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Thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly comprise TAFRO syndrome, which was proposed as a distinct clinical entity from iMCD without TAFRO syndrome (iMCD-NOS) due to its aggressive clinical course, refractoriness to corticosteroids, presence of thrombocytopenia, increased level of alkaline phosphatase, and normal level of gammaglobulin. However, diagnosing TAFRO syndrome in its early stages is challenging because it is rare and its diagnostic criteria are complicated. We describe a patient with TAFRO syndrome and adrenal hemorrhage who demonstrated a rapid decline in her clinical condition and did not respond to steroid pulse therapy, resulting in a fatal outcome. In the early stage of her clinical course, she developed unilateral adrenal hemorrhage with mild thrombocytopenia and normal clotting times, suggesting adrenal hemorrhage as a unique manifestation of TAFRO syndrome. In general, patients with TAFRO syndrome exhibit a more aggressive clinical course and poorer outcome than those with iMCD-NOS. To ameliorate this poor prognosis, it is important to diagnose the disease early and immediately start powerful immunosuppressive agents such as tocilizumab. Based on this case, adrenal hemorrhage may suggest TAFRO syndrome, and facilitate the rapid diagnosis of this complicated and rare disease.

Background Chronic active Epstein–Barr virus infection (CAEBV) is defined as Epstein–Barr virus (EBV)-positive T/NK cell-related neoplasia, and its major clinical symptom is systemic inflammation presenting as infectious mononucleocytosis, whereas enteritis and diarrhea are minor clinical symptoms. The complex mixture of tumorigenic processes of EBV-positive cells and physical symptoms of systemic inflammatory disease constitutes the varied phenotypes of CAEBV. Herein, we describe a case of CAEBV that was initially diagnosed as Crohn’s disease (CD) based on ileal ulcers and clinical symptoms of enteritis. Case presentation A 19-year-old woman complained of abdominal pain and fever. Blood examination showed normal blood cell counts without atypical lymphocyte but detected modest inflammation, hypoalbuminemia, slight liver dysfunction, and evidence of past EBV infection. The esophagogastroduodenoscopic findings were normal. However, colonoscopy revealed a few small ulcers in the terminal ileum. The jejunum and ileum also exhibited various forms of ulcers, exhibiting a cobblestone appearance, on capsule endoscopy. Based on these clinical findings, she was strongly suspected with CD. In the course of treatment by steroid and biologics for refractory enteritis, skin ulcers appeared about 50 months after her initial hospital visit. Immunohistology of her skin biopsy revealed proliferation of EBV-encoded small RNA (EBER)-positive atypical lymphocytes. We retrospectively assessed her previous ileal ulcer biopsy before treatment and found many EBER-positive lymphocytes. Blood EBV DNA was also positive. Therefore, she was diagnosed with extranodal NK/T-cell lymphoma with CAEBV-related enteritis rather than CD. She was treated with cyclosporine and prednisolone combination therapy for CAEBV-related systemic inflammation and chemotherapy for malignant lymphoma. Unfortunately, her disease continued to progress, leading to multiple organ failure and death at the age of 23 years. Conclusion Clinicians need to remember the possibility of CAEBV as a differential diagnosis of refractory enteritis. Enteritis with intestinal ulcer is a rare symptom of CAEBV, and it is impossible to acquire a definitive diagnosis by ulcer morphology only. In cases where the possibility of CAEBV remains, tissue EBVR expression should be checked by in situ hybridization and blood EBV DNA.

A compact, low loss and high power handling high temperature superconducting filter using dual-mode double-strip resonators (DSRs) was developed. We proposed new superconducting feeding structure, which was replaced from the previously reported brass center pin feeding structure, to improve insertion loss. A four-pole elliptic function dual-mode DSR filter was designed by the electromagnetic simulator based on the moment method. The center frequency and bandwidth of the filter are a 5.0-GHz and an 80-MHz. The compact filter was fabricated using YB2Cu3Oy thin films on r-Al2O3 substrates (25 mm × 25 mm). The measured frequency responses of the filter were in reasonable agreement with the simulated ones. The measured insertion loss was 0.08 dB. The measured power handling capability of the proposed filter was more than 40 W at 60 K.

Background Since the emergence of Coronavirus disease 2019 (COVID-19), safety management in gymnastics classrooms has been difficult. As a result, healthy older adults are more likely to voluntarily refrain from attending because of fear of contracting COVID-19, and thus engage in less exercise. In this context, it is important to develop methods for self-prevention of frailty that can be conducted safely and easily at home. We examined the effectiveness of providing ankle weights to older adults as a frailty prevention device. Methods All participants were 50–90 years old and were screened for falls using the Motor Fitness Scale (MFS). Participants were divided into two groups (≤ 70 and ≥ 71 years old) and analyzed. We rented ankle weights for 3 months to older adults in the community and evaluated changes in physical and motor function before and after wearing them. A total of 75 people who responded to the call for participants used ankle weights for 3 months, and underwent various measures of physical condition, cognitive condition, and performance (body composition, grip strength, standing on one leg with eyes open, 30-second chair stand test [CS-30], timed up-and-go test [TUG], walking speed, body sway measurement, and the Japanese version of Montreal Cognitive Assessment [MOCA-J]) before and 3 months after wearing ankle weights. Results CS-30 performance improved in both younger and older participants. Conclusions CS-30 reflects lower limb/trunk muscle strength and can be used as an index of fall risk. Our results suggest that wearing ankle weights can be recommended as a fall-prevention measure. Trial registration: University hospital Medical Information Network ID 000038073) and registration date at April 14th 2020

