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Demosthenes Bouros

Publications and source records attributed to Demosthenes Bouros.

At least 37 records · Page 2Linked to original sources

Serum biomarkers in acute respiratory distress syndrome an ailing prognosticator.

The use of biomarkers in medicine lies in their ability to detect disease and support diagnostic and therapeutic decisions. New research and novel understanding of the molecular basis of the disease reveals an abundance of exciting new biomarkers who present a promise for use in the everyday clinical practice. The past fifteen years have seen the emergence of numerous clinical applications of several new molecules as biologic markers in the research field relevant to acute respiratory distress syndrome (translational research). The scope of this review is to summarize the current state of knowledge about serum biomarkers in acute lung injury and acute respiratory distress syndrome and their potential value as prognostic tools and present some of the future perspectives and challenges.

Animals↗

Variations in alveolar cell populations, lymphocyte subsets and NK-cells in different stages of active pulmonary sarcoidosis.

BACKGROUND: The type and mode of presentation of pulmonary sarcoidosis (radiologic stage, activity) influence alveolar lymphocyte number and subsets as well as other inflammatory cells. AIM: To investigate the variations in alveolar cells, lymphocyte subsets and NK-cells in different radiological stages of active pulmonary sarcoidosis. METHODS: 85 untreated, newly diagnosed patients (32 male, 53 female), median age 47.2+/-14.7 years were investigated. Patients were classified into chest x-ray stages (33 stage I, 27 stage II, 14 stage III and 11 stage IV disease). Bronchoalveolar lavage was performed with 4 portions of 50 mL. Total cells and cell differentials were counted, while CD3+, CD4+, CD8+, CD19+, CD3-CD16/56+ (NK-cells) and CD3+CD16/56+ (NKT-cells) were determined by flow cytometry. RESULTS: Lymphocytosis was high in all stages. Significant differences were found in: a) CD4 between stages I and II and I and IV. b) CD8 between stages I and IV and c) NK and NKT cells between stages I and III. CONCLUSIONS: Variations were observed in alveolar cells and lymphocyte subsets in different stages of pulmonary sarcoidosis. Cells exhibiting cytotoxic activity were increased with stage progression, CD8 from stage I to IV, NK and NKT cells from stage I to III. These cells may be involved in the inflammatory process regulating granuloma formation.

Adult↗

Evaluation of health-related quality-of-life and dyspnea scales in patients with idiopathic pulmonary fibrosis. Correlation with pulmonary function tests.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) has a profound impact on the functional status of patients. We sought to determine whether the health-related quality of life is affected in patients with IPF. METHODS: A total of 25 patients with IPF (aged 41-72 years) and 30 healthy subjects were evaluated in a cross-sectional study. All subjects were asked to complete three dyspnea scales-the Borg (BORG), the oxygen-cost diagram (OCD) and the modified MRC questionnaire-as well as a number of health-related quality-of-life (HRQoL) questionnaires, i.e., the Saint-George Respiratory Questionnaire (SGRQ), the Quality of Well-Being (QWB) and the Hospital Anxiety and Depression Questionnaire (HAD). Pulmonary function tests, arterial blood gas measurements at rest and during exercise, chest radiographs and the duration of disease were used for correlation. RESULTS: The mean total values of all of the scales used were near the lower best values of each scale in IPF patients and were significantly different from values in the control group. Lung volumes (FVC and TLC) correlated significantly with the SGRQ. All dyspnea scales (BORG, OCD and MRC) showed a significant correlation with diffusing capacity and blood oxygenation at rest and during exercise. The duration of the disease correlated with all dyspnea scales used and with the SGRQ and HAD Questionnaires. CONCLUSIONS: Our results suggest that dyspnea scales and the SGRQ are sensitive tools for assessing health-related quality of life in patients with IPF.

Journal Article↗

Expression of apoptotic and antiapoptotic markers in epithelial cells in idiopathic pulmonary fibrosis.

