Tohoku Medical and Pharmaceutical University Wakabayashi Hospital

BACKGROUND: Glenohumeral dislocations often recur, probably because a Bankart lesion does not heal sufficiently during the period of immobilization. Using magnetic resonance imaging, we assessed the position of the Bankart lesion, with the arm in internal and external rotation, in shoulders that had had a dislocation. METHODS: Coaptation of a Bankart lesion was examined with use of magnetic resonance imaging, with the arm held at the side of the trunk and positioned first in internal rotation (mean, 29 degrees) and then in external rotation (mean, 35 degrees), in nineteen shoulders. Six shoulders (six patients) had had an initial anterior dislocation, and thirteen shoulders (twelve patients) had had recurrent anterior dislocation. Fast-spin-echo T2-weighted axial images were made when the dislocation had occurred less than two weeks earlier, and spin-echo T1-weighted axial images after intra-articular injection of gadolinium-diethylenetriamine pentaacetic acid were made when the dislocation had occurred more than two weeks earlier. Separation and displacement of the anteroinferior portion of the labrum from the glenoid rim were measured on the axial images, and coaptation of the anterior part of the capsule to the glenoid neck was assessed by measurement of the detached area, opening angle, and detached length. RESULTS: Separation and displacement of the labrum were both significantly less (p = 0.0047 and p = 0.0017, respectively) when the arm was in external rotation than when it was in internal rotation. The detached area and the opening angle of the anteroinferior portion of the capsule were both significantly smaller (p = 0.0003 and p < 0.0001, respectively), and the detached length was significantly shorter (p < 0.0001) with the arm in external rotation. CONCLUSION: Immobilization of the arm in external rotation better approximates the Bankart lesion to the glenoid neck than does the conventional position of internal rotation.

OBJECTIVE Type 2 diabetes is frequently complicated with atherogenic dyslipidemia. This study aimed to evaluate the efficacy and safety of pemafibrate (K-877) in patients with type 2 diabetes comorbid with hypertriglyceridemia. RESEARCH DESIGN AND METHODS Patients were randomly assigned to three groups and received placebo (n = 57), 0.2 mg/day pemafibrate (n = 54), or 0.4 mg/day pemafibrate (n = 55) for 24 weeks (treatment period 1). Subsequently, the patients received follow-up treatment for another 28 weeks (treatment period 2), in which the placebo was switched to 0.2 mg/day pemafibrate. This article presents the results of treatment period 1, which were the primary objectives. RESULTS The pemafibrate groups showed significantly reduced fasting serum triglyceride levels by ∼45% compared with the placebo group (P &amp;lt; 0.001). Additionally, the pemafibrate groups displayed significant decreases in non-HDL and remnant lipoprotein cholesterol, apolipoprotein (Apo) B100, ApoB48, and ApoCIII levels and significant increases in HDL cholesterol and ApoA-I levels. LDL cholesterol levels were not considerably altered in the pemafibrate groups. Furthermore, the 0.2 mg/day pemafibrate group showed a significantly reduced HOMA–insulin resistance score compared with the placebo group; however, no significant changes compared with placebo were found in fasting plasma glucose, fasting insulin, glycoalbumin, or HbA1c levels. The pemafibrate groups also showed significantly increased fibroblast growth factor 21 levels compared with the placebo group. All groups displayed comparable rates of adverse events and drug reactions. CONCLUSIONS Pemafibrate significantly ameliorated lipid abnormalities and was well tolerated in patients with type 2 diabetes comorbid with hypertriglyceridemia.

