[The Pathogenesis of Pulmonary Emphysema - Laennec was right!] / Die Pathophysiologie des Lungenemphysems ­ Laënnec (1781­1826) hatte Recht!

Pulmonary emphysema is characterised by irreversible destruction and enlargement of alveolar structure distal to terminal bronchioles. Small conducting airways < 2 mm in diameter are the major site of chronic airway inflammation and obstruction in COPD patients. 80 - 90 % of the last generation of small conducting airways, the terminal bronchioles, are destroyed in patients with very severe COPD. Recent data showing, that small airways disease is also a pathological feature in patients with COPD GOLD stage 1 and 2. Although 40 % of terminal and 60 % of transitional bronchioles were destroyed, there was no sign for emphysema. Only a significant loss of terminal and respiratory bronchioles seems to be able to induce pulmonary emphysema and respiratory symptoms.

[Apnea Detection by Means of Respiratory Sound Recordings and Polysomnography - A Comparative Study]. / Ein Vergleich der Apnoeerkennung bei Patienten mit obstruktiver Schlafapnoe (OSA) anhand von Atemgeräuschaufzeichnungen und Polysomnografie.

Introduction In this study, recognition of apnoeas by means of polysomnography (PSG) and nocturnal respiratory sound recordings in patients with obstructive sleep apnoea (OSA) was analyzed and compared. Methods In 45 patients with OSA requiring treatment (AHI > 15/h), concomitant polysomnographic recordings and long term respiratory sound recordings by means of LEOSound were performed. Patients' average age was 58 ±â€Š12 years (mean ± standard deviation), average BMI was 33 ±â€Š7 kg/m2. Audio-visual apnoea detection by LEOSound was compared to polysomnographic apnoea detection. Increased artifact rate due to dislocation of microphones led to rejection of 11 out of 45 recordings for detailed analysis. Results Comparison of apnea detection by audio-visual analysis and polysomnography yielded a median of 164 apneas for LEOSound recordings and 158 apneas for PSG. Median apnoea index (AI) was calculated to be 20/h for respiratory sounds recording and 21/h for PSG. The correlation of apnea indices from acoustic long term registration and PSG was 0.939 (p < 0.001). Discussion Acoustic long term registration of primary and secondary respiratory sounds is also capable to recognize apnoeas. Exact differentiation between apnoeas and hypopnoeas is only possible in a limited fashion.

[Normal and Adventitious Breath Sounds]. / Atemgeräusche und Atem-Nebengeräusche.

Auscultation of the lung is an inexpensive, noninvasive and easy-to-perform tool. It is an important part of the physical examination and is help ful to distinguish physiological respiratory sounds from pathophysiological events. Computerized lung sound analysis is a powerful tool for optimizing and quantifying electronic auscultation based on the specific lung sound spectral characteristics. The automatic analysis of respiratory sounds assumes that physiological and pathological sounds are reliably analyzed based on special algorithms. The development of automated long-term lungsound monitors enables objective assessment of different respiratory symptoms.

[What is Important for Diagnosis and Therapy Follow-up in Chronic Cough?]. / Was ist für die Diagnostik und Therapieverlaufskontrolle von chronischem Husten wichtig?

Within the last years there has been significant progress in the field of chronic cough. So far, the analysis and evaluation of chronic cough was done mainly on the basis of subjective methods such as manual counts of cough events, questionnaires and diaries. Testing cough hypersensitivity and monitoring 24 h cough represent objective criteria. Validated questionnaires on cough frequency and quality of life represent the impact of chronic cough. Cough frequency monitoring, the preferred tool to objectively assess cough, should be used as primary end-point in clinical trials. It will also be possible to discriminate between productive and non-productive cough. The relationship with subjective measures of cough is weak. In the future, cough and its therapy should therefore be assessed with a combination of subjective and objective tools.

[Determination of Hypercapnic Ventilatory Response in COPD Patients]. / Bestimmung der hyperkapnischen Atemantwort bei Patienten mit COPD.

