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Objective: Our study was conducted to validate the Japanese version of the Ford Insomnia Response to Stress Test (FIRST-J) and to clarify the association of the measure with trait anxiety and insomnia in healthy subjects and insomnia patients., Methods: We studied 161 healthy subjects and 177 insomnia patients who completed the FIRST-J, Pittsburgh Sleep Quality Index (PSQI), Athens Insomnia Scale (AIS), and State-Trait Anxiety Inventory-Trait (STAI). The healthy subjects and the insomnia patients were classified, respectively, into two groups with high FIRST-J and low FIRST-J scores (divided by the median value of healthy subjects)., Results: Cronbach α coefficients of the FIRST-J in the insomnia patients and healthy subjects were 0.89 and 0.87, respectively. Factor analysis revealed that the FIRST-J had a single-factor structure. The FIRST-J score significantly correlated with all other measures in the healthy subjects, though the score only correlated with the score of the STAI in the insomnia patients. The healthy subjects with high FIRST-J scores showed higher scores of the AIS and STAI than those with low FIRST-J scores. Furthermore, insomnia patients had a higher total score of the FIRST-J than the healthy subjects., Conclusions: The FIRST-J is an important tool for assessing vulnerability to insomnia., (Copyright © 2013 Elsevier B.V. All rights reserved.)

We investigated daytime dysfunction in children with restless legs syndrome (RLS) and the effects of treatment primarily with iron supplements on RLS symptoms and daytime dysfunction. We recruited 25 children with RLS (male:female=6:19, mean age at study onset: 12.3 years) for this prospective study, assessing their demographics, symptomatic characteristics, serum ferritin levels, and daytime functioning using the ADHD Rating Scale IV (ADHD-RS-IV), the Pediatric Symptom Checklist (PSC), and the Pediatric Quality of Life Inventory (PedsQL™). Children with RLS were compared with 28 controls (male:female=10:18, mean age: 13.2 years) on these measures, pre- and post-treatment. Before treatment, ADHD-RS-IV (all ps<0.05) and PSC scores (p<0.05) were significantly higher and PedsQL™ scores (all ps<0.05) significantly lower in the RLS group than in the control group. Eight and one of the RLS group had abnormally high PSC and ADHD-RS-IV scores, respectively. Following treatment, participants' daytime function had improved to levels similar to those of controls. Sixteen out of twenty-three cases were successfully treated primarily with iron supplement. Some children with RLS have daytime dysfunction; however, this can be treated with iron supplements., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: The status of night-to-night variability for periodic limb movements in sleep (PLMS) has not been clarified. With this in mind, we investigated the validity of PLMS measurement by actigraphy with the PAM-RL device in Japanese patients with suspected restless legs syndrome (RLS) or periodic limb movement disorder (PLMD) and the night-to-night variability of PLMS among the subjects., Methods: Forty-one subjects (mean age, 52.1±16.1 years) underwent polysomnography (PSG) and PAM-RL measurement simultaneously. Thereafter, subjects used the PAM-RL at home on four more consecutive nights., Results: The correlation between PLMS index on PSG (PLMSI-PSG) and PLM index on PAM-RL (PLMI-PAM) was 0.781 (P<.001). When the PLMSI cutoff value on PSG was set at 15 episodes per hour, the cutoff value for predicting this PLMSI level was 16.0 episodes per hour. When the condition was set to the level in which the mean interclass correlation coefficient reached ≥0.9, the number of required nights for repeated measurements was 26 nights for subjects with PLMI of <15 episodes per hour and three nights for those with PLMI ≥15 episodes per hour on PAM-RL., Conclusions: PAM-RL is thought to be valuable for assessing PLMS even in Japanese subjects. Recording of PAM-RL for three or more consecutive nights may be required to ensure the screening reliability of a patient with suspected pathologically frequent PLMS., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A platelet aggregation inhibitor, named snake venom platelet aggregation dissociator (SV-PAD)-1, with a dissociative reaction of ADP-induced platelet aggregation, was purified from the venom of Protobothrops elegans (Sakishima-habu) by gel-filtration employing Sephadex G-100, and ion-exchange chromatographies using DEAE-Sepharose Fast Flow, CM-Sepharose Fast Flow, and Mono S. By this procedure, about 1.5mg of purified protein was obtained from 1.0g of P. elegans venom. The purified protein showed a single protein band and the molecular weight was about 110kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. The pI of purified protein showed four-bands of 7.7, 7.8, 7.95, and 8.15. This protein strongly inhibited ADP-induced platelet aggregation in rabbit platelet-rich plasma (PRP), and its IC(50) was about 58nM. It inhibited ristocetin-induced platelet aggregation in rabbit PRP (IC(50): 100nM), but hardly blocked collagen-induced platelet aggregation. This protein promptly dissociated platelet aggregation in rabbit PRP stimulated by high-concentration ADP.

