Publications by authors named "Tetsuya Nishimura"

40 Publications

Exposure-response modeling of peficitinib efficacy in patients with rheumatoid arthritis.

Pharmacol Res Perspect 2021 05;9(3):e00744

Astellas Pharma Inc, Tokyo, Japan.

The aim was to analyze the relationship between peficitinib exposure and efficacy response according to American College of Rheumatology (ACR) 20 criteria and 28-joint disease activity score based on C-reactive protein (DAS28-CRP) in rheumatoid arthritis (RA) patients, and to identify relevant covariates by developing exposure-response models. The analysis incorporated results from three multicenter, placebo-controlled, double-blind studies. As an exposure parameter, individual post hoc pharmacokinetic (PK) parameters were obtained from a previously constructed population PK model. Longitudinal ACR20 response rate and individual longitudinal DAS28-CRP measurements were modeled by a non-linear mixed effect model. Influential covariates were explored, and their effects on efficacy were quantitatively assessed and compared. The exposure-response models of effect of peficitinib on duration-dependent increase in ACR20 response rate and decrease in DAS28-CRP were adequately described by a continuous time Markov model and an indirect response model, respectively, with a sigmoidal E saturable of drug exposure in RA patients. The significant covariates were DAS28-CRP and total bilirubin at baseline for the ACR20 response model, and CRP at baseline and concomitant methotrexate treatment for the DAS28-CRP model. The covariate effects were highly consistent between the two models. Our exposure-response models of peficitinib in RA patients satisfactorily described duration-dependent improvements in ACR20 response rates and DAS28-CRP measurements, and provided consistent covariate effects. Only the ACR20 model incorporated a patient's subjective high expectations just after the start of the treatment. Therefore, due to their similarities and differences, both models may have relevant applications in the development of RA treatment. CLINICAL TRIAL REGISTRATION: NCT01649999 (RAJ1), NCT02308163 (RAJ3), NCT02305849 (RAJ4).
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http://dx.doi.org/10.1002/prp2.744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085977PMC
May 2021

Population pharmacokinetic analysis of peficitinib in patients with rheumatoid arthritis.

Br J Clin Pharmacol 2021 04 1;87(4):2014-2022. Epub 2020 Dec 1.

Astellas Pharma Inc., Tokyo, Japan.

Aims: To analyse the population pharmacokinetics (PK) of peficitinib in patients with rheumatoid arthritis (RA) and assess the potential PK covariates to identify the requirement for dose adjustment in RA patients.

Methods: The analysis incorporated 2464 observations from 98 healthy volunteers and 4919 observations from 989 RA patients. A population PK model for peficitinib in RA patients was constructed by a nonlinear mixed effect model using NONMEM with prior information from a healthy volunteer model.

Results: A 2-compartment model with sequential zero- and first-order absorption and lag time was constructed for RA patients. Covariate exploration in the RA patient model revealed that estimated glomerular filtration rate (eGFR) and lymphocyte count had a significant effect on apparent total systemic clearance (CL), which was 91.7 L/h (2.3% relative standard error). Compared with the mean population CL, the model predicted mean changes in CL of 12.3 and -10.7% in patients with observed minimum and maximum lymphocyte count of 500 and 4600 10 /L, respectively, and mean changes in CL of -17.8 and 16.7% in patients with minimum and maximum eGFR of 36.4 and 188 mL/min/1.73m , respectively. The simulated population mean area under plasma concentration-time curve for 24 hours after dosing showed a 1.35-fold increase in patients with severe renal impairment (eGFR 22.5 mL/min/1.73m ) compared with patients with reference eGFR (91.5 mL/min/1.73m ).

Conclusion: The population PK model identified eGFR and lymphocyte count as covariates for CL. The magnitude of changes was not considered clinically relevant, indicating no requirement for dose adjustment.
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http://dx.doi.org/10.1111/bcp.14605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056739PMC
April 2021

The Bioequivalence of Two Peficitinib Formulations, and the Effect of Food on the Pharmacokinetics of Peficitinib: Two-Way Crossover Studies of a Single Dose of 150 mg Peficitinib in Healthy Volunteers.

Clin Pharmacol Drug Dev 2021 03 3;10(3):283-290. Epub 2020 Jul 3.

Astellas Pharma Inc., Tokyo, Japan.

The marketed tablet formulation of peficitinib differs from the tablet used during the clinical trials. The bioequivalence of the marketed formulation and developmental tablet, and the food effect on the marketed formulation, were analyzed in 2 Japanese open-label, randomized, 2-way crossover studies in healthy male volunteers. Volunteers received a single oral dose of the marketed 150-mg peficitinib tablet under fasted conditions (bioequivalence), and under fed or fasted conditions (food effect). Bioequivalence was compared with the developmental 150-mg tablet. Samples for pharmacokinetic analysis were collected before dose and ≤72 hours after dose. Safety assessments included adverse events, vital signs, and laboratory variables. In total, 40 and 18 subjects were randomized to the bioequivalence and food effect studies, respectively. The 2 peficitinib formulations were bioequivalent (90% confidence intervals of the geometric mean ratios for C and AUC of peficitinib were within predefined limits of 0.8 to 1.25). The AUC and the C of the marketed tablet were 36.8% and 56.4% higher, respectively, under fed versus fasted conditions. Peficitinib was well tolerated. The marketed 150-mg tablet formulation of peficitinib was bioequivalent to the developmental 150-mg formulation, with no discernible safety differences. Bioavailability increased under fed conditions with the marketed tablet formulation.
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http://dx.doi.org/10.1002/cpdd.843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984322PMC
March 2021

A drug-drug interaction study to evaluate the impact of peficitinib on OCT1- and MATE1-mediated transport of metformin in healthy volunteers.

Eur J Clin Pharmacol 2020 Aug 16;76(8):1135-1141. Epub 2020 May 16.

Astellas Pharma Inc., 2-5-1 Nihonbashi-Honcho, Chuo-Ku, Tokyo, 103-8411, Japan.

Purpose: Peficitinib is an oral pan-Janus kinase inhibitor for the treatment of rheumatoid arthritis. Co-administration of peficitinib with metformin, a type 2 diabetes therapy, can occur in clinical practice. Hepatic and renal uptake of metformin is mediated by organic cation transporter 1 (OCT1) and OCT2, respectively, and its renal excretion by multidrug and toxin extrusion 1 (MATE1) and MATE2-K. This study investigated the effect of peficitinib on metformin pharmacokinetics in vitro and in healthy volunteers.