The Japan Meteorological Agency (JMA) is conducting the third Japanese global atmospheric reanalysis named Japanese Reanalysis for Three Quarters of a Century (JRA-3Q) using the JMA operational data assimilation system that has been upgraded and improved since the Japanese 55-year Reanalysis (JRA-55) was conducted. Main points of improvement in the specifications of the data assimilation system are as follows (specifications of the JRA-55 data assimilation system are shown in parentheses for comparison): Vertical levels are increased up to 100 (60) layers; The top level of the system is 0.01 (0.1) hPa; The inner model resolution for 4D-Var is also increased up to TL319 (T106); Various parameterization schemes have been improved and several new schemes have been implemented. In addition, we use observations newly rescued and digitized by the ERA-CLIM and other projects as well as newly reprocessed and improved satellite observations. As for GNSS radio occultation, bending angle is assimilated up to 60 km (refractivity up to 30 km).The early results show that both overestimation of precipitation in the tropics and dry bias in the middle troposphere are diminished compared with those in JRA-55, and the representation of diabatic heating rate is also improved. In addition, biases of surface heat fluxes and radiation fluxes at the top of the atmosphere are also reduced.

Objective To evaluate the efficacy and safety of intravesical KRP-116D, 50% dimethyl sulfoxide solution compared with placebo, in interstitial cystitis/bladder pain syndrome patients. Methods Japanese interstitial cystitis/bladder pain syndrome patients with an O'Leary-Sant Interstitial Cystitis Symptom Index score of ≥9, who exhibited the bladder-centric phenotype of interstitial cystitis/bladder pain syndrome diagnosed by cystoscopy and bladder-derived pain, were enrolled. Patients were allocated to receive either KRP-116D (n = 49) or placebo (n = 47). The study drug was intravesically administered every 2 weeks for 12 weeks. Results For the primary endpoint, the change in the mean O'Leary-Sant Interstitial Cystitis Symptom Index score from baseline to week 12 was -5.2 in the KRP-116D group and -3.4 in the placebo group. The estimated difference between the KRP-116D and placebo groups was -1.8 (95% confidence interval -3.3, -0.3; P = 0.0188). Statistically significant improvements for KRP-116D were also observed in the secondary endpoints including O'Leary-Sant Interstitial Cystitis Problem Index score, micturition episodes/24 h, voided volume/micturition, maximum voided volume/micturition, numerical rating scale score for bladder pain, and global response assessment score. The adverse drug reactions were mild to moderate, and manageable. Conclusions This first randomized, double-blind, placebo-controlled trial shows that KRP-116D improves symptoms, voiding parameters, and global response assessment, compared with placebo, and has a well-tolerated safety profile in interstitial cystitis/bladder pain syndrome patients with the bladder-centric phenotype.

Background We aimed to demonstrate the contribution of anti-inflammatory and anti-virulence effects of azithromycin (AZM) in ocular surface infection treatment. Methods Staphylococcus aureus was injected into the corneal stroma of rabbits to induce keratitis. AZM at concentrations of 0.01, 0.1, and 1% was instilled into the eye twice daily. The eyes were examined using a slit lamp and scored. The viable bacteria in the cornea were counted at 48 h post infection. To evaluate the anti-inflammatory efficacy of AZM, S. aureus culture supernatant-induced anterior ocular inflammation in rabbit was examined using a slit lamp and scored. To evaluate the inhibitory effect of AZM on bacterial toxin production, S. aureus was cultured with AZM and hemolytic reaction in the culture supernatant was determined. Results In the bacterial keratitis model, AZM dose-dependently inhibited the increase in the clinical score. The viable bacterial count in the cornea treated with 1% AZM significantly decreased compared with that of the vehicle, whereas bacterial count in 0.01 and 0.1% AZM-treated corneas was similar to that of the vehicle. In the anterior ocular inflammation model, 0.1 and 1% AZM inhibited the increase in the clinical score. AZM inhibited hemolytic reaction at concentrations that did not inhibit bacterial growth. Conclusions The results demonstrated that AZM has not only anti-bacterial, but also anti-inflammatory effects, and inhibits bacterial toxin production leading to ocular surface damage in bacterial infection. Thus, the therapeutic effect of AZM against ocular infections is expected to be higher than that which could be assumed if it only had anti-bacterial activity.

This report outlines the structure of and summarizes the recommendations made at the 5th International Conference on Reanalysis (ICR5), attended by 259 participants from 37 countries, in Rome (Italy), on 13-17 November 2017. It first summarizes the conference structure. Then, the key recommendations of ICR5 are given for the five main conference topics: production; observations (data rescue and preparation); data assimilation methods; quality assurance of reanalysis; and applications in science, services, and policymaking. Lastly, five high-level recommendations are proposed to managing agencies on how best to advance the field of reanalyses, which serves tens of thousands of users, via enhanced research, development, and operations.

