Professor of Respiratory Medicine, University of Thessaly Director of Pulmonary Clinic Rector of University of Thessaly
STUDIES - Medical School, 1982.
- PhD thesis, Medical School, University of Athens, 1988
- Pulmonary specialist, 1989.
HONORS - Expert-judge for research programs of the European Union's Pneumology, Physiology of breathing.
- Member of the Advisory Board of the Hellenic Medical Society of Athens on the organization of the Panhellenic Conference.
- Honorary President of the Scientific Committee of the 7th Annual Scientific Conference of Greek Medical Students, 2001.
- Participation in euresnet (expert panel meeting) on ​​respiratory, 2001.
- Member of the Selection Committee for the scholarship of the Greek Thoracic Society in 2002.
MANAGEMENT POSITIONS Participate as a member of the Research Committee of the University of Thessaly in the years 1994-1997. By decision of the Medical Department and the Executive Committee of the University of Thessaly was appointed again as a member for three years 1998-2001.
Deputy Head of Liaison Office, University of Thessaly in 1996.
Deputy Coordinator of the Panel "Physiology, Pathological Physiology of the Respiratory System of the Thoracic Society from 1995 to 1999.
Director of the Vocational Training Centre, University of Thessaly in Health and Welfare from 1997 until today.
Reviewer ratings in Pneumology, Allergology and Medical Job Boards in Crisis and Choice of Medical Personnel in the regions of Thessaly and Central Greece.
Judge of Biomedical Research of the Central Health (Ministry of Health).
Referee for all the latest lung conferences.
Chairman of the Scientific Committee of the University Hospital of Larissa for two terms from 1999 to 2001.
Chairman of the Ethics of the University Hospital of Larissa in 1999.
Special Secretary of the Greek Society of Thoracic years 1999-2001.
Secretary of the Association members of Thessaly Medical School faculty for two terms 1999 and 2001.
Board member of Greek Society of Sleep Research, Athens 2000.
Member of the Scientific Council of the University Hospital of Larissa in 2002.
Vice Univ. Thessaly Economic Development and Planning since 2002.
Chairman of the Research University. Thessaly since 2002.
Director of Pathology Division of Larissa University Hospital since 2002.
Deputy Chairman of the Department of Special Education, University of Thessaly.
Participation in the preparation of Development Plan, University of Thessaly.
Coordinator of the Economic Development, University of Thessaly.
Board Member of IEK of Volos in 2003.
Chairman of the Department of Biochemistry and Biotechnology, University of Thessaly.
Abstract: Histamine is involved in the pathogenesis of numerous diseases and regulates the permeability of different tissues. The aim of this study is to investigate the effects of histamine on the electrophysiology of human parietal pleura and the underlying mechanisms involved.
Abstract: Early diagnosis of Chronic Obstructive Pulmonary Disease (COPD) remains the cornerstone for effective management. In this study we compared an open spirometry programme and a case-finding programme providing spirometry to high-risk subjects selected by primary care physicians.
Abstract: Eur J Clin Invest 2011; 41 (4): 349-356 ABSTRACT: Background  The imbalance between oxidants and antioxidants is referred to as oxidative stress and has been associated with various respiratory disorders. The aim of this study was the assessment of 8-isoprostane (8-iso-PGF(2α) ) and Cu/Zn superoxide dismutase (Cu/Zn SOD) in exudative pleural effusions in order to examine the diagnostic accuracy of these markers in the differentiation between complicated and uncomplicated parapneumonic effusions. Methods  The study included 214 consecutive patients with pleural effusions [68 parapneumonic (31 uncomplicated parapneumonic, 20 complicated parapneumonic, 17 empyemas), 24 tuberculous, 88 malignant and 34 transudates]. 8-Isoprostane and Cu/Zn SOD were determined by ELISA in pleural fluid and serum. Results  Parapneumonic effusions were characterized by higher pleural fluid 8-isoprostane levels compared to transudative, malignant and tuberculous effusions. Pleural fluid Cu/Zn SOD levels were lower in transudates, while serum levels were higher in transudative compared to all exudative pleural effusions. Both pleural fluid 8-isoprostane and Cu/Zn SOD were higher in complicated parapneumonic effusions and empyemas compared to uncomplicated parapneumonic effusions. Pleural fluid 8-isoprostane was the most accurate test to differentiate between complicated and uncomplicated parapneumonic pleural effusions with a sensitivity of 100% and a specificity of 58·1% at a cut-off point of 35·1 (AUC = 0·848). Conclusions  Pleural fluid 8-isoprostane and Cu/Zn SOD may provide useful information for the differentiation between uncomplicated and complicated parapneumonic effusions and empyemas.
Abstract: Asthma is a chronic inflammatory airways disorder. However, no biomarker of airways inflammation has been included in the assessment of asthma control.
Abstract: Systemic inflammation may represent a possible cause of anemia. Previous data support that anemic patients with COPD present high erythropoietin (EPO) levels, suggestive of EPO resistance, possibly mediated through inflammatory mechanisms.
Abstract: We investigated the effects of insulin on the electrophysiology of sheep pleural specimens obtained from the upper and lower parts of the pleural cavity and the insulin receptor abundance in these regions.
Abstract: Diminished nitric oxide (NO) levels have been reported in adults with obstructive sleep apnea but no data are available for children with obstructive sleep-disordered breathing (SDB).
Abstract: Boosting pre-existing, naturally occurring cytolytic CD8(+) T-cell (CTLs) responses directed against class-I MHC-restricted peptides of tumor antigens, represents a primary goal of cancer immunotherapy. The number of pre-existing antitumor CTLs and their impaired function has been incriminated as the most likely candidates for the reduced clinical efficacy of these trials. This study was scheduled to determine possible differences in the frequency and the function of naturally occurring CTL precursors (pCTLs) against multiple peptides derived from the cancer-testis antigens MAGE-A1 and MAGE-A3, and the overexpressed antigen hTERT, in newly diagnosed lung cancer patients as compared with aged-matched healthy individuals. The cumulative frequency of circulating peptide-specific pCTLs was found significantly higher in the cancer patients, varied widely and was not affected by radiotherapy and chemotherapy. Furthermore, this frequency was greatly different between the various tumor-antigen peptides. Under the light of recent evidence provided from animal models, these results indicate that the peptide-specific pCTL frequency might represent an important determinant for the fate of cancer immunotherapy. In addition, our results show that tumor-specific pCTLs of cancer patients can present functional differences regarding their proliferative capacity, intensity of multimer staining and lytic capacity, when compared with those of healthy individuals. Hence, our findings could have an important role for the design of improved immunotherapeutic approaches for lung cancer.
Abstract: Chronic obstructive pulmonary disease (COPD) is characterised by increased oxidative stress. Dietary factors, such as ample consumption of foods rich in antioxidants, such as fruit and vegetables, might have beneficial effects in COPD patients. The association between dietary shift to foods rich in antioxidants and lung function in COPD was investigated in a 3-yr prospective study. A total of 120 COPD patients were randomised to follow either a diet based on increased consumption of fresh fruit and vegetables (intervention group (IG)) or a free diet (control group (CG)). The mean consumption of foods containing antioxidants was higher in the IG than in the CG throughout the study period (p<0.05). The relationship between consumption of foods rich in antioxidants and percentage predicted forced expiratory volume in 1 s was assessed using a general linear model for repeated measures; the two groups overall were different in time (p = 0.03), with the IG showing a better outcome. In investigating the effect of several confounders (sex, age, smoking status, comorbid conditions and exacerbation) of group response over time, nonsignificant interactions were found between confounders, group and time. These findings suggest that a dietary shift to higher-antioxidant food intake may be associated with improvement in lung function, and, in this respect, dietary interventions might be considered in COPD management.
Abstract: A questionnaire survey on the attitude of healthcare workers towards pandemic influenza vaccination showed low acceptance (17%) of the pandemic vaccine. Factors associated with vaccine uptake were acceptance of seasonal influenza vaccination, medical profession and age. The main reason for refusal of vaccination was fear of side effects, which was stronger in those who received information on the safety of the vaccine mainly from mass media.
Abstract: Obstructive sleep-disordered breathing (SDB) in children has been associated with increased ventricular strain and decreased left ventricle (LV) diastolic function. The aim of this study was to assess systolic myocardial function in children with SDB of variable severity.
Abstract: INTRODUCTION: Sleep disruption and blood gas abnormalities, observed in patients with obstructive sleep apnoea (OSA) syndrome, prevent sleep-related restorative processes and induce chemical or structural central nervous system cellular injury. The aim of the study was to determine electroencephalogram (EEG) alterations related to the severity of OSA in patients with OSAS and the effect of the nasal continuous positive air pressure (nCPAP) treatment. MATERIALS AND METHODS: Polysomnography and vigilant EEGs were performed in subjects with possible OSA. The mean relative power was calculated for delta, theta, alpha and beta frequency bands. Thirty subjects without and 131 with OSA participated in this study. In 29 male patients with severe OSA, quantitative EEGs were re-evaluated after 6 months of CPAP treatment. RESULTS: Compared to subjects without OSA, patients with severe OSA showed an increase in relative theta and delta power (occipital, temporal and parietal areas). Six months of nCPAP treatment improved daytime sleepiness of OSA patients. EEG demonstrated a decrease in alpha (frontal, central and temporal areas) and theta (frontal areas) relative power. However, beta relative power was increased mainly in central, and delta relative power, in all brain areas. DISCUSSION: In conclusion, EEG slowing was observed in OSA patients. CPAP treatment improved daytime sleepiness of OSA patients in contrast to the alterations in alpha (decreased) and delta (increased) relative power suggesting a possible persistent brain dysfunction.
Abstract: Insulin induces electrochemical alterations in sheep visceral and parietal pleura, an effect abolished by the Na (+)-channel blocker amiloride and the Na (+)-K (+) pump inhibitor ouabain. The aim of this study was to further investigate the role of different electrolytes and glucose in these electrochemical changes.
Abstract: The aim of this study was to determine the impact of HRCT-confirmed emphysema on biomarkers evaluating airway and systemic inflammation in COPD patients. Forty-nine consecutive male COPD outpatients with stable COPD were divided in two groups according to the presence or absence of emphysema on HRCT. Patients underwent pulmonary function tests, plus assessment of exercise capacity, body composition and quality of life. Biomarkers were measured in serum (CRP, interleukin-6, TNF-alpha, leptin, adiponectin, osteocalcin, insulin growth factor-1, and systemic oxidative stress), in plasma (fibrinogen and VEGF) and in whole blood (B-type natriuretic peptide). TNF-alpha, 8-isoprostane and pH were additionally measured in exhaled breath condensate. Patients with emphysema had more severe lung function impairment, lower body-mass index and fat-free mass index, and poorer quality of life. Additionally, they presented increased systemic oxidative stress and plasma fibrinogen and lower BNP compared to patients without emphysema. After proper adjustment for disease severity, all differences remained with the exceptions of body-mass index, fat-free mass index and BNP. COPD patients with HRCT-confirmed emphysema present increased systemic oxidative stress and fibrinogen, suggesting that they may be more prone to the systemic consequences of COPD compared to patients without emphysema.
Abstract: Various systemic inflammatory markers have been evaluated for their value in acute exacerbations of chronic obstructive pulmonary disease (COPD). Leptin and adiponectin have been linked to acute exacerbations and stable COPD.
Abstract: Transmembrane resistance is a measure of ionic permeability. The occurrence of ionic permeability on the leptomeningeal tissue may suggest its contribution to the cerebrospinal fluid turnover. This property will support the background for a new in vitro model for the study of subarachnoid physiology. The aim of this study is to identify the occurrence and mean value of transmembrane resistance of leptomeninges in sheep at the basal state.
Abstract: Insulin promotes ion transportation across epithelia, mainly kidneys, leading to water and electrolyte abnormalities, possibly causing 'insulin oedema syndrome', which rarely presents as pleural effusion. Direct stimulation of sheep pleura by insulin and the possible electrophysiology mechanisms involved were investigated.
Abstract: Acute exposure to cigarette smoke is related to airway and systemic inflammation and oxidative stress. Little is known about the acute effect of cigarette smoking in smoking asthmatics. The aim of this study was to evaluate the acute effect of smoking in airway and systemic inflammation and oxidative stress in normal smokers and patients with properly treated well-controlled persistent asthma.
Abstract: Many patients with pneumonia develop pleural effusions. Pleural fluid vascular endothelial growth factor (VEGF) levels are known to be elevated in complicated parapneumonic effusion and seem to play a major role in the fibrotic process in the pleura.
Abstract: We evaluated pulmonologists variability in the interpretation of Vibration response imaging (VRI) obtained from healthy subjects and patients hospitalized for community acquired pneumonia.
Abstract: Physiology changes of the pleura in spontaneous pneumothorax (SP) patients are not known with its etiology remaining unclear. The aim of the study was to investigate the pleural electrophysiology profile of SP patients and to compare it with the normal pleural electrophysiology. Specimens from nine patients who underwent surgery for persistent SP were obtained after wedge resection (apical visceral) and apical pleurectomy (apical parietal) alongside with parietal specimens over the 8th-9th rib (caudal parietal). Specimens were mounted in Ussing chambers and trans-mesothelial resistance (R(TM)) was determined as a permeability indicator. Amiloride (Na(+) channel inhibitor) was used as an ion channel transportation inhibitor. R(TM) of apical visceral, apical parietal and caudal parietal pleura of SP patients was increased (P=0.042, 0.025 and 0.001, respectively) when compared to disease-free specimens obtained from lung lesion patients. Amiloride was unable to increase R(TM) in all cases. Histopathology of apical and caudal parietal specimens revealed inflammatory infiltration. In conclusion, pleural electrophysiology is altered in SP patients when compared with the electrophysiology of disease-free specimens. A similar observation was made for caudal pleura suggesting diffuse process that possibly involves inflammation as shown by the histopathology.
Abstract: Responses to nocturnal hypoxemia accompanying sleep-disordered breathing (SDB) may vary in different populations. Aims of this study were to (1) assess whether severity of SDB is related to uric acid excretion in North American and Southeast European children and (2) evaluate the interaction between nocturnal hypoxemia and country of children's origin in uric acid excretion.
Abstract: In Greece there is lack of large epidemiological studies regarding morbidity and mortality in primary health care. The aim of the present study was to estimate the prevalence and morbidity of the most common diseases in a large population sample from primary health care.
Abstract: To investigate whether there are any changes in the tidal breathing flow volume loop (TBFVL) in calm, non-dyspnoeic dogs with intratracheal masses.
Abstract: This study assessed the effect of corticosteroid treatment in the clearance of hydrothoraces in mice. Twenty-four C57BL/6 mice were divided into four groups and were injected intrapleurally with 500 microL sterilized PBS-BSA 1% to create isosmotic hydrothoraces. Two groups served as control and two groups were treated with dexamethasone. The control groups received intraperitoneally PBS, while the corticosteroid treatment groups received dexamethasone (1 mg/kg), both 5 min after the induction of hydrothorax. Control and treated animals were sacrificed 2 and 4 h after the induction of hydrothorax, and pleural fluid volume was measured. The pleural fluid volume 2 and 4 h after the induction of hydrothoraces was significantly lower in the dexamethasone-treated group compared to the untreated group. The rate of pleural fluid absorption 2 and 4 h after the induction of hydrothoraces was significantly higher in the dexamethasone-treated groups. The present study demonstrated that dexamethasone accelerates pleural fluid absorption in induced isosmotic hydrothoraces in mice. This newly reported property of dexamethasone may partly account for the clinical observation of faster resolution of pleural effusions when corticosteroids are administered in patients with pleural effusions of certain etiologies.
Abstract: To investigate whether surgical trauma in a rabbit adhesion formation model and the administration of normal saline (N/S), icodextrin (ID) and/or dimetindene maleate (DM) changes the permeability of the normal rabbit parietal peritoneum.
Abstract: BACKGROUND: Although obstructive sleep apnea (OSA) is related to dyslipidemia in adults, limited data are available regarding its effects on serum lipids during childhood. Aim of this study was to assess the potential relationships between severity of OSA and cholesterol or triglyceride levels in a cohort of Greek children. METHODS: Data from children with snoring who underwent polysomnography and complete serum lipids measurements during a specified study period were analyzed retrospectively. RESULTS: Overall, obese children (n = 261) had lower HDL cholesterol levels than non-obese subjects (n = 113) (49.6 ± 10.5 vs. 53.9 ± 11.4 mg/dL; p = 0.001) and higher triglyceride concentrations (69.8 ± 32.2 vs. 63.2 ± 27 mg/dL; p = 0.041). Non-obese subjects with moderate-to-severe OSA did not differ in triglycerides, total, and LDL cholesterol concentrations but had lower HDL cholesterol, when compared to non-obese children with primary snoring/mild OSA (50.4 ± 13.1 vs. 54.9 ± 10.7 mg/dL; p = 0.008). The risk for having low HDL cholesterol (≤40 mg/dL) was threefold higher in non-obese subjects with moderate-to-severe OSA than in those with primary snoring/mild OSA, even after adjustment for age and gender [OR = 3.44 (95% CI 1.44 to 8.24; p = 0.006)]. Concentrations of serum lipids in obese children were not associated with severity of OSA. HDL cholesterol was 48.5 ± 8.7 mg/dL in subjects with moderate-to-severe OSA and 50.0 ± 11.1 mg/dL in children with primary snoring/mild OSA (p = 0.519). CONCLUSIONS: HDL cholesterol levels are inversely related to severity of OSA in non-obese children with snoring.
