Kazui H.,Osaka University |
Miyajima M.,Juntendo University |
Mori E.,Tohoku University |
Mori E.,Juntendo University |
And 27 more authors.
The Lancet Neurology | Year: 2015
Background: Lumboperitoneal shunt surgery has the potential to alleviate symptoms of normal pressure hydrocephalus but the benefits of such surgery have not been tested in a randomised trial. The aim of this trial was to determine the safety and efficacy of the lumboperitoneal shunt surgery for this disorder. Methods: For the open-label randomised SINPHONI-2 trial, eligible participants (60-85 years of age) with idiopathic normal pressure hydrocephalus, with ventriculomegaly, and tightness of the high-convexity and medial subarachnoid spaces on MRI, were recruited from 20 neurological and neurosurgical centres in Japan. Enrolled participants were randomly assigned in a 1:1 ratio according to a random code generated by the trial statistician, with a permuted block design (using a block size of 4 or 6) within each centre, to receive lumboperitoneal shunt surgery within 1 month after randomisation, or to surgery postponed for 3 months. Patients and assessors were not masked to treatment assignment. The primary endpoint was favourable outcome, defined as an improvement of one point or more on the modified Rankin scale (mRS) at 3 months after randomisation, analysed by intention to treat, and the main secondary endpoint was the same outcome 12 months after surgery, analysed per protocol. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), number UMIN000002730. Findings: Between March 1, 2010, and Oct 19, 2011, 93 patients with idiopathic normal pressure hydrocephalus were enrolled and randomly assigned to the immediate treatment group (n=49) or the postponed treatment group (n=44). More patients in the immediate treatment group than in the postponed treatment group had an improvement of one point or more on the mRS at 3 months: 32 (65%) of 49 in the immediate group vs 2 (5%) of 44 in the postponed group (difference 61% [95% CI 42-68]; p<0·0001). The number of patients who had an improvement of one point or more on the mRS at 12 months after surgery was similar between the two groups: 30 (67%) of 45 patients in the immediate group vs 22 (58%) of 38 in the postponed group (difference 9% [95% CI -14 to 31]; p=0·496). The proportions of patients with serious adverse events did not differ significantly between the groups during the 3 months post-randomisation (7 [15%] of 46 in the immediate group vs 1 [2%] of 42 in the postponed group; p=0·060). During the 12 months after surgery, 19 (22%) of 87 patients had serious adverse events, the most common of which was cerebral infarction (six patients [7%]). Interpretation: Our results suggest that lumboperitoneal shunt surgery might be beneficial for patients with idiopathic normal pressure hydrocephalus and, if these findings are confirmed in larger studies, could be a first-line treatment option for this disease. Funding: Johnson & Johnson and Nihon Medi-Physics. © 2015 Elsevier Ltd.
PubMed | Juntendo University, Toshiba Corporation, Megumino Hospital, Tokyo Kyosai Hospital and 3 more.
Type: Journal Article | Journal: PloS one | Year: 2016
Little is known about genetic risk factors for idiopathic normal pressure hydrocephalus (iNPH). We examined whether a copy number loss in intron 2 of the SFMBT1 gene could be a genetic risk for shunt-responsive, definite iNPH. Quantitative and digital PCR analyses revealed that 26.0% of shunt-responsive definite iNPH patients (n = 50) had such a genetic change, as compared with 4.2% of the healthy elderly (n = 191) (OR = 7.94, 95%CI: 2.82-23.79, p = 1.8 x 10-5) and 6.3% of patients with Parkinsons disease (n = 32) (OR = 5.18, 95%CI: 1.1-50.8, p = 0.038). The present study demonstrates that a copy number loss within intron 2 of the SFMBT1 gene may be a genetic risk factor for shunt-responsive definite iNPH.
Iuchi H.,Megumino Hospital |
Watabe Y.,Megumino Hospital |
Hashimoto H.,Megumino Hospital |
Kitahara K.,JR Sapporo Hospital |
And 2 more authors.
Nishinihon Journal of Urology | Year: 2012
A 68-year-old man was referred to our outpatient clinic with left renal cell cancer and bladder cancer. He had undergone combination therapy comprising chemotherapy plus radiation therapy following radical orchiectomy for testicular cancer at the age of 48 years. The right testis could be felt within the scrotum, however the left testis could not Blood tests showed no abnormality in regard to testicular tumor markers. Urine cytology was class V. Computed tomography revealed a 3.0 × 3.4 cm mass in the left kidney and a 4.5 × 1.5 cm mass in the left wall of the bladder. We made it a priority to treat the bladder cancer which was strongly suspected to be invasive cancer. At first the patient underwent radical cystectomy. Then left partial nephrectomy was carried out. Our case would appear to be the 24th case of triple primary urogenital cancer in Japan that consisted of left testicular cancer, left renal cancer and bladder cancer. Our case was also thought to be a case of secondary cancer that developed following treatment for testicular cancer.
