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The classification accuracy of an event-related potential (ERP) induced by a tactile stimulus is investigated to create a brain-computer interface (BCI). Mechanical tactile stimuli were applied to the left and right index fingers using two piezo actuator probes that were used as a Braille display for the visually impaired. In an experiment, two-class classification was investigated using three kinds of tactile stimulus pattern. The subjects were instructed to pay attention to unusual target stimuli while avoiding other frequent nontarget stimuli. The extracted features were classified using stepwise linear discriminant analysis. As a result, high accuracy was obtained by the task of random intervals compared with the task of constant intervals. It was suggested that the accuracy of the BCI using tactile stimuli is influenced by the concentration on the task.

Objectives: To examine the long-term persistence rate with mirabegron in a real-world clinical setting., Methods: We retrospectively collected the data of patients who were prescribed mirabegron. We investigated the persistence rate and the reason for the discontinuation. The analysis included patient's age, diagnosis, Overactive Bladder Symptom Score, prostatic volume, the prescription by specialists for lower urinary tract dysfunction, drug-naïve patients, replacement of antimuscarinics or add-on therapy to antimuscarinics., Results: A total of 556 patients were included. Among them, 401 patients (72%) had overactive bladder and the other 155 (28%) were categorized as having other storage symptoms. During the observation period, 170 patients (42%) with overactive bladder discontinued mirabegron. The reasons for discontinuation in patients with overactive bladder included unmet expectation of treatment (45 patients, 26%), any adverse events (38 patients, 22%) or symptom improvement (37 patients, 22%). The persistence or discontinuation was not related with age, Overactive Bladder Symptom Score, prostatic volume or the prescription by specialists, while older male patients tended to continue mirabegron. The 3-year persistence rates in female and male overactive bladder patients were 46% and 51%, respectively, and these were better than those in patients with storage symptoms without urgency. In female overactive bladder patients, the persistence rate with mirabegron used as add-on therapy to antimuscarinics was higher than that in the drug-naïve patients on the Kaplan-Meier curve., Conclusions: The present study shows a relatively good long-term persistence rate with mirabegron in overactive bladder patients, notwithstanding the retrospective study in an academic hospital. The combined treatment with antimuscarinics could result in a good persistence rate with mirabegron., (© 2018 The Japanese Urological Association.)

Objectives: To evaluate the diagnostic efficacy of percutaneous renal tumor biopsy., Methods: We retrospectively investigated 23 patients who underwent percutaneous renal tumor biopsy since 2008 at Department of Renal and Urologic Surgery, Asahikawa Medical University Hospital. We examined indications of biopsy, diagnostic concordance rate between urologists, radiologists and biopsy findings, pathological findings and biopsy-related complications., Results: Renal tumor biopsy was performed under ultrasonography guidance in 21 patients and computed tomography guidance in 2. The most frequent indication to perform biopsy was to determine histological subtype of renal cell carcinoma(RCC)before treatment. The second indication was to clarify the nature of renal tumor. Biopsy findings revealed RCC in 17 patients and urothelial carcino- ma(UC)in 6. Diagnostic concordance rate between urologist's diagnosis and biopsy findings was 91%(21/23), which showed the same result between radiologists and biopsy findings. Biopsy-related adverse event included needle tract implantation in 1 patient with UC. Another patient who had central necrosis in the tumor showed insufficient material causing repeat biopsy with frozen section. Except this patient, initial renal tumor biopsy was successful in all patients by concomitant use of frozen section for tumor with central necrosis. The overall diagnostic rate of initial biopsy was 95.7%(22/23)., Conclusions: Despite a small number of patients and a retrospective nature, the present study shows that renal tumor biopsy plays an important role in diagnosis of renal tumor. Concomitant use of frozen section might be considered at the time of renal tumor biopsy in patients with necrotic renal tumor to avoid repeat biopsy. However, we should take into consideration that there are some possible risks of needle tract implantation in cases with UC when we perform percutaneous renal tumor biopsy.

Antimalarials have demonstrated beneficial effects in Systemic Lupus Erithematosus and Rheumatoid Arthritis. However, the mechanisms and the molecular players targeted by these drugs remain obscure. Although hydroxychloroquine (HCQ) is a known ion channel inhibitor, this property has not been linked to its anti-inflammatory effects. We aimed to study whether HCQ inhibits pro-inflammatory ion channels. Electrophysiology experiments demonstrated that HCQ inhibited Ca ++ -activated K + conductance in THP-1 macrophages in a dose-dependent manner. In macrophages, ATP-induced K + efflux plays a key role in activating the NLRP3 inflammasome. ATP-induced IL-1beta secretion was controlled by the KCa1.1 inhibitor iberiotoxin. NS1619 and NS309 (KCa1.1 and KCa3.1 activators respectively) induced the secretion of IL-1beta. This effect was inhibited by HCQ and also by iberiotoxin and clotrimazol (KCa3.1 inhibitor), arguing against off-target effect. In vitro, HCQ inhibited IL-1beta and caspase 1 activation induced by ATP in a dose-dependent manner. HCQ impaired K + efflux induced by ATP. In vivo, HCQ inhibited caspase 1-dependent ATP-induced neutrophil recruitment. Our results show that HCQ inhibits Ca ++ -activated K + channels. This effect may lead to impaired inflammasome activation. These results are the basis for i) a novel anti-inflammatory mechanism for HCQ and ii) a new strategy to target pro-rheumatic Ca ++ -activated K + channels.

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Purpose: Corneal endothelial cell density undergoes a progressive decrease for many years after transplantation, eventually threatening patients with late endothelial failure. The purpose of this study was to investigate the possibility of an immunologic response in successfully grafted corneal endothelium., Methods: The corneal endothelium of patients who had undergone corneal transplantation was evaluated by specular microscopy. Rabbit models were subjected to penetrating keratoplasty (PK) with either syngeneic or allogeneic corneal transplants and Descemet's stripping endothelial keratoplasty (DSEK) with allogeneic corneal transplants. The presence of immune cells and expression of proinflammatory cytokines were determined by immunostaining. The corneal endothelium and immune cells were also evaluated by scanning electron microscopy., Results: Scanning slit contact specular microscopy of patients with no features of graft rejection revealed cell-like white dots on the grafted corneal endothelium. The corneal endothelium of the allogeneic PK and DSEK rabbit models displayed the presence of immune cells, including CD4+ T-helper cells, CD8+ cytotoxic T cells, CD20+ B lymphocytes, CD68+ macrophages, and neutrophils, but these immune cells were rarely observed in the syngeneic PK model. These immune cells also produced proinflammatory cytokines. Notably, some of the corneal endothelial cells situated near these immune cells exhibited features of apoptosis., Conclusions: T lymphocytes, B lymphocytes, macrophages, and neutrophils are present on the grafted corneal endothelium in both PK and DSEK allogeneic rabbit models. The potential involvement of immune cells as an underlying pathophysiology for late endothelial failure deserves further examination.

