Inhibition of histamine release from human granulocytes by ions of the rare earth elements lanthanum and cerium.

The influence of the ATPase inhibitors, lanthanum or cerium, on histamine release in basophils and mast cells was studied. Both compounds inhibited IgE- or A23187-induced histamine release. To exclude a general inhibition of calcium-dependent reactions in the cell, we tested the influence of these compounds on phagocytosis and superoxide production of neutrophil granulocytes. Phagocytosis of Candida albicans was inhibited partially, superoxide generation, measured by the INT test after stimulation with zymosan or aggregated gamma globulin, was not affected. Because of the inhibitory effect of lanthanum or cerium compounds on membrane ATPase and immunological function of epidermal Langerhans cells we propose that these compounds may be used in the treatment of atopic eczema, where both histamine-releasing mast cells and IgE-bearing Langerhans cell play a pathogenetically important role.

[Splenectomy in sarcoidosis]. / Splenektomie bei Sarkoidose.

It is reported about 6 patients suffering from sarcoidosis with splenomegaly. In these cases indication for splenectomy was given by symptoms of hypersplenism, abdominal pain and ineffective cortisone therapy. In general after operation activity of sarcoidosis is unchanged. Different markers of activity were used after a time interval of 2-11 years. In one case it has to be discussed an overwhelming postsplenectomy infection (OPSI).

[Immunohistochemically detected activity of lysozyme in sarcoidosis granulomas--a parameter for the activity of the illness process?]. / Immunhistochemisch erfasste Aktivität des Lysozyms in den Sarkoidose-granulomen--ein Parameter für die Aktivität des Krankheitsprozesses?

In 30 patients with sarcoidosis we estimated immunohistochemically the activity of lysozyme in correlation to the activity of ACE in serum and found a positive correlation between these two parameters. We conclude, that the lysozyme content of sarcoidotic granulomas, estimated immunohistochemically, may be a useful morphological parameter of the activity of the disease, applicable on formol fixed and paraffin embedded bioptical material.

[Value of gallium-67 scintigraphy in the diagnosis and assessment of activity in sarcoidosis]. / Zum Stellenwert der Gallium-67-Szintigraphie in der Diagnostik und Aktivitätsbeurteilung der Sarkoidose.

Gallium-67 scan has an increased importance in the examination of activity in sarcoidosis. Compared with other markers of activity only gallium-67 can give an information about the localization of active granulomas in the body. It is profitable to distinguish between the accumulation of 67-gallium in the region of hilus and of lung parenchyma. SACE and gallium-67 scan complement each other. There is a good correlation between SACE and gallium-67 score, especially if there is an involvement of lung parenchyma.

[Value of bronchoalveolar lavage in assessing the activity of sarcoidosis]. / Stellenwert der bronchoalveolären Lavage (BAL) in der Aktivittsbeurteilung der Sarkoidose.

BAL was performed in different courses of sarcoidosis in order to evaluate the importance of this examination. We found a higher degree of lymphocytosis in Löfgren's syndrome and in relapses than in the others. Probably there is a direct connection between high intensity alveolitis and reduction of diffusing capacity. There could not be found any correlation to other markers of activity (lung function, SACE, 67-Gallium-Scan).

Are lectins of Viscum album interesting tools in lung diseases? A review of recent results.

The data presented provide evidence that lectins isolated from different sources such as Abrus and Ricinus seeds and Viscum leaves are structurally related proteins and are probably homologues. The lectins have overall similarities in physical, chemical and biological properties. These proteins appear to be immunologically closely related and possess a high degree of conservation in their primary structures, anticipating a role in fundamental pathways common to all plants. Methods for the preparation, purification and characterization of the Viscum album lectins and comparative crossreactions with closely related lectins of the "toxic lectin" group are summarized. The biological properties of Viscum album lectins, especially their reaction with phagocytes, (phagocytosis), basophil granulocytes (histamine release) and tumour cells (inhibition of tumour growth) are presented and compared with those obtained with an anti-tumoral preparation derived from Viscum album, ISCADOR.

Comparative study of kinin destroying activity of blood enzymes in respiratory sarcoidosis patients.

A total of 192 patients with active sarcoidosis of the stages I and II were examined. The state of the kinin system of the blood was studied on the basis of the values of the rate of kininogenesis and kinin-destroying activity of the blood. The rate of kininogenesis was assessed by the content of kininogen and prekallikrein in the blood and by kallikrein activity. Antikinin potential was measured by the values of the activity of carboxypeptidase N (KI), angiotensin-converting enzyme (ACE) and total kininase activity (TKA) of the blood. KI and ACE were estimated by the rate of hydrolysis of synthetic substrates, TKA was estimated biologically by inactivation of the native substrate bradykinin. In sarcoidosis patients activation of the kinin system is detected which at early stages of the disease is accompanied by stimulation and later by depression of TKA. No correlation is found between values of KI, ACE and TKA. Possible mechanisms of these disturbances detected are discussed.

