Theodoros C. Constantinidis

Influence of sleep disturbance on quality of life of patients with epilepsy

The frequency of sleep disturbances in patients with epilepsy and their impact on quality of life (QoL) have been documented in a few reports, and the results are conflicting. We identified 124 consecutive epilepsy out-patients who visited the epilepsy out-patient clinics at the University Hospital of Alexandroupolis, the AHEPA Hospital in Thessaloniki and the Aeginitio Hospital in Athens. We measured excessive daytime sleepiness (EDS) with the Epworth Sleepiness Scale (ESS), obstructive sleep apnea (OSA) with the Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ), and insomnia with the Athens Insomnia Scale (AIS). We evaluated quality of life by the Quality of Life in Epilepsy Inventory (QOLIE-31). EDS was found in 16.9% (21/124) of epileptic patients, OSA in 28.2% (35/124), and insomnia in 24.6% (30/122). In multivariate analysis, we found that insomnia was an independent negative factor for Total score (p<0.001), Overall QoL (p=0.002), Emotional well-being (p<0.001), Energy/fatigue (p<0.001), Cognitive functioning (p=0.04) and Social functioning (p=0.03), and OSA only for Cognitive functioning (p=0.01). According to our findings, EDS, OSA, and insomnia are frequent in epileptic patients. Epileptic patients with sleep disturbance, mainly insomnia, have significant QoL impairment.

Methylenetetrahydrofolate reductase polymorphism C677T is not associated to the risk of cervical dysplasia

The aim of the study was to explore a possible association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and cervical neoplasia. A total of 229 women were subjected to cytologic and colposcopic evaluation. Ninety-one of them were found to be normal, and served as the control group, while the other 138 of them had present or past histologically proven cervical pathology (patients group). All patients and controls were investigated for the MTHFR C677T polymorphism. Statistical analysis between the groups of cases with cervical intraepithelial neoplasia or invasive cervical cancer and the control group did not reveal any statistically significant difference in the frequency of the MTHFR C677T polymorphism.

Corticotropin-releasing factor (CRF) receptor type 2 in the human stomach: Protective biological role by inhibition of apoptosis

Corticotropin‐releasing factor agonists exert inhibitory effects in stomach functions possibly through peripheral routes. We have previously reported the expression of Urocortin (Ucn) I, an endogenous ligand of both CRF receptor types CRF1 and CRF2, in the human stomach. We examined CRF1 and CRF2 expression in the same tissue. Using RT‐PCR, CRF2 but not CRF1 transcripts were detected in RNA extracts from normal human stomach. In addition, immunohistochemical analysis revealed receptor protein in epithelial gastric cells. In order to investigate the biological role of CRF2 in these cells, an in vitro model was established, using the gastric cancer cell line AGS transiently transfected to express functional CRF2. The effect of the CRF2 endogenous ligands CRF, Ucns I and II on the growth parameters of the AGS/CRF2 was examined. After 1 day of exposure, all three ligands reduced the degree of apoptosis (16%–19%, n = 9, P < 0.05) compared to non‐treated controls and this effect was observed for 3 days of treatment. No such effect was detected in non‐transfected cells, suggesting mediation through CRF2 receptors. Administration of CRF, Ucns I and II had no effect on the proliferation rate of AGS/CRF2 cells or on the release of PGE2 by them. Our results demonstrate CRF2 expression in the human gastric mucosa and indicate a physiological role of this receptor type in regulating apoptosis, an important parameter of gastric cell regeneration. Paracrine effects exerted by locally expressed endogenous ligands, such as Ucn I, support a significant role of the peripheral CRF system in gastric physiology. J. Cell. Physiol. 209: 905–911, 2006.

Factor V Leiden and prothrombin G20210A mutations in pregnancies with adverse outcome

Background: Inherited thrombophilia has been associated with obstetric complications through mechanisms that are not yet fully elucidated. The aim of this study was to investigate the relationship between specific obstetric adverse outcomes and factor V Leiden and prothrombin G20210A mutations. Methods: Forty-five women with adverse pregnancy outcome defined as severe pre-eclampsia, abruptio placentae, intrauterine growth restriction and stillbirth, were tested for factor V Leiden and prothrombin G20210A mutations. The control group comprised 100 women with at least one normal pregnancy and no history of thrombosis. Results: Overall, 13 women with one or more of the above-mentioned pregnancy complications (28%) had either thrombophilic mutation, as compared with six in the control group (6%) (p < 0.001, odds ratio (OR) 6.1; 95% confidence interval (CI) 1.9-20). The factor V Leiden mutation was detected in ten of the women with complicated pregnancies (22%) and in four of the controls (4%) (p < 0.001, OR 6.6; 95% CI 1.7-27.2). The prothrombin G20210A mutation was detected in three women in the group with complications (6%) and in two of the controls (2%) (p = 0.17, OR 3.4; 95% CI 0.4-30.5). Compared to controls, the prevalence of the factor V Leiden mutation was significantly higher in the subgroups of severe pre-eclampsia, abruptio placentae and fetal growth restriction. The prevalence of the prothrombin G20210A mutation does not appear to be significantly different from that in the controls in any of the groups studied. Conclusions: Our data suggest that inherited thrombophilia, and specifically the factor V Leiden mutation, may be associated with adverse pregnancy outcome. The role of the prothrombin G20210A mutation remains to be elucidated.

