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Purpose: This study aimed to identify patient’s reason for no-show at a university eye clinic after ophthalmic examination via a mobile ophthalmic unit, which provides comprehensive ophthalmic care to underserved communities in a region of Brazil. Methods: In 2017/2018, this prospective observational study searched for no-shows at referrals to a university eye clinic after an outreach program screening via a mobile ophthalmic unit in 10 municipalities in the central-western region of São Paulo, Brazil. A total of 1,928 patients underwent a comprehensive eye examination at no cost, and 37.1% of them needed referral to a university eye clinic for specialized examinations or surgeries. We used the following two main tools: (1) comparative analysis between patients who attended the referral and those who did not; (2) active search using a questionnaire to assess reasons for no-show. Results: Attendance to referrals was not influenced by age, gender, distance from the university hospital, number of ophthalmologists in the municipality, average family income, and visual acuity. The main cause for referrals was cataract (350 cases). No-show was most common among glaucoma/suspected glaucoma (54.1%) cases, followed by strabismus (45%) and anterior segment disease (33.6%) cases. Many patients who did not attend the referral sought another service. Conclusion: Patient’s issues and lack of knowledge regarding their ophthalmic condition are the main reasons for no-show at referrals for free ophthalmic care. Thus, educational campaigns are needed to achieve consistently high attendance to prevent avoidable blindness. RESUMO Objetivo: Avaliar as razões para não comparecimento à clínica oftalmológica da universidade após triagem oftalmológica realizada usando uma unidade móvel oftalmológica que fornece exame oftalmológico para comunidades não assistidas em uma região do Brasil. Métodos: Foi realizado um estudo observacional prospectivo no ano de 2017/2018 para avaliar as razões que fizeram com que os indivíduos triados usando uma unidade móvel oftalmológica e referenciados para a clínica oftalmológica da universidade não comparecessem à consulta agendada. A triagem foi feita em 10 municípios da região centro-oeste do estado de São Paulo, Brasil. Todos os 1.928 participantes fizeram o exame oftalmológico sem custo e 37,1% deles necessitaram de encaminhamento para a clínica oftalmológica da universidade para exames especializados ou cirurgias. O estudo usou duas ferramentas: (1) análise comparativa entre os dados dos indivíduos encaminhados que compareceram ao agendamento com os que não compareceram; (2) busca ativa dos indivíduos que não compareceram à consulta agendada, aplicando-se um questionário para avaliar os motivos para o não comparecimento. Resultados: Fatores como idade, sexo, distância entre a cidade de origem e o hospital universitário, número de oftalmologistas na cidade de procedência, renda familiar média e acuidade visual não influenciaram no comparecimento ao encaminhamento. Catarata foi a maior causa para o encaminhamento (350 casos). O não comparecimento foi maior nos portadores de glaucoma/glaucoma suspeitos (54,1%), estrabismo (45%) e afecções do segmento anterior (33,6%). Muitos indivíduos que não compareceram ao serviço de referência procuraram por outro local para o atendimento oftalmológico. Conclusão: O não comparecimento para tratamento oftalmológico sem custo depende de fatores relacionados ao paciente ou à falta de conhecimento das próprias condições oftalmológicas. Campanhas educativas nas comunidades assistidas devem ser feitas para alcançar maior comparecimento às consultas e melhor prevenir a cegueira evitável.

Takanori Numata, Jun Araya, Hanae Miyagawa, Keitaro Okuda, Yu Fujita, Hirofumi Utsumi, Daisuke Takekoshi, Mitsuo Hashimoto, Shunsuke Minagawa, Takeo Ishikawa, Hiromichi Hara, Kazuyoshi Kuwano Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, JapanCorrespondence: Takanori Numata Tel +81-3-3433-1111 (ex 3271)Fax +81-3-3433-1020Email t-numata@jikei.ac.jpBackground: In Japan, biologic therapy was initiated for patients with severe asthma in 2009. In recent years, four biologics with different mechanisms of action have become available in the clinical setting. However, the efficacy of switching between biologics remains uncertain.Methods: To elucidate the efficacy of switching between biologics, 97 patients were enrolled who had received any biologic therapy for severe asthma at Jikei University Hospital, Tokyo, Japan, from July 2009 to December 2020. We retrospectively examined the patient characteristics, biomarkers, pulmonary function test results, selected biologics, and efficacy.Results: Thirty-one males and 66 females received any biologics. The mean age was 53.3 years at the initiation of biologic therapy. Initially, 33, 41, 15 and eight patients received omalizumab, mepolizumab, benralizumab, and dupilumab, respectively. Among three representative indicators for biologics administration, the peripheral blood eosinophil count, serum IgE levels and fractional exhaled nitric oxide, 64% of the patients had two indicators, and 28% had three indicators. Thirty-four patients (35%) switched from the initial biologic to another, and the reasons for switching included persistent asthmatic symptoms (n=22), schedule of hospital visits (n=5), and other reasons. Thus, the treatment was effective in 11 patients after switching. In addition, two patients received combination therapy with different biologics. Eighteen patients (19%) interrupted treatment for various reasons. Regardless of whether the biologic was the initial therapy, the overall efficacy of the four biologics was 60% based on the global evaluation of treatment effectiveness.Conclusion: Switching between biologics can be a promising option for severe asthma patients in whom treatment with an initial biologic is ineffective.Keywords: benralizumab, dupilumab, mepolizumab, omalizumab, switching

For the hydrogen tanks of type 2 and 3, the metal lining and composite wrapping are bonded together by adhesive. To ensure the safety of these tanks for long-term use, nondestructive testing (NDT) and nondestructive evaluation (NDE) of their plastic composite/metal adhesive bonds are required. However, up to now, there is no effective NDT method for the debonding detection of hydrogen tanks of type 2 and 3. In this study, we propose the use of electromagnetic-pulse-induced acoustic testing (EPAT) to generate guided waves in plastic composite/metal adhesive bonding to detect debonding in adhesive parts. The EPAT method can excite the electromagnetic force from outside of the plastic composite material without contact, thereby directly exciting sound waves on the metal contacting the plastic composite. Through reasonable design, the intensity of the pulsed magnetic field can pass through a very thick plastic composite material and directly induces guided waves in the inner side metal. Therefore, EPAT method has the potential to detect the debonding of plastic composite/metal adhesive bonding in hydrogen tanks of type 2 and type 3 at the site of use. EPAT testing of acrylic/aluminum, glass-fiber-reinforced plastic/aluminum, and carbon-fiber-reinforced plastic/aluminum specimens was performed. The testing signals were analyzed in the time domain and frequency domain. The results indicate that the time-domain signals exhibited guided wave dispersion characteristics. In addition, the guided wave signals showed significant differences between the specimen with debonding and that without debonding, which could be used for the detection of debonding. In addition, different frequency guided waves had different sensitivities to debonding defects.

