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1.
Forensic Sci Int ; 306: 110063, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31790891

RESUMO

Diagnosis of carbon monoxide (CO) poisonings has always been a challenging task due to the susceptibility to alterations of the optical state and degradation of blood samples during sampling, transport and storage, which highly affects the analysis with spectrophotometric methods. Methodological improvements are then required urgently because of increased reports of cases with discrepancies between results of the measured biomarker carboxyhemoglobin (COHb) and reported symptoms. Total blood CO (TBCO) measured chromatographically was thus proposed in a previous study as alternative biomarker to COHb. This approach was investigated in this study by comparing the two biomarkers and assessing the effects of various storage parameters (temperature, preservative, time, tube headspace (HS) volume, initial saturation level, freeze- and thaw- and reopening-cycles) over a period of one month. Results show that while for TBCO, concentrations are relatively stable over the observation period regardless of parameters such as temperature, time and HS volume, for COHb, concentrations are altered significantly during storage. Therefore, the use of TBCO as alternative biomarker for CO poisonings has been proposed, since it provides more valid results and is more stable even under non-optimal storage conditions. Additionally, it can be used to predict COHb in cases where sample degradation hinders optical measurement. Furthermore, a correction formula for COHb and TBCO is provided to be used in laboratories or circumstances where optimal storage or analysis is not possible, to obtain more accurate results.


Assuntos
Intoxicação por Monóxido de Carbono/diagnóstico , Monóxido de Carbono/sangue , Carboxihemoglobina/análise , Medicina Legal/métodos , Biomarcadores/sangue , Cromatografia Gasosa , Interpretação Estatística de Dados , Humanos , Oximetria , Manejo de Espécimes , Espectrofotometria
2.
Forensic Sci Int ; 299: 1-5, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30952069

RESUMO

The presented manuscript describes the carbon monoxide (CO) related deaths in Portugal over a period of 3 years, based on autopsies carried out at the National Institute of Legal Medicine and Forensic Sciences, from January 2012 to December 2014. Three hundred and forty-seven forensic autopsy reports with carboxyhaemoglobin (COHb) analysis requests were analysed and subdivided into three main groups: (1) improbable CO intoxication; (2) possible CO intoxication; (3) highly probable CO intoxication. In group 1, COHb analysis was negative, and the death circumstances, as well as the post mortem findings, didn't corroborate an exposition to CO. In group 2, with COHb positive in 1/3 of the cases, the death circumstances corroborated an exposition to CO, but the post mortem findings weren't enough to confirm an exposition to this substance. In group 3, the results of COHb were positive, and both circumstances of death and post mortem findings corroborated an exposition to CO. The first group (113 cases) had no specific suspicion of a CO intoxication and, thus, the request of a COHb analysis had no particular basis, reflected in the low COHb achieved percentage (between 0 and 12). In the second group (164 cases), 29% of the cases were directly or indirectly related to CO exposure (between 0% and 94%). In the third group (70 cases), 56 deaths were due to CO intoxication and 14 due to burns after CO inhalation (between 18% and 91%). This study intended to do, not only a 3-year assessment of CO poisoning, but also to enhance the fact that circumstantial information, as well as a correct evaluation at the forensic autopsy data are crucial, and allow an enhanced diagnosis of possible intoxication, as well as a better guidance for the consequent toxicological analysis requests.


Assuntos
Intoxicação por Monóxido de Carbono/mortalidade , Acidentes/mortalidade , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Queimaduras/patologia , Monóxido de Carbono/sangue , Carboxihemoglobina/análise , Criança , Esôfago/patologia , Feminino , Fogo , Medicina Legal , Utensílios Domésticos , Humanos , Masculino , Pessoa de Meia-Idade , Portugal/epidemiologia , Estações do Ano , Distribuição por Sexo , Fuligem , Suicídio/estatística & dados numéricos , Emissões de Veículos , Adulto Jovem
3.
Eur J Intern Med ; 59: 34-38, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30243511

