Nikos Tzanakis

On the practical solution of the Thue equation

This invention relates to apparatus for converting into useful energy movements imparted thereto by movement of water, preferably sea waves and/or sea currents, the apparatus comprising two or more interconnected members of which at least one is buoyant and which in use of the apparatus are movable relative to each other due to vertical motions of the water, at least one of said members being provided with or connected to means which in use of the apparatus is responsive to horizontal motions of the water, and means for converting the relative movements of said interconnected members and operation of the means responsive to horizontal motions of the water into useful energy, such as electricity.

Lung function in patients with inflammatory bowel disease

Previous studies on baseline pulmonary function testing (PFT) abnormalities in patients with inflammatory bowel disease (IBD) are conflicting because most of them have incorporated patients suffering from both ulcerative colitis (UC) and Crohns disease (CD). The aim of the study is to investigate whether any PFT abnormalities could be detected in a large group of IBD patients and whether there are differences between the two IBD entities. A total of 132 patients, 47 with CD (mean age 35 years) and 85 with UC (mean age 40 years) were studied. Pulmonary function tests (PFTs), lung transfer factor for carbon monoxide (TLCO) were examined and compared with those of 36 healthy controls. No significant difference of mean values of spirometric indices, TLCO and ABG was found between the two groups of patients and controls, or between patients with CD and UC. However, nine (19%) patients with CD and 15 (17.6%) with UC had a reduction in TLCO, a percentage significantly higher than in controls (P < 0.05). The majority of the patients with TLCO reduction were in an active phase of disease (P < 0.05). Our results suggest that there is no difference in routine PFTs between UC and CD patients, as well as between both these groups and normal controls. However, TLCO abnormalities related to the degree of disease activity are found in patients with both UC and CD.

Intrapleural urokinase in the treatment of complicated parapneumonic pleural effusions and empyema

Intrapleural urokinase has not been evaluated systemically in terms of efficacy, safety, and cost of treatment in a large series of patients with complicated (parapneumonic) pleural effusions (CPE) and pleural empyemas (PE). Furthermore, the optimal dose and duration of treatment is not known. Twenty consecutive patients with multiloculated parapneumonic effusions (13 with CPE and 7 with PE), in whom a single chest tube failed to drain the fluid, were studied prospectively. The age of the patients ranged 15-92 yrs (median 51 yrs). Urokinase was administered intrapleurally, in a low single daily dose of 50,000 U in 100 mL normal saline via the chest tube. Previous intrapleural instillation of 100 mL normal saline failed to promote drainage in all patients. Urokinase enhanced drainage in all patients. Clinical and radiological improvement was noted in all but one patient. The mean (SD) volume of fluid significantly increased in the first 24 h post-urokinase (p<0.001). The number of urokinase instillations ranged 3-7 (median 5). Radiological evaluation showed excellent improvement in 13 of the 20 (65%) patients. Urokinase was well-tolerated in all patients. The clinical course of patients was uneventful at a mean follow-up of 15 months (range 6-30 months) later. Mean total cost of treatment was

Induced sputum in the investigation of airway inflammation of COPD

530 +/- 34.6. Our results show that intrapleural instillation of small doses of urokinase is a cost-effective and safe mode of treatment of complicated pleural effusions and pleural empyema and could be the fibrinolytic of choice.

Exhaled Breath Condensate 8-Isoprostane, Clinical Parameters, Radiological Indices and Airway Inflammation in COPD

During the last decade, the method of sputum induction (SI) has offered the opportunity to study inflammation in patients with chronic obstructive pulmonary disease (COPD). This paper reviews methodological aspects of SI and summarizes its uses in the research of inflammation in COPD, including sputum cellularity and soluble markers. SI is a relatively safe, reliable, and reproducible technique, used to investigate different aspects of airway inflammation. Although various methods of induction and processing have been proved safe and highly reproducible, a generally accepted method is needed. Sputum analysis has given evidence for increased numbers of macrophages and neutrophils in COPD patients compared to normal subjects. In some studies, increased numbers of eosinophils have been also reported. Changes in various mediators have been found in sputum supernatant of COPD patients (IL-8, LTB-4 and TNF-a). The clinical usefulness of the method in the follow-up of the disease has not been explored extensively. A number of observations in patients with different clinical characteristics could be proven useful in identifying patterns of inflammation associated with different prognosis. Finally, SI could also guide treatment; such as, sputum eosinophilia in COPD could predict response to inhaled corticosteroids.

