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1.
Sci Rep ; 10(1): 4437, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157204

RESUMO

Xanthine oxidoreductase (XOR) inhibitor administration reduces uric acid and reactive oxygen species (ROS) production, and also lowers blood pressure (BP). However, the associations of plasma XOR activity, uric acid level, and oxidative stress levels with BP remain unclear. This cross-sectional study included 156 subjects (68 males, 88 females) registered in the MedCity21 health examination registry without anti-hypertensive or anti-hyperuricemic agent administration. Plasma XOR activity was measured using our highly sensitive novel assay, which is unaffected by uric acid in the sample. BP was also determined, and serum uric acid and derivative of reactive oxygen metabolites (d-ROMs) levels were simultaneously measured. Median plasma XOR activity, serum uric acid, d-ROMs, and mean arterial pressure (MAP) values were 25.7 pmol/h/mL, 5.4 mg/dL, 305 Carr U, and 89.0 mmHg, respectively. Multiple regression analysis showed that plasma XOR activity (ß = 0.211, p = 0.019), but not serum uric acid (ß = 0.072, p = 0.502), was significantly associated with MAP. In subjects with lower but not higher d-ROMs level, an independent association of plasma XOR activity with MAP was observed (ß = 0.428, p = 0.001 and ß = 0.019, p = 0.891, respectively; p for interaction = 0.046). XOR may contribute to the pathophysiology of higher BP through ROS but not uric acid production, especially in patients with lower oxidative stress.

2.
Lung Cancer ; 139: 80-88, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31751804

RESUMO

OBJECTIVES: Low-frequency epidermal growth factor receptor (EGFR) T790M mutation could be detected by ultrasensitive methods in EGFR tyrosine kinase inhibitor (TKI)-naïve non-small cell lung cancer (NSCLC). However, the impact of pretreatment T790M (preT790M) on the efficacy of EGFR-TKIs and on resistance remains unclear. MATERIALS AND METHODS: Two independent cohorts consisting of advanced EGFR-mutated NSCLC patients treated with first-line EGFR-TKIs, a derivation cohort that started treatment between August 2013 and July 2016 (cohort A, n = 44) and a validation cohort between August 2016 and December 2017 (cohort B, n = 22), were examined in this study. Among these, 28 patients underwent re-biopsy at disease progression. DNAs from pretreatment tumor biopsy samples and re-biopsy samples were assessed to detect T790M by the Cobas EGFR Mutation Test v2 (Cobas) and for quantitating T790M by droplet digital polymerase chain reaction (ddPCR). RESULTS: Detection rates of preT790M were 40.9% (18/44) in cohort A and 45.5% (10/22) in cohort B by ddPCR, and none by Cobas. A cutoff value of 0.3% for dividing into high- vs. low-preT790M allele frequency was determined by receiver operating characteristic curve analysis in cohort A. Progression-free survival (PFS) was significantly shorter in the high- preT790M group (n = 12) than in the low-preT790M (n = 6) and negative (n = 26) groups (combined low-preT790M) (median: 6.9 vs. 13.8 months, P =  0.00073). These observations were validated in cohort B [median: 6.2 (n = 5) vs. 15.3 months (n = 17), P =  0.0029]. In 28 paired biopsies, Cobas detected post-progression T790M in 60% (3/5) of the high-preT790M, in 57% (4/7) of the low-preT790M, and in 56% (9/16) of the negative-preT790M groups. CONCLUSION: EGFR-mutated NSCLC with high preT790M had significantly shorter PFS on EGFR-TKIs. However, preT790M abundance may not necessarily confer post-TKI T790M resistance.

3.
Mar Drugs ; 17(12)2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795292

RESUMO

Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is a key cellular defense mechanism against oxidative stress. Recent studies have shown that astaxanthin protects against oxidative stress via Nrf2. In this study, we investigated the emphysema suppression effect of astaxanthin via Nrf2 in mice. Mice were divided into four groups: control, smoking, astaxanthin, and astaxanthin + smoking. The mice in the smoking and astaxanthin + smoking groups were exposed to cigarette smoke for 12 weeks, and the mice in the astaxanthin and astaxanthin + smoking groups were fed a diet containing astaxanthin. Significantly increased expression levels of Nrf2 and its target gene, heme oxygenase-1 (HO-1), were found in the lung homogenates of astaxanthin-fed mice. The number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) was significantly decreased, and emphysema was significantly suppressed. In conclusion, astaxanthin protects against oxidative stress via Nrf2 and ameliorates cigarette smoke-induced emphysema. Therapy with astaxanthin directed toward activating the Nrf2 pathway has the potential to be a novel preventive and therapeutic strategy for COPD.