RESUMO

BACKGROUND: We examine the ability of pre-existing measures of Forced Expiratory Volume in 1 s (FEV1), and Diffusion Capacity for Carbon Monoxide (DLCO) to determine the subsequent 30-day mortality outcome following unselected acute medical admission. METHODS: Between 2002 and 2017, we studied all emergency medical admissions (106,586 episodes in 54,928 patients) of whom 8071 were classified as respiratory. We employed logisitic multiple variable regression models to evaluate the ability of FEV1 or DLCO to predict the 30-day hospital mortality outcome. RESULTS: The 30-day hospital episode mortality outcome demonstrated curvilinear relationships to the underlying FEV1 or DLCO values; adjusted for major outcome predictors, a higher FEV1 - OR 0.85 (95% CI: 0.82, 0.89) or DLCO OR 0.76 (95% CI: 0.73, 0.79) values predicted survival. The range of predicted mortalities was from 3.3% (95% CI: 2.5, 4.0) to 23.5% (95% CI: 20.8, 26.2); the FEV1 (Model1) and DLCO (Model2) outcome prediction was essentially equivalent (Chi2 = 2.9: p = 0.08). CONCLUSION: The 30-day mortality outcome was clearly related to the pre-admission FEV1 and DLCO value. The outcome relationship was curvilinear. Either parameter appears a useful tool to explore hospital outcomes. Previously suggested cut-points are likely an artefact and not supported by these data.


Assuntos
Monóxido de Carbono/sangue , Serviço Hospitalar de Emergência/estatística & dados numéricos , Volume Expiratório Forçado , Mortalidade Hospitalar , Pulmão/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Irlanda/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença
5.
J Anal Toxicol ; 43(2): 79-87, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30371866

RESUMO

As one of the most abundant toxic contaminants in the atmosphere, carbon monoxide (CO) plays a significant role in toxicology and public health. Every year, around half of the accidental non-fire-related poisoning deaths are attributed to CO in the USA, UK and many other countries. However, due to the non-specificity of the symptoms and often encountered inconsistency of these with the results obtained from measurements of the biomarker for CO poisonings, carboxyhemoglobin (COHb), there is a high rate of misdiagnoses. The mechanism of toxicity of CO includes not only the reduced transport of oxygen caused by COHb but also the impairment of cellular respiration and activation of oxidative metabolism by binding to other proteins. Therefore, in this study we propose the measurement of the total amount of CO in blood (TBCO) by airtight gas syringe-gas chromatography-mass spectrometry (AGS-GC-MS) as an alternative to COHb for the determination of CO exposures. The method is validated for a clinical range with TBCO concentrations of 1.63-104 nmol/mL of headspace (HS) (0.65-41.6 µmol/mL blood). The limit of quantification was found between 2 and 5 nmol/mL HS (0.8 and 2 µmol/mL blood). The method is applied to a cohort of 13 patients, who were exposed to CO under controlled conditions, and the results are compared to those obtained by CO-oximetry. Furthermore, samples were compared before and after a "flushing" step to remove excess CO. Results showed a significant decrease in TBCO when samples were flushed (10-60%), whereas no constant trend was observed for COHb. Therefore, measurement of TBCO by AGS-GC-MS suggests the presence of more dissolved CO than previously known. This constitutes a first step into the acknowledgment of a possibly significant amount of CO present not in the form of COHb, but as free CO, which might help explain the incongruences with symptoms and decrease misdiagnoses.


Assuntos
Gasometria/métodos , Intoxicação por Monóxido de Carbono/sangue , Monóxido de Carbono/sangue , Carboxihemoglobina/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Biomarcadores/sangue , Calibragem , Humanos , Limite de Detecção , Reprodutibilidade dos Testes
6.
Kidney Int ; 95(1): 173-177, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30522768

RESUMO

The production of erythropoietin (Epo) is modulated by renal tissue oxygen tension, which in principle depends on both arterial oxygen content (CaO2) and arterial oxygen tension (PaO2). Uncontrolled observational studies suggest that alterations in CaO2 fundamentally regulate Epo synthesis. We sought to establish whether reduced CaO2 enhances plasma Epo concentration independently of PaO2. In a blinded crossover study, 8 healthy young subjects were exposed to three conditions: room air (normoxia); 11% oxygen balanced in nitrogen, which lowers both CaO2 and PaO2 (hypoxia); and carbon monoxide plus normoxia, which decreases CaO2 to the same degree as hypoxia while preserving PaO2 (hypoxemia). Arterial blood samples were obtained prior to and throughout the 5 hours of exposure to each condition. In the hypoxic conditions, average CaO2 was reduced to similar levels, whereas PaO2 was only decreased with exposure to hypoxia. Plasma Epo concentration was increased in both hypoxic conditions relative to normoxia after 150 min of exposure and was augmented more than two-fold after 300 min, with no difference between hypoxic conditions. Reduced CaO2 induces similar increases in circulating Epo concentration irrespective of PaO2 manipulation, demonstrating that CaO2 is the critical variable regulating Epo production.


