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Demosthenes Bouros

Publications and source records attributed to Demosthenes Bouros.

At least 19 recordsLinked to original sources

Pulmonary sarcoidosis associated with psoriasis vulgaris: coincidental occurrence or causal association? Case report.

BACKGROUND: Sarcoidosis is rarely associated with a distinct disease. One disease infrequently associated with sarcoidosis is psoriasis. CASE PRESENTATION: This case study describes a 38-year-old male, who presented with chest pain, high-grade fever, arthralgias and a skin rash accompanied by bilateral hilar lymphadenopathy on his chest radiograph. Extensive investigations including fiber-optic bronchoscopy with bronchoalveolar lavage and labial and skin biopsies, demonstrated that two distinct clinical entities co-existed in the same patient: pulmonary sarcoidosis and psoriasis vulgaris. Combination therapy for both diseases was applied and the patient was greatly improved. CONCLUSION: This is the first well-documented case of sarcoidosis and psoriasis in the same patient, reported on the basis of safe and widely-used techniques that were not available until fairly recently. These disorders might share common pathogenic mechanisms that could explain their co-existence in the patient.

Adult↗

Intrapleural fibrinolytic therapy for pleural infection.

Pneumonia with secondary pleural infection causes considerable morbidity and mortality. Intrapleural instillation of fibrinolytic agents to dissolve fibrinous adhesions is intended to improve pleural fluid drainage and prevent pleural loculations. In the last 20 years their application in the every day clinical practice has dragged much of attention and several studies have supported their use in the management of parapneumonic pleural effusions (PPE) and pleural empyema (PE). However, recent published data cast doubt on the effectiveness of intrapleural fibrinolytic agents in promoting drainage of infected pleural effusions. Pending future clinical trials, fibrinolytic therapy may be used selectively in patients who fail drainage with appropriately sized, image-guided chest tubes if reasons exist to delay or avoid definitive surgical drainage. The scope of this article is to systematically review evidence for the efficacy of intrapleural fibrinolytic therapy in the treatment of PPE and PE with emphasis on controlled trials and present some of the future perspectives.

Empyema, Pleural↗

Angiogenesis in interstitial lung diseases: a pathogenetic hallmark or a bystander?

The past ten years parallels have been drawn between the biology of cancer and pulmonary fibrosis. The unremitting recruitment and maintenance of the altered fibroblast phenotype with generation and proliferation of immortal myofibroblasts is reminiscent with the transformation of cancer cells. A hallmark of tumorigenesis is the production of new blood vessels to facilitate tumor growth and mediate organ-specific metastases. On the other hand several chronic fibroproliferative disorders including fibrotic lung diseases are associated with aberrant angiogenesis. Angiogenesis, the process of new blood vessel formation is under strict regulation determined by a dual, yet opposing balance of angiogenic and angiostatic factors that promote or inhibit neovascularization, respectively. While numerous studies have examined so far the interplay between aberrant vascular and matrix remodeling the relative role of angiogenesis in the initiation and/or progression of the fibrotic cascade still remains elusive and controversial. The current article reviews data concerning the pathogenetic role of angiogenesis in the most prevalent and studied members of ILD disease-group such as IIPs and sarcoidosis, presents some of the future perspectives and formulates questions for potential further research.

