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We report on laser cooling of a large fraction of positronium (Ps) in free flight by strongly saturating the 1^{3}S-2^{3}P transition with a broadband, long-pulsed 243 nm alexandrite laser. The ground state Ps cloud is produced in a magnetic and electric field-free environment. We observe two different laser-induced effects. The first effect is an increase in the number of atoms in the ground state after the time Ps has spent in the long-lived 2^{3}P states. The second effect is one-dimensional Doppler cooling of Ps, reducing the cloud's temperature from 380(20) to 170(20) K. We demonstrate a 58(9)% increase in the fraction of Ps atoms with v&#95;{1D}<3.7×10^{4}  ms^{-1}.

Measurements were made of the return current instability growth rate, demonstrating its concurrence with nonlocal transport. Thomson scattering was used to measure a maximum growth rate of 5.1×10^{9}  Hz, which was 3 times less than classical Spitzer-Härm theory predicts. The measured plasma conditions indicate the heat flux was nonlocal, and Vlasov-Fokker-Planck simulations that account for nonlocality reproduce the measured growth rates. Furthermore, the threshold for the return current instability was measured (δ&#95;{T}=0.017±0.002) to be in good agreement with previous theoretical models.

This Letter reports the first results of a direct dark matter search with the DEAP-3600 single-phase liquid argon (LAr) detector. The experiment was performed 2 km underground at SNOLAB (Sudbury, Canada) utilizing a large target mass, with the LAr target contained in a spherical acrylic vessel of 3600 kg capacity. The LAr is viewed by an array of PMTs, which would register scintillation light produced by rare nuclear recoil signals induced by dark matter particle scattering. An analysis of 4.44 live days (fiducial exposure of 9.87 ton day) of data taken during the initial filling phase demonstrates the best electronic recoil rejection using pulse-shape discrimination in argon, with leakage <1.2×10^{-7} (90% C.L.) between 15 and 31  keV&#95;{ee}. No candidate signal events are observed, which results in the leading limit on weakly interacting massive particle (WIMP)-nucleon spin-independent cross section on argon, <1.2×10^{-44}  cm^{2} for a 100  GeV/c^{2} WIMP mass (90% C.L.).

Cytochrome P450 enzymes (CYPs) are responsible for the phase I metabolism of drugs, xenobiotics and endogenous substances. Knowledge of single CYPs and their substrates is important for drug metabolism, helps to predict adverse effects and may prevent reduced drug efficacy in polypharmacy. In this study, three equine isoenzymes of the 3A subfamily, the equine flavoprotein NADPH-P450 oxidoreductase (POR), and the cytochrome b5 (CYB5) were cloned, sequenced and heterologously expressed in a baculovirus expression system. Testosterone, the standard compound for characterization of the human CYP3A4, was used to characterize the newly expressed equine CYPs. The metabolite pattern was similar in equine and the human CYPs, but the amounts of metabolites were isoform-dependent. All equine CYPs produced 2-hydroxytestosterone (2-OH-TES), a metabolite never described in equines. The main metabolite of CYP3A4 6β-hydroxytestosterone (6β-OH-TES) was measured in CYPs 3A95 and 3A97 with levels close to the detection limit. Ketoconazole inhibited 2-OH-TES in the human CYP3A4 and the equine CYP3A94 and CYP3A97 completely, whereas a 70% inhibition was found in CYP3A95. Testosterone 6β- and 2-hydroxylation was significantly different in the equine CYPs compared to CYP3A4. The expression of single equine CYPs allows characterizing drug metabolism and may allow prevention of drug-drug interactions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Testosterone (TES) 6-β-hydroxylation is a significant metabolic step in the biotransformation of TES in human liver microsomes and reflects cytochrome P450 (CYP) 3A4/5 specific metabolic activity. Several CYP3A enzymes have been annotated in the horse genome, but functional characterization is missing. This descriptive study investigates TES metabolism in the horse liver in vitro and the qualitative contribution of three CYP3A isoforms of the horse. Metabolism of TES was investigated by using equine hepatocyte primary cultures and liver microsomes. Chemical inhibitors were used to determine the CYPs involved in TES biotransformation in equine microsomes. Single CYPs 3A89, 3A94, and 3A95, recombinantly expressed in V79 hamster lung fibroblasts, were incubated with TES and the fluorescent metabolite 7-benzyloxy-4-trifluoromethylcoumarin (BFC). The effect of ketoconazole and troleandomycin was evaluated on single CYPs. Testosterone metabolites were analyzed by HPLC and confirmed by GC/MS. In hepatocyte primary cultures, the most abundant metabolite was androstenedione (AS), whereas in liver microsomes, 6-β-hydroxytestosterone showed the largest peak. Formation of 6-β-hydroxytestosterone and 11-β-hydroxytestosterone in liver microsomes was inhibited by ketoconazole, troleandomycin, and quercetin. Equine recombinant CYP3A95 catalyzed 11-β-hydroxylation of testosterone (TES). Metabolism of BFC was significantly inhibited by ketoconazole in CYP3A95, whereas troleandomycin affected the activities of CYP3A94 and CYP3A95. Both inhibitors had no significant effect on CYP3A89. Metabolic reactions and effects of inhibitors differed between the equine CYP3A isoforms investigated. This has to be considered in future in vitro studies., (© 2014 John Wiley & Sons Ltd.)

Ketamine is an anesthetic and analgesic regularly used in veterinary patients. As ketamine is almost always administered in combination with other drugs, interactions between ketamine and other drugs bear the risk of either adverse effects or diminished efficacy. Since cytochrome P450 enzymes (CYPs) play a pivotal role in the phase I metabolism of the majority of all marketed drugs, drug-drug interactions often occur at the active site of these enzymes. CYPs have been thoroughly examined in humans and laboratory animals, but little is known about equine CYPs. The characterization of equine CYPs is essential for a better understanding of drug metabolism in horses. We report annotation, cloning and heterologous expression of the equine CYP2B6 in V79 Chinese hamster fibroblasts. After computational annotation of all CYP2B genes, the coding sequence (CDS) of equine CYP2B6 was amplified by RT-PCR from horse liver total RNA and revealed an amino acid sequence identity of 77% and a similarity of 93.7% to its human ortholog. A non-synonymous variant c.226G>A in exon 2 of the equine CYP2B6 was detected in 97 horses. The mutant A-allele showed an allele frequency of 82%. Two further variants in exon 3 were detected in one and two horses of this group, respectively. Transfected V79 cells were incubated with racemic ketamine and norketamine as probe substrates to determine metabolic activity. The recombinant equine CYP2B6 N-demethylated ketamine to norketamine and produced metabolites of norketamine, such as hydroxylated norketamines and 5,6-dehydronorketamine. V(max) for S-/and R-norketamine formation was 0.49 and 0.45nmol/h/mg cellular protein and K(m) was 3.41 and 2.66μM, respectively. The N-demethylation of S-/R-ketamine was inhibited concentration-dependently with clopidogrel showing an IC(50) of 5.63 and 6.26μM, respectively. The functional importance of the recorded genetic variants remains to be explored. Equine CYP2B6 was determined to be a CYP enzyme involved in ketamine and norketamine metabolism, thus confirming results from inhibition studies with horse liver microsomes. Clopidogrel seems to be a feasible inhibitor for equine CYP2B6. The specificity still needs to be established with other single equine CYPs. Heterologous expression of single equine CYP enzymes opens new possibilities to substantially improve the understanding of drug metabolism and drug interactions in horses., (Copyright © 2012 Elsevier Inc. All rights reserved.)

