Search

Purpose: Rho-associated kinase-inhibitor ripasudil 0.4% eye drops are reportedly effective for the reduction of intraocular pressure (IOP) in glaucoma patients. However, the previous studies invest...

Background/AimsTo investigate the time-dependent change of corneal endothelial cell (CEC) morphology and density (CECD) in patients with glaucoma post instillation of rho-associated protein kinase inhibitor ripasudil (Rip) 0.4% eye drops.MethodsThis observational study involved 163 eyes of 163 patients with glaucoma in whom CEC morphological change was evaluated by CECD calculated via non-contact specular microscopy (NCSM) before and at 1 or 3 months post-Rip instillation. The change of CECD was plotted along with elapsed time from last instillation of Rip. The patients were divided into the following three groups based on the elapsed time post-Rip instillation: Early Group (ResultsMorphological changes in the CECs appeared within 1 hour and recovered to normal within 6 hours post instillation. In the Early, Middle and Late Group, the median rate of CECD change as calculated by the NCSM automated software was −5.68%, −4.95% and −0.07%, respectively. The CEC images showed the same morphological changes with observational study in all four cases.ConclusionDue to transient morphological changes, the NCSM software produced misleading data for determining CECD within 1 hour post-Rip instillation, yet revealed that CEC morphology gradually recovered to normal within 6 hours.

We propose a new classification model to serve as a control for future genomic studies of glaucoma by distinguishing normal subjects maintaining non-glaucoma status for 10 years using the vertical cup-to-disc ratio.This study aimed to develop a classification for distinguishing subjects maintaining non-glaucoma status for 10 years using the vertical cup-to-disc ratio (VCDR).Among 842 volunteers 40 years and older, 421 volunteers participated in the second ophthalmic examination 10 years after their first examination. Each volunteer was diagnosed either as healthy normal or glaucoma suspect (GS) in the first glaucoma screening examinations. The former was further classified into the three grades of N1, N2, and N3. Specifically, N1 represented (1) VCDR0.3; (2) no notching or nerve fiber layer defect; and (3) no undermining, N2 indicated 0.3 ≤ VCDR0.6 and conditions (2) and (3) of N1; and N3 represented 0.3≤VCDR0.6 with undermining and condition (2), or 0.6≤VCDR0.7 and condition (2) of N1. Glaucoma transition rates (GTRs) were evaluated in 421 volunteers who returned to participate after a 10-year period.GTRs were calculated as 1.3% in both N1 and N2, 3.9% in N3, and 18.2% in GS. The ratio of volunteers in the same category maintenance rate increased from N1 to N3.GTRs were lower in N1 and N2 than in N3 or GS during the 10-year study period. This novel classification of healthy non-glaucoma subjects may help identify those, especially Japanese males, who maintain a non-glaucoma status for an extended period of 10 years.

Analytical technique using the τ−β diagram offers variations to evaluate aqueous complex systems. Those recent applications of the fractal analysis offer us simple and clear understanding of water structures as one of most effective tools for moist materials including living tissues. The newer application studies are summarized as follows; 1. Only a single plot: comparison with our database, 2. Structured water: such as water in cement materials, 3. Ion migrations: Maxwell-Wagner effect, 4. Stability of materials including homeostasis for biological tissues. As the skin condition recovers over a longer period after coating glycerol aqueous solutions, the τ−β diagram indicated more typical hyperbolic behavior for plots obtained at 60 minutes after coating. This result indicates that the fractal analysis can be used for evaluations of homeostasis.

To investigate the trend of seasonal variation of intraocular pressure (IOP) in patients with normal-tension glaucoma over a 20-year period by retrospectively analyzing the Kyoto Prefectural University of Medicine Glaucoma Registry database as real-world data.Retrospective cohort study.Data points (n = 49,007) were extracted retrospectively from the medical records of 1774 patients with normal-tension glaucoma (665 male patients and 1109 female patients; mean ± SD age was 59.8 ± 14.4 years; and mean ± SD observation period was 5.6 ± 4.4 years) seen over the 20-year period. We first calculated the mean IOP from all available data of each month from January 1997 through December 2016. The data were then categorized into 5 groups of 4 consecutive years each (1997-2000, 2001-2004, 2005-2008, 2009-2012, and 2013-2016) and the mean IOP of each month within the group was calculated. Seasonal variations of IOP over the 20-year study period and in the 5 consecutive groups were then investigated via nonlinear multiple regression analysis.A continuous decrease of IOP was detected throughout the 20-year period (P.001), with distinct seasonal variation. The annual mean ± SD IOP was highest (13.9 ± 2.7 mm Hg) in the oldest group (1997-2000), with a gradual decrease in each subsequent group, finally becoming lowest (12.3 ± 2.7 mm Hg) in the most recent group (2013-2016) (P.001), and all of them were accompanied by distinct seasonal variation (P.001).Based on the Kyoto Prefectural University of Medicine Glaucoma Registry real-world longitudinal data, our findings revealed a continuous decrease and distinct seasonal variation of IOP in patients with normal-tension glaucoma throughout the 20-year study period.

