrhetinic acid in human serum using the fully automated ALCA-system.

We report a method for the determination of 18 beta-glycyrrhetinic acid (glycyrrhetinic acid) in human serum using the ALCA-system. The technology of the ALCA-system is based on the principles of adsorptive and desorptive processes between liquid and solid phases. The assay is run fully automated and selective. Procedural losses throughout the analysis are negligible, thereby allowing for external calibration. The calibration curve is linear up to 10 mg/l and concentrations as low as 10 micrograms/l are detectable. CV is 2.5% for within- and 7.5% for between-assay precision at a level of 50 micrograms/l and 1.2% for within- and 8.5% for between-assay precision at a level of 500 micrograms/l. Specific and expensive reagents are not necessary and time-consuming manual operations are not involved. This assay can be selected from a wide spectrum of methods at any time. Thus, the present method is well-suited for drug monitoring purposes in the routine laboratory. In a pharmacokinetic study we measured serum levels of glycyrrhetinic acid in ten healthy young volunteers after ingestion of 500 mg glycyrrhetinic acid. Maximum levels of glycyrrhetinic acid were 6.3 mg/l 2 to 4 hours after ingestion. Twenty-four (24) hours after ingestion seven probands still had glycyrrhetinic acid levels above the detection limit with a mean level of 0.33 mg/l.

Adult↗
PubMed1996

Human kidney 11 beta-hydroxysteroid dehydrogenase: regulation by adrenocorticotropin?

In ectopic adrenocorticotropin (ACTH) syndrome (EAS) with higher ACTH levels than in pituitary Cushing's syndrome and during ACTH infusion, the ratio of cortisol to cortisone in plasma and urine is increased, suggesting inhibition of renal 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) by ACTH or by ACTH-dependent steroids. Measuring the conversion of cortisol to cortisone by human kidney slices under different conditions, we tested the possibility of 11 beta-HSD regulation by ACTH and corticosteroids. Slices prepared from unaffected parts of kidneys removed because of renal cell carcinoma were incubated with unlabeled or labeled cortisol, and cortisol and cortisone were quantitated after HPLC separation by UV or radioactive detection. The 11 beta HSD activity was not influenced by incubation with increasing concentrations (10(-12)-10(-9) mol/l) of ACTH (1-24 or 1-39) for 1 h. Among 12 ACTH-dependent steroids tested (10(-9)-10(-6) mol/l), only corticosterone (IC50 = 2 x 10(-7) mol/l), 18-OH-corticosterone and 11 beta-OH-androstenedione showed a significant dose-dependent inhibition of 11 beta-HSD activity. The percentage conversion rate of cortisol to cortisone was concentration dependent over the whole range of cortisol concentrations tested (10(-8) - 10(-5) mol/l. A direct inhibitory effect of ACTH on 11 beta-HSD is, therefore, unlikely. The only steroids inhibiting the conversion of cortisol to cortisone are natural substrates for 11 beta-HSD. Kinetic studies show a saturation of the enzyme at high cortisol concentrations. Thus, the reduced percentage renal cortisol inactivation in EAS seems to be due mainly to overload of the enzyme with endogenous substrates (cortisol, corticosterone and others) rather than to direct inhibition of 11 beta-HSD by ACTH or ACTH-dependent steroids, not being substrates of 11 beta-HSD.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Decidua and placenta in mice after treatment with a synthetic glucocorticoid.

To investigate a possible long-term effect of glucocorticoids on decidua and placenta of mice, a single dose of 24 mg kg-1 body weight triamcinolone acetonide in crystalline suspension was given subcutaneously to NMRI mice on gestational day (GD) 2. Deciduae and placentae, as well as corticosterone and triamcinolone concentrations in maternal plasma of GDs 10 and 17 were examined. NADPH-cytochrome P450 reductase involved in drug biotransformation was detected immunocytochemically and showed co-localization with NADPH diaphorase histochemistry in the decidua and placenta. Both reactions were higher in endothelial cells of decidual sinusoids on GD 10, but were lower on GD 17 in the trophoblast, spongiotrophoblast and extraplacental visceral yolk-sac epithelial cells of treated mice than in untreated animals. Histochemistry of 11 beta-hydroxysteroid dehydrogenase, an enzyme that metabolizes biologically active adrenocortical steroids and their synthetic congeners in the placenta, showed higher activity on GD 17 in enlarged labyrinthic trophoblast I cells of treated mice than in untreated animals. As corticosterone concentrations were still decreased on GD 17, when triamcinolone concentrations were no longer detectable, a long-term suppression of adrenal gland function seems obvious.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Aqueous flare measurement with a laser flare cellmeter in eyes with diabetic retinopathy.