Assuntos
Artérias/metabolismo , Eritropoetina/metabolismo , Hipóxia/sangue , Rim/metabolismo , Oxigênio/sangue , Adulto , Gasometria , Monóxido de Carbono/sangue , Estudos Cross-Over , Eritropoetina/sangue , Voluntários Saudáveis , Humanos , Hipóxia/diagnóstico , Rim/irrigação sanguínea , Masculino , Consumo de Oxigênio , Adulto Jovem
8.
Bull Exp Biol Med ; 165(6): 725-727, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30353346

RESUMO

Gaseous transmitters were assayed in rat blood during catecholamine-induced damage to the heart. Hypercatecholaminemia was modeled by single subcutaneous injection of 0.1% epinephrine hydrochloride in a dose of 2 mg/kg. The blood concentrations of NO, H2S, and CO were measured. The catecholamine-induced damage to the myocardium resulted in phasic changes in the blood levels of gaseous transmitters: CO concentration increased in 1 h, H2S increased in 24 h, and NO concentration increased in 72 h after injection.


Assuntos
Monóxido de Carbono/sangue , Catecolaminas/efeitos adversos , Coração/efeitos dos fármacos , Sulfeto de Hidrogênio/sangue , Miocárdio/metabolismo , Óxido Nítrico/sangue , Animais , Epinefrina/farmacologia , Masculino , Ratos , Ratos Wistar , Transdução de Sinais , Fatores de Tempo
9.
Physiol Rep ; 6(17): e13829, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30203465

RESUMO

Hemoglobin concentration ([Hb]) is a function of total hemoglobin mass (tHb-mass) and plasma volume. [Hb] may fall by dilution due to plasma volume expansion and changes in the perioperative period may therefore correlate poorly with blood loss. A simple, reliable, repeatable way to measure plasma volume and tHb-mass would have substantial clinical utility. The "optimized carbon monoxide re-breathing method" (oCOR) meets these criteria. However, it is recommended that a minimum of 12 h (when breathing room air) is left between repeat measurements. Twenty-four subjects underwent 3 days of testing. Two oCOR tests were performed (T1 and T2), 3 h apart, with a different CO clearance method employed between tests aiming to keep the carboxyhemoglobin level below 10%. The primary aim was to ascertain whether tHb-mass testing could be safely repeated within 3 h if carboxyhemoglobin levels were actively reduced by breathing supplemental oxygen (PROCA ). Secondary aims were to compare two other clearance methods; moderate exercise (PROCB ), or a combination of the two (PROCC ). Finally, the reliability of the oCOR method was assessed. Mean (SD) tHb-mass was 807.9 ± (189.7 g) (for T1 on day 1). PROCA lowered the carboxyhemoglobin level from the end of T1 (mean 6.64%) to the start of T2 (mean 2.95%) by a mean absolute value of 3.69%. For PROCB and PROCC the mean absolute decreases in carboxyhemoglobin were 4.00% and 4.31%, respectively. The fall in carboxyhemoglobin between T1 and T2 was greatest in PROCC ; this was statistically significantly lower than that of PROCA (P = 0.0039) and PROCB (P = 0.0289). The test-retest reliability for the measurement of total hemoglobin mass was good with a mean typical error (TE) of 2.0%. The oCOR method is safe and can be repeated within 3 h when carbon monoxide is suitably cleared between tests. Using oxygen therapy alone adequately achieves this.


Assuntos
Monóxido de Carbono/sangue , Carboxihemoglobina/análise , Índices de Eritrócitos , Oxigênio/sangue , Adulto , Monóxido de Carbono/farmacocinética , Exercício Físico , Feminino , Hemoglobinometria/efeitos adversos , Hemoglobinometria/métodos , Hemoglobinometria/normas , Humanos , Masculino , Taxa de Depuração Metabólica , Volume Plasmático , Reprodutibilidade dos Testes
10.
J Heart Lung Transplant ; 37(11): 1361-1371, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30195831