Abstract: Since its cloning in 1994, leptin has emerged in the literature as a pleiotropic hormone whose actions extend from immune system homeostasis to reproduction and angiogenesis. Recent investigations have identified the lung as a leptin responsive and producing organ, while extensive research has been published concerning the role of leptin in the respiratory system. Animal studies have provided evidence indicating that leptin is a stimulant of ventilation, whereas researchers have proposed an important role for leptin in lung maturation and development. Studies further suggest a significant impact of leptin on specific respiratory diseases, including obstructive sleep apnoea-hypopnoea syndrome, asthma, COPD and lung cancer. However, as new investigations are under way, the picture is becoming more complex. The scope of this review is to decode the existing data concerning the actions of leptin in the lung and provide a detailed description of leptin's involvement in the most common disorders of the respiratory system.
Abstract: Body composition is an important parameter for patients with chronic obstructive pulmonary disease (COPD) whereas the association between asthma and obesity is not fully understood. The impact of severe refractory asthma (SRA) on fat free mass (FFM) has not been investigated.
Abstract: Background: The role of hormones in the transport mechanisms of human fetal membranes in pregnancy is unclear. Estrogens are essential hormones in pregnancy and they play an important role in the ion transport via membranes. Aim: The aim of this study was to investigate the effect of 17beta-estradiol on transepithelial electrical resistance in the human amniochorion. Material and Methods: Specimens of human fetal membranes were obtained. 17beta-estradiol, tamoxifen and their combination were added in an Ussing chamber. Transepithelial resistance was measured before and after the addition of each solution. Results: An increase in transepithelial resistance was seen after the addition of estradiol to both sides of the membranes. The effect was rapid with a peak at the 1st min of application and dose-depended. Tamoxifen, caused a similar effect but smaller in magnitude and shorter in duration. Tamoxifen in combination with estradiol inhibited only in part the action of estradiol. Conclusions: These results suggest that estradiol induces a rapid increase of transepithelial resistance in human fetal membranes in vitro via a non-genomic pathway. It is possible those changes in transepithelial resistance play a role in the control of permeability of human amniochorion.
Abstract: Insulin directly changes the sheep pleural electrophysiology. The aim of this study was to investigate whether insulin induces similar effects in human pleura, to clarify insulin receptor's involvement, and to demonstrate if glibenclamide (hypoglycemic agent) reverses this effect.
Abstract: Matrix metalloproteinases (MMPs) have been implicated in the escalation of fibrosis and remodeling which are central to the subsequent progression of a parapneumonic pleural effusion to empyema.
Abstract: To evaluate the prevalence and severity of COPD in a primary care population participating in a spirometry program. Differences between newly and previously diagnosed COPD patients were identified.
Abstract: This study aimed to examine whether EBV seropositive patients with lung cancer have an altered virus-specific CTL response, as compared to age-matched healthy controls and whether any variation in this response could be attributed to senescence.
Abstract: Nocturnal urinary sodium excretion is related to blood pressure (BP) levels. Elevated BP and increased nocturnal natriuresis have been demonstrated in adults with sleep apnea. Although evidence indicates increased BP in children with obstructive sleep-disordered breathing (SDB), it is unknown whether these children have also enhanced urinary sodium excretion.
Abstract: Background: Noninvasive ventilation (NIV) has been found to be an essential technique to treat chronic respiratory failure (CRF) resulting from restrictive thoracic disorders (RTD). The last decades were characterized by the expansion of NIV to treat patients suffering from various other conditions, such as chronic obstructive pulmonary disease (COPD) and obesity hypoventilation syndrome (OHS). Objectives: The aim of this study was to evaluate the effect of NIV on health-related quality of life (HRQoL) of patients with CRF during 2 years and to identify parameters associated with changes in HRQoL. Methods: Ninety-one patients with CRF [35 COPD; 17 RTD; 28 OHS; 11 neuromuscular diseases (NMD)] participated. HRQoL was assessed with the SF-36 questionnaire. Additional measurements included blood gases, pulmonary function tests, dyspnea, daytime sleepiness, exacerbations and hospitalizations. The patients were evaluated every 3-6 months. Results: Improvements in SF-36 physical component summary (PCS, p < 0.0001) and mental component summary (MCS, p < 0.0001) scores in RTD and MCS in OHS (p = 0.01) and COPD (p = 0.003) were observed by the third month. PCS in OHS and COPD patients improved by the sixth month (p = 0.003 and p < 0.0001, respectively). NMD patients did not present improvements in HRQoL. Improvements in HRQoL were associated with improvements in PaO(2) and dyspnea in COPD patients, and with total hours of daily ventilator use, improvement in dyspnea, pressure support and expiratory positive airway pressure in RTD patients. Conclusion: Home NIV is consistently effective in improving HRQoL and physiological parameters in patients with CRF. Randomized trials to identify subgroups of COPD responders are justified by our results.
Abstract: Matrix metalloproteinase-9 (MMP-9) plasma levels correlate with C-reactive protein (CRP) concentrations and they are both increased in adults with obstructive sleep apnea (OSA). No studies have evaluated MMP-9 levels in children with sleep apnea and CRP is not consistently elevated in pediatric OSA. The aim of this investigation was to evaluate the association of severity of OSA, adiposity, and CRP with MMP-9 plasma levels in Greek children.
Abstract: COPD is a diverse disease entity with multiple dimensions that uniquely define the patient's performance, morbidity and mortality. FEV(1) is both the traditional metric used to define the progression of COPD as well as the strongest spirometric predictor of mortality in COPD patients. However, besides pulmonary functional abnormalities, COPD is also associated with significant systemic effects. Therefore, the global assessment of an affected patient should include different aspects of the consequences of this disorder, beyond the "gold-standard" assessment of airflow limitation. Quantification of the patient's dyspnea, body composition as expressed by BMI, simple measures of exercise capacity such as the 6MWD, assessment of comorbidities and identification of characteristics related to different phenotypes are features that may lead to more optimal management of such patients.
Abstract: Accumulating evidence confirms the presence of pan-airway inflammation in allergic rhinitis patients. Smoking is known to affect the asthmatic airway inflammation. However, no study has evaluated the impact of smoking on airway inflammation of allergic rhinitis patients.
Abstract: Adenotonsillar tissue of children with obstructive sleep-disordered breathing (SDB) has increased content of cysteinyl leukotrienes (CysLTs) and expression of CysLTs receptors. Furthermore, CysLTs concentrations in the nasal exhaled breath condensate of children with sleep apnea are elevated.
Abstract: Defects in the human DNA mismatch repair genes (MMR) hMSH2 and hMLH1 are responsible for the development of sporadic and hereditary colorectal cancers. The role of MMR genes in the pathogenesis of lung cancer has not been elucidated. The aim of this study was to address the phenotypic mRNA expression profiles of mismatch DNA repair system in lung cancer.
Abstract: The aim of the present study was to evaluate the levels of VEGF, 8-isoprostane and TNF-alpha in EBC and serum of patients with primary lung cancer prior to the initiation of any treatment, in order to evaluate their possible diagnostic role. Furthermore, associations between VEGF, 8-isoprostane and TNF-alpha levels in EBC and serum with clinicopathologic factors were investigated. We enrolled 30 patients with lung cancer (mean age 65.2+/-10.5 years) and 15 age and gender-matched healthy smokers as controls. Serum and EBC were collected before any treatment. TNF-alpha, VEGF and 8-isoprostane levels in EBC and serum were analyzed by an immunoenzymatic method (ELISA). A statistically significant difference was observed between lung cancer patients and the control group regarding the values of TNF-alpha, both in EBC (52.9+/-5.0 pg/ml vs. 19.4+/-3.9 pg/ml, p<0.0001) and serum (44.5+/-6.3 pg/ml vs. 22.2+/-4.3 pg/ml, p=0.035). Moreover, EBC VEGF levels were higher in patients with T3-T4 tumor stage compared to T1-T2 (9.3+/-2.8 pg/ml vs. 2.3+/-0.7pg/ml, p=0.047). A statistically significant correlation was also observed between serum and EBC values of VEGF (r=0.52, p=0.019). In addition, serum levels of VEGF were higher in lung cancer patients than in controls (369.3+/-55.1 pg/ml vs. 180.5+/-14.7 pg/ml, p=0.046). VEGF serum levels were also found higher in patients with advanced stage of disease (IIIB-IV) and distant nodal metastasis (N2-N3). No differences were observed in 8-isoprostane in EBC between lung cancer patients and controls. In contrast, serum 8-isoprostane levels were higher in lung cancer patients compared to controls (24.9+/-3.6 pg/ml vs. 12.9+/-1.6 pg/ml, p=0.027) and were higher in patients with advanced disease. All three biomarkers presented acceptable reproducibility in the EBC on two consecutive days. In conclusion, we have shown that TNF-alpha, VEGF and 8-isoprostane are elevated in the serum of lung cancer patients and increased serum VEGF and 8-isoprostane levels are related to advanced disease. In EBC, increased TNF-alpha levels were observed in lung cancer patients, whereas increased VEGF levels were observed in advanced T-stage. Further longitudinal studies are warranted for the evaluation of the prognostic role of these biomarkers in lung cancer.
Abstract: Several studies have indicated considerable variability in the biological results of different tuberculin preparations in different geographical areas or even within a single region.
Abstract: Adults with obstructive sleep apnea have increased sympathetic activity. It was hypothesized that in children with symptoms of obstructive sleep-disordered breathing (SDB), morning urine levels of catecholamines correlate with severity of nocturnal hypoxemia.
Abstract: The pathways underlying chronic obstructive pulmonary disease exacerbations (ECOPD) remain unclear. This study describes the clinical, functional and biochemical changes during recovery from ECOPD. Thirty hospitalized patients with Anthonisen's type-I ECOPD were evaluated on days 0 (admission), 3, 10 and 40. A five-symptom score (TSS), performance status and quality of life were evaluated. Post-bronchodilator spirometry, blood gases, oxidative stress, C-reactive protein (CRP), serum amyloid-A (SAA), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and fibrinogen were also measured. Patients were classified as early- or late-recoverers, based on whether dyspnea had returned to pre-exacerbation level by day 10. Most clinical, functional and biochemical parameters improved during follow-up. CRP and IL-6 levels reduced on Day 3 (p<0.05), whereas SAA on Day 10 (p<0.01). TNF-alpha was reduced on Days 3 and 10, but on Day 40 its levels returned to baseline. Fibrinogen and WBC reduced only by day 40. TSS and dyspnea were correlated inversely with FEV(1) on days 3, 10 and 40. Although late-recoverers had lower FEV(1) on admission, none of the reported measurements on admission and day 3 predicted early recovery. During recovery from ECOPD, symptomatic improvement correlates only with post-bronchodilator FEV(1) whereas systemic inflammatory burden subsidence does not correlate with clinical and functional changes. Although late-recoverers have lower FEV(1) on admission, none of the measured parameters is able to predict early symptomatic recovery.
Abstract: Matrix metalloproteinases (MMPs) are zinc-endopeptidases responsible for degradation of the extracellular matrix (ECM) components including basement membrane collagen, interstitial collagen, fibronectin, and various proteoglycans, during normal remodeling and repair processes. The turnover and remodeling of ECM must be tightly regulated since excessive or inappropriate expression of MMPs may contribute to the pathogenesis of tissue destructive processes associated with lung inflammation and disease. Despite the fact that our knowledge in the field of MMP biology is rapidly expanding, the role of MMPs in the pathogenesis of lung diseases is still not clear. The aim of the present review is to present the basic principles of MMP biology and, subsequently, to focus on the clinical and experimental evidence related to MMP activity in various lung disorders, including lung cancer, pleural effusions, chronic obstructive pulmonary disease, asthma, acute respiratory distress syndrome and interstitial lung diseases.
Abstract: Tobacco smoking has been considered the most important risk factor for chronic obstructive pulmonary disease (COPD) development. However, not all smokers develop COPD and other environmental and genetic susceptibility factors underlie disease pathogenesis. Recent studies have indicated that the impairment of TLR signaling might play a crucial role in the development of emphysema. For this purpose we investigated the prevalence and any possible associations of common TLR polymorphisms (TLR2-R753Q, TLR4-D299G, and TLR4-T399I) in a group of 240 heavy smokers (>20 pack years), without overt atherosclerosis disease, of whom 136 had developed COPD and 104 had not. The presence of TLR4-T399I polymorphism was associated with a 2.4-fold increased risk for COPD development (P = .044), but not with disease stage or frequency of exacerbations. Considering that infections contribute to COPD and emphysema pathogenesis, our findings possibly indicate that dysfunctional polymorphisms of innate immune genes can affect the development of COPD in smokers. Although this finding warrants further investigation, it highlights the importance of impaired innate immunity towards COPD development.
Abstract: A local redox imbalance has been reported in pulmonary sarcoidosis. However, so far no study has described a systemic redox imbalance in this context. The aim of the present study was to evaluate the systemic oxidative stress in patients with sarcoidosis and determine its relationship to treatment and indices of disease severity.
Abstract: In cases of patients with disseminated lymphadenopathy, the differential diagnosis has to include both benign and malignant causes, including sarcoidosis, metastatic disease, lymphoma and, although rarely present, tuberculosis. Tuberculosis is still one of the most frequently occurring infectious diseases worldwide. However, disseminated mycobacterial lymphadenitis is rare in immunocompetent patients.
Abstract: The peritoneal mesothelium is a barrier to ion transport in peritoneal dialysis. Cimetidine is an H2 receptor antagonist and a potent inhibitor of Na+/H+ antiporter, which is found in the plasma membranes of various cell types, including mesothelial cells. Recent reports linked Na+/H+ antiporter stimulation with increasing peritoneal fibroblast proliferation. The aim of the present study was to investigate by means of Ussing chamber experiments the effect of cimetidine on the transmesothelial electrical resistance (R) of isolated visceral sheep peritoneum. Peritoneal samples obtained from adult sheep were collected from the slaughterhouse and transferred in oxygenated Krebs-Ringer bicarbonate (KRB) solution to the laboratory within 30 minutes of the animal's death. The peritoneal tissue was transferred in a cooled KRB solution (4 degrees C, pH 7.5) bubbled with 95% O2/5% CO2. A planar sheet of the visceral peritoneum was mounted in an Ussing-type chamber and cimetidine (10(-3) mol/L) was added to the solution on the apical and basolateral sides. The R was measured before and for 15 minutes serially after addition of the cimetidine. Results presented are the means +/- standard error of the mean of 12 experiments. Addition of cimetidine basolaterally induced, within 1 minute, an increase in the deltaR of 35.97% +/- 12.01% (p < 0.05), which returned to baseline after 15 minutes. The action of cimetidine on the apical side of the membrane was similar, with a rapid rise in the deltaR of 47.3% +/- 16.4% (p < 0.05) and a subsequent decline to control values. The R is inversely correlated with membrane permeability. The results of the present study indicate a rapid action of cimetidine on the permeability of visceral sheep peritoneum, probably through inhibition of mesothelial Na+/H+ antiporter. The increase in R observed after addition of the cimetidine clearly indicates the existence of Na+/H+ antiporter on both sides of visceral sheep peritoneum. The clinical implications of our results should be further investigated.
Abstract: Neoangiogenesis has been documented in small cell lung carcinoma (SCLC). In addition, antiangiogenic therapies are being tested in clinical trials that involve SCLC. However, study of the underlying mechanisms has been performed almost exclusively in cell lines. In the current study, we immunostained 30 biopsy samples of SCLC with antibodies to hypoxia inducible factor-1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF), vascular endothelial growth factor-receptor 1 (VEGF-R1/flt-1) and vascular endothelial growth factor-receptor 2 (VEGF-R1/flk-1). The immunoreactivity was analyzed using a bivariate Spearman correlation test and linear regression analysis. We found significant correlation between HIF-1 alpha nuclear staining and VEGF staining. Moreover HIF-1 alpha+/VEGF+ cases were associated with poor survival. We also found a positive correlation between VEGF and VEGF-R2 expression. We suggest that a HIF-1 alpha/VEGF angiogenic pathway may exist in vivo in SCLC, similar to that in non-SCLC. Our data also suggest a potential VEGF/VEGFR-2 autocrine pathway in SCLC. The inclusion of novel inhibitors to HIF-1 alpha and other factors may optimize antiangiogenic interventions in SCLC.
Abstract: Aldosterone is a key component of the renin-angiotensin-aldosterone system, and spironolactone, an aldosterone receptor blocker, shows beneficial effects in patients with end-stage renal disease and heart failure. The aim of the present study was to investigate by means of Ussing chamber technique the effect of spironolactone on the transmesothelial permeability of visceral sheep peritoneum in vitro. Peritoneal samples from the omentum of adult sheep were collected immediately after slaughter in a cooled and oxygenated Krebs-Ringer bicarbonate (KRB) solution. Isolated intact sheets of peritoneum were mounted in an Ussing-type chamber. Spironolactone (10(-5) mol/L) was added apically and basolaterally to the KRB solution. The transmesothelial resistance (R) was measured before and serially for 30 minutes after the addition of the substances. Data present the mean +/- standard error of 6 experiments in each case. The control R was 19.8 +/- 0.36 omega x cm2. The addition of spironolactone resulted in a reduction in the R, which became significant on both sides of the membrane within 10 minutes and remained significantly different thereafter. The maximum reduction of R (deltaR%) reached 24.8% +/- 2.3% (p < 0.01) apically and 26.3% +/- 3.2% (p < 0.01) basolaterally. Our data clearly show that spironolactone increases the permeability of visceral sheep peritoneum in a lasting manner. Increased peritoneal permeability could result in increased sodium removal, which has acknowledged beneficial effects both in patients undergoing peritoneal dialysis and in patients with heart failure. Further clinical studies investigating the effect of spironolactone on sodium removal in peritoneal dialysis are justified.