Angiogenesis Inhibitors↗

Pathogenetic pathways and novel pharmacotherapeutic targets in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a poorly understood disease that usually leads to death within 5 years of diagnosis. Despite our better understanding of IPF pathogenesis, the etiology and the precise cellular and molecular mechanisms involved are not well known. Current therapies are of unproven benefit. The aim of this review is to identify possible candidate pathways that might offer novel therapeutic targets changing the natural course of this disease. Current therapeutic approaches target at apoptosis, epithelial replacement, fibroblasts/myofibroblasts, procoagulant activity, growth factors production, angiogenesis, Th1 and Th2 cytokines and oxidative stress. Increased epithelial cells apoptosis can contribute to fibrosis, while on the other hand, decreased fibroblast or myofibroblast apoptosis promotes fibrosis. Recent findings support the notion that therapy directed at either inhibition of angiogenic or augmentation of angiostatic CXC chemokines may be a novel approach in the treatment of IPF. Additionally, there is little doubt that the development of novel therapeutic strategies for pulmonary fibrosis should target some profibrotic growth factors and key type II cytokines, such as inteleukin-13. Importantly, persistent activation of intra-alveolar procoagulant activity and subsequent abnormal fibrin turnover enhances a fibrotic response. Furthermore, increased procoagulant activity may interfere with fibrin accumulation and lack of activation of some matrix metalloproteinases responsible for an imbalance in matrix turnover. Finally, oxidative stress with increased production of oxidants in IPF is an additional mechanism proposed to explain epithelial cell apoptosis in this disease. The challenge of future targets for therapeutic intervention is to reconcile different pathogenetic pathways, and we strongly suspect that no single approach will be sufficient for a lethal disease with few therapeutic options.

Apoptosis↗

Prevention of nosocomial maxillary sinusitis in the ICU: the effects of topically applied alpha-adrenergic agonists and corticosteroids.

OBJECTIVE: We investigated the efficacy of locally applied nasal decongestant agents and corticosteroids for preventing nosocomial maxillary sinusitis in mechanically ventilated patients with multiple trauma. DESIGN AND SETTING: A prospective, open-label randomized study in two intensive care units (ICUs). PATIENTS: 79 consecutive multiple trauma patients admitted to the ICU who were expected to be mechanically ventilated for more than 3 days. INTERVENTIONS: Patients were randomly assigned to receive either a combination of a locally applied nasal decongestant agents: 2 drops twice/day of xylometazoline nasal solution 0.1% and 100microg budesonide (NDCA group, n=39) or placebo (control group, n=40). MEASUREMENTS: For the diagnosis of radiological maxillary sinusitis patients underwent paranasal computed tomography within 48h of admission and thereafter every 4-7 days. Infectious maxillary sinusitis was diagnosed by microbiological analysis of fluid aspirated after transnasal puncture of maxillary sinuses. RESULTS: Radiological maxillary sinusitis was detected in 54% of patients in the NDCA group (n=21) but in 82% of controls (p<0.01), and infectious maxillary sinusitis in 8% of the NDCA group (n=3) but in 20% of controls (n=8; p=0.11). The most common pathogen micro-organisms identified from maxillary aspirates were Acinetobacter (32%) followed by anaerobes (21%). CONCLUSION: Our results indicate that the combination of locally applied xylometazoline hydrochloride and budesonide reduces the incidence of radiological maxillary sinusitis and may reduce also that of nosocomial maxillary sinusitis in mechanically ventilated patients with multiple trauma.

Administration, Topical↗

Clearance of technetium-99m-DTPA and HRCT findings in the evaluation of patients with Idiopathic Pulmonary Fibrosis.

BACKGROUND: Clearance of inhaled technetium-labeled diethylenetriamine pentaacetate (99mTc-DTPA) is a marker of epithelial damage and an index of lung epithelial permeability. The aim of this study was to investigate the role of 99mTc-DTPA scan in patients with Idiopathic Pulmonary Fibrosis (IPF). Our hypothesis is that the rate of pulmonary 99mTc-DTPA clearance could be associated with extent of High Resolution Computed Tomography (HRCT) abnormalities, cell differential of bronchoalveolar lavage fluid (BALF) and pulmonary function tests (PFTs) in patients with IPF. METHODS: We studied prospectively 18 patients (14 male, 4 female) of median age 67 yr (range 55-81) with histologically proven IPF. HRCT scoring included the mean values of extent of disease. Mean values of these percentages represented the Total Interstitial Disease Score (TID). DTPA clearance was analyzed according to a dynamic study using a Venticis II radioaerosol delivery system. RESULTS: The mean (SD) TID score was 36 +/- 12%, 3 patients had mild, 11 moderate and 4 severe TID. Abnormal DTPA clearance half-time (t1/2 < 40 min) was found in 17/18 (94.5%) [mean (SD) 29.1 +/- 8.6 min]. TID was weakly correlated with the DTPA clearance (r = -0.47, p = 0.048) and with % eosinophils (r = 0.475, p = 0.05). No correlation was found between TID score or DTPA and PFTs in IPF patients. CONCLUSION: Our data suggest that 99mTc-DTPA lung scan is not well associated with HRCT abnormalities, PFTs, and BALF cellularity in patients with IPF. Further studies in large scale of patients are needed to define the role of this technique in pulmonary fibrosis.

