-
[show abstract]
[hide abstract]
ABSTRACT: Hemorrhagic shock and resuscitation is frequently associated with liver ischemia-reperfusion injury. The aim of the study was to investigate whether hypoxemic resuscitation attenuates liver injury.
Anesthetized, mechanically ventilated New Zealand white rabbits were exsanguinated to a mean arterial pressure of 30 mmHg for 60 minutes. Resuscitation under normoxemia (Normox-Res group, n = 16, PaO(2) = 95-105 mmHg) or hypoxemia (Hypox-Res group, n = 15, PaO(2) = 35-40 mmHg) followed, modifying the FiO(2). Animals not subjected to shock constituted the sham group (n = 11, PaO(2) = 95-105 mmHg). Indices of the inflammatory, oxidative and nitrosative response were measured and histopathological and immunohistochemical studies of the liver were performed.
Normox-Res group animals exhibited increased serum alanine aminotransferase, tumor necrosis factor--alpha, interleukin (IL) -1β and IL-6 levels compared with Hypox-Res and sham groups. Reactive oxygen species generation, malondialdehyde formation and myeloperoxidase activity were all elevated in Normox-Res rabbits compared with Hypox-Res and sham groups. Similarly, endothelial NO synthase and inducible NO synthase mRNA expression was up-regulated and nitrotyrosine immunostaining increased in animals resuscitated normoxemically, indicating a more intense nitrosative stress. Hypox-Res animals demonstrated a less prominent histopathologic injury which was similar to sham animals.
Hypoxemic resuscitation prevents liver reperfusion injury through attenuation of the inflammatory response and oxidative and nitrosative stresses.
PLoS ONE 01/2012; 7(3):e32968. · 4.09 Impact Factor
-
Emmanuel E Douzinas,
Alex Betrosian,
Evangelos J Giamarellos-Bourboulis,
Marios-Konstantinos Tasoulis,
Panagiotis Prigouris,
Olga Livaditi,
Ilias Andrianakis,
Nikolaos Goutas,
Dimitrios Vlachodimitropoulos,
Aimilia Pelekanou,
Vassiliki Villiotou,
Ioannis Legakis,
George P Chrousos
[show abstract]
[hide abstract]
ABSTRACT: We investigated whether hypoxemic resuscitation from hemorrhagic shock prevents lung injury and explored the mechanisms involved. We subjected rabbits to hemorrhagic shock for 60 min by exsanguination to a mean arterial pressure of 40 mm Hg. By modifying the fraction of the inspired oxygen, we performed resuscitation under normoxemia (group NormoxRes, P(a)O(2)=95-105 mm Hg) or hypoxemia (group HypoxRes, P(a)O(2)=35-40 mm Hg). Animals not subjected to shock constituted the sham group (P(a)O(2)=95-105 mm Hg). We performed bronchoalveolar lavage (BAL) fluid, lung wet-to-dry weight ratio, and morphological studies. U937 monocyte-like cells were incubated with BAL fluid from each group. Cell peroxides, malondialdehyde, proteins, and cytokines in the BAL fluid were lower in sham than in shocked animals and in HypoxRes than in NormoxRes animals. The inverse was true for ascorbic acid and reduced glutathione. Lung edema, lung neutrophil infiltration, myeloperoxidase, and interleukin (IL)-8 gene expression were reduced in lungs of HypoxRes compared with NormoxRes animals. A colocalized higher expression of IL-8 and nitrotyrosine was found in lungs of NormoxRes animals compared to HypoxRes animals. The BAL fluid of NormoxRes animals compared with HypoxRes animals exerted a greater stimulation of U937 monocyte-like cells for proinflammatory cytokine release, particularly for IL-8. In the presence of p38-MAPK and Syk inhibitors and monosodium urate crystals, IL-8 release was reduced. We conclude that hypoxemic resuscitation from hemorrhagic shock ameliorates lung injury and reduces oxygen radical generation and lung IL-8 expression.
Free radical biology & medicine 11/2010; 50(2):245-53. · 5.42 Impact Factor
-
The Journal of thoracic and cardiovascular surgery 05/2010; 139(5):1357-8. · 3.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We present a case of severe Pneumocystis jirovecii pneumonia and coexisting cytomegalovirus infection in a glucose-6-phosphate dehydrogenase (G6PD) enzyme deficient woman with anaplastic astrocytoma on temozolomide and corticosteroid therapy. She was successfully treated with oral atovaquone and ganciclovir. Atovaquone represents a safe alternative in severe Pneumocystis infection when trimethoprim-sulfamethoxazole (co-trimoxazole) is contraindicated.