Purpose: It is widely accepted that intravitreous levels of erythropoietin (Epo) are elevated in patients with ischaemic retinal diseases such as proliferative diabetic retinopathy (PDR). The aim of this study was to examine the expression of Epo and the Epo receptor (EpoR) in epiretinal membranes with and without diabetes., Methods: Eighteen epiretinal membranes (PDR (n = 10), idiopathic epiretinal membranes (IERMs) without diabetes (n = 4) and inner limiting membranes (ILMs) (n = 4)) were obtained during pars plana vitrectomy. Formalin-fixed and paraffin-embedded tissues were examined by immunohistochemistry with anti-Epo and EpoR antibodies., Results: The histopathological findings demonstrated that PDR membranes consisted of a variety of endothelial cells forming a microvascular cavity with red blood cells and non-vascular stromal mononuclear cells. Membranous and cytoplasmic immunoreactivity for EpoR was strongly detected in endothelial cells and stromal cells in all PDR patients. Although microvessels were not observed in IERMs and ILMs, immunoreactivity for EpoR was noted in the cellular component of IERMs, and was weakly detected in ILMs. Epo was not expressed in any membrane., Conclusion: EpoR was strongly expressed in microvessels of all PDR membranes. The in vivo evidence in this study suggests that Epo in the vitreous binds to EpoR in PDR membranes, which subsequently leads to the proliferation of new retinal vessels. EpoR immunoreactivity in non-vascular stromal cells in PDR membranes, and IERMs and ILMs might be indirectly correlated with ischaemia.

Background: The etiology of punctate inner choroidopathy (PIC) and acute zonal occult outer retinopathy (AZOOR) are currently unknown, although both diseases are hypothesized to be part of the spectrum of a single disorder., Case: We report indocyanine green (ICG) angiographic findings in a 24-year-old woman in whom PIC was associated with AZOOR., Observations: The patient had been diagnosed with bilateral PIC. She noticed a visual field defect in her right eye 8 months later, and a defect in her left eye 25 months later. Perimetry showed an arcuate scotoma (right eye) and a central scotoma (left eye), which could not be explained by funduscopy or late-phase fluorescein angiography. Multifocal electroretinography led to a diagnosis of bilateral AZOOR. ICG angiography demonstrated late multiple patchy hypofluorescent spots throughout the posterior pole in the right eye and geographic hypofluorescence in the macular region from initial to late phase in the left eye. However, these findings were not evident at the onset of PIC., Conclusion: These angiographic results suggest that at the onset of AZOOR, choriocapillaris injuries had occurred in the areas corresponding to the scotomas.

Purpose: Osteopontin (OPN) has diverse functions such as cell adhesion, chemoattraction, immunomodulation, and angiogenesis. The aim of this study is to analyze the OPN levels in vitreous fluid obtained from diabetic retinopathy (DR) and non-DR patients., Methods: Nineteen patients out of 11 with DR and 8 without DR underwent pars plana vitrectomy and vitreous fluid was obtained simultaneously. Two distinct sandwich enzyme-linked immunosorbent assay systems (systems 1 and 2) were applied, which have been developed in our laboratories to quantify the OPN concentrations in vitreous fluid., Results: The non-thrombin-cleaved full-length OPN levels in the vitreous fluid were 921.63 +/- 45.38 ng/ml in DR and 632.80 +/- 83.43 ng/ml in non-DR using system 1. Also, vitreous thrombin-cleaved and noncleaved OPN levels were increased to 2,109.22 +/- 151.651 and 1,651.13 +/- 229.82 ng/ml in patients with DR and non-DR using system 2. The vitreous OPN levels were significantly higher in DR than those in non-DR (p < 0.01 by system 1 and p < 0.05 by system 2)., Conclusion: Thrombin-cleaved and noncleaved vitreous OPN levels in patients with DR were increased compared with control subjects, suggesting that OPN plays a potential role in the pathogenesis of diabetic retinal ischemia.

