Kawakami K.,Nagasaki Kawatana Medical Center |
Ohkusa Y.,National Institute of Infectious Disease |
Kuroki R.,Nagasaki Kawatana Medical Center |
Tanaka T.,Nagasaki Kawatana Medical Center |
And 5 more authors.
Vaccine | Year: 2010
To determine the clinical efficacy and cost-saving effect of pneumococcal polysaccharide vaccine (PPV) against community-acquired pneumonia (CAP), an open-label, randomized clinical trial was conducted involving 786 Japanese subjects older than 65 years of age receiving a routine influenza vaccine during the 2-year period. Study subjects were randomly assigned to either a PPV group (n= 394) or to a non-PPV group (n= 392). The incidence, admission and the medical cost for all-cause pneumonia were compared between these two groups. PPV vaccination significantly reduced the incidence of admission for all-cause pneumonia for subjects older than 75 years of age (41.5%, P= 0.039) and for those who had difficulty walking (62.7%, P= 0.005), but not for all study subjects older than 65 years of age (P= 0.183), for the 2-year period. The Kaplan-Meier survival curves for subjects who had difficulty walking free from all-cause pneumonia demonstrated a significant difference (P= 0.0146) between the two groups. PPV vaccination significantly reduced medical costs for all study subjects during the first year period (P= 0.027). Our present data demonstrated that PPV was effective for all-cause pneumonia for study subjects older than 75 years of age, although the effect was not significant for all study subjects older than 65 years of age. © 2010 Elsevier Ltd.
PubMed | Anjo Kosei Hospital, Uwajima City Hospital, Kitano Hospital Medical Research Institute, Sapporo Yamanoue Hospital and 7 more.
Type: Journal Article | Journal: Modern rheumatology | Year: 2016
It is not known whether autonomic neuropathy is a feature of Sjgrens syndrome (SS) or whether it is related to circulating antiganglionic acetylcholine receptor (gAChR) antibodies. The goal of the present study was to investigate the autonomic dysfunction in patients with SS and the associations between autonomic dysfunction, anti-gAChR antibodies, and clinical features of SS.(1) The first observational study tested for the presence of gAChR antibodies in the serum samples from 39 patients with SS (absent information regarding autonomic symptoms) and healthy volunteers. (2) In the second study, serological and clinical data from 10 Japanese patients diagnosed with SS were reviewed. These patients showed autonomic dysfunction, and luciferase immunoprecipitation systems (LIPS) test was conducted to detect anti-3 and anti-4 gAChR antibodies. (3) In the final analysis, we combined the data of seropositive SS patients with autonomic symptom from the first study with all of the patients from the second study, and analyzed the clinical features.(1) The LIPS assay revealed that anti-gAChR3 and anti-gAChR4 antibodies were detected in the sera from patients with SS (23.1%, 9/39). Five of nine SS patients had autonomic symptoms. (2) Anti-3 and anti-4 gAChR antibodies were also detected in 80.0% (8/10) of patients with SS with autonomic symptoms. Six of the ten patients were diagnosed as having SS after neurological symptoms developed. These seropositive patients had predominant and severe autonomic symptoms and were diagnosed with autonomic neuropathy. (3) Thirteen of fifteen SS patients with autonomic symptoms (86.7%) were seropositive for anti-gAChR antibodies, and we confirmed sicca complex, orthostatic hypotension, upper and lower gastrointestinal (GI) symptoms, and bladder dysfunction at high rates.The present results suggest the possibility of anti-gAChR antibodies aiding the diagnostics of SS with autonomic dysfunction.
PubMed | Tokyo Women's Medical University, Juntendo University, NHO Utano National Hospital, Sapporo Neurology Clinic and 16 more.
