Histological analysis of trabeculotomy - An investigation on the intraocular pressure lowering mechanism.

The primary aim of trabeculotomy (TLO) and/or minimally invasive glaucoma surgery (MIGS) is to produce a direct communication between the anterior chamber (AC) and collector channels (CC), which is believed to be the process by which intraocular pressure (IOP) is normalized. However, we previously reported our finding of the large opening of the Schlemm's canal (SC) into the AC in eyes with failed TLO (Amari et al., 2015). If the routes from the AC to the CC by TLO/MIGS are direct, IOP should be stabilized at around aqueous vein pressure if the SC and CC are undamaged. However, in eyes in which TLO/MIGS is successful, IOP usually stays at around the middle or high teens post surgery. In this current study, we retrospectively investigated the specific reason for middle- or high-teens IOP following TLO/MIGS via the histological examination of trabeculectomy (TRAB) specimens that include the area of previous TLO/MIGS in eyes with failed TLO or insufficient IOP control following TLO by specifically focusing on the behavior of the SC endothelium (SCE). Patient background, maximum IOP prior to TLO/MIGS and TRAB, the number medications administered, and elapsed time between TLO/MIGS and TRAB were reviewed. In 42 TRAB specimens of 31 120-180° TLO eyes (Group A; 27 ab-externo and 4 ab-interno eyes) and 11 360° suture TLO eyes (Group B), SC length (SCL), the site of the incision in the trabecular meshwork (TM) [i.e., the center (CEN)/anterior-tip (TIP)], and TM opening into the AC [i.e., open (OPN)/closed (CLS)] were histologically investigated. The correlation between the clinical parameters of the maximum IOP of pre-TLO/MIGS, the maximum IOP of pre-TRAB, the percentage of IOP reduction (PIR), and the histological results were statistically evaluated. Our findings revealed a significant negative correlation between the maximum IOP of pre-TRAB and SCL (P = 0.0167), and a significantly higher PIR in the eyes with OPN than those with CLS in Group A (P = 0.0045). However, no significant difference in SCL was found between the OPN and CLS eyes in both groups. In comparison to Group A, a higher percentage of OPN (82%) yet a smaller SCL (P = 0.0024) was observed in Group B. No significant correlation between clinical and histological parameters was found in Group B. In both groups, the common finding was sealing of the SC openings by SC endothelium (SCE) and no direct communication between the AC and the CC. This fact indicates that the nature by which SCE seals off the opened SC lumen into the AC created by TLO may be very important for maintaining the blood-aqueous barrier. Based on these results, we concluded that accessibility for aqueous humor to the SC and preservation of the SC may be important for lowering IOP by TLO. However, the opening of the SC into the AC (OPN type) does not guarantee an adequate IOP lowering effect if the SC is widely collapsed. Thus, TLO may be improved only by eliminating the most resistant part of the TM with minimal SCE damage.

Influence of the difference of breastfeeding volume on a rat model of oxygen-induced retinopathy.

This study aimed to investigate the effects of abundant breast milk intake on rats model of oxygen-induced retinopathy (OIR). Neonatal Sprague-Dawley rats were randomly assigned to expand litters of 7 pups/litter (7-rats group) and 14 pups/litter (14-rats group). They were exposed to 80% oxygen from postnatal day (P) 0 to P12. Body weights were measured daily. At P13 and 18, rats were sacrificed, and the blood and eyes were collected. Retinal neovascularization (NV) score, total retinal area (TRA), avascular area (AVA), and vascularized area (VA) were measured in ADPase stained retinas. Retinal vascular endothelial growth factor (VEGF) and serum insulin-like growth factor (IGF-1) were measured using ELISA. Body weight gain was significantly greater in 7-rats group from P2. Serum IGF-1 levels at P13 and 18 were significantly higher in 7-rats group. Retinal VEGF and TRA at P18 were significantly larger in 7-rats group. NV score at P18 tended to be higher in 7-rats group. There was no significant difference in VA between the 2 groups at P13 and 18. Excess breast milk intake in OIR rat pups caused body weight gain and retinal development, whereas there was less effect on retinal vascularization in our study.