Methods: Inhibitory effects of peficitinib and its metabolite H2 on metformin uptake into human OCT1/2- and MATE1/2-K-expressing cells were assessed in vitro. In an open-label, drug-drug interaction study, 24 healthy volunteers received a single dose of metformin 750 mg on Days 1 and 10, and a single dose of peficitinib 150 mg on Days 3 and 5-11. Blood and urine samples were collected pre-dose on Days 1 and 10, and at intervals ≤ 48 h post-dose. Metformin concentration was determined by liquid chromatography-tandem mass spectrometry and its pharmacokinetic parameters calculated.

Results: Peficitinib, but not H2, inhibited metformin uptake into OCT1- and MATE1/2-K-expressing cells. Repeated-dose administration of peficitinib reduced metformin area under the concentration-time curve from 0 h extrapolated to infinity (AUC) by 17.4%, maximum plasma concentration (C) by 17.0%, and renal clearance (CL) by 12.9%. Co-administration of peficitinib with metformin was generally well tolerated.

Conclusion: Slight changes in AUC, C and CL of metformin were observed when co-administered with peficitinib; however, these changes were considered not clinically relevant.
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http://dx.doi.org/10.1007/s00228-020-02876-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351850PMC
August 2020

Pharmacokinetics, Pharmacodynamics, and Safety of Peficitinib (ASP015K) in Healthy Male Caucasian and Japanese Subjects.

Clin Drug Investig 2020 May;40(5):469-484

Astellas Pharma Inc., 2-5-1, Nihonbashi-Honcho, Chuo-Ku, Tokyo, 103-8411, Japan.

Background And Objective: Peficitinib pharmacokinetics and pharmacodynamics have been characterized mainly in Caucasian subjects. This study investigated the pharmacokinetics, pharmacodynamics, safety, and tolerability of peficitinib in healthy Japanese subjects compared with Caucasian subjects.

Methods: In this single-center, randomized, double-blind, placebo-controlled study, a cohort of healthy Japanese (n = 24) and Caucasian (n = 24) men received a single oral dose of peficitinib (20, 60, or 200 mg) or placebo. Another cohort of Japanese men (n = 24) received peficitinib (10, 30, or 100 mg) or placebo twice daily for 7 days. Pharmacokinetic and pharmacodynamic parameters were assessed, and adverse events (AEs) monitored throughout.

Results: Dose proportionality of maximum plasma drug concentration (C) and area under the plasma concentration-time curve extrapolated to infinity (AUC) was demonstrated for both ethnicities. The geometric mean ratio for dose-normalized C was 45.7-98.8% higher and AUC was 33.8-66.4% higher in Japanese versus Caucasian subjects. Mean peak inhibition of STAT5 phosphorylation was higher in Japanese than Caucasian subjects for a given peficitinib dose, but inhibition was comparable across ethnicities for a given plasma peficitinib concentration. In the multiple-dose study, plasma peficitinib concentrations were similar on day 1 and day 7. All AEs were mild, and none resulted in study discontinuation.

Conclusions: Peficitinib was well tolerated at doses up to 200 mg daily for 7 days in healthy Japanese subjects. Dose-proportional exposure was demonstrated across the single-dose range of 20-200 mg, with greater peficitinib exposure in Japanese compared with Caucasian subjects. The pharmacokinetic/pharmacodynamic relationships were considered comparable between these populations. CLINICALTRIALS.

Gov Identifier: NCT01225224.
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http://dx.doi.org/10.1007/s40261-020-00910-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181426PMC
May 2020

Pharmacokinetics and Safety of a Single Oral Dose of Peficitinib (ASP015K) in Japanese Subjects With Normal and Impaired Hepatic Function.

Clin Pharmacol Drug Dev 2020 08 12;9(6):699-708. Epub 2019 Dec 12.

Mediscience Planning, Inc, Tokyo, Japan.

Peficitinib (ASP015K) is a novel Janus kinase inhibitor developed for the treatment of rheumatoid arthritis (RA). The impact of hepatic impairment on the peficitinib pharmacokinetic (PK) and safety profile was investigated in non-RA subjects (n = 24) in an open-label, parallel-group, multicenter comparative study in Japan. Subjects received a single, clinically relevant, oral dose of a peficitinib 150 mg tablet under fasting conditions. Plasma PK parameters were measured for peficitinib and its metabolites H1 (sulfate and methylated metabolite), H2 (sulfate metabolite), and H4 (methylated metabolite) in subjects with normal hepatic function, mild hepatic impairment, or moderate hepatic impairment. The peficitinib area under the plasma-concentration-time curve from time 0 to infinity (AUC ) and maximum observed concentration (C ) were not markedly different in subjects with mild hepatic impairment versus normal hepatic function. In subjects with moderate hepatic impairment versus normal hepatic function, the geometric mean ratios for peficitinib AUC and C , were 1.92 (90% CI: 1.39, 2.66) and 1.82 (90% CI: 1.24, 2.69), respectively. Five treatment-emergent adverse events (TEAEs) were experienced by 3 subjects, 1 in each group. There were no deaths, no serious TEAEs, and no TEAEs leading to withdrawal. In summary, the PK profile was unaltered in subjects with mild hepatic impairment after a single clinically relevant dose of peficitinib, but exposure almost doubled in subjects with moderate hepatic impairment. Peficitinib dose reduction may be considered in RA patients with moderate hepatic impairment.
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http://dx.doi.org/10.1002/cpdd.751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496893PMC
August 2020

Pharmacokinetics and Safety of a Single Oral Dose of Peficitinib (ASP015K) in Japanese Subjects with Normal and Impaired Renal Function.

Clin Drug Investig 2020 Feb;40(2):149-159

Mediscience Planning Inc., Tokyo, Japan.

Background And Objective: This study measured and compared the exposure and safety of peficitinib (ASP015K), a novel oral Janus kinase inhibitor, in subjects with normal and impaired renal function after a single oral, clinically relevant peficitinib dose.

Methods: This was an open-label, parallel-group study conducted at two centres in Japan. Subjects with normal and mildly, moderately, or severely impaired renal function received a single oral dose of peficitinib (one 150 mg tablet) under fasting conditions in a hospital setting. Blood samples were collected prior to administration and up to 72 h post-dose for pharmacokinetic assessment. Safety was assessed up to 7 days post-dose.

Results: Peficitinib plasma concentration-time profiles were similar between those with normal and impaired renal function. In subjects with impaired renal function, area under the plasma concentration-time curve and maximum concentration were 0.8- to 1.1-fold those in subjects with no impairment. Two subjects (one in the normal group and one in the mildly impaired group) each experienced a treatment-emergent adverse event (TEAE). There were no serious TEAEs, deaths or TEAEs leading to treatment withdrawal.

Conclusions: Peficitinib exposure and TEAEs were similar in subjects with and without renal impairment after a single oral 150 mg dose. Based on these findings, it is not expected that peficitinib dose adjustment will be required in clinical practice, according to the degree of renal impairment. CLINICALTRIALS.