Type: Journal Article | Journal: Multiple sclerosis (Houndmills, Basingstoke, England) | Year: 2016
No large-scale studies have compared the efficacy of intravenous methylprednisolone pulse therapy (IVMP) for multiple sclerosis (MS) and neuromyelitis optica (NMO).To explain differences in treatment responses of MS and NMO patients to IVMP.Changes in neurological symptoms/signs and Expanded Disability Status Scale (EDSS) scores before and within 1week of IVMP completion were obtained in 2010 at 28 institutions, and retrospectively collated from 271 MS (478 courses) and 73 NMO (118 courses) cases.In MS patients, decreased EDSS score was significant after the first (-0.80.9), second (-0.70.9), and third (-0.70.8) courses (p<0.05), but not after the fourth (-0.30.7) and fifth (-0.50.6). However, decreased EDSS score was only significant after the first course (-0.51.5, p<0.05) in NMO patients. EDSS score was significantly decreased in MS compared with NMO patients at the first course (p<0.05), but not thereafter. Model analysis for EDSS score improvement at the first course, adjusting for covariates, showed significantly greater decreases in MS compared with NMO patients (p<0.05).IVMP is effective in MS from the first to third courses, and in NMO at the first course. Additionally, IVMP is more efficacious in MS than NMO patients, even at the first course.
PubMed | Kumamoto University, Nagasaki Kawatana Medical Center and Kyoto Prefectural University of Medicine
Type: Journal Article | Journal: BMC neurology | Year: 2016
Myasthenic symptoms can be present in patients with amyotrophic lateral sclerosis (ALS). These symptoms have been considered to be caused by the degeneration of distal motor neurons and the neuromuscular junction (NMJ). Recent studies suggested that antibody to low-density lipoprotein receptor-related protein 4 (LRP4) was a pathogenic agent of myasthenia gravis (MG), and it was also detected in ALS patients.Patient 1: A 58-year-old Japanese man developed progressive weakness and subsequent myasthenic symptoms including oculomotor disturbance. Clinical examination and electrophysiological studies confirmed upper and lower motor neuron involvement and NMJ dysfunction, and anti-LRP4 antibody was detected in his serum. A series of immunotherapies, including steroid pulse therapy, intravenous immunoglobulin, and plasmapheresis, was performed, and the myasthenic symptoms partially improved. The titer of anti-LRP4 antibody subsequently decreased. However, the therapeutic effect was transient, and ALS symptoms progressed. His clinical findings fulfilled the criteria of probable ALS using the Awaji criteria. Patient 2: A 74-year-old Japanese man suffered from progressive weakness of all limbs and dropped head in the evening. He complained of diplopia with a lateral horizontal gaze. Probable ALS was diagnosed because of the upper and lower motor neuron signs, whereas anti-LRP4 antibody was detected. Several immunotherapies were administered, and the myasthenic symptoms partially responded to each therapy. However, the truncal muscle weakness progressed, and he died of respiratory failure.We report two anti-LRP4 antibody-seropositive ALS patients with myasthenia who were not typical of ALS patients, and showed partial responses to immunotherapies. The anti-LRP4 antibody-seropositive status may influence developing ALS and cause additional ALS symptoms.
Kinoshita T.,Shinshu University |
Abe R.-T.,Shinshu University |
Hineno A.,Shinshu University |
Tsunekawa K.,Shinshu University |
And 2 more authors.
