Athanasios Alegakis

Docetaxel Versus Docetaxel Plus Cisplatin As Front-Line Treatment of Patients With Advanced Non—Small-Cell Lung Cancer: A Randomized, Multicenter Phase III Trial

PURPOSE To compare the overall survival (OS) of patients with advanced non-small-cell lung cancer (NSCLC) treated with docetaxel plus cisplatin (DC) or docetaxel (D) alone. PATIENTS AND METHODS Chemotherapy-naïve patients with advanced/metastatic NSCLC were randomly assigned to receive either DC (n = 167; docetaxel 100 mg/m(2) on day 1, cisplatin 80 mg/m(2) on day 2, and recombinant human granulocyte colony-stimulating factor (rhG-CSF) 150 microg/m(2)/d on days 3 to 9) or D (n = 152; 100 mg/m(2) on day 1 without rhG-CSF) every 3 weeks. RESULTS The overall response rates were 36.5% for DC (three complete responses and 58 partial responses) and 21.7% for D (one complete response and 32 partial responses; P =.004). The median OS was 10.5 months (range, 0.5 to 41 months) and 8.0 months (range, 0.5 to 41 months) for DC and D, respectively (P =.200). The 1- and 2-year survival rates were 44% and 19% for DC and 43% and 15% for D, respectively. Median times to tumor progression were 4.0 and 2.5 months for DC and D, respectively (P =.580). Grade 2/3 anemia was significantly higher with DC than with D (33% v 16%; P =.0001). Fifteen (9%) DC and 12 (8%) D patients developed febrile neutropenia. Grade 3/4 nausea/vomiting (P =.0001), diarrhea (P =.007), neurotoxicity (P =.017), and nephroroxicity (P =.006) were significantly more common with DC than with D. There were five treatment-related deaths in the DC group and one in the D (P =.098). CONCLUSION DC regimen resulted in a higher response rate but without improvement in median time to tumor progression or OS compared with D. D could be a reasonable front-line chemotherapy for patients who cannot tolerate cisplatin.

Three-year study of fenthion and dimethoate pesticides in olive oil from organic and conventional cultivation

Residues of fenthion and dimethoate pesticides were determined in organic and conventional olive oils by liquid-liquid and solid-phase extractions with subsequent gas chromatography and mass spectrometric analysis. The olive oil samples were collected from Crete during 1997–99. The average concentrations of fenthion in conventional olive oils were 0.1222, 0.145 and 0.1702 mg kg−1, and for dimethoate were 0.0226, 0.0264 and 0.0271 mg kg−1 for 1997, 1998 and 1999, respectively. The average concentrations of fenthion in organic olive oils were 0.0215, 0.0099 and 0.0035 mg kg−1 for 1997, 1998 and 1999, while for dimethoate they were 0.0098, 0.0038 and 0.0010 mg kg−1, respectively. All the olive oils contained residue levels lower than the maximum resi-due levels according to the FAO/WHOCodex Alimentarius. The organic olive oil contained significantly lower concentrations of the two pesticides. The levels of fenthion and dimethoate in organic olive oils exhibited a decreasing trend following the implementation of the new cultivation method. We propose procedures that should be established in the organic cultivation in order to maximize its effectiveness.

Risk assessment scenarios of children’s exposure to aflatoxin M1 residues in different milk types from the Greek market

Occurrence of aflatoxin M1 (AFM1) was determined in 196 milk samples (conventional, organic and kids milk) from the Greek market during November 2009 to June 2010. AFM1 content was analyzed using an Enzyme-Linked Immunosorbent Assay (ELISA) commercial kit. Aflatoxin M1 was detected in 46.5% of the samples. 46.5% of the samples were found positive for AFM1. The most frequent range of detection was between 5 and 10 ng/l. Based on the EU regulation only 2 milk samples presented AFM1 levels higher than the maximum residue limits. Two different scenarios were used for the determination of hazard index: (a) scenario 1 using only positive (detected AFM1) samples and (b) scenario 2 when missing values where imputed with Limit of Detection (LOD) divided by 2. Significant statistical differences between different milk categories were presented only when the results were imputed with LOD/2 values. Exposure assessment scenarios were developed for ages 1, 3, 5, 7 and 12 and their respective estimated weights and daily milk consumption. Under the worst-case scenario all milk types presented a Hazard Index (HI) less than one. The highest HI values appear in the ages of 1-3.

