Ohtsuka T.,International University of Health and Welfare
Journal of Dermatology | Year: 2014
Entero-Behçet's disease coexisting with long-term epilepsy and schizophrenia-like symptoms is presented. A 43-year-old woman presented with repeatedly occurring aphthous stomatitis for several years. She had been treated for absence seizures, epilepsy and schizophrenia since she was 9 years old. She presented with multiple aphthous stomatitis on her gingiva, erythema nodosum-like symptoms on the right lateral aspect of her leg and genital ulcers on her perianal area. She also showed polyarthritis. Laboratory examinations revealed elevated C-reactive protein, elevated neutrophil counts, decreased serum Fe and elevated serum Cu. Histological examination showed perivascular neutrophil and mononuclear cell infiltrates and eosinophilic change of the vessel wall in the lobules of subcutaneous fat tissue. Six weeks after the oral prednisolone therapy, she showed resolution of aphthous stomatitis, folliculitis-like eruption and genital ulcer. She experienced severe abdominal pain after the start of treatment of Behçet's disease. Plain computed tomography revealed edematous change in the appendix, and ascending and transverse colon. These results led to the diagnosis of entero-Behçet's disease acute exaggeration. Treatment with infliximab (300 mg/once) was started. Eight weeks after the start of infliximab, her abdominal pain disappeared and C-reactive protein decreased, followed by the successful change to adalimumab infusion therapy. © 2014 Japanese Dermatological Association.
Suzuki Y.,International University of Health and Welfare
Brain and Development | Year: 2013
Chaperone therapy is a newly developed molecular therapeutic approach to lysosomal diseases, a group of human genetic diseases causing severe brain damage. Based on early molecular studies during the last decade of the 20th century and early years of the 21st century, mainly on Fabry disease and GM1-gangliosidosis, we found some mutant enzyme proteins were unstable in the cell, and unable to express catalytic activities. Subsequently galactose and other active-site binding substrate analogs were found stabilized and enhance the mutant enzyme activity in culture cells. We concluded that the mutant misfolding enzyme protein and substrate analog competitive inhibitor (chemical chaperone) form a stable complex to be transported to the lysosome, to restore the catalytic activity of mutant enzyme after spontaneous dissociation under the acidic condition. This gene mutation-specific molecular interaction is a paradoxical phenomenon that an enzyme inhibitor in vitro serves as an enzyme stabilizer in situ. First we developed a commercially available compound 1-deoxygalactonojirimycin (DGJ) for Fabry disease, and confirmed the above molecular phenomenon. Currently DGJ has become a new candidate of oral medicine for Fabry disease, generalized vasculopathy involving the kidneys, heart and central nervous system in the middle age. This drug development has reached the phase 3 of human clinical study. Then we found two valienamine derivatives, N-octyl-4-epi-β-valienamine (NOEV) and N-octyl-β-valienamine (NOV), as promising therapeutic agents for human β-galactosidase deficiency disorders (GM1-gangliosidosis and Morquio B disease) and β-glucosidase deficiency disorders (phenotypic variations of Gaucher disease), respectively. Originally NOEV and NOV had been discovered as competitive inhibitors, and then their paradoxical bioactivities as chaperones were confirmed in cultured fibroblasts from patients with these disorders. Subsequently GM1-gangliosidosis model mice have been used for confirmation of clinical effectiveness, adverse effects and pharmacokinetic studies. Orally administered NOEV entered the brain through the blood-brain barrier, enhanced β-galactosidase activity, reduced substrate storage, and improved neurological deterioration clinically. Computational analysis revealed pH-dependent enzyme-chaperone interactions. Our recent study indicated chaperone activity of a new DGJ derivative, MTD118, for β-galactosidase complementary to NOEV. NOV also showed the chaperone effect toward several β-glucosidase gene mutants in Gaucher disease. Furthermore a commercial expectorant drug ambroxol was found to be a chaperone for β-glucosidase. A few Gaucher patients responded to this drug with remarkable improvement of oculomotor dysfunction and myoclonus. We hope chaperone therapy will become available for some patients with Fabry disease, GM1-gangliosidosis, Gaucher disease, and other lysosomal storage diseases particularly with central nervous system involvement. © 2013 The Japanese Society of Child Neurology.
