Angiotensin-converting-enzyme gene polymorphisms, smoking and chronic obstructive pulmonary disease

While tobacco smoking is the main risk factor for chronic obstructive pulmonary disease (COPD) only a fraction of smokers go on to develop the disease. We investigated the relationship between the insertion (I) – deletion (D) polymorphisms in the Angiotensin converting enzyme (ACE) gene and the risk of developing COPD in smokers by determining the distribution of the ACE genotypes (DD, ID and II) in 151 life-long male smokers. 74 of the smokers had developed COPD (62 ± 2 years; FEV1 44 ± 6 % reference) whereas the rest retained normal lung function (56 ± 2 yrs; FEV1 95 ± 3 % reference). In addition, we genotyped 159 males recruited randomly from the general population. The prevalence of the DD genotype was highest (p = 0.01) in the smokers that developed COPD and its presence was associated with a 2-fold increase in the risk for COPD (OR 2.2; IC95% 1.1 to 5.5). Surprisingly, the 151 individuals in the smoking population did not demonstrate Hardy-Weinberg equilibrium unlike the 159 recruited from the general population. Our results suggest that ACE polymorphisms are associated with both the smoking history of an individual and their risk of developing COPD

Некоторые подходы к совершенствованию регионально-институциональной основы курортно-гостиничных услуг в Автономной республике Крым

Рассмотрены подходы (институциональный, региональный, проблемно-ориентированный и маркетинговый) к разработке регионально-институциональной модели курортно-гостиничного хозяйства как одной из важнейших составляющих институциональной модели курортно-рекреационного комплекса Автономной Республики Крым.Розглядаються підходи (інституційний, регіональний, проблемно-орієнтований і маркетинговий) до розробки регіонально-інституційної моделі курортно-готельного господарства як однієї з найважливіших складових інституційної моделі курортно-рекреаційного комплексу Автономної Республіки Крим

High-resolution hepatitis C virus subtyping using NS5B deep sequencing and phylogeny, an alternative to current methods

HepatitisCvirus(HCV)is classified into seven major genotypesand67 subtypes. Recent studies haveshownthat inHCVgenotype 1-infected patients, response rates to regimens containingdirect-acting antivirals(DAAs)are subtype dependent. Currently available genotypingmethods have limited subtyping accuracy.Wehave evaluated theperformanceof adeep-sequencing-basedHCVsubtyping assay, developed for the 454/GS-Junior platform, in comparisonwith thoseof two commercial assays (VersantHCVgenotype 2.0andAbbott Real-timeHCVGenotype II)andusingdirectNS5Bsequencing as a gold standard (direct sequencing), in 114 clinical specimenspreviously tested by first-generation hybridization assay (82 genotype 1and32 with uninterpretable results). Phylogenetic analysis of deep-sequencing reads matched subtype 1 callingbypopulation Sanger sequencing(69%1b,31%1a) in 81 specimensandidentified amixed-subtype infection (1b/3a/1a) in one sample. Similarly,amongthe 32previously indeterminate specimens, identical genotypeandsubtype results were obtained by directanddeep sequencing in all but four samples with dual infection. In contrast, both VersantHCVGenotype 2.0andAbbott Real-timeHCVGenotype II failed subtype 1 calling in 13 (16%) samples eachandwere unable to identify theHCVgenotype and/or subtype inmore than half of the nongenotype 1 samples.Weconcluded that deep sequencing ismore efficient forHCVsubtyping than currently available methodsandallows qualitative identificationofmixed infectionsandmay bemorehelpfulwith respect to informing treatment strategies withnewDAA-containing regimens across allHCVsubtypesThis study has been supported by CDTI (Centro para el Desarrollo Tecnológico Industrial), Spanish Ministry of Economics and Competitiveness (MINECO), IDI-20110115; MINECO projects SAF 2009-10403; and also by the Spanish Ministry of Health, Instituto de Salud Carlos III (FIS) projects PI10/01505, PI12/01893, and PI13/00456. CIBERehd is funded by the Instituto de Salud Carlos III, Madrid, Spain. Work at CBMSO was supported by grant MINECO-BFU2011-23604, FIPSE, and Fundación Ramón Areces. X. Forns received unrestricted grant support from Roche and has acted as advisor for MSD, Gilead, and Abbvie. M. Alvarez-Tejado, J. Gregori, and J. M. Muñoz work in Roche Diagnostic

Pulmonary and systemic hepatocyte and keratinocyte growth factors in patients with chronic obstructive pulmonary disease