Eighty-one patients (147 eyes) with non-proliferative or proliferative diabetic retinopathy were examined with a laser flare cellmeter with regard to function of the blood-anterior chamber barrier. The protein content of the aqueous in patients with proliferative diabetic retinopathy was significantly higher than that in patient with the non-proliferative form. A statistically significant association was found between the age of diabetic patients and the flare concentration. In the group with non-proliferative diabetic retinopathy, a distinct increased flare concentration was measured in particular cases. Long-term controls will have to show whether this is an indication of imminent complications.

Adult↗
PubMed1994

Morphologic effects of a sulfur(IV) aerosol on the nasal cavity of beagle dogs.

Morphologic changes were observed in nasal cavities of beagle dogs after long-term exposure to a respirable sulfur(IV) aerosol at a concentration equivalent to a sulfur dioxide (SO2) concentration of 0.6 mg/m3. The changes were characterized by a thickened epithelial layer resulting from epithelial proliferation, by a loss of secretory material, and by moderate mononuclear cell infiltration.

Administration, Inhalation↗
PubMed1994

Pulmonary dead space and airway dimensions in dogs at different levels of lung inflation.

The quasi-stationary front that separates inspired gas from mixed alveolar gas is largely determined by the balance between diffusive and convective forces of gas transport. To investigate parameters influencing this balance, a study was performed on eight anesthetized ventilated beagle dogs. Measurements were made of the volume of pulmonary dead space corresponding to four end-inspiratory lung volumes. Aerosol recovery techniques were used to determine airway sizes at lung depths corresponding to those respective dead space volumes as well as at fixed volumetric depths between 70 and 250 ml. Mean dead space volumes as measured by a single inhalation of He (and SF6) were 112 +/- 15 (SD) ml (127 +/- 15 ml), 120 +/- 18 ml (137 +/- 20 ml), 127 +/- 18 ml (145 +/- 20 ml), and 133 +/- 19 ml (155 +/- 21 ml) at end-inspiratory lung volumes of 64, 71, 79, and 86%, respectively, of total lung capacity. At fixed lung depths the airway diameters increased with higher levels of lung inflation. However, airway diameters "at the end of the dead space" did not change significantly. They were approximately 0.5 mm for SF6 dead space and approximately 0.75 mm for He dead space. These findings support the theoretical prediction that the position of the diffusion front during breathing is strongly dependent on airway geometry and much less dependent on parameters of the breathing maneuver.

Animals↗
PubMed1993

[Aerogenous immunostimulation of weaner swine against experimentally induced respiratory infections with Pasteurella multocida].

The clearance of Pasteurella, Bordetella and Haemophilus from the lung of weaners was increased by aerogenous immunostimulations using a lysate mixture consisting of 12 strains of 8 bacterial species, as well as live and inactivated temperature sensitive mutants of Pasteurella multocida. The severity of experimental pneumonias caused by Pasteurella has also been decreased by this treatment. The effect of the lysate was shown to be unspecific and short, as antibody production against Pasteurella was not induced and no booster effect of subsequent aerogenous immunizations with Pasteurella antigens could be detected.

Animals↗
PubMed1993

[Measurement of the mucociliary transport velocity in the trachea of calves].

A measuring method is presented for the determination of the velocity of intratracheal mucociliary transport in calves, which is applicable for nonanaesthetized animals directly in the calf stable. The transport velocity in the trachea of clinically healthy calves was found to be about 15 mm/min, which is in agreement with other reports.

Animals↗
PubMed1992

Convective and diffusive gas transport in canine intrapulmonary airways.

The significance of convective and diffusive gas transport in the respiratory system was assessed from the response of combined inert gas and particle boluses inhaled into the conducting airways. Particles, considered as "nondiffusing gas," served as tracers for convection and two inert gases with widely different diffusive characteristics (He and SF6) as tracers for convection and diffusion. Six-milliliter boluses labeled with monodisperse di-2-ethylhexyl sebacate droplets of 0.86-microns aerodynamic diameter, 2% He, and 2% SF6 were inspired by three anesthetized mechanically ventilated beagle dogs to volumetric lung depths up to 170 ml. Mixing between inspired and residual air caused dispersion of the inspired bolus, which was quantified in terms of the bolus half-width. Dispersion of particles increased with increasing lung depth to which the boluses were inhaled. The increase followed a power law with exponents less than 0.5 (mean 0.39), indicating that the effect of convective mixing per unit volume was reduced with depth. Within the pulmonary dead space, the behavior of the inert gases He and SF6 was similar to that of the particles, suggesting that gas transport was almost solely due to convection. Beyond the dead space, dispersion of He and SF6 increased more rapidly than dispersion of particles, indicating that diffusion became significant. The gas and particle bolus technique offers a suitable approach to differential analysis of gas transport in intrapulmonary airways of lungs.