Ohtsuka T.,International University of Health and Welfare
Journal of Dermatology | Year: 2012
The diagnosis of systemic sclerosis (SSc) is often difficult. The purpose of the present study was to find the distribution of nail fold capillary abnormality in SSc. Sixty-two patients with SSc (male: female = 7:55, age 21-86 years, mean 60.1) admitted to the outpatient clinics were studied. Eighteen age- and sex-matched normal subjects, 28 patients with systemic lupus erythematosus (SLE) and 10 with dermatomyositis (DM) were also studied. Nail fold capillary loops were observed under immersion oil at a magnification of Ã - 40 with a light microscope. Dilated capillaries, nail fold bleeding and avascular areas were found by dermoscopic observation. The distribution of dilated capillaries, nail fold bleeding and avascular areas in normal controls showed in one (5.6%), one (5.6%) and four cases (22.2%), respectively. The distribution of dilated capillaries, nail fold bleeding and avascular area in SSc patients showed in 27 cases (43.5%), eight cases (12.9%) and 16 cases (25.8%), respectively. The distribution of dilated capillaries and/or nail fold bleeding in SSc patients (29/62, 46.8%) was significantly elevated than that of normal controls (2/18, 11.1%) (P < 0.01). The distribution of overall abnormality in SSc (30/62, 48.4%) showed no significant difference compared with that of normal controls (4/18, 22.2%). Sensitivity and specificity for dilated capillaries and/or nail fold bleeding and overall nail fold abnormality in SSc patients compared with normal controls was calculated as 40.8% and 93.5%, 34.8% and 88.2%, respectively. Dermoscopic observation of dilated capillaries and/or nail fold bleeding is a sensitive and specific method for the detection of SSc. © 2011 Japanese Dermatological Association.
Sato A.,International University of Health and Welfare
Hypertension Research | Year: 2015
Diabetes mellitus is a major cause of chronic kidney disease (CKD), and diabetic nephropathy is the most common primary disease necessitating dialysis treatment in the world including Japan. Major guidelines for treatment of hypertension in Japan, the United States and Europe recommend the use of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, which suppress the renin-angiotensin system (RAS), as the antihypertensive drugs of first choice in patients with coexisting diabetes. However, even with the administration of RAS inhibitors, failure to achieve adequate anti-albuminuric, renoprotective effects and a reduction in cardiovascular events has also been reported. Inadequate blockade of aldosterone may be one of the reasons why long-term administration of RAS inhibitors may not be sufficiently effective in patients with diabetic nephropathy. This review focuses on treatment in diabetic nephropathy and discusses the significance of aldosterone blockade. In pre-nephropathy without overt nephropathy, a mineralocorticoid receptor antagonist can be used to enhance the blood pressure-lowering effects of RAS inhibitors, improve insulin resistance and prevent clinical progression of nephropathy. In CKD categories A2 and A3, the addition of a mineralocorticoid receptor antagonist to an RAS inhibitor can help to maintain 'long-term' antiproteinuric and anti-albuminuric effects. However, in category G3a and higher, sufficient attention must be paid to hyperkalemia. Mineralocorticoid receptor antagonists are not currently recommended as standard treatment in diabetic nephropathy. However, many studies have shown promise of better renoprotective effects if mineralocorticoid receptor antagonists are appropriately used. © 2015 The Japanese Society of Hypertension All rights reserved.