Purpose: The interaction between the inducible costimulatory molecule (ICOS) and ICOS ligand (ICOSL) has been implicated in the differentiation and functions of T cells. The purpose of the present study was to determine the role of ICOS-ICOSL in the immune privilege of corneal allografts., Methods: Expression of ICOS and ICOSL mRNA from mouse eyes was assessed by RT-PCR. Corneas of C57BL/6 mice were orthotopically transplanted into the eyes of ICOS-/- BALB/c recipients and BALB/c wild-type (WT) recipients treated with anti-ICOSL mAb, and graft survival was assessed. A separate set of WT and ICOS-/- BALB/c mice received an anterior chamber injection of C57BL/6 splenocytes, and induction of allospecific anterior chamber-associated immune deviation (ACAID) was assessed. In vitro, cornea was incubated with T cells from WT and ICOS-/- BALB/c mice, and destruction of corneal endothelial cells (CECs) and the population of Foxp3+ CD25+ CD4+ T cells was assessed., Results: Inducible costimulatory molecule ligand mRNA was constitutively expressed in the cornea, iris-ciliary body, and retina. Allograft survival in ICOS-/- recipients and WT recipients treated with anti-ICOSL mAb was significantly shorter than in control recipients. Anterior chamber-associated immune deviation was induced less efficiently in ICOS-/- mice. Destruction of CECs by alloreactive ICOS-/- T cells was enhanced compared with WT T cells. After coincubation with allogeneic corneal tissue, the proportion of regulatory T cells was significantly greater among WT T cells than in ICOS-/- T cells., Conclusions: The expression of ICOSL in the cornea and the ICOS-mediated induction of Foxp3+ CD4+ regulatory T cells may contribute to successful corneal allograft survival.

Objectives: Behçet's disease (BD) is a systemic inflammatory disorder polarised to the Th1 and Th17 immune systems. Allergic diseases are polarised to the Th2 immune system. The aim of the present study is to investigate the prevalence of allergic diseases in patients who have BD., Methods: The study involved a large-scale interview survey of Japanese patients with BD at 21 institutes of ophthalmology; 353 patients (255 males and 98 females) were recruited for this study. We analysed the history of allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), bronchial asthma (BA) and drug/food allergies (FA)., Results: Oral aphthous ulcers, ocular lesions, skin lesions, genital ulcers, arthritis, neurological lesions, intestinal lesions, deep vein thrombosis and epididymitis were reported in 95.8%, 98.6%, 72.5%, 44.8%, 13.9%, 6.8%, 6.2%, 3.7% and 1.4% of the patients, respectively. It was also reported that 73 patients (20.7%) had histories of allergic diseases: AD (5 cases, 1.4%), AR (36 cases, 10.2%), BA (19 cases, 5.4%) and FA (30 cases, 8.5%). This percentage was significantly lower than in a survey that Japan's Ministry of Health, Labour and Welfare conducted for healthy population (47.6%) (odds ratio = 0.29, 95% confidence interval = 0.22-0.38, p=4.9×10-22). Frequencies of posterior/pan-uveitis, relatively severe ocular findings, and visual prognosis were not affected by a history of allergic diseases in BD., Conclusions: Patients with BD had fewer complications from allergic diseases than did the entire population of Japan.

Objectives: To investigate the efficacy of combination treatment of degarelix and antiandrogen in patients with prostate cancer., Methods: We prospectively investigated the efficacy of combination treatment of degarelix and antiandrogen in 12 patients with treatment-naive prostate cancer. We surveyed PSA, LH, FSH and testosterone at day 3, 7, 14 and 28 during the initial month and thereafter once a month for 1 year. In cases with bone metastasis, we analyzed serum bone markers such as alkaline phosphatase(ALP), bone-type ALP and carboxyterminal telopeptide of type- I collagen once a month. Skeletal related events (SREs) were also monitored., Results: PSA progression free survival was 65%. PSA was reduced from baseline by 80% at day 14 and by 93% at day 28. In all patients serum testosterone immediately reached castrate level at day 3 and was maintained for 1 year without breakthrough escape. Both LH and FSH were reduced to within normal range at day 3. In contrast, all bone markers temporarily increased at day 28, and thereafter decreased. Although 2 patients had suffered from SREs before treatment, there were no SREs after combination treatment., Conclusions: The present study showed that combination of degarelix and antiandrogen could lead to favorable PSA reduction and immediate castrate level at an earlier phase. However, further study is needed to compare the difference between degarelix monotherapy and these combinations.

An 81-year-old man was referred to our hospital because of a right renal tumor with vena cava thrombus and multiple lung metastases that were detected by computed tomography (CT) scan during evaluation of respiratory discomfort. We started medical treatment with sunitinib at a dose of 50 mg daily in a 2-week-on, 1-week-off schedule after confirming clear cell renal cell carcinoma by tumor biopsy. After 2-week sunitinib treatment, thrombocytopenia continued and platelet count decreased to 1.8×10(9)/l at day 11 after stopping sunitinib. We needed to administer a total of 60 units platelet transfusion because of persistent thrombocytopenia. Bone marrow aspiration did not reveal myelosuppression or carcinoma invasion to bone marrow. Under the clinical diagnosis of drug-induced thrombocytopenia secondary to sunitinib, we started immunoglobulin therapy at day 23 after stopping sunitinib. Platelet count returned to normal 10 days after starting immunoglobulin. The patient developed exacerbating lung metastasis and carcinomatous lymphangiosis during subsequent course and died of renal cell carcinoma 79 days after starting sunitinib. Thrombocytopenia after sunitinib therapy is often encountered but prolonged thrombocytopenia is rare after stopping sunitinib. This case suggests that immunoglobulin therapy is effective for drug-induced prolonged thrombocytopenia through immunological mechanism.