Gov Identifier: NCT02603497.
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http://dx.doi.org/10.1007/s40261-019-00873-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989572PMC
February 2020

Results of switchback from ranibizumab to aflibercept in patients with exudative age-related macular degeneration.

Clin Ophthalmol 2019 15;13:1247-1251. Epub 2019 Jul 15.

Department of Ophthalmology, Kansai Medical University, Osaka, Japan.

Purpose: Intravitreal injection of anti-VEGF drugs has become standard therapy for patients with exudative age-related macular degeneration (AMD). However, some patients do not exhibit sufficient response to the drugs for suppression of choroidal neovascularization activity. We investigated the efficacy of switchback from ranibizumab to aflibercept in patients with AMD who could not achieve further benefit beyond initial therapy of aflibercept injection.

Methods: Eleven eyes of eleven patients were included in this study. Two patients were nonresponders, and nine exhibited tachyphylaxis to aflibercept. All patients received three monthly injections of ranibizumab as an initial phase of switching and received aflibercept as a switchback drug. We investigated changes in injection interval, visual acuity, and central retinal thickness.

Results: In four patients (36.4%), injection interval was extended. The interval was 6.73 weeks before switch and 9.27 weeks after switchback (=0.96). LogMAR visual acuity was 0.22 before switch and 0.24 after switchback (=0.62). Central retinal thickness was 306.8 µm before switch and 256.1 after switchback (=0.13). In all patients who were nonresponders to aflibercept, injection interval could not be extended.

Conclusion: A switchback from ranibizumab to aflibercept may be beneficial in some patients with AMD who exhibit tachyphylaxis to aflibercept.
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http://dx.doi.org/10.2147/OPTH.S206910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643053PMC
July 2019

Reduction of Intraocular Pressure by Additional Trabeculotomy Ab Externo in Eyes With Primary Open-angle Glaucoma.

J Glaucoma 2018 10;27(10):914-919

Department of Ophthalmology, Kansai Medical University.

Purpose: The purpose of this study was to determine whether a second trabeculotomy (LOT) can reduce the intraocular pressure (IOP) in eyes with primary open-angle glaucoma (POAG) that had undergone an unsuccessful LOT as the initial surgery.

Patients And Methods: LOT ab externo was performed as a second surgery on 37 eyes of 34 POAG patients who had undergone an unsuccessful LOT as the initial surgery. The main outcome measure was the postoperative IOPs, and surgical failures were defined as eyes with a post-LOT IOP>20 mm Hg. The eyes were divided into 3 groups; those that underwent LOT as both the initial and additional surgery (L-L group), those that underwent LOT as the initial surgery and combined LOT and cataract surgery (cLOT-IOL) as the additional surgery (L-cL group), and those that underwent cLOT-IOL as the initial surgery and LOT as the additional surgery (cL-L group).

Results: The IOP was reduced after the additional LOT at postoperative 24 months in the L-L group from 20.0±3.0 mm Hg to 15.3±2.6 mm Hg (P<0.001), the L-cL group from 19.8±1.6 mm Hg to 15.8±3.2 mm Hg (P=0.029), and the cL-L group from 20.1±2.7 mm Hg to 15.5±2.3 mm Hg (P=0.014). There were no differences in the preoperative and postoperative IOPs between the initial-operated and additional-operated eyes. The success rates were improved by the additional surgery in the L-L group (P<0.001) and the L-cL group (P=0.029), but the rate was worsened in the cL-L group (P<0.001).

Conclusions: These results indicate that LOT is a reasonable choice as an additional glaucoma surgery after failure of an initial LOT.
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http://dx.doi.org/10.1097/IJG.0000000000001006DOI Listing
October 2018

Selegiline increases on time without exacerbation of dyskinesia in 6-hydroxydopamine-lesioned rats displaying l-Dopa-induced wearing-off and abnormal involuntary movements.

Behav Brain Res 2018 07 8;347:350-359. Epub 2018 Mar 8.

Department of Scientific Research, Fujimoto Pharmaceutical Corporation, 1-3-40 Nishiotsuka, Matsubara, Osaka 580-8503, Japan.

3,4-Dihydroxy-l-phenylalanine (l-Dopa) remains the most effective drug for treating the motor symptoms of Parkinson's disease (PD). However, its long-term use is limited due to motor complications such as wearing-off and dyskinesia. A clinical study in PD patients with motor complications has demonstrated that selegiline, a monoamine oxidase type B inhibitor, is effective in reducing off time without worsening dyskinesia, although another study has shown worsening dyskinesia. Here, using unilateral 6-hydroxydopamine-lesioned rats showing degeneration of nigrostriatal dopaminergic neurons and l-Dopa-induced motor complications, we determined the efficacy of selegiline in controlling l-Dopa-induced motor fluctuations and exacerbated dyskinesia. Repeated administration of l-Dopa/benserazide (25/6.25 mg/kg, intraperitoneally, twice daily for 22 days) progressively shortened rotational response duration (on time) and augmented peak rotation in lesioned rats. Single subcutaneous injection of selegiline (10 mg/kg) extended l-Dopa-induced shortened on time without augmenting peak rotation. Furthermore, l-Dopa/benserazide (25/6.25 mg/kg, intraperitoneally, once daily for 7 days) progressively increased abnormal involuntary movements (l-Dopa-induced dyskinesia, LID) and peak rotation. Single subcutaneous injection of selegiline (10 mg/kg) did not exacerbate LID or alter mRNA expression of prodynorphin (PDy) and activity-regulated cytoskeleton-associated protein (Arc), both mRNAs associated with LID in the lesioned striatum. Despite undetectable plasma concentrations of selegiline and its metabolites at 24 h post-administration, these on time and LID effects did not decrease, suggesting involvement of irreversible mechanisms. Altogether, these results indicate that selegiline is effective in increasing on time without worsening dyskinesia.
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http://dx.doi.org/10.1016/j.bbr.2018.03.002DOI Listing
July 2018

Long-Term Stability of Minimally Invasive Radial Keratotomy for Mild to Moderate Keratoconus.

Asia Pac J Ophthalmol (Phila) 2017 Sep-Oct;6(5):407-411. Epub 2017 Apr 10.

Tane Memorial Eye Hospital, Nishi-ku, Osaka, Japan.

Purpose: This study aimed to evaluate the long-term stability of minimally invasive radial keratotomy (mini-RK) for eyes with mild to moderate keratoconus.

Design: Retrospective observational case series.