Abstract: Existing evidence regarding spontaneous anti-survivin humoral responses in lung cancer is inconclusive. Moreover, despite that cancer cell death elicited by radiotherapy and some chemotherapeutic agents seems to be immunogenic, information about the possible effect of treatment on these responses, is lacking. Serum samples from 33 small cell lung cancer (SCLC) and 117 non-small cell lung cancer (NSCLC) patients upon diagnosis, and from 100 controls, were tested by ELISA for anti-survivin antibodies. Cutoff was set to the mean+2SD of controls. 7.7% of NSCLC, none of the SCLC patients and 2% of the controls appeared with elevated antibody levels (OR 3.6, 95% CI 0.7-17.3 for NSCLC, OR 0.6, 95% CI 0.03-12.6 for SCLC). Measurement of antibodies in 76 NSCLC patients post therapies and during their follow-up, revealed that in 12 NSCLC patients the antibody levels increased up to 2-38 times, and in seven others, they decreased by 2-8 times. No significant correlation was uncovered between either the antibody levels upon diagnosis or their changes post therapies and during follow-up, and any clinicopathological parameter, their response to therapy and survival. Survivin does not induce considerable humoral responses in lung cancer. Potentially, however, strong anti-survivin antibody responses can be elicited during the post therapy and follow-up of the patients, whose clinical significance remains to be elucidated. These findings, together with our previous data concerning survivin expression and the related cytolytic T cell responses in lung cancer, signify a high tolerogenic potential of this tumor-associated antigen.
Abstract: The aim of the study was to compare the electrophysiology profile of sheep pleura originated from different locations of the pleural cavity with the respective profile in humans. Sheep specimens obtained from upper and lower lung lobes, 1st-4th and 8th-12th rib, ventral-dorsal diaphragm and mediastinum were mounted between Ussing chambers. Human visceral tissues were obtained from patients subjected to lobectomy. Trans-mesothelial resistance (R(TM)) was determined as an indicator of the tissue permeability, while amiloride and ouabain were used as inhibitors of cellular transportation via ion transporters. Control values R(TM) were low in lower lobe visceral, caudal costal parietal and diaphragmatic pleura. Amiloride increased R(TM) at all locations except upper visceral and mediastinum. Higher R(TM) increases were found in caudal parietal and dorsal diaphragmatic samples. Ouabain increased R(TM) of lower visceral, caudal parietal and diaphragmatic pleura but not of mediastinal specimens. Observations made in sheep tissue were comparable with human visceral, parietal and mediastinal regions. In conclusion, results suggest heterogeneity of trans-mesothelial permeability among different pleural locations in sheep as was the case for humans. Thoracic surgeons should consider physiology function of each part of pleural cavity before pleural tissue manipulation. Observations made in sheep may be used to understand human physiology.
Abstract: Azithromycin is used in long-term, low-dose treatment of airway diseases where airway wall remodelling is present. Since it improves total score symptom and respiratory function of such patients, we hypothesise that azithromycin's additional clinical benefits are due to an inhibition of airway smooth muscle cell (SMC) proliferation. Rabbit tracheal SMCs were treated with azithromycin (10(-5) to 10(-6) M) in the presence or absence of 10% fetal bovine serum (FBS). The proliferation was estimated using the Cell Titer 96(R) AQ(ueous) One Solution Assay (Promega, Madison, WI, USA). Cell viability was assessed with Trypan blue staining and flow cytometry after 7-aminoactinomycin D (7-AAD) staining. Induction of autophagy was studied by indirect immmunofluorescence and/or Western blotting with antibodies against human smooth muscle alpha-actin, beclin 1, light chain 3 and caspase 3. The involvement of the phosphoinositide 3-kinase pathway was investigated with the inhibitors LY294002 and wortmannin. Incubation with azithromycin for 72 h in the presence of FBS reduced SMC proliferation and viability in a dose-dependent manner. Azithromycin treatment was accompanied by the formation of cytoplasmic vacuoles, characteristic of autophagy. All these effects were reversible after azithromycin removal and prevented by the autophagy inhibitor, 3-methyladenine, or LY294002, but not by wortmannin. In conclusion, azithromycin reduces proliferation and causes autophagy of airway SMCs.
Abstract: The association between systemic sclerosis and pulmonary arterial hypertension (PAH) is well recognized. Vascular endothelial growth factor (VEGF) has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis.
Abstract: The effect of dexamethasone on the transmesothelial electrical resistance (R(TM)) of sheep pleura was investigated by Ussing chamber experiments. Our results show that dexamethasone decreases the R(TM) of sheep pleurae, in part by stimulation of glucocorticoid receptors. This finding may be of importance in regard to the faster resolution of corticosteroid-treated pleural effusions.
Abstract: The data on long-term application of non-invasive ventilation (NIV) in patients with chronic respiratory failure due to COPD are contradictory. We evaluated the effect of the addition of NIV to optimal treatment for 1 year on the quality of life of stable hypercapnic COPD patients. NIV was offered to 49 of 58 initially enrolled consecutive patients, of whom 22 refused NIV and comprised the standard treatment group whereas 27 received NIV. Quality of life was assessed with the SF-36 questionnaire. Additional measurements included blood gases, pulmonary function tests, dyspnea, daytime sleepiness, exacerbations and hospitalizations. The NIV group showed a significant improvement in quality of life in the third month, both in the Physical (31+/-4 to 38+/-8, p<0.0001) and the Mental Component Summary Score (28+/-7 to 40+/-10, p=0.009), that was maintained until the twelfth month. PaCO2 decreased by the first month in the NIV group (54+/-4.5 to 44.6+/-5.6 mmHg, p<0.0001), and PaO2 rose during the sixth month (58.9+/-5.7 to 64.4+/-6.5 mmHg, p=0.004). Dyspnea and diurnal sleepiness improved significantly. No significant improvements were observed in the control group. Patients on NIV spent less days in the hospital compared to controls. NIV when added to optimal medical treatment has beneficial effects on quality of life in stable hypercapnic COPD patients, with additional improvements in arterial blood gases, dyspnea and daytime sleepiness.
Abstract: Although QuantiFERON-TB Gold (QFT-G) has been approved for the diagnosis of latent tuberculosis infection (LTBI), there are limited data regarding its performance in routine clinical practice. The aim of this study was to compare QFT-G 'In Tube' results, based on stimulation with Mycobacterium tuberculosis-specific antigens, with tuberculin skin test (TST) results in an unselected hospital-based Greek population.
Abstract: Exhaled breath condensate (EBC) analysis, a rather appealing and promising method, can be used to evaluate conveniently and non-invasively a wide range of molecules from the respiratory tract, and to understand better the pathways propagating airway inflammation. A large number of mediators of inflammation, including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, prostanoids, nitrogen oxides, peptides and cytokines, have been studied in EBC. Concentrations of such mediators have been shown to be related to the underlying asthma and its severity and to be modulated by therapeutic interventions. Despite the encouraging positive results to date, the introduction of EBC in everyday clinical practice requires the resolution of some methodological pitfalls, the standardization of EBC collection and finally the identification of a reliable biomarker that is reproducible has normal values and provides information regarding the underlying inflammatory process and the response to treatment. So far, none of the parameters studied in EBC fulfils the aforementioned requirements with one possible exception: pH. EBC pH is reproducible, has normal values, reflects a significant part of asthma pathophysiology and is measurable on-site with standardized methodology although some methodological aspects of measurement of pH in EBC (e.g. the effect of ambient CO(2), sample de-aeration, time for pH measurement) require further research. However, EBC pH has not been evaluated prospectively as a guide for treatment, in a manner similar to exhaled NO and sputum eosinophils. EBC represents a simple and totally non-invasive procedure that may contribute towards our understanding of asthma pathophysiology. Besides the evaluation of new biomarkers, the standardization of the already existing procedures is warranted for the introduction of EBC in clinical practice.
Abstract: Vascular endothelial growth factor (VEGF) is known to play crucial role in tumour angiogenesis. It is demonstrated that VEGF can be up-regulated by oxidative stress. The aim of this study was to determine the serum VEGF levels and oxidative stress in patients with primary lung cancer and to investigate their association with clinicopathologic factors. We measured serum VEGF levels and oxidative stress in 63 patients (age 63.02+/-1.12 S.E.M.) with primary lung cancer before any treatment (39 NSCLC and 24 SCLC; 6 patients stage I, 3 stage II, 25 stage III and 29 stage IV) and 25 normal subjects. The serum VEGF levels were measured with enzyme linked immunosorbent assay. Serum oxidative stress levels were detected by a commercially available assay (D-ROMs test, Diacron, Grossetto, Italy). The levels of oxidative stress in patients were higher than those in normal subjects (555.3+/-30.35 UCarr vs. 360.1+/-17.46 UCarr). Additionally, a significant difference was found in serum VEGF levels between lung cancer patients and healthy control subjects (428.1+/-38.42pg/ml vs. 298.8+/-19.89pg/ml, respectively, p=0.040). Interestingly, serum oxidative stress presented a significant correlation with serum VEGF levels in patients with lung cancer (r=0.542, p=0.002). Serum VEGF levels were significantly associated with the clinical staging (N-stage) of the patients (p=0.023), performance status (p=0.004) and age (p=0.004). In conclusion, oxidative stress and VEGF are significantly increased in patients with primary lung cancer. The correlation between them might implicate new aspects of the mechanisms controlling tumour angiogenesis and may present clinical interest in the future. Further studies are warranted to evaluate the role of oxidative stress and VEGF as possible biomarkers for the diagnosis and follow-up of patients with lung cancer.
Abstract: The need for non-invasive assessment of airway inflammation is imperative, since inflammatory airway diseases, such as asthma and COPD, are characterized by variation in their clinical presentation throughout their course. Exhaled breath condensate (EBC) collection represents a rather appealing method that can be used to conveniently and noninvasively collect a wide range of volatile and non-volatile molecules from the respiratory tract, without affecting airway function or inflammation. Although promising, EBC is currently used only as a research tool, due to the lack of appropriate standardization and the absence of reference values. The large number of measurable biomarkers and the diversity of the used methodologies are some of the points that hamper its wide clinical application. This review focuses mainly on the presentation of normal values of the most widely studied EBC markers as reported by investigators that have used healthy subjects as controls or as a basic study population. These biomarkers include hydrogen peroxide, NO-related products, arachidonic acid metabolites and pH. From those biomarkers, the only one with established reference values in healthy subjects is EBC pH, whereas the majority of the rest need further refinement and standardization of the methodologies used. Different subpopulations and the effect of various factors on healthy subjects are also reported, in an effort to delineate future directions that may lead to the establishment of reference values.
Abstract: Idiopathic pulmonary fibrosis (IPF) is a fatal illness characterized by progressive fibrosis resulting in severe dyspnea and impairment of lung function. Although the mechanisms by which lung fibrosis develops are not fully ascertained, recent findings suggest that oxidative stress may play an important role in the pathogenesis of tissue fibrosis.
Abstract: Obesity is the major confounding factor in the relationship between obstructive sleep apnea and increased risk for cardiovascular disease. The aim of the study was to investigate the association of sleep apnea severity with insulin resistance, leptin, and CRP levels in a cohort of male patients. Sixty-seven men referred to our sleep laboratory for evaluation of suspected obstructive sleep apnea syndrome (OSAS) were divided into three groups according to apnea severity: non-OSAS group (n=15), mild to moderate OSAS group (n=26), and severe OSAS (n=26). Insulin resistance was estimated by the homeostasis model assessment method. HOMA values were similar in the three groups: (3.2+/-2.2 vs. 3.3+/-1.8 vs. 3.6+/-1.5, respectively, p=0.71). Leptin levels were higher in the mild to moderate OSAS group (23.1+/-21.8 ng/ml, p<0.05) and in the severe OSAS group (20.2+/-17.5 ng/ml, p<0.05) than in the non-OSAS group (9.4+/-6.4 ng/ml). CRP levels were significantly higher in severe sleep apnea (0.35+/-0.3 vs. 0.19+/-0.1 mg/dl, p<0.05). In multiple regression analyses, waist-to-hip ratio (WHR) was the most significant determinant of HOMA estimation for insulin resistance. WHR and the percentage of total sleep time spent with hypoxemia (%TST with SaO2 <90%) were significant predictors for leptin levels, while body mass index (BMI) and the %TST with SaO2 <90% were the best predicting parameters for CRP levels. Insulin resistance estimated by the HOMA method in male patients with OSAS was not associated with sleep apnea severity independent of obesity. The severity of nocturnal hypoxemia was associated with leptin and CRP levels independent of obesity.
Abstract: Correlation between obesity and obstructive sleep apnea has been documented in both adults and children. This investigation evaluated importance of body mass index (BMI) in relation to age as predictor of severity of obstructive sleep-disordered breathing (SDB). Children with habitual snoring referred for polysomnography were recruited. BMI Z score (> or =1.036 vs <1.036, i.e. at risk for overweight or overweight vs normal) was assessed as predictor of severity of SDB (apnea-hypopnea index [AHI] >five vs < or =five episodes per hour) at different ages (< or =6 vs >6 years). Two hundered eighty-four participants were recruited: 75 young children (4.6 +/- 1 years) with high BMI (1.9 +/- 0.7); 95 young subjects (4.5 +/- 1.1 years) with low BMI (-0.2 +/- 1.3); 55 older children (9.2 +/- 1.8 years) with high BMI (1.8 +/- 0.5); and 59 older participants (9.7 +/- 2.2 years) with low BMI (-0.2 +/- 1.1). Odds ratios for AHI >5 in young/high BMI children, young/low BMI subjects, and older/high BMI subjects relative to older/low BMI participants were: 6.5 (95% confidence interval 2.1-19.9), 7.3 (2.4-22) and 2 (0.6-7.3), respectively. Large tonsil size was associated with young age (odds ratio 1.97; 1.2-3.3). Among children with habitual snoring, adiposity does not predict severity of obstructive SDB in early childhood probably due to the prominent role of adenotonsillar hypertrophy. However, it may have a more important contribution to severity of SDB in older children.
Abstract: Sleep apnoea frequently affects patients with end-stage renal disease. However, it is still unclear whether or to what extent sleep disorders may affect functional capacity and quality of life in haemodialysis patients. We tested the hypothesis that apneic dialysis patients due to the lack of restorative sleep will have a further reduced functional capacity and further compromised quality of life compared to their non-apneic counterparts.
Abstract: 1. The factors that regulate human fetal membrane transport mechanisms are unknown. The aim of the present study was to investigate the effect of progesterone on transepithelial electrical resistance (R(TE)) in the human amniochorion. 2. Fetal membranes from uncomplicated term pregnancies were obtained immediately after vaginal or Caesarean deliveries. Intact pieces were mounted as planar sheets separating an Ussing chamber. Progesterone (10(-4) to 10(-7) mol/L), mifepristone (10(-4) to 10(-8) mol/L) and combinations of progesterone plus mifepristone were applied to the chambers facing the fetal or maternal sides of the membrane. The R(TE) was measured before and 1, 5, 10, 15, 20, 25, 30, 45 and 60 min after each solution was added (at 37 degrees C). The R(TE) was calculated in Omega.cm(2), according to Ohm's law. 3. The mean (+/-SEM) basal value of R(TE) before the application of any substance in all experiments was 29.1 +/- 0.4 Omega.cm(2). The net change in the R(TE) (Delta R(TE)) in relation to the basal value was calculated in each experiment. Progesterone, mifepristone and the combination of progesterone and mifepristone induced a rapid, surge-type increase in R(TE) during the 1st min on both sides of the membrane. The combination of progesterone plus mifepristone exerted a synergistic action. The effect was stronger on the fetal side than on the maternal side for all substances tested (P < 0.05). The highest Delta R(TE) during the 1st min on the fetal side was seen with the combination of progesterone plus mifepristone (4.0 +/- 0.3 Omega.cm(2)) and the lowest Delta R(TE) occurred with mifepristone (1.5 +/- 0.1 Omega.cm(2)). 4. The present results demonstrated that the R(TE) of human fetal membranes increases rapidly in response to progesterone. It is possible that changes in R(TE) play a role in the control of membrane permeability during pregnancy.
Abstract: Cytokines are proteins produced by leukocytes and other cells that function as intercellular mediators acting on several target tissues, resulting in multiple biologic actions. Over the last decade, medical research has explored the interaction between cytokines and sleep disorders. The aim of this review is to illustrate recent advances in knowledge about the relationship between cytokines and disorders of excessive sleepiness. Cytokines may have an important role in mediating excessive daytime sleepiness in sleep loss or insomnia. Alterations of the immune system have also been associated with narcolepsy. The relationship between cytokines and hormonal regulatory mechanisms may explain symptoms like fatigue and sleepiness in chronic inflammatory diseases. Cytokines may play an important role in the pathogenesis of obstructive sleep apnea and cardiovascular consequences of this condition. New biologic treatments targeting cytokines have been investigated in conditions characterized by sleep disturbance.
Abstract: The fraction of exhaled NO (FeNO) is valuable for the follow-up of asthmatic patients. However, its usefulness as a screening tool for asthma is not established.
Abstract: Polyvalent vaccination represents a recent attempt to improve the effectiveness of lung cancer immunotherapy. This study aimed to investigate whether a gene expression pattern of tumor-associated antigens (TAA) would exist indicating that their use will be most appropriate for the polyvalent vaccination of Caucasian non-small cell lung carcinoma (NSCLC) patients. We examined the concomitant expression of genes belonging to different TAA families for which expression frequencies either have never been detected in NSCLC or vary widely in the literature.
Abstract: Transcription factor forkhead box protein 3 (Foxp3) specifically characterizes the thymically derived naturally occurring regulatory T cells (Tregs). Limited evidence indicates that it is also expressed, albeit to a lesser extent, in tissues other than thymus and spleen, while, very recently, it was shown that Foxp3 is expressed by pancreatic carcinoma. This study was scheduled to investigate whether expression of Foxp3 transcripts and mature protein occurs constitutively in various tumor types.