4.
Int J Chron Obstruct Pulmon Dis ; 14: 2507-2516, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814716

RESUMO

Background: Oxidative stress is one of the important mechanisms underlying the pathogenesis of chronic obstructive pulmonary disease (COPD). Irisin is a type of myokine secreted from the muscle during exercise and acts against oxidative stress via nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor with antioxidant properties. Here, we examined the emphysema suppressive effects of the exercise-irisin-Nrf2 axis in mice. Methods: Mice were divided into three groups, namely, the control, smoking, and exercise + smoking groups. All mice from the smoking and exercise + smoking groups were exposed to cigarette smoke once a day. The mice from the exercise + smoking group were adapted to a treadmill once a day. To investigate the Nrf2 cascade, after 12 weeks, serum irisin concentration and Nrf2 and heme oxygenase-1 (HO-1) expression in the lung homogenate were determined. To evaluate cigarette smoke-induced COPD, the number of inflammatory cells in bronchoalveolar lavage fluid (BALF), mean linear intercept (MLI), and destructive index in the lung tissue were examined. Results: Serum irisin concentration and the expression levels of Nrf2 and HO-1 in the lung homogenate were significantly higher in mice from the exercise + smoking group than in those from the control and smoking groups. The proportion of neutrophils in the BALF was significantly lower in the exercise + smoking group than in the smoking group. The MLI and destructive index were also significantly smaller in mice from the exercise + smoking group than mice from the smoking group. Conclusion: Irisin secreted from the muscle during exercise may exert protective effects against oxidative stress via Nrf2 and HO-1, and ameliorate emphysema of cigarette smoke-induced COPD. The exercise-irisin-Nrf2 axis may serve as a novel target for COPD treatment.

5.
Sci Rep ; 9(1): 15214, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645621

RESUMO

Superconducting quantum interference devices (SQUIDs) are currently used as magnetic flux detectors with ultra-high sensitivity for various applications such as medical diagnostics and magnetic material microstructure analysis. Single-crystalline superconducting boron-doped diamond is an excellent candidate for fabricating high-performance SQUIDs because of its robustness and high transition temperature, critical current density, and critical field. Here, we propose a fabrication process for a single-crystalline boron-doped diamond Josephson junction with regrowth-induced step edge structure and demonstrate the first operation of a single-crystalline boron-doped diamond SQUID above 2 K. We demonstrate that the step angle is a significant parameter for forming the Josephson junction and that the step angle can be controlled by adjusting the microwave plasma-enhanced chemical vapour deposition conditions of the regrowth layer. The fabricated junction exhibits superconductor-weak superconductor-superconductor-type behaviour without hysteresis and a high critical current density of 5800 A/cm2.

6.
Nutrients ; 11(9)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470503

RESUMO

Chronic obstructive pulmonary disease (COPD), a lung disease caused by chronic exposure to cigarette smoke, increases the number of inflammatory cells such as macrophages and neutrophils and emphysema. Isoflavone is a polyphenolic compound that exists in soybeans. Daidzein and genistein, two types of isoflavones, have been reported to have anti-inflammatory effects in various organs. We hypothesized that the daidzein-rich soy isoflavone aglycones (DRIAs) attenuate cigarette smoke-induced emphysema in mice. Mice were divided into four groups: the (i) control group, (ii) isoflavone group, (iii) smoking group, and (iv) isoflavone + smoking group. The number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and the airspace enlargement using the mean linear intercept (MLI) were determined 12 weeks after smoking exposure. Expressions of neutrophilic inflammatory cytokines and chemokines were also examined. In the isoflavone + smoking group, the number of neutrophils in BALF and MLI was significantly less than that in the smoking group. Furthermore, the gene-expressions of TNF-α and CXCL2 (MIP-2) in the isoflavone + smoking group were significantly less than those in the smoking group. Supplementation of the COPD murine model with DRIAs significantly attenuates pathological changes of COPD via suppression of neutrophilic inflammation.