Ito Y.,International University of Health and Welfare
Pediatrics International | Year: 2014
The aim of this systematic review was to critically examine the existing literature regarding the effectiveness of tongue-tie division in infants with ankyloglossia, using the new grades of recommendations, assessment, development, and evaluation (GRADE) rating system. A clinical question was structured according to patient, intervention, comparison, and outcome, as follows: in infants with poor breast-feeding and ankyloglossia (patient), does frenotomy (intervention), compared to lactation support alone (comparison), improve feeding (outcome)? An electronic literature search was systematically conducted from databases including PubMed, Japana Centra Revuo Medicina (Igaku Chuo Zasshi), CINAHL, and Cochrane Library using the key words "ankyloglossia," "tongue-tie," "frenotomy," and/or "breastfeeding" in English and equivalent terms in Japanese. The literature search yielded four randomized clinical trials, and 12 observational studies for analysis. The quality of the literature was rated in regard to the two most important outcomes (sucking/latching, and nipple pain) and five less important outcomes (milk supply/milk production, continuation of breast-feeding, weight gain, adverse events, and dyad distress) in accordance with the GRADE system. Evidence levels of the most important outcomes were rated either A (strong evidence) or B (moderate evidence), and less important outcomes were rated C (weak evidence); every outcome consistently showed a favorable effect of frenotomy on breast-feeding. The literature review supported an overall moderate quality of evidence for the effectiveness of frenotomy for the treatment of breast-feeding difficulties in infants with ankyloglossia. No major complications from frenotomy were reported. © 2014 Japan Pediatric Society.
Kaneko H.,International University of Health and Welfare
Respiratory Care | Year: 2014
BACKGROUND: The 3-dimensional (3D) distances of specific points on the chest and abdominal wall are useful for assessing the characteristics of breathing movement. This study aimed to determine whether the 3D distances on the chest and abdominal wall during deep breathing (DB) could be estimated using a newly developed breathing movement-measuring device (BMMD). METHODS: Breathing movement distances on the chest (bilateral third and eighth ribs) and abdomen (upper abdomen) of 10 healthy young males were measured using a pen-sized mechanical BMMD and a 3D motion analysis system during DB. DB was controlled and based on the distances targeted by the BMMD (ie, 1, 2, and 3 cm), which was placed on the observation points and fixed on a tripod. Simultaneously, the 3D distances of reflective markers on the observation points were measured. The obtained data were statistically analyzed using a paired t test, repeated measures analysis of variance with multiple comparisons tests, and linear regression with mixed effects. RESULTS: All the BMMD distances were less than the 3D distances. The differences between the 3D and BMMD distances on the chest and abdomen, except for the left lower chest (eighth rib), were significantly greater at a target distance of 3 cm than that of 1 cm. The coefficients of determination ranged from 0.98 to 0.99. CONCLUSIONS: Linear regression equations provided adequate estimates of the 3D distances of markers on the chest and abdominal wall during DB. The results suggest that this BMMD is useful for quantitatively assessing DB movement of the chest and abdominal wall in healthy young males. © 2014 by Daedalus Enterprises.
Suzuki Y.,International University of Health and Welfare
World journal of gastroenterology : WJG | Year: 2010
To examine the long term survival of geriatric patients treated with percutaneous endoscopic gastrostomy (PEG) in Japan. We retrospectively included 46 Japanese community and tertiary hospitals to investigate 931 consecutive geriatric patients (≥ 65 years old) with swallowing difficulty and newly performed PEG between Jan 1st 2005 and Dec 31st 2008. We set death as an outcome and explored the associations among patient's characteristics at PEG using log-rank tests and Cox proportional hazard models. Nine hundred and thirty one patients were followed up for a median of 468 d. A total of 502 deaths were observed (mortality 53%). However, 99%, 95%, 88%, 75% and 66% of 931 patients survived more than 7, 30, 60 d, a half year and one year, respectively. In addition, 50% and 25% of the patients survived 753 and 1647 d, respectively. Eight deaths were considered as PEG-related, and were associated with lower serum albumin levels (P = 0.002). On the other hand, among 28 surviving patients (6.5%), PEG was removed. In a multivariate hazard model, older age [hazard ratio (HR), 1.02; 95% confidence interval (CI), 1.00-1.03; P = 0.009], higher C-reactive protein (HR, 1.04; 95% CI: 1.01-1.07; P = 0.005), and higher blood urea nitrogen (HR, 1.01; 95% CI: 1.00-1.02; P = 0.003) were significant poor prognostic factors, whereas higher albumin (HR, 0.67; 95% CI: 0.52-0.85; P = 0.001), female gender (HR, 0.60; 95% CI: 0.48-0.75; P < 0.001) and no previous history of ischemic heart disease (HR, 0.69; 95% CI: 0.54-0.88, P = 0.003) were markedly better prognostic factors. These results suggest that more than half of geriatric patients with PEG may survive longer than 2 years. The analysis elucidated prognostic factors.