AIM OF STUDY: The aim of this study is to compare demographic and clinical data as well as applied treatment methods in patients with rare benign and malignant tumours of the oesophagus. METHODS: Eight hundred and thirty patients with oesophageal cancer were treated in the Department of Surgical Oncology in 1960-2005. In 15 cases (1.8 %), rare benign (n = 11) or malignant (n = 4) types of tumours were diagnosed. Patients with rare oesophageal tumours were included in the study, excluding those with squamous cell carcinoma or adenocarcinoma of the oesophagus. Demographic and clinical data were analysed from each patient qualified for the study. Oesophageal X-rays with contrast medium, gastroscopies and, as of 1991, computed tomographies (CTs) were performed as preoperative diagnostic procedures. RESULTS: In the postoperative histopathological examinations, all benign tumours proved to be oesophageal leiomyomas. Four different malignant tumours-a sarcoma, a neuroendocrine carcinoma, a lymphoma, and a squamous cell carcinoma in a patient with Crohn's disease, were diagnosed in the other four patients. In a group of 15 patients with rare oesophageal tumours there were ten (66.7 %) males and five (33.3 %) females. In patients with benign and malignant tumours, the mean age for the benign group reached 44 years (range: 26-75 years old) and 54.7 years (range: 47-59 years old) for the malignant group. In the preoperative period, symptoms such as swallowing disturbances, retrosternal pains, and epigastric pains were observed. Dysphagia was the leading symptom in patients with benign and malignant oesophageal tumours. Out of 15 patients, surgical procedure was carried out in 13 cases with rare oesophageal tumours. In the group of 11 patients, with benign tumours, ten (90.2 %) warranted surgical treatment. Three patients (75 %) with malignant oesophageal tumours underwent an extensive Akiyama procedure of oesophageal resection. Chemo- and radiotherapy alone were performed on one (25 %) patient with oesophageal lymphoma. Postoperative complications were observed in only four (26.6 %) patients; pneumonia in the postoperative period was diagnosed in two patients who underwent surgery; infections of the postoperative wounds were diagnosed in the other two patients. CONCLUSIONS: Benign oesophageal tumours are characterised by similar clinical symptoms to malignant tumours of this organ. It is more complicated to obtain biopsy specimens for a histopathological examination in cases of benign tumours in comparison to malignant tumours. Treatment methods should be adjusted individually for each patient with a rare oesophageal tumour. For rare benign oesophageal tumours, the results of treatment are very good; however, for malignant tumours the prognosis depends on their histopathological type.

The prevalence of chronic obstructive pulmonary disease (COPD) has been extensively studied, especially in Western Europe and North America. Few of these data are directly comparable because of differences between the surveys regarding composition of study populations, diagnostic criteria of the disease and definitions of the risk factors. Few community studies have examined phenotypes of COPD and included other ways of characterising the disease beyond that of spirometry. The objective of the present Task Force report is to present recommendations for the performance of general population studies in COPD in order to facilitate comparable and valid estimates on COPD prevalence by various risk factors. Diagnostic criteria in epidemiological settings, and standardised methods to examine the disease and its potential risk factors are discussed. The paper also offers practical advice for planning and performing an epidemiological study on COPD. The main message of the paper is that thorough planning is worth half the study. It is crucial to stick to standardised methods and good quality control during sampling. We recommend collecting biological markers, depending on the specific objectives of the study. Finally, studies of COPD in the population at large should assess various phenotypes of the disease.

The European Sleep Apnoea Database (ESADA) reflects a network of 22 sleep disorder centres in Europe enabled by a COST action B26 programme. This ongoing project aims to describe differences in standard clinical care of patients with obstructive sleep apnoea (OSA) and to establish a resource for genetic research in this disorder. Patients with suspected OSA are consecutively included and followed up according to local clinical standards. Anthropometrics, medical history, medication, daytime symptoms and sleep data (polysomnography or cardiorespiratory polygraphy) are recorded in a structured web-based report form. 5,103 patients (1,426 females, mean±sd age 51.8±12.6 yrs, 79.4% with apnoea/hypopnoea index (AHI) ≥5 events·h(-1)) were included from March 15, 2007 to August 1, 2009. Morbid obesity (body mass index ≥35 kg·m(-2)) was present in 21.1% of males and 28.6% of females. Cardiovascular, metabolic and pulmonary comorbidities were frequent (49.1%, 32.9% and 14.2%, respectively). Patients investigated with a polygraphic method had a lower AHI than those undergoing polysomnography (23.2±23.5 versus 29.1±26.3 events·h(-1), p<0.0001). The ESADA is a rapidly growing multicentre patient cohort that enables unique outcome research opportunities and genotyping. The first cross-sectional analysis reveals a high prevalence of cardiovascular and metabolic morbidity in patients investigated for OSA.