[Support provided by public health nurses to adolescents with pervasive developmental disorders and their families].

OBJECTIVES: The objective of this study was to describe the process of support provided by public health nurses (PHNs) to adolescents with pervasive developmental disorders. The support given to the families of these adolescents was also examined. METHODS: The subjects in the study were PHNs with at least a 10-year experience at a public health center, who had been engaged in providing continuous support to adolescents with pervasive developmental disorders and their families. The patients investigated included young people in their adolescence who were diagnosed by psychiatrists as having pervasive developmental disorders (ICD.10: F84), including doubtful cases. Semi-structured interviews were conducted, and the data were analyzed using the Modified Grounded Theory Approach. RESULTS: The subjects included 10 female PHNs with 10-28 years of work experience. The number of patients supported by the PHNs was 10, with their ages ranging from 22 to 37 years. The analysis included 14 categories derived from 38 concepts. The categories for the support process provided by the PHNs for these adolescents with pervasive developmental disorders and their families included "generating trust," "thinking together during times of trouble," "weighing the difficulties in daily life and the influence of personal characteristics," "deepening the understanding of the patient's characteristics," "confronting difficulties in decision making," "identifying timing and intervention," "trying to live by themselves in the community," "promoting conversations using easy-to-understand communication," "enhancing self-understanding," "providing support for self-decisions and coping behaviors," "using and developing resources available in the community," "collaboration and coordination for responding to trouble," and "building a community in which it is easy to live." CONCLUSION: While supporting these adolescents and their families, the PHNs could increase their understanding of the person's characteristics as well as trust. They also continued trying to make communication easier and supported the family's coping behaviors, as well as collaborated with the people concerned to meet their needs and build a community in which it was easy to live. These findings suggest that it is necessary for PHNs to have an active role during their working life in order to promote a support network and system for the whole community. This will require the PHNs to consider measures that meet the person's characteristics and to establish coping mechanisms for the various problems that adolescent with developmental disorders and their families may encounter.

Convergent validity of the developmental coordination disorder checklist using soft neurological signs.

AIMS: To investigate the convergent validity of a new questionnaire, the Developmental Coordination Disorder Checklist (DCDC), we examined the relationship between the DCDC score and Soft Neurological Signs (SNS) which highly correlated with the Movement Assessment Battery for Children (MABC), which is widely applied to assess fine and gross motor skills. METHODS: The patients were 70 elementary school children without intellectual disabilities who were referred to our clinic, examined for SNS, and whose parents completed the DCDC. The DCDC consists of 16 items that focus on three factors: fine motor, gross motor, and catch and throw. We used a previously described method to assess SNS, which included five tasks: (1) standing on one leg with closed eyes, (2) finger opposition test, (3) diadochokinesis, (4) associated movements during diadochokinesis, and (5) motor persistence (laterally fixed gaze). RESULTS: DCDC scores and SNS were strongly and positively correlated, with higher DCDC scores (indicating greater coordination problems) associated with a higher number of positive SNS. CONCLUSIONS: DCDC scores have been proven to be strongly correlated with SNS, and these data suggest that DCDC has good convergent validity.

Peripheral T cell cytotoxicity predicts the efficacy of anti-PD-1 therapy for advanced non-small cell lung cancer patients.