STUDY OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a chronic, usually fatal lung disease of unknown etiology. A common feature is the presence of microscopic areas of epithelial cell dropout. Increased apoptosis of these cells could elucidate the speculative pathogenesis of the disease. Therefore, the aim of our study was to examine the expression of p53, p21, bcl-2, bax, and caspase-3 in association with DNA strand breaks in bronchial and alveolar epithelial cells in lung specimens from IPF patients and control subjects. PATIENTS AND METHODS: We examined by immunohistochemistry the expression of p53, p21, bax, bcl-2, and caspase-3 in association with DNA strand breaks detected by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) in bronchial and alveolar epithelial cells in lung specimens taken by biopsy in 12 IPF patients and 10 control subjects. An independent tissue evaluation by two pathologists graded semiquantatively the degree of staining present. RESULTS: TUNEL was positive in epithelial cells in all IPF patients and only in one control subject. The expression of p53, p21, bax, and caspase-3 was up-regulated in IPF patients compared to control subjects. Bcl-2 was expressed less in IPF patients than in control subjects. CONCLUSIONS: These results confirm that apoptotic hyperplastic epithelial cells are present in patients with IPF and that the expression of p53, p21, bax, and caspase-3 appears to be up-regulated and that of bcl-2 down-regulated in these cells. The increased expression of proapoptotic molecules in epithelial cells in IPF may be involved in the inadequate and delayed reepithelialization, which in turn contributes to fibroblast proliferation.

Apoptosis↗

Cytokine network in the pathogenesis of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) remains a relentlessly progressive lung disorder despite four decades of interest in its pathogenesis and treatment. It is important to emphasize that IPF is a progressive and irreversible illness, and, until now, there has been no available drug that has been capable of modifying the progressive natural course of IPF and its usual terminal outcome. Although the pathogenesis of this disease is complex and poorly understood, growth factors, cytokines, chemokines, and regulators of apoptosis have all been implicated in its pathogenesis and disease progression. This review summarizes the evidence implicating these molecules as primarily involved in the pathogenesis of IPF such as cytokines, chemokines and growth factors, with particular emphasis to novel interactions. The elucidation of mediators that orchestrate this aberrant tissue repair will allow the development of novel interventions to treat this devastating disorder.

Animals↗

Application of microarray technology in pulmonary diseases.

Microarrays are a powerful tool that have multiple applications both in clinical and cell biology arenas of common lung diseases. To exemplify how this tool can be useful, in this review, we will provide an overview of the application of microarray technology in research relevant to common lung diseases and present some of the future perspectives.

Biomarkers↗

Use of interrupter technique in assessment of bronchial responsiveness in normal subjects.

BACKGROUND: A number of subjects, especially the very young and the elderly, are unable to cooperate and to perform forced expiratory manoeuvres in the evaluation of bronchial hyperresponsiveness (BHR). The objective of our study was to investigate the use of the interrupter technique as a method to measure the response to provocation and to compare it with the conventional PD20 FEV1. METHODS: We studied 170 normal subjects, 100 male and 70 female (mean +/- SD age, 38 +/- 8.5 and 35 +/- 7.5 years, respectively), non-smoking from healthy families. These subjects had no respiratory symptoms, rhinitis or atopic history. A dosimetric cumulative inhalation of methacholine was used and the response was measured by the dose which increases baseline end interruption resistance by 100% (PD100Rint, EI) as well as by percent dose response ratio (DRR). RESULTS: BHR at a cut-off level of 0.8 mg methacholine exhibited 31 (18%) of the subjects (specificity 81.2%), 21 male and 10 female, while 3% showed a response in the asthmatic range. The method was reproducible and showed good correlation with PD20FEV1 (r = 0.76, p < 0.005), with relatively narrow limits of agreement at -1.39 mumol and 1.27 mumol methacholine, respectively, but the interrupter methodology proved more sensitive than FEV1 in terms of reactivity (DRR). CONCLUSIONS: Interrupter methodology is clinically useful and may be used to evaluate bronchial responsiveness in normal subjects and in situations when forced expirations cannot be performed.

Journal Article↗

The clinical significance of serum and bronchoalveolar lavage inflammatory cytokines in patients at risk for Acute Respiratory Distress Syndrome.