Abstract: Survivin and its variant survivin-2B have been considered as potential candidates for cancer immunotherapy. The magnitude however of spontaneously occurring CD8(+) T cells circulating precursor CTLs (pCTL), has never been evaluated. We set out to measure in 20 patients with lung carcinomas and 5 aged matched healthy male individuals (expressing HLA-A2 and/or -A24), the frequency of pCTLs specific for two naturally processed and presented peptides of survivin (LTLGEFLKL presented by HLA-A2) and survivin-2B (AYACNTSTL presented by HLA-A24) since these peptides are the only ones used in immunotherapeutic trials. The frequency of peptide-specific pCTLs was estimated using a sensitive method that combines HLA-multimer flow cytometric technology with a previous step of in vitro amplification under limiting dilution conditions. Anti-survivin or anti-survivin-2B specific CTL clones were not detected in 17 out of the 21 tested patients, and in none of the healthy individuals. In a number of peripheral blood mononuclear cell microcultures of the remaining 4 patients, diffuse clusters stained weakly by the HLA-multimers were observed which were not amplified after further stimulation and, therefore, they were finally considered as negative. The significance of the levels of spontaneously occurring CTL-responses against survivin and survivin-2B peptides, in cancer patients and cancer-free subjects, remains to be elucidated and it would be interesting to be considered in relation to the clinical efficacy of anti-cancer vaccination protocols.
Abstract: We report a case of endobronchial metastasis from prostate adenocarcinoma. A patient with a history of prostate cancer under complete androgen blockade presented to the respiratory department complaining of dyspnea and dry coughing. Flexible bronchoscopy showed multiple polypoid lesions in the tracheobronchial tree and the immunohistochemical studies on the biopsy specimen determined the diagnosis. The patient was treated with paclitaxel, estramustine phosphate and carboplatine, and experienced symptoms suppression. To our knowledge, this is the first case of endobronchial metastasis of a patient with androgen refractory prostate cancer without any evidence of extrathoracic metastasis. The current report also emphasises the need for a multidisciplinary approach for cases of endobronchial metastases, with the collaboration of pneumologists, urologists, pathologists and oncologists.
Abstract: The relative importance of obesity and adenotonsillar hypertrophy in the pathogenesis of obstructive sleep-disordered breathing (SDB) in childhood is unclear. Adenotonsillectomy (AT) for SDB is not always curative, and obese children are at increased risk for residual disease postoperatively.
Abstract: Data about the predictors of smoking among adolescents in Greece are sparse. We tried to identify factors associated with current cigarette smoking among in-school adolescents in Greece in the context of GYTS study.
Abstract: Legionnaires' disease continues to be a public health concern in passenger ships. This study was scheduled in order to investigate Legionella spp. colonization of water distribution systems (WDS), recreational pools, and air-conditioning systems on board ferries and cruise ships in an attempt to identify risk factors for Legionella spp. colonization associated with ship water systems and water characteristics.
Abstract: The peritoneal mesothelium is a biologic barrier to water and ion transport. Its functional and structural integrity is crucial for peritoneal dialysis treatment. In vivo studies have shown that corticosteroids increase transcellular water transport and ultrafiltration of the rat peritoneum. In the present study, we used Ussing chamber technique to investigate the effect of dexamethasone on the transmesothelial permeability of the visceral sheep peritoneum in vitro. Peritoneal samples from the omentum of adult sheep were collected in a cooled and oxygenated Krebs-Ringer bicarbonate (KRB) solution immediately after the death of the animals. Isolated intact sheets were mounted in an Ussing-type chamber. Dexamethasone (10(-6) mol/L) and its inhibitor mifepristone (10(-5) mol/L) were added apically and basolaterally, alone and in combination to the KRB solution. The transmesothelial resistance (R) was measured for 1 hour before and serially after the addition of the substances. Data are expressed as mean +/- standard error of 6 experiments in each case. The control R was 21.5 +/- 0.42 omega x cm2. Dexamethasone induced a significant reduction of R within 15 minutes, which continued for the entire experiment. The maximum effect (% deltaR) was observed at 30 - 60 minutes after the addition of dexamethasone apically 46.2% +/- 7.14% (p < 0.01) and basolaterally 35.3% +/- 7.76% (p < 0.01). Mifepristone acted as an agonist on both sides of the membrane and significantly inhibited the dexamethasone effect. Our findings clearly indicate that dexamethasone rapidly increases the transmesothelial permeability of visceral sheep peritoneum. The rapid effect implicates dexamethasone and probably mifepristone as being involved in a common nongenomic pathway. Further investigation is necessary to elucidate the underlying mechanisms and perspectives of these findings.
Abstract: Cardiac secretion of brain natriuretic peptide (BNP) increases with the progression of congestive heart failure (CHF). The plasma measurement of BNP emerged recently as a useful, cost-effective biomarker for the diagnosis and prognosis of CHF.
Abstract: The aim of the study was to investigate if human pleura from different anatomical locations presents electrophysiology differences. Specimens were stripped over the 2nd-5th rib (cranial), 8th-10th rib (caudal), and mediastinum during open surgery and were mounted between Ussing chambers. Amiloride and ouabain were added towards mesothelial surface and trans-mesothelial potential difference (PD) was measured after 1, 5, 10 and 20 min. Trans-membrane resistance (R) was calculated from Ohm's law. R increased after amiloride addition, for cranial (net increase of 0.40 Omega x cm(2)) and caudal (1.16 Omega x cm(2)) pleural pieces. Mediastinal pleura R remained unchanged (0.09 Omega x cm(2)). R increase was higher for caudal than cranial (P=0.029) or mediastinal tissues (P=0.002). R increased after ouabain addition for caudal (1.35 Omega x cm(2)) and cranial (0.56 Omega x cm(2)) pleural pieces. Mediastinal pleural tissue did not respond (0.20 Omega x cm(2)). Caudally located pleura responded greater than cranial (P=0.043) or mediastinal (P=0.003) pleural tissues. Human pleura shows electrophysiology differences according to the location within the pleural cavity. Surgeons may waste mediastinal pleura when needed but should leave intact caudal parietal pleura, which seems to be electrophysiologically the most important part of the pleural cavity.
Abstract: T lymphocytes and especially the subpopulations of CD8+ cells are believed to have a key role in COPD pathophysiology, but there are only few data regarding the role of these cells in COPD exacerbation. Aim: We aimed to study prospectively changes of CD8+ T-lymphocyte subpopulations in the sputum of COPD patients at the onset of mild exacerbations and at a stable condition in order to provide further insight in the pathophysiology of the disease.
Abstract: Increased expression of cysteinyl leukotriene receptors (cysteinyl leukotriene receptor-1 [LT1-R]; cysteinyl leukotriene receptor-2 [LT2-R]) has been detected in adenotonsillar tissue from children with sleep-disordered breathing (SDB) compared to control subjects. LT1-R has been localized in myeloperoxidase-positive cells. This phenomenon possibly contributes to lymphoid tissue enlargement and may be related to systemic inflammation.
Abstract: Pediatric studies revealed associations of obstructive sleep-disordered breathing (SDB) with inflammation, metabolic dysfunction, and elevated blood pressure. Evidence about effects of adenotonsillectomy on these abnormalities is scarce. Aim of this investigation was to assess changes in C-reactive protein (CRP), circulating intercellular adhesion molecule-1 (cICAM-1), insulin and blood pressure levels after adenotonsillectomy for SDB in Greek children.
Abstract: The aim of our study was to identify predictive factors for the development of residual pleural thickening (RPT) in patients with tuberculous pleurisy (TP).
Abstract: Values of spirometry indices vary among subjects of similar age, gender and somatometrics but of different ethnic origins. Low socioeconomic status in childhood is inversely related to lung growth. The aim of this investigation was to assess spirometry values in Gypsy children and compare them to reported values for Caucasians. Gypsy students attending primary schools in Central Greece were recruited. Spirometry indices were measured using a portable spirometer. Regression analysis was applied to construct prediction equations for forced vital capacity (FVC) and other spirometric indices (FEV(1), FEF(50), FEF(25), FEF(25-75)) based on standing height. Predicted spirometric values were compared to values for Caucasians from published studies. In 152 children (ages 5-14 years; 57 girls) lung function increased linearly with height: spirometry index=intercept+[slopexheight], (r(2)=0.68 for FVC and FEV(1) in girls; r(2)=0.78 for FVC and r(2)=0.74 for FEV(1) in boys). Excluding boys-but not girls-in puberty increased fit for FVC (r(2)=0.83) and FEV(1) (r(2)=0.79). Mean predicted values were 5-10% lower than values for Caucasians. In Gypsy children, FVC and expiratory flow function increase linearly with standing height and predicted values are lower than those for Caucasians of similar height.
Abstract: The mesothelium is part of the peritoneal water and ion transport barrier essential for peritoneal dialysis (PD) treatment and has a central role in the pathogenesis of peritoneal fibrosis and ultrafiltration failure observed in many PD patients. We investigated the effect of amiloride on the transmesothelial electrical resistance (RTM) of isolated parietal human peritoneum. Intact sheets were obtained from seven patients (three men, four women; mean age, 64 +/- 8 years). Fourteen peritoneal planar sheets were transferred to the laboratory in oxygenated Krebs-Ringer bicarbonate solution at 4 degrees C within 30 minutes after removal and mounted in an Ussing-type chamber. Amiloride (10(-3) mol/L) added apically (n = 8) caused a rapid rise of the RTM to 24.15 +/- 0.76 [OMEGA]H cm2 and a subsequent value persistence (p < 0.05); added basolaterally (n = 6), it increased the RTM to 22.66 +/- 0.59 [OMEGA]H cm2 within 1 minute, which persisted throughout the experiment. RTM was measured before and serially for 30 minutes after addition of amiloride. Control RTM was 20.29 +/- 0.86 [OMEGA]H cm2. These results indicate a rapid inhibitory effect of amiloride on the ionic permeability of parietal human peritoneum. The increase in the RTM observed after addition of amiloride clearly indicates the existence of amiloride-sensitive sodium channels on the human parietal peritoneal membrane, which may play some role in the ultrafiltration process and sodium removal during PD.
Abstract: The alteration of resting tension (RT) from 0.5 g to 2.5 g increased significantly airway smooth muscle contractions induced by acetylcholine (ACh) in rabbit trachea. The decrease in extracellular calcium concentration [Ca2+]o from 2 mM to 0.2 mM reduced ACh-induced contractions only at 2.5 g RT with no effect at 0.5 g RT. The nonselective inhibitor of nitric oxide synthase (NOS), N(G)-nitro-L-arginine methyl ester (L-NAME) increased ACh-induced contractions at 2.5 g RT. The inhibitor of inducible NOS, S-methylsothiourea or neuronal NOS, 7-nitroindazole had no effect. At 2.5 g RT, the reduction of [Ca2+]o from 2 mM to 0.2 mM abolished the effect of L-NAME on ACh-induced contractions. The NO precursor L-arginine or the tyrosine kinase inhibitors erbstatin A and genistein had no effect on ACh-induced contractions obtained at 2.5 g RT. Our results suggest that in airways, RT affects ACh-induced contractions by modulating the activity of epithelial NOS in a calcium-dependent, tyrosine-phosphorylation-independent way.
Abstract: We report the case of a 56-y-old male admitted with a left-sided post-pneumonic empyema. Clostridium sordellii DNA was directly detected in its pleural fluid by a broad-range 16S rRNA PCR, after 24 h of specimen collection. This is the third case of pleural infection caused by C. sordellii in the literature.
Abstract: This article reports on the development of a simple and cost-effective bioassay for the detection of biotin in urine and serum, based on the very selective binding of avidin and biotin. Avidin was allowed to react without isolating it from egg white. Egg white was treated with the dye HABA, which binds to avidin. Upon subsequent treatment with biotin, HABA is released due to the high affinity of biotin to avidin. The amount of HABA released is proportional to the amount of biotin used.
Abstract: 1. Pleural permeability may contribute to pleural fluid turnover. The transmesothelial resistance (R(TM)), is an established surrogate of mesothelial permeability. The aim of the present study was to compare the electrophysiological properties of costal and diaphragmatic parietal pleura. 2. Specimens of the parietal pleura were isolated from 12 adult sheep from the chest wall and the diaphragm. Electrophysiological measurements were conducted with the Ussing system. Specimens of the parietal pleura of both types (diaphragmatic and costal) were compared histologically and total protein content measurements were also made. 3. The R(TM) of the diaphragmatic parietal pleura was significantly higher than that of the costal parietal pleura throughout the experiment. The diaphragmatic parietal pleura contains more cuboidal cells than the costal parietal pleura and its protein content was higher, however this difference was not statistically significant. 4. The costal parietal pleura consists of a more 'leaky' mesothelium than the diaphragmatic pleura. The morphological differences between the two types of parietal pleura may underline the electrophysiological findings.
Abstract: It is well-known that parapneumonic effusions lead to the formation of inflammatory exudates which contain an increasing amount of inflammatory cells, especially polymorphonuclear. At these pathological conditions characterized by oxidative stress, ascorbic acid (AA) plays an important role in quenching free radicals, so that it could protect neutrophils and mesothelial cells from oxidative damage. Besides that ascorbic acid and its metabolite dehydroascorbic acid (DHA) alters the sheep visceral and parietal pleura permeability. More specific ascorbic acid as well as dehydroascorbic acid decreases the permeability of pleura after addition on apical and basolateral side in both visceral and parietal pleurae. It seems that, AA and DHA have an opposite action upon pleura from that of the inflammatory mediators, like VEGF, which increases the permeability of pleura and causes mesothelial barrier dysfunction. The decrease of pleura permeability induced by AA and DHA suggest the hypothesis that AA and/or its metabolite DHA during inflammatory reactions not only protects mesothelial cells from oxidative damage, but also contributes to maintaining the mesothelial barrier function. Consequently, the inflammatory pleural fluid may be trapped in pleural space and the inflammation may be restricted, and have extension avoided.
Abstract: Acute-phase markers, such as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), have been studied in inflammatory and malignant disorders. We examined the diagnostic value of these markers for the differentiation among parapneumonic, tuberculous and malignant effusions. We studied 124 patients with pleural effusions, classified as exudates [total (n=97), parapneumonic (n=15), tuberculous (n=25), malignant (n=57)] and transudates due to congestive heart failure (n=27). CRP, IL-6 and TNF-alpha were measured in pleural fluid and serum. Pleural fluid CRP was higher in parapneumonic compared to tuberculous and malignant effusions, providing 100% sensitivity for a cut-off point of 5.3mg/dL. IL-6 was higher in both parapneumonic and tuberculous compared to malignant effusions. TNF-alpha was higher in tuberculous compared to malignant effusions, providing 96.0% sensitivity, and 93.0% specificity for a cut-off point of 88.1 pg/mL. Pleural fluid CRP levels were lower than serum in all groups, probably reflecting systemic inflammation, whereas IL-6 and TNF-alpha were higher in pleural fluid indicating local production. Our data suggest that these markers may provide useful information for the differentiation of infectious and malignant effusions in clinical practice. However, further studies are needed for the validation of these findings in usual clinical circumstances.
Abstract: Insulin regulates glucose metabolism and activates cell growth. As the respiratory system is an alternative route for insulin administration in patients with diabetes mellitus, we studied the effect of insulin on rabbit tracheal airway smooth muscle (ASM) cell proliferation. We show that treatment of quiescent ASM cells with insulin for 24 h increased cell number compared to control cells. This increase was similar to the increase caused by the addition of fetal bovine serum (FBS). Moreover, in contrast to cells treated with FBS, exposure of ASM cells with insulin for longer periods (48 and 72 h) did not have any further influence on cell proliferation. In ASM cells, insulin activated the phosphatidylinositol 3-kinase (PI3 K) pathway, while FBS activated both PI3 K and the mitogen-activated protein kinase (MAPK) pathway. The PI3K pathway inhibitors LY294002 and wortmannin abolished the stimulation of cell proliferation by insulin, indicating a role for this pathway in the cellular response to insulin. These results show that while insulin has a mitogenic effect on ASM cells, prolonged insulin treatment does not lead to excessive ASM cell proliferation and suggest that the use of aerosolized insulin does not represent a potential hazard for airway remodeling.
Abstract: The present study describes a case of severe pulmonary arterial hypertension (PAH) associated with unilateral lung destruction due to bronchiectasis in a patient with common variable immunodeficiency (CVID). Initially, the patient's treatment included antibiotics, oral anticoagulants, diuretics, and immunoglobulin replacement therapy. However, the patient's condition improved significantly only after inhaled iloprost was administered. Three months later, his PAH was almost reversed. The hemodynamic response of our patient suggests that inhaled iloprost may have a role in the treatment of sustained PAH related to unilateral lung destruction.
Abstract: Restless legs syndrome (RLS) is a sensorimotor disorder with a general population prevalence of 3-10%. A single, previous epidemiological study performed in south-east Europe reported the lowest prevalence rate amongst European countries. We conducted a population-based survey of RLS in central Greece. A total of 4200 subjects were randomly recruited. We used the international RLS study group criteria for diagnosis and the severity scale for severity assessment in subjects with RLS. We also included questions to assess the level of awareness of RLS in our region. A total of 3033 subjects were screened. The overall lifetime prevalence was 3.9% with a female-to-male ratio of 2.6:1. Nearly half of RLS patients reported moderate to severe intensity of symptoms. After adjustment for multiple comparisons we found no association of RLS with education level, smoking, alcohol intake, caffeine consumption, shift work, professional pesticide use or comorbid illness. Our study revealed a low level of awareness amongst the population and physicians in our region and sub-optimal management. We provide further evidence for low prevalence of RLS in south-east Europe and a low level of awareness of RLS in our region.