We report the case of a 56-year-old man with chronic myeloid leukemia (CML) who developed dasatinib-induced interstitial lung disease (ILD) 7 years after starting dasatinib, a BCR-ABL1 inhibitor. The patient presented with dyspnea. Chest imaging showed diffuse ground-glass opacities. A surgical lung biopsy showed cellular non-specific interstitial pneumonia (NSIP). Corticosteroid treatment ameliorated his condition. Bosutinib, another BCR-ABL1 inhibitor, was successfully re-instituted. The present case and relevant literature suggest that dasatinib-induced ILD can present as NSIP after an extended period, responds to corticosteroids, and is amenable to re-challenge at a lower-dose or with alternative BCR-ABL1 inhibitors.

Introduction: Insufficient autophagic degradation has been implicated in accelerated cellular senescence during chronic obstructive pulmonary disease (COPD) pathogenesis. Cigarette smoke (CS)-induced functional deterioration of lysosomes may be associated with impaired autophagy. Lysosomal membrane permeabilization (LMP) is indicative of damaged lysosomes, and galectin-3 and tripartite motif proteins (TRIM)16 play a cooperative role in recognizing LMP and inducing lysophagy, a lysosome selective autophagy for maintaining lysosome function. Methods: To examine the role of TRIM16-mediated lysophagy in regulating CS-induced LMP and cellular senescence during COPD pathogenesis, using human bronchial epithelial cells (HBEC) and lung tissues. Results: CS extract (CSE) induced LMP as detected by galectin-3 accumulation and TRIM16 was involved in CSE-induced lysophagy. Impaired lysophagy was associated with lysosomal dysfunction and accelerated cellular senescence. Airway epithelial cells in COPD lungs showed increase in lipofuscin, aggresome, and galectin-3 puncta reflecting accumulation of lysosomal damage with concomitantly reduced TRIM16 expression levels. HBEC isolated from COPD patients showed reduced TRIM16 but increased galectin-3, and a negative correlation between TRIM16 and galectin-3 protein levels was demonstrated. Conclusion: Damaged lysosomes with LMP are accumulated in epithelial cells in COPD lungs, which can be at least partly attributed to impaired TRIM16-mediated lysophagy. Increased LMP in lung epithelial cells may be responsible for COPD pathogenesis through the enhancement of cellular senescence.

Materials composed of metals and plastic composites joined through adhesive bonding are being increasingly used. However, debonding of such materials may occur during manufacture or use. Non-destructive testing of adhesive bonding structures is required to evaluate their debonding. Herein, electromagnetic pulse-induced acoustic testing (EPAT) was used to detect debonding at the adhesive joint in plastic composite/metal specimens. EPAT uses a pulsed excitation current to generate guided waves in a specimen to detect debonding without contact, which makes it suitable for testing from the plastic composite side. Simulations were performed to analyze acrylic/aluminum (Al) and carbon fiber-reinforced plastic (CFRP)/Al specimens. The results showed that the Lorentz force in the z direction was the dominant mechanism in the generation of guided waves, and mainly the A0-mode Lamb wave was excited. The simulation and experimental results revealed that for specimens where the mechanical parameters of the plastic composite layer differed greatly from those of the metal, such as the acrylic/Al specimen, debonding could only be detected directly above debonding. Therefore, it is necessary to evaluate the debonding position by scanning the receiver sensor. Conversely, for specimens with reasonably similar mechanical parameters of the plastic composite and metal layers, like the CFRP/Al specimen, the debonding position could be evaluated by scanning the receiver sensor or excitation coil.

Insufficient autophagic degradation has been implicated in accelerated cellular senescence during chronic obstructive pulmonary disease (COPD) pathogenesis. Aging-linked and cigarette smoke (CS)–induced functional deterioration of lysosomes may be associated with impaired autophagy. Lysosomal membrane permeabilization (LMP) is indicative of damaged lysosomes. Galectin-3 and tripartite motif protein (TRIM) 16 play a cooperative role in recognizing LMP and inducing lysophagy, a lysosome-selective autophagy, to maintain lysosome function. In this study, we sought to examine the role of TRIM16-mediated lysophagy in regulating CS-induced LMP and cellular senescence during COPD pathogenesis by using human bronchial epithelial cells and lung tissues. CS extract (CSE) induced lysosomal damage via LMP, as detected by galectin-3 accumulation. Autophagy was responsible for modulating LMP and lysosome function during CSE exposure. TRIM16 was involved in CSE-induced lysophagy, with impaired lysophagy associated with lysosomal dysfunction and accelerated cellular senescence. Airway epithelial cells in COPD lungs showed an increase in lipofuscin, aggresome and galectin-3 puncta, reflecting accumulation of lysosomal damage with concomitantly reduced TRIM16 expression levels. Human bronchial epithelial cells isolated from COPD patients showed reduced TRIM16 but increased galectin-3, and a negative correlation between TRIM16 and galectin-3 protein levels was demonstrated. Damaged lysosomes with LMP are accumulated in epithelial cells in COPD lungs, which can be at least partly attributed to impaired TRIM16-mediated lysophagy. Increased LMP in lung epithelial cells may be responsible for COPD pathogenesis through the enhancement of cellular senescence.

This paper describes the detectability of eddy current testing (ECT) using directional eddy current for detection of in-plane fibre waviness in unidirectional carbon fibre reinforced plastic (CFRP) laminate. Three different types of probes, such as circular driving, symmetrical driving and uniform driving probe, were proposed, and the waviness angle was extracted from the contour map of the ECT signal by applying a Canny filter and a Hough transform. By comparing both the waviness angle estimated by ECT and that obtained by an X-ray CT image, the standard deviation (precision) and root mean square error (accuracy) were evaluated to discuss the detectability of these probes. The directional uniform driving probe shows the best detectability and can detect fibre waviness with a waviness angle of more than 2° in unidirectional CFRP. The probe shows a root mean square error of 1.90° and a standard deviation of 4.49° between the actual waviness angle and the angle estimated by ECT. This article is part of the theme issue ‘Advanced electromagnetic non-destructive evaluation and smart monitoring’.

Background Benralizumab, an anti-interleukin-5 (IL-5) receptor α monoclonal antibody, significantly reduces the number of annual exacerbations and oral corticosteroid (OCS) maintenance doses for patients with severe eosinophilic asthma (SEA). However, few studies on the efficacy of this biologic in real life are available. The aim was to elucidate the efficacy of benralizumab by evaluating changes in clinical parameters after benralizumab treatment in patients with SEA. Methods From July 2018 to December 2019, 24 Japanese patients with SEA received benralizumab at Jikei University Hospital. We retrospectively evaluated the patients’ characteristics, parameters, numbers of exacerbations and maintenance OCS doses. Results Among the 24 patients, eleven patients had received mepolizumab treatment and were directly switched to benralizumab. The peripheral blood eosinophil and basophil counts significantly decreased after benralizumab treatment regardless of previous mepolizumab treatment. Pulmonary function, Asthma Control Test scores, the numbers of annual exacerbations and maintenance OCS doses in patients without previous mepolizumab treatment tended to improve without significant differences. Fourteen patients (58%) were responders according to the Global Evaluation of Treatment Effectiveness (GETE) score. The proportion of GETE responders among patients with aspirin-exacerbated respiratory disease (AERD) tended to be lower than that among patients without AERD (p = 0.085). After benralizumab treatment, the change in the forced expiratory volume in 1 s from baseline was 200 ml or greater in eight patients (33%), including three patients who were switched from mepolizumab. Conclusion Benralizumab treatment improved and controlled asthma symptoms based on the GETE score.