Meiotic prophase I (MPI), is an initial stage of meiosis characterized by intricate homologous chromosome interactions, synapsis, and DNA recombination. These processes depend on the complex, but poorly understood early MPI events of homologous chromosome search, alignment, and pairing. Detailed molecular investigation of these early events requires isolation of individual MPI substages. Enrichment for Pachytene (P) and Diplotene (D) substages of late MPI was previously accomplished using flow cytometry. However, separation of early MPI spermatocytes, specifically, of Leptotene (L) and Zygotene (Z) substages, has been a challenge due to these cells' similar characteristics. In this report, we describe an optimized Hoechst-33342 (Hoechst)-based flow cytometry approach for isolating individual MPI populations from adult mouse testis. We get significant enrichment for individual L and Z spermatocytes, previously inseparable from each other, and optimize the isolation of other MPI substages. Our flow cytometry approach is a combination of three optimized strategies. The first is optimization of testis dissociation protocol that yields more consistent and reproducible testicular single cell suspension. The second involves optimization of flow cytometric gating protocol where a critical addition to the standard protocol for cell discrimination based on Hoechst fluorescence, involves a back-gating technique based on light scattering parameters. This step specifies selection of individual MPI substages. The third, is an addition of DNA content restriction to the gating protocol to minimize contamination from non-meiotic cells. Finally, we confirm significant enrichment of high-purity Preleptotene (PreL), L, Z, P, and D MPI spermatocytes using stage-specific marker distribution. The technique will facilitate understanding of the molecular events underlying MPI.

PURPOSE: The purpose of this study was to evaluate the effectiveness of intravitreal bevacizumab (IVB) on the reduction of diffuse diabetic macular edema in patients with different optical coherence tomography patterns. DESIGN: Prospective interventional case series. METHODS: One hundred and forty-three eyes with diffuse diabetic macular edema, without a history of any previous treatment, were classified according to their optical coherence tomography patterns: sponge-like diffuse retinal thickening (SDRT) (n = 50), cystoid macular edema (CME) (n = 38), serous retinal detachment (SRD) (n = 25), and the combination of all patterns (FULL: n = 30). All the participants received a single dose (1.25 mg in 0.05 mL) of IVB. The foveal thickness obtained with optical coherence tomography images and logarithm of the minimum angle of resolution visual acuity were assessed before receiving IVB and subsequently every 2 weeks for 12 weeks. RESULTS: After IVB, the foveal thickness in all the groups was reduced but the reduction ratio in the SDRT (29.6 ± 15.6%) and CME (27.1 ± 20.5%) groups was significantly greater than in the SRD group (16.4 ± 17.7%) (P < 0.001). Similarly, improvement of visual acuity in the SDRT (-0.21 ± 0.16) and CME (-0.17 ± 0.24) groups was significantly greater than in the SRD (-0.12 ± 0.15) and FULL (-0.11 ± 0.13) (P = 0.047) groups. Interestingly, the efficacy of IVB for regression of diffuse diabetic macular edema was dependent on the duration of diabetes in the SDRT and CME groups but not in the SRD or FULL groups. CONCLUSION: The effectiveness of IVB on diffuse diabetic macular edema was dependent on the optical coherence tomography pattern (SDRT ≥ CME >> SRD), indicating that vascular endothelial growth factor plays a critical role in the pathogenesis of SDRT and CME, and was greater in patients having diabetes for a shorter duration of time.

Excitotoxicity is a major cause of retinal ganglion cell (RGC) death during ischemic diseases such as vessel occlusion and diabetic retinopathy. However, the underlying mechanisms are not well understood. Statins, inhibitors of the HMG-CoA reductase, have neuroprotective effects in addition to their original role in lowering cholesterol. We hypothesize that pitavastatin, a recently introduced potent statin, is protective against N-methyl-d-aspartic acid (NMDA)-induced RGC death. Pitavastatin, administered by gavage, abolished NMDA-induced loss of RGCs. To elucidate the mechanisms underlying the neuroprotective effect of pitavastatin, we investigated its impact on inflammation. NMDA increased the expression of interleukin-1beta and TNF-alpha, and endothelial adhesion molecules, including ICAM-1, and induced leukocyte accumulation in the retinal vessels. Pitavastatin significantly reduced NMDA-induced leukocyte accumulation and up-regulation of endothelial adhesion molecules, whereas cytokine expression was unaffected. Systemic blockade of ICAM-1 in wild-type mice or absence of CD18 in gene-deficient (CD18(-/-)) mice significantly suppressed NMDA-induced leukocyte accumulation and RGC death. These findings suggest a novel and causative role for inflammatory leukocyte recruitment in NMDA-induced excitotoxicity. Furthermore, we show the novel neuroprotective effect of statins against excitotoxicity-induced RGC death. Statins or other anti-inflammatory agents may thus have therapeutic benefits in excitotoxicity-associated neuronal diseases through blockade of leukocyte recruitment.