Abstract: Hypoxia promotes adherence of leukocytes to endothelial cells by inducing expression of adhesion molecules like intercellular adhesion molecule 1 (ICAM-1). Increased serum levels of circulating ICAM-1 (cICAM-1) have been reported in adults with sleep apnea and associated hypoxemia. This investigation assessed the hypothesis that the overnight change of cICAM-1 levels in children with snoring is correlated with the severity of obstructive sleep-disordered breathing. Evening and morning serum levels of cICAM-1 were measured in children with snoring referred for polysomnography. Twenty-five children with an apnea-hypopnea index greater than or equal to 5 episodes/h (5.5 +/- 1.8 years), 30 subjects with an index less than 5 and greater than 1 (6.3 +/- 2 years), and 19 children with an index less than or equal to 1 (7.1 +/- 3 years) were recruited. Overnight change in cICAM-1 (log-transformed ratio of morning-to-evening levels) was similar in subjects with an apnea-hypopnea index greater than or equal to 5 episodes/h compared to those with an index less than 5 and greater than 1 or to children with an index less than or equal to 1 (-0.001 +/- 0.08 vs -0.03 +/- 0.09 vs -0.06 +/- 0.1; p > 0.05). When multiple regression analysis was applied, apnea-hypopnea index, respiratory arousal index, and oxygen saturation of hemoglobin nadir were not significant predictors of overnight change in cICAM-1 levels. Thus, in children with snoring, overnight change in cICAM-1 levels is not related to severity of obstructive sleep-disordered breathing.
Abstract: Current guidelines suggest the use of non-invasive ventilation (NIV) in hypercapnic chronic obstructive pulmonary disease (COPD) exacerbations in patients presenting with a pH of 7.25-7.35. The aim of this study was to investigate the role of NIV in COPD patients with chronic hypercapnic respiratory failure admitted to the hospital with acute exacerbations and an arterial pH of 7.35 or higher.
Abstract: Obstructive sleep apnea (OSA) syndrome is a respiratory disease that is linked to heart attacks and high blood pressure. In the present study, we used the Comet assay to compare basal DNA damage and DNA damage induction by hydrogen peroxide, ethanol, and gamma-irradiation in lymphocytes from 35 OSA patients and 35 controls. We also measured the apoptosis and necrosis produced by these agents and the ability of the lymphocytes to repair the induced DNA damage. It was found that lymphocytes isolated from OSA patients had higher basal levels of DNA damage and were more sensitive to the effects of the DNA-damaging agents than lymphocytes from controls. OSA patients also had a reduced capacity to repair the DNA damage induced by the three agents, but apoptosis and necrosis were similar in OSA patients and the controls.
Abstract: Sleep apnoea disorders affect a large proportion of patients with renal failure. However, it is unknown whether body composition and visceral adiposity predispose haemodialysis patients to sleep apnoea disorders.
Abstract: The mesothelium is part of the peritoneal barrier that manages the water and ion transport essential for peritoneal dialysis (PD) treatment. In addition, it has a central role in the pathogenesis of peritoneal fibrosis and the resulting ultrafiltration failure observed in many PD patients. Endothelin-1 (ET-1) is a potent vasoactive peptide originally described as an endothelial cell-derived factor In addition, ET-1 has been shown to stimulate fibrogenic activity in various organs by regulating the production and turnover of matrix components. The aim of the present study was to investigate, by means of Ussing chamber experiments, the effect of ET-1 on the transmesothelial electrical resistance (RTM) of isolated visceral sheep peritoneum. Intact sheets of visceral sheep peritoneum were obtained from 12 adult sheep. The samples were collected from the slaughterhouse immediately after the deaths of the animals and, within 30 minutes, were transferred in oxygenated Krebs-Ringer bicarbonate (KRB) solution at 4 degrees C to the laboratory to be mounted in an Ussing-type chamber. Endothelin-1 (10(-7) mol/L) was then added to the KRB solution apically or basolaterally, and the RTM was measured before and serially for 10 minutes after the addition of the ET-1. The control RTM (before addition of ET-1) was 22.8 +/- 0.56 Omega x cm2. Addition of ET-1 apically significantly increased the RTM by 63.82% +/- 16.93% (p < 0.05) within 1 minute. After addition of ET-1 basolaterally, the RTM also increased significantly by 90.91% +/- 57.31% within 1 minute (p < 0.05). In both cases, these values persisted throughout the experiment. These results clearly indicate an inhibitory effect of ET-1 on the ionic permeability of visceral sheep peritoneum. The rapid increase in RTM observed after the addition of ET-1 suggests the existence of endothelin receptors (ET-A or ET-B, or both) on visceral sheep peritoneum. Previous studies demonstrated that ET-1, acting on ET-B receptors, potently inhibits epithelial sodium channels in mammalian cell cultures. Nevertheless, the exact pathways that underlie these findings remain unclear; their elucidation requires further investigation.
Abstract: The permeability for small solutes and the ultrafiltration capacity of the peritoneum are essential for effective peritoneal dialysis (PD) treatment. Elucidation of the factors that regulate these two properties is therefore of great importance. Ouabain, a potent inhibitor of the Na+-K+ pump has been shown to reduce fluid absorption in animal models of PD. In the present study, we used Ussing chamber experiments to investigate the effect of ouabain on the transmesothelial electrical resistance (RTM) of isolated visceral sheep peritoneum. Peritoneal samples from the omentum of adult sheep were isolated immediately after the deaths of the animals and were transferred to the laboratory in cooled Krebs-Ringer bicarbonate solution (4 degrees C, pH 7.5) bubbled with 95% O2/5% CO2. A planar sheet of visceral peritoneum was mounted in an Ussing-type chamber, and ouabain (10(-3) mol/L) was added apically and basolaterally. The RTM was measured before and serially for 30 minutes after the addition of ouabain. Because active ion transport is temperature-dependent, all measurements were taken at 37 degrees C. The results presented are the mean +/- standard error of 6 experiments. Before the addition of ouabain, the control RTM was measured as 21.26 +/- 0.57 Omega x cm2. Addition of ouabain basolaterally induced an increase in the RTM to 27.62 +/- 0.72 Omega x cm2 within 1 minute (p < 0.05), and this level persisted throughout the experiment. The effect of ouabain, when added apically, was similar, characterized by a rapid rise in the RTM to 24.66 +/- 0. 76 Omega x cm2 at 1 minute (p < 0. 05), with subsequent persistence at that level. A clear association between RTM and active ion transport has been shown in previous studies. The results of the present study, showing a rapid effect of ouabain on the RTM of visceral peritoneum, therefore clearly suggest that cell membrane Na+K+-ATPase is important for peritoneal ionic transport. In addition, ouabain was previously shown to reduce vasodilation and intraperitoneal sodium or to increase intraperitoneal volume, especially in the presence of conventional acidic solutions. Those findings, combined with the results of the present study, clearly indicate that intraperitoneal administration of digitalis glycosides may have some beneficial effect in PD patients; however the specific clinical implications need further investigation.
Abstract: The peritoneal mesothelium is one of the main barriers to ion transport in peritoneal dialysis. In a previous study, we showed the existence of a micro-opioid influence on the in vitro ionic permeability of serosal membranes (specifically, pleura and pericardium), which become less permeable to ionic currents after the action of morphine. In the present study, we used Ussing chamber experiments to investigate the effect of morphine on the transmesothelial electrical resistance (RTM) of isolated parietal sheep peritoneum. Peritoneal samples from the diaphragm of adult sheep were isolated directly after the death of the animals and were transferred to the laboratory within 30 minutes in a cooled Krebs-Ringer bicarbonate solution (4 degrees C, pH 7.5) bubbled with 95% O2/5% CO2. A planar sheet of parietal peritoneum was mounted in an Ussing-type chamber and morphine (10(-9) mol/L) was added apically and basolaterally. The RTM was measured before and serially for 30 minutes after the addition of morphine. Because active ion transport is temperature dependent, the Ussing chamber was held at 37 degrees C. Results presented are the mean +/- standard error of 6 experiments. The control RTM (before the addition of morphine) was 20.26 +/- 0.57 Omega x cm2. Addition of morphine basolaterally induced, within 1 minute, an increase in RTM of 24% +/- 4.8%, which declined thereafter (p < 0.01). When morphine was added apically, the results were not similar, because no significant change occurred in the RTM. The RTM is an established surrogate of peritoneal permeability. The results of the present study indicate rapid action of basolaterally added morphine on the permeability of the parietal peritoneum. The observed increase in the RTM indicates the existence in the parietal peritoneum of micro-opioid receptors that seem to prevail basolaterally. The clinical implications of these results should be further investigated.
Abstract: The aim of the present study was to investigate whether low glucose and pH level, which are usually measured in complicated pleural effusions, alter the electrochemical function of healthy human parietal pleura. Parietal pleural pieces were stripped from 66 patients during thoracic surgery and were mounted in Ussing chambers. Krebs' solutions containing different glucose levels (0, 40 and 100 mg) and balanced at different pH levels (7.4, 7.3 and 7.2) were added to the pleural cavity surface of the pieces. Transmesothelial potential difference was measured at various time-points as an electrophysiological variable and transmesothelial resistance (R(TM)) was calculated using Ohm's law. When normal-glucose Krebs at pH 7.45 was used, R(TM) remained unchanged over time, but when low-glucose Krebs was used, R(TM) decreased. Krebs without glucose caused the greatest decrease in R(TM). Use of low-pH Krebs decreased R(TM). The lower the pH of the Krebs, the faster the decrease in R(TM) and the greater the effect. The decrease in R(TM) was greater with low-pH than with low-glucose Krebs. Low glucose and low pH caused an additive decrease in R(TM). Low glucose concentration and low pH cause alteration of the electrochemical function of human parietal pleura and could act as agents that lead to further exudate progression.
Abstract: Pleural effusion is a common complication of various diseases. Conventional methods are not always capable of establishing the cause of pleural effusion, so alternative tests are needed. The aim of this study was to explore means of discriminating between different pleural effusion groups, malignant, parapneumonic and tuberculous, based on the combined function of seven biological markers. Adenosine deaminase (ADA), interferon-gamma, C-reactive protein (CRP), carcinoembryonic antigen, interleukin-6, tumour necrosis factor-alpha and vascular endothelial growth factor concentration levels were measured in pleural fluid from 45 patients with malignant, 15 with parapneumonic and 12 with tuberculous pleural effusion. Receiver operating characteristic curve analysis, multinomial logit modelling and canonical variate analysis were applied to discriminate the pleural effusion groups. The three groups could be discriminated successfully using the measured markers. The most important parameters for discrimination were ADA and CRP concentration levels. An individual with an ADA concentration level of >45 U.L(-1) and a CRP concentration of <4 mg.dL(-1) was more likely to belong to the tuberculous pleural effusion group, whereas one with an ADA concentration level of <40 U.L(-1) and a CRP concentration of >6 mg.dL(-1) was more likely to belong to the parapneumonic pleural effusion group, and one with a CRP concentration of <4 mg.dL(-1) to the malignant pleural effusion group. The combination of adenosine deaminase and C-reactive protein levels might be sufficient for discriminating between the three different groups of exudative pleural effusion: malignant, tuberculous and parapneumonic.
Abstract: The aim of this study was to clarify the association between obstructive sleep apnoea/hypopnoea syndrome (OSAHS)-related symptoms and physician-diagnosed asthma and COPD.
Abstract: The expression of indoleamine 2,3-dioxygenase (IDO) by tumor cells has been considered as a major tumor immune escape mechanism. The aim of this study was to investigate the expression of IDO in lung cancer cell lines as well as in surgically resected lung cancer specimens comparing the latter, to the expression in autologous samples from the corresponding non malignant lung tissue. Correlations of IDO expression with clinicopathological parameters of the disease were performed.
Abstract: The possible causes and genetic mechanisms of pulmonary carcinoid tumor development are unclear. In this study, we examined genetic alterations at the MEN1 locus in archival material from 15 pulmonary carcinoids. We employed, for the first time in this setting, real-time PCR with melting curve analysis in order to identify loss of heterozygosity (LOH) or microsatellite instability (MI) in two polymorphic markers (PYGM, D11S449) at the MEN1 locus and one additional marker (D11S906) of a putative oncosuppressive region distal to the MEN1 gene. Sequencing data were available in a selected subset of tumors in order to verify the reliability of real-time PCR analysis. We observed LOH at PYGM in 38% of the cases and MI in 13.3% of the cases. Our data indicate that real-time PCR with melting curve analysis is a reliable technique for LOH and MI detection and indicate that genetic errors at the MEN1 locus but also distal to it may be involved in the development of sporadic pulmonary carcinoid tumors.
Abstract: The effect of adrenaline on the transmesothelial resistance (RTM) of sheep's visceral and parietal pleura was studied using the Ussing chamber technique. Basal transmesothelial resistance of visceral pleura was found to be 20.71 +/- 0.31 Omega cm2, whereas that of parietal pleura was found to be 19.53 +/- 0.34 Omega cm2. Immediately after the addition of adrenaline (10(-7) M) both apically and basolaterally on the visceral and parietal pleura, these values were significantly increased (P < 0.05). Addition of the nonselective beta-receptor blocker, propranolol (10(-5) M), suppressed this effect in both visceral and parietal pleura, while addition of the nonselective alpha-receptor blocker, phentolamine (10(-5) M), partly suppressed the above-mentioned increase in the parietal pleura. In conclusion, our results show that adrenaline has a rapid effect on both pleurae. This rapid effect is mediated by the stimulation of beta-adrenergic receptors in the case of visceral pleura, while in the case of parietal pleura this effect seems to be due to a stimulation of alpha- and beta-adrenergic receptors. On the visceral pleura the effect of adrenaline vanishes after some minutes and on the parietal this effect is more permanent than the visceral's one, suggesting differences in the distribution of the adrenergic receptors between the visceral and parietal pleura.
Abstract: Epidemiological studies have shown an inverse relationship between dietary vitamin A intake and the risk of developing lung cancer. The aim of this study was to investigate the vitamin A status in patients with lung cancer, by determining the serum levels of retinoic acid, retinol and retinyl palmitate.
Abstract: Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative disorder. Cytokines contribute an important but yet undefined role to its pathogenesis.
Abstract: Vascular endothelial growth factor (VEGF) may be one of the pathophysiologic links in the association between obstructive sleep apnea-hypopnea and cardiovascular disease. Morning serum VEGF levels are increased in children with obstructive sleep apnea. However, release of VEGF by platelets and leukocytes during blood clotting may affect its concentration in serum. In the present study, VEGF levels were measured in children with and without habitual snoring using plasma specimens. Evening and morning plasma VEGF concentrations were determined in: (i) 20 children with habitual snoring and apnea-hypopnea index (AHI)5 episodes/h (median age 5; range 1.9-13 years); (ii) 55 children with snoring and AHI<5 episodes/h (median age 6; 2-13 years); and (iii) 25 controls without snoring (median age 6.5; 3-13 years). No differences were identified between the three study groups regarding evening [median 2.5 (range 2.5-174.5) versus 22.5 (2.5-159.4) versus 26.8 (2.5-108) pg/mL; P>0.05] and morning VEGF levels [median 7.7 (range 2.5-120.5) versus 25.1 (2.5-198.4) versus 48.4 (2.5-147.7) pg/mL; P>0.05]. AHI and % sleep time with oxygen saturation of hemoglobin less than 90% were not significant predictors of log-transformed morning VEGF concentrations (P>0.05). In summary, both evening and morning plasma VEGF levels were similar in children with obstructive sleep-disordered breathing of variable severity and in controls without snoring. VEGF may not play an important pathophysiologic role in all cases of obstructive sleep-disordered breathing in childhood.
Abstract: Hepatic encephalopathy in patients with end-stage liver cirrhosis is associated with alterations in sleep patterns. Cirrhosis may also affect pulmonary function and it might be involved in the development of obstructive sleep apnoea syndrome (OSAS) in patients with ascites. We carried out a study to evaluate the presence of OSAS in cirrhotic patients without evidence of ascites (early stage cirrhosis).
Abstract: The effect of morphine (mu-opioid receptor agonist) on the transmesothelial resistance (R(TM)) of sheep's pleura and parietal pericardium was studied using the Ussing chamber technique. Basal transmesothelial resistance of parietal pleura was found to be 19.57+/-0.32 Omega cm2 and of visceral pleura was found to be 19.41+/-0.31 Omega cm2, whereas that of parietal pericardium was found to be 22.83+/-0.4 Omega cm2. Immediately after the addition of morphine (10(-9) M) both apically and basolaterally on the parietal pleura and parietal pericardium, these values were significantly increased (P<0.05). On the contrary, addition of morphine (10(-9) M) resulted in a rapid increase, only when placed basolaterally on the visceral pleura (P<0.05). In conclusion, our findings suggest that morphine, probably through mu-opioid stimulation, increases in vitro the transmesothelial resistance of the parietal pleura, of the visceral pleura when added basolaterally and of the parietal pericardium.
Abstract: The aim of the study was to investigate the career choices, location preferences and criteria among medical students in Greece. We applied a questionnaire-based analysis using a sample of 591 students of four out of seven Greek Medical Schools. The sample included students of all academic years. The vast majority of students wish to specialize (97.6%), while general practice gathered a very low percentage (1.7%). The scientific challenge (61.4%) and interaction with patients (60.6%) seem to be the major influencing factors for most of the students' specialty preferences, whilst less common variables influencing career choice are the high demand/supply ratio for certain health services (40.4%), the income potential (31.4%), the active tempo (26.2%) and prestige (15%). 70.3% of those asked consider the possibility of specializing abroad. The low concern of Greek medical students for general practice reveals today's drastic deficiency in Greek primary health care. Such a situation will escalate, unless targeted strategies to produce more general practitioners are adopted. Furthermore, the results reflect a lower education and organizing level urging students to specialize abroad. The National Health System (NHS) should be reformed towards a rationalistic distribution of the medical specialties and medical workforce.