Methods: Eleven eyes from 6 patients with hard contact lens (HCL)-intolerant keratoconus underwent mini-RK and were followed up for more than 5 years. The mini-RK consisted of 8 radial incisions with depths of 90% of the thinnest corneal thickness, based on the Lindstrom nomogram. Best-corrected visual acuity (BCVA), keratometry, and corneal endothelial cell density (ECD) were examined preoperatively and for 5 to 10 years postoperatively. Changes in keratometric astigmatism were evaluated using power vector analysis. Severities of keratoconus preoperatively and 1 year postoperatively were graded using the Amsler-Krumeich classification.

Results: The postoperative observation periods were from 6 to 10 years (mean, 7.9 years). There were no changes in the BCVA, ECD, and keratometric astigmatism. The mean keratometric refraction significantly decreased from 47.5 diopters (D) preoperatively to 44.0 D at 1 month after mini-RK (P = 0.037) and was stable over 5 years, whereas keratometric astigmatism did not change from preoperatively through the postoperative period (P > 0.59). Keratoconus of grade 2 or higher improved to lower grades.

Conclusions: The mini-RK treatment was safe and effective for HCL-intolerant eyes with mild to moderate keratoconus.
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http://dx.doi.org/10.22608/APO.2016204DOI Listing
December 2017

Psychomotor effect differences between l-methamphetamine and d-methamphetamine are independent of murine plasma and brain pharmacokinetics profiles.

J Neural Transm (Vienna) 2017 05 17;124(5):519-523. Epub 2017 Feb 17.

Department of Scientific Research, Fujimoto Pharmaceutical Corporation, 1-3-40 Nishiotsuka, Matsubara, Osaka, 580-8503, Japan.

l-Methamphetamine has been occasionally referred to as a stimulant similar to d-methamphetamine, probably owing to insufficient comparative studies. Here, we directly compared psychomotor efficacies and pharmacokinetics of methamphetamine enantiomers in mice. Only d-methamphetamine, but not l-methamphetamine, induced stereotypy and sensitization at 1-10 mg/kg. However, plasma pharmacokinetic parameters of 10 mg/kg l-methamphetamine were ≥tenfold those of 1 mg/kg d-methamphetamine. These results clearly indicate that differential psychomotor efficacies of methamphetamine enantiomers are independent of their pharmacokinetic profiles.
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http://dx.doi.org/10.1007/s00702-017-1694-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399046PMC
May 2017

Drug Interactions Between Peficitinib, an Orally Administered, Once-Daily Janus Kinase Inhibitor, and Rosuvastatin in Healthy Subjects.

Clin Pharmacokinet 2017 07;56(7):747-757

Clinical Pharmacology and Exploratory Development, Astellas Pharma Global Development Inc., 1 Astellas Way, Northbrook, IL, 60062, USA.

Background And Objective: Peficitinib is an orally administered, once-daily Janus kinase inhibitor in development for the treatment of rheumatoid arthritis. Peficitinib and its major metabolite H2 inhibit the hepatic uptake transporter organic anion transporting polypeptide 1B1 (OATP1B1) in vitro. This article reports a clinical study evaluating the effects of peficitinib on the pharmacokinetics of rosuvastatin, a substrate for the OATP1B1 transporter, and vice versa.

Methods: In an open-label, single-sequence clinical study, 24 healthy adults of East Asian and non-East Asian origin received a single dose of rosuvastatin 10 mg on days 1 and 10. On days 5-13, subjects received a daily dose of 150 mg peficitinib. Serial blood samples for pharmacokinetic assessment of rosuvastatin were collected up to 96 h post-dose on days 1 and 10, and for peficitinib were collected up to 24 h post-dose on days 9 and 10.

Results: Co-administration of peficitinib with rosuvastatin increased rosuvastatin area under the concentration-time curve (AUC) and maximum plasma concentration (C ) by 18 and 15%, respectively and increased peficitinib AUC and C by 16 and 28%, respectively. In East Asian (n = 6) vs. non-East Asian subjects (n = 18), peficitinib mean AUC for a dosing interval was 45 and 21% higher, and mean C was 67 and 34% higher, when administered alone or with rosuvastatin. Peficitinib was well tolerated with few adverse events overall.

Conclusion: In this study, once-daily oral administration of peficitinib had no clinically significant effect on the pharmacokinetics of rosuvastatin, a probe substrate for OATP1B1. Therefore, it is unlikely that peficitinib will have a clinically significant effect on the exposure of other substrates for OATP1B1. CLINICALTRIALS.

Gov Number: NCT01959399.
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http://dx.doi.org/10.1007/s40262-016-0474-4DOI Listing
July 2017

Case of Primary Intraocular Lymphoma with Extraocular Extension.

Ocul Oncol Pathol 2015 Dec 17;2(2):66-70. Epub 2015 Sep 17.

Department of Ophthalmology, Hirakata Hospital, Kansai Medical University, Hirakata, Japan.

Purpose: To describe a case of primary intraocular lymphoma (PIOL) with an extension through the sclera that was confirmed to be part of the PIOL by histopathological examinations.

Case: An 89-year-old woman was referred to a local clinic with a 1-year history of persistent blurred vision in her left eye. After 2 years without aggressive treatments, she had a marked reduction of vision and pain in her left eye. The clinical diagnosis was panophthalmitis, and the eye was enucleated and submitted for histopathological study.

Results: Light microscope examination showed that atypical lymphocytic cells had infiltrated into both the intraocular and extraocular areas. The anterior chamber angle was blocked by infiltrating tumor cells, which were also detected around the optic nerve. The tumor cells destroyed Bruch's membrane and infiltrated around the perineural and perivascular areas within the sclera. Immunohistochemistry showed that the tumor cells were positive for B-lymphocyte surface antigen (CD20), B-cell antigen receptor complex-associated protein alpha chain (CD79-alpha), and had a high positive rate for anti-Ki-67 antibody.

Conclusion: The finding in our case indicates that early diagnosis and treatment are important for eyes with PIOL because the tumor can spread and penetrate the sclera and invade extraocular tissues.
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http://dx.doi.org/10.1159/000439053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847667PMC
December 2015

Three-year results of a modified photodynamic therapy procedure (Ironing PDT) for age-related macular degeneration patients with large lesions.

Clin Ophthalmol 2016 11;10:431-6. Epub 2016 Mar 11.

Department of Ophthalmology, Kansai Medical University, Hirakata Hospital, Osaka, Japan.

Background: To evaluate the effect of photodynamic therapy (PDT) using a modified procedure on exudative age-related macular degeneration having been conventionally difficult to treat.

Methods: The medical records of eight consecutive patients (eight eyes) with age-related macular degeneration treated with modified PDT were reviewed retrospectively. Modified PDT was used for the lesions that could not be covered by conventional use of PDT, either because the lesion was too large or too close to the optic disc. A moving PDT laser spot at constant speed, for 83 seconds, was used to cover the entire lesion, and was named "Ironing PDT." This retrospective study was performed with informed patient consent. It was approved by the Institutional Review Board of Kansai Medical University.