Anti-programmed cell death-1 (PD-1) therapy exerts beneficial effects in a limited population of cancer patients. Therefore, more accurate diagnostics to predict the efficacy of anti-PD-1 therapy are desired. The present study investigated whether peripheral T cell cytotoxicity predicts the efficacy of anti-PD-1 therapy for advanced non-small cell lung cancer (NSCLC) patients. Advanced NSCLC patients treated with anti-PD-1 monotherapy (nivolumab or pembrolizumab) were consecutively enrolled in the present study. Peripheral blood samples were subjected to an analysis of peripheral T cell cytotoxicity and flow cytometry prior to the initiation of anti-PD-1 therapy. Peripheral T cell cytotoxicity was assessed using bispecific T-cell engager (BiTE) technology. We found that progression-free survival was significantly longer in patients with high peripheral T cell cytotoxicity (p = 0.0094). In the multivariate analysis, treatment line and peripheral T cell cytotoxicity were independent prognostic factors for progression-free survival. The analysis of T cell profiles revealed that peripheral T cell cytotoxicity correlated with the ratio of the effector memory population in CD4+ or CD8+ T cells. Furthermore, the results of flow cytometry showed that the peripheral CD45RA+CD25+/CD4+ T cell ratio was higher in patients with than in those without severe adverse events (p = 0.0076). These results indicated that the peripheral T cell cytotoxicity predicted the efficacy of anti-PD-1 therapy for advanced NSCLC patients.

Noninferiority of Microhook to Trabectome: Trabectome versus Ab Interno Microhook Trabeculotomy Comparative Study (Tram Trac Study).

PURPOSE: To elucidate the noninferiority of ab interno microhook trabeculotomy (µTLO) using a recently developed reusable stainless spatula-type microhook device to incise the trabecular meshwork to Trabectome (Neomeix, Inc) surgery in terms of the 1-year postoperative outcomes of Japanese patients with glaucoma by means of propensity score analyses. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: We enrolled 553 and 392 patients who underwent Trabectome surgery and µTLO, respectively, between January 2014 and March 2020 at 10 facilities. METHODS: Logistic regression analysis was conducted to calculate the propensity score, which indicates the likelihood of treatment assignment (Trabectome or µTLO). We set the following factors as outcome-related covariates: age, sex, facility, glaucoma disease types, preoperative intraocular pressure (IOP), glaucoma drug score, mean deviation of Humphrey visual field test results, antithrombotic drug use, the presence or absence of combined cataract surgery, and incision range of the trabecular meshwork (1 or 2 quadrants). We analyzed 4 different methods (matching, inverse probability of treatment weighting [IPTW], stratification, and regression adjustment) using the propensity score. We set 15% as the noninferiority margin based on previous Trabectome meta-analysis results. MAIN OUTCOME MEASURES: The primary outcome was surgical success at 1 year after surgery. We defined surgical success as satisfying all 3 criteria: (1) IOP within 5 to 21 mmHg, (2) IOP reduction of 20% or more from preoperative IOP, and (3) no additional glaucoma surgery. RESULTS: The 95% confidence interval of risk difference of surgical failure in µTLO in reference to Trabectome surgery was -12.1% to +9.5% in matching, -12.7% to +11.1% in IPTW, -12.2 to +7.0 in stratification, and -9.7% to +8.1% in regression adjustment, all of which fell within the predetermined noninferiority margin of 15%. CONCLUSIONS: Surgical success of µTLO at 1 year after was not inferior to that of Trabectome surgery.

[Long term clinical outcomes of Baerveldt glaucoma implantation via the pars plana].

PURPOSE: To present the long-term follow-up results of Baerveldt glaucoma implant (BGI) with a drainage tube from the pars plana in secondary glaucoma patients. METHODS: The subjects were patients with light perception and secondary glaucoma (> 21 mmHg) who had received more than 2 glaucoma operations: 11 were neovascular glaucoma patients and 5 angle-closure glaucoma patients with peripheral anterior synechia. After vitreous surgery, a BGI plate was fixed at the sclera in the superior temporal equator, and a drainage tube inserted from the pars plana into the vitreous cavity. The successful criteria needed to satisfy the 3 following conditions: 1) vision of more than light perception, 2) IOP > or = 5 mmHg and not higher than 22 mmHg, 3) no need for further glaucoma operations. RESULTS: The follow-up period was 82.5 months (from 5 to 172 months). Eight patients were judged a success, 4 patients a failure and 4 patients quit for personal reasons. The 10-year success rate was estimated at 72.8%. CONCLUSIONS: BGI via the pars plana is a useful method for long term IOP lowering effect in secondary glaucoma.