To better understand the impacts of climate change, environmental monitoring capabilities must be enhanced by deploying additional and more accurate satellite- and ground-based (including in situ) sensors. In addition, reanalysis of observations collected decades ago but long forgotten can unlock precious information about the recent past. Historical, in situ observations mainly cover densely inhabited areas and frequently traveled routes. In contrast, large selections of early meteorological satellite data, waiting to be exploited today, provide information about remote areas unavailable from any other source. When initially collected, these satellite data posed great challenges to transmission and archiving facilities. As a result, data access was limited to the main teams of scientific investigators associated with the instruments. As archive media have aged, so have the mission scientists and other pioneers of satellite meteorology, who sometimes retired in possession of unique and unpublished information. This paper presents examples of recently recovered satellite data records, including satellite imagery, early infrared hyperspectral soundings, and early microwave humidity soundings. Their value for climate applications today can be realized using methods and techniques that were not yet available when the data were first collected, including efficient and accurate observation simulators and data assimilation into reanalyses. Modern technical infrastructure allows serving entire mission datasets online, enabling easy access and exploration by a broad range of users, including new and old generations of climate scientists.

BACKGROUND Recurrent aneurysms after initial clipping have been discussed as an important issue in the surgical management of aneurysm. OBJECTIVE To report our experience with recurrent cerebral aneurysms after neck clipping and to discuss classification and recommended management. METHODS Aneurysm treatments from a single institution over a 20-year period were retrospectively reviewed. Twenty-three recurrent aneurysms in 23 patients were managed during the study period. Recurrent aneurysms were classified using the concepts of closure line and closure plane, as follows. Type 1: neck situated in an almost different site from the previous clip. Type 2: existing closure plane and reconstructive closure plane are almost the same. Type 3: existing closure plane and reconstructive closure plane cross (type 3a); in rare cases, the existing closure line is sufficiently distant from the neck (type 3b). Type 4: no reconstructive closure line is identifiable. RESULTS Nine patients presented with subarachnoid hemorrhage at recurrence. The mean interval to recurrence was 15.0 years. Management comprised clipping with elective subsequent old-clip removal (n = 7), clipping with preceding old-clip removal (n = 2), bypass occlusion (n = 1), coating (n = 1), combined surgery (n = 1), endovascular surgery (n = 4), and observation (n = 3). Therapeutic intervention was not indicated in 4 patients. Types 3a and 4 required more complex surgical procedures or coil embolization. Procedural complications were observed in 2 patients. CONCLUSION A small but definite propensity toward recurrence after neck clipping exists, and most recurrent aneurysms require some form of retreatment. The novel classification scheme may provide conceptual clarity and therapeutic guidance for decision making.

Purpose This paper aims to consider implications of the IMF Global Financial Stability Report (April 2016 edition) for the regulation and supervision of insurers. Design/methodology/approach This paper first summarises the IMF Report and then discusses possible implications, examining the underlying hypothesis on which the “Tsunami view” has been formulated. Findings This paper finds that the Report provides some important implications for the regulation and supervision of insurers, although no commonalities in life insurers’ asset composition, which is the underlying hypothesis of the Tsunami view expressed in the Report, have been observed at a global level. One of the key implications is the importance of monitoring insurers’ exposures at granular levels in a more intensive manner from the perspective of macro-prudential supervision. Originality/value This is one of the first papers that try to challenge the findings and recommendations of the IMF Report and, at the same time, consider what implications can be taken for enhanced regulation and supervision of insurers.

Background We examined the effect of all-trans retinoic acid on collagen degradation mediated by corneal fibroblasts. Methods Rabbit corneal fibroblasts were cultured with or without all-trans retinoic acid in a three-dimensional collagen gel, and the extent of collagen degradation was determined by measurement of hydroxyproline in acid hydrolysates of culture supernatants. Matrix metalloproteinase expression was examined by immunoblot analysis and gelatin zymography. The abundance and phosphorylation state of the endogenous nuclear factor-kappaB inhibitor IκB-α were examined by immunoblot analysis. Corneal ulceration was induced by injection of lipopolysaccharide into the central corneal stroma of rabbits and was assessed by observation with a slitlamp microscope. Results All-trans retinoic acid inhibited interleukin-1β-induced collagen degradation by corneal fibroblasts in a concentration- and time-dependent manner. It also attenuated the release and activation of matrix metalloproteinases as well as the phosphorylation and degradation of IκB-α induced by interleukin-1β in these cells. Topical application of all-trans retinoic acid suppressed corneal ulceration induced by injection of lipopolysaccharide into the corneal stroma. Conclusions All-trans retinoic acid inhibited collagen degradation mediated by corneal fibroblasts exposed to interleukin-1β, with this effect being accompanied by suppression of nuclear factor-kappaB signalling as well as of matrix metalloproteinase release and activation in these cells. All-trans retinoic acid also attenuated lipopolysaccharide-induced corneal ulceration in vivo. Our results therefore suggest that all-trans retinoic acid might prove effective for the treatment of patients with corneal ulceration.