Scandinavian Journal of Infectious Diseases 11/2009; 42(1):76-8. · 1.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate factors predicting failure of percutaneous endoscopic gastrostomy (PEG) to eliminate gastroesophageal reflux (GER).
Twenty-nine consecutive mechanically ventilated patients were investigated. Patients were evaluated for GER by pH-metry pre-PEG and on the 7th post-PEG day. Endoscopic and histologic evidence of reflux esophagitis was also carried out. A beneficial response to PEG was considered when pH-metry on the 7th post-PEG day showed that GER was below 4%.
Seventeen patients responded (RESP group) and 12 did not respond (N-RESP) to PEG. The mean age, sex, weight and APACHE II score were similar in both groups. GER (%) values were similar in both groups at baseline, but were significantly reduced in the RESP group compared with the N-RESP group on the 7th post-PEG day [2.5 (0.6-3.8) vs 8.1 (7.4-9.2, P < 0.001)]. Reflux esophagitis and the gastroesophageal flap valve (GEFV) grading differed significantly between the two groups (P = 0.031 and P = 0.020, respectively). Histology revealed no significant differences between the two groups.
Endoscopic grading of GEFV and the presence of severe reflux esophagitis are predisposing factors for failure of PEG to reduce GER in mechanically ventilated patients.
World Journal of Gastroenterology 11/2009; 15(43):5455-60. · 2.47 Impact Factor
-
Marios-Konstantinos Tasoulis,
Olga Livaditi,
Michalis Stamatakos,
Charikleia Stefanaki,
Pantelis Paneris,
Panagiotis Prigouris,
Aikaterini Flevari,
Nikos Goutas,
Dimitrios Vlachodimitropoulos,
Vassiliki Villiotou, Emmanuel E Douzinas
[show abstract]
[hide abstract]
ABSTRACT: Increased levels of cytokines or reactive oxygen species (ROS) in the bronchoalveolar lavage (BAL) fluid are associated with acute lung injury after ischemia/reperfusion. We investigated the correlation of these markers with the degree of lung injury in a rabbit model of hemorrhagic shock. Rabbits, maintained by mechanical ventilation, were left untreated (control) or subjected to hemorrhagic shock by withdrawing blood (n = 12 for each group). Shock animals were re-infused their shed blood for resuscitation. At the end of the experiment, BAL fluid was recovered, in which parameters of oxidative stress and cytokines were measured. Macrophages and malondialdehyde levels were increased (p = 0.043 and p = 0.003, respectively), and total antioxidant capacity (TAC) was decreased in the shock animals compared with control (p = 0.009). Production of ROS was significantly enhanced in shock animals compared with controls (p < 0.001). BAL fluid levels of tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6 were higher in shock rabbits by more than twofold (p < 0.001 for each). Shock animals also showed higher histopathological scores that represent severe tissue damage than controls (p = 0.022). Numbers of macrophages and levels of ROS and TAC were correlated with the degree of lung injury (p = 0.006, p = 0.02, and p = 0.04, respectively), but not cytokines. Therefore, resuscitation from hemorrhagic shock results in acute lung injury, with enhanced pulmonary oxidative and inflammatory responses. In conclusion, ROS in the BAL fluid are good markers that predict lung injury following hemorrhagic shock and resuscitation.
The Tohoku Journal of Experimental Medicine 11/2009; 219(3):193-9. · 1.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Ampicillin-sulbactam has a wide range of antibacterial activity that includes Gram-positive and Gram-negative aerobic and anaerobic bacteria. However, the drug is not active against Pseudomonas aeruginosa and pathogens producing extended-spectrum beta-lactamases. The combination could be considered particularly active against Acinetobacter baumannii infections due to the intrinsic activity of sulbactam. The drug is indicated as empirical therapy for a broad range of community acquired infections supervened in adults or children and is effective in either parenteral (ampicillin-sulbactam) or oral (as a mutual prodrug sultamicillin) form. In clinical trials, sultamicillin has proved clinically and bacteriologically effective in adults and children against a variety of frequently encountered infections, including mild upper and lower respiratory tract infections, urinary tract infections, diabetic foot and skin and soft tissue infections. Furthermore, adverse effects rarely occur with the diarrhoea to represent the most commonly reported. The parenteral ampicillin-sulbactam is indicated for community infections of mild-to-moderate severity acquired infections such as intra-abdominal or gynecological. Moreover, it seems to represent the alternative of choice for the treatment of A. baumannii infections for carbapenem-resistant strains in the nosocomial setting. Thus, ampicillin-sulbactam remains a valuable agent in the physician's armamentarium in the management of adult and pediatric infections.