Objectives: Anthracycline cardiotoxicity is known to occur from the subendocardial side of the left ventricular wall. Recent advances of tissue Doppler echocardiography may allow the evaluation of anthracycline cardiotoxicity by dividing the left ventricular wall into the subendocardial half and subepicardial half. The present study assessed the feasibility using the tissue Doppler echo tracking system (M-mode) and myocardial strain rate imaging (B-mode) to noninvasively detect anthracycline cardiotoxicity., Methods: The tissue Doppler echo tracking system (M-mode) was used to measure systolic thickening of the subendocardial layer (delta Endo), subepicardial layer (delta Epi), and whole wall (delta Total) of the left ventricular posterior wall in 41 normal subjects and three groups of patients receiving anthracycline: 34 patients in the low dose group, 19 in the middle dose group, and 12 in the high dose group. Strain rate is the spatial gradient of local velocities, reflecting local compression and expansion rates not affected by overall heart motion. Myocardial strain rate imaging (B-mode) was used in 25 normal subjects, 9 patients in the low dose group, and 10 patients in the high dose group. The ratio of peak systolic strain rate of subendocardium to that of subepicardium (peak strain rate endo/epi), and the ratio of integrated strain rate during ejection time of subendocardium to that of subepicardium (integrated strain rate endo/epi) were measured., Results: Tissue Doppler echo tracking system (M-mode) measurement of delta Endo/delta Epi showed the most distinct difference and the least overlap of the data between normal subjects and patients, whereas delta Total failed to show significant differences. Myocardial strain rate imaging (B-mode) measurement of integrated strain rate endo/epi showed the most distinct difference and the least overlap of the data between normal subjects and patients, but ejection fraction failed to show statistically significant differences., Conclusions: These methods are highly sensitive tools for monitoring anthracycline cardiotoxicity.

Background: Etiological characteristics of endogenous uveitis vary among areas and races around the world. There are few epidemiological reports on the etiology of uveitis from areas within Asia. We report statistical data on uveitis in Japan., Methods: We reviewed all of the records of patients with endogenous uveitis who visited the Uveitis Survey Clinic of Hokkaido University Hospital in 1981 and 1994 and extended the survey to include new patients with uveitis seen over the 3-year period from 1992 to 1994., Results: Bechcet's disease, sarcoidosis and Vogt-Koy-anagi-Harada disease were the three most frequently diagnosed diseases in both 1981 and 1994. The proportion of patients with unclassified uveitis decreased from 38% to 30% during the 13-year period from 1981 to 1994 as a result of the establishment of new disease categories during this time. Notable additions included human T-lymphotropic virus type 1-associated uveitis and tubuloinerstitial nephritis and uveitis syndrome. Sarcoidosis is now the most frequent endogenous uveitis in our clinic., Conclusion: Not only does the etiological basis of uveitis vary among ethnic groups but advances in clinical and basic research have changed the diagnostic approach to uveitis, altering the etiological profile over time.

Background: Etiological characteristics of endogenous uveitis vary around the world. There are few epidemiological reports on the etiology of uveitis from areas within Asia. We set out to examine the statistical data on uveitis in Japan., Methods: We reviewed all the records of patients with endogenous uveitis who visited the Uveitis Survey Clinic of Hokkaido University Hospital in 1981 and 1994 and extended the survey to include new patients with uveitis seen over the past 3 years., Results: Behçet's disease, sarcoidosis and Vogt-Koyanagi-Harada disease were the three most frequently diagnosed diseases in patients with endogenous uveitis in both 1981 and and 1994. The proportion of patients with unclassified disease entities decreased (from 38% to 30%) during the 13-year period from 1981 to 1994 as a result of the new disease categories established during this interval. Notable additions included human T-lymphotropic virus type 1-associated uveitis and tubulointerstitial nephritis and uveitis syndrome. Sarcoidosis is now the most frequent cause of endogenous uveitis in our clinic., Conclusion: Not only does the etiological basis of uveitis vary with ethnicity, but advances in clinical and basic research have changed the approach to the diagnosis of uveitis, altering the etiological profile over time.

Behçet's disease is the most frequently encountered form of endogenous uveitis in Japan. The authors examined the clinical manifestations in cases with Behçet's disease over six years (1987-1992), and compared the results with those of a previous study (1978-1983). In the more recent study the number of new patients who visited our clinic was 54, compared to 180 in the previous study. As for the frequencies of the four major symptoms in the recent study, oral aphtha were seen in 100%, skin lesions in 88.9%, ocular lesions in 74.0%, and genital ulcers in 61.1% of the patients. The frequencies of these major symptoms were not significantly different between the two time periods investigated. Analysis of the type of ocular involvement showed that 94.4% of the patients in the more recent study belonged to the uveoretinitis type and 5.6% of the patients belonged to the iridocyclitis type, whereas in the previous study the figures were 71.5% and 28.5%, respectively. The ratio of the patients with severe eye involvement has increased recently. However the visual prognosis of patients was better in the more recent study than in the previous study. In the previous study a marked decrease in visual acuity was observed during a two-year follow-up, whereas in the 1987-1992 period it was observed that visual acuity hardly changed over two years. The observed improvement in the visual prognosis may be due to the fact that the treatment of Behçet's disease has become more effective in recent years.