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Biomedical subjects

V Hartmann

Publications and source records attributed to V Hartmann.

16 recordsLinked to original sources

Tissue PO2 and growth rate in early chick embryos.

We determined dry mass, frequency distribution of tissue PO2 and microvascular density of head and trunk of early chick embryos between day 4 and day 6 of incubation. During this period the percentage of the dry mass of the head on total dry mass increased from 31% to 48% indicating that the head grows faster than the trunk. Tissue PO2 values ranged between zero and arterial PO2. About half of the numbers were less than 5 Torr. Mean tissue PO2 was significantly higher in the head than in the trunk. This was paralleled by a significantly higher microvascular density in the head. The high frequency of low tissue PO2 values found at each day at all measuring sites suggests that the embryonic tissue of both head and trunk extracts as much oxygen from the capillary blood as possible. Consequently, growth rate strongly depends on oxygen availability. Since the arterial PO2 is the same in the head and in the trunk (Meuer and Baumann, 1988), the diversity of tissue PO2 and growth rate found in this study is probably caused by differences in the structure of the microvascular bed resulting in variations of tissue blood perfusion, capillary transit time and diffusion distance.

Animals

Bronchodilator effect of theophylline preparations and aerosol fenoterol in stable asthma.

To compare the acute bronchodilator effect of increasing doses of intravenous theophylline and inhaled beta adrenergic agonists, we administered intravenous theophylline dissolved in ethylenediamine or proxyphylline and diprophylline or placebo in a double blind fashion to nine asthmatics on three different days. At each session, 100 mg theophylline or placebo were given during each of five subsequent periods of 30 minutes' duration and followed by inhalation of 0.4 mg fenoterol. In contrast to placebo, 500 mg theophylline in ethylenediamine or proxyphylline and diprophylline significantly decreased mean specific airway resistance (SRaw in cmH2O.s) from 31.2 to 23.6 or 34.2 to 23.5 at theophylline serum concentrations of 14.4 or 16.6 mg/L, respectively. Fenoterol lowered SRaw to about 40 percent of the respective baseline values independent of theophylline or placebo pretreatment. We conclude that the acute bronchodilator effect of theophylline is weak in comparison to inhaled beta agonists. Furthermore, proxyphylline and diprophylline cause a weak but not significant bronchodilation when compared to ethylenediamine.

Airway Resistance

Effect of diltiazem on histamine- and carbachol-induced bronchospasm in normal and asthmatic subjects.

Recently, several transmembrane calcium-channel blockers have been used in experimental models to investigate the mechanisms through which Ca++ ions contribute to the regulation of the contractile response of airway smooth muscle and to determine the therapeutic use of these drugs in bronchial asthma. Since the data from these studies are inconsistent and inconclusive, we studied the effect of diltiazem, a calcium-channel blocker previously not examined to our knowledge, on histamine- and carbachol-induced bronchoconstriction in healthy and in asymptomatic allergic bronchial asthma. The study was performed in a double-blind, randomized, placebo-controlled fashion, using a single oral dose of 60 mg of diltiazem. Airway reactivity to histamine and carbachol expressed by PD35SGaw was significantly but weakly attenuated by diltiazem in the asthmatic, but not in the normal subjects. Baseline lung function was not significantly influenced by diltiazem. We concluded that the effect of diltiazem on unspecific airway hyperresponsiveness in asthmatic subjects is too weak to justify a recommendation as therapy.

Adult

[Comparison of the oscillatory measurement of airway resistance with plethysmography and spirometry in juvenile patients].

In 78 children (age 4 to 17 years, height 102 to 179 cm) with and without clinical signs of airway obstruction, spirometric and plethysmographic measurements were compared with the forced oscillation method for determination of resistance to breathing (Ros). Ros was measured with a recently developed apparatus (Siregnost FD5. Siemens) and showed a close correlation with resistance (r = 0.84; n = 78). The spirometric values did not, however, exhibit a definite relationship to Ros. This study demonstrates that airway obstruction in children can be equally well estimated by oscillatory and plethysmographic techniques. Compared with plethysmography, determination of Ros has the particular advantage of being better tolerated by young subjects.

Adolescent

Dco at various breath-holding times: comparison in patients with chronic bronchial asthma and emphysema.

Measurement of Dco is known to be dependent upon functional inhomogeneities. Because different types of inhomogeneities are operative in patients with bronchial asthma and patients with emphysema, different changes of Dco with increasing breath-holding time, tA, are to be expected. We studied the change of Dco with increasing breath-holding time in healthy subjects, patients with asthma bronchiale and patients with emphysema. In the patients the severity of airway obstruction was about the same. The following results were obtained: (a) in healthy subjects and in the asthmatics Dco decreased with tA, in a similar manner, approaching a value (ml . min-1 . Terror-1) of 34.7 and 31.6 at 10 sec, respectively, and (b) in patients with emphysema Dco increased with tA, yielding negative values at small tA: 1.5 sec-23.4; 10 sec: 11.7. From these results we suggest that in healthy subjects and in patients with bronchial asthma parallel inhomogeneities influence the course of Dco. In emphysema the time couse of Dco is best explained with a faster intrapulmonary mixing of He compared to CO. This behavior indicates that in emphysema low Dco values can be mainly attributed to large diffusional resistances (stratification) within the lungs.