Results: No exudation could be found 36 months after treatment in five eyes (62.5%). There was no significant difference between the best-corrected visual acuity before PDT (0.95 logMAR) and after PDT (1.09 logMAR). The logMAR best-corrected visual acuity was improved in one eye, maintained in five eyes, and deteriorated in two eyes.

Conclusion: Ironing PDT decreased subfoveal fluid and preserved visual acuity in some patients with age-related macular degeneration difficult to treat with conventional therapy.
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http://dx.doi.org/10.2147/OPTH.S102171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795568PMC
April 2016

Favorable anatomic and visual outcomes with 25-gauge vitrectomy for myopic foveoschisis.

Clin Ophthalmol 2014 12;8:1837-44. Epub 2014 Sep 12.

Department of Ophthalmology, Kansai Medical University, Takii Hospital, Osaka, Japan.

Purpose: To report the surgical outcomes of 25-gauge vitrectomy in eyes with myopic foveoschisis (MF).

Methods: The medical records of 40 eyes of 36 patients that had undergone 25-gauge vitrectomy with internal limiting membrane peeling for MF were studied. The main outcome measures were the best-corrected visual acuity (BCVA) and the optical coherence tomography (OCT) findings. The eyes were divided into two groups: 1) those with a foveal detachment (FD; FD group); and 2) those without a FD (no-FD group).

Results: The postoperative OCT images showed a resolution of the MF with a significant reduction in the central foveal thickness from the preoperative values in both the FD group (479±150 μm to 196±56 μm; P=0.002, mean ± standard deviation) and in the no-FD group (369±116 μm to 245±50 μm; P=0.001). The final mean BCVA significantly improved from the preoperative values in the FD group (0.96±0.53 logarithm of the minimum angle of resolution [logMAR] units to 0.70±0.56 logMAR units; P=0.009) and in the no-FD group (0.46±0.38 logMAR units to 0.34±0.36 logMAR units; P=0.007). The final BCVA in the FD group improved in 63%, remained unchanged in 31%, and worsened in 6%. In the no-FD group, the final BCVA improved in 21%, remained unchanged in 71%, and worsened in 8% of the eyes. A better final BCVA was significantly correlated with a better preoperative BCVA in both groups (P<0.001).

Conclusion: Twenty five-gauge vitrectomy results in favorable visual and anatomic outcomes for MF. We recommend that 25-gauge vitrectomy be used to treat eyes with MF.
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http://dx.doi.org/10.2147/OPTH.S67619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4168853PMC
September 2014

Clinical features of diabetic patients referred by general physicians due to less ophthalmic examinations.

Clin Ophthalmol 2014 16;8:1331-5. Epub 2014 Jul 16.

Department of Ophthalmology, Kansai Medical University, Takii Hospital, Osaka, Japan.

Background: The purpose of this study was to determine the clinical features of patients with type 2 diabetes, and less ophthalmic examinations, referred by general physicians to ophthalmologists.

Methods: The medical charts of 327 patients with type 2 diabetes referred to our department from general physicians were reviewed. A detailed medical history was taken and a complete ophthalmic examination was performed for all patients. The patients were divided into two groups, ie, those with a history of missing ophthalmic examinations for more than a year (noncompliant group) and those with no previous ophthalmic examinations (never-examined group). Serum levels of glycosylated hemoglobin and creatinine, estimated glomerular filtration rate, and urine albumin/creatinine ratio were obtained from medical records.

Results: Of the 327 patients, 102 had diabetic retinopathy (31.2%), with a mean best-corrected visual acuity of 0.037±0.36 logMAR (logarithm of the minimum angle of resolution) units. Of the 327 patients, 203 were in the never-examined group and 124 were in the noncompliant group. The incidence of diabetic retinopathy in the noncompliant group was significantly higher than that in the never-examined group (P<0.001). Best-corrected visual acuity in the noncompliant group was significantly worse than in the never-examined group (P=0.004). Glycosylated hemoglobin levels and estimated glomerular filtration rate in the noncompliant group were significantly lower than in the never-examined group (P<0.001 and P<0.003, respectively); serum creatinine levels and urine albumin/creatinine ratio were significantly higher (P=0.020 and P=0.001, respectively). The severity of the diabetic retinopathy was significantly correlated with compliance in terms of ophthalmic examinations and with urine albumin/creatinine ratio (multiple regression analysis, P=0.047 and P<0.001, respectively).

Conclusion: Our results show that diabetic patients referred from general physicians due to less ophthalmic examinations generally have good visual acuity, but one third of them have diabetic retinopathy. A history of missing ophthalmic examinations and albuminuria are risk factors for diabetic retinopathy.
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http://dx.doi.org/10.2147/OPTH.S65707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106958PMC
July 2014

Usefulness of dual echo volumetric isotropic turbo spin echo acquisition (VISTA) in MR imaging of the temporomandibular joint.

Magn Reson Med Sci 2013 Dec 29;12(4):249-59. Epub 2013 Oct 29.

Department of Radiology, Wakakusa Daiichi Hospital.

Purpose: We investigated the ability to detect the articular disk and joint effusion of the temporomandibular joint (TMJ) of a method of dual echo volumetric isotropic turbo spin echo acquisition (DE-VISTA) additional fusion images (AFI).

Methods: DE-VISTA was performed in the 26 TMJ of 13 volunteers and 26 TMJ of 13 patients. Two-dimensional (2D) dual echo turbo spin echo was performed in the 26 TMJ of 13 volunteers. On a workstation, we added proton density-weighted images (PDWI) and T2 weighted images (T2WI) of the DE-VISTA per voxel to reconstruct DE-VISTA-AFI. Two radiologists reviewed these images visually and quantitatively.

Results: Visual evaluation of the articular disk was equivalent between DE-VISTA-AFI and 2D-PDWI. The sliding thin-slab multiplanar reformation (MPR) method of DE-VISTA-AFI could detect all articular disks. The ratio of contrast (CR) of adipose tissue by the articular disk to that of the articular disk itself was significantly higher in DE-VISTA-AFI than DE-VISTA-PDWI (P<0.05) in patients and volunteers with closed or open mouth. In volunteers, the CR between adipose tissue and the disk on DE-VISTA-AFI was marginally significant to that on 2D-PDWI at opened mouth (P=0.071) and not significantly different (P=0.18) from that at closed mouth. Joint effusion could be identified in DE-VISTA-AFI in all 8 joints that had joint effusion in DE-VISTA-T2WI but in only 3 of those joints in 2D-T2WI. The CR of joint effusion to adipose tissue on DE-VISTA-AFI did not differ significantly from that on DE-VISTA-PDWI. However, using DE-VISTA-T2WI in addition to DE-VISTA-PDWI, we could visually identify joint effusion on DE-VISTA-AFI that could not be identified on DE-VISTA-PDWI alone.