Abstract: Recent studies on blood vessels have provided evidence that testosterone may exert direct effects on smooth muscle. However, an acute effect on airway reactivity has not been shown yet. The aim of this study was to assess the direct effect of testosterone on the responsiveness of male adult rabbit airway smooth muscle (ASM), precontracted with 10 microM acetylcholine, 10microM carbachol or 80 mM KCl.
Abstract: Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis which has multiple effects in lung development and physiology. VEGF is expressed in several parts of the lung and the pleura while it has been shown that changes in its expression play a significant role in the pathophysiology of some of the most common respiratory disorders, such as acute lung injury, asthma, chronic obstructive pulmonary disease, obstructive sleep apnea, idiopathic pulmonary fibrosis, pulmonary hypertension, pleural disease, and lung cancer. However, the exact role of VEGF in the lung is not clear yet, as there is contradictory evidence that suggests either a protective or a harmful role. VEGF seems to interfere in a different manner, depending on its amount, the location, and the underlying pathologic process in lung tissue. The lack of VEGF in some disease entities may provide implications for its substitution, whereas its overexpression in other lung disorders has led to interventions for the attenuation of its action. Many efforts have been made in order to regulate the expression of VEGF and anti-VEGF antibodies are already in use for the management of lung cancer. Further research is still needed for the complete understanding of the exact role of VEGF in health and disease, in order to take advantage of its benefits and avoid its adverse effects. The scope of the present review is to summarize from a clinical point of view the changes in VEGF expression in several disorders of the respiratory system and focus on its diagnostic and therapeutic implications.
Abstract: Obstructive sleep-disordered breathing is accompanied by episodic increases in left ventricle afterload due to large negative swings in intrathoracic pressure and repetitive surges in arterial pressure. Brain natriuretic peptide (BNP) is released by ventricular myocytes in response to pressure and volume overload. It was hypothesized that in children with snoring, overnight change in BNP levels is correlated with severity of disturbance in respiration.
Abstract: Recent studies suggest an epidemiological association between Helicobacter pylori infection and several extra-gastroduodenal pathologies, including cardiovascular, rheumatic, skin and liver diseases. The observed associations might be explained by a role of H. pylori infection in the pathogenesis of certain extra-digestive disorders, as a variety of inflammatory mediators are activated by H. pylori infection. The present review summarizes the current literature, including our own studies, concerning the association between respiratory diseases and H. pylori infection. A small number of epidemiological and serologic case-control studies suggest that patients with chronic obstructive pulmonary disease have an increased seroprevalence of H. pylori. A frequent coexistence of bronchiectasis and H. pylori infection has also been found. Moreover, recent studies have shown an increased prevalence of H. pylori infection in patients with pulmonary tuberculosis and in those with lung cancer. On the other hand, bronchial asthma does not seem to be related to H. pylori infection. At present, there is no definite proof of a causal relationship between H. pylori and respiratory diseases. The primary evidence rests on case-control studies, concerning relatively small numbers of patients. Future studies should be large enough for moderate-sized effects to be assessed or registered reliably. The activation of inflammatory mediators by H. pylori infection might be the pathogenetic mechanism underlying the observed associations. Therefore, the role of genetic predisposition of the infected host, the presence of strain-specific virulence factors and the serum concentration of proinflammatory markers in H. pylori-infected patients with respiratory diseases need further evaluation.
Abstract: Macrolides have been proven to have beneficial bacteriostatic and anti-inflammatory properties, but very little is known about the potential value of their bronchodilatory effect. Therefore, in the present study we investigated the effect of azithromycin on contractile responses of isolated rabbit tracheal strips to carbachol or KCl. Azithromycin has a relaxant, concentration-dependent effect on tracheal strips precontracted with carbachol (300 nM), significant from the concentration of 1 muM. The mechanical removal of epithelium did not alter the effect of azithromycin. Azithromycin (100 microM) also relaxed tracheal strips precontracted with KCl (80 mM) even in the presence of atropine (100 microM). Moreover, azithromycin (100 microM) decreased contractions induced by 300 nM and 10 microM carbachol to 55.4% and 80.5% of initial contraction, respectively. The relaxant effect of azithromycin persisted in both calcium free solution and in the presence of the calcium channel antagonist, verapamil. The relaxant effect of azithromycin was not altered by the pre-treatment of preparations with the inhibitors of Ca(2+)-ATPase (cyclopiazonic acid), Na(+)-K(+) ATPase (ouabain), Rho-associated kinase [(R)-(+)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride] (Y-27632) or the non-specific cAMP and cGMP phosphodiesterases inhibitor 3-isobutyl-1-methyl-2,6(1H,3H)-purinedione (IBMX). These results suggest that azithromycin has a concentration-dependent, epithelium-independent, direct relaxant effect on precontracted tracheal strips that is not mediated via inhibition of Ca(2+) influx or Ca(2+) release from intracellular stores. Also, it is not due to alteration of the function of Na(+)-K(+) ATPase and does not depend on the formation of cAMP/cGMP or the Rho/Rho-activated kinase pathway.
Abstract: The peritoneal mesothelium is a barrier to ion transport in peritoneal dialysis. In this study, we used Ussing-chamber experiments to investigate the effect of HgCl2, an aquaporin-1 inhibitor, on the transmesothelial electrical resistance (RTM) of isolated sheep parietal peritoneum. Peritoneal samples from the diaphragm of adult sheep were isolated immediately after the death of the animal and were transferred within 30 minutes to the laboratory in a cooled Krebs-Ringer bicarbonate solution (4 degrees C, pH 7.5) bubbled with 95% O(2)/5% CO2. A planar sheet of the parietal peritoneum was mounted in an Ussing-type chamber and HgCl2 (10(-4) mol/L) was added apically or basolaterally. The RTM was measured before and serially after the addition of the HgCl2. The entire experimental apparatus was held at 37 degrees C, because active ion transport is temperature-dependent. The results presented are the mean +/- standard error of 12 experiments. The control RTM (that is, before the addition of HgCl) was 19.3 +/- 0.38 omega x cm2. Addition of HgCl2 apically induced a decrease in the RTM to 16.25 +/- 0.86 omega x cm2 within 1 minute. When added basolaterally, HgCl2 action was similar, with a rapid reduction in the RTM to 18.1 +/- 0.51 omega x cm2 (p < 0.05). A clear association between the RTM and the active transmesothelial ion transport was shown in previous studies. In the present study, rapid action of HgCl2 on the permeability ofthe parietal peritoneum was observed, resulting in a reduction in the RTM Taken together, these findings indicate that inhibition of aquaporin-1 alters the ionic permeability of the parietal peritoneal membrane.
Abstract: The purpose of this study was to determine whether reactive oxygen metabolite species (ROMs) correlated with lung function in patients with chronic obstructive pulmonary disease (COPD) and to investigate whether ROMs could be used as an index of COPD severity.
Abstract: We describe a case of necrotizing pneumonia in Greece caused by a community-acquired methicillin-resistant Staphylococcus aureus (MRSA) producing Panton-Valentine leukocidin (PVL) carrying the staphylococcal chromosome cassette mec (SCCmec) type V. The pulse field gel electrophoresis (PFGE) pattern of this strain differed significantly from the PVL-positive multi-locus sequence typing (MLST)-80 clone of MRSA, which predominates in Greece and in Europe. Further analysis of this strain revealed that it belonged to the agr1 allele type, and its resistance to tobramycin, gentamicin, and kanamycin was associated to the presence of aac-(6')-Ie+aph(2') gene. This is the 1st report that documents the emergence of CA-MRSA with PVL genes in combination with the SCCmec type V in Europe.
Abstract: Nocturnal enuresis has been associated with obstructive sleep-disordered breathing mostly in hospital-referred adults and children. To investigate whether primary nocturnal enuresis is significantly associated with habitual snoring in the general pediatric population irrespective of subjects' age and sex, we studied children attending six randomly selected schools in a city in central Greece.
Abstract: We studied the influence of resting tension (RT) on rabbit tracheal smooth muscle (TSM) contractions induced by acetylcholine or KCl as well as the role of epithelium and the endogenously produced nitric oxide, prostanoids and endothelin on these responses. The alteration of RT from 0.5 to 2.5 g increased the responsiveness of TSM to KCl. The presence of atropine decreased KCl-induced contractions obtained only at 2.5 g RT. The removal of epithelium increased acetylcholine-induced contractions, only at 2.5 g RT. At 0.5 g RT, the presence of L-NAME had no effect on acetylcholine-induced contractions while indomethacin decreased contractions induced by 10(-3) M acetylcholine. At 2.5 g RT, the presence of L-NAME increased acetylcholine-induced contractions while indomethacin, BQ-123 and BQ-788 had no effect. These results demonstrate that RT affects the responsiveness of TSM differentially, depending on the agonist or integrity of the epithelium. Airway epithelium modulates acetylcholine-induced contractions, only at 2.5 g RT partly via NO release. At 0.5 g RT, the endogenous production of prostanoids by sources other than epithelium modulates the contractility of TSM to acetylcholine.
Abstract: Higher or similar systolic and/or diastolic blood pressure has been recorded in children with sleep apnea compared to subjects with primary snoring or in those with primary snoring compared to controls. To investigate the association between blood pressure and habitual snoring, we studied children in four randomly selected schools in central Greece. A symptom questionnaire was answered by parents, and children's weight, height, and blood pressure were measured. Seven hundred and sixty children (4-14 years old; 352 female) were recruited. Fifty of 760 (6.6%) participants were snoring more than 3 nights/week (habitual snorers). Mean (+/- SD) systolic blood pressure was 106.9 (+/-10.6) mmHg in habitual snorers vs. 107 (+/- 12) in nonhabitual snorers (P > 0.05). Mean diastolic blood pressure was 61.9 (+/- 7.6) in the former vs. 61.8 (+/- 6.8) in the latter (P > 0.05). While age, gender, and body mass index were significant predictors of systolic blood pressure in a general linear model, snoring was not. Similarly, that gender and body mass index but not snoring were significant predictors of diastolic blood pressure. In a community sample of children, habitual snorers do not have higher morning systolic or diastolic blood pressure than nonhabitual snorers.
Abstract: Risk factors for atherosclerosis such as hypertension, type 2 diabetes, obesity and dyslipidemia affect endothelial function and stimulate adhesion molecules expression. The aim of the study was to examine endothelial activation in type 2 diabetes and hypertension as indicated by adhesion molecule levels and further to investigate whether the coexistence of the above conditions has a different effect.
Abstract: The purpose of this study was to assess the agreement of asthma and chronic obstructive pulmonary disease (COPD) treatment prescribed by physicians and pulmonologists in comparison to asthma and COPD guidelines and the need of the implementation of COPD guidelines in primary health care physicians.
Abstract: An increased seroprevalence of Helicobacter pylori (H. pylori) and especially of the high virulent cytotoxin-associated gene-A (CagA) positive strains has been found in several extragastroduodenal pathologies, characterized by activation of inflammatory mediators. Moreover, it has been reported that the risk of chronic bronchitis may be increased in H. pylori infected patients. The aim of the present study was to assess the seroprevalence of H. pylori and in particular of CagA-positive virulent strains in patients with chronic obstructive pulmonary disease (COPD). We evaluated 126 COPD patients (88 males and 38 females, aged 61.3+/-8.1 years) and 126, age and sex-matched, control subjects. All subjects enrolled underwent an enzyme-linked immunosorbent assay (ELISA) IgG serologic test for H. pylori and CagA protein. The prevalence of H. pylori infection in patients and controls was 77.8% and 54.7%, respectively (P<0.001) and that of CagA-positive H. pylori infection was 53.9% and 29.3%, respectively (P<0.001). Moreover, COPD patients had a significantly increased mean serum concentration of both anti-H. pylori IgG (118.3+/-24.4 vs. 61.9+/-12.9U/ml, P<0.001) and anti-CagA IgG antibodies (33.8+/-3.4 vs. 19.0+/-1.5U/ml, P<0.001). Finally, no statistically significant difference, as regards the spirometric values, was detected between H. pylori infected COPD patients and uninfected ones. In conclusion, H. pylori infection may be associated with COPD. Further studies should be undertaken to clarify the potential underlying pathogenetic mechanisms.
Abstract: The small amount of liquid that, under physiological conditions, is presented in the pleural cavity has been the focus of extensive research for more than a century. However, there are still unanswered questions and considerable controversies about the nature of the forces governing its movement into and out of the pleural cavity. Early in the 20th century has been proposed that pleural fluid turnover is simple based on the balance between hydraulic and colloid osmotic pressures existing across the pleural membranes. This original hypothesis has not been validated by data accumulating over the last 20 years. Pleural tissues and renal proximal tubules present high water permeability, small transepithelial electrical resistance (22.02 Omega cm2) and the same cation transportation such as Na+ channels, Na+-K+ ATPase channels, and Na+-H+ exchanger. In contrast to previous conflicting theories concerning pleura fluid movement, the same functional characteristics suggest the hypothesis that physiology of pleura is similar to proximal tubules.
Abstract: Obstructive sleep-disordered breathing is associated with cardiovascular disease in adults, and elevated C-reactive protein (CRP) has been proposed as a link between the two disorders. We hypothesized that children with sleep-disordered breathing have higher CRP values than do control subjects. CRP was measured in 39 children (mean age +/- SD: 6.9 +/- 3.2 years) without snoring (controls) and in 102 children (6.2 +/- 2.2 years) with habitual snoring who underwent polysomnography. No significant differences were found in mean CRP values between control subjects (0.12 +/- 0.16 mg/dl; n = 39) and snorers with an apnea-hypopnea index of less than 1 episode/hour (0.15 +/- 0.26; n = 18), snorers with an index of 1 or more and less than 5 (0.15 +/- 0.26; n = 54), and snorers with an index of 5 or more (0.22 +/- 0.43; n = 30; p > 0.05). There was no correlation between CRP or log-transformed CRP values and apnea-hypopnea index, respiratory movement/arousal index, Sa(O(2)) nadir, oxygen desaturation (>/= 4%) of hemoglobin index, or percentage of sleep time with saturation less than 95% (p > 0.05). Thus, findings of higher CRP values in adults with sleep-disordered breathing and correlations of these values with polysomnography indices were not confirmed in children.
Abstract: A positive correlation of severity of sleep-disordered breathing with morning fasting insulin levels, which is independent of obesity, was reported in adults and obese children. We hypothesized that both severity of sleep-disordered breathing and relative body mass index predict fasting insulin and homeostasis model assessment (HOMA) index values in nonobese children with habitual snoring. One hundred and ten subjects with habitual snoring (median age, 6 years; range, 2-13 years) underwent polysomnography and measurement of morning fasting insulin and glucose levels. The HOMA index was calculated. Thirty children had an apnea-hypopnea index (AHI) >/= 5 episodes/hr (median, 7.8 episodes/hr; range, 5-42.3 episodes/hr), and 80 subjects had an AHI < 5 episodes/hr (median, 1.9 episodes/hr; range, 0.2-4.9 episodes/hr). Insulin and HOMA index values were similar in children with AHI >/= 5 episodes/hr (median insulin, 4.9 mU/l; range, 1.66-19.9 mU/l; and median HOMA, 1; range, 0.36-4.95) and in subjects with AHI < 5 episodes/hr (median insulin, 5.8 mU/l; range, 0.74-41.1 mU/l; and median HOMA, 1.3; range, 0.13-9.72) (P > 0.05). No significant correlations were identified between insulin or HOMA index values and any polysomnography indices (P > 0.05). When multiple linear regression was carried out, relative body mass index was a significant predictor of log-transformed insulin levels or HOMA index values, but AHI and percentage of sleep time with saturation <95% were not. In conclusion, contrary to findings in adults and in obese children, severity of sleep-disordered breathing is not a significant predictor of fasting insulin or HOMA index values in nonobese children with habitual snoring.
Abstract: Oxidative stress has been associated with various respiratory disorders. We tested the hypothesis that exudates would present higher levels of oxidative stress compared to transudates, expressing the increased local oxidative burst in the former.
Abstract: The peritoneal mesothelium is a barrier to ion transport in peritoneal dialysis. In the present study, we used Ussing chamber experiments to investigate the effect of amiloride on the transmesothelial electrical resistance (R(TM)) of isolated visceral sheep peritoneum. Peritoneal samples from the omentum of adult sheep were isolated directly after the death of the animals and were transferred to the laboratory within 30 minutes in a cooled Krebs-Ringer bicarbonate solution (4 degrees C, pH 7.5) bubbled with 95% O2/5% CO2. A visceral peritoneal planar sheet was mounted in an Ussing-type chamber and amiloride (10(-3) mol/L) was added apically and basolaterally. The R(TM) was measured before and serially for 30 minutes after the addition of amiloride. Because active ion transport is temperature dependent, the Ussing chambers were held at 37 degrees C. The results presented are the means + standard error of 12 experiments. The control R(TM) (before the addition of amiloride) was 21.86 +/- 0.46 omega x cm2. Basolateral addition of amiloride induced, within 1 minute, an increase in R(TM) to 27.26 +/- 0.39 omega x cm2, a level that persisted throughout the experiment. When amiloride was added apically, the results were similar with a rapid rise of R(TM) to 24.18 +/- 0.9 omega x cm2 and subsequent value persistence (p < 0.05). A clear association between R(TM) and active ion transport was shown in previous studies. The results of the present study indicate rapid action of amiloride on the permeability of the visceral peritoneum. The observed increase in the R(TM) indicates the existence of amiloride-sensitive sodium channels in the visceral peritoneal membrane. The clinical implications of these results should be further investigated.