Hattori A.,Megumino Hospital |
Imai M.,Megumino Hospital |
Moriai T.,Megumino Hospital
Journal of the Japan Diabetes Society | Year: 2013
We herein describe the case of an 87-year-old female with type 2 diabetes treated with sitagliptin who developed bullous pemphigoid (BP). Approximately one month after the administration of sitagliptin, she was admitted with erythema multiforme spreading from the lower legs. Five days after admission, blisters appeared on the patient's palms and thighs. She was diagnosed with BP based on the results of a pathological examination and an elevated BP antigen level in the serum. The BP was controlled after withdrawing the suspected medication and administering steroid therapy. Recently, the development of BP has been reported in patients treated with DPP-4 inhibitors. We also report a case of BP that developed following the administration of a DPP-4 inhibitor.
Toi H.,Megumino Hospital |
Morita T.,Megumino Hospital |
Nakamura T.,Megumino Hospital |
Muranaga S.,Megumino Hospital |
Hase T.,Megumino Hospital
Japanese Journal of Cancer and Chemotherapy | Year: 2011
Background: Oxaliplatin is one of the key drugs for the treatment of colorectal cancer, although it is known to cause hepatic sinusoidal injury. Method: Thirty-one patients underwent modified FOLFOX6 therapy from April 2006 and December 2009 at our hospital. Four patients were excluded from this study because they had too many intervals in their therapeutic courses. The size of the spleen and the blood platelet count were analyzed before and after 6 months of FOLFOX therapy. The spleen was measured using CT scan, and the splenic index (SI=length X width X height) was evaluated. Results: After 6 months of treatment, the mean SI was increased from 229 cm3 to 323 cm 3 (p<0. 01). At the same time, the mean platelet count was decreased from 26.9 × 104/mm3 to 17.1 × 104/mm3 (p<0.01). Anegative correlation was found between the ratio of SI and the platelet count after 6 months of treatment to baseline (ρ=-0.42, p=0.030). SI increased by >50% in 12 patients (44.4%). The platelet count decreased more severely in patients whose SI increased by >50% (p=0.028). Conclusions: Splenomegaly and thrombocytopenia were observed in patients who underwent FOLFOX therapy. These are candidate parameters for evaluating hepatic sinusoidal injury.
Cho Y.,Hokkaido University |
Iizuka S.,Tenshi Hospital |
Hatae Y.,Megumino Hospital |
Kobayashi K.,Sapporo Hokuyu Hospital |
And 3 more authors.
Hemoglobin | Year: 2012
We undertook a 25-year observation of a female patient with an unstable variant, Hb Nottingham or β98(FG5)Val→Gly, GTG>GGG. The proband was diagnosed with Hb Nottingham at the age of 9 years. Splenectomy was performed in order to successfully aid her height growth due to chronic anemia at the age of 11, although anemia improvement was transient. She experienced pregnancy/delivery twice, at age 23 and 26, respectively. During both pregnancies, a large number of nucleated red blood cells (NRBCs) appeared in her peripheral blood. No developmental delay of the fetus was noted in either pregnancy, and she gave birth without any maternal complications or perinatal problems. Both babies were diagnosed with Hb Nottingham. To the best of our knowledge, this is the first report of a long-term observation of a proband with Hb Nottingham, including her pregnancy/delivery and the neonatal course of her children with the same disorder. © 2012 Informa Healthcare USA, Inc.
Miura Y.,Megumino Hospital |
Ogawa K.,Megumino Hospital
Gastroenterological Endoscopy | Year: 2014
Intestinal spirochetosis (IS) is a zoonotic infection caused by gram-negative, spiral-shaped bacilli belonging to the genus Brachyspira and an entity characterized histologically by spirochetes attached to the surface of colorectal epithelium resulting in a basophilic fringe. Although, as in animals, Brachyspira spp. can infect the colon in humans, their pathogenicity in humans remains controversial. Brachyspira infection is weak and subtle in most cases, and clinicians usually pay little attention to this bacillus; however, it is severe enough in some cases to be mistaken for inflammatory bowel disease. We report herein our experience with a 16-year-old female who suffered from diarrhea for 2 months. Her colonoscopy findings showed edema and reddening at the ascending and transverse coloa The biopsy specimen showed gram-negative, spiral-shaped bacilli, confirming the diagnosis of IS. The pathological and clinical features of IS are discussed along with a review of the literature.
Toi H.,Roswell Park Cancer Institute |
Toi H.,Megumino Hospital |
Tsujie M.,Roswell Park Cancer Institute |
Tsujie M.,Kinki University |
And 5 more authors.
