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Obstructive sleep apnea (OSA) is a rising problem, with important implications for public health. Recent evidence has revealed a link between OSA and reduced male fertility. We investigated the association between OSA and sexual and erectile function, as well as semen quality, and the effect of treatment by continuous positive airway pressure (CPAP). A total of 41 male subjects, who underwent polysomnography for suspected OSA, participated in the study. Erectile and sexual function were assessed with the 15-item International Index of Erectile Function (IIEF-15) questionnaire, blood samples, and sperm analysis. OSA patients after the initiation of CPAP treatment were followed for a period of 1 year. Thirty-two patients were diagnosed with OSA, and nine subjects without OSA were used as a control group. OSA patients demonstrated significantly impaired erectile function, reduced testosterone levels, and lower semen quality. Multivariable regression analysis showed that BMI and IIEF score were independent determinants of AHI. Sexual function improved after a year of CPAP therapy in OSA patients. This study provides further evidence regarding the association between OSA and erectile function impairment, as well as semen quality. Longitudinal adherence to CPAP treatment has a beneficial effect on erectile function.

Chronic exposure of workers to powder containing crystalline silica (Silicon dioxide; SiO 2 ) can lead to chronic lung diseases (lung cancer, silicosis, etc.). Aim of this study was to evaluate the exposure of Greek construction workers to SiO 2 and describe their pulmonary function. The study involved 86 outdoor and underground workers. Medical and professional history was obtained, and breath samples were collected at morning hours through a mask for the determination of SiO 2 levels. Pulmonary function tests, radiological examination and evaluation of radiographs were also performed. Pulmonary function examination showed that the majority of the workers were within normal range (61.4%) while the rest were diagnosed with mild (26.5%) and more severe impairment (7.24%). Working conditions (underground-outdoor) were statistically significantly related to the categorization of pulmonary function (P=0.038). During radiological examination, the type of working activity/ conditions (underground-outdoor) were statistically significantly related to the categorization of these findings (P=0.044). Of the 69 employees, 52 did not present findings (75.4%) and 5 were diagnosed with findings specific to occupational diseases (7.23%). Environmental exposure to respirable crystalline silica (RCS) was detected at 0.0125 mg/m 3 in the workplace, which is not beyond the legal limits. Underground workers with more than 15 years of exposure to SiO 2 are more likely to present chronic silicosis compared to the workers of outdoor activities., (Copyright: © Keramydas et al.)

Background: The effect of biphasic positive airway pressure (BPAP) at individualized pressures on the postoperative pulmonary recovery of morbidly obese patients (MOP) undergoing open bariatric surgery (OBS) and possible placebo device-related effects (sham BPAP) were investigated., Methods: Forty-eight MOP scheduled for OBS were initially enrolled. Subjects were randomly assigned to: A) the BPAP group in which BPAP, at individualized inspiratory positive airway pressure/expiratory positive airway pressure (IPAP/EPAP), was applied for 3 days postoperatively and B) the sham BPAP group in which sham BPAP was applied for the same time. Pulmonary function was assessed by spirometry 24 h prior to surgery and at 24, 48 and 72 h postoperatively and respiratory complications were recorded., Results: Thirty-five subjects, 21 in the BPAP group and 14 in the sham BPAP group, completed the study. Baseline characteristics and pulmonary function were similar between groups preoperatively. Subjects in the BPAP group showed in general better spirometric performance and SpO2 values postoperatively and expedited pulmonary recovery. Atelectasis combined with respiratory distress syndrome (RDS) symptoms was observed in 21% of subjects in the sham BPAP group and one of these subjects developed lower respiratory tract infection. No respiratory complications were recorded in the BPAP group. Use of higher BPAP pressures was not associated with anastomosis leakage or disruption in any patient., Conclusion: Use of BPAP, at individualized pressures, expedites postoperative pulmonary recovery and eliminates respiratory complications in MOP who have undergone OBS.

Purpose: Pulmonary rehabilitation (PR) has well documented positive effects in patients with chronic obstructive pulmonary disease (COPD). The BODE (body mass index, airflow obstruction, dyspnea, and exercise) index reflects the multicomponent nature of COPD. We aimed to determine whether changes in BODE quartiles after a PR program might affect 2-year survival and which characteristics drive changes in BODE quartiles after PR intervention., Methods: Ninety-five patients with COPD participated in a PR program. The BODE index and anxiety, depression, and quality of life questionnaires were completed before and after the PR program. Five-year survival was recorded for all patients, irrespective of changes in BODE quartiles., Results: Up to 62% of patients with COPD had an improvement in the BODE index, whereas 42% of patients had a change in BODE quartile. Survival did not differ between patients who did not and who did show an improvement in BODE quartiles, despite a trend in favor of the latter (log-rank P = .202). Similar results were observed for patients who did and did not demonstrate a change in the BODE index ≥2 (log-rank P = .679). Significant changes in BODE quartiles were mainly attributed to the duration of the disease, current smoking status, hospitalization rate in the previous year, and the presence of poorer quality of life, as well as to anxiety and depression at baseline., Conclusions: Pulmonary rehabilitation significantly influenced the BODE index. The significant changes in BODE quartiles were associated with the duration of the disease, current smoking status, increased hospitalization rate, poorer quality of life, anxiety, and depression at baseline, but failed to predict 2-year survival.

Background: The 2009 pandemic influenza A (H1N1) virus was accompanied by high morbidity and mortality. The aim of this study was to describe the clinical characteristics of patients with documented 2009 influenza A (H1N1) virus admitted to a reference chest hospital, the disease outcome, and risk factors associated with ICU admission., Methods: We assessed 109 subjects admitted to the respiratory infection unit of a hospital for chest disease with signs and symptoms of the 2009 influenza A (H1N1) virus between April 2009 and December 2010. Demographic data, comorbidities, clinical signs and symptoms, laboratory tests, radiographic findings, treatment, and final outcomes were all recorded. Factors associated with severe disease requiring ICU admission were determined., Results: Ninety subjects (82.5%) had laboratory-confirmed 2009 influenza A (H1N1). Sixty-four percent of these subjects had pneumonia on admission, 26% had respiratory failure, and 11% required care in the ICU. Dyspnea and the presence of infiltrates on chest x-rays were the most common signs among the subjects with H1N1. All subjects were treated with antiviral therapy, and 75% received antibiotic treatment based on their clinical and laboratory findings. The predictive factors of ICU admission were severe hypoxemia and lymphocytosis., Conclusions: The outcome of subjects with influenza A (H1N1) virus infection was influenced by the severity of the disease on admission, the subjects' underlying conditions, and complications during hospitalization., (Copyright © 2014 by Daedalus Enterprises.)