Assuntos
Anti-Inflamatórios/farmacologia , Isoflavonas/farmacologia , Pulmão/efeitos dos fármacos , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Pneumonia/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Enfisema Pulmonar/tratamento farmacológico , Fumaça , Produtos do Tabaco , beta-Glucanas/farmacologia , Animais , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Neutrófilos/metabolismo , Pneumonia/etiologia , Pneumonia/imunologia , Pneumonia/metabolismo , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Enfisema Pulmonar/etiologia , Enfisema Pulmonar/imunologia , Enfisema Pulmonar/metabolismo , Transdução de Sinais
7.
Int J Chron Obstruct Pulmon Dis ; 14: 1789-1801, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496678

RESUMO

Background: Patients with COPD are less physically active. This post hoc analysis of a randomized, double-blind, active-controlled, crossover trial assessed the efficacy of once-daily tiotropium/olodaterol combination therapy versus tiotropium monotherapy in Japanese patients with COPD. Patients and methods: Patients were provided with a three-axis accelerometer to measure sedentary and active behavior defined as 1.0-1.5 metabolic equivalents (METs), ≥2.0 METs, and ≥3.0 METs, respectively. Of the 182 patients enrolled, 131 satisfied the conditions for the present analysis and were randomized to tiotropium monotherapy (n=62) or tiotropium/olodaterol combination therapy (n=69). Results: Tiotropium/olodaterol combination therapy significantly reduced the duration of 1.0-1.5 MET activity by 8.64 mins (p=0.040) and significantly increased the duration of ≥2.0 MET and ≥3.0 MET activity by 6.51 mins (p=0.017) and 2.60 mins (p=0.008), respectively, compared with tiotropium alone. Subgroup analyses showed that better lung function, milder dyspnea, and higher levels of physical activity at baseline were associated with reduced sedentary time and increased duration of physical activity. Conclusion: Tiotropium/olodaterol combination therapy significantly reduced sedentary time and improved physical activity compared with tiotropium monotherapy. This trial was registered in ClinicalTrials.gov (NCT02629965).

8.
Respir Investig ; 57(5): 499-505, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31085119

RESUMO

BACKGROUND: Impaired exercise capacity is one of the most important prognostic factors for patients with chronic obstructive pulmonary disease (COPD). The 6-min walk test (6MWT) is a widely used method for assessing exercise capacity in patients with COPD. However, the 6MWT requires considerable effort from patients. Therefore, a less physically demanding, but also noninvasive, method is warranted. The objective of this study was to determine the predictors of the 6MWT distance (6MWD) in patients with COPD. METHODS: This retrospective observational study enrolled 133 Japanese patients with COPD. All patients underwent the 6MWT, COPD assessment test (CAT), spirometry, respiratory muscle strength evaluation, body composition assessment, and handgrip strength (HGS) measurement. We examined the associations between the 6MWD and evaluated parameters. RESULTS: From single regression analysis, the 6MWD was significantly correlated with age, CAT score, several spirometric measurements (e.g., percentages of forced vital capacity, forced expiratory volume in 1 s, and carbon monoxide diffusing capacity of the lungs [%DLCO]), respiratory muscle strength parameters (e.g., percentages of maximal expiratory and inspiratory pressures), skeletal muscle mass index, and HGS. In multiple regression analysis, age, CAT score, %DLCO, and HGS were independent predictors of the 6MWD. The %DLCO and HGS were strongly correlated as predictors of the 6MWD (p < 0.001). CONCLUSIONS: We found that HGS was significantly correlated with the 6MWD compared with spirometric measurements or respiratory muscle strength parameters in Japanese patients with COPD, suggesting that HGS could be a simple and noninvasive predictor of the 6MWD in patients with COPD.

