Defect of Adaptation to Hypoxia in Patients With COPD Due to Reduction of Histone Deacetylase 7

BackgroundHypoxia inducible factor (HIF)-1 plays an important role in cellular adaptation to hypoxia by activating oxygen-regulated genes such as vascular endothelial growth factor (VEGF) and erythropoietin. Sputum VEGF levels are reported to be decreased in COPD, despite hypoxia. Here we show that patients with COPD fail to induce HIF-1α and VEGF under hypoxic condition because of a reduction in histone deacetylase (HDAC) 7.MethodsPeripheral blood mononuclear cells (PBMCs) were obtained from patients with moderate to severe COPD (n = 21), smokers without COPD (n = 12), and nonsmokers (n = 15). PBMCs were exposed to hypoxia (1% oxygen, 5% CO2, and 94% N2) for 24 h, and HIF-1α and HDAC7 protein expression in nuclear extracts were determined by sodium dodecyl sulfate poly acrylamide gel electrophoresis (SDS-PAGE)/Western blotting.ResultsHIF-1α was significantly induced by hypoxia in each group when compared with the normoxic condition (12-fold induction in nonsmokers, 24-fold induction in smokers without COPD, fourfold induction in COPD), but induction of HIF-1α under hypoxia was significantly lower in patients with COPD than in nonsmokers and smokers without COPD (P < .05 and P < .01, respectively). VEGF messenger RNA detected by quantitative real-time polymerase chain reaction was correlated with HIF-1α protein in nuclei (r = 0.79, P < .05), and HDAC7 protein expression was correlated with HIF-1α protein in nuclei (r = 0.46, P < .05). HDAC7 knockdown inhibited hypoxia-induced HIF-1α activity in U937 cells, and HIF-1α nuclear translocation and HIF-1α binding to the VEGF promoter in A549 cells.ConclusionsHDAC7 reduction in COPD causes a defect of HIF-1α induction response to hypoxia with impaired VEGF gene expression. This poor cellular adaptation might play a role in the pathogenesis of COPD

Are clinicians being prepared to care for abused women? A survey of health professional education in Ontario, Canada

Background: The current project undertook a province-wide survey and environmental scan of educational opportunities available to future health care providers on the topic of intimate partner violence (IPV) against women. Methods: A team of experts identified university and college programs in Ontario, Canada as potential providers of IPV education to students in health care professions at the undergraduate and post-graduate levels. A telephone survey with contacts representing these programs was conducted between October 2005 and March 2006. The survey asked whether IPV-specific education was provided to learners, and if so, how and by whom. Results: In total, 222 eligible programs in dentistry, medicine, nursing and other allied health professions were surveyed, and 95% (212/222) of programs responded. Of these, 57% reported offering some form of IPV-specific education, with undergraduate nursing (83%) and allied health (82%) programs having the highest rates. Fewer than half of undergraduate medical (43%) and dentistry (46%) programs offered IPV content. Postgraduate programs ranged from no IPV content provision (dentistry) to 41% offering content (nursing). Conclusion: Significant variability exists across program areas regarding the methods for IPV education, its delivery and evaluation. The results of this project highlight that expectations for an active and consistent response by health care professionals to women experiencing the effects of violence may not match the realities of professional preparation

イリョウ ケア カンレン ハイエン ニ カンスル マエムキ エキガク チョウサ

医療ケア関連肺炎(HCAP)は,ATS/IDSAの肺炎のガイドライン(2005年)にて提唱された概念である.当院におけるHCAPの特徴を明らかにする目的で前向き研究を行った.2010年1～12月に獨協医科大学越谷病院呼吸器内科に市中肺炎で入院した患者を対象とした.HCAPと市中肺炎(CAP)の判断にあたっては, HCAP疑い因子の有無をアンケートにより調査した.それ以外の介入は行わず,背景因子,肺炎重症度,肺炎の再燃の有無について調査した.年齢はHCAP 73±10歳,CAP 65±9歳(p<0.05)と両群間で有意差を認め,HCAP群では悪性腫瘍の合併が多く(p<0.05),自立度が低かった(p<0.05).入院時検査所見,胸部X線点数は,両群間に有意差を認めなかった.肺炎重症度は,A-DROPでは,HCAP群が,軽症30%,中等症63%,重症7%,CAP群が,軽症75%,中等症12%,重症13%で,有意差がみられた(p<0.05)が,PSIスコアでは,重症度に有意差を認めなかった.30日以内の肺炎再燃はHCAP群で21%,CAP群では0%であった.本研究より,HCAPでは,入院時の重症度に関らず,より慎重な経過観察が必要であることが示唆された.詳細にHCAP危険因子に関する病歴を聴取し,HCAPをCAPと誤認しないようにすることが重要である.Backgrounds:Healthcare associated pneumonia(HCAP) is a new concept proposed in guidelines for themanagement of adults with hospital-acquired, ventilatorassociated,and healthcare-associated pneumonia by ATS/IDSA. Several retrospective studies investigating the characteristicof HCAP in Japan have been performed. However,at present, a cohort study exploring the characteristic ofHCAP in Japan has not been published.Patients and Methods:This study was a prospectiveobservational study. Patients with pneumonia who admittedto Dokkyo Medical University Koshigaya Hospital betweenJanuary and December in 2010 were enrolled in this study.After giving informed consent, the patients were requestedto fill out a questionnaire designed to obtain informationabout risk factors of HCAP and divided into groups, HCAPor CAP, and their clinical characteristics were observed.Results:Mean age of enrolled patients were 73±10 yr inHCAP and 65±9 yr in CAP (p<0.05). The percentage ofpatients with malignant diseases were higher in HCAPgroup (p<0.05). There were no statistically significant differencesin WBC, CRP or chest X ray score on admissionbetween the groups. A-DROP score showed statistically asignificant difference between the groups while PSI scoredid not. The recurrence of pneumonia within 30 days afterdischarge of hospital was 21 % in HCAP groups but 0 % inCAP group.Conclusion:This study showed that patients withHCAP need to receive more careful care and observation toprevent recurrence even though the severity of pneumoniaon admission was not very high. It is crucial to take patients\u27history carefully to identify correctly whether a patientis with HCAP or CAP