This pilot study aimed to investigate the utility of near-infrared spectroscopy/indocyanine green (NIRS/ICG) for examining patients with occlusive cerebrovascular disease. Twenty-nine patients with chronic-stage atherosclerotic occlusive cerebrovascular disease were included. The patients were monitored using NIRS at the bedside. Using ICG time-intensity curves, the affected-to-unaffected side ratios were calculated for several parameters, including the maximum ICG concentration (ΔICGmax), time to peak (TTP), rise time (RT), and blood flow index (BFI = ΔICGmax/RT), and were compared to the affected-to-unaffected side ratios of the regional cerebral blood flow (rCBF) and regional oxygen extraction fraction (rOEF) obtained using positron emission tomography with 15O-labeled gas. The BFI ratio showed the best correlation with the rCBF ratio among these parameters (r = 0.618; P = 0.0004), and the RT ratio showed the best correlation with the rOEF ratio (r = 0.593; P = 0.0007). The patients were further divided into reduced rCBF or elevated rOEF groups, and the analysis revealed significant related differences. The present results advance the measurement of ICG kinetics using NIRS as a useful tool for the detection of severely impaired perfusion with reduced rCBF or elevated rOEF. This method may be applicable as a monitoring tool for patients with acute ischemic stroke.

Malicious software is defined as malware but in recent years, the amount of software that behaves maliciously while still acting legally has been increasing. We propose that this type of software should be referred to as “slyware.” Typical examples of slyware are implemented as smartphone websites with hyperlinks (links) that are designed to induce the visitor to make accidental taps, which we call “mistap-slyware.” Mistap-slyware can initiate the performance of illegal or dishonest acts, although mistap-slyware is not actually illegal. Thus, we propose a cancelable transition method as a countermeasure. In the proposed method, a link will start blinking when it is tapped. If the user taps the link again, then moving to the page is canceled; otherwise, moving to the page occurs after a few seconds. We evaluated the proposed method and an existing method in terms of their usability and safety.

A 76-year-old man with lung cancer and multiple metastases was admitted for purpura and rapidly progressive glomerulonephritis. Adenosquamous cell carcinoma of the lung had been diagnosed 6 months earlier. Two anti-cancer drug regimens had no effect. At admission, his survival with his malignancy was estimated to be several months. Renal biopsy revealed pauci-immune necrotizing crescentic glomerulonephritis (CrGN). Negative results were obtained for myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA) and proteinase-3-ANCA by enzyme-linked immunosorbent assay, and for peripheral-ANCA and cytoplasmic-ANCA by indirect immunofluorescence. He was diagnosed with ANCA-negative pauci-immune CrGN. Although steroids were initiated, the patient died of renal failure and intestinal bleeding 2 weeks later. It was later found that cancer cells were positive for interleukin (IL)-6 and that serum IL-6 levels were significantly elevated, concomitantly with increased IL-8, granulocyte-colony stimulating factor and transforming growth factor-β levels. Some kinds of lung cancer are known to produce IL-6 that activate neutrophils and are related to ANCA-associated CrGN. It appears that IL-6 can activate neutrophils in the pathogenesis of ANCA-negative pauci-immune CrGN with lung cancer. Therapy that blocks IL-6 may prove to be effective in vasculitis and cancer-related symptoms in such cases.

Reconstruction of the obliterated vesicourethral junction is both complex and difficult. Here, we report an innovative method using a mobilized bulbar urethra as a continent valve. Three patients with major problems at the vesicourethral junction underwent continent valve reconstruction. In cases 1 and 2, in which there were problems at the anastomosing site after radical prostatectomy, the bladder wall was closed, wedge resection of the midline pubic bone was performed, and a fully mobilized bulbar urethra was implanted submucosally into the anterior bladder wall. In case 2, augmentation cystoplasty using an ileal segment was required due to the small capacity of the bladder. In case 3, in which there was posterior urethra disruption associated with pelvic fracture, the bulbar urethra was implanted into the bladder wall in the same manner as in cases 1 and 2 without pubectomy. The postoperative follow-up periods were 48, 36, and 12 months, respectively. In all patients, urinary management was achieved by self-catheterization postoperatively, and the patients were satisfied with their status. This newly devised continent valve construction using a bulbar urethra is effective for reconstruction of the obliterated vesicourethral junction, which markedly improves patients' quality of life.