Abstract: Laboratory and clinical data provide evidence that a biological linkage exists between asthma and depression. Cytokines are key molecules in both diseases. They promote allergic reaction as well as depressive symptomatology. Antidepressants may have a therapeutic role in asthma by suppressing production of proinflammatory cytokines, inducing production of anti-inflammatory ones and preventing their brain effects. Most antidepressants also induce adaptive changes in central monoaminergic neurotransmission, which itself might modulate immune reactivity and central actions of cytokines. Antidepressants may also have direct effects on the immune cells. Their impact on hypothalamus-pituitary-adrenal axis is discussed. Antidepressants are expected to terminate the cascade of inflammatory events in other inflammatory diseases as well. The use of antidepressants in experimental clinical trials in patients with asthma is suggested.
Abstract: The peritoneal mesothelium constitutes an ion transport barrier that is taken advantage of in peritoneal dialysis. The aim of this study was to investigate the effects of epinephrine on the electrical transmesothelial resistance (R(TM)) of the isolated parietal sheep peritoneum by means of Ussing-type chamber experiments. Intact parietal (diaphragmatic) peritoneal samples were obtained from adult sheep immediately after sacrifice and transferred within 0.5 h to the laboratory in a cooled Krebs-Ringer bicarbonate solution (4 degrees C, pH 7.5), bubbled with 95% O2-5% CO2. A parietal peritoneal planar sheet was mounted in a Ussing-type chamber. Epinephrine (10(-7) M) was added to the apical and the basolateral side. The R(TM) was measured before and serially after the addition of epinephrine for 30 min. As active ion transport is temperature-dependent, all measurements were performed at 37 degrees C. The results were calculated as means with standard errors (x +/- SE) of six independent experiments. The control R(TM) was 20.05 +/- 0.61 ohm x cm2. The addition of epinephrine to the basolateral side within 1 min induced an increase of R(TM) to 21.8 +/- 0.45 ohm x cm2, which decreased thereafter progressively to reach control values again after 15 min. A similar effect of epinephrine on the apical side was apparent with a rapid rise of R(TM) to 22.5 +/- 0.66 ohm x cm2 and a subsequent decrease (P < 0.05). A clear association between the R(TM) and active ion transport was established from previous studies. The results of our study indicate a rapid action of epinephrine on the parietal peritoneum permeability.
Abstract: Nocturnal enuresis has been associated with obstructive sleep apnea-hypopnea and may resolve after adenotonsillectomy. Nasal corticosteroids have improved symptoms and polysomnography findings in children with snoring. Two children with primary nocturnal enuresis, chronic nasal obstruction, and loud snoring underwent polysomnography. The apnea-hypopnea index was 4.9 and 7.3 episodes/hr, and the oxygen desaturation of hemoglobin index was 4.6 and 5.2 episodes/hr. After administration of budesonide, the frequency of snoring decreased, the polysomnography findings improved, and the enuresis resolved completely. Six months after treatment, both children were still dry at night. Administration of nasal corticosteroids is associated with resolution of enuresis in children with mild obstructive sleep-disordered breathing.
Abstract: The goal of the present investigation was to describe the prevalence of and clinical factors associated with sleep-disordered breathing in children and adolescents. Children and adolescents (3,680 in all, 1-18 years old) attending schools in central Greece were surveyed by questionnaires distributed to parents. We found a similar prevalence of habitual snoring (present every night) among three different age groups (5.3%, 4%, and 3.8% in 1-6-, 7-12-, and 13-18-year-old subjects, P = NS). Several children with an adenoidectomy and/or tonsillectomy were snoring every night (6.1%), whereas sleepiness at school was more common in habitual snorers than in nonhabitual snorers (4.6 vs. 2%, P = 0.03). Seventy randomly selected subjects among 307 snorers without adenoidectomy and/or tonsillectomy underwent polysomnography. The estimated frequency of obstructive sleep apnea-hypopnea among children without adenoidectomy and/or tonsillectomy was 4.3%. Factors associated with snoring were: male gender (odds ratio 1.5 (confidence interval, 1.2-1.9)); chronic rhinitis (2.1 (1.6-2.7)); snoring in father (1.5 (1.2-1.9)), mother (1.5 (1.1-2.0)), or siblings (1.7 (1.2-2.4)); adenoidectomy in mother (1.5 (1.0-2.2)); and passive smoking (1.4 (1.1-1.8)). In conclusion, snoring every night was equally prevalent in younger and older ages, more frequent in males, and present even in some children with a history of adenoidectomy and/or tonsillectomy. Chronic rhinitis, family history of snoring, and exposure to cigarette smoke were associated with an increased frequency of habitual snoring.
Abstract: Abnormal endothelial function is well known in patients with type 2 diabetes mellitus and thought to induce macroangiopathy. Increased levels of adhesion molecules have been found in type 2 diabetic patients and it has been suggested that they play an important role in the initiation of atherosclerosis. The aim of the present study was to clarify the relationship between objectively proven peripheral arterial disease (pAVD) and serum levels of soluble adhesion molecules in patients with type 2 diabetes mellitus.
Abstract: In contrast to Geschwind, Behan and Galaburda (GBG) theory, there is strong evidence that inheritance through maternal line is responsible for the coexistence of asthma and left-handedness early in childhood. A new model that incorporates GBG's theory and maternal inheritance is proposed. This hypothesis suggests that maternal atopy is the most important factor in the evolution of asthma and that GBG's theory applies mainly in childhood. An inherited enhanced sensitivity of fetus to testosterone may be the underlying mechanism that leads to the development of bronchial asthma.
Abstract: The purpose of this study was to examine the relation between depression, anxiety and pulmonary function in asthmatics. Thirty-eight adult asthmatic patients underwent psychometric evaluation with the DSSI/sAD questionnaire, filled in an asthma questionnaire and underwent spirometry. The majority of patients suffered from mild-persistent asthma. Twenty-six reported symptoms of anxiety and 25 reported symptoms of depression. A statistically significant reduction in FEV1 and FEV1/FVC values was observed in asthmatic patients with symptoms of depression. The mean value of FEV1 was 81.84(+/-20.83) in patients without symptoms and 63.73(+/-17.99) in patients with symptoms of depression. The mean values of FEV1/FVC were 0.85(+/-0.11) and 0.75(+/-0.10), respectively. These findings indicate a high frequency of depression and anxiety in adult asthmatic patients. A biological linkage between depression and impaired pulmonary function is proposed.
Abstract: The peritoneal mesothelium is a barrier to ion transport in peritoneal dialysis. In the present study, we investigated, by means of Ussing chamber experiments, the effect of adrenaline on the electrical transepithelial resistance (R(TE)) of isolated visceral sheep peritoneum. Peritoneal samples from the omentum of adult sheep were isolated within 30 minutes of the animal's death and were transferred to the laboratory in a cooled Krebs-Ringer bicarbonate solution (4 degrees C, pH 7.5) bubbled with 95% O2/5% CO2. A visceral peritoneal planar sheet was mounted in an Ussing-type chamber and adrenaline (10(-7) mol/L) was added to the apical and the basolateral side in turn. We measured R(TE) before and serially for 30 minutes after addition of the adrenaline. Because active ion transport is temperature-dependent, all experiments were performed at 37 degrees C. All results are presented as mean and standard error (x +/- SE) of 6 experiments. The control R(TE0 (before adrenaline) was 20.05 +/- 0.61 omega x cm2. Within 1 minute after the addition of adrenaline to the basolateral side of the membrane, R(TE) increased to 21.8 omega x cm2, a rate that thereafter progressively decayed, returning to the control value. Adrenaline action on the apical side of the membrane was similar, with a rapid rise of R(TE) to 22.5 omega x cm2 and a subsequent decrease (p < 0.05). Previous studies provide evidence for a clear association between R(TE) and active ion transport. The results of the present study indicate rapid action of adrenaline on the permeability of the visceral peritoneum.
Abstract: Raised serum levels of adhesion molecules are believed to reflect endothelial activation and may contribute to the development of diabetic vascular complications. The aim of this study was to clarify the association between soluble adhesion molecules levels and retinopathy in type 2 diabetic patients. Levels of soluble E-selectin, ICAM-1 and VCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 47 type 2 diabetic patients classified in two subgroups according to the presence (n=34) or absence (n=13) of retinopathy as determined by fundus ophthalmoscopy; 22 control subjects were also studied. Soluble E-selectin levels were significantly elevated in both diabetic subgroups compared to control subjects (p<0.01), while no significant difference was found in sICAM-1 and sVCAM-1 levels. However, sE-selectin, sICAM-1 and sVCAM-1 levels were comparable in diabetic subgroups. The progression of retinopathy was not associated with an increase in soluble adhesion molecules levels. Stepwise multiple regression analysis revealed that only diabetes duration and microalbuminuria were independent determinants of retinopathy (p<0.01). Our results confirm the contribution of endothelial activation in the development of diabetic complications as indicated by increased levels of soluble adhesion molecules. However, a direct implication of adhesion molecules in the pathogenesis or progression of type 2 diabetic retinopathy cannot be supported.
Abstract: Nasal corticosteroids improve polysomnography indices but not symptoms in children with mild to moderate sleep-disordered breathing. We hypothesized that administration of nasal corticosteroids for 4 weeks to snoring children with only mild elevation in their apnea-hypopnea index would improve both polysomnography findings and symptoms of sleep-disordered breathing. Budesonide 50 mcg per nostril twice daily was administered for 4 weeks to children (2-14 years old) with habitual snoring and an apnea-hypopnea index of 1-10 episodes/hr. Subjects were evaluated before treatment and at 2 weeks and 9 months after its completion. Primary outcome variables were changes in apnea-hypopnea index and symptom score. Twenty-seven children were studied. At 2 weeks, the mean apnea-hypopnea index decreased from 5.2 (+/-2.2) episodes/hr to 3.2 (+/-1.5) episodes/hr, and median oxygen desaturation of hemoglobin index fell from 3.1 (0.4-8.2) to 1.9 (0.2-5.4) (P < 0.0001). Mean symptom score was 1.33 (+/-2.11) at baseline, and decreased to -0.008 (+/-2.24) at 2 weeks after treatment and to -1.08 (+/-1.75) at 9 months after treatment (P < 0.05). Four weeks of nasal budesonide improved both polysomnography findings and symptoms in children with mild sleep-disordered breathing. The clinical effect is maintained for several months after treatment.
Abstract: Elevated fibrinogen level is a predictor of cardiovascular disease in adults, and it is associated with sleep-disordered breathing. Levels of fibrinogen in adults are affected by other co-existing cardiovascular risk factors, which are not usually present in children. To investigate the association between fibrinogen and sleep-disordered breathing, a case-control study was carried out in children with and without habitual snoring. All snoring children underwent polysomnography. Morning fibrinogen values in 30 children with snoring and an apnoea-hypopnoea index (AHI) > or =5 episodes x h(-1) (median (interquartile range) 318 mg x dL(-1) (290-374)) were similar to values in 61 children with snoring and an AHI <5 episodes x h(-1) (307 (269-346)). Both groups had higher fibrinogen values than those in 23 controls without snoring (271 mg x dL(-1) (244-294)). There was no correlation between fibrinogen values and AHI, respiratory movement/arousal index or haemoglobin desaturation index. In conclusion, fibrinogen values are higher in children with snoring than in controls, but there is no association between these values and polysomnography indices.
Abstract: In order to test the serum levels of ICAM-1, ICAM-2 and ICAM-3 in patients with idiopathic pulmonary fibrosis (IPF), twenty patients with IPF and eleven with secondary interstitial fibrosis (SIF), as well as forty healthy volunteers (HV) were studied. Serum intracellular adhesion molecules (ICAM) 1, 2 and 3 were assessed by ELISA. Functional respiratory tests, which included spirometry and lung diffusing capacity were simultaneously performed. Median values of serum ICAM-1 and ICAM-2 were higher in the patients' than in the healthy volunteers' (HV) group: IPF group: 946.60 ng/ml and 400.14 ng/ml; SIF group: 901.58 ng/ml and 378.27 ng/ml; HV group: 308.40 ng/ml and 217.55 ng/ml, respectively (p<0.05). ICAM-3 serum levels were equal between the three groups. ICAM-2 negatively correlated to DLCO values. (p<0.005). It can be concluded that ICAM 1 and 2 are elevated in the sera of patients with pulmonary fibrosis. ICAM-2 might be associated with a more impaired clinical status.
Abstract: It is expected that asthmatic students in a health science department would avoid the hazards of cigarette smoking due to the knowledge they gain through their studies. Surprisingly, health science students with asthma had a higher prevalence of smoking than their healthy colleagues.
Abstract: Left-handedness has been associated with asthma and allergic disorders. The Geschwind-Behan-Galaburda (GBG) hypothesis could explain this association. In view of previous findings, we investigated the distribution of laterality scores among asthmatic children and controls aged 4-8 years old. Seventy families with asthmatic children were administered the International Study of Asthma and Allergy in Childhood (ISAAC) questionnaire and the Edinburgh Left-handedness Inventory. A sample of 70 families with non-asthmatic, healthy children was used as controls. The majority of children had mild asthma. Ambidexterity was the main feature in the asthmatic children. A statistically significant difference in the laterality quotient (LQ) distribution was found in the group of asthmatic children with allergic rhinitis (LQ mean value in the asthmatic children with allergic rhinitis: 42.85 vs. 79.50 in the rest of the asthmatic children). These results suggest that there is a tendency towards left-handedness in asthmatic children and lend support to the GBG hypothesis.
Abstract: To assess the nature of pulmonary dysfunction in type 1 diabetes and the relationship of pulmonary function tests to diabetic factors and complication.
Abstract: Medications identified for the treatment of recurrent wheezing in preschool children by the Expert Panel Report of the NHLBI Guidelines for the Diagnosis and Management of Asthma include inhaled corticosteroids, chromones, theophylline, and leukotriene pathway modifiers. However, these various agents differ in their mechanism, extent of action on the airway inflammatory process, and degree of clinical efficacy. Inhaled corticosteroids can control symptoms in many young children with even severe persistent wheezing, but data on their long-term safety when administered in preschool-age children are scarce. There is some information on the uninterrupted use of inhaled corticosteroids in school-age children and the absence of an adverse effect on ultimate adult height. Despite laboratory evidence of adrenal suppression in some studies, few pediatric cases of clinical adrenal insufficiency have been reported. Low-dose inhaled corticosteroid (<400 mcg/day for beclomethasone), which is adequate for controlling mild persistent symptoms, is generally safe. Chromones have a remarkable safety profile, but they are most effective for symptoms of mild severity. Promising data have been published on the efficacy and safety of leukotriene pathway modifiers when used in young children with persistent symptoms. It is uncertain whether early introduction and long-term administration of inhaled corticosteroids prevent development of irreversible airway obstruction. Nevertheless, they may be especially useful for patients with moderate to severe disease in whom other agents (chromones or leukotriene pathway modifiers) will most likely fail to control symptoms. Pediatr Pulmonol. 2003; 35:241-252.
Abstract: A 51-year-old-woman presented with chronic eosinophilia, a diffuse interstitial lung pattern on CT and splenomegaly with hypodense lesions. A diagnosis of sarcoidosis was determined from a lung biopsy. Hyperinfection with strongyloides following treatment with systemic steroids explains the presence of eosinophilia and splenic involvement.
Abstract: In the past few years, a variety of extradigestive disorders, including cardiovascular, skin, rheumatic and liver diseases, have been associated with Helicobacter pylori (H. pylori) infection. The activation of inflammatory mediators by H. pylori seems to be the pathogenetic mechanism underlying the observed associations. The present review summarizes the current literature, including our own studies, concerning the association between H. pylori infection and respiratory diseases. A small number of epidemiological and serologic, case-control studies suggest that H. pylori infection may be associated with the development of chronic bronchitis. A frequent coexistence of pulmonary tuberculosis and H. pylori infection has also been found. Moreover, recent studies have shown an increased H. pylori seroprevalence in patients with bronchiectasis and in those with lung cancer. On the other hand, bronchial asthma seems not to be related with H. pylori infection. All associations between H. pylori infection and respiratory diseases are primarily based on case-control studies, concerning relatively small numbers of patients. Moreover, there is a lack of studies focused on the pathogenetic link between respiratory diseases and H. pylori infection. Therefore, we believe that larger studies should be undertaken to confirm the observed results and to clarify the underlying pathogenetic mechanisms.
Abstract: Obstructive sleep apnea syndrome (OSA) is accompanied by oxygen desaturation and arousal from sleep. Free oxygen radicals are highly reactive molecules which could be produced by the OSA phenomenon of hypoxia/reoxygenation: cyclical alterations of arterial oxygen saturation with oxygen desaturation developing in response to apneas followed by resumption of oxygen saturation during hyperventilation. On the basis of these considerations, it was hypothesized that OSA may be linked to increased oxidative stress.
Abstract: Lung function in diabetes has been reported in several studies with contradictory results. Diabetes mellitus increases expression of adhesion molecules through hyperglycemia. These molecules play an important role in the pathophysiological dysfunction of the vasculature.
Abstract: Obstructive sleep apnea syndrome (OSA) results in oxygen desaturation and arousal from sleep. Free oxygen radicals are highly reactive molecules, which can be produced by the OSA phenomenon known as hypoxia/reoxygenation. Hypoxic conditions, such as OSA, may also result in transient depletion of cellular reductants, which constitute a main line of antioxidant defense. Both apneas and hypopneas usually end in arousal, where reoxygenation causes the production of reactive oxygen species (free radicals). Living organisms have developed complex antioxidant systems to counteract reactive oxygen species and to reduce their damage. We evaluated the antioxidant capacity in serum from OSA patients and healthy people in order to confirm the hypothesis that there is a relationship between oxidative stress and OSA.
