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T Beinert

Publications and source records attributed to T Beinert.

At least 19 recordsLinked to original sources

Aerosol bolus dispersion in healthy subjects.

Aerosol bolus dispersion is a physiological test of lungs, which uses monodisperse submicron particles to measure intrapulmonary convective gas mixing. In this study, aerosol bolus dispersion was measured in healthy subjects in order to assess reference values for possible clinical applications, to assess the reproducibility of these values, and to identify physical and physiological factors influencing aerosol bolus dispersion. Aerosol bolus dispersion was measured in 79 healthy subjects using 20 cm3 aerosol boluses consisting of monodisperse di-2-ethylhexyl sebacate (DEHS) particles. The reproducibility of parameters characterizing the width of the exhaled bolus was of the same order as that of parameters of the flow-volume curve (10%). Aerosol bolus dispersion was independent of the level of lung inflation, and the slope of the relationship between flow rate and dispersion was on average not significantly different from zero (range 100-700 cm3.s-1). Multiple linear regression showed that aerosol bolus dispersion increased with increasing total lung capacity of the subject. We conclude that differences in total lung capacity between individuals should be taken into account when using measures of aerosol bolus dispersion for possible clinical applications.

Administration, Inhalation

[Differentiation of solitary pulmonary coin lesions by high-resolution computerized tomography].

PURPOSE: The aim of this prospective study was not to describe individual morphological findings in benign and malignant solitary intrapulmonary nodules; it was instead to examine in a critical manner the indications for differentiation found in the literature in order to facilitate safe differential diagnosis of benign and malignant nodules. PATIENTS AND METHODS: A total of 64 solitary pulmonary nodules were examined with high-resolution computed tomography and correlated with histological findings. Only lesions that had been removed by surgery were used. No lesion was excluded on the grounds of size. RESULTS: Useful characteristics for the differentiation of benign from malignant pulmonary nodules were: diameter and density of the lesion, air inclusion, unsharp and dystelectatic margin, the presence of spicules, length of spicules, spicules extending to the visceral pleura, pleural tail sign and cirumscribed pleural thickening. CONCLUSION: For the differentiation of benign and malignant solitary pulmonary nodules meticulous assessment of the margin of the nodule is necessary. Using the criteria mentioned, a sensitivity of 85% and a specifity of 78% can be achieved for the identification of malignant pulmonary nodules. Since it was not possible to differentiate between benign and malignant nodules with certainty using imaging methods, the chance of patient survival could only be promoted by early surgery.

Adult

Hemostatic parameters in sepsis patients treated with anti-TNF alpha-monoclonal antibodies.

Tumor necrosis factor-alpha (TNF alpha) is a central mediator in the pathogenesis of sepsis. It also interferes with the hemostatic system and exerts and a net procoagulant effect. Since TNF alpha may contribute to thrombotic complications in sepsis patients, we determined markers of thrombin activation, parameters of the fibrinolytic system (D-dimer, tissue plasminogen activator antigen (tPA) urinary type plasminogen activator antigen (uPA), plasminogen activator inhibitor antigen (PAI-1) and von Willebrand factor antigen (vWF) in 30 patients with sepsis or septic shock. All patients were treated with standard therapy, but 14 patients were treated additionally with an anti-TNF alpha monoclonal antibody (MAK 195F); 16 patients served as historical controls. No significant effect of the antibody on the parameters of the hemostatic system could be determined. Our data speak against a modulation of coagulation or the fibrinolytic system by the monoclonal anti-TNF alpha antibody MAK 195F in this cohort of sepsis patients.

Adult

Bronchoalveolar lavage for evaluation and management of scleroderma disease of the lung.