Objective To compare length of stay (LOS) in neonatal care for babies born extremely preterm admitted to networks participating in the International Network for Evaluating Outcomes of Neonates (iNeo). Study design Data were extracted for babies admitted from 2014 to 2016 and born at 24 to 28 weeks of gestational age (n = 28 204). Median LOS was calculated for each network for babies who survived and those who died while in neonatal care. A linear regression model was used to investigate differences in LOS between networks after adjusting for gestational age, birth weight z score, sex, and multiplicity. A sensitivity analysis was conducted for babies who were discharged home directly. Results Observed median LOS for babies who survived was longest in Japan (107 days); this result persisted after adjustment (20.7 days more than reference, 95% CI 19.3-22.1). Finland had the shortest adjusted LOS (−4.8 days less than reference, 95% CI –7.3 to −2.3). For each week's increase in gestational age at birth, LOS decreased by 12.1 days (95% CI –12.3 to −11.9). Multiplicity and male sex predicted mean increases in LOS of 2.6 (95% CI 2.0-3.2) and 2.1 (95% CI 1.6-2.6) days, respectively. Conclusions We identified between-network differences in LOS of up to 3 weeks for babies born extremely preterm. Some of these may be partly explained by differences in mortality, but unexplained variations also may be related to differences in clinical care practices and healthcare systems between countries.

Background Very preterm infants are at high risk of death or severe morbidity. The objective was to determine the significance of severe congenital heart defects ( CHDs ) for these risks. Methods and Results This cohort study included infants from 10 countries born from 2007–2015 at 24 to 31 weeks’ gestation with birth weights CHDs were defined by International Classification of Diseases, Ninth Revision ( ICD‐9 ) and Tenth ( ICD‐10 ) codes and categorized as those compromising systemic output, causing sustained cyanosis, or resulting in congestive heart failure. The primary outcome was in‐hospital mortality. Secondary outcomes were neonatal brain injury, necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity. Adjusted and propensity score–matched odds ratios ( ORs ) were calculated. Analyses were stratified by type of CHD , gestational age, and network. A total of 609 (0.77%) infants had severe CHD and 76 371 without any malformation served as controls. The mean gestational age and birth weight were 27.8 weeks and 1018 g, respectively. The mortality rate was 18.6% in infants with CHD and 8.9% in controls (propensity score–matched OR , 2.30; 95% CI , 1.61–3.27). Severe CHD was not associated with neonatal brain injury, necrotizing enterocolitis, or retinopathy of prematurity, whereas the OR for bronchopulmonary dysplasia increased. Mortality was higher in all types, with the highest propensity score–matched OR (4.96; 95% CI, 2.11–11.7) for CHD causing congestive heart failure. While mortality did not differ between groups at OR for mortality in infants with CHD increased to 10.9 (95% CI, 5.76–20.70) at 31 weeks’ gestational age. Rates of CHD and mortality differed significantly between networks. Conclusions Severe CHD is associated with significantly increased mortality in very preterm infants.

OBJECTIVE The hemodialysis (HD) diet, which is a high-calorie and high-fat regimen, may inadvertently lead to an inadequate dietary intake, resulting in undernutrition among elderly HD patients. Therefore, an attempt was made to improve the dietary intake by implementing a modified diet regimen in eligible elderly HD patients. SUBJECTS Elderly HD patients who had ingested < 50% of the meals provided and were diagnosed with undernutrition among all elderly patients institutionalized at the special elderly nursing home annexed to Nagasaki Kidney Hospital between June and November 2012. RESULTS Of the elderly HD patients in the nursing home (n = 27), the study included a total of 7 consecutive patients (male/female, 1/6; mean age, 84.1±6.4 years old; duration of HD, 4.3±3.8 years; geriatric nutritional index [GNRI], 83.5±8.3; normalized protein catabolic ratio [nPCR], 0.78±0.14). The modified diet regimen, which involved reducing food portion sizes and incorporating a liquid diet, led to a significant increase in their dietary intake from 48.1% at baseline to 97.1% of the meals provided 3 months after the start of the modified HD diet regimen. Their GNRI also significantly increased from 83.5±8.3 to 86.1±10.2, and their serum albumin levels significantly increased from 3.2±0.2 g/dL to 3.4±0.4 g/dL, suggesting improvements in their nutritional status. CONCLUSIONS The attempted dietary approach for elderly HD patients was shown to potentially increase their dietary intake and improve their nutritional status without affecting the efficiency of HD being implemented.

We investigated the incidence of thromboembolism in patients receiving combination chemotherapy with bevacizumab (BV)for colorectal cancer and examined its association with clinical factors. Between July 2007 and April 2014, 250 patients with colorectal cancer received combination chemotherapy with BV. Thromboembolism occurred in 24 cases(9.6%). Five predictive risk factors(platelet count B350,000/µL, hemoglobin10 g/dL, leukocyte count11,000/mL, body mass index B25.3 kg/m2, and D-dimer B1.44 µg/mL)were set based on a previous report, and the corresponding number of risk factors for thromboembolism and incidence of thromboembolism were examined. The results of multivariate analysis showed that the occurrence of 3 or more risk factors conferred a significant risk for the incidence of thromboembolism. Due to the increased risk of developing thromboembolism in such patients, special attention during management is required.

