Biomedical subjects

T Beinert

Publications and source records attributed to T Beinert.

51 records · Page 3Linked to original sources

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

[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↗

PubMed1995

[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↗

PubMed1994

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↗

PubMed1994

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↗

PubMed1993

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↗

PubMed1993

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↗

PubMed1993

[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↗

PubMed1986

[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↗

PubMedDate not supplied

Standardized quantitative high resolution CT in lung diseases.

Twenty-seven patients with diffuse fibrosing alveolitis (DFA), 27 patients with granulomatous lung disease (GLD), 3 patients with homozygous alpha 1-proteinase inhibitor deficiency (alpha 1-PID), and 6 healthy volunteers (C) were studied using thin section high resolution CT (HRCT) at 50% of actual vital capacity (VC), determined and controlled spirometrically during each exposure. A fast contour tracing algorithm was used to isolate the lung parenchyma followed by a quantitative histogram analysis of the frequencies of CT values. Mean CT values enabled us to discriminate significantly between the groups of C and alpha 1-PID. Significant differences were found between the groups of GLD and DFA versus C by applying suitably selected intervals of CT values. Moreover, if the patients were assigned to four different groups according to their lung function results (normal, restrictive, obstructive, restrictive and obstructive), again significant differences existed with respect to defined intervals of CT values. Mean CT values showed a significant negative correlation with lung function tests representative of lung parenchymal disease, i.e., VC, diffusing capacity, and exercise PaO2. Moreover, CT values ranging from -899 to -800 HU correlated positively, whereas CT value frequencies above -699 HU correlated inversely with these same lung function parameters. These results indicated that certain intervals of CT values do reflect functionally different abnormalities of lung parenchyma. It is concluded that an analysis of frequencies of CT values determined by spirometrically standardized HRCT provides objective quantitative data that reflect changes of pulmonary structure corresponding to lung function impairments. Thus, spirometrically standardized HRCT may be helpful for evaluating and staging patients with diffuse pulmonary disease.

Adult↗

PubMedDate not supplied

Spirometrically controlled quantitative CT for assessing diffuse parenchymal lung disease.

OBJECTIVE: Assessment of lung attenuation by CT reflects changes in the air-to-tissue ratio of the lung. We have analyzed the interdependence of intrathoracic gas volume, lung morphology, and functional disorder by high resolution CT (HRCT) to assess quantitative disease threshold in obstructive and restrictive diffuse lung disease. MATERIALS AND METHODS: Pulmonary HRCT was performed on 24 healthy volunteers, 11 patients with chronic obstructive pulmonary disease (COPD), and 16 patients with idiopathic lung fibrosis (IPF). HRCT measurement was standardized by taking three scans at the carina +/- 5 cm and by defining inspiration levels by percent vital capacity (VC) via spirometrically gating to the scanner. RESULTS: The mean lung density at 50% VC (DL50) for healthy subjects was -819 +/- 3.8 (mean +/- SEM) HU. In contrast, COPD DL50 was lower, averaging -861 +/- 6.4 HU, and the IPF DL50 was considerably higher (-731 +/- 17.7 HU), both significantly different (p < 0.001) compared with the control group. The accuracy of quantitative HRCT at different inspiration levels was evaluated by scanning the basal layer at 20, 50, and 80% VC. The control values were -747 +/- 5.6, -816 +/- 3.6, and -855 +/- 3.0 HU, respectively, which were significantly higher (p < 0.001) than those seen in COPD patients at 20 and 50% VC. Again, the IPF patients exhibited increased lung density (p < 0.001) at all inspiratory levels. Discrimination power was best among all cohorts at 20 and 50% VC. Position-dependent artifacts on lung density were quantified by the anteroposterior density gradient (APG). Irrespective of the underlying disease, APG at 50 and 80% VC was similar, but was up to twofold higher at 20% VC, indicating that quantitative estimates near RV may misrepresent mean lung density. CONCLUSION: Our data indicate that quantitative HRCT measurements should be performed not near full inspiration or expiration, but at an intermediate degree of lung inflation, e.g., 50% VC, for reasons of accuracy, intra- and intersubjective comparability, and feasibility. We conclude quantitative HRCT to be a sensitive tool for the evaluation of diffuse parenchymal lung disease.

Adult↗