[Serum angiotensin convertase activity and clinical course of sarcoidosis. Course studies in Löfgren syndrome]. / Serumangiotensinkonvertaseaktivität und klinischer Verlauf der Sarkoidose. Verlaufsuntersuchungen beim Löfgren-Syndrom.

Serial measurements of SACE were performed in 24 patients with Löfgren's syndrome during a period of 32,4 +/- 8,0 months. Initially only 21% (5 patients) had elevated SACE, but the percentage increased during the first weeks of disease reaching 46% (11 patients). After regression SACE activities were in the normal range. In two patients (8%) 18 and 21 months, respectively, after onset of disease pathologically elevated SACE values were measured. Clinically relapses were observed. Our observations demonstrate that serial measurements of SACE are suitable for controlling patients with Löfgren's syndrome, indicating relapses and change to chronic course of sarcoidosis.

[Possibilities for optimizing therapy with theophylline preparations. III. Ventilatory effect and pharmacokinetics of "new" Pulmophyllin]. / Optimierungsmöglichkeiten bei der Therapie mit Theophyllinpräparaten. III. Ventilatorische Wirkung und Pharmakokinetik von Pulmophyllin "neu".

Investigations comparing the preparations Pulmophylline "new", Pulmophylline and Aminophylline show that Pulmophylline "new" has a position between the two other drugs concerning the ventilatory effect and the pharmacokinetics. The effect of this preparation starts in a slower rate and lasts longer than that of Pulmophylline, the effect decreases in a quicker manner than that of Aminophylline. Replacement of the Ethoxytheophylline by the more efficient Theophylline seems to be the first step for the optimization of this drug-preparation. The diminished rate of side effects of Ethoxytheophylline is connected with an unfavourable pharmacokinetics and a smaller effect, as it is shown by investigations of other authors and by our own results.

[Possibilities for optimizing therapy with theophylline preparations. I. On the pharmacokinetics of theophylline preparations]. / Optimierungsmöglichkeiten bei der Therapie mit Theophyllinpräparaten. I. Zur Pharmakokinetik von Theophyllinpräparaten.

In the treatment of obstructive lung diseases theophylline is one of the most important drugs. But its therapeutic range is narrow, therefore attempts are made for an optimal therapy (dosage adjusted to the theophylline concentration in the serum, treatment with microcrystalline theophylline or retard preparations). Pharmacokinetic studies are undertaken with two theophylline formulations commercially available and the commonly used aminophylline to achieve the optimal therapeutic benefit. Regarding the results Aminophylline retard belongs to the formulations with diminished bioavailability and is therefore not satisfactorily qualified for an optimal treatment. On the other hand the development of a formulation of microcrystalline theophylline like Bronkodyl promises advantages for the long-continued treatment of obstructive lung diseases because of the smaller differences of the individual pharmacokinetic values from the median values.

[Possibilities for optimizing therapy with theophylline preparations. Clinical effectiveness and side effects of microcrystalline theophylline]. / Optimierungsmöglichkeiten bei der Therapie mit Theophyllinpräparaten. II. Klinische Wirksamkeit und Nebenwirkungen von mikrokristallinem Theophyllin.

The efficacy of microcrystalline theophylline is examined in patients with stabilized bronchial asthma. Beside the concentration of theophylline in the serum are estimated: the changes of subjective state of health, the consumption of beta2-stimulants, VC and FEV1. Although in 8 of 10 patients the theophylline concentration in the serum was below the therapeutical range for a considerable period of time, an improvement of the subjectively estimated state of health, a diminished consumption of beta2-stimulants and an increasing VC and FEV1 are evident after 6-7 days, also statistically confirmed. Proposals are suggested for using all possibilities for an improved therapy with theophylline.

[Serum angiotensin convertase activity and clinical course in sarcoidosis. Course studies in primary chronic sarcoidosis]. / Serumangiotensinkonvertaseaktivität und klinischer Verlauf der Sarkoidose. Verlaufsuntersuchungen bei der primär-chronischen Sarkoidose.