Aged↗

Quality of life in patients with active sarcoidosis in Greece.

BACKGROUND: The health status of patients with sarcoidosis has rarely been studied, despite the increasing numbers of health-related quality of life publications on other respiratory diseases. The aim of this cross-sectional study was to investigate whether sarcoidosis affects quality of life (QoL), using specifically designed questionnaires for respiratory diseases as well as general health measures, and to compare these with pulmonary function indices. Our secondary aim was to determine whether these measurements are correlated with pulmonary function tests and duration of the disease. METHODS: Included in the study were 75 consecutive patients with histologically confirmed active sarcoidosis. Self-completed dyspnea scales (Borg's scale, oxygen cost diagram, modified MRC questionnaire) and health-related quality of life (HRQoL) questionnaires (St George's Respiratory Questionnaire, Quality of Well-Being, and Anxiety and Depression) were used. Pulmonary function tests, measurements of arterial blood gases at rest and after exercise, chest radiographs, and duration of disease were used for correlation. RESULTS: We found that QoL was affected in sarcoidosis patients in comparison with healthy controls. Secondly, we found that the duration of the disease was correlated with all three dyspnea scales under evaluation, as well as with the SGRQ questionnaire. Furthermore, a significant correlation was shown between lung function tests (FVC, % pred and FEV(1), % pred) and both the BORG dyspnea scale and the SGRQ questionnaire. CONCLUSION: Quality of life is affected in patients with active sarcoidosis. The SGRQ questionnaire could be a useful tool for the investigation of HRQoL in an active sarcoid population with varying degrees of lung function impairment. Future studies are needed to address the ability of these instruments to measure HRQoL in the course of this chronic disease.

Journal Article↗

Upregulation of Th1 cytokine profile (IL-12, IL-18) in bronchoalveolar lavage fluid in patients with pulmonary sarcoidosis.

Sarcoidosis, a systemic granulomatous disease of unknown etiology, is characterized by a predominantly Th1 cytokine milieu, which is involved in its immunopathogenesis. The role of novel immunologic markers reflecting T cell activity of the sarcoid immunologic response needs to be determined. The present study aims to evaluate the role of the Th1 cytokine pattern by estimating the local and systemic levels of interleukin-12 (IL-12) and IL-18 in bronchoalveolar lavage fluid (BALF), induced sputum, and serum of patients with pulmonary sarcoidosis. We studied prospectively 20 patients (12 women, 8 men) of median age 46 years (range 25-65) with sarcoidosis and 10 normal subjects (5 women, 5 men) of median age 39 years (range 26-60). IL-12 and IL-18 levels were measured using ELISA kits. The IL-12 BALF levels were significantly higher in sarcoidosis patients than in healthy subjects (5.64 +/- 0.21 pg/mL vs. 5.16 +/- 0.15 pg/mL, p < 0.001). In addition, IL-18 levels were significantly increased in BALF samples (47.69 +/- 6.29 pg/mL vs. 16.73 +/- 3.00 pg/mL, p < 0.001). A statistically significant decrease in IL-12 serum levels was detected in the sarcoid population compared with controls (5.77 +/- 0.50 pg/mL vs. 7.87 +/- 2.00 pg/mL, p < 0.001). No significant differences were detected in IL-12 and IL-18 levels between patients and controls in induced sputum samples. Our data suggest a potential role of IL-12 and IL-18 in the local immunologic response in pulmonary sarcoidosis. Further large-scale studies are needed to define the precise role of IL-12 and IL-18 in the immunopathogenesis of this disorder.