[Long-term results and analysis of multiple surgical approaches for ischemic cardiomyopathy with left ventricular reconstruction, including scarred endocardiectomy for arrhythmia therapy, and mitral valve surgery].

Among 73 patients with ischemic cardiomyopathy [ejection fraction (EF) < 40%, left ventricular end systolic volume index (LVESVI) > 60 ml/m2], 65 patients with large scar underwent left ventricular reconstruction (LVR) including scarred endocardiectomy against arrhythmia and 13 with 3 + mitral regurgitation (MR) mitral valve surgery [mitral annular plasty (MAP): n = 9, mitral valve replacement (MVR): n = 4]. Eight-year survival including 1 perioperative death (1.4%) was 773% without death due to arrhythmia. 69 survivors revealed significant improvement in New York Heart Association (NYHA) class, and lefe ventricular (LV) function in pulmonary artery pressure (PAP) and EF. LV volume significantly reduced from 103.6 to 57.5 ml/m2 in LVESVI (44% volume reduction) [p < 0.0001]. Postoperative LV shape became significantly spherical [eccentricity index (EI) closer to 0], however, MR grade was significantly reduced from 2.0 to 1.6 (p < 0.0003). Freedom from all deaths including hospitalization for cardiac causes was 71.1% at 8 years. One patient required implantable cardioverter defibrillator (ICD) for spontaneous ventricular tachycardia (VT). Multivariate Cox's regression model showed that preoperative large left ventricular end diastolic volume index (LVEDVI) [hazard ratio (HR) 1.02], postoperative large LVESVI (HR 1.03) and preoperative high NYHA class (HR 3.05) were significant risk factors affecting all deaths including hospitalization for cardiac causes. Of 24 patients with 2.5 + MR, mitral valve surgery (MAP, MVR or MAP + LVR) demonstrated significant improvement of MR (3.6 to 1.3 in MAP/MVR and 3.5 to 1.0 in MAP + LVR) compared with isolated LVR (2.6 to 2.2), although, there was no significant change in LV volume reduction. Our surgical approach to ischemic cardiomyopathy revealed excellent long-term results without death due to arrhythmia. Risk factor analysis recommended earlier and more aggressive surgical approach to achieve both LV volume reduction, MR and arrhythmia control.

Periostin, discovered by nano-flow liquid chromatography and mass spectrometry, is a novel marker of diabetic retinopathy.

Diabetes can lead to serious microvascular complications including proliferative diabetic retinopathy (PDR), the leading cause of blindness in adults. Recent studies using gene array technology have attempted to apply a hypothesis-generating approach to elucidate the pathogenesis of PDR, but these studies rely on mRNA differences, which may or may not be related to significant biological processes. To better understand the basic mechanisms of PDR and to identify potential new biomarkers, we performed shotgun liquid chromatography (LC)/tandem mass spectrometry (MS/MS) analysis on pooled protein extracts from neovascular membranes obtained from PDR specimens and compared the results with those from non-vascular epiretinal membrane (ERM) specimens. We detected 226 distinct proteins in neovascular membranes and 154 in ERM. Among these proteins, 102 were specific to neovascular membranes and 30 were specific to ERM. We identified a candidate marker, periostin, as well as several known PDR markers such as pigment epithelium-derived factor (PEDF). We then performed RT-PCR using these markers. The expression of periostin was significantly up-regulated in proliferative membrane specimens. Periostin induces cell attachment and spreading and plays a role in cell adhesion. Proteomic analysis by LC/MS/MS, which permits accurate quantitative comparison, was useful in identifying new candidates such as periostin potentially involved in the pathogenesis of PDR.

