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Pulmonary oxalosis can be fatal, and Aspergillus tubingensis is commonly resistant to azoles in Japan. We report a case of bronchopulmonary oxalosis caused by A. tubingensis in a non-neutropenic patient who was successfully treated with voriconazole monotherapy. The susceptibility of the isolates to voriconazole and the effective elimination of contagious necrotic tissue by expectoration seemed to be two major factors contributing to the patient's survival. According to the literature review, pulmonary oxalosis is associated with a high mortality rate over a short term. An exploration of detailed information about the genomic characteristics and drug susceptibility of Aspergillus isolates is important for the development of treatment strategies for this life-threatening disease.

Background Parenteral anticoagulants and vitamin K antagonists (VKAs) have constituted the cornerstone of venous thromboembolism (VTE) treatment. Meanwhile, direct oral anticoagulants (DOACs) provide physicians with an alternative. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE observes real-world treatment practices. Objectives Describe initial anticoagulation (AC) treatment patterns in VTE patients who received parenteral AC, VKAs, and/or DOACs within ±30 days of diagnosis. Methods VTE patients were categorized into parenteral AC only, parenteral AC with transition to VKA, VKA only, parenteral AC with transition to DOAC, and DOAC only. Results A total of 9647 patients were initiated on AC treatment alone. 4781 (49.6%) patients received DOACs ± parenteral ACs; 3187 (33.0%), VKA ± parenteral ACs; and 1679 (17.4%) parenteral ACs alone. Rivaroxaban was the most frequently used DOAC (79.4%). DOACs were more frequently used in North America/Australia (58.1%), Europe (52.2%), and Asia (47.6%) than in Latin America (29.7%) and the Middle East/South Africa (32.5%). In patients with suspected VTE, most received parenteral AC monotherapy (67.7%). Patients with deep vein thrombosis were more likely to receive DOACs alone than those with pulmonary embolism with or without deep vein thrombosis (36.2% vs 25.9%). Active cancer patients received parenteral AC alone (58.9%), with 25.5% receiving DOAC ± parenteral AC and 12.8% parenteral AC and VKA. A total of 46.5% of pregnant patients received parenteral AC monotherapy, 34.0% were treated with VKA ± parenteral AC, and 19.5% received a DOAC (± parenteral AC). Conclusion AC treatment patterns vary by patient population, geographic region and site of VTE. Guidelines for AC therapy are not always adhered to.

Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation with endothelial dysfunction. Cadherins are adhesion molecules on epithelial (E-) and vascular endothelial (VE-) cells. Soluble (s) cadherin is released from the cell surface by the effects of proteases including matrix metalloproteinases (MMPs).The aim of this study was to examine the associations of sE-/sVE-cadherin levels in plasma with the development of COPD.Plasma sE-/VE-cadherin levels were measured by an enzyme-linked immunosorbent assay in 115 patients with COPD, 36 symptomatic smokers (SS), 63 healthy smokers (HS) and 78 healthy non-smokers (HN). sE-cadherin and MMP-7 levels in epithelial lining fluid (ELF) were measured in 24 patients (12 COPD and 12 control).Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios were significantly higher in COPD and SS than in HS and HN groups, while plasma sVE-cadherin levels were lower in COPD than in HS and HN groups (p 0.0001). sE-cadherin levels paralleled the severity of airflow limitation in both plasma (p 0.01) and ELF (p 0.05), while plasma sVE-cadherin levels were inversely correlated with the extent of emphysema (p 0.05). MMP-7 levels were correlated with sE-cadherin levels in ELF.Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios are potential biomarkers for COPD.

Controversy exists regarding the similarity between depression as seen in patients with epilepsy and in those with idiopathic major depression. The objective of this study was to examine whether anger is a distinctive feature of depression in epilepsy. Participants included 487 adult patients with epilepsy (study group) and 85 patients with idiopathic major depression according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria, and without other neurological complications (control group). All participants completed the Inventory of Depressive Symptomatology Self-Report (IDS-SR) and the Buss-Perry Aggression Questionnaire (BAQ). The IDS-SR is a self-report questionnaire that measures depression severity and assesses all symptoms of depression as defined by the DSM-IV. The BAQ is a self-rating scale designed for assessing aggression. After examining potential confounding factors (i.e., demographic and clinical variables) using a multivariate linear regression model, BAQ scores were compared between the study (n = 85) and control groups (n = 54) for patients with moderate or severe depression using established cut-off points (IDS-SR score > 25). BAQ scores were significantly higher in the study group (P = 0.009). Among the BAQ subscales, only anger showed a statistically significant difference (P = 0.013). Although a significant correlation was revealed between the IDS-SR and BAQ scores in the study group, no such correlation was found in the control group. Thus, anger might be a constituent component of depression among epilepsy patients, but not among idiopathic major depression patients.