Expert Opinion on Drug Metabolism & Toxicology 08/2009; 5(9):1099-112. · 3.12 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate whether angiopoietin-2 (Ang2) and vascular endothelial growth factor (VEGF) are implicated in the hypoxemic resuscitation from hemorrhagic shock.
Twenty rabbits were subjected to hemorrhagic shock after blood exsanguination; resuscitation was performed by infusion of the shed blood in ten rabbits under normoxemic conditions (NormoxRes) and in 10 under hypoxemic conditions (HypoxRes); four rabbits were subjected to sham operation. Serum was drawn at serial time intervals; serum was applied for stimulation of U937 monocytes.
Serum concentrations of Ang2 were higher in the NormoxRes group compared to the HypoxRes group at 90 min (p: 0.049) and at 120 min (p: 0.028). Serum concentrations of VEGF did not differ between groups. Concentrations of VEGF in the supernatants of U937 stimulated with sera of all groups were below detection limit. The wet to dry lung ratio of the HypoxRes group was significantly lower than the NormoxRes group (p<0.0001).
Hypoxemic resuscitation from hemorrhagic shock is a process accompanied by reduced serum levels of Ang2. These findings add significantly to our understanding of that experimental treatment strategy of resuscitation.
Cytokine 06/2009; 47(2):82-4. · 3.02 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hypoxemic reperfusion attenuates brain injury secondary to severe cerebral ischemia, myocardial, and intestinal injury occurring in intestinal postischemic shock, and offers hemodynamic stabilization and attenuation of inflammatory response when applied in the resuscitation from hemorrhagic shock. In this study, we sought to investigate the effect of hypoxemic resuscitation on pulmonary endothelium.
Prospective, randomized, controlled animal study.
Experimental laboratory of a university intensive care unit.
Male New Zealand White rabbits weighting 3-3.5 kg.
Hemorrhagic shock at mean arterial pressure of 40 mm Hg was induced by exsanguinations in anesthetized, mechanically ventilated animals for 60 minutes and thereafter rabbits were resuscitated by homologous blood and Ringer's lactate infusion under normoxemia (Normox-Res group, Pao2 = 95-105 mm Hg, n = 9) or hypoxemia (Hypox-Res group, Pao2 = 35-40 mm Hg, n = 7).
Using indicator-dilution techniques we measured at baseline and post resuscitation pulmonary capillary endothelial angiotensin converting enzyme activity expressed as percentage of metabolism (%M) and hydrolysis (v) of the substrate H-benzoyl-Phe-Ala-Pro. Normox-Res rabbits exhibited decreased %M (p < 0.05) and v (p < 0.05) post resuscitation as compared with baseline, while no differences occurred in the Hypox-Res group. Myeloperoxidase was measured in lung tissue and was higher in Normox-Res than Hypox-Res animals (p < 0.01). Lung injury was estimated microscopically, whereas the expression of the intercellular adhesion molecule-1 and the vascular cell adhesion molecule-1 were assessed by immunohistochemistry on sections coming from the same tissue block. Compared with Normox-Res, Hypox-Res animals exhibited lower lung injury histopathological score (p < 0.01) and lung malondialdehyde concentration (p < 0.01), and lower intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expressions in both the inflammatory cells (p < 0.01) and the blood vessels (p < 0.05).
Normoxemic resuscitation of hemorrhagic shock is associated with pulmonary endothelial dysfunction and lung injury that may be attenuated by hypoxemic resuscitation.
Critical care medicine 04/2009; 37(3):869-75. · 6.37 Impact Factor
-
Intensive Care Medicine 10/2008; 34(10):1932. · 5.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We investigated whether hypoxemic resuscitation from hemorrhagic shock prevents the late circulatory instability and attenuates the oxidative and inflammatory responses associated with the standard strategy.