Animals↗
PubMed1992

Intraphagolysosomal pH in canine and rat alveolar macrophages: flow cytometric measurements.

Intracellular dissolution of inhaled inorganic particles is an important clearance mechanism of the lung and occurs in phagolysosomal vacuoles of phagocytes. Flow cytometric measurements of intraphagolysosomal pH in alveolar macrophages (AM) obtained from beagle dogs, Wistar rats, and from a baboon were made using fluorescein isothiocyanate-labeled amorphous silica particles (FSP). AM were obtained by bronchoalveolar lavage. FSP were phagocytized by AM in cell suspensions incubated in full media for 24 hr up to 6 days. Dual laser flow cytometry was performed and six-parameter list mode data were recorded from forward scatter, side scatter, and fluorescence intensities at 530 nm excited at 457 nm and 488 nm as well as logarithmic fluorescence intensity at wavelengths 630 nm excited at 488 nm. In this way it was possible to discriminate viable AM with phagocytized FSP from lysing AM with phagocytized FSP and from cells without FSP and from free FSP. Viable cells were distinguished from lysing cells by staining with propidium iodide immediately before the flow cytometric measurement. A calibration curve for the pH value was determined from FSP suspended in buffered media at pH values ranging from 3.5 to 7.5. First flow cytometrical results indicated that after an incubation time of 24 hr, the mean intraphagolysosomal pH of viable AM was 4.7 +/- 0.3 for dogs and 5.1 +/- 0.5 for rats. The intraphagolysosomal pH of the baboon AM was 4.5.

Animals↗
PubMed1990

Effect of canine surfactant protein (SP-A) on the respiratory burst of phagocytic cells.

Cells obtained from bronchoalveolar lavage, or neutrophils of peripheral blood of dog, were incubated with the canine surfactant-associated protein A (SP-A). A significant decrease of the production of superoxide anion was observed after subsequent stimulation with phorbol-12-myristate-13-acetate (PMA) as measured by the lucigenin-dependent chemiluminescence (CL). Several other proteins used for control experiments did not decrease lucigenin-dependent CL, indicating a specific effect of SP-A on phagocytes. Treatment of SP-A with collagenase prior to incubation with neutrophils destroyed the depleting effect on oxygen radical production of PMA-stimulated cells. We propose that SP-A acts as a regulatory factor of the respiratory burst of alveolar macrophages and neutrophils in the lungs. The inhibitory effect of SP-A is down-regulated by collagenase released from stimulated alveolar macrophages.

Acridines↗
PubMed1990

[The effect of local and systemic immunization of suckling pigs on bronchoalveolar clearance and on intrabronchial infections with Pasteurella multocida].

In vivo investigations of bactericidal bronchoalveolar clearance of weaning pigs locally or systemically immunized with Pasteurella antigens exhibited clearly distinctive results, as early as 3 days after the last immunization. They differed from controls by significant increase in the elimination of the homologous Pasteurella multocida A wild strain. That increase in the clearance remains for 21 days and is specific only to the immunized capsular type. There are no relations of this result to the cytological findings of the lavage fluids and to results of the intrabronchial challenge infection. Frequency and severity of pneumonias were reduced by as little as 3 aerogenic immunizations with Pasteurella mutants.

Animals↗
PubMed1989

Urinary oestriol-16-glucuronide determined by "on-line" liquid chromatography.

A fully automated method for the specific assessment of oestriol-16-glucuronide in urine is described. "On-line" sample preparation, including enrichment, pre-purification, focusing and injection, is combined with automated high-performance liquid chromatographic separation and fluorimetric quantification. Losses of oestriol-16-glucuronide throughout the total procedure are negligible. Thus, external calibration is feasible for quantification. Coefficients of variation are 4.44% (n = 12) for intra- and 7.85% (n = 9) for interassay variability. Assay sensitivity is 430 nmol/l. The excretion rates of oestriol-16-glucuronide relative to creatinine were estimated in 85 pregnancy urines. These oestriol-16-glucuronide estimates correlated well with those of total urinary oestriol, determined by high-performance liquid chromatography after acid hydrolysis (r = 0.957). The reference ranges of oestriol-16-glucuronide for the different weeks of gestation were evaluated. Unlike the determination of total oestriol, the present method does not need an hydrolysis step. The method is therefore well suited for the biochemical monitoring of fetal well-being under emergency conditions.

Chromatography, High Pressure Liquid↗