9.
J Thorac Dis ; 11(3): 936-943, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31019783

RESUMO

Background: Ultrasound (US)-guided percutaneous needle biopsy is a useful diagnostic technique with short examination time and real-time monitoring at the bedside. However, there are only a few studies that report on thoracic lesions, whereas the computed tomography (CT)-guided biopsy is well established. There is also limited data comparing US- and CT-guided biopsy. We aimed to clarify the efficacy and safety of US-guided biopsy for thoracic lesions adjacent to the chest wall. Methods: We retrospectively enrolled consecutive patients who underwent US- or CT-guided percutaneous biopsies for thoracic lesions adjacent to the chest wall between April 2012 and December 2017. Clinical characteristics, lesion size, lesion-pleura contact arc length (LPCAL), diagnostic rate, and complications were compared between the 2 groups. Results: This study enrolled 61 US-guided and 70 CT-guided biopsies. No significant difference was found in age or sex. The lesion size and LPCAL in the US-guided group were significantly larger than those in the CT-guided group (P<0.0001). The diagnostic rate was marginally higher in the US-guided group (93.4%) than in the CT-guided group (84.3%) (P=0.101). When the median cut-off of the LPCAL was defined as 40 mm in all cases, the diagnostic rate for lesion size >40 mm was significantly higher in the US-guided group than in the CT-guided group (P=0.009). Complication rates were significantly lower in the US-guided group (3.3%) than in the CT-guided group (24.3%) (P<0.001). Conclusions: US-guided percutaneous needle biopsy for thoracic lesions adjacent to the chest wall is a feasible technique compared with CT-guided biopsy because of its higher diagnostic rate with a longer LPCAL and reduced complications.

10.
Esophagus ; 16(3): 309-315, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30927164

RESUMO

BACKGROUND: Esophageal eosinophilia (EE) is a basal condition of eosinophilic esophageal disorders including eosinophilic esophagitis (EoE) and asymptomatic EE. EoE is considered as an allergic disorder, while it is unclear whether other non-allergic conditions are involved in the pathophysiology of EE. The aim of this study is to investigate the non-allergic risk factors for EE. METHODS: This cross-sectional study included subjects who underwent esophagogastroduodenoscopy on a medical health check-up. We compared clinical characteristics between subjects with EE (n = 27) and those without EE (n = 5937). RESULTS: The detection rate of EE was 0.45% (27/5964 persons). Of 27 subjects with EE, 20 subjects were symptomatic and 7 were asymptomatic. On univariate analysis, subjects with EE significantly had higher body mass index (BMI) compared to those without EE; 23.4 (4.4) vs 22.3 (4.5) kg/m2, median (interquartile range), p = 0.005. Endoscopic findings revealed that subjects with EE had significantly higher proportion of hiatal hernia (29.6% vs 14.7%; p = 0.049). Subjects with EE were significantly younger and had higher proportion of bronchial asthma; 45 (11.5) vs 51 (18) years, p = 0.013; 25.9% vs 5.2%, p < 0.001, respectively. Multivariate analysis showed that subjects with EE were positively associated with BMI [odds ratio (OR) 1.11; 95% confidence interval (CI) 1.03-1.20; p = 0.010) and hiatal hernia (OR 2.63; 95% CI 1.12-6.18; p = 0.026) compared to those without EE. On trend test, advanced BMI classification had significant trend for increased prevalence of EE (p = 0.002). CONCLUSIONS: Obesity and hiatal hernia may be non-allergic risk factors for EE in Japanese adults.

