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Biomedical subjects

T Beinert

Publications and source records attributed to T Beinert.

At least 37 records · Page 2Linked to original sources

Eosinophilia during fludarabine treatment of chronic lymphocytic leukemia.

Although eosinophilia has been reported as a side effect of purine analogues, there is no report on fludarabine-induced eosinophilia in chronic lymphocytic leukemia (CLL). During chemotherapy with fludarabine and cyclophosphamide, we observed two cases of significant eosinophilia. A 67-year-old patient with CLL developed bone marrow and peripheral blood eosinophilia up to 7.9x10(9)/l, the highest eosinophil count ever reported during treatment with a purine analogue. The eosinophilia persisted for 33 days. Another patient developed bone marrow eosinophilia without eosinophilia in the peripheral blood. These are the first documented cases of fludarabine-induced eosinophilia in CLL, and this side effect may conceivably be more common than previously recognized.

Aged↗

Usefulness of morphological characteristics for the differentiation of benign from malignant solitary pulmonary lesions using HRCT.

The aim of this study was to analyze different characteristics on high-resolution computed tomography (HRCT) that help differentiate benign solitary pulmonary lesions (BSPLs) from malignant solitary pulmonary lesions (MSPLs). High-resolution computed tomography was performed on 104 consecutive patients with SPLs. The whole lesion was examined with a slice thickness of 1 mm and a 12-cm field of view. All lesions were surgically excised within 24 h of the CT examination. Satellite nodules, cavitations, and necrosis were found only in MSPLs. Useful characteristics for the differentiation of BSPLs from MSPLs were the presence of spicules (p < 0.00005), spicules extending to the visceral pleura (p < 0.0005), the vessel sign (p < 0.0005), pleural retraction (p < 0.001), circumscribed pleural thickening (p < 0.001), the bronchus sign (p < 0.005), the presence of ground-glass attenuation adjacent to the SPL (p < 0.01), the density of the lesion (p < 0.05), and the length of spicules (p < 0.05). Using the significant characteristics p < 0.01 for the identification of MSPLs, a sensitivity of 91.4 % and a specificity of 56.5 % (accuracy of 83.7 %) was found. A precise morphological assessment of the periphery of the pulmonary lesion is necessary. The HRCT technique is useful in differentiation of BSPLs from MSPLs. However, metastases strongly resembled benign lesions in terms of size and edge type, and chronic inflammatory pseudotumors as a group mimic MSPLs.

Biopsy, Needle↗

Molecular genetic characteristics of lung cancer--useful as real' tumor markers?

The increased knowledge about the molecular mechanisms leading to the development of a tumor has opened new horizons for basic and applied research. Lung cancer is among the tumor entities with the highest incidence and mortality rates. Recently new drugs and therapeutic options for patients with lung cancer were developed. These developments demand new and improved techniques for the sensitive and specific detection of lung tumor cells. Some of the molecular genetic features of lung tumor cells are summarized and the possibilities to use these characteristics as new tumor markers are discussed.

Biomarkers, Tumor↗

An evaluation of the tumour markers, carcinoembryonic antigen (CEA), cytokeratin marker (CYFRA 21-1) and neuron-specific enolase (NSE) in the differentiation of malignant from benign solitary pulmonary lesions.

PURPOSE: The aim of this prospective study was to assess the diagnostic value of the tumour markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment marker (CYFRA 21-1) and neuron-specific enolase (NSE) in the differentiation of malignant (MSPLs) from benign solitary pulmonary lesions (BSPLs). METHODS: Solitary pulmonary lesions (SPLs) were diagnosed using plain radiography and spiral computed tomography (SCT) and then completely removed by surgery in 104 consecutive patients (MSPLs; n = 81, BSPLs; n = 23). The serum concentrations of the tumour markers were determined 1-3 days prior to surgery by ELISA for CEA and CYFRA 21-1 and by IRMA for NSE using commercially available assay kits. The cut-off values were set at 3 ng/ml (for non-smokers) and 5 ng/ml (for smokers) for CEA, at 3.3 ng/ml for CYFRA 21-1 and at 12.5 ng/ml for NSE. RESULTS: MSPLs were identified with a sensitivity between 13.6 and 45.7%, a specificity between 87.0 and 100% and an accuracy between 32.7 and 54.8%. Using the tumour markers alone, the highest sensitivity (27.2%) and accuracy (40.4%) was found with CEA, the highest specificity (100%) with CYFRA 21-1 and with NSE. Primary lung cancers (n = 39) were identified with a sensitivity between 17.9 and 61.5%, a specificity between 87.0 and 100% and an accuracy between 48.4 and 71.0%. Using the tumour markers alone, the highest sensitivity (35.9%) and accuracy (59.7%) was found with CYFRA 21-1, the highest specificity (100%) with CYFRA 21-1 and with NSE. The combination of all three tumour markers resulted in a greater sensitivity and greater diagnostic accuracy but a loss in specificity compared with CYFRA 21-1 and NSE. CONCLUSION: The use of the tumour markers alone or in combination showed a low sensitivity and low accuracy for the diagnostic differentiation of MSPLs from BSPLs and primary lung cancers from BSPLs. However, both CYFRA 21-1 and NSE exhibited a specificity of 100% and may be useful complements to standard clinical imaging methods.