Cigarette smoke (CS) induces accumulation of misfolded proteins with concomitantly enhanced unfolded protein response (UPR). Increased apoptosis linked to UPR has been demonstrated in chronic obstructive pulmonary disease (COPD) pathogenesis. Chaperone-mediated autophagy (CMA) is a type of selective autophagy for lysosomal degradation of proteins with the KFERQ peptide motif. CMA has been implicated in not only maintaining nutritional homeostasis but also adapting the cell to stressed conditions. Although recent papers have shown functional cross-talk between UPR and CMA, mechanistic implications for CMA in COPD pathogenesis, especially in association with CS-evoked UPR, remain obscure. In this study, we sought to examine the role of CMA in regulating CS-induced apoptosis linked to UPR during COPD pathogenesis using human bronchial epithelial cells (HBEC) and lung tissues. CS extract (CSE) induced LAMP2A expression and CMA activation through a Nrf2-dependent manner in HBEC. LAMP2A knockdown and the subsequent CMA inhibition enhanced UPR, including CHOP expression, and was accompanied by increased apoptosis during CSE exposure, which was reversed by LAMP2A overexpression. Immunohistochemistry showed that Nrf2 and LAMP2A levels were reduced in small airway epithelial cells in COPD compared with non-COPD lungs. Both Nrf2 and LAMP2A levels were significantly reduced in HBEC isolated from COPD, whereas LAMP2A levels in HBEC were positively correlated with pulmonary function tests. These findings suggest the existence of functional cross-talk between CMA and UPR during CSE exposure and also that impaired CMA may be causally associated with COPD pathogenesis through enhanced UPR-mediated apoptosis in epithelial cells.

Background Postoperative pulmonary complications (PPC) in patients with pulmonary diseases remain to be resolved clinical issue. However, most evidence regarding PPC has been established more than 10 years ago. Therefore, it is necessary to evaluate perioperative management using new inhalant drugs in patients with obstructive pulmonary diseases. Methods April 2014 through March 2015, 346 adult patients with pulmonary diseases (257 asthma, 89 chronic obstructive pulmonary disease (COPD)) underwent non-pulmonary surgery except cataract surgery in our university hospital. To analyze the risk factors for PPC, we retrospectively evaluated physiological backgrounds, surgical factors and perioperative specific treatment for asthma and COPD. Results Finally, 29 patients with pulmonary diseases (22 asthma, 7 COPD) had PPC. In patients with asthma, smoking index (≥ 20 pack-years), peripheral blood eosinophil count (≥ 200/mm3) and severity (Global INitiative for Asthma(GINA) STEP ≥ 3) were significantly associated with PPC in the multivariate logistic regression analysis [odds ratio (95% confidence interval) = 5.4(1.4–20.8), 0.31 (0.11–0.84) and 3.2 (1.04–9.9), respectively]. In patients with COPD, age, introducing treatment for COPD, upper abdominal surgery and operation time (≥ 5 h) were significantly associated with PPC [1.18 (1.00–1.40), 0.09 (0.01–0.81), 21.2 (1.3–349) and 9.5 (1.2–77.4), respectively]. Conclusions History of smoking or severe asthma is a risk factor of PPC in patients with asthma, and age, upper abdominal surgery, or long operation time is a risk factor of PPC in patients with COPD. Adequate inhaled corticosteroids treatment in patients with eosinophilic asthma and introducing treatment for COPD in patients with COPD could reduce PPCs.

Immune checkpoint inhibitor (ICI)-related pneumonitis is a relatively rare but clinically serious and potentially life-threatening adverse event. The majority of cases can be managed by drug discontinuation, with the administration of corticosteroids added in severe cases. However, worsening of pneumonitis can develop in a subset of patients despite treatment with high doses of corticosteroids. We herein report a case of steroid-refractory ICI-related pneumonitis in a recurrent non-small cell lung cancer (NSCLC) patient treated with pembrolizumab that was successfully improved by triple combination therapy (high-dose corticosteroids, tacrolimus, and cyclophosphamide). After 3 weeks of initial pembrolizumab administration, the patient was diagnosed with ICI-related pneumonitis. Chest computed tomography (CT) showed patchy distributed bilateral consolidation and ground-glass opacities (GGOs) with traction bronchiectasis and bronchiolectasis resembling the diffuse alveolar damage (DAD) radiographic pattern. Although methylprednisolone pulse therapy was initiated, worsening of respiratory failure resulted in the patient being transferred to the intensive care unit. Because of an insufficient therapeutic response to high-dose corticosteroids, tacrolimus and cyclophosphamide pulse therapy were additively performed as triple combination therapy according to the treatment strategy for pulmonary complications of clinically amyopathic dermatomyositis (CADM). In response to this triple combination therapy, the patient’s respiratory condition gradually improved, and chest CT showed the marked amelioration of pulmonary opacities. This is the first report suggesting the efficacy of triple combination therapy (high-dose corticosteroids, tacrolimus, and cyclophosphamide) for steroid-refractory ICI-related pneumonitis complicated with respiratory failure.

Mepolizumab significantly reduces the number of annual exacerbations (AEs) and the maintenance dose of systemic corticosteroids (CSs) in patients with severe eosinophilic asthma (SEA). However, there are few studies based on real life with a long-term observational period in Japan. Between July 2016 and December 2019, 24 Japanese patients received mepolizumab at Jikei University Hospital for at least 12 months. We retrospectively evaluated these characteristics, AEs and CS doses. To elucidate the predictors of the enhanced responders, we performed multivariate logistic regression analysis. After introduction, asthma symptoms improved and were maintained for over a year. The number of AEs and CS doses significantly decreased. In the subgroup analysis, the younger than 65 years-old, body mass index (BMI) < 25 kg/m2, eosinophilic chronic rhinosinusitis, or eosinophil count ≥ 400/mm3 exhibited effective reductions in either AEs or CS doses with mepolizumab treatment. The percentage change in the AEs (≤ −75%) was significantly decreased in the patients with a BMI < 25 using multivariate logistic regression analysis (odds ratio 31, 95% confidence interval: 1.4–700, P = 0.03). In real-life, BMI < 25 could be a predictor for reductions in AEs with mepolizumab treatment in the patients with SEA. Abbreviations IL, interleukin; CS, corticosteroid; SEA, severe eosinophilic asthma; BMI, body mass index; ECRS, eosinophilic chronic rhinosinusitis; CRSwNP, chronic rhinosinusitis with nasal polyps