Purpose: To examine the clinical usefulness of heart rate recovery (HRR) post 6-minute walking test (6MWT) as a simple marker of cardiovascular risk in obstructive sleep apnea (OSA) patients in comparison to HRR post cycle ergometry, the validated and more sophisticated protocol., Methods: Seventy-four participants underwent full overnight polysomnography, cycle ergometry and 6MWT. The HRR at 1, 2 and 3 min (HRR-1, HRR-2 and HRR-3) 6MWT was compared to HRR at 1, 2, and 3 min post cycle ergometry in normal subjects and in moderate and severe OSA patients before and after 6-month CPAP treatment., Results: The HRR-1, HRR-2 and HRR-3 in 6MWT were significantly different between normal, moderate and severe OSA patients with higher rates achieved in normal. The higher the severity of OSA the lower the HRR was. There were also no differences found between work rate and distance walked during cycle ergometry or 6MWT, respectively, concerning normal, moderate and severe OSA patients. Heart rate recovery was further associated with minimum saturation of oxygen during sleep independently of the duration of apnea episodes of BMI and ESS. The treatment with CPAP had a beneficial effect on HRR both post-6MWT and post cycle ergometry., Conclusions: Autonomic nervous system dysfunction in OSA can be found even with submaximal exertion. Heart rate recovery post-6MWT, such as HRR post cycle ergometry, was significantly impaired in OSA patients in comparison to normals and was favorably influenced from CPAP treatment. Furthermore, it was found to be more sensitive compared with distance walked in 6MWT in discriminating severity of OSA. The HRR post-6MWT was found to be an easily measured and reliable marker of OSA severity both before and after CPAP treatment.

Background: A variety of studies have demonstrated improvement in quality of life and depressive symptoms in obstructive sleep apnea (OSA) patients after continuous positive airway pressure (CPAP) treatment. However, very little is known about the effect of OSA treatment on physical activity and energy consumption., Objectives: The aim of this study was to evaluate the changes in depression, physical activity, energy expenditure, and quality of life (QoL) in OSA patients before and after CPAP therapy., Methods: Forty-one patients with OSA as revealed by polysomnography, were included to the study. They responded to the generic World Health Organization Quality of Life (WHOQoL) questionnaire, to the specific-disease Quebec Sleep Questionnaire, and to Center for Epidemiologic Studies Depression Scale (CES-D) in order to evaluate QoL and the incidence of depression. In addition, all patients wore an accelerometer which measured physical activity and energy expenditure during a week. At least 6 months after initiation of CPAP treatment (mean time, 9 months) we re-examined 24 patients who met the compliance with the treatment criteria., Results: Patients after CPAP therapy had significantly higher scores in all domains of the Quebec Sleep Questionnaire and in the domains of physical health/level of independence and psychological health/spirituality of the WHOQoL. Depression scores were also better in CES-D after treatment. However, despite the improvement in QoL and psychological status, CPAP therapy had no impact on physical activity and energy expenditure., Conclusions: CPAP therapy improves QoL and lessens depressive symptoms in our group of well-treated OSA patients. However, physical activity and energy expenditure did not present statistically significant improvement in the same group of OSA patients.

Background: Recent studies suggest poor sleep quality in patients with idiopathic pulmonary fibrosis (IPF). However, so far, the impact of IPF-related sleep breathing disorders (SBDs) on survival has not been extensively studied., Methods: In a cohort of 31 (24 males) treatment-naïve, newly diagnosed consecutive IPF patients, we prospectively investigated the relationship of SBD parameters such as apnea-hypopnea index (AHI), maximal difference in oxygen saturation between wakefulness and sleep (maxdiff SpO2), and lowest sleep oxygen saturation (lowest SpO2) with clinical (survival, dyspnea, daytime sleepiness), pulmonary function, submaximal (6-min walk test [6MWT]) and maximal exercise variables (cardiopulmonary exercise test [CPET]), and right ventricular systolic pressure (RVSP)., Results: Sleep oxygen desaturation exceeded significantly that of maximal exercise (p < 0.001). Maxdiff SpO2 was inversely related to survival, DLCO%, and SpO2 after 6MWT, and directly with dyspnea, AHI, and RVSP. The lowest SpO2 was directly related to survival and to functional (TLC%, DLCO%) as well as submaximal and maximal exercise variables (6MWT distance, SpO2 after 6MWT, peak oxygen consumption/kg, SpO2 at peak exercise), while an inverse association with dyspnea score, AHI, and RVSP was observed., Conclusions: Our findings provide evidence that intermittent sleep oxygen desaturation significantly exceeds that of maximal exercise and is associated with survival in IPF patients. Furthermore, they imply the existence of a link between lung damage and apnea events resulting to the induction and severity of intermittent sleep oxygen desaturation that aggravate pulmonary arterial hypertension and influence IPF survival.

Introduction: Increased levels of inflammatory mediators, such as hs-CRP, have been detected in patients with obstructive sleep apnea (OSA) and used as cardiovascular risk and disease outcome predictors. Calprotectin is an inflammatory marker regulating atherogenic processes not investigated in adult OSA patients. The aim of the present study as primary objective was to examine the role of calprotectin as an inflammatory molecule, acting through a distinct pathway to the atherogenic process in adult OSA patients and its associations with hs-CRP and the lipidemic profile of the patients. As a secondary objective was the evaluation of the atherogenic markers post-CPAP treatment., Materials and Methods: Seventy-four participants underwent full overnight polysomnography. Blood samples were collected for calprotectin, hs-CRP, total cholesterol, triglycerides, LDL, HDL and glucose levels. Thirty-two OSA patients were reexamined 6 months post-CPAP treatment., Results: Out of 74 participants included in the study, 33 had moderate OSA, 27 had severe OSA and 14 were controls. Calprotectin and hs-CRP were significantly increased in patients with moderate and severe OSA compared to controls (p<0.0001). Calprotectin and hs-CRP levels were positively correlated with apnea-hypopnea index, BMI and total time of sleep with SaO(2)<90% and inversely correlated with SaO(2) minimum and mean values. Calprotectin and hs-CRP levels were significantly improved post-CPAP treatment (p<0.0001)., Discussion: Calprotectin may serve as a novel and reliable, biomarker of cardiovascular risk severity in OSA patients. The decrease of calprotectin levels post-CPAP treatment combined with hs-CRP amelioration could provide evidence for reduction of cardiovascular risk post CPAP treatment., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: Several studies have reported a small yet significant decrease in blood pressure (BP) with continuous positive airway pressure (CPAP) application in patients with obstructive sleep apnea (OSA). We investigated the long-term efficiency of CPAP in the management of hypertensive patients with OSA on top of conventional antihypertensive medication., Methods: We followed 91 nonsleepy patients (aged 54 ± 9 years, 69 men) with essential hypertension and newly diagnosed moderate-to-severe OSA (apnea-hypopnea index, 38 ± 24 events/h on polysomnography) for a mean period of 3.1 years, after switching them to antihypertensive treatment targeting office BP less than 140/90 mmHg (<130/80 mmHg in diabetic patients). Participants were defined as on-CPAP if they adhered to CPAP treatment during the whole follow-up period (N = 41), whereas those that did not follow CPAP therapy served as controls (N = 50)., Results: By the end of follow-up, on-CPAP patients and controls exhibited similar SBP and DBP levels (133 ± 12 versus 133 ± 13 mmHg, 84 ± 9 versus 85 ± 9 mmHg, respectively, P > 0.05 for all), number of patients with controlled hypertension (71 versus 70%, P > 0.05), and number of antihypertensive drugs needed to achieve BP control (2.28 ± 1.09 versus 2.11 ± 0.72, P > 0.05). In a subgroup of patients (N = 34) in whom ambulatory BP monitoring was also performed, 24-h BP levels did not differ between the two groups (125 ± 10/76 ± 7 mmHg versus 123 ± 11/75 ± 10 mmHg, P > 0.05). In multiple regression models, CPAP application was not associated with changes in BP levels., Conclusion: In nonsleepy, hypertensive, OSA patients on conventional antihypertensive treatment, long-term CPAP application is not associated with lower BP levels or a need for less antihypertensive drugs for BP control.