Previous studies showed a reduced hypercapnic ventilatory response (HCVR) in patients with COPD. However, the association between HCVR and COPD GOLD stages is unknown. The measurement of the HCVR is a methodological option to test the function of the breathing feedback cycle. The aim of this feasibility study was to present a new automatic and standardized device (MATAM) to measure and interpret the HCVR. This device determines if exposure to CO2 leads to an adequate increase in breathing frequency and tidal volume. Recordings are performed in a closed system that allows selective changes of each gas component. The minute ventilation (AMV) under hypercapnic stimulation is plotted against the end-tidal CO2 (ETCO2). The HCVR is defined as the linear regression line.28 patients (18 male; 10 female) with COPD GOLD stages 0 to IV were studied. The patients had a mean age of 57 ±â€Š14 (standard deviation) years and a mean BMI of 32 ±â€Š9 kg/m(2). We could show that the HCVR measurement in patients with COPD using MATAM was feasible. Patients with more severe COPD stages had a significantly more reduced HCVR. This could be an indication of reduced chemosensitivity due to a worsening of blood values (pH and pCO2) which affect the central chemoreceptors in the long term. Further studies will be needed to validate the MATAM device for healthy individuals and other patient groups, and for the investigation of standard values.

[LEOSound, an innovative procedure for acoustic long-term monitoring of asthma symptoms (wheezing and coughing) in children and adults]. / LEOSound - Ein innovatives Verfahren zum akustischen Langzeit-Monitoring von asthmatischen Symptomen (Wheezing und Husten) bei Kindern und Erwachsenen.

Particularly in young children the diagnosis of asthma is difficult and mostly based on clinical symptoms like wheezing, cough and dyspnea. Children with nocturnal wheezing often suffer from a low quality of sleep and impaired sense of well-being during the day. Physicians recommend that parents record the frequency of asthma attacks or symptoms to help manage their children's disease. The lack of an appropriate method for standardized and objective monitoring makes asthma management difficult. The aim of this paper is to present a new method for automated wheeze and cough detection and analysis. The mobile LEOSound recording and analysing system described here should help improve diagnosis and monitoring of asthma symptoms in children.

[Telemonitoring in patients with COPD and acute exacerbations]. / Die akute Exazerbation der COPD.

A major problem associated with COPD is exacerbation. Symptoms include increased shortness of breathing, coughing, wheezing and sputum production. The frequency and severity of exacerbations are associated with a higher mortality risk. Early recognition and treatment have been shown to reduce severity of exacerbations, consecutive morbidity and hospital admissions. Telemonitoring of (nocturnal) lungsounds, oxygen saturation and frequency of breathing may offer the opportunity to detect symptoms of exacerbations very early. Therefore further research is needed to clarify precisely the role of telemonitoring in patients with COPD and exacerbations.

Formation of cytosine arabinoside-5'-triphosphate in different cultured lymphoblastic leukaemic cells with reference to their drug sensitivity.

The accumulation of intracellular cytosine arabinoside-5'-triphosphate (Ara-CTP) is determined in five lymphoblastic cell lines: Molt 4, H9 and three newly established cell lines from paediatric patients, KFB-1, KFB-2, KFT-1. The cell lines KFB-1 and KFB-2 are B-lymphoblastic (B-ALL), the others are T-lymphoblastic leukaemic cells (T-ALL). The Ara-CTP levels were compared with the sensitivity of the cells to Ara-C. The cells were incubated at different concentrations (100 nM-100 microM) of Ara-C for 4 h or incubated for variable times (30 min-11 h) at 0.1, 1 and 10 microM Ara-C to form Ara-CTP. The Ara-CTP-concentrations were measured by high pressure liquid chromatography (HPLC). To determine the sensitivity of the cells to Ara-C, the MTT colorimetric-assay was used. The studies indicate that different B- and T-lymphoblastic leukaemia cell lines accumulate Ara-CTP to a markedly different extent. Ara-CTP plateau levels and sensitivity of the cells to Ara-C correlated well in four of the five cells lines studied.

Decreased anti-human immunodeficiency virus type-1 activities of 2',3'-dideoxynucleoside analogs in MOLT-4 cell sublines resistant to 2',3'-dideoxynucleoside analogs.