We examined the immunopathology and the expression of human immunodeficiency virus type 1 (HIV-1) in lumbosacral dorsal root ganglia (DRGs) from 16 patients with acquired immunodeficiency syndrome (AIDS) and 10 HIV-1-seronegative controls. Using in situ hybridization, we detected HIV-1 RNA in a few perivascular cells in DRGs from five of 16 AIDS patients (31%). In addition, using polymerase chain reaction, we detected HIV-1 DNA more frequently in DRGs from four of five AIDS patients (80%) examined. We detected interleukin-6 (IL-6) immunoreactivity in endothelial cells in DRGs from seven of 16 AIDS patients (44%) but from none of 10 HIV-1-seronegative controls (0%). We found more nodules of Nageotte, CD8+ T lymphocytes, and intercellular adhesion molecule-1 (ICAM-1)-positive endothelial cells and mononuclear cells in DRGs from AIDS patients than in DRGs from controls. Increased numbers of nodules of Nageotte in DRGs of AIDS patients were associated with detection of HIV-1 RNA by in situ hybridization and detection of IL-6 by immunohistochemistry. We conclude that low levels of replication of HIV-1, through cytotoxic T lymphocytes or expression of cytokines, may play a role in the subclinical degeneration of sensory neurons frequently observed in DRGs of AIDS patients.

BACKGROUND: The primary abnormal manifestation in immunoglobulin A nephropathy (IgAN) is recurring bouts of hematuria with or without proteinuria. Although immunohistochemical analysis of renal biopsy tissue remains the gold standard not only for diagnosis but also for evaluating the activity of IgAN, new sensitive and reasonably specific noninvasive tests are emerging to guide therapeutic strategy applicable to all stages of IgAN. The present study examined serum levels of galactose-deficient IgA1 (Gd-IgA1) and its immune complex (IgA/IgG-IC) as noninvasive markers for the disease activity. METHODS: We enrolled 50 IgAN patients (male 40 %, median age 37 years) showing complete or partial clinical remission after steroid pulse therapy with tonsillectomy (TSP) whose clinical data and serum could be followed up for 3-5 years. RESULTS: Cross-sectional analysis revealed that the degree of hematuria and proteinuria were significantly associated with levels of Gd-IgA1 and levels of IgA/IgG-IC. Longitudinal analysis further showed that from the group of 44 patients with heavy hematuria before TSP, 31 patients showed complete disappearance of hematuria (group A), but the remaining patients did not (group B). Although the levels of Gd-IgA1 and IgA/IgG-IC in the two groups before TSP were similar, percentage decrease of Gd-IgA1 and IgA/IgG-IC levels in group A was significantly higher than in group B. CONCLUSION: Disease activity of IgAN assessed by hematuria and proteinuria correlated with serum levels and changes of Gd-IgA1 and IgA/IgG-IC. These new noninvasive disease activity markers can be useful for future activity scoring system and guiding therapeutic approaches.