Background: Obstructive sleep apnea (OSA) is known to be related to nocturnal blood pressure (BP) and nondipping hypertension. This pilot study evaluated night-time BP assessed using a home monitor in patients with OSA., Participants and Methods: Patients referred to a sleep clinic were subjected to polysomnography, clinic BP measurements, and home BP monitoring using a device that allows daytime (3 days, two duplicate readings per day) and automated night-time BP measurement (3 nights, three readings per night)., Results: Thirty-nine patients were included [72% men, mean age 48.7±10.8 years, clinic BP 131.2±19.6/84.1±11.9 mmHg, apnea-hypopnea index (AHI): 35.2±25.7]. All BP measurements were significantly correlated with the polysomnography indices. There was a consistent trend toward stronger correlations of the night-time diastolic home BP with the AHI (r=0.56), the duration of desaturation (0.53), and the maximum (-0.57) and minimum (-0.48) arterial oxygen saturation (all P<0.001). In stepwise multivariate analysis (independent variables age, sex, body weight, smoking status, and BP parameters), the AHI was associated independently with weight and night-time diastolic home BP (R=0.53)., Conclusion: In patients with OSA, the assessment of night-time BP using a home monitor appears to be feasible and related to the severity of OSA. Given the wide availability of home BP monitoring in clinical practice, this method appears to be useful in the evaluation of BP in patients with OSA.

Background. In IPF, defects in lung mechanics and gas exchange manifest with exercise limitation due to dyspnea, the most prominent and disabling symptom. Aim. To evaluate the role of exercise testing through the 6MWT (6-minute walk test) and CPET (cardiopulmonary exercise testing) in the survival of patients with IPF. Methods. This is a prospective, observational study evaluating in 25 patients the relationship between exercise variables through both the 6MWT and CPET and survival. Results. By the end of the observational period 17 patients were alive (33% mortality). Observation ranged from 9 to 64 months. VE/VCO2 slope (slope of relation between minute ventilation and CO2 production), VO2 peak/kg (peak oxygen consumption/kg), VE/VCO2 ratio at anaerobic threshold, 6MWT distance, desaturation, and DLCO% were significant predictors of survival while VE/VCO2 slope and VO2 peak/kg had the strongest correlation with outcome. The optimal model for mortality risk estimation was VO2 peak/kg + DLCO% combined. Furthermore, VE/VCO2 slope and VO2 peak/kg were correlated with distance and desaturation during the 6MWT. Conclusion. The integration of oxygen consumption and diffusing capacity proved to be a reliable predictor of survival because both variables reflect major underlying physiologic determinants of exercise limitation.

Pathological features of chronic obstructive pulmonary disease (COPD) include lung vascular remodeling and angiogenesis. Angiopoietin-1 (Ang-1), is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor. We determined the levels of angiopoietins in sputum supernatants of patients with COPD and investigated their possible association with mediators and cells involved in the inflammatory and remodeling process. Fifty-nine patients with COPD, 25 healthy smokers and 20 healthy non-smokers were studied. All subjects underwent lung function tests, sputum induction for cell count identification and Ang-1, Ang-2, VEGF, TGF-β1, MMP-2, LTB4, IL-8, albumin measurement in sputum supernatants. Airway vascular permeability (AVP) index was also assessed. Ang-2 levels were significantly higher in patients with COPD compared to healthy smokers and healthy non-smokers [median, interquartile ranges pg/ml, 267 (147-367) vs. 112 (67-171) and 98 (95-107), respectively; p<0.001]. Regression analysis showed a significant association between Ang-2 levels and AVP index, VEGF, IL-8 and MMP-2 levels in COPD, the strongest being with VEGF. Our results indicate that induced sputum Ang-2 levels are higher in COPD compared to healthy smokers and healthy non-smokers. Moreover, Ang-2 is associated with AVP, IL-8, MMP-2, and VEGF, indicating a possible role for Ang-2 in the pathogenesis of the disease., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Exercise-induced dynamic hyperinflation and large intrathoracic pressure swings may compromise the normal increase in cardiac output (Q) in Chronic Obstructive Pulmonary Disease (COPD). Therefore, it is anticipated that the greater the disease severity, the greater would be the impairment in cardiac output during exercise. Eighty COPD patients (20 at each GOLD Stage) and 10 healthy age-matched individuals undertook a constant-load test on a cycle-ergometer (75% WR(peak)) and a 6min walking test (6MWT). Cardiac output was measured by bioimpedance (PhysioFlow, Enduro) to determine the mean response time at the onset of exercise (MRTon) and during recovery (MRToff). Whilst cardiac output mean response time was not different between the two exercise protocols, MRT responses during cycling were slower in GOLD Stages III and IV compared to Stages I and II (MRTon: Stage I: 45±2, Stage II: 65±3, Stage III: 90±3, Stage IV: 106±3s; MRToff: Stage I: 42±2, Stage II: 68±3, Stage III: 87±3, Stage IV: 104±3s, respectively). In conclusion, the more advanced the disease severity the more impaired is the hemodynamic response to constant-load exercise and the 6MWT, possibly reflecting greater cardiovascular impairment and/or greater physical deconditioning., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Airway and vascular remodeling may play a prominent role in the clinical severity of severe refractory asthma (SRA). Angiopoietin-1 (Ang-1) is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor., Objective: We aimed to determine the levels of angiopoietins in sputum supernatants of patients with SRA and to investigate the possible associations with mediators and cells involved in both the inflammatory and the vascular remodeling processes., Methods: Thirty-eight patients with SRA, 35 patients with moderate asthma, and 20 healthy subjects were studied. All participants underwent lung function tests, bronchial hyperresponsiveness assessment and sputum induction for cell count identification and Ang-1, Ang-2, VEGF, TGF-β1, Cys-LTs, MMP-2, IL-13, ECP, and IL-8 measurement in supernatants. Airway vascular permeability (AVP) index was also assessed., Results: Ang-1 (ng/ml) and Ang-2 (pg/ml) levels were significantly elevated in patients with SRA compared with patients with moderate asthma and control subjects [median, interquartile ranges: 30 (17-39) vs 7.5 (5-11) vs 4.7 (3.8-5.9) respectively, P < 0.001; and 506 (400-700) vs 190 (146-236) vs 96 (89-120) respectively, P < 0.001]. Regression analysis showed a significant positive association between Ang-2 and AVP index, MMP-2, Ang-1, and VEGF in SRA. A weak association was also observed between Ang-1 and sputum eosinophils% in SRA., Conclusion: Our results indicate that both angiopoietins levels are higher in SRA compared with moderate asthma and healthy subjects. In SRA, Ang-2 is associated with mediators involved in both the inflammatory and the vascular remodeling processes., (© 2012 John Wiley & Sons A/S.)