Eye damage control by reduced blue illumination.

The aim of this study was to demonstrate that a blue light and ultraviolet cut-off filter (blue filter) could reduce short-wavelength retina/RPE damage threshold by a continuous spectrum source. Sixteen normal eyes of two rhesus monkeys and six cynomolgus monkeys were subjected to macular irradiation of 20, 24, 27.4, 30, 35, 45, 50 and 60 J/cm(2) energy densities. The values of energy density were measured before the blue filter. Lesions were measured before and at 2 and 30 days after irradiation of a 2.8 mm diameter region within the macular arcade. Measures were fundoscopy, fluorescein angiography and long wavelength scanning by the Heidelberg Retinal Tomograph (HRT) unit. The lesions, which were produced, were scored and compared to irradiant energy density of the blue LED (NSPB500S, Nichia, Tokushima, Japan). The exposure at the 20 J/cm(2) produced no detectable result at 2 or 30 days. Exposure at 35 J/cm(2) showed definite lesion production without blue filter. With the filter added there was one indication of minor change. At 60 J/cm(2) there was extensive heavy, enduring damage without the filter and with the filter damage was present but was significantly attenuated. These results strongly support the conclusion that the blue filter attenuation reduces the frequency of damage by exposure. This experimental system is a useful model for normal human eye aging and continuous spectrum environment irradiance.

"De-airing" in open heart surgery: report from the CVSAP nation-wide survey and literature review.

Since the beginning of cardiac surgery, retained intracardiac air has been an important problem. While transesophageal echocardiography enabled to visualize the air and de-airing procedures have been routinely done, they appear to vary much among institutions not necessarily based on firm scientific evidence. Thus, "de-airing" was chosen as the theme of 2016 CVSAP (cardiovascular surgery and anesthesia and perfusion) symposium and a nation-wide questionnaire survey was carried out prior to it. This paper reports on its results and illustrate "the best of de-airing" based on literature review. The collection rate of the questionnaire survey was 77.9% (278/357) and 83.3% (85/102) from the major institutions of surgeons and anesthesiologists, respectively. More than 90% of both consider de-airing as important, since adverse events of air embolism were actually encountered including critical ones. Most routinely performed de-airing procedures are posture change, lung inflation and aspiration through the vent cannulae. Direct aspiration is performed in one-third of institutions. Carbon dioxide insufflation is performed in 82.5% of institutions (mostly 2-3 L/min). However, not a few surgeons are skeptical for its significance. While many surgeons are grateful for collaboration by anesthesiologists, some expect more information sharing between them. They also expect that clinical engineers understand "de-airing" better and operate the extracorporeal circulation system appropriately to avoid an occurrence of undesirable event. Some surgeons anticipated a convenient device for de-airing. Furthermore, some questions to be solved in the future were raised, including how meticulously the bubbles should be removed or how efficient carbon dioxide insufflation is.

[Oxidative stress in ocular disease].

The definition of oxidative stress implies increased oxidant production in animal cells characterized by the release of free radicals, resulting in cellular degeneration. The imbalance between excess free radical production and the antioxidant defense causes cellular damage resulting in lipid peroxidation. Oxidative stress is involved in many ocular diseases such as age-related macular degeneration, retinopathy of prematurity, retinal light damage, and cataract. Reactive oxygen species are involved in this process. The pathogenesis of age-related macular degeneration is largely unknown. Excessive light and iron may enhance the progression of this disease. In in vitro study of the ciliary body, gamma irradiation inhibits TPR53BP2 expression associated with apoptotic cell death, and increased BCL2 is evident just after gamma irradiation. Exposure to ultraviolet light has been postulated as a cause of age-related macular degeneration (AMD), perhaps through damage to the retinal pigment epithelium. It seems logical, therefore, to replace the aging, yellowing lens with a blue light-absorbing yellow intraocular lens (IOL) in cataract surgery. The issue of whether cataract surgery is a risk factor for the development or progression of AMD remains controversial. In vivo studies suggest that lipid peroxidation decreases in the vitreous and retina after cataract surgery with or without intraocular lens implantation.