We examined whether the effects (efficacy on the urethra and hypotension) of silodosin (alpha(1A)-adrenoceptor antagonist) and tamsulosin (alpha(1A+1D)-adrenoceptor antagonist) in dogs with benign prostatic hyperplasia altered with age. We used young and old dogs, diagnosed as having benign prostatic hyperplasia by veterinarian's palpation. Under anesthesia, the increase in intraurethral pressure evoked by hypogastric nerve stimulation was measured, together with the level of systemic mean blood pressure. Each drug was administered intravenously in progressively increasing doses. At the end of the experiment, the prostate was isolated from each dog, then weighed and investigated pathologically to confirm benign prostatic hyperplasia. The wet weight of the prostate was greater in old dogs with benign prostatic hyperplasia than in young dogs with benign prostatic hyperplasia. By light microscopy, hyperplasia in the prostatic epithelium was confirmed in both groups. Silodosin (0.3-300 microg/kg) dose-dependently inhibited the hypogastric nerve stimulation-induced increase in intraurethral pressure (without significant hypotensive effects) in both young and old dogs with benign prostatic hyperplasia. Tamsulosin (0.3-300 microg/kg) also dose-dependently inhibited the intraurethral pressure increase in both groups, but it had a hypotensive effect that was significantly greater in old than in young dogs with benign prostatic hyperplasia. In conclusion, as regards the effect of silodosin on intraurethral pressure, potency was similar between young and old dogs with benign prostatic hyperplasia, and it was without significant hypotensive effects. We therefore suggest that silodosin might be a good medication for lower urinary tract symptoms in patients with benign prostatic hyperplasia in all age groups.

It is important to consider a strategy to halt the development of cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Oral adsorbent AST-120 retards deterioration in renal function, reducing indoxyl sulfate (IS) accumulation. The aim of this study was to determine whether AST-120 improves endothelial dysfunction by reducing oxidative/nitrative stress in a rat-CKD model. Subtotally nephrectomized (Nx) rats aged 17 weeks were divided into two groups: control rats and rats orally treated with AST-120. Two weeks after initiation of AST-120, serum and urinary IS levels, renal histological scores and endothelium-dependent vascular responses (EDVRs) in the aorta were investigated. EDVR in 5-h incubation with 250 microg ml(-1) IS was also examined in normal rat aortas. Nitrotyrosine content, mRNA expression of p47phox, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase component, and expression and phosphorylation (serine-1177) of endothelial nitric oxide synthase (eNOS) in the aorta were examined in untreated and treated Nx rats. At the end of treatment, renal function and histological scores were not different in the two groups. AST-120 prevented the elevation of serum IS level in Nx rats, reducing urinary IS excretion, and ameliorated decreased EDVR in Nx rats. Incubation with IS tended to reduce EDVR in normal aortas, albeit insignificantly. AST-120 also suppressed nitrotyrosine accumulation and inhibited p47phox expression in Nx rats. The eNOS expression and phosphorylation were similar in the two groups. In conclusion, AST-120 ameliorated endothelial dysfunction and alleviated oxidative/nitrative stress in the aorta through reduced accumulation of IS, independent of renal function, in a rat CKD model.

To compare the efficacy of the selective alpha(1A)-adrenoceptor antagonist silodosin with those of doxazosin, terazosin, and alfuzosin against alpha-adrenoceptor agonist-induced contractions in mouse and hamster ureters.The four alpha(1)-adrenoceptor antagonists were evaluated against norepinephrine-induced phasic contractions in mouse isolated ureteral preparations and against phenylephrine-induced sustained contractions in hamster isolated ureteral preparations using a functional experimental technique.In mouse ureters, silodosin (a selective alpha(1A)-adrenoceptor antagonist), doxazosin (a nonselective alpha(1)-adrenoceptor antagonist), terazosin (a nonselective alpha(1)-adrenoceptor antagonist), and alfuzosin (a nonselective alpha(1)-adrenoceptor antagonist) all shifted the norepinephrine concentration-response curve to the right. The rank order of potencies (pK(B) value) was silodosin (9.47 +/- 0.16)doxazosin (8.62 +/- 0.15)terazosin (8.39 +/- 0.16)alfuzosin (8.03 +/- 0.12). In hamster ureters, all four antagonists shifted the phenylephrine concentration-response curve to the right, the rank order of potencies being silodosin (10.09 +/- 0.13)doxazosin (8.22 +/- 0.16)terazosin (7.75 +/- 0.15)alfuzosin (7.70 +/- 0.10). In each case, silodosin was much more potent than the other three drugs.In this study, silodosin suppressed both mouse and hamster ureteral contractions more potently than doxazosin, terazosin, or alfuzosin. Hence, this alpha(1A)-adrenoceptor antagonist warrants further study as a potentially very useful medication for stone passage in urolithiasis patients.

Serotonin (5-HT) is involved in vascular inflammation and atherosclerogenesis. Serum 5-HT concentrations are elevated in diabetes, and 5-HT is involved in diabetic vasculopathies. Sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, has renoprotective effects, but its effect in diabetic nephropathy is not elucidated. The aim of this study was to examine the effects of sarpogrelate on endothelial dysfunction in rats with streptozotocin (STZ)-induced diabetes. Rats with STZ-induced diabetes were either untreated or treated with sarpogrelate (30 mg/kg P.O.) for 8 weeks. At the end of the experiment, we measured urinary albumin excretion, serum adiponectin concentration and platelet-derived microparticles. Intraglomerular coagulation was detected by immunostaining for platelets. Production of renal reactive oxygen species (ROS) and nitric oxide (NO) was investigated by confocal laser microscopy and used as an index of glomerular endothelial dysfunction. Diabetic nephropathy was associated with enhanced production of ROS and diminished bioavailable NO in the glomeruli. Treatment with sarpogrelate improved ROS/NO imbalance in glomeruli, suppressed platelet aggregation in glomeruli, reduced platelet-derived microparticles, increased serum adiponectin level and reduced the level of albuminuria, compared with non-treated diabetic rats. Our results indicate that sarpogrelate improves endothelial function in rats with STZ-induced diabetes through a reduction of glomerular platelet activation and an increase in serum adiponectin concentrations and suggest that sarpogrelate is potentially useful for the treatment of diabetic nephropathy.