Background The dynamic behavior of water molecules remains an important subject for understanding human skin. The change in the dynamics of water molecules from those in bulk water can be effectively observed by dielectric spectroscopy. To study water in the human skin in vivo, non‐invasive and non‐destructive measurements are essential. Since many unknowns remain from previous research, in this report we employ a two‐layer dielectric model to evaluate the penetration depth of the electric field and use the results in measurements on human skin. Materials and Methods We used open‐ended coaxial probes with different diameters to perform time‐domain reflectometry (TDR) measurements for an acetone‐Teflon double‐layer model and for human skin from various parts of the body. Results The electric‐field penetration depth obtained from model measurements increases with the increasing outer diameter of open‐ended coaxial electrodes. For skin measurements, the relaxation strength corresponding to the water content shows a clear dependence on the epidermal thickness of the measured body parts. Conclusion We determined the depth distribution of the water content of skin from results of dielectric measurements obtained using electrodes with various electric‐field penetration depths. We found exponential decays with the thickness of the epidermis of each body part for several examinees. This study suggests an effective method for detailed evaluations of human skin.

The dynamics of a hydrogen bonding network (HBN) relating to macroscopic properties of hydrogen bonding liquids were observed as a significant relaxation process by dielectric spectroscopy measurements. In the cases of water and water rich mixtures including biological systems, a GHz frequency relaxation process appearing at around 20 GHz with the relaxation time of 8.2 ps is generally observed at 25 &deg, C. The GHz frequency process can be explained as a rate process of exchanges in hydrogen bond (HB) and the rate becomes higher with increasing HB density. In the present work, this study analyzed the GHz frequency process observed by suitable open-ended coaxial electrodes, and physical meanings of the fractal nature of water structures were clarified in various aqueous systems. Dynamic behaviors of HBN were characterized by a combination of the average relaxation time and the distribution of the relaxation time. This fractal analysis offered an available approach to both solution and dispersion systems with characterization of the aggregation or dispersion state of water molecules. In the case of polymer-water mixtures, the HBN and polymer networks penetrate each other, however, the HBN were segmented and isolated more by dispersed and aggregated particles in the case of dispersion systems. These HBN fragments were characterized by smaller values of the fractal dimension obtained from the fractal analysis. Some examples of actual usages suggest that the fractal analysis is now one of the most effective tools to understand the molecular mechanism of HBN in aqueous complex materials including biological systems.

To assess associations between neonatal intensive care unit (NICU)-level patent ductus arteriosus (PDA) treatment rates (pharmacologic or surgical) and neonatal outcomes.This cohort study included infants born at 24-28 weeks of gestation and birth weight1500 g in 2007-2015 in NICUs caring for ≥100 eligible infants in 6 countries. The ratio of observed/expected (O/E) PDA treatment rates was derived for each NICU by estimating the expected rate using a logistic regression model adjusted for potential confounders and network. The primary composite outcome was death or severe neurologic injury (grades III-IV intraventricular hemorrhage or periventricular leukomalacia). The associations between the NICU-level O/E PDA treatment ratio and neonatal outcomes were assessed using linear regression analyses including a quadratic effect (a square term) of the O/E PDA treatment ratio.From 139 NICUs, 39 096 infants were included. The overall PDA treatment rate was 45% in the cohort (13%-77% by NICU) and the O/E PDA treatment ratio ranged from 0.30 to 2.14. The relationship between the O/E PDA treatment ratio and primary composite outcome was U-shaped, with the nadir at a ratio of 1.13 and a significant quadratic effect (P.001). U-shaped relationships were also identified with death, severe neurologic injury, and necrotizing enterocolitis.Both low and high PDA treatment rates were associated with death or severe neurologic injury, whereas a moderate approach was associated with optimal outcomes.

Dynamics of Hydrogen Bonding Network (HBN) relating to macroscopic properties of hydrogen bonding liquids were observed as the largest relaxation process by dielectric spectroscopy measurements. In the cases of water and water rich mixtures including biological systems, a GHz frequency relaxation process appearing at around 20GHz with the relaxation time of 8.2ps is generally observed at 25°C. The GHz frequency process can be explained as a rate process of exchanges in HB and the rate becomes higher with increasing HB density. In the present work, we analyzed the GHz frequency process and clarified physical meanings of the fractal nature of water structures in various aqueous systems. Dynamic behaviors of HBN were characterized by a combination of the average relaxation time and the distribution of the relaxation time. The fractal analysis offered an available approach to both solution and dispersion systems with characterization of the aggregation or dispersion state of water molecules. In the case of polymer-water mixtures, the HBN and polymer networks well penetrate each other. However, the HBN were segmented and isolated more by dispersed and aggregated particles in the case of dispersion systems. These HBN fragments were dominantly evaluated by smaller values of the fractal dimension obtained from the fractal analysis, but it is also related with other two parameters. The fractal analysis is now one of the most effective tools to understand molecular mechanism of HBN in aqueous complex materials including biological systems.

Kazuhiko Mori, Yoko Ikeda, Yuko Maruyama, Shigeta Naruse, Morio Ueno, Shigeru Kinoshita Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan Purpose: To report the cases of six consecutive patients who underwent amniotic membrane (AM)-assisted trabeculectomy (TLE) to treat refractory glaucoma with severe corneal disorders. Methods: This study involved six patients (three males and three females, mean age: 69.5±15.8 years) with refractory glaucoma and severe corneal disorders. The surgical procedure for each patient involved trabecular tissue being excised, and human AM then being placed epithelial side up on the corneal surface, sutured at the limbal sclera, and flipped over onto the sclera to cover the TLE area. The remaining edge of the AM was then inserted into the subconjunctival space and sutured. Medical records of all cases were reviewed with regard to intraocular pressure (IOP), visual acuity, and condition of the filtering bleb and ocular surface. Results: The mean observation period was 69.5±15.8 months, and mean IOP at presurgery and at 1, 3, and 7 years postoperative was 40.3±6.9, 23.0±12.1, 25.6±12.8, and 28.5±19.1 mmHg, respectively. Glaucoma medications decreased from 3.0±1.1 drugs (presurgery) to 0.8±1.0 drugs (7 years postoperative). However, in some cases, ocular surface conditions or visual acuity worsened during the follow-up period. Conclusion: Using AM as an internal patch for TLE, moderately good IOP control was obtained initially for the refractory glaucoma with severe corneal disorders; however, ocular surface conditions required special care, and the long-term IOP control was limited in some cases. Keywords: amniotic membrane, refractory glaucoma, trabeculectomy