Objectives: In Europe, the services provided for the investigation and management of obstructive sleep apnoea (OSA) varies from country to country. The aim of this questionnaire-based study was to investigate the current status of diagnostic pathways and therapeutic approaches applied in the treatment of OSA in Europe, qualification requirements of physicians involved in diagnosis and treatment of OSA, and reimbursement of these services., Methods: Two questionnaires were sent to 39 physicians in 22 countries in Europe. In order to standardize the responses, the questionnaire was accompanied by an example., Results: Sleep centers from 21 countries (38 physicians) participated. A broad consistency among countries with respect to the following was found: pathways included referral to sleep physicians/sleep laboratories, necessity for objective diagnosis (primarily by polysomnography), use of polygraphic methods, analysis of polysomnography (PSG), indications for positive airway pressure (PAP) therapy, application of standard continuous PAP (CPAP) therapy (100% with an CPAP/APAP ratio of 2.24:1), and the need (90.5%) and management of follow-up. Differences were apparent in reimbursement of the diagnostic procedures and follow-up, in the procedures for PAP titration from home APAP titration with portable sleep apnea monitoring (38.1%) up to hospital monitoring with PSG and APAP (85.7%), and in the qualification requirements of sleep physicians., Conclusions: Management of OSA in different European countries is similar except for reimbursement rules, qualification of sleep specialists and procedures for titration of the CPAP treatment. A European network (such as the one accomplished by the European Cooperation in Science and Technology [COST] B26 Action) could be helpful for implementing these findings into health-service research in order to standardize management in a cost effective perspective., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: The current study was designed to study hip spica casted and uncasted child dummies in front- and side-impact tests using a variety of restraints., Methods: Casted one- and three-year-old ATDs were restrained by a traditional child seat, a special hip spica child seat, and the vehicle seat belts. All tests positioned the child upright in either the rear-facing (one-year-old) or forward-facing (three-year-old) direction. One exception was vehicle seat belt tests for the one-year-old, which required the child to be positioned supine due to the position of the child's body imposed by the cast. The ATDs were tested in frontal impacts per FMVSS 213 (delta V of 30 mph) and in side impact using the pulse proposed for 213 (delta V of 20 mph). Corresponding control tests were performed with the uncasted ATDs. The FMVSS 213 mandated injury metrics (HIC36, 3 ms chest gs) and nonmandated due care metrics (HIC15, Nij) were evaluated., Results: For the one-year-old casted tests, 50 percent of the responses increased when compared to the uncasted control. A similar comparison for the three-year-old revealed an 80 percent increase when the dummy was fit with a body cast. HIC36 and chest gs were below the limits established in FMVSS 213 for all casted and uncasted tests. Frontal peak Nij values were in the tension-extension in nine out of ten cases and ranged from 0.8 to 0.83 (uncasted) and 1.02 to 1.92 (casted). Side-impact Nij was approximately 50 percent of the corresponding frontal tests., Conclusions: The addition of a body cast increases head, neck, and chest responses in front- and side-impact tests. The increases are greatest for the three-year-old who was forward facing.

Background: Chronic obstructive pulmonary disease (COPD) is a common disease with a steadily increasing prevalence and mortality. However, recent epidemiological estimates differ depending on the population studied and methods used., Aim: To investigate the prevalence, severity and burden of COPD in a primary care setting., Methods: From 4730 patients registered in a single primary care practice, all 2250 patients aged 40 years or more were invited to participate. Participants completed a questionnaire on smoking, respiratory symptoms, education and social status. A physical examination was followed by pre- and post-bronchodilator (BD) spirometry., Results: Of the eligible patients, 1960 (87%) participated. 92% of spirometric tests met the ATS criteria. Airflow limitation was demonstrated in 299 (15%) of the participants pre-BD and in 211 (11%) post-BD. COPD was diagnosed in 183 patients (9.3%). Of these patients, the degree of post-BD airflow limitation was mild in 30.6%, moderate in 51.4%, severe in 15.3% and very severe in 2.7%. Only 18.6% of these patients had previously been diagnosed with COPD; almost all of these had severe or very severe airflow limitation. As a result of the study, a diagnosis of asthma was made in 122 patients., Conclusions: The prevalence and underdiagnosis of COPD in adult patients in this primary care setting made case finding worthwhile. Large numbers of newly detected patients were symptomatic and needed treatment. Limiting investigations to smokers would have reduced the number of COPD diagnoses by 26%.

Background: Sleep apnoea syndrome (SAS), one of the main medical causes of excessive daytime sleepiness, has been shown to be a risk factor for traffic accidents. Treating SAS results in a normalized rate of traffic accidents. As part of the COST Action B-26, we looked at driving license regulations, and especially at its medical aspects in the European region., Methods: We obtained data from Transport Authorities in 25 countries (Austria, AT; Belgium, BE; Czech Republic, CZ; Denmark, DK; Estonia, EE; Finland, FI; France, FR; Germany, DE; Greece, GR; Hungary, HU; Ireland, IE; Italy, IT; Lithuania, LT; Luxembourg, LU; Malta, MT; Netherlands, NL; Norway, EC; Poland, PL; Portugal, PT; Slovakia, SK; Slovenia, SI; Spain, ES; Sweden, SE; Switzerland, CH; United Kingdom, UK)., Results: Driving license regulations date from 1997 onwards. Excessive daytime sleepiness is mentioned in nine, whereas sleep apnoea syndrome is mentioned in 10 countries. A patient with untreated sleep apnoea is always considered unfit to drive. To recover the driving capacity, seven countries rely on a physician's medical certificate based on symptom control and compliance with therapy, whereas in two countries it is up to the patient to decide (on his doctor's advice) to drive again. Only FR requires a normalized electroencephalography (EEG)-based Maintenance of Wakefulness Test for professional drivers. Rare conditions (e.g., narcolepsy) are considered a driving safety risk more frequently than sleep apnoea syndrome., Conclusion: Despite the available scientific evidence, most countries in Europe do not include sleep apnoea syndrome or excessive daytime sleepiness among the specific medical conditions to be considered when judging whether or not a person is fit to drive. A unified European Directive seems desirable.

Background: Chronic obstructive pulmonary disease (COPD), usually caused by tobacco smoking, is one of the leading causes of morbidity and mortality. Smoking cessation at an early stage of the disease usually stops further progression. A study was undertaken to determine if diagnosis of airway obstruction was associated with subsequent success in smoking cessation, as advised by a physician., Methods: 4494 current smokers (57.4% men) with a history of at least 10 pack-years of smoking were recruited from 100 000 subjects screened by spirometric testing for signs of airway obstruction. At the time of screening all received simple smoking cessation advice. 1177 (26.2%) subjects had airway obstruction and were told that they had COPD and that smoking cessation would halt rapid progression of their lung disease. No pharmacological treatment was proposed. After 1 year all subjects were invited for a follow up visit. Smoking status was assessed by history and validated by exhaled carbon monoxide level., Results: Nearly 70% attended a follow up visit (n = 3077): 61% were men, mean (SD) age was 52 (10) years, mean (SD) tobacco exposure 30 (17) pack-years, and 33.3% had airway obstruction during the baseline examination. The validated smoking cessation rate in those with airway obstruction was 16.3% compared with 12.0% in those with normal spirometric parameters (p = 0.0003). After correction for age, sex, nicotine dependence, number of cigarettes smoked daily, and lung function, success in smoking cessation was predicted by lower lung function, lower nicotine dependence, and lower tobacco exposure., Conclusions: Simple smoking cessation advice combined with spirometric testing resulted in good 1 year cessation rates, especially in subjects with airway obstruction.

