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The impact of bisphosphonate therapy on survival of lung cancer patients with bone metastasis
Konstantinos Zarogoulidis,Efimia Boutsikou,Vasiliki Zarogoulidou,Hellie Lithoxopoulou
Pneumon , 2009,
Abstract: SUMMARY. INTRODUCTION: Bone metastases occur in 20% to 40% of patients with lung cancer. Recent studies (most in vitro) demonstrate an anti-proliferative effect of third-generation biphosphonates (BPs) on lung tumours which may, indirectly, have an impact on the survival. OBJECTIVES: This was a study of the effects of treatment with BPs on the course and survival of lung cancer patients with bone metastases. PATIENTS AND METHODS: For the study 108 male patients with lung cancer (stage IV) were recruited consecutively. Of these, 55/108 patients with positive bone scan experienced bone pain and received Nitrogen BPs (NBPs), specifically zoledronic acid (ZOL), 4 mg i.v. every 21 days (Group A). The other 53 patients received no NBPs, of which 30/53 had a positive bone scan (Group B) and 23/53 a negative bone scan (Group C). All patients were treated with combination chemotherapy consisting of Docitaxel 100 mg/m2 and Carboplatin AUC = 6. RESULTS: Group A had a statistically significantly longer mean survival and time to progression than Groups B and C (p<0.001). A statistically significant positive correlation was found between the number of cycles of therapy with NBPs and total patient survival (p<0.01, Pearson Correlation) and time to progression (p<0.01). Regarding the pain effect in relation to baseline, no significant difference was observed between the two groups of patients (with and without NBPs) with positive bone scan (p>0.05). CONCLUSION: The addition of NBPs to the treatment regime appears to increase overall survival in lung cancer patients with bone metastases. Further studies are needed to support the potential usefulness of NBPs as an independent therapeutic agent against lung cancer. Pneumon 2009; 22(1):25–37
Image Analysis of Soil Micromorphology: Feature Extraction, Segmentation, and Quality Inference
George P. Stamou,Efimia Papatheodorou,Vassilis Tzouvaras,Giorgos B. Stamou
EURASIP Journal on Advances in Signal Processing , 2004, DOI: 10.1155/s1687617204402054
Abstract: We present an automated system that we have developed for estimation of the bioecological quality of soils using various image analysis methodologies. Its goal is to analyze soilsection images, extract features related to their micromorphology, and relate the visual features to various degrees of soil fertility inferred from biochemical characteristics of the soil. The image methodologies used range from low-level image processing tasks, such as nonlinear enhancement, multiscale analysis, geometric feature detection, and size distributions, to object-oriented analysis, such as segmentation, region texture, and shape analysis.
Docetaxel-carboplatin in combination with erlotinib and/or bevacizumab in patients with non-small cell lung cancer
Boutsikou E,Kontakiotis T,Zarogoulidis P,Darwiche K
OncoTargets and Therapy , 2013,
Abstract: Eftimia Boutsikou,1 Theodoros Kontakiotis,1 Paul Zarogoulidis,1 Kaid Darwiche,2 Ellada Eleptheriadou,1 Konstantinos Porpodis,1 Grammati Galaktidou,3 Leonidas Sakkas,4 Wolfgang Hohenforst-Schmidt,5 Kosmas Tsakiridis,6 Theodoros Karaiskos,7 Konstantinos Zarogoulidis11Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Greece; 2University Pulmonary Department-Interventional Unit, Ruhrland Klinic, University of Duisburg-Essen, Essen, Germany; 3Theagenio Anticancer Institute Research Laboratory, 4Department of Pathology, G Papanikolaou Hospital, Thessaloniki, Greece; 5II Medical Clinic, Hospital Coburg, University of Wuerzburg, Coburg, Germany; 6Cardiothoracic Surgery Department, Saint Luke Private Hospital, Panorama, 7Cardiothoracic Surgery Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, GreeceBackground: Bevacizumab and erlotinib have been demonstrated to prolong overall survival in patients with non-squamous non-small cell lung cancer (NSCLC). We designed a four-arm Phase III trial to evaluate the efficacy and toxicity of the combination of docetaxel, carboplatin, bevacizumab, and erlotinib in the first-line treatment of patients with NSCLC.Methods: A total of 229 patients with stage IIIb/IV non-squamous NSCLC were treated with two cycles of carboplatin (area under the concentration-time curve 5.5) and docetaxel 100 mg/m2 as chemotherapy. After completion of two treatment cycles, patients were evaluated for response and divided into