RESUMO

BACKGROUND: Increasing left ventricular assist device (LVAD) pump speed according to the patient's activity is a fascinating hypothesis. This study analyzed the short-term effects of LVAD speed increase on cardiopulmonary exercise test (CPET) performance, muscle oxygenation (near-infrared spectroscopy), diffusion capacity of the lung for carbon monoxide (Dlco) and nitric oxide (Dlno), and sleep quality. METHODS: We analyzed CPET, Dlco and Dlno, and sleep in 33 patients supported with the Jarvik 2000 (Jarvik Heart Inc., New York, NY). After a maximal CPET (n = 28), patients underwent 2 maximal CPETs with LVAD speed randomly set at 3 or increased from 3 to 5 during effort (n = 15). Then, at LVAD speed randomly set at 2 or 4, we performed (1) constant workload CPETs assessing O2 kinetics, cardiac output (CO), and muscle oxygenation (n = 15); (2) resting Dlco and Dlno (n = 18); and (3) nocturnal cardiorespiratory monitoring (n = 29). RESULTS: The progressive pump speed increase raised peak volume of oxygen consumption (12.5 ± 2.5 ml/min/kg vs 11.7 ± 2.8 ml/min/kg at speed 3; p = 0.001). During constant workload, from speed 2 to 4, CO increased (at rest: 3.18 ± 0.76 liters/min vs 3.69 ± 0.75 liters/min, p = 0.015; during exercise: 5.91 ± 1.31 liters/min vs 6.69 ± 0.99 liters/min, p = 0.014), and system efficiency (τ = 65.8 ± 15.1 seconds vs 49.9 ± 14.8 seconds, p = 0.002) and muscle oxygenation improved. At speed 4, Dlco decreased, and obstructive apneas increased despite a significant apnea/hypopnea index and a reduction of central apneas. CONCLUSIONS: Short-term LVAD speed increase improves exercise performance, CO, O2 kinetics, and muscle oxygenation. However, it deteriorates lung diffusion and increases obstructive apneas, likely due to an increase of intrathoracic fluids. Self-adjusting LVAD speed is a fascinating but possibly unsafe option, probably requiring a monitoring of intrathoracic fluids.


Assuntos
Exercício Físico/fisiologia , Insuficiência Cardíaca/terapia , Coração Auxiliar , Troca Gasosa Pulmonar/fisiologia , Sono/fisiologia , Idoso , Monóxido de Carbono/sangue , Desenho de Equipamento , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/irrigação sanguínea , Óxido Nítrico/sangue , Consumo de Oxigênio/fisiologia , Capacidade de Difusão Pulmonar/fisiologia
11.
Clin Rheumatol ; 37(11): 3043-3050, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30143960

RESUMO

The study aims to analyze the effects of induction treatment with cyclophosphamide (CYC) pulse therapy followed by maintenance treatment with other mild immunosuppressive agents on lung function in scleroderma (SSc) patients. Thirty patients with SSc (mean age 52 years, mean disease duration < 2 years) with forced vital capacity (FVC) ≤ 80% and/or diffusing capacity of carbon monoxide (DLco) ≤ 70% were included. Monthly CYC pulses were given for 6 months (induction treatment), followed by 3-monthly maintenance pulses for the next 18 months, and during the next 5 years patients received other mild immunosupressive therapy brought by the competent rheumatologist. The efficacy was evaluated by comparing FVC% and DLco% after 6, 24, and 84 months from the baseline. All patients completed induction and maintenance treatment with CYC. Three patients were lost to follow-up. The rest of 27 patients, during the next 5 years, received other immunosupressive agents (14 azathioprine, 9 methotrexate, and 4 mycophenolate mofetil). Three patients died in the 4 years of follow-up. By 6, 24, and 84 months, the mean FVC and DLco changes were + 0.47 and + 2.10, + 3.30 and - 2.49, and + 1.53 and - 3.76%, respectively. These changes were not significantly different from the baseline values. CYC does not appear to result in clinically significant improvement of pulmonary function but fulfilled criteria of stable disease. Maintenance treatment with other mild immunosupressive agents preserves the benefits achieved during CYC treatment.


Assuntos
Ciclofosfamida/administração & dosagem , Imunossupressores/administração & dosagem , Pulmão/fisiopatologia , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/fisiopatologia , Adulto , Monóxido de Carbono/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pulsoterapia/métodos , Fatores de Tempo , Resultado do Tratamento , Capacidade Vital
12.
Artigo em Inglês | MEDLINE | ID: mdl-29793099

RESUMO

Carbon monoxide is one of the most abundant toxic air pollutants. Symptoms of a CO intoxication are non-specific, leading to a high number of misdiagnosed CO poisoning cases that are missing in the disease statistics. The chemical nature of the molecule makes it difficult to detect for long periods and at low levels, thus requiring a very accurate and sensitive method. Current methods capable of accurate and sensitive analyses are available, however an inconsistency between results and symptoms are frequently reported. Therefore, an improved method for the analysis of carbon monoxide in blood and in the headspace (HS) of the sampling tube with the use of Airtight Gas Syringe - Gas Chromatography - Mass Spectrometry (AGS-GC-MS) is hereby presented and validated, for CO concentrations in a range of 10-200 nmol/mL HS (2-40 µmol/mL blood). Analytical LOQ is found at 0.9 nmol/mL HS (0.18 µmol/mL blood) and LOD at 0.1 nmol/mL gas. Application to intoxicated samples from autopsies and comparison to previously published methods show that this method is more appropriate, since performed under fully controlled conditions. Results show higher CO concentrations compared to previous approaches, indicating that results might have been underestimating the true blood CO burden. Therefore, this approach has the potential to help reduce the misdiagnosed cases and the gap between measurement and diagnosis of CO poisonings.


