[Enzyme histochemical and immunopathological findings in intrathoracic lymph node sarcoidosis (author's transl)]. / Enzymhistochemische und immunpathologische Befunde bei intrathorakaler Lymphknotensarkoidose.

Comparative investigations on the value of modern morphological methods (enzyme-histochemistry, immunopathology) are carried out in 40 patients with intrathoracic lymph node sarcoidosis. These studies show that by means of enzyme-histochemical and immunopathological methods additional knowledge is got in comparison with routine histology, concerning especially the floridity of the disease, humoral immunity and collagen synthesis. This information is an important factor for both the clinical assessment of the process and an effective therapy.

[Leucocyte histamine release assay and its use in the diagnosis of atopic extrinsic asthma (author's transl)]. / Der Histaminfreisetzungstest und seine Einsatzmöglichkeiten.

Quantitative estimation of histamine, the most important mediator of immedite hypersensitivity reaction, is described. Leucocytes, isolated from the peripheral blood of patients suspected to suffer from atopic extrinsic asthma are washed and incubated with the antigens to be tested. The amount of histamine released is measured by a fluorometric method. The leucocyte histamine release assay is compared with several commonly used methods for the diagnosis of an atopic sensitisation (cutaneous skin test, inhalative provocation test, serum IgE concentration). The usefulness of the application of this relevant and reliable in vitro test especially in patients with advanced obstruction of the respiratory tract or with superelevated rate of sensitisation, in infants and in any acute or subacute state of disease is discussed.

[Diagnostic value of serum angiotensin converting enzyme activity in sarcoidosis (author's transl)]. / Diagnostischer Wert der Aktivitätsbestimmung des Angiotensin-Umwandlungsenzyms (angiotensin converting enzyme) bei der Sarkoidose.

Serum angiotensin converting enzyme activity was measured in 60 blood donors and 100 patients with sarcoidosis histologically confirmed using a spectrophotometric assay with hippurylhistidylleucine as substrate. Sex related differences in the enzyme activity could not be observed. ACE was found to be markedly raised above the normal range (the mean of the control subjects plus 2 standard deviations) in 53 (58.2%) out of 91 untreated patients. The distribution of the enzyme activities was significantly different as compared to the control group. Nine patients with sarcoidosis receiving steroids had a mean level within the normal range. ACE level in stage II group tended to be more elevated compared to stage I, but this difference was not significant. Extrapulmonary sarcoidosis (with and without pulmonary involvement) appeared to be associated with especially high ACE activities. The distribution of the enzyme activities within the groups of untreated patients failed to reveal statistically significant differences. Therefore it was not possible to determine the clinical state of the disease and to discriminate between the stages (I and II) of sarcoidosis by the measurement of serum ACE level. However as the results suggest serum ACE assays can be a useful aid in diagnosis of sarcoidosis. Further investigations may demonstrate the value of this in vitro method for the clinical management of the disease including prognosis and therapeutic effects.

[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.

[Detection of niacin with the paper strip test (author's transl)]. / Nachweis von Niazin mit dem Papierstreifentest

Preparation and application of reagent impregnated paper strips for the detection of niacin are described. 170 cultures of mycobacteria were tested with the paper strips and by the conventional aniline-cyanogen bromide method. The results obtained demonstrate a high degree of correlation. Because of its advantages in comparison to the aniline-cyanogen bromide method-the toxic cyanogen bromide is omitted; malachite green does not disturb the reaction-the paper strip test can be recommended without reservation for the detection of niacin in microbiological laboratories.

[Theophylline therapy--foundations and possibilities (author's transl)]. / Tehophyllinbehandlung--Grundlagen und Möglichkeiten.

Theophylline is one of the best drugs for the therapy of bronchial asthma. There is no great difference between therapeutic and toxic concentration. Several endogenous and exogenous factors influence the pharmacokinetics. Changes in a short time are possible in situations complicated by further diseases. Estimations of the theophylline concentration in plasma or serum are necessary for optimizing therapy. The frequency is depending on the individual situation.

[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.

[Behaviour of drugs under conditions of ultrasonic thermo aerosols (author's transl)]. / Zum Verhalten von Arzneimitteln unter Bedingungen des Ultraschall- Thermo-Aerosols.

The behaviour os histamine, acetylcholine, mucosolvine, panthenol, prednisolute and dexamethasone is investigated under conditions of thermoaerosol in the USI 50. The concentration of the drug is estimated in the original solution, in the aerosol and in the solution remaining in the nebulizer by means of specific chemical methods. The concentration in the aerosol is nearly unchanged in the case of acetylcholine, panthenol and dexamethasone. In the case of histamine there is only an insignificant decrease. Using prednisolute and dexamethasone the concentration amounts to 86%. Generally the concentration of the solution in the nebulizer increases. Decompositions or alterations of the drugs are not to be seen spectrophotometrically and by means of thin layer chromatography, nor is the pH-value changed. Signs for reactions or interferences with the nebulizer are to be observed in some cases. Therefore regular controls are necessary. In all cases of changing parts of the apparatus the needed material is to be tested concerning its indifference against the drugs used under conditions of thermoaerosol.

[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.

[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.

The value of modern morphological methods (histochemistry, immunopathology) in sarcoidosis.