Adult

[An experimental and clinical study of the effect of ketotifen in the treatment of extrinsic bronchial asthma (author's transl)].

The therapeutic value of ketotifen (Zaditen), a new anti-allergic drug, was studied in patients with extrinsic bronchial asthma. a) In 8 persons the protective effect on bronchial provocation tests with allergen was examined 3 and 14 days after treatment and compared with cromoglycate (Intal); b) 19 patients were treated for 6 months with 2 x 1 milligram ketotifen (n = 7), 2 x 2 mg ketotifen (n = 7), 2 x 1 mg clemastine (Tavegil) (n = 5). The results were as follows: a) The amount of inhaled allergen causing a fall of 20% in FEV1.0/VC was 9-12 times larger with both therapeutic regimens. b) Ketotifen definitely improved the asthmatic symptoms as compared with clemastine. The improvement was independent of the dosage. Side-effects occurred more frequently with clemastine. The study confirms the in vitro demonstrated anti-analphylactic properties of ketotifen; that it can be taken by mouth is of particular clinical interest.

Asthma

[The value of measurements of oscillatory resistance in the evaluation of lung function. A comparative study in adults and children (author's transl)].

Measurements of total oscillatory impedance (ROS) together with spirometric and body plethysmographic determinations were made in adults and children and the results were compared. In adults (n = 260) correlation was less close (r = 0.53) than it was in 88 children (r = 0.82). Even if ROS was of similar magnitude the phase shift between pressure and flow tended to be more negative than it was in children. These differences are presumably due to anatomical differences between the adult and the growing lung. In interpretation of the results it is suggested that the differences in the ratio: airways compliance/airways resistance reflect changes arising from age and disease processes.

Adolescent

Dihydroergotoxine: separation and determination of four components by high-performance liquid chromatography.

The evaluation of a new high-performance liquid chromatographic method is described. It permits the separation and determination of the four components of dihydroergotoxine (dihydroergocristine, dihydroergocornine, dihydro-alpha-ergocryptine, and dihydro-beta-ergocryptine) in a single step. On reversed-phase microparticles, complete baseline separation is possible with different mobile phases containing about 10(-2) M base. The analysis of dihydroergotoxine mesylate drug substance or its dosage forms can be carried out in about 15 min. No reference substance is required for the determination of the proportions of the components. This method is simple and exhibits high accuracy, reproducibility, and selectivity. It permits the analytical control of dosage forms containing dihydroergotoxine mesylate to ensure that they comply with the specifications for the drug substance used in clinical and pharmacological studies.

Chemical Phenomena

[Stability of liquid ergotalkaloid preparations as a function of the solvent polarity (author's transl)].

The degradation of dihydroergotamine-, dihydroergocornine-, dihydroergocryptine- (both isomers) and dihydroergocristine-mesilate in solution was studied as a function of the temperature and the dielectric constant of the composition. The degradation reactions of the studied hydrogenated ergopeptide alkaloids gave pseudo first-order kinetics. The pseudo first-order rate constants at room temperature were calculated using the Arrhenius equation. It was found that the stability of the studied hydrogenated ergopeptide alkaloids in solution is a function of the dielectric constant of the composition, and that stable solutions can be obtained by the use of water-alcohol mixtures having dielectric constants between 30 and 45. Solutions of the hydrogenated ergot alkaloids in predominantly organic media have the advantage that the degradation to the corresponding aci-forms, hydrolysis products and oxidation products is reduced. For this reason it is not necessary to carry out the filling operation under an inert gas atmosphere in order to protect the hydrogenated ergot alkaloids from oxidation. These results present an important technological advance.

Chemical Phenomena

Brain metastases of an amelanotic melanoma as the primary manifestation in a 15-year old boy.

A 15-year old boy was admitted to hospital with an acute left hemiparesis because of a 3.5 cm-diameter-tumor in the right frontoparietal region. In CCT 4 other tumors were to be seen in both hemispheres after giving contrast medium. Upon a diagnostic operation, a hemorrhage into a metastasis of an amelanotic melanoma was found. The boy survived 2.5 months. In the pathological examination the primary tumor was not found, but there were 12 other intracerebral metastases and two metastases in the left lung and the thyroid gland. Histologically it was an amelanotic melanoma.

Adolescent