Adult↗

Perforin down-regulation and adhesion molecules activation in pulmonary sarcoidosis: an induced sputum and BAL study.

BACKGROUND: Sarcoidosis is thought to be a T-helper type 1 cytokine-mediated disorder. Sputum induction has been proposed as a useful noninvasive method mainly for the assessment of airway diseases. However, it is unknown whether the balance of T-cytotoxic (Tc1) type 1 and Tc2 cells is altered in sarcoidosis. STUDY OBJECTIVES: The primary aim of this study was to characterize the CD8+ T lymphocyte subpopulations in induced sputum from sarcoidosis patients, and to compare these subpopulations to those found in BAL fluid (BALF) from sarcoidosis patients. To further investigate the mechanism of the cytotoxic activity of CD8+ lymphocytes, we measured their perforin expression. Additionally, two adhesion molecules (CD62 and CD71), which are expressed on CD8+ T cells and may serve as novel immunologic markers, were detected. SETTINGS: Department of Thoracic Medicine, University of Crete, and Department of Pneumonology, Democritus University of Thrace, Alexandroupolis, Greece. PATIENTS: We prospectively studied 22 patients with sarcoidosis (median age, 48 years; age range, 25 to 65 years) and 10 healthy subjects (5 female and 5 male; median age, 39 years; age range, 26 to 60 years). INTERVENTIONS: The stimulation of lymphocytes with phorbol 12-myristate 13-acetate was followed by the use of double immunocytochemical methods to identify CD8+ interferon (IFN)-gamma producing cells (ie, Tc1) and CD8+ interleukin-4 producing cells (ie, Tc2). MEASUREMENTS AND RESULTS: We found a significant decrease in the prestimulation percentage of IFN-gamma-positive CD8+ T cells in the BALF (p = 0.001) and induced sputum (p = 0.001) of sarcoidosis patients compared to the number in samples from healthy control subjects. However, no significant difference was documented between lymphocyte subsets poststimulation. Decreased levels of perforin expression were found in BALF (p = 0.001) and induced sputum (p < 0.001) of sarcoidosis patients compared to those in control subjects. The adhesion molecules were significantly increased in both the BALF and induced sputum of the sarcoid population compared to those in healthy control subjects. CONCLUSIONS: Our results suggest that inflammation could be effectively and noninvasively determined by using sputum induction in sarcoidosis patients. In addition, we have provided evidence suggesting the possibility that CD8+ lymphocytes might not play a major role in sarcoidosis.

Adult↗

Different angiogenic activity in pulmonary sarcoidosis and idiopathic pulmonary fibrosis.

BACKGROUND: Recent evidence has shown that several chemokines--including those involved in angiogenesis--have been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and sarcoidosis. We speculated that these differences could be attributed to distinct angiogenic and angiostatic profiles. This hypothesis was investigated by estimating the levels of three angiogenic chemokines (growth-related gene [GRO]-alpha, epithelial neutrophil-activating protein [ENA]-78, and interleukin [IL]-8), and three angiostatic chemokines (monokine induced by interferon (IFN)-gamma [MIG], IFN-gamma-inducible protein [IP]-10, and IFN-gamma-inducible T-cell alpha chemoattractant) in serum and BAL fluid (BALF). METHODS: We studied prospectively 20 patients with sarcoidosis (median age, 46 years; range, 25 to 65 years), 20 patients with IPF (median age, 68 years; range, 40 to 75 years), and 10 normal subjects (median age, 39 years; range, 26 to 60 years). RESULTS: The GRO-a serum and BALF levels of IPF patients were found significantly increased in comparison with healthy subjects (799 pg/mL vs 294 pg/mL [p = 0.022] and 1,827 pg/mL vs 94 pg/mL [p < 0.001], respectively) and sarcoidosis patients (799 pg/mL vs 44 pg/mL [p < 0.001] and 1,827 pg/mL vs 214 pg/mL [p < 0.001], respectively). Moreover, ENA-78 and IL-8 BALF levels in IPF patients were significantly higher compared with sarcoidosis patients (191 pg/mL vs 30 pg/mL [p < 0.001] and 640 pg/mL vs 94 pg/mL [p = 0.03], respectively). MIG serum levels in IPF patients were found significantly upregulated in comparison with sarcoidosis patients and healthy control subjects. However, MIG and IP-10 BALF levels (1,136 pg/mL vs 66 pg/mL [p < 0.001] and 112 pg/mL vs 56 pg/mL [p = 0.037], respectively) were significantly higher in sarcoidosis patients compared with IPF patients. CONCLUSIONS: Our data suggest distinct angiogenic profiles between IPF and sarcoidosis, indicating a potential different role of CXC chemokines in the local immunologic response in IPF and pulmonary sarcoidosis.