Early diagnosis and smoking cessation are the only available methods to stop the progression of chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the effects of early detection of airflow limitation (AL) in a population with high risk for COPD, using spirometric screening. Smokers aged 40 yrs with a smoking history of 10 pack-yrs were invited to visit a local outpatient chest clinic for simple spirometry (forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)). Smoking history was recorded, followed by smoking cessation advice relating the results of spirometry to the smoking behaviour. Subjects who did not fulfil the above criteria (younger and/or nonsmokers) were also screened. A total 110,355 subjects were investigated; they were aged 53.5+/-11.5 yrs and 58.2% were males. Of the total amount of subjects, 64% were current smokers, 25.1% were former smokers and 10.9% were lifelong nonsmokers. Spirometry tests were within normal values for 70.3%, and 20.3% showed signs of AL: this was mild in 7.6%, moderate in 6.7% and severe in 5.9%. The remaining 8.3% of subjects presented with a restrictive pattern of ventilatory impairment. Airflow limitation was found in 23% of smokers aged 40 yrs with a history of 10 pack-yrs. This study concluded that large-scale voluntary spirometry screening of the population with high risk for COPD detects a large number of subjects with AL.

Inhaled corticosteroids (ICS) are widely used for the treatment of COPD despite of controversial statements concerning their efficacy. The use of N-acetylcysteine (NAC), a mucolytic drug with antioxidant properties, is less clear, but it may counteract the oxidant-antioxidant imbalance in COPD. The aim of this study was to evaluate whether treatment of COPD patients with ICS or NAC is able to improve inflammatory indices and to enhance lung function. ICS treatment enhanced protective markers for oxidative stress such as glutathione peroxidase (GPx) (51.2 +/-5.8 vs. 62.2 +/-8.6 U/g Hb, P<0.02) and trolox-equivalent antioxidant capacity (TEAC) (1.44 +/-0.05 vs. 1.52 +/-0.06 mM, P<0.05). NAC decreased sputum eosinophil cationic protein (318 +/-73 vs. 163 +/-30 ng/ml, P<0.01) and sputum IL-8 (429 +/-80 vs. 347 +/-70 ng/ml, P<0.05). The increased antioxidant capacity prevented an up-regulation of adhesion molecules, since the levels of intracellular adhesion molecule 1 (ICAM-1) correlated negatively with GPx (P<0.0001) and TEAC (P<0.0001). On the other hand, expression of adhesion molecules was promoted by inflammation, reflected by a positive correlation between the levels of IL-8 and ICAM-1 (P<0.0001). The effects of treatment on lung function were only reflected in the FEV(1) values. The absolute value of FEV(1), both before and after salbutamol inhalation, increased from 1690 +/-98 to 1764 +/-110 ml, and 1818 +/-106 to 1906 +/-116 ml, respectively, after ICS (P<0.05) . Ten weeks after treatment, FEV(1) values dropped to 1716 +/-120 ml post-salbutamol (P<0.05). When followed by treatment with NAC, these values decreased even further to 1666 +/-84 ml. These results suggest that ICS improved lung function in COPD patients with moderate airflow obstruction, beside a minor improvement in the oxidant-antioxidant imbalance leading to a lesser expression of ICAM-1. Treatment with NAC decreased some inflammatory parameters and had indirectly an inhibitory effect on the expression of adhesion molecules.

Induced sputum represents a useful and non-invasive tool to isolate different cells from the airways. Complete homogenization of sputum is important for dispersion of cells and is usually achieved by use of dithiothreitol (DTT). However, it is not known if DTT will influence the viability and functionality of cells obtained by induced sputum. In the present study, induced sputum was processed by DTT or by PBS treatment. The obtained neutrophils were compared with neutrophils obtained from peripheral blood and from bronchoalveolar lavage fluid (BAL). These isolated neutrophils were treated in a similar way as the sputum neutrophils with DTT or PBS. All isolated cells were used for chemiluminescence tests and for the measurement of elastase and myeloperoxidase release after stimulation with fMLP. The results showed that the maximum chemiluminescence response was always significantly lower after DTT treatment: blood, 16.68 +/-1.89 vs. 2.62 +/-0.43 mV, P<0.0001; sputum, 2.96 +/-0.30 vs. 1.09 +/-0.01 mV, P<0.01; BAL, 25.47 +/-0.88 vs. 8.22+/-0.20 mV, P<0.0001. Both spontaneous and fMLP-induced release of elastase and myeloperoxidase (MPO) was in most cases enhanced after DTT-treatment (P-values range from 0.24 to <0.01). We conclude that the use of DTT to homogenize sputum for dispersion of cells is harmful to cell functions and these cells are hampered for the evaluation of their normal functional characteristics.

Background: Chronic obstructive pulmonary disease (COPD) is accompanied by both airway and systemic inflammation and by oxidative stress. This study aimed to characterise the relationship between oxidative stress and inflammatory components in induced sputum and blood., Material & Methods: We studied blood and sputum samples from stable COPD patients (mean FEV1 60.5+/-7.5% predicted) at baseline (no treatment) and after 10 weeks treatment with either inhaled steroid, fluticasone propionate (FP) (1000 microg/d) or 10 weeks treatment with N-acetylcysteine (600mg/d) (NAC). We assessed the inflammatory markers (IL-8, ECP, sICAM-1, NE) in sputum and serum and we compared them with blood markers of oxidative stress (SOD, GPx, TEAC, albumin, vitamin E and A)., Results: At baseline blood sICAM-1 correlated with IL-8 levels (P<0.01, r = 0.62) and negatively with GPx (P<0.01, r = -0.63) and with TEAC (P<0.05, r = -0.53). TEAC correlated positively with GPx (P<0.01, r = 0.70). Correlation between sICAM and IL-8 disappeared after NAC treatment. The correlation between sICAM and GPx disappeared after FP treatment. The correlation between TEAC and GPx was maintained after both NAC and FP., Conclusions: The relationship between markers of inflammation, adhesion and antioxidant capacity is significantly modulated by treatment with N-acetylcysteine or inhaled corticosteroids.

Genetic factors, in particular human leukocyte antigens (HLAs) are important determinants of susceptibility to sarcoidosis, a chronic granulomatous disease of undetermined etiology. To clarify the role of HLA in sarcoidosis we determined HLA-DR and -DQ alleles in case-control samples from three European populations (United Kingdom, Czech, and Polish) and compared these results with those published for three additional populations (Italian, Japanese, and Scandinavian) to determine whether the HLA-DR and/or -DQ alleles act as ethnic-dependent, or ethnic-independent modifiers of disease risk. Although variations were apparent in the alleles associated with susceptibility, reductions in the frequency of alleles associated with protection were remarkably consistent in the six populations. Previously detected associations between single-nucleotide polymorphisms at the TAP2 locus and sarcoidosis were shown to be due to linkage disequilibrium with the HLA-DR locus. The protective HLA-DR alleles, which encode the DR1 and DR4 antigens, were found to share characteristic small hydrophobic residues at position 11, which were replaced by small hydrophilic residues in the remaining, nonprotective, HLA-DR alleles. This residue position is within a pocket of the HLA-DR complex antigen binding groove (designated P6), where it is the only variable amino acid and therefore determines the peptide binding preferences of this pocket. A highly significant reduction in the frequency of individuals carrying HLA-DR alleles with a hydrophobic residue at position 11 was observed in the sarcoidosis cases in the three populations we examined. This suggests this HLA-DR residue is an important protective marker in sarcoidosis.