Studying the association between musculoskeletal disorders, quality of life and mental health. A primary care pilot study in rural Crete, Greece

BackgroundThe burden of musculoskeletal disorders (MSD) on the general health and well-being of the population has been documented in various studies. The objective of this study was to explore the association between MSD and the quality of life and mental health of patients and to discuss issues concerning care seeking patterns in rural Greece.MethodsPatients registered at one rural Primary Care Centre (PCC) in Crete were invited to complete the Nordic Musculoskeletal Questionnaire (NMQ) for the analysis of musculoskeletal symptoms, together with validated instruments for measuring health related quality of life (SF-36) and mental distress (GHQ-28).ResultsThe prevalence rate of MSD was found to be 71.2%, with low back and knee pain being the most common symptoms. Most conditions significantly impaired the quality of life, especially the physical dimensions of SF-36. Depression was strongly correlated to most MSD (p < 0.001). Multiple logistic analyses revealed that patients who consulted the PCC due to MSD were likely to have more mental distress or impaired physical functioning compared to those who did not.ConclusionMusculoskeletal disorders were common in patients attending the rural PCC of this study and were associated with a poor quality of life and mental distress that affected their consultation behaviour.

Assessment of levels of organochlorine pesticides and their metabolites in the hair of a Greek rural human population

We present the assessment of chronic exposure of the rural population of Helia Peloponnesus, Greece to banned organochlorine pesticides, hexachlorocyclohexane (HCH), and 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), using hair analysis. A total of 222 head hair samples were collected and analyzed for the presence of those organochlorine pesticides and their metabolites or isomers. Gas chromatography coupled to mass spectrometry was used to measure the levels of the pollutants. The median concentrations of α-HCH, hexachlorobenzene, lindane, ortho para 1,1-dichloro-2,2-bis-(4-chlorophenyl)ethylene (opDDE), para para 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (ppDDE), ortho para 1,1-dichloro-2,2-bis(4-chlorophenyl)ethane (opDDD), para para 1,1-dichloro-2,2-bis(4-chlorophenyl)ethane (ppDDD) + ortho para 1,1,1-trichloro-2,2-bis(4-chlorophenyl)-ethane, and para para 1,1,1-trichloro-2,2-bis(4-chlorophenyl)-ethane were determined at 40.4, 19.7, 124.2, 6.2, 7.8, 73.1, 8.0, and 5.7 pg/mg. The median concentration of total HCHs and DDTs were 117.8 pg/mg and 9.4 pg/mg, respectively. The levels of total HCHs were much higher than the levels of DDTs in the hair samples of the studied population. This may be attributed to the presence of lindane, a pesticide officially banned in 2002. It is interesting to see that DDTs are still traced in samples despite their use being banned for more than three decades. There was no difference in the levels of the detected pesticides in hair sampled from men or women. The concentration of HCHs remains high and relatively stable across the age groups, suggesting constant exposure until very recently. The concentration of the total DDTs and the parent compound, pp-DDT presents a statistically significant decreasing trend across the age groups.

Association of allergic rhinitis with pesticide use among grape farmers in Crete, Greece

Objective: To explore the association of allergic rhinitis with the use of pesticides among grape farmers in Crete. Methods: A cross-sectional study of 120 grape farmers and 100 controls at the Malevisi region in Northern Crete was conducted. The protocol consisted of a questionnaire, skin prick tests for 16 common allergens, measurement of specific IgE antibodies against 8 allergens, and spirometry before and after bronchodilatation. Results: Grape farmers who used pesticides had higher prevalence rates of allergic rhinitis symptoms (OR, 3.0; 95% CI, 1.4 to 6.2) compared with grape farmers who reported no current use of pesticides, and control subjects. Logistic regression models controlling for age, sex and smoking status showed that 6 of the 12 predefined groups of major pesticides were significantly related to allergic rhinitis symptoms. The highest risks were observed for paraquat and other bipyridyl herbicides (OR, 2.2; 95% CI, 1.0 to 4.8), dithiocarbamate fungicides (OR, 2.5; 95% CI, 1.1 to 5.3) and carbamate insecticides (OR, 3.0; 95% CI, 1.4 to 6.5). A factor analysis of pesticides used identified 3 distinct factors. The most common factor was that of multiple pesticide use that included 9 pesticides and was significantly associated with allergic rhinitis (OR, 1.5; 95% CI, 1.0 to 2.3). ORs were higher when allergic rhinitis was defined using both questionnaire data on symptoms and atopy. Conclusions: Occupational exposure to multiple agricultural chemicals could be related to allergic rhinitis in grape farmers.