Introduction. Very few epilepsy phenotypes have been associated with causative genes; nevertheless, it is becoming possible, for some epilepsy phenotypes, to predict the most efficacious anti-epileptic drugs for patients based on their genetic makeup. The development of individualized medicine based on genetic information and the genetic diagnosis of epilepsy are expected to greatly improve the diagnosis and treatment of epilepsy. Here, we developed a DNA array (resequencing array) for the genetic diagnosis of epilepsies in which 14 epilepsy – related genes (SCN1A, SCN1B, CHRNA4, CHRNA7, CHRNB2, GABRA1, GABRD, GABRG2, CACNB4, CLCN2, KCNQ2, KCNQ3, CACNA1A, and CACNA1H) have been mounted. Aim. The aim of the present study is to evaluate the performance of our custom array in detecting the SCN1A mutations in patients with severe myoclonic epilepsy in infancy. Material and methods. We compared mutation data generated by DNA array sequencing of DNA samples from patients with severe myoclonic epilepsy in infancy to the data generated by capillary sequencing. Results. Heterozygosity was detected in 44 of 48 patients (92%). We successfully identified epilepsy mutations, and the results of DNA array analyses were largely consistent with the results of capillary sequencing analysis. Conclusion. These findings indicate that this DNA array is likely to be a useful tool in clinical settings.

The association between the superoxide dismutase 2 (SOD2) Val16Ala polymorphism and the serum aminotransferase levels was retrospectively investigated in 207 valproic acid-treated patients with epilepsy. The Val/Val genotype tended to show elevated alanine aminotransferase levels (odds ratio=3.5; P=0.056). In addition, an elevated γ-glutamyltransferase level was associated with the Val/Val genotype (odds ratio=3.1; P=0.022). The SOD2 Val/Val genotype may therefore contribute to a valproic acid-induced elevation in the serum aminotransferase levels.

Epilepsy is a relatively common maternal complication affecting 0.3-0.5% of pregnant women. For most mothers with epilepsy, the use of antiepileptic drugs (AED) is unavoidable, even during pregnancy and lactation. Therefore, the fetus is indirectly exposed to AED via the placenta and breast milk. AED are also prescribed for female patients with other diseases, such as bipolar disorders. In clinical settings, physicians are frequently questioned whether or not women patients taking AED should breast-feed their offspring. Thus, it is necessary to establish an optimum AED regimen for women taking AED, in particular for those with epilepsy during pregnancy and lactation. In this article, we critically review the effects of AED on infants via breast milk and attempt to provide suggestions for clinicians regarding these effects during breast-feeding, based on the data of transplacental passage of AED, breast milk concentration/maternal serum concentration ratios, AED metabolism in infants and the effects of AED in breast milk on infants.

Current antiepileptic drug (AED) therapy requires trial and error in determining the most effective AED and dosage for a patient, and almost one-fourth of patients are resistant to AED therapy. The introduction of individualized medicine for epilepsy based on genetic information is a new avenue to improve current AED therapy. However, several crucial issues remain to be resolved before the development of individualized medicine for epilepsy can proceed further. The epilepsy genes responsible for common phenotypes have not yet been identified, and ongoing pharmacogenetic studies continue to search for an explanation of why 25 to 30% of patients do not respond to AEDs. There is no convincing clinical evidence indicating the impact of P-glycoprotein on prediction of clinical response. This article provides a critical review of the status and perspectives for the development of individualized medicine for epilepsy based on genetic polymorphisms/mutations in relation to core elements such as pharmacodynamic pathway, pharmacokinetic pathway, prediction of idiosyncratic reaction to AED, and mechanisms of action of AEDs.

Despite the continuous development and release of new anti-epileptic drugs (AEDs), almost one in four patients are resistant to AED therapy. Current therapy requires trial and error to determine the most effective AED and dosage for a patient. The development of individualized medicine for epilepsy is critical for improving AED treatment, particularly that based on genetic information. However, several crucial issues remain to be resolved before the development of AED therapy can proceed further. The epilepsy genes responsible for common phenotypes have not yet been identified and ongoing pharmacogenetic studies continue to search for an explanation as to why 20-25% of patients do not respond to AEDs. There is no convincing clinical evidence that P-glycoprotein at the blood-brain barrier limits the uptake of AEDs into the brain of epileptic patients and contributes to the development of the drug-resistant phenotype. This article provides a critical review of the status and perspectives for the development of individualized medicine for epilepsy, based on genetic polymorphisms/mutations in relation to three major components: the pharmacodynamic pathway, the pharmacokinetic pathway and the mechanisms of action of AEDs. The development of multiplex assay technologies, together with the generation of epilepsy animal models bearing human epilepsy genes, are also discussed.