Fibrosing alveolitis (FA) is a frequent and often fatal complication of systemic sclerosis (SSC). Alveolar inflammation has been recognized as a primary event in the pulmonary manifestation of SSC. To evaluate the significance of the alveolitis in SSC, we performed bronchoalveolar lavage (BAL) and correlated the generated data with changes in lung function over time. Seventy nine SSC patients with pulmonary involvement were followed for 56.8 +/- 3.1 wk (mean +/- SEM) with a repeat lung function test at the end of the follow-up period. During follow-up, 38 patients were treated with a systemic immunosuppressive regimen. For evaluation, patients were assigned to two groups according to whether their BAL cell differential was normal (inactive BAL) or abnormal (active BAL: i.e., polymorphonuclear leukocytes > 5% and/or lymphocytes > 15%). Active BAL was associated with more severe lung function impairment than was inactive BAL, and patients with active BAL deteriorated during follow-up if untreated. In contrast, treated patients with active BAL stabilized or improved. In summary, active alveolitis as characterized by BAL is associated with progressive pulmonary disease in SSC patients, and a significant positive effect of immunosuppressive therapy on the course of pulmonary disease was observed in patients with active BAL.

Bronchoalveolar Lavage

Characterization and quantification of alveolar monocyte-like cells in human chronic inflammatory lung disease.

This flow cytometric study was designed to identify, characterize and quantify alveolar monocyte-like cells in healthy volunteers and in patients with chronic inflammatory lung disease. Cells were obtained by bronchoalveolar lavage (BAL) from 19 patients with sarcoidosis, 29 with idiopathic pulmonary fibrosis, 10 with extrinsic allergic alveolitis, 19 with collagen vascular disease, and from 10 healthy volunteers. By taking advantage of the distinct electro-optical features of alveolar macrophages (AMs) and monocyte-like cells, the numbers of alveolar monocyte-like cells were counted, the cell dimensions calculated, and the densities of antigens on the surface of alveolar monocyte-like cells and AMs were compared. By using a panel of monoclonal antibodies detecting CD11b, CD14, CD16, and human leucocyte antigen-DR (HLA-DR), the immunophenotypes of these cells were selectively characterized. In the BAL fluid of patients with chronic inflammatory lung disease, significantly increased numbers of alveolar monocyte-like cells were detected that exhibited an immunophenotype intermediate between blood monocytes and mature AMs. Positive correlations were found between numbers of monocyte-like cells and expression of the monocyte-associated surface antigens CD11b and CD14 on total AMs; in contrast, an inverse relationship existed between monocyte numbers and expression of the macrophage-associated surface antigens CD16 and HLA-DR. When the patients were assigned to two groups according to the percentage of BAL monocyte-like cells being lower or higher than 13% (= mean value of the controls +2SD), it could be demonstrated that a high percentage of BAL monocyte-like cells was associated with significantly reduced lung function parameters. In summary, our flow cytometric data strongly support the view that considerable numbers of blood monocytes are recruited to the bronchoalveolar space in patients with chronic inflammatory lung disease.

Adult

Reproducibility of quantitative, spirometrically controlled CT.

Quantitative spirometrically controlled computed tomography (with 1-mm-thick sections) was performed twice (with a 5-minute break) in 24 adult patients with pulmonary disease to objectively evaluate parenchymal changes in the lung. Twelve measurements of attenuation were made on apical, carinal, and basal scans (right, left, total of each level, total right, total left, total of all three scans), obtained at 50% vital capacity. Since differences in measurements between the first and second examination were not significant, the method provides highly reproducible results.

Adult

Pathogenetic and clinical significance of fibroblast activation in scleroderma lung disease.

Fibrosing alveolitis (FA) is a major and often fatal complication of systemic sclerosis (SSC). The critical role of fibroblasts in the pathogenesis of FA has long been recognized. Characterization of fibroblast activation in the lungs may improve our understanding and the management of this disease. We analyzed bronchoalveolar lavage (BAL) fluid samples from 9 healthy controls and 43 patients with FA caused by lung involvement form SSC. The chemoattractant activity (CAA) of cultured human fibroblasts elicited by native BAL fluid was measured in Boyden chambers. In addition, procollagen III peptide was measured in BAL fluid as a marker of collagen synthesis. CAA (expressed as percentage of the chemoattractant effect of 0.25 ng/ml platelet-derived growth factor; PDGF) was elevated in the SSC patients compared with that of the controls (control: 12.6 +/- 4.0%; SSC: 68.8 +/- 15.2%; p < 0.01). A positive correlation was found between BAL total cell count and CAA (r = 0.60, p < 0.01). An inverse correlation existed between CAA and total lung capacity (r = -0.55, p < 0.05). The patients were followed up for 13.3 +/- 1.4 months (mean +/- SEM). Twenty-seven patients received immunosuppressive therapy, whereas 16 refused therapy. The patients were assigned to two groups according to their CAA being lower or higher than 36% of the PDGF response (= mean value of the controls + 2 SD).