コキュウ キノウ ケンサ ニ オケル ヒマン ノ エイキョウ

肥満が呼吸機能に及ぼす影響に関しては,既に多くの報告がなされているが一定の見解が得られていないのが現状である.今回,われわれは喫煙歴がなく呼吸器疾患を有さない患者を対象とし,男女別にそれぞれ非肥満者群がBody Mass Index (以下BMI) を25未満とし,肥満者群がBMIを25以上として2群に分け,各検査値に対する肥満の影響を基準値との比率 (%) で比較検討した.今回の検討では,特に%予備呼気量 (%Expiratory Reserve Volume;以下%ERV) と%最大呼気口腔内圧(%Maximal mouth Expiratory Pressure;以下%MEP) で男女とも肥満の影響が認められた.%ERVは,非肥満者群に比べ肥満者群が男女ともに有意な低値となった.一方,%MEPでは非肥満者群に比べ肥満者群が男女ともに有意な高値となった.呼吸機能検査の基準値を求める予測式は,体重 (肥満) が考慮されていないため,判読の際には肥満の影響を考慮する必要性が示唆された.Backgrounds:Recently, the number of people with obesity is increasing. It is known that obesity affects respiratory systems including functions of diaphragm. However, the influence of obesity on respiratory function test is not clearly elucidated.Patients and Methods:Subjects who received pulmonary function tests in Department of Laboratory Medicine Dokkyo Medical University Koshigaya Hospital between November 2007 and June in 2008 were enrolled in this study. Smokers and Subjects with respiratory diseases were excluded. Enrolled subjects were divided into 2 groups, obesity group( Body Mass Index( BMI)≧25) and non-obesity( BMI<25) group, and pulmonary function test results were compared.Results:%Expiratory Reserve Volume (ERV) in obesity groups was significantly lower than that in non-obesity group. %Maximal mouth Expiratory Pressure (MEP) in obesity groups was significantly higher than that in non-obesity group. No significant differences were detected between 2 groups in %Vital Capacity, %Forced Expiratory Volume 1.0 % and V50/V25.Conclusion:A body weight value is not included in the predicting formula for calculation of standard value of each pulmonary function data. Therefore, the influence of obesity required to be considered when the pulmonary function test is carried out for patients with obesity