Purpose: The aim of this study was to evaluate markers of systemic oxidative stress and antioxidant capacity in subjects with and without OSAS in order to investigate the most important factors that determine the oxidant-antioxidant status., Methods: A total of 66 subjects referred to our Sleep laboratory were examined by full polysomnography. Oxidative stress and antioxidant activity were assessed by measurement of the derivatives of reactive oxygen metabolites (d-ROMs) and the biological antioxidant capacity (BAP) in blood samples taken in the morning after the sleep study. Known risk factors for oxidative stress, such as age, sex, obesity, smoking, hypelipidemia, and hypertension, were investigated as possible confounding factors., Results: 42 patients with OSAS (Apnea-Hypopnea index >15 events/hour) were compared with 24 controls (AHI<5). The levels of d-ROMS were significantly higher (p = 0.005) in the control group but the levels of antioxidant capacity were significantly lower (p = 0.004) in OSAS patients. The most important factors predicting the variance of oxidative stress were obesity, smoking habit, and sex. Parameters of sleep apnea severity were not associated with oxidative stress. Minimal oxygen desaturation and smoking habit were the most important predicting factors of BAP levels., Conclusion: Obesity, smoking, and sex are the most important determinants of oxidative stress in OSAS subjects. Sleep apnea might enhance oxidative stress by the reduction of antioxidant capacity of blood due to nocturnal hypoxia.

Background: COPD is a multicomponent disease and systemic inflammation represents one of the possible mechanisms responsible for its systemic manifestations, including skeletal muscle weakness and cachexia. Fat-free mass index (FFMI) that reflects the skeletal muscle mass, has been shown to be associated with both dyspnoea and exercise capacity. We hypothesized that the multidimensional BODE index, that reflects the multicomponent nature of COPD, might be related to biomarkers of systemic inflammation. We further evaluated associations between FFMI and systemic inflammation., Methods: BODE index and FFMI were calculated in 222 stable COPD patients and 132 smokers or ex-smokers with normal lung function. Systemic inflammation was evaluated with the measurement of leptin, adiponectin, CRP, IL-6, and TNF-α in serum samples of COPD patients., Results: In patients with COPD, both BODE index and FFMI presented significant positive and negative associations respectively with leptin levels (R(2) 0.61 and 0.65, respectively), whereas FFMI presented an additional negative association with the levels of TNF-α (R(2) 0.38). No significant associations were observed in smokers or ex-smokers with normal lung function., Conclusions: Both BODE index and FFMI, are related to the circulating levels of leptin in patients with COPD, suggesting a possible role for leptin in the systemic component of COPD. The additional association of FFMI with TNF-α may further support a role of systemic inflammation in muscle wasting in COPD.

Introduction: Heart failure (HF) is a major public health problem associated with high rates of morbidity and mortality. Patients with HF exhibit a high prevalence of sleep-disordered breathing (SDB). We have investigated the long-term impact of positive airway pressure (PAP) therapy on heart function and clinical outcomes in patients with advanced HF and concomitant SDB., Materials and Methods: We assessed 18 patients with advanced HF (New York Heart Association (NYHA) functional classification III-IV) and concomitant SDB (diagnosed with polysomnography) either of obstructive or central type. Eleven patients who received PAP therapy (auto-titrating PAP or adaptive servo-ventilation) for 12 months were compared with seven patients who refused this therapy. All participants were assessed at both baseline and end of follow-up for NYHA functional status, left and right ventricular function, neurohormonal activation, and exercise tolerance. The rates of hospitalization, deaths, and the combination of both were also recorded., Results: Patients treated with PAP achieved better functional status, higher left ventricular ejection fraction, improved longitudinal right ventricular contractile function, lower levels of b-type natriuretic peptide, and greater exercise performance compared to those who remained untreated. PAP-treated group had a significantly lower incidence of the prespecified combined end-point (i.e., hospital admissions and death) than the control group (87.5 vs. 18.2%, p = 0.013). Interestingly, the mortality rate was 28% (two out of seven patients) in the control group, while no deaths were recorded in the PAP-treated group., Discussion: In this preliminary study, we found that treatment of SDB, irrespective of type, in stable patients with advanced HF receiving optimal medical therapy was associated with improvement in cardiac functional status, ventricular contraction, physical performance, and neurohormonal status, leading to better clinical outcomes.

Background and Objective: Smoking is thought to modify the pattern of airway inflammation. Induced sputum provides useful information on cellular phenotype in inflammatory airways disorders; however, it is time-consuming and difficult to implement in everyday clinical practice. The aim of this study was to determine whether exhaled NO (FeNO) and exhaled breath condensate (EBC) pH differed in asthmatic smokers compared with asthmatic non-smokers and healthy subjects, and to evaluate the performance of FeNO and EBC pH for predicting the cellular phenotype of induced sputum., Methods: Asthmatic smokers (n = 40) and non-smoking asthmatic patients (n = 43) were recruited for the study. Healthy smoking (n = 30) or non-smoking (n = 30) subjects served as controls. FeNO and EBC pH were measured and all subjects underwent sputum induction for assessment of cell counts., Results: EBC pH was significantly lower in asthmatic smokers compared with non-smokers (P < 0.01). FeNO levels were also significantly lower in asthmatic smokers compared with non-smokers (P < 0.001). EBC pH was inversely associated with sputum eosinophils in both asthmatic smokers and non-smokers (P < 0.001), whereas it was inversely associated with sputum neutrophils only in asthmatic smokers (P < 0.001). FeNO was positively associated with sputum eosinophils both in asthmatic smokers and non-smokers (P < 0.001) but was not associated with sputum neutrophils. In asthmatic smokers, FeNO was a better predictor of sputum eosinophilia, whereas EBC pH was a better predictor of sputum neutrophilia. A combination of FeNO ≤ 14 ppb together with EBC pH > 7.20 predicted the paucigranulocytic induced sputum phenotype., Conclusions: EBC pH and FeNO levels were significantly lower in asthmatic smokers compared with non-smokers. Combined specific cut-off levels for FeNO and EBC pH may predict the paucigranulocytic phenotype in asthmatic smokers., (© 2011 The Authors; Respirology © 2011 Asian Pacific Society of Respirology.)