Adult

Increased oxidation of extracellular glutathione by bronchoalveolar inflammatory cells in diffuse fibrosing alveolitis.

An unbalanced oxidative stress is thought to be an important element in the pathogenesis of diffuse fibrosing alveolitis (DFA). The purpose of our study was to investigate the role of reactive oxygen metabolites (ROMs) released from cultured bronchoalveolar inflammatory cells (BA-cells) on glutathione oxidation. We studied bronchoalveolar lavage samples from 10 healthy controls and from 20 patients with diffuse fibrosing alveolitis (all were nonsmokers). BA-cells obtained by bronchoalveolar lavage (BAL) were incubated with 50 microM of reduced glutathione (GSH). Oxidation of GSH to glutathione disulphide (GSSG) by BA-cell derived oxidants was detected as a decline of GSH in the supernatants. Total glutathione (GSHtot = GSH + 2 GSSG) and GSSG in the epithelial lining fluid (ELF), and methionine sulphoxide (Met(O)) content of BAL proteins were determined. In diffuse fibrosing alveolitis the oxidative activity of BA-cells was enhanced, GSHtot and GSH were decreased, whereas the GSSG:GSH ratio was increased. The oxidative activity of BA-cells correlated positively with the GSSG:GSH ratio, but not with the methionine sulphoxide content. The methionine sulphoxide content was elevated in diffuse fibrosing alveolitis and inversely correlated with GSHtot. The methionine sulphoxide content also correlated positively with the percentage of BAL neutrophils. We conclude that BA-cell-derived reactive oxygen species are capable of oxidizing extracellular GSH in vitro. The positive correlation between the BA-cell oxidative activity in vitro and GSSG:GSH ratio in ELF suggests that a similar oxidative effect on extracellular GSH may also occur in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Aerosol derived airway morphometry in healthy subjects.

Monodisperse aerosol particles can be used to non-invasively probe intrapulmonary airspace dimensions. In this study, the aerosol-derived airway morphometry technique was used to study airspace dimensions in 79 healthy subjects, in order to assess reference data for the future clinical application of aerosol-derived airway morphometry, and to investigate the effect of lung inflation, anthropometric, and lung function parameters on aerosol-derived airway morphometry. Intrapulmonary airspace dimensions were assessed by measuring the deposition of monodisperse, hydrophobic submicron aerosol particles during breathholding. Additionally, measurements of spirometric and body plethysmographic lung function were performed. Airspace dimensions were in good agreement with morphometric lung data. Airspace dimensions increased with increasing lung inflation. Interindividual variation of airspace dimensions was lowest in the lung periphery, at high levels of lung inflation, and when the volumetric lung depth was normalized to the end-inspiratory lung volume. Analysis of variance showed an increase of airspace dimensions with age. The results of this study indicate that aerosol-derived airway morphometry is dependent on the level of lung inflation and the age of the subject. These results suggest that in contrast to conventional lung function techniques, aerosol-derived airway morphometry might be a powerful tool for the detection of small changes in peripheral airway geometry.

Adult

Peripheral airspace dimensions in patients with COPD.

Monodisperse aerosol particles can be used to assess noninvasively intrapulmonary airspace dimensions. Since emphysematic changes in the peripheral lung are difficult to detect with most of the common lung function tests, aerosol-derived airway morphometry was used to assess the peripheral airspace dimensions (EAD800) in 25 patients with COPD and in 36 healthy volunteers. Spirometric and body plethysmographic measurements were performed in all patients. In ten patients, high-resolution CT-derived mean lung density (MLD) was additionally assessed. In healthy subjects, EAD800 was 0.39 +/- 0.05 mm. In patients, EAD800 was significantly increased (0.82 +/- 0.33 mm). In a subset of nine patients with severe alpha 1-antitrypsin deficiency and clinically severe emphysema, EAD800 was even larger (1.14 +/- 0.32 mm). In patients, EAD800 correlated with MLD (r = 0.82), diffusion capacity (DCO) (r = 0.78), and FEV1 (r = -0.75). Since MLD is considered a valid indicator for lung emphysema, the close correlation between EAD800 and MLD suggests that EAD800 reflects enlarged peripheral airspace dimensions in patients with emphysema.