International Journal of Cancer | Year: 2015
Endoglin (ENG) is a TGF-β coreceptor and essential for vascular development and angiogenesis. A chimeric antihuman ENG (hENG) monoclonal antibody (mAb) c-SN6j (also known as TRC105) shows promising safety and clinical efficacy features in multiple clinical trials of patients with various advanced solid tumors. Here we developed a novel genetically engineered mouse model to optimize the ENG-targeting clinical trials. We designed a new targeting vector that contains exons 4-8 of hENG gene to generate novel genetically engineered mice (GEMs) expressing functional human/mouse chimeric (humanized) ENG with desired epitopes. Genotyping of the generated mice confirmed that we generated the desired GEMs. Immunohistochemical analysis demonstrated that humanized ENG protein of the GEMs expresses epitopes defined by 7 of our 8 anti-hENG mAbs tested. Surprisingly the homozygous GEMs develop normally and are healthy. Established breast and colon tumors as well as metastasis and tumor microvessels in the GEMs were effectively suppressed by systemic administration of anti-hENG mAbs. Additionally, test result indicates that synergistic potentiation of antitumor efficacy can be induced by simultaneous targeting of two distinct epitopes by anti-hENG mAbs. Sorafenib and capecitabine also showed antitumor efficacy in the GEMs. The presented novel GEMs are the first GEMs that express the targetable humanized ENG. Test results indicate utility of the GEMs for the clinically relevant studies. Additionally, we generated GEMs expressing a different humanized ENG containing exons 5-6 of hENG gene, and the homozygous GEMs develop normally and are healthy. What's new? Endoglin (ENG) is a TGF-β coreceptor that is essential for vascular development and angiogenesis. A chimeric anti-human ENG (hENG) monoclonal antibody has shown promising safety and clinical efficacy in clinical trials of patients with various advanced solid tumors. Here, the authors developed a novel genetically engineered mouse model expressing a functional humanized ENG to optimize ongoing and future hENG antibody-based cancer therapy in patients. The homozygous genetically engineered mice developed normally and were healthy. Growth of established breast and colon tumors as well as metastasis and microvessel density in the mice were effectively suppressed by systemic administration of hENG mAbs. © 2014 UICC.
PubMed | Megumino Hospital
Type: Journal Article | Journal: Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2011
Oxaliplatin is one of the key drugs for the treatment of colorectal cancer, although it is known to cause hepatic sinusoidal injury.Thirty-one patients underwent modified FOLFOX6 therapy from April 2006 and December 2009 at our hospital. Four patients were excluded from this study because they had too many intervals in their therapeutic courses. The size of the spleen and the blood platelet count were analyzed before and after 6 months of FOLFOX therapy. The spleen was measured using CT scan, and the splenic index(SI=lengthwidthheight)was evaluated.After 6 months of treatment, the mean SI was increased from 229 cm3 to 323 cm3(p<0. 01). At the same time, the mean platelet count was decreased from 26. 9 10 / / 4 mm3 to 17. 1104 mm3(p<0. 01). A negative correlation was found between the ratio of SI and the platelet count after 6 months of treatment to baseline(r=-0. 42, p=0. 030). SI increased by>50% in 12 patients (44. 4%). The platelet count decreased more severely in patients whose SI increased by>50%(p=0. 028).Splenomegaly and thrombocytopenia were observed in patients who underwent FOLFOX therapy. These are candidate parameters for evaluating hepatic sinusoidal injury.
PubMed | Asahikawa University and Megumino Hospital
Type: Journal Article | Journal: Lower urinary tract symptoms | Year: 2016
To investigate urodynamic efficacy and safety of mirabegron add-on treatment with tamsulosin for Japanese male patients with overactive bladder (OAB).A prospective study was conducted in 26 consecutive male patients with OAB who had been taking tamsulosin. OAB was diagnosed by overactive bladder symptom score (OABSS). Before and 8weeks after mirabegron add-on treatment with preceding tamsulosin, we assessed OABSS, International Prostate Symptom Score (IPSS), free uroflowmetry (UFM), filling cystometry and pressure-flow study (PFS).Mean age and prostate volume of the study patients were 757years and 3219mL, respectively. Mirabegron significantly improved OABSS (from 8.52.3 to 4.72.5, P<0.001). On free UFM, mirabegron significantly increased voided volume (from 13547 to 182102mL, P=0.01), maximum (from 10.73.7 to 13.56.4mL/sec, P<0.01) and average flow rate (from 5.51.9 to 7.13.3mL/sec, P<0.01), while postvoid residual urine volume did not change significantly (from 4738 to 6361mL, P=0.23). Before mirabegron, 24 patients (92%) had detrusor overactivity (DO). After mirabegron add-on, maximum cystometric capacity significantly increased from 17098 to 21295mL (P=0.01) and DO disappeared in six patients (25%). In the other 18 patients with persistent DO, amplitude of involuntary contraction decreased and bladder volume at first involuntary contraction increased with statistical significance. On PFS, detrusor pressure at maximum flow rate (from 7931 to 6819cmH2 O, P=0.10) or bladder contractility index (from 12639 to 12027, P=0.45) did not change significantly.Mirabegron add-on treatment with tamsulosin has efficacy and safety because it improves storage symptom without impairment of bladder contractility during voiding in male patients with OAB.