Internal Medicine | Year: 2014
Objective To investigate the causes of neurological manifestations in girls immunized with the human papillomavirus (HPV) vaccine.Methods During the past nine months, 44 girls visited us complaining of several symptoms after HPV vaccination. Four patients with other proven disorders were excluded, and the remaining forty subjects were enrolled in this study.Results The age at initial vaccination ranged from 11 to 17 years, and the average incubation period after the first dose of the vaccine was 5.47±5.00 months. Frequent manifestations included headaches, general fatigue, coldness of the legs, limb pain and weakness. The skin temperature examined in 28 girls with limb symptoms exhibited a slight decrease in the fingers (30.4±2.6°C) and a moderate decrease in the toes (27.1±3.7°C). Digital plethysmograms revealed a reduced height of the waves, especially in the toes. The limb symptoms of four girls were compatible with the Japanese clinical diagnostic criteria for complex regional pain syndrome (CRPS), while those in the other 14 girls were consistent with foreign diagnostic criteria for CRPS. The Schellong test identified eight patients with orthostatic hypotension and four patients with postural orthostatic tachycardia syndrome. The girls with orthostatic intolerance and CRPS commonly experienced transient violent tremors and persistent asthenia. Electron-microscopic examinations of the intradermal nerves showed an abnormal pathology in the unmyelinated fibers in two of the three girls examined.Conclusion The symptoms observed in this study can be explained by abnormal peripheral sympathetic responses. The most common previous diagnosis in the studied girls was psychosomatic disease. The social problems of the study participants remained unresolved in that the severely disabled girls stopped going to school. © 2014 The Japanese Society of Internal Medicine.
Motomura M.,Nagasaki University |
Higuchi O.,Nagasaki Kawatana Medical Center
Clinical Neurology | Year: 2012
Myasthenia gravis (MG) is caused by the failure of neuromuscular transmission mediated by pathogenic autoantibodies (Abs) against acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK). The seropositivity rates for routine AChR binding Ab and MuSK Ab in MG are 80-85% and 5-10% for MG patients in Japan, respectively. The autoimmune target in the remaining patients is unknown. In 2011, autoantibodies against low-density lipoprotein receptor-related protein 4 (Lrp4) were identified in Japanese MG patients and thereafter have been reported in Germany and the USA. We developed a simple technique termed Gaussia luciferase immunoprecipitation for detecting antibodies to Lrp4. As a result, nine generalized MG patients from 300 lacking AChR Ab are positive for Lrp4 antibodies. Thymoma was not observed in any of these patients. These antibodies inhibit binding of Lrp4 to its ligand and are predominantly of the IgGl subclass. In other reports of Lrp4 ab, Lrp4 ab positive sera inhibited agrin-induced aggregation of AChRs in cultured myotubes, suggesting a pathogenic role regarding the dysfunction of the neuromuscular endplate. These results indicate that Lrp4 is a third autoantigen in patients with MG, and anti-Lrp4 autoantibodies may be pathogenic. Further studies including neuromuscular junction biopsy are needed to clarify the pathomechanism of Lrp4 ab positive MG.
PubMed | Osaka City General Hospital and Nagasaki Kawatana Medical Center
Type: Case Reports | Journal: Brain & development | Year: 2016
Autoimmune autonomic ganglionopathy (AAG) is an acquired immune-mediated disorder that leads to systemic autonomic failure. Autoantibodies to the ganglionic nicotinic acetylcholine receptor (gAChR) are detected in 50% of AAG patients. We report the first pediatric case of AAG presenting with acute encephalitis. The patient was a 13-year-old boy who presented with orthostatic hypotension, followed by rapidly progressing disturbance of consciousness. Cerebrospinal fluid analysis revealed significant pleocytosis and increased neopterin concentration. Head MRI showed hyperintensities in bilateral caudate nuclei, putamen, hippocampus, and insula cortex. Severe autonomic dysfunctions such as severe orthostatic hypotension, bradycardia, dysuria, prolonged constipation and vomiting appeared. These symptoms were successfully controlled by repeated immunomodulating therapy with intravenous methylprednisolone pulse therapy and intravenous immunoglobulin. Autoantibodies to the 3 subunit of gAChR were detected at neurological onset, but were undetectable five months later. This observation indicates that AAG should be suspected in patients manifesting acute encephalitis characterized by preceding and prolonged autonomic symptoms, and immunomodulating therapy from an early stage can be effective.