A 66-year-old male patient was referred to our hospital for bilateral renal pelvic tumors. Ureteroscopic biopsy revealed urothelial carcinoma (UC) of low grade (G1) of the renal pelvis. Renal sparing treatment with systemic chemotherapy and percutaneous tumor resection was performed. However, during subsequent follow up, a recurrent tumor was found on the left ureter. After ureteroscopic laser ablation of the tumor, Bacillus Calmette-Guerin (BCG) perfusion therapy (once a week, total 6 weeks) was performed via a single J ureteral catheter with no adverse events. Later, another recurrent recurrence was found on the right ureter, and was managed by ureteroscopic laser ablation followed by BCG perfusion therapy via a single J ureteral catheter. However, the patient developed high fever with chill from the day after initial BCG perfusion therapy on the right side. Although we started antibiotics, high fever continued. Then antituberculous drugs were administered and his condition was improved. Computed tomographic scan revealed a right renal mass 57 mm in diameter, which was consistent with tuberculous granuloma. The tuberculous granuloma persisted despite the continuation of anti-tuberculous drugs. In exceptional cases of upper tract UC such as single kidney and bilateral tumor, BCG perfusion therapy has been used as adjunctive treatment to cure or prevent UC. However, dosages and administration methods of BCG perfusion therapy for upper tract UC still remain to be standardized. Serious adverse events after BCG perfusion therapy require prompt and proper management including the use of anti-tuberculous drugs.

Cortical dipole imaging has been developed to visualize brain electrical activity in high spatial resolution. It is necessary to solve an inverse problem to estimate the cortical dipole distribution from the scalp potentials. In the present study, the accuracy of cortical dipole imaging was improved by focusing on filtering property of the spatial inverse filter. We proposed an inverse filter that optimizes filtering property using a sigmoid function. The ability of the proposed method was compared with the traditional inverse techniques, such as Tikhonov regularization, truncated singular value decomposition (TSVD), and truncated total least squares (TTLS), in a computer simulation. The proposed method was applied to human experimental data of visual evoked potentials. As a result, the estimation accuracy was improved and the localized dipole distribution was obtained with less noise.

We retrospectively reviewed 67 patients who presented with metastatic urothelial carcinoma to the Department of Urology, Asahikawa Medical University Hospital between 2000 and 2013. Furthermore, 13 patients with comparatively longer survival (2 years or longer after diagnosis) were analyzed to find any clinical characteristics among these patients. The primary site was the upper tract in 41 patients and bladder in 26. The most frequent metastatic site was regional lymph nodes (49 patients), followed by viscera (36 patients) and distant lymph nodes (17 patients). Primary tumor resections were performed on 83% of the patients with only regional lymph node metastasis, but on only 35% of the patients with distant metastasis. Median overall survival (OS) of patients was 8.5 months in this series. Median OS of patients with only regional lymph node metastasis was 15 months, which was significantly longer than that (8 months) of patients with distant metastasis. Multivariate analysis revealed only regional lymph node metastasis and the number of metastatic sites were significant prognostic factors for OS. We further investigated the clinical characteristics of 13 patients with comparatively longer survival. Other than a small number of metastatic sites (1 or 2) and no distant lymph node metastasis, we could not find any significant characteristics to predict longer prognosis. The present study showed that primary tumor resection did not have a significant benefit on survival in patients with metastatic urothelial carcinoma at initial presentation. However, primary tumor resection should be considered when there is only regional lymph node metastasis and few metastatic sites.

Purpose: To report the clinical statistical analysis of patients with endogenous intraocular inflammation who visited Nippon Medical School Hospital during the 8 years from 2004 to 2012., Subjects and Methods: This retrospective study involved 759 new patients with endogenous intraocular inflammation who visited Nippon Medical School Hospital during the 8 years from April 2004 to April 2012., Results: The subjects comprised 357 men and 402 women. The ratio of men to women was 1 : 1.1. The age averaged 50.8 ± 16.6 years. Definitive diagnosis was made in 464 cases (61.1%). The most frequent clinical entity was sarcoidosis, followed by scleritis, Vogt-Koyanagi-Harada disease, herpetic iridocyclitis without acute retinal necrosis, acute anterior uveitis associated with human leukocyte antigen (HLA) -B27 and Behçet's disease. Anterior uveitis was the most frequent compared with intermediate, posterior, and pan-uveitis. The incidence of secondary glaucoma was 28.6%, and steroid responder was 28.6%., Conclusion: Sarcoidosis, scleritis and Vogt-Koyanagi-Harada disease were frequent intraocular inflammations in ophthalmologic patients at Nippon Medical School Hospital.

Objective: To investigate the relationship between chronic periodontal disease (CPD) and lower urinary tract symptoms (LUTS) in both sexes., Methods: The interview sheet of the CPD self-checklist and LUTS was distributed to 600 adult men and women (300 each) who visited the first dental examination at dental clinics. The International Prostate Symptom Score (IPSS) questionnaire/Quality Of Life (IPSS/QOL) and Overactive Bladder Symptom Score (OABSS) were used to assess LUTS. The relationship between the CPD score and LUTS or OAB was examined., Results: The interview sheet was collected from 88 men (50.9 ± 16.6 years old) and 97 women (51.1 ± 15.5 years old). There was no statistically significant correlation between the CPD score and age, or between the CPD score and the presence of LUTS in either men or women. However, urgency and weak stream score of IPSS were significantly correlated with the severity of CPD in both sexes. Significant correlation between the severity of CPD and the presence of OAB was only noted in men but not in women., Conclusions: The present study demonstrated for the first time that some storage and voiding symptoms were significantly associated with CPD in both sexes. Thus, although CPD and LUTS seem to have common pathophysiological factors, the interrelationship between CPD and LUTS is slightly different between men and women., (© 2013 Wiley Publishing Asia Pty Ltd.)

In the existing walking support system, the range of detection is limited, and it is very difficult to detect obstacles such as a step or a hollow. Therefore, we aim at the development of a new walking support system for a visually-impaired person detecting neighboring obstacles by making use of a smartphone which is a high-performance portable information terminal. In this study, we have developed a walking support system combining the orientation sensor of the smartphone and a small distance sensor at the first stage. When we investigated its precision in detecting an obstacle, it was found that the system could detect obstacles which disturbed the walking of a visually-impaired person such as a step and a wall. We will find an appropriate key to detection to improve the detection precision of the system and make further improvements in the system by trial experiments in the future.