four groups: 61/229 continued with four more cycles of chemotherapy (control group), 52/229 received chemotherapy plus erlotinib 150 mg daily, 56/229 received chemotherapy plus bevacizumab 7.5 mg/kg, and 60/229 were treated with the combination of chemotherapy, erlotinib, and bevacizumab until disease progression. The primary endpoint was overall survival.Results: Over 4 years of follow-up, there was no statistically significant difference in survival and time to progression between the four treatment groups. After two cycles of chemotherapy, responders and nonresponders were divided according to their response in order to examine the role of initial response as an independent factor in survival and response when a biological agent is combined with chemotherapy. Nonresponders, who received additional therapy with bevacizumab or combination therapy, had a survival benefit [657 days (95% confidence interval 349–970) and 681 days (95% confidence interval 315–912), respectively], which was statistically significant compared with
Cord Blood Ischemia-Modified Albumin Levels in Normal and Intrauterine Growth Restricted Pregnancies
Nicoletta Iacovidou,Despina D. Briana,Maria Boutsikou,Sophia Liosi,Stavroula Baka,Theodora Boutsikou,Demetrios Hassiakos,Ariadne Malamitsi-Puchner
Mediators of Inflammation , 2008, DOI: 10.1155/2008/523081
Abstract: Ischemia-modified albumin (IMA) is a sensitive biomarker of cardiac ischemia. Intrauterine growth restriction (IUGR) may imply fetal hypoxia, resulting in blood flow centralization in favour of vital organs (brain, heart, adrenals—‘‘brain sparing effect’’). Based on the latter, we hypothesized that cord blood IMA levels should not differ between IUGR and appropriate-for-gestational-age (AGA) full-term pregnancies. IMA was measured in blood samples from doubly-clamped umbilical cords of 110 AGA and 57 asymmetric IUGR pregnancies. No significant differences in IMA levels were documented between AGA and IUGR groups. IMA levels were elevated in cases of elective cesarean section (P = .035), and offspring of multigravidas (P = .021). In conclusion, ‘‘brain sparing effect’’ is possibly responsible for the lack of differences in cord blood IMA levels at term, between IUGR and AGA groups. Furthermore, higher oxidative stress could account for the elevated IMA levels in cases of elective cesarean section, and offspring of multigravidas.
Is Routine Ultrasound Examination of the Gallbladder Justified in Critical Care Patients?
Pavlos Myrianthefs,Efimia Evodia,Ioanna Vlachou,Glykeria Petrocheilou,Alexandra Gavala,Maria Pappa,George Baltopoulos,Dimitrios Karakitsos
Critical Care Research and Practice , 2012, DOI: 10.1155/2012/565617
Abstract: Objective. We evaluated whether routine ultrasound examination may illustrate gallbladder abnormalities, including acute acalculous cholecystitis (AAC) in the intensive care unit (ICU). Patients and Methods. Ultrasound monitoring of the GB was performed by two blinded radiologists in mechanically ventilated patients irrespective of clinical and laboratory findings. We evaluated major (gallbladder wall thickening and edema, sonographic Murphy’s sign, pericholecystic fluid) and minor (gallbladder distention and sludge) ultrasound criteria. Measurements and Results. We included 53 patients (42 males; mean age years; APACHE II score ; mean ICU stay days). Twenty-five patients (47.2%) exhibited at least one abnormal imaging finding, while only six out of them had hepatic dysfunction. No correlation existed between liver biochemistry and ultrasound results in the total population. Three male patients (5.7%), on the grounds of unexplained sepsis, were diagnosed with AAC as incited by ultrasound, and surgical intervention was lifesaving. Patients who exhibited ≥2 ultrasound findings (30.2%) were managed successfully under the guidance of evolving ultrasound, clinical, and laboratory findings. Conclusions. Ultrasound gallbladder monitoring guided lifesaving surgical treatment in 3 cases of AAC; however, its routine application is questionable and still entails high levels of clinical suspicion. 