Yuko Maruyama,1,2 Yoko Ikeda,1,3 Kazuhiko Mori,1 Morio Ueno,1 Haruna Yoshikawa,1 Shigeru Kinoshita41Department of Ophthalmology, Kyoto Prefectural University of Medicine, 2Fukuchiyama City Hospital, 3Oike-Ganka Ikeda Clinic, 4Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, JapanBackground: The purpose of this study was to prospectively evaluate and compare intraocular pressure (IOP) reduction efficacy and safety between bimatoprost and latanoprost-timolol fixed combination (LTFC) in Japanese patients with open-angle glaucoma.Methods: In this prospective, randomized, non-masked study, after enrolling 70 eyes of 70 Japanese open-angle glaucoma patients who had used latanoprost monotherapy for more than 4 weeks, the subjects were randomly divided into a bimatoprost group or an LTFC group. Both groups were switched from latanoprost to bimatoprost or LTFC for 12 weeks. IOP, conjunctival injection score, corneal epitheliopathy score (area density classification; AD score), tear film break-up time, heart rate, and blood pressure were evaluated at 0, 4, and 12 weeks after switching. The paired t-test and Mann–Whitney U-test were used for the statistical analysis.Results: After 13 of the 70 patients dropped out, 57 were analyzed for IOP reduction and safety. There was a significant decrease in mean IOP at 4 weeks compared with week 0 in both groups (both P

Developing mouse retina has been serving as an ideal model for investigating the molecular mechanism of neural development and angiogenesis, because several significant events associated with these physiological phenomena are drastically occurring in conjunction with retinal development. However, as many genes are influencing on each other to establish mature retina within 21 days from E10 to P12, we must carefully design the experiments, such as in the case of quantitating the amount of altered gene expression toward the establishment of retina by quantitative PCR. As we have seen considerable variations of quantitative results in different developmental stages of retina depending on the reference genes used for compensation, we here attempted to determine a reliable reference gene to accurately quantitate the target genes in each stage. According to the results of in silico prediction and comparison with a database of SAGE, we found that the most stable gene from early to late stages was Sdha, whereas one of the most popular housekeeping genes, Actb, was the one that could mislead the quantitative results even in the adult stage. Consequently, we pointed out the importance of selecting an appropriate reference gene, especially to quantitate the amount of gene expression in the developmental stages of a certain tissue.

Background The aim of this study was to investigate the relationship between prognosis and the changes in serum-ionized calcium concentration in neonates with hypoxic–ischemic encephalopathy (HIE) before and during brain hypothermia (BHT). Methods Serum samples were obtained from 16 HIE neonates who underwent BHT. All patients underwent developmental testing at 18 months of age. Results Mean serum-ionized calcium concentration in the poor outcome group (developmental quotient [DQ], 80; seven infants), both immediately before and after 6 h of BHT. Mean serum-ionized calcium concentration significantly decreased in both groups for 6 h, and the lowest adjusted serum-ionized calcium during 6 h of BHT was

Purpose The primary side effects associated with 0.1% brimonidine tartrate (BT) ophthalmic solution with sodium chlorite are allergic conjunctivitis, blepharitis, and conjunctival hyperemia. However, cornea-related side effects are rare. In this study, we report 2 similar cases in which corneal neovascularization, corneal infiltration, and corneal opacity developed after BT eye-drop use. Methods Retrospective report of 2 cases of corneal infiltration after BT eye-drop use. Results Case 1 involved a 78-year-old woman with follicular conjunctivitis, corneal neovascularization, and infiltration in her left eye after unilateral instillation of BT eye drops in that eye. Case 2 involved a 75-year-old woman with bilateral corneal neovascularization and infiltration after instillation of BT eye drops. In both cases, the corneal complications were deemed to be side effects of BT, so those eye drops were replaced with 0.1% fluorometholone eye drops. After replacement, blepharitis and corneal neovascularization successfully resolved; however, a layer of opacity remained across the transparent layer of the cornea in both cases. Conclusions We encountered 2 cases of corneal and conjunctival complications that developed as side effects after BT eye-drop use, thus indicating that strict attention should be paid to the possibility of side effects after initiation of antiglaucoma eye-drop use.

Water structures in protein–water mixtures and cheeses were examined by Time Domain Reflectometry (TDR) and Nuclear Magnetic Resonance (NMR). The relaxation time obtained from TDR increased and the diffusion coefficient obtained from NMR decreased with increasing protein concentration, even if those physical quantities and time scales of respective observation techniques were considerably different. The correlation of these dynamic behaviors obtained from TDR and NMR is also found for water structures in cheeses. Fractal analysis of protein solutions by TDR measurements suggested that water structures in both systems were same with usual dispersion systems much more than solution systems. The fractal analysis with the τ– β diagram using geometric characteristics of the whole diagram is effective to characterize various water structures.