We describe three male sib fetuses with isolated myocardial calcifications resulting in intrauterine fetal death (IUFD) as early as the second trimester. No evidence for an underlying mitochondrial cytopathy, dystrophinopathy or myopathy was found. There were no signs of inflammation or a metabolic disorder, and the mother had no prenatal exposure of teratogenic drugs. Furthermore, no mutation in the Barth syndrome gene (G4.5) could be detected. Because isolated calcification of the heart and IUFD are not typical of any previously described inherited cardiomyopathy, it may represent a new familial fetal cardiomyopathy., (Copyright 2001 Wiley-Liss, Inc.)

The aim of the present study was to compare the evolution of pulmonary haemodynamics and of arterial blood gases in chronic obstructive pulmonary disease (COPD) patients with mild-to-moderate hypoxaemia, with or without sleep-related oxygen desaturation. COPD patients with daytime arterial oxygen partial pressure in the range 56-69 mmHg were included prospectively. Sleep-related oxygen desaturation was defined as spending > or = 30% of the nocturnal recording time with arterial oxygen saturation <90%. From the 64 patients included, 35 were desaturators (group 1) and 29 were nondesaturators (group 2). At baseline (t0), patients with sleep-related desaturation had a significantly higher daytime (mean +/- SD) arterial carbon dioxide partial pressure (Pa,CO2) (44.9 +/- 4.9 mmHg versus 41.0 +/- 4.1 mmHg, p=0.001) whereas mean pulmonary artery pressure (mPAP) was similar in the two groups. After 2 yrs (t2) of follow-up, 22 desaturators and 14 nondesaturators could be re-evaluated, including pulmonary haemodynamic measurements. None of the nondesaturator patients became desaturators at t2. The difference between the two groups in terms of daytime Pa,CO2 was still present at t2. The mean changes in mPAP from t0 to t2 were similar between the two groups, as were the rates of death or requirement for long-term oxygen therapy (American Thoracic Society criteria) during follow-up of up to 6 yrs. The presence of sleep-related oxygen desaturation is not a transitional state before the worsening of daytime arterial blood gases, but is a characteristic of some chronic obstructive pulmonary disease patients who have a higher daytime arterial carbon dioxide partial pressure. Such isolated nocturnal hypoxaemia or sleep-related worsening of moderate daytime hypoxaemia does not appear to favour the development of pulmonary hypertension, nor to lead to worsening of daytime blood gases.

Background: Exposure to two or more carcinogens may result in interactive effects in which the joint effect may be greater or less than that expected to arise as the sum of the effects of the two agents alone. In this article, we investigate the joint effects of exposure to two carcinogens within the context of the two-stage clonal expansion model of carcinogenesis., Methods: Different measures of interaction are considered based on the notions of response and dose additivity, and an index of synergy S due to Thomas (1982) used to broadly characterise the effects of joint exposure., Results: Interactive effects based on the index S were found to be qualitatively similar, regardless of whether cancer risk was defined in terms of age-specific relative risk, or the cumulative probability of cancer occurrence at the same age. For joint exposure to two initiators or to two completers (affecting the first or second mutation rate in the two-mutation model, respectively), S assumed values near zero, reflecting an additive relative-risk relationship. For joint exposure to two promoters (which increase the rate of proliferation of initiated cells that have sustained the first mutation), the relative-risk relationship was found to range from supramultiplicative (S > 1) in younger age groups, to subadditive (S < 0) in older ages. Other combinations of carcinogens involving promotion also displayed a broad range of interaction effects., Conclusions: These results differ markedly from those reported previously by Kodell et al. (1991) for an approximate form of the two-stage model, which predicts much higher values of the index of synergy S than the exact form of the model when promotion is involved.

Wolf-Hirschhorn Syndrome (WHS) is caused by distal deletion of the short arm of chromosome 4 and is characterized by growth deficiency, mental retardation, a distinctive, 'greek-helmet' facial appearance, microcephaly, ear lobe anomalies, and sacral dimples. We report a family with a balanced chromosomal translocation 4;18(p15.32;p11.21) in the father and an unbalanced translocation resulting in partial monosomy 4 and partial trisomy 18 in one living boy and a prenatally diagnosed male fetus. Both showed abnormalities consistent with WHS and had in addition aplasia of one umbilical artery. Karyotyping of another stillborn fetus revealed a supernumerary derivative chromosome der(18)t(4;18)(p15.32;p11.21) of paternal origin and two normal chromosomes 4. The umbilical cord had three normal vessels. A third stillborn fetus with the same balanced translocation as the father had a single umbilical artery and hygroma colli., (Copyright 2000 John Wiley & Sons, Ltd.)

The beneficial effects of nocturnal oxygen therapy (NOT) in chronic obstructive pulmonary disease (COPD) patients with mild-to-moderate daytime hypoxaemia (arterial oxygen tension (Pa,O2) in the range 7.4-9.2 kPa (56-69 mmHg)) and exhibiting sleep-related oxygen desaturation remains controversial. The effectiveness of NOT in that category of COPD patients was studied. The end points included pulmonary haemodynamic effects after 2 yrs of follow-up, survival and requirement for long-term oxygen therapy (LTOT). Seventy-six patients could be randomized, 41 were allocated to NOT and 35 to no NOT (control). The goal of NOT was to achieve an arterial oxygen saturation of >90% throughout the night. All these patients underwent polysomnography to exclude an associated obstructive sleep apnoea syndrome. The two groups exhibited an identical meansD daytime Pa,O2 of 8.4+/-0.4 kPa (63+/-3 mmHg) at baseline. Twenty-two patients (12 in the NOT group and 10 in the control group, p=0.98) required LTOT during the whole follow-up (35+/-14 months). Sixteen patients died, nine in the NOT group and seven in the control group (p=0.84). Forty-six patients were able to undergo pulmonary haemodynamic re-evaluation after 2 yrs, 24 in the NOT and 22 in the control group. In the control group, mean resting pulmonary artery pressure increased from 19.8+/-5.6 to 20.5+6.5 mmHg, which was not different from the change in mean pulmonary artery pressure in the NOT group, from 18.3+/-4.7 to 19.5+/-5.3 mmHg (p= 0.79). Nocturnal oxygen therapy did not modify the evolution of pulmonary haemodynamics and did not allow delay in the prescription of long-term oxygen therapy. No effect of NOT on survival was observed, but the small number of deaths precluded any firm conclusion. These results suggest that the prescription of nocturnal oxygen therapy in isolation is probably not justified in chronic obstructive pulmonary disease patients.