Conclusion: DE-VISTA-AFI can depict the articular disk and a small amount of joint effusion by the required plane of MPR using the sliding thin-slab MPR method.
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http://dx.doi.org/10.2463/mrms.2013-0009DOI Listing
December 2013

Fever of unknown origin successfully treated by oren-gedoku-to (huanglian-jie-du-tang).

Int J Gen Med 2013 7;6:829-32. Epub 2013 Oct 7.

Division of Traditional Japanese Medicine, Department of General Medicine and Emergency Care, Faculty of Medicine, Toho University, Tokyo, Japan.

Oren-gedoku-to is a traditional medicine used for treating inflammatory conditions and is given by prescription in Japan, People's Republic of China, and Korea. Its anti-inflammatory effect is related to the arachidonate cascade and inhibition of cyclo-oxygenase, but research on other anti-inflammatory pathways is ongoing. We report a case of fever of unknown origin in a 33-year-old woman. The possibility of infection due to human immunodeficiency virus, autoimmune, neoplastic, or other disease was examined and excluded. Oren-gedoku-to was successfully used to treat her symptoms and may thus be a suitable treatment for patients with undiagnosed fever of unknown origin.
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http://dx.doi.org/10.2147/IJGM.S52488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794967PMC
October 2013

Initial non-responders to ranibizumab in the treatment of age-related macular degeneration (AMD).

Clin Ophthalmol 2013 22;7:1487-90. Epub 2013 Jul 22.

Department of Ophthalmology, Kansai Medical University, Takii Hospital, Osaka, Japan.

Background: Patients with exudative age-related macular degeneration (AMD) who did not respond to ranibizumab at the induction phase were assessed and referred to as initial non-responders.

Methods: We retrospectively reviewed the medical records of 215 patients (218 eyes) with exudative AMD. For the initial treatments, patients received three intravitreal injections of ranibizumab (IVR) every 4 weeks. Minimum follow-up period was 12 months. We defined patients with no improvement of best corrected logMAR visual acuity (BCVA), and with no decrease of central retinal thickness (CRT) at the end of the initial treatment, as initial non-responders. Patients who had previous treatment history prior to this investigation were included, but patients who had photodynamic therapy (PDT) with IVR were excluded.

Results: Twenty-two eyes (10.1%) were identified as initial non-responders. The mean BCVA of initial non-responders before IVR and after induction phase were 0.39 and 0.36, respectively. There was no significant difference between these values, however the mean BCVA decreased significantly to 0.55 at 12 months after the beginning of the induction phase (P = 0.021). The mean greatest linear dimension (GLD) of the lesion before IVR of initial non-responders was 4,121 μm. We found 16 eyes with typical AMD, and six eyes with polypoidal choroidal vasculopathy. One eye had predominantly classic choroidal neovascularization (CNV), and others had occult CNV of typical AMD. As additional treatments, twelve eyes received PDT, and in three of the eyes exudation remained after PDT.

Conclusion: Initial non-responders were more prevalent in patients with occult CNV than in patients with other CNV types. Some of the initial non-responders did not respond to PDT. This study suggested possible involvement of other factors, in addition to vascular endothelial growth factor, in the occurrence of CNV in initial non-responder patients.
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http://dx.doi.org/10.2147/OPTH.S46317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726592PMC
July 2013

Two cases of intraocular lymphoma diagnosed by analyses of vitreous and infusion fluid.

Clin Ophthalmol 2013 4;7:691-4. Epub 2013 Apr 4.

Department of Ophthalmology, Kansai Medical University, Takii Hospital, Osaka, Japan.

Purpose: Intraocular lymphomas are rare, and they have poor prognosis. Thus, early diagnosis and treatment are needed. A definitive diagnosis of a lymphoma is based on cytological analysis of the intraocular fluids or tissues. We report two cases of intraocular lymphoma diagnosed by the analyses of vitreous and infusion fluid.

Patients: Case 1 was a 66-year-old woman who complained of eye floaters and was found to have diffuse vitreous opacification bilaterally. She received corticosteroid therapy, however the vitreous opacification was not resolved, and her visual acuity (VA) remained reduced. She underwent pars plana vitrectomy (PPV), and vitreous and infusion fluid were collected to determine the cause of the reduced VA. The undiluted vitreous obtained from core PPV was submitted for cytokine analysis, and infusion fluid was obtained from the machine cassette after full PPV and used for cytological analysis. Case 2 was a 62-year-old man referred with low vision and was found to have diffuse vitreous opacification in the right eye and dot hemorrhages in both eyes. Four years earlier, he had been diagnosed with diffuse large B-cell lymphoma of the paranasal sinuses and was in remission after chemotherapy. Because metastasis of the lymphoma was suspected, he underwent PPV, and intraocular samples were collected as in Case 1.

Results: Atypical lymphoid cells were detected from the infusion fluid in both cases. The ratio of interleukin (IL)-10 to IL-6 was greater than 1.0 in both cases. These results allowed us to make a diagnosis of intraocular lymphoma: primary intraocular lymphoma in Case 1 and metastatic intraocular lymphoma in Case 2.

Conclusion: Vitreous and infusion fluid collected during PPV can be used for diagnosing an intraocular lymphoma.
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http://dx.doi.org/10.2147/OPTH.S44353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3622399PMC
April 2013

A long-term follow-up of peripapillary retinoschisis with optic disc hypoplasia.

Int Ophthalmol 2013 Aug 13;33(4):425-8. Epub 2012 Nov 13.

Department of Ophthalmology, Takii Hospital, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, Japan.

Peripapillary and macular retinoschisis are usually associated with optic disc pits. We report a rare case of peripapillary retinoschisis with optic disc hypoplasia. A 59-year-old woman presented with asthenopia. Her best-corrected visual acuity was 20/20 OD. Ophthalmoscopy of the right eye revealed peripapillary retinoschisis, optic disc hypoplasia and dilated and tortuous radial peripapillary capillaries. There was no obvious optic disc pit or vitreous traction on optical coherence tomography (OCT) or fluorescein angiography. OCT showed retinoschisis around the optic disc, a thin sheet of fenestrated tissue on the optic disc and absence of serous retinal detachment. These findings had been almost the same at a previous visit to our hospital 17 years previously. Peripapillary retinoschisis may occur in patients with optic disc hypoplasia. We report a case in which visual acuity and symptoms did not change significantly after 17 years of follow-up.
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http://dx.doi.org/10.1007/s10792-012-9673-7DOI Listing
August 2013

Two cases of ocular sarcoidosis in which vitreous cytology was useful for supporting the diagnosis.