A 60-year-old woman was referred to our hospital because of gross hematuria, right lumbar pain and lower abdominal pain. Computed tomography (CT) scan revealed hydronephrosis of the right kidney, irregular bladder wall thickening at the right lateral and posterior portion and external iliac lymph node swelling of the right side. Laboratory data revealed disseminated intravascular coagulation syndrome (DIC) and eosinophilia. Because she developed a high fever that was caused by acute obstructive pyelonephritis of the right kidney, percutaneous nephrostomy was placed and the therapy for DIC was initiated. Pathological examination of transurethral resection of bladder tumor performed twice showed no malignancy but inflammatory infiltration of many eosinocytes, leading to the diagnosis of eosinophilic cystitis (EC). We considered the possibility of allergic reaction to the drugs she was taking as the etiology of EC and discontinued all drugs. Although eosinophilia was resolved afterward, she then developed brain infarction, followed by cerebral hemorrhage. She was transferred to a rehabilitation hospital for long-term care. CT scan that was performed 4 months after the initial presentation showed the resolution of hydronephrosis of the right kidney and external iliac lymph node swelling and the improvement of bladder wall thickness. Hydronephrosis of the right kidney has not recurred after removing the nephrostomy catheter. EC is a rare condition that could mimic an invasive bladder cancer. EC should be considered if bladder tumor is associated with eosinophilia. Therapeutic consideration for thromboembolic events should be made in patients with EC.

We examined perioperative complications of transurethral resection of bladder tumor (TURBT) in patients receiving antithrombotic therapy. We retrospectively studied 276 patients who underwent TURBT in our institute from January 2007 to March 2013. The study group consisted of 105 patients (38%) who were receiving antithrombotic agents, and the other 171 patients (62%) without antithrombotic agents were assigned to the control group. The period of discontinuation of antithrombotic agents complied with our institutional rule. The most frequently used agent was aspirin (69 patients : 66%), followed by warfarin (25 patients : 24%). Fourteen patients receiving warfarin (56%) needed heparin bridging therapy. There was no significant difference in average operative time (51 minutes versus 54 minutes), or average days to removal of urethral catheter (3.7 days versus 3.3 days) between the study and control groups. Hemorrhagic and ischemic complications were noted in 11 (10.5%) and 2 (1.9%) patients in the study group and 11 (6.4%) and none (0%) of the patients in the control group, respectively, with no significant difference between the 2 groups. However, prevalence of hemorrhagic complications in patients receiving heparin bridging therapy (21.4%) was significantly higher than that in the control group. Ischemic complications in the study group included chest pain suggestive of angina in one patient and acute myocardial infarction leading to death in another patient. We should pay attention to hemorrhagic complications in patients receiving heparin bridging therapy and keep in mind the possibility of lethal ischemic complications after discontinuation of antithrombotic agents.

Purpose: To evaluate the long-term efficacy and safety of infliximab for the treatment of uveitis in Behçet's disease (BD)., Design: Retrospective multicenter study using a questionnaire., Participants: A total of 164 consecutive patients with BD treated with infliximab for more than 1 year were studied. The mean age at initiation of infliximab treatment was 42.6±11.7 years, and the mean treatment duration was 32.9±14.4 months., Methods: Data before and at the last visit during infliximab treatment were analyzed in 4 groups divided by duration of treatment: group A (n = 43, 12-<24 months), group B (n = 62, 24-<36 months), group C (n = 42, 36-<48 months), and group D (n = 17, ≥48 months)., Main Outcome Measures: Best-corrected visual acuity (BCVA), relapse of ocular inflammation, numbers of ocular inflammatory attacks per year, and adverse effects of infliximab therapy., Results: The frequency of ocular attacks decreased in all groups (from 5.3±3.0 to 1.0±0.3 in group A, 4.8±4.6 to 1.4±0.3 in group B, 4.1±2.9 to 0.9±0.3 in group C, and 9.5±5.8 to 1.6±0.5 in group D; all P < 0.05). The BCVA was improved in approximately 55% of the eyes after treatment. Mean BCVA converted to logarithm of the minimum angle of resolution was improved after treatment with infliximab in groups A to C (from 0.79±1.04 to 0.59±0.94 in group A, 0.59±1.07 to 0.41±1.04 in group B, and 1.15±1.77 to 0.92±1.73 in group C; all P < 0.05) but not in group D. Uveitis relapsed in 59.1% of all patients after infliximab treatment, and no difference in duration until relapse was observed between individual groups. Approximately 80% of relapses occurred within 1 year after the initiation of infliximab treatment in all groups, 90% of which were controlled by increasing doses of topical corticosteroids and shortening the interval of infliximab infusion. Adverse effects were observed in 65 cases or 35% of all subjects. Infliximab treatment was continued in 85% of the patients, but 15% of the patients discontinued infliximab treatment because of adverse effects or insufficient efficacy., Conclusions: Infliximab reduced the frequency of ocular attacks and improved visual acuity in patients with BD-related uveitis and was generally well tolerated with few serious adverse events., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

A 73-year-old man visited our hospital for consultation regarding a pancreatic tumor. Abdominal computed tomography, magnetic resonance imaging, and endoscopic ultrasound scan (EUS) revealed tumor 2 cm in diameter located in the pancreatic tail. EUS-guided fine needle aspiration (EUS-FNA) suggested pancreatic mixed acinar-endocrine carcinoma, and he underwent distal pancreatectomy. Few reports exist where preoperative EUS-FNA suggested pancreatic mixed acinar-endocrine carcinoma; thus, we report this case.