Software was developed for the 3D simulation of SAR distribution for a 500 kHz localized current field hyperthermia system to be used in patients with carcinoma of the cervix. This hyperthermia system was specifically designed for use with a modified Fletcher-Suit intracavitary applicator. It consists of software modules for data input, tetrahedral grid generation and a numerical calculation of SAR distribution using an adaptive, multilevel finite element code. The AVS (Advanced Visual System, Inc.) system was used for the visual presentation of the results. A quasi-static approach was employed for the determination of SAR distribution. Results of the performed numerical tests were presented and they showed an important, clinically relevant ability to obtain a selective power deposition. This selective power deposition depended on the applicator geometry, i.e. the distance between the components of a Fletcher-Suit applicator and their relative position and the use of different modes of excitation.

Sarcoidosis is a chronic granulomatous disease of unknown etiology. Several studies have suggested involvement of human leukocyte antigen (HLA) genes in sarcoidosis susceptibility. HLA associations described have not been consistent, possibly because of additional susceptibility genes adjacent to or within the major histocompatibility complex (MHC) such as genes for the transporter associated with antigen processing (TAP). The aim of this study was to analyze TAP gene polymorphisms in patients with sarcoidosis using the amplificatory refraction mutation system (ARMS) PCR. To determine whether any association between TAP gene variation and sarcoidosis was ethnic-independent we examined two European populations: 117 unrelated UK Caucasoid patients with sarcoidosis and 290 healthy UK control subjects, and 87 unrelated Polish Slavonic patients with sarcoidosis and 158 healthy Polish control subjects. We detected significant differences in TAP2 between the UK control and patient groups, and in TAP2 between the Polish control and patient groups. Comparing the UK and Polish control groups, we observed a difference in TAP1. Examination of HLA-DPB1 in our UK population showed no associations with disease or between variants at the TAP gene loci and HLA-DPB1 variants. These results suggest associations at the TAP loci occur independently of HLA-DPB1 associations, that TAP associations seen may be involved in determining sarcoidosis susceptibility, and that such susceptibilities differ between UK and Polish populations. This first study of TAP genes in UK and Polish sarcoid populations has demonstrated the importance of using multiple defined ethnic populations in defining the role genetic factors play in sarcoidosis susceptibility and the importance of candidate gene studies.

Exercise tolerance in chronic obstructive pulmonary disease (COPD) patients has been shown to be related to airway limitation and dyspnoea, but little is known about the effects of an emotional status on physical performance. We examined 49 COPD patients with a wide spectrum of airway limitation severity and hypoxaemia. Exercise tolerance was evaluated using the Six-minute Walking Distance Test (6MWD), dyspnoea at rest and on exercise was measured using the visual analogue scale, and the emotional status was evaluated using the battery of psychological tests. The average 6MWD (mean+/-SD) was 355+/-112 m. In the majority of patients a fall in arterial blood oxygen saturation (Sa,O2) on exercise of >3% was found. The mean dyspnoea score of 21+/-19 at rest increased to 66+/-19 on exercise. All subjects demonstrated an increased level of anxiety. The majority also demonstrated elevated emotional tension, and half of the study group showed signs of depression. Step-wise multiple regression analysis with results of 6MWD as dependent and other studied variables as independent variables showed that exercise tolerance depended mainly on airway limitation. The forced expiratory volume in one second (FEV1) explained 24% of the variance. The forced vital capacity added a further 10%, and arterial blood carbon dioxide tension contributed 7%. The dyspnoea level on exercise added only 0.9%. All four variables explained 42% of the variance. There was no correlation between 6MWD and any of the variables characterizing the emotional status. We conclude that the emotional status of chronic obstructive pulmonary disease patients is characterized by an increased level of psychological tension, anxiety and depression, but these do not affect exercise tolerance as assessed by the six-minute walking distance test.

During exercise, dynamic hyperinflation-induced intrinsic positive end-expiratory pressure (PEEPi) and decreased dynamic lung compliance (CL,dyn) of patients with chronic obstructive pulmonary disease (COPD) increase the elastic work of inspiration (Wi) more than would be predicted from the increase in tidal volume (VT). This contributes significantly to their exertional breathlessness. In 10 stable patients with COPD, the dynamic Wi was measured during incremental bicycle exercise to exhaustion. The total Wi was then partitioned into the portion required to overcome PEEPi (Wi,PEEPi) and nonPEEPi elastic load (Wi,nonPEEPi). The latter is used to overcome the increase in the total respiratory system elastance during inflation. From resting breathing to peak exercise, Wi more than doubled (p<0.001). This increase was largely due to Wi,PEEPi, which significantly rose from 1.7+/-0.3 to 5.3+/-0.8 L x cm H2O(-1) (p<0.001). In comparison, Wi,nonPEEPi increased from only 3.0+/-0.4 to 5.1+/-0.5 L x cm H2O(-1) (p<0.01). Consequently, Wi,PEEPi as a fraction of total Wi increased from 35.5+/-5.6 to 51.0+/-3.3% (p<0.02). In addition, the measured Wi,nonPEEPi at peak exercise, when expressed as a percentage of its value during resting breathing, was 25% more than that predicted from the increase in VT alone. Assuming a constant chest wall compliance, this can be attributed to the exercise-induced decrease in CL,dyn, which was 0.27+/-0.04 and 0.17+/-0.02 L x cm H2O(-1) (p<0.01), respectively, during resting breathing and peak exercise. In conclusion, the dynamic hyperinflation-induced intrinsic positive end-expiratory pressure is more important than the increase in tidal volume in raising the work of inspiration during exercise in patients with chronic obstructive pulmonary disease; the decrease in dynamic lung compliance plays a definite but less important role.

It has been hypothesized but not firmly established that sleep-related hypoxaemia could favour the development of pulmonary hypertension in chronic obstructive pulmonary disease (COPD) patients without marked daytime hypoxaemia. We have investigated the relationships between pulmonary function data, sleep-related desaturation and daytime pulmonary haemodynamics in a group of 94 COPD patients not qualifying for conventional O2 therapy (daytime arterial oxygen tension (Pa,O2) in the range 7.4-9.2 kPa (56-69 mmHg)). Nocturnal desaturation was defined by spending > or = 30% of the recording time with a transcutaneous O2 saturation < 90%. An obstructive sleep apnoea syndrome was excluded by polysomnography. Sixty six patients were desaturators (Group 1) and 28 were nondesaturators (Group 2). There was no significant difference between Groups 1 and 2 with regard to pulmonary volumes and Pa,O2 (8.4+/-0.6 vs 8.4+/-0.4 kPa (63+/-4 vs 63+/-3 mmHg)) but arterial carbon dioxide tension (Pa,CO2) was higher in Group 1 (6.0+/-0.7 vs 53+/-0.5 kPa (45+/-5 vs 40+/-4 mmHg); p<0.0001). Mean pulmonary artery pressure (Ppa) was very similar in the two groups (2.6+/-0.7 vs 2.5+/-0.6 kPa (19+/-5 vs 19+/-4 mmHg)). No individual variable or combination of variables could predict the presence of pulmonary hypertension. It is concluded that in these patients with chronic obstructive pulmonary disease with modest daytime hypoxaemia, functional and gasometric variables (with the noticeable exception of arterial carbon dioxide tension) cannot predict the presence of nocturnal desaturation; and that mean pulmonary artery pressure is not correlated with the degree and duration of nocturnal hypoxaemia. These results do not support the hypothesis that sleep-related hypoxaemia favours the development of pulmonary hypertension.