Febrile seizure (FS), autosomal dominant epilepsy with FS plus (ADEFS+), and severe myoclonic epilepsy of infancy (SMEI) are all triggered by high fever at the onset of disorder, but are clinically distinct from each other. Although various identified gene mutations account for approximately 15% of families with ADEFS+ and 80% of patients with SMEI, the responsible gene for FS is essentially unknown. The present study was conducted to identify the loci associated with the risk of these 3 disorders. Among 154 patients (77 with SMEI, 34 with ADEFS+ and 43 with FS), we found 21, 24 and 27 novel susceptibility loci associated with the three diseases, respectively. This is the first phase of a two-part study on the genetic risk profile for fever-related seizure disorders.

Purpose. This study aimed to examine whether plasma levels of cathepsin S or its inhibitor, cystatin C, may serve as biomarkers for COPD.Patients and Methods. We measured anthropometrics and performed pulmonary function tests and chest CT scans on 94 patients with COPD and 31 subjects with productive cough but no airflow obstruction (“at risk”; AR). In these subjects and in 52 healthy nonsmokers (NS) and 66 healthy smokers (HS) we measured plasma concentrations of cathepsin S and cystatin C using an ELISA. Data were analyzed using simple and logistic regression and receiver operating characteristic analyses.Results. Cathepsin S and cystatin C plasma levels were significantly higher in the COPD and AR groups than in the NS and HS groups (p<0.01). Among the COPD patients and AR subjects, plasma cathepsin S levels and cathepsin S/cystatin C ratios, but not cystatin C levels, were negatively related to severe airflow limitation (% FEV1predicted < 50%;p=0.005) and severe emphysema as assessed by low attenuation area (LAA) score on chest CT scans (LAA≥8.0;p=0.001).Conclusion. Plasma cathepsin S and cathepsin S/cystatin C ratios may serve as potential biomarkers for COPD.

Small cell lung cancer (SCLC) causes paraneoplastic syndromes, such as diabetes mellitus, by eliciting the expression of various antibodies including anti-glutamate decarboxylase (GAD) antibody. A 62-year-old woman presented to our hospital with a 1-week history of progressive dyspnea and difficulty in walking. Computed tomography showed a tumor obstructing the left bronchus and obstructive lung abscesses with pleural effusions. A biopsy during bronchoscopy revealed SCLC, and the clinical stage was ultimately determined to be IIIB. SCLC was complicated by diabetes mellitus with high titers of serum anti-GAD antibody. An immunohistochemical analysis showed GAD expression in the cancer cells, which is a novel finding.

This study proposes a recycling system of sludge into active cokes and the fundamental examinations for the application were carried out. In the system, active cokes were produced by carbonizing pellets of sludge in a steam stream. Pyrolysis gas yielded by carbonization can be available to a fuel for a steam generation boiler. The exhaust heat from the boiler is used sequentially for drying of sludge. The active cokes are applied to the adsorbent for dioxin removal in exhaust gas from incinerators of wastes, or for purification of gas obtained in a gasification process of wastes, particularly removal of H2S. The used adsorbent is not recycled, but incinerated in the furnace without a desorption process to decompose adsorbed dioxin or to oxidize H2S for a sequential desulfurization process of SO2. Dry pellets of sludge were carbonized in a quartz tube reactor under various atmospheres. The micro pore structure and the adsorption performance of the cokes produced without activation process were examined. The micro pore structure was influenced by the temperature, the sort of flow gas (N2, CO2 and steam) and carbonization time, and the active cokes produced under the condition of the temperature 823 K for 60 min in the steam atmosphere had a largest specific surface area in the diameter less than 5 nm. The amount of benzene adsorption as an alternative substance of dioxin into the active cokes had a similar quality to a commercial active char produced from coal if it was evaluated by adsorption per a unit specific surface area. This fundamental knowledge must be reflected to an optimum design for development of a simple continuous process to produce the active cokes by a fluidized bed type of the carbonization furnace.

Chronic obstructive pulmonary disease (COPD) develops only in smoking-sensitive smokers and manifests heterogeneous phenotypes, including emphysema and non-emphysema types. We aimed to identify biomarkers related to the smoking-sensitivity and phenotypes of COPD. Among 240 smokers suggestive of COPD, we studied on four groups defined by % forced expiratory volume in one second (FEV1) and computed tomography-based pulmonary emphysema. Plasma concentrations of 33 inflammatory markers were measured in four groups as well as Non-smokers using multiplex protein arrays. IL-5, IL-7 and IL-13 were identified to be associated with smoking sensitivity and IL-6 and IL-10 were candidate biomarkers for airway-lesion dominant COPD.