Adolescent

[Immunopathogenesis of extrinsic allergic alveolitis].

Inhalation of a variety of organic dusts may cause the onset of hypersensitivity pneumonitis (HP) finally leading to irreversible pulmonary fibrosis in some individuals. So far, the pathogenesis of HP remains partially unclear. Besides patient-related factors this is probably attributable to the complex composition of the causative dusts: in addition to specific antigens that may induce type III and type IV reactions they contain a variety of additional components like particles and toxins with the ability to promote several antigen-independent reactions. During an acute episode of HP a marked alveolitis dominated by polymorphonuclear cells develops. As we showed these polymorphonuclear cells are in an activated state and may therefore cause pronounced damage in the lung interstitium. Based on these and other findings we believe that polymorphonuclear cells are of predominant importance for the pathogenesis of HP.

Acute Disease

[Quantitative computerized tomography of the lung--respiration controlled diagnosis of diffuse lung diseases].

STUDY OBJECTIVE: Computed tomography provides measurements of lung attenuation which reflect changes in the air to tissue ratio and can thereby be employed for diagnosis of diffuse lung disease. In this prospective study, we quantitatively analyzed lung density by high resolution computed tomography (HRCT) in 26 healthy volunteers, 15 patients with chronic obstructive pulmonary disease (COPD), and 15 patients with idiopathic lung fibrosis (IPF). The procedure was standardized by examination of 3 scans at the carina +/- 5 cm and by defining inflation levels by %VC using an on-line hand held spirometer. RESULTS: Performance of HRCT at 50% VC provides not only significant and distinguishable group data, but is the easiest to carry out for dyspneic patients. The mean lung density at 50% VC for healthy subjects was -820 +/- 4.2 (mean +/- SEM) Hounsfield units (HU). It was significantly lower (p < 0.01) in COPD patients (-865 +/- 9.2 HU), and considerably higher (-697 +/- 17.8 HU, p < 0.001) in the IPF group. At an inflation level of 20% VC, mean lung density values were similarly distributed, at significantly lower values relative to those at 50% VC, but the procedure was more difficult to perform for patients with dyspnea. In contrast, at 80% VC, lung density values for the COPD and control groups were not significantly different (p = 0.08). The sensitivity to detect COPD was improved by selecting HRCT values lower than -900 HU, which represent the part of the lung with an increased air/tissue ratio. For IPF patients an increase of lung density values above -699 HU was characteristic, indicating a decrease of the air/tissue relationship. CONCLUSION: From our data we propose to perform quantitative HRCT measurements at 50% VC. Diagnosis of diffuse lung disease can be further improved by consideration of specific CT -value intervals. Spirometrically controlled quantitative HRCT is a clinically meaningful tool for the assessment of diffuse parenchymal lung disease.

Adult

Detection of early lung impairment with aerosol bolus dispersion.

The broadening of inhaled aerosol boluses (aerosol bolus dispersion) during respiration provides a noninvasive measure of convective gas mixing in the lungs. In this study, the sensitivity and specificity of this technique for the diagnosis of early lung impairment due to cigarette smoking was evaluated. Two hundred and sixteen randomly selected subjects (126 smokers and 90 nonsmokers) were investigated with aerosol dispersion in comparison to conventional lung function tests. The cumulative cigarette consumption of the subjects was quantified by "pack-years" (PY). Smokers were classified into the following groups: 0 < PY < or = 10; 10 < PY < or = 20; 20 < PY < or = 30; and PY > 30. Forced expiratory volume in one second (FEV1), maximal expiratory flow at 25, 50 and 75% vital capacity (MEF25, MEF50 and MEF75) decreased significantly with increasing cigarette consumption. In comparison to nonsmokers, FEV1 was significantly reduced in smokers of 10 < PY < or = 30, and MEF75 was significantly reduced in smokers of PY > 20. Aerosol bolus dispersion increased with increasing PY. For all groups of smokers, even those with PY < 10, bolus dispersion was significantly increased in comparison to lifelong nonsmokers, indicating alterations in convective gas mixing in the lungs. Calculation of receiver operating characteristics for the lung function parameters under consideration showed that bolus dispersion has a higher sensitivity and specificity than conventional lung function parameters. Hence, the aerosol bolus dispersion test could be a promising epidemiological tool to study early abnormalities in intrapulmonary gas mixing due to environmental factors.