ドッキョウ イカ ダイガク コシガヤ ビョウイン ニオケル, フクブ チョウ オンパ ケンサ ニヨル タンノウ リュウキセイ ビョウヘン ノ ケントウ

腹部超音波検査が施行された3572 例を対象として胆嚢隆起性病変の検討を行った.胆嚢隆起性病変は3572例中791例( 22.1%) に認められ,重複検査例を除いた773例の平均年齢は59.6±13.6歳であり,男性370 例,女性403 例であった.胆嚢隆起性病変の最大径の平均は4.7±5.8 mm で,単発が256 例 (33.1%),多発が517例( 66.9%) であった.773例中,10 mm 以上の病変を有する症例は44 例( 5.6%) であった.これら44例の最終診断は,胆嚢良性ポリープ19例( 43.2%),胆嚢腺筋症2 例( 4.6%),胆泥貯留2 例( 4.6%),胆嚢結石2例( 4.6%) 切除可能胆嚢癌6例( 13.6%),切除不能胆嚢癌6 例( 13.6%),その他の癌2 例( 4.6%),不明5例( 11.3%) であり,胆嚢癌の半数が切除不能であった.今後,超音波検査を用いて切除可能な胆嚢癌をより多く拾い上げるためには,人間ドック等による,より幅広いスクリーニングが必要であると考えられた.The present study investigated the presence and characteristicsof elevated gallbladder lesions in 3572 patients whounderwent abdominal ultrasonography in our hospital betweenApril 2011 and March 2012. Elevated gallbladder lesionswere present in 791 patients (22.1 %). After excludingpatients who underwent repeat examination, 44 of theremaining 773 patients (5.6 %) had lesions &#8805; 10 mm. Finaldiagnoses in these 44 patients were as follows:benign gallbladderpolyp, n=19 (43.2 %);gallbladder adenomyosis,n=2 (4.6 %);biliary sludge accumulation, n=2 (4.6 %);gallbladder stone, n=2( 4.6%);resectable gallbladder cancer,n=6( 13.6%);non-resectable gallbladder cancer, n=6(13.6%);other cancers, n=2( 4.6%);and unknown, n=5(11.3 %). Wider screening during routine medical examinationssuch as annual health checks is required to enable increasedidentification of gallbladder cancer at an early stagewhen resection is still possible

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1-4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0-8·4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6-9·2) for males and 6·5% (5·4-7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs 1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-harm and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury

Global, regional, and national age-sex-specific mortality and life expectancy, 1950-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. Methods: The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. Findings: Globally, 18·7% (95% uncertainty interval 18·4–19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2–59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5–49·6) to 70·5 years (70·1–70·8) for men and from 52·9 years (51·7–54·0) to 75·6 years (75·3–75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5–51·7) for men in the Central African Republic to 87·6 years (86·9–88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3–238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6–42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2–5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. Interpretation: This analysis of age-sex-specific mortality shows that there are remarkably complex patterns in population mortality across countries. The findings of this study highlight global successes, such as the large decline in under-5 mortality, which reflects significant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing

Risk Factors of Local Oropharyngeal and Laryngeal Adverse Effects from Use of Single Inhaled Corticosteroids and Long-Acting Beta-Agonists

Background: : Single inhaled corticosteroids and long-acting beta-agonists (ICS/LABA) are clinically effective and safe. However, if local oropharyngeal and laryngeal adverse effects (LOLAE) appear, adherence to the use of ICS is impaired. To minimize the development of adverse effects, it is essential to identify the underlying risk factors. Methods: : The study included 481 asthmatic patients who were prescribed ICS/LABA for the first time in their life between January and September of 2010. Patients ranged in age from 14 to 86 years old and consisted of 281 never smokers and 200 smokers. All data were collected retrospectively by respirologists. Results: : Seventy-three out of 481 patients suffered from one or more adverse effects, with 54 of these exhibiting LOLAE. Patients with LOLAE (51.4 ± 16.2 yrs) were significantly older than those without LOLAE (43.7 ± 15.9 yrs) (p = 0.0011) and were also prescribed a significantly higher dose of ICS. The pack-years of patients with LOLAE (2.1 ± 4.9) were significantly lowerthan those without LOLAE (6.0 ± 13.0) (p = 0.0087). The type of administered ICS was also significantly associated with a risk of developing LOLAE. Conclusions: : Our survey indicated that a greater age, a higher dose of ICS, and the type of ICS were potential risk factors of LOLAE. The identified factors should be considered in a clinical setting in order to prevent the development of LOLAE and provide optimal treatment to patients

Clinical characteristics and cytokine profiles of adult obese asthma with type2 inflammation

Abstract Obesity-related non-eosinophilic asthma has been identified as a phenotype of asthma. However, mepolizumab and omalizumab improve asthma control in severe asthma with obesity, implying that type-2 cytokines may be involved in the deterioration of control in obese asthma. Despite this, the clinical details of obese asthma with positive type-2 inflammation markers have not yet been reported. The objective of this study was to investigate the clinical characteristics of patients with obese asthma with positive type-2 inflammation markers. Adult obese asthmatic patients were enrolled and were classified into two groups: obese asthma with positive type-2 inflammation markers (T2) and obese asthma with negative type-2 inflammation markers (NT2), then data were compared. In total, 434 patients were enrolled (85% of patients were at GINA therapy step 4–5). The T2 group had a higher proportion of patients with persistent asthma since childhood and with allergic rhinitis. A higher percentage of patients used high-dose inhaled corticosteroids (ICS) and experienced acute exacerbations (annual exacerbation ratio ≥ 1) in the T2 group. Multivariate logistic regression analysis showed that the T2 group was independently associated with younger age, comorbidity of allergic rhinitis, persistent asthma since childhood, use of high-dose ICS, and acute exacerbation rate ≥ 1. Adipocytokine levels were similar between the groups. Collectively, obese asthma with positive type-2 inflammation markers is characterised by a higher percentage of persistent asthma since childhood and more severe asthma