We propose a new apparatus and method to estimate accurate urea reduction ratio without influence of any rebound. For this purpose, we have developed an improved version of a chemiluminescence-based urea sensor capable of measuring urea concentration in spent dialysate (CD ) at 2-min intervals. The correlation coefficient between the readouts of the sensor and the conventional enzyme-UV method was 0.97 and the sensor was not affected by 9 mmol/L uric acid, creatinine, or ammonia. Using the urea sensor, CD was measured as a function of dialysis time t during dialysis sessions for various blood flow rates. The urea reduction ratio based on the mass of the urea reduced (m URR) was estimated from the integrated value of CD (t). When in vitro urea concentrations are measured during a dialysis session in model blood (urea solution) at a constant volume (V) in a vessel, the plots of m URR were congruous with theoretical curves of conventional URR calculated based on the one-pool model, and thus the accuracy of m URR was confirmed. On the other hand, in in vivo measurements of CD (t) during dialysis treatment for two patients, the plots of the m URR were not congruous with the theoretical curves of URR. Such a difference between URR and m URR was explained by the deviation of actual dialysis from the one-pool model, and it was concluded that m URR might be accurate under any dialysis condition., (© 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.)

An 11-year-old girl visited the emergency room of our hospital with complaints of pain, nausea and gross hematuria after abdominal injury due to a fall from a fence. Computed tomography (CT) showed ruptured right kidney, hematoma, urinoma, and slight liver damage in S7 area. According to the Classification of Renal Injury by the Japanese Association for the Surgery of Trauma, this case was Type IIIb, but according to the American Association for the Surgery of Trauma Organ Injury Severity Scale for the Kidney, it was Type V. Because her vital signs were stable after admission, conservative management was initiated. There was no progression of anemia, and blood transfusion was not required. Right ureteral stenting was performed on the 4th hospital day because of an increase in fluid accumulation around the right kidney. Percutaneous drainage was performed on the 9th hospital day because of a further increase in fluid accumulation around the right kidney. After percutaneous drainage, fluid accumulation around the kidney was improved, and the drainage tube was removed on the 20th hospital day. The patient was discharged on the 22nd day. Although the decreased blood flow in the ruptured portion of the right kidney was observed in a subsequent CT scan, renal scintigraphy showed a relatively well maintained function of the right kidney (split renal function; right 38% and left 62%). She had no increase in blood pressure one year after renal injury.

Objective: To investigate whether bladder dysfunction after bladder outlet obstruction (BOO) could be altered by treatment with cilostazol, a phosphodiesterase 3 inhibitor (PDE3i)., Methods: Twelve-week-old female Sprague-Dawley rats were divided into 5 groups: groups 1 and 2, sham-operated rats and groups 3-5, BOO rats. Group 1 and 3 rats were given normal diet, group 2 and 5 rats were given high-dose PDE3i diet, and group 4 rats were given low-dose PDE3i diet. PDE3i was given within diet from the day of surgery. Four weeks after BOO, the bladder was excised and dissected into 4 longitudinal strips for isometric organ-bath assay. Contractile responses of bladder strips to electrical field stimulation (EFS), carbachol, and potassium chloride (KCl) were determined for each group., Results: BOO induced a significant increase in bladder weight in groups 3-5 compared with groups 1 and 2. PDE3i treatment did not affect bladder weight in sham or BOO rats. Contractile forces in response to EFS, carbachol, and KCl in group 3 were about 20%-40% of those in group 1. Contractile responses to EFS or KCl in PDE3i-treated BOO rats were not significantly different from those in group 3. Only high dose of PDE3i treatment in BOO rats caused a statistically significant increase in the response to carbachol compared with group 3., Conclusion: PDE3i has a small but significant protective effect on the contractile dysfunction induced by a 4-week BOO in rats, although the increase in bladder mass was not altered. PDE3i could be a useful protection against contractile dysfunction of the obstructed bladder., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The spatial resolution of scalp potential mapping is limited because of low conductivity of a skull. Cortical dipole layer imaging has been proposed as a method to visualize brain electrical activity with high spatial resolution. According to this method, about 100 electrodes were required to measure whole brain electrical activity. In the present study, we investigated simplified cortical dipole imaging with a small number of electrodes. The density of electrodes and the spatial resolution are in a trade-off relation. Thus, the number of electrodes was reduced by limiting the visualization region of interest, without lowering the density of electrodes. Moreover, independent component analysis was applied to the multiple signal sources to extract an attention signal from the other signals and noise. In simulation, even if the number of electrodes was reduced to 25, the obtained results were almost equivalent to the case with whole brain electrodes. The proposed method was applied to human experimental data of movement-related potential. We confirmed that the proposed method provided high resolution cortical dipole imaging with localized distribution.

To examine the relationship between chronic periodontal disease (CPD) and ED, the interview sheet including the CPD self-checklist (CPD score) and the five-item version of the International Index of Erectile Function (IIEF-5) was distributed to 300 adult men who received a comprehensive dental examination. Statistical analyses were performed by the Spearman's rank correlation coefficient and other methods. Statistical significance was accepted at the level of P<0.05. The interview sheets were collected from 88 men (response rate 29.3%, 50.9±16.6 years old). There was a statistically significant correlation between the CPD score and the presence of ED (P=0.0415). The results in the present study suggest that ED is related to the damage caused by endothelial dysfunction and the systematic inflammatory changes associated with CPD. The present study also suggests that dental health is important as a preventive medicine for ED.

Objectives: To investigate bladder function in a model of nonbacterial prostatitis (NBP) induced in castrated rats by 17β-estradiol injection., Methods: Ten-month-old male Wistar rats were divided into two groups, sham and NBP (both N = 8). NBP was induced by castration followed by daily subcutaneous injection of 17β-estradiol for 30 days. On the 31st day after surgery, we investigated (1) voiding behavior, (2) bladder blood flow (BBF), (3) prostate and bladder weight, and proinflammatory cytokines (TNF-α and CXCL1) levels and (4) bladder contractile responses to electrical field stimulation (EFS), carbachol and KCl., Results: (1) Voiding behavior (average micturition volume, total urine volume and number of micturitions) and (2) BBF were not significantly different between the sham and NBP groups. (3) NBP led to a significant decrease in prostatic weight and increase in proinflammatory cytokine levels in the prostate, but NBP did not cause a significant change in bladder weight or proinflammatory cytokine levels in the bladder. (4) Bladder contractile forces in response to EFS, carbachol and KCl were not significantly affected by NBP., Conclusions: In this rat model, NBP did not cause a significant change in the level of proinflammatory cytokines in the bladder and affect bladder function.