Endogenous airway acidification, as assessed by exhaled breath condensate (EBC) pH, is present in patients with stable COPD. The aim of this study was to measure EBC pH levels in a large cohort of COPD patients and to evaluate associations with functional parameters according to their smoking status.EBC was collected from 161 patients with stable COPD and 112 controls (current and ex-smokers). EBC pH was measured after Argon deaeration and all subjects underwent pulmonary function testing.EBC pH was lower in COPD patients compared to controls [7.21 (7.02, 7.44) vs. 7.50 (7.40, 7.66); p < 0.001] and ex-smokers with COPD had lower EBC pH compared to current smokers [7.16 (6.89, 7.36) vs 7.24 (7.09, 7.54), p = 0.03]. In ex-smokers with COPD, EBC pH was lower in patients with GOLD stage III and IV compared to patients with stage I disease (p = 0.026 and 0.004 respectively). No differences were observed among current smokers with different disease severity. EBC pH levels in ex-smokers were associated with static hyperinflation (as expressed by IC/TLC ratio), air trapping (as expressed by RV/TLC ratio) and diffusing capacity for carbon monoxide, whereas no associations were observed in current smokers.Endogenous airway acidification is related to disease severity and to parameters expressing hyperinflation and air trapping in ex-smokers with COPD. The possible role of EBC pH in COPD needs to be further evaluated in longitudinal studies.

Background: Systemic inflammation may represent a possible cause of anemia. Previous data support that anemic patients with COPD present high erythropoietin (EPO) levels, suggestive of EPO resistance, possibly mediated through inflammatory mechanisms., Objectives: We aimed to determine whether systemic inflammation, which is usually up-regulated during exacerbations of COPD (ECOPD) is associated with low hemoglobin levels expressing erythropoietin resistance., Methods: Hemoglobin (Hb), EPO and serum biomarkers of systemic inflammation [CRP, TNF-α, fibrinogen and IL-6] were assessed at three time points (admission, resolution and stable phases) in a selected cohort of 93 COPD patients., Results: Hemoglobin levels were significantly lower on admission compared to resolution and stable phases (median 12.1 g/dl [interquartile ranges 11.2-12.7], vs 13.5 [12.4-14.3] vs 13.4 [12.7-14.08], respectively p=0.002), whereas EPO was significantly higher on admission compared to resolution and stable phases. A negative association between Hb and IL-6 and a positive association between EPO and IL-6 were observed only during the acute phase of exacerbation. EPO and Hb were negatively associated during the acute phase, whereas they were positively associated during discharge and stable phase., Conclusions: In this observational study we have shown that during admission for ECOPD Hb levels are decreased and EPO levels are increased. We have also identified a negative association between Hb and EPO. The above association is mainly related to increased IL-6 levels, indicating a possible EPO resistance through the mechanism of increased systemic inflammatory process., (Copyright © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objectives: Brain metastases (BMs) often advance the course of non-small cell lung cancer (NSCLC). We performed an observational study in order to investigate the possible correlation of selected clinical and epidemiological factors with BM appearance in patients suffering from different histological subtypes of NSCLC stage I-IV., Methods: The study included 161 consecutive patients with NSCLC. Analyzed data included patient- and tumor-related characteristics., Results: Thirty-nine patients (24.2%) presented BMs within 12 (0-36) weeks of diagnosis. BMs decreased the mean overall survival significantly (15.6 versus 50.7 weeks, P < 0.001), with hazard ratio (95% confidence interval) 3.60 (2.42-5.35). The age of the patients with BM was significantly lower than that of the patients without BM (60.8 ± 8.9 versus 66.5 ± 8.5, P < 0.001). Patients with BM had significantly higher pack-years consumption (75.9 ± 23.9 versus 58.9 ± 31.9, P = 0.003) and larger tumor size compared with patients without BM (size in mm: 55.1 ± 20.1 versus 45.9 ± 19.3, P = 0.012). The presence of BM was also correlated with the absence of lung (P < 0.001), bone (P = 0.005), and adrenal (P = 0.046) metastases., Conclusion: Younger NSCLC patients with high tobacco consumption, large tumor size, and absence of metastases in other organs (lung, bones, adrenal metastases) are at high risk of BM appearance during the course of NSCLC and are candidates for prophylactic cranial irradiation early in the course of the disease.

Recent advances in technology and novel pharmaceutical research findings have added new grounds in the fields of medical treatment and quality of life of patients diagnosed with pulmonary arterial hypertension (PAH). Collective assessment of new data is mandatory and useful for specialist medical doctors. This review aims to present the latest therapeutic developments of the last two years (2009-2010) in PAH. Moreover, recent patents (of the year 2010) regarding therapeutic novelties in PAH that expand treatment modalities, are hereby presented.

Background: Obesity and asthma are characterized by the presence of inflammation. Leptin and adiponectin are circulating hormones produced by adipose tissue that regulate several metabolic and inflammatory functions. We aimed to determine whether obesity influences asthmatic inflammation as well as the contribution of leptin or/and adiponectin to a possible linkage between asthmatic and obesity-related inflammation., Materials and Methods: One hundred patients with asthma and 60 healthy controls were studied. Subjects who had a comorbid illness that could interfere with the proposed tests were excluded. All subjects were divided into three groups (normal range, pre-obese, obese) according to the criteria of the current WHO international classification for body mass index (BMI). Possible associations between variables expressing airway inflammation, bronchial hyper-responsiveness, systemic inflammation and obesity, as assessed by BMI, were evaluated. Leptin and adiponectin were also measured and were associated with asthma airway and systemic inflammatory variables to elucidate possible associations., Results: Obese patients had significant higher values of LTE(4) /creatinine in urine compared with pre-obese and normal range ones. In a linear regression model, the only significant associations were those between BMI and LTE(4) /creatinine in urine. Using the same model, log leptin and log adiponectin presented positive and negative associations, respectively with LTE(4) /creatinine in urine. No other significant associations were observed in both patients and healthy subjects., Conclusions: In a selected cohort of asthmatic patients, obesity is significantly associated with increased urinary leukotriene levels. Alterations of leptin/adiponectin balance may be related to the presence of leukotriene inflammation in obese asthmatic patients., (© 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.)

During recent years there has been a growing interest in using non-invasive biomarkers to understand and monitor the airway inflammation in subjects with respiratory tract disorders and mainly asthma and chronic obstructive pulmonary disease (COPD). Sputum induction is generally a well-tolerated and safe procedure and a European Respiratory Society Task Force has published a comprehensive review on sputum methodology. Induced sputum cell count and, to a lesser extent, mediator measurements have been particularly well validated. In asthma, the sputum and the cell culture supernatant can be used for the measurement of a variety of soluble mediators, including eosinophil-derived proteins, nitric oxide (NO) derivatives, cytokines and remodelling-associated proteins. Sputum eosinophilia (> 3%) is a classic feature of asthma although half of the patients seems to be non eosinophilic. Measuring the percentage of sputum eosinophils has proved to be useful in the clinical arena in helping to predict short term response to inhaled corticosteroids (ICS) and tailor the dose of ICS in the severe patients but there is scope for the application of other induced sputum markers potentially useful in clinical practice. The widespread application of induced sputum in asthma across the spectrum of disease severity has given insight into the relationship between airway function and airway inflammation, proposed new disease phenotypes and defined which of these phenotypes respond to current therapy, and perhaps most importantly provided an additional tool to guide the clinical management of asthmatic patients. To date sputum induction is the only non-invasive measure of airway inflammation that has a clearly proven role in asthma management.