Primary Screening for Cervical Cancer Based on High-Risk Human Papillomavirus (HPV) Detection and HPV 16 and HPV 18 Genotyping, in Comparison to Cytology

Objectives The objective of the present study is to assess the performance of a high-risk human papillomavirus (HR-HPV) DNA test with individual HPV-16/HPV-18 genotyping as a method for primary cervical cancer screening compared with liquid-based cytology (LBC) in a population of Greek women taking part in routine cervical cancer screening. Methods The study, conducted by the “HEllenic Real life Multicentric cErvical Screening” (HERMES) study group, involved the recruitment of 4,009 women, aged 25–55, who took part in routine cervical screening at nine Gynecology Departments in Greece. At first visit cervical specimens were collected for LBC and HPV testing using the Roche Cobas 4800 system. Women found positive for either cytology or HPV were referred for colposcopy, whereas women negative for both tests will be retested after three years. The study is ongoing and the results of the first screening round are reported herein. Results Valid results for cytology and HPV testing were obtained for 3,993 women. The overall prevalence of HR-HPV was 12.7%, of HPV-16 2.7% and of HPV-18 1.4%. Of those referred for colposcopy, cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was detected in 41 women (1.07%). At the threshold of CIN2+, cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] and HPV testing showed a sensitivity of 53.7% and 100% respectively, without change between age groups. Cytology and HPV testing showed specificity of 96.8% and 90.3% respectively, which was increased in older women (≥30) in comparison to younger ones (25–29). Genotyping for HPV16/18 had similar accuracy to cytology for the detection of CIN2+ (sensitivity: 58.5%; specificity 97.5%) as well as for triage to colposcopy (sensitivity: 58.5% vs 53.7% for cytology). Conclusion HPV testing has much better sensitivity than cytology to identify high-grade cervical lesions with slightly lower specificity. HPV testing with individual HPV-16/HPV-18 genotyping could represent a more accurate methodology for primary cervical cancer screening in comparison to liquid-based cytology, especially in older women.

A Phase II study of docetaxel and carboplatin in the treatment of non-small cell lung cancer.

We investigated the efficacy of docetaxel (D) in combination with carboplatin (C) in the treatment of non-small cell lung cancer (NSCLC) patients. Since 1996, 123 with inoperable NSCLC were enrolled in the study; 120 (108 males, 12 females; mean age 58.0+/-8.3 years) were evaluated. Of those, 46 patients had squamous carcinoma, 44 adenocarcinoma, 11 large cell carcinoma and 19 undifferentiated tumours. Eligibility criteria included, documented inoperable NSCLC, WHO performance status (PS) 0-1, age up to 70 years, and normal renal and hepatic function. A total of 622 cycles of chemotherapy (CHT) (median 7 (95% CI 6.2-7.47), courses per patient) were administered. Each cycle consisted of 100 mg/m(2) of docetaxel in a 2-h infusion with C at a dose of area under the curve (AUC) of 6 on day 1. This regimen was repeated every 28 days up to eight cycles. Of the patients, five (4%) achieved complete response, 49 (40%) partial response, 47 (39%) had stable disease and 19 (15%) had progressive disease. The median survival was 12 months for all patients, 12 for the four patients with stage IIb disease, 18 for the patients with stage IIIa disease, 20 for the 29 patients with stage IIIb disease, and 11 for the 65 stage IV patients. The median time to progression was 8 months (90 patients). Toxicity was, grade 3/4 neutropenia, 18 patients (15%); grade 3/4 anaemia, 6 patients (5%); and tolerable peripheral neuropathy, 16 patients (13.3%). Responders received radiotherapy (total dose, 50 Gy in 4 weeks) between the 6th and 8th cycle. Among responders with initial stage IIIb disease, 7 (5%) underwent surgical resection. Patients with early progression of the disease received the same dose of radiotherapy between 2nd and 3rd cycle. The study is ongoing, and six patients (5%) are still alive (after 3 years). Preliminary results indicate that the D/C combination is very active in the treatment of NSCLC with tolerable toxicity. It appears that this drug combination is also good as neoadjuvant therapy in inoperable NSCLC patients.