Assuntos
Gasometria/métodos , Monóxido de Carbono/sangue , Cromatografia Gasosa-Espectrometria de Massas/métodos , Adulto , Idoso , Autopsia , Carboxihemoglobina/análise , Feminino , Toxicologia Forense , Humanos , Limite de Detecção , Modelos Lineares , Masculino , Reprodutibilidade dos Testes , Adulto Jovem
13.
Sheng Li Xue Bao ; 70(2): 115-122, 2018 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-29691575

RESUMO

The present study is aimed to explore the effects of endogenous carbon monoxide on the ischemia-reperfusion in rats. Wistar rats were intraperitoneally injected with protoporphyrin cobalt chloride (CoPP, an endogenous carbon monoxide agonist, 5 mg/kg), zinc protoporphyrin (ZnPP, an endogenous carbon monoxide inhibitor, 5 mg/kg) or saline. Twenty-four hours after injection, the myocardial ischemia-reperfusion model was made by Langendorff isolated cardiac perfusion system, and cardiac function parameters were collected. Myocardial cGMP content was measured by ELISA, and the endogenous carbon monoxide in plasma and myocardial enzymes in perfusate at 10 min after reperfusion were measured by colorimetry. The results showed that before ischemia the cardiac functions of CoPP, ZnPP and control groups were stable, and there were no significant differences. After reperfusion, cardiac functions had significant differences among the three groups (P < 0.05). Compared with pre-ischemia, the cardiac function decreased and obvious cardiac arrest was shown in control and ZnPP groups, while the cardiac function in CoPP group did not change significantly, maintaining a relatively stable level. At the same time, three groups' carbon monoxide level, myocardial enzymology and the cardiac function recovery time after reperfusion also had significant differences (P < 0.05). Compared with those in control group, recovery after reperfusion was faster, activities of creatine kinase and lactic dehydrogenase were significantly decreased, plasma CO and myocardial cGMP contents were significantly increased in CoPP group, while these changes were completely opposite in ZnPP group. It is concluded that endogenous carbon monoxide can maintain cardiac function, shorten the time of cardiac function recovery, and play a protective role in cardiac ischemia-reperfusion.


Assuntos
Monóxido de Carbono/sangue , Traumatismo por Reperfusão Miocárdica , Animais , Monóxido de Carbono/agonistas , Monóxido de Carbono/antagonistas & inibidores , Creatina Quinase/metabolismo , GMP Cíclico/metabolismo , Coração , L-Lactato Desidrogenase/metabolismo , Miocárdio/enzimologia , Protoporfirinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Ratos Wistar
14.
Eur Respir J ; 51(4)2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29519926

RESUMO

The value of rates of change in forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) to predict disease progression, and initiation of mTOR (mechanistic target of rapamycin) inhibitor therapy has not been evaluated.In 84 premenopausal lymphangioleiomyomatosis patients, individual rates of change in FEV1 and DLCO and their 95% confidence intervals were used to derive subsequent lowest values of FEV1 and DLCO that would prompt initiation of sirolimus therapy. These treatment criteria were compared with a criterion based on FEV1 or DLCO ≤70% predicted. In 12 patients undergoing sirolimus therapy both methods for determining the optimal point for initiation of therapy were evaluated.27 and 35 patients who experienced greater than expected rates of change in FEV1 and DLCO, respectively, would have been excluded from therapy based on an FEV1 or DLCO >70% pred. 25 of the 84 patients were eventually treated, but only when FEV1 or DLCO were ≤70% pred. Applying such treatment criteria to 12 patients undergoing sirolimus therapy would have delayed treatment for many years.Premenopausal females in whom FEV1 or DLCO are declining at rates above the expected based on their individual rates of decline, should be considered for sirolimus therapy before the FEV1 or DLCO falls to ≤70% pred.


Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Pulmão/fisiopatologia , Linfangioleiomiomatose/tratamento farmacológico , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adolescente , Adulto , Monóxido de Carbono/sangue , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Pessoa de Meia-Idade , Pré-Menopausa , Resultado do Tratamento , Adulto Jovem
15.
J Addict Med ; 12(3): 227-233, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29438157

RESUMO

OBJECTIVES: Heavy-drinking tobacco users are less likely to successfully quit smoking than their moderate-drinking counterparts, even when they are prescribed smoking cessation medication. One strategy for improving treatment outcomes in this subgroup of tobacco users may be to combine medication therapies to target both alcohol and tobacco use simultaneously. Adding naltrexone to frontline smoking cessation treatments may improve treatment outcomes in this group. METHOD: This double-blind, placebo-controlled human laboratory study examined the effects of varenicline (2 mg/d) and varenicline (2 mg/d), combined with a low dose of naltrexone (25 mg/d) on alcohol-primed smoking behavior in a laboratory model of smoking relapse in heavy-drinking tobacco users (n = 30). Participants attended a laboratory session and received an alcohol challenge (target breath alcohol concentration = 0.030 g/dL). They completed a smoking delay task that assessed their ability to resist smoking followed by an ad libitum smoking phase (primary outcomes). They also provided ratings of subjective drug effects and craving, and carbon monoxide levels were measured after smoking (secondary outcomes). RESULTS: Participants receiving varenicline monotherapy delayed smoking longer and smoked fewer cigarettes than those on placebo. Participants receiving varenicline + low-dose naltrexone did not delay smoking longer than those receiving varenicline alone. Participants in both active medication arms smoked fewer cigarettes ad libitum than those receiving placebo. CONCLUSIONS: Varenicline can improve smoking outcomes even after an alcohol prime, supporting its use in heavy drinkers who wish to quit smoking. Findings did not support increased efficacy of combined varenicline + low-dose naltrexone relative to varenicline monotherapy.


Assuntos
Alcoolismo/tratamento farmacológico , Naltrexona/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Fumar Tabaco/tratamento farmacológico , Vareniclina/administração & dosagem , Adulto , Monóxido de Carbono/sangue , Comorbidade , Fissura/efeitos dos fármacos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Nicotínicos/efeitos adversos , Modelos de Riscos Proporcionais , Autorrelato , Resultado do Tratamento , Vareniclina/efeitos adversos , Adulto Jovem
16.
Respir Med ; 135: 51-56, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29414453

RESUMO

BACKGROUND: Pre-flight risk assessments are currently recommended for all Interstitial Lung Disease (ILD) patients. Hypoxic challenge testing (HCT) can inform regarding the need for supplemental in-flight oxygen but variables which might predict the outcome of HCT and thus guide referral for assessment, are unknown. METHODS: A retrospective analysis of ILD patients attending for HCT at three tertiary care ILD referral centres was undertaken to investigate the concordance between HCT and existing predictive equations for prediction of in-flight hypoxia. Physiological variables that might predict a hypoxaemic response to HCT were also explored with the aim of developing a practical pre-flight assessment algorithm for ILD patients. RESULTS: A total of 106 ILD patients (69 of whom (65%) had Idiopathic Pulmonary Fibrosis (IPF)) underwent HCT. Of these, 54 (51%) patients (of whom 37 (69%) had IPF) failed HCT and were recommended supplemental in-flight oxygen. Existing predictive equations were unable to accurately predict the outcome of HCT. ILD patients who failed HCT had significantly lower resting SpO2, baseline PaO2, reduced walking distance, FEV1, FVC and TLCO, but higher GAP index than those who passed HCT. CONCLUSIONS: TLCO >50% predicted and PaO2 >9.42 kPa were independent predictors for passing HCT. Using these discriminators, a novel, practical pre-flight algorithm for evaluation of ILD patients is proposed.


Assuntos
Aeronaves/normas , Hipóxia/fisiopatologia , Fibrose Pulmonar Idiopática/fisiopatologia , Doenças Pulmonares Intersticiais/fisiopatologia , Medicina Aeroespacial/normas , Idoso , Algoritmos , Monóxido de Carbono/sangue , Feminino , Humanos , Hipóxia/sangue , Hipóxia/diagnóstico , Fibrose Pulmonar Idiopática/sangue , Doenças Pulmonares Intersticiais/sangue , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Oxigênio/provisão & distribução , Oxigênio/uso terapêutico , Valor Preditivo dos Testes , Testes de Função Respiratória/métodos , Estudos Retrospectivos , Atenção Terciária à Saúde/normas , Reino Unido/epidemiologia
17.
FASEB J ; 32(5): 2630-2643, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29295856