Introduction: Sarcopenia characterized by the loss of skeletal muscle mass and strength is prevalent in COPD. Sarcopenia has a huge impact on physical activity and is associated with increased mortality in COPD, but detailed molecular mechanism is still unclear. Increased reactive oxygen species (ROS) production and altered mitochondrial function has been reported in limb skeletal muscle of COPD. Previous study reported that muscle-specific depletion of autophagy was associated with increased ROS production in skeletal muscle. Although we have demonstrated the involvement of impaired Parkin-mediated mitochondria-selective autophagy, mitophagy in COPD pathogenesis, participation of mitophagy in sarcopenia progression associated with cigarette smoke (CS) exposure remains to be elucidated. Methods: Myoblasts were isolated from mouse limbs. CS extracts (CSE) was used to examine the effect of CS on myotube differentiation, reflecting myogenesis ability of myoblasts. Wild type (WT) myoblasts and Parkin knockout (KO) derived myoblasts were treated with 0.5 % CSE. Fusion index (the degree of differentiation from myoblast to myotube) and quantitative reverse transcription (RT)-PCR for myogenin (a marker for myotube differentiation) were performed. Results: Fusion index was significantly reduced by CSE exposure in WT myoblasts. Parkin KO myoblasts also showed reduced fusion index even in the absence of CSE. The expression levels of myogenin mRNA were decreased in CSE-exposed WT myoblasts and in Parkin KO myoblasts without CSE treatment. Conclusion: These results suggest that Parkin-mediated mitophagy may have a regulatory role in myogenesis during CS exposure as a part of sarcopenia pathogenesis in COPD.

The imbalanced redox status in lung has been widely implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis. To regulate redox status, hydrogen peroxide must be adequately reduced to water by glutathione peroxidases (GPx). Among GPx isoforms, GPx4 is a unique antioxidant enzyme that can directly reduce phospholipid hydroperoxide. Increased lipid peroxidation products have been demonstrated in IPF lungs, suggesting the participation of imbalanced lipid peroxidation in IPF pathogenesis, which can be modulated by GPx4. In this study, we sought to examine the involvement of GPx4-modulated lipid peroxidation in regulating TGF-β–induced myofibroblast differentiation. Bleomycin-induced lung fibrosis development in mouse models with genetic manipulation of GPx4 were examined. Immunohistochemical evaluations for GPx4 and lipid peroxidation were performed in IPF lung tissues. Immunohistochemical evaluations showed reduced GPx4 expression levels accompanied by increased 4-hydroxy-2-nonenal in fibroblastic focus in IPF lungs. TGF-β–induced myofibroblast differentiation was enhanced by GPx4 knockdown with concomitantly enhanced lipid peroxidation and SMAD2/SMAD3 signaling. Heterozygous GPx4-deficient mice showed enhancement of bleomycin-induced lung fibrosis, which was attenuated in GPx4-transgenic mice in association with lipid peroxidation and SMAD signaling. Regulating lipid peroxidation by Trolox showed efficient attenuation of bleomycin-induced lung fibrosis development. These findings suggest that increased lipid peroxidation resulting from reduced GPx4 expression levels may be causally associated with lung fibrosis development through enhanced TGF-β signaling linked to myofibroblast accumulation of fibroblastic focus formation during IPF pathogenesis. It is likely that regulating lipid peroxidation caused by reduced GPx4 can be a promising target for an antifibrotic modality of treatment for IPF.

Background Several major randomized control studies have demonstrated that mepolizumab, an anti-IL-5 monoclonal antibody, is effective for patients with severe eosinophilic asthma who show exacerbation or require systemic corticosteroid maintenance therapy. However, the predictive factors of the response to mepolizumab other than blood eosinophil count are unclear in clinical practice. Objective To elucidate the predictive factors of the response to mepolizumab for patients with severe eosinophilic asthma. Methods From July 2016 to December 2017, 28 patients with severe asthma received mepolizumab in our hospital. To determine the predictive factors, we retrospectively evaluated patient characteristics, comorbidities, biomarkers, pulmonary function, maintenance dose of systemic corticosteroids and number of exacerbations. Results The response rate to mepolizumab treatment was 70% (19/27; one pregnant woman was excluded from analysis). Compared with 11 patients without eosinophilic chronic rhinosinusitis (ECRS), 16 patients with ECRS showed significantly improved systemic corticosteroid-sparing effects [− 71.3 ± 37.0% vs − 10.7 ± 20.1%, P = 0.006], change from baseline FeNO [− 19 ± 57 (%) vs 30 ± 77 (%), P = 0.023] and symptoms [14 patients (88%) vs five patients (45%), P = 0.033]. ECRS was identified as a predictive factor of the response to mepolizumab in a multivariate logistic regression analysis [odds ratio = 22.5, 95% CI (1.5–336), P = 0.024]. Of the eight patients previously administered omalizumab, five responded to mepolizumab. Staphylococcus aureus enterotoxin B IgE results were negative in 80% of responders (P = 0.14). Conclusion Both groups showed improved symptom scores and a decreased number of exacerbations. Mepolizumab substantially improved the clinical variables of patients with eosinophilic asthma complicated with ECRS.

Chronic airway inflammation and fibrosis, known as airway remodeling, are defining features of chronic obstructive pulmonary disease and are refractory to current treatments. How and whether chronic inflammation contributes to airway fibrosis remain controversial. In this study, we use a model of chronic obstructive pulmonary disease airway disease utilizing adenoviral delivery of IL-1β to determine that adaptive T cell immunity is required for airway remodeling because mice deficient in α/β T cells (tcra−/−) are protected. Dendritic cells (DCs) accumulate around chronic obstructive pulmonary disease airways and are critical to prime adaptive immunity, but they have not been shown to directly influence airway remodeling. We show that DC depletion or deficiency in the crucial DC chemokine receptor ccr6 both protect from adenoviral IL-1β–induced airway adaptive T cell immune responses and fibrosis in mice. These results provide evidence that chronic airway inflammation, mediated by accumulation of α/β T cells and driven by DCs, is critical to airway fibrosis.

Introduction: Downregulation of lamin B1 has been recognized to be a crucial step for development of full senescence. Accelerated cellular senescence linked to dysregulated autophagy and mTOR activation have been implicated in COPD pathogenesis. We have demonstrated reduced lamin B1 was associated with COPD pathogenesis through activating mTOR during cigarette smoke extract (CSE) exposure in human bronchial epithelial cells (HBEC). Methods: To further elucidate the mechanisms for lamin B1 downregulation related to autophagy, confocal microscopic evaluation and immunoprecipitation were performed in HBEC. DNA microarray and mass spectrometry were examined. C57BL/6J mice were exposed to cigarette smoke over a 6-month period as COPD model. Results: LaminB1 reduction during CSE exposure was recovered by lysosomal protease inhibitors and ATG5 knockdown. Confocal microscopic evaluation detected cytoplasmic colocarization between lamin B1 and LC3, reflecting autophagic degradation. DNA microarray and mass spectrometry demonstrated decrease in DEPTOR expression, an mTOR inhibitor by lamin B1 knockdown, which was responsible for subsequent autophagy impairment and cellular senescence. Lamin B1 knockdown also enhanced histone modification of H4K20me3. Decreased lamin B1 and DEPTOR with concomitantly increased p62 reflecting insufficient autophagic degradation were demonstrated in lung homogenate from cigarette smoke exposed-mice. Conclusion: These findings suggest CSE-induced autophagic degradation is involved in the mechanisms of lamin B1 reduction. Phenotypic alterations linked to cellular senescence can be attributed to epigenetic histone modifications by reduced laminB1.