Prospective, randomized, controlled animal study in an experimental laboratory of a university intensive care unit.
Thirty-one New Zealand white rabbits weighting 3.1-3.4 kg
Anesthetized animals were subjected to hemorrhagic shock by exsanguinations to a mean arterial pressure of 40 mmHg for 60 min. Resuscitation was performed by reinfusing the shed blood for 30 min under normoxemia (PaO(2) 95-105 mmHg, control group, n=10) or hypoxemia (PaO(2) 35-40 mmHg, hypox-res group, n=10); Ringer's lactate was given from 30 to 60 min to restore arterial pressure within baseline values. A sham group was assigned (n=11). Animals were recorded for 120 min postresuscitation and for further 360 min to assess the early mortality rate.
Hypoxemic resuscitation compared with normoxemic resuscitation from hemorrhagic shock was associated with (a) a better hemodynamic condition assessed by the gradual restoration of blood pressure, higher urinary output associated with less fluid infusion; (b) lower reactive oxygen species production assessed by the reduced blood geometric mean fluorescence intensity, lower malondialdehyde, and higher ratio of reduced to total glutathione levels; (c) attenuation in the plasma concentrations of IL-1beta, TNF-alpha, and IL-6; and (d) no difference in mortality rate.
Hypoxemic resuscitation from hemorrhagic shock is more efficient than normoxemic in restoring the blood pressure and in attenuating the excessive oxidative and inflammatory responses observed during normoxemic resuscitation.
Intensive Care Medicine 07/2008; 34(6):1133-41. · 5.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To compare the safety and efficacy of ampicillin/sulbactam (Amp/Sulb) and colistin (COL) in the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP).
A prospective cohort study in adult critically ill patients with VAP. Patients were randomly assigned to receive Amp/Sulb (9 g every 8h) or COL (3 MIU every 8h) intravenously. Dosage was adjusted according to creatinine clearance.
A total of 28 patients were enrolled (15 COL, 13 Amp/Sulb). Resolution of symptoms and signs occurred in 60% (9/15) of the COL group and 61.5% (9/13) of the Amp/Sulb group, improvement in 13.3% (2/15) vs. 15.3% (1/13) and failure in 26.6% (4/15) vs. 23% (3/13), respectively. The difference was not statistically significant. Bacteriologic success was achieved in 66.6% (10/15) vs. 61.5% (8/13) in the COL and Amp/Sulb groups, respectively (p<0.2). Mortality rates (14 days and 28 days) were 15.3% and 30% for the Amp/Sulb and 20% and 33% for the COL group, respectively. Adverse events were 39.6% (including 33% nephrotoxicity) for the COL group and 30.7% (15.3% nephrotoxicity) for the Amp/Sulb group (p=NS).
Colistin and high-dose ampicillin/sulbactam were comparably safe and effective treatments for critically ill patients with MDR A. baumannii VAP.
The Journal of infection 06/2008; 56(6):432-6. · 4.13 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate whether the level of hypotension during hemorrhagic shock may influence the oxidative and inflammatory responses developed during post-ischemic resuscitation.
Fifteen rabbits were equally allocated into three groups: sham-operated (group sham); bled within 30 minutes to mean arterial pressure (MAP) of 40 mmHg (group shock-40); bled within 30 minutes to MAP of 30 mmHg (group shock-30). Shock was maintained for 60 min. Resuscitation was performed by reinfusing shed blood with two volumes of Ringer's lactate and blood was sampled for estimation of serum levels aminotransferases, creatinine, TNF-alpha, IL-1beta, IL-6, malondialdehyde (MDA) and total antioxidant status (TAS) and for the determination of oxidative burst of polymorhonuclears (PMNs) and mononuclear cells (MCs).
Serum AST of group shock-30 was higher than that of group shock-40 at 60 and 120 minutes after start of resuscitation; serum creatinine of group shock-30 was higher than group shock-40 at 120 minutes. Measured cytokines, MDA and cellular oxidative burst of groups, shock-40 and shock-30 were higher than group sham within the first 60 minutes after start of resuscitation. Serum concentrations of IL-1beta, IL-6 and TNF-alpha of group shock-30 were higher than group shock-40 at 120 minutes (p < 0.05). No differences were found between two groups regarding serum MDA and TAS and oxidative burst on PMNs and MCs but both groups were different to group sham.