BACKGROUND: The predictive role of many cytokines has not been well defined in Acute Respiratory Distress Syndrome (ARDS). METHODS: We measured prospectively IL-4, IL-6, IL-6 receptor, IL-8, and IL-10, in the serum and bronchoalveolar lavage fluid (BALF) in 59 patients who were admitted to ICU in order to identify predictive factors for the course and outcome of ARDS. The patients were divided into three groups: those fulfilling the criteria for ARDS (n = 20, group A), those at risk for ARDS and developed ARDS within 48 hours (n = 12, group B), and those at risk for ARDS but never developed ARDS (n = 27, group C). RESULTS: An excellent negative predictive value for ARDS development was found for IL-6 in BALF and serum (100% and 95%, respectively). IL-8 in BALF and IL-8 and IL-10 serum levels were higher in non-survivors in all studied groups, and were associated with a high negative predictive value. A significant correlation was found between IL-8 and APACHE score (r = 0.60, p < 0.0001). Similarly, IL-6 and IL-6r were highly correlated with PaO2/FiO2 (r = -0.27, p < 0.05 and r = -0.55, p < 0.0001, respectively). CONCLUSIONS: BALF and serum levels of the studied cytokines on admission may provide valuable information for ARDS development in patients at risk, and outcome in patients either in ARDS or in at risk for ARDS.

Journal Article↗

Video-assisted thoracoscopic surgery for thoracic empyema: primarily, or after fibrinolytic therapy failure?

BACKGROUND: Traditional and modern treatments are proposed for thoracic empyema. The efficacy of video-assisted thocoscopic surgery (VATS) has been studied when the method is applied either as primary treatment for thoracic empyema or after the failure of fibrinolytic therapy. METHODS: Thirty-eight patients treated with VATS for thoracic empyema have been reviewed. Of those, 20 patients (group 1) with empyema thoracis were referred to VATS after failure of the fibrinolytic treatment. Another 18 patients (group 2) with primary empyema thoracis were treated thoracoscopically immediately when empyema was diagnosed. Both groups were staged 5, 6, or 7 according to Light's criteria. RESULTS: The group 2 patients showed a higher empyema resolving rate (95% versus 85%), shorter hospital stay (4.5 versus 7.5 days), and significantly shorter duration of the procedure (70 +/- 14 versus 62 +/- 10 minutes) in comparison with the patients of group 1. CONCLUSIONS: The VATS technique for thoracic empyema is a well-tolerated, minimally invasive technique, with excellent therapeutic results, mild postoperative complications, and reduced hospitalization. VATS should be considered as the treatment of choice for thoracic empyema, in the fibrinopurulent stage, as it is more effective when applied primarily than when applied after fibrinolytic therapy.

Adult↗

Involvement of lymphatic metastatic spread in non-small cell lung cancer accordingly to the primary cancer location.

OBJECTIVES: The purpose of the study is to investigate the contribution of lymphatic spread in operable non-small cell lung cancer (NSCLC) in relation to the cancer location. METHODS: We retrospectively studied 557 consecutive patients [514 males and 43 females, mean age 62.5 +/- 9.1 years (range, 20-84)] who underwent a major lung resection due to NSCLC in our department, from January 1995 to December 1999. Preoperative staging for metastatic disease was negative. Extended mediastinal lymph node dissection was performed in all lung resections. RESULTS: The pathology report revealed 220 adenocarcinomas, 276 squamous-cell, 34 undifferentiated, 25 adenosquamous and 2 large-cell carcinomas. The TNM stage was IA in 52 patients, IB in 109, IIA in 20, IIB in 146, IIIA in 190, IIIB in 35 and IV in 5. The classification of disease was N0 in 240 (40.1%) patients, N1 in 179 (32.1%) and N2 in 138 (24.8%). Twenty-eight patients (5.03%) presented a skip metastasis to hilar lymph nodes, while 27 patients (4.85%) presented with skip metastasis to the mediastinum. The size of the primary tumors presenting with metastases was significantly smaller in adenocarcinomas compared to squamous-cell carcinomas (P = 0.046). Regarding the right lung, tumors originating in the upper lobe mainly metastasized to level No. 4, while tumors of the middle lobe spread to stations Nos. 4 and 7, and those in the lower lobe to level No. 7. Regarding the left lung, tumors originating in the upper lobe metastasized to level No. 5, while tumors within the lower lobe spread to stations, Nos. 7-9. CONCLUSIONS: Mediastinal lymph nodal dissection is necessary for the accurate determination of pTNM stage. It seems that there is no definite way for lymphatic spreading in relation to the location of the cancer. Skip metastasis to the mediastinal lymph nodes was present in 4.85% of our patients, while adenocarcinomas, even small-sized ones, are more aggressive than squamous-cell carcinomas.

Adult↗

Induced sputum CD8+ T-lymphocyte subpopulations in chronic obstructive pulmonary disease.