Background: Prostaglandin E2 (PGE2) is metabolized to prostaglandin E-major urinary metabolite (PGE-MUM). Enhanced cyclooxygenase-2 (COX-2) expression demonstrated in lung adenocarcinoma indicates increased PGE-MUM levels in patients with lung adenocarcinoma. Objectives: We aimed to elucidate the clinical usefulness of measuring PGE-MUM as an indicator of tumor burden in patients with lung adenocarcinoma. Methods: PGE-MUM was measured by a radioimmunoassay in control healthy volunteers (n = 124) and patients with lung adenocarcinoma (n = 54). Associations between PGE-MUM levels and clinical characteristics of the patients (including lung cancer stage and TNM factors (T: Tumor, N: Node, M: Metastasis) were examined. Results: PGE-MUM levels were significantly elevated in patients with lung adenocarcinoma. A PGE-MUM level of 14.9 &mu, g/g∙Cr showed 70.4% sensitivity and 67.7% specificity for the diagnosis of lung adenocarcinoma. PGE-MUM levels tended to be positively correlated with cancer progression as determined by the TNM staging system. Advanced stage (stage III, stage IV, and recurrence) was significantly associated with high PGE-MUM levels by logistic regression analysis. No apparent correlation was demonstrated between PGE-MUM and carcinoma embryonic antigen (CEA) levels. Conclusions: PGE-MUM can be a promising biomarker reflecting the systemic tumor burden of lung adenocarcinoma.

© 2017 the American Physiological Society. Small airway fibrosis is a major pathological feature of chronic obstructive pulmonary disease (COPD) and is refractory to current treatments. Chronic inflammatory cells accumulate around small airways in COPD and are thought to play a major role in small airway fibrosis. Mice deficient in α/β T cells have recently been shown to be protected from both experimental airway inflammation and fibrosis. In these models, CD4+Th17 cells and secretion of IL-17A are increased. However, a pathogenic role for IL-17 in specifically mediating fibrosis around airways has not been demonstrated. Here a role for IL-17A in airway fibrosis was demonstrated using mice deficient in the IL-17 receptor A (il17ra). Il17ra-deficient mice were protected from both airway inflammation and fibrosis in two different models of airway fibrosis that employ COPD-relevant stimuli. In these models, CD4+ Th17 are a major source of IL-17A with other expressing cell types including γδ T cells, type 3 innate lymphoid cells, polymorphonuclear cells, and CD8+ T cells. Antibody neutralization of IL-17RA or IL-17A confirmed that IL-17A was the relevant pathogenic IL-17 isoform and IL-17RA was the relevant receptor in airway inflammation and fibrosis. These results demonstrate that the IL-17A/IL-17 RA axis is crucial to murine airway fibrosis. These findings suggest that IL-17 might be targeted to prevent the progression of airway fibrosis in COPD.

Background Fatigue is an important clinical state and limits physical, mental activities in the patients with chronic lung diseases. However mechanisms and evaluation methods of fatigue are not well established. Recently reactivation of human herpesvirus (HHV)6/7 and HHV6 related molecules, named SITH-1 (Small protein encoded by the Intermediate Stage Transcript of HHV6-1) and its serum antibody (aSITH-1Ab) have been studied as novel biomarkers for fatigue.1),2) Fatigue due to chronic stress can cause increase of HHV6/7 DNAs in saliva, and aSITH-1Ab in blood of patients with mental disturbance. The HHV-related biomarkers could be good candidates to evaluate the pathological fatigue. Method To evaluate fatigue state, patients in stable conditions with COPD, asthma (BA) and BA COPD overlap syndrome (ACOS) were enrolled. The fatigue markers, depression score, and inflammation markers were measured. Result 60 patients were enrolled (mean age=60±14.8y, M/F=45/15, COPD/BA/ACOS=15/32/14). The rates (%) of high HHV DNA in saliva, meaning fatigue state, in COPD/BA/ACOS were 40/36/30, for both viruses equally. aSITH-1Ab positive rates (%) in COPD/BA/ACOS were 15.8/57.9/26.3. The markers for systemic inflammation were higher in COPD/ACOS than BA alone. Conclusion 30∼40% of the patients with COPD/BA/ACOS were estimated as fatigue. The patients with COPD (COPD/ACOS) showed higher systemic inflammation than BA alone, whereas those with BA (BA/ACOS) showed higher prevalence of mental disturbance than COPD alone. 1) Kondo K. et al. Journal of Virology 2002; 76: 4145-4151 2) Kondo K. et al. US Patent Application US 2013/0137088 A1 May 30, 2013.

Background The postoperative pulmonary complication (PPC) is an important surgical risk as common as the cardiac one, containing atelectasis, pneumonia, and respiratory failure. Objective The purpose of this study is to evaluate the risk factors for PPC in the patients with major respiratory underlying diseases such as bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) in our university hospital. Methods Totally 10699 patients were surgically treated in our university hospital from April to December in 2014. Among them, there were 68 COPD patients and 181 BA ones studied here. Eight of 68 COPD patients (11.8%) had PPC with 6 consolidations and 2 consolidations + respiratory failures, whereas 16 of 181 BA patients (8.8%) had PPC with 14 asthma attacks and 2 consolidations. We retrospectively evaluated physiological background, pulmonary function, duration of surgery, and perioperative specific treatment for pulmonary diseases to analyze the risk for PPC in these patients. Results In the BA patients, smoking index> 20 pack-year was significantly associated with PPC [OR (95%CI) = 11.7(2.6-52.1), P= 0.0013]. In the COPD patients, induction of COPD specific treatment and duration of surgery >300minites were significantly associated with PPC [OR (95%CI) = 0.09(0.01-0.63), P= 0.016; OR (95%CI) = 9.5(1.4-65.3), P= 0.022, respectively] Conclusions To prevent PPC, smoking cessation in BA and induction of specific treatment and shortening of surgery time in COPD were critically important.