目的：慢性透析患者（以下，透析患者）の医療・療養における意思決定希求度・情報希求度の現状と，医療・療養における意思決定場面においての医療者の関わりを透析患者がどう感じているかを明らかにすることで，透析患者の意思決定を支援する医療者の役割についての示唆を得る．方法：S病院・Sクリニック外来に通院中の透析患者で，研究の同意が得られた63名を対象とし自記式質問紙調査を行った．意思決定希求度・情報希求度の測定はEndeらが開発したAutonomy Preference Index（以下，API尺度）をOhkiらが邦訳版に作成したものを使用した．また，意思決定場面における医療者の関わりについては研究者がCharlesらの提唱するThe Shared Treatment Decision-Making Modelをもとに独自に作成した質問項目（以下，SDM質問項目）を用いた．なお，本研究は医療法人衆和会桜町病院倫理委員会の承認を得て実施した．結果と考察：1．API尺度により透析患者は医療における意思決定場面において，医師に決定を委ねたいと思う傾向にあることが明らかになった．2．透析患者の意思決定希求度は年齢・職業の有無により有意差が生じることが明らかになった．3．SDM質問項目により，医療者から十分な情報の提供と不安や悩みの傾聴が行われた透析患者は医療者との信頼関係の構築ができ，透析患者の納得のいく意思決定が行われることが推察された．結論：意思決定場面において医療者が慢性透析患者の不安や悩みを十分に傾聴し共感することが，医療者と透析患者との信頼関係を形成する上で不可欠であるということ，また，透析患者が決定において独断と偏見の中で誤った決定を下したり後悔の念を抱いたりすることを防ぐために必要であることが示唆された．

Aim: To examine if we could predict periventricular leukomalacia (PVL) from the area of the lateral ventricle (LV). Methods: Six neonates in whom cystic PVL could be detected by magnetic resonance imaging (MRI) but not by ultrasound (US) were termed the ‘invisible group’. Six neonates in whom cystic PVL could be detected by MRI and US were termed the ‘visible group’. Eleven neonates in whom cystic PVL could not be detected by MRI or US were termed the ‘control group’. The ratio of LV to head circumference (HC) was calculated as the area of LV (cm2)/HC (cm) × 100. Receiver operating characteristic (ROC) curve analysis was carried out to find the cutoff value. Result: There were no significant differences among the three groups with respect to gestational age, birthweight, postnatal age and HC. The ratio of LV to HC in the control group was a median value of 0.38, it was 0.79 in the invisible group, and 0.96 in the visible group. The ratio was significantly higher in the visible group (P

Advances in treatment have significantly improved cure rates in childhood malignancies as well as long-term survival.Some malignancies,like acute lymphocytic leukemia or non-Hodgkin lymphoma,require long-term maintenance therapies and recently chemotherapy has been switched to an outpatient basis to improve quality of life.In the present study,we investigated the current situation of adverse events due to chemotherapy in pediatric outpatients and gathered information for use in devising measures to prevent them.We studied 572 instances of chemotherapy in 43 outpatients (two to 28 years old) from April 2005 to March 2006.The regimens were mainly for maintenance therapy and they were mild in intensity.The three major adverse events that we observed were neutropenia,infection and liver dysfunction,and in some cases they were treated symptomatically.Owing to adverse events,chemotherapy was postponed in 63 instances and in 13,hospitalization was necessary.However,in no instance was discontinuation of chemotherapy required.The chemotherapy execution ratio was 89%.Our findings indicate that chemotherapy was well-tolerated in pediatric outpatients and that it would be feasible to conduct it largely on an outpatient basis.

We have been promoting proper antiemetic therapy for chemotherapy induced emesis based on antiemetic treatment guidelines.In doing this,we have formulated our own antiemetic usage criteria,and classified registered regimens according to emetic risk based on ASCO,MASCC and NCCN guidelines.We investigated the compatibility situation of currently registered regimens by assigning them either to a compatible group (antiemetic agent prescriptions for acute nausea and vomiting meeting the usage criteria) or a non-compatible group (prescriptions not meeting the usage criteria).Patients who had received chemotherapy were targeted for investigation of drug management and guidance records,and a comparison of the 2 groups was made regarding acute nausea and vomiting incidence.Regimens with a high emetic risk accounted for 57.3% of the total,the compatibility rate with the acute anti-emesis usage criteria was 36.3% and a large percentage of regimens with high emetic risk were in the non-compatible group (45.9%).Common deviations from the usage criteria in the non-compatible group were multiple doses of 5HT3 receptor antagonists and insufficient dosages of adrenal corticosteroids.Further,nausea and vomiting greater than grade 2 frequently occurred in this group,and this pattern became more evident as the emetic risk increased.We demonstrated that the improvement of antiemetic therapy based on the guidelines was effective in alleviating emetic risk and our findings indicated that there was a particular need for improvement of therapy for high emetic risk regimens.