Background: Laparoscopic Roux-en-Y gastric bypass (RYGBP) for morbid obesity is a challenging operation. The application of robotic techniques has been shown to ease the technical difficulties and reduce perioperative morbidity, mainly because it facilitates the construction of the gastrojejunal anastomosis (GJ). Robotic laparoscopic RYGBP (LRYGBP) has been reported either as totally robotic with manual suturing of the GJ or as robotically assisted with the use of the robot only for the construction of the GJ. A totally robotic LRYGBP with a combined stapled and manual GJ has never been reported., Patients and Methods: Nine consecutive patients underwent totally robotic LRYGBP. The GJ was fashioned with a combination of the linear stapler and manual suturing., Results: Mean preoperative body mass index was 45.3 ± 4.7 kg/m(2). In 1 case, we had to undock the Da Vinci Surgical System at the time of the jejunojejunostomy due to unfavorable ergonomics. Mean time to dock the robot was 16.3 ± 3.3 minutes, whereas mean total operative time was 197.2 ± 12.3 minutes. Immediate postoperative morbidity and mortality equaled zero. One patient developed a stenosis of the GJ amenable to endoscopic dilatation. The mean excess weight loss rate 1-year postoperative was 79% ± 15%., Conclusion: Totally robotic LRYGBP can duplicate precisely any conventional technique without any compromise in operative time, short- or long-term results.

Background: Local and systemic inflammation is implicated in the pathophysiology of Obstructive Sleep Apnea (OSA). Exhaled breath condensate (EBC) is a non-invasive sampling method for the lower airways. However, it is important to consider the potential effect of the systemic origin whereas systemic inflammation is significantly elevated. This prospective study was designed to investigate whether airway inflammation is significantly related to plasma leptin levels in OSA patients. Simultaneously, it was designed to investigate whether inflammatory variables predict parameters expressing disease severity and finally whether smoking habit affect the above measurements., Patients & Methods: About 45 OSA patients (mean AHI 40+/-25, 28 smokers) and 25 healthy controls (AHI<5, 15 smokers) were studied and underwent overnight diagnostic polysomnography. We measured pH, 8-isoprostane, TNF-alpha and IL-6 in EBC and leptin in plasma. Plausible associations between leptin and inflammatory parameters were analyzed after adjustment for proper variables. Similar associations between inflammatory variables and parameters of disease severity were also performed., Results: An increased level of leptin and respective increase of inflammatory variables was found. No significant association was observed between parameters of EBC and plasma leptin levels. A part of the parameters of disease severity is significantly associated with pH and 8-isoprostane. Smoking did not seem to be a critical confounding factor for evaluation of the above measurements., Conclusions: Increased levels of leptin were not associated with the observed airway inflammation in OSA. The observed airway inflammation seemed to be independent of smoking habit with limited association with disease severity.

The aim of this study was to evaluate the effect of obstructive sleep apnea syndrome on the cognitive performance of young and middle-aged patients. Patients were divided into two groups, one consisting of 30 patients less than 50 years of age and the other consisting of 28 patients 50 years and over. Normal subjects were similarly divided into two groups, composed of 17 younger and 24 older controls. Patients and controls were examined with all-night polysomnography and subsequently underwent cognitive testing via attention-alertness tests. Comparing young to middle-aged patients, there were statistically significant differences in cognitive performance, especially in attention tests. Younger patients' cognitive performance was similar to their age-matched controls, while middle-aged patients showed cognitive decline in comparison with their age-matched controls. Although we studied only two age groups using 50 years of age as a cut-off, we could demonstrate that cognitive deterioration of untreated sleep apnea patients is age dependent, and several factors may contribute to this effect including brain hypoxia, sleep fragmentation, or comorbidities. Aging patients with sleep apnea demonstrate cognitive decline, while younger patients with the same disease severity are (somehow) able to compensate for this effect.

Background: Asthma and rhinitis often coexist, and there is evidence to suggest that they have similar histopathologic features., Objective: To examine whether the inflammatory infiltration in the nasal mucosa in rhinitis is affected by the presence of asthma and allergy., Methods: Nasal mucosa biopsy samples were collected from 44 individuals: 18 with rhinitis and asthma (9 allergic and 9 nonallergic), 16 with rhinitis and no asthma (8 allergic and 8 nonallergic), and 10 nonallergic control subjects. The alkaline phosphatase-anti-alkaline phosphatase method was applied to 6-microm-thick cryostat sections using monoclonal antibodies against T cells (CD4 and CD8) and eosinophils (EG2). Slides were counted blindly, and results are expressed as cells per high-power field., Results: Eosinophil counts were higher in the nasal mucosa of rhinitic patients vs controls. No differences in cellular infiltration were detected between rhinitic patients with and without asthma or between allergic and nonallergic patients. A trend toward higher CD4+ T-cell counts in the nasal mucosa of rhinitic patients was observed, whereas no differences were noted in CD8+ T-cell infiltration among the groups., Conclusion: Inflammatory infiltration, characterized by the presence of eosinophils and CD4+ T cells, was similar in the nasal mucosa in noninfectious rhinitis irrespective of the presence of asthma or the allergic status of the patient.

Purpose: To assess the improvement of concurrent erectile dysfunction (ED) in men with overlap syndrome (obstructive sleep apnea and chronic obstructive pulmonary disease), treated with continuous positive airway pressure (CPAP) and bronchodilators., Material and Methods: We evaluated 48 men of a mean age of 52.8+/-10 years suffering from both obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), and concurrent ED. They were treated with conventional for pulmonary obstruction therapy (CPAP and bronchodilators) for 6 months and then their erectile function (EF) status was reassessed. ED was considered as improved, if ED intensity score increased for at least five points compared to that of baseline. The determinants for improvement of ED were also evaluated, as well as patient's personal degree of satisfaction with the treatment they received as far as the disorder was concerned., Results: EF was improved in 12 patients (25%), but only two thirds of them were satisfied with the grade of improvement after treatment. ED improvement was related positively with age and apnea/hypopnea index and negatively with ED duration. ED intensity score, O(2) saturation at night and BMI were not significantly related to the outcome of EF improvement., Conclusions: Conventional treatment for OSA and COPD, has a positive effect on concurrent ED on the minority of patients. This effect is possibly due to the improvement of respiration during sleep with CPAP and of oxygenation with bronchodilators continuously. Of the improved men, one third was not satisfied with the impact of this treatment modality on their EF. It is likely that specific for ED treatment is needed in these individuals.