PURPOSE: We investigated the accuracy and reproducibility of relative flow volume (RFV), a novel index of blood flow in the human retina derived from laser speckle flowgraphy (LSFG). METHODS: Pre- and postbranch retinal RFV measurements were compared in 34 retinal venous bifurcations in 34 healthy volunteers (mean age, 49.0 ± 14.8 years) to determine the accuracy of RFV. Next, the coefficient of variation (COV) of RFV was determined for 30 temporal retinal arteries in a second group of 18 healthy volunteers (mean age, 30.3 ± 7.7 years). Finally, laser Doppler velocimetry (LDV) data were obtained from the same study population and compared to RFV data from the retinal vessels. RESULTS: A comparison of RFV measurements in a trunk vessel of the retina and the sum of its two daughter vessels revealed a strong correlation (r = 0.98, P < 0.001). Reproducibility analysis showed that the COV for RFV was 5.9% ± 3.6%. Linear regression analysis revealed that RFV was correlated significantly with LDV measurements of mean retinal blood velocity (vmean) and retinal blood flow (FLDV, vmean, r = 0.61, P < 0.001; FLDV, r = 0.51, P = 0.004, respectively), but not significantly correlated with ocular perfusion pressure (r = -0.04, P = 0.76). CONCLUSIONS: These results suggest that RFV values obtained with LSFG can be considered an accurate and reliable index of relative blood flow in the human retina. Thus, RFV, a novel LSFG-derived variable, has potential for assessing retinal blood flow alterations in ocular disease.

AIM: Advanced glycation end products (AGE) are considered to be among the critical pathogenic factors involved in the progression of diabetic complications. Skin autofluorescence (AF), a noninvasive measurement of AGE accumulation, has been recognized as a useful and convenient marker for diabetic vascular diseases in Caucasians. This study aimed to evaluate the association of tissue AGE, assessed using skin AF, with coronary artery calcification in Japanese subjects with type 2 diabetes. METHODS: In total, 122 Japanese subjects with type 2 diabetes enrolled in this cross-sectional study underwent multi-slice computed tomography for total coronary artery calcium scores (CACS) estimation and examination with a skin AF reader. RESULTS: Skin AF positively correlated with age, sex, diabetes duration, pulse wave velocity, systolic blood pressure, serum creatinine, and CACS. In addition, skin AF results negatively correlated with BMI, eGFR, and serum C-peptide concentration. According to multivariate analysis, age and systolic blood pressure showed strong positive correlation and eGFR showed negative correlation with skin AF values. Multiple linear regression analyses revealed a significant positive correlation between skin AF values and logCACS, independent of age, sex, diabetes duration, HbA1c, BMI, IMT, and blood pressure. However, skin AF showed no association with serum levels of AGE, such as Nε-(carboxymethyl) lysine and 3-deoxyglucosone. CONCLUSION: Skin AF results positively correlated with CACS in Japanese subjects with type 2 diabetes. This result indicates that AGE plays a role in the pathogenesis of diabetic macrovascular disease. Measurement of skin AF values may be useful for assessing the severity of diabetic complications in Japanese subjects.

PURPOSE: To evaluate the effectiveness of intravitreal triamcinolone acetonide (IVTA) on the reduction of diffuse diabetic macular edema with different optical coherence tomographic patterns. METHODS: One hundred and thirty-five eyes with diffuse diabetic macular edema without any treatment that had received a single dose (4 mg in 0.1 mL) of IVTA were retrospectively examined. Each preoperative macular optical coherence tomographic image was classified according to its appearance as follows: sponge-like diffuse retinal thickening, cystoid macular edema (CME), and serous retinal detachment (SRD). Central macular thickness with optical coherence tomographic images and visual acuity with a logarithm of the minimum angle of resolution chart were assessed at 3 months postoperatively. RESULTS: Of 135 eligible eyes, 49 eyes were identified as having only sponge-like diffuse retinal thickening, 45 eyes with CME, and 26 eyes with SRD. Of those 135 eyes, 15 eyes exhibited the combination of all types of diffuse diabetic macular edema, defined as FULL. After IVTA, central macular thickness was reduced to 31.0 ± 15.9% in the sponge-like diffuse retinal thickening, 40.7 ± 14.2% in the CME, 23.4 ± 15.0% in the SRD, and 25.8 ± 14.8% in the FULL group (P < 0.001; one-factor analysis of variance), while improvement in logarithm of the minimum angle of resolution visual acuity was -0.26 ± 0.21 in the sponge-like diffuse retinal thickening, -0.32 ± 0.20 in the CME, -0.17 ± 0.20 in the SRD, and -0.14 ± 0.22 in the FULL group (P = 0.018; one-factor analysis of variance). CONCLUSION: The effectiveness of IVTA on diffuse diabetic macular edema was dependent on the optical coherence tomographic pattern, and IVTA was found to be more effective in patients with CME, while IVTA was less effective in those with SRD.