Correlative studies concerning the value of modern of morphological methods in correlation to the clinical picture were undertaken in patients with sarcoidosis. The investigations comprised immunopathological and histochemical studies of mediastinal lymph nodes, normal lymph nodes and lymphnodes by inflammatory lung diseases. The metabolic state of the granulomas in sarcoidosis is expressed by enzymehistochemical investigations and shows a strong activity of enzymes of the pentose cycle, cancer cycle, anaerobic glycolysis, respiratory chain and of hydrolytic enzymes. Of special interest is the activity of aminopeptidase in the granulomas, found only positive in progressive stage of the disease. With the aid of some hydrolases (acid phosphatase, nonspecific esterase) information is given about phagocytotic activity in granulomas. Antibody formation (anti-human-IgG, -IgA and -IgM) is visible in fresh cases around granulomas in the cytoplasms of large lymphoid cells, in some cases also in the walls of vessels. With longer duration of the disease immunoglobulins were found extracellulary first in little focal areas and later as a dense homogen material around the granulomas. In long existing cases only a weak or negative fluorescence was observed in this material, expressed by light microscopy as hyaline transformation. The value of this methods is given in additional information concerning the metabolic activity (especially phagozytosis) and immunological state (antibody formation) of the disease as an important factor for a well-timed and effective therapy.

[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.

[Efficacy of theophylline aerosols in obstructive lung diseases (author's transl)]. / Wirkung von Theophyllin-Aerosolen bei obstruktiven Erkrankungen der Atemwege.

We investigated aethophylline and aminophylline aerosols using a jet or an ultrasonic nebulizer in 51 patients suffering from NSLD with reversible bronchospasm. FEV1 was controlled in fixed intervals, and the patients were questioned about their subjective statements. A bronchospasmolytic test with isoprenaline spray at the end was performed to demonstrate the actual reversibility of the bronchospasm. Only theophylline aerosols produced by a ultrasonic nebulizer had a subjective and a functional efficacy. Theophylline aerosols of a 2.5% solution were proved to be better than aerosols of a 5% solution, but in comparison with the used sympathicomimetic drug isoprenaline spray, they were less effective. There was a good correlation with the subjective statements of the patients concerning the clinical effects. The concentration of the therapeutic aerosol seemed to be an important factor for the local tolerance and the ventilatory effects, measurable serum levels of theophylline could not be found. Therefore, the topical action of theophylline is considered to be responsible for the clinical effect.

[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.

[Differentiation and identification of mycobacteria by means of thin-layer chromatography of their lipids. I. Application for the classification of rapidly growing mycobacteria (author's transl)]. / Zur Differenzierung und Identifizierung von Mykobakterien mit Hilfe der Lipid-Dünnschichtchromatographie

Experiences with the analysis of mycobacterial lipids by means of thin-layer chromatography are described. The influence of different media used for the cultivation of the strains, the age of cultures and heating of the bacteria on the lipid patterns was investigated. 25 strains of rapid growers belonging to various species were examined by a definite procedure. As the results indicate the lipid analysis allows a differentiation of more species than with the usual culture and enzymatic methods. The conclusions especially for taxonomic problems are discussed.

[Differentiation and identification of mycobacteria by means of thin-layer chromatography of their lipids. III. Application for the classification of scotochromogenic mycobacteria (author's transl)]. / Zur Differenzierung und Identifizierung von Mykobakterien mit Hilfe der Lipid-Dünnschichtchromatographie II. Anwendung bei skotochromogenen Mykobakterien

Experiences with the lipid analysis of scotochromogenic mycobacteria by means of thin-layer chromatography are described. Out of 18 strains of M. scrofulaceum 11 belong to the serotypes Lunning, Gause, and Scrofulaceum. The similarity of the lipid patterns of the M. scrofulaceum strains to the ones of the M. avium-M. intracellulare group supports the contention of some authors that these species are closely related. Lipid analysis of further species of RUNYON's group II (M. xenopi, M. gordonae, M. kansasii var. aurantiacum, M. flavescens, M. acapulcensis, M. paraffinicum, M. thermoresistibile) gives the evidence that a differentiation by means of thin-layer separation is possible in these cases, too. The answer to the question whether these lipid patterns are species specific or not can only be given when a large number of strains of every species will be investigated.

[Differentiation and identification of mycobacteria by means of thin-layer chromatography of their lipids. II. Application for the classification of slowly growing mycobacteria: M. avium and M. intracellulare (author's transl)]. / Zur Differenzierung und Identifizierung von Mykobakterien mit Hilfe der Lipid-Dünnschichtchromatographie. II. Anwendung bei langsam wachsenden Mykobakterien: M. avium und M. intracellulare

Experiences with the thin-layer chromatography of mycobacterial lipids for the differentiation of the species M. avium and M. intracellulare are described. Details of the procedure used have been published in a recent paper. The 61 strains investigated belong to 16 different serotypes. Twenty of the 21 strains of M. avium present three distinct lipid patterns corresponding to the serotypes 1, 2 and 3. One strain had an aberrant lipid pattern suggesting that serotyping was at fault. The results obtained with 40 M. intracellulare strains of the serotypes III, IV, VI, VII, Davis, Watson, Howell, Chance, Boone, Yandle, Wilson, Altman and Arnold show that a differentiation by thin-layer chromatography of their lipids--using two different developing solvents--is possible. In allbut one case there was a complete correspondence between classification by lipid analysis and the results of serological typing. The distinction between M. avium and M intracellulare on the basis of species specific lipid patterns is not possible. This supports the conclusion that M. avium and M. intracellulare appear to be the same species having a number of distinctive serotypes.

[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.