The eye is an immune-privileged organ, and corneal transplantation is therefore one of the most successful organ transplantation. The immunosuppressive intraocular microenvironment is known as one of the mechanisms underlying immune privilege in the eye. T-cell immunoglobulin and mucin domain (Tim)-3 is a regulatory molecule for T-cell function, and galectin (Gal)-9 is a Tim-3 ligand. We investigated the role of this pathway in establishing the immune-privileged status of corneal allografts in mice. Gal-9 is constitutively expressed on the corneal epithelium, endothelium and iris-ciliary body in normal mouse eyes and eyes bearing surviving allografts, and Tim-3 was expressed on CD8 T cells infiltrating the allografts. Allograft survival in recipients treated with anti-Tim-3 monoclonal antibody (mAb) or anti-Gal-9 mAb was significantly shorter than that in control recipients. In vitro, destruction of corneal endothelial cells by allo-reactive T cells was enhanced when the cornea was pretreated with anti-Gal-9 mAb. Blockade of Tim-3 or Gal-9 did not abolish anterior chamber-associated immune deviation. We propose that constitutive expression of Gal-9 plays an immunosuppressive role in corneal allografts. Gal-9 expressed on corneal endothelial cells protects them from destruction by allo-reactive T cells within the cornea.

Unlabelled: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: There is known to be an association between overactive bladder (OAB) and irritable bowel syndrome (IBS). The study investigates the association between OAB and IBS using an internet-based survey in Japan. It is the first to investigate the prevalence and severity of OAB in the general population using the OAB symptom score questionnaire., Objective: To investigate the association between overactive bladder (OAB) and irritable bowel syndrome (IBS) by using an internet-based survey in Japan., Subjects and Methods: Questionnaires were sent via the internet to Japanese adults. The overactive bladder symptom score was used for screening OAB, and the Japanese version of the Rome III criteria for the diagnosis of IBS was used for screening this syndrome., Results: The overall prevalence of OAB and IBS was 9.3% and 21.2%, respectively. Among the subjects with OAB, 33.3% had concurrent IBS. The prevalence of OAB among men was 9.7% and among women it was 8.9%, while 18.6% of men and 23.9% of women had IBS. Concurrent IBS was noted in 32.0% of men and 34.8% of women with OAB., Conclusion: Taking into account a high rate of concurrent IBS in patients with OAB, it seems to be important for physicians to assess the defaecation habits of patients when diagnosing and treating OAB., (© 2012 The Authors. BJU International © 2012 BJU International.)

Cortical dipole imaging has been proposed as a method to visualize electroencephalogram in high spatial resolution. We investigated the inverse technique of cortical dipole imaging using a truncated total least squares (TTLS). The TTLS is a regularization technique to reduce the influence from both the measurement noise and the transfer matrix error caused by the head model distortion. The estimation of the regularization parameter was also investigated based on L-curve. The computer simulation suggested that the estimation accuracy was improved by the TTLS compared with Tikhonov regularization. The proposed method was applied to human experimental data of visual evoked potentials. We confirmed the TTLS provided the high spatial resolution of cortical dipole imaging.

Introduction: The thrust plate hip prosthesis (TPP) is a bone-reserving prosthesis for cementless fixation at the metaphysis of the proximal femur. We retrospectively evaluated the results of 162 patients (179 hips) who underwent hip arthroplasty using TPP., Patients and Methods: Eighty-three patients (87 hips) suffered from osteoarthritis of the hip joint (OA group), 79 patients (92 hips) from osteonecrosis of the femoral head (ON group). The mean age at surgery was 55 years in the OA group and 47.4 years in the ON group. The mean follow-up period was 97 months in the OA group and 104 months in the ON group. For these patients, we evaluated the results clinically and radiographically., Results: The mean Merle d'Aubigne's score improved from 8.2 to 16.9 in the OA group and from 9.1 to 16.6 in the ON group at the final follow-up. Early mechanical loosening of TPP was observed in two hips of OA and one hip of ON. In one patient of ON, bilateral TPPs had to be removed 5 years postoperatively because of infection. Two female patients with ON suffered from a spontaneous femoral fracture below the tip of the lateral plate. Kaplan-Meier survivorship using TPP removed for any reason as the end point was 97.7% in the OA group and 90.3% in the ON group after 13 years., Conclusion: The middle-term results of the TPP were satisfactory if the indication for the TPP and the operative procedure were appropriate. The TPP is a useful and safe prosthesis for relatively young patients with not only osteoarthritis of the hip but also osteonecrosis of the femoral head.

The purpose of this study was to evaluate the outcome of femoral impaction bone grafting with an allograft combined with hydroxyapatite (HA). Fifty-four consecutive femoral reconstructions that were performed with the use of frozen morselized allografts and HA were followed up retrospectively. The average follow-up period was 92 months. A femoral head and HA were mixed and used as allograft. The average Merle d'Aubigné clinical score improved from 8.9 preoperatively to 13.1 points postoperatively. Stem subsidence was seen in 26 hips; however, it was not progressive after 1 year postoperatively. Cortical repair was detected at an average of 7 months postoperatively. Impaction bone grafting with an allograft combined with HA provided favorable results, with bone remodeling and less subsidence., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The objective evaluation of somatic sensations is expected without a patient's subjective opinions to reduce social problems such as those related to lawsuits for nerve injuries or malingering. In this study, the somatosensory evoked potential (SEP) using the mechanical stimulations of the tactile sensation was measured and analyzed in spatiotemporal domains. The cortical potential mapping projected onto the realistic-shaped model was estimated to improve the spatial resolution of the SEP maps by application of cortical dipole layer imaging. The experimentally obtained results suggest that the spatiotemporal distributions of the SEPs reflect the differences for positions, strengths, and patterns of somatosensory stimulations.

Purpose: The purpose of this study was to investigate the mid-term results of 32 acetabular reconstructions performed using a Kerboull-type acetabular reinforcement device and bone graft between June 1997 and January 2009., Methods: The mean age of the patients at the time of surgery was 71.4 years (range 55-85). Patients were followed-up for a mean of 7.5 years (range 2.1-13.7). The acetabular bone defects according to the American Academy of Orthopaedic Surgeons system was type III for 29 hips and type IV for three hips. Bulk allografts were performed in 30 hips and morselised autografts (iliac bone) were performed in two hips. Clinical evaluations were made according to the criteria of Postel/Merle d'Aubigné., Results: The mean pre-operative Postel/Merle d'Aubigné hip score was 7.0 ± 2.9, and the final follow-up hip score was 12.6 ± 2.8. Six hips showed radiographic loosening, and two hips required further revision. A Kaplan-Meier analysis showed that the five-year and ten-year survival rates were 96.9% and 92.3%, respectively, using further revision of the acetabular device as an end point., Conclusion: Acetabular reconstruction using a Kerboull-type acetabular reinforcement device and bone graft gives satisfactory mid-term results.