AIMS/INTRODUCTION: Diabetic polyneuropathy is one of the most frequent diabetic complications, and impairs patients' quality of life. We evaluated the efficacy and safety of ranirestat (40 mg/day) in patients with diabetic polyneuropathy. MATERIALS AND METHODS: This was a multicenter, placebo-controlled, randomized double-blind, parallel-group, phase III study in which 557 patients were randomly assigned to either the ranirestat or placebo group and assessed for 52 weeks. The co-primary end-points were the changes in tibial motor nerve conduction velocity and total modified Toronto Clinical Neuropathy Score as a measure of clinical symptoms. RESULTS: There was a significant increase in tibial motor nerve conduction velocity in the ranirestat group compared with the placebo group. The difference between groups in the change at last observation was 0.52 m/s (P = 0.021). Increases in nerve conduction velocity in the ranirestat group were found not only in the tibial motor nerves, but also in the median motor nerves, proximal median sensory nerves and distal median sensory nerves. No significant differences in modified Toronto Clinical Neuropathy Score or safety parameters were found between the two groups. CONCLUSIONS: Ranirestat (40 mg/day) was well tolerated and improved nerve conduction velocity. Regarding symptoms and signs, no detectable benefits over the placebo were observed in the ranirestat group during the 52 weeks of treatment.

Abstract Despite great strides in pharmacotherapy for diabetes, there is increasing concern over the risk of hypoglycemia in patients with diabetes receiving pharmacotherapy as they become increasingly older. This has prompted the Japan Diabetes Society ( JDS ) to initiate a survey on the current status of severe hypoglycemia in clinical settings. In July 2015, following approval from the JDS Scientific Survey/Research Ethics Committee, the JDS extended an invitation to executive educators, who represented a total of 631 healthcare facilities accredited by the JDS for diabetes education, to participate in the proposed survey. Of these, those who expressed their willingness to participate in the survey were sent an application form required for obtaining ethical approval at these healthcare facilities and were then asked, following approval, to enter relevant clinical data on an unlinked, anonymous basis in a web‐based registry. The current survey was fully funded by the JDS Scientific Survey/Research Committee. A case registry (clinical case database) was launched after facility‐specific information (healthcare facility database) was collected from all participating facilities and after informed consent was obtained from all participating patients. With severe hypoglycemia defined as the “presence of hypoglycemic symptoms requiring assistance from another person to treat and preferably venous plasma glucose levels at onset/diagnosis of disease or at presentation clearly less than 60 mg/ dL (capillary whole blood glucose, less than 50 mg/ dL )”, the current survey was conducted between April 1, 2014 and March 31, 2015, during which facility‐specific information was collected from a total of 193 facilities with a total of 798 case reports collected from 113 facilities. Of the 193 respondent facilities, 149 reported having an emergency department as well, with the median number of patients who required emergency transportation services to reach these facilities totaling 4,962 annually, of which those with severe hypoglycemia accounted for 0.34% (17). The respondent facilities accommodated a total of 2,237 patients with severe hypoglycemia annually, with the number of patients thus accommodated being 6.5 patients per site. A total of 1,171 patients were admitted for severe hypoglycemia, with the number of patients thus admitted being 4.0 per site, who accounted for 52.3% of all patients visiting annually for severe hypoglycemia. A review of the 798 case reports collected during the survey revealed that 240, 480 and 78 patients had type 1 diabetes, type 2 diabetes, and other types of diabetes, respectively; those with type 2 diabetes were shown to be significantly older (median [interquartile range], 77.0 [68.0–83.0]) than those with type 1 diabetes (54.0 [41.0–67.0]) ( P &lt; 0.001); and the BMI was shown to be significantly higher for those with type 2 diabetes (22.0 [19.5–24.8] kg/m 2 ) than for those with type 1 diabetes (21.3 [18.9–24.0] kg/m 2 ) ( P = 0.003). It was also found that the median estimated glomerular filtration rate ( eGFR ) was significantly lower among those with type 2 diabetes (50.6 mL [31.8–71.1]/min/1.73 m 2 ) than among those with type 1 diabetes (73.3 [53.5–91.1] mL /min/1.73 m 2 ) ( P &lt; 0.001). Again, the median HbA1c value at onset of severe hypoglycemia was shown to be 7.0 (6.3–8.1)% among all patients examined, 7.5 (6.9–8.6)% among those with type 1 diabetes, and 6.8 (6.1–7.6)% among those with type 2 diabetes, with the HbA1c value at onset of hypoglycemia being significantly lower among those with type 2 diabetes ( P &lt; 0.001). Antecedent symptoms of severe hypoglycemia were shown to be present, absent and unknown in 35.5, 35.6, and 28.9% of all patients, respectively, with the incidence of symptomatic hypoglycemia being significantly lower among those with type 1 diabetes (41.0%) than among those with type 2 diabetes (56.9%). The antidiabetic agents used in those with type 2 diabetes were insulin preparations (292 patients including 29 receiving concomitant sulfonylureas [ SU s]) (60.8%), SU s (159 insulin‐naïve patients) (33.1%), and no insulin preparations or SU s (29 patients) (6.0%). Of the 798 patients surveyed, 296 patients (37.2%) were shown to have required emergency transportation services for severe hypoglycemia before. Thus, the survey revealed, for the first time, the current status of treatment‐related severe hypoglycemia in Japan and clearly highlights the acute need for implementing preventive measures against hypoglycemia not only through education on hypoglycemia but through optimization of antidiabetic therapy for those at high risk of severe hypoglycemia or those with a history of severe hypoglycemia.