Aim: Hypoxic–ischemic reperfusion injury causes either necrosis or apoptosis, and the influx of ionized calcium into cells is the major cause of both types of cell death. The aim of this study was to investigate whether or not the serum ionized calcium concentration in neonates with hypoxic–ischemic encephalopathy (HIE) could be used to predict their outcome. Methods: Serum samples were obtained shortly after birth from 20 HIE neonates who had not urinated or received treatment with calcium. Serum ionized calcium concentrations were adjusted for pH using a correction formula. Twelve neonates without any disease were selected as a control. The results were compared between nine HIE neonates who made a full recovery, 11 who died or had neurologic deficits, and 12 normal neonates. Results: Considered together, the two HIE groups had lower serum ionized calcium concentrations (1.05 ± 0.10 mmol/L) than the control group (1.22 ± 0.07 mmol/L; P

Neurotrophin-4/5 (NT-4/5) - a member of the neurotrophic factors - is a ligand for TrkB, which has been reported to be expressed in the mechanoreceptive Ruffini endings of the periodontal ligament. The present study examined developmental changes in the terminal morphology and neural density in homozygous mice with a targeted disruption of the nt-4/5 gene and wild-type mice by immunohistochemistry for protein gene product 9.5 (PGP 9.5), a general neuronal marker, and by quantitative analysis using an image analyzer. Postnatal development of terminal Schwann cells was also investigated by enzymatic histochemistry for non-specific cholinesterase activity (ChE). Furthermore, the immuno-expression of TrkB and low affinity nerve growth factor receptor (p75-NGFR) was surveyed in the periodontal Ruffini endings as well as trigeminal ganglion. At postnatal 1 week, the lingual periodontal ligament of both types of mice contained PGP 9.5-positive nerve fibers showing a tree-like ramification with axonal swellings in their course. In both types of mice at 2 weeks of age, comparatively thick nerve fibers with a smooth outline increased in number, and frequently ramified to form nerve terminals with dendritic profiles. However, no typical Ruffini endings with irregular outlines observed in the adult wild-type mice were found in the periodontal ligament at this stage. At postnatal 3 weeks, typical Ruffini endings with irregular outlines were discernable in the periodontal ligament of the wild-type mice while the dendritic endings showing smooth outlines were restricted to the homozygous mice. After postnatal 8 weeks, both types of mice showed an increase in the number of Ruffini endings, but the morphology differed between the wild-type and NT-4/5 homozygous mice. In the wild-type mice, a major population of the Ruffini endings expanded their axonal branches and developed many microprojections, resulting in a reduction of endings with smooth outlines. In contrast, we failed to find such typical Ruffini endings in the periodontal ligament of the homozygous mice: A majority of the periodontal Ruffini endings continued to show smooth outlines at postnatal 12 weeks. Quantitative analysis on neural density demonstrated a reduction in the homozygous mice with a significant difference by postnatal 8 weeks. Enzymatic histochemistry for non-specific ChE did not exhibit a distinct difference in the distribution and density of terminal Schwann cells between wild-type and homozygous mice. Furthermore, TrkB and p75-NGFR mRNA and proteins did not differ in the trigeminal ganglion between the two types. The periodontal Ruffini endings also displayed immunoreactivities for TrkB and p75- NGFR in both phenotypes. These findings suggest that the nt-4/5 gene depletion caused a delay in the formation and maturation of the periodontal Ruffini endings in the mice by inhibiting the growth of the periodontal nerves at an early stage, and indicate that multiple neurotrophins such as NT- 4/5 and BDNF might play roles in the development and/or maturation of the periodontal Ruffini endings.

As the effects of supplementary oxygen on urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG) are poorly understood, urinary 8-OHdG levels (ng/mg creatinine) were determined longitudinally on the postnatal day (PND) 1, 3, and 30 in 16 neonates with birth weight < 1000 g. No supplementary oxygen was required in 9 neonates during the first 24 h of life. Urinary 8-OHdG level on PND 1 was inversely correlated with birth weight in these 9 neonates (P = 0.0323) and was higher in four with birth weight < 750 g than five with birth weight > 750 g (41.0 +/- 6.9 vs. 5.6 +/- 2.7, respectively, P = 0.0200). Median urinary 8-OHdG on PND 1 of these 9 neonates was significantly lower than that of 7 neonates with oxygen (9.3 vs. 60.2, respectively), although there were no significant differences in clinical background, such as birth weight, between the two groups. Five of the 9 did not require supplemental oxygen at all during the first 30 days of life. Median urinary 8-OHdG levels were consistently significantly lower in the 5 neonates than in 11 neonates with oxygen transiently or persistently (9.3 vs. 54.6, 19.1 vs. 61.4, and 28.3 vs. 145 on PND 1, 3, and 30, respectively), although there were no differences in clinical background, such as birth weight, between the two groups. Urinary 8-OHdG on PND 30 was significantly positively correlated with supplemental oxygen dose on PND 30 (P < 0.0001), but not with birth weight in the 16 neonates. These results suggest that higher supplemental oxygen tension caused higher urinary 8-OHdG in this population.

Yuko Maruyama, Kazuhiko Mori, Yoko Ikeda, Morio Ueno, Shigeru Kinoshita Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan Purpose: To analyze age-related morphological changes of the iridocorneal angle in normal subjects and glaucomatous cases, using anterior segment optical coherence tomography (AS-OCT). Methods: This study involved 58 eyes of 58 open-angle glaucoma cases and 72 eyes of 72 age-matched normal-open-angle control subjects. Iridocorneal angle structures in nasal and temporal regions and anterior chamber depth (ACD) were measured using AS-OCT. Axial length and refractive error were measured by use of an ocular biometer and auto refractor keratometer. Angle opening distance (AOD), angle recess area (ARA), and trabecular-iris space area (TISA), measured at 500 µm (TISA500) and 750 µm (TISA750) distant from the scleral spur, were calculated, in the nasal and temporal regions. A new index, the peripheral angle frame index (PAFI), which represents the peripheral angle structure, was proposed, and was defined as (TISA750-TISA500)/TISA500. Results: Refractive power in the glaucoma cases was less than in control cases (P