11.
Intern Med ; 58(3): 321-328, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30210122

RESUMO

Objective The association between functional dyspepsia (FD) and endoscopic findings has not been fully elucidated. Helicobacter pylori infection is considered a key factor in the pathophysiology of FD. The Kyoto Classification of Gastritis (KCG) was proposed in 2014 to evaluate endoscopic findings based on the H. pylori status. We investigated the endoscopic findings associated with FD according to the KCG. Methods This cross-sectional study included subjects who underwent esophagogastroduodenoscopy during a medical health check-up. We compared the endoscopic findings between subjects with FD and healthy controls (HCs) according to the KCG. Results A total of 456 subjects were analyzed. Among them, the detection rate of FD was 5.5% (25/456 persons). In a univariate analysis of the endoscopic findings, a significantly lower proportion of subjects with FD had gastric red streak in comparison to HCs (0% vs. 18.6%, respectively; p=0.0124). Subjects with FD were more likely to have gastric depressive erosion (20.0% vs. 7.9%; p=0.0522). A higher proportion of the erosion-positive subjects had FD in comparison to erosion-negative subjects (12.8% vs. 4.8%). There were no significant differences in the other endoscopic findings, including gastric atrophy, intestinal metaplasia, enlarged fold, nodularity, and diffuse redness. A multivariate analysis revealed that gastric depressive erosion was significantly and independently associated with FD (odds ratio, 2.92; 95% confidence interval, 1.03-8.26; p=0.0436). In contrast, gastric red streak was not associated with FD (p=0.989). Conclusion Gastric depressive erosions may be associated with dyspepsia.


Assuntos
Dispepsia/diagnóstico , Dispepsia/psicologia , Gastrite/complicações , Infecções por Helicobacter/complicações , Úlcera Gástrica/complicações , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Estudos Transversais , Dispepsia/epidemiologia , Dispepsia/fisiopatologia , Feminino , Infecções por Helicobacter/epidemiologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances
12.
Int J Chron Obstruct Pulmon Dis ; 13: 2629-2641, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30214181

RESUMO

Background: COPD remains a major health problem in Japan. Patients with COPD experience a reduced quality of life (QoL) and have a higher chance of work impairment and productivity loss. However, there is a lack of data on the impact of COPD in terms of QoL and work activity impairment in Japan. This study assessed the socioeconomic burden of COPD in Japan and the impact it may have on the working age population. Patients and methods: This was a 2-year retrospective chart review in COPD patients aged ≥40 years, with at least one health care visit to clinic or hospital in the previous 12 months. Patients were required to have available medical charts for at least the previous 24 months. Symptoms were assessed using COPD assessment test score; EuroQoL Group 5 Dimension (EQ-5D-5L) and work productivity and activity impairment general health questionnaires were used to evaluate health-related QoL and work productivity, and health care resource utilization data were obtained from clinical charts. Results: In total, 71 patients aged <65 years, and 151 patients aged ≥65 years were included; the majority of patients had moderate or severe airflow limitation. Exacerbations (moderate or severe) were reported by ~35% of patients in both age groups; 52.1% and 62.9% of patients in the <65-year and ≥65-year age groups had COPD assessment test scores ≥10. EQ-5D-5L index scores in the <65-year and ≥65-year age groups were 0.79 and 0.77, respectively. Work productivity and activity impairment scores were higher in <65-year age group. Annual costs of health care resource use per patient in the <65-year and ≥65-year age groups were ¥438,975 (US$4,389) and ¥467,871 (US$4,678), respectively. Costs due to productivity loss were estimated to be ¥5,287,024 (US$52,870) in the <65-year age group and ¥3,018,974 (US$30,187) in the ≥65-year age group. Conclusion: COPD represents a significant socioeconomic burden in Japan. Patients with COPD report significant use of health care resources. Higher impact on work impairment and productivity loss was observed frequently in the working age population.


Assuntos
Doença Pulmonar Obstrutiva Crônica/economia , Qualidade de Vida , Fatores Socioeconômicos , Desempenho Profissional , Adulto , Idoso , Estudos Transversais , Progressão da Doença , Eficiência , Ex-Fumantes , Feminino , Custos de Cuidados de Saúde , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fumantes , Inquéritos e Questionários , Fatores de Tempo
13.
Int J Chron Obstruct Pulmon Dis ; 13: 1407-1419, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29750027