Utsunomiya H.,International University of Health and Welfare
Brain and Development | Year: 2011
Diffusion-weighted imaging (DWI) makes it possible to measure early changes in cellular function in the central nervous system. The purpose of this article is to discuss the diagnostic value of diffusion-weighted and diffusion tensor imaging (DTI) in different pediatric cerebral disorders. First, the principles of DWI and DTI are briefly reviewed. The clinical usefulness of these imaging techniques is then discussed using cases with pediatric neurological disorders, such as hypoxic-ischemic encephalopathy in neonates, trauma (shaken baby syndrome), encephalopathy or encephalitis in infants, posterior reversible encephalopathy syndrome and congenital brain anomaly (callosal dysgenesis). In addition, using DTI, we evaluate normal brain development, particularly in the corpus callosum and cortico-spinal tract, and discuss the application of DTI to the study of white matter in the developing brain. © 2010 The Japanese Society of Child Neurology.
Nishiki M.,International University of Health and Welfare
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2015
Evaluation of the effective focal spot size of X-ray tube has been made utilizing the slit or the pin-hole camera, but is not widely used in a daily practice due to the need of specialized tools. The author proposes a simplified method in which only a metal edge and a digital detector are used, together with a process of removing detector blur inherently associated with the adoption of such a detector. The evaluation was made through the OTF (Optical Transfer Function) measurements by using the edge response analysis. Through the whole study, the use of OTF instead of MTF (Modulation Transfer Function) was essential in order to stay within the linear systems theory framework, at cost of handling complex functions. Evaluation steps were as follows; 1. The inherent OTF of the detector (OTFdet) was measured by acquiring an image of the edge being closely contacted to the detector. 2. The second OTF (OTFmulti) was measured with the edge placed apart from the detector so as to implement 2 times geometrical magnification of the edge. OTFmulti is the product of OTFdet and the focal spot OTF (OTFfocus). 3. OTFfocus was obtained by calculating OTFmulti / OTFdet, thus removing the detector blur completely. 4. The LSF of the focal spot was obtained through the inverse Fourier transform of OTFfocus. The resultant LSFfocus was assured to be a real function due to the fact that original LSFdet and LSFmulti were both real functions. Preliminary results well matched those obtained by the pinhole camera. © 2015 SPIE.
Sato A.,International University of Health and Welfare
Hypertension Research | Year: 2013
In the presence of salt, aldosterone causes hypertension and organ damage via the mineralocorticoid receptor (MR) through various mechanisms. MR antagonists are considered to be potassium-sparing diuretics that exert their effect by blocking MR in the kidney, and they are not the first choice for treating hypertension. However, the importance and usefulness of inhibiting aldosterone in the management of hypertension have recently been revealed in both the basic and clinical fields. In Japan, both the selective MR antagonist eplerenone and the non-selective MR antagonist spironolactone are indicated for the treatment of hypertension. Although these drugs are generally used in the same manner, in some cases they require differentiation. This differentiation is divided into two types due to the differences in their features and differences in their contraindications in Japan. Based on a number of studies on MR antagonists that have been recently published, the diseases and clinical conditions targeted by MR antagonists appear to be likely to increase in the future. In Japan, we consider it necessary to carefully differentiate spironolactone from eplerenone in regard to their intended uses. © 2013 The Japanese Society of Hypertension All rights reserved.