BACKGROUND: Previous studies have shown that the inflammatory response to cigarette smoking differs between smokers who develop chronic obstructive pulmonary disease (COPD) and those who do not and that the CD8+ T-lymphocytes have been identified as a key player in this process. The aim of this study was to investigate further the role of CD8+ cells and their subtypes in sputum cells. METHODS: Sputum induction was performed in 36 COPD patients, 25 smokers without COPD and 10 non-smoking healthy controls. After stimulation of sputum lymphocytes with phorbol-myristate-acetate, we used double immunocytochemical methods to identify CD4+, CD8+ cells and CD8+ INFgamma or IL4 cells (Tc1,Tc2). RESULTS: COPD patients had an increased number of CD8+ cells in sputum as compared with smokers without COPD (P = 0.0001) and control subjects (P = 0.001). CD8+-IL4 cells were reduced both in COPD and in smokers without COPD compared to controls (P = 0.0001), while CD8+-IFNgamma cells were significantly reduced only in COPD (P = 0.001) as compared with controls. A significant (P = 0.02) relationship between the CD8+-IL4/CD8+-IFNgamma ratio and FEV1 (% pred) was found only in COPD patients. CONCLUSION: These findings suggest that an imbalance both in T-lymphocyte subpopulation (CD4/CD8) and in CD8+ cell subsets (Tc1/Tc2) characterizes the inflammatory responses of smokers with established COPD.

Aged↗

Effects of formoterol and salmeterol on resting inspiratory capacity in COPD patients with poor FEV(1) reversibility.

BACKGROUND: Recent studies suggest that inspiratory capacity (IC) measured at rest can be used to predict improvements in dyspnea and exercise tolerance in chronic obstructive pulmonary disease (COPD) patients. In this study we compared the effect of formoterol (Foradil, Aerolizer) and salmeterol (Serevent, Diskus) in terms of IC in patients with COPD. METHODS: This was a multicentre, randomized, placebo-controlled, single-dose, double-dummy, crossover study conducted in five secondary care centres in four European countries. A total of 47 patients with Stage II and III COPD, as defined by ATS criteria, with an increase in forced expiratory volume in 1s (FEV(1)) of <or= 12% from the patient's predicted normal value after salbutamol inhalation were included. Patients inhaled single doses of formoterol (12 and 24 microg), salmeterol (50 and 100 microg) or matching placebo. IC was recorded before dosing and at 5, 10, 15 and 30 min and 1, 2, 3 and 4 h post-dose. RESULTS: Formoterol was significantly superior to salmeterol during the first hour post-dose as indicated by notable differences at all times during the first hour post-dose and by the ANCOVA analysis of the Area Under the IC Curve (AUC(0-1 h)). CONCLUSIONS: Both formoterol and salmeterol increase IC in patients with COPD, with formoterol 12 microg showing a significantly greater increase in IC over the first hour post-dose than salmeterol 50 microg, consistent with a more rapid onset of action.

Administration, Inhalation↗

8-Isoprostane, a marker of oxidative stress, is increased in the expired breath condensate of patients with pulmonary sarcoidosis.

STUDY OBJECTIVE: 8-Isoprostane is considered an index of oxidative stress. Measurement of 8-isoprostane in the expired breath condensate, a totally noninvasive method, has not been used to explore the level of inflammation in pulmonary sarcoidosis. Therefore, the aim of our study was to measure the levels of 8-isoprostane in the expired breath condensate of patients with sarcoidosis, and to investigate the relation of 8-isoprostane level to disease activity. PATIENTS: We investigated 30 patients with pulmonary sarcoidosis (active disease, n = 14; nonactive disease, n = 16) and 12 healthy subjects as control group. METHODS: 8-Isoprostane was measured in the expired breath condensate of all subjects, and its levels were compared between the control and sarcoidosis groups as well as between the subgroups of patients with active and nonactive disease. In the group with sarcoidosis, 8-isoprostane levels were further correlated with markers that may reflect disease activity, such as serum angiotensin-converting enzyme (sACE) level, serum calcium level, and pulmonary function test results. RESULTS: The concentration of 8-isoprostane was increased in patients with sarcoidosis compared to control subjects (mean, 64.23 pg/mL; 95% confidence interval [CI], 37.00 to 91.46 pg/mL; vs mean, 20.75 pg/mL; 95% CI, 16.06 to 25.44 pg/mL; p = 0.04). The difference was primarily due to the patients with active disease, who had significantly higher levels of 8-isoprostane (mean, 111.4 pg/mL; 95% CI, 62.56 to 160.30 pg/mL; p < 0.001) compared to patients with nonactive disease (mean, 22.94 pg/mL; 95% CI, 15.89 to 29.99 pg/mL) or healthy subjects. 8-Isoprostane levels in patients with nonactive disease did not differ from those in healthy subjects (p > 0.05). In the patients with sarcoidosis, 8-isoprostane levels were positively correlated with sACE level (p < 0.0001, r = 0.69), but was not correlated with serum calcium level or pulmonary function test values. CONCLUSIONS: Our data suggest that 8-isoprostane levels are increased in the expired breath condensate of patients with sarcoidosis and might serve as an index of disease activity.