Antigens, Neoplasm↗

Relations between cardiopulmonary exercise testing and quantitative high-resolution computed tomography associated in patients with alpha-1-antitrypsin deficiency.

High-resolution computed tomography (HRCT) can be used to diagnose and quantify emphysema noninvasively, as significant correlations have been found between the histological grade on resected lung specimens and quantified (q) computed tomography (CT). In this study, we performed thin section qHRCT in patients with severe hereditary alpha-1-antitrypsin (AAT) deficiency. AAT deficiency is the most common genetic cause of emphysema in adults, and exercise intolerance is the most disabling, distressing consequence of emphysema for the majority of patients. qHRCT was used to quantify precisely the alterations in the lung parenchyma due to pulmonary emphysema. Up until now, the important relationship between the severity of emphysema and the reduced exercise capacity has received little attention. Therefore the purpose of the study was to investigate the relationship between emphysema as displayed by qHRCT and cardiopulmonary exercise testing (CPX) in patients with severe cardiopulmonary impairment. - qHRCT was performed in 21 patients with homozygous AAT deficiency. CT scans were obtained at three spirometrically standardized levels at the carina and (5 cm above and below the carina). The mean lung density at 50% of vital capacity and a quantitative histogram analysis of the frequencies of CT values were determined. All patients underwent symptom-limited CPX to analyse simultaneously cardiovascular and ventilatory systems responses. - In all patients, qualitative CT assessment demonstrated panlobular emphysema with large and extensive areas of uniform low attenuation, characteristically with a lower-lobe distribution. Mean CT density values of the patients (-845 +/- 6.9 (mean +/- SEM)) were significantly correlated with work capacity (r = 0.55, p <0.01), oxygen-pulse (r = 0.54, p <0.01) and functional dead space ventilation (r = -0.54, p <0.01). Moreover, severe emphysema index (CT values below a threshold value of 950 HU) correlated positively with functional dead space ventilation (r = 0.60, p <0.01) and alveolar-arterial oxygen difference (r = 0.70, p <0.001). - These results clearly demonstrate that CPX parameters, indicating a disturbed pulmonary gas exchange and a ventilation-perfusion-mismatch during exercise, are significantly related to the extent of lung emphysema.

Adult↗

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↗

Cardiopulmonary exercise testing following hay exposure challenge in farmer's lung.

In patients experiencing an acute episode of hypersensitivity pneumonitis (HP), the alveoli and interstitium show a marked inflammation. The effects of this infiltration with effector cells on gas exchange and the cardiopulmonary system are not well characterized, and there are no data regarding cardiopulmonary exercise testing during hypersensitivity pneumonitis. The aim of this study was to gain new insights into the pathophysiology of acute farmer's lung using cardiopulmonary exercise testing. Cardiopulmonary exercise testing was performed in patients who had farmer's lung (n=21) before and 4 h after a standardized exposure with mouldy hay. Farmers who were asymptomatic for this condition (n=15) served as controls. At baseline, patients who had farmer's lung had a decreased breathing reserve and a greater alveolar to arterial oxygen difference. Following exposure, all of these patients developed hypersensitivity pneumonitis. Compared to the asymptomatic farmers, they showed an increase of alveolar to arterial oxygen difference and functional dead space ventilation during exercise and a reduction of the breathing reserve. In addition, 40% of the asymptomatic farmers demonstrated a pathological increase of the alveolar to arterial oxygen difference during exercise following exposure. In conclusion, our data signify that acute hypersensitivity pneumonitis induces significant changes in pulmonary gas exchange during exercise. Cardiopulmonary exercise testing may help to identify individuals with possible subclinical farmer's lung disease.