Endothelial dysfunction is a key event in the development of renovascular complications in the metabolic syndrome. The aim of this study was to elucidate the pathogenetic mechanisms involved in renovascular injuries in the Zucker obese rat, a model of the metabolic syndrome, and to examine the therapeutic effects of pioglitazone, a thiazolidinedione. Obese rats fed high-protein diet (OHP) for 12 weeks exhibited nephropathy and endothelial dysfunction, which were improved by pioglitazone. Accumulation of nitrotyrosine, a tracer of nitrative stress, was increased in aorta of the OHP group. The mRNA expressions of NADPH oxidase components and inducible nitric oxide synthase in the aorta were enhanced in the OHP group. Pioglitazone reduced nitrotyrosine in the aorta of the OHP group, inhibiting the augmented expression levels of both. These results suggest that nitrative stress could cause endothelial dysfunction in the rat model of metabolic syndrome with nephropathy, and that pioglitazone ameliorates these injuries, presumably by reducing nitrative stress.

症例は52歳男性, アルコール性肝硬変の既往あり. 2003年9月に末期腎不全で血液透析療法を開始. 2004年6月30日, 内シャントが閉塞し当院血管外科受診. 術前の出血傾向検査では異常値を認めていない. 入院後, 透析用カテーテルを右内頸静脈に挿入, 穿刺30分後より挿入部から出血し, 呼吸困難となり気管内挿管後, ICUに入室. 入室時の検査では, 血小板数に変化は認めず, APTT, PTの著明な延長, Thrombo Test (TTO), Hepaplastin Test (HPT) の著明な低下を認めた. 急性Vit K欠乏症と診断しVit K製剤の投与を開始した. 投与開始後, カテーテル刺入部からの出血は止血し, 凝固時間も速やかに改善した. 入院直前に市販薬であるキチンーキトサン製剤 (1日30錠: 推薦容量1日10錠) を内服したことが判明した.以上より, 本例の出血傾向の原因としてキチンーキトサン製剤によるVit K欠乏症が考えられた.

Aims Our main aim was to compare the prostatic selectivity of silodosin with that of other α1-adrenoceptor (AR) antagonists. Methods We examined uroselectivities in two sets of experiments namely, in vitro and in vivo functional studies using male dogs. In the in vitro study, after evaluating the inhibitory effects of silodosin on noradrenaline (NA)-induced contractions in the isolated prostate and isolated carotid artery using the Magnus method, we calculated prostatic selectivity. In the in vivo study, we examined the effects of drugs on the hypogastric nerve stimulation (HNS)-induced increase in intraurethral pressure (IUP) and on blood pressure. The uroselectivity of silodosin was compared with those of tamsulosin and naftopidil. Results In vitro, all drugs antagonized NA-induced contraction in both prostate and carotid artery. The prostatic selectivity of silodosin (79.4) was much higher than those of tamsulosin (1.78), naftopidil (0.55), BMY 7378 (0.115), and prazosin (0.01). In vivo, intravenously (i.v.) administered silodosin dose-dependently inhibited the HNS-induced increase in IUP with much less hypotensive effect than either tamsulosin or naftopidil, the uroselectivity (ED15/ID50) of silodosin (237) being significantly higher than those of tamsulosin (1.21) and naftopidil (2.65). Conclusions Our results clearly demonstrate that silodosin is a potent and highly selective α1A-AR antagonist. A selective α1A-AR antagonist such as silodosin may have good potential as a less-hypotensive drug for the treatment of urinary dysfunction in benign prostatic hyperplasia patients. Neurourol. Urodynam. 25:792–799, 2006. © 2006 Wiley-Liss, Inc.

We compared the urethral and cardiovascular eSects of silodosin (selective a1A-adrenoceptor antagonist) ,an ovel medication for benign prostatic hyperplasia (BPH), with those of tamsulosin (selective a1A/a1D-adrenoceptor antagonist) and naftopidil (selective a1D-adrenoceptor antagonist) .W e evaluated the eSects of these three drugs on the increase in intraurethral pressure (IUP) induced by electrical stimulation of the hypogastric nerve in anesthetized dogs with spontaneous BPH. All three drugs dose-dependently reduced both the increase in IUP and the mean blood pressure (MBP). The rank order of potencies was tamsulosin＞silodosin＞naftopidil for the reductions in both IUP and MBP. However, the uroselectivity (ED15 value for hypotensive eSect/ID50 value for reduction in IUP) of silodosin (uroselectivity, 19.8) was about 21 and 4 times higher than that of tamsulosin (0.939) and naftopidil (4.94), respectively. These data suggest that silodosin might be one of the most useful medications for dysuria in BPH patients. Key words―silodosin (KMD-3213); a1A-adrenoceptor; benign prostatic hyperplasia; intraurethral pressure