Multicomponent Analysis of Replacement Liquids of Electronic Cigarettes Using Chromatographic Techniques

The electronic cigarette (e-cig) is an invention of the past few years and its popularity is rapidly growing all over the world. A rapid multicomponent analytical protocol for the analysis of the replacement liquids (e-liquids) of e-cig was developed using gas (GC) and liquid chromatography (LC)-mass spectrometry (MS). GC-MS-based methods were developed for the determination of the main humectants and polycyclic aromatic hydrocarbons (PAHs). For the determination and quantification of nicotine (NIC) and nitrosamines, appropriate LC-MS-based methods were developed. The approbated methods were applied for the analysis of 263 e-liquid samples obtained from the Greek market. The instruments response was linear; the limits of quantification ranged from 0.003 μg/mL for three PAHs to 1.187 μg/mL for glycerol. The precision was <16% for all analytes, while the mean accuracy ranged from 99.1% for NIC to 106.6% for the flavor 2,5-dimethylpyrazine. The measured concentrations of NIC were correlated with the theoretical concentrations as reported by the manufacturers. An analog relation between the concentration of the glycerol and of propylene glycol was noticed. The frequency of detection of flavors ranged from 30.4% for the methyl cyclopentenolone to 5.3% for 3.4-dimethoxybenzaldehyde. Nitrosamines and PAHs were not detected in any sample. Because a similar analytical protocol was not available from the existing literature so far, our study offers the advantage of complete analytical methods for rapid and simultaneous multicomponent identification.

Role of platelet-derived growth factor-AB in tumour growth and angiogenesis in relation with other angiogenic cytokines in multiple myeloma

Angiogenesis is a complex process essential for the growth, invasion, and metastasis of various malignant tumours, including multiple myeloma (MM). Various angiogenic cytokines have been implicated in the angiogenic process. Among them, platelet‐derived growth factor‐AB (PDGF‐AB) has been reported to be a potent stimulator of angiogenesis in many solid tumours and haematological malignancies, including MM. The aim of the study was to investigate the relationship between PDGF‐AB, microvascular density (MVD), and various angiogenic cytokines, such as basic fibroblast growth factor (b‐FGF), angiogenin (ANG), and interleukin‐6 (IL‐6), in MM patients. Forty‐seven MM patients before treatment, 22 of whom were in plateau phase, were studied. We determined the serum levels of the aforementioned cytokines and MVD in bone marrow biopsies before and after treatment. Mean serum values of PDGF‐AB, b‐FGF, ANG, and MVD were significantly higher in patients compared with controls and with increasing disease stage. Significant positive correlations were observed between serum PDGF‐AB, ANG, and IL‐6 levels and MVD. Furthermore, we found significant positive correlations between PDGF‐AB and b‐FGF, IL‐6, ANG, and β2 microglobulin. We also found that patients with high MVD had statistically significantly higher serum levels of PDGF‐AB when a median MVD value of 7.7 was used as the cutoff point. Furthermore, a significant difference was found in serum levels of PDGF‐AB between pre‐ and post‐treatment patients. Finally, survival time was significantly higher in the low MVD group versus the high MVD group (76 vs 51 months). Our results showed that there is a strong positive correlation between PDGF‐AB and the studied angiogenic cytokines and MVD. It seems that PDGF‐AB plays a role in the complex network of cytokines inducing bone marrow neovascularization in patients with MM. Copyright

Hypospadias in offspring is associated with chronic exposure of parents to organophosphate and organochlorine pesticides.

We have currently evaluated the possible association between hypospadias and exposure to organophosphorus (OP) and organochlorine (OC) pesticides. For this purpose, we measured the dialkyl phosphate metabolites of organophosphate pesticides (DAPs) in the hair and blood, as well as OC pesticides (DDTs, HCHs) in the hair collected from children with hypospadias and their parents. The concentration of HCHs in the hair samples obtained from mothers was higher than that previously reported for people working in open cultivations, while the concentration of DDTs in the hair samples obtained from mothers, fathers and their children with hypospadias was much higher than that previously reported for occupationally exposed individuals. The DMP concentration in hair samples obtained from mothers was much higher not only from that reported for the general population, but even higher than that reported for occupationally exposed individuals. Furthermore, SUMDEPs and SUMDAPs in the hair samples obtained both from the hypospadiac boys, as well as from their parents were higher than the corresponding values previously reported for the general population. Our study supports the hypothesis that organophosphate and organochlorine pesticide exposure may be a potential risk factor for hypospadias.

Deactivation of mycotoxins. I. An in vitro study of zearalenone adsorption on new polymeric adsorbents

This study describes the elimination of zearalenone concentrations in vitro using two new polymeric forms of cross-linked polyvinylpyrrolidone (cryogels of cross-linked PVP). Adsorption of zearalenone was studied under isothermal conditions and simulating pH of intestinal environment. A Freundlich isotherm was used to describe the adsorption data obtained. The results showed significant decrease of zearalenone concentrations, ranging from 33.5-66.2% per 25 mg of polymer. Adsorption capacity (k) was estimated to be higher than that of previously tested adsorbents, including crospovidone. The data indicate the need to investigate structure peculiarities in order to improve mycotoxin deactivation procedures using PVP derivatives.