Tc2 Response at the Onset of COPD Exacerbations

Background: Exhaled breath condensate (EBC) 8-isoprostane levels were found increased in chronic obstructive pulmonary disease. However, the relation between EBC 8-isoprostane and parameters which have a known predictive value in COPD, remains vastly unknown, and so does subsequently its clinical value. Objectives: To investigate the relationship between 8-isoprostane level in EBC and clinical parameters, radiological indices and airway inflammation in COPD patients. Materials and Methods: We studied 18 COPD patients (all ex-smokers) and 12 healthy controls (5 ex-smokers and 7 never-smokers). All patients underwent clinical evaluation, sputum induction, high-resolution computed tomography (HRCT) of the thorax and EBC 8-isoprostane measurement. 8-Isoprostane levels were correlated with markers that reflect disease severity, such as dyspnea severity, FEV1 (%pred), emphysema changes and bronchiectasis in HRCT. Emphysema was quantified as the percentage of lung area with attenuation values < –950 Hounsfield units. Results: 8-Isoprostane levels were significantly elevated in EBC of patients with COPD [mean (SE) 18.1 (2) vs. 5.6 (0.7) pg/ml, p = 0.0001], irrespective of lung function impairment. 8-Isoprostane levels were correlated with emphysema score in HRCT (r2 = 0.43, p = 0.001) as well as with Medical Research Council dyspnea scale score (rho = 0.61, p = 0.005). Conclusion: Our findings suggest that EBC 8-isoprostane levels may reflect the extension of lung emphysema in COPD patients. In this respect, further investigation is required in order to evaluate the possible role of EBC 8-isoprostane in assessing disease progress in COPD patients.

Innate immunity proteins in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis

BACKGROUND 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. METHODS Induced-sputum samples were collected from 24 COPD patients with median age of 52 years (interquartile range [IQR], 44 to 58 years) and FEV(1) percentage of predicted of 78.05% (IQR, 75.8 to 80.1%) at the onset of mild exacerbations not requiring hospitalization and when stable. Inflammatory cells and T-lymphocyte subpopulations (CD4+, CD8+, and cells producing interferon [IFN]-gamma or interleukin [IL]-4) were measured using flow cytometry and immunocytochemical methods. RESULTS A significant increase in sputum CD8+ T lymphocytes (p < 0.0001) and significant decreases in CD4+ T lymphocytes as well as in CD4+/CD8+ (p = 0.0001) and CD8+IFN-gamma+/CD8+IL-4+ (p = 0.001), CD4+IFN-gamma+/CD4+IL-4+ (p = 0.0003) sputum cells ratios were found decreased at the onset of exacerbations compared to stable condition. The changes in T-lymphocyte subpopulations were not associated with smoking history, demographic characteristics, or disease severity. CONCLUSION The findings of the present study suggest that CD8+ lymphocytes are increased and potentially polarized toward a Tc2 profile in the airways of COPD patients at the onset of COPD exacerbations with respect to stable condition. The clinical impact of the observed phenomenon requires further investigation.