The aim of this study was to investigate the relationship between prognosis and the changes in serum-ionized calcium concentration in neonates with hypoxic-ischemic encephalopathy (HIE) before and during brain hypothermia (BHT).Serum samples were obtained from 16 HIE neonates who underwent BHT. All patients underwent developmental testing at 18 months of age.Mean serum-ionized calcium concentration in the poor outcome group (developmental quotient [DQ],80; nine infants) was significantly lower than in the good outcome group (DQ80; seven infants), both immediately before and after 6 h of BHT. Mean serum-ionized calcium concentration significantly decreased in both groups for 6 h, and the lowest adjusted serum-ionized calcium during 6 h of BHT was1.05 mmol/L, known as the cut-off value for poor outcome, in 57.1% of the good outcome group.The influx of calcium into cells continues regardless of neurological prognosis during the early phase of BHT, but BHT might protect some high-risk patients against neurological damage at low adjusted serum-ionized calcium concentration.

Background Fetomaternal hemorrhage (FMH) can cause severe morbidity. However, perinatal risk factors for long-term poor outcome due to FMH have not been extensively studied. Aims To determine which FMH infants are likely to have neurological sequelae. Study design A single-center retrospective observational study. Perinatal factors, including demographic characteristics, Kleihauer–Betke test, blood gas analysis, and neonatal blood hemoglobin concentration ([Hb]), were analyzed in association with long-term outcomes. Subjects All 18 neonates referred to a Neonatal Intensive Care Unit of Kagoshima City Hospital and diagnosed with FMH during a 15-year study period. All had a neonatal [Hb] 4.0%. Outcome measures Poor long-term outcome was defined as any of the following determined at 12 month old or more: cerebral palsy, mental retardation, attention deficit/hyperactivity disorder, and epilepsy. Results Nine of the 18 neonates exhibited poor outcomes. Among demographic characteristics and blood variables compared between two groups with poor and favorable outcomes, significant differences were observed in [Hb] (3.6 ± 1.4 vs. 5.4 ± 1.1 g/dL, P = 0.01), pH (7.09 ± 0.11 vs. 7.25 ± 0.13, P = 0.02) and base deficits (17.5 ± 5.4 vs. 10.4 ± 6.0 mmol/L, P = 0.02) in neonatal blood, and a number of infants with [Hb] ≤ 4.5 g/dL (78%[7/9] vs. 22%[2/9], P = 0.03), respectively. The base deficit in neonatal arterial blood increased significantly with decreasing neonatal [Hb]. Conclusions Severe anemia causing severe base deficit is associated with neurological sequelae in FMH infants.

PURPOSE It has been shown previously that the presence in the cornea of antigen-presenting cells (APC), such as macrophages (MPS) and lymphangiogenesis, is a risk for corneal transplantation. We sought to determine whether the existence of lymphatic vessels in the non-inflamed cornea is associated with the presence of MPS. METHODS Flat mounts were prepared from corneas of untreated C57BL/6, CD11b(-/-), F4/80(-/-), and BALB/c mice, and after suture placement or corneal transplantation, observed by immunofluorescence for the presence of lymphatic vessels using LYVE-1 as a marker of lymphatic endothelium. Innate immune cells were detected in normal mouse corneas using CD11b, F4/80, CD40, as well as MHC-class II. Digital images of the flat mounts were taken using a spot image analysis system, and the area covered by lymphatic vessels was measured using NIH Image software. RESULTS The number of spontaneous lymphatic vessels in C57BL/6 corneas was significantly greater than in BALB/c corneas (P = 0.03). There were more CD11b(+) (P < 0.01) and CD40(+), MHC-class II (+) cells in the C57BL/6 corneas than in BALB/c mouse corneas. MPS depletion via clodronate liposome in C57BL/6 mice led to fewer spontaneous lymphatic vessels and reduced inflammation-induced lymphangiogenesis relative to control mice. Mice deficient in CD11b or F4/80 had fewer spontaneous lymphatic vessels and less lymphangiogenesis than control C57BL/6 mice. CONCLUSIONS C57BL/6 mouse corneas have more endogenous CD11b(+) cells and lymphatic vessels. The endogenous lymphatic vessels, along with pro-inflammatory MPS, account for the high risk of corneal graft rejection in C57BL/6 mice. CD11b(+) and F4/80(+) MPS appear to have an important role in of the formation of new lymphatic vessels.

To examine if we could predict periventricular leukomalacia (PVL) from the area of the lateral ventricle (LV).Six neonates in whom cystic PVL could be detected by magnetic resonance imaging (MRI) but not by ultrasound (US) were termed the 'invisible group'. Six neonates in whom cystic PVL could be detected by MRI and US were termed the 'visible group'. Eleven neonates in whom cystic PVL could not be detected by MRI or US were termed the 'control group'. The ratio of LV to head circumference (HC) was calculated as the area of LV (cm²)/HC (cm) × 100. Receiver operating characteristic (ROC) curve analysis was carried out to find the cutoff value.There were no significant differences among the three groups with respect to gestational age, birthweight, postnatal age and HC. The ratio of LV to HC in the control group was a median value of 0.38, it was 0.79 in the invisible group, and 0.96 in the visible group. The ratio was significantly higher in the visible group (P0.001) and in the invisible group (P0.05) than in the control group. This ratio was low in the two infants who had PVL only in the collateral trigone. The ROC curve suggested a cutoff value of 0.6 (sensitivity 79.17%, specificity 100%) to suspect PVL.We may need to suspect PVL in infants whose lateral ventricle is enlarged even if cystic PVL is not detected by ultrasound. PVL present only in the collateral trigone needs to be evaluated using cerebral MRI.