The relationship between the clinical course and SACE activity was analyzed by observing 133 patients with histologically confirmed sarcoidosis (74 stage I, 59 stage II) at intervals of 6.2 +/- 2.6 months during a period of 32.9 +/- 11.9 months. At the end of the follow-up period the patients were grouped into 4 categories concerning their chest x-ray changes: (a) improved (53); (b) unchanged (38); (c) progressive (9); (d) relapses (33). In group (a) initially elevated SACE always decreased, in (b) it often remained above the normal range; (c) and (d) always coincided with rising SACE. Out of 56 relapses observed 53 (95%) were associated with pathologically elevated SACE. There were significantly more relapses (35) in stage II compared to 21 in stage I sarcoidosis. SACE activities were measured in 109 patients placed on steroids. As a rule initially elevated SACE concentrations fell rapidly after initiation of steroid therapy. However SACE was found to be above the normal range after four weeks of therapy in 21 patients (19,3%), 5 in stage I and 16 in stage II, indicating an unfavourable course of the disease. Serial measurements of SACE are a very useful indicator of the activity of sarcoidosis and are helpful for monitoring the effects of corticosteroid therapy, having also some prognostic significance.

[Thin-layer chromatography of mycobacterial lipids and its importance for the differentiation and identification of mycobacteria]. / Dünschichtchromatographie der Lipidfraktionen von Mykobakterien und ihre Bedeutung für die Artdifferenzierung.

Methodical prerequisites to the differentiation of mycobacteria using thin-layer chromatography of their lipids described. The results of the identification of 112 strains belonging to 22 different species of Runyon's groups II, and III and IV are presented indicating that the lipid analysis permits the subdivision of mycobacteria into more species than with usual culture and biochemical methods. The technique even permits to differentiate between serotypes. In M. fortuitum strains several characteristic lipid patterns can be clearly distinguished, supporting the old opinion that different species are collected in the M. fortuitum-complex: M. giae, M. perigrinum, M. fortuitum, M, minetti. Three distinct lipid patterns were found in the M. avium strains investigated corresponding to the serotypes 1, 2, and 3. Using lipid analysis with two solvent systems it was possible to differentiate between 13 serotypes of M. intracellulare. In this way 9 species of Runyon's groups II could be identified, too. The serotypes Lunning, Gause and scrofulaceum were found to have characteristic lipid patterns permitting their differentiation by the technique described. Lipid analysis by means of thin-layer chromatography has been demonstrated to be a reliable inexpensive method, very useful for the identification and classification of mycobacteria not only for routine procedures but also for taxonomical problems and epidemiological purposes.

[Application of theophylline as an inhalant (author's transl)]. / Zur inhalativen Anwendung von Theophyllin.

The local tolerance and the functional efficacy of theophylline inhalant were investigated in 51 patients suffering from NSLD with reversible bronchospasm. In different doses aethophylline and aminophylline were nebulized using a jet or an ultrasonic nebulizer. FEV1 was controlled in fixed intervals and the patients were questioned about their subjective statements. At the end, a test with novodrin (isoprenaline)-spray was performed demonstrating the actual reversibility of the bronchospasm. In conclusion of our findings we can state: 1. Theophylline aerosols produced by a jet have neither an important subjective nor a functional efficacy. A prolongation of the inhalation time and the nebulized dose, respectively, has no better effects. 2. Aerosols of a 5% solution of theophylline produced by an ultrasonic nebulizer caused intensive local side-effects. Contrary to these aerosols those of a 2.5% solution were proved to be better tolerable and functionally effective, too, but only on patients with reversible bronchospasm. 3. Subjective statements and functional parameters were in a good accordance. 4. Serum levels of theophylline are not detectable with the method of SCHACK and WAXLER. The positive ventilatory effects after inhalation may suggest a topical action of the inhaled theophylline on the mucous membrane in the bronchial tree. 5. The increased values of FEV1 after the inhalation of theophylline are further increasing after the test with novodrin-spray. Therefore investigations of combination of theophylline and beta 2-sympathicomimetics in an aerosol seem usefully for optimization of the effect and for decreasing the side effects.

[The stability of drugs under the conditions of the ultrasonic thermo aerosol (author's transl)]. / Zur Stabilität von Arzneimitteln unter Bedingungen des Ultraschall-Thermo-Aerosols (2. Mitteilung).

Under conditions of the ultrasonic thermo aerosol the stability of selected drugs is investigated by estimation of their concentration and by spectrophotometric and thin-layer chromatographic analysis, respectively. Using an ultrasonic nebulizer USI 50 of the common production neither the spectrophotometric nor the thin-layer chromatographic analysis give any sign of destruction processes of the drugs used. As a rule the concentration of the drugs is lower in the condensed aerosol than in the stock solution. For clinical use this decrease in unimportant. Producing the stock solution of nystatin corresponding to the recommendations of the committee "Aerosols in the Medicine" of the Society of Bronchopneumonology and Tuberculosis of the GDR, only very low concentrations of nystatin can be detected in the aerosol. Producing the solution in another way--chosen by us--50% of the concentration in the stock solution can be fund in the aerosol. But this manner of production still needs the approval of the central expert evidence committee.