RESUMO

Purpose: This study evaluated the efficacy of tiotropium/olodaterol vs tiotropium on lung function, exercise capacity, and physical activity in patients with COPD. Patients and methods: A total of 184 patients aged ≥40 years with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II-IV) received tiotropium/olodaterol for 6 weeks, then tiotropium for 6 weeks, or vice versa. The primary endpoint was inspiratory capacity (IC) at peak post-dose. Results: Adjusted mean IC after 6-week treatment was 1.990 L with tiotropium/olodaterol vs 1.875 L with tiotropium (difference: 115 mL; 95% CI: 77, 153; p<0.0001). Forced expiratory volume in 1 s (difference: 105 mL; 95% CI: 88, 123), forced vital capacity (difference: 163 mL; 95% CI: 130, 197), and slow vital capacity (difference: 134 mL; 95% CI: 91, 176) improved with tiotropium/olodaterol (all p<0.0001). Adjusted mean 6-min walk distance was similar between treatments in the overall population but was significantly increased with tiotropium/olodaterol in the subgroup with Global Initiative for Chronic Obstructive Lung Disease stage III/IV at baseline (difference: 18.1 m; 95% CI: 2.3, 33.9; p=0.0254). In a post hoc analysis, tiotropium/olodaterol improved the values for ≥2.0 metabolic equivalents (difference: 5.0 min; 95% CI: 0.4, 9.7; p=0.0337). Conclusion: Tiotropium/olodaterol significantly improved IC compared with tiotropium and potentially enhanced the exercise capacity in COPD patients. A slight improvement in physical activity of relatively more than moderate intensity was also seen with tiotropium/olodaterol.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Benzoxazinas/uso terapêutico , Broncodilatadores/uso terapêutico , Tolerância ao Exercício/efeitos dos fármacos , Exercício Físico , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Brometo de Tiotrópio/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Adulto , Idoso , Benzoxazinas/efeitos adversos , Broncodilatadores/efeitos adversos , Estudos Cross-Over , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Volume Expiratório Forçado , Nível de Saúde , Humanos , Capacidade Inspiratória , Japão , Pulmão/fisiopatologia , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fatores de Tempo , Brometo de Tiotrópio/efeitos adversos , Resultado do Tratamento , Teste de Caminhada
14.
BMC Res Notes ; 11(1): 34, 2018 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-29338781

RESUMO

BACKGROUND: Clinically amyopathic dermatomyositis with anti-Melanoma Differentiation-Associated gene 5 (MDA5) antibody often presents with severe interstitial lung disease. Although serum ferritin level is known to reflect interstitial lung disease activity, there are few case reports describing this association. CASE PRESENTATION: A 58-year-old man was referred to our outpatient clinic with a 3-week history of cough and respiratory distress. He had erythema over the V area of the neck and a Gottron's sign. Chest computed tomography revealed diffuse ground-glass opacities and reticular shadows in both lungs. Test for anti-MDA5 antibody was positive. After admission, he received triple combination therapy (methylprednisolone pulse therapy, tacrolimus, and cyclophosphamide). However, his respiratory condition worsened as the serum ferritin level increased. Despite no apparent deterioration on chest radiography, he ultimately died due to respiratory failure. CONCLUSIONS: In this case, triple combination therapy was not effective for the patient's respiratory condition. The serum ferritin level was correlated with disease activity and was more useful than chest radiography for monitoring clinical status.


Assuntos
Dermatomiosite/patologia , Ferritinas/sangue , Doenças Pulmonares Intersticiais/patologia , Anti-Inflamatórios/uso terapêutico , Ciclofosfamida/uso terapêutico , Dermatomiosite/complicações , Dermatomiosite/tratamento farmacológico , Progressão da Doença , Quimioterapia Combinada , Evolução Fatal , Humanos , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/tratamento farmacológico , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Tacrolimo/uso terapêutico
15.
Am J Clin Oncol ; 41(10): 967-971, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29045265