Work productivity in obstructive sleep apnea patients.

Objectives: Purpose of the study was to assess work productivity in otherwise healthy obstructive sleep apnea (OSA) patients and to explore correlations between work productivity and different characteristics of OSA patients. Methods: Work productivity was assessed by the Endicott Work Productivity Scale (EWPS) to 115 polysomnographically confirmed OSA patients of working age, without comorbidities. Daytime sleepiness was measured by the Epworth Sleepiness Scale. Results: A significant correlation was revealed between EWPS and Epworth Sleepiness Scale scores (r2 = 0.127, P < 0.001). Mean EWPS score was significantly higher in somnolent versus nonsomnolent OSA patients (31.2 ± 16.2 vs 20.8 ± 11, respectively; P < 0.001). No other sleep or anthropometric characteristic correlated with EWPS. Conclusions: This study demonstrates the negative effect of daytime sleepiness on work productivity of otherwise healthy OSA patients, highlighting the need of screening for OSA and sleepiness among working individuals.

Sleep-Disordered Breathing and Quality of Life of Railway Drivers in Greece

BACKGROUND Sleep-disordered breathing (SDB) and especially obstructive sleep apnea (OSA) are associated with daytime sleepiness and an increased risk for motor vehicle crashes. Previous studies have assessed the prevalence of OSA among professional drivers, but no study so far has focused on railway drivers. The aim of this study was to assess the prevalence of SDB among Greek railway drivers, and correlate it with daytime sleepiness, quality of life, and symptoms. METHODS The following three different questionnaires were anonymously answered by 226 train drivers: a general questionnaire on their demographics and sleep habits; the Greek version of the Epworth sleepiness scale (ESS); and the Medical Outcomes Study 36-item short form (SF-36). Of the 226 drivers, 50 underwent a sleep study, a physical examination, and an assessment of their respiratory function. RESULTS Participants were all men, had a mean (+/-SD) age of 46.9+/-3.9 years, were overweight (mean body mass index [BMI], 28.7+/-3.7 kg/m2), and were smokers (59.7%). Snoring was reported by 69.9% of them, and apneas by 11.5%. The mean ESS score was 5.4+/-3.2. SF-36 scores were similar to those of the Greek population. The mean apnea-hypopnea index (AHI) was 11+/-14 events per hour, and the mean pulse oximetric saturation was 93.2+/-2.5%. According to AHI severity, they were divided into the following three groups: group 1, normal breathing function in sleep (n=19; AHI, <5 events per hour); group 2, mild OSA (n=20; AHI, 5.1 to 15 events per hour); group 3, moderate/severe OSA (n=11; AHI, >15 events per hour). The three groups differed in terms of BMI, and neck, waist, and hip circumferences. No difference was detected, though, in ESS and SF-36 scores. CONCLUSION The majority of the Greek railway drivers are overweight and smokers. The most common reported symptom in the questionnaires is snoring, without significant daytime impairment, while sleep studies show a potentially higher prevalence of OSA. TRIAL REGISTRATION Democritus University of Thrace Identifier: 2979/5-2003. TRIAL REGISTRATION Union of the Greek Railway Drivers Identifier: 536/10-2003.

Can Procalcitonin in Cerebrospinal Fluid be a Diagnostic Tool for Meningitis

To study the levels of procalcitonin (PCT) in patients with meningitis and control group and compare them with established markers of infection—such as C‐reactive protein (CRP), high‐sensitivity CRP, and WBC—in cerebrospinal fluid (CSF) and assess the possible discriminative role of PCT in the differential diagnosis of meningitis from other noninfectious diseases.

Efficacy versus safety concerns for aerosol chemotherapy in non-small-cell lung cancer: a future dilemma for micro-oncology

Inhaled chemotherapy was first used more than 30 years ago. Since then, numerous chemotherapeutic agents have been used in either in vitro or in vivo studies. Several aspects of the methodology of the drug administration have been thoroughly demonstrated and explained. However, the safety concerns of these studies were not thoroughly investigated and different results regarding the same drug formulations have been reported. There are cases where the studies failed to demonstrate the long-term effects of the chemotherapeutic drug formulations to the lung parenchyma. Acute and latent effects observed in a small number of human trial studies are still under investigation of inhaled chemotherapy administration. This review provides data regarding all up-to-date inhaled chemotherapy studies and presents the methodological parameters of the safety measures incorporated. In addition, a commentary regarding the safety concerns for the medical staff participating in these studies will be presented.