The progress and status of a new atmospheric re-analysis, JRA-25 the Japanese 25-year Re-analysis which covers the 26 years from 1979 to 2004, are introduced. Observational data include some newly produced for JRA-25 and advantages and drawbacks of performance are briefly described. JRA-25 has many advantages such as its handling of precipitation amounts, tropical cyclone analysis, and the extent of low-level cloud along western continents that are among the best compared to other re-analyses. The snow analysis is also good and stable. JRA-25 outputs analysis products every 6 hours. Copyright © 2005 Royal Meteorological Society

Background: We examined so-called Mullerian duct cysts both histologically and immunohistochemically with anatomical observation to investigate the etiology of the ‘Mullerian duct cyst’. Methods: Five cystic lesions located in the prostatic midline were obtained from surgical specimens. A communication between the cystic lesion and the urethra via the utricular orifice was looked for and the specimens were subjected to histological and immunohistochemical testing. Results: A communication between the cyst and the urethra was confirmed in four cases, but not in one case. Histological and immunohistochemical examinations of the epithelium lining indicated that its characteristics were identical to those of the prostatic utricle in all cases. Conclusions: The so-called Mullerian duct cyst exhibits features comparable to those previously described in the prostatic utricle. There is no evidence that these cystic lesions originate from the Mullerian duct remnant, at least in the epithelial lining. We suggest that they should be termed a prostatic utricular cyst or cystic dilation of the prostatic utricle, depending on whether an outlet to the urethra is absent or present, respectively.

Background Sclerosing cholangitis with autoimmune pancreatitis has a cholangiographic appearance that is similar to that of primary sclerosing cholangitis, but only the former responds well to corticosteroid therapy. It, therefore, is necessary to distinguish between these two diseases. Cholangiography is the reference standard for the diagnosis of primary sclerosing cholangitis. The present study compared the characteristic findings for these two types of sclerosing cholangitis. Methods Cholangiograms from patients with primary sclerosing cholangitis (n=29) and sclerosing cholangitis with autoimmune pancreatitis (n=26) were studied with regard to length and region of stricture formation, and other characteristic findings. Results Band-like stricture, beaded or pruned-tree appearance, and diverticulum-like formation were significantly more frequent in primary sclerosing cholangitis. In contrast, segmental stricture, long stricture with prestenotic dilatation and stricture of the distal common bile duct were significantly more common in sclerosing cholangitis with autoimmune pancreatitis. Discriminant analysis based on these findings correctly identified 27 of 28 patients with primary sclerosing cholangitis and 25 of 26 patients with sclerosing cholangitis with autoimmune pancreatitis. It also identified a patient with an incorrect diagnosis of primary sclerosing cholangitis who proved, on review of a surgical specimen, to have findings consistent with lymphoplasmacytic sclerosing cholangitis. Conclusions Characteristic cholangiographic features allow discrimination of sclerosing cholangitis with autoimmune pancreatitis and lymphoplasmacytic sclerosing cholangitis without pancreatitis from primary sclerosing cholangitis.

原発性上皮小体機能亢進症(PHPT)の原因が上皮小体癌であることは稀であり,その術前診断は困難である.今回当科で経験した上皮小体癌症例の臨床的特徴を解析し,術前診断の指標となりうる項目について検討した.過去36年間に当科で手術を施行したPHPT 235例中癌と診断された6例(2.6%)を対象とし, 1995年と1996年に手術を施行したPHPT腺腫20例をcontrolとして比較検討した.その結果上皮小体癌に有意な所見として,腫瘤を触れる(p

Background: A study was conducted to evaluate our experience of ileal-conduit formation in tetraplegic patients with special reference to late complications due to upper urinary tract stones and pyocystis. Methods: Ileal-conduit formation was performed in 16 patients with tetraplegia to improve urinary management. The mean age at operation was 46 years (range 19–70) and the mean follow-up period was 8.7 years (range 2–17). We evaluated the results retrospectively from patients’ medical records. Results: Two patients died 2 years after the procedure and one patient died 8 years after the ileal-conduit formation. Five patients suffered from repeated renal or ureteral stone. In three of these cases, serious urinary tract infections developed whenever the stone caused an obstruction. Three patients received a cystectomy at the time of the ileal-conduit formation. Eight patients suffered from empyema of the bladder and in two of these cases a subsequent cystectomy was required. Conclusions: Ileal-conduit formation should be cautiously considered as an option in the urinary management of tetraplegic patients, particularly when more conservative management strategies have proved unsuccessful. However, an antirefluxing mechanism for the ileal conduit may be necessary, and a simultaneous cystectomy may improve the results.