[The effect of theanine on oxygen-induced retinal neovascularization in the neonatal rat].

PURPOSE: This study was aimed to investigate the preventive effects of theanine treatment on a rat model of oxygen-induced ischemic retinopathy (OIR). METHODS: OIR was induced by maintaining the Sprague-Dawley neonatal rats in 80% oxygen. The rats were treated once daily with gastric gavage of theanine (5 or 50 mg/kg) or distilled water (DW) from postnatal days 6 to 17. The retinal neovascularization (NV) was scored and avascular areas(AVAs) were measured as a % of total retinal area (% AVAs) at day 18. RESULTS: The % AVAs in 5 mg/kg theanine (13.2 +/- 2.8%) and 50 mg/kg theanine (9.4 +/- 2.2%, p < 0.05) treatment were lower than those in DW (18.9 +/- 2.9 %). The NV scores with 5 mg/kg theanine(4.2 +/- 0.5) or 50 mg/kg theanine (3.4 +/- 0.6) treatment were lower than those with DW (4.7 +/- 0.6). CONCLUSION: Theanine treatment suppresses the neovascularization in a rat model of OIR. These results suggest that theanine may prevent retinopathy of prematurity.

Distal aortic arch aneurysm in an adult case of PHACE syndrome.

A rare case of adult PHACE syndrome with a distal aortic arch aneurysm was treated surgically. The patient had several anomalies including uneven cerebral blood flow, a small left common carotid artery and a narrowed transverse aorta. Under deep hypothermic circulatory arrest, aortic replacement with reconstruction of the left subclavian artery was performed uneventfully. Cystic degeneration of the tunica media was observed in the aneurysm wall.

The Correlation Between Aqueous Humor Flow and IOP Before and After Trabectome: Developing a Grading System to Quantify Flow.

INTRODUCTION: To develop a grading system that provides objective quantification of flow through the conventional aqueous humor outflow (AHO) system. The technique gives clinicians an additional assessment option in the evaluation of glaucoma treatment approaches. METHODS: This was a retrospective observational study. This study evaluated the eyes of all primary open-angle glaucoma patients who underwent a Trabectome (NeoMedix Corp., Tustin, CA, USA) procedure with or without cataract surgery in the interval between April and September 2016 (n = 73). The nasal hemisphere was divided into three regions. Utilizing a four-level grading system designed for this study, an aqueous humor outflow grade (G0-G3) was assigned to each region using a video taken during examinations. The individual grade levels of the three regions were combined to get a composite AHO score. The correlation between the composite AHO score and intraocular pressure (IOP) was then analyzed. Additionally, the speed of red blood cell (RBC) clusters in the episcleral veins (ESV) was calculated when made possible by the existence of pulsatile flow. RESULTS: At 3 months following the Trabectome procedure, average IOP decreased from 26 to 15 mmHg. Assessment of the relationship between AHO grade and IOP demonstrated that a high composite AHO score was correlated with lowered IOP (Tukey-Kramer method p < 0.05). Additionally, it was found that if one of the three regions had an AHO grade of ≥ G2, an IOP of < 20 mmHg could be predicted. (Fischer's exact test p < 0.0001). Calculated speed was as follows: at G1, the speed was 0.68 ± 0.26 mm/s (n = 7), at G2, the speed was 1.8 ± 0.84 mm/s (n = 5), and at G3, the speed was 6.8 ± 3.3 mm/s (n = 6). CONCLUSION: There was a significant correlation between an increase in the composite AHO score and a decrease in IOP. Additionally, the speed of RBC clusters as they traveled through the ESVs remained consistent for each of the grades, and the span of the speeds from lower to higher grades represented a significant range. These findings suggest that the grading system is a reliable measure of AHO. TRIAL REGISTRATION IDENTIFIER: UMIN 000031745.