Adult↗

Interferon-gamma 1b for the treatment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) represents a particularly aggressive disease, the aetiology of which still remains unknown. The natural history of the disease often leads to respiratory failure and death, with a mortality rate greater than some cancers. To date, no management approach has proven to be efficacious for the treatment of this disease. IPF has been characterised as an 'epithelial-fibroblastic disorder', characterised by abnormal wound healing with excessive fibrosis and minimal inflammation. These emerging data have focused attention on antifibrotic drugs. Interferon-gamma1b (IFN-gamma1b) has recently been proposed as a promising candidate for the treatment of IPF. The reason for this is that IFN-gamma1b has the ability to modulate the Th1/Th2 imbalance and to suppress fibroblast activation. The view that IPF is untreatable at present requires reconsideration, as improved survival has been suggested in three controlled trials of IFN-gamma1b in IPF therapy.

Animals↗

Serum biomarkers in interstitial lung diseases.

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 interstitial lung diseases (translational research). The scope of this review is to summarize the current state of knowledge about serum biomarkers in interstitial lung diseases and their potential value as prognostic and diagnostic tools and present some of the future perspectives and challenges.

Animals↗

Th1/Th2 cytokine pattern in bronchoalveolar lavage fluid and induced sputum in pulmonary sarcoidosis.

BACKGROUND: Sarcoidosis is thought to be a T-helper type 1 cytokine (Th2 cytokine) mediated disorder. Induced sputum (IS) has been proposed as a useful non-invasive method, mainly for the assessment of the airway diseases. The aim of this study was to explore induced sputum (IS) CD4+ Th1 T-lymphocyte subpopulation and to compare them with those of bronchoalveolar lavage fluid (BALF) in patients with sarcoidosis. METHODS: We studied prospectively 21 patients (12 female, 9 male) of median age 46 yr (range, 25-65) with sarcoidosis and 10 normal subjects (5 female, 5 male) of median age 39 yr (range, 26-60). IS was performed with hypertonic saline solution using an ultrasonic nebulizer. BALF was performed within 10 days of IS. After stimulation of sputum lymphocytes with phorbol-myristate-acetate, we used double immunocytochemical methods to identify CD4+ IFN-gamma positive and IL-4 positive cells (Th1 and Th2, respectively). RESULTS: Sarcoidosis patients had an increased number of CD4+ -IFN-gamma producing cells in IS (p = 0.003) and BALF (p = 0.01) in comparison with normal subjects. No significant differences were detected between CD4+ -IL-4 cells in BALF (p = 0.053, NS) and IS (p = 0.46, NS) between sarcoidosis patients and healthy controls. The ratio of Th1 to Th2 cells in BALF and IS was statistically different in sarcoidosis when compared with normal subjects (p = 0.007 in BALF and IS). A significant correlation was found between CD4+ IFN-gamma positive cells in IS and those in BALF in sarcoidosis patients (r = 0.685, p = 0.0006). CONCLUSION: These data suggests that a Th1-like cytokine pattern can be observed in CD4+ T-lymphocytes in IS in patients with pulmonary sarcoidosis. Further studies are needed to explore the value of IS vs BALF in the follow-up of these patients.

Adult↗