PubMed | Kumamoto University, Nagasaki Kawatana Medical Center, University of Tsukuba, Nagasaki University and Clinical Research Center
Type: Comparative Study | Journal: PloS one | Year: 2016
Anti-ganglionic nicotinic acetylcholine receptor (gAChR) antibodies are observed in autoimmune diseases, as well as in patients with autoimmune autonomic ganglionopathy. However, the genetic background of anti-gAChR antibodies is unclear. Here, we investigated HLA alleles in autoimmune hepatitis (AIH) patients with or without anti-gAChR antibodies.Genomic DNA from 260 patients with type-1 autoimmune hepatitis (AIH) were genotyped for HLA-A, B, DRB1, and DQB1 loci. Anti-gAChR antibodies in the sera form AIH patients were measured using the luciferase immunoprecipitation system, and examined allelic association in patients with or without anti-gAChR antibodies.We detected anti-3 or -4 gAChR antibodies in 11.5% (30/260) of patients with AIH. Among AIH patients there was no significant association between HLA-A, B DQB1 alleles and the positivity for anti-gAChR antibodies. Whereas the HLA-DRB1*0403 allele showed a significantly increased frequency in AIH patients with anti-gAChR antibodies compared with those without anti-gAChR antibodies.The frequency of the HLA-DRB1*0403 allele differed among Japanese patients with AIH according to the presence or absence of anti-gAChR antibodies. Our findings suggest that particular HLA class II molecules might control the development of anti-gAChR antibodies in the autoimmune response to gAChR.
Urasaki E.,Nagasaki Kawatana Medical Center |
Fukudome T.,Nagasaki Kawatana Medical Center |
Hirose M.,Nagasaki Kawatana Medical Center |
Nakane S.,Nagasaki Kawatana Medical Center |
And 2 more authors.
Journal of Clinical Neuroscience | Year: 2013
Neuroleptic malignant syndrome (NMS), also called parkinsonism-hyperpyrexia syndrome (PHS), is a severe, general, sometimes fatal, physical reaction, induced by sudden and strong blockade of dopamine receptors. When subthalamic nucleus (STN)-deep brain stimulation (DBS) is used on patients with Parkinson disease (PD), dopaminergic medications are transiently stopped prior to the procedure, and a reduction in the use of drugs is routinely attempted after the procedure. Although a sudden stop or abrupt reduction of dopaminergic medications may set the stage for NMS/PHS, only three cases have been reported after STN-DBS surgery. Here, we describe a 75-year-old woman with PD who experienced delayed onset, yet fatal, PHS after STN-DBS. Although STN-DBS might prevent or suppress PHS, its protective effect is not always complete. We must be aware that fatal PHS can occur when the use of medication for PD is reduced or altered, even when patients are under continuous STN stimulation. © 2012 Elsevier Ltd. All rights reserved.
Nakane S.,Nagasaki Kawatana Medical Center
Clinical Neurology | Year: 2013
Autoimmune autonomic ganglionopathy (AAG) is a disorder of isolated autonomic failure associated with antibodies to the nitotinic acetylcholine receptor of the autonomic ganglia resulting in severe autonomic dysfunction. The disorder is associated with and most likely caused by antibodies to gAChR. In this study, we attempted to develop a novel technique to detect antibodies that bind to gAChR. We established a simple in vitro system termed GLIP (gaussia luciferase-reporter immunoprecipitation), which can detect protein-protein interactions with high sensitivity and using no radioisotope. Using this new method, we extensively reviewed the case histories with current clinical and laboratory evaluations that include testing for antibodies to p3 and 34 subunits of gAChR in serum available from the time of symptom onset. Here, we describe 7 patients with gAChR autoantibody and autonomic dysfunction. Our observations also suggest that autoimmune-mediated impairment of autonomic function may be partially reversible. Six of 7 patients improved in response to immunotherapy (e.g. PP, IVMP, IVIg, and immunosuppressant drugs) with symptomatic therapy. We interpreted the improvement in clinical symptoms correlated with the decrease in the levels of anti gAChR antibodies in each case. Some patients with seropositive AAG respond to treatment with IVMP or PP or IVIg, although when used as a single agent, subsequent treatments are required in patients to maintain the improvement.