1. Introduction Abnormalities of the gallbladder (GB) are frequent in the intensive care unit (ICU) [1, 2]. Critical care patients have many risk factors for acute acalculous cholecystitis (AAC) which is an acute inflammation of the GB in the absence of gallstones and accounts for 2–14% of all cases of acute cholecystitis [3–5]. AAC is an insidious complication that has been increasingly recognized in the critically ill with an incidence ranging from 0.2 to 3% [6–8]. Although the etiology is uncertain, AAC in the ICU has been associated with prolonged enteral fasting, total parenteral nutrition (TPN), duration of mechanical ventilation (MV) and the use of positive end-expiratory pressure (PEEP), activation of factor XII, trauma, sepsis, drugs (opiates, sedatives, and vasopressors), multiple transfusions, dehydration, and shock states [6, 9, 10]. Ultimately these factors may lead to bile stasis and GB hypoperfusion/ischemia resulting in acute inflammation of the GB. AAC is an emergency condition, and without immediate treatment there may be rapid progression to gangrenous cholecystitis (approximately 50%) or perforation (approximately 10%), with mortality rates as high as
Vascular Endothelial Growth Factor and Placenta Growth Factor in Intrauterine Growth-Restricted Fetuses and Neonates
Ariadne Malamitsi-Puchner,Theodora Boutsikou,Emmanuel Economou,Angeliki Sarandakou,Evangelos Makrakis,Dimitrios Hassiakos,George Creatsas
Mediators of Inflammation , 2005, DOI: 10.1155/mi.2005.293
Abstract: The angiogenic factors vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) are respectively up- and downregulated by hypoxia. We aimed to study circulating levels of the above factors in intrauterine growth restriction (IUGR) and to correlate their levels with the customized centiles of the infants. The study included 25 IUGR and 25 appropriate for gestational age (AGA) full-term, singleton infants and their mothers. Maternal (MS), fetal (UC), and neonatal day 1 (N1) and 4 (N4) blood was examined. MS and N1 PlGF, as well as UC VEGF levels correlated with the customized centiles of the infants (r=0.39, P=.007, r=0.34, P=.01, and r=−0.41, P=.004, resp). Furthermore, UC, N1, and N4 VEGF levels were higher in girls (r=0.36, P=.01, r=0.33, P=.02, and r=0.41, P=.005 resp). In conclusion, positive and negative correlations of examined factors with the customized centiles of the infant could rely on placental function and intrauterine oxygen concentrations—both being usually lower in IUGR cases—while higher VEGF levels in girls should possibly be attributed to the stimulating action of estrogens.
Neurotrophin-3 and FLT3 Tyrosine Kinase Receptor in Perinatal Life
Ariadne Malamitsi-Puchner,Emmanouel Economou,Theodora Boutsikou,Konstantinos E. Nikolaou,Nikolaos Vrachnis
Mediators of Inflammation , 2005, DOI: 10.1155/mi.2005.53
Abstract: Our aim is to determine—in 30 healthy full-term infants and their mothers—circulating levels of neurotrophin-3 (NT-3) (important for antenatal and postnatal brain development and implicated in the immune response) and FLT3 tyrosine kinase receptor (FLT3) (controlling hematopoiesis and found in the nervous tissue), in the fetal and neonatal life. NT-3 levels, in contrast to FLT3 ones, increased significantly on the fourth postnatal day in relation to the low levels found in the mother, fetus, and day 1 neonate (P=.03, respectively). Maternal and umbilical NT3 levels positively correlated with respective FLT3 levels (P=.003 and P=.03). Circulating NT-3 levels increased in early neonatal life, possibly due to exposure to various stimuli soon after birth. FLT3 levels do not seem to behave accordingly, although these two substances probably synergize.
Perinatal Plasma Monocyte Chemotactic Protein-1 Concentrations in Intrauterine Growth Restriction
Despina D. Briana,Maria Boutsikou,Stavroula Baka,George Papadopoulos,Dimitrios Gourgiotis,Karl Philipp Puchner,Dimitrios Hassiakos,Ariadne Malamitsi-Puchner
Mediators of Inflammation , 2007, DOI: 10.1155/2007/65032
Abstract: Monocyte chemotactic protein-1 (MCP-1) plays vital roles in immune response, angiogenesis, and pregnancy outcome. We investigated plasma MCP-1 concentrations in 40 mothers and their 20 intrauterine-growth-restricted (IUGR) and 20 appropriate-for-gestational-age (AGA) fetuses and neonates on postnatal days 1 (N1) and 4 (N4). Maternal and fetal MCP-1 concentrations were decreased (P<001 and P = .018, resp.), whereas N1 MCP-1 concentrations were elevated in IUGR group (P = .012). In both groups, fetal MCP-1 concentrations were lower compared to N1 and N4 ones (P = .045, P = .012, resp., for AGA, P< .001 in each case for IUGR). Reduced maternal and fetal MCP-1 concentrations in IUGR may reflect failure of trophoblast invasion, suggesting that down-regulation of MCP-1 may be involved in the pathogenesis of IUGR. Increased MCP-1 concentrations in IUGR neonates and higher postnatal ones in all infants may be attributed to gradual initiation of ex utero angiogenesis, which is possibly enhanced in IUGR.