RESUMO

The prevalence of metabolic diseases, including type 2 diabetes, obesity, and cardiovascular disease, has rapidly increased, yet the molecular mechanisms underlying the metabolic syndrome, a primary risk factor, remain incompletely understood. The small, gaseous molecule carbon monoxide (CO) has well-known anti-inflammatory, antiproliferative, and antiapoptotic effects in a variety of cellular- and tissue-injury models, whereas its potential effects on the complex pathways of metabolic disease remain unknown. We demonstrate here that CO can alleviate metabolic dysfunction in vivo and in vitro. We show that CO increased the expression and section of the fibroblast growth factor 21 (FGF21) in hepatocytes and liver. CO-stimulated PERK activation and enhanced the levels of FGF21 via the eIF2α-ATF4 signaling pathway. The induction of FGF21 by CO attenuated endoreticulum stress- or diet-induced, obesity-dependent hepatic steatosis. Moreover, CO inhalation lowered blood glucose levels, enhanced insulin sensitivity, and promoted energy expenditure by stimulating the emergence of beige adipose cells from white adipose cells. In conclusion, we suggest that CO acts as a potent inducer of FGF21 expression and that CO critically depends on FGF21 to regulate metabolic homeostasis.-Joe, Y., Kim, S., Kim, H. J., Park, J., Chen, Y., Park, H.-J., Jekal, S.-J., Ryter, S. W., Kim, U. H., Chung, H. T. FGF21 induced by carbon monoxide mediates metabolic homeostasis via the PERK/ATF4 pathway.


Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Monóxido de Carbono/sangue , Fatores de Crescimento de Fibroblastos/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Transdução de Sinais , eIF-2 Quinase/metabolismo , Fator 4 Ativador da Transcrição/genética , Animais , Glicemia/genética , Glicemia/metabolismo , Linhagem Celular Tumoral , Estresse do Retículo Endoplasmático/genética , Metabolismo Energético/genética , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fatores de Crescimento de Fibroblastos/genética , Hepatócitos/patologia , Fígado/patologia , Camundongos , Camundongos Knockout , eIF-2 Quinase/genética
18.
Chest ; 153(1): 124-132, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28533049

RESUMO

BACKGROUND: Sirolimus reduces serum levels of vascular endothelial growth factor D (VEGF-D); the size of chylous effusions, lymphangioleiomyomas, and angiomyolipomas; and stabilizes lung function in patients with lymphangioleiomyomatosis (LAM). METHODS: To determine whether reductions in VEGF-D levels are sustained over time, as well as parallel changes in lung function and lymphatic disease, we evaluated 25 patients with LAM and measured VEGF-D levels, lung function, and extent of lymphatic disease before and during sirolimus therapy. RESULTS: Treatment with sirolimus stabilized FEV1 and diffusion capacity for carbon monoxide (Dlco) over a period of 4.5 ± 1.6 years, caused resolution of lymphatic disease, and reduced the size of angiomyolipomas and VEGF-D levels (3,720 ± 3,020 pg/mL to 945 ± 591 pg/mL; P < .0001). Yearly changes in FEV1 % predicted and Dlco % predicted were reduced from -7.4% ± 1.4% to -0.3% ± 0.5% (P < .001) and -6.4% ± 0.9% to -0.4% ± 0.5% (P < .001), respectively. Lower VEGF-D levels correlated with sirolimus therapy (P < .001), but no significant relationship was observed between reduction in VEGF-D levels and FEV1 and Dlco during sirolimus therapy. The magnitude of VEGF-D decline was not related to the effect on lung function. Patients with lymphatic disease had higher serum VEGF-D levels, a greater reduction in VEGF-D levels, and better long-term sustained improvement in lung function during sirolimus therapy than did those without lymphatic disease. CONCLUSIONS: Sirolimus therapy stabilizes lung function over many years of therapy while producing a sustained reduction in VEGF-D levels in patients with elevated levels preceding therapy. An association was not demonstrated between the magnitude of VEGF-D decline and the beneficial effect of sirolimus on lung function. Persistent improvement in lung function was observed in patients with lymphatic disease.