Abstract: In the present study, WISC-III Verbal IQ and sleep disorders in children with Attention Deficit Hyperactivity Disorder (ADHD) and controls who were matched for age and sex were assessed. 18 children with ADHD, 14 boys and 4 girls, and 18 controls, 14 boys and 4 girls, participated. Polysomnographs were performed for all ADHD children during their night sleep. The Greek version of WISC-III was used to evaluate Verbal IQ. Analysis of the polysomnographs showed that the quality of night sleep of the children with ADHD was very poor, including apneas, low desaturation rates, and awakenings in combination with limb activity and snoring. This agreed with their low Verbal IQ, which was up to 20 points lower than the controls' Verbal IQ. Sleep disorders in ADHD children could contribute to lower Verbal IQ.
Abstract: The fluid and solute transport properties of human parietal pleura were studied and compared with sheep parietal pleura in vitro. The pleura was mounted as a planar sheet between Ussing-type chambers. The results presented are the mean values of nine different experiments. The transepithelial electrical resistance (R(TE)) of both pleurae species was measured before and after the addition of amiloride in both sides of pleura. The R(TE) for human was 25.74 +/- 1.23 Ohm x cm(2), while for the sheep it was 38.18 +/- 0.83 Ohm x cm(2). The addition of amiloride to the serosal bathing solution increased the R(TE) of human pleura to 30.48 +/- 1.01 Ohm x cm(2) and sheep pleura to 40.32 +/- 0.82 Ohm x cm(2), while amiloride had no effect on the basolateral side. From the above, it is strongly suggested that the human pleura seems to be more leaky than sheep pleura. Although the R(TE) was increased in both pleurae, the elevation in human pleura was significantly higher, thus results from experiments in sheep pleura could only partly be extrapolated in human pleura.
Abstract: We investigated the effects of 17beta-estradiol and progesterone on transepithelial electrical resistance (R(TE)) in sheep visceral and parietal pleurae. Specimens of intact pleurae from adult female sheep were used. The samples were transferred to the laboratory within 30 min after death of the animal in a Krebs-Ringer solution at 4 degrees C. The pleura was then mounted as a planar sheet in Ussing-type chambers, and electrical measurements were made. There was an increase in R(TE) in all of the samples examined after addition of 17beta-estradiol and progesterone in visceral and parietal pleurae. This increase was rapid within 1 min, lasted for ~15 min, returned to the basal level within 30-45 min, and was dose dependent. Tamoxifen, an estrogen receptor antagonist, did not significantly eliminate the effect of 17beta-estradiol. Furthermore, no steroid receptors were identified in cytosolic preparations of visceral and parietal pleura with ligand binding assays. The estrogen- and progesterone-induced increase in R(TE) in both visceral and parietal pleurae was affected by addition of an inhibitor of nitric oxide synthase. Indeed, previous administration of N(omega)-nitro-L-arginine methyl ester prevented the increase in R(TE) by 17beta-estradiol and progesterone. These results suggest that 17beta-estradiol and progesterone induce an increase in R(TE) in both visceral and parietal pleura and thus alter the transepithelial permeability. The effect of steroids may be accounted for by rapid release of nitric oxide in pleura.
Abstract: The aim of this study was to evaluate the effects of indoor smoking. Exhaled carbon monoxide (CO) concentrations were measured on a CO monitor by a vital capacity manoeuvre in three groups of adolescents: non-smokers with non-smoking families, non-smokers with smoking mothers, and smokers. Each group included eight families. Smokers had higher exhaled CO (mean +/- SD, 35.67 +/- 14.62 ppm) than non-smokers with smoking mothers (6 +/- 2.5 ppm) and non-smokers (2.37 +/- 0.56 ppm), late in the evening (21.00 h). The levels of exhaled CO in non-smoking adolescents doubled if their mothers smoked. CONCLUSION: Exhaled CO can be used as an indicator of indoor smoking. Maternal smoking plays a major role in the health of adolescents.
Abstract: Medical education in Greece is government-funded by constitution. Tuition fees are therefore not payable by students. This investigation aims to identify the sources of income of medical students in Greece.
Abstract: We investigated the effect of the excitatory amino acid (EAA) receptor agonists L-glutamate, N-methyl-D-aspartate (NMDA), (RS)-a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainic acid on KCl-induced contractions of rabbit tracheal smooth muscle, as well as the role of epithelium and endogenously produced nitric oxide and prostaglandins on these responses. L-Glutamate decreased KCI-induced contractions up to 30%. This effect was attenuated by epithelium removal, tetrodotoxin, methylene blue and indomethacin but not by NG-nitro-L-arginine methyl ester. While NMDA, AMPA and kainic acid had no effect, the combination of NMDA + kainic acid decreased KCI-induced contractions. These results suggest that, in rabbit trachea, L-glutamate has, at least in part, an epithelium-dependent effect mediated via prostaglandin formation and that the EAA receptors involved are non-classical.
Abstract: We report a man aged 68 years old with pneumothorax and chronic bilateral pleural effusion in association with a history of yellow nails. The diagnosis of yellow nail syndrome based on yellow nails, lymphedema, chronic pleural effusion and intestinal lymphangiectasia.
Abstract: In type II diabetes mellitus there are few data concerning pulmonary function abnormalities. In normal subjects and in patients with primary Raynaud phenomenon, cold pressor test induces a decrease in carbon monoxide single-breath diffusing capacity (DL,co) but not in secondary Raynaud phenomenon. Our objective was to assess evaluation of lung diffusion capacity postural changes in diabetes mellitus and in secondary Raynaud phenomenon, two diseases with different pulmonary capillaries functional disorders.
Abstract: Twelve subjects with Down syndrome underwent polysomnographic studies during night sleep and performed the Mini-Mental state test and the Raven Progressive Matrices (RPM), sets A, B, and B(1). Sleep-disordered breathing (SDB) deficits were observed in Down syndrome individuals and their Mini-Mental and RPM scores were extremely low. Regression analysis of the results revealed that the number of apneas per hour was related with the results of the RPM, set A, which were also related with the orientation of Mini-Mental test, indicating that the more apneas an individual has the more difficulties he has in the kind of visuoperceptual skills, including orientation, associated with normal right hemisphere functioning, which are tested by set A of the RPM.
Abstract: The fluid and solute transport properties of pleural tissue were studied by using specimens of intact visceral and parietal pleura from adult sheep lungs. The samples were transferred to the laboratory in a Krebs-Ringer solution at 4 degrees C within 1 h from the death of the animal. The pleura was then mounted as a planar sheet in a Ussing-type chamber. The results that are presented in this study are the means of six different experiments. The spontaneous potential difference and the inhibitory effects of sodium nitroprusside (SNP), ouabain, and amiloride on transepithelial electrical resistance (R(TE)) were measured. The spontaneous potential difference across parietal pleura was 0.5 +/- 0.1 mV, whereas that across visceral pleura was 0.4 +/- 0.1 mV. R(TE) of both pleura was very low: 22.02 +/- 4.1 Omega. cm2 for visceral pleura and 22.02 +/- 3.5 Omega. cm2 for parietal pleura. There was an increase in the R(TE) when SNP was added to the serosal bathing solution of parietal pleura and to the serosal or mucosal bathing solution in visceral pleura. The same was observed when ouabain was added to the mucosal surface of visceral pleura and to either the mucosal or serosal surface of parietal pleura. Furthermore, there was an increase in R(TE) when amiloride was added to the serosal bathing solution of parietal pleura. Consequently, the sheep pleura appears to play a role in the fluid and solute transport between the pleural capillaries and the pleural space. There results suggest that there is a Na+ and K+ transport across both the visceral and parietal pleura.
Abstract: In order to find out how insulin acts on airway smooth muscle and which mechanisms could be involved, we studied the effect of insulin on contraction induced, first, by KCl and, second, by Acetylcholine (Ach), before and after epithelium removal, and finally in the presence of N(omega)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor. Tracheal smooth muscle strips from 24 rabbits, 6 being used for each experiment. Each muscle strip was pretreated with a solution containing either 80 mM KCl or 10(-5) Ach and increasing doses of insulin (range 10(-10)--10(-5) M) in the presence or absence of 10(-4) M L-NAME. A reference curve for contraction evoked by 80 mM KCl or 10(-5) M Ach in the presence or absence of 10(-4) M L-NAME was recorded each time before the pretreatment mentioned above. Insulin evoked a concentration-dependent inhibition of tracheal smooth muscle contraction, induced by 80 mM KCl or 10(-5) M Ach. After epithelium removal, insulin (10(-8), 10(-7) M) evoked statistically significant increases to the contractions induced by 10(-5) M Ach compared to the contractions induced by 10(-5) M Ach and insulin in the presence of epithelium (P < 0.05). These increases were higher when 10(-4) M l-NAME was added to the bath (P < 0.05). In conclusion, these results indicate that insulin inhibits tracheal smooth muscle contraction by acting on epithelium and releasing NO.
Abstract: The concentration of NO(2) and SO(2) was measured in a commercial greenhouse from 23/9/1999 25/01/2000. The measurements showed that the level of the two gases is very high in the greenhouse atmosphere. Lung function tests in 42 workers showed that temporary work did not influence significantly the respiratory health status.
Abstract: In the search for effective treatment of a life-threatening asthma attack, intravenous magnesium infusion has been studied in asthmatic patients because of its potential effect to reverse bronchospasm and improve pulmonary function. To determine whether magnesium sulfate inhibits airway smooth muscle contraction and the possible mechanism of its action, in vitro experiments were performed on rabbit tracheas. Tracheal muscle strips were obtained from 12 rabbits. Initially, the muscle strip was pretreated with a solution containing MgSO4 (concentrations 10(-4) to 2 M) and 85 mM KCl. The response curve of the muscle was recorded. Application of the above solution led to a 40% relaxation at a magnesium concentration of 10(-1) M. The time to peak and to wash-out remained unchanged, and fixed to 66.6 and 123.3 sec, respectively, not influenced by magnesium concentration. On a second phase, the muscle strip was pretreated with KCl alone, and only after a full contractile response was obtained did we add 10(-1) M MgSO4, which led to full relaxation. We follow the same protocol using 10(-4) M acetylcholine (ACH). In this case, simultaneous application of 10(-1) M MgSO4 caused a 55.1% decrease in muscle contraction and a 60% decrease in time to peak. On a second phase, we added magnesium as we did with KCl, but without the same result. Magnesium caused a full relaxation when the constrictor agent was KCl, but a residual contraction was observed when the constrictor was ACH. Based on the knowledge that ACH and KCl cause Ca2+ influx into the cells and subsequent contraction by acting on different Ca2+ channels, we concluded that magnesium inhibits Ca2+ influx by blocking the voltage-dependent calcium channels.
Abstract: Some asthmatic children living in mountain areas experience significant improvement in daily symptoms and in the degree of bronchial obstruction. The aim of this study is to investigate the effect of altitude on the prevalence and morbidity of childhood bronchial asthma.
Abstract: A statistically significant difference in mean laterality quotients of 15 asthmatic and 106 nonasthmatic children showed a coexistence of left-handedness and asthma early in life. It is suggested that this phenomenon is not only a fetal event as the Geschwind-Galaburda hypothesis claims but it is mainly based on maternal line inheritance.
Abstract: The objective of the study was to investigate the effect of endothelin-1 (ET-1) on KCl-induced contractions. Tracheal strips were obtained from 12 male rabbits, perfused with Krebs solution and aerated continuously by bubbling with a mixture of 95% O(2)-5% CO(2). Increasing concentrations of ET-1 (10(-12)-10(-7) M) additionally to KCl caused more contractions than KCl-induced (P<0.05). A total of 10(-7) M ET-1-induced 14.56% more contraction. Methylene blue (10(-5) M) decreased all the contractions induced from simultaneous use of KCl and ET-1. Methylene blue caused about 18% relaxation of contraction induced from KCl (80 mM) and ET-1 (10(-8) M). Consequently ET-1 increases the KCl-induced contractions of airway smooth muscles. This effect seem to mediate by a nitric oxide (NO)-guanylate cyclase-cGMP pathway, in which methylene blue is inactivator of guanylate cyclase.
Abstract: The relationship between lung function and smoking and dietary habits was examined in 121 Gypsies (62 males, 59 females) who were 14-70 y of age and who lived in Greece. All were examined clinically, after which they all participated in spirometry tests. Half of the study group had abnormal (< 80% of predicted) forced vital capacity, 36.4% had abnormal (< 80% of predicted) forced expiratory volume in 1 sec, and 5% had serious lung function disturbances (forced vital capacity < 50% of predicted). Approximately 70% of subjects were smokers, and their diets were rich in alcohol and meat; they ate very few salads and oranges. Consequently, decreased lung function might be a major health problem in Gypsies in Greece. Organization of preventive health strategies should improve the overall health of this study group.
Abstract: The purpose of the study was the determination of prevalence of chronic bronchitis in people older than 55 years in rural and industrial areas. 569 people over 55 years old living in central Greece were studied. A protocol was completed for each patient that included smoking habits, job, age, weight, drugs used for respiratory system and symptoms. A chest radiograph was taken for each patient. Each patient was submitted to three trials of dynamic spirometry. The best results were used for the study. The patients who complained of expectoration for three months for two continuous years and had obstructive pattern of lung function were diagnosed with chronic bronchitis. 9.6% of the subjects in rural area and 17.1% in industrial area were diagnosed with chronic bronchitis. Half the COPD patients never visited a doctor for this specific problem and were diagnosed for the first time. One out of three examined people had abnormal lung function. Consequently, more than one out of ten people older than 55 years have chronic bronchitis. Industrial exposure seems to double the risk for chronic bronchitis.
Abstract: The purpose of this study was the effect of epithelium damage on mechanical responses of airway smooth muscles under different resting tension. We performed acetylcholine (ACh) (10(-5) M)-induced contraction on tracheal strips from 30 rabbits in five groups (0.5, 1, 1.5, 2 and 2.5 g) before and after epithelium removal. At low resting tension (0.5-1.5 g), the epithelium removal decreased the ACh-induced contractions. At 2 g resting tension, the epithelium removal increased the ACh-induced contractions of airways with intact epithelium about 20%. At 2.5 g resting tension, the elevation of contraction is about 25% (P<0.01). Consequently, after epithelium loss, the resting tension determines the airway smooth muscles responsiveness. In asthma, mediators such as ACh act on already contracted inflammatory airways, which results in additional increase of contraction. In contrast, low resting tension, a condition that simulates normal tidal breathing, protects from bronchoconstriction even when the epithelium is damaged.
Abstract: The purpose of this study was the evaluation of the extent of dissemination of asthma guidelines among primary health care physicians in Greece. Sixty-five of 80 primary care physicians (response rate 80.2%) answered a questionnaire about asthma morbidity, manner of choice of treatment and asthma management plans. One out of 12 patients who were examined by a primary care physician suffered from bronchial asthma. Forty-two physicians treated their asthma patients according to the pulmonologist's recommendations, and only 15 prescribed asthma treatment according to asthma guidelines. beta 2-agonist inhalers and theophylline tablets represent 41% of all prescribed medicines in asthma and corticosteroid inhalers 24% of medications. Eight physicians prescribed theophylline as the first and 20 physicians corticosteroid inhalers as the third choice of medication in asthma treatment. Consequently, the prescription of beta 2-agonist inhalers and theophylline tablets seems to be higher than asthma guidelines recommend. Better dissemination of guidelines among specialists and primary health care physicians will hopefully make asthma management optimal.
Abstract: The airway epithelium is responsible for the production of a number of arachidonic acid and non-prostanoid inhibitory factors. Epithelium synthesises nitric oxide (NO) which may be important in regulating the function of airways smooth muscles. We studied in vitro the effect of histamine (100 nM-100 microM) which increases the NO release on rabbit airway smooth muscles induced by 80 mM KC1 in the presence or not of 10(-5) Methylene blue (MB) (inactivator of guanylate cyclase) or N(G)-monomethyl L-arginine (L-NMMA), a NOS inhibitor. All experiments were done in tracheal muscle strips from 28 rabbits with epithelium and after epithelium removal. The additional use of histamine (1 microM) on KC1 contraction induced a relaxation of 10% of the initial contraction. The additional use of L-NMMA decreased the relaxation to 5% of initial contraction. MB rather than L-NMMA increased the contraction significantly (p<0.01). Epithelium removal increased the contraction induced by KC1 (80 mM) and histamine (1 microM) by about 30% (p<0.001). NO release especially from epithelium regulates the airways smooth muscle functions. Damage to the epithelium may contribute to an increase in airways sensitivity, observed in asthma.
Abstract: The conditions of labour appear to favour the development of pleural effusion. The frequency of postpartum pleural effusion was investigated in this study using thoracic ultrasonography. Thirty one postpartum and 22 healthy nonpregnant women of the same age-group were examined, both supine and seated, via an intercostal approach. Seven of the 31 (23%) postpartum women had pleural effusion within 1-24 h of normal delivery. None of the nonpregnant women had pleural effusion. No correlation was found between postpartum pleural effusion and age, weight-gain during pregnancy, duration of labour, use of intravenous fluid, or oxytocin administration. Pleural effusion seems to be a common finding postpartum, but of no clinical significance.
Abstract: With the purpose of estimating the use of bronchodilators in asthma management as prescribed by primary health physicians (PHCP) in Greece, 62 PHCP answered a questionnaire about the manner of choice of treatment, the person who trained the patients in the use of inhalers, and the pharmacological treatment. 65% of PHCP selected the treatment according to the pulmonologist's recommendations and 34% by themselves. 26% of the PHCP trained their patients in the use of inhalers, and 40% considered that it was done by another physician. Forty-three physicians used adrenergic inhalers as the first choice of medicine. The second most popular medicine in asthma management is theophylline tablets (15% of all medicines). Consequently, PHCP in Greece frequently select asthma treatment according to the pulmonologist's recommendations, and consider that another physician has trained the patients how to use the inhalers. They frequently prescribe adrenergic inhalers, theophylline tablets and corticosteroid inhalers.