Although the complication rate of endoscopy is low, EGD may induce cardiac stress. The aim of this study was to quantify cardiac stress during EGD.Heart rate, blood pressure, cardiac output, and peripheral oxygen saturation were measured during endoscopy without sedation in 7 volunteers. Cardiac output was measured with an automated echocardiographic technique. Cardiac index, left ventricular work index, and rate-pressure product were calculated. Serum catecholamine concentrations were measured before and after the examination.Heart rate increased significantly when the endoscope was located in the esophagus compared with the rate before insertion (p0.05). No significant changes in cardiac index and left ventricular work index were observed during endoscopy. Rate-pressure product increased significantly at the point of esophageal observation compared with that before insertion (p0.05). The rate-pressure product was maximally increased during esophageal observation at 66% over baseline (95% CI [45%, 86%]). Serum concentration of norepinephrine rose significantly after the examination (p0.05).Cardiac output did not increase during EGD without sedation in healthy male volunteers. Cardiac stress increased during EGD as indicated by a 66% increase in rate-pressure product. The cardiac stress was approximately equal to that observed in 3.3 to 5 metabolic equivalents of treadmill exercises.

In recent years, with growing demands towards big data application, various research on context-awareness has once again become active. This paper proposes a new type of context-aware user authentication that controls the authentication level of users, using the context of “physical trust relationship” that is built between users by visual contact. In our proposal, the authentication control is carried out by two mechanisms; “i-Contact” and “k-Contact”. i-Contact is the mechanism that visually confirms the user (owner of a mobile device) using the surrounding users' eyes. The authenticity of users can be reliably assessed by the people (witnesses), even when the user exhibits ambiguous behavior. k-Contact is the mechanism that dynamically changes the authentication level of each user using the context information collected through i-Contact. Once a user is authenticated by eyewitness reports, the user is no longer prompted for a password to unlock his/her mobile device and/or to access confidential resources. Thus, by leveraging the proposed authentication system, the usability for only trusted users can be securely enhanced. At the same time, our proposal anticipates the promotion of physical social communication as face-to-face communication between users is triggered by the proposed authentication system.

Background: Intraoperative qualitative indocyanine green (ICG) angiography has been used in cerebrovascular surgery. Hyperperfusion may lead to neurological complications after superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis. The purpose of this study is to quantitatively evaluate intraoperative cerebral perfusion using microscope-integrated dynamic ICG fluorescence analysis, and to assess whether this value predicts hyperperfusion syndrome (HPS) after STA-MCA anastomosis. Methods: Ten patients undergoing STA-MCA anastomosis due to unilateral major cerebral artery occlusive disease were included. Ten patients with normal cerebral perfusion served as controls. The ICG transit curve from six regions of interest (ROIs) on the cortex, corresponding to ROIs on positron emission tomography (PET) study, was recorded. Maximum intensity (IMAX), cerebral blood flow index (CBFi), rise time (RT), and time to peak (TTP) were evaluated. Results: RT/TTP, but not IMAX or CBFi, could differentiate between control and study subjects. RT/TTP correlated (|r| = 0.534-0.807; P < 0.01) with mean transit time (MTT)/MTT ratio in the ipsilateral to contralateral hemisphere by PET study. Bland–Altman analysis showed a wide limit of agreement between RT and MTT and between TTP and MTT. The ratio of RT before and after bypass procedures was significantly lower in patients with postoperative HPS than in patients without postoperative HPS (0.60 ± 0.032 and 0.80 ± 0.056, respectively; P = 0.017). The ratio of TTP was also significantly lower in patients with postoperative HPS than in patients without postoperative HPS (0.64 ± 0.081 and 0.85 ± 0.095, respectively; P = 0.017). Conclusions: Time-dependent intraoperative parameters from the ICG transit curve provide quantitative information regarding cerebral circulation time with quality and utility comparable to information obtained by PET. These parameters may help predict the occurrence of postoperative HPS.

A case is presented of prostatic cancer with marked neuroendocrine differentiation. Double-labeled immunohistochemical staining was performed with prostate-specific antigen and Chromogranin A. Both antibodies were localized to some of the cancer cells with Paneth cell-like features. Furthermore, most of the cancer cells were positively stained with luminal cell marker CAM 5.2, suggesting that neuroendocrine cells originated from the prostatic luminal cells.

Objective: To clarify whether or not the rate of tumour growth is a useful measure for distinguishing papillary thyroid cancer from benign nodules. Design: Retrospective study. Setting: Teaching hospital, Japan. Subjects: Fourteen patients with 27 nodules (

Primary leiomyosarcoma of the thyroid gland is extremely rare and radiological information on this tumor is scant. We presented radiological findings on primary thyroid leiomyosarcoma in a 66-year-old woman in which anaplastic carcinoma was suspected based on clinical and cytological features and discussed the radiological clues to distinguish between the two diseases. Ultrasonography showed an ill-defined hypoechoic mass without halo in the left lobe and the isthmus of the thyroid gland. Computed tomography depicted a low-density mass with calcification and necrosis, which invaded the thyroid cartilage. No lymphadenopathy was seen. The tumor was demonstrated as an isointense mass on T1-weighted MR images and a mass of intermediate signal on T2-weighted images. The tumor showed a fair enhancement on gadolinium-enhanced T1-weighted images. Although the radiological picture was nonspecific, primary thyroid leiomyosarcoma appeared less invasive and far less frequent in developing nodal metastasis than anaplastic carcinoma in light of the literature.