Adult↗

Quality monitoring, standardized documentation and management with a computerized system in oncology.

Within the last years the prerequisite was prepared to develop a computerized tumor--patient documentation system including quality monitoring and oncological therapy recommendations for every day use. In medicine today, there is an increasing need for quality oriented low cost and transparent management--what is especially true in the field of oncology. The German Federal Authority of Health demands the documentation of all tumor disorders for the establishment of an cancer registry. For these reasons our study group established the program "OncoDoc" in cooperation with the laboratory for Artificial Intelligence of the University Bremen.

Artificial Intelligence↗

Identification of characteristics for malignancy of solitary pulmonary nodules using high-resolution computed tomography.

The aim of this prospective study was to apply the described single pathological appearance and possibilities of differentiating signs from other studies and summarize them concerning their differential diagnostic importance to improve differential diagnostic strategies concerning the dignity of solitary pulmonary nodules. 55 consecutive patients with solitary pulmonary nodules were examinated using high-resolution computed tomography (HRCT) before surgery. Thereafter HRCT-diagnosis was proven by histological assessment. Only lesions which were removed by surgery were used. No lesion was excluded by size. Necrotic areas, cavitation, satellite lesions and circumscribed pleural thickening were only found in the malignant nodules. Discrimination between benign and malignant lesions was possible by: mean diameter (P<.01), mean density (P<.01) and air inclusion (P<.05), by air bronchogram/bronchiologram (P<.05), indistinct/fogged (P<.05) and dystelectatic (P<.01) margin, the presence (P<.01) and length (P<.01) of spiculae, spiculae extended into the pleura visceralis (P<.05) and pleural distension (P<.01). A single sign can be seen in either benign or malignant nodules, but if considered together with other signs it may have a different meaning. HRCT can enable a differentiation of BSPN from MSPN in the majority of cases. As imaging methods could not get a nearly complete certainty about the dignity the chance of survival of patients could be preserved exclusively by an early surgery.

Carcinoma↗

Late pulmonary impairment following allogeneic bone marrow transplantation.

The pulmonary function of 88 consecutive leukemic patients who had undergone allogeneic bone marrow transplantation (BMT) was studied beforehand, at 3 months, at 6 months, and annually thereafter until 5 years after grafting. The parameters for function which are indicative for obstructive and restrictive lung disease deteriorated in all patient groups during the first 3 to 6 months after BMT but partially recovered within one year. Long-term decline in lung function was similar in all patient groups, and neither the onset nor the magnitude of pulmonary dysfunction was related to the occurrence of pulmonary impairment within 6 months after grafting. Multivariate analysis was then employed to assess predictors for long-term pulmonary disease. Despite the obvious effect of chronic graft versus host disease on the course of lung function, it was in itself not a significant predictor of long-term pulmonary outcome. Rather, the conditioning regimen turned out to be indicative; compared with busulfan, fractionated total body irradiation was demonstrated to be clearly superior with a lower incidence of both restrictive and obstructive long-term lung impairment. Our data indicate a previously unknown long-term side effect of busulfan conditioning.

Adult↗

Spirometrically controlled high resolution computed tomography - quantitative assessment of density distribution in patients with diffuse fibrosing alveolitis.

STUDY OBJECTIVE: Lung density assessed by high resolution computed tomography (HRCT) is sufficiently sensitive for the diagnosis of interstitial lung disease, but may be hampered by uneven disease distribution. We determined the mean and subpleural density values in patients with diffuse fibrosing alveolitis (FA) and evaluated the diagnostic accuracy of both parameters, expressed as post-test odds ratios. MATERIALS AND METHODS: Pulmonary HRCT was performed on 21 FA patients and compared to scans of 27 healthy volunteers. The HRCT procedure was standardized by taking 3 scans at the carina +/- 5 cm, and by defining inspiration levels at 50% vital capacity. Mean lung density (MLD) and subpleural lung density (SLD) were calculated for all participants. RESULTS: MLD and SLD values for healthy subjects were significantly higher compared with the patient group. Odds ratios were 7.8:1 and 3.9:1 for SLD and MLD, respectively, demonstrating a superior discrimination power of SLD in the diagnosis of FA. CONCLUSION: Diagnostic accuracy of quantitative HRCT measurements in FA was improved by the separate evaluation of subpleural lung density, which is a better indicator of the presence or absence of lung fibrosis than is mean lung density.

Adult↗

[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↗