RESUMO

OBJECTIVES: A phase I study to determine a recommended dose of thoracic radiotherapy using accelerated hyperfractionation for unresectable non-small cell lung cancer was conducted. MATERIALS AND METHODS: We used chemotherapy of a cisplatin doublet and 2 dose levels of radiation with accelerated hyperfractionation. The radiation dose levels were: a total dose of 60 Gy in 40 fractions at level 1, and 66 Gy in 44 fractions at level 2. Eligible patients with unresectable stage III non-small cell lung cancer received cisplatin and vinorelbine. Radiation therapy started on day 2 of chemotherapy and was delivered twice daily for 5 days a week. RESULTS: Total 12 patients were enrolled, with 6 patients each at dose levels 1 and 2. Dose-limiting toxicity was noted in 2 patients at level 1; one patient had grade 3 febrile neutropenia and the other patient had grade 3 esophagitis. No dose-limiting toxicity was noted in the 6 patients at level 2. Grade 3 to 4 leukopenia, neutropenia, and anemia were noted in 11 (92%), 9 (75%), and 8 (67%) of the total 12 patients, respectively. Grade 3 anorexia and infection were noted in 2 patients (17%) at each level. Grade 3 nausea, fatigue, esophagitis, and febrile neutropenia were noted in 1 patient (8%) at each level. The response rate in the total 12 patients was 83.3%. The median progression-free survival time and the median overall survival time were 10.7 and 24.2 months, respectively. CONCLUSIONS: Sixty-six gray in 44 fractions is the recommended dose for the following phase II study.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Neoplasias Pulmonares/terapia , Recidiva Local de Neoplasia/terapia , Radioterapia Conformacional/métodos , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Cisplatino/administração & dosagem , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Taxa de Sobrevida , Vinorelbina/administração & dosagem
16.
J Gen Fam Med ; 18(1): 5-11, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-29263981

RESUMO

Japan is an aging society, and the number of elderly patients with asthma and chronic obstructive pulmonary disease (COPD) is consequently increasing, with an estimated incidence of approximately 5 million. In 2014, asthma-COPD overlap syndrome (ACOS) was defined by a joint project of Global Initiative for Asthma (GINA) committee and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) committee. The main aims of this consensus-based document are to assist clinicians, especially those in primary care or nonpulmonary specialties. In this article, we discussed parameters to differentiate asthma and COPD in elderly patients and showed prevalence, clinical features and treatment of ACOS on the basis of the guidelines of GINA and GOLD. Furthermore, we showed also referral for specialized investigations.

17.
J Gen Fam Med ; 18(6): 386-392, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29264069

RESUMO

Background: After the A/H1N1 influenza pandemic in 2009, two new drugs against the influenza virus, laninamivir and peramivir, were released in 2010 in Japan. We investigated the current usage and effectiveness of influenza medications and factors related to the time taken to alleviate fever. Methods: Patients diagnosed with influenza during the 2012-2013 season in Osaka Prefecture answered a postcard questionnaire that collected data regarding their demographic characteristics, flu vaccination status, symptoms, prescribed drugs, and drug-related adverse events. Results: The use of laninamivir consistently increased over the 3-year period and was prescribed at a similar rate as oseltamivir during the last year (39% and 45%, respectively). None of the neuraminidase inhibitors had a significant effect on the fever or other symptoms of influenza infection (P=.59 and P=.70, respectively). Vaccinated influenza patients experienced fever for a significantly longer duration than the nonvaccinated patients (P=.04). However, multivariate analysis showed that only influenza virus type, but not vaccination status, was related to the alleviation of fever within 2 days. Conclusions: There were no significant differences of effects on fever and symptoms among neuraminidase inhibitors. Virus type was only related to the alleviation of fever.

18.
Lung Cancer ; 112: 96-101, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-29191607

RESUMO

OBJECTIVES: Non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) have been proposed to have a mutual developmental mechanism, but their association has not been fully understood. We aimed to examine the association of the mutational landscape of NSCLC with co-morbid COPD. MATERIALS AND METHODS: A total of 197 surgical specimens of early stage NSCLC were retrospectively collected from two independent sources, namely, the Japan Molecular Epidemiology for Lung Cancer Study and the Osaka City University Hospital cohort from 2010 to 2013. COPD and its severity were defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and grading system. For molecular profiling of NSCLC patients with COPD, the extracted DNAs were deep-sequenced using next generation sequence technologies for somatic mutations in a maximum 72 cancer-associated genes. Logistic regression analysis was performed to evaluate the impact of COPD on the somatic mutations. RESULTS: The COPD group (n=77), including 56 GOLD 1 and 21 GOLD 2 or 3 patients, had 58 squamous cell lung carcinoma (SCC) cases and 19 adenocarcinoma cases. The non-COPD group (n=120) had 53 SCC cases, 64 adenocarcinoma cases, and three cases with other histology. The frequency of PIK3CA mutation was significantly higher in the COPD group than in the non-COPD group (10.4% vs. 1.7%, p=0.015). Meanwhile, NFE2L2 mutation was observed only in SCC cases, with no difference in the frequency between the two groups (17.2% vs. 17.0%). In the multivariate logistic regression model with consideration for COPD status, age, smoking dose, pathological stage, and histology, significantly more PIK3CA mutation was observed in the presence of COPD (odds ratio=5.31, 95% CI: 1.03-27.29, p=0.046). CONCLUSIONS: PIK3CA mutation is a distinctive genetic feature of NSCLC with COPD, regardless of age, smoking dose, pathological stage, and histology.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/genética , Mutação , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Taxa de Mutação , Estadiamento de Neoplasias , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Testes de Função Respiratória , Índice de Gravidade de Doença
19.
Intern Med ; 56(17): 2325-2328, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28794368