The level of hypotension is a major determinant of the severity of hepatic and renal dysfunction and of the inflammatory response arising during post-ischemic hemorrhagic shock resuscitation. These findings deserve further evaluation in the clinical setting.
BMC Physiology 01/2008; 8:15.
-
[show abstract]
[hide abstract]
ABSTRACT: The present study compared two different systems of classification of patients with common variable immunodeficiency (CVID); one based on in vitro immunoglobulin biosynthesis; and another on CD4-naïve cell counts. Peripheral blood mononuclear cells (PBMCs) were isolated from 35 patients with CVID and 20 healthy controls. They were stimulated for the secretion of IgM and IgG after stimulation with Staphylococcus aureus Cowan I (SAC) upon supplementation of interleukin-2 (IL-2) or with pokeweed mitogen. T cell subsets were estimated by flow cytometry. By the first system, patients were classified into group A (n=18) with secretion of neither IgG nor IgM; into group B (n=12) with detectable IgM but no IgG secretion; and into group C (n=5) with IgM and IgG secretion similar to controls. By the second system, patients were classified into group I (n=12) with less than 109 CD4-naïve cells/mul; into group II (n=12) with CD4-naïve cells within 109-225microl(-1); and into group III (n=11) with more than 225 CD4-naïve cells/mul. All groups I-III were defective for in vitro release of IgG and IgM. The likelihood ratio for splenomegaly in patients with <225 CD4-naïve cells/mul was 5.08 (p: 0.024). CD4-naïve cell counts of patients were positively correlated to serum levels of IgG and IgA of patients. The presented results revealed that the former system described adequately the function of B cells and the latter the clinical status of the patient. Our proposal is that both should be used for the characterization of patients with CVID.
Immunology Letters 12/2007; 114(2):103-9. · 2.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Renal dysfunction is common in liver diseases, either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. The presence of renal impairment in both groups is a poor prognostic indicator. Renal failure is often multifactorial and can present as pre-renal or intrinsic renal dysfunction. Obstructive or post renal dysfunction only rarely complicates liver disease. Hepatorenal syndrome (HRS) is a unique form of renal failure associated with advanced liver disease or cirrhosis, and is characterized by functional renal impairment without significant changes in renal histology. Irrespective of the type of renal failure, renal hypoperfusion is the central pathogenetic mechanism, due either to reduced perfusion pressure or increased renal vascular resistance. Volume expansion, avoidance of precipitating factors and treatment of underlying liver disease constitute the mainstay of therapy to prevent and reverse renal impairment. Splanchnic vasoconstrictor agents, such as terlipressin, along with volume expansion, and early placement of transjugular intrahepatic portosystemic shunt (TIPS) may be effective in improving renal function in HRS. Continuous renal replacement therapy (CRRT) and molecular absorbent recirculating system (MARS) in selected patients may be life saving while awaiting liver transplantation.
World Journal of Gastroenterology 12/2007; 13(42):5552-9. · 2.47 Impact Factor
-
Olga Livaditi,
Anastasia Kotanidou,
Aikaterini Psarra,
Ioanna Dimopoulou,
Christina Sotiropoulou,
Kallirroi Augustatou,
Chryssa Papasteriades,
Apostolos Armaganidis,
Charis Roussos,
Stylianos E Orfanos, Emmanuel E Douzinas
[show abstract]
[hide abstract]
ABSTRACT: The aim of the present study was to investigate which biomarker/s reliably assess severity and mortality early in the sepsis process. In 47 critically-ill patients within the 24h of septic onset, Interleukins (IL)-8, -1beta, -6, -10, and -12p70, tumor necrosis factor-alpha (TNF-alpha), procalcitonin (PCT) and C-reactive protein (CRP) were measured in serum. Additionally, CD64 expression was measured in neutrophils. In early sepsis, neutrophil CD64 expression and IL-8 levels are the only biomarkers that increased with sepsis severity, differentiating disease stages: sepsis, severe sepsis and septic shock (p<0.001). The biomarkers that best evaluate the severity of sepsis (via APACHE II) were CD64, IL-8 and IL-6 (p<0.01), and the severity of organ failure (via SOFA) were CD64 and IL-8 (p<0.01). CD64 expression and IL-8 levels were associated with mortality within 28-days (OR=1.3, p=0.01 for CD64 and OR=1.26, p=0.024 for IL-8 by logistic regression analysis) and ROC curve analysis showed high sensitivity and specificity for predicting sepsis stages and the 28 day mortality. We conclude that there is an early increase of neutrophil CD64 expression and IL-8 levels during sepsis. Based on this single measurement it is possible to reliably assess the stage, detect the severity and predict the 28-day mortality of sepsis.