The purpose of this study was to investigate the chondrogenic potential of magnetically labeled synovium-derived cells (M-SDCs) and examine whether M-SDCs could repair the articular cartilage using an intra-articular magnet after delivery to the lesion. Synovium-derived cells (SDCs) were cultured from the synovium of a rat knee, and were magnetically labeled with ferumoxides. M-SDCs were examined with a transmission electron microscope. A pellet culture system was used to evaluate the chondrogenic potential of M-SDCs in a magnetic field. In a rat model, allogeneic M-SDCs were injected into the knee after we made an osteochondral defect on the patellar groove and implanted an intra-articular magnet at the bottom of the defect. We histologically examined the defects at 48 h, 4 weeks, 8 weeks, and 12 weeks after treatment. Electron microscopy showed the transfection of ferumoxides into SDCs. The pellet cultures revealed the chondrogenic potential of M-SDCs in a magnetic field. M-SDCs accumulated in the osteochondral defect at 48 h after treatment, and we confirmed the regeneration of the articular cartilage at 4 weeks, 8 weeks, and 12 weeks after treatment using an intra-articular magnet. We demonstrated that articular cartilage defects could be repaired using an intra-articular magnet and M-SDCs. We believe that this system will be useful to repair human articular cartilage defects., (Copyright © 2010 Orthopaedic Research Society.)

In clinical situations, the objective evaluation of somatic sensations is expected without a patient's subjective opinions to reduce social problems such as those related to lawsuits for nerve injuries and malingering. In this study, the somatosensory evoked potential (SEP) using the mechanical stimulations of the tactile sensation was measured and analyzed in spatiotemporal domains. The spatial resolution of SEP maps was improved by application of cortical dipole layer imaging. The experimentally obtained results suggest that the spatiotemporal distributions of the SEPs reflect the differences for positions, strengths, and patterns of somatosensory stimulations.

Purpose: The pathway between the glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) and GITR ligand (GITRL) has been shown to control the function of regulatory T cells (Treg). The present study was conducted to investigate the role of this pathway and Treg in establishing immune privilege status for corneal allografts., Methods: Corneas of C57BL/6 mice were orthotopically transplanted into the eyes of BALB/c mice, and graft survival was assessed. A separate set of BALB/c mice received an anterior chamber injection of C57BL/6 splenocytes, and induction of allo-specific anterior chamber-associated immune deviation was assessed. Recipients were intraperitoneally administrated anti-GITRL, anti-CD25 monoclonal antibodies (mAb), or control immunoglobulin (IgG). Expressions of GITRL, GITR, and Foxp3 in the allografts were assessed. In vitro, cornea pretreated with anti-GITRL mAb or control IgG was incubated with T cells, and destruction of corneal endothelial cells and the population of Foxp3(+)CD25(+)CD4(+) T cells were assessed., Results: GITRL was expressed constitutively in the cornea and iris-ciliary body. GITRL-expressing allografts were infiltrated with Foxp3+GITR+CD25+CD4(+) T cells. Blockade of GITRL did not affect allo-specific ACAID but led to infiltration of Foxp3(-)CD4(+) T cells and allograft rejection. Depletion of CD25+CD4(+) Treg also accelerated allograft rejection. Destruction of corneal endothelial cells by T cells was significantly enhanced in GITRL-blocked cornea compared with control cornea. Foxp3+CD25+CD4(+) T cells were increased after incubation with GITRL-expressing cornea, but not with GITRL-blocked cornea., Conclusions: Presence of Foxp3+CD25+CD4(+) Treg in the allograft is necessary for allograft survival. GITRL-dependent expansion of Treg within the cornea is one mechanism underlying immune privilege in corneal allografts.

The original evidence for the existence of immunologically privileged sites in the body was based on the prolonged survival of genetically disparate transplanted tissue in the anterior chamber of the eye. The failure of the immune system to elicit an immune response in this and other such sites constitutes the hallmark of the immune privilege status. The remarkably successful field of corneal transplantation in clinical practice is undoubtedly associated with corneal immune privilege. Several investigations have addressed the regulatory mechanisms governing this phenomenon, which involves a complex interplay between multiple molecular and cellular pathways. Furthermore, the use of various transgenic mouse models has facilitated the identification of critical pathways, which upon disruption can modify the immune privileged status of the eye. Understanding these pathways not only reveals the mechanisms underlying various ocular inflammatory disease conditions, but also has clinical implications for the transplantation field and for the treatment of autoimmunity.

We have investigated the suitable spatial filters for inverse estimation of cortical dipole imaging from the scalp electroencephalogram. The effects of incorporating statistical information of noise into inverse procedures were examined by computer simulations and experimental studies. The parametric projection filter (PPF) was applied to an inhomogeneous three-sphere volume conductor head model. The noise covariance matrix was estimated by applying independent component analysis (ICA) to the scalp potentials. Moreover, the sampling method of the noise information was examined for calculating the noise covariance matrix. The simulation results suggest that the spatial resolution was improved while the effect of noise was suppressed by including the separated noise at the time instant of imaging and by adjusting the number of samples according to the signal to noise ratio.

The purpose of this study is to support communication of individuals with motor paralysis having difficulty verbally communicating due to illnesses such as Guillain-Barre Syndrome or brain-stem infarction. We have developed and describe a pointing device controlled by DC-coupled electrooculograms (EOGs). The visual angle of the subject is estimated from the amplitude of vertical and horizontal EOGs for determining the two-dimensional pointing position on a PC screen in real time. The eye blinking artifact is reduced using a median filter. Electrode displacement is corrected by considering the potential gradient. Moreover, the position error caused by drift phenomenon is adjusted using head movement based on the vestibule-ocular reflex. The accuracy and operating speed of the proposed method were evaluated among a group of human subjects.