An 87-year-old man was admitted to Jikei University Hospital presenting with fever and fatigue. Physical examinations revealed inspiratory coarse crackles on the left lung field. A chest CT detected a tumour-like consolidation around the thoracic aorta (figure 1A). Biochemical examinations found a high number of white blood cells and elevated C-reactive protein level, and a diagnosis of pneumonia was made. Penicillin antibiotics (ampicillin/sulbactam) were administered. Two days later, methicillin-sensitive Staphylococcus aureus (MSSA) was detected in two sets of blood cultures. An echocardiogram showed no vegetation and a urine culture was negative. A sputum culture was unobtainable, but pneumonia was the only focus of infection for the MSSA. Penicillin antibiotics were continued, but the patient suddenly developed cardiopulmonary arrest …

The objectives of this study are to develop a new inspection probe for complex structures using eddy current testing method (ECT), to establish the recognition technique of real flaw shape such as stress corrosion cracking (SCC), and to develop a rapid nondestructive inspection system. An ECT system consists of measurement and computational modules that are connected via a network circuit. The measurement module includes a flexible ECT sensor, which could fit on the curvature surface of radius larger than 25 mm with a mechanical manipulator. The computational module is used for SCC sizing. It includes a database of ECT signals that are used to execute numerical calculations. SCC sizing can be evaluated by comparing the measured ECT signals with the calculated ECT signals within the database. We have demonstrated that the system could be used to estimate the SCC length and depth sizing in 140 s. The accuracy of length sizing showed an RMS error of 3.7 mm and the depth sizing was 0.63 mm in this work.

Objetivo: Avaliar a utilidade do tonometro de ar (TA) em estudos populacionais em individuos suspeitos de hipertensao ocular, comparando os valores com os fornecidos pelo tonometro de aplanacao de Goldmann (TG). Metodos: Estudo transversal, de amostra probabilistica, composta por 11.452 individuos e"20 anos, compondo-se uma subamostra dos que apresentaram valores de pressao intraocular (PIO) obtidos com o TA e"20mmHg, nos quais a PIO foi repetida com o TG. Os resultados dos dois tonmetros foram comparados considerando sexo, cor da pele referida, lateralidade, relacao escavacao/disco (Â0,6; entre e"0,6 e

By transferring electric charges in a vertical register of a CCD imager,we have made a new imagestabilizing method.Furthermore,we have measured its effect.A small digital still camera(DSC),such as the camera module that is employed in mobile phones,needs image-stabilizing means that are both low-cost and durable.With this method,multiple short exposures of an object are taken and electric charges in the vertical register are added to make non-blurring still pictures.The first exposure in the vertical register is transferred upward or downward until the next one is read out in the same direction of a moving optical image in order to automatically add the same object.Miniaturized cameras can thus be made much more cheaply than previously because flame memory and calculations are not needed to detect motion vectors.

The establishment of the nondestructive inspection technology with plant structures has been stimulated by the recent occurrence of cracks in the nuclear power plant structures. In this research, a uniform eddy current multi-probe to apply to the complex structure and inspect the cracks at high-speed data acquisition was developed. Pick-up coils of the developed probe were arranged on a flexible printed circuit board. This probe was able to obtain clear signal for an EDM (electro-discharge machining) slit with 0.5 mm depth and distinguish EDM slits arranged at 2 mm intervals. It was confirmed that the SCC (stress corrosion cracking) of real flaw was able to be detected with developed uniform eddy current multi-probe by using the ferrite core for the exciting coil and considering the impedance matching of the exciting coil and the flaw detection device.

A 76-year-old man with ulcerative colitis presented with a 1-week history of low-grade fever and progressive dyspnea. He was taking infliximab for the ulcerative colitis. He was known to be negative for human immunodeficiency virus. Computed tomography (CT) of the chest revealed infiltrates in the

The eddy current testing is used for a testing of the steam generator tubes in pressurized water reactor nuclear power plants because of its high accuracy and high speed. It is important to judge shape of cracks from measured signals. We have developed a rotating type probe using an excitation coil that generates uniform eddy current distribution. Because the shape of excitation current source has no influence on detecting cracks, numerical analyses for this probe are handled simply by devising boundary condition. Aid of numerical analyses has enhanced the evaluation of complicated cracks.

We report 2 patients with acute cholecystitis for which percutaneous transhepatic gallbladder aspiration (PTGBA) was useful. In Case 1, the patient was a 75-year-old woman who experienced a sudden onset of back pain and upper abdominal pain at night. Abdominal ultrasound (US) showed enlargement of the gallbladder with thickening of the wall, a sonolucent layer, and a stone in the neck of the gallbladder, which led to a diagnosis of acute cholecystitis. Magnetic resonance imaging (MRI) demonstrated thickening of the gallbladder wall and 2 areas of low-intensity signal. The pain and fever persisted, for which we performed PTGBA, aspirating about 113 ml of infected bile. Subsequently, the pain and fever subsided, and abdominal US revealed a reduction in the enlargement of the gallbladder with the persistence of thickening of the wall. On the eighth day after PTGBA, open abdominal cholecystectomy was performed. In Case 2, the patient was a 56-year-old woman who had right hypochondriac pain after supper. The pain gradually increased in severity. Abdominal US showed enlargement of the gallbladder with a thickened wall, a sonolucent layer, and a gallstone in the neck of the gallbladder, which led to a diagnosis of acute cholecystitis. Magnetic resonance cholangiopancreatography (MRCP) showed enlargement of the gallbladder with no abnormalities in the common bile duct. After admission to hospital, the pain and fever persisted, for which we performed PTGBA, aspirating about 50 ml of infected bile. Subsequently, the pain and fever vanished. Abdominal US revealed a reduction in the enlargement of the gallbladder with the persistence of thickening of the wall. On the seventh day after PTGBA, laparoscopic cholecystectomy was performed. PTGBA seems useful for early alleviation of the symptoms of acute cholecystitis because of low invasiveness and ease of performance.

Between 1978 and 1999, 86 patients with chronic pancreatitis were surgically treated at the Surgical Department of Kurume University Hospital. Of these patients, 30 were treated by pancreatic duct drainage operation (drainage operation), while 40 were treated by pancreatic resection, and the results were compared between the two groups. In patients who underwent drainage operation, pain disappeared in 85.7%, slightly relieved in 10.7%, and not relieved in 3.6%. In patients who underwent pancreatic resection, pain disappeared in 73.4%, slightly relieved in 13.3%, and not relieved in 13.3%. Therefore, there was no significant difference in the pain-relieving effect between the two groups. However, the pain-relieving effect was poorer in patients who underwent pancreatic resection than in those who underwent drainage operation. In addition, all patients who showed poor results for pain relief had alcoholic pancreatitis. Endocrine and exocrine functions of the pancreas were improved in 6, maintained in 2, and exacerbated in 4 patients who underwent drainage operation. In patients who underwent pancreatic resection, endocrine and exocrine function of the pancreas were improved in 3, maintained in 3, and exacerbated in 13. Therefore, endocrine and exocrine function of the pancreas were poorer in patients who underwent pancreatic resection than in those who underwent drainage operation. Distant results in patients who underwent drainage operation were good in 75.0%, fair in 15.0%, and poor in 10.0%. In patients who underwent pancreatic resection, distant results were good in 80.0%, fair in 13.3%, and poor in 6.7%. Therefore, favorable distant results were obtained in both groups. These findings suggest that surgical techniques that preserve functions of the pancreas should be selected during surgical treatment for chronic pancreatitis. We consider that the presence or absence of main pancreatic duct dilation and the site of pancreatic lesions are important indices for selecting surgical techniques. Therefore, drainage operation consisting of pancreaticojejunostomy should be indicated for patients with main pancreatic duct dilation, while pancreatic resection should be indicated for those without main pancreatic duct dilation, those with localized pancreatic lesions, and those with suspected pancreatic cancer.