Objective: Although obstructive sleep apnoea syndrome (OSAS) is accompanied by an increased atherosclerotic cardiovascular disease burden, its relationship with arterial stiffness is not yet well determined. We investigated whether essential hypertensive individuals with OSAS are characterized by increased arterial stiffness., Methods: Our study population consisted of 46 consecutive patients with newly diagnosed untreated stage I-II essential hypertension suffering from OSAS (35 men, aged 49 +/- 8 years) and 53 hypertensive individuals without OSAS, matched for age, sex, and smoking status. All subjects underwent polysomnography, echocardiography and aortic stiffness evaluation by means of carotid-femoral pulse wave velocity (c-fPWV) measurements., Results: Hypertensive subjects with OSAS [apnoea/hypopnoea index (AHI)>or =5] compared with hypertensive subjects without OSAS (AHI < 5) demonstrated increased levels of body mass index (31.4 +/- 4 versus 29.3 +/- 4 kg/m2, P = 0.015), office systolic/diastolic blood pressure (151/99 versus 145/94 mmHg, respectively, P < 0.05, for both cases) and relative wall thickness (RWT; 0.46 +/- 0.06 versus 0.42 +/- 0.07, P=0.010). Hypertensive subjects with OSAS compared with those without OSAS had significantly increased c-fPWV by 9% (8.56 +/- 0.49 versus 7.85 +/- 0.93 m/s, P=0.001) and this difference remained significant even after adjustment for confounders (P=0.04). In the total study population, c-fPWV was correlated with age (r=0.35, P=0.015), office systolic blood pressure (r=0.30, P=0.007), RWT (r=0.30, P=0.03), logAHI (r=0.389, P=0.0001) and minimum oxygen saturation (r=-0.418, P=0.0001)., Conclusions: OSAS has a significant incremental effect on aortic stiffening in the setting of middle-aged essential hypertensive subjects. This finding suggests that the presence of OSAS in a hypertensive patient accelerates vascular damage, increasing cardiovascular risk.

Cognitive deficits in patients with obstructive sleep apnea syndrome (OSAS) are well demonstrated, but the pathophysiology of these deficits is still controversial, as the relationship between OSA severity and cognitive deficits is usually weak. Our study considers the possible relationship between OSA-related cognitive deficits and the overall intellectual function of OSA patients. Forty-seven OSA patients and 36 normal individuals underwent a neuropsychological battery test assessing attention and alertness. According to the resulting IQ score, patients and controls were divided into a high-intelligence group (IQ > or = 90th percentile) and a normal-intelligence group (50 < or = IQ < 90%ile). Between the two patient groups there were no significant differences noticed, regarding OSA severity or sleepiness. High-intelligence patients showed the same attention/alertness performance compared with the high-intelligence controls. On the contrary, patients with normal-intelligence showed attention/alertness decline compared with the normal-intelligence control group. The two patient groups were re-examined with the same battery test after at least 1 year of CPAP treatment. At re-examination neither patient group showed any differences regarding attention and alertness compared with the control groups. We assume that high-intelligence may have a protective effect against OSA-related cognitive decline, perhaps due to increased cognitive reserve.

Patients with obstructive sleep apnoea syndrome frequently have cognitive deficits, especially related to executive functions, which cannot be fully explained by daytime sleepiness and are partial irreversible after nasal continuous positive airway pressure treatment. The causal mechanism of these cognitive deficits is not yet known, but it has been proposed that they are associated with chemical and structural brain cell injury. The aim of this study was to investigate brain metabolism in patients with sleep apnoea syndrome. Twenty-two patients with severe sleep apnoea and 10 healthy volunteers of comparable age were studied using single voxel proton magnetic resonance spectroscopy. Magnetic resonance spectra were obtained from prefrontal cortex, parieto-occipital and frontal periventricular white matter. N-acetylaspartate-to-creatine and choline-to-creatine ratios were significantly lower in the frontal white matter of obstructive sleep apnoea patients when compared to controls. Absolute concentrations of N-acetylaspartate and choline were also significantly reduced in the frontal white matter of patients with sleep apnoea. Frontal lobe white matter lesions are known to be associated with cognitive executive dysfunction. The findings of this study may offer an explanation for the sometimes irreversible cognitive deficits associated with sleep apnoea.

There is limited information on the development of left ventricular (LV) dysfunction in patients with obstructive sleep apnoea (OSA) in the absence of lung and cardiac comorbidity. This study aimed to investigate whether OSA patients without heart morbidity develop LV dysfunction, and to assess the effect of continuous positive airway pressure (CPAP) on LV function. Twenty-nine OSA patients and 12 control subjects were studied using technetium-99m ventriculography to estimate LV ejection fraction (LVEF), LV peak emptying rate (LVPER), time to peak emptying rate (TPER), peak filling rate (LVPFR) and time to peak filling rate (TPFR) before and after 6 months of treatment with CPAP. A significantly lower LVEF was found in OSA patients, compared to control subjects, (53+/-7 versus 61+/-6%) along with a reduced LVPER (2.82+/-0.58 versus 3.82+/-0.77 end-diastolic volumes x s(-1)). Furthermore, OSA patients had significantly lower LVPFR (2.67+/-0.71 versus 3.93+/-0.58 end-diastolic volumes x s(-1)) and delayed TPFR (0.19+/-0.04 versus 0.15+/-0.03 s) in comparison with the control group. Six-months of CPAP treatment was effective in significantly improving LVEF, LVPER, LVPFR and TPFR. In conclusion, obstructive sleep apnoea patients without any cardiovascular disease seem to develop left ventricular systolic and diastolic dysfunction, which may be reversed, either partially or completely, after 6 months of continuous positive airway pressure treatment.

Background: Limited information exists regarding the development of pulmonary hypertension in patients with obstructive sleep apnea (OSA) in the absence of lung and heart comorbidity., Objectives: The aims of this study were to investigate whether OSA patients without any other cardiac or lung disease develop pulmonary hypertension, and to assess the effect of continuous positive airway pressure (CPAP) treatment on pulmonary artery pressure (P(PA))., Methods: Twenty-nine patients aged 51 +/- 10 years with OSA and 12 control subjects were studied with pulsed-wave Doppler echocardiography for estimation of P(PA) before and after 6-month effective treatment with CPAP., Results: A significantly higher mean P(PA) was found in OSA patients as compared to control subjects (17.2 +/- 5.2 vs. 12.1 +/- 1.9 mm Hg, p < 0.001). Six out of the 29 OSA patients had mild pulmonary hypertension (P(PA) > or = 20 mm Hg). Significant differences were observed between pulmonary hypertensive and normotensive OSA patients with respect to age (62 +/- 4 vs. 48 +/- 15 years, respectively, p < 0.05), body mass index (41 +/- 7 vs. 32 +/- 4 kg/m(2), p < 0.02) and daytime P(a)O(2) (81 +/- 9 vs. 92 +/- 9 mm Hg, p < 0.05). CPAP treatment was effective in reducing mean P(PA) in both groups of pulmonary hypertensive and normotensive OSA patients (decreases in P(PA) from 25.6 +/- 4.0 to 19.5 +/- 1.5 mm Hg, p < 0.001; from 14.9 +/- 2.2 to 11.5 +/- 2.0 mm Hg, respectively, p < 0.001)., Conclusions: A proportion (20.7%) of OSA patients without any other lung or heart disease and characterized by older age, greater obesity and lower daytime oxygenation develop mild pulmonary hypertension which has been partially or completely reversed after 6-month CPAP treatment. In conclusion, OSA alone constitutes an independent risk factor for the development of pulmonary hypertension., (Copyright 2001 S. Karger AG, Basel)