Adult

Colchicine antagonizes the activity of human smooth muscle cells cultivated from arteriosclerotic lesions after atherectomy.

AIM: Proliferative, migratory, and secretory activities of vascular smooth muscle cells are functional determinants of human atherosclerotic plaque and restenosis formation. The present study was designed to examine the effects of interfering with these processes using drugs. MATERIALS AND METHODS: For in-vitro studies of smooth muscle cell activity, arterial smooth muscle cells were cultivated from human plaque tissue excised from 22 coronary and peripheral lesions and treated with the antitubulin colchicine. Smooth muscle cell migratory activity was analyzed by a standardized semi-automatic video system. Transmission electron microscopy was used to examine cytoplasmic structures. RESULTS: Colchicine caused a concentration-dependent decrease in smooth muscle cell proliferative activity at a half-maximal inhibitory concentration (IC50) of 5 nmol/l. Smooth muscle cell migratory activity was reduced by colchicine in a concentration-dependent manner (IC50, 3 nmol/l). Concordantly, transmission electron microscopy revealed severe disorganization of cytoplasmic structures, especially of organelles, indicating metabolic activation. CONCLUSIONS: In-vitro studies with human smooth muscle cells from arteriosclerotic lesions suggest that the antitubulin principle may be useful in producing anti-arteriosclerotic effects, since a pronounced antagonization of smooth muscle cell proliferative, migratory, and secretory processes, indirectly inferred from ultrastructural analysis, was demonstrated with low concentrations of colchicine.

Actin Cytoskeleton

Fibroblast chemotactic response elicited by native bronchoalveolar lavage fluid from patients with fibrosing alveolitis.

BACKGROUND: In fibrosing alveolitis activation of lung fibroblasts is the decisive event in the pathogenetic sequence leading to pulmonary fibrosis. Fibroblast stimulating activity was measured in bronchoalveolar lavage (BAL) fluid to assess its relationship to the activity of fibrosing alveolitis. METHODS: Nine control subjects and 40 patients with fibrosing alveolitis caused by idiopathic pulmonary fibrosis (n = 22) or pulmonary involvement in systemic sclerosis (n = 18) were studied. All patients were followed up by lung function testing for a minimum of six months (mean (SE) 13.3 (1.4) months). Twenty five patients received immunosuppressive therapy and 15 refused. At the beginning of follow up BAL was performed and, as a possible indicator of fibroblast stimulating mediators within the lungs, chemotactic migration of cultured human fibroblasts elicited by native BAL fluid was measured in Boyden-type chambers and expressed as a percentage of the chemoattractant effect of 25 ng/ml platelet derived growth factor. The procollagen III peptide level in BAL fluid served as a marker for collagen synthesis. RESULTS: Chemoattractant activity was elevated in the patients with idiopathic pulmonary fibrosis and systemic sclerosis compared with the control group, (mean (SE) 56.4% (8.5%)) and 72.3% (16.3%) v 12.6% (4.0%). Chemoattractant activity was inversely correlated with total lung capacity (TLC) (r = -0.45) and with vital capacity (VC) (r = -0.33). Procollagen III peptide concentrations in BAL fluid and chemoattractant activity were not significantly correlated. For further evaluation chemoattractant activity of 36% (mean value of controls +2 SD) was used to separate normal (< 36%) from elevated (> or = 36%) activity. At the end of follow up, untreated patients with high chemoattractant activity (> or = 36%) showed a significant reduction of VC, TLC, and exercise arterial oxygen tension (PaO2) and a small decrease in carbon monoxide transfer factor (TLCO), whereas a significant improvement in VC, TLC, and TLCO and a small increase of exercise PaO2 occurred in treated patients with high chemoattractant activity. Patients with low chemoattractant activity (< 36%) showed no consistent change in lung function measurements, irrespective of treatment. In contrast, lung function results and differential cell counts in BAL fluid failed to identify progressive disease. CONCLUSIONS: In patients with fibrosing alveolitis the chemoattractant activity of BAL fluid seems to be an independent indicator of lung fibroblast stimulating activity providing relevant information about disease activity, and may help to improve the clinical management of these patients.