A rotating cerium anode X-ray system allows visualization of intramural coronary vessels after cardiac stem cell therapy for myocardial infarction.

Conventional angiography is insufficient for evaluating the therapeutic effect of cardiac regeneration therapy. A microangiographic X-ray system using a cerium anode was developed. Cerium has a characteristic X-ray with a peak at 34.6 keV, which allows visualization of tiny amounts of iodine. The performance of the cerium anode X-ray system was evaluated in two excised normal canine hearts and in excised ischemic canine hearts treated with c-kit-positive cardiac stem cells (5 canines) or without cells (5 control canines). In the normal canines, branches penetrating from the left anterior descending artery into the myocardium were visualized, down to third-order branches. In just the treated hearts treated with stem cells, small vessels characterized by irregular vessel walls were observed. The cerium anode X-ray system allowed visualization of microvessels in excised ischemic canine hearts, and may evaluate the effect of cardiac stem cell therapy.

Ascending aorta cannulation in acute type A aortic dissection.

OBJECTIVE: Antegrade perfusion for type A acute aortic dissection prevents malperfusion and retrograde cerebral embolism during cardiopulmonary bypass. Prompt establishment of antegrade perfusion via ascending aorta may improve the surgical results of type A dissections, especially in the situations of hemodynamic instability. Thus, we evaluated the efficacy of use of the dissected ascending aorta as an alternative arterial inflow. METHODS: Between 2002 and 2006, 32 patients underwent prosthetic graft replacement of the ascending aorta or hemiarch for acute type A aortic dissection. The ascending aorta was routinely cannulated, in addition to the femoral artery, with a heparin-coating flexible cannula for arterial inflow, using Seldinger technique, and by epiaortic ultrasonographic guidance (n=6). Antegrade systemic perfusion via ascending aorta was performed. RESULTS: Ascending aorta cannulation was safely performed in all cases. There was no malperfusion or thromboembolism due to ascending aorta cannulation. Cardiopulmonary bypass was established within 30 min after skin incision. There was one in-hospital death due to duodenal bleeding (1/32=3.1%), two cases of cerebral infarction (2/32=6.3%), and one case of pulmonary embolism. Twenty-nine patients (29/32=90.6%) were discharged in New York Heart Association class I and have been followed up uneventfully for a mean of 17 months. CONCLUSIONS: Antegrade perfusion via the ascending aorta was successfully performed with low mortality and morbidity. With ultrasound-guided Seldinger technique, ascending aorta cannulation has a potential to be a simple and safe option that enables rapid establishment of antegrade systemic perfusion in patients with acute type A aortic dissection.

Effects of green tea fractions on oxygen-induced retinal neovascularization in the neonatal rat.

This study aimed to investigate the preventive effects of green tea fractions (GTFs) on rat model of oxygen-induced retinopathy (OIR). Neonatal Sprague-Dawley rats were exposed to daily cycles of 80% oxygen (20.5 h), ambient air (0.5 h), and progressive return to 80% oxygen (3 h) until postnatal day 12 (P12), then the rats were placed in ambient air until P18. The green tea was fractionated by DM-A50, DM-W, M-B, and M-W. The rats were treated once daily from P6 to P17 by gastric gavage of GTFs (0.05 or 0.01 g/ml) or distilled water (DW) at 50 microl/10 g body weight. On P18, the rats were sacrificed and the retinal samples were collected. The retinal neovascularization (NV) was scored and avascular areas (AVAs) were measured as a % of total retinal area (%AVAs) in ADPase stained retinas. The NV scores in 0.01 g/ml M-W were significantly lower than those in DW. The %AVAs in 0.05 g/ml DM-A50 and in 0.05 g/ml and 0.01 g/ml M-W were significantly lower than those in DW. There were less catechins, and less caffeine in M-W fraction compared with other GTFs, suggesting components of green tea except for catechins and caffeine might suppress the neovascularization in rat model of OIR.