The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) is a concise health status measure for COPD. COPD patients have a variety of comorbidities, but little is known about their impact on quality of life. This study was designed to investigate comorbid factors that may contribute to high CAT scores. An observational study at Keio University and affiliated hospitals enrolled 336 COPD patients and 67 non-COPD subjects. Health status was assessed by the CAT, the St. Georges Respiratory Questionnaire (SGRQ), and all components of the Medical Outcomes Study Short-Form 36-Item (SF-36) version 2, which is a generic measure of health. Comorbidities were identified based on patients’ reports, physicians’ records, and questionnaires, including the Frequency Scale for the Symptoms of Gastro-esophageal reflux disease (GERD) and the Hospital Anxiety and Depression Scale. Dual X-ray absorptiometry measurements of bone mineral density were performed. The CAT showed moderate-good correlations with the SGRQ and all components of the SF-36. The presence of GERD, depression, arrhythmia, and anxiety was significantly associated with a high CAT score in the COPD patients. Symptomatic COPD patients have a high prevalence of comorbidities. A high CAT score should alert the clinician to a higher likelihood of certain comorbidities such as GERD and depression, because these diseases may co-exist unrecognized. Clinical trial registered with UMIN (UMIN000003470) .

Spirometry is practically the only tool to evaluate pulmonary functions. Other automatic systems comparable to spirometry are expected. A fiber-grating (FG) vision sensor is a non-contact respiratory monitoring system to detect changes in volumes by measuring the movement of laser spots on the body surface. We examined the contributions of the FG sensor to evaluating pulmonary functions. The FG sensor showed a linear correlation with spirometry in tidal volumes (TV) obtained from five controls (R = 0.98, P < 0.0001). We also showed agreement of TV between the two devices using Bland-Altman analysis. TV measured by the FG sensor were reproducible and applicable to distinct subjects. To detect airway obstruction, we performed forced expiration in controls (n = 16) and chronic obstructive pulmonary disease (COPD) patients (n = 18) with the FG sensor and spirometry. Forced expiratory volume in 1 s (FEV(1)) and FEV(1)/forced vital capacity in COPD patients were lower than those in controls by the FG sensor. In addition, prolonged expiration in natural breathing by the FG sensor was related to airflow limitation by spirometry. The FG sensor was helpful to measure volume changes and to evaluate pulmonary functions in controls and patients with COPD. Its upcoming clinical applications are promising for simplicity and feasibility.

Epilepsy affects 0.6% of Japanese population, and monotherapy has been the gold standard in epilepsy treatment in the past two decades. However, up to one third of patients do not achieve sufficient seizure control with antiepileptic (AED) monotherapy. Further, in case of patients with partial seizures, 25% of them are not rendered seizure free with 3 AEDs combination therapy. In spite of these facts, AEDs are the mainstay of treatment, and monotherapy should be remain the treatment of choice for newly diagnosed epilepsy. Recently, new AEDs such as gabapentin (GBP), topiramate (TPM) and lamotrigine (LTG) have been introduced in Japan, and levetiracetam will be introduced within this year. Some of them are better tolerated and less prone to complex pharmacokinetic drug interactions than their older counterparts, consequently AED therapy has entered a new stage.

The prognosis of metastatic pheochromocytoma is poor in general. There have been few instances of long-term survival reported. We report a case of a 44-year-old woman who has survived for 26 years after bone metastasis. She was diagnosed as having pheochromocytoma arising in the left adrenal medulla in 1974. Metastasis of pheochromocytoma in the first and third lumbar vertebrae and the right ilium was observed at the same time. The primary lesion was removed, and posterior lumbar spinal fusion was performed for immobilization. The metastatic lesion in the ilium was left untouched. After 26 years, she is well despite a recurrence of the tumors in the skull and a new metastasis in the left abdomen.

We will report on a magnetic head positioning control system and a track following control method through which increased capacity and high speed has been achieved and in which a 3.5 inch 16 MB high density flexible disk drives (FDD) is employed.

The authors have developed a 3.5-in, 16-Mbyte, large-capacity, high-speed floppy disk drive (FDD). A novel embedded sector server technology with a learning-forward control and a double-loop multisampling system, as well as a microstepping motor with an optical encoder, were used to achieve high density of 542 tracks/in with an accurate trackability of +or-2.5 mu m and a high-speed average seek time of less than 50 msec as well as high vibration resistance. The authors describe the overall FDD system, the head positioning control system, and the control performance. >