Nocturnal hypoxic stress activates invasive ability of monocytes in patients with obstructive sleep apnea syndrome

Backgrounds: Obstructive sleep apnea syndrome (OSAS) is known to be a risk factor of cardiovascular events. However, the precise mechanism has not been fully elucidated. OSAS-induced hypoxic stress may promote the production of inflammatory cytokines and chemokines by monocytes, which has a crucial role in the development of atherosclerosis. In addition, adhesion to the vascular endothelium and transendothelial migration of monocytes are considered to induce atherosclerosis. The aim of this study was to investigate the effects of hypoxic stress on the invasive ability of monocytes in OSAS. Methods; Twenty-one male OSAS patients and 17 male healthy control subjects, age- and body mass index-matched, were enrolled. Venous blood samples were collected not only before and after sleep but also after CPAP titration for the purpose of monocyte isolation. The invasive ability of monocytes was evaluated by counting the number of invasive cells using a BD BioCoat Matrigel Invasion Chamber. Results; The number of cells which represents invasive ability was significantly higher in OSAS patients as compared to control subjects in the early morning (p<0.001). Invasive ability in the early morning was significantly elevated as compared to that before sleep in OSAS patients (p<0.001), and it was positively correlated with oxygen desaturation index (p<0.05). CPAP titration led to alleviation of the invasive ability (p<0.001). Conclusions; The results indicate that OSAS-induced hypoxic stress activates the invasive ability of monocytes, and that this phenomenon observed during sleep may contribute to the development of atherosclerosis in OSAS.The definitive version is available at " http://dx.doi.org/10.1111/j.1440-1843.2009.01540.x "アジア太平洋呼吸器学会（APSR：Asia Pacific Society of Respirology）第1回最優秀論文賞「Fukuchi Award」受賞論

慢性閉塞性肺疾患患者における骨塩量の分布と体重および運動能との関連

Background: Although low bone mineral density is highly prevalent in patients with chronic obstructive pulmonary disease (COPD), the distribution of the reduced bone mass has not been fully elucidated. Objectives: To determine regional bone mass loss in patients with COPD and investigate whether the change in distribution may be associated with body weight loss and functional capacity. Methods: Body mass index (BMI) was assessed, and height squared indices were derived for the bone mineral content index (BMCI) of the arms, legs and trunk by dual-energy X-ray absorptiometry in 45 male patients with COPD and 12 age- and sex-matched control subjects. Pulmonary function tests were performed, and maximal oxygen uptake (V·O2max) was measured. Results: The BMCI was lower in the total bone, legs and trunk of patients with COPD than in control subjects, although the BMCI in the arms was similar between the groups. BMI correlated significantly with the BMCI in all 3 segments. Bone mineral content (BMC) in the trunk, expressed as a percentage of total BMC (BMC trunk/total BMC), correlated significantly with BMI. The BMCI in the trunk was closely related with V·O2max but not with airflow limitation. Conclusions: There was a regional difference in BMC reduction, but a predominant reduction of bone mass in the trunk was not associated with the severity of airflow limitation but rather with body weight loss and exercise intolerance. These data suggest that body weight loss and exercise intolerance are important risk factors for vertebral fracture in patients with COPD.博士（医学）・乙第1341号・平成26年7月22日The definitive version is available at " http://dx.doi.org/10.1159/000355095

Effect of Laughter Yoga on Pulmonary Rehabilitation in Patients with Chronic Obstructive Pulmonary Disease.

Objective: To evaluate the clinical usefulness of laughter yoga for patients with chronic obstructive pulmonary disease (COPD) in a pulmonary rehabilitation setting. Design: Pilot study, with randomization of participants. Setting: This study was conducted by the Yoshino-cho National Health Insurance Yoshino Hospital Department of Internal Medicine. Participants: Stable outpatients with COPD (7 men and 1 woman, age 64 to 84 years) participated in the pulmonary rehabilitation program during a 2-week period. Intervention : The patients were divided into two groups based on a sealed envelope randomization method. The laughter yoga group had a 10-min laughter yoga session before exercise training. Patients in both groups had exercise training, educational programs, lung physiotherapy, and nutrition counseling. Outcome Measures: Health-related quality of life using the St. George's Respiratory Questionnaire (SGRQ) and the Medical Research Council (MRC) Health Survey Short Form 36-item (SF-36), depression scores using the Self-rating Depression Scale (SDS), anxiety scores using State-Trait Anxiety Inventory (STAI), and spirometry, the 6-minute walk test and mMRC dyspnea scale results were evaluated before and at 2 weeks after the program in both groups. Results: There were significant improvements in the SGRQ impacts domain and the SF-36 general health domain in the laughter yoga group, while the SF-36 physical functioning domain significantly improved in the control group. SDS and STAI result did not significantly change in either group. Spirometry, the 6-minute walk test, and MRC dyspnea scale results did not significantly change in either group. Conclusion: Laughter yoga may improve the psychological quality of life in patients with COPD