Human T-lymphoid MOLT-4 cells were grown continuously for more than 1 year in medium containing either 3'-azido-2',3'-dideoxythymidine (AZT), 2',3'-dideoxyinosine (ddI) or 2',3'-dideoxycytidine (ddC) at concentrations similar to peak plasma levels found in clinical trials in patients with AIDS. To test antiviral activities of the nucleoside analogs against HIV-1 in the cell sublines designated MOLT-4r-AZT, MOLT-4r-ddI and MOLT-4r-ddC, the number of infected cells, p24 HIV-1 antigen in culture medium and syncytium formation of infected cultures were determined. The results showed that anti-HIV-1 activities of AZT, ddI and ddC were significantly decreased in the resistant MOLT-4 cell sublines grown continuously with the respective nucleoside analog, probably due to the development of cell populations resistant to the drugs.

In vitro differentiation of human neuroblastoma cells induced by sodium phenylacetate.

Sodium phenylacetate (NaPA) at concentrations ranging from 2 to 6 mM stimulated morphological differentiation of two human neuroblastoma cell lines IMR-32 and UKF-NB-3. These concentrations inhibited growth and DNA synthesis of the cells in a dose dependent manner without significant effect on cell viability. The differentiated cells showed pseudoganglia formation and extension of cellular processes. The morphological differentiation in both cell lines was accompanied by decreased expression of N-myc oncoprotein. These results suggest that NaPA at concentrations, which have been achieved in humans with no significant adverse effects, promotes differentiation of cultured human neuroblastoma cells in association with the reduced expression of the malignant phenotype.

Aphidicolin selectively kills neuroblastoma cells in vitro.

Aphidicolin is a tetracyclic diterpene antibiotic which is known to inhibit the growth of eucaryotic cells by reversible binding to DNA polymerase alpha without significant effect on cell viability in most common human cell lines. We observed that aphidicolin at a concentration of 5 x 10(-7) M kills all cells of four human neuroblastoma cell lines. In contrast, viability of normal human embryonal cells and of human continuous cell lines including HeLa, H9, A549 and Caco-2 was influenced only moderately by aphidicolin. In addition, neuroblastoma cells were killed after treatment with 5 x 10(-7) M aphidicolin in cocultures with normal embryonal cells which continued to proliferate after removal of aphidicolin. These results show that aphidicolin provides an agent which selectively kills neuroblastoma cells in vitro.

Plasma exchange for removal of anti-A and anti-B group antibodies in AB0 major-incompatible bone marrow transplantation.

Between 1980-1986 seven patients underwent AB0-major incompatible bone marrow transplantation. Incompatible anti-A and anti-B antibodies could be decreased by the plasma exchange from titers 8-256 down to 0-8. Our practice combined with additional depletion of erythrocytes from marrow allowed to transplant all patients successfully, however, one patient demonstrated an acute haemolytic reaction during infusion of marrow. Plasma exchange was fairly well tolerated, however, 4 patients developed slight urticarial reactions. Both thrombocytopenic patients overcompensated the platelet loss caused by the exchange.

[Valuation of autologous bone marrow transplantation in radio- and chemotherapy of malignant tumours (author's transl)]. / Zur Wertigkeit der Auto-Human-Knoehenmarktransplantation bei der Strahlen- und Chemotherapie maligner Tumoren.

This paper discusses the prerequisites of bone marrow autotransplantation performed as part of cancer therapy, the emphasis being on the condition of the patient, the facilities available to the institution for the treatment of cancer patients, the biology of the tumour, and the present possibilities of carrying out what is called superdose cancer therapy. The practical performance of a bone marrow autograft is based upon the withdrawal of bone marrow with indefinite vital stem cell preservation by deep cooling at a time when the tumour has not yet led to bone marrow metastasizing. The conserved bone marrow is used, in subsequent radiological and/or cytostatic superdose therapy, as a reserve in the case of extreme damage to hematopoiesis. The discussion of the current status of this method and the prospects for its general use reflects the whole spectrum of the problems associated with the most favorable procedure to be used, the type of superdose therapy to be employed, the time of regrafting, and the accurate assessment of the results obtained.