Adult↗

Pleural effusions in hematologic malignancies.

Nearly all hematologic malignancies can occasionally present with or develop pleural effusions during the clinical course of disease. Among the most common disorders are Hodgkin and non-Hodgkin lymphomas, with a frequency of 20 to 30%, especially if mediastinal involvement is present. Acute and chronic leukemias, myelodysplastic syndromes, are rarely accompanied by pleural involvement. Furthermore, 10 to 30% of patients receiving bone marrow transplantation develop pleural effusions. In cases of hematologic pleural effusions, drug toxicity, underlying infectious, secondary malignant or rarely autoimmune causes should be carefully sought. In most cases, the pleural fluid responds to treatment of the primary disease, whereas resistant or relapsing cases may necessitate pleurodesis.

Bone Marrow Transplantation↗

Interferons and their application in the diseases of the lung.

Interferons (IFNs) are a family of cytokine mediators that are critically involved in alerting the cellular immune system to viral infections of host cells. There are three major classes of IFNs, as follows: IFN-alpha; IFN-beta; and IFN-gamma. IFNs are being investigated and applied in various respiratory disorders, including interstitial lung diseases, lung cancer, malignant mesothelioma, malignant pleural effusions, and respiratory infections. Recent promising preliminary results concerning patients with idiopathic pulmonary fibrosis who have been treated with IFN-gamma1b should prompt the performance of further confirmatory well-designed multicenter trials. IFN-gamma is emerging as an important cytokine for use in the treatment of patients with infectious diseases, including multidrug-resistant pulmonary TB. A better understanding of IFN biology, indications, side effect profiles, and toxicity management will aid in optimizing its use in the treatment of patients. The purpose of this article is, therefore, to review the current clinical use of IFNs in the treatment of patients with respiratory diseases.

Humans↗

The predictive role of serum and bronchoalveolar lavage cytokines and adhesion molecules for acute respiratory distress syndrome development and outcome.

BACKGROUND: The predictive role of many cytokines and adhesion molecules has not been studied systematically in acute respiratory distress syndrome (ARDS). METHODS: We measured prospectively tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-1, soluble vascular adhesion molecule-1 (VCAM-1) and soluble intercellular adhesion molecule-1 (ICAM-1) in serum and bronchoalveolar lavage fluid (BALF) within 2 hours following admission, in 65 patients. The patients were divided into: those fulfilling the criteria for ARDS (n = 23, group A), those who were pre-ARDS and who developed ARDS within 24 hours (n = 14, group B), and those on pre-ARDS but who never developed ARDS (n = 28, group C). RESULTS: All the measured molecules were only found at higher levels in the serum of patients that died either with or without ARDS (P < 0.05 - P < 0.0001). Patients at risk exhibited a good negative predictive value (NPV) of the measured molecules for ARDS development both in their serum (89 to 95%) and BALF (86 to 92%) levels. In contrast to BALF, serum levels of IL-1 and adhesion molecules exhibited a good NPV (68 to 96%), sensitivity (60 to 88%) and survival specificity (74 to 96%) in all groups. All molecules in serum and BALF IL-1 were correlated with the APACHE II (P < 0.05 - P < 0.0001). Serum and BALF IL-1 as well as BALF TNF-alpha were negatively correlated to PaO2/FiO2 (all P < 0.05). CONCLUSIONS: The studied molecules have good NPV for ARDS development both in serum and BALF. Serum rather than BALF levels seem to be related to outcome.

Acute Disease↗