We examined the colloid materials in two Spodosols (Tihoi and Mangorewa) and two Andepts (Taupo and Oturoa) formed from the same volanic ash beds, using a combination of chemical and instrumental techniques. The dominant colloid material in all horizons of the Vitrandepts was allophane, except for the A horizon of the Taupo soil, which contained humus-Al complexes and opaline silica and had low pH (H2O) and high amounts of organic matter. Humus-Al, kaolin, and 2:1 layer silicates were the main colloidal materials in the two Haplo-humods, except in the C horizon of the Tihoi soil and the 2Bsh and 3Bsh horizons of the Mangorewa soil, which contained allophane. In these exceptions the release of Al from primary minerals is considered to exceed the accumulation of organic matter, thus allowing the formation of allophane. Allophane formation in the soils studied tends to be related to both the (Al + Fe)/C atomic ratio and soil pH (H2O). The presence of significant amounts of opaline silica, even in the A horizon of the Spodosol where intensive leaching occurs, suggests that the limiting factor in allophane formation, both in the Spodosols and the Andepts, is the concentration of Al, rather than Si, in soil solution.

The aim of this study was to evaluate the efficacy and safety of pemafibrate in people with type 2 diabetes and hypertriglyceridaemia over a 52-week period. Participants were randomly assigned to receive treatment with placebo or pemafibrate at a dose of 0.2 or 0.4 mg/d for 24 weeks (treatment period 1). The main results from treatment period 1 have been reported previously. The assigned treatment was continued up to week 52, except that the placebo was changed to pemafibrate 0.2 mg/d after week 24 (treatment period 2). The percentage changes in fasting serum triglyceride (TG) levels at week 52 (last observation carried forward) were -48.2%, -42.3%, and -46.4% in the placebo/pemafibrate 0.2 mg/d (n = 57), pemafibrate 0.2 mg/d (n = 54), and pemafibrate 0.4 mg/d (n = 55) groups, respectively. Levels of TG, non-HDL cholesterol and total cholesterol stably decreased, whereas levels of HDL cholesterol increased with pemafibrate treatments over 52 weeks. Pemafibrate was well tolerated throughout the study period. The present study is the first to show that pemafibrate treatment substantially ameliorated lipid abnormalities and was well tolerated for 52 weeks in people with type 2 diabetes and hypertriglyceridaemia.