Jaume Sauleda1, Aina Noguera2, David Blanquer3, Jaume Pons4, Meritxell López1, et al1Servei de Pneumologia, Hospital Universitari Son Dureta, Fundació Caubet-Cimera Illes Balears, Illes Balears, CIBER Enfermedades respiratorias, Illes Balears, Spain; 2Inmunologia, 4Anàlisis Clínique, Hospital Universitari Son Dureta. Palma Mallorca, Spain; 3Fundació Hospital Manacor, Manacor, Illes Balears SpainBackground: The potential role of growth factors in chronic obstructive pulmonary disease (COPD) has begun to be addressed only recently and is still poorly understood. For this study, we investigated potential abnormalities of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) in patients with COPD.Methods: To this end, we compared the levels of HGF and KGF, measured by enzyme-linked immunosorbent assay (ELISA), in bronchoalveolar lavage (BAL) fluid and in serum in 18 patients with COPD (62 ± 9 yrs, forced expiratory volume in one second [FEV1] 57 ± 12% ref, X ± standard deviation of mean), 18 smokers with normal lung function (58 ± 8 yrs, FEV1 90 ± 6% ref) and 8 never smokers (67 ± 9 yrs, 94 ± 14% ref).Results: We found that in BAL, HGF levels were higher in patients with COPD than in the other two groups whereas, in serum, HGF concentration was highest in smokers with normal lung function (p < 0.01). KGF levels were not significantly different between groups, neither in blood nor in BAL (most values were below the detection limit).Conclusions: These results highlight a different response of HGF in BAL and serum in smokers with and without COPD that may be relevant for tissue repair in COPD.Keywords: COPD, growth factors, tissue repai

Systemic inflammation after inspiratory loading in chronic obstructive pulmonary disease

Antonia Fuster, Jaume Sauleda, Ernest Sala, Bernardí Barceló1, Jaume Pons2, Miguel Carrera, Aina Noguera1, Bernat Togores, Alvar GN AgustíServeis de Pneumologia, 1Analisis Clinics, and 2Inmunología, Hospital Universitari Son Dureta, Fundación Caubet-Cimera and CIBER Enfermedades Respiratorias, Mallorca, SpainObjective: Patients with chronic obstructive pulmonary disease (COPD) present systemic inflammation. Strenuous resistive breathing induces systemic inflammation in healthy subjects. We hypothesized that the increased respiratory load that characterizes COPD can contribute to systemic inflammation in these patients.Patients and methods: To test this hypothesis, we compared leukocyte numbers and levels of circulating cytokines (tumor necrosis factor alpha [TNFα], interleukin-1β [IL-1β], IL-6, IL-8, and IL-10), before and 1 hour after maximal incremental inspiratory loading in 13 patients with stable COPD (forced expiratory volume in one second [FEV1] 29 ± 2.5% ref) and in 8 healthy sedentary subjects (FEV1 98 ± 5% ref).Results: We found that: (1) at baseline, patients with COPD showed higher leukocyte counts and IL-8 levels than controls (p < 0.01); and, (2) one hour after maximal inspiratory loading these values were unchanged, except for IL-10, which increased in controls (p < 0.05) but not in patients with COPD.Conclusions: This study confirms the presence of systemic inflammation in COPD, shows that maximal inspiratory loading does not increase the levels of pro-inflammatory cytokines (IL-1β, IL-8) in COPD patients or controls, but suggests that the former may be unable to mount an appropriate systemic anti-inflammatory response to exercise.Keywords: COPD, endurance, exercise, IL-10, respiratory muscles, systemic inflammatio

Orientación diagnóstica y manejo de los síndromes pericárdicos agudos

Los síndromes pericárdicos agudos incluyen básicamente la pericarditis aguda y el taponamiento cardíaco. El presente trabajo está dedicado fundamentalmente al manejo diagnóstico y terapéutico de la pericarditis aguda. En nuestro medio, la gran mayoría de pericarditis cuya causa no es evidente en la presentación clínica inicial corresponde a pericarditis idiopáticas o virales, que tienen un curso benigno y autolimitado (aunque algunos pacientes pueden desarrollar taponamiento cardíaco). Esta noción de prevalencia es fundamental para establecer un protocolo de manejo lógico que evite, por un lado, el excesivo uso de procedimientos invasivos del pericardio, pero que permita, por otro lado, diagnosticar los casos de pericarditis específicas (tuberculosa, purulenta y neoplásica). Según estas consideraciones y nuestra propia experiencia proponemos un protocolo de estudio y manejo de las enfermedades agudas del pericardio que difieren sustancialmente de las recientes «Guías de práctica clínica para el diagnóstico y tratamiento de las enfermedades del pericardio» de la Sociedad Europea de Cardiología. También se comentan aspectos del taponamiento cardíaco y de las formas de constricción aguda y subaguda que se pueden presentar en la fase de resolución de las pericarditis agudas