Increased apoptosis of neutrophils in induced sputum of COPD patients

ABSTRACT Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) may be caused by epithelial cell injury. Epithelial cells respond to injury by secreting innate immunity proteins. To investigate whether altered levels of innate immunity proteins are observed in COPD and IPF, the authors assessed secretory leukocyte protease inhibitor (SLPI), elafin, CC16, and β-defensin-2 levels by enzyme-linked immunosorbent assay (ELISA) in sputum supernatants from COPD patients (n = 19), smokers without COPD (n = 21), and never-smokers (n = 10) and in BALF supernatants from patients with IPF (n = 11) and subjects without IPF (n = 11). CC16 levels were decreased, whereas SLPI and elafin levels were increased in COPD patients (0.8 [0–4.2] μg/mL, 2.5 [0.3–10.5] μg/mL, 213 [152–318] pg/mL, respectively) compared to smokers without COPD (1.8 [0.1–21.2] μg/mL, 0.8 [0.2–2.6] μg/mL, 172 [71–473] pg/mL, respectively) and never-smokers (0.5 [0–4.8] μg/mL, 0.1 [0.05–0.6] μg/mL, 188 [129–218] pg/mL, respectively) (CC16: P = .001; SLPI: P <.001; elafin: P = .041). β-Defensin-2 was detected in smokers without COPD (98 [10–729] pg/mL) and never-smokers (74 [35–410] pg/mL), but not in COPD. SLPI and elafin levels did not differ between IPF patients and controls, but CC16 levels were increased in IPF (0.5 [0–2.3] versus 0.2 [0–0.3] μg/mL; P = .019). β-Defensin-2 was not detected in BALF. In conclusion, in COPD, secretion of CC16 and β-defensin-2 might be suppressed, whereas SLPI and elafin secretion is up-regulated. In IPF, only CC16 secretion is up-regulated.

Microsatellite DNA instability and loss of heterozygosity in bronchial asthma.

AIM The aim of the current study was to evaluate apoptosis in induced sputum neutrophils and to investigate the relationship between the number of apoptotic cells and clinical parameters in COPD patients. METHODS Twenty-four COPD ex-smoker patients and 10 healthy controls were included in the study. All subjects underwent clinical evaluation and sputum induction. Sputum cell in situ apoptosis was identified using white light microscopy and TUNEL assay technique. Apoptosis of neutrophils obtained by sputum induction was expressed as apoptotic rate (AR=percentage of apoptotic neutrophils over the number of neutrophils measured). RESULTS TUNEL assay revealed statistically significant higher AR in COPD patients than controls (p=0.004). Patients with FEV(1)<50%pred had significantly higher median (IQR) AR (%) compared to patients with FEV(1)>or=50% [26.3 (16-29) vs 13.1 (8.6-21), p=0.01]. No significant association was found between the number of apoptotic cells and age, symptoms or medication used. CONCLUSION The significantly increased apoptotic rate of neutrophils that were found in COPD patients with advanced disease compared to controls might reflect either a deregulation of apoptosis of neutrophils or, a reduced clearance of apoptotic neutrophils from the airways. The pathophysiologic significance of the observed phenomenon has to be further explored.

On a family of cubics

Genetic alterations, such as loss of heterozygosity (LOH) or microsatellite instability (MI), have been reported in both malignant and benign disorders. In order to identify loci of deoxyribonucleic acid (DNA) mutation in asthma, MI and LOH were studied in sputum cells. DNA was extracted from cells in the sputum and blood cells of 22 patients with moderate asthma. Cells were analysed for MI and LOH using 18 polymorphic markers on chromosome 5q, 6p, 11q, 14q. Microsatellite analysis was also performed in six healthy subjects. None of the healthy individuals exhibited any genetic alteration. Genetic alterations were found in 16 of 22 asthmatic patients (73%). In total, 12 (54.5%) patients exhibited LOH only, one (4.5%) MI only, while three showed both MI and LOH. The highest incidence of LOH and MI was found on chromosome 14q. Mean immunoglobulin E and blood eosinophil levels were significantly higher in asthmatics with three or more genetic alterations. A high incidence of genetic alterations in the deoxyribonucleic acid of the sputum cells was found in asthmatic patients. Further studies are needed to identify the role of loss of heterozygosity and microsatellite instability in the investigation of genetic susceptibility of asthma and thus, in its pathogenesis.