This paper presents the development of a practical system for super-precise evaluation of zero-CTE temperatures T(zero- CTE) of TiO 2 -SiO 2 glasses for extreme ultraviolet lithography (EUVL) by measuring leaky surface-acoustic-wave (LSAW) velocity VLSAW with a line-focus-beam ultrasonic material characterization (LFB-UMC) system. This new system can evaluate T(zero-CTE) from 20 to 150°C on the surfaces of glass substrates for photomasks and optical mirrors located at different positions in EUVL systems. This system operates in a stabilized temperature measurement environment (e.g., 23.00°C). It was demonstrated at 225 MHz for homogenized TiO 2 -SiO 2 glass specimens with different annealing temperatures and realized an extremely homogeneous glass ingot with a ΔT(zero-CTE) of 1.6°C around 23.2°C. This ultrasonic system enables both glass manufacturers and users to speedily inspect all glass substrates with reliable data of T(zero-CTE).

ブタ卵子の核移植を行なうために,体外で成熟させたブタ卵胞卵の単為発生誘起条件,ならびに抜き取った細胞質と除核未受精卵との電気的再融合条件について検討した.卵胞卵は屠場で得た卵巣から回収し,10%ブタ去勢雄血清,FSH,および抗生物質を含むTCM-199液中で44-48時間培養して成熟させ,第1極体の放出が認められた卵子を実験に供した.25-100V⁄mm,25μsecのパルスを2度与えることにより,体外成熟卵の79-100%に単為発生が誘起された.一方,7%濃度のェタノール処理は,卵胞卵の単為発生誘起には効果がなかった,ついで,8細胞期胚割球の融合を想定し,およそ1⁄8細胞質を吸引除去した除核未受精卵への除去細胞質の再融合条件を検討したところ,50-100V⁄mmの電圧下25-50μsecのパルスを2度与えることによって,高率(88-95%)に細胞融合が観察された.ブタ体外成熟卵子を用いた,1⁄8吸引除去細胞質の除核未受精卵への移植においては,50-100V⁄mm,25μsec,2回のパルス条件が適しているものと推察された.

Aim: This retrospective study was performed to reveal the natural history of cytomegalovirus (CMV) infected fetuses during the perinatal period and to find prenatal findings associated with poor outcomes. Methods: 33 neonates with CMV infection, born after 30 weeks of gestation, were registered from a total of 12 414 infants between 1995 and 2003. Maternal and neonatal medical records were reviewed regarding fetal growth; abdominal signs including ascites and hepatosplenomegaly; cerebral signs including ventriculomegaly, microcephaly, and calcification; and fetal heart rate monitoring, for signs which may have been detected by the standard obstetric ultrasonography. Univariate and multivariate analyses were performed to test for any associations between these manifestations and poor outcomes such as death and neurological damages. Results: Among the 33 infants, 6 died, 10 developed neurological damage including cerebral palsy (n = 8), epilepsy (n = 5), and hearing difficulties (n = 5), and the remaining 17 were normal. After adjusting for ganciclovir treatment and gender, death was 40-fold more likely associated with infants having abdominal signs (OR 40, 95%CI 4.6–930) than those without abdominal signs. Similarly, poor outcomes (death or neurological damage) were more likely associated with infants having either abdominal or cerebral signs (OR 39, 95%CI 3.8–1323). Fetal growth restriction and non-reassuring fetal heart rate patterns were not significantly associated with poor outcomes. Conclusion: The absence of abdominal signs guarantees the infant's survival. The presence of abdominal or cerebral signs is associated with poor outcomes, suggesting that these fetuses are possible candidates to receive in-utero therapy of congenital CMV infection.

We developed a procedure for fabricating a Fabry–Perot optical cavity with less long-term length variation. We fabricated a homogenized TiO2–SiO2 ultralow-expansion (ULE) glass ingot from a commercial TiO2–SiO2 ULE glass ingot with striae. We also controlled the zero-crossing temperature of the coefficient of thermal expansion of the homogenized ingot to approximately 30 °C by heat treatment at 970 °C for 72 h to change the fictive temperature of the ingot. A 100-mm-long cavity spacer was carefully fabricated while reducing the mechanical residual stress introduced by machining. A cavity composed of the spacer and two mirrors of 39-layered Ta2O5/SiO2 films exhibited a high finesse of 420,000 at 729 nm and a high length stability of 13 fm/day after 500 days from the beginning of the measurement at a constant temperature of 29.78 °C.

An asphyxiated infant with severe hypoxic-ischemic encephalopathy was treated by brain hypothermia using extracorporeal membrane oxygenation (ECMO). The brain hypothermia using ECMO maintained cardiopulmonary functions and stabilized brain temperatures by stably supply of the cooled blood to the brain. Moreover,we measured the levels of glucose, lactate, ionized calcium and glutamate in plasma. The comparison between these levels in the artery and in the cephalic vein, suggests that glucose, lactate, ionized calcium and glutamate might be used as markers of the effects of hypothermia therapy.