Adult

Activation of blood neutrophils in acute episodes of farmer's lung.

Farmer's lung often presents clinically as recurring acute episodes several hours after exposure to moldy hay. During these episodes the blood neutrophil count increases. Because activated neutrophils release toxic oxygen metabolites and proteinases, we hypothesized that the pulmonary reaction in farmer's lung may be induced by the secretory products of activated neutrophils. To evaluate this concept, we quantified the respiratory burst of separated blood neutrophils from patients with farmer's lung (n = 12) during standardized exposure tests with moldy hay. The respiratory burst of these cells was evaluated by measuring zymosan-stimulated and lucigenin-amplified chemiluminescence (CL). Asymptomatic farmers (n = 12) and normal volunteers with no prior exposure to moldy hay (n = 15) were used as control subjects. As expected, following exposure in the group of patients with farmer's lung, striking changes in VC, TLCO, and PaO2 were observed, whereas there were only minor changes in these parameters in both control groups. In all three groups a considerable increase in the blood leukocyte count was observed. The CL response of the blood neutrophils from patients with farmer's lung 6 h after exposure was significantly higher than before or 1 h after exposure (p < 0.05 for both comparisons), whereas there was no significant change in the CL response in either control group during the observation period. Our results indicate that antigen inhalation induces an increase in the number of circulating neutrophils in patients and controls, but in patients with an acute episode of farmer's lung the neutrophils are primed for an enhanced respiratory burst and may thereby damage the lung.

Acridines

[Cellularity and ultrastructural characteristics of human atherectomy specimens: comparison between restenosis and primary stenotic tissue of coronary and peripheral lesions].

Restenosis in patients treated by angioplasty is clinically and angiographically defined. The question remains to which extent each restenotic lesion can be attributed to residual plaque material and/or neointimal tissue formation post primary intervention. In an effort to reveal distinct anatomical characteristics which may allow conclusions to pathogenetic mechanisms involved in restenosis, histopathologic and electron microscopic examinations of human restenotic tissue were performed. To compare tissue samples from clinically restenotic lesions with those from untreated primary lesions for cell number and ultrastructural characteristics, a total of 64 percutaneously excised tissue specimens from coronary (n = 9) and femoral lesions (n = 18) of 27 patients treated by directional atherectomy were analyzed. Semiquantitative assessment of plaque slices for cell number (12 fields of view/lesion; magnification x500) revealed a spectrum of 11.7 to 35.3 cell nuclei/field of view (C/F) for clinical restenoses (n = 10) and of 0.9 to 28.2 C/F for primary lesions (n = 17). When comparing tissue specimens from restenotic origin with those of native lesions, there was a highly significant (p < 0.001) difference in cell number (ave: 22.2 +/- 7.1 versus 8.6 +/- 7.9 C/F; x +/- SD). Hypercellularity (mean cell density defined with > 20 C/F) was observed in 6/10 restenoses, hypocellularity (< 10 C/F) in 0/10 restenoses. For primary lesions, hypocellularity was found in 10/17 lesions, but hypercellularity in 2/17 lesions. Ultrastructural analysis of hypocellular lesions by transmission electron microscopy revealed large extracellular matrix fields with infrequently embedded smooth muscle cells (SMCs). These cells were characterized by a microfilament-rich intermediate phenotype, thereby indicating decreased metabolic activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[Esophageal injuries caused by a swallowed foreign body. A life-threatening condition].

Report on a case in which a protracted foreign body in the esophagus (chicken bone) had perforated the wall in the cervical area and had led to premonitory bleeding and finally to massive hemorrhage. Neither before had further symptoms occurred regarding to the esophageal perforation such as mediastinitis or subcutaneous emphysema nor had the attempt been successful to picture the transmural lesion. With an appropriate history of the foreign body and relapsing gastro-intestinal hemorrhage--despite a negative endoscopic result--an esophageal lesion must be highly suspected as causing bleeding. The immediate thoracotomy for wound repair is strongly indicated.

Aged