Circulating Levels of Inflammatory Markers in Intrauterine Growth Restriction
Theodora Boutsikou,George Mastorakos,Marialena Kyriakakou,Alexandra Margeli,Demetrios Hassiakos,Ioannis Papassotiriou,Christina Kanaka-Gantenbein,Ariadne Malamitsi-Puchner
Mediators of Inflammation , 2010, DOI: 10.1155/2010/790605
Abstract: We aimed to investigate possible alterations in circulating levels of the perinatal stress markers high sensitivity (hs)-CRP, PAI-1, and S100B—probably reflecting brain and adipose tissue inflammation—in intrauterine growth-restricted-(IUGR) and appropriate-for-gestational-age-(AGA) pregnancies, given that these groups differ in fat mass and metabolic mechanisms involving aseptic inflammation. Serum hs-CRP, PAI-1, and S100B levels were measured in 40 mothers, and their 20 AGA and 20 IUGR full-term fetuses and neonates on postnatal days 1 and 4. hs-CRP, PAI-1, and S100B levels did not differ at all time points between AGA and IUGR groups. We conclude that the lack of difference in hs-CRP, PAI-1 and S100B levels, between IUGR and AGA fetuses/neonates—despite the lower birth weight, reflecting reduced fat mass in the former—might indicate more intense adipose tissue and nervous system inflammation in IUGRs. However, implication of other inflammation-related mechanisms, common in the IUGR state (e.g. preeclampsia), cannot be excluded. 1. Introduction Intrauterine growth restriction (IUGR), a major cause of infant mortality and morbidity [1, 2], is strongly related to the later development of the metabolic syndrome in adult life [3–5]. The metabolic syndrome represents a cluster of cardiovascular risk factors, such as visceral obesity, lipid and glucose metabolism abnormalities, leading to type 2 diabetes mellitus and arterial hypertension [6]. Insulin resistance has been proposed to be the underlying pathogenic link between metabolic syndrome and cardiovascular disease [7–9] and is associated with a state of low-grade aseptic inflammation that precedes the onset of metabolic syndrome [10, 11]. Data suggest that, compared with appropriate for gestational age (AGA) newborns, those with low birth weight may have relatively increased visceral fat stores [12, 13], as well as elevated levels of adipocytokines, such as leptin [14–16] and visfatin [17], which link the adipose depot to insulin resistance and sensitivity, respectively, as well as to aseptic inflammation [18]. C-reactive protein (CRP) is considered the major acute-phase reactant in humans. It is an important first-line host defence molecule, which recognises pathogens and damaged cells and promotes their elimination by activating the complement system and mediating their phagocytic clearance [19, 20]. Moreover, using high-sensitivity assays for CRP (hs-CRP), several studies have shown elevated CRP levels in obesity, since adiposity resembles a low grade systemic inflammatory state and hs-CRP is
Liver histology in ICU patients dying from sepsis: A clinico-pathological study
John Koskinas, Ilias P Gomatos, Dina G Tiniakos, Nikolaos Memos, Maria Boutsikou, Aspasia Garatzioti, Athanasios Archimandritis, Alexander Betrosian
World Journal of Gastroenterology , 2008,
Abstract: AIM: To determine end-stage pathologic changes in the liver of septic patients dying in the intensive care unit.METHODS: Needle liver biopsies obtained immediately after death from 15 consecutive patients with sepsis and no underlying liver disease were subjected to routine histological examination. Liver function tests and clinical monitoring measurements were also recorded.RESULTS: Liver biochemistries were increased in the majority of patients before death. Histology of liver biopsy specimens showed portal inflammation in 73.3%, centrilobular necrosis in 80%, lobular inflammation in 66.7%, hepatocellular apoptosis in 66.6% and cholangitis/cholangiolitis in 20% of patients. Mixed hepatitic/cholestatic type of liver injury was observed in 6/15 (40%) patients and hepatitc in 9/15 (60%). Steatosis was observed in 11/15 (73.3%) patients affecting 5%-80% of liver parenchyma. Among the histological features, the presence of portal inflammation in liver biopsy was associated with increased hospitalization in the ICU prior death (P = 0.026).CONCLUSION: Features of hepatitis and steatosis are the main histological findings in the liver in the majority of patients dying from sepsis.
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