HFA-BDP Metered-Dose Inhaler Exhaled Through the Nose Improves Eosinophilic Chronic Rhinosinusitis With Bronchial Asthma: A Blinded, Placebo-Controlled Study

Background: Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis with nasal polyps in Japanese. ECRS highly associated with asthma is a refractory eosinophilic airway inflammation and requires comprehensive care as part of the united airway concept. We recently reported a series of ECRS patients with asthma treated with fine-particle inhaled corticosteroid (ICS) exhalation through the nose (ETN).Objective: To evaluate fine-particle ICS ETN treatment as a potential therapeutic option in ECRS with asthma.Methods: Twenty-three patients with severe ECRS under refractory to intranasal corticosteroid treatment were randomized in a double-blind fashion to receive either HFA-134a-beclomethasone dipropionate (HFA-BDP) metered-dose inhaler (MDI) ETN (n = 11) or placebo MDI ETN (n = 12) for 4 weeks. Changes in nasal polyp score, computed tomographic (CT) score, smell test, and quality of life (QOL) score from baseline were assessed. Fractionated exhaled nitric oxide (FENO) was measured as a marker of eosinophilic airway inflammation. Response to corticosteroids was evaluated before and after treatment. Additionally, deposition of fine-particles was visualized using a particle deposition model. To examine the role of eosinophils on airway inflammation, BEAS-2B human bronchial epithelial cells were co-incubated with purified eosinophils to determine corticosteroid sensitivity.Results: HFA-BDP MDI ETN treatment improved all assessed clinical endpoints and corticosteroid sensitivity without any deterioration in pulmonary function. FENO and blood eosinophil number were reduced by HFA-BDP MDI ETN treatment. The visualization study suggested that ETN at expiratory flow rates of 10–30 L/min led to fine particle deposition in the middle meatus, including the sinus ostia. Co-incubation of eosinophils with BEAS-2B cells induced corticosteroid resistance.Conclusions: Additional HFA-BDP MDI ETN treatment was beneficial in patients with ECRS and should be considered as a potential therapeutic option for eosinophilic airway inflammation such as ECRS with asthma. (UMIN-CTR: R000019325) (http://www.umin.ac.jp/ctr/index.htm)

A case of meningitis-retention sydrome

　無菌性髄膜炎に尿閉や排尿障害が合併することがあり，髄膜炎尿閉症候群（meningitisretention syndrome：MRS）と呼ばれる．我々は，尿閉を合併した無菌性髄膜炎の１例を経験した．患者は28歳男性．38℃台の発熱，頭痛の後，排尿困難が出現した．抗菌薬レボフロキサシン 500mg/ 日を投与されたが解熱せず，当院を紹介受診した．受診した時点では頭痛は消失していた．血液検査，尿検査，頭部および胸腹部 CT 検査では，発熱の原因となる異常所見が見られず，精査目的で入院した．入院後も排尿困難が持続し，尿閉となった．無菌性髄膜炎に尿閉が合併した症例報告があることから，髄液検査を施行し，単核球優位の細胞増加を認め，髄膜炎と診断した．単純ヘルペスウイルス性髄膜炎の可能性を考慮し，抗ウイルス薬アシクロビル 750 mg/ 日の投与を開始し，解熱を認めた．髄液単純ヘルペスウイルスの PCR 検査が陰性と判明したため，アシクロビルの投与を中止した．髄液の細菌培養検査で細菌は検出されなかった．髄液再検にて，細胞数の改善を認めた．髄膜炎の改善に伴って，徐々に自尿が増加し，最終的には完全に自力で排尿が可能な状態に改善した．無菌性髄膜炎に尿閉や排尿障害が合併する場合があることを認識する必要がある．原因不明の尿閉をみた場合は，MRS も念頭に置くべきと考える．　Occurrence of urinary retention or dysuria during the clinical course of aseptic meningitis is called meningitis-retention syndrome (MRS). We report the case of a 28-year-old man who developed acute urinary retention during the clinical course of aseptic meningitis. He had presented high fever and headache followed by dysuria, and had been given antibiotics (Levofloxacin, 500 mg/day). As his fever did not subside, he was referred to our hospital. On admission, blood tests, urinalysis, and brain, chest, and abdominal CT revealed no abnormality. Later. he developed acute urinary retention and we performed a lumbar puncture. The results of cerebrospinal fluid (CSF) examination showed mononuclear leukocytosis, indicating he had meningitis. We suspected his meningitis could have been caused by herpes simplex, and started him on acyclovir (750 mg/day, on Day 14). His fever subsided and as PCR exmanination for herpes simplex virus was negative, acyclovir was withdrawn. Bacterial culture of CSF was also negative. Thereafter, examination of CSF showed an improvement of the cellularity profile. Finally, on Day 49 he could start to urinate by himself. Clinicians should be able to recognize MRS in a patient with refractory fever, who develops acute urinary retention or dysuria of unknown origin during the clinical course of hospitalization