Although the factors associated with mortality, such as forced expiratory volume in one second (FEV1), arterial oxygen tension (Pa,O2) and pulmonary arterial pressure, have been well described, there is limited information on the circumstances of death in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the causes and circumstances of death in patients with COPD and chronic respiratory failure (Pa,O2 < 8.0 kPa (60 mmHg) breathing air), treated with long-term oxygen therapy (LTOT). Ten European centres participated in the study and data were collected from patients both during a period of clinical stability and at the time of death. Of the 215 patients evaluated (161 males and 54 females; aged 66 +/- 10 yrs), the major causes of death were: acute on chronic respiratory failure (38%); heart failure (13%); pulmonary infection (11%); pulmonary embolism (10%); cardiac arrhythmia (8%); and lung cancer (7%). Seventy five percent of patients died in hospital. There was no difference in the number of patients who died in the morning, afternoon and night hours. Twenty percent of the total died during sleep and in 26% death was unexpected. A lower arterial carbon dioxide tension (Pa,CO2), less oxygen usage per 24 h, and increased incidence of arrhythmias were seen in those patients who died suddenly. Drug therapy was not related to unexpected death. The majority of patients with chronic obstructive pulmonary disease on long-term oxygen therapy died from chronic or acute on chronic respiratory failure. Prevention and treatment of respiratory failure in patients with chronic obstructive pulmonary disease is likely to have the greatest impact in reducing mortality.

Study Objective: To demonstrate that palpation of the omentum, mesentery, and intestine can be omitted from the laparoscopic staging of stage I carcinoma of the ovary., Design: Retrospective analysis of 223 women with stages III and IV ovarian cancer treated by laparotomy., Setting: Gynecological Oncology Clinic, M. Sklodowska-Curie Memorial Cancer Institute of Oncology, Warsaw, Poland., Interventions: Observation of macroscopic spread of tumor to areas accessible to laparoscopic inspection versus spread to areas inaccessible to laparoscopic evaluation., Measurements and Main Results: Macroscopically detectable disease in the areas easily accessible to laparoscopic inspection was present in all cases of metastases to the mesentery, omentum, or intestine., Conclusion: The diagnosis of FIGO stage I ovarian cancer can be made with confidence if laparoscopic inspection of certain areas reveals no evidence of metastases.

In some patients obstructive sleep apnoea (OSA) may co-exist with chronic obstructive pulmonary disease (COPD) and respiratory failure; the so-called "overlap syndrome". Obstructive, hypercapnic patients have both blunted ventilatory and mouth occlusion pressure responses during CO2 stimulation. The purpose of this study was to compare the pattern of breathing and CO2 response between OSA patients and those with the overlap syndrome. Twenty obese men with OSA and normal lung function (Group A), 11 obese men with overlap syndrome (Group B) and 13 healthy nonobese subjects (Group C) were examined. Lung function tests, breathing pattern, mouth occlusion pressure (P0.2) at rest, and respiratory responses during CO2 rebreathing were investigated. Diagnosis of OSA was established by standard polysomnography. There were no statistical differences between Groups A and B in apnoea & hypopnoea index (62 vs 54), mean arterial oxygen saturation (SaO2) during sleep (85 vs 84%) and in body mass index (BMI) 34.3 vs 36.3 kg.m-2. Minute ventilation, mean inspiratory flow and P0.2 at rest were increased in both groups of patients in comparison to controls. During CO2 rebreathing, group A had normal ventilatory and P0.2 responses, similar to controls, (2.7 +/- 1.1 vs 2.1 +/- 0.4 l.min-1.mmHg-1 and 0.7 +/- 0.3 vs 0.71 +/- 0.25 cmH2O.mmHg-1, respectively). However, Group B had significantly decreased ventilatory and P0.2 responses to CO2 (0.71 +/- 0.23 l.min-1.mmHg-1 and 0.34 +/- 0.17 cmH2O.mmHg-1, respectively). This comparison showed that patients with OSA had normal CO2 response when awake, whereas those with overlap syndrome had diminished CO2 response when awake.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of the study was to assess effects of acetazolamide in prevention of acute mountain sickness (AMS) and on overnight oxygenation, in patients with asthma treated at the altitude of 3,200 m. Sixteen patients with asthma, 6 males and 10 females, mean age 32 yrs, were first investigated at low altitude (760 m). They presented with mild airways obstruction, normal arterial blood gases, and normal oxygenation at night studied by pulse oximetry. After initial investigations, patients were divided by random number into the treated (T) and control (C) groups of eight patients each. T group patients received acetazolamide, 750 mg daily for 2 days, before the ascent and on the first day at altitude (3,200 m). Symptoms of AMS developed in seven patients from group C and in three from group T. The overnight pulse oximetry, performed on the first night at altitude, revealed that group T patients had statistically higher (p < 0.05) initial, 91 vs 87%, mean, 90 vs 86%, and minimum, 84 vs 75%, arterial oxygen saturation than group C patients. Overnight pulse oximetry was repeated on the 5th, 10th and 17th day at altitude, and showed that in group C patients, from the 5th day onwards, oxygenation improved to the level observed in group T patients on the first night. We conclude that pretreatment with acetazolamide before the ascent prevented patients with asthma from developing symptoms of AMS, and alleviated acute changes in arterial oxygen saturation brought about by the high altitude hypoxia.

The aim of this investigation was to compare inhaled budesonide with oral prednisone in maintenance treatment of pulmonary sarcoidosis. A double-blind controlled study was performed in 40 patients with stage II or III pulmonary sarcoidosis. After initial systemic 6 weeks treatment with prednisone (40 reduced to 20 mg daily) patients were allocated either to the systematically (S) or topically (T) treated group. S patients continued with 10 mg prednisone daily, T patients were given inhaled budesonide 1.6 mg daily. The progress of treatment was assessed by serial radiography, spirometry, serum Angiotensin Converting Enzyme (ACE) activity and plasma cortisol levels. All patients completed the 12 months treatment. Using the numerical score to assess changes on the chest radiograms S patients improved by 1.7 +/- 0.66 points; T patients improved by 1.15 +/- 0.81 points. Spirometric changes were not statistically significant. Serum ACE fell from 107 +/- 51 U/L in the S group and 92 +/- 40 U/L in the T group to 46 +/- 11 U/L and 38 +/- 21 U/L respectively during the initial phase of treatment. In the maintenance phase ACE levels remained lower than the initial ones in both groups. Morning plasma cortisol levels studied in 10 patients (5 in each group) decreased significantly during the initial phase. Thereafter cortisol levels remained low in the S patients returning to the lower limit of normal values in the T patients. We conclude that inhaled budesonide may be a safe and effective alternative to oral steroids in the maintenance treatment of pulmonary sarcoidosis especially in the early stage of the disease.