RESUMO

A 75-year-old man with stage IV lung adenocarcinoma was treated with osimertinib due to disease progression despite having been administered erlotinib. Both an epidermal growth factor receptor (EGFR) L858R mutation on exon 21 and a T790M mutation on exon 20 were detected in a specimen from a recurrent primary tumor. Five weeks after osimertinib initiation, he developed general fatigue and dyspnea. Chest computed tomography scan revealed diffuse ground glass opacities and consolidation on both lungs. An analysis of the bronchoalveolar lavage fluid revealed marked lymphocytosis, and a transbronchial lung biopsy specimen showed a thickened interstitium with fibrosis and prominent lymphocytic infiltration. We diagnosed the patient to have interstitial lung disease induced by osimertinib.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Piperazinas/efeitos adversos , Acrilamidas , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Idoso , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Cloridrato de Erlotinib/uso terapêutico , Humanos , Neoplasias Pulmonares/patologia , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico
20.
Adv Ther ; 34(7): 1622-1635, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28537001

RESUMO

INTRODUCTION: The superiority of tiotropium/olodaterol is demonstrated in improvement of lung function, dyspnea, lung hyperinflation, and quality of life compared with either monotherapy in patients with chronic obstructive pulmonary disease (COPD). Japanese Respiratory Society Guidelines for COPD management include improvement of exercise tolerance and daily physical activity as the treatment goals; however, there is limited evidence in Japanese patients with COPD. METHODS: A protocol is developed for the VESUTO® study that investigates the efficacy of tiotropium/olodaterol fixed-dose combination (FDC) compared with tiotropium alone on inspiratory capacity (IC, volume from functional residual capacity to total lung capacity), exercise capacity, and daily physical activity in Japanese patients with COPD. RESULTS: A total of 180 Japanese patients with COPD, aged ≥40 years will be enrolled into the double-blind, multicenter, active-controlled, crossover study (NCT02629965) and will be randomized to receive either tiotropium/olodaterol FDC or tiotropium for 6 weeks each [two puffs via RESPIMAT® (Boehringer Ingelheim, Ingelheim, Germany) inhaler in the morning]. The primary endpoint is IC at rest measured at 60 min post-dose after 6 weeks treatment. The secondary endpoints include the 6-min walk distance (6MWD) at 90 min post-dose and physical activity measured by the activity monitor in the last 2 weeks of the 6-week treatment periods. Lung function tests will also be assessed after 6 weeks treatment. A mixed-effects model repeated measures approach will be used for the primary and secondary endpoints. CONCLUSION: The VESUTO® study is the first randomized interventional study to investigate exercise capacity (6MWD) and physical activity measured by a 3-axis accelerometer in Japanese patients with COPD. The study could provide additional evidence of long-acting muscarinic antagonist (LAMA) + long-acting ß2-agonist (LABA) combination therapy on patients' physical activities as well as lung function. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02629965 (registered on December 1, 2015). FUNDING: The VESUTO study was funded by Nippon Boehringer Ingelheim Co., Ltd., Tokyo, Japan.


Assuntos
Benzoxazinas/administração & dosagem , Benzoxazinas/uso terapêutico , Broncodilatadores/uso terapêutico , Tolerância ao Exercício/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Brometo de Tiotrópio/administração & dosagem , Brometo de Tiotrópio/uso terapêutico , Administração por Inalação , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Testes de Função Respiratória
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