Deletions in the 5q14 region have been described in a variety of neoplasms, such as testicular germ cell tumors, ovarian, gastric and lung cancer. The high frequency of allelic losses observed in this region implies the presence of putative tumor suppressor gene(s) (TSGs). In the present study, we investigated in a series of 56 non-small cell lung carcinomas (NSCLCs) the allelic imbalance (Alm) within the 5q14 region, employing the D5S644 marker, and its relationship with p53 abnormalities, the kinetic parameters [proliferation index (PI) and apoptotic index (AI)] and the ploidy status of the carcinomas. AI at D5S644 was found at a frequency of 51.2%. The rather high percentage of Alm in stage I tumors suggests an early involvement in NSCLC development. LOH at 5q14 was associated with decreased AR in lung tumors insinuating the presence of a putative TSG(s) (P=0.008). Simultaneous alterations of both p53 and D5S644 locus were the most frequent pattern observed (37.5%). Cases demonstrating this profile also exhibited a marked decrease in AI (P=0.001). These findings imply a synergistic mechanism of co-operation between different TSGs. However, proliferation activity was dependent only on p53 status, leading to the assumption that the putative TSG(s) present at 5q14 may probably be involved in normal apoptotic procedures. Further studies are needed to identify the candidate gene(s).

Background: Previous studies have yielded disparate results regarding the effect of obstructive sleep apnoea (OSA) syndrome on left ventricular (LV) function., Objectives: In order to clarify this, we performed a prospective study investigating OSA patients with no history of systemic hypertension, coronary artery disease, myocardial, pericardial or valvular problems, asthma or chronic obstructive pulmonary disease before and after treatment with nasal continuous positive airway pressure (nCPAP)., Methods: Fifteen patients (3 women, 12 men) with an apnoea/hypopnoea index >15 (mean +/- SD = 52 +/- 21) were studied with complete polysomnography, ambulatory blood pressure monitoring, M-mode two-dimensional echocardiography and pulsed Doppler echocardiography in two phases, i.e. before and after 12-14 weeks of nCPAP therapy. We measured systolic and diastolic blood pressure (BP) separately in the daytime and night-time, isovolumic relaxation time (IVRT), the ratio of peak early filling velocity (E) to peak late velocity (A) diastolic transmitral flow (E/A), posterior wall thickness (PWT) and septal thickness (IVST). The shortening fraction (SF) was also calculated. Eleven overweight non-apnoeic normal subjects matched for age were used as the control group., Results: Our results showed that the patient group exhibited, before treatment, LV diastolic, but not systolic, dysfunction compared with the normal group (IVRT = 94.3 +/- 11.6 ms, p < 0.05; E/A = 0.94 +/- 0.26, p < 0.02; SF = 39.9 +/- 4.1%, not significant (NS); IVST = 9.9 +/- 1.2 mm, NS; PWT = 8.3 +/- 1.2 mm, NS). Moreover, the patient group developed diastolic hypertension both in the daytime and night-time (BP/diastolic/daytime = 93.3 +/- 9.2 mm Hg, BP/diastolic/night-time = 90.3 +/- 10.7 mm Hg). After 12-14 weeks of nCPAP treatment (no change in body mass index), significant improvement in LV diastolic function and a drop in blood pressure were noticed (IVRT = 85.6 +/- 8.8 ms, p < 0.05; E/A = 1.07 +/- 0.3, p < 0.05; BP/diastolic/daytime = 86.3 +/- 5.5 mm Hg, p < 0.02; BP/diastolic/night-time = 83.9 +/- 8. 6 mm Hg, p < 0.05) in our patient group., Conclusions: We conclude that repetitive apnoeas/hypopnoeas are very important factors in the development of both LV diastolic dysfunction and diastolic systemic hypertension in patients with OSA syndrome. Treatment with nCPAP leads to significant improvement in both ventricular function and systemic hypertension., (Copyright 2000 S. Karger AG, Basel)

CYFRA 21-1 was evaluated in 115 untreated patients with malignant pleural effusions (96 with primary lung cancer and 19 with non lung cancer) and 99 patients with benign pleural effusions. The levels of pleural fluid CYFRA 21-1 were from 1 to 385 times higher than those in serum, in all the examined patients. The mean level of pleural fluid CYFRA 21-1 was significantly higher in cancer patients than in patients with benign pleural effusion (96.1 ng/ml vs 26.2 ng/ml, p < 0.001). At 92% specificity for benign pleural effusion (> 50 ng/ml) the overall sensitivity of CYFRA 21-1 in malignant pleural effusions was 69.6%. When the histology was considered the highest sensitivity was found in squamous cell lung cancer (90%), followed by adenocarcinoma cell lung cancer (74%), non lung cancer (54%) and small cell lung cancer (25%). These results indicate that CYFRA 21-1 could be a useful pleural fluid marker in discriminating benign from malignant pleural effusion and particularly from those due to squamous and adenocarcinoma cell lung cancer.

Thymidine kinase (TK), carbohydrate antigen 19-9 (CA 19-9), carbohydrate antigen 125 (CA 125), squamous cell carcinoma antigen (SCC) and tissue polypeptide antigen (TPA), were evaluated in 104 untreated patients with primary lung cancer acid 55 patients with benign lung disease. The mean concentrations of TPA and CA 125 were significantly higher in lung cancer patients than in benign controls (p<0.001). The concentrations of all the tumor markers were well correlated with the stage of lung cancer. In respect to sensitivity, specificity and accuracy, TPA was superior to the other tumor markers tested (70.2%, 88.8% and 75.8% respectively). When TPA was combined with the other markers, sensitivity increased from 70.2% to 98%, but as the number of combined markers became larger, specificity decreased (from 88.8% to 40%). Nevertheless, the combination of TPA and CA 19-9 showed significantly higher sensitivity in patients with resectable non small eel lung cancer (NSCLC) and limited small cell lung cancer (SCLC) than TPA alone (87% vs 49% and 88.8% vs 44.4% respectively) without significant differences in specificity. The relative possibility of lung cancer was 15% when one tumor marker was positive. This possibility increased to 82%-100% when more than three markers were positive.