OBJECTIVES: To investigate whether pulsed fluoroscopy reduces a patient's exposure compared with the exposure owing to conventional (continuous) fluoroscopy, we simulated the skin radiation doses of patients at cardiac catheterization facilities with various X-ray systems used in fluoroscopically guided intervention procedures. BACKGROUND: Although many reports have noted that "pulsed fluoroscopy" provides important further reductions in radiation exposure, it has been determined that when comparing dose rates between different vendor systems, "pulsed fluoroscopy" does not reduce patients' exposure as compared with "conventional fluoroscopy". METHODS: We examined 13 X-ray systems; 10 used pulsed fluoroscopy and three used conventional fluoroscopy. The entrance surface doses with fluoroscopy were compared for the 13 X-ray systems by using acrylic plates (20-cm thick) and a skin dose monitor. The X-ray conditions used in the measurements were those normally used in the facilities performing percutaneous coronary intervention. RESULTS: The average surface dose for systems from three different vendors producing conventional fluoroscopy systems was 23.93+/-2.77 mGy/min vs. an average surface dose of 22.52+/-4.50 mGy/min from five vendors of pulsed fluoroscopy systems (25, 30, and 50 pulses/sec) (P=0.646). The average entrance surface dose was significantly (P<0.0001) higher with conventional fluoroscopy and pulsed fluoroscopy at 25, 30, and 50 pulses/sec (23.05+/-3.78 mGy/min) than with pulsed fluoroscopy at 15 pulses/sec (13.86+/-3.22 mGy/min). CONCLUSIONS: Pulsed fluoroscopy did not in itself reduce radiation exposure. In general, the use of pulsed fluoroscopy at a pulse rate lower than 25 pulses/sec should reduce the skin dose in fluoroscopically guided intervention procedures. Nevertheless, some X-ray systems are not designed to reduce the dose rate as the number of pulses per second is decreased. Physicians should be aware of the entrance surface dose of the X-ray system that they use for cardiac IVR.

PURPOSE: To prospectively determine the magnetic resonance (MR) signal intensity characteristics of structures of the ampullary region and to assess the potential use of MR imaging in evaluation of the extent of periampullary tumors in resected specimens. MATERIALS AND METHODS: Twenty-five specimens from the ampullary region obtained in four autopsy cases without periampullary tumors and in 21 patients with periampullary tumors were examined with a 1.5-T MR system and a circular surface coil with 5-inch (12.7-cm) diameter. High-spatial-resolution MR images were obtained with field of view of 100 x 100 mm, matrix of 256 x 256 or 512 x 256, and section thickness of 2 mm. MR imaging findings were compared with histopathologic findings. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of high-spatial-resolution MR imaging for assessment of tumor invasion into surrounding tissues were evaluated by two radiologists. RESULTS: T1- and T2-weighted MR images clearly depicted normal structures in the ampullary region that included Oddi muscle, duodenal wall, common bile duct, and pancreas; these findings corresponded well with histologic findings. In 20 (95%) of 21 tumors, high-spatial-resolution MR imaging depicted location and extension of periampullary tumors precisely. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of high-spatial-resolution MR imaging for assessment of tumor invasion into surrounding tissue were 88%, 100%, 96%, 100%, and 94%, respectively. CONCLUSION: In this study, MR imaging correctly depicted location, extension, and origin of tumor. High-spatial-resolution MR imaging has potential for presurgical staging of tumors in this region.