Evaluation of Intracranial Microvessel Visualization in Mouse and Dog Models by Using a New Rotating Cerium Anode X-ray System.

OBJECTIVE: Lacunar stroke may be caused by infarction of small perforating branches of the middle cerebral artery. We developed a microangiographic X-ray system using a cerium anode to evaluate the perforating branches. METHODS: Iodine has K-edges at 33.2 kilo electron volts. Cerium yields a characteristic X-ray of 34.6 kilo electron volts, therefore, the cerium anode X-ray system could detect tiny amounts of contrast material. First, an X-ray chart was used to evaluate the resolution. Second, the brains of mice were dissected and irradiated. Third, the brains of dogs were excluded and irradiated. Fourth, iodine was perfused into the carotid artery of living dogs during brain imaging. RESULTS: In the first experiment, the cerium anode X-ray system elicited 4.86 clear line pairs. In mice, the perforating branches of the middle cerebral artery could be visualized. The perforating branches were clearly observed in dog brains ex situ even through an acrylic plate, but not in conventional X-ray images. Iodine moving inside the perforating branches was visualized in dog brains in situ using the cerium anode X-ray system. CONCLUSION: The cerium anode X-ray system allowed us to visualize the perforating branches of the middle cerebral artery in living dogs.

Multicenter, Randomized, Investigator-Masked Study Comparing Brimonidine Tartrate 0.1% and Timolol Maleate 0.5% as Adjunctive Therapies to Prostaglandin Analogues in Normal-Tension Glaucoma.

INTRODUCTION: This study compared the efficacy and safety of adjunctive brimonidine tartrate 0.1% ophthalmic solution (brimonidine) and timolol maleate 0.5% ophthalmic solution (timolol) in prostaglandin analogue (PGA)-treated normal-tension glaucoma (NTG), assessing the non-inferiority of brimonidine in terms of intraocular pressure (IOP) reduction. METHODS: In this multicenter, randomized, investigator-masked, parallel-group, clinical study, adjunctive brimonidine or timolol was administered twice daily for 12 weeks in eyes with NTG that had been treated with PGA for at least 90 days and required additional treatment despite an IOP of 16 mmHg or less. IOP was measured on at least three visits before add-on therapy (mean baseline IOP), and at weeks 4, 8, and 12 after adjunctive administration. Systolic/diastolic blood pressure, pulse rate, and adverse events (AEs) were recorded at each visit. RESULTS: A total of 152 individuals were enrolled and 128 (84.2%) were eligible for efficacy analyses. IOP in both groups at each visit decreased significantly from baseline (P < 0.001). However, the difference in the change from baseline IOP at week 12 between the brimonidine (-1.05 ± 1.81 mmHg) and timolol (-1.41 ± 1.40 mmHg) groups was 0.36 mmHg (95% confidence interval [CI] [-0.21, 0.92]), which exceeded the value of the non-inferiority margin (0.75 mmHg). Baseline systolic/diastolic blood pressure decreased significantly in both groups at certain visits (P < 0.05), while baseline pulse rates decreased significantly in the timolol group (P < 0.001), with no significant differences in the brimonidine group. AE-related treatment discontinuation occurred in 2/71 (2.8%) and 2/75 (2.7%) patients in the brimonidine and timolol groups, respectively. CONCLUSION: This study demonstrated an add-on effect of brimonidine to PGAs, although non-inferiority of brimonidine to timolol as adjunctive therapy in PGA-treated NTG in terms of IOP reduction was not observed. Brimonidine was associated with no adverse effects on pulse rate. FUNDING: Senju Pharmaceutical Co., Ltd. TRIAL REGISTRATION: UMIN Clinical Trials Registry identifier, UMIN000014810.