Dynamic computed tomography is useful for prediction of pathological grade in pancreatic neuroendocrine neoplasm

BACKGROUND AND AIM: Pathological grading is important in defining the therapeutic strategy in pancreatic neuroendocrine neoplasm (PNEN) but is difficult for unresectable cases. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is useful in the diagnosis of PNEN, but its usefulness for pathological grading is not well established. No studies have examined the diagnostic ability of dynamic computed tomography (CT) for pathological grading of PNEN. We investigated the usefulness of EUS-FNA and dynamic CT in the diagnosis and pathological grading of PNEN. METHODS: In this retrospective study, 39 PNEN patients finally diagnosed via EUS-FNA and/or surgical resection underwent dynamic CT. Pathological samples were diagnosed based on WHO2010; staging was based on the European Neuroendocrine Tumor Society classification. The proportion of the quantification value in the tumor to the pancreatic parenchyma in arterial phase was defined as the CT ratio. Immunohistochemical staining with CD31 was performed to evaluate microvessel density (MVD). We evaluated the relationship between pathological grade, CT ratio, and MVD. RESULTS: By using EUS-FNA, 35 of 39 (90%) cases were diagnosed as PNEN. As for pathological grade, 15 of 35 (43%) cases could be identified correctly. CT ratio could predict pathological Grade 3 disease. The sensitivity, specificity, and diagnostic accuracy were 100%, 94%, and 95%. MVD was significantly correlated with CT ratio (r = 0.83, P < 0.0001) and pathological grade (P = 0.0074). CONCLUSIONS: Computed tomography ratio has a relationship with pathological grade in PNEN, which would help decide therapeutic strategy in unresectable cases and cases in which pathological grading is difficult

柴朴湯が著効を示した呼吸困難の１例

　西洋医学的検査に異常を認めない呼吸困難に，柴朴湯が著効した症例を経験したので報告する．症例は，２年間続く呼吸困難を訴える68歳の男性である．胸部Ｘ線，心電図，肺機能検査に異常なく，吸入ステロイド薬，吸入β2刺激薬の効果はなかった．そこで，柴朴湯を投与したところ，１週後には，呼吸困難が軽減し，２週後には，呼吸困難は完全に消失した．柴朴湯は，気管支喘息に用いる漢方薬として有名であるが，不安神経症にも効果があるとされる．本例のように，西洋医学的に異常がなく，心身症的な要素の強い呼吸困難患者に柴朴湯が有効であると考えられた．　A case in which Saibokuto has been effective for dyspnea without abnormalities in Western medical examination is reported. The case was 68-year-old male who complained of dyspnea lasting 2 years. His chest X-ray, electrocardiogram and pulmonary function test showed no abnormality, and inhaled corticosteroids and inhaled β2 stimulants had no effects on his dyspnea. Therefore, Saibokuto was administered, as a result, dyspnea was alleviated after one week and disappeared completely after two weeks. Saibokuto is famous as herbal medicine to be used for bronchial asthma, and it is said to have an effect on anxiety neurosis. As shown in this case, it is considered that Saibokuto is effective for dyspnea with strong psychosomatic factor showing no abnormality in Western medical examination