Estramustine is an estradiol-based agent that has been shown to accumulate in human glioma cells, resulting in a concentration-dependent alteration in cell size and shape within minutes and an inhibition of proliferation over 3 to 6 days. We evaluated human glioblastoma cultures with [3H]thymidine incorporation assays to determine estramustine's early effects on deoxyribonucleic acid synthesis in these tumors. Because estramustine shares a common structural motif with other antimicrotubule drugs, we synthesized four A-ring conjugates of estrone that contained a carbamate moiety but lacked nitrogen mustard. These analogs were examined by [3H]thymidine incorporation and compared with vinblastine. Greater than 70% inhibition of [3H]thymidine incorporation occurred within 1 hour of treatment with estramustine at 10(-5) mol/L, which increased to 80% inhibition at 4 hours. Ethyl carbamate JE208 was nearly as effective as estramustine in inhibiting deoxyribonucleic acid synthesis, and both were more effective than vinblastine. The inhibitory effects of estramustine and estrone analogs were reversible; vinblastine was not reversible. Although estramustine and JE208 induced similar antiproliferative and morphological changes in glioblastoma cells that persisted for at least 4 days, there was a modest recovery of morphology and thymidine incorporation with JE208 after prolonged treatment. The common findings with estramustine and JE208 suggest that these agents may have a similar mechanism of action and form the basis for the investigation of new agents that may rapidly and reversibly inhibit glioblastoma.

The control of gynaecological cancers in Poland has developed from three factors: 1) the organization of the Committee for Cancer Research and Control in 1906, which considered these activities as extremely important; 2) the personal commitment of Maria Skłodowska-Curie, and 3) the opportunity to train Polish physicians at the Foundation Curie in Paris after 1921, enhanced by the support of Head of the Fondation Professor Claude Regaud in introducing the "Paris Method" as a therapy against cervical cancer, to be provided for patients at the Radium Institute in Warsaw. The separation of gynaecological oncology as an independent branch of oncology occurred in Poland in 1951 when the Gynaecological Oncology Departments were opened first at the Institute of Oncology and later in other oncological clinics. The establishment of the Polish Gynaecological Society in 1992 was the next milestone.

There have been few studies examining the relationship between NOD and mortality in patients with COPD and none examining this relationship in those patients with a daytime PaO2 greater than 60 mm Hg. Is NOD related to early death, and if so, should nocturnal supplemental oxygen be considered as therapy for altering survival? We examined survival in 169 COPD subjects. Two definitions were used to classify subjects as NOD and non-NOD, one considering episodic desaturation associated mainly with REM sleep (definition 1) and one considering greater than 30 percent of time in bed spent below an SaO2 of 90 percent (definition 2) to be significant. Survival corrected for age was significantly better in non-NOD subjects. However, when stratified for supplemental oxygen use, survival remained better only in subjects separated by definition 1. There was a trend toward increased survival in 35 oxygen-treated vs 38 non-oxygen-treated NOD subjects (definition 1), but this difference was not statistically significant.

It has been hypothesized that in chronic obstructive pulmonary disease (COPD), sleep-related hypoxaemia could lead to pulmonary hypertension (PH) and cor pulmonale, even in patients with only mild daytime hypoxaemia. We investigated the relationships between sleep variables and daytime pulmonary haemodynamics in 40 COPD patients with daytime arterial oxygen tension (PaO2) between 60-70 mmHg (8-9.3 kPa). Patients were considered as desaturators if they spent at least 30% of the sleep recording time with a transcutaneous O2 saturation (StcO2) less than 90%. Daytime arterial blood gases and pulmonary volumes could not discriminate desaturators "D" (n = 18) from non-desaturators "ND" (n = 22), but awake baseline StcO2, measured just prior to the onset of sleep, was lower in group D. Pulmonary artery mean pressure was significantly higher in group D (19.1 +/- 4.7 vs 16.8 +/- 1.9 mmHg, p less than 0.05) and all patients with PH (6 out of 40) belonged to group D. PH was observed in 6 of the 15 patients whose mean nocturnal StcO2 was less than 90% but in none of the 25 with a mean nocturnal StcO2 greater than 90%. The PH patients (n = 6), all desaturators, differed from the desaturators with no PH (n = 12), and from ND (n = 22) in having higher numbers of desaturation dips, longer durations of dips, and lower mean nocturnal arterial oxygen saturation (SaO2). We conclude that a causal relation between nocturnal desaturation and permanent PH is very likely. Further studies are needed to see whether oxygen therapy can prevent PH in these patients.

Long-term oxygen is the only therapy that has been shown to improve survival in patients with chronic obstructive pulmonary disease. The aim of this study was to assess the predictors of survival in such patients treated with long-term oxygen therapy. We studied 179 patients who were assessed for long-term oxygen therapy in two Departments of Respiratory Medicine: in Warsaw and in Edinburgh. Those who died following the prescription of long-term oxygen therapy had a similar forced expiratory volume in the first second (FEV1) and arterial carbon dioxide tension, but a slightly lower arterial oxygen tensions (p less than 0.05) than those who survived (p less than 0.05). A small but significant fall in FEV1 and a rise in arterial carbon dioxide tension (p less than 0.05) occurred in both survivors and nonsurvivors after treatment with oxygen, but arterial oxygen tension breathing air continued to fall only in those who died (p less than 0.005). Only two variables were independent predictors of survival in patients with chronic obstructive pulmonary disease treated with long-term oxygen therapy. These were the arterial oxygen tension and the mean pulmonary arterial pressure (Ppa). However, when the calculation was made on patients with PaO2 less than or equal to 60 mm Hg (n = 154), then FEV1 and PaO2 but not Ppa were found to predict survival.

We present data concerning the frequency of airways obstruction among 1630 patients with pulmonary sarcoidosis diagnosed and followed up in our centre between 1960 and 1988. Airways obstruction was diagnosed when FEV1% VC was below 70%. There were 93 patients in whom ventilatory impairment of the obstructive type was found (5.7%). Further, we divided them into two groups of-pure obstruction and mixed-when obstruction was accompanied by reduced vital capacity. Possible mechanisms of the obstructive pattern in spirography are discussed.