Cytokine 01/2007; 36(5-6):283-90. · 3.02 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Resuscitation of hemorrhagic shock is associated with tissue injury. The effect of hypoxemia during resuscitation was investigated.
Shock was induced by withdrawing blood to mean arterial pressure (MAP) 40 mm Hg and maintained for 60 minutes in 25 Wistar rats. Animals were randomly divided to receive either normoxemic (controls, FiO2 = 21%, n = 14) or hypoxemic (HypRes, FiO2 = 12%, n = 11) resuscitation by re-infusing their shed blood. Outcome was assessed through hemodynamic and inflammatory parameters. Another nine rats served to correlate different FiO2 to the corresponding PaO2.
At 60 minutes of resuscitation HypRes had higher MAP than control animals (p = 0.008). The respective median (range) malondialdehyde and TNF-alpha levels was 1.7 (1-2.1) versus 3.1 (2.4-4.3) micromol/L, (p = 0.02) and 0 versus 5.8 (0-5.8) pg/mL, (p = 0.025). Glutathione, endotoxin, interferon-gamma, and nitric oxide values were similar between groups. FiO2 of 12% induced only a mild hypoxemia (PaO2 approximately 80 mm Hg).
Even mild hypoxemia during resuscitation of shock leads to effective hemodynamic stabilization.
The Journal of trauma 11/2006; 61(4):918-23. · 2.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Encouraging results have recently been reported in patients (pts) with locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN) when induction chemotherapy (IC) is used and followed by radiotherapy (RT). The present study assessed the therapeutic response of an aggressive regimen consisting of docetaxel (TXT), cisplatin (CDDP) and 5-fluorouracil (5-Fu) as IC and concurrent with RT in pts with locally advanced (stages III and IV) SCCHN. 42 pts (35 male and 7 female) with a mean age of 58 years suffering from stages III and IV (Mo) SCCHN were included to this organ preservation phase II clinical trial. The site of the primary tumors was the anterior mouth in 9 pts, base of tongue and oropharynx in 12, middle third of the face in 8 and larynx in 13. The performance status of the pts was 0-1 according to WHO and above 80% according to Karnofsky classification. IC consisted of TXT (40 mg/m2), CDDP (40 mg/m2) and 5-Fu (350 mg/m2) every two weeks (wks) for a total of four courses and repeated, coupled with RT (66-68 cGys total dose fractionated at 200 Gy per day, 5 days a week), for up to seven wks. In total, pts received eight courses of chemotherapy (CT) at the end of RT treatment. Pts were evaluated at the end of IC, after RT and every six wks thereafter. 41 pts were eligible for evaluation after IC (one died from myocardial infarction) and 39 after completion of treatment (two died during RT). Statistical multivariate analysis was performed using SPSS (11) package. Complications from IC and RT were evaluated according to WHO criteria and included mucositis Grade (Gr) IV in 10% of the pts, Gr III in 50%, Gr II in 20%. Anemia presented in 40% of the pts with Gr II, 40% with Gr I, neutropenia 17% with Gr IV, 20% with Gr III, 30% with Gr II, thrombocytopenia 3% with Gr III, 10% with Gr I and xerostomia up to Gr II in 70% of the pts. The response rate (RR) after IC was complete response (CR) for 10 pts (24.4%), partial response (PR) for 22 (53.7%) and no response (NR) for 9 (21.9%). At the end of the treatment the RR in the intention-to-treat population were CR for 25 pts (64.1%), and PR for 14 (35.9%). Follow up ranges from 18 to 56 months (mts). 14 pts died during follow-up time. The mean survival time is 41 mts and the median 40. 2 pts with CR developed local recurrence and two distant metastases, whereas all pts with PR developed progressive disease (PD) and all but two are dead from disease. It is evident from this phase II study that TXT-CDDP-5Fu based IC followed by the same regimen coupled with RT improves local control. Pts that showed CR after IC continued to maintain disease status during RT (P-value=0.0181). In pts with SD concurrent RT did not alter dramatically disease outcome. Patients who showed complete response after both IC and RT presented a four-year survival rate of 74% compared to a 30% to partial responders (P-value=0.0001). Results are encouraging and further study of the toxicity and follow-up is needed to validate treatment effectiveness.