Clin Ophthalmol 2012 31;6:1207-9. Epub 2012 Jul 31.

Department of Ophthalmology, Kansai Medical University, Takii Hospital, Osaka.

The purpose of this paper is to report two cases of sarcoidosis with conflicting signs in which vitreous cytology was useful for supporting the diagnosis. Case 1 was a 56-year-old man who was referred with blurred vision, and was found to have iridocyclitis, vitreous opacities, and optic neuritis bilaterally. He also had a swelling of both mandibular glands. He received pulsed corticosteroid therapy, but the vitreous opacities and papilledema did not resolve. The second case was a 77-year-old man referred with blurred vision, and both eyes had snowball-like vitreous opacities and optic neuritis. The ocular findings in both cases strongly suggested sarcoidosis, but the systemic findings did not meet the diagnostic criteria for sarcoidosis. We performed pars plana vitrectomy to remove the vitreous opacities, and the collected vitreous samples were sent for cytological analyses. Epithelioid and multinucleated giant cells pathognomonic of sarcoidosis were found in the vitreous samples which enabled us to make a diagnosis of sarcoidosis. Vitreous cytology can help in supporting a diagnosis of sarcoidosis, especially in cases of ocular inflammation suggesting sarcoidosis but systemic findings that do not satisfy the diagnostic criteria for this disease.
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http://dx.doi.org/10.2147/OPTH.S34344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422143PMC
October 2012

Population pharmacokinetic modeling of sepantronium bromide (YM155), a small molecule survivin suppressant, in patients with non-small cell lung cancer, hormone refractory prostate cancer, or unresectable stage III or IV melanoma.

Invest New Drugs 2013 Apr 16;31(2):443-51. Epub 2012 Aug 16.

Clinical Pharmacology, Astellas Pharma Inc., 3-17-1, Hasune, Tokyo 174-8612, Japan.

Purpose Population pharmacokinetics (PK) of sepantronium bromide (YM155) was characterized in patients with non-small cell lung cancer, hormone refractory prostate cancer, or unresectable stage III or IV melanoma and enrolled in one of three phase 2 studies conducted in Europe or the U.S. Method Sepantronium was administered as a continuous intravenous infusion (CIVI) at 4.8 mg/m(2)/day over 7 days every 21 days. Population PK analysis was performed using a linear one-compartment model involving total body clearance (CL) and volume of distribution with an inter-individual random effect on CL and a proportional residual errors to describe 578 plasma sepantronium concentrations obtained from a total of 96 patients by NONMEM Version VI. The first-order conditional estimation method with interaction was applied. Results The one-compartment model with one random effect on CL and two different proportional error models provided an adequate description of the data. Creatinine clearance (CLCR), cancer type, and alanine aminotransferase (ALT) were recognized as significant covariates of CL. CLCR was the most influential covariate on sepantronium exposure and predicted to contribute to a 25 % decrease in CL for patients with moderately impaired renal function (CLCR = 40 mL/min) compared to patients with normal CLCR. Cancer type and ALT had a smaller but nonetheless significant contribution. Other patient characteristics such as age, gender, and race were not considered as significant covariates of CL. Conclusions The results provide the important information for optimizing the therapeutic efficacy and minimizing the toxicity for sepantronium in cancer therapy.
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http://dx.doi.org/10.1007/s10637-012-9867-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589632PMC
April 2013

Pharmacokinetics of sepantronium bromide (YM155), a small-molecule suppressor of survivin, in Japanese patients with advanced solid tumors: dose proportionality and influence of renal impairment.

Cancer Chemother Pharmacol 2012 Sep 18;70(3):373-80. Epub 2012 Jul 18.

Clinical Pharmacology, Development, Astellas Pharma Inc., Hasune, Itabashi-ku, Tokyo, Japan.

Purpose: The purpose of this analysis was to investigate the pharmacokinetics (PK) of sepantronium (YM155), a small-molecule suppressor of the expression of the antiapoptosis protein survivin, in Japanese patients with advanced solid tumors and to evaluate the effect of renal impairment on the PK profile of sepantronium.

Methods: Sepantronium was administered as a continuous intravenous infusion of 1.8-10.6 mg/m(2)/day for 168 h (7 days) to 33 patients. PK parameters were estimated via non-compartmental method. Renal function was categorized for the analysis based on the chronic kidney disease guidance using eGFR values at pre-dose.

Results: The PK of sepantronium was dose proportional in the dose range of 1.8-10.6 mg/m(2)/day. Age and sex did not significantly affect the PK of sepantronium. Results suggested that total clearance and renal clearance in patients with moderate renal impairment were 0.7-fold lower than those in patients with normal renal function, resulting in 1.3-fold higher steady-state concentration and area under the curve values. The PK parameters of sepantronium in patients with mild renal impairment were comparable to those in the patients with normal renal function.

Conclusions: While age and sex did not significantly affect the PK of sepantronium, moderate renal impairment increased exposure of sepantronium by about 30 %. The results suggest that no dose adjustment is required for patients with mild renal impairment.
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http://dx.doi.org/10.1007/s00280-012-1913-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428524PMC
September 2012

Primary vitrectomy versus scleral buckling for the treatment of rhegmatogenous retinal detachment: a meta-analysis of randomized controlled clinical trials.

Curr Eye Res 2012 Jun;37(6):492-9

Department of Ophthalmology, Affiliated First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.

Purpose: To compare the efficacy of pars plana vitrectomy (PPV) with that of scleral buckling (SB) in the treatment of uncomplicated, primary rhegmatogenous retinal detachment (RRD).

Materials And Methods: Meta-analysis of randomized controlled trials (RCTs) were performed. Phakic and pseudophakic/aphakic eyes were analyzed separately. Searches of PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials were conducted. Outcome measures included primary and final anatomic success, final visual success, and development of post-operative proliferative vitreoretinopathy (PVR) and/or post-operative cataract.

Results: Three RCTs of phakic eyes (n = 523) and four RCTs of pseudophakic/aphakic eyes (n = 690) were included in the meta-analysis. For the phakic group, searches of PPV and SB yielded similar results in terms of primary/final retinal re-attachment and post-operative PVR. In the SB arm, visual acuity (VA) was better (heterogeneity p = 0.14; OR = 0.50, 95%CI, 0.31-0.82; p = 0.005) and the rate of post-operative cataract lower (heterogeneity p = 0.42; OR = 4.18; 95%CI, 2.75-6.35, p < 0.00001) than in the PPV group. In the pseudophakic/aphakic group, re-attachment rates after a single operation did not differ between the two procedures (random effect model: OR = 1.77; 95% CI, 0.80-3.91; p = 0.16). Final anatomic success outcomes were in favor of PPV (OR = 1.97; 95% CI, 1.04-3.73; p = 0.04). Final visual success and post-operative PVR rates did not differ statistically between the two arms (OR = 1.49; 95%CI, 0.82-2.68; p = 0.19; and OR = 0.85; 95% CI, 0.58-1.26; p = 0.42, respectively).