Assuntos
Imunossupressores/uso terapêutico , Linfangioleiomiomatose/tratamento farmacológico , Sirolimo/uso terapêutico , Fator D de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idade de Início , Monóxido de Carbono/sangue , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Assistência de Longa Duração , Linfangioleiomiomatose/sangue , Linfangioleiomiomatose/fisiopatologia , Menopausa/fisiologia , Pessoa de Meia-Idade , Pré-Menopausa/fisiologia , Adulto Jovem
19.
Clin Physiol Funct Imaging ; 38(2): 240-245, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28135764

RESUMO

INTRODUCTION: The carbon monoxide (CO) rebreathing method used for the determination of haemoglobin mass (Hbmass ) is associated with blood sample analysis (in this study: Radiometer ABL800). As an alternative hereto the aim of the present study was to evaluate the use of a portable and non-invasive CO pulse oximeter (Rad-57). METHOD: With simultaneous determination of CO in the circulation by ABL800 (%HbCO) and Rad-57 (SpCO), Hbmass and blood volume (BV) were determined in duplicates in 24 volunteers. Percentage of typical errors (%TE) within methods and linear correlations between the two procedures were computed. RESULTS: Hbmass (Rad-57 = 798 ± 230 g; ABL800 = 781 ± 192 g) and BV (Rad-57 = 5700 ± 1373 ml; ABL800 = 5581 ± 1096 ml) were similar between methods. However, the %TE for Hbmass was higher (P<0·001) for Rad-57 (5·84 ± 5·29%) than for ABL800 (1·35 ± 1·13%). Similarly, the %TE for BV was higher (P<0·001) for Rad-57 (6·06 ± 5·76%) than for ABL800 (1·48 ± 1·25%). Lower (P<0·05) correlation coefficients between the methods were found when Hbmass  > 905 g and BV > 6193 ml. CONCLUSION: Assessment of SpCO by Rad-57 resulted in considerably less precise determinations of Hbmass and BV, especially for high values. Thus, non-invasive assessment of Hbmass and BV cannot be recommended for scientific purposes, but may nonetheless be useful in clinical settings.


Assuntos
Determinação do Volume Sanguíneo/instrumentação , Volume Sanguíneo , Monóxido de Carbono/sangue , Hemoglobinas/metabolismo , Oximetria/instrumentação , Administração por Inalação , Adulto , Biomarcadores/sangue , Monóxido de Carbono/administração & dosagem , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Humanos , Modelos Lineares , Masculino , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto Jovem
20.
Nicotine Tob Res ; 20(2): 183-191, 2018 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-27798089

RESUMO

Background: Cigar smoking in the United States continues despite decreases in cigarette smoking and increased tobacco control efforts. We compared large cigar and cigarette smoking for use patterns, smoking topography, and toxicant exposure. Methods: Dual users (n = 17, 94% men, 77% African American) smoked ad libitum either their usual cigarette brand or a study large cigar (Phillies Blunt) in two laboratory sessions. Plasma nicotine and exhaled carbon monoxide were collected before and after smoking. Smoking topography measures of puff volume, puff duration, puff velocity, and interpuff interval were also collected. Results: Both cigarettes and large cigars significantly increased plasma nicotine and carbon monoxide and significantly decreased the urge to smoke. Cigarettes delivered more nicotine per gram of tobacco smoked and per 1000 mL of puff volume. Number of puffs, time to smoke, puff volume, and puff velocity were significantly larger and interpuff interval was significantly shorter in large cigar smoking. The temporal pattern of puffing more intensely at the beginning of smoking was similar for both large cigars and cigarettes. Conclusions: People who regularly use both large cigars and cigarettes adapt their smoking pattern such that they are exposed to similar levels of nicotine from each product. The immediate increase in plasma nicotine and carbon monoxide suggest significant inhalation of large cigar smoke. These data call to question the assumption that cigar smoking is less toxic than cigarette smoking. By smoking large cigars, dual users expose themselves to toxic components that have been linked with the addiction risk, morbidity, and mortality of cigarette smoking. Implications: This study found that dual users of large cigars and cigarettes inhale significant quantities of carbon monoxide, nicotine, and presumably other components of mainstream smoke. Large cigar smoke exposure may lead to or sustain nicotine addiction as wells as subject large cigar consumers to similar risks associated with cigarette smoking such as lung cancer and cardiovascular disease.


Assuntos
Monóxido de Carbono/sangue , Exposição por Inalação/efeitos adversos , Nicotina/sangue , Fumaça/análise , Fumar/epidemiologia , Produtos do Tabaco/efeitos adversos , Tabagismo/epidemiologia , Administração por Inalação , Adulto , Feminino , Humanos , Exposição por Inalação/análise , Masculino , Pessoa de Meia-Idade , Nicotina/administração & dosagem , Fumar/efeitos adversos , Fumar/sangue , Produtos do Tabaco/análise , Tabagismo/sangue , Tabagismo/etiologia , Estados Unidos/epidemiologia
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