Airway remodeling, caused by inflammation and fibrosis, is a major component of chronic obstructive pulmonary disease (COPD) and currently has no effective treatment. Transforming growth factor–β (TGF-β) has been widely implicated in the pathogenesis of airway remodeling in COPD. TGF-β is expressed in a latent form that requires activation. The integrin αvβ8 (encoded by the itgb8 gene) is a receptor for latent TGF-β and is essential for its activation. Expression of integrin αvβ8 is increased in airway fibroblasts in COPD and thus is an attractive therapeutic target for the treatment of airway remodeling in COPD. We demonstrate that an engineered optimized antibody to human αvβ8 (B5) inhibited TGF-β activation in transgenic mice expressing only human and not mouse ITGB8. The B5 engineered antibody blocked fibroinflammatory responses induced by tobacco smoke, cytokines, and allergens by inhibiting TGF-β activation. To clarify the mechanism of action of B5, we used hydrodynamic, mutational, and electron microscopic methods to demonstrate that αvβ8 predominantly adopts a constitutively active, extended-closed headpiece conformation. Epitope mapping and functional characterization of B5 revealed an allosteric mechanism of action due to locking-in of a low-affinity αvβ8 conformation. Collectively, these data demonstrate a new model for integrin function and present a strategy to selectively target the TGF-β pathway to treat fibroinflammatory airway diseases.

We report a case of primary hepatocellular carcinoma (referred to as hepatocellular carcinoma below) apparently rupturing after angiography. The patient was a 62-year-old male who was admitted for the treatment of hepatocellular carcinoma. Ultrasonography (US) and computed tomography (CT) on admission showed a tumor occupying the entire left lobe of the liver and partly protruding outside the liver and a tumor embolus in the portal vein. We performed preoperative angiography, after which fever and abdominal discomfort appeared. Two days after the angiography, abdominal pain and a rapid increase in the size of the abdominal tumor were noted. US also revealed an unquestionable increase in the size of the tumor, leading to a diagnosis of intratumoral hemorrhage due to the rupture of hepatocellular carcinoma. Since child classification A, clinical stage I and ICG 11.7% indicated an adequate functional reserve of the liver, we performed an emergency operation. Laparotomy revealed that the tumor occupied almost the entire left lobe of the liver, partly protruded outside it, and was bleeding from part of its anterior surface. The volume of intra-abdominal hemorrhage was about 100 ml. A portal tumor embolus was present in the portal vein from the horizontal part to the trunk. We performed resection of the left and caudate lobes of the liver with removal of the portal tumor embolus. The resected specimens showed a hemorrhage in and around the tumor. We speculated that in a hepatocellular carcinoma that involves the surface of the liver and is complicated by tumor embolism of the portal vein, angiography could trigger the rupture of the carcinoma.

We present a patient with duodenal papillary carcinoma who repeatedly developed acute pancreatitis preoperatively. The patient was a 65-year-old male. In February 1997, the patient consulted a local hospital due to vomiting, high fever, and jaundice. With the diagnosis of obstructive jaundice, percutaneous transhepatic biliary drainage (PTBD) was performed, revealing a distal bile duct obstruction. Because duodenal papillary carcinoma was diagnosed based on endoscopic findings, the patient was admitted to Kurume University Hospital. Hypotonic duodenography (HDG) disclosed a protruding lesion with an irregular surface in the descending part of the duodenum, resulting in a diagnosis of positive duodenal invasion (du1). Because computed tomography (CT) demonstrated a protruding lesion on the medial side of the second portion of the duodenum, positive pancreatic invasion (panc2) was diagnosed. On March 18 and April 22, sudden abdominal pain, leukocytosis, and an increase in serum amylase were noted. CT revealed that the pancreas was diffusely enlarged, showing an ill-defined boundary between the pancreas and adipose tissue and fluid collection. On CT, the lesion was evaluated as Grade 3 and moderate. For treatment, pancreatic enzyme inhibitors and antibiotics were intravenously injected. Peritoneal perfusion was concomitantly performed during the second treatment. Because symptoms remitted thereafter, a pylorus preserving pancreatoduodenectomy (PpPD) was carried out. The postoperative histologic examination revealed negative pancreatic invasion. Concerning the etiology of acute pancreatitis, not pancreatic invasion, but impaction of the liberated tumor mass in the common canal was considered responsible for the repeated pancreatitis because the tumor showed a cauliflower-like shape.

A case of gallbladder carcinoma was reported. A 42-year-old woman was admitted with epigastralgia. Abdominal ultrasonography, computed tomography, and other diagnostic modalities suggested gallbladder carcinoma with multiple liver metastases. These findings indicated no surgical procedure because of the advanced nature of her disease. After the hepatic arterial chemoinfusion therapy, her multiple liver metastatic lesions showed a decrease in size and number. Therefore, extended left lobectomy of the liver with gallbladder and bile duct resection were performed. Five years after initial operation, a solitary liver metastatic lesion (S5) was diagnosed by ultrasonography. Partial resection of the liver was performed for the liver metastasis, and her postoperative recovery was uneventful and had a good follow-up course. One year after the second operation bone metastases occurred, therefore, peroral administration of UFT (Tegafur + Uracil) and radiation therapy for the metastatic lesions of sternum and lumbar vertebra (L1) were performed.

A 58-year-old male underwent pancreatoduodenectomy based on a diagnosis of middle bile duct cancer. Because abdominal drainage revealed bile leakage 5 days postoperatively, leakage at the site of cholangiojejunostomy was diagnosed, and continuous aspiration was performed. Seventeen days postoperatively, pus was discharged through the abdominal drain. Because bleeding was detected by abdominal drainage, and shock ensued 20 days postoperatively, emergency abdominal angiography was carried out to identify the bleeding site. A false aneurysm in the proper hepatic artery and extravasation from the gastroduodenal artery stump were recognized, and therefore, the proper hepatic artery and common hepatic artery were embolized at a site distal to the false aneurysm using microcoils. Celiac arteriography after transcatheter arterial embolization (TAE) did not show extravasation, and revealed blood flow from the right inferior phrenic artery to the liver. Liver function was normal after TAE, and the patient recovered and was discharged from the hospital 54 days postoperatively. This paper presents a patient in whom intraabdominal bleeding due to leakage at the site of cholangiojejunostomy complicated by infection was successfully treated by hemostasis with TAE.

A 77-year-old woman complaining of anorexia and nausea was referred to the hospital with a diagnosis of advanced gastric cancer. The patient also had congestive heart failure with atrial fibrillation and severe hypoproteinemia. Proteinuria, hypoproteinemia and other laboratory data suggested that she had nephrotic syndrome. Total protein level was 4.6 g/dl and albumin level was 1.6 g/dl. In order to avoid postoperative complications such as wound dehiscence, anastomotic leakage and so on, careful pre- and post-operative management of nephrotic syndrome is necessary. Administration of albumin and fresh frozen plasma regimen was continued after the operation. Urinary protein level started to decrease after subtotal gastrectomy. Histological examination revealed moderately differentiated tubular adenocarcinoma with nodal metastases. Her post-operative course was uneventful. Although the signs and symptoms of nephrotic syndrome did not improve immediately, twelve months after operation she has become well and has no symptoms of ascites and hypoproteinemia.