院内肺炎重症群（Ｃ群）に対するTazobactam/Piperacillin, Pazufloxacin 併用療法の有効性と安全性に関する検討

　院内肺炎重症群（Ｃ群）に対するTazobactam/Piperacillin（TAZ/PIPC），Pazufloxacin（PZFX）併用療法の有効性と安全性を検討した．院内肺炎重症群（C 群）20例を対象とし，TAZ/PIPC １回4.5g，１日３回， PZFX １回500mg，１日２回の併用投与を行い，その臨床効果，細菌学的効果，副作用などにつき検討した．その結果，臨床効果は，有効率60.0％（20例中12例有効）であった．細菌学的効果は，除菌率69.2％（13株中９株除菌）であり，Escherichia coli ３株中３株，Streptococcus pneumoniae ２株中２株，methicillin-sensitive Staphylococcus aureus ，Serratiamarcescense 各々１株中１株，Enterococcus faealis ，Pseudomonas aeruginosa 各々２株中１株が除菌された．副作用として，注射部位静脈炎が３例（15.0％）にみられ，臨床検査値の異常変動は８例（40.0％：肝機能障害４例，腎機能障害４例）にみられたが，いずれも軽度であった．以上より，TAZ/PIPC, PZFX 併用投与は，院内肺炎重症群（Ｃ群）に対して推奨できる治療法と考えられた．　The clinical effect and safety of Tazobactam/piperacillin and Pazufloxacin combination therapy on hospital-acquired pneumonia severe group (C group) was evaluated. Twenty patients were treated by combination of TAZ/PIPC (4.5g per dose, 3 times daily) and PZFX (500mg per dose, twice daily) .　Clinical effect, bacteriological effect, and adverse events were examined. Clinical efficacy rate was 60.0% (effectiveness in 12 of 20 patients). As for bacteriological effect, 3 of 3 Escherichia coli strais , 2 of 2 Streptococcus pneumoniae strains, 1 of 1 methicillin-sensitive Staphylococcus aureus strain and Serratia marcescense strain respectively, 1 of 2 Enterococcus faealis strains and Pseudomonas aeruginosa strains respectively were eradicated. In total, 9 (69.2%) of 13 strains were eradicated. Adverse events were infection site phlebitis in 3 patients (15.0%), and abnormal laboratory findings were observed including mild liver dysfunction in 4 patients and mild renal dysfunction in 4 patients. Consequently, TAZ/PIPC and PZFX combination therapy is recommended for hospital-acquired pneumonia severe group(C group)

An adult female suspected case of herpangina presenting with fever, headache, and oral phlyctenula

　ヘルパンギーナは，発熱と口腔粘膜の水疱性の発疹が特徴の急性のウイルス性咽頭炎で，おもに小児にみられ，夏に流行する．我々は，発熱，頭痛，軟口蓋の小水疱を呈し，ヘルパンギーナが疑われた成人女性の１例を経験したので報告する．患者は25歳，女性．７月に発熱，頭痛，嘔気を主訴に受診し，入院となった．血液検査では，CRP とプロカルシトニンの上昇を認めた．頭部 CT では，出血や占拠性病変は見られなかった．胸腹部 CT では，熱源となる異常所見は見られなかった．抗菌薬投与と対症療法を行い，発熱，頭痛は改善を認めた．口腔内違和感の訴えがあり，口腔内所見で軟口蓋に紅暈を伴う小水疱を数個認め，エンテロウイルス属感染症（ヘルパンギーナ）が疑われた．エンテロウイルス属のウイルス抗体検査では，原因ウイルスは特定できなかった．夏期に発熱，口内炎を呈する場合には，成人でもへルパンギーナを鑑別に挙げる必要があると考える．　Herpangina is an acute viral pharyngitis which presents with fever and oral phlyctenula. It is commonly seen in children, usually during summer. We report an adult female suspected of having developed herpangina because on admission she presented with fever, headache, and oral phlyctenula. The 25-year-old female underwent a medical check at our hospital because of fever, headache, and nausea in July. She was admitted to our hospital. The blood test showed elevation of C-reactive protein and procalcitonin. Brain CT scan showed no bleeding nor any space occupying lesion. Chest and abdominal CT scan showed no lesion of fever origin. Her fever and headache improved after antibiotics and symptomatic treatment. But the patient felt that something was wrong within her oral cavity. Herpangina was suspected because of the presence of phlyctenula with a red halo in the soft palate. Viral antibody test of enteroviruses did not identify viruses that commonly cause herpangina. This case indicates that herpangina should be considered for the differential diagnosis during medical examination of an adult patient who presents with fever and stomatitis during summer