Conclusions: SB is superior in terms of final VA and occurrence of post-operative cataract in uncomplicated phakic RRDs. PPV is more likely to achieve a favorable final re-attachment in pseudophakic/aphakic RRDs.
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http://dx.doi.org/10.3109/02713683.2012.663854DOI Listing
June 2012

Dampening of diurnal intraocular pressure fluctuation by combined trabeculotomy and sinusotomy in eyes with open-angle glaucoma.

J Glaucoma 2013 Apr-May;22(4):290-3

Department of Ophthalmology, Kansai Medical University, Takii Hospital, Osaka, Japan.

Purpose: Large diurnal intraocular pressure (IOP) fluctuation ([INCREMENT]IOP) is believed to be one of the causes of progression in glaucomatous changes. Some fully medicated glaucoma patients whose IOPs are controlled during the regular office hours (10:00 to 16:00 h) still have progression in glaucomatous changes and IOP elevation during off-office hours. The purpose of this study was to determine whether [INCREMENT]IOP is dampened after combined trabeculotomy and sinusotomy (LOT+SIN) in glaucoma patients with low IOPs during the regular office hours.

Patients And Methods: Fourteen eyes of 8 open-angle glaucoma patients who had large [INCREMENT]IOP despite low IOPs during the office hours were studied. The IOP was measured every 3 hours for 24 hours before and >3 months after the operation. The IOPs were measured in the sitting position with a Goldmann applanation tonometer. All patients underwent LOT+SIN.

Results: All patients had IOP elevations >20 mm Hg between 0:00 and 3:00 hours before the operation, and none had an IOP peak after the operation. The postoperative mean IOP (16.5±1.7 to 13.9±2.0 mm Hg, P=0.00064), the maximum IOP (21.9±2.4 to 16.1±2.5 mm Hg, P=0.0020), and [INCREMENT]IOP (8.9±2.7 to 4.3±1.2 mm Hg, P=0.0032) were significantly lower than the preoperative values. However, the minimum IOP was not reduced significantly (13.0±1.9 to 11.7±1.7 mm Hg).

Conclusions: The diurnal [INCREMENT]IOPs are dampened by LOT+SIN in glaucoma patients with controlled IOPs during regular office hours. These results indicate that these surgical procedures can be used for the treatment of open-angle glaucoma patients.
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http://dx.doi.org/10.1097/IJG.0b013e31824479e6DOI Listing
July 2013

Genetic analysis of human adenovirus type 54 detected in Osaka, Japan.

Jpn J Infect Dis 2011 ;64(6):535-7

Department of Infectious Diseases, Osaka Prefectural Institute of Public Health, Osaka, Japan. hiroi@iph.pref.osaka.jp

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March 2012

Effects of intravitreally injected bevacizumab on vascular endothelial growth factor in fellow eyes.

J Ocul Pharmacol Ther 2011 Aug;27(4):379-83

Department of Ophthalmology, Kansai Medical University, Takii Hospital, Osaka, Japan.

Purpose: Whether an intravitreal injection of bevacizumab in 1 eye will have any effect on the fellow eye has been discussed. The aim of this study was to determine the level of vascular endothelial growth factor (VEGF) in the fellow eyes after an intravitreal injection of bevacizumab in 1 eye with proliferative diabetic retinopathy.

Methods: Eight patients who had similar findings of proliferative diabetic retinopathy in both eyes were studied. Four patients had rubeosis (rubeosis group), and 4 patients did not have rubeosis (no-rubeosis group) in the anterior chamber. All patients received an intravitreal injection of bevacizumab (1.25 mg) in 1 eye. Samples of aqueous humor were collected from the injected eyes just before the injection of bevacizumab and 1 day after the first injection just before vitrectomy. Samples of aqueous humor from the fellow eyes were collected just before a second injection of bevacizumab in the fellow eye at 7 days after the first injection. The concentration of VEGF in the aqueous humor was measured by enzyme-linked immunosorbent assay.

Results: After 1 day, the concentration of VEGF in injected eyes was significantly reduced from 3,230.3±2,136.8 to 3.1±3.6 pg/mL (P<0.05) in eyes with rubeosis and 465.0±78.8 to 0 pg/mL (P<0.05) in those without rubeosis. After 7 days, the VEGF level of the fellow eyes was still significantly lower than that in the injected eye just before the injection of bevacizumab (688.5±443.1 pg/mL) in the rubeosis group, and it was 7.8±13.2 pg/mL in the no-rubeosis group (P<0.05).

Conclusions: A single intravitreal injection of bevacizumab significantly reduced the VEGF concentrations in the aqueous humor of the fellow untreated eye. Thus, we need to be observant of the fellow eyes after a unilateral injection and also examine the patients for systemic changes.
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http://dx.doi.org/10.1089/jop.2010.0194DOI Listing
August 2011

Bifunctional tri(ethylene glycol) alkanethiol monolayer modified gold electrode for on-chip electrochemical immunoassay of pg level leptin.

Anal Sci 2011 ;27(5):465

National Institute of Advanced Industrial Science and Technology, Ibaraki, Japan.

An on-chip enzyme-linked immunosorbent assay combined with an electrochemical detection method (EC-ELISA) was employed to detect a leptin, one of the most important adipose derived hormones, using gold electrodes modified with a tri(ethylene glycol) terminated short alkanethiol (TEGCnSH, Cn = (CH(2))n, n = 2, 4, 6, and 8) monolayer. These TEGCnSH monolayers on gold electrodes can suppress non-specific protein adsorption without affecting the electrochemical activity required for detecting p-aminophenol (PAP), which is an alkaline phosphatase (ALP) product. We measured leptin with a highly sensitive detection range (100 pg mL(-1) to 10 ng mL(-1) level) and with the desired detection limit (13.6 pg mL(-1)) by using electrochemical detection. For detecting leptin, the EC-ELISA method using TEGC4SH modified gold electrode with a poly(dimethylsiloxane) based microchannel was superior to the conventional ELISA method. With the EC-ELISA method, we were able to measure leptin with a satisfactory detection range and a pg level detection limit within 30 min, which is a much lower detection level than that obtained with conventional plate based ELISA.
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http://dx.doi.org/10.2116/analsci.27.465DOI Listing
October 2011
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