A 63 year-old-man was admitted to our hospital with the chief complaint of dyschezia. Digital examination revealed a large solid mass on the posterior wall of the rectum. Endoscopically, the tumor was covered by an intact mucosal layer. Under the diagnosis of rectal leiomyosarcoma, abdominoperineal resection of the rectum was performed. The tumor was 10 x 9 x 8 cm in size, and its cross section showed a gray-white tumor with central necrosis. Microscopically, the large tumor of the rectum was mainly located in the proper muscle layer and adventitia, and showed cellular proliferation of spindle-shaped and mild pleomorphic stromal cells, arranged in interlacing fashion, and focal necrosis. The histologic findings support the diagnosis of leiomyosarcoma. Leiomyosarcoma of the rectum is a relatively uncommon disease. We report our case with reference to the literature.

Pseudomyxoma peritonei is a disease characterized by the progressive accumulation of mucinous ascites within the abdomen and pelvis. Metastatic disease outside the peritoneal cavity is unusual. Gastrointestinal function is lost from external compression of stomach, small bowel, and large bowel. We present three cases of pseudomyxoma peritonei which were treated by different therapeutic methods. Case 1 was a 61-year-old man who underwent treatment by appendectomy with administration of Cisplatin and Doxorubicin hydrochloride into the intraperitoneal cavity. Case 2 was a 64-year-old woman who underwent bilateral oophorectomy with administration of Cisplatin and ADM into the intraperitoneal cavity. About 4 years after the first operation, she died of peritonitis due to small and large bowel' perforations underlying recurrent tumors. Case 3 was a 79-year-old woman who underwent surgery to evacuate about 4000 ml of mucinous ascites, and received intraperitoneal administration of 5-Fluorouracil (500 mg/day) for 5 days without severe complications.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:30:35Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:43:30Z : No. of bitstreams: 1 2-s2.0-84883645775.pdf: 1430537 bytes, checksum: be814d3a2faed94d06e76f67ab70f8a7 (MD5) Made available in DSpace on 2014-05-27T11:30:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-09-01 PURPOSE: To investigate and compare the biocompatibility of two types of Ferrara intracorneal ring segment: with and without chondroitin sulfate coating by clinical and histopathological evaluation. METHODS: A randomized experimental study was carried out on thirty right-eye corneas from 30 Norfolk albino rabbits allocated into two experimental groups: Group G1 - implanted with Ferrara intracorneal ring segment without coating (FICRS) and Group G2 - implanted with Ferrara intracorneal ring segment with chondroitin sulfate coating (FICRS-CS). Left eyes formed the control group. Clinical parameters analyzed were: presence of edema, vascularization, infection and ring extrusion one, 30, and 60 days after surgery. Histopathological parameters analyzed were: number of corneal epithelial layers over and adjacent to the ring, presence of spongiosis, hydropic degeneration, basement membrane thinning, inflammatory cells, neovascularization and pseudocapsule formation. RESULTS: At clinical examination 60 days after implant, edema, vascularization and extrusion were observed respectively in 20%, 26.7%, 6.7% of FICRS corneas and in 6.7%, 6.7%, and 0% of FICRS-CS corneas. Histopathological evaluation showed epithelial-layer reduction from 5 (5;6) to 3 (3;3) with FICRS and from 5 (5;5) to 4 (3;5) with FICRS-CS in the region over the ring. Epithelial spongiosis, hydropic degeneration, and basement membrane thinning were present in 69.2%, 53.8%, and 69.2% of FICRS and in 73.3%, 73.3%, and 46.7% with FICRS-CS, respectively. Vascularization was present in 38.5% of FICRS and 13.3% with FICRS-CS, inflammatory cells in 75% of FICRS and 33.3% with FICRS-CS, and pseudocapsule in 66.7% of FICRS and 93.3% with FICRS-CS. Giant cells occurred only in the FICRS-CS group (20%). CONCLUSION: Ferrara intracorneal rings coated with chondroitin sulfate (FICRS-CS) caused lower frequency of clinical and histopathological alterations than Ferrara intracorneal rings without the coating (FICRS), demonstrating higher biocompatibility of the FICRS-CS. Sao Paulo State University (UNESP), Botucatu-SP FMB UNESP, Botucatu-SP Division of Ophthalmology, Department of Ophthalmology Otolaryngology and Head and Neck Surgery FMB, UNESP, Botucatu-SP Sao Paulo State University (UNESP), Botucatu-SP FMB UNESP, Botucatu-SP Division of Ophthalmology, Department of Ophthalmology Otolaryngology and Head and Neck Surgery FMB, UNESP, Botucatu-SP

Wavelength switchings of a Fabry-Perot semiconductor laser are experimentally demonstrated by applying externally optical input pulses detuned from a cavity-resonant wavelength of the semiconductor laser with a constant injection current. The wavelength region of optical switching ranges from less than 0.1 nm to several nm over gain spectrum, being locked to the wavelength of optical inputs. These behaviors are based on multistability and multi-split branches in the optical output versus detuned optical input characteristics, caused by the carrier-induced refractive index change accompanied by optical injections. The experimental results are believed to be useful for wavelength division multiplexing and exchange in optical communication.

The currently study focused on the influence of delayed graft function on the long-term graft success rate in cadaver kidneys without any mismatches for HLA-DRB1. Donor-recipient HLA-DRB1 was determined by the significant two-locus linkages of HLA-B and -DRB1. The overall 5-year graft success rate was 88 % in an HLA-DRB1-compatible group, significantly higher than the 69 % in an HLA-DRB1 mismatch group (P < 0.05) and the 66 % in an HLA-DR mismatch (P < 0.01). Delayed graft function was observed in 182 of 223 transplants. This high incidence of 82 % is due to the fact that, in Japan, kidney procurement may only occur after cardiac arrest. The incidence did not differ in each group. The 5-year success rate for grafts with delayed function was 87 % in the HLA-DRB1-compatible group, again significantly superior to the 68 % in the HLA-DRB1 mismatch group and the 63 % in the HLA-DR mismatch cases (P < 0.05). There was, thus, no difference in graft success rate for each group, with or without delayed graft function. Consequently, we feel that delayed graft function has no impact on the long-term outcome in transplants without mismatches for HLA-DRB1.

Optical multistability of a Fabry-Perot semiconductor laser is analyzed when multi-optical inputs detuned from the cavity-resonant wavelength of a semiconductor laser are injected. Many split branches are shown to be produced in the optical output versus optical input characteristics for different detuned optical inputs. It is also shown that optical outputs can be switched in any one of the optical input wavelengths by optical input pulses, based on the optical output versus input characteristics with multi-split branches.