The eye, like the brain and reproductive organs, possesses inherent immune privilege, and inflammation is self-regulated so as to preserve the organ functions. Studies over the past 30 years have provided insights of the multiple mechanisms of immune privilege. At present, three major lines of thought prevail regarding the molecular mechanisms of immune privilege in the eye: there are (1) anatomical, cellular, and molecular barriers in the eye; (2) eye-derived immunological tolerance, the so-called anterior chamber-associated immune deviation; and (3) immune suppressive intraocular microenvironment. In this review, the mechanisms of immune privilege that have been learned from ocular inflammation animal models, especially corneal transplantation, are described. Roles of new B7 family molecules on local immune regulation within the cornea are also introduced.

Background and Aim: Metallothionein (MT) has a proven relationship with various kinds of cancer and reduces tissue damage. Helicobacter pylori (H. pylori) infection is associated with the alteration of gastric epithelial cell cycle events, a condition implicated in the initiation and development of gastric cancer. This study investigates the role of MT in H. pylori-induced gastritis with or without early gastric cancer (ECG) and evaluates the effect on MT expression after eradication therapy., Methods: Gastric biopsy samples were immunohistochemically examined for MT expression in 36 H. pylori-negative patients without ECG and 98 positive patients with or without ECG. Real time polymerase chain reaction was performed in 14 antral biopsy samples with or without H. pylori. The severity of gastritis was also evaluated according to the updated Sydney System. In 31 successfully eradicated patients, the above assessment was repeated for two consecutive years., Results: MT expression was higher in H. pylori-negative patients than in positive patients (P < 0.01). Moreover, in the corpus it was higher in H. pylori-positive patients without ECG compared to those with ECG (P < 0.05). The MT labeling index had a negative correlation with the severity of gastritis (P < 0.01). A positive correlation was shown between the MT labeling index and apoptosis: proliferation ratio (r = 0.41, P < 0.01). The MT labeling index in H. pylori-positive patients was gradually recovered after eradication (P < 0.05)., Conclusion: The decrease of MT expression cannot prevent tissue damage in H. pylori-positive gastric mucosa and leads to more severe gastritis. This phenomenon may be attributed to gastric carcinogenesis. H. pylori eradication increases MT expression and may reduce the risk of ECG.

Objective: Severe urinary tract infection may lead to sepsis in some cases. In these cases, treatment must not only include drainage of the source of infection, but also management of systemic inflammatory response syndrome (SIRS). Blood purification therapy focused on endotoxin adsorption is thought to be a useful treatment method for this purpose. Herein, we clinically investigated the cases in which this treatment method was applied., Subjects and Methods: A total of 22 patients underwent endotoxin adsorption therapy following diagnosis of sepsis at the department of urology, Hokkaido Social Welfare Association Furano Hospital during the last six years. Of these patients, six patients whose primary disease was urinary tract infection were included in the study., Results: Patients comprised four men and two women with either pyelonephritis (n = 5; complicated by prostatitis in one patient) or pyonephrosis (n = 1). Primary diseases included urolithiasis (n = 4), vesicoureteral reflux (n = 1), and ureteric stenosis (n = 1). Urinary tract drainage included ureteral stent (n = 4), nephrostomy (n = 1), and cystostomy (n = 1), with concomitant use of continuous hemodiafiltration in one patient. Serum endotoxin levels were 3.2 pg/ml on average, and returned to normal following endotoxin adsorption therapy in all patients. A total of four strains of Escherichia coli and one strain of Klebsiella pneumoniae were identified as pathogenic bacteria., Conclusion: Hemodynamics was markedly stabilized following endotoxin adsorption therapy, and all patients survived. These findings indicate that endotoxin adsorption therapy should be actively considered as a treatment method for patients with sepsis secondary to urinary tract infection.

We report a case of a 32-year-old man with hyper IgE syndrome (Job syndrome) who developed Fournier gangrene due to infectious multiple atheromas of the scrotal skin that progressed to the right groin and thigh. The patient required surgical debridement and subsequent skin grafting. This is a rare case of Fournier gangrene associated with hyper IgE syndrome (Job syndrome). When a patient without diabetes mellitus has repeated infections and atopic-like dermatitis, Job syndrome should be considered.

The present study determined whether topical latanoprost, a prostaglandin (PG) F(2alpha) analog, influences the induction of anterior chamber-associated immune deviation (ACAID), corneal neovascularization (NV) or survival of corneal allografts in mice. BALB/c mice received topical latanoprost or PGE(2) once or multiple times daily starting 4 weeks prior to or the day of anterior chamber injection of C57BL/6 splenocytes. Induction of allo-specific ACAID was assessed by ear challenge with C57BL/6 splenocytes 1 week after subcutaneous immunization. In a separate experiment, orthotopic corneal transplantation was performed using C57BL/6 mice as donors and BALB/c mice as recipients. Recipients were randomized in a masked fashion to receive topical latanoprost or PGE(2). Graft fate was assessed clinically under surgical microscopy. Presence of MHC class II(+) CD11c(+) or CD11b(+) cells in normal BALB/c mouse eyes following latanoprost or PGE(2) administration was assessed immunohistochemically. Control mice received topical 20% dimethyl sulfoxide or no treatment. Allo-specific ACAID was induced after 2 or 6 weeks of once daily treatment with latanoprost, and was induced even after 6 weeks of multiple treatments with latanoprost. Conversely, mice receiving PGE(2) failed to develop ACAID. Opacity and corneal NV scores for allografts treated with latanoprost were statistically indistinguishable from those for control allografts (p>0.05), whereas all allografts treated with PGE(2) were rejected. Opacity and NV scores were significantly higher in these allografts than in controls (p<0.05). A number of MHC class II(+) CD11c(+) cells were present in the central cornea after PGE(2) treatment. Topical application of latanoprost does not influence induction of ACAID or graft outcomes including opacity and NV, whereas PGE(2) does. Immune privilege of corneal allograft is maintained after topical latanoprost application in mice.

Suitable spatial filters were explored for inverse estimation of cortical dipole imaging from a scalp electroencephalogram. Computer simulations were used to examine the effects of incorporating statistical information of signal and noise into inverse procedures. Actually, the parametric projection filter (PPF) and parametric Wiener filter (PWF) were applied to an inhomogeneous three-sphere head model. The signal and noise covariance matrices were estimated by applying independent component analysis (ICA) to the scalp potentials. The simulation results described herein suggest that the PPF using differential noise between EEG and separated signal were equivalent to those obtained using the method with actual noise. Moreover, the PWF using separated signals has better performance than traditional inverse techniques.