Oral Oncology 09/2006; 42(7):675-84. · 2.86 Impact Factor
-
Evanthia Diamanti-Kandarakis,
Christina Piperi,
Krystallenia Alexandraki,
Nikolaos Katsilambros,
Eirini Kouroupi,
Joanna Papailiou,
Stefanos Lazaridis,
Ekaterini Koulouri,
Helen A Kandarakis, Emmanuel E Douzinas,
George Creatsas,
Anastasios Kalofoutis
[show abstract]
[hide abstract]
ABSTRACT: Exogenous advanced glycation endproducts (AGEs, known atherogenic molecules) abundant in everyday precooked, rich in fat, overheated meals can possibly contribute to the increased risk for diabetes and cardiovascular disease in women with polycystic ovary syndrome (PCOS). The aim of the present study was to investigate the effect of a lipase inhibitor on absorbed food glycotoxins in healthy women and those with PCOS. A 2-day protocol was followed. In the first day, a meal rich in AGE was provided, which on the second day was followed by two 120-mg capsules of lipase inhibitor, orlistat. Serum AGE levels were evaluated at baseline (0 hours), and at 3 and 5 hours postmeal during the study. Thirty-six women were studied, 15 controls (mean age, 28.80 +/- 5.47 years; body mass index, 25.85 +/- 6.73 kg/m(2)) and 21 with PCOS (mean age, 25.29 +/- 5.06 years; body mass index, 30.40 +/- 7.51 kg/m(2)) (University Hospital, Athens, Greece, institutional practice). Serum AGE levels, on day 1, were significantly increased both in the control group and in the PCOS group as compared with basal values (control group, 14.1%; PCOS group, 6.0%; P < .001). The corresponding rise was significantly lower on day 2 when the same meal was combined with orlistat (control group, 4.1%; PCOS group, 2.0%; P < .01). A limitation of the study is that it is a nonplacebo, nonrandomized therapeutic trial where each subject is considered as its own control. In conclusion, this study demonstrated the beneficial effect of orlistat on the absorption of food glycotoxins.
Metabolism 04/2006; 55(4):494-500. · 2.66 Impact Factor
-
Diamantis Plachouras,
Christina Routsi,
Evangelos J Giamarellos-Bourboulis,
Ekaterini Spyridaki,
Ilias Andrianakis,
Spyridon Metzelopoulos,
Thomas Tsaganos,
Ioannis Floros, Emmanuel E Douzinas,
Apostolos Armaganidis,
Charis Roussos,
Helen Giamarellou
[show abstract]
[hide abstract]
ABSTRACT: The role of blood monocytes in the secretion of soluble triggering receptor expressed on myeloiod cells (sTREM-1) was studied in 90 patients with septic syndrome due to ventilator-associated pneumonia. Blood monocytes were isolated on 7 consecutive d after initiation of symptoms. Monocytes were incubated in the absence or presence of LPS and concentrations of sTREM-1 and TNFalpha in cell supernatants and serum were estimated by an enzyme-immunoassay. sTREM-1 and TNFalpha were consistently present at detectable levels in the cell supernatants. LPS induced increased levels of TNFalpha but not of sTREM-1. Supernatants recovered from monocytes on d 1 showed levels of sTREM-1 higher than those recovered on any of the following 6 d (p<0.05); these levels were higher in non-survivors than in survivors. Supernatants recovered from monocytes on d 1 of patients with severe sepsis had elevated concentrations of sTREM-1 compared to patients with septic shock and similar to patients with sepsis. A negative correlation was found between levels of sTREM-1 in the cell supernatants and the percentage of apoptotic monocytes. In essence, the above results suggest that monocytes contribute to the production of sTREM-1 in the event of septic syndrome.
Scandinavian Journal of Infectious Diseases 01/2006; 38(10):909-15. · 1.72 Impact Factor