Excitotoxicity has been implicated in several ischemic diseases of the retina, including retinal vessel occlusion and diabetic retinopathy. Glutamate signaling mediated through the N-methyl-D-aspartate (NMDA) receptor contributes to ischemic cell death. The NMDA receptor antagonists MK-801 and memantine have substantial neuroprotective effects in experimental retinal disease models, but the mechanisms by which NMDA receptor activity leads to cell death is not clear. Here we describe a previously unknown role for retinal glial cells in NMDA-induced retinal injury that involves the activation of ERK1/2. Within 1 hr after injecting NMDA intravitreally, activation of ERK1/2 and c-Fos induction were observed in retinal Müller cells. The roles of activated ERK1/2 in neuronal damage were examined using ERK1 gene deficient mice (homozygous ERK1(-/-) mice). NMDA-induced ERK1/2 activation in retina was significantly suppressed in ERK1(-/-) mice, and these mice had significantly higher numbers of TUNEL-positive retinal cells than wild-type mice 24 hr after NMDA injection. These data suggest that, during NMDA injury, Müller cells are activated and play a protective role against NMDA-induced retinal cell death. ERK1 appears to play a major role in this process. These new findings on retinal glial cell response during NMDA injury offer an important new therapeutic target for preventing many retinal disorders associated with excitotoxicity.

Recently, there have been several reports concerning the efficacy of intravitreal bevacizumab injection (IVB) in reducing macular oedema in patients with retinal vein occlusion (RVO).1 2 According to a safety survey of IVB, adverse ocular events are extremely rare.3 At our clinic, we have performed more than 300 IVB for RVO, and the majority of these injections did not have any adverse results. However, we experienced two cases of progression of macular ischaemia despite an improvement in macular oedema after IVB for central retinal vein occlusion (CRVO) in patients with poor glycaemic control of their diabetes and a history of systemic vascular disease. ### Case 1 A 76-year-old female with diabetes for 26 years, without a history of retinopathy, presented with CRVO in the right eye (figure 1A) and no retinopathy in the left eye. She was treated with insulin, but had poor glycaemic control (HbA1c 9.6%). General blood examination revealed mild renal dysfunction (BUN: …

Wilson disease (WD) is an autosomal recessive disorder of copper accumulation leading to liver and/or brain damage. In this paper, we describe the results of a pilot study of screening for WD using ceruloplasmin determinations in dried blood samples. Specimens were collected from children aged 1 to 6 years who were seen at local paediatric outpatient clinics in the Miyagi Prefecture. We measured ceruloplasmin (CP) concentrations in 2789 children using an enzyme-linked immunosorbent assay. The mean value was 12.4 +/- 3.95 mg/dl blood. Among these children, we identified two (case 1, male, 2 years old; case 2, female, 3 years old) with markedly reduced CP concentrations. Apart from low serum copper concentrations, their biochemical findings were almost normal, as were growth and development. To confirm the diagnosis, we analysed the WD gene and detected A803T/2871delC mutations in case 1 and R778L/G1035V mutations in case 2. We conclude that these children were presymptomatic WD patients. The CP level in dried blood samples from children aged 1 to 6 years appears to be a reliable marker for early detection of WD.

PURPOSE: To investigate, using laser speckle flowgraphy (LSFG), the autoregulation of ocular blood flow (BF) in response to posture change. METHODS: This study comprised 20 healthy volunteers (mean age 30.0 ± 8.5). The mean blur rate (MBR) of the ocular circulation in the subjects was assessed in both a sitting and a supine position every 2 min over the course of 10 min. Baseline measurements of the MBR at the optic nerve head (ONH) and the choroid were taken in a sitting position. Increases in the MBR ratio in a supine position were calculated with reference to this baseline. Intraocular pressure (IOP), systemic blood pressure and heart rate in the brachial artery were also recorded. RESULTS: In the ONH, the MBR ratio increased significantly over the baseline after 2 min (104.8 ± 5.0%, p = 0.001) and 4 min (104.4 ± 5.6%, p = 0.005), in a supine position, but decreased to the initial level after only 6 min. In the choroid, on the other hand, while the MBR ratio also increased significantly after 2 min in a supine position (113.7 ± 8.1%, p < 0.001), it kept this significant increase over the time course of 10 min. After 10 min in a supine position, IOP increased significantly (p < 0.001), systolic blood pressure decreased significantly (p < 0.001), but diastolic blood pressure did not change significantly compared to the baseline. (p = 0.07) CONCLUSIONS: ONH and choroidal circulation have significantly different hemodynamics in response to posture change in healthy volunteers. This finding suggests that LSFG enables us to assess the autoregulation of BF in the ONH.